A systematic review of the effects of probiotic administration in inflammatory arthritis.

OBJECTIVE: To systematically identify and appraise evidence of the formulation specific effects and population specific responses of probiotics in inflammatory arthritis. METHODS: MEDLINE (PubMed), CINAHL, EMBASE, and SCOPUS databases were searched for studies utilising probiotics in populations with inflammatory arthritis. The Joanna Briggs Institute (JBI) method was used to conduct the systematic review. A single reviewer undertook screening and data extraction. Two independent reviewers assessed the quality of evidence using JBI tools. RESULTS: The search identified 5876 unique articles, with 154 potentially relevant full text articles retrieved. Twelve studies met the inclusion criteria and were included in the review, of which ten (83%) were randomised control trials (RCT) and two (17%) were quasi-experimental studies. Four studies included a variety of spondyloarthopathies (SpAs) and eight studies focused on rheumatoid arthritis (RA). Probiotics were supplied for a median of 60 days and mode of 56 days across all included studies (range 7-365 days). Overall, 17 different probiotics were supplied in colony forming units (CFU) per 24 hrs ranging from 1 × 108 to 2.25 × 1011. The order of probiotics supplied to the most participants and across the most studies was Lactobacillales. There was no statistical difference in the relative risk (RR) of minor adverse events between probiotic and control groups (RR 1.02, 95% CI 0.69 to 1.51) when including nil event studies. Meta-analysis identified a statistically significant benefit of probiotics on quality of life with a standard mean difference (SMD) of -0.37 (95% CI -0.59,-0.15) with subgroup analysis favouring Lactobacillales-only formulations. Small but statistically significant reductions in pain were identified, with a mean difference (MD) of -8.97 (95% CI-15.38, -2.56) on a 100mm visual analogue scale, independent of formulation. Meta-analysis confirmed the known statistically significant benefit of probiotics on the inflammatory marker C-reactive protein (CRP) concentration MD (mg/L) -2.33 (95% CI -4.26, -0.41), with subgroup analysis demonstrating a greater effect in RA and from combined Bifidobacteriales and Lactobacillales formulations. CONCLUSION: This review indicates there may be differential benefits to combined formulations of Bifidobacteriales and Lactobacillales compared to purely Lactobacillales formulations, with respect to reducing pain, lowering CRP and improving quality of life. It also suggests variable benefits associated with the type of inflammatory arthritis. Relatively less benefit for lowering CRP was attributed to individuals with SpA compared to individuals with RA. Generalisability of results to clinical practice is limited by the dominant demographic of older individuals with established disease beyond the 'therapeutic window of intervention'. Small but statistically significant benefits require confirmation in clinical studies with greater consideration to potentially confounding factors of age, gender, diet and individual microbial signature.

The impact of integrated care for people with chronic conditions on hospital and emergency department utilization: a rapid review.

AIM: Integrated care commonly involves provision of comprehensive community-based care for people with chronic conditions. It is anticipated that implementation of integrated care, with a proactive approach to management of chronic conditions, will reduce reliance on hospital and emergency department (ED) services. The aim of this rapid review was to summarize the best available evidence on the impact of integrated care for patients with chronic conditions on hospital and ED utilization and investigate trends in outcomes over time. METHODS: Given the large body of literature available on this topic, this rapid review considered existing systematic reviews and meta-analyses that included adults with chronic conditions. Any model of integrated care that involved management of patients across the continuum of care, with the aim to provide more care in community settings, was considered for inclusion. A search of PubMed, CINAHL, Google Advanced, and websites of international healthcare provider organizations was conducted to locate relevant published and gray literature. RESULTS: A total of 13 systematic reviews were included. Overall, evidence suggests that integrated care may reduce the risk of hospitalization, with reviews including patients with diverse chronic conditions showing a 19% reduction. Integrated care appears effective in reducing readmissions for patients with heart failure, with an absolute risk reduction of 8% for first and 19% for subsequent rehospitalization. For ED presentations, evidence indicates that integrated care has no effect overall but may reduce ED visits for patients aged 65 years or more. For patients with chronic obstructive pulmonary disease, integrated care was associated with reductions in length of stay ranging from 2.5 to 4 days. Studies with shorter follow-up, from 3 to 12 months, in general appeared to show a greater impact of integrated care than studies with longer follow-up of 18 months or more. CONCLUSION: The evidence identified suggests integrated care generally reduces utilization of hospital services. In some instances, there were no differences observed between integrated care and usual care, but no included reviews reported increased utilization of these services. The impact of integrated care may be greater in the short-term, given the ultimate deterioration associated with advanced chronic disease which may negate any long-term benefits.

Metformin Use Associated with Reduced Risk of Dementia in Patients with Diabetes: A Systematic Review and Meta-Analysis.

