journal of the indian academy of geriatrics 2008.pdf · sangariya, jodhpur (raj.) editor dr arvind...

JOURNAL OF THE INDIAN ACADEMY OF GERIATRICSOfficial Publication of The Indian Academy of Geriatrics

June 2008 ISSN 0974-3405 Vol. 4, No. 2

C O N T E N T S

Editorial Biomarkers in Population Aging Research

Mathur A ........................................................................................... .... 51

Original Articles Influence of Vitamin E Supplementation on Aging

Saxena R, Lal A M ................................................................................ 55

Tuberculosis in Patients Below and Above 60 yearsand Their Treatment Outcome Under RNTCP - A Studyin Rural West Bengal, India.

Mukherjee A, Saha I, Paul B .................................................................... 60

Contemporary Issue Ageing and Healthy Life Expectancy:Will the Extended Years be Spent in Good or Poor Health?

Johnson CS ......................................................................................... ... 64

Review Article Drug Induced Liver Diseases in the Elderly

Chandy GM, Chandy RG ........................................................................ 68

Journal Scan .................................................................................................... ............ 72

Announcements .................................................................................................... ............ 54, 71, 81-84

JOURNAL OF THE INDIAN ACADEMY OF GERIATRICSPeer-reviewed, Official Publication of the Indian Academy of Geriatrics

Journal of The Indian Academy ofGeriatrics is published quarterly (inMarch, June, September and December).

ISSN 0974-3405

The information and opinions presentedin Journal of The Indian Academy ofGeriatrics ref lect the views of theauthors and not of the Academy or theEditorial Board. Acceptance does notconstitute endorsement by The IndianAcademy of Geriatrics.All the rights are reserved. Apartfrom any fair dealing for the purposesof research or private study, or criticismor review, no part of the publication canbe reproduced, stored, or transmitted,in any form or by any means, withoutthe prior permission.

Journal of The Indian Academy ofGeriatrics and/or its publisher cannotbe held responsible for errors or forany consequences arising from the useof the information contained in thisjournal. The appearance of advertisingor product information in the varioussections in the journal does notconstitute an endorsement or approvalby the journal and/or its publisher ofthe quality or value of the said productor of claims made for it by itsmanufacturer.

PUBLISHERDr Arvind Mathurfor and on behalf ofThe Indian Academy of Geriatrics

PUBLISHED ATRoom No. 9, Deptt. of MedicineMDM Hospital, Shastri Nagar,Jodhpur - 342 003Fax : 0291-2441678E-mail : [email protected]

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Website: www.jiag.orgRNI REG. NO.:RAJENG/2005/15244

INTERNATIONAL ADVISORY BOARD

EDITOR Arvind Mathur

EXECUTIVE EDITOR Lt Col Pratap Sanchetee

ASSOCIATE EDITORS Manish Chaturvedy KR HaldiyaAsha Mathur SL Mathur

ASSISTANT EDITORS

SK Acharya (New Delhi)GL Avasthi (Ludhiana)CS Bal (New Delhi)Mahaveer Chand (Jodhpur)Rama Chaudhry (New Delhi)D Dalus (Trivandrum)SK Das (Lucknow)Tapas Das (Bankure)AB Dey (New Delhi)RS Gahlot (Jodhpur)IS Gambhir (Varanasi)Alka Ganesh (Vellore)S Dutta Gupta (New Delhi)R Handa (New Delhi)AK Jain (Jodhpur)Rajeshwar Kalla (Jodhpur)Sandhya Kamath (Mumbai)Kamal Kant (Jodhpur)MS Kanungo (Varanasi)Kamal Kishor (New Delhi)Dinesh Kothari (Jodhpur)B Krishnaswamy (Chennai)Manoj Lakhotia (Jodhpur)Sarabmeet Singh Lehl (Chandigarh)Neelakshi Mahanta (Guwahati)DR Mathur (Jodhpur)Jagmohan Mathur (Jodhpur)

Anirudh Mishra (Shillong)Ramnath Misra (Lucknow)VS Natrajan (Chennai)N S Neki (Amritsar)R Veera Pandiyan (Chennai)Jai Prakash (Varanasi)H Krishna Prasad (New Delhi)Sathyanarayana Raju (Hyderabad)Medha Y Rao (Bangalore)S Rastogi (New Delhi)SK Saraf (Varanasi)R Sathianathen (Chennai)N Shah (New Delhi)GS Shanti (Chennai)S Sinha (New Delhi)Santokh Singh (Amritsar)SM Singh (Varanasi)VB Singh (Bikaner)R Sivaraman (Chennai)S Subramaniam (Chidambaram)Nikhil Tandon (New Delhi)MK Thakur (Varanasi)JS Titiyal (New Delhi)Manjari Tripathi (New Delhi)Arvind Kumar Vaish (Lucknow)

NATIONAL ADVISORY BOARD

Stephen C Allen (UK)JA Edwardson (UK)Laima Jankauskieni (Lithuania)RA Kenny (UK)Paul Roman Kowal (Switzerland)Marion E T McMurdo (UK)

Tony Setiabudhi (Indonesia)Dalip Singh (USA)R Knight Steel (USA)Cameron Swift (UK)Joseph Troisi (Malta)Pauline Weir (Jamaica)

Harish AgarwalGautam BhandariVivek BharadwajPradeep BhatiaNaveen Kishoria

Naveen MathurSuneet MathurVimlesh PurohitIndu Thanvi

Editorial

Biomarkers in Population Aging ResearchArvind Mathur

Professor, Department of Medicine,Dr S N Medical College, Jodhpur

Rapid progress in the field of biological assessmenthas expanded the possibilities for enhanced biologicalmeasurement in population research. Incorporatingbiomarkers in social sciences, public health, andbehavioural research creates exciting opportunities thatinclude better measurement of health and disease,validation of self-reported behaviours, and measurementof exposures to environmental agents. Biological Marker(Biomarker) is defined as a characteristic that isobjectively measured and evaluated as an indicator ofnormal biologic processes, pathogenic processes, orpharmacologic responses to a therapeutic intervention.

Biological measures collected in the populationsetting can include direct measures of physical orphysiological characteristics (eg height, weight, BMI,waist-hip circumference or blood pressure), functionaltesting (eg cognitive function, balance, grip strength),or collection of specimens that require laboratoryprocessing in order to generate analyzable data. Suchdata may also be generated via experiments embeddedin population studies (eg neuropsychiatric,psychophysiological, or sensory testing). Biomeasuresalso include measures of the physical environment thatinfluence human biology (eg radiation or noise).

The National Research Council recommends thatbiomarkers be incorporated in a social survey toa) capture health data from a portion of the populationthat otherwise would not have this type of datarecorded, b) investigate molecular determinants ofcommon health outcomes, and c) study interactionsbetween biomarkers and social conditions that maysubsequently lead to declines in health outcomes.1

The inclusion of biomarkers is particularly importantfor less-developed countries like India, where accessto health care tends to be limited due to low incomeand the lack of insurance. According to the World Bank,the 2005 gross national income per capita in India was$720, and less than 10% of the Indian population hadhealth insurance (either public or private).2 India’s agingpopulation is particularly at risk for undiagnoseddiseases, furthermore a significant level of self-reporting

bias exists. Education is also known to be an importantdeterminant for identifying health problems, but literacyrate in India was just 61% in 2004.3 Therefore, theimportance of biomarkers is critical to gauge the healthconditions of the Indian population, particularly the olderadults.

There are people who reach the age of 85 in avery good physical and mental condition. There areothers who have extensive cognitive difficulties andphysical disorders already by the age of 60. A person’sbiological age is more indicative of their health thantheir chronological age. Understanding the mechanismsof aging and the relationship between aging and diseaseis essential to help us address the health needs ofolder population. However, the inability to quantify agingin individuals has limited the study of the biology ofaging. Currently, aging is indirectly measured as afunction of the increasing rate of mortality withinpopulations. While aging contributes to the progressiveincrease in mortality, it is only indirectly related to lifespan.Life span and chronological age gives littleindication of the dynamic changes that occur withinan individual and the functional capabilities of thatindividual. Currently there is no way to relate thepopulation-level phenomenon of increasing mortality tothe age-related biological declines within individuals. Aswell, the field of aging is left without a standardizedmeasure for measuring aging in studies or monitoringpotential interventions in the aging process. Evaluationof an anti-aging theory or program is feasible in thelaboratory, using experimental animals, not so withhumans. The proposed solution to this problem is tofind a set of biomarkers to act as a meter of the agingprocess. A biomarker would be a physiological orgenetic parameter that changes with age, and it wouldpredict mortality and morbidity better than chronologicalage.4 It should be able to predict mortality while themajority of the population was still alive, and it wouldbe able to predict the outcome of other age-sensitivetests.5

It is generally believed that seven major healthareas are affected by aging: cardiovascular health,glucose regulation, brain function, muscle and skeletalhealth, endocrine function, immune system and oxidativestress.

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Journal of The Indian Academy of Geriatrics, Vol. 4, No. 2, June, 2008

Biomarkers of aging are physical properties in thehuman body which indicate that the body is aging. Thebest markers will be the ones which are not susceptibleto influence from the outside environment and have aclear association with aging. Ideally a true biomarkermust predict the rate of aging and be a better predictorof life span than chronological age. It must be ableto be tested on a regular basis and must work bothfor humans and other species, such as laboratoryanimals. A set of biomarkers would allow researchersto assess an individual’s biological age, and theirexpected individual life span, as opposed to theirchronological age. It is difficult to quantify aging withinand between individuals for two major reasons, whichis primarily why biomarker research has thus far yieldedno positive results. First, genotype alone does notexplain the rate of aging. In human twins, as well asgenetically identical organisms raised in the lab lifespan varies substantially. A second major problem inquantifying aging is variation within individuals. Differentorgan systems age at various rates within the body,so the existence of a single indicator of the rate ofaging seems unlikely. Traits that most directly relateto the aging process would make the best biomarkers;that is, their effect would not be influenced by othervariables. However, without an established theory ofaging it is difficult to determine which traits or systemsbest reflect aging. The use of multiple biomarkers canpredict mortality more accurately than chronologicalage.

Biomarkers of aging could be divided in three majorcategories; a) markers which determine the biologicalage, eg skin elasticity and visual accommodation,b) markers which predict the remaining life expectancyeg DHEA-S, hand grip strength, etc and c) markerswhich determine disease susceptibility eg systolicblood pressure and glucose tolerance tests. All of thebiomarker tests can be classified either as laboratorytests (eg blood and urine tests) or as physical testsundertaken in a clinic. Frequently used and validatedbiomarkers are: 17-ketosteroid/ 17-hydroxycortiosteroidratio (male), ascorbic acid, IL-6, APOE, norepinephrine,epinephrine - plasma (male), creatinine clearance,DHEA-S, PSA total (male), fibrinogen, testosterone free(male), zinc- serum, hemoglobin A1C, maximum oxygenupdate (male), basal metabolic rate, blood pressure-pulse, blood pressure- systolic, lung capacity- FEV1,lung capacity- FVC, handgrip strength, body massindex (female), near vision, caries index, peridontalindex, skin elasticity, hair baldness (male), and hairgrayness. In addition, there are also a number of otherfactors with insufficient experimental data like body

flexibility, blood urea nitrogen, LDL cholesterol, melatoninlevels, static balance, serotonin levels and manyothers.

Common anthropometric and performancebiomarkers used in population research area) Anthropometric measures: height, weight, waist andhip circumferences b) Blood pressure and pulsesystolic and diastolic blood pressure and pulse rate;c) Lung function: lung peak flow rate d) Walking speed;e) Grip strength f) Chair stands and g) Cognitivefunction by Mini-Mental State Examination (MMSE).Among blood based biomarkers, measures ofinflammation, apolipoproteins, hemoglobin, and immunefunction have important prognostic values.

The inflammatory response is the body’s integratedyet diverse reaction and defense against homeostaticdisturbances, particularly infection and injury. However,chronic inflammation may nonetheless be harmful andcan lead to atherosclerosis.6,7 Peripheral blood markersof inflammation, such as CRP, have been identified asindependent prognostic indicators for increasedincidence of cardiovascular events and mortality, andfunctional impairment in older adults.8,9

Apolipoproteins are the protein components of low-density lipoprotein (LDL) and HDL cholesterols. Themajor apolipoprotein of LDL is apolipoprotein B100 (ApoB), while apolipoprotein A-I (Apo A-I) has been frequentlyused to estimate the HDL levels.10 Although high LDLand low HDL cholesterols are classic cardiovascularrisk factors, the available data from the recent, large,well-conducted, prospective epidemiologic studiessupport the conclusion that Apo B and Apo A-1 arebetter markers for the risk of atherosclerosis andcardiovascular events than LDL and HDL cholesterols,respectively.11

Anemia, decreased Hb concentration in the blood,has been shown to independently predict mortality,morbidity, and various measures of functional status,including lower muscle strength, mobility difficulty,difficulties with basic and instrumental activities of dailyliving, and worsening cognitive functioning.12,13

Primary EBV infection occurs during the first fewmonths to years of life in developing countries.Adequate cell-mediated immune function is critical formaintaining the virus in a latent state over the lifetimeof an individual. Therefore, impaired cell-mediatedimmune function would allow EBV to reactivate andrelease viral antigens into blood circulation, leading toEBV antibody production. Previous studies in developingcountries have demonstrated a linkage between a

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higher degree of psychosocial stress and lower levelsof cell-mediated immune function, measured byincreased EBV antibody levels.14

The benefit of using more than one biomarker tobetter predict health outcomes has been welldemonstrated in health research.15 For example,allostatic load has been proposed as a cumulativemeasure of dysregulation across multiple physiologicalsystems, and has been postulated to impact healthrisks. In the allostatic load model, increased risk ishypothesized to result not only from large and clinicallysignificant dysregulation in individual systems, but alsofrom more modest dysregulation present in multiplesystems. These biomarkers along with other measures(blood pressure, body mass index (BMI), waist-to-hipratio (WHR), lung peak flow rate, HbA1c allow us tobetter characterize health status by assessing thecardiovascular (blood pressure, apolipoproteins),respiratory (lung peak flow), metabolic (BMI, WHR,HbA1c, apolipoproteins), inflammatory (CRP), immune(EBV antibody), and hematological (Hb) systemssimultaneously.

