Optimizing Medication Appropriateness in Older Adults: A Randomized Clinical Interventional Trial to Decrease Anticholinergic Burden

Background The complexity of medication therapy in older adults with multiple comorbidities often leads to inappropriate prescribing. Drugs with anticholinergic properties are of particular interest because many are not recognized for this property; their use may lead to increased anticholinergic burden resulting in significant health risks, as well as negatively impacting cognition. Medication therapy management (MTM) interventions showed promise in addressing inappropriate medication use, but the effectiveness of targeted multidisciplinary team interventions addressing anticholinergic medications in older populations is yet to be determined. Methods We conducted an 8-week, parallel-arm, randomized trial to evaluate whether a targeted patient-centered pharmacist–physician team MTM intervention (“targeted MTM intervention”) reduced the use of inappropriate anticholinergic medications in older patients enrolled in a longitudinal cohort at University of Kentucky’s Alzheimer’s Disease Center. Study outcomes included changes in the medication appropriateness index (MAI) targeting anticholinergic medications and in the anticholinergic drug scale (ADS) score from baseline to the end of study. Results Between October 1, 2014 and September 30, 2015 we enrolled and randomized 50 participants taking at least one medication with anticholinergic properties. Of these, 35 (70%) were women, 45 (90%) were white, and 33 (66%) were cognitively intact (clinical dementia rating [CDR] = 0); mean age was 77.7 ± 6.6 years. At baseline, the mean MAI was 12.6 ± 6.3; 25 (50%) of the participants used two or more anticholinergics, and the mean ADS score was 2.8 ± 1.6. After randomization, although no statistically significant difference was noted between groups, we identified a potentially meaningful imbalance as the intervention group had more participants with intact cognition, and thus included CDR in all of the analyses. The targeted MTM intervention resulted in statistically significant CDR adjusted differences between groups with regard to improved MAI (change score of 3.6 (1.1) for the MTM group as compared with 1.0 (0.9) for the control group, p = 0.04) and ADS (change score of 1.0 (0.3) for the MTM group as compared with 0.2 (0.3) for the control group, p = 0.03). Conclusions Our targeted MTM intervention resulted in improvement in anticholinergic medication appropriateness and reduced the use of inappropriate anticholinergic medications in older patients. Our results show promise in an area of great importance to ensure optimum outcomes for medications used in older adults. Trial registration ClinicalTrials.gov NCT02172612. Registered 20 June 2014

Directly observed antiretroviral therapy: a systematic review and meta-analysis of randomised clinical trials.

BACKGROUND: Directly observed therapy has been recommended to improve adherence for patients with HIV infection who are on highly active antiretroviral therapy, but the benefit and cost-effectiveness of this approach has not been established conclusively. We did a systematic review and meta-analysis of randomised trials of directly observed versus self-administered antiretroviral treatment. METHODS: We did duplicate searches of databases (from inception to July 27, 2009), searchable websites of major HIV conferences (up to July, 2009), and lay publications and websites (March-July, 2009) to identify randomised trials assessing directly observed therapy to promote adherence to antiretroviral therapy in adults. Our primary outcome was virological suppression at study completion. We calculated relative risks (95% CIs), and pooled estimates using a random-effects method. FINDINGS: 12 studies met our inclusion criteria; four of these were done in groups that were judged to be at high risk of poor adherence (drug users and homeless people). Ten studies reported on the primary outcome (n=1862 participants); we calculated a pooled relative risk of 1.04 (95% CI 0.91-1.20, p=0.55), and noted moderate heterogeneity between the studies (I(2)= 53.8%, 95% CI 0-75.7, p=0.0247) for directly observed versus self-administered treatment. INTERPRETATION: Directly observed antiretroviral therapy seems to offer no benefit over self-administered treatment, which calls into question the use of such an approach to support adherence in the general patient population. FUNDING: None

Clinically Actionable Hypercholesterolemia and Hypertriglyceridemia in Children with Nonalcoholic Fatty Liver Disease

OBJECTIVE: To determine the percentage of children with nonalcoholic fatty liver disease (NAFLD) in whom intervention for low-density lipoprotein cholesterol or triglycerides was indicated based on National Heart, Lung, and Blood Institute guidelines. STUDY DESIGN: This multicenter, longitudinal cohort study included children with NAFLD enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network. Fasting lipid profiles were obtained at diagnosis. Standardized dietary recommendations were provided. After 1 year, lipid profiles were repeated and interpreted according to National Heart, Lung, and Blood Institute Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction. Main outcomes were meeting criteria for clinically actionable dyslipidemia at baseline, and either achieving lipid goal at follow-up or meeting criteria for ongoing intervention. RESULTS: There were 585 participants, with a mean age of 12.8 years. The prevalence of children warranting intervention for low-density lipoprotein cholesterol at baseline was 14%. After 1 year of recommended dietary changes, 51% achieved goal low-density lipoprotein cholesterol, 27% qualified for enhanced dietary and lifestyle modifications, and 22% met criteria for pharmacologic intervention. Elevated triglycerides were more prevalent, with 51% meeting criteria for intervention. At 1 year, 25% achieved goal triglycerides with diet and lifestyle changes, 38% met criteria for advanced dietary modifications, and 37% qualified for antihyperlipidemic medications. CONCLUSIONS: More than one-half of children with NAFLD met intervention thresholds for dyslipidemia. Based on the burden of clinically relevant dyslipidemia, lipid screening in children with NAFLD is warranted. Clinicians caring for children with NAFLD should be familiar with lipid management

Glacial-Interglacial changes in moisture balance and the impact on vegetation in the southern hemisphere tropical Andes (Bolivia/Peru)

A palynological investigation of the last glacial-interglacial cycle in the southern hemisphere tropical Andes reveals changes in the moisture balance as the main driver in vegetation change. Thirty accelerated mass spectrometry radiocarbon dates, biostratigraphy and tephra correlation reveal that a 119 metre sediment core recovered from the Huiñaimarca sub-basin of Lake Titicaca (16.0° to 17.5° S, 68.5° to 70° W; 3810 masl) contains sediments covering >151,000 years. Correlation of aridity indicators with precessional variations in insolation is used to fine tune the structure of the age-depth curve within this period. Variations in Isoëtes concentration (above/below 10,000 grains/cm3) identify the extent of shallow water environments. Examination of other palaeolimnological indicators (Pediastrum) and consideration of the bathymetry of the Huiñaimarca sub-basin allow the reconstruction of lake level fluctuations. These data indicate five wet/dry cycles between c. 151,000 and 14,200 cal yr BP. High stands are suggested during the transition into (c. 134,000 cal yr BP), and out of (c. 114,000, 92,000 cal yr BP), the last interglacial,and during full glacial conditions (c. 70,000 and 45,000 cal yr BP). These cycles are superimposed on a general trend of deepening lake levels through the glacial period. This interpretation is supported by correlation with sediments from Salar de Uyuni (20oS, 68oW; 3653 masl). The youngest wet episode is concurrent with palaeolake Minchin (c. 45,000 cal yr BP), with further evidence for an additional wet period commencing c. 28,000 cal yr BP, concomitant with palaeolake Tauca. The timing of lake level fluctuations is also supported by palaeoshoreline reconstructions from the Uyuni-Poopó region. However, our data do not suggest a major peak in lake level in Huiñaimarca during the Ouki lake cycle (c. 120,000-98,000 cal yr BP) as inferred from U-Th ages obtained from palaeoshorelines around Lago Poopó. The most extreme dry event occurs during the last interglacial period and resulted in a sedimentary hiatus tentatively dated to c. 121,000-129,000 cal yr BP. The observed wet/dry cycles are shown to have a marked and rapid impact on the vegetation. The aridity of the last interglacial promoted a community dominated by Chenopodiaceae/Amaranthacae, with no modern Andean analogue. Polylepis/Acaena pollen is also shown to fluctuate markedly (0-20%), particularly during the transitions into, and out of, the last interglacial. It is probable that this pollen taxon is primarily representative of the high altitude arboreal genus Polylepis, which is a key component of highly biodiverse Andean woodlands today. Rapid fluctuations indicate the sensitivity of this ecosystem to natural environmental pressure and potential vulnerability to future human impact and climate change. The 100,000 year (eccentricity) solar cycle is shown to be the major controlling factor in moisture balance and vegetation over the last glacial-interglacial cycle. However, significant fluctuations in moisture balance are also evident on timescales considerably shorter than the full glacial-interglacial cycle. We have linked these to precessional (21,000 year) forcing. Nevertheless, precise independent dating during the full glacial cycle is required to confirm the importance of this forcing mechanism

Intramyocellular Lipid and Insulin Resistance: Differential Relationships in European and African Americans

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93716/1/oby.2011.45.pd

Reducing repeat pregnancies in adolescence: applying realist principles as part of a mixed-methods systematic review to explore what works, for whom, how and under what circumstances

