Frailty Confers High Mortality Risk across Different Populations:Evidence from an Overview of Systematic Reviews and Meta-Analyses

We performed an overview of systematic reviews and meta-analyses to summarize available data regarding the association between frailty and all-cause mortality. Medline, Embase, CINAHL, Web of Science, PsycINFO, and AMED (Allied and Complementary Medicine) databases were searched until February 2020 for meta-analyses examining the association between frailty and all-cause mortality. The AMSTAR2 checklist was used to evaluate methodological quality. Frailty exposure and the risk of all-cause mortality (hazard ratio [HR] or relative risk [RR]) were displayed in forest plots. We included 25 meta-analyses that pooled data from between 3 and 20 studies. The number of participants included in these meta-analyses ranged between 500,000. Overall, 56%, 32%, and 12% of studies were rated as of moderate, low, and critically low quality, respectively. Frailty was associated with increased risk of all-cause mortality in 24/24 studies where the HR/RRs ranged from 1.35 [95% confidence interval (CI) 1.05-1.74] (patients with diabetes) to 7.95 [95% CI 4.88-12.96] (hospitalized patients). The median HR/RR across different meta-analyses was 1.98 (interquartile range 1.65-2.67). Pre-frailty was associated with a significantly increased risk of all-cause mortality in 7/7 studies with the HR/RR ranging from 1.09 to 3.65 (median 1.51, IQR 1.38-1.73). These data suggest that interventions to prevent frailty and pre-frailty are needed

Patterns and predictors of adherence to statin therapy among older patients: Protocol for a systematic review

Background: The benefits of statin therapy are significantly compromised by noncompliance. Although elderly patients may have particular challenges with medication adherence and persistence, previous reviews on statin adherence have not focused on this population. Additionally, comparisons of adherence and persistence specific to statin indication (primary or secondary prevention) have not been thoroughly explored.Objective: We aim to assess the extent of, and factors associated with, adherence and persistence to statin therapy among older populations (aged ≥65 years).Methods: A systematic review will be undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. Searches will be performed using multiple electronic databases (Ovid MEDLINE, EMBASE, PsycINFO, CINAHL, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, and the National Health Service Economic Evaluation Database) to identify relevant randomized trials and observational studies that evaluated statin adherence and/or persistence as an outcome. Eligible studies will include those involving community-living or outpatient elderly individuals. The methodological quality of randomized controlled trials (RCTs) will be assessed via the Joanna Briggs Institute's critical appraisal checklist for RCTs, and the quality assessment of observational studies will be undertaken using a set of questions formulated with resort to the National Institute of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. When possible, meta-analyses will be conducted using random-effect modeling and generic inverse variance analyses for adjusted-effect estimates. Heterogeneity across studies will be quantified using the I2 statistic. The presence of publication bias will be assessed using funnel plots and Egger's regression tests. A leave-one-out sensitivity analysis will also be conducted to assess the impact of individual study results on pooled estimates. To explore possible sources of heterogeneity across studies, subgroup analyses will be performed based on covariates such as study design, statin indication, country of study, and length of patient follow-up.Results: The electronic database searches were completed in December 2016. Retrieved articles are currently being screened and the entire study is expected to be completed by June 2017.Conclusions: This systematic review will provide further understanding of the patterns of, and barriers to, statin adherence and persistence among older patients. The findings will inform clinical practice and the design of appropriate interventions

Systematic review with meta-analysis: Effects of probiotic supplementation on symptoms in functional dyspepsia

