The effect of digital interventions on related health literacy and skills for individuals living with chronic diseases: A systematic review and meta-analysis.

BACKGROUND: Chronic diseases are a leading cause of death and disease burden globally. Digital interventions could be an approach to improve patients' ability to find, evaluate, and use health information. OBJECTIVES: The main objective was to conduct a systematic review to determine the effect of digital interventions on digital health literacy for patients living with chronic disease. Secondary objectives were to provide an overviewof the design and delivery characteristics of interventions that impact digital health literacy in people with chronic disease. METHODS: Randomized controlled trials examining digital health literacy (and related components) for individuals with cardiovascular disease, chronic lung disease, osteoarthritis, diabetes, chronic kidney disease, and HIV were identified. This review was conducted following the PRIMSA guidelines. Certainty was assessed using GRADE and the Cochrane risk of bias tool. Meta-analyses were conducted using Review Manager 5.1. The protocol was registered on PROSPERO (CRD42022375967). RESULTS: 9386 articles were identified and 17 articles representing 16 unique trials were included. Studies evaluated 5138 individuals with one or more chronic conditions (50% women, ages 42 ± 7-71 ± 12 years). The most targeted conditions were cancer, diabetes, cardiovascular disease, and HIV. Interventions included: skills training, websites, electronic personal health records, remote patient monitoring, and education. The effects of the interventions were related to: (i) digital health literacy, (ii) health literacy, (iii) health information skills, (iv) technology skills and access, and (v) self-management and participation in care. A meta-analysis of three studies identified the effect of digital interventions was better than usual care for eHealth literacy (1.22 [CI 0.55, 1.89], p < 0.001). CONCLUSIONS: The evidence of the effects of digital interventions on related health literacy is limited. Existing studies reflect the heterogeneity in study design, population, and outcome measures. There is a need for further studies on the effects of digital interventions on related health literacy for individuals with chronic conditions.

Leukocytes, microRNA, and complement activity in raw, heat-treated, and frozen colostrum and their dynamics as colostrum transitions to mature milk in dairy cows.

The objectives of this study were to evaluate the abundance and viability of leukocytes, the abundance of microRNA, and the activity of the complement pathway in (1) colostrum following heat-treatment or freezing, and (2) colostrum, transition milk, and mature milk. In experiment 1, composite colostrum samples were harvested from individual cows (n = 14) on a commercial dairy farm in NY and split into 3 aliquots using single-use colostrum bags. One aliquot was immediately cooled on ice following harvest (RAW) and stored at 4°C overnight, one was heat-treated for 60 min at 60°C (HT) before being cooled on ice and stored at 4°C overnight, and one was frozen at -20°C overnight (FR). The following morning, all samples were warmed to 40°C before further processing. In experiment 2, cows were sampled in a longitudinal study where composite samples were collected from colostrum (first milking, n = 23), transition milk (3 to 4 d postpartum, n = 13), and mature milk (6 to 7 d postpartum, n = 13). In both experiments colostrum was harvested from the first milking within 8 h of calving and samples were processed within 14 h of collection. Colostral leukocytes were isolated before viability was determined by trypan blue exclusion and manual differential cell counts were performed. Extracellular vesicles were isolated from whey by ultracentrifugation to isolate and quantify microRNA. Activity of the alternative complement pathway was determined in casein-depleted whey by semi-solid phase hemolysis assay. Somatic cell counts were determined for all raw samples. Macrophages and neutrophils made up the greatest proportion of leukocytes in colostrum followed by lymphocytes. Lymphocyte proportion increased as colostrum transitioned to mature milk, but overall somatic cell numbers declined concurrently. Viable cells were not isolated from HT or FR samples. Abundance of microRNA isolated from transition and mature milk was decreased compared with colostrum, did not differ between HT and RAW, but was increased in FR compared with RAW. Alternative complement pathway activity was decreased in HT, but not FR compared with RAW, and was not measurable in transition or mature milk. Postharvest heat-treatment and freezing of colostrum eliminated viable colostral leukocytes and affected microRNA abundance and complement activity. Leukocyte proportions, microRNA abundance, and complement activity changed as colostrum transitioned to mature milk. Although there were clear changes in the colostral components under study in relation to treatment and transition to mature milk, the biological significance of the described treatment effects and temporal changes were not investigated here.