The collection of biomarkers in a population studycan add a significant cost to the project with a needto plan logistics. Dried blood spot (DBS) specimens,blood spots on filter paper made from capillary bloodcollected from a finger prick, have greatly simplified theprocess of collection of blood sample in non-clinicalstudies. The use of filter paper for the collection andanalysis of human blood dates back to the early 1960s,when DBS specimens were used to measurephenylalanine in newborns for the detection ofphenylketonuria.16 For bioassays, the collection ofcapillary blood on filter paper has several advantagesover venous puncture that make it ideal for field-basedresearch. Finger-prick blood sampling eliminates theneed for a trained phlebotomist to collect and processblood samples. Sample collection is relatively painlessand noninvasive, with minimal inconvenience and burdenimposed on participants. Samples collected do nothave to be centrifuged, separated, or immediatelyfrozen. Because the filter papers can be stacked andpackaged in air-tight containers and kept at ambienttemperatures without significant deterioration for anumber of days, transportation to a centralized locationfor freezer storage is comparatively uncomplicated. Ingeneral, any analyte that can be measured from wholeblood, serum, or plasma can in principle be measuredfrom DBS specimens for epidemiological studies.17

The Newborn Screening Quality Assurance Program atthe Centers for Disease Control and Prevention in theUnited States has been providing external quality

assurance for the filter paper blood collection device,for newborn-screening laboratories and for epidemiologicalresearch using DBS specimens.

Some of the major datasets that have collectedbiomarker data include Coronary Artery Risk Developmentin Young Adults (CARDIA); Cardiovascular Health Study(CHS); The Atherosclerosis Risk in Communities Study(ARIC); Social Environment and Biomarkers of AgingStudy (SEBAS) in Taiwan; English Longitudinal Studyof Ageing (ELSA); MacArthur Study of SuccessfulAging; Dynamics of Health, Aging and Body Composition(HEALTH ABC); Hispanic Epidemiologic Studies of theElderly (Hispanic EPESE) 1993-2004; The SwedishAdoption/Twin Study of Aging (SATSA); Individualdifferences among the oldest-old (OCTO-Twin); NationalHealth and Nutrition Examination (NHANES III, IV)Whitehall Study; and WHO Study of Ageing and AdultHealth (SAGE) .

There are several ethical issues related to researchinvolving human subjects and the collection of biologicalspecimens regarding confidentiality and disclosure ofresults, treatment arrangements, long-term storage andfuture use of specimens.

Although biomarker research faces many biologicaland technical obstacles, the discovery of valid biomarkerscould have significant social impact. The ability tomeasure biological age could be an important clinicaltool in assessing risk for medical procedures, or thelikelihood of developing an early onset of age-relateddiseases. The results of biomarkers of aging could alsobe of great interest to insurance companies andemployers for setting premiums and retirement age,respectively. Second, the discovery of biomarkers couldaccelerate the development of anti-aging interventionsin humans. Despite some scientific pessimism,biomarker research should remain a fundamental partof gerontology in order to better study aging andhopefully improve the health of an aging population.

References1. National Research Council. Preparing for an Aging World: The

Case for Cross-National Research, Panel on ResearchAgenda and New Data for an Aging World. 2001; Committeeon Publication and Committee on National Statistics, Divisionof Behavioral and Social Sciences and Education. Washington,D.C., National Academy Press.

2. World Bank. India at glance, 2007; http://devdata.worldbank.org/AAG/ind_aag.

3. WHO Study of Global Ageing and Adult Health (SAGE).Proposal summary document. 2006; World Health Organization,Geneva.

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4. Sprott, R. Biomarkers of Aging Journal of Gerontology. 1999:54A; B464-B465.

5. Miller RA. Biomarkers of Aging. Science: Sage KE. 2001 Oct3. http://sageke.sciengemag.org

6. Bisoendial RJ, Kastelein JJ, Stroes ES. C-reactive protein andatherogenesis: from fatty streak to clinical event.Atherosclerosis. 2007;195:10-18.

7. Wilson AM, Ryan MC, Boyle AJ. The novel role of C-reactiveprotein in cardiovascular disease: risk marker or pathogen.Int J Cardiol 2006;106:291-297.

8. Ravaglia G, Forti P, Maioli F, et al. Peripheral blood markersof inflammation and functional impairment in elderly community-dwellers. Exp Gerontol 2004;39:1415-1422.

9. Lindahl B, Toss H, Siegbahn A, et al. Markers of myocardialdamage and inflammation in relation to long-term mortality inunstable coronary artery disease. N Engl J Med 2000 ; 343:1139-1147.

10. Olofsson SO, Wiklund O, Borén J. Apolipoproteins A-I andB: biosynthesis, role in the development of atherosclerosisand targets for intervention against cardiovascular disease.Vasc Health Risk Manag 2007 ; 3: 491-502.

11. Walldius G, Jungner I. The apoB/apoA-I ratio: a strong, newrisk factor for cardiovascular disease and a target for lipid-

lowering therapy—a review of the evidence. J Intern Med2006 ; 259: 493-519.

12. Penninx BW, Pahor M, Cesari M, et al. Anemia is associatedwith disability and decreased physical performance andmuscle strength in the elderly. J Am Geriatr Soc 2004; 52:719-724.

13. Denny SD, Kuchibhatla MN, Cohen HJ. Impact of anemia onmortality, cognition, and function in community-dwelling elderly.Am J Med 2006; 119: 327-334.

14. McDade TW, Stallings JF, Worthman CM. Culture change andstress in Western Samoan youth: Methodological issues inthe cross-cultural study of stress and immune function. AmJ Hum Biol 2000; 12: 792-802.

15. Zethelius B, Berglund L, Sundström J, et al. Use of multiplebiomarkers to improve the prediction of death fromcardiovascular causes. N Engl J Med 2008; 358: 2107-2116.

16. Guthrie R, Susi A. A simple phenylalanine method for detectingphenylketonuria in large populations of newborn infants.Pediatrics 1963; 32: 338-343.

17. Mei JV, Alexander JR, Adam BW, et al. Use of filter paperfor the collection and analysis of human whole bloodspecimens. J Nutr 2001; 131: 1631-1666.

CARE OF THE ELDERLYIN GENERAL PRACTICE

A Guide to Geriatric Care

AP JainDirector, Professor & Head

Department of Medicine, MGIMSSewagram, Maharashtra

Amit D BhattLecturer

Department of Medicine, MGIMSSewagram, Maharashtra

ForewordShri Dhirubhai Mehta

PreviewDr AB Dey

Paras Medical PublisherHyderabad, New Delhi

Influence of Vitamin E Supplementation on AgingSaxena R*, Lal A M**

Original Article

Abstract

Background: Despite massive and costly efforts, progressive deterioration of biomolecules due toaugmented oxidative stress with advancing age has yet not been controlled. It is conceivable thatexogenous vitamin E supplementation ameliorate the modifiable indexes via regulating free radicalproduction and consumption of antioxidant reserve.

Aim: The objectives of present study were to investigate the therapeutic effect of vitamin Esupplementation in ameliorating the altered activity of antioxidant enzymes (superoxide dismutase,ceruloplasmin & glutathione peroxidase) and erythrocyte malionaldehyde level (MDA, i.e. marker oflipid peroxidation) in middle aged and elderly people.

Material & Methods: Antioxidant enzymes status & MDA levels were estimated by using standardmethods in 30 healthy younger individuals (20-30 years) who served as controls and in 60 healthysubjects categorized into two groups i.e. group I (40-55 years) and group II ( 56 years) before andafter 3 months of vitamin E supplementation. The obtained values were compared statistically byusing student’s t-test.

Result: Marked reduction in erythrocyte superoxide dismutase activity and glutathione peroxidase wereobserved in group I (p<0.05) and group II (p<0.05), after vitamin E supplementation. On the other hand,significant increased levels of erythrocyte MDA were observed in group I and group II (p<0.001) whichameliorate significantly (p<0.05) after vitamin E supplementation. However, plasma ceruloplasminlevels were increased significantly only in group II (p<0.05) but remain unaltered (p<0.1) on vitaminE supplementation.

Conclusion: Exogenous vitamin E supplementation provides protection against oxidative stressmediated aging processes and diet rich in vitamin E should be increased with advancing age.

Keywords: Aging, superoxide dismutase, ceruloplasmin, malionaldehyde, glutathione peroxidase.

IntroductionOxidative damage induced by reactive oxygen

species is caused by increased production of superoxideanion (O

2) and its metabolites or by reduced

bioavailability of antioxidant defenses. The imbalancebetween pro-oxidants and antioxidants gives rise tocellular oxidative stress, which plays an important rolein the progression of aging processes.1 Reactiveoxygen species may act through several mechanismsto mediate major interrelated derangements of cell

metabolism such as peroxidation of lipids, DNA strandbreakage, rise in intracellular free Ca2+, damage tomembrane ion transporters and other specific proteins.2

Lipid peroxidation is a free radical process in whichthe polyunsaturated fatty acids contained in LDL orpresent in cell membrane are degraded to a greatvariety of aldehydes (i.e. malionaldehyde, propanal andhexanal etc). As a result, excess binding of aldehydeto cellular protein may alter cellular function, membranepermeability, electrolyte balance and thereby leadingto progressive deterioration of biological systemassociated with aging process.3

Protection of cells from potentially injurioussuperoxide anion (O

2-) is provided by superoxide

*Senior Resident, **Professor & Head, Department of Biochemistry,M L N Medical College, Allahabad

Address for correspondence:Dr Rahul SaxenaC/o Dr Geeta Jaiswal, 234, Attarsuia, Allahabad.email: [email protected]

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dismutases, intracellular (CuZnSOD and MnSOD) andextracellular enzymes (E.C. SOD) that catalyse thedismutation of O

2- to H

2O

2 and O

2.3 In addition, the

action of cytoplasmic SOD in scavenging O2- and in

inhibiting O2- mediated reactions can be mimicked by

other copper-containing plasma protein i.e. ceruloplasmin.The antioxidant property of ceruloplasmin is due to itsferroxidase activity towards ferrous ions and, it canprevent the generation of OH- radicals via Haber’sreaction.4 Hydrogen peroxide (H

2O

2) formed from

superoxide anion, either in presence of transition metal(Fe2+& Cu2+) produces highly toxic hydroxyl radical orproduces hypochlorous acid (HOCl) by the action ofenzyme myeloperoxidase in neutrophils andmacrophages which amplify further destruction.Glutathione peroxidase (GSHPx), a selenium containingenzyme, catalyses the decomposition of H

2O

2 with the

help of reduced glutathione and prevents the oxidationof lipids and phospholipids.5 Alterations in the levelsof these enzymes and increased levels of lipid peroxidesfurther amplify the disturbances in biological processeswith increasing age.

A wide range of antioxidants both natural andsynthetic have been proposed for treatment of agerelated biochemical and physiological alterations relatedto oxidative stress. Increased oxidative stress is theresult of either an increased production of free radicalsor a depletion of endogenous antioxidants. Considerableattention has been devoted to the potential use of -tocopherol, a potent chain breaking antioxidant, in theprevention of age related alterations.6 Although inprevious epidemiological and experimental animalstudies, vitamin E reduces oxidative stress mediateddamages and facilitates various physiological activities,the mechanism underlying its effect in ameliorating theenzyme activities and levels of MDA (i.e. marker of lipidperoxidation) in different age group subjects have notbeen fully elucidated.7,8 Therefore, the objective ofpresent study was to investigate the therapeutic effectof vitamin E supplementation in replenishing theantioxidant enzyme activity and in controlling theprogression of lipid peroxidation in different age groupsubjects.

Material and MethodsIn the present study, 90 healthy subjects of either

sex (15 males & 15 females in each group) and differentage groups were included from urban area of Allahabadcity after taking their informed consent and approval

of protocol by ethics committee of college. Thesesubjects were selected randomly and categorized intothree groups depending upon age i.e. control group(younger people) included 30 healthy subjects of agegroup 20–30 years, group I included 30 healthy subjects(middle aged people) of age group 40-55 years andgroup II included 30 healthy subjects (elderly people)of age group 56 years onwards. A general informationor pre-experimental questionnaire regarding demographicinformation, family history and limited physicalexamination was completed from all subjects. Patientswith diabetes mellitus, hypertension, renal insufficiency,hepatic disease or under any medicinal treatment wereexcluded. Height and weight were measured withsubject barefoot and light dressed. The body massindex (BMI) was calculated as BMI = weight (kg) /height (meter2). Obese (BMI > 25), hypertensives (BP>120/80 mmHg) and smokers were excluded from thestudy.

Fasting blood samples were collected in EDTAvials from the anticubital vein of the subjects andprocessed immediately. Antioxidant enzymes and MDAlevels were estimated before (non supplemented groupi.e. Group I A & Group II A) and after 3 months of vitaminE supplementation (200 mg/day; Group I B & GroupII B) and compared it with that of younger controls.Erythrocyte SOD activity was measured by Marklundand Marklund’s method.9 This method is based on thepresence of superoxide anions. The enzyme SODinhibits the autooxidation of pyrogallol by catalyzingthe breakdown of superoxide. The inhibition of pyrogalloloxidation by SOD is monitored at 420 nm and theamount of enzyme producing 50% inhibition is definedas one unit of enzyme activity.

Plasma ceruloplasmin level was estimated byRavins’s method.10 Ceruloplasmin due to its oxidaseactivity, catalyses the oxidation of substrate p-phenylenediamine chloride into purple colouredoxidation product which is measuredspectrophotometrically.

GSHPx activity was estimated by Beutler’s method,after preparation of hemolysate.11 GSHPx catalyses theoxidation of reduced glutathione (GSH) to oxidizedglutathione (GSSG) by H

2O

2. The rate of formation of

GSSG is measured by means of glutathione reductasereaction in which NADPH is oxidized and is measuredat 340 nm.

Erythrocyte malionaldehyde (MDA) level was

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measured as thiobarbituric acid reactive substances,after preparation of hemolysate.12 The heat inducedreaction of malionaldehyde (MDA) with thiobarbituricacid (TBA) in the acid solution forms a trimethinecoloured substance, which is measuredspectrophotometrically at 532nm. Values wereexpressed as Mean±SD. The significance of meandifference between groups was compared by usingStudent’s t test and distribution of probability (p).

