Evaluating the Dual-Target Aptima HIV-1 Quant Dx Assay: Comparison between Viral Loads Measured with pol and LTR Targets in the Same Samples.

For effective management of HIV-1 patients, accurate measurement of HIV-1-RNA viral load (VL) is fundamental. The latest generation molecular assays for monitoring VL perform simultaneous detection of two regions of the viral genome, but without specifying the target used for VL quantitation. By using the "open" software (research use only [RUO]) of Aptima HIV-1 Quant Dx Assay (Aptima) which provides both results obtained with the pol and LTR targets, we were able to compare n = 500 plasma samples results from chronically HIV-1-infected patients under antiretroviral therapy (ART). Correlation and concordance were analyzed. By stratifying VL into two groups (<30 and ≥30 copies/mL HIV-1-RNA) according to pol-based results and matching them with their respective LTR values, concordance was substantial (κ = 0.635; 95%CI = 0.569 to 0.700) as expected. Considering the specimens (n = 224) with VL exactly quantified (i.e., ≥30 copies/mL) with both targets, an optimal correlation subsisted (r = 0.8882; P < 0.0001) and Bland-Altman plot showed no significant mean difference between them. However, by stratifying all these data in three ranges (30 to 200, 201 to 1,000, and >1,000 copies/mL) according to pol-based results, concordance analysis showed fair agreement (κ = 0.344; 95%CI = 0.257 to 0.432). Indeed, after excluding mutually concordant VL values in each range (n = 134), the remaining discordant samples (n = 90; 40.1%) showed significant (P < 0.05) difference between VL measured with the two targets. With the Aptima "open" software, samples with pol-based VL <1,000 copies (cp)/mL HIV-1-RNA, the corresponding LTR values were on average 0.5 log10 cp/mL higher. Further studies on these discrepancies and the nature of viral RNA elements detected only with the LTR despite efficient ART are in progress. IMPORTANCE The last generation dual-target platforms for quantification of HIV-1 RNA return a single value of viral load (VL) derived from a combined reading of two HIV-1 genome targets. By using a modified version of Aptima software, providing both the VL results obtained from pol and LTR amplification separately, we observed discordant VL results in some samples from HIV-1-infected patients on antiretroviral therapy. In particular, some samples with pol-based quantified <1,000 copies/mL VL showed the LTR-based value on average 0.5 log10 copies/mL higher, and other samples, always by treated patients, showed VL exclusively quantified with LTR target while the corresponding pol-based VL results were completely undetected. Standard software of double-target based diagnostic systems does not allow recognizing discrepant VL values in these particular, but not rare, clinical specimens. This issue could have implications for clinical management by leading physicians to consider changing antiretroviral regimen based on presumed failure of antiretroviral therapy.

Vitamin D deficiency predicts cognitive decline in older men and women: The Pro.V.A. Study.

OBJECTIVE: To test the hypothesis that hypovitaminosis D is associated with a higher risk of cognitive decline over a 4.4-year follow-up in a large sample of older adults. METHODS: This research was part of the Progetto Veneto Anziani (Pro.V.A.), an Italian population-based cohort study of 1,927 elderly subjects. Serum 25-hydroxyvitamin D (25OHD) levels were measured at the baseline. Global cognitive function was measured with the Mini-Mental State Examination (MMSE); scores lower than 24 were indicative of cognitive dysfunction, and a decline of 3 or more points on the MMSE over the follow-up was considered as clinically significant. Analyses were adjusted for relevant confounders, including health and performance status. RESULTS: Participants with 25OHD deficiency (<50 nmol/L) or insufficiency (50-75 nmol/L) were more likely to have declining MMSE scores during the follow-up than those who were 25OHD sufficient (≥75 nmol/L). Among participants cognitively intact (baseline MMSE scores ≥24 and without diagnosis of dementia), the multivariate adjusted relative risk (95% confidence interval [CI]) of the onset of cognitive dysfunction was 1.36 (95% CI: 1.04-1.80; p = 0.02) for those with vitamin D deficiency and 1.29 (95% CI: 1.00-1.76; p = 0.05) for those with vitamin D insufficiency by comparison with individuals with normal 25OHD levels. CONCLUSION: The results of our study support an independent association between low 25OHD levels and cognitive decline in elderly individuals. In cognitively intact elderly subjects, 25OHD levels below 75 nmol/L are already predictive of global cognitive dysfunction at 4.4 years.

