Publications by authors named "Nathalie de Rekeneire"

64 Publications

Prevalence and factors associated with physical function limitation in older West African people living with HIV.

PLoS One 2020 22;15(10):e0240906. Epub 2020 Oct 22.

Univ. Bordeaux, INSERM, Bordeaux Population Health Research Center, UMR 1219, Bordeaux, France.

Although physical function decline is common with aging, the burden of this impairment remains underestimated in patients living with HIV (PLHIV), particularly in the older people receiving antiretroviral treatment (ART) and living in sub-Saharan Africa (SSA). PLHIV aged ≥50 years old and on ART since ≥6 months were included (N = 333) from three clinics (two in Côte d'Ivoire, one in Senegal) participating in the International epidemiological Databases to Evaluate AIDS (IeDEA) West Africa collaboration. Physical function was measured using the Short Physical Performance Battery (SPPB), the unipodal balance test and self-reported questionnaires. Grip strength was also assessed. Logistic regression was used to identify the factors associated with SPPB performance specifically. Median age was 57 (54-61) years, 57.7% were female and 82.7% had an undetectable viral load. The mean SPPB score was 10.2 ±1.8. Almost 30% had low SPPB performance with the 5-sit-to-stand test being the most altered subtest (64%). PLHIV with low SPPB performance also had significantly low performance on the unipodal balance test (54.2%, p = 0.001) and low mean grip strength (but only in men (p = 0.005)). They also showed some difficulties in daily life activities (climbing stairs, walking one block, both p<0.0001). Age ≥60 years (adjusted OR (aOR) = 3.4; CI95% = 1.9-5.9,), being a female (aOR = 2.1; CI95% = 1.1-4.1), having an abdominal obesity (aOR = 2.1; CI95% = 1.2-4.0), a longer duration of HIV infection (aOR = 2.9; CI95% = 1.5-5.7), old Nucleoside reverse transcriptase inhibitors (NRTIs) (i.e., AZT: zidovudine, ddI: didanosine, DDC: zalcitabine, D4T: stavudine) in current ART (aOR = 2.0 CI95% = 1.1-3.7) were associated with low SPPB performance. As in western countries, physical function limitation is now part of the burden of HIV disease complications of older PLHIV living in West Africa, putting this population at risk for disability. How to screen those impairments and integrate their management in the standards of care should be investigated, and specific research on developing adapted daily physical activity program might be conducted.
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December 2020

Prevalence and factors associated with severe depressive symptoms in older west African people living with HIV.

BMC Psychiatry 2020 09 10;20(1):442. Epub 2020 Sep 10.

Bordeaux Population Health Research Center, Univ. Bordeaux, Inserm, UMR 1219, F-33000, Bordeaux, France.

Background: Depression is one of the most common psychiatric disorders in people living with HIV (PLHIV). Depression has a negative impact on both mental and physical health and is mainly associated with suboptimal HIV treatment outcomes. To encourage successful aging and the achievement of the 3 × 90 objectives in older PLHIV, the psychological domain must not be neglected. In this context and as data are scarce in West Africa, this study aimed to evaluate the prevalence and the factors associated with severe depressive symptoms in older PLHIV living in this region of the world.

Methods: Data from PLHIV aged ≥50 years and on ART since ≥6 months were collected in three clinics (two in Côte d'Ivoire, one in Senegal) participating in the West Africa International epidemiological Databases to Evaluate AIDS (IeDEA) collaboration. The severity of depressive symptoms was measured using the Center for Epidemiological Studies Depression scale (CES-D), and associated factors were identified using logistic regressions.

Results: The median age of the 334 PLHIV included in the study was 56.7 (53.5-61.1), 57.8% were female, and 87.1% had an undetectable viral load. The prevalence of severe depressive symptoms was 17.9% [95% Confidence Interval (95% CI): 13.8-22.0]. PLHIV with severe depressive symptoms were more likely to be unemployed (adjusted Odd Ratio (aOR) = 2.8; 95% CI: 1.4-5.7), and to be current or former tobacco smokers (aOR = 2.6; 95% CI: 1.3-5.4) but were less likely to be overweight or obese (aOR = 0.4; 95% CI: 0.2-0.8).

Conclusions: The prevalence of severe depressive symptoms is high among older PLHIV living in West Africa. Unemployed PLHIV and tobacco smokers should be seen as vulnerable and in need of additional support. Further studies are needed to describe in more details the reality of the aging experience for PLHIV living in SSA. The integration of screening and management of depression in the standard of care of PLHIV is crucial.
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September 2020

Impact of Baseline Fatigue on a Physical Activity Intervention to Prevent Mobility Disability.

J Am Geriatr Soc 2020 03 22;68(3):619-624. Epub 2019 Dec 22.

Center for Aging and Population Health, Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.

Objectives: Our aim was to examine the impacts of baseline fatigue on the effectiveness of a physical activity (PA) intervention to prevent major mobility disability (MMD) and persistent major mobility disability (PMMD) in participants from the Lifestyle Interventions and Independence for Elders (LIFE) study.

Design: Prospective cohort of individuals aged 65 years or older undergoing structured PA intervention or health education (HE) for a mean of 2.6 years.

Setting: LIFE was a multicenter eight-site randomized trial that compared the efficacy of a structured PA intervention with an HE program in reducing the incidence of MMD.

Participants: Study participants (N = 1591) at baseline were 78.9 ± 5.2 years of age, with low PA and at risk for mobility impairment.

Measurements: Self-reported fatigue was assessed using the modified trait version of the Exercise-Induced Feelings Inventory, a six-question scale rating energy levels in the past week. Responses ranged from 0 (none of the time) to 5 (all of the time). Total score was calculated by averaging across questions; baseline fatigue was based on the median split: 2 or higher = more fatigue (N = 856) and lower than 2 = less fatigue (N = 735). Participants performed a usual-paced 400-m walk every 6 months. We defined incident MMD as the inability to walk 400-m at follow-up visits; PMMD was defined as two consecutive walk failures. Cox proportional hazard models quantified the risk of MMD and PMMD in PA vs HE stratified by baseline fatigue adjusted for covariates.

Results: Among those with higher baseline fatigue, PA participants had a 29% and 40% lower risk of MMD and PMMD, respectively, over the trial compared with HE (hazard ratio [HR] for MMD = .71; 95% confidence interval [CI] = .57-.90; P = .004) and PMMD (HR = .60; 95% CI = .44-.82; P = .001). For those with lower baseline fatigue, no group differences in MMD (P = .36) or PMMD (P = .82) were found. Results of baseline fatigue by intervention interaction was MMD (P = .18) and PMMD (P = .05).

Conclusion: A long-term moderate intensity PA intervention was particularly effective at preserving mobility in older adults with higher levels of baseline fatigue. J Am Geriatr Soc 68:619-624, 2020.
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March 2020

Public health burden of pre-diabetes and diabetes in Luxembourg: finding from the 2013-2015 European Health Examination Survey.

BMJ Open 2019 01 21;9(1):e022206. Epub 2019 Jan 21.

Epidemiology and Public Health Research Unit, Department of Population Health, Luxembourg Institute of Health, Strassen, Luxembourg.