ResultThe mean blood pressure and demographic indices

of the study groups are depicted in Table 1. Theobservations made reveal significant changes inantioxidant enzyme status and MDA levels before andafter vitamin E supplementation as represented in Table2 and 3. Erythrocyte SOD activity was significantly lowin Group I A (29.5 %; p<0.05) and Group II A subjects(33.8 %; p<0.05) as compared to younger controls.It was found to be increased significantly in Group IB and Group II B (p<0.05; 23.0 % & 21.8 %respectively) on vitamin E supplementation. Plasmaceruloplasmin levels were significantly high only in

Group II A subjects (20.8 %; p<0.05) whereas insignificantchange occur (p<0.1; 10.3 %) in Group I A subjects.However, these levels remain unchanged in study groupsubjects (p<0.1) after vitamin E supplementation.Erythrocyte GSHPx activity was significantly low(22.5%; p<0.05) in Group I A and ( 29.92 %; p<0.05)in Group II A subjects as compared to healthy controls.It increased significantly (p<0.05; 21.6 % & 19.4 %high respectively) in both groups after vitamin Esupplementing. Similarly, significantly elevated levelsof erythrocyte malionaldehyde (MDA) were observed innon supplemented groups (i.e. 23.8 % high in GroupI A & 37.3 % high in Group II A; p<0.001) comparedto healthy controls. In supplemented group, MDA levelsdecreased significantly (p<0.05; 27.7 % & 23.5 % low)in Group I B and II B, as compared to non-supplementedgroup.

DiscussionExcessive ROS generation leading to oxidative

stress and damage of cellular biomolecules (proteins,lipids, and nucleic acids) has been hypothesized tobe the major contributor to aging process and many

Table 1: Demographic profile of study subjects (Mean ± SD)

S No Particulars Control group Group I Group II(n=30) (n=30) (n=30)

1) Age (years) 23.5 ± 5.0 45.0 ± 7.0 67.0 ± 9.02) M:F ratio 1:1 1:1 1:13) Height (meter) 1.58 ± 0.07 1.54 ± 0.06 1.60 ± 0.08

4) Weight (kg) 55.2 ± 3.8 57.0 ± 2.9 59.4 ± 3.45) BMI (kg/m2) 22.0 24.3 23.66) Systolic blood pressure (mmHg) 104 ± 6.0 110 ± 5.4 120 ± 4.87) Diastolic blood pressure (mmHg) 72.0 ± 3.0 76.0 ± 4.2 70.0 ± 3.4

Table 2: Antioxidant enzymes and Malionaldehyde levels in different age group before vitamin E supplementation.(Mean ± SD)

S No Particulars Control group(n=30) Group I A(n=30) Group II A(n=30)

1. SOD level(U/gm Hb) 1970.24± 251.7 1389.02 ± 197.42** 1304.3 ± 172.36**

2. Ceruloplasmin(mg%) 22.9 ± 7.3 25.28 ± 6.3* 27.5 ± 8.0 **

3. GSHPx(IU/gm Hb) 38.4 ± 8.3 29.76 ± 6.0 ** 26.92 ± 5.6 **

4. Malionaldehyde 2.78 ± 0.26 3.44 ± 0.33 ** 3.81± 0.35 ***

(µmolMDA/ml)* p<0.1 : Non significant ** p<0.05 : Significant *** p<0.001 : Highly significant

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diseases, such as cardiovascular diseases andcancers.1, 2 In particular, altered antioxidant enzymeactivities and lipid peroxidation are considered to bea major phenomenon by which ROS can cause tissuedamage leading to impaired cellular function andalterations in physicochemical properties of cellmembranes, which in turn disrupt vital functions.13

Several evidences have documented overproduction offree radicals with increasing age.1, 14

Vitamins directly scavenge ROS and regulate theactivities of antioxidant enzymes. In this context,vitamin E has been recognized as one of the mostpotent lipophilic chain breaking antioxidants.3 Althoughfew studies explicitly show the effects of vitamin E onthe activities of antioxidant enzymes, the mechanismunderlying its effect in ameliorating the enzyme activitiesand levels of MDA in different age group subjects haveyet not been fully elucidated.6, 15 In the present study,we observed that superoxide dismutase activity in bothmiddle aged and elderly subjects were significantly low(p<0.05) compared to healthy controls.It was found toincrease significantly with vitamine E supplementation(p<0.05). However, Li et al, have found no effect ofvitamin E supplementation on SOD activity.17

Superoxide anion scavenging action of SOD canbe mimicked by other copper containing enzymeceruloplasmin, which also has the capacity to scavengeO

2-. In the present study, plasma ceruloplasmin levels

were found to be significantly high only in elderly(p<0.05) whereas insignificant change occur (p<0.1) inGroup I A subjects. However, these levels remainunchanged in study group subjects (p<0.1) after vitaminE supplementation. On vitamin E supplementation, itslevel remain unaltered (p<0.1) in supplemented group,which were in concordance with findings of Reunanenet al.18 Although, the precise mechanism involved

behind this result is still unknown, it could be explainedon the basis of pro-oxidant property of vitamin E withceruloplasmin by which it converts Cu2+ of ceruloplasminto Cu+ which in turn catalyses lipid peroxide (LOO°)production from lipid hydroperoxide (LOOH) and itselfreduced back to Cu2+. On the other hand, tocopherolradical and LOO° radical, formed during this step isutilized in the formation of adduct as reported byMaiorino et al.19

-Toc-OH + Ceruloplasmin (Cu2+) -Toco + Ceruloplasmin (Cu+ )

Ceruloplasmin(Cu+)+ LOOHCeruloplasmin (Cu2+) + LOOo

-Toco + LOOo

ADDUCT (-TocOOL)

Moreover, GSHPx plays a crucial role in the finaldetoxification of H

2O

2. It spontaneously reacts with and

scavenges many forms of ROS, prevents oxidation oflipids and phospholipids, maintains intracellular redoxmilieu, replenishes a number of crucial antioxidants(vitamin E and C) and produces vasodilatory prostacyclinby the endothelium to maintain normal blood pressure.1,5

In the present study, low GSHPx activities wereobserved in both middle age and elderly subjects ascompared to younger controls which on vitamin Esupplementation, increased significantly in both thesupplemented groups. It could be explained as aglutathione sparing action of vitamin E by inhibiting lipidperoxidation and thereby replenishes GSHPx activity.20

Recently, similar findings were reported by Jaiswal etal and Garg et al, in their vitamin E supplementationstudies on subjects of different age relatedcomplications.15,21 Conversely, Li et al had found noeffect of vitamin E supplementation on GSHPx activity.17

Table 3: Antioxidant enzymes and Malionaldehyde levels in different age group after vitamin E supplementation. (Mean ± SD)

S No Particulars Control group(n=30) Group I B(n=30) Group II B(n=30)

1. SOD level(U/gm Hb) 1970.24± 251.7 1708.49 ± 204.3** 1588.6 ± 188.0**

2. Ceruloplasmin(mg%) 22.9 ± 7.3 24.53 ± 4.0 * 26.84 ± 6.2 *

3. GSHPx(IU/gm Hb) 38.4 ± 8.3 36.19 ± 7.2 ** 32.16 ± 6.4 **

4. Malionaldehyde 2.78 ± 0.26 2.49 ± 0.20 ** 2.92 ± 0.28 **

(µmolMDA/ml)

* p<0.1 : Non significant ** p<0.05 : Significant *** p<0.001 : Highly significant

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Above mentioned observation is well supported bymarked reduction in MDA levels (p<0.05) in supplementedgroup subjects which was 23.8% & 37.3% high in non-supplemented middle age and elderly subjectsrespectively. These findings clarify the chain breakingantioxidant property of vitamin E by which it protectsthe membrane bound lipids and nascent LDL againstfree radical mediated lipid peroxidation (i.e. key factorof atherosclerosis), prevents lipid peroxidation mediateddestruction in cell, subcellular organelles andbiomolecules and thereby plays a significant role inthe reduction of age associated destructive events.

-Toc-OH + LOOo -Toc o + LOOH

-Toc o + LOOo ADDUCT (a-TocOOL)

Furthermore, its cardioprotective, antihypertensive,anti-inflammatory, analgesic activity and its role inextending the life span of non-vertebrates, in preventingneurological dysfunction, memory or slow thinkingproblems, skin problems and cataract formation inelderly have been well documented.22

ConclusionIn view of substantial evidence from previous

studies and present findings supporting the critical roleof vitamin E in amelioration of antioxidant enzymeactivity and prevention of lipid peroxidation, the presentstudy is strong enough to convince nutritionist that dailyconsumption of diet rich in vitamin E should beincreased with advancing age. In addition, presentstudy authenticates the fact that oxidative stress playsa crucial role in aging process which can be regulatedby exogenous antioxidant supplementation. However,more work is needed to shed light on the therapeuticuse of vitamin E.

References1 Harman D. The aging process. Proc Nat Acad Sci USA1981;

78: 7124-7128.

2 Hallliwell B, Gutteridge JMC, and Cross CE. Free radicals,antioxidants and human disease. Where are we now? J LabClin Med 1992; 598-620.

3 Sen CK. Oxygen Toxicity and antioxidants: state of the art.Ind J Physiol Pharmacol 1995; 39: 177-196.

4 Wiyard PG, Hider CR, Brailsford S, et al. Effects of oxidativestress on some physiochemical properties of ceruloplasmin.Biochem J 1989; 258: 435-445.

5 Nawrot TS, Staessen JA, Roels HA, Hond DE. Blood pressureand blood selenium: a cross-sectional and longitudinalpopulation study. Euro Heart. 2007; 28: 628-633.

6 Yu BP, Kang CM, Han JS, Kim DS. Can antioxidantsupplementation slow the aging process? Biofactors 1998;7: 93-101.

7 Rimm E B, Stampfer MJ, Ascherio A. Vitamin E consumptionand risk of Coronary Heart Disease in men. N Eng J Med1993; 328: 1450–1456.

8 Epstein J, Gershon D. Studies on aging in nematodes, theeffect of antioxidants on cellular damage and life span.Mechanism of Aging and Development 1972; 1: 257-264.

9 Marklund S, Marklund G. Involvement of the superoxide anionradical in the autoxidation of pyrogallol and a convenientassay for superoxide dismutase. Eur J Biochem 1974; 47: 469-474.

10 Beutler E. Red cell metabolism. A manual of Biochemicalmethods. New York. Grune & Stratlon Inc., 1971, 3

rd ed, p

112-114.

11 Ravin HA. Photometric method of ceruloplasmin. J Lab ClinMed 1961; 58 : 161.

12 Sinnhuber RO, Yu TC, Yu TC. Characterization of the redpigment formed in the thiobarbituric acid determination ofoxidative rancidity. Food Res 1958; 23: 626-630.

13 Rikans LE, Hornbrook KR. Lipid peroxidation, antioxidantprotection and aging. Biochem Biophys Acta 1997; 1312:119-127.

14 Yu BP. Cellular defenses against damage from reactiveoxygen species. Physiological reviews 1994; 74:139-162.

15 Jaiswal G, Saxena R, Kumar B. Effect of vitamin Esupplementation on antioxidant enzymes and lipid peroxidationin Myocardial infarction patients. Saudi German Hosp Med2007; 2: 31-36.

16 Chen X, Tonyz RM, Park JB, Schiffrin EL. Antioxidant effectsof Vitamin C and E are associated with altered activation ofvascular NADPH oxidase and superoxide dismutase instroke-prone SHR. Hypertension 2001; 38: 606-611.

17 Li RK, Cowan DB, Mickle DAG, et al. Effect of Vitamin E onhuman glutathione peroxidase expression in cardiomyocytes.Free Rad Biol Med 1996; 21: 419-426.

18 Reunanen A, Knekt P, Aaran RK. Serum Ceruloplasmin leveland the risk of MI and Stroke. Am J Epidem 1992;136:1082-1090.

19 Maiorino M, Zamburlini A, Roveri A, Urine F. Copper inducedlipid peroxidation in liposomes, micelles and LDL: which isthe role of Vitamin E ? Free Rad Biol Med 1995; 18:67-74.

20 Costaghiola C, Libondi T, Menzione M, et al. Vitamin E andred blood cell glutathione. Metabolism 1985; 49: 712-714.

21 Garg MC, Chaudhary DP, Bansal DD. Effect of Vitamin Esupplementation on diabetes induced oxidative stress inexperimental diabetes in rats. Ind J Exp Biol 2005;43:177-180.

22 Malik A. Vitamin E: Role in postmenopausal women. Obs &Gynae. 2001; 6:448-452.

Original Article

Tuberculosis in Patients Below and Above 60 yearsand Their Treatment Outcome Under RNTCP- A study in Rural West Bengal, India.Mukherjee A*, Saha I**, Paul B***

AbstractElderly are at increased risk of tuberculosis. The present study aims to find out the disease characteristics

and treatment outcome of elderly tuberculosis patients. It was carried out at a rural Tuberculosis Unit (TU),West Bengal, India. All cases registered between January 1999 and June 2005 were divided into two groupsas age below 60 years and age 60 years or more, and the results were analyzed and compared. Out ofthe total of 3676 cases, 2868 (78%) were below 60 years, while 808 (22%) were elderly (age60 years).New smear positive and extrapulmonary cases were significantly more in young while new smear negativeand retreatment cases were significantly more in geriatric population (p < 0.001). Cure and treatmentcompleted cases were significantly lower while death and default were significantly higher in the geriatricpopulation. Sputum conversion rate at end of 2 months was also significantly lower in the geriatric group.These patients need to be further studied to plan effective interventions, so that unfavourable outcomes canbe brought down.

Key Words: RNTCP, Elderly, Tuberculosis, Outcome.