The Design and Rationale of a Phase 2b, Randomized, Double-Blinded, and Placebo-Controlled Trial to Evaluate the Safety and Efficacy of Lomecel-B in Older Adults with Frailty.

BACKGROUND: Frailty in older adults is a rapidly growing unmet medical need. It is an aging-related syndrome characterized by physical decline leading to higher risk of adverse health outcomes. OBJECTIVES: To evaluate the efficacy of Lomecel-B, an allogeneic medicinal signaling cell (MSC) formulation, in older adults with frailty. DESIGN: This multicenter, randomized, parallel-arm, double-blinded, and placebo-controlled phase 2b trial is designed to evaluate dose-range effects of Lomecel-B for frailty on physical functioning, patient-reported outcomes (PROs), frailty status, and biomarkers. SETTING: Eight enrolling clinical research centers, including the Miami Veterans Affairs Medical Center. PARTICIPANTS: Target enrollment is 150 subjects aged 70-85 years of any race, ethnicity, or gender. Enrollment criteria include a Clinical Frailty Score of 5 ("mild") or 6 ("moderate"), a 6MWT of 200-400 m, and serum tumor necrosis factor-alpha (TNF-α) ≥2.5 pg/mL. INTERVENTION: A single intravenous infusion of Lomecel-B (25, 50, 100, or 200 million cells) or placebo (N=30/arm). Patients are followed for 365 days for safety, and the efficacy assessments performed at 90, 180, and 270 days. MEASUREMENTS: The primary endpoint is change in 6MWT in the Lomecel-B-treated arms versus placebo at 180 days post-infusion. Secondary and exploratory endpoints include change in: 6MWT and other physical function measures at all time points; PROs; frailty status; cognitive status; and an inflammatory biomarkers panel. A pre-specified sub-study examines vascular/endothelial biomarkers. Safety is evaluated throughout the trial. RESULTS: The trial is conducted under a Food and Drug Administration Investigational New Drug (IND), with Institutional Review Board approval, and monitoring by an NIH-appointed independent Data Safety Monitoring Board. CONCLUSION: This clinical trial investigates the use of a regenerative medicine strategy for frailty in older adults. The results will further the understanding of the potential for Lomecel-B in the geriatric condition of frailty.

A pilot denture service collaboration between Den-Tech denture charity and Crisis at Christmas Dental Service (CCDS): A Plan-Do-Study-Act analysis.

Introduction The Crisis at Christmas Dental Service (CCDS) provides dental treatment for homeless and vulnerably housed people each year during the Christmas period. In 2017, Den-Tech piloted a same-day field-laboratory denture service alongside CCDS to provide new dentures, additions and repairs for people experiencing social exclusion who have limited access to dental care.Objectives To evaluate the service in terms of: (i) treatment need for denture service; (ii) patient-reported feedback; (iii) clinician-reported feedback; and (iv) learning outcomes from the pilot denture service.Methods Clinicians recorded their dental activity on a standard pro forma and records of the dentures were maintained by the Den-Tech volunteer laboratory technicians. Patient feedback was collected on standardised feedback forms at the dental reception and volunteer feedback was collected via an online survey. The team undertook a quality improvement evaluation using the Plan-Do-Study-Act methodology.Results During the seven-day treatment period in 2017, 24 dentures were produced by the Den-Tech technicians, and in 2018, 31 dentures were created for people experiencing homelessness. In 2017, feedback was collected from 353 patients who attended the service: 99.4% were satisfied with their treatment and 98.3% would have recommended the service to others. Similarly, high levels of positive feedback were received in 2018. Of the dental volunteers who responded, 97.8% of volunteers felt that the denture service benefitted the patients.Conclusions The Den-Tech denture service was well-received by patients and volunteers alike. For the first time at Crisis at Christmas, patients were able to have dental extractions and immediate replacement of these teeth without compromising their dignity and overall appearance.Learning outcomes A quality improvement project utilising real-time volunteer and patient feedback can be a useful tool in reflecting upon the challenges and successes of a service as well as supporting its continual development.