Prevalence of sarcopenia based on different diagnostic criteria using DEXA and appendicular skeletal muscle mass reference values in an Italian population aged 20 to 80.

OBJECTIVE: To identify the mean values and percentiles for ASMM (appendicular skeletal muscle mass) and the prevalence of sarcopenia, in terms of muscle mass reduction, using different cutoffs in a European population. DESIGN: A retrospective analysis on the dataset from a multicenter study on apparently healthy Italian adults conducted between 1999 and 2002. A significant muscle mass loss, necessary to diagnose sarcopenia, was defined in 3 different ways: (1) by subtracting 2 SDs from the mean ASMM index (ASMMI) of a young adult population (20-39 year-olds), as in the Rosetta study and the NHANES survey; (2) by calculating the 15th percentile of the distribution of our young population, corresponding to about 1 SD below the mean ASMMI; (3) by calculating the 20th percentile of the distribution of the ASMMI (as in the Health ABC study) of an elderly population. SETTING: Five centers for the diagnosis and treatment of osteoporosis in various parts of the country (Padova, Verona, Parma, Roma, Napoli). PARTICIPANTS: Participants were 1535 volunteers (1208 women and 327 men) aged 20 to 80 years, drawn from among staff members, university students, lay people contacted by word of mouth, and patients presenting spontaneously for osteoporosis screening. MEASUREMENTS: Body weight and height were measured for all participants. Body composition was assessed by DEXA, and the ASMMI was calculated as the ASMM divided by body height in meters squared. RESULTS: Both men's and women's lean mass in the arms and ASMM were highest in the young group and became lower in older age. In men, the ASMMI dropped gradually from age 20 to 29 to age 60 to 69, then remained stable in the oldest group. In women, the ASMMI gradually increased from age 20 to 29 to age 60 to 69, then dropped among the 70- to 80-year-olds. Based on the 15th percentile of the ASMMI for our young adult reference population, the cutoffs for sarcopenia were 7.59 kg/m(2) in men and 5.47 kg/m(2) in women; if the 20th percentile of the ASMMI in our elderly subjects (>65 years) was considered, the cutoffs were 7.64 kg/m(2) in men and 5.78 kg/m(2) in women. Applying the different diagnostic criteria to the those older than 65, the prevalence of sarcopenia ranged from 0% to about 20% in both genders. CONCLUSION: The 15th percentile (or 1 SD below the mean) of the ASMMI of our young adults, and the 20th percentile of this index for an elderly reference population proved more effective in identifying cases of sarcopenia than subtracting 2 SD from the mean ASMMI of a young adult population.

Association between serum 25-hydroxyvitamin d levels, bone geometry, and bone mineral density in healthy older adults.

PURPOSE: The association between serum 25-hydroxyvitamin D values and cortical/trabecular bone parameters in older adults has been incompletely explored. This study was designed to investigate the relationship between serum 25-hydroxyvitamin D levels and bone parameters for the tibia and radius using peripheral quantitative computed tomography in free-living healthy older adults. METHODS: The study involved 134 older adults attending a twice-weekly low-intensity fitness program. In addition to clinical history and serum parameters, we assessed fat-free mass using dual-energy X-ray absorptiometry, total bone and cortical bone cross-sectional areas, and trabecular and cortical bone mineral density for the tibia and radius by peripheral quantitative computed tomography. RESULTS: After applying multivariate linear regression models, adjusting for sex, age, body mass index, fat mass and fat-free mass, and creatinine, the association between 25-hydroxyvitamin D and bone parameters was significant for total bone and cortical bone cross-sectional areas in the radius (partial R (2) = 0.05 and 0.09, respectively) and for trabecular bone mineral density and cortical bone cross-sectional area in the tibia (partial R (2) = 0.11 and 0.02, respectively). CONCLUSION: These findings support the idea that serum 25-hydroxyvitamin D levels and bone parameters are linked in older adults. Longitudinal studies are needed to establish whether vitamin D levels over time are associated with changes in these parameters.

Dietary intake and physical performance in healthy elderly women: a 3-year follow-up.

BACKGROUND: Aging is generally accompanied by changes in body composition, muscle mass and strength, leading to a decline in motor and functional performance. Physical activity and eating habits could be involved in modulating this paraphysiological deterioration. Aim of our study was to investigate changes in body composition, diet and physical performance in healthy, elderly females over a 3-year follow-up. METHODS: 92 healthy elderly females (70.9±4.0 years) attending a twice-weekly mild fitness program were eligible for the study. They were assessed at baseline and again after 3 years in terms of clinical history, diet, body composition by DEXA, resting energy expenditure, handgrip strength, knee extensor isometric/isotonic strength, and functional performance measured using the Short Physical Performance Battery (SPPB). RESULTS: After 3 years, women had a significant decline in muscle strength (∆ isotonic: -1.4±4.3 kg, ∆ isokinetic: -2.0±6.3 kg, ∆ handgrip: -3.2±5.0 kg; p<0.001) and physical performance (∆ walking time: 0.71±0.9 s, ∆ walking speed: -0.25±0.35 m/s; p<0.001), while their weight and body composition parameters did not change, except for a small decrease in appendicular skeletal muscle mass (-0.4±1.4 kg). There was a significant drop in calorie (∆:-345.7±533.1 kcal/d; p<0.001) and protein intake (∆:-0.14±0.23 g/d; p<0.001), while resting energy expenditure remained stable. ∆ calorie intake correlated with the variation in 4-meter walking time (r: 0.34; p<0.01). CONCLUSIONS: With advancing age, physical performance declines even in healthy, fit females despite a spare of weight and body composition. This decline in physical activity could lead to a lower calorie intake, which would explain why there is no variation in body weight.

Changes in healthy elderly women's physical performance: a 3-year follow-up.

BACKGROUND: Inflammatory states, hypovitaminosis D and secondary hyperparathyroidism may have a role in the age-related loss of muscle mass, and physical performance in healthy old people. The aim of this study is to investigate changes in muscle mass, strength and physical performance in healthy, active elderly females over a 3-year follow-up, correlating them with any inflammatory states and PTH and 25-hydroxyvitamin D (25-OHD) levels. METHODS: One hundred healthy females over 65 years of age routinely attending a twice-weekly mild fitness program were eligible for the study. Clinical history, serum parameters, body composition by DEXA, handgrip strength, knee extensor isometric/isotonic strength and functional performance measured using the Short Physical Performance Battery (SPPB) were evaluated at the baseline and after 3 years. RESULTS: After 3 years, the women had a significant decrease in weight (∆:-0.8±3.1 kg; p<0.05) and height (∆:-0.4±0,6 cm; p<0.001), while their BMI and body composition parameters did not change. Only IL-6 (∆: 0.6±2.0; p<0.01) and PTH (∆: 30.7±29.2 ng/L; p<0.001) increased significantly, while there were no changes in 25-OHD levels. There was a significant decrease in all the SPPB results and in muscle strength. ∆ PTH only correlated with the variation in 4-meter walking speed (r: 0.41; p<0.01). CONCLUSIONS: With advancing age, physical performance declines even in healthy, active females despite a spare of muscle mass. The increase in PTH seems to have a role in this decline, that could be clarified by further investigations.

Polypharmacy in the elderly: can comprehensive geriatric assessment reduce inappropriate medication use?

