Potentially Modifiable Risk Factors for Dementia and Mild Cognitive Impairment: An Umbrella Review and Meta-Analysis.

INTRODUCTION: The prevalence of mild and major neurocognitive disorders (NCDs), also referred to as mild cognitive impairment and dementia, is rising globally. The prevention of NCDs is a major global public health interest. We sought to synthesize the literature on potentially modifiable risk factors for NCDs. METHODS: We conducted an umbrella review using a systematic search across multiple databases to identify relevant systematic reviews and meta-analyses. Eligible reviews examined potentially modifiable risk factors for mild or major NCDs. We used a random-effects multi-level meta-analytic approach to synthesize risk ratios for each risk factor while accounting for overlap in the reviews. We further examined risk factors for major NCD due to two common etiologies: Alzheimer's disease and vascular dementia. RESULTS: A total of 45 reviews with 212 meta-analyses were synthesized. We identified fourteen broadly defined modifiable risk factors that were significantly associated with these disorders: alcohol consumption, body weight, depression, diabetes mellitus, diet, hypertension, less education, physical inactivity, sensory loss, sleep disturbance, smoking, social isolation, traumatic brain injury, and vitamin D deficiency. All 14 factors were associated with the risk of major NCD, and five were associated with mild NCD. We found considerably less research for vascular dementia and mild NCD. CONCLUSION: Our review quantifies the risk associated with 14 potentially modifiable risk factors for mild and major NCDs, including several factors infrequently included in dementia action plans. Prevention strategies should consider approaches that reduce the incidence and severity of these risk factors through health promotion, identification, and early management.

Influence of Diabetes Mellitus on Oncological Outcomes for Patients Living With Cancer.

PURPOSE: The purpose of this meta-analysis was to examine the association between preexisting diabetes in persons living with cancer on diabetes and oncology-related health outcomes. Understanding this association is of priority because the incidence of both cancer and diabetes mellitus is increasing worldwide. METHODS: A comprehensive review of the literature was conducted in collaboration with an expert health sciences librarian. Two authors independently conducted the screening, data collection, and extraction processes. The risk of bias was assessed using several tools, depending on the study design. Relative risks with 95% confidence intervals were calculated. The alpha threshold was 0.05. All analyses were performed using R statistical software (Metaphor and Demeter packages). RESULTS: A total of 45 studies met the selection criteria, but 23 were excluded from the synthesis because they did not have the ranked outcome or correct comparison (persons with and without diabetes), totaling 22 studies included in the meta-analysis. In comparison to participants without preexisting diabetes, participants with preexisting diabetes and cancer were found to have a significantly higher risk of infection and cardiovascular, neurological, gastrointestinal, hepatic, and renal complications. Concurrent preexisting diabetes and cancer were also associated with increased health care service utilization and length of hospital stay. CONCLUSION: The findings from this review highlight the importance of optimal concurrent management of both diseases by overcoming the compartmentalization of medical specializations through (1) integrated, multidisciplinary, shared, and coordinated clinical care pathways between oncology and diabetes health care providers/teams and (2) the continued development of evidence-based clinical guidelines.

Interventions to address polypharmacy in older adults living with multimorbidity: Review of reviews.

OBJECTIVE: To summarize evidence from published systematic reviews evaluating the effect of polypharmacy interventions on clinical and intermediate outcomes. It also summarizes the adverse events that may occur as a result of these interventions. DATA SOURCES: A literature search was conducted using the electronic databases MEDLINE, Embase, CINAHL, Cochrane Central, and Cochrane Database of Systematic Reviews (PROSPERO registration number: CRD42018085767). STUDY SELECTION: The search yielded a total of 21,329 citations, of which 619 were reviewed as full text and 5 met the selection criteria. SYNTHESIS: The polypharmacy interventions were found to produce statistically significant reductions in potentially inappropriate prescribing and improved medication adherence; however, the observed effects on clinical and intermediate outcomes were inconsistent. None of the included reviews reported any significant benefit of polypharmacy interventions for quality-of-life outcomes. Specific to health care utilization and cost, polypharmacy interventions reduced health care resource usage and expenditure. The reviews reported no differences in adverse drug events between polypharmacy interventions and usual care groups. The overall certainty of evidence was reported as low to very low across included reviews. CONCLUSION: Polypharmacy interventions are associated with reductions in potentially inappropriate prescribing and improvements in medication adherence. However, there is limited evidence of their effectiveness for clinical and intermediate outcomes.

Systematic review and meta-analysis of protein intake to support muscle mass and function in healthy adults.