Transition to a More even Distribution of Daily Protein intake Is Associated with Enhanced Fat Loss during a Hypocaloric and Physical Activity Intervention in Obese Older Adults.

BACKGROUND: Optimization of intentional weight loss in obese older adults, through preferential fat mass reduction, is challenging, as the concomitant lean mass loss may exacerbate sarcopenia. Recent studies have suggested within-day distribution of protein intake plays a role in determining body composition remodeling. Here, we assessed whether changes in within-day protein intake distribution are related to improvements in body composition in overweight/obese older adults during a hypocaloric and exercise intervention. METHODS: Thirty-six community-dwelling, overweight-to-obese (BMI 28.0-39.9 kg/m2), sedentary older adults (aged 70.6±6.1 years) were randomized into either physical activity plus successful aging health education (PA+SA; n=15) or physical activity plus weight loss (PA+WL; n=21) programs. Body composition (by CT and DXA) and dietary intake (by three-day food records) were determined at baseline, 6-month, and 12-month follow-up visits. Within-day protein distribution was calculated as the coefficient of variation (CV) of protein ingested per defined time periods (breakfast [5:00-10:59], lunch [11:00-16:59] and dinner [17:00-1:00]). Secondary analysis was performed to determine associations between changes in protein intake distribution and body composition. RESULTS: In both groups, baseline protein intake was skewed towards dinner (PA+SA: 49.1%; PA+WL: 54.1%). The pattern of protein intake changed towards a more even within-day distribution in PA+WL during the intervention period, but it remained unchanged in PA+SA. Transition towards a more even pattern of protein intake was independently associated with a greater decline in BMI (P<0.05) and abdominal subcutaneous fat (P<0.05) in PA+WL. However, changes in protein CV were not associated with changes in body weight in PA+SA. CONCLUSION: Our results show that mealtime distribution of protein intake throughout the day was associated with improved weight and fat loss under hypocaloric diet combined with physical activity. This finding provides a novel insight into the potential role of within-day protein intake on weight management in obese older people.

Intermittent low dose carbon monoxide inhalation does not influence glucose regulation in overweight adults: a randomized controlled crossover trial.

NEW FINDINGS: What is the central question of this study? Low dose carbon monoxide (CO) inhalation plays a role in regulating proteins involved in glucose metabolism; does low dose CO improve glucose and insulin responses to an oral glucose tolerance test in overweight adults? What is the main finding and its importance? Five days of intermittent CO inhalation does not alter the glucose or insulin responses to ingestion of a glucose bolus in overweight adults. Low dose CO is utilized in various physiological assessment procedures; these findings allow researchers and clinicians to utilize these procedures without concern of altering glucose metabolism. ABSTRACT: Low dose carbon monoxide (CO) inhalation upregulates several proteins important for glucose metabolism. Such changes could be clinically significant and may be relevant to those who use CO as a research tool. We hypothesized that low dose CO inhalation would improve glucose and insulin responses to an oral glucose bolus in overweight humans. Eleven young adults (5 men, 6 women; body mass index: 25-35 kg m-2 ) were included in this randomized, placebo-controlled, single-blinded crossover study. Following screening, participants completed two 7-day protocols with a 4-week washout. Twenty-four hours prior to and following five consecutive days of either once daily CO (men: 1.2 ml (kg body mass)-1 ; women: 1.0 ml (kg body mass)-1 ) or placebo (room air) inhalation, participants underwent oral glucose tolerance tests (OGTT). For key outcome variables, there were no significant main effects or interactions across condition or time point (mean ± SD), including fasting glucose (mg dl-1 : pre-placebo: 85.2 ± 10.1; post-placebo: 82.9 ± 10.6; pre-CO: 83.6 ± 7.7; post-CO: 84.0 ± 9.0), 2 h post glucose (mg dl-1 : pre-placebo: 100.9 ± 20.0; post-placebo: 98.7 ± 13.1; pre-CO: 94.2 ± 23.2; post-CO: 94.4 ± 14.9), or the Matsuda index (pre-placebo: 16.1 ± 11.5; post-placebo: 20.3 ± 24.7; pre-CO: 15.6 ± 15.3; post-CO: 17.5 ± 16.8). In conclusion, 5 days of low dose CO administration did not influence glucose and insulin responses to an OGTT in overweight adults. Low dose CO inhalation is utilized in a variety of physiological assessment procedures; these findings allow researchers to utilize these procedures without concern of altering glucose metabolism.

