OBJECTIVE: We conducted this systematic review to support the U.S. Preventive Services Task Force in updating its 2014 recommendation on screening for cognitive impairment in older adults. Our review addressed the direct evidence on the benefits and harms of screening for cognitive impairment versus no screening, the test accuracy of screening instruments to detect mild cognitive impairment (MCI) and dementia, and the benefits and harms of treatment for MCI and mild to moderate dementia among community-dwelling older adults age 65 years and older.
DATA SOURCES: We performed an updated search of MEDLINE, PubMed Publisher-Supplied, PsycINFO, and the Cochrane Central Register of Controlled Trials for studies published through January 2019. We supplemented searches by examining reference lists from related articles and expert recommendations and searched federal and international trial registries for ongoing trials.
STUDY SELECTION: Two researchers reviewed 11,644 titles and abstracts and 966 full-text articles against prespecified inclusion criteria. We included test accuracy studies that included screening instruments that could be delivered in primary care in 10 minutes or less by a clinician or self-administered in 20 minutes or less compared with a reference standard. We included trials of major pharmacologic and nonpharmacologic interventions in persons with MCI or mild to moderate dementia and large, observational studies examining adverse effects of these interventions. We conducted dual, independent critical appraisal of all provisionally included studies and abstracted all important study details and results from all studies rated fair or good quality. Data were abstracted by one reviewer and confirmed by another.
DATA ANALYSIS: We synthesized data separately for each key question and within subcategories of screening instruments and treatments. For diagnostic accuracy studies, we focused on sensitivity and specificity of instruments that were evaluated in more than one study. We conducted a qualitative synthesis of results using summary tables and figures to capture key study characteristics, sources of clinical heterogeneity, and overall results of each study. Quantitative synthesis was limited to test performance of the Mini Mental State Examination (MMSE) (due to insufficient number of homogeneous studies for other instruments) and U.S. Food and Drug Administration (FDA)–approved medications to treat Alzheimer’s Disease on global cognitive outcomes, global function, and harms; nonpharmacologic interventions aimed at the patient on global cognitive outcomes; and caregiver and caregiver-patient dyad interventions on caregiver burden and depression outcomes. We ran random-effects meta-analyses using the DerSimonian and Laird method and sensitivity analyses using a Restricted Likelihood Estimation Model with the Knapp-Hartung correction to calculate the pooled differences in mean changes (for continuous data) and pooled risk ratio (for binary data). We used meta-regression to explore potential effect modification by various study, population, and intervention characteristics in cases where 10 or more studies were pooled. We generated funnel plots and conducted tests for small-study effects for all pooled analyses. Using established methods, we assessed the strength of evidence for each question.
RESULTS: Screening (Key Questions 1–3): Only one trial was identified that examined the direct effect of screening for cognitive impairment on important patient outcomes, including potential harms. In that trial, at 12 months, there was no difference in health-related quality of life between those who were screened vs. not screened. Symptoms of depression and anxiety were also similar between groups at 1, 6, and 12 months as was health care utilization and advance care planning. We identified 59 studies that addressed the diagnostic accuracy of 49 screening instruments to detect cognitive impairment. Most instruments were only studied in a handful of well-designed diagnostic accuracy studies in primary care–relevant populations. The MMSE, a brief test taking 7 to 10 minutes to complete, remains the most thoroughly studied instrument. The pooled estimate across 15 studies (n=12,796) resulted in 89 percent sensitivity (95% CI, 0.85 to 0.92) and 89 percent specificity (95% CI, 0.85 to 0.93) to detect dementia at a cutoff of 23 or less or 24 or less. Other screening instruments evaluated in more than one study included the very brief instruments (≤5 minutes) of the CDT, MIS, MSQ, Mini-Cog, Lawton IADL, VF, AD8, and FAQ and the brief instruments (6 to 10 minutes) of the 7MS, AMT, MoCA, SLUMS, and TICS with sensitivity to detect dementia usually at 0.75 or higher and specificity at 0.80 or higher for all instruments. For self-administered, longer tests (>10 minutes), only the IQCODE was assessed in more than one study, with sensitivity to detect dementia ranging from 0.80 to 0.88 and specificity ranging from 0.51 to 0.91. Across all instruments, test performance was generally higher in the detection of dementia vs. mild cognitive impairment, although confidence intervals overlapped. No studies directly addressed the adverse psychological effects of screening or adverse effects from false-positive or false-negative testing. Treatment (Key Questions 4 and 5): We identified 224 trials and 3 observational studies representing more than 240,000 patients and/or caregivers that addressed the treatment or management of MCI or mild to moderate dementia. None of the treatment trials were linked with a screening program; in all cases, trial participants were persons with known MCI or dementia. Pharmacologic Interventions: Based on 45 trials (n=22,431) and three observational studies (n=190,076) that evaluated acetylcholinesterase inhibitors (AChEIs) (i.e., donepezil, galantamine, rivastigmine) and memantine, these medications may improve measures of global cognitive function in the short term, but the magnitude of change is small. In meta-analyses, the differences in changes between those on AChEIs or memantine compared with those on placebo ranged from approximately 1 to 2.5 points on the ADAS-Cog-11 and 0.5 to 1 point on the MMSE over 3 months to 3 years of followup. AChEIs and memantine appeared to increase the likelihood of improving or maintaining patients’ global function by 15 percent (for memantine) to 50 percent (for rivastigmine) in the short term (pooled 95% confidence interval range, 0.49 to 2.69). Other outcome measures were inconsistently reported. Total adverse events and discontinuation due to adverse events were more common with AChEIs, but not memantine, compared with placebo. Rates of serious adverse events overall were not higher among those taking medications vs. placebo, but individual studies noted increased rates of serious adverse events. Trials evaluating other medications or dietary supplements (k=29; n=6,489), including discontinuing antihypertensives, 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors (atorvastatin and simvastatin), nonsteroidal anti-inflammatory drugs (ibuprofen, naproxen, indomethacin, and celecoxib), gonadal steroids (estrogen [plus or minus progesterone] and testosterone), and dietary supplements and vitamins (multivitamins, B vitamins, vitamin E, and omega-3 fatty acids) showed no benefit on global cognitive or physical function in persons with mild to moderate dementia or MCI. Nonpharmacologic Interventions: We identified 61 trials (n=7,847) that evaluated nonpharmacologic patient-level interventions, including cognitive-focused, exercise, and multicomponent and other interventions. Among all interventions, there was no clear benefit on global or domain-specific measures of cognitive function compared with control conditions at 3 months to 2 years followup. Effect estimates generally favored the intervention groups over control groups, but the magnitude of effect was inconsistent across trials and represented very wide confidence intervals (ranging from no effect to a large effect). Physical function outcomes, including change in activities of daily living and independent activities of daily living, as well as quality of life and mental and neuropsychiatric symptoms, were inconsistently reported. There was, however, a pattern of effect for exercise interventions, with small improvements seen in measures of physical function and symptoms for intervention groups, whereas control groups reported worsening function. Caregiver and caregiver-patient dyad interventions including psychoeducation for the caregiver and care and case management interventions, reported in 88 trials (n=14,880), resulted in a consistent benefit on caregiver burden and depression outcomes. Effect sizes were mostly small, however, and were of unclear clinical significance. Little harm was evident in the few nonpharmacologic intervention trials that reported harms.
LIMITATIONS: There is a lack of evidence around how screening for and treating MCI and early-stage dementia affects decision making outcomes. Furthermore, there has been little reproducibility in testing specific screening instruments in primary care populations. The treatment literature is limited by a lack of consistency in the specific outcomes reported and short followup duration. It is difficult to interpret the clinical importance of the small average effects seen among treatment trials, and many measures likely have limited responsiveness for patients with less pronounced cognitive impairment. Consistent and standardized reporting of results according to meaningful thresholds of clinical significance would be helpful in interpreting the small average effects on continuous outcome measures. Other important measures such as quality of life, physical function, and institutionalization, were inconsistently reported.
CONCLUSIONS: Several brief screening instruments can adequately detect cognitive impairment, especially in populations with a higher prevalence of underlying dementia. There is no empiric evidence, however, that screening for cognitive impairment or early diagnosis of cognitive impairment improves patient, caregiver, family, or clinician decision making or other important outcomes nor causes harm. In general, there is support that AChEIs and memantine and interventions that support caregivers, including those that help coordinate care for patients and caregivers, can result in small improvements in the short term. Unfortunately, the average effects of these benefits are quite small and likely not of clinical significance. Any benefits are further limited by the commonly experienced side effects of medications and the limited availability of complex caregiver interventions. Cognitive stimulation and training, exercise interventions, and other medications and supplements showed some favorable effects on patients’ cognitive and physical function, but trial evidence lacked consistency and the estimates of benefit were imprecise. There is less evidence related to screening for and treating MCI. The test performance of the few instruments evaluated to detect MCI was lower than the sensitivity and specificity to detect dementia and there is little evidence for any pharmacologic or nonpharmacologic interventions to preserve or improve patient functioning in persons with MCI.
AIMS: (1) To evaluate the effectiveness of different types of psychosocial interventions on the health-related quality of life among caregivers of individuals with dementia; and (2) To present an overview and assessment of the quality of the most recent intervention studies.
DESIGN: A systematic review and meta-analysis.
DATA SOURCES: MEDLINE, CINAHL, PsycINFO and Cochrane Library electronic databases were searched to find randomized controlled trials (RCTs) published from 2005 to 2017. Using a Boolean search, the key words "caregivers," "dementia," and "quality of life" were combined. The search was completed in January 2018.
REVIEW METHODS: A total of 26 RCTs were included. Intervention details such as content, mode of delivery and duration were reviewed, and each study's risk of bias was assessed. The effectiveness of each type of intervention was calculated using the Hedges G and a random-effects model.
RESULTS: Multicomponent interventions, cognitive-behavioral therapy and complementary alternative medicine therapy showed significant effects on improving caregiver's health-related quality of life. Psychoeducation, social support, case management and cognitive rehabilitation therapy failed to produce significant effects.
CONCLUSION: Via this evidence-based systematic review, multicomponent interventions addressing a variety of caregiver needs can be an effective method for enhancing caregiver health-related quality of life. Further large number of studies are needed to verify this study results.
IMPACT: The findings of this study inform clinicians which interventions are effective in improving caregivers' health-related quality of life. Defining a standardized protocol for multicomponent interventions will be helpful for clinicians to apply the intervention.
IMPORTANCE: Early identification of cognitive impairment may improve patient and caregiver health outcomes.
OBJECTIVE: To systematically review the test accuracy of cognitive screening instruments and benefits and harms of interventions to treat cognitive impairment in older adults (≥65 years) to inform the US Preventive Services Task Force.
DATA SOURCES: MEDLINE, PubMed, PsycINFO, and Cochrane Central Register of Controlled Trials through January 2019, with literature surveillance through November 22, 2019.
STUDY SELECTION: Fair- to good-quality English-language studies of cognitive impairment screening instruments, and pharmacologic and nonpharmacologic treatments aimed at persons with mild cognitive impairment (MCI), mild to moderate dementia, or their caregivers.
DATA EXTRACTION AND SYNTHESIS: Independent critical appraisal and data abstraction; random-effects meta-analyses and qualitative synthesis.
MAIN OUTCOMES AND MEASURES: Sensitivity, specificity; patient, caregiver, and clinician decision-making; patient function, quality of life, and neuropsychiatric symptoms; caregiver burden and well-being.
RESULTS: The review included 287 studies with more than 280 000 older adults. One randomized clinical trial (RCT) (n = 4005) examined the direct effect of screening for cognitive impairment on patient outcomes, including potential harms, finding no significant differences in health-related quality of life at 12 months (effect size, 0.009 [95% CI, -0.063 to 0.080]). Fifty-nine studies (n = 38 531) addressed the accuracy of 49 screening instruments to detect cognitive impairment. The Mini-Mental State Examination was the most-studied instrument, with a pooled sensitivity of 0.89 (95% CI, 0.85 to 0.92) and specificity of 0.89 (95% CI, 0.85 to 0.93) to detect dementia using a cutoff of 23 or less or 24 or less (15 studies, n = 12 796). Two hundred twenty-four RCTs and 3 observational studies including more than 240 000 patients or caregivers addressed the treatment of MCI or mild to moderate dementia. None of the treatment trials were linked with a screening program; in all cases, participants were persons with known cognitive impairment. Medications approved to treat Alzheimer disease (donepezil, galantamine, rivastigmine, and memantine) improved scores on the ADAS-Cog 11 by 1 to 2.5 points over 3 months to 3 years. Psychoeducation interventions for caregivers resulted in a small benefit for caregiver burden (standardized mean difference, -0.24 [95% CI, -0.36 to -0.13) over 3 to 12 months. Intervention benefits were small and of uncertain clinical importance.
CONCLUSIONS AND RELEVANCE: Screening instruments can adequately detect cognitive impairment. There is no empirical evidence, however, that screening for cognitive impairment improves patient or caregiver outcomes or causes harm. It remains unclear whether interventions for patients or caregivers provide clinically important benefits for older adults with earlier detected cognitive impairment or their caregivers.
BACKGROUND: Persons with dementia have twice the acute hospital use as older persons without dementia. In addition to straining overburdened healthcare systems, acute hospital use impacts patient and caregiver quality of life and is associated with increased risk of adverse outcomes including death. Reducing avoidable acute hospital use in persons with dementia is thus a global healthcare priority. However, evidence regarding the impact of health service interventions as defined by the Effective Practice and Organization of Care Cochrane Group on acute hospital use is scant and inconclusive. The aim of this systematic review and meta-analysis was to synthesize available evidence on the impact of health service interventions on acute hospital use in community-dwelling persons with dementia compared to usual care.
METHODS: Data Sources: MEDLINE, EMBASE, CINAHL and Cochrane CENTRAL (from 01/1995 to 08/2017). Study eligibility criteria: Randomised controlled trials measuring the impact of health service interventions on acute hospital use (proportion and mean number of emergency department visits and hospitalisations, mean number of hospital days, measured at 12 months, and at longest follow-up) in community-dwelling persons with dementia, compared to usual care. Study selection, appraisal and synthesis methods: Reviewers independently identified studies, extracted data, and assessed the risk of bias, with the Cochrane risk of bias tool. Authors of relevant trials were queried about unpublished data. Random effects model was used for meta-analyses. Effect heterogeneity was assessed through prediction intervals, and explored using sub-group analyses.
FINDINGS: Seventeen trials provided data on 4,549 persons. Unpublished data were obtained for 13 trials, representing 65% of synthesized data. Most interventions included a case management or a self-management component. None of the outcome comparisons provided conclusive evidence supporting the hypothesis that these interventions would lead to a decrease in acute hospital use. Furthermore, prediction intervals indicated possible and important increased service use associated with these interventions, such as emergency department visits, hospital admissions, and hospital days. Subgroup analyses did not favour any type of intervention. A limitation of this study is the inclusion of any type of health service intervention, which may have increased the observed heterogeneity.
CONCLUSION: Despite a comprehensive systematic review and meta-analysis, including predominantly unpublished data, no health service intervention beyond usual care was found to reduce acute hospital use in community-dwelling persons with dementia. An important increase in service use may be associated with these interventions. Further research is urgently needed to identify effective interventions for this vulnerable population to limit rising acute hospital use, associated costs and adverse outcomes. Systematic review registration PROSPERO CRD42016046444.
Despite convincing evidence of short-term symptom control and functional recovery of patients with psychosis after receiving early intervention (EI) services, little is known about the long-term outcomes of EI for these patients. This review aims to evaluate the effectiveness of EI services in improving long-term outcomes of patients with psychosis. A systematic literature search was conducted on PubMed, PsycINFO, Scopus, Medline, CINAHL, BIOSIS, and EMBASE electronic databases to identify studies that evaluated long-term outcomes of patients with psychosis measured 5 years or beyond after entering the EI service. Of 13,005 articles returned from the search, 14 eligible articles reporting study cohorts from nine EI services in seven countries and regions were identified. Data on study design, patient characteristics, intervention components, and outcomes were extracted and reviewed. Only a few studies reported better longitudinal outcomes for negative symptoms, mortality, employment, and hospitalization in patients received EI services. However, results from cross-sectional measurements provided little evidence for long-term impacts of EI services on clinical and functional outcomes. A dilution effect of benefits over time was also demonstrated in several studies. This review highlights the gap in current EI service provision and suggests possible future directions for service improvement and further research.
OBJECTIVE: To evaluate the impact of water, sanitation and hygiene (WASH) interventions in children (age <18 y) on growth, non-diarrheal morbidity and mortality in children.
DESIGN: Systematic review of randomized controlled trials, non-randomized controlled trials and controlled before-after studies.
SETTING: Low- and middle-income countries.
PARTICIPANTS: 41 trials with WASH intervention, incorporating data on 113055 children.
INTERVENTION: Hygiene promotion and education (15 trials); water intervention (10 trials), sanitation improvement (7 trials), all three components of WASH (4 trials), combined water and sanitation (1 trial) and sanitation and hygiene (1 trial).
OUTCOME MEASURES: (i) Anthropometry: weight, height, weight-for-height, mid-arm circumference; (ii) Prevalence of malnutrition; (iii) Non-diarrheal morbidity; and (iv) mortality.
RESULTS: There was no effect of hygiene intervention on most anthropometric parameters (low to very low quality evidence). Hygiene intervention reduced the risk of developing Acute respiratory infections by 24% (RR 0.76; 95% CI 0.59, 0.98; moderate quality evidence), cough by 10% (RR 0.90; 95% CI 0.83, 0.97; moderate quality evidence), laboratory-confirmed influenza by 50% (RR 0.5; 95% CI 0.41, 0.62; very low quality evidence), fever by 13% (RR 0.87; 95% CI 0.74, 1.02; moderate quality evidence), and conjunctivitis by 51% (RR 0.49; 95% CI 0.45, 0.55; low quality evidence). There was low quality evidence to suggest no impact of intervention on mortality (RR 0.65; 95% CI 0.25, 1.7). Improvement in water supply and quality was associated with slightly higher weight-for-age Z-score (MD 0.03; 95% CI 0, 0.06; low quality evidence), but no significant impact on other anthropometric parameters or infectious morbidity (low to very low quality evidence). There was very low quality evidence to suggest reduction in mortality (RR 0.45; 95% CI 0.25, 0.81). Improvement in sanitation had a variable effect on the anthropometry and infectious morbidity. Combined water, sanitation and hygiene intervention improved height-for-age z scores (MD 0.22; 95% CI 0.12, 0.32) and decreased the risk of stunting by 13% (RR 0.87; 95% CI 0.81, 0.94) (very low quality of evidence). There was no evidence of significant effect of combined WASH interventions on non-diarrheal morbidity (fever, respiratory infections, intestinal helminth infection and school absenteeism) were not altered by intervention (low to very low quality of evidence). Any WASH intervention (considered together) resulted in lower risk of underweight (RR 0.81; 95% CI 0.69, 0.96), stunting (RR 0.77; 95% CI 0.68, 0.86) and wasting (RR 0.12, 0.85) (low to very low quality of evidence).
CONCLUSION: Available evidence suggests that there may be little or no effect of WASH interventions on the anthropometric indices in children from low- and middle-income countries. There is low to very low quality of evidence to suggest decrease in prevalence of wasting, stunting and underweight. WASH interventions (especially hygiene intervention) were associated with lower risk of non-diarrheal morbidity (very low to moderate quality evidence). There was very low quality evidence to suggest some decrease to no change in mortality. These potential health benefits lend support to the ongoing efforts for provision of safe and adequate water supply, sanitation and hygiene.
IMPORTANCE: The value of early intervention in psychosis and allocation of public resources has long been debated because outcomes in people with schizophrenia spectrum disorders have remained suboptimal.
OBJECTIVE: To compare early intervention services (EIS) with treatment as usual (TAU) for early-phase psychosis.
DATA SOURCES: Systematic literature search of PubMed, PsycINFO, EMBASE, and ClinicalTrials.gov without language restrictions through June 6, 2017.
STUDY SELECTION: Randomized trials comparing EIS vs TAU in first-episode psychosis or early-phase schizophrenia spectrum disorders.
DATA EXTRACTION AND SYNTHESIS: This systematic review was conducted according to PRISMA guidelines. Three independent investigators extracted data for a random-effects meta-analysis and prespecified subgroup and meta-regression analyses.
MAIN OUTCOMES AND MEASURES: The coprimary outcomes were all-cause treatment discontinuation and at least 1 psychiatric hospitalization during the treatment period.
RESULTS: Across 10 randomized clinical trials (mean [SD] trial duration, 16.2 [7.4] months; range, 9-24 months) among 2176 patients (mean [SD] age, 27.5 [4.6] years; 1355 [62.3%] male), EIS was associated with better outcomes than TAU at the end of treatment for all 13 meta-analyzable outcomes. These outcomes included the following: all-cause treatment discontinuation (risk ratio [RR], 0.70; 95% CI, 0.61-0.80; P < .001), at least 1 psychiatric hospitalization (RR, 0.74; 95% CI, 0.61-0.90; P = .003), involvement in school or work (RR, 1.13; 95% CI, 1.03-1.24; P = .01), total symptom severity (standardized mean difference [SMD], -0.32; 95% CI, -0.47 to -0.17; P < .001), positive symptom severity (SMD, -0.22; 95% CI, -0.32 to -0.11; P < .001), and negative symptom severity (SMD, -0.28; 95% CI, -0.42 to -0.14; P < .001). Superiority of EIS regarding all outcomes was evident at 6, 9 to 12, and 18 to 24 months of treatment (except for general symptom severity and depressive symptom severity at 18-24 months).
CONCLUSIONS AND RELEVANCE: In early-phase psychosis, EIS are superior to TAU across all meta-analyzable outcomes. These results support the need for funding and use of EIS in patients with early-phase psychosis.
BACKGROUND: Teachers and school staff should be competent in managing asthma in schools. Demonstrated low levels of asthma knowledge mean that staff may not know how best to protect a child with asthma in their care, or may fail to take appropriate action in the event of a serious attack. Education about asthma could help to improve this knowledge and lead to better asthma outcomes for children.
OBJECTIVES: To assess the effectiveness and safety of asthma education programmes for school staff, and to identify content and attributes underpinning them.
SEARCH METHODS: We conducted the most recent searches on 29 November 2016.
SELECTION CRITERIA: We included randomised controlled trials comparing an intervention to educate school staff about asthma versus a control group. We included studies reported as full text, those published as abstract only and unpublished data.
DATA COLLECTION AND ANALYSIS: At least two review authors screened the searches, extracted outcome data and intervention characteristics from included studies and assessed risk of bias. