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.

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.

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.

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.

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.

Screening for lung cancer: A systematic review and meta-analysis.

OBJECTIVES: To examine evidence on benefits and harms of screening average to high-risk adults for lung cancer using chest radiology (CXR), sputum cytology (SC) and low-dose computed tomography (LDCT). METHODS: This systematic review was conducted to provide up to date evidence for Canadian Task Force on Preventive Health Care (CTFPHC) lung cancer screening guidelines. Four databases were searched to March 31, 2015 along with utilizing a previous Cochrane review search. Randomized trials reporting benefits were included; any design was included for harms. Meta-analyses were performed if possible. PROSPERO #CRD42014009984. RESULTS: Thirty-four studies were included. For lung cancer mortality there was no benefit of CXR screening, with or without SC. Pooled results from three small trials comparing LDCT to usual care found no significant benefits for lung cancer mortality. One large high quality trial showed statistically significant reductions of 20% in lung cancer mortality over a follow-up of 6.5years, for LDCT compared with CXR. LDCT screening was associated with: overdiagnosis of 10.99-25.83%; 11.18 deaths and 52.03 patients with major complications per 1000 undergoing invasive follow-up procedures; median estimate for false positives of 25.53% for baseline/once-only screening and 23.28% for multiple rounds; and 9.74 and 5.28 individuals per 1000 screened, with benign conditions underwent minor and major invasive follow-up procedures. CONCLUSION: The evidence does not support CXR screening with or without sputum cytology for lung cancer. High quality evidence showed that in selected high-risk individuals, LDCT screening significantly reduced lung cancer mortality and all-cause mortality. However, for its implementation at a population level, the current evidence warrants the development of standardized practices for screening with LDCT and follow-up invasive testing to maximize accuracy and reduce potential associated harms.

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.