Polypharmacy is a problem of growing interest in geriatrics with the increase in drug consumption in recent years, particularly among people aged >65 years. The main reasons for polypharmacy are longer life expectancy, co-morbidity and the implementation of evidence-based clinical practice guidelines. However, polypharmacy also has important negative consequences, such as a higher risk of adverse drug reactions and a decline in medication efficacy because of reduced compliance. Comprehensive geriatric assessment (CGA) has proved effective in reducing the number of prescriptions and daily drug doses for patients by facilitating discontinuation of unnecessary or inappropriate medications. CGA has also demonstrated an ability to optimize treatment by increasing the number of drugs taken in cases where under-treatment has been identified. Greater multidimensional and multidisciplinary efforts are nonetheless needed to tackle polypharmacy-related problems in frail elderly patients. CGA should help geriatrics staff identify diseases with higher priority for treatment, thereby achieving better pharmacological treatment overall in elderly patients. The patient's prognosis should also be considered in the treatment prioritization process. The most appropriate medication regimen should combine existing evidence-based clinical practice guidelines with data gathered from CGA, including social and economic considerations. Furthermore, for prescriptions to remain appropriate, the elderly should periodically undergo medication review, particularly as the risk or presence of multiple co-morbidities increases. This article aims to highlight the increasing impact of polypharmacy in the elderly and to underscore the role of CGA in achieving the most appropriate pharmacological treatment in this age group.

Predictors of low bone mineral density in elderly males with chronic obstructive pulmonary disease: the role of body mass index.

OBJECTIVE: The aim of this study was to investigate the relationships between nutritional indices (Body mass index (BMI), serum albumin), sarcopenia, bone mineral density (BMD) and the severity of their pulmonary obstruction in elderly patients with chronic obstructive pulmonary disease (COPD). METHODS: The method involved was a prospective transversal study; 82 males >65 years old, 41 stable patients with COPD and 41 healthy elderly individuals (controls). All subjects underwent spirometry, biochemical analyses and dual energy X-ray absorptiometry. The significance of the differences between mean values and prevalence rates was tested. The relationships between BMD and independent predictors were analysed by multiple linear regressions. Logistic regression models were applied on dichotomised variables. RESULTS: In patients with COPD, the prevalence of osteoporosis was higher in subjects with sarcopenia (46% vs. 0%; p < 0.05) and with BMI < 25.1 kg/m(2) (58% vs. 15%; p < 0.02). Multiple regression analysis indicated that BMI, appendicular skeletal muscle mass (ASMM), albumin, and forced expiration volume after 1 s (FEV1) explained the 70% of BMD variability at the hip and 56% at the spine. Logistic regression showed that a BMI < 25.1 kg/m(2) was independently associated with osteoporosis risk (OR = 10.0; 95%CI 1.3-76); no independent effect emerged for FEV1% (

Resting VO2, maximal VO2 and metabolic equivalents in free-living healthy elderly women.

BACKGROUND & AIMS: Maximal VO2 (VO2max) and metabolic equivalents (METs) decline with aging due to body composition and cardiovascular modifications. However, a detailed evaluation of these variables for this population has not been done. The aim of this study was to evaluate VO2max and METs in healthy elderly women, and to establish whether the calculated resting VO2 (3.5 ml/min/kg) underestimates the true METs. METHODS: 81 females over 65 years old attending a twice-weekly mild fitness program were studied. Body composition was measured by DEXA. VO2max and resting VO2 (VO(2rest-meas)) were measured by indirect calorimetry. METs were measured (METs-meas) using the VO2max/VO(2rest-meas) ratio, and calculated (METs-cal) from the ratio between measured VO2max and calculated resting VO2 (3.5 ml/min/kg of body weight). RESULTS: The VO(2rest-meas) and VO2max measured by indirect calorimetry were 2.9+/-0.4 ml/min/kg and 17.5+/-2.8 ml/min/kg, respectively. The METs-meas were higher than the METs-cal (6.1+/-1.2 vs 5.0+/-0.8; p<0.001). The 25th-75th percentile range of measured METs was 5.2-6.8. CONCLUSIONS: Our study confirmed that, in elderly women, METs values ranging between 5 and 7 are compatible with an acceptable physical activity. The estimated resting VO2 (3.5 ml/min/kg) does not appear to be applicable to elderly women, because it underestimates the real METs in this population.