Objective: The aim of this study was to determine the burden and risk factors of prediabetes and diabetes in the general adult population of Luxembourg.

Design: Cross-sectional survey between 2013 and 2015.

Setting: Data were collected as part of the European Health Examination Survey in Luxembourg (EHES-LUX).

Participants: 1451 individuals were recruited in a random sample of the 25-64-year-old population of Luxembourg.

Outcomes: Diabetes was defined by a glycaemic biomarker (fasting plasma glucose (FPG) ≥7.0 mmol/L), self-reported medication and medical diagnosis; prediabetes by a glycaemic biomarker (FPG 5.6-6.9 mmol/L), no self-reported medication and no medical diagnosis. Undiagnosed diabetes was defined only from the glycaemic biomarker; the difference between total and undiagnosed diabetes was defined as diagnosed diabetes. Odds of diabetes and prediabetes as well as associated risk factors were estimated.

Results: The weighted prevalence of prediabetes and diabetes was 25.6% and 6.5%, respectively. Nearly 4.8% (men: 5.8%; women: 3.8%) were diagnosed diabetes and 1.7% (men: 2.6%; women: 0.7%) were undiagnosed diabetes. The multivariable-adjusted OR (MVOR) for diabetes risk were: age 1.05 (95% CI 1.01 to 1.09), family history of diabetes 3.24 (1.95-5.38), abdominal obesity 2.63 (1.53-4.52), hypertension 3.18 (1.76-5.72), one-unit increase of triglycerides 1.16 (1.10-1.22) and total cholesterol 0.74 (0.64-0.86). The MVOR for prediabetes risk were: age 1.04 (95% CI 1.02 to 1.06), male sex 1.84 (1.30-2.60), moderate alcohol consumption 1.38 (1.01-1.89), family history of diabetes 1.52 (1.13-2.05), abdominal obesity 1.44 (1.06-1.97), second-generation immigrants 0.61 (0.39-0.95) and a one-unit increase of serum high-density lipoprotein cholesterol 0.70 (0.54-0.90).

Conclusions: In Luxembourg, an unexpectedly high number of adults may be affected by prediabetes and diabetes. Therefore, these conditions should be addressed as a public health priority for the country, requiring measures for enhanced detection and surveillance, which are currently lacking, especially in primary care settings.
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January 2019

"To survey or to register" is that the question for estimating population incidence of injuries?

Arch Public Health 2018 17;76:76. Epub 2018 Dec 17.

Directorate of Health, Luxembourg, Luxembourg.

Background: Measuring the true incidence of injury or medically attended injury is challenging. Population surveys, despite problems with recall and selection bias, remain the only source of information for injury incidence calculation in many countries. Emergency department (ED) registry based data provide an alternative source.The aim of this study is to compare the yearly incidence of hospital treated Home and Leisure Injuries (HLI), and Road Traffic Injuries (RTI) estimated by survey-based and register-based methods and combine information from both sources in to a comprehensive injury burden pyramide.

Methods: Data from Luxemburg's European Health Examination Survey (EHES-LUX), European Health Interview Survey (EHIS) and ED surveillance system Injury Data Base (IDB) collected in 2013, were used. EHES-LUX data on 1529 residents 25-64 years old, were collected between February 2013-January 2015. EHIS data on 4004 other residents aged 15+ years old, were collected between February and December 2014. Participants reported last year's injuries at home, leisure and traffic and treatment received. Two-sided exact binomial tests were used to compare incidences from registry with the incidences of each survey by age group and prevention domain. Data from surveys and register were combined to build an RTI and HLI burden pyramide for the 25-64 years old. This project was part of the European Union project BRIDGE-Health (BRidging Information and Data Generation for Evidence-based Health Policy and Research).

Results: Among 25-64 years old the incidence of hospital treated injuries per thousand population was 60.1 (95% CI: 59.2-60.9) according to IDB, 62.1 (95% CI: 50.6-75.4) according to EHES-LUX and 53.2 (95% CI: 45.0-62.4) according to EHIS. The incidence of hospital admissions was 3.7 (95% CI: 3.5-4.0) per thousand population from IDB-Luxembourg, 12.4 (95% CI: 7.5-19.3) from EHES-LUX and 18.0 (95% CI: 13.3-23.8) from EHIS. For 15+ years-old incidence of hospital treated HLI was 62.8 (95% CI: 62.1-63.5) per thousand population according to IDB whereas the corresponding EHIS estimate was lower at 46.9 (95% CI: 40.4-54.0). About half of HLI and RTI of the 25-64 years old were treated in hospital.

Conclusion: The overall incidence estimate of hospital treated injuries from both methods does not differ for the 25-64 years old. Surveys overestimate the number of hospital admissions, probably due to memory bias. For people aged 15+ years, the survey estimate is lower than the register estimate for hospital treated HLI injuries, probably due to selection and recall biases. ED based registry data is to be preferred as single source for estimating the incidence of hospital treated injuries in all age groups.
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December 2018

Aging with HIV: what effect on mortality and loss to follow-up in the course of antiretroviral therapy? The IeDEA West Africa Cohort Collaboration.

HIV AIDS (Auckl) 2018 16;10:239-252. Epub 2018 Nov 16.

INSERM, Centre INSERM U1219-Epidémiologie-Biostatistique, Bordeaux, France,

Background: Reporting mortality and lost to follow-up (LTFU) by age is essential as older HIV-positive patients might be at risk of long-term effects of living with HIV and/or taking antiretroviral therapy (ART). As age effects might not be linear and might impact HIV outcomes in the oldest more severely, people living with HIV (PLHIV) aged 50-59 years and PLHIV aged >60 years were considered separately.

Setting: Seventeen adult HIV/AIDS clinics spread over nine countries in West Africa.

Methods: Data were collected within the International Epidemiological Databases to Evaluate AIDS West Africa Collaboration. ART-naïve PLHIV-1 adults aged >16 years initiating ART and attending ≥2 clinic visits were included (N=73,525). Age was divided into five groups: 16-29/30-39/40-49/50-59/≥60 years. The age effect on mortality and LTFU was evaluated with Kaplan-Meier curves and multivariable Cox proportional hazard regressions.

Results: At month 36, 5.9% of the patients had died and 47.3% were LTFU. Patients aged ≥60 (N=1,736) and between 50-59 years old (N=6,792) had an increased risk of death in the first 36 months on ART (adjusted hazard ratio=1.66; 95% CI: 1.36-2.03 and adjusted hazard ratio=1.31; 95% CI: 1.15-1.49, respectively; reference: <30 years old). Patients ≥60 years old tend to be more often LTFU.

Conclusion: The oldest PLHIV presented the poorest outcomes, suggesting that the PLHIV aged >50 years old should not be considered as a unique group irrespective of their age. Tailored programs focusing on improving the care services for older PLHIV in Sub-Saharan Africa are clearly needed to improve basic program outcomes.
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November 2018

Sex-based differences in antiretroviral therapy initiation, switching and treatment interruptions: global overview from the International Epidemiologic Databases to Evaluate AIDS (IeDEA).

J Int AIDS Soc 2018 06;21(6):e25149

Kirby Institute, UNSW, Sydney, Australia.