IntroductionAgeing is a natural process. Discoveries in

medical sciences and improved social conditions duringpast few decades have increased the life span of man.This is more evident in the developed countries. Theexpectation of life at birth in developed countries is over70 years. The age structure of population in thedeveloped countries has so evolved that the numbersof old people is continually on the rise. In India, althoughthe percentage of aged persons to the total populationis low in comparison to developed countries, nevertheless,the absolute size of aged population is considerable.In India too there has been a steady increase in thelife expectancy from 36.7 years in 1951 to 64.6 years

in 2000.1 At present there are more than 70 millionpeople above the age of 60 years in India. This numberis expected to rise to 177 million by 2025.2

It has been suggested that tuberculosis differsclinically and radiologically in the elderly compared tothe young. Moreover with the decrease in cellularimmune responses and an increase in the incidenceof diabetes mellitus, malignancy and other co morbiditiesthe final outcome of elderly patients is likely to beworse. This is compounded with the increased incidenceof adverse effects with antitubercular drugs in the elderlyresulting in increased morbidity and default fromtherapy.

The Revised National Tuberculosis ControlProgramme (RNTCP) has been operational in Indiasince 1993 as pilot projects in 5 states. From 2006onwards, it has covered the entire country. Over thelast several years all patients are being treated withDirectly Observed Treatment. Short CourseChemotherapy (DOTS) under the RNTCP. The presentstudy was undertaken to find out the diseasecharacteristics as well as final outcome of these elderly

*Medical Officer, Habibpur Block Primary Health Centre, Nadia**Assistant Professor, Community Medicine, R G Kar MedicalCollege, Kolkata.*** Assistant Professor, Community Medicine, Institute of PostGraduate Medical Education and Research. Kolkata.

Address for correspondence:Dr Abhijit Mukherjee.34, S. N. Banerjee Road, New Barrackpore,Kolkata: 700131.email: [email protected]

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subjects treated with DOTS.

Material and MethodsIt was a record based study carried out at the

Bagula Tuberculosis Unit (TU), Nadia district, WestBengal, India. The TU caters to a population ofapproximately five lakhs where most of the peoplebelong to lower socioeconomic status. The Bagula TUhas 5 Designated Microscopy Centres (DMC) mannedby 5 trained laboratory technicians and supervised bya Senior Tuberculosis Laboratory Supervisor (STLS).All these microscopy centres are attached to peripheralhealth institutions and all health care providers in theseinstitutions have been trained in RNTCP. A total of 3676cases, registered for tuberculosis treatment betweenJanuary 1999 and June 2005 were taken for the study.All cases were divided into two groups as age below60 years and age 60 years or more, and the resultswere analyzed and compared. The outcome cured,treatment completed, failure, died, default and transferredout were in accordance with the RNTCP definitions.3Chi-square test (2 test) was performed for statisticalanalysis of categorical variables to see association.Yate’s correction was done in this analysis when onecell value was less than 5.

ResultsOut of the total 3676 cases, 2868 (78%) were

below 60 years while 808 (22%) were elderly (age 60 years). Occurrence of new smear positive andextrapulmonary cases were significantly more in 60years age group compared to geriatric age group (p< 0.001). However, new smear negative cases weresignificantly more in geriatric population (p < 0.001)while retreatment cases were marginally higher (p >0.05) in geriatric patients (Table 1). There were 1194and 264 new sputum positive cases in less than 60years and 60 years respectively. Cure or treatment

completion and failure were higher among less than60 years age group, but it was statistically significantin cure or treatment completed only (p < 0.01). Bothdefault and death was significantly more amonggeriatric age group, 6.4% and 8.3% respectively. Thesame was true in case of new sputum negative andnew extrapulmonary cases. Cure or treatment completionwas significantly higher in less than 60 years, defaultand death was more among elderly age group, whiledeath being statistically significant (p < 0.01). Strikingly,failure was absent in both the age groups in newextrapulmonary cases and death was too small (0.7%)in this case in less than 60 years (Table 2). Sputumconversion rate at end of 2 months was significantly(2 test = 5.52, p < 0.05) higher (84.3%) among lessthan 60 years compared to 60 years (77.9%) (Table3). While male population was more among geriatricpopulation (78.6% vs. 65.6%) and female predominancewas observed in less than 60 years (34.4% vs. 21.4%),and this association of tuberculosis with age and sexwas found to be statistically significant (2 test = 43.68,p < 0.05) (Table 4).

DiscussionWith increasing age, there is a decrease in

lymphocytes especially the T lymphocytes and theproliferative responses.4-6 There is also a decrease inthe synthesis of gamma interferon levels, important inthe activation of macrophage, with increased age.7These factors cause a progressive immune dysregulationin the elderly. Along with this malnutrition, socialneglect and poverty are more common in elderlyincreasing the risk of tuberculosis in this group.

A high index of clinical suspicion is necessaryin diagnosis of tuberculosis in elderly. Inability to givean accurate account of their symptoms due to poormemory, impairment of speech and hearing, alongwith

Table 1: Disease classification< 60 years 60 years 2 p value(n = 2868) (n = 808) testno. (%) no. (%)

New smear positive 1194 (41.6) 264 (32.7) 21.14 0.001New smear negative 1003 (34.9) 409 (50.6) 65.24 0.001Extrapulmonary 306 (10.8) 32 (3.9) 33.98 0.001Retreatment 353 (12.3) 101 (12.5) 0.02 0.88Incomplete records 12 (0.4) 2 (0.3) - -

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absence of typical clinico-radiological signs oftuberculosis make the diagnosis of tuberculosis inelderly difficult.8,9 Classical symptoms of cough,expectoration or breathlessness when present areattributed to causes other than tuberculosis eg chronicbronchitis, smoking or old age.10

In present study the number of tuberculosispatients in the elderly group was much higher than inmost studies probably because this tuberculosis unitwas almost 15 kilometers from the nearest city.8, 11

There are only few private practitioners in the area.Moreover most people living in the area belong to thelower socioeconomic strata and hence attended thegovernment health facilities for diagnosis and treatment.

While in control group (age<60 years) oneextrapulmonary case was noted for every 7 pulmonarycases; one extrapulmonary case was seen for every22 cases of pulmonary tuberculosis in the elderly. Asimilar finding has been observed by Arora and coworkers.11

Similar to the findings in other studies, occurrenceof new smear positive pulmonary and extrapulmonarycases in the elderly was significantly lower than theyounger age group.12 However, smear negative pulmonarytuberculosis was significantly higher in elderly patients.This difference could be due to the difference in theclinical course of the disease in the elderly or to theinability of the elderly especially the very old to cough

Table 2: Treatment outcome in elderly and control group.

< 60 years 60 years 2 test p valueno. (%) no. (%)

New sputum positive n=1194 n=264Cure/Treatment completion 1066 (89.3) 218 (82.6) 9.25 < 0.01Default 44 (3.7) 17 (6.4) 4.09 < 0.05Death 32 (2.7) 22 (8.3) 19.37 < 0.01Failure 32 (2.7) 4 (1.6) 0.78 * > 0.05Transferred out 20 (1.6) 3 (1.1) 0.13 * > 0.05New sputum negative n=1003 n=409Cure/Treatment completion 877 (87.4) 311 (76.0) 28.28 < 0.01Default 53 (5.3) 32 (7.8) 3.31 > 0.05Death 40 (4.0) 56 (13.8) 43.17 < 0.01Failure 15 (1.5) 6 (1.5) 0.00 > 0.05Transferred out 18 (1.8) 4 (0.9) 0.79 * > 0.05New extrapulmonary n=306 n=32Cure/Treatment completion 289 (94.4) 25 (78.1) 11.70 < 0.01Default 13 (4.2) 4 (12.5) 2.58 * > 0.05Death 2 (0.7) 3 (9.4) 9.73 * < 0.01Failure 0 (0.0) 0 (0.0) - -Transferred Out 2 (0.7) 0 (0.0) - -

*Yates corrected Chi-square test

Table 3: Sputum conversion rate of total sputum positive cases in two groups of < 60 and 60 years age groups.

< 60 years 60 years 2 test p value

no. (%) no. (%)

Total sputum positive cases 1194 264 5.52 < 0.05

Sputum conversion at 2 months 943 (84.3%) 180 (77.9%)

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out sputum for examination.

The rate of favourable outcome (cured and treatmentcompleted) is less in the elderly and this has beenattributed to the higher rates of default and death inthe elderly. In the present study, incidence of defaultamong patients less than 60 years of age was 3.7%,5.3% and 4.2% in new sputum positive, new sputumnegative and extrapulmonary tuberculosis respectively.The default rates were 6.4, 7.8 and 12.5 in these groupsin geriatric patients. Similar increased default rateshave been seen in other studies too.9, 13 Poor compliancewith therapy, irregular intake of drugs, and interactionswith concomitant drugs for comorbid illnesses, lack ofmotivation and operational factors are considered to bethe principal reasons for default.8

Death in tuberculosis under the RNTCP is definedas death due to any cause during the period that thepatient is undergoing therapy for tuberculosis. Apartfrom the physiological causes of increased death inthe elderly, other factors like COPD, diabetes andmalignancy may be responsible for the increasedincidence of death in these elderly patients. This findingalso corroborates with the findings from other studies8.

Elderly patients are frequently intolerant to standardantitubercular drugs.14,15 This causes modifications inthe drug regimens resulting in the prescription ofregimens not potent to affect cure or sputum sterilization.This causes a decreased incidence of sputum conversionat 2 months. This has been shown by several studiesas also in the present one.16,17

An interesting observation was an equal or lowerincidence of failure in the elderly in the new sputumnegative and new sputum positive groups respectively.This apparent decrease in the incidence of failure casesis probably because of the high rates of default, anda decreased tendency to report to the health centersamong the elderly and their family members. Thisresults in most cases being classified as defaults.Indeed a major proportion of defaults will include failurecases.

ConclusionsClinical presentations of tuberculosis in the elderly

are different from those observed in the young. Itremains a diagnostic problem and is associated witha worse treatment outcome. However the control oftuberculosis in the elderly is essential for the successfulimplementation of the RNTCP. Due to these peculiarities

in geriatric tuberculosis, special attention should begiven to these patients in diagnosis, monitoring of sideeffects of drugs, arranging for social support and ininitiation of defaulter action.

References1 GOI National Health Policy 2002, Ministry of Health and Family

Welfare, Government of India, New Delhi.

2 Preiser WFE, Elaine Ostroff E. Universal design handbook.McGraw-Hill Professional, 2001.

3 Revised National Tuberculosis Control Programme. TechnicalGuidelines for Tuberculosis Control. Central TB Division:Directorate General of Health Services. Ministry of Health andfamily Welfare. New Delhi, India; May 1997: p 17-20.

4 Davies PD. The effects of poverty and ageing on the increasein tuberculosis. Monaldi Arch Chest Dis 1999; 54: 168-171.

5 Lesourd B, Mazari L. Nutrition and immunity in the elderly. ProcNut Soc 1999 ; 58: 685-695.

6 Ben-Yehuda A, Weksler ME. Host resistance and the immunesystem. Clin Geriatr Med 1994 ; 8: 701-711.

7 Pedrazzini T, Hug K, Louis J A. Importance of L3T4+ nd Lyt2+cells in the immunologic control of infection with Mycobacteriumbovis strain bacillus Calmette Guerin in mice. Assessment byelimination of T cells subsets in vivo. J Immunnol 1987;139:2032-2037.

8 Sood R. The problem of geriatric tuberculosis. J Indian AcadClin Med 5; 2: 156-162.

9 Gaur SN, Dhingra VK, Rajpal S, et al. Tuberculosis in theelderly and their treatment outcome under DOTS. Indian JTuberc 2004; 51: 83-88.

10 Khan MA, Kovnat DM, Bachus B, et al: Clinical and roentgenographic spectrum of pulmonary tuberculosis in the adult.Am J Med.1977; 62: 31-38.

11 Arora VK, Singla N, Sarin R. Profile of geriatric patients underDOTS in Revised National Tuberculosis Control Programme.Indian J Chest Dis Allied Sci 2003; 45: 231-235.

12 Pardeshi G, Deshmukh D. Disease characteristics andtreatment outcome in elderly tuberculosis patients on DOTS.Indian Journal of Community Medicine. 2007; 32 :292-294.

13 M Chan-Yeung, K Noertjojo, J Tan,et al. Tuberculosis in theelderly in Hong Kong. Int Tuberc Lung Dis 2002; 6: 771-779.

14 Chan CH, Or KK, Cheung W, Woo J. Adverse drug-reactionsand outcome of elderly patients on anti tuberculosischemotherapy with and without rifampicin. J Med 1995; 26:43-52.

15 Woo J, Chan HS. Therapeutic problems in the managemenrof elderly patients with tuberculosis. Adv Drug React ToxicolRev 1992; 11: 13-18.

16 Nakagawa M. Factors for the onset of and exacerbation oftuberculosis. Kakkakv 1999; 74: 747-52.

17 Davies PD. Tuberculosis in the elderly : Epidemiology andoptimal management. Drugs Aging 1996; 8: 436-444.

Ageing and Healthy Life Expectancy:Will the Extended Years be Spent in Good or PoorHealth?Johnson CS

Contemporary Issue

Abstract

Globally, a significant increase in the life expectancy has been observed. Improvement in life expectancy atall ages has allowed more elderly people to survive thus intensifying the ageing process. In India, the lifeexpectancy at birth has doubled in last 50 years. While extended life expectancy is a great achievement,it does not mean that extra years will be healthy. The present review highlights the concept of healthy lifeexpectancy, which can be considered a family of summary measures of population health, and provides adetailed review of the procedure used to calculate this health indicator. The health expectancy reflects thecurrent health of a real population adjusted for mortality levels and independent of age structure. It alsomeasures the number of remaining years, at a particular age, that an individual can expect to live in healthystate. This technique is a powerful tool for estimating the remaining years of life that a group of individualscan expect to live once they reach a certain age. In India, the second most populous country in the worldwith a rapidly growing population of older adults, there is an urgent need to estimate healthy life expectancy.

