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Drugs with relatively short elimination half-lives typ-ically require more-frequent daily dosing to avoid largepeak-to-trough concentration variation. Conversely, drugswith long elimination half-lives generally require less-frequent dosing because plasma concentration variationsbetween doses are smaller.

The pharmacokinetic comparison of memantine 20mgone daily and 10 mg twice daily demonstrates that peak-to-

trough fluctuations with once-daily dosing regimens is sim-ilar to twice-daily dosing. Therefore, it is expected that theefficacy and adverse effect profile would be comparablebetween these dosing schemes. Recent clinical studies inwhich the safety and tolerability of once-daily dosing hasbeen shown to be comparable with that of twice daily dos-ing support the results of the analysis.47 Recent clinicaltrials also suggest that an extended-release once-daily for-mulation is well tolerated and effective for the treatment ofmoderate to severe Alzheimers disease.810 Based on thecurrent pharmacokinetic analysis, a single conventional-release 20-mg dose (two 10-mg tablets) may offer the samedaily convenience as a single extended-release formulationand with similar tolerability as 10 mg taken twice daily.

Irving H. Gomolin, MDCM, AGSFDivision of Geriatric Medicine and Clinical Pharmacology

Winthrop University HospitalMineola, NY

Department of MedicineStony Brook University

Stony Brook, NY

Candace Smith, PharmDDepartment of Clinical Pharmacy Practice

St. Johns University College of Pharmacy & AlliedHealth Professions

Queens, NY

Thomas M. Jeitner, PhDApplied Bench Core

Winthrop University HospitalMineola, NY

Department of MedicineStony Brook University

Stony Brook, NY

ACKNOWLEDGMENTS

Conflict of Interest: Dr. Jeitner is supported by the T. Sant-

mann Award. There are no or related paper presentations.Author Contributions: Gomolin: conception, interpre-tation of data, preparation of manuscript. Smith: pharma-cokinetic analysis, interpretation of data, preparation ofmanuscript. Jeitner: critical review of data and analysis,preparation of manuscript

Sponsors Role: No sponsors were involved in theconduct of this study.

REFERENCES

1. Namenda (memantine hydrochloride) current U.S. prescribing information.

Forest Pharmaceuticals; 2007.

2. Periclou A, Ventura D, Rao N et al. Pharmacokinetic study of memantine in

healthy and renally impaired subjects.Clin Pharmacol Ther2006;79:134143.

3. Liu MY, Sheng-Nan M, Hui-Zhe W et al. Pharmacokinetics of single-dose and

multiple-dose memantine in healthy Chinese volunteers using an analytic

method of liquid chromatography-tandem mass spectrometry. Clin Therapeut

2008;30:641653.

4. Forest laboratories Clinical Trial Registry. A long term extension study eval-

uating the safety and tolerability of four memantine dosing regimens in pa-

tientswithmoderateto severedementia of theAlzheimers type-PhasesA andB

[on-line].Availableat http://www.forestclinicaltrials.com/CTR/CTRController/

CTRViewPdf?_file_id=scsr/SCSR_MEM-MD-03AB_final.pdf Accessed May

11, 2010.

5. Forest laboratories Clinical Trial Registry. A long-term extension study eval-uating the safety and tolerability of BID and QD administration of memantine

in patients with mild to moderate dementia of the Alzheimers type-Phases A

and B [on-line]. Available at http://www.forestclinicaltrials.com/CTR/CTR

Controller/CTRViewPdf?_file_id=scsr/SCSR_MEM-MD-11AB_final.pdf Ac-

cessed May 11, 2010.

6. Jones RW, Bayer A, Inglis F et al. Safety and tolerability of once-daily versus

twice-daily memantine: A randomized, double-blind study in moderate to se-

vere Alzheimers disease. Int J Geriatr Psychiatry 2007;22:258262.

7. Ott BR, Blake LM, Kagan E et al. Open label, multicenter, 28-week extension

study of the safety and tolerability of memantine in patients with mild to

moderate Alzheimers disease. J Neurol 2007;254:351358.

8. Forest laboratories Clinical Trial Registry. A randomized, double-blind, pla-

cebo-controlled evaluation of the safety and efficacy of memantine in patients

with moderate-to-severe dementia of the Alzheimers type [on-line]. Available

at http://www.forestclinicaltrials.com/CTR/CTRController/CTRViewPdf?_

file_id=scsr/SCSR_MEM-MD-50_final.pdf Accessed May 11, 2010.

9. Forest laboratories Clinical Trial Registry. An open-label evaluation of thesafety of memantine in patients with moderate-to-severe dementia of the Alz-

heimers type [on-line]. Available at http://www.forestclinicaltrials.com/CTR/

CTRController/CTRViewPdf?_file_id=scsr/SCSR_MEM-MD-51_final.pdf

Accessed May 11, 2010.

10. Forest laboratories Clinical Trial Registry. An open-label extension study

evaluating the safety and tolerability of memantine in patients with moderate

to severe dementia of the Alzheimers type [on-line]. Available at http://www.

forestclinicaltrials.com/CTR/CTRController/CTRViewPdf?_file_id=scsr/SCSR_

MEM-MD-54_final.pdf Accessed May 11, 2010.

LOWER MORTALITY FROM H1N1 INFLUENZA IN

OLDER ARGENTINEANS: MEN MORE AFFECTED

To the Editor: Argentina was the first nation in 2009 todeclare an H1N1 epidemic in the southern hemisphere.1,2

Up to the end of 2009 southern hemisphere winter, Argen-tina was second only to the United States in the number ofreported deaths from H1N1.2 Only one pediatric study hasreported H1N1 influenza mortality in Argentina.3

Conversely, several studies in North America andEurope have reported that the age distribution of the2009 pandemic H1N1 virus differs from the populationstraditionally at risk for seasonal influenza.46 During peakperiods of seasonal influenza, most hospitalizations occur in

toddlers and frail elderly people, but reports from thenorthern hemisphere showed that older people were atlower risk of current H1N1 infection, although they were atgreater risk of hospitalization and death once infectedby this virus.47 Consequently, H1N1 population attribut-able mortality risk did not differ significantly betweenolder and younger adults during 2009 in the northernhemisphere.46

This letter reports H1N1 mortality risk in Argentina in2009, stratified according to age group (Figure 1A). Caseswere confirmed using reverse transcription polymerasechain reaction (RT-PCR). Mortality per 100,000 inhabit-ants was 0.6 for people aged 10 to 19, 2.5 for people aged

50 to 59, and 0.9 in people aged 60 and older. Except for

LETTERS TO THE EDITOR 1813 JAGS SEPTEMBER 2010VOL. 58, NO. 9

http://www.forestclinicaltrials.com/CTR/CTRController/CTRViewPdf?_file_id=scsr/SCSR_MEM-MD-03AB_final.pdfhttp://www.forestclinicaltrials.com/CTR/CTRController/CTRViewPdf?_file_id=scsr/SCSR_MEM-MD-03AB_final.pdfhttp://www.forestclinicaltrials.com/CTR/CTRController/CTRViewPdf?_file_id=scsr/SCSR_MEM-MD-03AB_final.pdfhttp://www.forestclinicaltrials.com/CTR/CTRController/CTRViewPdf?_file_id=scsr/SCSR_MEM-MD-11AB_final.pdfhttp://www.forestclinicaltrials.com/CTR/CTRController/CTRViewPdf?_file_id=scsr/SCSR_MEM-MD-11AB_final.pdfhttp://www.forestclinicaltrials.com/CTR/CTRController/CTRViewPdf?_file_id=scsr/SCSR_MEM-MD-11AB_final.pdfhttp://www.forestclinicaltrials.com/CTR/CTRController/CTRViewPdf?_file_id=scsr/SCSR_MEM-MD-50_final.pdfhttp://www.forestclinicaltrials.com/CTR/CTRController/CTRViewPdf?_file_id=scsr/SCSR_MEM-MD-50_final.pdfhttp://www.forestclinicaltrials.com/CTR/CTRController/CTRViewPdf?_file_id=scsr/SCSR_MEM-MD-51_final.pdfhttp://www.forestclinicaltrials.com/CTR/CTRController/CTRViewPdf?_file_id=scsr/SCSR_MEM-MD-51_final.pdfhttp://www.forestclinicaltrials.com/CTR/CTRController/CTRViewPdf?_file_id=scsr/SCSR_MEM-MD-51_final.pdfhttp://www.forestclinicaltrials.com/CTR/CTRController/CTRViewPdf?_file_id=scsr/SCSR_MEM-MD-54_final.pdfhttp://www.forestclinicaltrials.com/CTR/CTRController/CTRViewPdf?_file_id=scsr/SCSR_MEM-MD-54_final.pdfhttp://www.forestclinicaltrials.com/CTR/CTRController/CTRViewPdf?_file_id=scsr/SCSR_MEM-MD-54_final.pdfhttp://www.forestclinicaltrials.com/CTR/CTRController/CTRViewPdf?_file_id=scsr/SCSR_MEM-MD-54_final.pdfhttp://www.forestclinicaltrials.com/CTR/CTRController/CTRViewPdf?_file_id=scsr/SCSR_MEM-MD-54_final.pdfhttp://www.forestclinicaltrials.com/CTR/CTRController/CTRViewPdf?_file_id=scsr/SCSR_MEM-MD-54_final.pdfhttp://www.forestclinicaltrials.com/CTR/CTRController/CTRViewPdf?_file_id=scsr/SCSR_MEM-MD-51_final.pdfhttp://www.forestclinicaltrials.com/CTR/CTRController/CTRViewPdf?_file_id=scsr/SCSR_MEM-MD-51_final.pdfhttp://www.forestclinicaltrials.com/CTR/CTRController/CTRViewPdf?_file_id=scsr/SCSR_MEM-MD-51_final.pdfhttp://www.forestclinicaltrials.com/CTR/CTRController/CTRViewPdf?_file_id=scsr/SCSR_MEM-MD-50_final.pdfhttp://www.forestclinicaltrials.com/CTR/CTRController/CTRViewPdf?_file_id=scsr/SCSR_MEM-MD-50_final.pdfhttp://www.forestclinicaltrials.com/CTR/CTRController/CTRViewPdf?_file_id=scsr/SCSR_MEM-MD-11AB_final.pdfhttp://www.forestclinicaltrials.com/CTR/CTRController/CTRViewPdf?_file_id=scsr/SCSR_MEM-MD-11AB_final.pdfhttp://www.forestclinicaltrials.com/CTR/CTRController/CTRViewPdf?_file_id=scsr/SCSR_MEM-MD-11AB_final.pdfhttp://www.forestclinicaltrials.com/CTR/CTRController/CTRViewPdf?_file_id=scsr/SCSR_MEM-MD-03AB_final.pdfhttp://www.forestclinicaltrials.com/CTR/CTRController/CTRViewPdf?_file_id=scsr/SCSR_MEM-MD-03AB_final.pdfhttp://www.forestclinicaltrials.com/CTR/CTRController/CTRViewPdf?_file_id=scsr/SCSR_MEM-MD-03AB_final.pdf

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children younger than 10, the mortality rate increased withage but started to decrease in adults aged 60 and older. Themortality of people aged 60 and older was 64% lower thanin those aged 50 to 59. Possible explanations include min-imal contact by older age groups with young travelers andschool-aged children who amplify transmission during theearly stage of the epidemic.1 Alternatively, young adults aremore likely to be exposed, to exhibit fever, and to be testedfor H1N1 once infected.

Nevertheless, there is compelling evidence to suggestthat a main reason why older Argentineans had much lowermortality is due to immune cross-protection from prior ex-posure to H1N1 strains circulating worldwide from 1918(Spanish influenza) to 1957, when they were replaced byH2N2 viruses.8,9 Many of the older immigrants to Argen-tine are survivors of the Spanish influenza, and the highesttiters of cross-reactive antibodies to H1N1 are elicited inthe European population born before 1950, whereas indi-viduals born after 1950 generally have lower titers and lackthis cross-protection.10

These findings are in agreement with previous obser-vations demonstrating that the smaller number of infections

in older Americans was not simply a reflection of less testing

in this group.7 In Finland, there was an age-related differ-ence in the prevalence of neutralizing antibody titers againstthe 2009 H1N1 virusF96% in those born before 1919 andless than 5% in those born after 1950.10 This fact is con-sistent with the low frequency of the 2009 H1N1 influenzain nursing homes and the high frequency of outbreaks inschools in Argentina.2,3

Traditionally, in immunologically naive populations,

mortality follows a U-shaped curve because younger adultshave stronger immune responses.8 Therefore, the findingthat older Argentineans have a lower mortality than mid-dle-aged adults is unusual but explainable in terms of im-munological memory acquired from 1918 to 1957, whenH1N1 circulated world wide.810

Using mathematical modeling based on previous H1N1epidemics,8 the tread of increasing mortality from the age of20 to 59 in current H1N1 pandemic, and on previous sea-sonal influenza epidemics in Argentina (20072008), it canbe estimated that expected mortality in people aged 60 andolder would be 4.9 per 100,000 when the immune memoryfactor was removed from the model (Figure 1B). The actualmortality rate of 0.9 per 100.000 supports the hypothesis ofcross-protection acquired in prior exposure to H1N1strains circulating worldwide from 1918 to 1957.

Unexpectedly, mortality in older Argentinean men wastwice that in older women. The reasons for this differenceare unknown but may involve cultural factors such as olderArgentinean men leaving home to work or engaging in so-cial activities more often than women. Another possibleexplanation is the difference in life expectancies betweenthe sexes in older Argentineans (men, 72 vs women, 79).Antibodies titles against H1N1 tend to be higher in olderage groups and this 7-year gap in life expectancy betweenthe sexes might lead to a survival effect (lower levels ofimmunity in young-old groups).

In conclusion, lower mortality was found in older Ar-gentineans in the current H1N1 pandemic, which may havepotential implications for future health policies, such aslower priority for immunization of nonfrail older peopleagainst H1N1. Only the final effect of the H1N1 epidemicupon mortality was analyzed, and reliable data on generalincidence and hospitalization rates according to age groupare not available from official Argentinean sources. Eventhough H1N1 geriatric mortality was low in Argentina, it ispossible that, once infected, older Argentineans have higherrisk of hospitalization and death than younger adults.46 Inthis sense, elderly people would have a lower priority foranti-H1N1 immunization campaigns but a greater need for

oseltamivir indication and hospitalization than nonpreg-nant younger adults.

Matheus Roriz-Cruz, MD, PhDIdiane Rosset, GNP, MPH, PhD

Collaborative Study Group on AgingDepartment of Internal Medicine and Faculty of Nursing

Federal University of Rio Grande do SulRio Grande do Sul, Brazil

Manuel Montero-Odasso, MD, PhDDivision of Geriatric MedicineUniversity of Western Ontario

London, Ontario, Canada

Figure 1. (A) H1N1 incident mortality according to age group inArgentina, 2009. (B) 2009 H1N1 mortality in Argentina ac-cording to age group. The broken line shows expected mortalityfor the older age group. Expected mortality of people aged 60and older was estimated using mathematical modeling based onprevious H1N1 epidemics,8 the rhythm of increasing mortality

from the age of 20 to 59 in current H1N1 pandemic and onprevious seasonal influenza epidemics in Argentina (2007/08).

1814 LETTERS TO THE EDITOR SEPTEMBER 2010VOL. 58, NO. 9 JAGS

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Manuel Montero-Odasso, MD, PhDGeriatric Medicine Specialist Career

Faculty of MedicineUniversity of Buenos Aires

Buenos Aires, Argentina

ACKNOWLEDGMENTS

Conflict of Interest: The editor in chief has reviewed the

conflict of interest checklist provided by the authors and hasdetermined that the authors have no financial or any otherkind of personal conflicts with this paper.

Author Contributions: Roriz-Cruz: study concept.Roriz-Cruz, Idiane Rosset, and Montero-Odasso: obtainedraw data from Argentinean Ministry of Health, interpretedand analyzed data, and wrote the manuscript.

Sponsors Role: None.

REFERENCES

1. World Health Organization. Human Infection with Pandemic (H1N1) 2009

Virus: Updated Interim WHO Guidance on Global Surveillance (10 July

2009). Geneva: WHO, 2009.

2. Ministry of Health of Argentine. Influenza pandemica (H1N1) 2009.Repu blica Argentina. Informe semana epidemiolo gica n1 52 (06/Jan/2010).

Buenos Aires: Ministry of Health, 2010.

3. Libster R, Bugna J, Coviello S et al. Pediatric hospitalizations associated with

2009 pandemic influenza A (H1N1) in Argentina. N Engl J Med 2010;362:

4555.

4. Echevarra-Zuno S, Meja-Arangure JM, Mar-Obeso A et al. Infection and

death from influenzaA H1N1 virus in Mexico: A retrospective analysis.Lancet

2009;374:20722079.

5. Louie JK, Acosta MCalifornia Pandemic (H1N1) Working Group. et al. Fac-

tors associated with death or hospitalizationdue to pandemic 2009influenzaA

(H1N1) infection in California. JAMA 2009;302:1896902.

6. Donaldson LJ, Rutter PD, Ellis BM et al. Mortality from pandemic A/H1N1

2009 influenza in England: Public health surveillance study. BMJ 2009;339:

b5213.

7. Fisman DN, Savage R, Gubbay J et al. Older age and a reduced likelihood of

2009 H1N1 virus infection. N Engl J Med 2009;361:20002001.

8. Palese P, TumpeyTM, Garcia-SastreA. What can we learn fromreconstructingthe extinct 1918 pandemic influenza virus? Immunity 2006;24:121124.

9. Xu R, Ekiert DC, Krause JC et al. Structural basis of preexisting immunity to

the 2009 H1N1 pandemic influenza virus. Science 2010;328:357360.

10. Ikonen N, Strengell M, Kinnunen L et al. High frequency of cross-reacting

antibodies against 2009 pandemic influenza A(H1N1) virus among the elderly

in Finland. EuroSurveill 2010;15: pii: 19478.

COMFORT FEEDING ALWAYS

To the Editor: Kudos to Palecek and colleagues for theirproposal to add comfort feeding only to our armament-

arium when eating difficulties arise in patients with ad-vanced dementia.1 For most, providing food and water is adeeply held core value defining what it means to care wellfor another human being. Families, even those with cleardirectives from their loved ones, struggle when the onlyoption to tube feeding is no feeding. From the trenches Imight suggest a slight change in the term to comfort feed-ing always. The word only implies restriction, when thegoal of this proposed new order is to emphasize that ap-propriate attention to nutritional needs will always be ren-dered. With respect to Dr. Brauners excellent companioneditorial, only does not need to be promulgated to standup against a default practice of tube feeding.2 The order

defines a practice plan that offers food and liquids as tol-

erated and, when they can no longer be tolerated, the pres-ence and attention of a caregiver to provide human contact.It brings the best and most appropriate standard of care wecan offer these patients and their loved ones.

Margaret A. Noel, MDMemoryCare

Asheville, NC

ACKNOWLEDGMENTS

Conflict of Interest: The editor in chief has reviewed theconflict of interest checklist provided by the author and hasdetermined that the author has no financial or any otherkind of personal conflicts with this paper.

Author Contributions: Margaret Noel prepared andwrote this letter.

Sponsors Role: There was no sponsor involved in thisletter.

REFERENCES

1. Palecek EJ, Teno JM, Casarett DJ et al. Comfort feeding only: A proposal tobring clarity to decision-making regarding difficulty with eating for persons

with advanced dementia. J Am Geriatr Soc 2010;58:580584.

2. Brauner DJ. Reconsidering default medicine. J Am Geriatr Soc 2010;58:

599601.

AN UNUSUAL CASE OF EPISTAXIS ANDSTAPHYLOCOCCUS AUREUS BACTEREMIA IN ANOLDER CHINESE WOMAN

To the Editor: An 80-year-old Chinese woman with ad-vanced Alzheimers disease, ischemic heart disease, hyper-

tension, and hyperlipidemia presented with a 1-weekhistory of recurrent epistaxis and bloody ear discharge.She was a known nasal carrier of methicillin-resistantStaphylococcus aureus (SA) and had been admitted to thehospital three times in recent months for urinary tract in-fections and lower limb cellulitis. Physical examination wasunremarkable. Nasal endoscopy and otoscopy revealedcrusting in the nasal cavity with a fleshy mass at the rightexternal auditory canal floor extending posteriorly to theright postnasal space (PNS). In addition, she had a bilateralsubtotal perforation of the tympanic membrane andchronic suppurative otitis media. A computed tomographyscan detailed the heterogeneous enhancing right PNS mass

extending toward the left nasopharynx. Histology revealedextensive necrosis, fibrinopurulent exudates, mixed-typeinflammatory infiltrate, and clusters of gram-positive cocci.No malignant cells, granulomas, giant cells, or acid-fastbacilli were seen. Anti-Epstein-barr virus viral capsidantigen titers were normal (immunoglobulin Ao5, earlyantigeno5). Because the suspicion of nasopharyngeal car-cinoma (NPC) was high, a repeat biopsy was performedthat was again negative for malignancy.

Six days after the biopsy, she presented with heavyepistaxis, altered consciousness, and a high white blood cellcount (24.79 109 /L). Physical examination was unre-markable, and initial investigations with chest X-ray and

urinalysis did not reveal a likely source of infection. She was

LETTERS TO THE EDITOR 1815 JAGS SEPTEMBER 2010VOL. 58, NO. 9