Reuse of materials from a Sustainable Drainage System device: Health, Safety and Environment assessment for an end-of-life Pervious Pavement Structure.

Pervious pavement systems can have a life span of about 20years but, at end-of-life, it becomes necessary to evaluate the state of the infrastructure to determine whether they pose a health and safety risk to workers during dismantling, and also determine potential reuse of the waste material generated. In this paper, we report of an investigation conducted to evaluate whether Pervious pavement systems are hazardous to human health at end-of-life and also to assess the mobility of the stormwater pollutants trapped in the system as a measure of their potential release to receiving systems such as water-bodies and groundwater systems. After decommissioning, the pervious pavement structure was sampled for analysis including Gas Chromatography, inductively coupled plasma spectroscopy and, leachate analysis. Results show that carcinogenic risks were significantly below the regulatory limit of 1×10-6 while, the hazard quotients and cumulative hazard indices were also below regulatory value of 1, based on United States Environmental Protection Agency standards. Furthermore, mean concentrations of benzene, toluene, ethylbenzene and xylene were significantly less than the UK soil guideline values. The results of the leachate analysis show that the metals of concern, Pb, Zn, Cr, Ni, Cd and Cu were all below the threshold for reuse applications such as irrigation purposes as they were all below the regulatory limits such as Food and Agriculture Organization and, United States Environmental Protection Agency standards. Finally, the evaluation of potential reuse and recycling purposes indicate that wastes generated from the dismantling of the PPS are within limits for recycling as aggregates for other civil engineering projects as per European Union standards. This has potential to enhance UK's drive to achieve the target of 70% level of construction & demolition waste recovery for reuse and recycling by the year 2020 as per European Union Water Framework Directive.

Invited Review: APOE at the interface of inflammation, neurodegeneration and pathological protein spread in Alzheimer's disease.

Despite more than a century of research, the aetiology of sporadic Alzheimer's disease (AD) remains unclear and finding disease modifying treatments for AD presents one of the biggest medical challenges of our time. AD pathology is characterized by deposits of aggregated amyloid beta (Aß) in amyloid plaques and aggregated tau in neurofibrillary tangles. These aggregates begin in distinct brain regions and spread throughout the brain in stereotypical patterns. Neurodegeneration, comprising loss of synapses and neurons, occurs in brain regions with high tangle pathology, and an inflammatory response of glial cells appears in brain regions with pathological aggregates. Inheriting an apolipoprotein E ε4 (APOE4) allele strongly increases the risk of developing AD for reasons that are not yet entirely clear. Substantial amounts of evidence support a role for APOE in modulating the aggregation and clearance of Aß, and data have been accumulating recently implicating APOE4 in exacerbating neurodegeneration, tau pathology and inflammation. We hypothesize that APOE4 influences all the pathological hallmarks of AD and may sit at the interface between neurodegeneration, inflammation and the spread of pathologies through the brain. Here, we conducted a systematic search of the literature and review evidence supporting a role for APOE4 in neurodegeneration and inflammation. While there is no direct evidence yet for APOE4 influencing the spread of pathology, we postulate that this may be found in future based on the literature reviewed here. In conclusion, this review highlights the importance of understanding the role of APOE in multiple important pathological mechanisms in AD.

Evidence-based nutritional and pharmacological interventions targeting chronic low-grade inflammation in middle-age and older adults: A systematic review and meta-analysis.