Globally, a significant increase in the life expectancyhas been observed. The combination of low fertility anddeclining mortality rates has resulted in large and rapidincreases in the elderly population, as successivelylarger cohorts step into old age. The transition fromhigh to low fertility is beginning to narrow the agestructure at its base and broaden the same at the top,contributing to the expected shift from a populationpyramid to a population tower. In addition, improvementin life expectancy at all ages has allowed more elderlypeople to survive thus intensifying the ageing process.The resulting higher growth in the proportion of theelderly within the population has been referred to asthe population ageing phenomenon.1 The proportionof the elderly in the world population is expected toincrease rapidly from 10.0% in 2000, 15.0% in 2025and 21.1% in 2050.2

It has been estimated that 70% of the world’selderly population are and will be in developing countries.3In India, the second most populous country in the world,

there is a rapidly growing population of older adults.The absolute number of the elderly in India is projectedto reach 137 million by the year 2021 a drastic increasefrom 81 million in 2002. The growth in the ageingpopulation in India has been faster than in otherdeveloping countries. In 1947, when India becameindependent of British rule, life expectancy waveredaround 32 years. The life expectancy has nearlydoubled to 63 years in 2000 with the projected increaseto 74 years by 2045-2050.1 While countries like Franceexperienced the shift over a period of 125 years, Indiahas seen this change in a greatly condensed time-span of approximately 35 years. While extended lifeexpectancy is a great achievement, it does not meanthat extra years will be healthy.

Health Challenges in India: Disability among theelderly

Ageing is said to put an increased burden on thesocial, economic, and health care demands of allcountries.1 A challenge to ensuring the quality of lifeof the ageing population is the double burden ofdiseases and disability, especially in developingcountries. These countries still struggle with infectiousdiseases and malnutrition along with the recent, rapidgrowth of non-communicable diseases such as diabetes,

Address for correspondance:Shanthi Johnson, PhD, RDProfessor, Faculty of Kinesiology and Health Studies,University of Regina,3737 Wascana Parkway, Regina, SK S4S 0A2email: [email protected]

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cardiovascular diseases, and hypertension, as well asdisability caused by age-related changes in physicalhealth, including mobility and ability to perform activitiesof daily living.3,4

Indian Census for the first time collected data ondisability in 1872. However, concerns related to under-reporting lead to the intermittent discontinuation of thegathering of this information through the nationalCensus. It was resumed again in the 2001 Census.In India, 75% of the elderly individuals are afflicted byphysical disabilities such as vision and hearing problems,locomotor and speech difficulties and mental healthissues.5 Gender differentials can be observed with ahigher percentage of females reporting vision andhearing disabilities. Males have reported highermovement and mental disabilities. Of these individuals,about 75% of disabled live in rural areas and only 25%reside in urban areas. Similarly, vision and mentaldisabilities have been higher in urban areas as comparedwith rural areas. On the other hand, hearing andmovement disabilities are higher in rural areas. Inmapping chronic disease patterns, similar trends areobserved for the prevalence of chronic diseases. Sixtypercent of old age population above 70 years in Indiaare reported to be having at least one chronic ailment,and 40% of rural elderly women and 36% of rural mensuffer from joint pains.6 In urban India, 25% of femaleand 20% of male elderly have high blood pressure.7However, the pattern of diseases between males andfemales differed and problems related to blood pressure,heart disease, urinary problems and diabetes weredominant in the urban areas.

Considering Active Ageing and Healthy LifeExpectancy

Given that people are living longer and theproportion of older adults in our society is higher,meeting these challenges requires a clear understandingof the health needs of older adults, innovative planningto develop programs, systems and structures whichwill support the health and welfare of the ageingpopulation, and substantial reforms and policies atglobal, national, and local levels.The World HealthOrganization (WHO) discussion paper on health andageing indicated that “we can afford to get old ifcountries, regions and international organizations enact‘active ageing’ policies and programmes that enhancethe health, independence, and productivity of olderwomen and men.3 The time to plan and to act is now”.3Active ageing is the process of optimizing opportunities

for physical, social and mental well-being throughoutthe life course in order to extend healthy life expectancy.Here active refers to continuing involvement in social,economic, spiritual, cultural and civic affairs, not justthe ability to be physically active; active ageing refersto the process of extending healthy life expectancy,productivity, and quality of life in old age. Similarsentiments have been conveyed in the 2002 InternationalStrategy for Action on Ageing and other nationalstrategies on aging such as the Indian National Policyon Older Persons (1999) and the Older Persons(Maintenance, Care, and Protection) Bill (2005).1

Healthy life expectancy can be considered afamily of summary measures of population health. Itis also understood that life expectancy alone does notserve the purpose of measuring health status any morefor the ageing population with increasing prevalence ofdisability and chronic diseases. Increased longevitywithout quality of life is an empty prize. Healthy lifeexpectancy combines information on mortality andmorbidity to indicate the health of a particular population.This summary measure or index also provides meaningfulhealth indicators at the population level of a particularcountry over time, allows for comparisons between andwithin countries or regions of the world, helps to identifyand quantify overall health inequalities amongsubpopulations based on age, gender, socioeconomicstatus, living situations (rural versus urban) and otherfactors, and helps identify and quantify effects ofmorbidity on overall population health. It is veryimportant to monitor the level of and change in physicaland/or mental well being of a population.

The concept of healthy life expectancy wasintroduced in the 1960s and was developed by Sullivanin 1970s. Recently, there has been great interest inthe estimation of health expectancy between bothpolicy makers and members of the research community.Within the last five years, there have been a numberof studies examining healthy life expectancy in theOECD countries (such as Canada, United States ofAmerica, & Australia), Brazil, Japan, Netherlands,Lithuania, Russian Federation, China and other partsof the world.8-15 These studies have shown differentialsin healthy life expectancy based on factors such asage, gender, socioeconomic status, regional variation,and lifestyle practices such as smoking. Given theavailability of healthy life expectancy data, nationalhealth plan goals in developed countries such as Japan,UK and USA, for example, have identified action plansand goals to prolong healthy life expectancy. In India,

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there is a paucity of studies examining healthy lifeexpectancy, with the exception of work done byMathers and co workers in 2001 and 2004.12 Whilethis evidence is very useful, more in-depth countryspecific analysis is needed to provide directions fornational health plans.

Healthy life expectancy is commonly analysedusing Sullivan method.16,17 In this method, a life tableis constructed from mortality data as the first step.A life table starts with a hypothetical cohort of 100,000persons, and uses the mortality data to calculate howmany of these are still alive at each age, and how manyyears will be lived in each age range. From this lifetable, life expectancy can be calculated by dividing thetotal number of years lived by the entire cohort of100,000.7 To calculate healthy life expectancy, theSullivan method allows for differentiation of the numberof years lived in good health versus ill health. Thismethod consists of subtracting the years lived in an“unhealthy” state from the years lived by a theoreticalcohort of 100,000 people under their current conditions.For estimating health expectancy by the Sullivanmethod, information on the age specific proportions ofthe population in unhealthy or disability states gatheredin cross-sectional surveys is required. These proportionsare prevalence measures of the actual current healthstatus of a real population, so for the disability it wouldbe a measure of the health composition of the observedpopulation measured by disability status. The healthylife expectancy or expectancy of a life free of disability,proposed by Sullivan, can be calculated using anadaptation of the traditional life table. The expectancyof healthy life will then reflect the state of health ofa determined population adjusted by the level ofmortality and,as in a life table, it is not affected bythe age structure of a population. The procedure forcalculating the Sullivan’s method is outlined below:

1. For each age/gender group obtain the life tableschedules and the expectation of life for the year ofinterest. Then, calculate:

nL

x = e xl

x-ex +

nlx+n

,

where nL

x is the conventional life table measure

of the average number of person years lived in the ageinterval x and x + n

2. Obtain the ill-health rate nd

x in each age-group

observed in a survey or census. Calculate the averagenumber of persons aged x to x + n living without ill-health in each age/gender group as:

nL

x (Healthy) =

nLx(1 -

nd

x),

3. Calculate life expectancy without ill-health asHealthy Life Expectancy = (

nL

x (Healthy) / l

x

Where the summation is from age x upwards.Hence the last equation presents the proportion ofyears lived in a healthy state.

In summary,

Healthy Life expectancy, ex = Tx (healthy) / l

x,

Un-healthy Life expectancy, ex = Tx (un-healthy) / l

x,

Total Life expectancy, ex = ex (healthy) + ex

(unhealthy)

Hence, Life Expectancy = Healthy Life Expectancy+ Unhealthy Life Expectancy, for example, 77 Yearsof Life = 75 Years of Healthy Years + 2 Years ofUnhealthy Years (2 years of unhealthy years do notmean the last 2 consecutive years of life).

Since the Sullivan method depends on the measuresof healthiness, many different dimensions of morbiditysuch as self-rated health, presence of long-termdisease or disability, and functional limitations couldbe used. The responses from self-rated health couldbe dichotomized into poor health and good health. Onecould also include information related to long-termdisease or disability that limits one’s activities of dailyliving. In the third estimate, researchers could take intoconsideration the continuum of the severity of functionallimitation such as the approach proposed by the WHOin the International Classification of Functionality,Disability and Health (ICF), in which the limitations ofactivities and functionality are not only viewed as aconsequence of illnesses, but principally as importantcomponents of an individual’s health. The final methodfor measuring state of health is a proposed extensionof the Sullivan method, which allows more than onehealthy life-defining event to be used simultaneously.18

In addition, a weight is attributed to each event,establishing the degree of its severity. To illustrate themethod, three criteria should be considered: (1)individuals do not have long-term disease or disability;(2) individuals have a long-term disease or disabilitythat does not limit daily activities; and (3) individualshave a long-term disease or disability that limit dailyactivities. The weights which characterize the degreeof severity in each situation will be calculated by agegroup, as the arithmetic mean of the scores offunctional limitations in a scale varying from 0 to 1,will be obtained from factor analysis. Given that manydifferent indicators of health can be used based on the

67


data availability in different countries, Sullivan methodof calculating healthy expectancy is not only possiblebut it is extremely important for program policy changesto address the health needs of the elderly population.The health expectancy reflects the current health ofa real population adjusted for mortality levels andindependent of age structure. It also measures thenumber of remaining years, at a particular age, thatan individual can expect to live in healthy state. Thistechnique is a powerful tool for estimating the remainingyears of life that a group of individuals can expect tolive once they reach a certain age. There is an urgentneed to estimate healthy life expectancy (HLE) in India.Specifically, how is the life expectancy distributednationally and regionally within India? What is therelationship between life expectancy and healthy lifeexpectancy within the Indian context? How doeshealthy life expectancy relate to factors such as age,gender and living situation (urban vs. rural)? Severalof the East Asian countries are dealing with similarageing phenomenon with a similar cultural context andfinancial constraints of the people and the health caresystem. Also, there is a need to carry out cross-culturalcomparison with other areas within South East Asiaor other developing countries. This will be a very usefulindicator for population level health planning useful forthe Government of India Planning Commission, as wellas the Ministry of Health at national and state level.Calculation of healthy life expectancy at the nationaland regional levels could lead to policy recommendationsfor the elderly in support of improved health practicesand access to quality health care. It is hoped that thepresent article will promote research and dialogue inthis area of healthy life expectancy.

References1. United Nations Population Division, Department of Economic

and Social Affairs, United Nations Secretariat. The Ageing ofthe World’s Population, 2002.

2. United Nations Statistics Division. Demographic Yearbook1999. United Nations, New York or Geneva [cited 2008 Mar23]. Available from: http://www.un.org/depts/unsd. http://www.un.org/News/Press/docs/2001/dev2342.doc.htm

3. World Health Organization. Healthy Ageing. A WHO publication,Geneva, 2001.

4. Manton KG, Stallard E, Corder LS. The dynamics of dimensionsof age-related disability 1982 to 1994 in the US elderlypopulation. J Gerontol A Biol Sci Med Sci 1998; 53: 59-70.

5. National Sample Survey Organisation. The aged in India: asocio-economic profile. A Socio-Economic Profile ReportNo.446 (52/25.0/3) http://mospi.nic.in/rept%20_%20pubn/446_final.pdf

6. Gupta I, Sankar D. Health of the elderly in India: a multivariateanalysis. Journal of Health & Population in DevelopingCountries / URL: http://www.jhpdc.unc.edu/Date Published 24June, 2003 p1-11. http://www.iegindia.org/dis_ind_46.pdf

7. Goyal RS. Disease and disability burden of elderly womenin India. Bold 2004; 15(1):19.

8. Andreev, E.M., McKee M., Shkolnikov, V.M. Health expectancyin the Russian Federation: a new perspective on the healthdivide in Europe. Bulletin of the World Health Organization,81:11 ;778-788.

9. Fukuda Y, Nakamura K, Takano T. Municipal health expectancyin Japan: decreased healthy longevity of older people insocioeconomically disadvantage areas. BMC Public Health2005; 5:65.

10. Groenewegan PP, Westert GP, Boshuizen HC. Regionaldifferences in healthy life expectancy in the Netherlands.Public health 2003; 17,424-429.

11. Kalediene R, Petrauskiene J. Healthy life expectancy—animportant indicator for health policy development in Lithuania.Medicina (Kaunas) 2004; 40 : 582-588.

12. Mathers CD, Sadana R, Salomon JA, et al. Healthy lifeexpectancy in 191 countries,1999. Lancet 2001; 357:1685-1691.

13. Mathers CD, Iburg KM, Salomon JA, et al. Global patterns ofhealthy life expectancy in the year 2002. BMC Public Health2004; 4:66.

14. Matthews JR, Jagger C, Hancock RM . Does socio-economicadvantage lead to a longer, healthier old age? Soc Sci Med2006; 62:2489-2499.

15. Romero DE, Leite IC, Szwarcwald CL. Healthy life expectancyin Brazil: applying the Sullivan method. Cad Saude Publica2005; 21:7-18.

16. Sullivan DF. A single index of mortality and morbidity. HSMHAHealth Rep 1971; 86:347-354.

17. Sullivan DF. Disability components for an index of health. Vitaland health statistics.Series 2(42) Rockville, MD. NationalCentre for Health Statistics. 1971.

18. Rajan SI, Mishra US. In: Agnihotri V, editor. Socio-economicprofile of rural India. New Delhi: Concept Publishing House;2002.

Review Article

Drug Induced Liver Diseases in the ElderlyChandy GM, Chandy RG

Department of Gastrointestinal Sciences,Christian Medical College,Vellore

Address for correspondence:George M Chandy,Department of Gastrointestinal Sciences,Christian Medical College, Vellore 632 004.email: [email protected]

IntroductionThe ever increasing exposure to drugs and an

increase in longevity in the population has given riseto an increase in incidence of drug-induced liverdiseases. Paralleling this, there has been an explosionin the basic science understanding in hepaticpharmacology, toxicology and immunology. Excitingnew developments have provided better insights, whichhave then helped us plan newer strategies to preventor deal with drug - induced liver disease. Informationabout apoptosis, cloning of numerous genes encodingfor P450 isoenzymes and the understanding of druginduced impairment of bile acid transporters in intacthepatocytes resulting in cholestasis have helped usunderstand the phenomenon of drug induced livertoxicity better. Translating this knowledge into practicalapplication– prevention and treatment is the excitingchallenge ahead of us.

Age and drug toxicity in liver

About 20% of hepatitis in the elderly is druginduced as compared to 2-5% in all age groups.1 Thereare several reasons for this:

1. Elderly tend to use more medications. TheNational Health and Nutrition ExaminationSurvey (NHANES) III data obtained between1988 and 1994 showed that 74% of people over65 years of age used prescription drugs asagainst 39% of adults between the ages 19and 64.2 The elderly are more likely to be onmultiple medications and this increases therisk of toxicity.3,4 51 % of individuals betweenages 65 and 74 used two or more medicationswhile 12% were on five or more drugs. Incontrast, only 19% of individuals studiedbetween ages 19 and 64 were on two or more

drugs.2

2. The elderly are likely to have more seriousillnesses and may have conditions like renalinsufficiency which predispose to drug toxicity.

3. With increase in age, there is more likelihoodof previous exposure to a drug and thepossibility of immunoallergic reactions.

4. Age related impairment of drug metabolism anddisposition can contribute to an increase inincidence of drug toxicity.

5. There is a gradual decline in renal functionwhich can potentiate drug accumulation inliver.5

6. Age related decline in blood flow to the livercan result in drug accumulation. Age dependentdecrease in hepatic blood flow has beenestimated to be 20 to 50%.

7. Decrease in liver mass and serum albumin,increase in body fat and decrease in musclemass alter the distribution of drugs in the tissuedistribution.6

8. Capillarisation, which is the loss of fenestraein sinusoidal endothelial cells with increasedbasement membrane formation in the spaceof Disse precedes fibrosis. Age-relatedcapillarisation can result in reduced oxidativedrug metabolism and hepatic drug clearance.7

Older patients on multidrug regimens with Isoniazid(INH), rifampicin or pyrazinamide have a high incidenceof elevated liver enzymes and/or liver toxicity. Byrd etal, in a study of 1000 patients treated with INH foundthat liver enzymes more than five times the upper limitof normal were more frequent in older patients.8

Clinical presentation

The presentation is often as an asymptomaticpatient with raised liver enzymes. A symptomaticpatient with jaundice merits immediate attention andcorrective action. Making a diagnosis in a patient on

68

69


hepatotoxic drugs is not difficult when there are signsof liver cell failure.

In an asymptomatic patient with enzyme elevation,it is important to take a history of intake of drugs likelyto be hepatotoxic. INH, used in the prevention ofpulmonary tuberculosis, antiepileptics like phenytoinand statins are known to cause elevation of enzymes.Studies have shown that 10 – 20 % of patients on INHand 2–5 % of patients on statins develop abnormal liverenzymes.9,10 Loss of appetite, fatigue, lassitude andabdominal discomfort are some of the symptomspatient presents with. In case of hypersensitivityreactions due to drugs, patients tend to have fever, rashand/or eosinophilia. Liver dysfunction due to non-steroidal anti inflammatory drugs (NSAIDs) is fortunatelyrare. NSAIDs can cause a spectrum of livermanifestations– asymptomatic elevation of liver enzymes,acute hepatitis, cholestatic hepatitis, and very rarely,acute hepatic failure.10,11 Elderly women are found tobe more prone to develop severe injury.

One of the criteria for diagnosis of drug – inducedliver disease is the recurrence on re-exposure to thedrug. This happens when the physician considers therisk-benefit and administers a drug known to haveresulted in raised liver enzymes earlier.12 The far morecommon situation is the inadvertent re-exposure of apatient to a drug that has previously resulted inhepatotoxicity, which went unnoticed or when thetreating physician is unaware of the event.13 Anotherexample of such a possibility is when a patient hasbeen on a combination drug and the offending componentis not identified.

The often quoted example of inadvertent re-exposure to a drug leading to hepatotoxicity ishalothane. Repeated exposure may occur owing tocontamination by halothane of the equipment used toadminister the anesthetic for a previous surgery.14

Treatment of tuberculosis and epilepsy requiresthe use of drugs known to cause liver injury. Co-administration of drugs that potentiate liver cell damageis often the cause for the presentation.

Acute icteric hepatitis (hepatocellular jaundice) isof grave significance as the mortality can be up to10 % irrespective of the drug. This is called Hy’s Lawafter the late Hy Zimmerman, who noted that mortalityfrom drug-induced hepatocellular jaundice rangedbetween 10 – 50%.15 Zimmerman also noted that inmost cases at risk of fatal outcome, alanine

aminotranferase was between 8 and 100 times theupper limit of normal. Such a presentation is associatedwith systemic symtoms, jaundice, and in more severecases, coagulopathy and encephalopathy indicative ofacute or fulminant hepatic failure.

It is important to be aware of the ‘signals’ ofhepatotoxicity. These signals have been classified byMaddrey WC as major, intermediate and minor asshown in Table 1.16

Table 1: Signals of hepatotoxicity.

Major: development of acute liver failuredevelopment of symptomsonset of clinically apparent jaundiceonset of ascites, encephalopathy,coagulopathy

Intermediate: ALT > 8 x ULNALT > 5 x ULNALT > 3 x ULN

Minor: any elevation of ALT (<3xULN) in anasymptomatic patient

(ALT – Alanine aminotransferase, ULN – Upperlimit of normal)

General observations

Some general observations can help the clinicianin dealing with drug induced liver disease. Diagnosisof drug induced liver disease is one of exclusion ofother etiologies. Hepatocellular injury is more likely tolead to a fatal outcome than cholestatic injury. Patientspresenting with drug induced hepatocellular injury don’tfare as well as those who suffer from acute viral hepatitisof similar severity. Histological evidence of injury is oftenmore severe than is suggested by clinical signs andbiochemical parameters. In patients in whom there isgranulomatous inflammation, liver disease is lesssevere than in those in whom hepatocellular injury isseen without granulomatous inflammation.

Several drugs cause chronic hepatitis whichcannot be distinguished from autoimmune hepatitis.17

If the correct diagnosis is not made, the offending drugwill not be withdrawn and corticosteriods may beinstituted. Such a course can lead to further damagewhile corticosteroids may temporarily reduce themanifestation of the injury. Nitrofurantoin and methyldopaare drugs that can cause liver injury which mimicsautoimmune hepatitis type 1.18 Most of the reported

70


cases were in women.

Management

The most important aspect of management istimely identification of toxic changes in the liver asevidenced by a rise in liver enzymes. The offendingdrug should be withdrawn immediately. If the patientneeds immediate or continued treatment for the condition,the physician should introduce another drug that is nothepatotoxic with caution. In elderly patients withtuberculosis, rifampicin and INH should be stopped anda combination of drugs like cycloserine and ethambutolcan be introduced. Some physicians favour a challengewith either rifampicin or INH. In our opinion, this isa risky option.

In the case of statins causing elevated liverenzymes, we would advocate continuing the drug whilemonitoring the patient closely. The incidence of raisedliver enzymes in patients on statins is 2–5 % andprobably dose related. With lovastatin, the incidenceof severe hepatitis is 1/1.4 million.19 Besides, thepresence of liver disease does not increase the riskof an adverse reaction with statins.20

The continued use of a drug like amiodarone maybe indicated even in the presence of raised liverenzymes, if it is the only drug available to prevent alethal event like ventricular tachycardia.21 The risk-benefit to the patient will have to be assessed in sucha situation. In the treatment of patients with epilepsy,phenytoin can be replaced with valproic Acid.

Among the antidotes that prevent significantdamage to the liver, the best known is N-acetylcysteine(NAC) which limits the injury by the toxic metabolicproducts of acetaminophen by generating glutathione.Most other adverse drug reactions do not have specifictherapy. Physicians often use steroids or ursodeoxycholicacid (UDCA) in the hope of hastening recovery but thereis inadequate data in literature to support such a courseof action. Though there are anecdotal reports of thesuccessful use of steroids or UDCA, there has beenno randomised control trial done so far. The onlyexception is in treating drug induced autoimmunehepatitis caused by alpha-methyldopa ornitrofurantoin.22,23

Acute liver cell failure

Acute liver cell failure is most dreaded complicationof drug hepatotoxicity. Liver injury may occur due to

a known hepatotoxin like acetaminophen or from anidiosyncratic reaction seen with drugs like halothane,isoniazid or phenytoin. In a patient with drug-inducedliver disease, jaundice as a presentation associatedwith raised liver enzymes is predictive of an increasedrisk of death. Bjornsson et al showed that age is arisk factor in the prognosis. Elderly patients have apoorer outcome.24 The important step in the managementof these patients is the early identification of theassociation and stopping the drug. Once jaundiceappears, prognosis is much worse. If bilirubin exceedstwice the upper limit of normal, the mortality rate is9.2%. Patients with predominantly cholestatic patternhave a lower risk for death (7.8%) while those withhepatocellular type injury have a higher risk (9.2%) oncethey become jaundiced.24

Liver transplantation

Liver transplantation is often the only solutionwhen faced with acute liver cell failure in the contextof drug hepatotoxicity. The authors saw an elderlygentleman who was on cloxacillin for a skin infectionand presented with jaundice as well as raised liverenzymes. He had developed liver cell failure. The onlytreatment option was liver transplantation. In view ofhis age and the overall prognosis, we were unable toconsider that option. Overall outcome following livertransplantation at advanced centers is not veryencouraging.25 An early diagnosis followed by correctivemeasures is the best option.

Summary

Drug induced hepatotoxicity in the elderly callsfor an early, effective response from the clinician.Identifying the problem and offending drug expeditiouslyis of paramount importance. In the case of drugs likeisoniazid, a quick withdrawal of the drug before bilirubinlevels rise is critical for success. With drugs likestatins which cause elevated liver enzymes, but rarelycause serious liver injury, the decision should be tocontinue treatment with close monitoring. In situationswhere the benefit far outweighs the risk of significantliver injury, the clinician will have to make a decisionbased on a careful risk-benefit analysis.

References1. Schenker S, Bay M. Drug disposition and hepatotoxicity in

the elderly. J Clin Gastroenterol 1994; 18: 232-237.

2. National Health and Nutrition Examination Survey (NHANES)III. Patterns of prescription drug use in the United States, 1988-

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94. In; 1988, http://www.cdc.gov/nchs/data/nhans/databriefs/preuse.pdf

3. May FE, Stewart RB, Cluff LE. Drug interactions and multipledrug administration. Clin Pharmacol Ther 1977; 22; 322-328.

4. Williamson J, Chopin JM. Adverse reactions to prescribeddrugs in the elderly: a multicentre investigation. Age Ageing1980; 9: 73-80.

5. Fehrman-Ekholm I, Skeppholm L. Renal function in the elderly(>70 years old) measured by means of iohexol clearance,serum creatinine, serum urea and estimated clearance.Scand J Urol Nephrol 2004: 38: 73-77.

6. Herrlinger C, Klotz U. Drug metabolism and drug interactionsin the elderly. Best Pract Res Clin Gastroenterol 2001; 15:897-918.

7. Schaffner F, Popper H. Capillarisation of hepatic sinusoidsin man. Gastroenterology 1963; 44: 239-242.

8. Byrd RB, Horn Br, Solomon DA, Griggs GA. Toxic effects ofisoniazid in tuberculosis prophylaxis. Role of biochemicalmonitoring in 1000 patients. J Am Med Assoc 1979; 241:1239-1241.

9. Boyer TD. Management of the patient with drug-induced liverdisease. In: Kaplowitz N, Deleve LD (eds). Drug-induced liverdisease. 2

nd ed, Informa healthcare, 2007,P 345-351.

10. Larrey D. Drug-induced liver disease. J Hepatol 2000; 32:77-88.

11. Maddrey WC. Drug-induced hepatotoxicity. J ClinGastroenterol 2005; 39: 583-589.

12. Boyer TD, Sun N, Reynolds TB. Allopurinol hypersensitivityvasculitis and liver damage. West J Med 1977; 126: 143-147.

13. Larrey D, Vial T, Miclaeff A, et al. Hepatitis associated withamoxicillin – clavulnic acid combination: reports of 15 cases.Gut 1992; 33: 368-371.

14. Varma RR, Whitezell RC, Iskandarani MM. Halothane hepatitis

without halothane: role of inapparent circuit contaminationand its prevention. Hepatology 1985; 5: 1159-1162.

15. Lewis JH. ‘Hy’s Law’, the ‘Rezulin rule’ and other predictorsof severe drug-induced hepatotoxicity: putting risk-benefit inperspective. Pharmacoepidemiol Drug Saf 2006; 15: 221-229.

16. Maddrey WC. Clinicopathological patterns of drug-inducedliver disease. In Kaplowitz N, Deleve LD (eds). Drug-inducedliver disease. 2

nd ed, Informahealthcare, 2007,P 229-230.

17. Maddrey WC, Boitnott JK. Drug-induced chronic liver disease.Gastroenterology 1977; 72: 1384-1353.

18. Black M, Rabin L, Schatz N. Nitrofurantoin-induced chronicactive hepatitis. Ann Intern Med 1980; 92: 62-64.

19. Tolman KG. The liver and lovastatin. Ann J Cardiol 2002;890: 1374-1380.

20. Chalasani N, Aljadhey H, Kesterson J, et al. Patients withelevated liver enzymes are not at higher risk for statinhepatotoxicity. Gastroenterology 2004; 126: 1287-1292.

21. Lewis JH, Ranard RC, Caruso A, et al. Amiodaronehepatotoxicity. Prevalence and clinicopathologic correlationsamong 104 patients. Hepatology 1989; 9: 679-685.

22. Sharp JR, Ishak KG, Zimmermann HF. Chronic active hepatitisand severe hepatic necrosis associated with nitrofurantoin.Ann Intern Med 1980; 92: 14-19.

23. Rodman JS, Deutsch DJ, Gutman SI. Methyldopa hepatitis: areport of six cases and review of the literature. Ann J Med1976: 60; 942-948.

24. Bjornsson E, Olsson R. Outcome and prognostic markers insevere drug-induced liver disease. Hepatology 2005; 42:481-489.

25. Barshes NR, Lee TC, Balkrishnam R, et al. Risk stratificationof adult patients undergoing orthotopic liver transplantationfor fulminant hepatic failure. Transplantation 2006; 81: 195-201.

Post Graduate Diploma in Geriatric MedicineSchool of Health Sciences

Indira Gandhi National Open UniversityMaidan Garhi, New Delhi-110068, India

www.ignou.ac.in

This programme is a Diploma Programme of one year duration. It is aimed at MBBS doctors. Thisprogramme will equip the in-service doctors with knowledge and skills in the field of Geriatric Medicineand further enable them to deal with the special problems faced by the elderly.The broad Objectives of the Programme are to: Upgrade the knowledge and skills for providing comprehensive health care to elderly Inculcate the inter-disciplinary approach for diagnosing and management of geriatric health

problems Improve the clinical, social and communication skills by providing hands on training in

medical colleges and district hospitals

Journal Scan

Influenza and pneumococcal vaccineuptake among nursing home residents inNottingham, England: a postalquestionnaire surveyAmir Shroufi, Joanna Copping, Roberto Vivancosand Richard CB Slack

BMC Geriatrics 2008, 8:11

Abstract (provisional)

Background: Previous studies have shown influenzavaccine uptake in UK nursing home residents to below. Very little information exists regarding the uptakeof pneumococcal vaccine in this population. Theformulation of policies relating to the vaccination ofresidents has been proposed as a simple step thatmay help improve vaccine uptake in care homes.

Methods: A postal questionnaire was sent to matronsof all care homes with nursing within the GreaterNottingham area in January 2006. Non respondentswere followed up with up to 3 phone calls.

Results: 30% (16/53) of respondents reported havinga policy addressing influenza vaccination and 15% (8/53) had a policy addressing pneumococcal vaccination.Seasonal influenza vaccine coverage in care homeswith a vaccination policy was 87% compared with 84%in care homes without a policy (p=0.47). The uptakeof pneumococcal vaccination was found to be low,particularly in care homes with no vaccination policy.Coverage was 60% and 32% in care homes with andwithout a vaccination policy respectively (p=0.06). Thisresult was found to be statistically significant onmultivariate analysis (p=0.03, R=0.46)

Conclusions: The uptake of influenza vaccine amongcare home residents in the Nottingham region isrelatively high, although pneumococcal vaccine uptakeis low. This study shows that there is an associationbetween pneumococcal vaccine uptake and theexistence of a vaccination policy in care homes, andhighlights that few care homes have vaccinationpolicies in place.

Adverse outcomes followinghospitalization in acutely ill older patientsRoger Y Wong and William C Miller


Abstract

Background: The longitudinal outcomes of patientsadmitted to acute care for elders units (ACE) are mixed.We studied the associations between socio-demographic and functional measures with hospitallength of stay (LOS), and which variables predictedadverse events (non-independent living, readmission,death) 3 and 6 months later.

Methods: Prospective cohort study of community-living, medical patients age 75 or over admitted to ACEat a teaching hospital.

Results: The population included 147 subjects, medianLOS of 9 days (interquartile range 5–15 days). Allreturned home/community after hospitalization. Justprior to discharge, baseline timed up and go test (TUG,P < 0.001), bipedal stance balance (P = 0.001), andclinical frailty scale scores (P = 0.02) predicted LOS,with TUG as the only independent predictor (P < 0.001)in multiple regression analysis. By 3 months, 59.9%of subjects remained free of an adverse event, and by6 months, 49.0% were event free. The 3 and 6-monthmortality was 10.2% and 12.9% respectively. Almostone-third of subjects had developed an adverse eventby 6 months, with the highest risk within the first 3months post discharge. An abnormal TUG score wasassociated with increased adjusted hazard ratio [HR]1.28, 95% confidence interval [CI] 1.03 to 1.59, P =0.03. A higher FMMSE score (adjusted HR 0.89, 95%CI 0.82 to 0.96, P = 0.003) and independent living beforehospitalization (adjusted HR 0.42, 95% CI 0.21 to 0.84,P = 0.01) were associated with reduced risk of adverseoutcome.

Conclusion:Some ACE patients demonstrate furtherfunctional decline following hospitalization, resulting inloss of independence, repeat hospitalization, or death.Abnormal TUG is associated with prolonged LOS andfuture adverse outcomes.

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Assessing control of postural stability incommunity-living older adults usingperformance-based limits of stabilityMyriam Jbabdi, Patrick Boissy, and Mathieu Hamel


Abstract

Background: Balance disability measurements routinelyused to identify fall risks in frail populations have limitedvalue in the early detection of postural stability deficitsin community-living older adults. The objectives of thestudy were to 1) measure performance-based limits ofstability (LOS) in community-living older adults andcompare them to theoretical LOS computed from dataproposed by the Balance Master® system, 2) explorethe feasibility of a new measurement approach basedon the assessment of postural stability during weight-shifting tasks at performance-based LOS, 3) quantifyintra-session performance variability during multipletrials using the performance-based LOS paradigm.

Methods:Twenty-four healthy community-living olderadults (10 men, 14 women) aged between 62 to 85(mean age ± sd, 71.5 ± 6 yrs) participated in the study.Subjects’ performance-based LOS were established byasking them to transfer their body weight as far aspossible in three directions (forward, right and left)without changing their base of support. LOS werecomputed as the maximal excursion of the COP ineach direction among three trials. Participants thenperformed two experimental tasks that consisted incontrolling, with the assistance of visual feedback, theircentre of pressure (COP) within two predefined targetsset at 100% of their performance-based LOS. For eachtasks 8 trials were performed. Ground reaction forcesand torques during performance-based LOS evaluationand experimental tasks were recorded with a forceplate. Sway area and medio-lateral mean COPdisplacement speed variables were extracted from forceplate recordings.

Results: Significant differences between theoreticalLOS computed from maximum leaning angles derivedfrom anthropometric characteristics and performance-based LOS were observed. Results showed that amotor learning effect was present as the participantsoptimized their weight-shifting strategy through the firstthree trials of each task using the visual biofeedback

provided on their COP. Reliable measures of controlof postural stability at performance-based LOS can beobtained after two additional trials after the learningphase (0.69 > ICC > 1.0).

Conclusion:Establishing performance-based LOSinstead of relying on estimations of theoretical LOSoffers a more individualized and realistic insight on thetrue LOS of an individual. Performance-based LOS canbe used as targets during weight-shifting postural taskswith real time visual feedback of the COP displacementto assess postural stability of community-living olderadults. In order to obtain reliable results, a learningphase allowing subjects to learn how to control theirCOP displacement is needed.

Falls in advanced old age: recalled fallsand prospective follow-up of over-90-year-olds in the Cambridge City over-75s CohortstudyJane Fleming, Fiona E Matthews, Carol Brayneand the Cambridge City over-75s Cohort (CC75C)study collaboration


Abstract

Background:The “oldest old” are now the fastestgrowing section of most western populations, yet thereare scarcely any data concerning even the commonproblem of falls amongst the very old. Prospective datacollection is encouraged as the most reliable methodfor researching older people’s falls, though in clinicalpractice guidelines advise taking a history of anyrecalled falls. This study set out to inform serviceplanning by describing the epidemiology of falls inadvanced old age using both retrospectively andprospectively collected falls data.

Methods: Design: Re-survey of over-90-year-olds in alongitudinal cohort study – cross-sectional interviewand intensive 12-month follow-up.

Participants and setting: 90 women and 20 menparticipating in a population-based cohort (aged 91–105 years, in care-homes and community-dwelling)recruited from representative general practices inCambridge, UK

Measurements: Prospective falls data were collectedusing fall calendars and telephone follow-up for one

74


year after cross-sectional survey including fall history.

Results: 58% were reported to have fallen at least oncein the previous year and 60% in the 1-year follow-up.The proportion reported to have fallen more than oncewas lower using retrospective recall of the past yearthan prospective reports gathered the following year(34% versus 45%), as were fall rates (1.6 and 2.8 falls/person-year respectively). Repeated falls in the pastyear were more highly predictive of falls during thefollowing year – IRR 4.7, 95% CI 2.6–8.7 – than justone – IRR 3.6, 95% CI 2.0–6.3, using negative binomialregression. Only 1/5 reportedly did not fall during eitherthe year before or after interview.

Conclusion: Fall rates in this representative sampleof over-90-year-olds are even higher than previousreports from octogenarians. Recalled falls last year,particularly repeated falls, strongly predicted falls duringfollow-up. Similar proportions of people who fell werereported by retrospective and prospective methodscovering two consecutive years. Recall methods mayunderestimate numbers of repeated falls and the extentof recurrent falling. Professionals caring for people ofadvanced age can easily ask routinely whether someonehas fallen at all, or more than once, in the past yearto identify those at high risk of subsequent falls.

The accuracy of the MMSE in detectingcognitive impairment when administeredby general practitioners: A prospectiveobservational studyPatrizio Pezzotti, Silvia Scalmana, AntonioMastromattei and Domenico Di Lallo

BMC Family Practice 2008, 9:29

Abstract

Background: The Mini-Mental State Examination(MMSE) has contributed to detecting cognitiveimpairment, yet few studies have evaluated its accuracywhen used by general practitioners (GP) in an actualpublic-health setting. We evaluated the accuracy ofMMSE scores obtained by GPs by comparing themto scores obtained by Alzheimer’s Evaluation Units(UVA).

Methods: The study was observational in design andinvolved 59 volounter GPs who, after having undergonetraining, administered the MMSE to patients withsymptoms of cognitive disturbances. Individuals who

scored [less than or equal to]24 (adjusted by age andeducational level) were referred to Alzheimer’s EvaluationUnits (UVA) for diagnosis (including the MMSE). UVAswere unblinded to the MMSE score of the GP. Tomeasure interrater agreement, the weighted Kappastatistic was calculated. To evaluate factors associatedwith the magnitude of the difference between pairedscores, a linear regression model was applied. Toquantify the accuracy in discriminating no cognitiveimpairment from any cognitive impairment and fromAlzheimer’s disease (AD), the ROC curves (AUC) werecalculated.

Results: For the 317 patients, the mean score obtainedby GPs was significantly lower (15.8 vs. 17.4 for theUVAs; p<0.01). However, overall concordance was good(Kappa=0.86). Only the diagnosis made by the UVAwas associated with the difference between pairedscores: the adjusted mean difference was 3.1 for nocognitive impairment and 3.8 for mild cognitiveimpairment. The AUC of the scores for GPs was 0.80(95%CI: 0.75-0.86) for discriminating between noimpairment and any impairment and 0.89 (95%CI: 0.84-0.94) for distinguishing patients with AD, though theUVA scores discriminated better.

Conclusions: In a public-health setting involving patientswith symptoms of cognitive disturbances, the MMSEused by the GPs was sufficiently accurate to detectpatients with cognitive impairment, particularly thosewith dementia.

Effect of influenza and pneumococcalvaccines in elderly persons in years of lowinfluenza activityBrith Christenson, Karlis Pauksen and Staffan PESylvan

BMC Neurology 2008, 8:12

Abstract

Background: The present prospective study wasconducted from 2003–2005, among all individuals 65years and older in Uppsala County, a region with 300000 inhabitants situated close to the Stockholm urbanarea. The objective of this study was to assess thepreventive effect of influenza and pneumococcalvaccination in reducing hospitalisation and length ofhospital stay (LOHS) even during periods of lowinfluenza activity. The specificity of the apparent vaccine

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associations were evaluated in relation to the influenzaseasons.

Results: In 2003, the total study population was 41,059,of which 12,907 (31%) received influenza vaccine ofthese, 4,447 (11%) were administered the pneumococcalvaccine. In 2004, 14,799 (34%) individuals received theinfluenza vaccine and 8,843 (21%) the pneumococcalvaccine and in 2005 16,926 (39%) individuals were giventhe influenza vaccine and 12,340 (28%) thepneumococcal vaccine.

Our findings indicated that 35% of the vaccinated cohortbelonged to a medical risk category (mainly thosepersons that received the pneumococcal vaccine). Dataon hospitalisation and mortality during the 3-year periodwere obtained from the administrative database of theUppsala county council.

During the influenza seasons, reduction of hospitaladmissions and significantly shorter in-hospital stay forinfluenza was observed in the vaccinated cohort (below80 years of age). For individuals who also had receivedthe pneumococcal vaccine, a significant reduction ofhospital admissions and of in-hospital stay was observedfor invasive pneumococcal disease and for pneumococcalpneumonia. Effectiveness was observed for cardiacfailure even in persons that also had received thepneumococcal vaccine, despite that the pneumococcalvaccinated mainly belonged to a medical risk category.Reduction of death from all causes was observed duringthe influenza season of 2004, in the 75–84-year oldage group and in all age-groups during the influenzaseason 2005.

Conclusion: The present study confirmed the additiveeffect of the two vaccines in the elderly, which wasassociated with a reduced risk in hospitalisation anda reduction in mean LOHS in seasons with lowinfluenza activity.

Effects of intensive home visitingprograms for older people with poor healthstatus: A systematic reviewAns Bouman, Erik van Rossum, Patricia Nelemans,Gertrudis IJM Kempen and Paul Knipschild

BMC Health Services Research 2008, 8:74

Abstract

Background: Home visiting programs have been

developed aimed at improving the health and independentfunctioning of older people. Also, they intend to reducehospital and nursing home admission and associatedcost. A substantial number of studies have examinedthe effects of preventive home visiting programs on olderpeople living in the community; the findings have beeninconsistent. The objective of this review was to assessthe effectiveness of intensive home visiting programstargeting older people with poor health or otherwise withfunctional impairments.

Methods: A search for literature was based on includedtrials from four reviews on the effectiveness of homevisits published after 2000 and on a database searchof Cinahl, the Cochrane Central Register of ControlledTrials, Embase, Medline and PsycINFO from 2001onwards. We also manually searched reference listsfrom potentially relevant papers. Randomized controlledtrials were included assessing the effectiveness ofintervention programs consisting of at least four homevisits per year, an intervention duration of 12 monthsor more, and targeting older people (aged 65 years andover) with poor health. Two reviewers independentlyabstracted data from full papers on programcharacteristics and outcome measures; they alsoevaluated the methodological quality.