The pathophysiology of functional dyspepsia (FD) remains poorly understood, but alterations of the small intestinal microbiome have been observed. The place of probiotics in treatment is uncertain. We performed a systematic review and meta-analysis of the currently available randomized, controlled trials (RCTs) to evaluate the potential beneficial effects and risks of probiotics in FD. Pubmed, EMBASE, Scopus, Web of Science and the Cochrane Controlled Trials Register were searched (up to May 2019) for RCTs evaluating the effects of probiotic supplementation compared to placebo in adults with FD. Two reviewers independently assessed eligibility, trial quality and extracted information from identified articles. To compare the effects of probiotics with placebo, risk ratios (RRs) with 95 confidence intervals (CIs) were pooled using random effects models. Six trials, including 422 participants were included but only three RCTs could be included in the meta-analysis. Lactobacillus strains showed potential positive effects in terms of improving upper gastrointestinal (GI) symptoms in patients with FD. Probiotic supplementation tended to improve global dyspepsia score (n = 3 RCTs, risk ratio RR: 1.35, 95% CI 0.99 to 1.84; P = 0.061) and bacterial composition in the GI tract. Probiotics were well tolerated without any serious adverse events. While the available data suggest that supplementation with probiotics may improve GI symptoms in patients with FD, the evidence is insufficient to draw clear conclusions regarding efficacy. Thus, high-quality RCTs are needed to establish the beneficial effects of probiotic supplementation on FD outcomes. © 2020 The Author

Global Incidence of Frailty and Prefrailty Among Community-Dwelling Older Adults: A Systematic Review and Meta-analysis

Importance  Frailty is a common geriatric syndrome of significant public health importance, yet there is limited understanding of the risk of frailty development at a population level.Objective  To estimate the global incidence of frailty and prefrailty among community-dwelling adults 60 years or older.Data Sources  MEDLINE, Embase, PsycINFO, Web of Science, CINAHL Plus, and AMED (Allied and Complementary Medicine Database) were searched from inception to January 2019 without language restrictions using combinations of the keywords frailty, older adults, and incidence. The reference lists of eligible studies were hand searched.Study Selection  In the systematic review, 2 authors undertook the search, article screening, and study selection. Cohort studies that reported or had sufficient data to compute incidence of frailty or prefrailty among community-dwelling adults 60 years or older at baseline were eligible.Data Extraction and Synthesis  The methodological quality of included studies was assessed using The Joanna Briggs Institute’s Critical Appraisal Checklist for Prevalence and Incidence Studies. Meta-analysis was conducted using a random-effects (DerSimonian and Laird) model.Main Outcomes and Measures  Incidence of frailty (defined as new cases of frailty among robust or prefrail individuals) and incidence of prefrailty (defined as new cases of prefrailty among robust individuals), both over a specified duration.Results  Of 15 176 retrieved references, 46 observational studies involving 120 805 nonfrail (robust or prefrail) participants from 28 countries were included in this systematic review. Among the nonfrail individuals who survived a median follow-up of 3.0 (range, 1.0-11.7) years, 13.6% (13 678 of 100 313) became frail, with the pooled incidence rate being 43.4 (95% CI, 37.3-50.4; I2 = 98.5%) cases per 1000 person-years. The incidence of frailty was significantly higher in prefrail individuals than robust individuals (pooled incidence rates, 62.7 [95% CI, 49.2-79.8; I2 = 97.8%] vs 12.0 [95% CI, 8.2-17.5; I2 = 94.9%] cases per 1000 person-years, respectively; P for difference < .001). Among robust individuals in 21 studies who survived a median follow-up of 2.5 (range, 1.0-10.0) years, 30.9% (9974 of 32 268) became prefrail, with the pooled incidence rate being 150.6 (95% CI, 123.3-184.1; I2 = 98.9%) cases per 1000 person-years. The frailty and prefrailty incidence rates were significantly higher in women than men (frailty: 44.8 [95% CI, 36.7-61.3; I2 = 97.9%] vs 24.3 [95% CI, 19.6-30.1; I2 = 8.94%] cases per 1000 person-years; prefrailty: 173.2 [95% CI, 87.9-341.2; I2 = 99.1%] vs 129.0 [95% CI, 73.8-225.0; I2 = 98.5%] cases per 1000 person-years). The incidence rates varied by diagnostic criteria and country income level. The frailty and prefrailty incidence rates were significantly reduced when accounting for the risk of death.Conclusions and Relevance  Results of this study suggest that community-dwelling older adults are prone to developing frailty. Increased awareness of the factors that confer high risk of frailty in this population subgroup is vital to inform the design of interventions to prevent frailty and to minimize its consequences.</p

Prescribing indicators at primary health care centers within the WHO African region: a systematic analysis (1995-2015)