Introduction: In 2015, the World Health Organization recommended that all HIV-infected individuals consider ART initiation as soon as possible after diagnosis. Sex differences in choice of initial ART regimen, indications for switching, time to switching and choice of second-line regimens have not been well described. The aims of this study were to describe first-line ART and CD4 count at ART initiation by sex, calendar year and region, and to analyse time to change or interruption in first-line ART, according to sex in each region.

Methods: Participating cohorts included: Southern, East and West Africa (IeDEA-Africa), North America (NA-ACCORD), Caribbean, Central/South America (CCASAnet) and Asia-Pacific including Australia (IeDEA Asia-Pacific). The primary outcomes analysed for each region and according to sex were choice of initial ART, time to switching and time to discontinuation of the first-line regimen.

Results And Discussion: The combined cohort data set comprised of 715,252 participants across seven regions from low- to high-income settings. The median CD4 count at treatment initiation was lower in men compared with women in nearly all regions and time periods. Women from North America and Southern Africa were more likely to switch ART compared to men (p < 0.001) with approximately 90% of women reporting a major change after 10 years in North America. Overall, after 8 years on ART, >50% of HIV- positive men and women from Southern Africa, East Africa, South and Central America remained on their original regimen. Men were more likely to have a treatment interruption compared with women in low- and middle-income countries from the Asia/Pacific region (p < 0.001) as were men from Southern Africa (p < 0.001). Greater than 75% of men and women did not report a treatment interruption after 10 years on ART from all regions except North America and Southern Africa.

Conclusions: There are regional variations in the ART regimen commenced at baseline and rates of major change and treatment interruption according to sex. Some of this is likely to reflect changes in local and international antiretroviral guideline recommendations but other sex-specific factors such as pregnancy may contribute to these differences.
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June 2018

Prevalence and factors associated with depression in people living with HIV in sub-Saharan Africa: A systematic review and meta-analysis.

PLoS One 2017 4;12(8):e0181960. Epub 2017 Aug 4.

INSERM, Centre INSERM U1219-Epidémiologie-Biostatistique, Bordeaux, France.

Depression, one of the most common psychiatric disorders, is two- to three-times more prevalent in people living with HIV (PLHIV) than in the general population in many settings as shown in western countries but remains neglected in sub-Saharan Africa (SSA). We aimed to summarize the available evidence on the prevalence of depression and associated factors according to the scales used and the treatment status in PLHIV in SSA. The pooled prevalence estimates of depression ranged between 9% and 32% in PLHIV on antiretroviral treatment (ART) and in untreated or mixed (treated/untreated) ones, with a substantial variability according to the measurement scale used and also for a given scale. Low socio-economic conditions in PLHIV on ART, female sex and immunosuppression in mixed/untreated PLHIV were frequently reported as associated factors but with no consensus. As depression could have deleterious consequences on the PLHIV life, it is critical to encourage its screening and management, integrating these dimensions in HIV care throughout SSA.
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October 2017

Physical function, grip strength and frailty in people living with HIV in sub-Saharan Africa: systematic review.

Trop Med Int Health 2017 05 8;22(5):516-525. Epub 2017 Mar 8.

INSERM, Centre INSERM U1219, Bordeaux Population Health, Bordeaux, France.

Objective: To present the current knowledge on physical function, grip strength and frailty in HIV-infected patients living in sub-Saharan Africa, where the phenomenon is largely underestimated.

Methods: A systematic search was conducted on MEDLINE, Scopus and African Index Medicus. We reviewed articles on sub-Saharan African people living with HIV (PLHIV) >18 years old, published until November 2016.

Results: Of 537 articles, 12 were conducted in six African countries and included in this review. Five articles reported information on functional limitation and one on disability. Two of these five articles reported functional limitation (low gait speed) in PLHIV. Disability was observed in 27% and 3% of PLHIV living in rural and urban places, respectively. Two of three studies reporting grip strength reported lower grip strength (nearly 4 kg) in PLHIV in comparison with uninfected patients. One study reported that PLHIV were more likely to be frail than HIV-uninfected individuals (19.4% vs. 13.3%), whereas another reported no statistical difference.

Conclusion: Decline in physical function, grip strength and frailty are now part of the burden of PLHIV living in SSA countries, but current data are insufficient to characterise the real public health dimension of these impairments. Further studies are needed to depict this major public health challenge. As this is likely to contribute to a significant burden on the African healthcare systems and human resources in the near future, a holistic care approach should be developed to inform guidelines.
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May 2017

Has the phasing out of stavudine in accordance with changes in WHO guidelines led to a decrease in single-drug substitutions in first-line antiretroviral therapy for HIV in sub-Saharan Africa?

AIDS 2017 01;31(1):147-157

aDepartment of Global Health, Boston University, Boston, Massachusetts, USA bHealth Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa cDepartment of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, USA dCentre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa eDepartment of Infectious Diseases, Bern University Hospital, University of Bern fInstitute of Social and Preventive Medicine, University of Bern, Bern, Switzerland gThe Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town hDivision of Infectious Diseases, Department of Medicine, University of Stellenbosch & Tygerberg Academic Hospital, Cape Town iAfrica Center for Health and Population Studies, University of Kwazulu-Natal jKheth'Impilo AIDS Free Living, Cape Town kDepartment of Health, Provincial Government of the Western Cape, Cape Town, South Africa lCenter for Infectious Disease Research in Zambia, Lusaka, Zambia mIndiana University School of Medicine, Indianapolis nRichard M. Fairbanks School of Public Health, Indiana University, Indianapolis, Indiana, USA oINSERM U1027, Université Paul Sabatier Toulouse 3, Toulouse pUniversité Bordeaux, ISPED, Centre INSERM U1219 Epidémiologie-Biostatistique, Bordeaux, France.

Objective: We assessed the relationship between phasing out stavudine in first-line antiretroviral therapy (ART) in accordance with WHO 2010 policy and single-drug substitutions (SDS) (substituting the nucleoside reverse transcriptase inhibitor in first-line ART) in sub-Saharan Africa.

Design: Prospective cohort analysis (International epidemiological Databases to Evaluate AIDS-Multiregional) including ART-naive, HIV-infected patients aged at least 16 years, initiating ART between January 2005 and December 2012. Before April 2010 (July 2007 in Zambia) national guidelines called for patients to initiate stavudine-based or zidovudine-based regimen, whereas thereafter tenofovir or zidovudine replaced stavudine in first-line ART.

Methods: We evaluated the frequency of stavudine use and SDS by calendar year 2004-2014. Competing risk regression was used to assess the association between nucleoside reverse transcriptase inhibitor use and SDS in the first 24 months on ART.

Results: In all, 33 441 (8.9%; 95% confience interval 8.7-8.9%) SDS occurred among 377 656 patients in the first 24 months on ART, close to 40% of which were amongst patients on stavudine. The decrease in SDS corresponded with the phasing out of stavudine. Competing risks regression models showed that patients on tenofovir were 20-95% less likely to require a SDS than patients on stavudine, whereas patients on zidovudine had a 75-85% decrease in the hazards of SDS when compared to stavudine.