Results: The search identified 844 abstracts; eightpapers met the inclusion criteria. Seven trials were ofsufficient methodological quality; none of the trialsshowed a significant favorable effect for the mainanalysis comparing the intervention group with thecontrol group on mortality, health status, service useor cost. The inclusion of less-intensive interventionprograms for frail older persons would not have exerteda great influence on the findings of our review.

Conclusion: We conclude that home visiting programsappear not to be beneficial for older people with poorhealth within the health care setting of Westerncountries.

Instructions for AuthorsJournal of the Indian Academy of Geriatrics is an

official publication of the Indian Academy of Geriatrics. Thispeer-reviewed Journal would be published quarterly (March,June, September and December). It publishes regulararticles-original clinical studies and experimentalinvestigations, review of basic and clinical topics, briefcommunications, case reports concerning all aspects ofGeriatrics.

General information

Regular Articles are full length papers that addressresearch questions with exhaustive study design andmethodology. The entire manuscript including abstract andreferences should not exceed 15 typed pages in doublespace and should not contain more than 30 references.

Brief Communications should contain not more than2000 words (including abstract, figures, tables andreferences) describing important new observations inGeriatrics.

Review of basic and clinical topics of interest to thereadership will be solicited by the editors. The length ofreview articles should not exceed fifteen typed pages.

Case reports should be limited to 1200 words,should not have more than 4 authors and should notcontain over 2 illustrations and 10 references.

Letters to the editor containing interestingobservations and comments on the articles published inthe journal are welcome for publication. Due care shouldbe taken in the formation of the letter to avoid anymisunderstanding. The replies to such letters will also bepublished as and when received from the authors. Theletter and the reply should not exceed 300 words andshould not contain more than 5 references.

The manuscript would be forwarded to an associateeditor and two reviewers. Manuscripts that are outside therange of interest of Journal of The Indian Academy ofGeriatrics readership or that fail to satisfy the technicalrequirements would be rejected and returned to authorswithout further review. Only glossy prints and photographsof rejected manuscripts would be returned to reduceexpenditure on mailing. The rejected manuscript would bedestroyed. Manuscript returned to authors for modificationshould be returned to editorial office as early as possiblebut not later than 3 months, after which the article wouldbe filed and not considered for publication. The editorialboard reserves the right to assess suitability of the language,modify the letter and text, improve the photographs andillustrations to enhance clarity of expression and

presentation without affecting the message and meaningbeing conveyed by the article.

Manuscript preparation

Submit an original manuscript and three photocopies,typed double spaced in letter quality print on one side onlyof standard (8 ½ x 11 inch) white bond paper. Manuscriptsshould be organized as follows; title page, abstract,introduction, methods, results, discussion,acknowledgements, reference, tables and figure legends.Cite references and figures by numbers in the text.

All weights and measures must be given in metricunits. Avoid use of full stops in the middle of abbreviations(ECG, not E.C.G.).Serial number of each reference shouldbe superscripted and not written in parenthesis. It isadvised to follow the uniform requirements for manuscriptsubmission in Biomedical journals i.e as mentioned inBMJ 1988; 296

Title page

The title should be brief and comprehensive,preferably less than fifteen words with the first letter of eachword typed in capitals. The name of the authors (initialsfollowed by surnames) should be written in continuationfollowed by the name of the department and the Institutionwhere the study was carried out. A footnote may be addedto indicate address for correspondence and e-mail address.All authorship must fulfill Vancouver agreement (BMJ 1991;302)

Abstract

State the problem considered, methods, results andconclusions in less than 250 words, and key words. Theabstract should consist of four paragraphs, labeledBackground, Methods, Result and Conclusions.

Tables

Type double-spaced on separate sheets of standardsized white bond paper. Each table should have a title andbe numbered in the order of appearance in the text. Itshould be brief and self explanatory. Abbreviations, if used,should be explained in the footnote. The data presentedshould not be duplicated in the text and figures. Usesuperscript letters to indicate footnotes typed at the bottomof the table.

Figures

Four complete sets of glossy photographs of allfigures including graphs, black and white and colorphotographs must be submitted. The use of color

77


illustrations is encouraged, but authors should contact theeditor prior to their preparation for advice and assistance.All figures should be clearly labeled on the back with a leadpencil and an arrow indicating the top edge of the figure.Photomicrograph should be sized to fit one column (8cm)or two columns (17cm); the maximum plate size is 17 x22 cm.

Graphs must be of professional quality. Computergenerated graphs should be of laser quality. High contrastprints of roentgenographic photographs and electronmicrographs are essential. Clear photocopies of the figuresshould be included with the original and each copy of themanuscript.

References

References should be typed at the end of the text indouble space following the Vancouver style and numberedin the order of appearance in the text, with only onereference to a number. Citation of unpublished observationsor personal communications (include separatelypermission to quote from appropriate individual) shouldbe placed in the text in parenthesis. Reference number inthe text should be typed as superscript and not in thebrackets. e.g. Dyslipidemia in elderly10.It is desired tofollow the style and pattern for abbreviations as given inIndex Medicus.

Journal article

Luke RG, Jones P and Diethelm AG. Hypertensionin elderly. Am J Med1982; 75; 88-95

Abstract

Yoo KH, Norwood VF, Chevalier RL. Regulation ofAging (Abstract).Nature1995; 65:82-91

Chapters in Book

John T Potts: Disorders of the parathyroid gland;Harrison’s Principles of Internal Medicine,15 edn.,Braunwald, Fauci, Kasper, Hauser,et al (eds),McGrawHill,2001,p2224-6

General instructions

Use generic names of drugs. Do not use abbreviationsin the title. Define unusual abbreviations with the first usein the body of the manuscript. Text footnotes should betyped on a separate page. For references the names ofall authors should be mentioned instead of using et al.The abbreviations used for name of a particular journalshould be standard.

Manuscript on Compact Disks

Authors must submit compact disk of the final versionof their manuscripts along with the printout of the revised

manuscript in Microsoft word. Identify the diskette byproviding journal name, manuscript number, senior author’sname, manuscript title, name of computer file, type ofhardware, operating system and version number, andsoftware program and version number. The journal doesnot assume responsibility for errors in conversion ofcustomized software, new software, and special characters.Mathematics and tabular material will be processed in thetraditional manner. PDF format submission is not desired.The photographs should be submitted in .jpg file format.

Manuscripts submitted should not have beenpublished earlier or be under simultaneousconsideration for publication by any other journal. Astatement to this effect (Authors’ Declaration) signed by theauthors should accompany each manuscript. Violationmay lead to a published retraction of the article by theJournal and other actions as deemed necessary by theeditor. Accepted manuscripts become the permanentproperty of the Journal and may not be reproduced, inwhole or in part, without the written permission of the editor.

Studies involving intervention in human subjects oranimals should have received the approval of the institutionalethics committee. A statement to this effect must beincluded in the manuscript text. If the institution has noformal ethics committee, a statement signed by the authorsthat the terms of the Helsinki Agreement have beenadhered to will be necessary.

We encourage authors to submit manuscripts inelectronic version, as a Word document to e-mail address;accompanying Figures should be as .jpg file attachments.Printed copies need not be submitted then. If the articleis accepted, they will be required to submit Figures as hardcopies or in high-resolution format. A printed copy of thesigned Authors’ Declaration must be submitted if the articleis accepted for publication.

Manuscript for publication in Journal of The IndianAcademy of Geriatrics should be sent to Dr. Arvind Mathur,Editor, Journal of The Indian Academy of Geriatrics,Room No. 9, Department of Medicine, Mathura DasMathur Hospital, Shastri Nagar, Jodhpur 342003Rajasthan, India, Fax: 0291-2441678; Email -journal_geriatrics@ yahoo.com. The editor and thepublisher disclaim any responsibility or liability for thestatements made and opinion expressed by authors.

All manuscripts submitted to this Journal must beaccompanied by the declaration signed by all authors,before they can be processed editorially. If it cannot besigned by any authors, the principal or correspondingauthor can take responsibility and sign on behalf. Thisdocument can be photocopied as required for submission.

THE INDIAN ACADEMY OF GERIATRICS (IAG)

MEMBERSHIP APPLICATION FORM

Name _____________________________________________Date of Birth_____________________Sex__________

Educational Qualification ___________________________________________________________________________

University ________________________________________________________________________________________

Present position & Office Address __________________________________________________________________

________________________________________________________________________________________

Telephone No. _____________________________________________________________________________

Email ____________________________________________________________________________________

Fax ______________________________________________________________________________________

Type of Membership - Life member Regular / Life Member Associate Life Member Fees Rs. 2000/- by D.D./Cheque(Out Station Cheques, add Rs. 50/- extra as bank charges) drawn in favour of Secretary, The Indian Academyof Geriatrics.

I agree to become a member and if I admitted to abide by the rules and regulation of the association.

Signature of the applicant

Mail to : The Secretary, THE INDIAN ACADEMY OF GERIATRICS Dr.Shanthi G.S., AB-77,1st Street, Anna Nagar, Chennai, Tamilnadu,600040-India.

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The Indian Academics of Geriatrics was formed on 26th April 2002 atChennai and has been registered under the Indian Society Act. TheAcademy has been formed to associate Physicians practicing thescience and art of Geriatrics.

The Academy has the following objectives:

• To conduct meaningful research in geriatrics and to assist inproviding adequate technical knowledge in geriatrics

• To organize scientific programs, conferences, workshops andtraining programs in geriatrics

• To print and publish a journal, and other literature relating to thescience of geriatrics.

• To encourage scientific research and experimental work ongeriatrics & gerontology.

RULES AND REGULATIONS REGARDING ADMISSIONLife Member - RegularAny person with post graduate degree such as MD, or DNB in Geriatrics / Internal Medicine with training orexperience in Geriatrics, from any institution (or) University, recognised by the MCI or by the governing body ofthe Association, shall be enrolled. Any person qualified to be Life member regular, could be enrolled after payingone time subscription fees, that is non refundable.

Life Member - AssociateAny person having basic degree recognised by the MCI, who is not eligible for life membership regular and personswith post graduate qualification in allied non medical discipline like Psychology, Sociology and Social work shallbe enrolled as Life Member associate.Associate members have no voting right nor the right to propose, second or contest for any office of the ExecutiveCommittee.

THE INDIAN ACADEMY OF GERIATRICS

National Executive Committee(April 2007-March 2009)

PatronsDr. S. Sachdeva

Prof. V.S. NatarajanProf. R. Sivaraman

PresidentDr. I. S. Gambhir

Past PresidentDr. B. Krishnaswany

SecretaryDr. Alka Ganesh

Vice PresidentDr. Sandhya Kamath

TreasurerDr. Prasad Mathews

Editor JIAGDr. Arvind Mathur

Joint SecretariesDr. Tapas Das

Dr. Shanthi Raju

Members of Executive CommitteeDr. D.N. Mohrana

Dr. G.B. GuptaDr. M. SarkarDr. D. DalusDr. Y.S. Raju

Special Invitee Dr. A.B. Dey

Registered OfficeThe Joint Secretary, Indian Academy of Geriatrics

AB-77(New No. 16),1st Street, Anna Nagar, Chennai, Tamilnadu,600040-IndiaTel. : 93800 91192

Abstract Submission

Last Date for abstract submlmon - 30 October 2008All abstracts must be submitted by post/ email to congress secretriat Please read the instructions carefully,as abstracts not submitteit accorduig to these instructions will not be accepted.

Important Note

Authors of abstracts accepted for presentation MUST he registered delegates and be responsible for allexpanses incurred in the production of their presentations. travel and accommodation during the congress.

Please mention approptlately it you would like to present the paper as oral presentation. There are onlylimited slots available for oral pressntatiort.

Structure of Abstracts

Abstracts should comprise tIre following elements, with each begining a new paragraph.• Tttie : The abstract title should be all capitals.• Authors : Authors’ names should be in the surname first format and Institutional affiliations should be indicated.• Affiliation: All affiliations should contain institution and city.• Abstract taxt: The lout must be arranged according to the Iollowtrig headlines

lntroductionsMethodResultConclusion

Instructions for ORAL papers presentationThis is a 8-minutes presentation with 2 minutes bir questions from the audience.

• InstructIons for POSTER presentationThe poster should have a dear heeding which includes the title and name of authors. The font site should

be large enough to be read from a distance of 5 feet. Poster boards measuring 3 feet (wide) and 4 feet(high) will be provided.

Submission and notification -

1. All abstracts submitted will be acknowledged through a-mail upon raceipt. Please contact Conference.Secretariat If you do not receive the acknowledgement e-mail.

2. The organizing committee reserve the tight to make changen to all oral and poster presentation schedules.3. The Judges decisions are final4. Papers Selected for Best Paper Award Sussion will be inform by e-mail preferably. indicate if need it

by postal address.

GERICON - 200820TH & 21ST December 2008

Hotel Babylon, Raipur

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Send the Form duly singed alongwith Cheque/D.D. add Rs. 75/- for outstation cheque.

Address: Conference SecretariatDr. G.B. Gupta, MD, DMC/183, Tagora Nagar, Raipur (C.G.) 492 001Email: [email protected] No.: 0771-4263722, 2426668Fax No.: 0771-4269618Mobile: 099939 00004

* You will receive registration confirmation via e-mail/mail.* Cheque/D.D. in favour of GERICON - 2008, Payable at Raipur* You may available services of our official travel agent for prior conferncial booking of accomodation, local taxies and tours & etc.

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up to 30th September up to 30th November spot

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* Registration kits may not be available for spot registration**P.G. Students should attach a certificate from their H.O.D.

Hotel in Raipur Hotel Catagory Approximate Rate

A 2500/- and aboveB 1600/- to 2200/-C 1200/- to 1500/-

Have confirmed, Hotel booking to avoid last miniut problem*Taxes etc, Separate

• Hotel Babylon • Hotel Sudha Regency• Hotel Golden Tulip • Hotel Grand International• Hotel Chhattisgarh • Hotel Simran• Hotel Aditya • Hotel Celebration• Hotel Mayura • Hotel Shard• Hotel Grand Arjun • Hotel Satlej

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