Abstract Background Rational medicine use is essential to optimize quality of healthcare delivery and resource utilization. We aim to conduct a systematic review of changes in prescribing patterns in the WHO African region and comparison with WHO indicators in two time periods 1995–2005 and 2006–2015. Methods Systematic searches were conducted in PubMed, Scopus, Web of science, Africa-Wide Nipad, Africa Journals Online (AJOL), Google scholar and International Network for Rational Use of Drugs (INRUD) Bibliography databases to identify primary studies reporting prescribing indicators at primary healthcare centres (PHCs) in Africa. This was supplemented by a manual search of retrieved references. We assessed the quality of studies using a 14-point scoring system modified from the Downs and Black checklist with inclusions of recommendations in the WHO guidelines. Results Forty-three studies conducted in 11 African countries were included in the overall analysis. These studies presented prescribing indicators based on a total 141,323 patient encounters across 572 primary care facilities. The results of prescribing indicators were determined as follows; average number of medicines prescribed per patient encounter = 3.1 (IQR 2.3–4.8), percentage of medicines prescribed by generic name =68.0 % (IQR 55.4–80.3), Percentage of encounters with antibiotic prescribed =46.8 % (IQR 33.7–62.8), percentage of encounters with injection prescribed =25.0 % (IQR 18.7–39.5) and the percentage of medicines prescribed from essential medicines list =88.0 % (IQR 76.3–94.1). Prescribing indicators were generally worse in private compared with public facilities. Analysis of prescribing across two time points 1995–2005 and 2006–2015 showed no consistent trends. Conclusions Prescribing indicators for the African region deviate significantly from the WHO reference targets. Increased collaborative efforts are urgently needed to improve medicine prescribing practices in Africa with the aim of enhancing the optimal utilization of scarce resources and averting negative health consequences

Prescriptive variability of drugs by general practitioners

<div><p>Prescription drug spending is growing faster than any other sector of healthcare. However, very little is known about patterns of prescribing and cost of prescribing between general practices. In this study, we examined variation in prescription rates and prescription costs through time for 55 GP surgeries in Northern Ireland Western Health and Social Care Trust. Temporal changes in variability of prescribing rates and costs were assessed using the Mann–Kendall test. Outlier practices contributing to between practice variation in prescribing rates were identified with the interquartile range outlier detection method. The relationship between rates and cost of prescribing was explored with Spearman's statistics. The differences in variability and mean number of prescribing rates associated with the practice setting and socioeconomic deprivation were tested using t-test and <i>F</i>-test respectively. The largest between-practice difference in prescribing rates was observed for Apr-Jun 2015, with the number of prescriptions ranging from 3.34 to 8.36 per patient. We showed that practices with outlier prescribing rates greatly contributed to between-practice variability. The largest difference in prescribing costs was reported for Apr-Jun 2014, with the prescription cost per patient ranging from £26.4 to £64.5. In addition, the temporal changes in variability of prescribing rates and costs were shown to undergo an upward trend. We demonstrated that practice setting and socio-economic deprivation accounted for some of the between-practice variation in prescribing. Rural practices had higher between practice variability than urban practices at all time points. Practices situated in more deprived areas had higher prescribing rates but lower variability than those located in less deprived areas. Further analysis is recommended to assess if variation in prescribing can be explained by demographic characteristics of patient population and practice features. Identification of other factors contributing to prescribing variability can help us better address potential inappropriateness of prescribing.</p></div

Influence of drug safety advisories on drug utilisation: an international interrupted time series and meta-analysis

OBJECTIVE: To evaluate the association between regulatory drug safety advisories and changes in drug utilisation. DESIGN: We conducted controlled, interrupted times series analyses with administrative prescription claims data to estimate changes in drug utilisation following advisories. We used random-effects meta-analysis with inverse-variance weighting to estimate the average postadvisory change in drug utilisation across advisories. STUDY POPULATION: We included advisories issued in Canada, Denmark, the UK and the USA during 2009-2015, mainly concerning drugs in common use in primary care. We excluded advisories related to over-the-counter drugs, drug-drug interactions, vaccines, drugs used primarily in hospital and advisories with co-interventions within ±6 months. MAIN OUTCOME MEASURES: Change in drug utilisation, defined as actual versus predicted percentage change in the number of prescriptions (for advisories without dose-related advice), or in the number of defined daily doses (for dose-related advisories), per 100 000 population. RESULTS: Among advisories without dose-related advice (n=20), the average change in drug utilisation was -5.83% (95% CI -10.93 to -0.73; p=0.03). Advisories with dose-related advice (n=4) were not associated with a statistically significant change in drug utilisation (-1.93%; 95% CI -17.10 to 13.23; p=0.80). In a post hoc subgroup analysis of advisories without dose-related advice, we observed no statistically significant difference between the change in drug utilisation following advisories with explicit prescribing advice, such as a recommendation to consider the risk of a drug when prescribing, and the change in drug utilisation following advisories without such advice. CONCLUSIONS: Among safety advisories issued on a wide range of drugs during 2009-2015 in 4 countries (Canada, Denmark, the UK and the USA), the association of advisories with changes in drug utilisation was variable, and the average association was modest

Points to consider in cardiovascular disease risk management among patients with rheumatoid arthritis living in South Africa, an unequal middle income country

ABSTRACT: Background: It is plausible that optimal cardiovascular disease (CVD) risk management differs in patients with rheumatoid arthritis (RA) from low or middle income compared to high income populations. This study aimed at producing evidence-based points to consider for CVD prevention in South African RA patients. Methods: Five rheumatologists, one cardiologist and one epidemiologist with experience in CVD risk management in RA patients, as well as two patient representatives, two health professionals and one radiologist, one rheumatology fellow and 11 rheumatologists that treat RA patients regularly contributed. Systematic literature searches were performed and the level of evidence was determined according to standard guidelines. Results: Eighteen points to consider were formulated. These were grouped into 6 categories that comprised overall CVD risk assessment and management (n=4), and specific interventions aimed at reducing CVD risk including RA control with disease modifying anti-rheumatic drugs, glucocorticoids and non-steroidal anti-inflammatory drugs (n=3), lipid lowering agents (n=8), antihypertensive drugs (n=1), low dose aspirin (n=1) and lifestyle modification (n=1). Each point to consider differs partially or completely from recommendations previously reported for CVD risk management in RA patients from high income populations. Currently recommended CVD risk calculators do not reliably identify South African black RA patients with very high-risk atherosclerosis as represented by carotid artery plaque presence on ultrasound. Conclusions: Our findings indicate that optimal cardiovascular risk management likely differs substantially in RA patients from low or middle income compared to high income populations. There is an urgent need for future multicentre longitudinal studies on CVD risk in black African patients with RA.The first meeting held amongst local Rheumatologists was funded by the South African Arthritis and Rheumatology Association. The studies by Professor González-Gay have been supported by grants from “Fondo de Investigaciones Sanitarias” PI06/0024, PS09/00748, PI12/00060, PI15/00525, PI18/00043, and RD12/0009/0013 and RD16/0012 (RIER) from “Instituto de Salud Carlos III” (ISCIII) (Spain), co-funded by FEDER funds

Profiling the mental health of diabetic patients: a cross-sectional survey of Zimbabwean patients

Objective The burden of diabetes mellitus has exponentially increased in low resource settings. Patients with diabetes are more likely to exhibit poor mental health which negatively affects treatment outcomes. However, patients with high levels of social support (SS) are likely to report optimal mental health. We sought to determine how SS affects the report of psychiatric morbidity and health-related quality of life (HRQoL) in 108 diabetic patients in Harare, Zimbabwe. Results The average age of participants was 54.1 (SD 18.6) years. Most of the participants were; females (69.4%), married (51.9%), and were of low level of income (43.5%). 37.1% of the participants exhibited signs of psychiatric morbidity [mean Shona Symptoms Questionnaire score—6.7 (SD 3.2)]. Further, patients also reported lower HRQoL [mean EQ-5D-VAS score—64.1 (SD 15.3)] and high levels of SS [mean Multidimensional Scale of Perceived Social Support score—43.7 (SD 11.5)]. Patients who received greater amount of SS had optimal mental health. Being female, unmarried, lower education attainment, having more comorbid conditions, being diagnosed with type 2 diabetes and having been diagnosed of diabetes for a longer duration were associated with poorer mental health. It is important to develop context-specific interventions to improve diabetic patients’ mental health