BACKGROUND: Previous research has demonstrated emotional, psychological and educational harm to young mothers following unintended conceptions. The UK has one of the highest rates of pregnancies in adolescence in Western Europe with a high proportion of these being repeat pregnancies, making it a topic of interest for public health policy makers, and health and social care practitioners. As part of a wider mixed-methods systematic review, realist principles were applied to synthesise evidence about interventions aiming to reduce repeat pregnancies in adolescence.METHODS: A multi-streamed, mixed-methods systematic review was conducted searching 11 major electronic databases and 9 additional databases from 1995 onwards, using key terms such as pregnancy, teen or adolescent. The principles of realist synthesis were applied to all included literature to uncover theories about what works, for whom, how and in what context. Initial theory areas were developed through evidence scoping, group discussion by the authors and stakeholder engagement to uncover context + mechanism = outcome (CMO) configurations and related narratives.RESULTS: The searches identified 8,664 documents initially, and 403 in repeat searches, filtering to 81 included studies, including qualitative studies, randomised controlled trials, quantitative studies and grey literature. Three CMO configurations were developed. The individual experiences of young mothers' triggered self-efficacy, notions of perceived risks, susceptibility and benefits of pregnancy, resulting in the adolescent taking control of their fertility and sexual encounters. The choice between motherhood and other goals triggered notions of motivations, resulting in the adolescent managing their expectations of motherhood and controlling their fertility and sexual encounters. Barriers and facilitators to accessing services triggered notions of connectedness and self-determination; resulting in interventions that are tailored so they are relevant to young persons, and improve access to services and engagement with the issue of pregnancy in adolescence.CONCLUSIONS: Pregnancy in adolescence is a complex issue with many factors to consider. The conceptual platform described here could help guide policy makers and professionals towards a number of areas that need to be attended to in order to increase the likelihood of an intervention working to prevent rapid repeat pregnancy in adolescence.TRIAL REGISTRATION: PROSPERO CRD42012003168

Diet, physical exercise and cognitive behavioral training as a combined workplace based intervention to reduce body weight and increase physical capacity in health care workers - a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Health care workers comprise a high-risk workgroup with respect to deterioration and early retirement. There is high prevalence of obesity and many of the workers are overweight. Together, these factors play a significant role in the health-related problems within this sector. The present study evaluates the effects of the first 3-months of a cluster randomized controlled lifestyle intervention among health care workers. The intervention addresses body weight, general health variables, physical capacity and musculoskeletal pain.</p> <p>Methods</p> <p>98 female, overweight health care workers were cluster-randomized to an intervention group or a reference group. The intervention consisted of an individually dietary plan with an energy deficit of 1200 kcal/day (15 min/hour), strengthening exercises (15 min/hour) and cognitive behavioral training (30 min/hour) during working hours 1 hour/week. Leisure time aerobic fitness was planned for 2 hour/week. The reference group was offered monthly oral presentations. Body weight, BMI, body fat percentage (bioimpedance), waist circumference, blood pressure, musculoskeletal pain, maximal oxygen uptake (maximal bicycle test), and isometric maximal muscle strength of 3 body regions were measured before and after the intervention period.</p> <p>Results</p> <p>In an intention-to-treat analysis from pre to post tests, the intervention group significantly reduced body weight with 3.6 kg (p < 0.001), BMI from 30.5 to 29.2 (p < 0.001), body fat percentage from 40.9 to 39.3 (p < 0.001), waist circumference from 99.7 to 95.5 cm (p < 0.001) and blood pressure from 134/85 to 127/80 mmHg (p < 0.001), with significant difference between the intervention and control group (p < 0.001) on all measures. No effect of intervention was found in musculoskeletal pain, maximal oxygen uptake and muscle strength, but on aerobic fitness.</p> <p>Conclusion</p> <p>The significantly reduced body weight, body fat, waist circumference and blood pressure as well as increased aerobic fitness in the intervention group show the great potential of workplace health promotion among this high-risk workgroup. Long-term effects of the intervention remain to be investigated.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01015716">NCT01015716</a></p

In Children with Nonalcoholic Fatty Liver Disease, Zone 1 Steatosis is Associated with Advanced Fibrosis

Background & Aims Focal zone 1 steatosis, although rare in adults with nonalcoholic fatty liver disease (NAFLD), does occur in children with NAFLD. We investigated whether focal zone 1 steatosis and focal zone 3 steatosis are distinct subphenotypes of pediatric NAFLD. We aimed to determine associations between the zonality of steatosis and demographic, clinical, and histologic features in children with NAFLD. Methods We performed a cross-sectional study of baseline data from 813 children (age <18 years; mean age, 12.8 ± 2.7 years). The subjects had biopsy-proven NAFLD and were enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network. Liver histology was reviewed using the Nonalcoholic Steatohepatitis Clinical Research Network scoring system. Results Zone 1 steatosis was present in 18% of children with NAFLD (n = 146) and zone 3 steatosis was present in 32% (n = 244). Children with zone 1 steatosis were significantly younger (10 vs 14 years; P < .001) and a significantly higher proportion had any fibrosis (81% vs 51%; P < .001) or advanced fibrosis (13% vs 5%; P < .001) compared with children with zone 3 steatosis. In contrast, children with zone 3 steatosis were significantly more likely to have steatohepatitis (30% vs 6% in children with zone 1 steatosis; P < .001). Conclusions Children with zone 1 or zone 3 distribution of steatosis have an important subphenotype of pediatric NAFLD. Children with zone 1 steatosis are more likely to have advanced fibrosis and children with zone 3 steatosis are more likely to have steatohepatitis. To achieve a comprehensive understanding of pediatric NAFLD, studies of pathophysiology, natural history, and response to treatment should account for the zonality of steatosis