Prevalence and determinants for malnutrition in geriatric outpatients.

BACKGROUND & AIMS: Few data is available on the nutritional status of geriatric outpatients. The aim of this study is to describe the nutritional status and its clinical correlates of independently living geriatric older individuals visiting a geriatric outpatient department. METHODS: From 2005 to 2010, all consecutive patients visiting a geriatric outpatient department in the Netherlands were screened for malnutrition. Nutritional status was assessed by the Mini Nutritional Assessment (MNA). Determinants of malnutrition were categorized into somatic factors (medicine use, comorbidity, walking aid, falls, urinary incontinence), psychological factors (GDS-15 depression scale, MMSE cognition scale), functional status (Activities of Daily Life (ADL), Instrumental ADL (IADL)), social factors (children, marital status), and life style factors (smoking, alcohol use). Univariate and multivariate logistic regression analyses, adjusted for age and sex and all other risk factors were performed to identify correlates of malnutrition (MNA < 17). RESULTS: Included were 448 outpatients, mean (SD) age was 80 (7) years and 38% was men. Prevalence of malnutrition and risk for malnutrition were 17% and 58%. Depression, being IADL dependent, and smoking were independently associated with an increased risk of malnutrition with OR's (95%CI) of 2.6 (1.3-5.3), 2.8 (1.3-6.4), 5.5 (1.9-16.4) respectively. Alcohol use was associated with a decreased risk (OR 0.4 (0.2-0.9)). CONCLUSION: Malnutrition is highly prevalent among geriatric outpatients and is independently associated with depressive symptoms, poor functional status, and life style factors. Our results emphasize the importance of integrating nutritional assessment within a comprehensive geriatric assessment. Future longitudinal studies should be performed to examine the effects of causal relationships and multifactorial interventions.

Protease inhibitors atazanavir, lopinavir and ritonavir are potent blockers, but poor substrates, of ABC transporters in a broad panel of ABC transporter-overexpressing cell lines.

OBJECTIVES: A possible mechanism for HIV therapy failure is the efflux of HIV drugs from viral target cells or certain body compartments by ATP-binding cassette (ABC) transporters, allowing ongoing viral replication. Here, we investigated the interaction between protease inhibitors (PIs) and ABC transporters. METHODS: To explore the potential blocking capacity of PIs, we exposed cells overexpressing multidrug resistance 1 P-glycoprotein (MDR1 P-gp), multidrug resistance protein 1 (MRP1) and breast cancer resistance protein (BCRP) to established cytotoxic substrates with or without one of the PIs atazanavir, lopinavir or ritonavir. Furthermore, to assess whether PIs serve as substrates, cell growth-inhibitory effects of these PIs were evaluated on cells overexpressing 1 of 11 ABC transporters and their parental counterparts. RESULTS: Atazanavir, lopinavir and ritonavir were highly effective in reversing resistance against established substrates in cells overexpressing MDR1 P-gp and MRP1, and, to a lesser extent, BCRP. Concurrently, however, PIs appeared to be relatively poor substrates for ABC transporters. Only a moderate level of resistance to atazanavir was observed in cells overexpressing MRP6 and MRP9 [resistance factor (RF): 2.0-2.6]. Cells overexpressing MDR1 P-gp, MRP3, MRP4 and MRP5 displayed low levels of resistance to atazanavir (RF: 1.3-1.7); MRP7- and MRP9-overexpressing cells to lopinavir (RF: 1.4-1.5); and MRP9-overexpressing cells to ritonavir (RF: 1.4). CONCLUSIONS: PIs can act as potent blockers of MDR1 P-gp, MRP1 and BCRP, but they are poor substrates for 11 ABC transporters. Consequently, ABC transporters are unlikely to play a major role in PI failure, but still may contribute to drug-specific adverse events and drug-drug interactions.

Comparison of the risks of atherosclerotic events versus death from other causes associated with antiretroviral use.

BACKGROUND: Studies considering the risk of atherosclerotic disease (AtD) associated with the use of HAART have reported inconsistent results. METHODS: Data on antiretroviral therapy (ART) use, risk factors for cardiovascular disease (CVD), AtD and death from other causes in 18 603 HIV-infected patients from two established cohorts were evaluated. The relative hazards of AtD and death from other causes were calculated using a proportional hazards competing risks framework. The impact of protease inhibitor (PI)-containing, non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing or PI + NNRTI-containing regimens on these outcomes were compared to nucleoside reverse transcriptase inhibitor (NRTI)-only regimens or stopping therapy, adjusting for known CVD risk factors. RESULTS: In 77 480 person-years of follow-up (median duration 3.49 years) there were 318 AtD events including 92 myocardial infarctions and 2044 deaths. Older age, hypertension, diabetes mellitus, having smoked and HIV disease stage were significantly associated with increased risk of AtD. PI- and NNRTI-containing regimens significantly reduced the joint risk of either AtD or death from other causes compared to NRTI-only or stopping therapy [hazard ratio (HR) for PI-containing ART, 0.76, 95% confidence interval (CI), 0.73-0.78, P< 0.001; NNRTI-containing ART, 0.69, 95% CI, 0.65-0.74; P< 0.001). PI-containing ART was associated with a borderline significant increased risk of myocardial infarction (cause-specific HR for PI-containing ART 1.19, 95% CI, 1.01-1.40, P = 0.04) but not with increased risk of AtD compared to NRTI-only regimens or stopping therapy (cause-specific HR for PI-containing ART, 1.03, 95% CI, 0.95-1.13, P = 0.44). CONCLUSIONS: Overall benefits of PI- and NNRTI-based ART in reducing mortality significantly outweigh any risks of AtD in the "short-term" follow-up of this study. Traditional cardiac risk factors play an important role in determining AtD risk status.

Post-exposure prophylaxis.

The mean risk of acquiring HIV after an occupational exposure, injecting drug use or sexual exposure varies from < 0.1 to 3%. A high plasma HIV-RNA of the source increases the risk of each of the exposures. Other factors, such as the volume of the inoculum involved to which the individual was exposed, other sexually transmitted diseases and ruptures of mucous membranes are associated with a higher risk of HIV transmission. Based on the calculated risk, post-exposure prophylaxis (PEP) should be recommended. In the Netherlands, prescription of PEP in the occupational setting is a standard procedure and has proved to be feasible. This was associated with a high percentage (62%) of mild and reversible toxicity and a small percentage (2%) of serious adverse events related to antiretroviral drugs, i.e. nephrolithiasis (due to indinavir) and toxic hepatitis (due to nevirapine). In The Netherlands so far no HIV-seroconversions have been recorded after an occupational accident.