We performed a systematic review, meta-analysis, and meta-regression to determine if increasing daily protein ingestion contributes to gaining lean body mass (LBM), muscle strength, and physical/functional test performance in healthy subjects. A protocol for the present study was registered (PROSPERO, CRD42020159001), and a systematic search of Medline, Embase, CINAHL, and Web of Sciences databases was undertaken. Only randomized controlled trials (RCT) where participants increased their daily protein intake and were healthy and non-obese adults were included. Research questions focused on the main effects on the outcomes of interest and subgroup analysis, splitting the studies by participation in a resistance exercise (RE), age (<65 or ≥65 years old), and levels of daily protein ingestion. Three-level random-effects meta-analyses and meta-regressions were conducted on data from 74 RCT. Most of the selected studies tested the effects of additional protein ingestion during RE training. The evidence suggests that increasing daily protein ingestion may enhance gains in LBM in studies enrolling subjects in RE (SMD [standardized mean difference] = 0.22, 95% CI [95% confidence interval] 0.14:0.30, P < 0.01, 62 studies, moderate level of evidence). The effect on LBM was significant in subjects ≥65 years old ingesting 1.2-1.59 g of protein/kg/day and for younger subjects (<65 years old) ingesting ≥1.6 g of protein/kg/day submitted to RE. Lower-body strength gain was slightly higher by additional protein ingestion at ≥1.6 g of protein/kg/day during RE training (SMD = 0.40, 95% CI 0.09:0.35, P < 0.01, 19 studies, low level of evidence). Bench press strength is slightly increased by ingesting more protein in <65 years old subjects during RE training (SMD = 0.18, 95% CI 0.03:0.33, P = 0.01, 32 studies, low level of evidence). The effects of ingesting more protein are unclear when assessing handgrip strength and only marginal for performance in physical function tests. In conclusion, increasing daily protein ingestion results in small additional gains in LBM and lower body muscle strength gains in healthy adults enrolled in resistance exercise training. There is a slight effect on bench press strength and minimal effect performance in physical function tests. The effect on handgrip strength is unclear.

The combined effect of behavioural risk factors on disability in aging adults from the Canadian Longitudinal Study on Aging (CLSA).

The objective of this study was to explore how behavioural risk factors (smoking, physical activity, and nutrition) cluster together and assess how clusters of behavioural risk factors are associated with functional disability by age and sex at the individual and population level. We used currently available baseline cross-sectional data from the Canadian Longitudinal Study on Aging (CLSA). The CLSA is a national, population-based longitudinal study established to understand and examine health of an aging population. This study included 51,338 Canadian men and women aged 45 to 85 years residing in the community in 10 Canadian provinces. Behavioural risk factors included smoking, physical activity, and nutrition. The main outcome used in the study was functional disability, which was assessed using a questionnaire adapted from the Older Americans Resources and Services Multidimensional Assessment Questionnaire. In this analyses of unique combinations of the risk factors of smoking, physical activity, and nutritional risk, the magnitude of the association of the behavioural risk factors with functional disability was dependent on which risk factors were included and differed by age and sex strata. Of the risk factors, physical activity accounted for between 70% to 90% of the total population level risk in individuals with all three risk factors, suggesting it is a key driver of the population burden of disability. Together, these results show that considering unique clusters of risk factors, as well as age and sex, is essential for tailoring public health strategies to reduce the burden of disability among aging populations.

Polypharmacy and mobility outcomes.

Polypharmacy is known to be associated with negative consequences of mobility related conditions such as falls, functional decline and disability. This systematic review highlights the effectiveness of deprescribing interventions on mobility related conditions in older adults in the community dwelling reported taking five or more medications daily.

Hemolytic Anemia: Sneaky Cause, Leaky Valve.

Intravascular hemolysis is a known complication of prosthetic heart valves. Severe hemolysis is rare (<1%) with the use of newer generation prosthetic valves. This usually occurs due to paravalvular leaks (PVLs). We present a case of hyperbilirubinemia and hemolytic anemia occurring as a result of a PVL of a prosthetic mechanical mitral valve. The patient was a 49-year-old female with a past medical history of rheumatic heart disease status following two mitral valve replacements each with a mechanical prosthesis; she presented with a complaint of worsening fatigue, epigastric pain, nausea, and vomiting. On examination, she had scleral icterus. Heart auscultation revealed a crisp mechanical S1 click and a soft 2/6 systolic murmur in the left lower sternal border. Her abdomen was soft with mild epigastric and right upper quadrant tenderness, and no Murphy's sign. Her labs revealed a white blood cell count of 7.0 x 103/microliter, hemoglobin 10.5 g/dL, hematocrit 29.7%, total bilirubin 6.9 mg/dL, direct bilirubin 0.8 mg/dL, alkaline phosphatase (ALP) 62 U/L, aspartate aminotransferase (AST) 79 U/L, and alanine aminotransferase (ALT) 56 U/L. An ultrasound of the abdomen revealed cholelithiasis without pericholecystic fluid collection and no ultrasonographic Murphy's sign. Magnetic resonance cholangiopancreatography ruled out acute cholecystitis or intra- or extra-hepatic biliary ductal dilatation. A transesophageal echocardiogram showed a well-seated mitral valve prosthesis with a significant PVL and likely moderate mitral regurgitation. The patient was evaluated for possible hemolysis. Lactate dehydrogenase was 1155 U/L, haptoglobin was <30 mg/dL, and reticulocyte count was 5.2%. She underwent a mitral valve re-replacement with a mechanical prosthesis. An echocardiogram after the surgery showed the mechanical prosthesis mitral valve with no residual PVL.

A systematic review of short-term vs long-term effectiveness of one-time abdominal aortic aneurysm screening in men with ultrasound.

BACKGROUND: An up-to-date systematic review on the long-term benefits of one-time abdominal aortic aneurysm (AAA) screening in men with ultrasound is required as new evidence is available. This report was produced for the Canadian Task Force on Preventive Health Care to provide evidence on screening for AAA with ultrasound. The aim of this systematic review was to examine the short-term (3-5 years of follow-up) vs long-term (13-15 years of follow-up) effectiveness of one-time screening for AAA in men. METHODS: This systematic review considered studies from the most recent U.S. Preventive Services Task Force review on AAA screening and passed through the screening process with citations identified in our search up to April 2017 (PROSPERO registration #CRD42015019047). RESULTS: Based on pooled estimates from four population-based randomized controlled trials with moderate-quality evidence, one-time AAA screening in men showed significant reductions in AAA-related mortality and AAA rupture rate, with a reduction of 43% for AAA-related mortality (risk ratio [RR], 0.57; 95% confidence interval [CI], 0.44-0.72; number needed to screen [NNS], 796) and 48% for AAA rupture rate (RR, 0.52; 95% CI, 0.35-0.79; NNS, 606) in short-term follow-up and a reduction of 34% for AAA-related mortality (RR, 0.66; 95% CI, 0.47-0.93; NNS, 311) and 35% for AAA rupture rate (RR, 0.65; 95% CI, 0.51-0.82; NNS, 264) in long-term follow-up. The effect on all-cause mortality was nonsignificant (P = .14) for short-term follow-up but marginally significant for long-term follow-up (RR, 0.99; 95% CI, 0.98-1.00; P = .03; NNS, 164). One-time AAA screening in men was also associated with a significant increase in the number of elective AAA-related procedures and a subsequent decrease in the number of emergency AAA procedures and 30-day postoperative mortality at both short-term and long-term follow-ups. We found no differences for one-time AAA screening in 30-day postoperative mortality due to elective and emergency operations compared with control groups. CONCLUSIONS: Population-based one-time screening for AAA with ultrasound in asymptomatic men aged 65 years and older remains beneficial during the longer term after screening has ceased, with significant reductions in AAA mortality and AAA rupture rate, and hence avoids unnecessary AAA-related deaths. The sensitivity analyses also showed that the benefits of AAA screening were more pronounced in men at a mean age of <70 years with a relatively lower prevalence of AAA than in men at a mean age of >70 years with a relatively higher prevalence of AAA. Future research should explore the long-term benefits of a targeted AAA screening approach based on risk factors such as age, sex, smoking status, family history, aortic diameter, and baseline risk of rupture.

The Effectiveness of eHealth Technologies on Weight Management in Pregnant and Postpartum Women: Systematic Review and Meta-Analysis.

BACKGROUND: The emergence and utilization of electronic health (eHealth) technologies has increased in a variety of health interventions. Exploiting the real-time advantages offered by mobile technologies during and after pregnancy has the potential to empower women and encourage behaviors that may improve maternal and child health. OBJECTIVE: The objective of this study was to assess the effectiveness of eHealth technologies for weight management during pregnancy and the postpartum period and to review the efficacy of eHealth technologies on health behaviors, specifically nutrition and physical activity. METHODS: A systematic search was conducted of the following databases: MEDLINE, EMBASE, Cochrane database of systematic reviews (CDSR), Cochrane central register of controlled trials (CENTRAL), CINAHL (Cumulative Index to Nursing and Allied Health Literature), and PsycINFO. The search included studies published from 1990 to July 5, 2016. All relevant primary studies that involved randomized controlled trials (RCTs), non-RCTs, before-and-after studies, historically controlled studies, and pilot studies were included. The study population was adult women of childbearing age either during pregnancy or the postpartum period. eHealth weight management intervention studies targeting physical activity, nutrition, or both, over a minimum 3-month period were included. Titles and abstracts, as well as full-text screening were conducted. Study quality was assessed using Cochrane's risk of bias tool. Data extraction was completed by a single reviewer, which was then verified by a second independent reviewer. Results were meta-analyzed to calculate pooled estimates of the effect, wherever possible. RESULTS: Overall, 1787 and 176 citations were reviewed at the abstract and full-text screening stages, respectively. A total of 10 studies met the inclusion criteria ranging from high to low risk of bias. Pooled estimates from studies of the effect for postpartum women resulted in a significant reduction in weight (-2.55 kg, 95% CI -3.81 to -1.28) after 3 to 12 months and six studies found a nonsignificant reduction in weight gain for pregnant women (-1.62 kg, 95% CI -3.57 to 0.33) at approximately 40 weeks. CONCLUSIONS: This review found evidence for benefits of eHealth technologies on weight management in postpartum women only. Further research is still needed regarding the use of these technologies during and after pregnancy.

Clinical profile of patients with biopsy proven lupus nephritis at a tertiary care hospital from Northern Pakistan, 1995 to 2012.

OBJECTIVE: TTo highlight the clinical spectrum of biopsy-proven lupus nephritis by analysing any variations in its histological subtypes across gender, varying age groups, serum creatinine levels and anti-double stranded deoxyribonucleic acid levels. METHODS: This retrospective, observational study was conducted at the Lady Reading Hospital in collaboration with the Fauji Foundation Hospital, Peshawar, Pakistan, and comprised patient records of biopsy-proven lupus nephritis from 1995 to 2012. The cases were analysed according to clinical presentations and histological pattern of systemic lupus erythematosus nephritis. EpiData 3.1 and SPSS 17 were used for data analyses. RESULTS: Of the 2,000 renal biopsies performed, lupus nephritis was found in 74(3.7%) cases. Of them, 63(85.1%) were females and 11(14.9%) males. The mean age of the cases was 23.88±9.73 years (range: 10-55 years). Class IV lupus nephritis was seen in 38(51.4%) patients, followed by Class II in 15(20.3%), Class III in 10(13.5%), Class V and VI in 4(5.4%) each and Class I in 3(4.1%). Out of the combined Class III and IV cases, 25(52.08%) had serum creatinine levels of >1.2 mg/dL, whereas positive anti-double stranded deoxyribonucleic acid titers up to 50 IU/L were seen in all of the 48(100%) such patients. Overall, microscopic haematuria was found in 52(70.3%) cases, followed by arthralgia in 40(54.1%). Moreover, 32(50.8%) females and 6(54.5%) males had Type IV nephritis. Class VI lupus nephritis, in particular, were significantly more prominent in 31-40 years of age group when compared to other histological subtypes and age groups (p=0.0096, odds ratio: 23.25, 95% confidence interval: 2.15-251.21). CONCLUSIONS: Female predominance was observed in all histological sub-types of lupus nephritis. Class IV lupus was the most common histological pattern. Microscopic haematuria was the most common clinical presentation.

Screening for abdominal aortic aneurysm in asymptomatic adults.

BACKGROUND: This report was produced for the Canadian Task Force on Preventive Health Care to provide guidelines on screening for abdominal aortic aneurysm (AAA) with ultrasound scan. PURPOSE: The aim of this systematic review is to examine the evidence on benefits and harms of AAA screening. SEARCH STRATEGY: This systematic review considered studies from the most recent United States Preventive Services Task Force review on AAA screening and passed through the screening process with citations identified in our search up to April 2015 (PROSPERO Registration #CRD42015019047). RESULTS: For benefits of one-time AAA screening in men compared with controls, pooled analyses from four randomized controlled trials with moderate quality evidence showed significant reductions in AAA-related mortality and AAA rupture rate up to 13 to 15 years of follow-up with 42% reduction (risk ratio [RR], 0.58; 95% confidence interval [CI], 0.39-0.88; number needed to screen = 212) and 38% reduction (RR, 0.62; 95% CI, 0.45-0.86; number needed to screen = 200), respectively. The effect of on all-cause mortality was marginally significant for longer follow-up. The Chichester trial examined the benefits of one-time AAA screening in women and found no significant differences between screening and control arms for up to 10 years of follow-up (RR, 0.88; 95% CI, 0.72-1.07). For consequences of one-time AAA screening in men compared with controls, there was a significant increase in the total number of AAA-related procedures over a follow-up of 13 to 15 years (2.16 times more likely) compared with controls. For harms of one-time AAA screening, no significant differences were observed in 30-day postoperative mortality for elective and emergency operations with compared control groups. Evidence from the Multicenter Aneurysm Screening Study trial using 13-year follow-up data showed that one-time AAA screening with ultrasound scan was potentially associated with an overdiagnosis of 45% (95% CI, 42%-47%) among screen-detected men. CONCLUSIONS: Population-based screening for AAA with ultrasound scan in asymptomatic men aged 65 years and older showed statistically significant reductions in AAA-related mortality and rupture and, hence, avoids unnecessary AAA-related deaths. The current evidence showed no benefit of one-time AAA screening in woman. Limited evidence is available on the benefits of repeat AAA screening and targeted screening approaches based on risk factors for AAA. Future research should explore the differential benefits of AAA screening based on risk factors that increase risk for developing AAA.

