MedicalResearch.comExclusive Interviews with Medical Research and

Health Care Researchers from Major and Specialty Medical Research Journals and Meetings

Editor: Marie Benz, MD info@medicalresearch.com

Sept. 12 2014

For Informational Purposes Only: Not for Specific Medical Advice.

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Ebola: Each Primary Infection Resulting In Spread To More Than One Additional CaseMedicalResearch.com: Interview with:Dr. Gerardo Chowell-Puente Ph.D.Associate Professor School of Human Evolution and Social Change

College of Liberal Arts and Sciences Arizona State University

• Medical Research: What are the main findings of the study?• Dr. Chowell-Puente:• 1.We estimated the effective reproduction number of Ebola virus disease, i.e. average number of

secondary cases produced by a single primary case at calendar time t (Rt), for the ongoing epidemic in West Africa from March to August 2014. Estimates of Rt for the Guinea, Sierra Leone and Liberia, countries that are experiencing sustained community transmission were consistently above 1.0 since June 2014.

• 2.Country-specific estimates of the reproduction number for Liberia and Sierra Leone lied between 1.0 and 2.0, reflecting continuous growth of cases in these countries

• 3. Effective reproduction number below 2 indicate that control could be attained by preventing over half of the secondary transmissions per primary case (e.g. by means of effective case isolation and contact tracing).

• Medical Research: What recommendations do you have for future research as a result of this study?• • Dr. Chowell-Puente: Our statistical analysis of the reproduction number of Ebola virus disease in West

Africa has demonstrated that the continuous growth of cases from June to August 2014 signaled a major epidemic, which is in line with estimates of the Rt above 1.0. Our estimated reproduction numbers, broadly ranging from 1 to 2, are consistent with published estimates from prior outbreaks in Central Africa (e.g. the reproduction number for Ebola virus disease has been estimated at 1.83 for an outbreak in Congo in 1995 and 1.34 in Uganda in 2000 prior to the implementation of control intervention). Our estimates of Rt below 2 indicate that the outbreak could be brought under control if more than half of secondary transmissions per primary case are prevented. Uncontrolled cross-border transmission could fuel a major epidemic to take off in new geographical areas (e.g. as seen in Liberia). Close monitoring of this evolving epidemic should continue in order to assess the status of the outbreak in real time and guide control interventions in the region.

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Increased Ectopic Heart Beats Linked to Less Effective Pacing with CRT TherapyMedicalResearch.com Interview with: Martin Huth Ruwald, MD, PhDPost doctoral research fellow Heart Research Follow-up ProgramUniversity of Rochester Medical

Center Rochester, NY, US

• Medical Research: What are the main findings of the study?• Dr. Ruwald: A high percentage of biventricular pacing is required for optimal outcome in

patients treated with cardiac resynchronization therapy (CRT), but the influence of ectopic beats on the success of biventricular pacing has not been well established.

• We found that patients with increasing amount of ectopic beats (the ectopic burden) (≥0.1%) were more likely to achieve low biventricular pacing <97% and had higher risk of heart failure or death and ventricular arrhythmias. Similarly the study identified patients with a very low amount of ectopic beats, less than 1 in 1000, who are very likely to obtain high biventricular pacing and who have very low risk of adverse outcomes.

Medical Research: Were any of the findings unexpected?• Dr. Ruwald: It was unexpected that such a relatively low burden of ectopic beats

independently influenced and reduced the biventricular pacing percentage and resulted in adverse outcomes to such a degree.

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Increased Ectopic Heart Beats Linked to Less Effective Pacing with CRT TherapyMedicalResearch.com Interview with: Martin Huth Ruwald, MD, PhDPost doctoral research fellow Heart Research Follow-up ProgramUniversity of Rochester Medical

Center Rochester, NY, US

• Dr. Ruwald: A 24-hour Holter recording can help identify both patients who are less likely to obtain high biventricular pacing percentage and those who will achieve improved clinical outcome based on evaluation of pre-implantation ectopic beats. This information can help guide clinicians selecting patients who potentially will not respond to cardiac resynchronization therapy or alternatively identify patients who require additional therapies such as ablations or antiarrhythmic therapy in order to benefit from this device

• Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Ruwald: Studies establishing a threshold of ectopic burden where CRT treatment is no longer beneficial because of ineffective biventricular pacing is needed. Further we need a trial or documentation of whether or not aggressive treatment with ablation or anti-arrhythmic drugs can actually improve outcome for these patients with CRT indication and a burden of ectopic beats above 0.1% of all beats.

• Citation:• Ruwald MH, Mittal S, Ruwald A, et al. Association Between Frequency of Atrial and Ventricula

r Ectopic Beats and Biventricular Pacing Percentage and Outcomes in Patients With Cardiac Resynchronization Therapy. J Am Coll Cardiol. 2014;64(10):971-981. doi:10.1016/j.jacc.2014.06.1177.

•

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How Does Prednisone Affect TB Infections in Patients With and Without HIV?MedicalResearch.com Interview with:Bongani M. Mayosi, M.B., Ch.B., D.Phil.Department of Medicine, Old Groote Schuur HospitalCape Town, South Africa

• Medical Research: What are the main findings of this study?• Dr. Mayosi: In those with definite or probable tuberculous pericardial effusion:• (1) Prednisolone for 6 weeks and Mycibacterium indicus pranii for three months had no

significant effect on the combined outcome of death from all causes, cardiac tamponade requiring pericardiocentesis or constrictive pericarditis.(2) Both therapies were associated with an increased risk of HIV-associated malignancy.(3) However, use of prednisolone reduced the incidence of constrictive pericarditis and hospitalization.(4) The beneficial effects of prednisolone on constriction and hospitalization were similar in HIV-positive and HIV-negative patients

•Medical Research: Were any of the findings unexpected?

• Dr. Mayosi: The two findings that were unexpected were(1) The neutral effect of steroids on death, and(2) The increase in incidence of cancer in HIV infected patients.

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How Does Prednisone Affect TB Infections in Patients With and Without HIV?MedicalResearch.com Interview with:Bongani M. Mayosi, M.B., Ch.B., D.Phil.Department of Medicine, Old Groote Schuur HospitalCape Town, South Africa

• Medical Research: What should clinicians and patients take away from your report?• Dr. Mayosi: A selective approach to the use of adjunctive steroids in tuberculous pericarditis

is required, as follows:(1) Adjunctive steroids should be avoided in patients with HIV-associated tuberculous pericardial effusion because of the risk of cancer;(2) Adjunctive steroids may be used in HIV negative patients for the beneficial effect on constrictive pericarditis and hospitalization.

• There is no role for M. indicus pranii in patients with tuberculous pericardial effusion.• Medical Research: What recommendations do you have for future research as a result of

this study?• Dr. Mayosi: The impact of adjunctive steroids in HIV positive patients on anti-retroviral

therapy is unknown.Citation:

• Prednisolone and Mycobacterium indicus pranii in Tuberculous Pericarditis• Bongani M. Mayosi, M.B., Ch.B., D.Phil., Mpiko Ntsekhe, M.D., Ph.D., Jackie Bosch, Ph.D., Sha

heen Pandie, M.Med. (Med.), Hyejung Jung, M.Sc., Freedom Gumedze, Ph.D., Janice Pogue, Ph.D., Lehana Thabane, Ph.D., Marek Smieja, M.D., Ph.D., Veronica Francis, R.N., Laura Joldersma, B.Sc., Kandithalal M. Thomas, M.B., B.S., Baby Thomas, M.B., B.S., Abolade A. Awotedu, M.B., B.S., Nombulelo P. Magula, M.B., Ch.B., Datshana P. Naidoo, M.B., Ch.B., Ph.D., Albertino Damasceno, M.D., Ph.D., Alfred Chitsa Banda, M.B., Ch.B., Basil Brown, M.B., Ch.B., Pravin Manga, M.B., B.Ch., Bruce Kirenga, M.B., Ch.B., Charles Mondo, M.B., Ch.B., Ph.D., Phindile Mntla, M.B., Ch.B., Jacob M. Tsitsi, M.B., B.Ch., Ferande Peters, M.B., B.Ch., Mohammed R. Essop, M.B., B.Ch., James B.W. Russell, M.B., Ch.B., James Hakim, M.D., Jonathan Matenga, M.B., Ch.B., Ayub F. Barasa, M.B., Ch.B., Mahmoud U. Sani, M.B., B.S., Taiwo Olunuga, M.B., B.Ch., Okechukwu Ogah, M.B., Ch.B., Victor Ansa, M.B., Ch.B., Akinyemi Aje, M.B., Ch.B., Solomon Danbauchi, M.B., Ch.B., Dike Ojji, M.B., B.S., Ph.D., and Salim Yusuf, M.B., B.S., D.Phil. for the IMPI Trial Investigators

• September 2, 2014DOI: 10.1056/NEJMoa140738

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Faster Resting Heart Rate Linked To Metabolic SyndromeMedicalResearch.com Interview with:Dr Weiguo Zhang, MD PhDCardiovascular and Neurological Institute 6771 San Fernando,Irving, TX 75039, USA

• Medical Research: What are the main findings of the study?• Dr. Zhang: The main finding is a strong and positive association between Resting heart rate

and metabolic syndrome (MetS) in a large population, that is the faster the resting heart rate, the higher prevalence of metabolic syndrome.

• More importantly, higher heart rate also predict the incidence of metabolic syndrome in future in people who don’t have metabolic syndrome now, that is the faster the resting heart rate the higher likelihood of developing metabolic syndrome in future. The study suggests that metabolic syndrome is likely one of the mechanisms by which higher resting heart rate causes higher cardiovascular and all cause mortality.

Medical Research: What should clinicians and patients take away from your report?

Dr. Zhang: Clinicians and patients should pay more attention to resting heart rate. Physicians should routinely check and record resting heart rate of clinic visitors. Those healthy and asymptomatic subjects with higher resting heart rate should be under medical surveillance.

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Faster Resting Heart Rate Linked To Metabolic SyndromeMedicalResearch.com Interview with:Dr Weiguo Zhang, MD PhDCardiovascular and Neurological Institute 6771 San Fernando,Irving, TX 75039, USA

• Medical Research: What recommendations do you have for future research as a result of this study?

• Dr. Zhang: From a cardiovascular and metabolic perspective, the significance of Resting heart rate in making therapeutic decisions and evaluating treatment outcomes cannot be overlooked. From a public health perspective, Resting heart rate measurement constitutes a simple and inexpensive approach in monitoring cardiovascular and metabolic health (or risks) in the population.

• Citation:• Metabolic syndrome is associated with and predicted by resting heart rate: a cross-sectional a

nd longitudinal study• Xiongjing Jiang, Xiaoxue Liu, Shouling Wu, Gus Q Zhang, Meng Peng, Yuntao Wu, Xiaoming Zh

eng, Chunyu Ruan, Weiguo Zhang• Heart heartjnl-2014-305685Published Online First: 1 September 2014 doi:10.1136/heartjnl-20

14-305685

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High Estrogen, Low Testosterone Linked To Sudden Cardiac ArrestMedicalResearch.com Interview with:Sumeet S. Chugh MDPauline and Harold Price Endowed Professor Associate Director, the Heart InstituteSection Chief, Clinical Cardiac

Electrophysiology Cedars-Sinai Medical Center, Los Angeles, CA

• Medical Research: What are the main findings of the study? • Dr. Chugh: Our study, conducted in the community, showed that there are unique alterations in sex hormone levels

identified among patients who have sudden cardiac arrest. Male victims have lower testosterone and both males and females have higher estrogren levels.

•Medical Research: Were any of the findings unexpected?

• Dr. Chugh: As you know there are multiple studies that link hormonal imbalances to increased risk of cardiovascular conditions and mortality; and this is a subject that has been hotly debated as well. However, a link between sex hormones and sudden cardiac arrest had not been evaluated previously. There is one aspect of our findings that we were quite surprised by: higher levels of estrogen in men correlating with higher risk of sudden cardiac arrest. While this hormone is present in men, finding of high levels are quite unexpected. However, there are potential mechanisms that could explain the phenomenon and need to be investigated further.

• Medical Research: What should clinicians and patients take away from your report?• Dr. Chugh: Sudden cardiac arrest remains a major health problem and 95% of patients who suffer this condition will

die within 10 minutes. Especially since sudden cardiac arrest accounts for 1000 US lives lost on a daily basis, we have no choice but to discover novel methods of prediction and prevention. While further research is warranted, these findings indicate the sex hormone levels can potentially be used to predict sudden cardiac arrest in the future.

• Citation:• Sex Hormone Levels in Patients with Sudden Cardiac Arrest

Kumar Narayanan, Rasmus Havmoeller, Kyndaron Reinier, Katherine Jerger, Carmen Teodorescu, Audrey Uy-Evanado, Jo Navarro, Adriana Huertas-Vazquez, Karen Gunson, Jonathan Jui, Sumeet S. Chugh.Heart Rhythm, 2014; DOI: 10.1016/j.hrthm.2014.08.031

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BPH Symptoms May Be Reduced By ExerciseMedicalResearch.com Interview with:Kate Wolin, ScD, FACSM Associate ProfessorDepartments of Surgery & Public Health SciencesLoyola University Chicago, Stritch School of Medicine

• Medical Research: What are the main findings of the study?• Answer: Men who are physically active are less likely to experience nocturia. • Medical Research: Were any of the findings unexpected?• Answer: Few other LUTS were associated with physical activity, in contrast with previous

reports. However, most of these reports relied on prevalent data, suggesting future studies should also focus on incident BPH-related outcomes.

• Medical Research: What should clinicians and patients take away from your report?• Answer: Promoting physical activity may be an effective nocturia management strategy for

men.• Medical Research: What recommendations do you have for future research as a result of

this study?• Answer: Research into the dose of activity necessary to reduce nocturia risk and into the

dose necessary to reduce nocturia symptoms among men with nocturia is certainly warranted.

• Citation:• Physical Activity and Benign Prostatic Hyperplasia-Related Outcomes and NocturiaWolin KY1

, Grubb RL 3rd, Pakpahan R, Ragard L, Mabie J, Andriole GL, Sutcliffe S.Med Sci Sports Exerc. 2014 Jul 9. [Epub ahead of print]

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Poor Sleep Linked To Missed Work DaysMedicalResearch.com Interview with:Tea Lallukka, PhDFinnish Institute of Occupational Health &University of Helsinki, Hjelt Institute, Department of Public Health University

of Helsinki, Finland

• Medical Research: What are the main findings of the study?• Dr. Lallukka: Our study used nationally representative survey data linked with

register data on medically certified sickness absence among working-aged Finnish women and men. We showed consistent associations betweeninsomnia symptoms, sleep duration, and being tired and sicknessabsence. The follow-up lasted around 7 years.Sickness absence days were derived from comprehensive registers fromthe Social Insurance Institution of Finland. The associations werebroadly similar among women and men. Furthermore, they remained evenafter considering key correlates of sleep and sickness absenceincluding socioeconomic position, working conditions, healthbehaviors, obesity, and mental and physical health. Health data werederived from physical examination conducted by field physicians. Thesedata are more objective, and help provide more robust evidence. Wefurther covered all key sleep disturbances and sleep duration for morecomprehensive understanding about the contribution of sleep tosickness absence. Finally, a novel method developed by the authors(Härkänen & Kaikkonen) allowed us to estimate the difference insickness absence days per working year among those reporting and notreporting different sleep disturbances. Using the difference in daysabsent from work, we were further able to estimate the hypotheticaldirect costs of sickness absence highlighting notable societalsignificance of sleep. Thus, a large part of all costs of sicknessabsence are attributable to poor sleep. For example, those sleeping 5hours or less or 10 hours or more, were absent from work ca 5-9 daysmore, as compared to those with optimal sleep length. The optimalsleep length with the lowest risk of sickness absence was 7 hours 46minutes for men and 7 hours 38 minutes for women.

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Poor Sleep Linked To Missed Work DaysMedicalResearch.com Interview with:Tea Lallukka, PhDFinnish Institute of Occupational Health &University of Helsinki, Hjelt Institute, Department of Public Health University

of Helsinki, Finland

• Medical Research: Were any of the findings unexpected?• Dr. Lallukka: The lack of an association between daytime sleepiness, apnea, and

seasonal variation in sleep duration and sickness absence could beseen as unexpected.

• Medical Research: What should clinicians and patients take away from your report?• Dr. Lallukka: Insomnia symptoms should be detected early. This could help prevent

them from becoming chronic, and could help prevent decline in workability and subsequent sickness absence. Sufficient quantity andquality of sleep likely promotes health, well-being, and functioningamong women and men.

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Poor Sleep Linked To Missed Work DaysMedicalResearch.com Interview with:Tea Lallukka, PhDFinnish Institute of Occupational Health &University of Helsinki, Hjelt Institute, Department of Public Health University

of Helsinki, Finland

• Medical Research: What recommendations do you have for future research as a result of this study?

• Dr. Lallukka: As insomnia symptoms are highly prevalent, and increase particularlyafter middle-age, it is vital to be able to tackle them early inefforts to promote employee well-being, wealth and work ability. Itwould be important to conduct further research on whether earlydetection and prevention of insomnia would lead to less sicknessabsence. Mechanisms on how sleep affects work ability and health alsoneed further elaboration, as the effects remain even after consideringhealth and working conditions, for example.

• Work disability is also a major public health and societal challenge,bearing huge costs for the employers and society, alongside individualsuffering related to ill- health and economical consequences.

• Citation:• Tea Lallukka, Risto Kaikkonen, Tommi Härkänen, Erkki Kronholm, Timo Partonen, Ossi

Rahkonen, Seppo Koskinen. Sleep and Sickness Absence: A Nationally Representative Register-Based Follow-Up StudySLEEP, 2014; DOI: 10.5665/sleep.3986

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New Ionic Liquids May Disrupt Pathogenic Biofilms, Enhance Antibiotic DeliveryMedicalResearch.com Interview with: David T. FoxBioenergy and Biome Science Group, Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM 87545 and

Prof. Samir MitragotriCenter for Bioengineering and Department of Chemical EngineeringUniversity of California, Santa Barbara, CA 93106

• Medical Research: What are the main findings of this study?• Answer: Our research team identified a molten salt, choline-geranate, that possessed multiple

beneficial biological traits. Specifically, when mixed in a 1:2 ratio (choline:geranate) this solvent is able to effectively disrupt and neutralize 72-hour biofilms formed by both Pseudomonas aeruginosa and Salmonella enterica. Further, our studies demonstrated the same solvent exhibited minimal cytotoxicity effects to normal human bronchial epithelial (NHBE) cells and was able to deliver an antibiotic, cefadroxil, through the stratum corneum into the epidermis and dermis. Most importantly, the research culminated in demonstrating the molten salt was able to neutralize ~95% of the bacteria found within a 24-hour P. aeruginosa biofilm when grown on a skin wound model (MatTek) and ~98% of the bacteria when formulated with the antibiotic, ceftazidime. When the biofilm was treated with only antibiotic in a saline solution, less than 20% of the bacteria were neutralized.

• Medical Research: Were any of the findings surprising?• Answer: The most surprising finding was the observation the neat ionic liquids were quite effective

antimicrobial agents in the absence of the antibiotic. We built a hypothesis that the ionic liquids would serve as a carrier of the antibiotic either to the bacteria or for facile penetration through the skin for subsequent antibiotic delivery. This was a serendipitous finding that ultimately opened the door for use of molten salts as both a standalone therapy and as a formulation with broad-spectrum antibiotics. Further, some of the ionic liquids were more effective than a 10% bleach solution on the microbes tested when applied for the same period of time yet did not exhibit the prototypical cytotoxicity effects that bleach had on the cell lines tested.

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New Ionic Liquids May Disrupt Pathogenic Biofilms, Enhance Antibiotic DeliveryMedicalResearch.com Interview with: David T. FoxBioenergy and Biome Science Group, Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM 87545 and

Prof. Samir MitragotriCenter for Bioengineering and Department of Chemical EngineeringUniversity of California, Santa Barbara, CA 93106

• Medical Research: What should patients and clinicians take away from this report?• Answer: Clinicians and patients should embrace the potential for reexamining previously discarded

antibiotics due to either poor bioavailability or where antibiotic resistance was observed. In addition, there is potential a new arsenal of therapeutic agents was added to an ever shrinking repertoire of current effective treatments on resilient bacteria both on the surface of skin and the underlying tissue layers.

• Medical Research: What future research do you suggest as a result of this study?• Answer: Two major routes of future research should be undertaken in order to further develop use

of this class of materials in a clinical setting.• First, a more exhaustive set of pathogens (both Gram positive and Gram negative) need to be

examined in order to assess the broad-spectrum ability of the ionic liquids for pathogen neutralization in conjunction with the molecular mechanism for biofilm disruption and/or skin penetration.

• The second, a more immediate, direction is to translate this research to in vivo studies to assess the effect of ionic liquids and their antibiotic formulations on the treatment of open wounds.

• Citation:• Ionic liquids as a class of materials for transdermal delivery and pathogen neutralization• Michael Zakrewsky, Katherine S. Lovejoy, Theresa L. Kern, Tarryn E. Miller, Vivian Le, Amber Nagy, A

ndrew M. Goumas, Rashi S. Iyer, Rico E. Del Sesto, Andrew T. Koppisch, David T. Fox, and Samir Mitragotri

• PNAS 2014 ; published ahead of print August 25, 2014, doi:10.1073/pnas.1403995111Read the rest of the interview on MedicalResearch.comContent Not Intended as Specific Medical Advice

How Well Do Fetal Ultrasound Measurement Predict Infant and Childhood Outcomes?MedicalResearch.com: Interview with:Dr. Steve TurnerChild Health, Royal Aberdeen Children’s Hospital Aberdeen,UK

• Medical Research: What are the main findings of the study?• Dr. Turner: There is evidence that being small for a given gestational age is associated with a

broad range of what could be loosely considered “disadvantageous” outcomes in early childhood, eg increased risk for wheeze, increased blood fat levels, increased blood pressure and low bone mineral density. Many of these outcomes are subclinical – ie unless they were measured no-one would be any the wiser – and what remains to be determined is whether as these individuals grow up these subclinical measurements become important. Follow up may take many years, decades for outcomes such as coronary artery disease and type II diabetes.

• Medical Research: Were any of the findings unexpected?• Dr. Turner: Yes, we had expected to find that fetuses who became smaller were at increased

risk for “disadvantageous” outcomes but fetuses who grew fast were spared these. What we found was that both faltering and accelerated growth were associated with “disadvantageous” outcomes. This is consistent with the concepts of developmental plasticity and predictive adaptive responses where the fetus anticipates the environment in which it will be born and, rather like the weather forecast, it can be wrong. If the fetus is too big this might be bad in one environment but not another, similarly a fetus which is too small may not be able to make the most of a “good” environment. Ultimately, as identical twin studies have shown, a given individual is initially “plastic” and might or might not go on to develop a number of illnesses.

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How Well Do Fetal Ultrasound Measurement Predict Infant and Childhood Outcomes?MedicalResearch.com: Interview with:Dr. Steve TurnerChild Health, Royal Aberdeen Children’s Hospital Aberdeen,UK

• Medical Research: What should clinicians and patients take away from your report?• Dr. Turner: At this stage, nothing. Our conclusions are based on observations and it is possible

that the same factor influencing fetal growth also leads to risk for disease and therefore manipulating fetal size may well not be helpful (and may paradoxically make risk for disease higher). This work gives some insight into the mechanisms leading/pre programming non-communicable diseases such as asthma, type II diabetes and hypertension. Mothers who are pregnant should continue to follow public health advice and eat and drink healthily, avoid cigarette smoke and exercise as much as they can.

• Medical Research: What recommendations do you have for future research as a result of this study?

• Dr. Turner: The results are based on observations made in young children and we need to replicate these findings in older children and even adults. It seems highly likely that the antenatal and post natal environment are important in predicting future health and wellbeing (the first 1000 days following conception is probably very important) so it is important to link up growth in both the antenatal and postnatal periods to health and wellbeing.

• Citation:• Fetal ultrasound measurements and associations with postnatal outcomes in infancy and childho

od: a systematic review of an emerging literature• Farah Alkandari, Awaiss Ellahi, Lorna Aucott, Graham Devereux, Steve Turner• J Epidemiol Community Health jech-2014-204091Published Online First: 4 September 2014 doi:10

.1136/jech-2014-204091Read the rest of the interview on MedicalResearch.comContent Not Intended as Specific Medical Advice

Bowel Cancer Screening May Have Small Unwanted Lifestyle EffectMedicalResearch.com Interview InvitationPaula Berstad, PhD, postdocTelemark HospitalOslo, Norway

• Medical Research: What are the main findings of the study?• Dr. Berstad: In general population of age 50-55 years, both those invited to bowel cancer

screening in year 2001 by flexible sigmoidoscopy and those not invited improved their lifestyle from year 2001 to 2012. Lifestyle was measured as adherence to public health guidelines; non-smoking, daily physical exercise, healthy diet and normal body weight. However, the 11-year improvement was smaller in those who were screened for bowel cancer compared to those not screened. Further, among those who attended the screening, the improvement was smaller in those with findings at screening (positive screening result) compared to those without findings (negative screening result). Our interpretation of the findings is that bowel cancer screening may have a small unwanted effect on lifestyle. Particularly, attention should be given to lifestyle among those testing positive at screening.

Medical Research: Were any of the findings unexpected?• Dr. Berstad: It was surprising that the differences in lifestyle change between the screened

and non-screened, first were observed three years after screening, still were observable eight years later.

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Bowel Cancer Screening May Have Small Unwanted Lifestyle EffectMedicalResearch.com Interview InvitationPaula Berstad, PhD, postdocTelemark HospitalOslo, Norway

• Medical Research: What should clinicians and patients take away from your report?• Dr. Berstad: Cancer screening may have a small “health certificate” effect which reduces

individual’s own incentives for healthy lifestyle choices. Although this effect is modest and without clinical importance, it may have impact on long-term health on the population level. Combining cancer screening with lifestyle counselling might be considered.

• Medical Research: What recommendations do you have for future research as a result of this study?

• Dr. Berstad: Future research should pursue to find an optimal way to do cancer screening, which motivates the participant for favorable health behaviour.

• Citation:• Long-term lifestyle changes after colorectal cancer screening: randomised controlled trial• Paula Berstad, Magnus Løberg, Inger Kristin Larsen, Mette Kalager, Øyvind Holme, Edoardo Bo

tteri, Michael Bretthauer, Geir Hoff• Gut gutjnl-2014-307376Published Online First: 2 September 2014 doi:10.1136/gutjnl-2014-30

7376

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Multiple Sclerosis: Slower Walking Speed Associated With Decreased Quality of LifeMedicalResearch.com Interview with:Jeffrey Cohen MDDepartment of NeurologyCleveland Clinic

• Medical Research: What are the main findings of the study?• Dr. Cohen: This study assessed the relationship between walking speed, as measured by the Timed 25-foot

Walk test, and patient-reported quality of life, as measured by the Physical Component Summary score of the 36-Item Short Form Health Survey (SF-36), in a pooled dataset from the AFFIRM, SENTINEL, and IMPACT multiple sclerosis Phase 3 trials. It showed that slowed walking speed is associated with decreased quality of life. It also showed that 20-25% slowing of walking speed is a clinically meaningful change.

Medical Research: What should clinicians and patients take away from your report?• Dr. Cohen: Waling ability is an important aspect of multiple sclerosis and the Timed 25-Foot Walk is an

appropriate way to assess it.• Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Cohen:

• 1) Determine whether other walking tests capture walking ability in multiple sclerosis better than the Timed 25-Foot Walk.

• 2) Assess other neuroperformance measures of e.g. the 9-Hole Peg Test of upper extremity function using a similar approach.

• Citation:• Cohen JA, Krishnan AV, Goodman AD, et al. The Clinical Meaning of Walking Speed as Measured by the Tim

ed 25-Foot Walk in Patients With Multiple Sclerosis. JAMA Neurol. Published online September 01, 2014. doi:10.1001/jamaneurol.2014.1895.

•

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MedicalResearch.com Interview with:Sylvia Wassertheil-Smoller, PhDDepartment of Epidemiology and Population HealthAlbert Einstein College of MedicineBronx, NY 10461.

• Medical Research: What are the main findings of the study?• Dr. Wassertheil-Smoller: We found in study of nearly 100,000 postmenopausal women in the

Women’s Health Initiative that a high intake of dietary potassium was associated with a lower risk of ischemic stroke and death from all causes.

• Medical Research: Were any of the findings unexpected?• Dr. Wassertheil-Smoller: The unexpected finding was that this effect was strongest in women

without hypertension (those whose blood pressure was normal and who were not on any medications for high blood pressure). In these women there was a 27% lower risk of ischemic stroke and a 21% % lower risk of all stroke types. There was no association with hemorrhagic stroke.

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MedicalResearch.com Interview with:Sylvia Wassertheil-Smoller, PhDDepartment of Epidemiology and Population HealthAlbert Einstein College of MedicineBronx, NY 10461.

• Medical Research: What should clinicians and patients take away from your report?• Dr. Wassertheil-Smoller: Clinicians should recommend a diet that includes potassium-rich foods. The

current recommendations for dietary intake of potassium from the Institute of Medicine and the U.S. Department of Agriculture are 4700 mg per day. The World Health Organization’s recommendations are for about 3500 mg per day. The average intake for Americans is considerably below that at about 2640 per day and in our study the women consumed on average 2611 mg per day so increasing potassium in the diet is important. There are many foods rich in potassium including the well-known banana, but also baked potatoes, orange juice, spinach, fruits and green vegetables in general, salmon, yogurt – it is quite ubiquitous. People should read the labels on processed foods they buy.

• Medical Research: What recommendations do you have for future research as a result of this study?• Dr. Wassertheil-Smoller: Since it is unlikely there will a randomized clinical trials of this issue due to

excessive costs and feasibility, we need to get the best information we can from observational, longitudinal studies. There are quite a few cohorts, nationally and internationally, that have dietary data and these studies should be analyzed with regard to potassium intake so that we get more information on different population groups, people of different ethnicities, ages, sex. A collaborative effort should be undertaken to pool data. Also, it is important to consider sodium intake as we are not clear about the balance of sodium and potassium that is best. Our next paper will deal with sodium intake.

• Citation:• Potassium Intake and Risk of Stroke in Women With Hypertension and Nonhypertension in the Women’s H

ealth Initiative• Arjun Seth, Yasmin Mossavar-Rahmani, Victor Kamensky, Brian Silver, Kamakshi Lakshminarayan, Ross Pren

tice, Linda Van Horn, and Sylvia Wassertheil-Smoller• Stroke. 2014;STROKEAHA.114.006046published online before print September 4 2014, doi:10.1161/STROK

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MedicalResearch.com: Interview with:Isabelle Bedrosian, M.D., F.A.C.S.Associate Professor, Department of Surgical Oncology, Division of SurgeryMedical Director, Nellie B. Connelly Breast Center

The University of Texas MD Anderson Cancer Center, Houston, TX

• Medical Research: What are the main findings of the study?Dr. Bedrosian:• National BCT (breast conserving therapy) rates have increased during the last two decades.• Disparities based on age, geographic facility location and type of cancer treatment facility have lessened over time.• Insurance type and travel distance remain persistently associated with underutilization of breast conserving therapy.• Annual income of less than $35K may be emerging as a new association with underutilization of breast conserving therapy.

Medical Research: Were any of the findings unexpected?• Dr. Bedrosian: The extent to which socio-economic factors were associated with breast

conserving therapy utilization and that in the most recent year of analysis, these socio-economic factors appear to be the greatest source driving the disparity in breast conserving therapy utilization.

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MedicalResearch.com: Interview with:Isabelle Bedrosian, M.D., F.A.C.S.Associate Professor, Department of Surgical Oncology, Division of SurgeryMedical Director, Nellie B. Connelly Breast Center

The University of Texas MD Anderson Cancer Center, Houston, TX

• Medical Research: What should clinicians and patients take away from your report?• Dr. Bedrosian: Clinicians should recognize that they have made significant strides in

democratizing care for breast cancer patients- these gains are reflecting in the reduction in practice based disparities. However, to address the socio-economic factors that currently appear to be behind the disparities in the surgical treatment of breast cancer will likely require policy level interventions.

• Medical Research: What recommendations do you have for future research as a result of this study?

• Dr. Bedrosian: To better define identify the factors behind the socio-economic disparities. These socio-economic factors are likely surrogates for a broad range of considerations such as child care, transportation challenges, time of work, cultural beliefs, etc. Better clarity on these fronts is needed in order to implement strategies to overcome these socio-economic disparities.

• Citation:• 2014 Breast Cancer Symposium abstract:• Abstract 63:

Late axillary recurrence after negative SLNB.•

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How Much Caffeine Should Kids and Teens Ingest?MedicalResearch.com Interview with:Naman Ahluwalia, PhD, DSc, FACNNutrition Monitoring Advisor Office of the DirectorDivision of Health and Nutrition Examination Surveys, NCHS, CDC

Hyattsville, MD 20782

• Medical Research: What are the main findings of the study?• Dr. Ahluwalia: Health Canada has put forth caffeine intake guidelines for children and

adolescents in absolute amounts (mg) and in mg/kg body weight for teens. The maximal caffeine intakes of 45, 63, and 85 mg/day are suggested for children ages 4-6, 7-9, and 10-12 years and for teens (13 y and over) Health Canada suggests that caffeine intake be no more than 2.5 mg/kg body weight/day. Although no such recommendations have been set in the US, the American Academy of Pediatrics (AAP) underlines that “caffeine and other stimulant substances contained in energy drinks have no place in the diet of children.”

• This study provides national estimates of dietary caffeine intake in US children 2-19 y of age, both in absolute amounts (mg) and in relation to body weight (mg/kg), to update estimates that were published in another study in 2005 based on older data from the Continuing Survey of Food Intakes by individuals in 1994-96 and 1998.

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How Much Caffeine Should Kids and Teens Ingest?MedicalResearch.com Interview with:Naman Ahluwalia, PhD, DSc, FACNNutrition Monitoring Advisor Office of the DirectorDivision of Health and Nutrition Examination Surveys, NCHS, CDC

Hyattsville, MD 20782

• The key findings were:• 1. Majority (71%) of children in the survey reported consuming caffeine on a given day; over

one-half of US children aged 2-5 y and 3 in 4 children ages 6 y and over consumed caffeine on a given day.

• 2. Certain socio-demographic patterns in caffeine intake were observed. More non-Hispanic white and Mexican American children reported consuming caffeine than non-Hispanic black children; in addition, the amount of caffeine consumed by non-Hispanic white and Mexican American children was higher than that consumed by non-Hispanic black children. Caffeine intake increased with age. For instance, 2-5 year-old caffeine consumers reported 5 mg of caffeine intake on a given day, compared to 9 mg for 6-11 y olds and ~ 40 mg for teens (12-19 y). For reference, a 8 fl oz can of soda contains about 24-50 mg of caffeine.

• 3. Another finding was that on a given day one in ten children (6-19 y) had caffeine intakes that exceeded the Canadian maximal guidelines.

• 4. Caffeine intake (mg or mg/kg) stayed relatively constant among teens over the last decade, but trends towards decreased intake were noted in younger (2-11 y old) children.

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How Much Caffeine Should Kids and Teens Ingest?MedicalResearch.com Interview with:Naman Ahluwalia, PhD, DSc, FACNNutrition Monitoring Advisor Office of the DirectorDivision of Health and Nutrition Examination Surveys, NCHS, CDC

Hyattsville, MD 20782

• Medical Research: Were any of the findings unexpected?• Dr. Ahluwalia: The common prevailing thought is that caffeine intake particularly in teens may be high

and that it is likely to have increased over the last decade; our results did not support these.• Medical Research: What should clinicians and patients take away from your report?• Dr. Ahluwalia: Although caffeine intake in younger children is small, a large percentage of children do

consume caffeine and this does not fit well with the AAP. About one in ten children 6 y of age and above reported intakes that exceeded the Canadian maximal guidelines; thus clinicians and health care-providers should stay vigilant to follow children closely regarding their caffeine consumption, so as to identify children that may be “heavy consumers” of caffeine and provide appropriate counselling on potential adverse effects.

• Medical Research: What recommendations do you have for future research as a result of this study?• Dr. Ahluwalia: Dietary sources of caffeine intake among children should be examined more closely,

and analysis of newer data from NHANES this year should be undertaken particularly among older children who were the highest consumers of caffeine. There is a need to continue monitoring caffeine intake (and sources) of children.

• Citation:• Caffeine intake in children in the United States and 10-y trends: 2001–2010

Namanjeet Ahluwalia, Kirsten Herrick, Alanna Moshfegh, and Michael Rybak• Am J Clin Nutr 2014 ajcn.082172; First published online August 27, 2014. doi:10.3945/ajcn.113.08217

2

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Blood Transfusions: Stored Blood Becomes Less Functional With TimeMedicalResearch.com Interview with:Gabriel Popescu Associate ProfessorDepartment of Electrical and Computer Engineering & Bioengineering

University of Illinois at Urbana-ChampaignBeckman Institute for Advanced Science Urbana, IL

• Medical Research: What are the main findings of the study?• Prof. Popescu: We used a new imaging method, which combines microscopy and interferometry, to measure nanoscale

fluctuations in the red blood cell membrane. We found that the fluctuations, known to be due to thermal or Brownian motion, decrease with blood storage time. These results indicate that the deformability of the cells degrades with time. It means that blood functionality is lower the longer the blood is stored.

• Medical Research: Were any of the findings unexpected?• Prof. Popescu: One surprising aspect we found was that this stiffening of the cells appears without chance in

morphology or hemoglobin concentration.• Medical Research: What should clinicians and patients take away from your report?• Prof. Popescu: Following blood transfusions, visual inspection by a hematologist involves smearing a droplet of blood

between on a glass slide and studying the cells using optical microscopy. Abnormalities in cell shapes can be easily identified by this procedure. However, our results show that, even if the cells exhibit a normal, discocyte shape, they may function improperly due to the limited deformability. We believe that our test can be added to the menu of assays at the hematologist’s disposal.

• Medical Research: What recommendations do you have for future research as a result of this study?• Prof. Popescu: We would like to follow up with studies dedicated to understanding the molecular mechanism

responsible for the cell stiffening during storage. Also, it would be very useful in clinical practice to come up with a drug that will restore the cell deformability, before it is administered to the patient.

• Citation:Optical Assay of Erythrocyte Function in Banked BloodBasanta Bhaduri,Mikhail Kandel,Carlo Brugnara , Krishna Tangella & Gabriel Popescu

• Scientific Reports 4, Article number: 6211• doi:10.1038/srep06211 Received 28 April 2014 Accepted 04 August 2014 Published 05 September 2014

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Obsessive-Compulsive Disorder Increases Risk Of SchizophreniaMedicalResearch.com Interview with:Sandra M. Meier, PhDThe Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH,National Centre for Register-Based Research Aarhus

University, Aarhus, Denmark

• Medical Research: What are the main findings of the study?• Dr. Meier: People with an obsessive-compulsive disorder are at a 6 to 7 times higher risk of developing

schizophrenia than people without an obsessive-compulsive disorder. If the parents are diagnosed with an obsessive-compulsive disorder, their offspring experience a 3 to 4 times higher chance to develop schizophrenia.

• Dr. Meier: The findings fit with observations in clinical practice linking obsessive-compulsive disorder to schizophrenia.

• Medical Research: What should clinicians and patients take away from your report?• Dr. Meier: Although only a small proportion of patients with obsessive-compulsive disorder will subsequently

develop schizophrenia, clinicians should be more aware of the associations of obsessive-compulsive disorder with schizophrenia. Treating comorbid obsessive-compulsive disorder may prevent and improve the symptoms of schizophrenia. Even if this association is not causal—and instead an epiphenomenon due to genetics or environmental factors—psychiatric patients with comorbid diseases would most likely still benefit through greater quality of life and improved survival.

• Medical Research: What recommendations do you have for future research as a result of this study?• Dr. Meier: Our findings indicate that obsessive-compulsive disorder and schizophrenia might share etiologic risk

factors. Future research is needed to disentangle which genetic and environmental risk factors are truly common to both disorders.

• Citation:• Obsessive-Compulsive Disorder as a Risk Factor for Schizophrenia: A Nationwide Study• Meier SM, Petersen L, Pedersen MG, et al. Obsessive-Compulsive Disorder as a Risk Factor for Schizophrenia: A N

ationwide Study. JAMA Psychiatry. Published online September 03, 2014. doi:10.1001/jamapsychiatry.2014.1011.

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Young Eyes Should Be Protected From UV LightMedicalResearch.com Interview with: Louis R. Pasquale, MDChanning Division of Network Medicine Department of Ophthalmology

Harvard Medical School, Massachusetts Eye and Ear InfirmaryBoston, Massachusetts

• Medical Research: What are the main findings of the study?• Dr. Pasquale: We found that more time spent outdoors in summer was associated with

increased risk of exfoliation syndrome.

Medical Research: What should clinicians and patients take away from your report?• Dr. Pasquale: The eye is a seeing organ but is is also vulnerable to climatic elements.

Protection from reflected UV rays during young adulthood could contribute to better ocular health in the elder years.

• Medical Research: What recommendations do you have for future research as a result of this study?

• Dr. Pasquale: A gene for exfoliation syndrome has been identified called LOXL1. A specific polymorphism in LOXL1 is found in 99% of exfoliation syndrome cases and 80% of controls. Why do 80% of people with the polymorphism NOT get the disease? It will be important to determine if increased ocular UV exposure modifies the relation between LOXL1 gene variants and the development of exfoliation syndrome.

• Citation:Pasquale LR, Jiwani AZ, Zehavi-Dorin T, et al. Solar Exposure and Residential Geographic History in Relation to Exfoliation Syndrome in the United States and Israel. JAMA Ophthalmol. Published online September 04, 2014. doi:10.1001/jamaophthalmol.2014.3326.

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Going Braless Doesn’t Increase Risk of Breast CancerMedicalResearch.com Interview with: Lu Chen, MPHResearcher in the Public Health Sciences DivisionFred Hutchinson Cancer Research Center

Doctoral student in the Department of EpidemiologyUniversity of Washington School of Public Health

• Medical Research: What are the main findings of the study?• Dr. Chen: We found no evidence that wearing a bra is associated with breast cancer risk. Further, breast cancer risk was

not impacted by bra wearing frequency, wearing a bra with an underwire, or starting to wear a bra at a young age.• Medical Research: Were any of the findings unexpected?• Dr. Chen: The biological plausibility for a relationship between bra wearing and breast cancer risk when we began this

study was quite weak, but since no other studies have really addressed this question in depth we were uncertain what we would find. The potential mechanism through which bra wearing could influence breast health is that bras could impair lymphatic drainage particularly in the lymph nodes located under a woman’s arm leading to compromised filtration of accumulated waste products. Given the very limited biologic evidence supporting a potential link between bra wearing and breast cancer risk, our results were not surprising.

• Medical Research: What should clinicians and patients take away from your report?

Dr. Chen: With our findings there is no published scientific evidence that bra wearing is related to breast cancer risk.• Medical Research: What recommendations do you have for future research as a result of this study?• Dr. Chen: Like all studies, our study had limitations. The main limitation was that almost every woman in our study wore a

bra, therefore we could not directly compare those who never wore a bra to those who wore. Alternatively, we compared how long they wore a bra every day, whether the bra had an underwire and when they began wearing a bra. Based on these factors we evaluated, the results were consistent that all these aspects of bra wearing were not relevant to breast cancer. If future studies can include women who never wore a bra in her lifetime and directly compare those who wore versus those who did not, it would strengthen the existing evidence.

• Citation:• Lu Chen, Kathleen E. Malone, and Christopher I. Li. Bra Wearing Not Associated with Breast Cancer Risk: A Population-

Based Case–Control Study. Cancer Epidemiology, Biomarkers & Prevention, September 2014 DOI: 10.1158/1055-9965.EPI-14-0414

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SSRIs May Increase Risk Of Dental Implants FailureMedicalResearch.com Interview with:Faleh Tamimi, BDS, PhD Assistant Professor,Faculty of Dentistry Strathcona Anatomy & Dent,Montreal, Quebec Canada

• Medical Research: What are the main findings of the study?• Dr. Tamimi: The main finding was that SSRIs usage was associated with an increased risk of

dental implants failure.

Medical Research: Were any of the findings unexpected?• Dr. Tamimi: SSRIs are widely used all over the world, but their impact on the oral health was

unknown.• Medical Research: What should clinicians and patients take away from your report?• Dr. Tamimi: Our findings indicate that treatment with SSRIs is associated with an increased

failure risk of osseointegrated implants, which might suggest a careful surgical treatment planning for SSRIs users.

• Medical Research: What recommendations do you have for future research as a result of this study?

• Dr. Tamimi: We suggest further studies investigating the influence of SSRIs on oral and dental health. As well as on other biomedical devices such as hip prosthesis and knee prosthesis.

• Citation:• SSRIs and the Risk of Osseointegrated Implant Failure – A Cohort Study

X. Wu, K. Al-Abedalla, E. Rastikerdar, S. Abi Nader, N.G. Daniel, B. Nicolau, and F. Tamimi• J DENT RES, 0022034514549378, first published on September 3, 20

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Poor Access To SSRIs May Result In Suicide InequalitiesMedicalResearch.com Interview with: Sean Clouston Ph.D. Assistant ProfessorCore Faculty, Program in Public HealthDepartment of Preventive MedicineStony Brook University Health Sciences

Center Stony Brook, NY 11794

• Medical Research: What is the background for this study:

• Dr. Clouston: A number of epidemiological studies have found that suicide rates have decreased rapidly with the widespread distribution of SSRI antidepressants. Our group has found that proliferation of preventive medicine has, with regard to other causes of death, tended to occur unequally. We hypothesized that if SSRI antidepressants prevent suicide by treating depression, then suicide might also be susceptible to such inequality. Our study used mortality data to show that decreases in suicide were concentrated in regions with higher socioeconomic status.

• Medical Research: What are the main findings of the study?• Dr. Clouston We used the best available data from the US and found that socioeconomic inequalities have increased dramatically in conjunction with the

proliferation of SSRI antidepressants.•

Medical Research: Were any of the findings unexpected?• Dr. Clouston: There were two surprising results:• Suicide has not historically been associated with socioeconomic inequality, so the main finding was quite surprising.• We were also somewhat surprised to have found that suicide has not decreased to the same extent in states within the U.S. where NAMI has rated the

mental health system as failing, suggesting perhaps that there is more that we can do to improve public health and prevent suicide.• Medical Research: What should clinicians and patients take away from your report?• Dr. Clouston: Socioeconomic inequalities are both inequitable and inefficient. It is unlikely that SSRIs will effectively prevent all suicides, but many suicides

may be preventable. Depression is a key determinant of suicide, and most individuals who commit suicide have sought help in the months prior to taking action. However, once individuals decide to take action they often act quickly and without warning. Prevention is therefore of primary importance, so clinicians and patients should be aware that if patients seem suicidal, they should seek immediate help from a trained mental health professional.

• Medical Research: What recommendations do you have for future research as a result of this study?• Dr. Clouston: Suicide is somewhat rare, so studying cause and effect can be difficult. Further research is needed to ensure that SSRIs have caused

reductions in suicide, as well as identifying for whom such treatments may not work. Furthermore, suicide reductions have been reported in the United Kingdom, Sweden, Denmark, and Canada, among others; international researchers should also be aware that socioeconomic inequalities may also be evident in suicide internationally.

• Citation:• Social Inequalities in Suicide: The Role of Selective Serotonin Reuptake Inhibitors

Am J Epidemiol. 2014 Aug 28. pii: kwu191. [Epub ahead of print]• Clouston SA, Rubin MS, Colen CG, Link BG.

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Contrast Media: PPIs One Of Risk Factors For Hypersensitivity ReactionMedicalResearch.com: Interview with: Elena Ramírez, MD, PhDClinical Pharmacology DepartmentHospital Universitario la Paz, IdiPaz School of Medicine, U.A.M.

• Medical Research: What are the main findings of the study?• Dr. Ramirez: We found that the presence of a past history of allergy, the use of proton pump

inhibitors (PPI), the number of times of previous administration of contrast media , and high values of creatinine are significant factors to hypersensitivity reactions to contrast media (CM). We found a low, but relevant, number of positive skin tests. The tolerability of an alternative skin test-negative contrast media or different contrast media was confirmed in all cases.

Medical Research: Were any of the findings unexpected?• Dr. Ramirez: To our knowledge, this is the first time that PPI are described as a specific factor

related hypersensitivity reactions to contrast media . The mechanisms by PPI may cause reactions to contrast media are hypothetical. The presence of undigested oligopeptides by treatment with PPI may induce a T-helper (Th)-2 response and immunoglobulin (Ig)-E sensitization of the immune system. This allergic status of the patient might be facilitating the reactions to intravenous contrast media .

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Contrast Media: PPIs One Of Risk Factors For Hypersensitivity ReactionMedicalResearch.com: Interview with: Elena Ramírez, MD, PhDClinical Pharmacology DepartmentHospital Universitario la Paz, IdiPaz School of Medicine, U.A.M.

• Medical Research: What should clinicians and patients take away from your report?• Dr. Ramirez: The incidence of hypersensitivity reactions to contrast media is low. A new risk

factor is PPI. The impaired renal function, in patients with history of allergy, and PPI use can significantly increase the risk of hypersensitivity reactions to contrast media , especially allergic reactions. Skin tests are useful for the diagnostic workup in patients with allergic reactions.

• Medical Research: What recommendations do you have for future research as a result of this study?

• Dr. Ramirez: Test the tolerability of an alternative skin test-negative contrast media different contast media before avoiding all contast media. However, there is still room for caution on the reliability of skin test for diagnosis of hypersensitivity reactions to contast media and for the choice of safe alternative CMcontast media.

• Citation:• Hypersensitivity reactions to contrast media injections: a nested case–control study

Ramírez, Elena et al.Annals of Allergy, Asthma & ImmunologyPublished Online: August 22, 2014DOI: http://dx.doi.org/10.1016/j.anai.2014.07.016

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Sleep Difficulties Linked To Shrinking BrainMedicalResearch.com Interview with:Dr. Claire Sexton Ph.D.University of Oxford

• Medical Research: What are the main findings of the study?• Dr. Sexton: We found that sleep difficulties (which can include trouble falling asleep, waking up during the night, or

waking up too early) were associated with an increased rate of decline in brain volumes over 3-5 years.•

Medical Research: Were any of the findings unexpected?• Dr. Sexton: Previous studies have linked a diagnosis of insomnia to reduced performance in cognitive tests and

reduced brain volumes in certain regions, so our results weren’t completely unexpected. However, it was striking to find that sleep quality was associated with increased rate of decline in brain volumes across widespread brain regions in community-dwelling adults.

• Medical Research: What should clinicians and patients take away from your report?• Dr. Sexton: Previous studies have linked a number of factors with an increased rate of decline in brain volumes, such

as physical inactivity, high blood pressure and high cholesterol. Our research indicates that sleep is also an important factor that needs to be examined in more detail in future studies. Since there are a number of effective treatments for sleep disorders, it could be an exciting avenue through which to promote brain health, but more research needs to be done to determine if poor sleep is a cause or consequence of increased decline in brain volumes.

• Medical Research: What recommendations do you have for future research as a result of this study?• Dr. Sexton: In future, it will be important to examine if improving sleep quality can help slow rates of decline in brain

volume.• Citation:• Poor sleep quality is associated with increased cortical atrophy in community-dwelling adults

Sexton CE1, Storsve AB2, Walhovd KB2, Johansen-Berg H2, Fjell AM2.Neurology. 2014 Sep 3. pii: 10.1212/WNL.0000000000000774. [Epub ahead of print]

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US Life Expectancy Varies By Sex, Race/Ethnicity and GeographyMedicalResearch.com Interview with:Dr. Benedict TrumanAssociate Director for ScienceCDC’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention

• Medical Research: What are the main findings of the study?• Dr. Truman: In 2008, healthy life expectancy, which isthe number of years a person is expected to live in good or

better health after a particular age, varied by sex, race/ethnicity and geographical regions in the United States. In each of four U.S. census regions, females were expected to live longer and healthier lives than males; non-Hispanic whites were expected to live shorter but healthier lives than Hispanics; and non-Hispanic whites were expected to live longer and healthier lives than non-Hispanic blacks.

Medical Research: Were any of the findings unexpected?• Dr. Truman: Expected years of life at any age is greater for Hispanic persons than for non-Hispanic white

persons. Therefore, a surprising finding of this study is that for people who are the same age, the expected years of healthy life remaining for Hispanics was less than that for Non-Hispanic white persons (Fig. 3).

• Medical Research: What should clinicians and patients take away from your report?• Dr. Truman: Clinicians should encourage patients to make healthier lifestyles choices, get recommended

preventive services, and use high quality health care when needed. Patients should follow this advice to live longer and healthier lives.

• Medical Research: What recommendations do you have for future research as a result of this study?• Dr. Truman: Future research should identify the factors that lead to differences in healthy life expectancy based

on sex, race/ethnicity, and geography. The effectiveness of interventions to address these factors also should be determined.

• Citation:• Chang MH1, Molla MT2, Truman BI1, Athar H3, Moonesinghe R4, Yoon PW3.

J Public Health (Oxf). 2014 Aug 30. pii: fdu059. [Epub ahead of print]

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Tuberculosis: Moxifloxacin Likely To Be Cornerstone Of New Treatment RegimenMedicalResearch.com Interview with:Stephen H. Gillespie, M.D., D.ScUniversity of St. Andrews Medical School, St. Andrews

• Medical Research: What are the main findings of the study?• Dr. Gillespie: REMox TB was a pioneering trial that has shown that a large-scale trial can be

run efficiently in resource-poor settings with a high TB burden, adhere to the highest standards of good clinical trial practices, and deliver a clear, unequivocal result. REMoxTB was among the most rigorous Tuberculosis drug trials ever conducted in the modern era of TB treatment and among the largest ever conducted for a new TB treatment. It enrolled 1,931 patients at 50 sites in nine countries, mostly in Africa and Asia. Previously, there were thought to be regional differences in way in which patients’ response to treatment across the world but we showed that a rigorous approach to trial conduct there was no evidence for that difference.

• The study confirmed that daily moxifloxacin was safe over four months of therapy and the moxifloxacin containing arms were more bactericidal initially. Despite its substantial anti-TB activity it did not prove possible to shorten therapy to four months. .

• These findings, with the safety of moxifloxacin, and its activity against TB, support the continued clinical testing of moxifloxacin as a component of other novel regimens.

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Tuberculosis: Moxifloxacin Likely To Be Cornerstone Of New Treatment RegimenMedicalResearch.com Interview with:Stephen H. Gillespie, M.D., D.ScUniversity of St. Andrews Medical School, St. Andrews

• Medical Research: Were any of the findings unexpected?• Dr. Gillespie: We undertake clinical trials because we don’t know the answer. What might have been

unexpected is that a trial of this scope and rigor could be conducted or completed. We have shown that it is possible to conduct high quality clinical trials for new Tuberculosis treatments using state of the art diagnostic methods in countries that have a high TB burden. More importantly, it is possible for clinicians and scientists in resource-poor nations to play a critical role in finding innovative solutions to this disease.

• Medical Research: What should clinicians and patients take away from your report?• Dr. Gillespie: Our report shows that moxifloxacin is safe over extended periods for tuberculosis and that it

is likely to be the cornerstone of a new regimen. It also shows that finding a better regimen is challenging, but when clinicians, scientists and health professionals across the world work together much can be achieved as REMoxTB has brought a four month regimen closer to reality.

• Medical Research: What recommendations do you have for future research as a result of this study?• Dr. Gillespie: REMoxTB paved the way for future progress by showing us that effective, markedly shorter

and safer treatments are just within our grasp. It is likely that we will need to build novel regimens that combine multiple novel agents to make a more bactericidal regimen. Moxifloxacin most certainly looks like it can play a role in such future treatments.

• Citation:• Four-Month Moxifloxacin-Based Regimens for Drug-Sensitive Tuberculosis

Stephen H. Gillespie, M.D., D.Sc., Angela M. Crook, Ph.D., Timothy D. McHugh, Ph.D., Carl M. Mendel, M.D., Sarah K. Meredith, M.B., B.S., Stephen R. Murray, M.D., Ph.D., Frances Pappas, M.A., Patrick P.J. Phillips, Ph.D., and Andrew J. Nunn, M.Sc. for the REMoxTB Consortium

• September 7, 2014DOI: 10.1056/NEJMoa1407426

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US Hospitals Spend At Least Double Other Countries on Billing and AdministrationMedicalResearch.com Interview with:Steffie Woolhandler MD MPHProfessor School of Public Health and Hunter College, CUNY;Professor of Medicine Harvard

Medical School Cambridge Hospital

• Medical Research: What are the main findings of the study?• Dr. Woolhandler: In 2011, U.S. hospitals spent $215 billion on

billing and administration. Meanwhile, othercountries spent far less. None of the otherseven countries we studied spent even half asmuch as the U.S., and they all have modern, highquality hospitals. While we spent nearly$700 per capita on hospital paperwork, Scotlandand Canada spent less than $200. This meansthat if U.S. hospitals ran as efficiently asCanada’s, the average family of four would save$2,000 annually on health care.

Medical Research: How was the study done?• Dr. Woolhandler: We put together an international team of hospital

experts to obtain official hospital cost datafrom eight nations. We then aligned the hospitalaccounting categories to do an apples to applescomparison of hospital administrative spending in8 nations: the U.S., Canada, England, Scotland,Wales, the Netherlands, France and Germany.

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US Hospitals Spend At Least Double Other Countries on Billing and AdministrationMedicalResearch.com Interview with:Steffie Woolhandler MD MPHProfessor School of Public Health and Hunter College, CUNY;Professor of Medicine Harvard

Medical School Cambridge Hospital

• Medical Research:Were any of the findings unexpected? • Dr. Woolhandler: The conventional wisdom is that market breed

efficiency. We found the reverse to be true.Nations with the most market oriented systems,like the U.S. and increasingly the Netherlands,had much higher administrative costs thatcountries with single payer systems, like Canadaand Scotland. Another unexpected finding wasthe explosion of administrative spending by UShospitals in the past decade. In 2000 hospitaladministration consumed 0.98% of total US GDP.By 2011, hospital administration costs had morethan doubled in inflation adjusted dollars, andwere consuming a whopping 1.43% ofGDP. Meanwhile, hospital administrative costs were falling in Canada.

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US Hospitals Spend At Least Double Other Countries on Billing and AdministrationMedicalResearch.com Interview with:Steffie Woolhandler MD MPHProfessor School of Public Health and Hunter College, CUNY;Professor of Medicine Harvard

Medical School Cambridge Hospital

• Medical Research: What should clinicians and patients take away from your report?

• Dr. Woolhandler: The major take-away point isthat doctors and patients need to be working togo beyond Obamacare to a single paperreform. The current payment systems is wastefulbecause every hospital has to negotiate ratesschedules with hundreds of different insuranceplans, each with its own set of billing anddocumentation requirements. And hospitalsneed staff to collect deductibles, co-paymentsand co-insurance from every patient who comesthrough the door. Single payer systems (likeCanada’s or Scotlands) can give hospitalssimple lump sum budgets, the way we fund localfire houses. And like fire departmentshospitals in single payer systems don’t need tocollect from each victim of misfortune. InScotland, even hospital parking is free.

• Medical Research: What recommendations do you have for future research as a result of this study?

• Dr. Woolhandler: Research is needed on how we can minimizeadministrative waste in payment of hospitals, physicians, andother health providers, and use the savings toprovide excellent care to every American.

• Citation:• A Comparison Of Hospital Administrative Costs In

Eight Nations: US Costs Exceed All Others By Far:David U. Himmelstein, Miraya Jun, Reinhard Busse, Karine Chevreul, Alexander Geissler, Patrick Jeurissen, Sarah Thomson, Marie-Amelie Vinet, and Steffie Woolhandler

Health Aff September 2014 33:91586-1594; doi:10.1377/hlthaff.2013.1327

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Osteoporosis Medications Differ in Joint Fracture Reduction, Adverse EffectsMedicalResearch.com Interview with:Carolyn J. Crandall, MD, MS Professor of MedicineDavid Geffen School of Medicine at University of California,Los Angeles

• Medical Research: What are the main findings of the study?Dr. Crandall:

• 1. We found high-strength evidence that several medications decrease fracture risk when used by persons with bone density in the osteoporotic range and/or with pre-existing hip or vertebral fracture. While many of the medications (alendronate, risedronate, zoledronic acid, ibandronate, denosumab, teriparatide, and raloxifene) reduce vertebral fractures, a reduction in the risk of hip fracture is not demonstrated for all of the medications. In particular, hip fracture reduction is only demonstrated for alendronate, risedronate, zoledronic acid, and denosumab. Unfortunately, due to a lack of head-to-head trials, the comparative effectiveness of the medications is unclear.

• 2. The adverse effects of the medications vary. For example, raloxifene is associated with an increased risk of thromboembolic events, whereas denosumab and the bisphosphonate medications have been associated with increased risk of osteonecrosis of the jaw and atypical subtrochanteric femoral fractures.Medical Research: Were any of the findings unexpected?

• Dr. Crandall: Many physicians and patients are likely to be surprised to know that there is such a tremendous lack of direct head-to-head comparisons of these medications, both for fracture reduction and for adverse effects.

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Osteoporosis Medications Differ in Joint Fracture Reduction, Adverse EffectsMedicalResearch.com Interview with:Carolyn J. Crandall, MD, MS Professor of MedicineDavid Geffen School of Medicine at University of California,Los Angeles

• Medical Research: What should clinicians and patients take away from your report?• Dr. Crandall: Clinicians and patients should realize that many agents are efficacious for

decreasing fracture risk, but they differ as to their adverse effect profiles, and not all of them are demonstrated to decrease hip fractures. Also, the absolute risk for atypical subtrochanteric femoral fractures during bisphosphonate use is low, ranging from about 2 per 100,000 for women receiving bisphosphonates for less than 2 years to 100 per 100,000 for women receiving bisphosphonates for 8 years or more.

• Medical Research: What recommendations do you have for future research as a result of this study?

• Dr. Crandall: We need more head-to-head (direct) comparisons of these medications to clarify how their anti-fracture and adverse effects differ. Also, there is only sparse information regarding anti-fracture efficacy of the medications in men, so we desperately need randomized controlled trials to be performed in men with osteoporosis. Finally, we don’t know the optimal treatment duration for these medications.

• Citation:• Crandall CJ, Newberry SJ, Diamant A, Lim Y, Gellad WF, Booth MJ, et al. Comparative Effective

ness of Pharmacologic Treatments to Prevent Fractures: An Updated Systematic Review. Ann Intern Med. [Epub ahead of print 9 September 2014] doi:10.7326/M14-0317

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Dignified Death Still Elusive On Many Cancer WardsMedicalResearch.com Interview with:Karin Jors MADepartment of Palliative Care, Comprehensive Cancer Center,University Medical Center Freiburg, Freiburg, Germany

• Medical Research: What are the main findings of the study?• Answer: The findings of our study shed light on the current circumstances for dying in cancer

centers. Physicians and nurses in our study reported that they rarely have enough time to care for dying patients. In addition, only a minority of staff members felt that they had been well-prepared during their training to care for dying patients and their families. Overall, only 56% of participants indicated that it is usually possible for patients to die in dignity on their ward. This is likely the result of various factors such as: inadequate rooms for dying patients and their families (i.e. shared rooms), poor communication with patients regarding burdensome treatments, an overuse of life-prolonging measures, etc. Striking differences were found between the responses of palliative care staff and staff from other wards (e.g. general care, oncology, intensive care). For example, palliative care staff reported that they usually have enough time to care for dying patients. In addition, 95% of palliative care staff indicated that it is usually possible for patients to die in dignity on their ward. Overall, nurses perceived the situation for dying patients more negatively than physicians. Whereas 72% of physicians reported that patients can usually die a dignified death on their ward, only 52% of nurses shared this opinion. Although only slightly more than half of participants believed that patients can usually die in dignity on their ward, this is a considerable improvement to the situation 25 years ago. In a similar study published in 1989, researchers found that 72% of physicians and nurses experienced the situation for patients dying on their hospital ward as undignified.

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Dignified Death Still Elusive On Many Cancer WardsMedicalResearch.com Interview with:Karin Jors MADepartment of Palliative Care, Comprehensive Cancer Center,University Medical Center Freiburg, Freiburg, Germany

• Medical Research: What should clinicians and patients take away from your report?• Answer: Over the last 25 years, considerable improvements in the care of patients dying in the

hospital setting have taken place. Patients can be comforted by the knowledge that the overwhelming majority of physicians and nurses in our study recognized the importance of honestly informing patients about their prognosis as well as all potential treatment options, even potentially burdensome ones. This stands in contrast to the study from 25 years ago, which found that 58% of physicians and nurses believed that patients did not wish to be informed about their prognosis, and 54% from the prior study were of the opinion that knowledge of a negative prognosis could be harmful to the patient. Furthermore, it can be viewed positively that the majority of physicians and nurses in our study expressed a desire for more training in end-of-life care, which suggests that they recognize the importance of this aspect of their work.

• The results of this study also have important implications for practicing physicians and nurses. Our study found that 72% of physicians believe it is usually possible for patients to die a dignified death on their ward, but only 52% of nurses shared this opinion. This difference in perception suggests that physicians and nurses may need to communicate more effectively with each other about the needs of dying patients in order to provide the best possible care. According to our results, physicians and nurses on palliative care wards work together more closely, and this appears to correspond with an overall more positive experience for dying patients. A majority of participants in this study also complained that they rarely have enough time to care for dying patients. Working in a team may also help to alleviate this burden by distributing responsibility among several people.

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Dignified Death Still Elusive On Many Cancer WardsMedicalResearch.com Interview with:Karin Jors MADepartment of Palliative Care, Comprehensive Cancer Center,University Medical Center Freiburg, Freiburg, Germany

• Medical Research: What recommendations do you have for future research as a result of this study?

• Answer: Although we aimed at a comprehensive investigation of the situation for patients dying in cancer centers, there are still other issues that should be explored, such as the role of other health care professionals including psychologists, social workers and chaplains.

• Our findings indicate that future research should be conducted to establish feasible, patient-oriented standards for end-of-life care. In addition, further research is necessary to develop comprehensive palliative care curricula and training for health care staff. To encourage such research, the Palliative Care Center of Excellence in Baden-Württemberg (KOMPACT) was established in 2014. This center combines the expertise of five academic, specialist palliative care departments. We believe that this cooperation is a valuable tool for improving patient care in the end-of-life setting.

• Citation: • Dying in cancer centers: Do the circumstances allow for a dignified death?• Jors, K., Adami, S., Xander, C., Meffert, C., Gaertner, J., Bardenheuer, H., Buchheidt, D., Mayer-

Steinacker, R., Viehrig, M., George, W. and Becker, G. (2014), Dying in cancer centers: Do the circumstances allow for a dignified death?. Cancer. doi: 10.1002/cncr.28702

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Prediabetes Associated With Increased Cancer RiskMedicalResearch.com Interview with:Professor Yuli HuangThe First People’s Hospital of Shunde, Daliang Town, China, and colleagues

• Medical Research: What are the main findings of the study? • Professor Huang: In this meta-analysis of 16 prospective cohort studies comprising more

than 890,000 individuals, we found that the presence of prediabetes at baseline associated with a 15% increased risk of cancer overall. The results were consistent across cancer endpoint, age, duration of follow-up and ethnicity. There was no significant difference for the risk of cancer with different definitions of prediabetes (impaired fasting glucose [IFG] and/or impaired glucose tolerance [IGT]).Medical Research: Were any of the findings unexpected?

• Professor Huang: Although the difference of risk of cancer was not significant between impaired glucose tolerance defined as 5.6-6.9 mmol/l or 6.1-6.9mmol/l. I think it is very interesting that the risks of cancer were increased even when a lower fasting plasma glucose value of 5.6–6.9 mmol/l was used, according to the current American Diabetes Association definition of IFG. These findings support the lower threshold definition impaired glucose tolerance proposed by the ADA, and highlight the clinical value of the early management of hyperglycemia to prevent cancer.

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Prediabetes Associated With Increased Cancer RiskMedicalResearch.com Interview with:Professor Yuli HuangThe First People’s Hospital of Shunde, Daliang Town, China, and colleagues

• Medical Research: What should clinicians and patients take away from your report?• Professor Huang: First, as the risk of cancer increased in people with prediabetes, clinicians should be

aware that it is important to screening for prediabetes with a view to cancer prevention. Second, lifestyle intervention (weight control, stop smoking and healthy diet etc.) should be suggested earlier and recommended as the mainstay of treatment for prediabetes in the general population.

• Medical Research: What recommendations do you have for future research as a result of this study?• Professor Huang: First, future researches are needed to explore the underlying mechanisms

associated with prediabetes and cancer. Second, Future prospective cohort studies that include testing of HbA1c may provide more information on the association between prediabetes and cancer. Third， long-term, large-scale studies are urgently needed to explore the effects of interventions (including lifestyle intervention and drug treatment) on the risk of cancer in people with prediabetes.

• Citation:• Prediabetes and the risk of cancer: a meta-analysis

Yi Huang & Xiaoyan Cai & Miaozhen Qiu & Peisong Chen &Hongfeng Tang & Yunzhao Hu & Yuli HuangDiabetologiaDOI 10.1007/s00125-014-3361-2Received: 16 May 2014 /Accepted: 31 July 2014# Springer-Verlag Berlin Heidelberg 2014

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More Than $60 Billion Spent On Proton Pump Drugs In Just Four YearsMedicalResearch.com Interview with:Michael Johansen, MD MSAssistant Professor Dept of Family MedicineOhio State University

• Medical Research: What are the main findings of the study?• Dr. Johansen: Between 2007-2011, the United States spent $63.4 billion on high-cost proton pump inhibitors of which $47.1

billion was in excess of using generic omeprazole.

Medical Research: Were any of the findings unexpected?• Dr. Johansen: Yes and no. While the finding of excess expenditure was expected to be high, I was shocked by the level of the

excess.• Medical Research: What should clinicians take away from your report?• Dr. Johansen: As a clinician, it became clear that we need to be good steward of societal resources. Prescribing one person an

unnecessary high cost drug doesn’t seem like a big deal until you think about it on a societal level. We end up spending more than $47.1 billion more over 5 years than needed within a single class of drugs. These billions are taken away from other aspects of society such as for roads, schools, or high value medical interventions.

• Medical Research: What should patients take away from your report?• Dr. Johansen: Patients were responsible for paying almost $7 billion more than if they had used omeprazole. It is a good idea to

ask your physician if there are cheaper options to branded medications (there normally are).• What recommendations do you have for future research as a result of this study?

Dr. Johansen: We are at a point that we need to try different ways of decreasing unnecessary use of high cost drugs. It is critical that policy makers intervene. Expecting different outcomes without changing the incentives and structures for pharmaceutical companies, physicians, and patients is highly unlikely. The goals of change should focus on incentivizing innovative new products, while decreasing the profitability of drugs that provide minimal value over cheaper alternative drugs.

• Citation:• Johansen ME, Huerta TR, Richardson CR. National Use of Proton Pump Inhibitors From 2007 to 2011. JAMA Intern Med.

Published online September 08, 2014. doi:10.1001/jamainternmed.2014.2900.

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Post Stent: Delaying Non-Emergency Surgery Reduced Adverse EventsMedicalResearch.com Interview with:Laura A. Graham, MPHCenter for Surgical, Medical Acute Care Research, and Transitions Birmingham

Veterans Affairs Medical CenterSection of Gastrointestinal Surgery, Department of SurgeryUniversity of Alabama at Birmingham, Birmingham

• Medical Research: What are the main findings of the study?• Answer: The main findings of the study are that the recommendations made in the guidelines

published by the American College of Cardiology / American Heart Association in 2007 were effective at reducing postoperative major adverse cardiac events following noncardiac surgery in patients with a cardiac stent.1 These guidelines recommended the delay of noncardiac surgeries in patients with a drug-eluting stent for 365 days if the surgery was not emergent or the delay of surgery for 4 to 6 weeks among patients with a bare metal stent.1 In addition to a 26% reduction in postoperative major adverse cardiac events, we also found an increase in the time between drug-eluting stent placement and non-cardiac surgery consistent with the guideline recommendations.

Medical Research: Were any of the findings unexpected?• Answer: In addition to our primary finding of a reduction in postoperative major adverse cardiac

events, we also found evidence of a shift in cardiac risk to patients with a bare metal stent for surgeries occurring between 2006 and 2009. Previous studies have suggested that differences in the outcomes of patients with a bare metal stent as compared to a drug-eluting stent are due to confounding by indication, where sicker patients needing more urgent operations were more likely to receive a bare metal stent and also more likely to experience adverse postoperative events. This study provides evidence of a shift toward higher cardiac risk in patients with a bare metal stent following the initial publication in 2006 of several case reports of postoperative stent thrombosis in patients with a drug-eluting stent.

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Post Stent: Delaying Non-Emergency Surgery Reduced Adverse EventsMedicalResearch.com Interview with:Laura A. Graham, MPHCenter for Surgical, Medical Acute Care Research, and Transitions Birmingham

Veterans Affairs Medical CenterSection of Gastrointestinal Surgery, Department of SurgeryUniversity of Alabama at Birmingham, Birmingham

• Medical Research: What should clinicians and patients take away from your report?• Answer: While the recommendations were effective at increasing time between drug-eluting stent placement

and surgery as well as reducing major adverse cardiac events, the trends in timing of surgery following drug-eluting stent placement suggest a high level of awareness among healthcare professionals treating patients with cardiac stents as well as an increased use of evidence-based practices. This resulted in an increase in surgery timing for drug-eluting stent patients which can be seen prior to the publication of the guidelines. While the publication of the guidelines marks a summary of this information into one document, it does not necessarily mark the time at which the information was officially available to healthcare providers in the field.

• Medical Research: What recommendations do you have for future research as a result of this study?• Answer: Further study should be done to examine other factors influencing the management of patients with

cardiac stents in need of subsequent surgery and their effect on outcomes.• Fleisher LA, Beckman JA, Brown KA, et al. ACC/AHA 2007 Guidelines on Perioperative Cardiovascular

Evaluation and Care for Noncardiac Surgery: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery) Developed in Collaboration With the American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, and Society for Vascular Surgery. J Am Coll Cardiol. Oct 23 2007;50(17):1707-1732.

• Citation:• Graham LA, Singletary BA, Richman JS, Maddox TM, Itani KF, Hawn MT. Improved Adverse Postoperative Outco

mes With Revised American College of Cardiology/American Heart Association Guidelines for Patients With Cardiac Stents. JAMA Surg. Published online September 03, 2014. doi:10.1001/jamasurg.2014.2044.

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Breath Temperature Test May Help Diagnose Lung CancerMedicalResearch.com Interview with:Dr. Giulia SciosciaCoauthor of this study with the Prof. CarpagnanoUniversity of Foggia.

• Medical Research: What are the main findings of this study?• Dr. Scioscia: The principal and newest findings of our study are:• Airways inflammation and neoangionesis are critical component of the lung cancer pathogenesis and

they contribute to the regulation of airways temperature. They cause a regional hyperthermia in the lung lesion.

• The exhaled Breath temperature has been proven to be the expression of the airways temperature and for this reason of their inflammation and neoangionesis.

• For the first time we have measured this hyperthermia in lung cancer patients with the xhalo. The patient with diagnosis of tumor shows an higher temperature than in healthy ones and this values correlate with cigarette smoking and tumor progression.

• Medical Research: What further research do you recommend as a result of this study? • Dr. Scioscia: Actually it is only a pilot study and the breath temperature in lung cancerogene requires a

standardization in large prospective studies. We could underline that our study opens up a new application of this non-invasive biomarkers in the protocols of early diagnosis of the lung cancer.

• Citation:• Breath temperature test could identify lung cancer• Abstract presented at the 2014 European Respiratory Society (ERS) International Congress• Abstract: Exhaled breath temperature in NSCLC: Could be a new non-invasive marker?

Session: Advances in diagnosis and therapy of thoracic tumoursDate and time: Monday 8 September, 10.45–11.45

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Long Term Benzodiazepines May Increase Alzheimer’s Disease RiskMedicalResearch.com Interview with:Sophie Billioti de Gage PharmDUniversity of Bordeaux SegalenFrance

• Medical Research: What are the main findings of the study?• Answer: The risk of Alzheimer’s disease was found increased by 43-51% in persons (>65) having initiated a

treatment with benzodiazepines in the past (>5 years before). Risk increased with the length of exposure and when long acting benzodiazepines were used.

Medical Research: What should clinicians and patients take away from your report?• Answer: Benzodiazepines remain valuable tools for managing anxiety and insomnia. We did not found any

increase in the risk of Alzheimer’s disease in individuals using benzodiazepines in accordance with international guidelines (short duration, not exceeding one month for hypnotics and three months for anxiolytics).

• For people needing or using benzodiazepines, it seems crucial to encourage physicians to carefully balance the benefits and risks when renewing the treatment. Abrupt discontinuation of long-term treatments with benzodiazepines should be avoided because of the risk of withdrawal effects.

• Medical Research: What recommendations do you have for future research as a result of this study?• Answer: Experimental animal or cellular models are needed to help in identifying a possible biological

mechanism linking benzodiazepines with risk of Alzheimer’s disease.• Studies based on a long follow-up—that is, at least 20-30 years—would make it possible to evaluate the risk of

long term use of benzodiazepines in younger adults and to better assess the exact role of anxiety, sleep disorders, and depression as putative early risk factors of future dementia.

• Citation:Risk of Alzheimer’s disease in benzodiazepine users: a case-control studyBMJ 2014; 349 doi: http://dx.doi.org/10.1136/bmj.g5205 (Published 09 September 2014) Cite this as: BMJ 2014;349:g5205

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Adolescent Cannabis Use Linked To Young Adult Adverse OutcomesMedicalResearch.com Interview with:Edmund Silins PhD, Research FellowNational Drug and Alcohol Research CentreUNSW Medicine University of New South Wales Sydney Australia

• Medical Research: What are the main findings of the study?• Dr. Silins: There were three particularly interesting aspects to the findings.• Firstly, we found clear and consistent associations between adolescent cannabis use and the

young adult outcomes investigated.• Secondly, there was evidence of a dose-response effect such that the more frequently

adolescents used cannabis the more likely they were to experience harms later in life.• Thirdly, for most outcomes, these associations remained even after taking into account a wide

range of other factors which might potentially explain them.• The adverse effects were greatest for daily cannabis users. Specifically, adolescents who were

daily cannabis users were, by the age of 25, more than 60% less likely to complete high school or obtain a university degree, seven times more likely to have attempted suicide, 18 times more likely to have been cannabis dependent, and eight times more likely to have used other illicit drugs, than adolescents who had never used the drug.

Medical Research: Were any of the findings unexpected?• Dr. Silins: We were surprised to find that for most outcomes the associations persisted even

after taking into account 53 individual, parental, and peer-level factors which may potentially explain them. The findings provide strong evidence of a more direct link between adolescent cannabis use and young adult wellbeing, mental health, and achievement.

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Adolescent Cannabis Use Linked To Young Adult Adverse OutcomesMedicalResearch.com Interview with:Edmund Silins PhD, Research FellowNational Drug and Alcohol Research CentreUNSW Medicine University of New South Wales Sydney Australia

• Medical Research: What should clinicians and patients take away from your report?• Dr. Silins: The findings suggest that the prevention or delay of regular cannabis use in adolescents will

have broad health and social benefits. As young people typically do not present to clinical services for management of cannabis use, screening for cannabis use in those under the age of 16 should be routine for GPs, paediatricians, child and adolescent psychiatrists, primary care nurses and school counsellors.

• It is important to encourage adolescents not to use cannabis, or at the very least, delay their use. This is a particularly important message because the developing adolescent brain is very susceptible to the harmful effects of cannabis use.

• Parents also have an important part in preventing or delaying their child’s cannabis use. One of the most important things a parent can do is develop good communication with their child and have conversations about cannabis which are open, honest and non-judgemental. If their teenager is already using cannabis, it’s important to raise the issue even though confronting them about their use will probably be difficult. Be open and non-judgemental, offer support, and be prepared to have ongoing conversations about cannabis. If all else fails, professional help can be sought through a general practitioner or counsellor.

• Citation:• Young adult sequelae of adolescent cannabis use: an integrative analysis

Dr Edmund Silins PhD,L John Horwood MSc,Prof George C Patton MD,Prof David M Fergusson PhD,Craig A Olsson PhD,Delyse M Hutchinson PhD,Elizabeth Spry BA,Prof John W Toumbourou PhD,Prof Louisa Degenhardt PhD,Wendy Swift PhD,Carolyn Coffey PhD,Robert J Tait PhD,Primrose Letcher PhD,Prof Jan Copeland PhD,Richard P Mattick PhD,for the Cannabis Cohorts Research Consortium

The Lancet Psychiatry – 1 September 2014 ( Vol. 1, Issue 4, Pages 286-293 ) DOI: 10.1016/S2215-0366(14)70307-4

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Obese Adolescents May Have Heightened Vulnerability To Food CommercialsMedicalResearch.com Interview with:Dr. Sonja Yokum Ph.D.Oregon Research InstituteEugene Oregon, 9740

• Medical Research: What are the main findings of the study? • Dr. Yokum: We found that adolescents showing elevated responses in reward regions to food

commercials gained more weight over 1-year follow-up compared to those with less activation in these brain regions. This suggests that there are individual differences in neural vulnerability to food commercials that appear to identify youth at risk for excess weight gain.

Medical Research: Were any of the findings unexpected?• Dr. Yokum: It was not completely unexpected as previous studies found that individual

differences in reward response to stationary food images correlate positively with future weight gain. However, the food images used in these studies are without branding/context. Our study is the first to investigate neural response to real-world stimuli (i.e. food commercials shown in the context of a television show). Our findings extend the findings of these prior studies.

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Obese Adolescents May Have Heightened Vulnerability To Food CommercialsMedicalResearch.com Interview with:Dr. Sonja Yokum Ph.D.Oregon Research InstituteEugene Oregon, 9740

• Medical Research What should clinicians and patients take away from your report?• Dr. Yokum:: Our findings suggest that interventions that focus on educating adolescents about

nutrition or media may have limited success because they do not address the activation of reward-related neural circuitry by food marketing. Novel interventions that focus on decreasing reward-related responses to food advertising may be needed. For example, reward-related neural response to food cues may be diminished through cognitive interventions that train individuals to focus on long-term consequences of eating the advertised food.

• Medical Research: What recommendations do you have for future research as a result of this study?

• Dr. Yokum: It will be important to replicate this study with larger samples. Further, identification of biological, psychological, and environmental factors that increase or decrease the susceptibility to food advertising will be essential in the development of successful prevention and treatment interventions to reduce the impact of food marketing on adolescents, as well as identifying those teens most in need of these initiatives.

• Citation:• Individual differences in striatum activity to food commercials predict weight gain in adolescent

s• Yokum S1, Gearhardt AN, Harris JL, Brownell KD, Stice E.

Obesity (Silver Spring). 2014 Aug 25. doi: 10.1002/oby.20882. [Epub ahead of print]

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Sleep Patterns Vary By Neighborhood and Socioeconomic StatusMedicalResearch.com Interview withDr. Shona E. Fang Sc.D.New England Research Institutes, IncWatertown, Massachusetts

• Medical Research: What are the main findings of the study?

Dr. Fang: Sleep duration varied by neighborhood in Boston, a diverse urban setting.• Individual factors, including socioeconomic status, explained some of this variation, while neighborhood

socioeconomic status (SES) explained a much larger portion.

Medical Research: Were any of the findings unexpected?• Dr. Fang: Just how much neighborhood socioeconomic status impacted variations in sleep duration was

surprising.• Medical Research: What should clinicians and patients take away from your report?• Dr. Fang: Clinicians should keep environmental factors in mind when treating patients with disturbed sleep.

Things associated with neighborhood socioeconomic status like ambient noise, light and perhaps even feelings of being safe during sleep should not be discounted as potentially modifiable factors for the nighttime environment.

• Medical Research: What recommendations do you have for future research as a result of this study?• Dr. Fang: Future research should aim to understand the mechanisms by which neighborhood socioeconomic

status can impact sleep.• Citation:• Geographic variations in sleep duration: a multilevel analysis from the Boston Area Community Health (BACH) Su

rvey

Shona C Fang, S V Subramanian, Rebecca Piccolo, May Yang, H Klar Yaggi, Donald L Bliwise, Andre B Araujo• J Epidemiol Community Health jech-2013-203256Published Online First: 8 September 2014 doi:10.1136/jech-201

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New Plastic Surgery Approach Allows For Total Face RejuvenationMedicalResearch.com Interview with:Achih H. Chen, MD, FACS, FAACSGeorgia Center for Facial Plastic Surgery, Evans, Ga

and the Division of Facial Plastic and Reconstructive Surgery, Department of Otolaryngology–Head and Neck Surgery Georgia Regents University, August, Ga

• Medical Research: What is the significance of the study?• Dr. Chen : This is the first time that facial rejuvenation surgery using surgical approaches in

three planes combined with ablative resurfacing has been reported in the medical literature. This approach was not previously thought possible in a single surgical setting because of the concern about disrupting the facial blood supply that may result in loss of the skin. The study demonstrates the safety of this “Total Face” approach. This approach allows simultaneous tightening of the jawline and neck, recreating the lost youthful volume of the midface region, and restoring of the smooth skin texture so characteristic of a young face. This allows for a more complete or “Total Face Rejuvenation” for patients while allowing them the flexibility for a single recovery period or downtime.

Medical Research: What are the main findings of the study?• Dr. Chen : The study demonstrates that facial rejuvenation surgery involving surgical

approaches in the sub-periosteal plane (below the lining of the bone), the sub-SMAS plane (superficial musculoaponeurotic system—layer of fat and muscle in the face and neck), and sub-cutaneous plane (below the skin) could be combined with ablative laser resurfacing without increased risk.

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New Plastic Surgery Approach Allows For Total Face RejuvenationMedicalResearch.com Interview with:Achih H. Chen, MD, FACS, FAACSGeorgia Center for Facial Plastic Surgery, Evans, Ga

and the Division of Facial Plastic and Reconstructive Surgery, Department of Otolaryngology–Head and Neck Surgery Georgia Regents University, August, Ga

• Medical Research: Why should surgeons and patients consider a three plane surgical approach to facial rejuvenation?

• Dr. Chen : Traditionally, the gold standard to rejuvenating the aging face has been thought of as a tightening procedure, specifically facelift surgery. However, aging of the face involves more than just sagging. Tightening only facial rejuvenation approaches often results in a “pulled” or “operated” appearance. A substantial portion of the aging face involves the loss of volume, especially in the midface region. The youthful face has fullness and volume. As time passes, the volume is lost. The result is very similar to air escaping from a balloon. As air escapes a balloon, it sags. This similar loss of volume causes downward sagging and flattening of the midface and a resulting deepening of the nasolabial folds (the lines running from the corners of the nose to the corners of the mouth or the “parentheses”). In addition, with aging the surface of the skin begins to show a cobblestone texture and pigment irregularities. Simultaneous three plane surgical facial rejuvenation with ablative laser resurfacing allows restoring the jawline and neck, recreating youthful midface volume, and smoothing of the texture of the skin in a single surgical setting.

• Medical Research: Were any of the findings unexpected?• Dr. Chen : This study contradicts conventional thought that a three plane surgical approach to facial rejuvenation

surgery should not be combined with ablative laser resurfacing in a single surgical setting.• Medical Research: What should clinicians and patients take away from your report? • Dr. Chen : More complete, natural-appearing facial rejuvenation surgery may be safely and effectively performed in

a single surgical setting allowing patients the flexibility for a single recovery period.• • Citation:• Achih H. Chen and Adam M. Becker (2014

) Total Face Rejuvenation: Simultaneous 3-Plane Surgical Approach Combined With Ablative Laser Resurfacing. American Journal of Cosmetic Surgery: September 2014, Vol. 31, No. 3, pp. 183-188.

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Medical Research Citation Rate May Lead To Treatment BiasMedicalResearch.com Interview with:Mintu Turakhia, MD MAS, FHRS FACC FAHAAssistant Professor of Medicine and (by courtesy) of Health Research & Policy

Stanford University School of Medicine Director of Cardiac ElectrophysiologyVA Palo Alto Healthcare System

• Medical Research: What are the main findings of the study• Dr. Turakhia: We found that the reported success rate of a study correlated with the number of times the study was

cited in the literature, even after adjustment for a wide range of factors.•

Medical Research: Were any of the findings unexpected• Dr. Turakhia: I was not entirely surprised with the findings but this is the first time such a formal analysis has been

done with cardiovascular therapies.• Medical Research: What should clinicians and patients take away from your report• Dr. Turakhia: The study does not change clinical practice. Rather, what it implies is that, to readers of the literature,

radiofrequency catheter ablation of atrial fibrillation could be perceived to be more effective than the data supports. Moreover, this type of bias may extend to a wide ranging of other therapies that have had highly varied published success rates, including renal denervation, left ventricular mechanical support, and left atrial appendage occlusion.

• Medical Research: What recommendations do you have for future research as a result of this study?• Dr. Turakhia: We should more formally evaluate whether citation bias is occurring with other treatments and try to

understand the downstream effect of this bias in quantitative and qualitative terms. Journals could also require that meta-analyses or systematic reviews be preferentially reported when describing success rates of procedures rather than individual studies, which may incompletely represent the totality of medical evidence.

• Citation:• Association Between Success Rate and Citation Count of Studies of Radiofrequency Catheter Ablation for Atrial Fibrill

ation: Possible Evidence of Citation Bias• Alexander C. Perino,Donald D. Hoang,Tyson H. Holmes,Pasquale Santangeli,

Paul A. Heidenreich,Marco V. Perez,Paul J. Wang, and Mintu P. Turakhia• Circ Cardiovasc Qual Outcomes. 2014;CIRCOUTCOMES.114.000912published online before print September 9 2014, d

oi:10.1161/CIRCOUTCOMES.114.000912

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Mandatory Flu Shots For Health Care Workers Boosts Vaccination RatesMedicalResearch.com Interview with:Allison Weinmann MBBS, FRACPSenior Staff, Division Infectious Diseases Director HFHS Immunization Team

Medical Director Infection Control and Prevention, West Bloomfield Hospital Henry Ford Health System

• Medical Research: What are the main findings of this study?• Dr. Weinmann: The main findings included:• Mandatory influenza immunization for health care workers without allowing optional opt-out

(and only allowing for documented medical or religious exemption) successfully raised our immunization uptake among all our employees to over 99% sustainable for the last 2 years which we consider a very important patient safety initiative.

• Less than 2% of workers met a medical or religious exemption.• A prior optional opt out with mask wearing was problematic for staff and patients and did not

reach our goal of close to 100% immunization uptake.• Medical Research: Were any of the findings unexpected?• Dr. Weinmann: The unexpected findings were:• Early and strong support from administration and hospital leaders.• Obtaining close to 100% immunization rates are achievable even in very large health care

system.• Despite a vocal minority of dissenters, the majority of our employees supported the mandate

as evidenced by our data.

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Mandatory Flu Shots For Health Care Workers Boosts Vaccination RatesMedicalResearch.com Interview with:Allison Weinmann MBBS, FRACPSenior Staff, Division Infectious Diseases Director HFHS Immunization Team

Medical Director Infection Control and Prevention, West Bloomfield Hospital Henry Ford Health System

• Medical Research: What should patients and clinicians take away from this report?• Dr. Weinmann: Take away messages:• Patient safety is one of health cares’ primary concerns – there is literature data associating

health care workers and low immunization rates with outbreaks in health care facilities – mandatory influenza vaccination for health care workers promotes patient safety.

• Mandatory immunization is achievable even in very large multihospital health care systems.• In order to be successful: Strong physician leadership; Buy in from administration; Strong

multidisciplinary System wide influenza committee with key players Infectious Diseases physicians, Infection Control, Human Resources, Employee Health, microbiology lab, pharmacy.

• High rates of immunization can be sustained over time without losing employees.• • Medical Research: What future research do you recommend as a result of this study?• Dr. Weinmann: Future initiatives should consider other immunization mandates on a case-by-

case basis eg Tdap.• • Citation:• ICAAC 2014 Abstract discussing:• Mandatory policy boosts flu vaccination rates among health care workers

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Do Arterial Catheters Improve ICU Patient Care?MedicalResearch.com Interview with: Hayley Gershengorn MDAssistant Professor, Department of Medicine (Critical Care)Assistant Professor, The Saul R. Korey Department of Neurology

Albert Einstein College of MedicineBronx, NY 10461

• Medical Research: What are the main findings of the study?• Dr. Gershengorn: Using a large national database, we found there to be no association between the use of arterial catheters and mortality in mechanically ventilated medical

intensive care unit patients. Similarly, we found no beneficial association between arterial catheters and mortality in any of the eight other critically ill subgroups evaluated.

Medical Research: Were any of the findings unexpected?• Dr. Gershengorn: Arterial catheters are commonly used in intensive care unit patients to monitor blood pressure and facilitate arterial blood sampling. Clinicians utilize these

catheters because they presume them to confer benefit to their patients. Our findings are the first to call this assumption into question.• Medical Research: What should clinicians and patients take away from your report?

Dr. Gershengorn: Monitoring devices such as arterial catheters are not without cost—both in terms of potential complications patients might suffer from them and financial costs. History has shown critical care practitioners that the prevalent use of certain intravascular monitoring devices (specifically, the pulmonary artery catheter) may not be in our patients’ best interests. In fact, it was a propensity-matched analysis similar to ours by Connors et al.1 which ignited a series of prospective randomized controlled trials all finding no benefit to use of the pulmonary artery catheter in intensive care unit patients.2-5 Given our study design, we cannot demonstrate a true causal relationship between arterial catheters and outcomes. As such, we view it as hypothesis generating—just as Connors et al.’s work was for the pulmonary artery catheter. We hope it will spur prospective study of this topic.

• Medical Research: What recommendations do you have for future research as a result of this study?• Dr. Gershengorn: As alluded to above, we believe our study has created the needed equipoise to compel a prospective randomized controlled trial to evaluate the causal

relationship between arterial catheter use and outcomes (e.g., mortality, morbidity, cost) in intensive care unit patients. Given the prevalent use of these catheters, 6 the potential complications associated with them, and the financial costs of inserting and maintaining them, we believe such a trial is greatly needed.

• References• Connors AF, Speroff T, Dawson NV, et al. The effectiveness of right heart catheterization in the initial care of critically ill patients. SUPPORT Investigators. JAMA.

1996;276(11):889-897.• Sandham JD, Hull RD, Brant RF, et al. A randomized, controlled trial of the use of pulmonary-artery catheters in high-risk surgical patients. N Engl J Med. 2003;348(1):5-14.• Richard C, Warszawski J, Anguel N, et al. Early use of the pulmonary artery catheter and outcomes in patients with shock and acute respiratory distress syndrome: a

randomized controlled trial. JAMA. 2003;290(20):2713-2720.• Harvey S, Harrison DA, Singer M, et al. Assessment of the clinical effectiveness of pulmonary artery catheters in management of patients in intensive care (PAC-Man): a

randomised controlled trial. Lancet. 2005;366(9484):472-477.• Wheeler AP, Bernard GR, Thompson BT, et al. Pulmonary-artery versus central venous catheter to guide treatment of acute lung injury. N Engl J Med. 2006;354(21):2213-

2224.• Gershengorn HB, Garland A, Kramer A, Scales DC, Rubenfeld G, Wunsch H. Variation of Arterial and Central Venous Catheter Use in United States Intensive Care Units.

Anesthesiology. 2014;120(3):650-664.• Citation:• Gershengorn HB, Wunsch H, Scales DC, Zarychanski R, Rubenfeld G, Garland A. Association Between Arterial Catheter Use and Hospital Mortality in Intensive Care Units.

JAMA Intern Med. Published online September 08, 2014. doi:10.1001/jamainternmed.2014.3297. •

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Diabetics on Statins May Have Fewer Microvascular Complications MedicalResearch.com Interview with: Børge G. Nordestgaard, MD, DMScProfessor, University of CopenhagenChief Physician, Herlev Hospital, Copenhagen University

Hospital Dept. Clinical BiochemistryHerlev Ringvej Herlev, Denmark

• Medical Research: What are the main findings of the study?• Dr. Nordestgaard: Among all patients with diabetes in Denmark during 1996-2009 and compared with non-

statin users, statin users had a 40% lower risk of diabetic retinopathy, a 34% lower risk of diabetic neuropathy, and a 12% lower risk of gangrene of the foot, while the risk of diabetic nephropathy was similar.

Medical Research: Were any of the findings unexpected?• Dr. Nordestgaard: Yes, we expected that the risk would be higher for microvascular disease among diabetic

statin users, while we observed the opposite.• Medical Research: What should clinicians and patients take away from your report?• Dr. Nordestgaard: Although statins may increase the risk of diabetes slightly while reducing cardiovascular

disease markedly, there seems to be no increased risk of microvascular disease in patients with diabetes on a statin.

• Medical Research: What recommendations do you have for future research as a result of this study?• Dr. Nordestgaard: Whether or not statins are protective against some forms of microvascular disease, a

possibility raised by our data, and by which mechanism, will need to be addressed in studies similar to ours, or in mendelian randomisation studies, but preferably in randomised controlled trials.

• Citation:Statin use before diabetes diagnosis and risk of microvascular disease: a nationwide nested matched studySune F Nielsen PhD,Prof Børge G Nordestgaard MDThe Lancet Diabetes & Endocrinology – 10 September 2014 DOI: 10.1016/S2213-8587(14)70173-

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Sleep Apnea May Be Improved By Moderate Calorie RestrictionMedicalResearch.com Interview with:Marcia Klein M.D., Ph.D.Adjunctive professor Rio de Janeiro State University.

• Medical Research: What was the main findings of the study?• Dr. Klein: The main findings were that a diet with moderate calories restriction in obese patients with

obstructive sleep apnea may be able not only to reduce body fat but also to reduce obstructive sleep apnea severity and blood pressure.

Medical Research: Were any findings unexpected? • Dr. Klein: The new and unexpected finding was that a moderate calories restriction was able to reduce

sleep apnea severity, because the previous studies that evaluated the effect of weight loss on obstructive sleep apnea used severe calorie restriction or the association of diet with physical activity or bariatric surgery.

• Medical Research: What should clinicians and patients take away from your report?

Dr. Klein: Moderate energy restriction besides improving several cardiovascular risk factors may improve sleep apnea. There is no need to make severe energy restriction, that is difficult to follow during a long period of time, to improve sleep apnea.

• Medical Research: What recommendations do you have for future studies on this topic?• Dr. Klein: Greater number of participants followed during a longer period of time.• Citation:• Restricting calories may improve sleep apnea, blood pressure in obese people• American Heart Association Meeting Report Abstract 461

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Isotretinoin Associated With Lower Risk of Inflammatory Bowel DiseaseMedicalResearch.com Interview with:Shadi Rashtak, MDDepartment of DermatologyMayo Clinic College of Medicine Rochester, Minnesota

• Medical Research: What are the main findings of the study?• Dr. Rashtak: We found that among a population of mainly acne patients those who received isotretinoin

had a lower risk of inflammatory bowel disease as compared to those who did not take this medication. We carefully reviewed the medical records of patients to ensure that this finding was not simply because the drug was avoided in patients with a previous personal or family history of IBD.

•Medical Research Were any of the findings unexpected?

• Dr. Rashtak: Yes, based on previous studies we had hypothesized to find no association between isotretinoin exposure and inflammatory bowel disease but instead we found a negative association between the two.

• Medical Research What should clinicians and patients take away from your report?• Dr. Rashtak: It does not appear that isotretinoin has any causal effect for IBD and therefore it should not

be witheld when indicated merely due to concerns for inflammatory bowel disease risk.• Medical Research What recommendations do you have for future research as a result of this study?• Dr. Rashtak: Although we had a large number of isotretinoin-exposed and non-exposed patients due to

rarity of inflammatory bowel disease, there were only small number of IBD patients in each group. More cohort studies with much larger sample size are needed to confirm if this negative association truly exists.

• Citation:• Rashtak S, Khaleghi S, Pittelkow MR, Larson JJ, Lahr BD, Murray JA. Isotretinoin Exposure and Risk of Inflam

matory Bowel Disease. JAMA Dermatol. Published online September 10, 2014. doi:10.1001/jamadermatol.2014.1540.

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Diabetes in Pregnancy: Lower HbA1c Threshold Improves DetectionMedicalResearch.com Interview With:Ruth C. E. Hughes Department of Obstetrics and GynecologyUniversity of Otago, Christchurch Women’s Hospital Christchurch, New Zealand

• Medical Research: What are the main findings of the study?• Dr. Hughes: The increasing prevalence of undiagnosed type 2 diabetes in women of childbearing age was the

main driver behind our study. In clinical practice, we were finding that women with probable undiagnosed diabetes (and pre-diabetes) had already started developing pregnancy complications at the time they were diagnosed with gestational diabetes diagnosis in the late second trimester. It seemed logical to try to identify them in early pregnancy, with the idea that they might benefit from earlier intervention. We thus explored the usefulness of first trimester HbA1c measurements to identify women with unrecognised pre-existing diabetes.

• In our study, an HbA1c of 5.9% (41mmol/mol) was the optimal screening threshold for diabetes in early pregnancy. We found that a threshold of 6.5% (48mmol/mol), which is endorsed by the World Health Organization and American Diabetes Association for diagnosing diabetes in pregnancy, would miss almost 50% of women with probable pre-existing diabetes. Of great relevance, women with an early HbA1c of 5.9%-6.4% (41-46mmol/mol) had poorer pregnancy outcomes than those with an HbA1c <5.9% (<41mmol/mol), with a 2.5-3 fold higher relative risk of major congenital anomaly, preeclampsia, shoulder dystocia, and perinatal death. These women were also more likely to deliver before 37 weeks gestation.

Medical Research: Were any of the findings unexpected?• Dr. Hughes: Not really, although the rates of adverse pregnancy outcomes in women with an HbA1c 5.9%-6.4%

(41-46mmol/mol) who did not meet New Zealand diagnostic criteria for gestational diabetes (and were therefore untreated) were possibly higher than we expected. It suggests that these HbA1c levels are clinically important and provides useful data for further studies to examine whether early intervention reduces these risks.

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Diabetes in Pregnancy: Lower HbA1c Threshold Improves DetectionMedicalResearch.com Interview With:Ruth C. E. Hughes Department of Obstetrics and GynecologyUniversity of Otago, Christchurch Women’s Hospital Christchurch, New Zealand

• Medical Research: What should clinicians and patients take away from your report?• Dr. Hughes: Clinicians and patients should not find an early pregnancy HbA1c result below

6.5% (48mmol/mol) reassuring. An early pregnancy HbA1c 5.9-6.5% (41-46mmol/mol) identifies a group of women who have a higher risk of adverse pregnancy outcomes, who may benefit from early referral and monitoring.

• Medical Research: What recommendations do you have for future research as a result of this study?

• Dr. Hughes: Our study was of a largely Caucasian population and confirmation of the results in studies of women from diverse ethnic backgrounds is required. The next step is to investigate whether early pregnancy intervention can modify these risks.

• • Citation:

An Early Pregnancy HbA1c

≥5.9% (41 mmol/mol) Is Optimal for Detecting Diabetes and Identifies Women at Increased Risk of Adverse Pregnancy Outcomes

• Ruth C.E. Hughes, M. Peter Moore, Joanna E. Gullam, Khadeeja Mohamed, and Janet Rowan• Diabetes Care published ahead of print September 4, 2014, doi:10.2337/dc14-1312 1935-554

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Study Examines Risk of Alopecia Areata and Vitiligo in Stem Cell RecipientsMedicalResearch.com Interview with:Rena Zuo, BS. MD Candidate at Duke University School of Medicine andEdward W. Cowen, MD, MHSc Senior Clinician Head

, Dermatology Consultation Service Dermatology BranchCenter for Cancer Research National Cancer Institute National Institutes of Health

• MedicalResearch: What are the main findings of the study?• Answer: Chronic graft-vs-host disease (cGVHD) is a debilitating multisystem disease that

occurs in patients receiving allogeneic hematopoietic stem cell transplantations as treatment for hematologic disorders. Although the diverse clinical presentations of cGVHD frequently mimic other autoimmune diseases such as Sjögren syndrome and systemic sclerosis, and low-titer antibodies are commonly found in patients with cGVHD, the exact pathogenesis and role of autoimmunity in cGVHD are incompletely understood.

• Our study is the first to characterize and identify risk factors associated with the development of two uncommon autoimmune phenomena, specifically alopecia areata and vitiligo, in the setting of cGVHD. Laboratory markers, including 11 antibodies, transplant-related factors, and other cGVHD systemic manifestations were analyzed.

• Several particularly interesting results were found:• Among 282 patients with cGVHD, 15 demonstrated vitiligo (14 of 282; 4.9%) and/or alopecia

areata (2 of 282; 0.7%).• Female donor and female donor to male recipient sex mismatch, in particular, are

significantly associated with the development of vitiligo and/or alopecia areata.• Positive anti-cardiolipin (ACA) IgG was also significantly associated with development of

vitiligo and/or alopecia areata.

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Study Examines Risk of Alopecia Areata and Vitiligo in Stem Cell RecipientsMedicalResearch.com Interview with:Rena Zuo, BS. MD Candidate at Duke University School of Medicine andEdward W. Cowen, MD, MHSc Senior Clinician Head

, Dermatology Consultation Service Dermatology BranchCenter for Cancer Research National Cancer Institute National Institutes of Health

• MedicalResearch: Were any of the findings unexpected?• Answer: We were surprised to find that all 14 patients with vitiligo and/or alopecia areata

who had information on donor sex received stem cells from a female donor. Nine of the 14 recipients were male, accounting for 64% cases. In addition, five patients were found to also have thyroid abnormalities.

• MedicalResearch: What should clinicians and patients take away from your report?• Answer: Our study provides further evidence that stem cell donor sex represents an

important transplant-related risk factor for the development of cGVHD. Specifically, our findings suggest that female donor sex is a risk factor for the development of concomitant cutaneous autoimmunity in the setting of cGVHD. Physicians should be aware of the potential for vitiligo and alopecia areata in addition to other more classic skin manifestations of cGVHD as these conditions may further impact the patient’s quality of life and psychosocial health.

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Study Examines Risk of Alopecia Areata and Vitiligo in Stem Cell RecipientsMedicalResearch.com Interview with:Rena Zuo, BS. MD Candidate at Duke University School of Medicine andEdward W. Cowen, MD, MHSc Senior Clinician Head

, Dermatology Consultation Service Dermatology BranchCenter for Cancer Research National Cancer Institute National Institutes of Health

• MedicalResearch: What recommendations do you have for future research as a result of this study?

• Answer: Our study aimed to comprehensively evaluate risk factors associated with concomitant cutaneous autoimmunity in the setting of cGVHD, but we did not analyze specific findings associated with other organ systems. Future research should be conducted to explore transplant-related risk factors, systemic manifestations and laboratory markers for the development of concomitant autoimmune manifestations in other organ systems such as the eye, mouth, liver, and gastrointestinal tract.

• Citation:• Zuo RC, Naik HB, Steinberg SM, et al. Risk Factors and Characterization of Vitiligo and Alopeci

a Areata in Patients With Chronic Graft-vs-Host Disease. JAMA Dermatol. Published online September 10, 2014. doi:10.1001/jamadermatol.2014.1550.

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Poor Appetite in Elderly Increases Mortality RiskMedicalResearch.com Interview with:Professor Mark L. Wahlqvist, M.D., Ph.D.Institute of Population Health Sciences, National Health Research Institutes, Taiwan

National Defense Medical Center, School of Public Health, TaiwanMonash Asia Institute, Monash University Melbourne, Australia

• Medical Research: What are the main findings of the study?• Prof. Wahlqvist: Poor appetite and dietary quality as judged by diversity separately (each by

about 50%) and together (by about 80%) increase the mortality risk in older persons living in the community.

Medical Research: Were any of the findings unexpected?• Prof. Wahlqvist: We generally associate poor appetite with illness and frailty with little

surprise that it is associated with decreased survival. But we found almost 10% of older people in the community to have poor appetites, placing them at risk of poorer health and shorter lives. To some extent, the risk this posed for premature death was direct and not related to general health. What was encouraging was that those who could still manage a diverse diet lived longer. Although we cannot be sure about causality, it is probable that a diverse diet will help maintain general health in the face of a poor appetite. Of course appetite and diet can affect each other so it is not too surprising that both need consideration.

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Poor Appetite in Elderly Increases Mortality RiskMedicalResearch.com Interview with:Professor Mark L. Wahlqvist, M.D., Ph.D.Institute of Population Health Sciences, National Health Research Institutes, Taiwan

National Defense Medical Center, School of Public Health, TaiwanMonash Asia Institute, Monash University Melbourne, Australia

• Medical Research: What should clinicians and patients take away from your report?• Prof. Wahlqvist: Loss of appetite is not to be ignored at any age, especially with advancing

years. It can be an early indicator of general health and dietary problems which can shorten life. While loss of appetite can be related to various social and psychological problems, like loneliness and depression, it can also be part of a vicious cycle with poor dietary quality, limited physical and outdoor activity (like shopping) playing a role, as in the present study. Simple enquiry about appetite could enable measures to be put in place to improve health and live longer.

• Medical Research: What recommendations do you have for future research as a result of this study?

• Prof. Wahlqvist: We would recommend efforts to identify and rectify poor appetite among older free-living people be encouraged and evaluated. Consideration should also be given as to how much poor appetite might be prevented and its consequences minimized by early interventions.

• Citation:• Appetite predicts mortality in free-living older adults in association with dietary diversity. A N

AHSIT cohort study• Appetite Volume 83, 1 December 2014, Pages 89–96• Yi-Chen Huang, , Meei-Shyuan Lee

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Eating Fish May Reduce Risk Of Hearing Loss In WomenMedicalResearch.com Interview with: Sharon G. Curhan, MD, ScMChanning Division of Network Medicine Department of Internal MedicineBrigham and Women’s Hospital Harvard Medical

School Boston, MA 02115

• Medical Research: What are the main findings of the study?• Dr. Curhan: We followed more than 65,000 women who were participants in the Nurses’

Health Study II over 18 years and found that eating 2 or more servings of fish per week was associated with a lower risk of hearing loss. For example, after adjusting for potential confounders in multivariable analyses, in comparison with women who rarely or never ate fish, women who consumed 2 or more servings of fish per week had a 20% lower risk of hearing loss. Eating any type of fish (tuna, dark fish, light fish or shellfish) tended to be associated with lower risk. Also, we found that higher intake of long-chain omega-3 polyunsaturated fatty acids (PUFAs) was inversely associated with risk. For example, in comparison with women with the lowest intake, women with the highest intake of long-chain omega-3 PUFAs had a 22% lower risk of hearing loss.

• Medical Research: Were any of the findings unexpected?• Dr. Curhan: Our hypothesis was that higher fish intake and higher intake of long-chain

omega-3 PUFAs are associated with lower risk of hearing loss. However, we did not know whether there might be substantial differences depending the specific type of fish consumed. When examined individually, and adjusting for consumption of the other fish types as well as other potential confounders in our multivariable analyses, we found that higher consumption of each specific fish type was inversely associated with risk of hearing loss.

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Eating Fish May Reduce Risk Of Hearing Loss In WomenMedicalResearch.com Interview with: Sharon G. Curhan, MD, ScMChanning Division of Network Medicine Department of Internal MedicineBrigham and Women’s Hospital Harvard Medical

School Boston, MA 02115

• Medical Research: What should clinicians and patients take away from your report?• Dr. Curhan: Acquired hearing loss is an extremely common and often disabling condition that can

adversely effect communication, quality of life, work productivity and health. According to recent estimates, 48 million Americans have some degree of hearing loss. Commonly, hearing loss is considered to be an unavoidable companion to aging, hover, hearing loss may not be inevitable.

• A complex interaction of factors all contribute to acquired hearing loss, including lifestyle and environmental factors, age, genetics, noise exposure, and some medical conditions and medications. However, at least some of hearing loss may be preventable and there may be factors that can be modified to help prevent or delay its onset. These findings provide evidence that modifiable dietary risk factors may help reduce the risk of hearing loss.

• Medical Research: What recommendations do you have for future research as a result of this study?

• Dr. Curhan: Our study examined a predominantly white population of women. It will be important to examine these relations in men and in other populations.

• Citation:• Fish and fatty acid consumption and the risk of hearing loss in women• Download to Citation Manager

Sharon G Curhan, Roland D Eavey, Molin Wang, Eric B Rimm, and Gary C Curhan• Am J Clin Nutr 2014 ajcn.091819; First published online September 10, 2014. doi:10.3945/ajcn.11

4.091819

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Physical Activity During School Improves Academic Achievement, Especially For BoysMedicalResearch.com Interview with:Eero Haapala, MSc in Exercise Medicine, BASc PhD studentUniversity of Eastern Finland,School of Medicine

Institute of Biomedicine, PhysiologyKuopio, Finland

• Medical Research: What are the main findings of the study?

Answer: Our study is one of the first studies to investigate the different types of physical activity and sedentary behavior with academic achievement in children. Our main finding was that children who were more physically active during school recess were better readers in Grades 1-3 than less active children. We also found a direct relationship between physically active school transportation, which was mainly walking and cycling, and reading skills in boys. These findings suggest that particularly physical activity within a school day benefits academic achievement and that physical activity benefit academic achievement more in boys than in girls 6-8 years of age.

Medical Research: Were any of the findings unexpected?• Answer: Yes, there were remarkable gender-differences in the associations of physical activity

and academic achievement. Whereas boys with more phyiscal activity had a better academic achievement, we found inverse associations of physical activity with reading and arithmetic skills in girls. Nevertheless, these unexpected findings were partly explained by body adiposity. We also found that parental education modified these association in girls. Among girls of highly educated parents, physical activity was directly related to academic achievement whereas among girls of less educated parents girls with higher levels of physical activity had a poorer academic achievement than less active girls. Thus, we concluded that physical activity by itself would not decrease academic achievement in girls.

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Physical Activity During School Improves Academic Achievement, Especially For BoysMedicalResearch.com Interview with:Eero Haapala, MSc in Exercise Medicine, BASc PhD studentUniversity of Eastern Finland,School of Medicine

Institute of Biomedicine, PhysiologyKuopio, Finland

• Medical Research: What should clinicians and patients take away from your report?

Answer: Clinicians and patients should acknowledge the importance of physical activity on children´s overall development, including academic development. Furthermore, both clinicians and patients should be aware of academic benefits of physically active trasnportation as well as including physically active breaks within a school day.

• Medical Research: What recommendations do you have for future research as a result of this study?

• Answer: Further research is warranted regarding the factors moderating and mediating the associations between physical activity and academic achievement. More studies using observational longitudinal and intervention designs are also needed to reveal possible causal relationships and mechanisms.

• Citation:• Associations of Physical Activity and Sedentary Behavior with Academic Skills – A Follow-Up

Study among Primary School ChildrenLink to the article: http://dx.plos.org/10.1371/journal.pone.0107031

•

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Diabetes: Patients Demonstrate Negative and Positive Coping MechanismsMedicalResearch.com: Interview with:Dr. Heather Stuckey D.EdDepartment of MedicinePennsylvania State University College of Medicine, Hershey, PA

• MedicalResearch: What are the main findings of this study?• Dr. Stuckey: The main findings were that people with diabetes had both negative psychosocial

and positive (adaptive) ways of coping with diabetes.Negative themes included: 1) Anxiety/fear, worry about hypoglycemia and complications of diabetes, depression and negative moods/hopelessness and 2) Discrimination at work and public misunderstanding about diabetes.Two psychosocial themes demonstrated adaptive ways of coping with diabetes: 1) Having a positive outlook and sense of resilience in the midst of having diabetes and 2) Receiving psychosocial support through caring and compassionate family, friends, healthcare professionals and other people with diabetes.

• Most diabetes social sciences research focuses on only the negative aspects of having diabetes. Although this paper discussed negative aspects, it also focused on the adaptive, or positive, ways in which people with diabetes viewed their disease. “We found that although these negative experiences with diabetes exist, people also held on to the positive aspects. Some said diabetes made their lives a little richer because they ate healthier foods, or they were able to connect with their family more to overcome challenges. It gave them a better appreciation of what they have. The discrimination at work and from society was a finding that was unexpected, but was evident throughout both the quantitative and qualitative data.

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Diabetes: Patients Demonstrate Negative and Positive Coping MechanismsMedicalResearch.com: Interview with:Dr. Heather Stuckey D.EdDepartment of MedicinePennsylvania State University College of Medicine, Hershey, PA

•MedicalResearch: What should patients and clinicians take away from the report?

• Dr. Stuckey: Clinicians and patients can take away the importance of letting the provider know what the patient needs. Our advice is to ask them outright, “Is there anything I can do for you about your diabetes care today, or until the next time I see you?” People with diabetes should have the courage to tell the health care provider what he/she needs to improve their diabetes care, including non-medical support. Family and friends can also educate themselves about the disease by visiting the websites of the American Diabetes Association and the International Diabetes Federation, and by attending doctors’ visits.

• MedicalResearch: What future research do you recommend as a result of this study?• Dr. Stuckey: Recommendations for future research are to investigate discrimination in diabetes

specifically. In a subsequent paper we hope to merge qualitative and quantitative DAWN2 data on this topic with an analysis of the policies of the different countries. Other research could include an expansion of the ‘turning points’ data or exploration of the factors that promote positive attitudes and resilience in people with diabetes.

• Citation:Personal Accounts of the Negative and Adaptive Psychosocial Experiences of People With Diabetes in the Second Diabetes Attitudes, Wishes and Needs (DAWN2) Study

Stuckey HL1, Mullan-Jensen CB2, Reach G3, Kovacs Burns K4, Piana N5, Vallis M6, Wens J7, Willaing I8

, Skovlund SE2, Peyrot M9.Diabetes Care. 2014 Sep;37(9):2466-74. doi: 10.2337/dc13-2536. Epub 2014 Jun 27.

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Stigma Hampers Patients From Seeking Mental Health CareMedicalResearch.com Interview with:Patrick Corrigan Psy.D.Distinguished Professor of Psychology Illinois Institute of TechnologyPI: National Consortium on Stigma and Empowerment

• Medical Research: What are the main findings of this review?• Dr. Corrigan: People with serious mental illness often do not seek out services, or drop out

early, when in need. Stigma is a major reason for why this happens. Stigma refers to the stereotypes about a group that undermine status and lead to discrimination. Discrimination refers to the behaviors that block the opportunities of group members. Some employers do not hire people with mental illness, some landlords do not rent to them, and some primary care practitioners offer a substandard of care. Stereotypes and discrimination undermine engagement in mental health services in three ways (Corrigan, 2005):

• Label Avoidance: In order to escape the pernicious effects of stigma, people avoid settings where they are labeled mentally ill; for example, people coming out of a psychiatrist’s office may be perceived as “nuts.”

• Self-Stigma: Some people who internalize stereotypes suffer diminished self-esteem and self-efficacy leading to the “why try” effect. “Why should I try to get a job? Someone like me is not worthy.” “Why should I try to get mental health treatment? I am not able to benefit from it.”

• Structural Stigma: Stereotypes and discrimination become institutionalized in the laws and practices of government and business. For example, insurance coverage for mental health services was significantly below that for most other conditions.

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Stigma Hampers Patients From Seeking Mental Health CareMedicalResearch.com Interview with:Patrick Corrigan Psy.D.Distinguished Professor of Psychology Illinois Institute of TechnologyPI: National Consortium on Stigma and Empowerment

• Medical Research: Were any of the findings unexpected?• Dr. Corrigan: Public health efforts in most of the major Western governments have sought programs to

decrease the impact of stigma. Many of these have used educational programs that counter the myths of mental illness (e.g., People choose to act schizophrenic.) with the facts (Most mental illness has biological precursors. People do not choose to be mentally ill.) Research, however, has failed to show positive benefits from these programs either at the local level (showing improvements in individuals completing these programs) or at the population levels. In fact, population studies from the U.S., Canada, the EU and Australia show the stigma of mental illness worsening even though people seem to know more about symptoms and treatment (Schomerus et al., 2012).

• Contact with people with mental illness yields more effective benefits. Contact represents programs where the public interact with people with mental illness who tell their stories of recovery. A recent meta-analysis (Corrigan et al., 2012) shows the effects of contact are significantly greater than those of educationand endure over time (Corrigan et al., 2014).

• Medical Research: What should clinicians and patients take away from your report?• Dr. Corrigan: A good place to start is language. Patient and clinician may be useful terms in the hospital but

person first language yield the words of choice in the world: “people with mental illness.” Clinicians diminish stigma by being aware of their language and the stereotypes they endorse about mental illness. However, clinicians mostly have back-seat roles in stigma change. Stigma is an issue of injustice which is only erased through the power of the stigmatized. Advocates say, “Nothing about us without us.” Advocacy groups run by people with mental illness have grown in the past 15 years to tackle this problem. Support of these programs is essential for tearing down stigma. The U.S. Substance Abuse and Mental Health Services Administration (SAMHSA) recognizes these efforts and is a fundamental booster of programs like these.

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Stigma Hampers Patients From Seeking Mental Health CareMedicalResearch.com Interview with:Patrick Corrigan Psy.D.Distinguished Professor of Psychology Illinois Institute of TechnologyPI: National Consortium on Stigma and Empowerment

• Medical Research: What recommendations do you have for future research as a result of this study?• Dr. Corrigan: The challenge is to help contact programs go big time by determining which strategies help people

with mental illness “come out” to undermine stigma (Corrigan & Kosyluk, 2013). SAMHSA has taken on this priority by partnering with the National Research Council of the National Academies of Science to set a plan for moving forward. The goal for scientists is to identify measures and methods to document the effects of these strategies.

• References: • Corrigan, P.W. (Ed.) (2005). On the stigma of mental illness: Implications for research

and social change. (pp. 343). Washington DC: American Psychological Association• Corrigan, P.W., Druss, B.G. & Perlick, D.A. (2014). The impact of mental illness stigma on

seeking and participating in mental health care. Psychological Science in the Public Interest, 15, 37-30.• Corrigan, P.W. & Kosyluk, K.A. (2013). Erasing the stigma: where science meets advocacy.

Basic and Applied Social Psychology, 35, 131-140.• Corrigan, P.W., Morris, S.B., Michaels, P.J., Rafacz, J.D., Rusch, N. (2012). Challenging the public stigma of mental

illness: a meta-analysis of outcome studies. Psychiatric Services, 63, 963-973.• Schomerus, G., Schwahn C., Holzinger, A., Corrigan, P.W., Grabe, H.J., Carta, M.G. &

Angermeyer, M.C. (2012). Evolution of public attitudes about mental illness: a systematic review and meta-analysis. Acta Psychiatrica Scandinavica, 125, 440-452.

• Citation:• The Impact of Mental Illness Stigma on Seeking and Participating in Mental Health Care• Patrick W. Corrigan, Benjamin G. Druss, and Deborah A. Perlick

Psychological Science in the Public Interest October 2014 15: 37-70, doi:10.1177/1529100614531398

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VA Effectively Uses Telemedicine To Screen for Diabetic Eye DiseaseMedicalResearch.com Interview with: Mary G. Lynch, MDProfessor of OphthalmologyAtlanta Veterans Affairs Medical Center Decatur, Georgia.

Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia

• Medical Research: What are the main findings of the study?• Dr. Lynch: • Since 2006, the VA has been systematically using teleretinal screening of patients with diabetes to screen for retinopathy in the Primary

Care Clinics. Under this program, 90% of veterans with diabetes are evaluated on a regular basis. A number of patients who are screened have findings that warrant a face-to-face ophthalmic exam. No information exists on the effect of such a program on medical center resources.

• 1,935 patients underwent teleretinal screening through the Atlanta VA over a 6 month period. We reviewed the charts of the 465 (24%) of the patients who were referred for a face to face exam in the Eye Clinic.

• Data was collected for these patients to determine the reasons for referral, the accuracy of the teleretinal interpretation, the resources needed in the Eye Clinic of the Medical Center to evaluate and care for the referred patients over a two year period and possible barriers to patient care.

• Of the 465 patients referred for an exam, 260 (55.9%) actually came in for an exam. Community notes were available for an additional 66 patients. Information was available for 326 (70.1%) of the referred patients.

• The most common referring diagnoses were nonmacular diabetic retinopathy (43.2% of referrals), nerve related issues (30.8%), lens or media opacity (19.1%), age-related macular degeneration (12.9%) and diabetic macular edema (5.6%).

• 16.9% of the referred patients had 2 or more concurrent problems that put them at high risk for visual loss.• The percentage agreement between teleretinal screening and the ophthalmic exam was high: 90.4%. Overall sensitivity was 73.6%. The

detection of diabetic macular edema had the lowest sensitivity.• A visually significant condition was detected for the first time through teleretinal screening for 142 of the patients examined (43.6%).• The resource burden to care for referred patients was substantial.• 36% of patients required 3 or more visits over the ensuing 2 year period.• The treatment of diabetic macular edema had the highest resource use involving on average 5 clinic visits, 6 diagnostic procedures and

2 surgical procedures• The most common non-refractive diagnostic procedures were visual fields and optical coherence tomography.• The average cost to care for the referred patients (in Medicare dollars) in work RVUs alone was approximately $1,000 per patient. The

cost to care for a patient with diabetic macular edema was $2673.36.

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VA Effectively Uses Telemedicine To Screen for Diabetic Eye DiseaseMedicalResearch.com Interview with: Mary G. Lynch, MDProfessor of OphthalmologyAtlanta Veterans Affairs Medical Center Decatur, Georgia.

Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia

• Medical Research: Were any of the findings unexpected?• Dr. Lynch: Yes. 21% of patients failed to show for their scheduled eye clinic appointment. Age and travel distance

did not contribute to the no show rate. The patient’s historical no show rate was actually the best predictor; a patient with a historical no show rate of 26% had a 58% chance of failing to show for the Eye appointment. Predicting and managing no shows is a critical factor in any large healthcare system.

• Medical Research: What should clinicians and patients take away from your report?• Dr. Lynch: Teleretinal imaging in the primary care setting is a highly effective tool to screen patients for eye

disease. The VA and other healthcare systems are going to have to look at innovative ways of bringing basic eye care services to the community in a cost effective way. Telemedicine is going to be one of those methods and eventually it will be expanded beyond screening for diabetes.

• Medical Research: What recommendations do you have for future research as a result of this study?• Dr. Lynch: The study generated ratios that could be used to predict the number of appointment slots, diagnostic

tests and surgical procedures that would be needed to care for patients who are referred from a teleretinal screening program. For example, placing a camera in a primary care clinic that includes 5,000 patients with diabetes may generate approximately 1,200 referrals to an eye clinic. Assuming that all patients are evaluated with an ophthalmic exam, these referrals might require 544 visual fields, 516 OCTs and 143 cataract extractions over the next 2 years. This is important information for clinic managers to have as they adjust personnel, equipment and space in anticipation of a telemedicine expansion.

• Citation:• Effect of a Teleretinal Screening Program on Eye Care Use and Resources

Joel E. Chasan, MD; Bill Delaune, PhD; April Y. Maa, MD; Mary G. Lynch, MDJAMA Ophthalmol. 2014; 132(9):1045-1051. doi: 10.1001/jamaophthalmol.2014.1051

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Rheumatoid Arthritis: Mycobacterial Infections Relatively CommonMedicalResearch.com Interview with:Theodore Marras, MD, FRCPC, M.Sc.Assistant Professor, University of Toronto Respirologist, Toronto Western HospitalUniversity Health

Network Toronto, ON, Canada

• Medical Research: What are the main findings of the study?• Dr. Marras: Mycobacterial infections (TB and nontuberculous mycobacteria (NTM)) are more common in patients with

rheumatoid arthritis (RA). Nontuberculous mycobacteria disease was far more common than TB disease in RA patients in Ontario, Canada. Nontuberculous mycobacteria disease was also associated with increased age, COPD, asthma, and GERD. The presence of nontuberculous mycobacteria disease was associated with increased mortality.

Medical Research: Were any of the findings unexpected?• Dr. Marras: The increased mortality associated with nontuberculous mycobacteria disease in rheumatoid arthritis

patients should be carefully considered by clinicians who care for these patients.• The association between nontuberculous mycobacteria and asthma is novel, and should be explored further.• Medical Research: What should clinicians and patients take away from your report?• Dr. Marras: In the presence of unexplained chronic or recurrent respiratory complaints, patients with

rheumatoid arthritis should be investigated for mycobacterial disease. In light of the increase in mortality, the clinical situation of rheumatoid arthritis patients with nontuberculous mycobacteria should be carefully considered.

• Medical Research: What recommendations do you have for future research as a result of this study?• Dr. Marras:• The associations between rheumatoid arthritis medications and mycobacterial diseases should be investigated.• Associations between asthma and nontuberculous mycobacteria should be studied in other patient cohorts.• Citation:• Risk of mycobacterial infections associated with rheumatoid arthritis in ontario, canada

Brode SK, Jamieson FB, Ng R, et al.Chest 2014;146(3):563-572.doi:10.1378/chest.13-2058.

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Does Melatonin Prevent Delirium In Elderly Surgery Patients?MedicalResearch.com Interview with: Annemarieke de JongheAcademic Medical Center University of Amsterdam Departement of Internal Medicine Section of Geriatric Medicine F4-218

Amsterdam, The Netherlands

• Medical Research: What are the main findings of the study?

Dr. de Jonghe: We investigated the preventive properties of melatonin versus placebo in a prospective cohort of elderly hip fracture patients (n=378). We found that 3mg melatonin vs placebo, given for 5 days from the day of admission, did not influence the incidence of delirium. However, in a posthoc analysis we found that more patients in the placebo group more often had a longer lasting delirium.

•Medical Research: Were any of the findings unexpected?

• Dr. de Jonghe: We started this study as we believed melatonin could be beneficial in the prevention of delirium. Clinical evidence linking melatonin to delirium was limited. Based on case reports of beneficial effects of melatonin in sundowning in dementia and on the observational evidence that a disrupted sleep wake cycle is present in delirium, we started this multicenter study. During the course of our study, 2 other studies (Sultan, Al-Aama) were published which showed very positive effects for both prevention and treatment of delirium with melatonin. We also noticed that incidence rates of delirium were lower than 5 years earlier in our hospital. So, by the time we started to analyse our data we were a bit surprised over the outcome. As we describe in our paper, there are different explanations possible for the lack of effect in our population.

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Does Melatonin Prevent Delirium In Elderly Surgery Patients?MedicalResearch.com Interview with: Annemarieke de JongheAcademic Medical Center University of Amsterdam Departement of Internal Medicine Section of Geriatric Medicine F4-218

Amsterdam, The Netherlands

• Medical Research: What should clinicians and patients take away from your report?

Dr. de Jonghe: Melatonin is a promising product for the prevention of delirium which needs further investigation. One may consider using it, especially because of the absence of other safe and effective medical interventions.

• Medical Research: What recommendations do you have for future research as a result of this study?• Dr. de Jonghe: More studies are warranted to explain the differences between the findings of the

three RCTs that have now been performed comparing melatonin vs placebo as a prophylaxis in delirium. These studies should also determine specific patient groups that could benefit most from a prophylaxis with melatonin. It is also important to determine the dosage of melatonin.

• Furthermore, we would recommend the inclusion of patients with cognitive impairment in delirium research. Most studies on delirium exclude patients with dementia whereas they are the most at risk for delirium and also delirium had negative impact on their cognitive function afterwards. In our study we included a real live population with a high mean age, 84 years and > 60% experienced cognitive problems.

• Citation:• Effect of melatonin on incidence of delirium among patients with hip fracture: a multicentre, double-b

lind randomized controlled trial

Annemarieke de Jonghe, Barbara C. van Munster, J. Carel Goslings, Peter Kloen, Carolien van Rees, Reinder Wolvius, Romuald van Velde, Marcel Levi, Rob J. de Haan, Sophia E. de Rooij, and on behalf of the Amsterdam Delirium Study Group

• CMAJ cmaj.140495; published ahead of print September 2, 2014, doi:10.1503/cmaj.140495Read the rest of the interview on MedicalResearch.comContent Not Intended as Specific Medical Advice

Global Variations in microRNAs Linked To Cancer DisparitiesMedicalResearch.com Interview with:Renata Afi Rawlings-Goss, Ph.D.Postdoctoral FellowTishkoff Lab, University of Pennsylvania

• Medical Research: What are the main findings of the study?• Dr. Rawlings-Goss: We found genetic mutations in key gene regulators that have been linked

to ethnic disparities in cancer. Our investigation identified more than 30 previously undescribed mutations in important regulatory molecules called microRNAs. Individual microRNA molecules can regulate large numbers of genes in some cases over 6000 genes at once. Therefore, mutations in these genes have been linked to numerous diseases. By and large, however, microRNA mutations have not been studied in people of diverse ethnic backgrounds.

Medical Research: Were any of the findings unexpected?• Dr. Rawlings-Goss: In our study, we looked at 69 individuals from 14 worldwide populations

from Africa, Europe and Asia. We were surprised to find that some mutations are more common in different parts of the world and these mutation are predominately associated with cancer.

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Global Variations in microRNAs Linked To Cancer DisparitiesMedicalResearch.com Interview with:Renata Afi Rawlings-Goss, Ph.D.Postdoctoral FellowTishkoff Lab, University of Pennsylvania

• Medical Research: What should clinicians and patients take away from your report?• Dr. Rawlings-Goss: MicroRNA disease discoveries have been made in primarily in people of

European or Asian ancestry, resulting in an incomplete picture of global genetic variation in disease vulnerability. For example, one variant has been associated with breast cancer mortality and our team’s discovery could help explain why, once diagnosed with breast cancer, women with African ancestry are more likely to die from the disease than other women, even when the cancer is less frequent. Knowing about these differences could inform efforts to develop diagnostic tests or even treatments for diseases like cancer.

• Medical Research: What recommendations do you have for future research as a result of this study?

• Dr. Rawlings-Goss: Further investigation is needed in order to understand the patterns of variation at microRNA and their role in human adaptation to disease. Particularly, as genetic testing is being considered as the next frontier of cancer screenings, clinicians should keep in mind the effect of ethnicity and population history on disease outcomes.

• Citation:• Global population-specific variation in miRNA associated with cancer risk and clinical biomarkers• Rawlings-Goss RA, Campbell MC, Tishkoff SA.

BMC Med Genomics. 2014 Aug 28;7:53. doi: 10.1186/1755-8794-7-53.• PMID: 2516989 [PubMed - in process]

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Melanoma Cells Alter Their Environment To Promote ProgessionMedicalResearch.com Interview with:Dr. Constance BrinckerhoffProfessor of Medicine Professor of BiochemistryGeisel School of Medicine at Dartmouth

• MedicalResearch.com Interview with:Dr. Constance BrinckerhoffProfessor of MedicineProfessor of BiochemistryGeisel School of Medicine at Dartmouth

•Medical Research: What are the main findings of the study?

• Dr. Brinckerhoff: The genetic mutation BRAFV600E , frequently found in metastatic melanoma, not only secretes a protein that promotes the growth of melanoma tumor cells, but can also modify the network of normal cells around the tumor to support the disease’s progression. Targeting this mutation with Vemurafenib reduces this interaction, and suggests possible new treatment options for melanoma therapy.

Medical Research: What should clinicians and patients take away from your report?• Dr. Brinckerhoff: This work supports the importance of the tumor cells “talking” with the

normal cells present in the tumor microenvironment. Targeting the tumor cells with specific therapy to reduce the secreted proteins can reduce the aggressive behavior of the tumor and inhibit disease progression.

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Melanoma Cells Alter Their Environment To Promote ProgessionMedicalResearch.com Interview with:Dr. Constance BrinckerhoffProfessor of Medicine Professor of BiochemistryGeisel School of Medicine at Dartmouth

• Medical Research: What recommendations do you have for future research as a result of this study?

• Dr. Brinckerhoff: Given that the data show that Vemurafenib is able to reduce the expression of several proteins that are essential for activating the tumor microenvironment (TME), a next step would be to ask whether Vemurafenib normalizes the tumor microenvironment , or keeps it from becoming activated, and if so, does it create a window of time where we could target the tumor microenvironment , normalize it, and enhance the patient’s therapeutic response.

• Citation:• BRAFV600E melanoma cells secrete factors that activate stromal fibroblasts and enhance tum

ourigenicity

C A Whipple and C E BrinckerhoffBritish Journal of Cancer , (12 August 2014) | doi:10.1038/bjc.2014.452

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Acute Lymphoblastic Leukemia: Tyrosine Kinase Inhibitors Target Resistant VariantSt. Jude Children’s Research HospitalMedicalResearch.com Interview with:Dr. Charles Mullighan, M.D., MBBS(Hons), MSc Department of Pathology St

. Jude Children’s Research HospitalMemphis, TN 38105

• MedicalResearch: What are the most important take home points from this study for practicing clinicians and their patients?

• Dr. Mullighan: Acute lymphoblastic leukemia (ALL) remains a leading cause of cancer death in children, and the prognosis worsens with increasing age. Current therapies are inadequate for many patients. This study has defined the genetic basis of a recently described subtype of Acute lymphoblastic leukemia called Ph-like ALL. We show that the prevalence increases with rising age, and that in both children and young adults the disease is driven by a diverse range of genetic changes that activate kinase signaling, which fuels the growth of leukemia cells. Ph-like Acute lymphoblastic leukemia currently has a poor outcome. The activated kinases may be inhibited by currently approved tyrosine kinase inhibitors (TKIs). We have shown efficacy of these inhibitors in cell lines and experimental models, and in a series of patients with Ph-like Acute lymphoblastic leukemia treated with TKIs.

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Acute Lymphoblastic Leukemia: Tyrosine Kinase Inhibitors Target Resistant VariantSt. Jude Children’s Research HospitalMedicalResearch.com Interview with:Dr. Charles Mullighan, M.D., MBBS(Hons), MSc Department of Pathology St

. Jude Children’s Research HospitalMemphis, TN 38105

• MedicalResearch: What is the clinical significance of the study and how can the information from the study be used in new approaches to patient care?

• Dr. Mullighan: The study is clinically significant as Ph-like ALL currently has a poor outcome and new treatments are needed, and we have shown efficacy of TKIs in cases of refractory Ph-like ALL.

• There are two key areas of clinical relevance.• The first is diagnosis. Ph-like ALL is characterized by a range of genetic alterations activating many

tyrosine kinases. Despite this complexity, accurate diagnosis of Ph-like Acute lymphoblastic leukemia may be achieved by screening approaches followed by genetic testing, or ultimately, genome sequencing at diagnosis.

• Secondly, this information is important not only to identify Ph-like ALL, but to direct patients to the appropriate TKI. In addition, while our data strongly suggest that TKI therapy will improve the success of ALL therapy, this requires formal testing in clinical trials. Such trials are under development in children and adults.

• Finally, our results have shown that the frequency of Ph-like Acute lymphoblastic leukemia rises with age, which is likely to in part explain the poor outcome of Acute lymphoblastic leukemia with increasing age. However, there is limited information about the genetics of Acute lymphoblastic leukemia in older adults, for whom treatment outcomes are poor. Such studies are needed and ongoing. In the near future, we envisage that all patients will be tested for the presence of Ph-like Acute lymphoblastic leukemia to enable the most appropriate treatment to be delivered.

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Acute Lymphoblastic Leukemia: Tyrosine Kinase Inhibitors Target Resistant VariantSt. Jude Children’s Research HospitalMedicalResearch.com Interview with:Dr. Charles Mullighan, M.D., MBBS(Hons), MSc Department of Pathology St

. Jude Children’s Research HospitalMemphis, TN 38105

• MedicalResearch: What recommendations do you have for future research as a result of this study?

• Dr. Mullighan: A key priority is testing the efficacy of TKAs in prospective trials of Ph-like ALL and adults and children. Such trials will incorporate genomic approaches to identify Ph-like ALL and direct patients to the appropriate drug. A second important area of research is detailed genomic characterization of Acute lymphoblastic leukemia in adults. This includes adults age 40 and older, who experience poor outcomes of treatment. It is important to define the prevalence and nature of Ph-like Acute lymphoblastic leukemia in this group, and also to continue to examine the genetic basis of ALL patients lacking known driver lesions.

• MedicalResearch: Do you have any additional comments?• Dr. Mullighan: The findings of this study were only possible with extensive collaboration

between childhood and adult cooperative groups, and the genomic sequencing capabilities of the St Jude – Washington University Pediatric Cancer Genome Project and the NCI TARGET initiative.

• Citation:• Targetable Kinase-Activating Lesions in Ph-like Acute Lymphoblastic Leukemia• Kathryn G. Roberts, Ph.D., Yongjin Li, Ph.D., Debbie Payne-Turner, B.S., Richard C. Harvey, Ph.

D., Yung-Li Yang, M.D., Deqing Pei, M.S., Kelly McCastlain, B.S., Li Ding, Ph.D., Charles Lu, Ph.D., Guangchun Song, M.S., Jing Ma, Ph.D., Jared Becksfort, M.S., Michael Rusch, B.A., Shann-Ching Chen, Ph.D., John Easton, Ph.D., Jinjun Cheng, M.D., Kristy Boggs, Ph.D., Natalia Santiago-Morales, B.S., Ilaria Iacobucci, Ph.D., Robert S. Fulton, Ph.D., Ji Wen, Ph.D., Marcus Valentine, B.A., Cheng Cheng, Ph.D., Steven W. Paugh, Ph.D., Meenakshi Devidas, Ph.D., I-Ming Chen, D.V.M., Shalini Reshmi, Ph.D., Amy Smith, B.S., Erin Hedlund, Ph.D., Pankaj Gupta, M.S., Panduka Nagahawatte, M.S., Gang Wu, Ph.D., Xiang Chen, Ph.D., Donald Yergeau, Ph.D., Bhavin Vadodaria, B.A., Heather Mulder, B.S., Naomi J. Winick, M.D., Eric C. Larsen, M.D., William L. Carroll, M.D., Nyla A. Heerema, Ph.D., Andrew J. Carroll, Ph.D., Guy Grayson, M.D., Sarah K. Tasian, M.D., Andrew S. Moore, M.D., Frank Keller, M.D., Melissa Frei-Jones, M.D., James A. Whitlock, M.D., Elizabeth A. Raetz, M.D., Deborah L. White, Ph.D., Timothy P. Hughes, M.D., Jaime M. Guidry Auvil, Ph.D., Malcolm A. Smith, M.D., Guido Marcucci, M.D., Clara D. Bloomfield, M.D., Krzysztof Mrózek, M.D., Jessica Kohlschmidt, Ph.D., Wendy Stock, M.D., Steven M. Kornblau, M.D., Marina Konopleva, M.D., Elisabeth Paietta, Ph.D., Ching-Hon Pui, M.D., Sima Jeha, M.D., Mary V. Relling, Pharm.D., William E. Evans, Pharm.D., Daniela S. Gerhard, Ph.D., Julie M. Gastier-Foster, Ph.D., Elaine Mardis, Ph.D., Richard K. Wilson, Ph.D., Mignon L. Loh, M.D., James R. Downing, M.D., Stephen P. Hunger, M.D., Cheryl L. Willman, M.D., Jinghui Zhang, Ph.D., and Charles G. Mullighan, M.D.

• N Engl J Med 2014; 371:1005-1015September 11, 2014DOI: 10.1056/NEJMoa1403088

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Autism Spectrum Disorder: Gene That Removes Defective Proteins May Be AlteredMedicalResearch.com: Interview with:Anilkumar Pillai, Ph.D.Associate Professor, Department of PsychiatryMedical College of Georgia, Georgia Regents University

• Medical Research: What are the main findings of the study?• Dr. Pillai: GABA receptors are responsible for binding GABA, the main inhibitory neurotransmitter

in the human brain. Recent studies have indicated a potential role for alterations in GABAA receptors in the pathophysiology of Autism Spectrum Disorder (ASD). However, the mechanism of regulation of GABAA receptor in Autism Spectrum Disorder is not known. Our study shows that GABAA levels are altered at the protein level, but not at the mRNA level in the middle frontal gyrus of Autism Spectrum Disorder subjects. Our study also finds that Synoviolin 1 (SYVN1) plays a critical role as an E3 ligase in GABAAα1 degradation. SYVN1 has been previously determined to function as a removal system of inappropriately folded or unfolded proteins from the ER to the cytosol of the cell for degradation. Our study ultimately provides a mechanism for GABAAα1 deficits in Autism Spectrum Disorder subjects and possible new treatment strategies to reverse deficits seen in ASD and other related disorders.

Medical Research: Were any of the findings unexpected?• Dr. Pillai: Our findings were not unexpected as some studies have previously indicated alterations

in GABAA signaling in Autism Spectrum Disorder. However, our studies are novel in that they provide a possible mechanism for these deficits. Our study provides a link between GABAergic deficits and ERAD-mediated proteasomal degradation, both of which have been previously implicated in Autism Spectrum Disorder.

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Autism Spectrum Disorder: Gene That Removes Defective Proteins May Be AlteredMedicalResearch.com: Interview with:Anilkumar Pillai, Ph.D.Associate Professor, Department of PsychiatryMedical College of Georgia, Georgia Regents University

• Medical Research: What should clinicians and patients take away from your report?• Dr. Pillai: Autism is a widespread disorder affecting 1 in 68 children in America and has a 1% prevalence worldwide.

This is a disorder that can be devastating to children and their families, but the cause of the disorder remains elusive. This study shows a new finding in inhibitory signaling in the brain, allowing for a better understanding of what is going on at the molecular level in the brains of individuals with Autism Spectrum Disorder. This study could have clinical implications in that use of a proteasome inhibitor or targeting specific elements of the ubiquitin proteasome system may allow for new treatment strategies in the deficits seen in Autism Spectrum Disorder and related disorders.

• • Medical Research: What recommendations do you have for future research as a result of this study?• Dr. Pillai: The findings of this study may have functional implications in the pathophysiology of Autism Spectrum

Disorder, but these findings need to be further tested in an appropriate animal model for ASD. Other literature in the field shows abnormalities in GABAergic function in other brain regions in patients with Autism Spectrum Disorder, so studying other brain regions from postmortem tissues of ASD subjects would be necessary to determine if our findings can provide a mechanism for some of these deficits as well.

• • Citation:• Ubiquitin-proteasome dependent degradation of GABAA

α1 in autism spectrum disorder Amanda Crider,Chirayu D Pandya,Diya Peter,Anthony O Ahmed,Anilkumar PillaiMolecular Autism September 2014, 5:45,Date: 01 Sep 2014

• Views vs UniqueViews2014-08-182014-08-232014-08-282014-09-022014-09-07

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