Conclusion: The decline in SDS in the first 24 months on treatment appears to be associated with phasing out stavudine for zidovudine or tenofovir in first-line ART in our study. Further efforts to decrease the cost of tenofovir and zidovudine for use in this setting is warranted to substitute all patients still receiving stavudine.
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January 2017

Targeted Spontaneous Reporting: Assessing Opportunities to Conduct Routine Pharmacovigilance for Antiretroviral Treatment on an International Scale.

Drug Saf 2016 10;39(10):959-76

Academic Model Providing Access to Healthcare, Eldoret, Kenya.

Introduction: Targeted spontaneous reporting (TSR) is a pharmacovigilance method that can enhance reporting of adverse drug reactions related to antiretroviral therapy (ART). Minimal data exist on the needs or capacity of facilities to conduct TSR.

Objectives: Using data from the International epidemiologic Databases to Evaluate AIDS (IeDEA) Consortium, the present study had two objectives: (1) to develop a list of facility characteristics that could constitute key assets in the conduct of TSR; (2) to use this list as a starting point to describe the existing capacity of IeDEA-participating facilities to conduct pharmacovigilance through TSR.

Methods: We generated our facility characteristics list using an iterative approach, through a review of relevant World Health Organization (WHO) and Uppsala Monitoring Centre documents focused on pharmacovigilance activities related to HIV and ART and consultation with expert stakeholders. IeDEA facility data were drawn from a 2009/2010 IeDEA site assessment that included reported characteristics of adult and pediatric HIV care programs, including outreach, staffing, laboratory capacity, adverse event monitoring, and non-HIV care.

Results: A total of 137 facilities were included: East Africa (43); Asia-Pacific (28); West Africa (21); Southern Africa (19); Central Africa (12); Caribbean, Central, and South America (7); and North America (7). Key facility characteristics were grouped as follows: outcome ascertainment and follow-up; laboratory monitoring; documentation-sources and management of data; and human resources. Facility characteristics ranged by facility and region. The majority of facilities reported that patients were assigned a unique identification number (n = 114; 83.2 %) and most sites recorded adverse drug reactions (n = 101; 73.7 %), while 82 facilities (59.9 %) reported having an electronic database on site.

Conclusion: We found minimal information is available about facility characteristics that may contribute to pharmacovigilance activities. Our findings, therefore, are a first step that can potentially assist implementers and facility staff to identify opportunities and leverage their existing capacities to incorporate TSR into their routine clinical programs.
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October 2016

Metabolic Syndrome Components Are Associated With Symptomatic Polyneuropathy Independent of Glycemic Status.

Diabetes Care 2016 May 10;39(5):801-7. Epub 2016 Mar 10.

School of Public Health, University of Pittsburgh, Pittsburgh, PA.

Objective: Previous studies demonstrate that the metabolic syndrome is associated with distal symmetric polyneuropathy (DSP). We aimed to determine the magnitude of this effect and the precise components involved.

Research Design And Methods: We determined the symptomatic DSP prevalence in the Health, Aging, and Body Composition (Health ABC) study (prospective cohort study, with subjects aged 70-79 years at baseline), stratified by glycemic status (glucose tolerance test) and the number of additional metabolic syndrome components (updated National Cholesterol Education Program/Adult Treatment Panel III definition). DSP was defined as neuropathic symptoms (questionnaire) plus at least one of three confirmatory tests (heavy monofilament, peroneal conduction velocity, and vibration threshold). Multivariable logistic and linear regression evaluated the association of metabolic syndrome components with DSP in cross-sectional and longitudinal analyses.

Results: Of 2,382 participants with neuropathy measures (mean age 73.5 ± 2.9 years, 38.2% black, 51.7% women), 21.0% had diabetes, 29.9% prediabetes, 52.8% metabolic syndrome, and 11.1% DSP. Stratified by glycemic status, DSP prevalence increased as the number of metabolic syndrome components increased (P = 0.03). Diabetes (cross-sectional model, odds ratio [OR] 1.65 [95% CI 1.18-2.31]) and baseline hemoglobin A1C (longitudinal model, OR 1.42 [95% CI 1.15-1.75]) were the only metabolic syndrome measures significantly associated with DSP. Waist circumference and HDL were significantly associated with multiple secondary neuropathy outcomes.

Conclusions: Independent of glycemic status, symptomatic DSP is more common in those with additional metabolic syndrome components. However, the issue of which metabolic syndrome components drive this association, in addition to hyperglycemia, remains unclear. Larger waist circumference and low HDL may be associated with DSP, but larger studies with more precise metabolic measures are needed.
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May 2016

Association between resistin levels and cardiovascular disease events in older adults: The health, aging and body composition study.

Atherosclerosis 2016 Feb 9;245:181-6. Epub 2015 Dec 9.

Department of General Internal Medicine, Bern University Hospital, Switzerland. Electronic address:

Objective: Prospective data on the association between resistin levels and cardiovascular disease (CVD) events are sparse with conflicting results.

Methods: We studied 3044 aged 70-79 years from the Health, Aging, and Body Composition Study. CVD events were defined as coronary heart disease (CHD) or stroke events. «Hard » CHD events were defined as CHD death or myocardial infarction. We estimated hazard ratio (HR) and 95% confidence intervals (CI) according to the quartiles of serum resistin concentrations and adjusted for clinical variables, and then further adjusted for metabolic disease (body mass index, fasting plasma glucose, abdominal visceral and subcutaneous adipose tissue, leptin, adiponectin, insulin) and inflammation (C-reactive protein, interleukin-6, tumor necrosis factors-α).

Results: During a median follow-up of 10.1 years, 559 patients had « hard » CHD events, 884 CHD events and 1106 CVD Events. Unadjusted incidence rate for CVD events was 36.6 (95% CI 32.1-41.1) per 1000 persons-year in the lowest quartile and 54.0 per 1000 persons-year in the highest quartile (95% CI 48.2-59.8, P for trend < 0.001). In the multivariate models adjusted for clinical variables, HRs for the highest vs. lowest quartile of resistin was 1.52 (95% CI 1.20-1.93, P < 0.001) for « Hard » CHD events, 1.41 (95% CI 1.16-1.70, P = 0.001) for CHD events and 1.35 (95% CI 1.14-1.59, P = 0.002) for CVD events. Further adjustment for metabolic disease slightly reduced the associations while adjustment for inflammation markedly reduced the associations.

Conclusions: In older adults, higher resistin levels are associated with CVD events independently of clinical risk factors and metabolic disease markers, but markedly attenuated by inflammation.
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February 2016

Impact of the Ebola epidemic on general and HIV care in Macenta, Forest Guinea, 2014.

AIDS 2015 Sep;29(14):1883-7

aCentre Médical de Macenta, Mission Philafricaine, Conakry, Guinea bINSERM U897 - Centre Inserm Epidémiologie et Biostatistique, Université de Bordeaux cUniversité de Bordeaux, ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Bordeaux, France dDepartment of Infectious Diseases, University Hospital Bern eInstitute of Social and Preventive Medicine, University of Bern, Bern, Switzerland fDepartment of Infectious Diseases, University of Dakar, Senegal.

Objective: The current Ebola epidemic massively affected the Macenta district in Forest Guinea. We aimed at investigating its impact on general and HIV care at the only HIV care facility in the district.

Design: Prospective observational single-facility study.