Screening for Colorectal Cancer: A Systematic Review and Meta-Analysis.

To evaluate the effectiveness of colorectal cancer (CRC) screening in asymptomatic adults. A search was conducted of the Medline, Embase, and the Cochrane Library databases. A targeted search of PubMed was conducted for on-topic randomized controlled trials (RCTs). Meta-analysis across 4 RCTs for guaiac fecal occult blood testing (gFOBT) and flexible sigmoidoscopy (FS) screening showed a reduction of 18% (risk ratio [RR], 0.82; 95% CI [CI], 0.73-0.92) and 26% (RR, 0.74; 95% CI, 0.67-0.83) in CRC mortality for the screening group compared to controls, respectively. The number needed to screen (NNS) were 377 (95% CI, 249-887) and 864 (95% CI, 672-1266) for gFOBT and FS screening, respectively. A reduction of 8% and 27% in incidence of late-stage CRC was also observed for gFOBT and FS screening, respectively, but both had no significant effect on all-cause mortality. A single RCT found that screening with immunochemical fecal occult blood test (iFOBT) had no significant impact on CRC mortality (RR, 0.88; 95% CI, 0.72-1.07). Screening with FS has potential harms such as perforation, major and minor bleeding, and death from the procedure or from follow-up colonoscopy. gFOBT and FS screening reduce CRC mortality and incidence of late-stage disease. The absolute effect and NNS were much more favorable for older adults (≥ 60 years), suggesting that a targeted screening approach may avoid exposing younger adults to the harms of CRC screening, from which they are unlikely to derive any significant benefit. Although there is insufficient RCT evidence on the impact of iFOBT on mortality outcomes. compared to gFOBT, this test showed higher sensitivity and comparable specificity, indicating the need to update and reevaluate the evidence in light of future high-quality research. The protocol for this systematic review have been published with PROSPERO 2014: CRD42014009777.

Interventions for prevention and treatment of tobacco smoking in school-aged children and adolescents: A systematic review and meta-analysis.

OBJECTIVES: To determine the effectiveness of primary health care relevant interventions to prevent and treat tobacco smoking in school-aged children and adolescents. METHODS: This systematic review considered studies included in a prior review. We adapted and updated the search to April 2015. Titles, abstracts and full-text articles were reviewed in duplicate; data extraction and quality assessments were performed by one reviewer and verified by another. Meta-analyses and pre-specified sub-group analyses were performed when possible. PROSPERO #CRD42015019051. RESULTS: After screening 2118 records, we included nine randomized controlled trials. The mostly moderate quality evidence suggested targeted behavioral interventions can prevent smoking and assist with cessation. Meta-analysis showed intervention participants were 18% less likely to report having initiated smoking at the end of intervention relative to controls (Risk Ratio 0.82; 95% confidence interval 0.72, 0.94); the absolute effect is 1.92% for smoking initiation, Number Needed to Treat is 52 (95% confidence interval 33, 161). For cessation, meta-analysis showed intervention participants were 34% more likely to report having quit smoking at the end of intervention relative to controls (Risk Ratio 1.34; 95% confidence interval 1.05, 1.69); the absolute effect is 7.98% for cessation, Number Needed to Treat is 13 (95% confidence interval 6, 77). Treatment harms were not mentioned in the literature and no data were available to assess long-term effectiveness. CONCLUSION: Primary care relevant behavioral interventions improve smoking outcomes for children and youth. The evidence on key components is limited by heterogeneity in methodology and intervention strategy. Future trials should target tailored prevention or treatment approaches, establish uniform definition and measurement of smoking, isolate optimal intervention components, and include long-term follow-up.