BACKGROUND: Metformin, a first line antihyperglycemic medication, is an AMPK activator and has been hypothesized to act as a geroprotective agent. Studies on its association with various classifications of age-related cognitive decline have shown mixed results with positive and negative findings. OBJECTIVE: To synthesize the best available evidence on the association of metformin-use with risk, progression, and severity of dementia. METHOD: Eligible research investigated the effect of metformin on dementia, Alzheimer's disease, or any measure of cognitive impairment compared to any control group who were not receiving metformin. The initial search resulted in 862 citations from which 14 studies (seven cohort, four cross-sectional, two RCTs, and one case control) were included. RESULTS: Meta-analysis of three studies showed that cognitive impairment was significantly less prevalent in diabetic metformin (Odds ratio = 0.55, 95% CI 0.38 to 0.78), while six studies showed that dementia incidence was also significantly reduced (Hazard ratio = 0.76, 95% CI 0.39 to 0.88). Mini-Mental State Examination scores were not significantly affected by metformin-use, although both RCTs showed that metformin had a neuroprotective effect compared to placebo. Some studies found negative or neutral effects for metformin use by people with diabetes; the potential mechanism of metformin-induced vitamin B12 deficiency is discussed. CONCLUSIONS: Metformin should continue to be used as a first line therapy for diabetes in patients at risk of developing dementia or Alzheimer's disease. The use of metformin by individuals without diabetes for the prevention of dementia is not supported by the available evidence.

Metformin and Alzheimer's disease, dementia and cognitive impairment: a systematic review protocol.

REVIEW QUESTION/OBJECTIVE: The objective of the review is to assess the effect of metformin on the risk, progression and severity of Alzheimer's disease and other forms of dementia, as well as any measures of cognitive performance or impairment.

Metformin reduces all-cause mortality and diseases of ageing independent of its effect on diabetes control: A systematic review and meta-analysis.

This systematic review investigated whether the insulin sensitiser metformin has a geroprotective effect in humans. Pubmed and Embase were searched along with databases of unpublished studies. Eligible research investigated the effect of metformin on all-cause mortality or diseases of ageing relative to non-diabetic populations or diabetics receiving other therapies with adjustment for disease control achieved. Overall, 260 full-texts were reviewed and 53 met the inclusion criteria. Diabetics taking metformin had significantly lower all-cause mortality than non-diabetics (hazard ratio (HR)=0.93, 95%CI 0.88-0.99), as did diabetics taking metformin compared to diabetics receiving non-metformin therapies (HR=0.72, 95%CI 0.65-0.80), insulin (HR=0.68, 95%CI 0.63-0.75) or sulphonylurea (HR=0.80, 95%CI 0.66-0.97). Metformin users also had reduced cancer compared to non-diabetics (rate ratio=0.94, 95%CI 0.92-0.97) and cardiovascular disease (CVD) compared to diabetics receiving non-metformin therapies (HR=0.76, 95%CI 0.66-0.87) or insulin (HR=0.78, 95%CI 0.73-0.83). Differences in baseline characteristics were observed which had the potential to bias findings, although statistical adjustments were made. The apparent reductions in all-cause mortality and diseases of ageing associated with metformin use suggest that metformin could be extending life and healthspans by acting as a geroprotective agent.

Assessing healthcare professionals' experiences of integrated care: do surveys tell the full story?

BACKGROUND: Integrated care is the combination of different healthcare services with the goal to provide comprehensive, seamless, effective and efficient patient care. Assessing the experiences of healthcare professionals (HCPs) is an important aspect when evaluating integrated care strategies. AIMS: The aim of this rapid review was to investigate if quantitative surveys used to assess HCPs' experiences with integrated care capture all the aspects highlighted as being important in qualitative research, with a view to informing future survey development. METHODS: The review considered all types of health professionals in primary care, and hospital and specialist services, with a specific focus on the provision of integrated care aimed at improving the patient journey. PubMed, CINAHL and grey literature sources were searched for relevant surveys/program evaluations and qualitative research studies. Full text articles deemed to be of relevance to the review were appraised for methodological quality using abridged critical appraisal instruments from the Joanna Briggs Institute. Data were extracted from included studies using standardized data extraction templates. Findings from included studies were grouped into domains based on similarity of meaning. Similarities and differences in the domains covered in quantitative surveys and those identified as being important in qualitative research were explored. RESULTS: A total of 37 studies (19 quantitative surveys, 14 qualitative studies and four mixed-method studies) were included in the review. A range of healthcare professions participated in the included studies, the majority being primary care providers. Common domains identified from quantitative surveys and qualitative studies included Communication, Agreement on Clear Roles and Responsibilities, Facilities, Information Systems, and Coordination of Care and Access. Qualitative research highlighted domains identified by HCPs as being relevant to their experiences with integrated care that have not routinely being surveyed, including Workload, Clear Leadership/Decision-Making, Management, Flexibility of Integrated Care Model, Engagement, Usefulness of Integrated Care and Collaboration, and Positive Impact/Clinical Benefits/Practice Level Benefits. CONCLUSION: There were several domains identified from qualitative research that are not routinely included in quantitative surveys to assess health professionals' experiences of integrated care. In addition, the qualitative findings suggest that the experiences of HCPs are often impacted by deeper aspects than those measured by existing surveys. Incorporation of targeted items within these domains in the design of surveys should enhance the capture of data that are relevant to the experiences of HCPs with integrated care, which may assist in more comprehensive evaluation and subsequent improvement of integrated care programs.