Growing evidence suggests chronic low-grade inflammation (LGI) as a possible mechanism underlying the aging process. Some biological and pharmaceutical compounds may reduce systemic inflammation and potentially avert functional decline occurring with aging. The aim of the present meta-analysis was to examine the association of pre-selected interventions on two established biomarkers of inflammation, interleukin-6 (IL-6), and C-reactive protein (CRP) in middle-age and older adults with chronic LGI. We reviewed the literature on potential anti-inflammatory compounds, selecting them based on safety, tolerability, acceptability, innovation, affordability, and evidence from randomized controlled trials. Six compounds met all five inclusion criteria for our systematic review and meta-analysis: angiotensin II receptor blockers (ARBs), metformin, omega-3, probiotics, resveratrol and vitamin D. We searched in MEDLINE, PubMed and EMBASE database until January 2017. A total of 49 articles fulfilled the selection criteria. Effect size of each study and pooled effect size for each compound were measured by the standardized mean difference. I2 was computed to measure heterogeneity of effects across studies. The following compounds showed a significant small to large effect in reducing IL-6 levels: probiotics (-0.68 pg/ml), ARBs (-0.37 pg/ml) and omega-3 (-0.19 pg/ml). For CRP, a significant small to medium effect was observed with probiotics (-0.43 mg/L), ARBs (-0.2 mg/L), omega-3 (-0.17 mg/L) and metformin (-0.16 mg/L). Resveratrol and vitamin D were not associated with any significant reductions in either biomarker. These results suggest that nutritional and pharmaceutical compounds can significantly reduce established biomarkers of systemic inflammation in middle-age and older adults. The findings should be interpreted with caution, however, due to the evidence of heterogeneity across the studies.

Two cases of differentiation syndrome with ocular manifestations in patients with acute promyelocytic leukaemia treated with all-trans retinoic acid and arsenic trioxide.

PURPOSE: To describe two cases of differentiation syndrome presenting with ocular manifestations including bilateral chorioretinopathy in patients with acute promyelocytic leukaemia treated with all-trans retinoic acid and arsenic trioxide differentiation therapy. OBSERVATIONS: This observational case series identifies two patients at a single tertiary institution diagnosed with differentiation syndrome with associated ophthalmic involvement. Both patients reported bilateral reduction in visual acuity at days fourteen and ten respectively following initiation of differentiation therapy in addition to developing other systemic manifestations of differentiation syndrome. Both patients received the same chemotherapeutic regimen including both all-trans retinoic acid and arsenic trioxide as well as ten days of routine differentiation syndrome prophylaxis with oral prednisolone. Case 1 presented with bilateral pale yellow sub-retinal lesions concentrated at the posterior poles with ocular coherence tomography (OCT) evidence of bilateral multifocal areas of focal RPE elevation and adhesion to the thickened outer retina with interspersed sub-retinal fluid. Fluorescein angiography revealed areas of early hyperflouresence corresponding to the yellow chorioretinal lesions with late diffuse leakage of fluid into the subretinal space. Case 2 presented with a similar characteristic retinal findings on fundoscopy and optical coherence tomography. Both patients experienced rapid improvement in the visual symptoms and marked resolution of the sub-retinal fluid within seven to fourteen days of onset with excellent long-term visual outcome. Both patients achieved molecular remission after induction and received standard consolidation and maintenance therapy without visual disturbance. CONCLUSION AND IMPORTANCE: Ocular manifestations of differentiation syndrome have been only recently recognised. We present a case series of two patients with differentiation syndrome with ocular involvement. Common to both presentations was the presence of bilateral reduction in visual acuity with multifocal serous retinal detachment secondary to chorioretinopathy. The visual outcome from both presentations was excellent with rapid normalisation of visual acuity and resolution of the sub-retinal fluid with only the first case having their differentiation therapy temporarily withheld during the acute phase of illness.

Contributions to lateral balance control in ambulatory older adults.

BACKGROUND: In older adults, impaired control of standing balance in the lateral direction is associated with the increased risk of falling. Assessing the factors that contribute to impaired standing balance control may identify areas to address to reduce falls risk. AIM: To investigate the contributions of physiological factors to standing lateral balance control. METHODS: Two hundred twenty-two participants from the Pittsburgh site of the Health, Aging and Body Composition Study had lateral balance control assessed using a clinical sensory integration balance test (standing on level and foam surface with eyes open and closed) and a lateral center of pressure tracking test using visual feedback. The center of pressure was recorded from a force platform. Multiple linear regression models examined contributors of lateral control of balance performance, including concurrently measured tests of lower extremity sensation, knee extensor strength, executive function, and clinical balance tests. Models were adjusted for age, body mass index, and sex. RESULTS: Larger lateral sway during the sensory integration test performed on foam was associated with longer repeated chair stands time. During the lateral center of pressure tracking task, the error in tracking increased at higher frequencies; greater error was associated with worse executive function. The relationship between sway performance and physical and cognitive function differed between women and men. DISCUSSION: Contributors to control of lateral balance were task-dependent. Lateral standing performance on an unstable surface may be more dependent upon general lower extremity strength, whereas visual tracking performance may be more dependent upon cognitive factors. CONCLUSIONS: Lateral balance control in ambulatory older adults is associated with deficits in strength and executive function.

In Vivo Imaging of Venous Side Cerebral Small-Vessel Disease in Older Adults: An MRI Method at 7T.

BACKGROUND AND PURPOSE: Traditional neuroimaging markers of small-vessel disease focus on late-stage changes. We aimed to adapt a method of venular assessment at 7T for use in older adults. We hypothesized that poorer venular morphologic characteristics would be related to other small-vessel disease neuroimaging markers and a higher prevalence of small-vessel disease-Alzheimer disease risk factors. MATERIALS AND METHODS: Venules were identified in periventricular ROIs on SWI and defined as tortuous or straight. The tortuosity ratio was defined as total tortuous venular length divided by total straight venular length. White matter hyperintensity burden (visually rated from 0 to 3) and the number of microbleeds (0, 1, >1) were determined. Differences in tortuous and straight venular lengths were evaluated. Relationships with demographic variables, allele producing the e4 type of apolipoprotein E (APOE4), growth factors, pulse pressure, physical activity, and Modified Mini-Mental State Examination were assessed via Spearman correlations. RESULTS: Participants had 42% more tortuous venular tissue than straight (median, 1.42; 95% CI, 1.13-1.62). APOE4 presence was associated with a greater tortuosity ratio (ρ = 0.454, P = .001), and these results were robust to adjustment for confounders and multiple comparisons. Associations of the tortuosity ratio with sex and vascular endothelial growth factor did not survive adjustment. Associations of the tortuosity ratio with other variables of interest were not significant. CONCLUSIONS: Morphologic measures of venules at 7T could be useful biomarkers of the early stages of small-vessel disease and Alzheimer disease. Longitudinal studies should examine the impact of apolipoprotein E and vascular endothelial growth factor on the risk of venular damage.

Outcomes for Patients with apparent Chronic Idiopathic Pelvic Pain and associated Pelvic Floor Disorders undergoing Laparoscopic Ventral Mesh Rectopexy.

This article has been temporarily withdrawn, with the agreement of all authors and the journal editor, whilst an investigated is being carried out by the North Bristol NHS Trust and the General Medical Council following some concerns raised.

Neurophysiological assessment of acute pain in infants: a scoping review of research methods.

A systematic scoping search to describe the neurophysiological methods used in infant acute pain assessment research was conducted. Of the 2411 abstracts screened, 19 articles were retained. Nine studies utilised near-infrared spectroscopy (NIRS), two utilised functional magnetic resonance imaging (fMRI), and eight utilised electroencephalography (EEG). There was methodological variability in studies utilising NIRS, whereas EEG and fMRI studies reported consistent methods. Of the eight EEG studies, six identified a nociceptive-specific event-related potential. CONCLUSION: While more methodologically rigorous studies are needed, ERPs appear to hold some promise as indicators of infant nociception during clinical procedures to supplement existing measures.

Potential drug-drug and drug-disease interactions in well-functioning community-dwelling older adults.

WHAT IS KNOWN AND OBJECTIVE: There are few studies examining both drug-drug and drug-disease interactions in older adults. Therefore, the objective of this study was to describe the prevalence of potential drug-drug and drug-disease interactions and associated factors in community-dwelling older adults. METHODS: This cross-sectional study included 3055 adults aged 70-79 without mobility limitations at their baseline visit in the Health Aging and Body Composition Study conducted in the communities of Pittsburgh PA and Memphis TN, USA. The outcome factors were potential drug-drug and drug-disease interactions as per the application of explicit criteria drawn from a number of sources to self-reported prescription and non-prescription medication use. RESULTS: Over one-third of participants had at least one type of interaction. Approximately one quarter (25·1%) had evidence of had one or more drug-drug interactions. Nearly 10·7% of the participants had a drug-drug interaction that involved a non-prescription medication. % The most common drug-drug interaction was non-steroidal anti-inflammatory drugs (NSAIDs) affecting antihypertensives. Additionally, 16·0% had a potential drug-disease interaction with 3·7% participants having one involving non-prescription medications. The most common drug-disease interaction was aspirin/NSAID use in those with history of peptic ulcer disease without gastroprotection. Over one-third (34·0%) had at least one type of drug interaction. Each prescription medication increased the odds of having at least one type of drug interaction by 35-40% [drug-drug interaction adjusted odds ratio (AOR) = 1·35, 95% confidence interval (CI) = 1·27-1·42; drug-disease interaction AOR = 1·30; CI = 1·21-1·40; and both AOR = 1·45; CI = 1·34-1·57]. A prior hospitalization increased the odds of having at least one type of drug interaction by 49-84% compared with those not hospitalized (drug-drug interaction AOR = 1·49, 95% CI = 1·11-2·01; drug-disease interaction AOR = 1·69, CI = 1·15-2·49; and both AOR = 1·84, CI = 1·20-2·84). WHAT IS NEW AND CONCLUSION: Drug interactions are common among community-dwelling older adults and are associated with the number of medications and hospitalization in the previous year. Longitudinal studies are needed to evaluate the impact of drug interactions on health-related outcomes.

The Effect of Chronic Kidney Disease on a Physical Activity Intervention: Impact on Physical Function, Adherence, and Safety.

BACKGROUND: Because chronic kidney disease (CKD) is associated with muscle wasting, older adults with CKD are likely to have physical function deficits. Physical activity can improve these deficits, but whether CKD attenuates the benefits is unknown. Our objective was to determine if CKD modified the effect of a physical activity intervention in older adults. METHODS: This is an exploratory analysis of the LIFE-P study, which compared a 12-month physical activity program (PA) to a successful aging education program (SA) in older adults. CKD was defined as a baseline eGFR < 60 mL/min/1.73 m2. We examined the Short Physical Performance Battery (SPPB) at baseline, 6 and 12 months. Secondary outcomes included serious adverse events (SAE) and adherence to intervention frequency. Linear mixed models were adjusted for age, sex, diabetes, hypertension, CKD, intervention, site, visit, baseline SPPB, and interactions of intervention and visit and of intervention, visit, and baseline CKD. RESULTS: The sample included 368 participants. CKD was present in 105 (28.5%) participants with a mean eGFR of 49.2 ± 8.1 mL/min/1.73 m2. Mean SPPB was 7.38 ± 1.41 in CKD participants; 7.59 ± 1.44 in those without CKD (p = 0.20). For CKD participants in PA, 12-month SPPBs increased to 8.90 (95% CI 8.32, 9.47), while PA participants without CKD increased to 8.40 (95% CI 8.01, 8.79, p = 0.43). For CKD participants in SA, 12-month SPPBs increased to 7.67 (95% CI 7.07, 8.27), while participants without CKD increased to 8.12 (95% CI 7.72, 8.52, p = 0.86). Interaction between CKD and intervention was non-significant (p = 0.88). Number and type of SAEs were not different between CKD and non-CKD participants (all p > 0.05). In PA, adherence for CKD participants was 65.5 ± 25.4%, while for those without CKD was 74.0 ± 22.2% (p = 0.12). CONCLUSION: Despite lower adherence, older adults with CKD likely derive clinically meaningful benefits from physical activity with no apparent impact on safety, compared to those without CKD.

Brain natriuretic peptide and insulin resistance in older adults.

AIMS: Higher levels of brain natriuretic peptide (BNP) have been associated with a decreased risk of diabetes in adults, but whether BNP is related to insulin resistance in older adults has not been established. METHODS: N-terminal of the pro hormone brain natriuretic peptide (NT-pro BNP) was measured among Cardiovascular Health Study participants at the 1989-1990, 1992-1993 and 1996-1997 examinations. We calculated measures of insulin resistance [homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), Gutt index, Matsuda index] from fasting and 2-h concentrations of glucose and insulin among 3318 individuals with at least one measure of NT-proBNP and free of heart failure, coronary heart disease and chronic kidney disease, and not taking diabetes medication. We used generalized estimating equations to assess the cross-sectional association of NT-proBNP with measures of insulin resistance. Instrumental variable analysis with an allele score derived from nine genetic variants (single nucleotide polymorphisms) within or near the NPPA and NPPB loci was used to estimate an un-confounded association of NT-proBNP levels on insulin resistance. RESULTS: Lower NT-proBNP levels were associated with higher insulin resistance even after adjustment for BMI, waist circumference and other risk factors (P < 0.001 for all four indices). Although the genetic score was strongly related to measured NT-proBNP levels amongst European Americans (F statistic = 71.08), we observed no association of genetically determined NT-proBNP with insulin resistance (P = 0.38; P = 0.01 for comparison with the association of measured levels of NT-proBNP). CONCLUSIONS: In older adults, lower NT-proBNP is associated with higher insulin resistance, even after adjustment for traditional risk factors. Because related genetic variants were not associated with insulin resistance, the causal nature of this association will require future study.

Genetic Moderators of the Impact of Physical Activity on Depressive Symptoms.

BACKGROUND: Converging evidence suggests that physical activity is an effective intervention for both clinical depression and sub-threshold depressive symptoms; however, findings are not always consistent. These mixed results might reflect heterogeneity in response to physical activity, with some subgroups of individuals responding positively, but not others. OBJECTIVES: 1) To examine the impact of genetic variation and sex on changes in depressive symptoms in older adults after a physical activity (PA) intervention, and 2) to determine if PA differentially improves particular symptom dimensions of depression. DESIGN: Randomized controlled trial. SETTING: Four field centers (Cooper Institute, Stanford University, University of Pittsburgh, and Wake Forest University). PARTICIPANTS: 396 community-dwelling adults aged 70-89 years who participated in the Lifestyle Interventions and Independence for Elders Pilot Study (LIFE-P). INTERVENTION: 12-month PA intervention compared to an education control. MEASUREMENTS: Polymorphisms in the serotonin transporter (5-HTT), brain-derived neurotrophic factor (BDNF), and apolipoprotein E (APOE) genes; 12-month change in the Center for Epidemiologic Studies Depression Scale total score, as well as scores on the depressed affect, somatic symptoms, and lack of positive affect subscales. RESULTS: Men randomized to the PA arm showed the greatest decreases in somatic symptoms, with a preferential benefit in male carriers of the BDNF Met allele. Symptoms of lack of positive affect decreased more in men compared to women, particularly in those possessing the 5-HTT L allele, but the effect did not differ by intervention arm. APOE status did not affect change in depressive symptoms. CONCLUSIONS: Results of this study suggest that the impact of PA on depressive symptoms varies by genotype and sex, and that PA may mitigate somatic symptoms of depression more than other symptoms. The results suggest that a targeted approach to recommending PA therapy for treatment of depression is viable.

Impact of dietary plane of energy during the dry period on lipoprotein parameters in the transition period in dairy cattle.

The high energy demands of dairy cows during the transition period from late gestation into early lactation can place them at an increased risk for the development of metabolic and infectious diseases. Modification of the dry period diet has been investigated as a preventive means to minimize the detrimental aspects of metabolic shifts during the transition period. Studies investigating the impact of dry period diet on lipid parameters during the transition period have largely focused on markers of lipolysis and ketogenesis. Total cholesterol declines during the periparturient period and increases in early lactation. The impact total energy in the dry period diet has on the ability of the cow to maintain total serum cholesterol, as well as its natural high-density lipoprotein-rich status, during this metabolically challenging window is not clear. The impact of lipoproteins on inflammation and immune function may have a clinical impact on the cow's ability to ward off production-related diseases. In this study, we hypothesized that the provision of adequate, but not excessive, total metabolizable energy, would better allow the cow to maintain total cholesterol and a higher relative proportion of HDL throughout the transition period. Cows were allocated to one of three dry period dietary treatment groups following a randomized block design. Total serum triglycerides, cholesterol and lipoprotein fractions were measured on a weekly basis from approximately 7 weeks pre-calving to 6 weeks post-calving. The cows on the high energy diet maintained total serum cholesterol as compared to the cows provided a lower energy diet, but there was no significant increase in the LDL fraction of lipoproteins between diet treatment groups.