Methods: Routinely collected data on use of general hospital services and HIV care were linked to Ebola surveillance data published by the Guinea Ministry of Health. In addition, we compared retention among HIV-infected patients enrolled into care in the first semesters of 2013 and 2014.

Results: Throughout 2014, service offer was continuous and unaltered at the facility. During the main epidemic period (August-December 2014), compared with the same period of 2013, there were important reductions in attendance at the primary care outpatient clinic (-40%), in HIV tests done (-46%), in new diagnoses of tuberculosis (-53%) and in patients enrolled into HIV care (-47%). There was a smaller reduction in attendance at the HIV follow-up clinic (-11%). Kaplan-Meier estimates of retention were similar among the patients enrolled into care in 2014 and 2013. In a multivariable Cox regression analysis, the year of enrolment was not associated with attrition (hazard ratio 1.02; 95% confidence interval: 0.72-1.43).

Conclusion: The Ebola epidemic resulted in an important decrease in utilization of the facility despite unaltered service offer. Effects on care of HIV-positive patients enrolled prior to the epidemic were limited. HIV care in such circumstances is challenging, but not impossible.
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September 2015

Severe morbidity after antiretroviral (ART) initiation: active surveillance in HIV care programs, the IeDEA West Africa collaboration.

BMC Infect Dis 2015 Apr 9;15:176. Epub 2015 Apr 9.

Programme PAC-CI, Centre Hospitalier Universitaire (CHU) de Treichville, 18 BP 1954, Abidjan 18, Côte d'Ivoire.

Background: The causes of severe morbidity in health facilities implementing Antiretroviral Treatment (ART) programmes are poorly documented in sub-Saharan Africa. We aimed to describe severe morbidity among HIV-infected patients after ART initiation, based on data from an active surveillance system established within a network of specialized care facilities in West African cities.

Methods: Within the International epidemiological Database to Evaluate AIDS (IeDEA)--West Africa collaboration, we conducted a prospective, multicenter data collection that involved two facilities in Abidjan, Côte d'Ivoire and one in Cotonou, Benin. Among HIV-infected adults receiving ART, events were recorded using a standardized form. A simple case-definition of severe morbidity (death, hospitalization, fever>38°5C, Karnofsky index<70%) was used at any patient contact point. Then a physician confirmed and classified the event as WHO stage 3 or 4 according to the WHO clinical classification or as degree 3 or 4 of the ANRS scale.

Results: From December 2009 to December 2011, 978 adults (71% women, median age 39 years) presented with 1449 severe events. The main diagnoses were: non-AIDS-defining infections (33%), AIDS-defining illnesses (33%), suspected adverse drug reactions (7%), other illnesses (4%) and syndromic diagnoses (16%). The most common specific diagnoses were: malaria (25%), pneumonia (13%) and tuberculosis (8%). The diagnoses were reported as syndromic in one out of five events recorded during this study.

Conclusions: This study highlights the ongoing importance of conventional infectious diseases among severe morbid events occurring in patients on ART in ambulatory HIV care facilities in West Africa. Meanwhile, additional studies are needed due to the undiagnosed aspect of severe morbidity in substantial proportion.
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April 2015

Prevalence of metabolic syndrome and its association with physical capacity, disability, and self-rated health in Lifestyle Interventions and Independence for Elders Study participants.

J Am Geriatr Soc 2015 Feb 30;63(2):222-32. Epub 2015 Jan 30.

Department of Health Policy Studies, University of Michigan, Ann Arbor, Dearborn, Michigan; Institute of Gerontology, University of Michigan, Ann Arbor, Dearborn, Michigan; Division of Geriatrics, Department of Internal Medicine, School of Medicine, Yale University, New Haven, Connecticut.

Objectives: To evaluate the prevalence of metabolic syndrome (MetS) and its association with physical capacity, disability, and self-rated health in older adults at high risk of mobility disability, including those with and without diabetes mellitus.

Design: Cross-sectional analysis.

Setting: Lifestyle Interventions and Independence for Elders (LIFE) Study.

Participants: Community-dwelling sedentary adults aged 70 to 89 at high risk of mobility disability (Short Physical Performance Battery (SPPB) score ≤9; mean 7.4 ± 1.6) (N = 1,535).

Measurements: Metabolic syndrome was defined according to the 2009 multiagency harmonized criteria; outcomes were physical capacity (400-m walk time, grip strength, SPPB score), disability (composite 19-item score), and self-rated health (5-point scale ranging from excellent to poor).

Results: The prevalence of MetS was 49.8% in the overall sample (83.2% of those with diabetes mellitus, 38.1% of those without). MetS was associated with stronger grip strength (mean difference (Δ) = 1.2 kg, P = .01) in the overall sample and in participants without diabetes mellitus and with poorer self-rated health (Δ = 0.1 kg, P < .001) in the overall sample only. No significant differences were found in 400-m walk time, SPPB score, or disability score between participants with and without MetS, in the overall sample or diabetes mellitus subgroups.

Conclusion: Metabolic dysfunction is highly prevalent in older adults at risk of mobility disability, yet consistent associations were not observed between MetS and walking speed, lower extremity function, or self-reported disability after adjusting for known and potential confounders. Longitudinal studies are needed to investigate whether MetS accelerates declines in functional status in high-risk older adults and to inform clinical and public health interventions aimed at preventing or delaying disability in this group.
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February 2015

Physical function and disability in older adults with diabetes.

Clin Geriatr Med 2015 Feb 15;31(1):51-65, viii. Epub 2014 Nov 15.

Section of Internal Medicine, Gerontology and Clinical, Nutrition, Department of Medical Sciences, Azienda Ospedaliero-Universitaria di Ferrara U.O. Medicina Interna Universitaria, University of Ferrara, Via Aldo Moro 8, 1B1 Stanza 1.35.30, Ferrara 44124, Italy.

Functional decline and physical disability are an important clinical and public health problem in older adults because they are associated with loss of independence, nursing home admission, and mortality. Several impairments and comorbidities related to or associated with diabetes are potential disabling conditions that could account for the excess risk of disability. But in most studies, no single condition explains this association. Accelerated loss of muscle strength is a potential mediator in the disabling effect of diabetes. Because some diabetes-related comorbidities are potential modifiable risk factors, preventing and reducing the excess risk of disability associated with diabetes needs further study.
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February 2015

Epidemiology of restricting fatigue in older adults: the precipitating events project.

J Am Geriatr Soc 2014 Mar 11;62(3):476-81. Epub 2014 Feb 11.

Section of Geriatrics, Department of Internal Medicine, School of Medicine, Yale University, New Haven, Connecticut.

Objectives: To estimate the rate of restricting fatigue in community-living older adults and to determine whether the rates differ according to age, sex, race, physical frailty, and depression.

Design: Prospective cohort study.

Setting: Greater New Haven, Connecticut.

Participants: Nondisabled community-living older men and women aged 70 and older (N = 754).

Measurements: Restricting fatigue was defined as staying in bed for at least half the day and/or cutting down on one's usual activities because of fatigue for 3 consecutive months or longer. Physical frailty was defined on the basis of slow gait speed, and depression was assessed using the Center for Epidemiologic Studies Depression Scale.

Results: During a median follow-up of 111 months, the cumulative incidence of restricting fatigue was 31.1% for men and 42.1% for women. The overall incidence rate of restricting fatigue was 6.7 per 1,000 person-months (7.8 for women and 4.4 for men, P < .001), which did not differ according to race. Rates were higher in persons who were physically frail than those who were not (P < .001), in those who were depressed than those who were not (P < .001), and in persons aged 75 to 79 and 80 to 84 than those aged 70 to 74 (both P < .01) but not in those aged 85 and older. Of the 459 episodes of restricting fatigue, the median duration was 3 months, which did not differ according to age, sex, race, physical frailty, or depression.

Conclusion: Restricting fatigue is common in community-living older adults. Women, individuals aged 75 to 84, and individuals with physical frailty or depression had higher rates of restricting fatigue than their respective counterparts.
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March 2014

Hyperleptinemia, adiposity, and risk of metabolic syndrome in older adults.

J Nutr Metab 2013 26;2013:327079. Epub 2013 Dec 26.

Department of Nutrition and Food Science, University of Maryland, College Park, MD 20742, USA.

Background. Abdominal adiposity and serum leptin increase with age as does risk of metabolic syndrome. This study investigates the prospective association between leptin and metabolic syndrome risk in relation to adiposity and cytokines. Methods. The Health, Aging, and Body Composition study is a prospective cohort of older adults aged 70 to 79 years. Baseline measurements included leptin, cytokines, BMI, total percent fat, and visceral and subcutaneous fat. Multivariate logistic regression was used to determine the association between leptin and metabolic syndrome (defined per NCEP ATP III) incidence after 6 years of follow-up among 1,120 men and women. Results. Leptin predicted metabolic syndrome in men (P for trend = 0.0002) and women (P for trend = 0.0001). In women, risk of metabolic syndrome increased with higher levels of leptin (compared with quintile 1, quintile 2 RR = 3.29, CI = 1.36, 7.95; quintile 3 RR = 3.25, CI = 1.33, 7.93; quintile 4 RR = 5.21, CI = 2.16, 12.56; and quintile 5 RR = 7.97, CI = 3.30, 19.24) after adjusting for potential confounders. Leptin remained independently associated with metabolic syndrome risk after additional adjustment for adiposity, cytokines, and CRP. Among men, this association was no longer significant after controlling for adiposity. Conclusion. Among older women, elevated concentrations of leptin may increase the risk of metabolic syndrome independent of adiposity and cytokines.
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January 2014

Diagnostic and prognostic value of procalcitonin and C-reactive protein in malnourished children.

Pediatrics 2014 Feb 20;133(2):e363-70. Epub 2014 Jan 20.

Epidemiology and Population Health, Epicentre, Paris, France;

Background: Early recognition of bacterial infections is crucial for their proper management, but is particularly difficult in children with severe acute malnutrition (SAM). The objectives of this study were to evaluate the accuracy of C-reactive protein (CRP) and procalcitonin (PCT) for diagnosing bacterial infections and assessing the prognosis of hospitalized children with SAM, and to determine the reliability of CRP and PCT rapid tests suitable for remote settings.

Methods: From November 2007 to July 2008, we prospectively recruited 311 children aged 6 to 59 months hospitalized with SAM plus a medical complication in Maradi, Niger. Blood, urine, and stool cultures and chest radiography were performed systematically on admission. CRP and PCT were measured by rapid tests and by reference quantitative methods using frozen serum sent to a reference laboratory.

Results: Median CRP and PCT levels were higher in children with bacteremia or pneumonia than in those with no proven bacterial infection (P < .002). However, both markers performed poorly in identifying invasive bacterial infection, with areas under the curve of 0.64 and 0.67 before and after excluding children with malaria, respectively. At a threshold of 40 mg/L, CRP was the best predictor of death (81% sensitivity, 58% specificity). Rapid test results were consistent with those from reference methods.

Conclusions: CRP and PCT are not sufficiently accurate for diagnosing invasive bacterial infections in this population of hospitalized children with complicated SAM. However, a rapid CRP test could be useful in these settings to identify children most at risk for dying.
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February 2014

Elevated HbA1c and fasting plasma glucose in predicting diabetes incidence among older adults: are two better than one?

Diabetes Care 2013 Dec 17;36(12):3923-9. Epub 2013 Oct 17.

Corresponding author: Kasia J. Lipska,

Objective: To determine which measures-impaired fasting glucose (IFG), elevated HbA1c, or both-best predict incident diabetes in older adults.

Research Design And Methods: From the Health, Aging, and Body Composition study, we selected individuals without diabetes, and we defined IFG (100-125 mg/dL) and elevated HbA1c (5.7-6.4%) per American Diabetes Association guidelines. Incident diabetes was based on self-report, use of antihyperglycemic medicines, or HbA1c ≥6.5% during 7 years of follow-up. Logistic regression analyses were adjusted for age, sex, race, site, BMI, smoking, blood pressure, and physical activity. Discrimination and calibration were assessed for models with IFG and with both IFG and elevated HbA1c.

Results: Among 1,690 adults (mean age 76.5, 46% men, 32% black), 183 (10.8%) developed diabetes over 7 years. Adjusted odds ratios of diabetes were 6.2 (95% CI 4.4-8.8) in those with IFG (versus those with fasting plasma glucose [FPG] <100 mg/dL) and 11.3 (7.8-16.4) in those with elevated HbA1c (versus those with HbA1c <5.7%). When FPG and HbA1c were considered together, odds ratios were 3.5 (1.9-6.3) in those with IFG only, 8.0 (4.8-13.2) in those with elevated HbA1c only, and 26.2 (16.3-42.1) in those with both IFG and elevated HbA1c (versus those with normal FPG and HbA1c). Addition of elevated HbA1c to the model with IFG resulted in improved discrimination and calibration.

Conclusions: Older adults with both IFG and elevated HbA1c have a substantially increased odds of developing diabetes over 7 years. Combined screening with FPG and HbA1c may identify older adults at very high risk for diabetes.
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December 2013

Diabetes and risk of hospitalized fall injury among older adults.

Diabetes Care 2013 Dec 15;36(12):3985-91. Epub 2013 Oct 15.

Corresponding author: Rebecca K. Yau,

Objective: To determine whether older adults with diabetes are at increased risk of an injurious fall requiring hospitalization.

Research Design And Methods: The longitudinal Health, Aging, and Body Composition Study included 3,075 adults aged 70-79 years at baseline. Hospitalizations that included ICD-9-Clinical Modification codes for a fall and an injury were identified. The effect of diabetes with and without insulin use on the rate of first fall-related injury hospitalization was assessed using proportional hazards models.

Results: At baseline, 719 participants had diabetes, and 117 of them were using insulin. Of the 293 participants who were hospitalized for a fall-related injury, 71 had diabetes, and 16 were using insulin. Diabetes was associated with a higher rate of injurious fall requiring hospitalization (hazard ratio [HR] 1.48 [95% CI 1.12-1.95]) in models adjusted for age, race, sex, BMI, and education. In those participants using insulin, compared with participants without diabetes, the HR was 3.00 (1.78-5.07). Additional adjustment for potential intermediaries, such as fainting in the past year, standing balance score, cystatin C level, and number of prescription medications, accounted for some of the increased risk associated with diabetes (1.41 [1.05-1.88]) and insulin-treated diabetes (2.24 [1.24-4.03]). Among participants with diabetes, a history of falling, poor standing balance score, and A1C level ≥8% were risk factors for an injurious fall requiring hospitalization.

Conclusions: Older adults with diabetes, in particular those using insulin, are at greater risk of an injurious fall requiring hospitalization than those without diabetes. Among those with diabetes, poor glycemic control may increase the risk of an injurious fall.
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December 2013

Infections in children admitted with complicated severe acute malnutrition in Niger.

PLoS One 2013 17;8(7):e68699. Epub 2013 Jul 17.

Epidemiology and Population Health, Epicentre, Paris, France.

Background: Although malnutrition affects thousands of children throughout the Sahel each year and predisposes them to infections, there is little data on the etiology of infections in these populations. We present a clinical and biological characterization of infections in hospitalized children with complicated severe acute malnutrition (SAM) in Maradi, Niger.

Methods: Children with complicated SAM hospitalized in the intensive care unit of a therapeutic feeding center, with no antibiotics in the previous 7 days, were included. A clinical examination, blood, urine and stool cultures, and chest radiography were performed systematically on admission.

Results: Among the 311 children included in the study, gastroenteritis was the most frequent clinical diagnosis on admission, followed by respiratory tract infections and malaria. Blood or urine culture was positive in 17% and 16% of cases, respectively, and 36% had abnormal chest radiography. Enterobacteria were sensitive to most antibiotics, except amoxicillin and cotrimoxazole. Twenty-nine (9%) children died, most frequently from sepsis. Clinical signs were poor indicators of infection and initial diagnoses correlated poorly with biologically or radiography-confirmed diagnoses.

Conclusions: These data confirm the high level of infections and poor correlation with clinical signs in children with complicated SAM, and provide antibiotic resistance profiles from an area with limited microbiological data. These results contribute unique data to the ongoing debate on the use and choice of broad-spectrum antibiotics as first-line treatment in children with complicated SAM and reinforce the call for an update of international guidelines on management of complicated SAM based on more recent data.
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March 2014

Modifiable risk factors for pneumonia requiring hospitalization of community-dwelling older adults: the Health, Aging, and Body Composition Study.

J Am Geriatr Soc 2013 Jul 17;61(7):1111-8. Epub 2013 Jun 17.

Section of Infectious Diseases, Department of Internal Medicine, School of Medicine, Yale University, New Haven, Connecticut 06520, USA.

Objectives: To identify novel modifiable risk factors, focusing on oral hygiene, for pneumonia requiring hospitalization of community-dwelling older adults.

Design: Prospective observational cohort study.

Setting: Memphis, Tennessee, and Pittsburgh, Pennsylvania.

Participants: Of 3,075 well-functioning community-dwelling adults aged 70 to 79 enrolled in the Health, Aging, and Body Composition Study from 1997 to 1998, 1,441 had complete data in the data set of all variables used, a dental examination within 6 months of baseline, and were eligible for this study.

Measurements: The primary outcome was pneumonia requiring hospitalization through 2008.

Results: Of 1,441 participants, 193 were hospitalized for pneumonia. In a multivariable model, male sex (hazard ratio (HR) = 2.07, 95% confidence interval (CI) = 1.51-2.83), white race (HR = 1.44, 95% CI = 1.03-2.01), history of pneumonia (HR = 3.09, 95% CI = 1.86-5.14), pack-years of smoking (HR = 1.006, 95% CI = 1.001-1.011), and percentage of predicted forced expiratory volume in 1 minute (moderate vs mild lung disease or normal lung function, HR = 1.78, 95% CI = 1.28-2.48; severe lung disease vs mild lung disease or normal lung function, HR = 2.90, 95% CI = 1.51-5.57) were nonmodifiable risk factors for pneumonia. Incident mobility limitation (HR = 1.77, 95% CI = 1.32-2.38) and higher mean oral plaque score (HR = 1.29, 95% CI = 1.02-1.64) were modifiable risk factors for pneumonia. Average attributable fractions revealed that 11.5% of cases of pneumonia were attributed to incident mobility limitation and 10.3% to a mean oral plaque score of 1 or greater.

Conclusion: Incident mobility limitation and higher mean oral plaque score were two modifiable risk factors that 22% of pneumonia requiring hospitalization could be attributed to. These data suggest innovative opportunities for pneumonia prevention among community-dwelling older adults.
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July 2013

Genome-wide association analysis identifies TYW3/CRYZ and NDST4 loci associated with circulating resistin levels.

Hum Mol Genet 2012 Nov 26;21(21):4774-80. Epub 2012 Jul 26.

Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.

Resistin is a polypeptide hormone that was reported to be associated with insulin resistance, inflammation and risk of type 2 diabetes and cardiovascular disease. We conducted a genome-wide association (GWA) study on circulating resistin levels in individuals of European ancestry drawn from the two independent studies: the Nurses' Health Study (n = 1590) and the Health, Aging and Body Composition Study (n = 1658). Single-nucleotide polymorphisms (SNPs) identified in the GWA analysis were replicated in an independent cohort of Europeans: the Gargano Family Study (n = 659). We confirmed the association with a previously known locus, the RETN gene (19p13.2), and identified two novel loci near the TYW3/CRYZ gene (1p31) and the NDST4 gene (4q25), associated with resistin levels at a genome-wide significant level, best represented by SNP rs3931020 (P = 6.37 × 10(-12)) and SNP rs13144478 (P = 6.19 × 10(-18)), respectively. Gene expression quantitative trait loci analyses showed a significant cis association between the SNP rs3931020 and CRYZ gene expression levels (P = 3.68 × 10(-7)). We also found that both of these two SNPs were significantly associated with resistin gene (RETN) mRNA levels in white blood cells from 68 subjects with type 2 diabetes (both P = 0.02). In addition, the resistin-rising allele of the TYW3/CRYZ SNP rs3931020, but not the NDST4 SNP rs13144478, showed a consistent association with increased coronary heart disease risk [odds ratio = 1.18 (95% CI, 1.03-1.34); P = 0.01]. Our results suggest that genetic variants in TYW3/CRYZ and NDST4 loci may be involved in the regulation of circulating resistin levels. More studies are needed to verify the associations of the SNP rs13144478 with NDST4 gene expression and resistin-related disease.
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November 2012

Cognitive Impairment and Medication Complexity in Community-Living Older Adults: The Health, Aging and Body Composition Study.

J Pharm Technol 2012 Jul;28(4):156-162

School of Pharmacy, University of Connecticut, Storrs, CT.

Background: Medication complexity is a large determinant of adherence. Few studies have explored the relationship between cognitive impairment and medication complexity.

Objective: To evaluate whether cognitive impairment is associated with medication complexity for prescription and over-the-counter (OTC) medications.

Methods: In this cross-sectional analysis, we studied the association between cognitive impairment and the complexity of prescription and OTC drug regimens. Baseline participants were from the Health, Aging and Body Composition study, consisting of 3075 well-functioning 70- to 79-year-old black and white men and women. Cognitive impairment was defined by having a Modified Mini-Mental State Examination score <80. The complexity of prescription and OTC (including supplements/herbals) medications was assessed using a modified version of the Medication Regimen Complexity Index (mMRCI). The mMRCI score increases with complexity of dosage forms, number of medications, pill burden, and nondaily dosing.

Results: The mean (SD) age was 74 (2.9) years (n = 3055; 52% female, 41% black). The median prescription mMRCI score was 6 (range 0-66). The median OTC mMRCI score was 4 (range 0-71). Adjusting for health status, demographics, and access to care, medication complexity was lower in participants with cognitive impairment for prescription (adjusted RR 0.89; 95% CI 0.80 to 0.99) and OTC medications (adjusted RR 0.76; 95% CI 0.64 to 0.93) compared to those without cognitive impairment. The number of prescription medications was not different, but the number of OTC drugs was lower for those with cognitive impairment.

Conclusions: In this cohort of well-functioning older adults, those with cognitive impairment had lower prescription complexity due to less-complex dosage forms, pill burden, or daily dosing. OTC complexity was also lower, primarily due to a lower number of OTC drugs. The results of this study show that further research on medication complexity and adherence and health outcomes in cognitively impaired individuals is warranted.
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July 2012

Relationship between vitamin B12 and sensory and motor peripheral nerve function in older adults.

J Am Geriatr Soc 2012 Jun;60(6):1057-63

Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Objectives: To examine whether deficient B12 status or low serum B12 levels are associated with worse sensory and motor peripheral nerve function in older adults.

Design: Cross-sectional.

Setting: Health, Aging and Body Composition Study.

Participants: Two thousand two hundred and eighty-seven adults aged 72 to 83 (mean 76.5 ± 2.9; 51.4% female; 38.3% black).

Measurements: Low serum B12 was defined as serum B12 less than 260 pmol/L, and deficient B12 status was defined as B12 less than 260 pmol/L, methylmalonic acid (MMA) greater than 271 nmol/L, and MMA greater than 2-methylcitrate. Peripheral nerve function was assessed according to peroneal nerve conduction amplitude and velocity (NCV) (motor), 1.4 g/10 g monofilament detection, average vibration threshold detection, and peripheral neuropathy symptoms (numbness, aching or burning pain, or both) (sensory).

Results: B12-deficient status was found in 7.0% of participants, and an additional 10.1% had low serum B12 levels. B12 deficient status was associated with greater insensitivity to light (1.4 g) touch (odds ratio = 1.50, 95% confidence interval = 1.06-2.13) and worse NCV (42.3 vs 43.5 m/s) (β = -1.16, P = .01) after multivariable adjustment for demographics, lifestyle factors, and health conditions. Associations were consistent for the alternative definition using low serum B12 only. No significant associations were found for deficient B12 status or the alternative low serum B12 definition and vibration detection, nerve conduction amplitude, or peripheral neuropathy symptoms.

Conclusion: Poor B12 (deficient B12 status and low serum B12) is associated with worse sensory and motor peripheral nerve function. Nerve function impairments may lead to physical function declines and disability in older adults, suggesting that prevention and treatment of low B12 levels may be important to evaluate.
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June 2012

Massive increase, spread, and exchange of extended spectrum β-lactamase-encoding genes among intestinal Enterobacteriaceae in hospitalized children with severe acute malnutrition in Niger.

Clin Infect Dis 2011 Oct;53(7):677-85

French National Reference Center for Bacterial Resistance in Commensal Flora, Laboratory of Bacteriology, Bichat-Claude Bernard Hospital, Assistance Publique-Hôpitaux de Paris.

Background: From the time of CTX-M emergence, extended-spectrum β-lactamase-producing enterobacteria (ESBL-E) have spread worldwide in community settings as well as in hospitals, particularly in developing countries. Although their dissemination appears linked to Escherichia coli intestinal carriage, precise paths of this dynamic are largely unknown.

Methods: Children from a pediatric renutrition center were prospectively enrolled in a fecal carriage study. Antibiotic exposure was recorded. ESBL-E strains were isolated using selective media from fecal samples obtained at admission and, when negative, also at discharge. ESBL-encoding genes were identified, their environments and plasmids were characterized, and clonality was assessed with polymerase chain reaction-based methods and pulsed-field gel electrophoresis for E. coli and Klebsiella pneumoniae. E. coli strains were subjected to multilocus sequence typing.

Results: The ESBL-E carriage rate was 31% at admission in the 55 children enrolled. All children enrolled received antibiotics during hospitalization. Among the ESBL-E-negative children, 16 were resampled at discharge, and the acquisition rate was 94%. The bla(CTX-M-15) gene was found in >90% of the carriers. Genetic environments and plasmid characterization evidenced the roles of a worldwide, previously described, multidrug-resistant region and of IncF plasmids in CTX-M-15 E. coli dissemination. Diversity of CTX-M-15-carrying genetic structures and clonality of acquired ESBL E. coli suggested horizontal genetic transfer and underlined the potential of some ST types for nosocomial cross-transmission.

Conclusions: Cross-transmission and high selective pressure lead to very high acquisition of ESBL-E carriage, contributing to dissemination in the community. Strict hygiene measures as well as careful balancing of benefit-risk ratio of current antibiotic policies need to be reevaluated.
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October 2011

Identifying dysglycemic states in older adults: implications of the emerging use of hemoglobin A1c.

J Clin Endocrinol Metab 2010 Dec 22;95(12):5289-95. Epub 2010 Sep 22.

Robert Wood Johnson Clinical Scholars Program, Yale University School of Medicine, P.O. Box 208088, 333 Cedar Street, SHM IE-61, New Haven, Connecticut 06520-8088, USA.

Context: Hemoglobin A1c (A1c) was recently added to the diagnostic criteria for diabetes and prediabetes.

Objective: Our objective was to examine performance of A1c in comparison with fasting plasma glucose (FPG) in diagnosing dysglycemia in older adults.

Design And Setting: We conducted a cross-sectional analysis of data from the Health, Aging, and Body Composition study at yr 4 (2000-2001) when FPG and standardized A1c measurements were available.

Participants: Of 3075 persons (aged 70-79 yr, 48% men, 42% Black) at study entry, 1865 participants without known diabetes who had appropriate measures were included.

Main Outcome Measures: Sensitivity and specificity of A1c-based diagnoses were compared with those based on FPG and the proportion of participants identified with dysglycemia by each measure.

Results: Of all participants, 2.7 and 3.1% had undiagnosed diabetes by FPG≥126 mg/dl and A1c≥6.5%, respectively. Among the remaining participants, 21.1% had prediabetes by impaired fasting glucose (≥100 mg/dl) and 22.2% by A1c≥5.7%. Roughly one third of individuals with diabetes and prediabetes were identified by either FPG or A1c alone and by both tests simultaneously. Sensitivities and specificities of A1c compared with FPG were 56.9 and 98.4% for diabetes and 47.0 and 84.5% for prediabetes, respectively. Blacks and women were more likely to be identified with dysglycemia by A1c than FPG.

Conclusions: In this older population, we found considerable discordance between FPG- and A1c-based diagnosis of diabetes and prediabetes, with differences accentuated by race and gender. Broad implementation of A1c to diagnose dysglycemic states may substantially alter the epidemiology of these conditions in older Americans.
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December 2010