Methotrexate-induced toxicity pharmacogenetics: an umbrella review of systematic reviews and meta-analyses.

PURPOSE: Methotrexate chemotherapy is associated with various toxicities which can result in the interruption or discontinuation of treatment and a subsequently raised risk of relapse. This umbrella systematic review was conducted to synthesize the results of all existing systematic reviews that investigate the pharmacogenetics of methotrexate-induced toxicity, with the aim of developing a comprehensive reference for personalized medicine. METHODS: Databases searched were PubMed, Embase, JBI Database of Systematic Reviews and Implementation Reports, DARE, and ProQuest. Papers were critically appraised by two reviewers, and data were extracted using a standardized tool. RESULTS: Three systematic reviews on methotrexate-induced toxicity were included in the review. Meta-analyses were reported across Asian, Caucasian, pediatric and adult patients for the MTHFR C677T and A1298C polymorphisms. Toxicity outcomes included different forms of hematologic, ectodermal and hepatic toxicities. Results varied considerably depending on the patient groups and subgroups investigated in the different systematic reviews, as well as the genetic models utilized. However, significant associations were found between the MTHFR C677T allele and; hepatic toxicity, myelosuppression, oral mucositis, gastrointestinal toxicity, and skin toxicity. Additionally, limited evidence suggests that the MTHFR A1298C polymorphism may be associated with decreased risk of skin toxicity and leukopenia. CONCLUSION: This umbrella systematic review has synthesized the best available evidence on the pharmacogenetics of methotrexate toxicity. The next step in making personalized medicine for methotrexate therapy a clinical reality is research on the effectiveness and cost-effectiveness of MTHFR genotype testing to enable the close monitoring of at-risk patients for the timely initiation of rescue therapies.

Fluoropyrimidine and platinum toxicity pharmacogenetics: an umbrella review of systematic reviews and meta-analyses.

Fluoropyrimidine (FU) and platinum-based chemotherapies are greatly complicated by their associated toxicities. This umbrella systematic review synthesized all systematic reviews that investigated associations between germline variations and toxicity, with the aim of informing personalized medicine. Systematic reviews are important in pharmacogenetics where false positives are common. Four systematic reviews were identified for FU-induced toxicity and three for platinum. Polymorphisms of DPYD and TYMS, but not MTHFR, were statistically significantly associated with FU-induced toxicity (although only DPYD had clinical significance). For platinum, GSTP1 was found to not be associated with toxicity. This umbrella systematic review has synthesized the best available evidence on the pharmacogenetics of FU and platinum toxicity. It provides a useful reference for clinicians and identifies important research gaps.

Anti-HCV confirmatory testing of voluntary blood donors: comparison of the sensitivity of two immunoblot assays.

BACKGROUND: In this study, the sensitivity of two commercially available anti-HCV immunoblot assays (HCV Western blot (Wellcozyme] and RIBA 3.0 SIA [RIBA-3, Chiron]) was compared in a voluntary blood donor population. STUDY DESIGN AND METHODS: Four groups of donor samples were retrospectively tested in this study. Groups 1 and 2 were donor samples that gave positive or indeterminate band patterns, respectively, when originally tested on the HCV Western blot between 1994 and 1998. These samples were tested on the RIBA 3.0. Donor samples in Groups 3 and 4 were originally tested on RIBA-3 during 1998 and 1999 and gave positive or indeterminate blot results, respectively. In this study these two groups were tested on the HCV Western blot. Samples with discrepant results on the two immunoblot assays were selected for genotyping or serotyping. RESULTS: The two immunoblots showed similar sensitivity to the core and NS5 proteins. However, of 35 samples positive on Western blot or RIBA-3, the Western blot failed to detect NS4 in 14 samples compared with only 5 for RIBA-3. As well, the Western blot failed to detect NS3 in 6 samples compared to 2 for RIBA-3. Five (27.8%) of 18 samples that were Western blot indeterminate due to core reactivity showed an additional NS3 band on RIBA-3. Of the samples with additional NS3 and/or NS4 reactivity on RIBA-3 that were genotyped or serotyped, all were HCV type 3. CONCLUSIONS: Western blot and RIBA-3 showed similar sensitivity to the HCV core and NS5 proteins. However, RIBA-3 showed greater sensitivity to both NS3 and NS4 compared to the Western blot. The reduced sensitivity of the Western blot to the NS3 and NS4 proteins was observed with HCV type 3 samples.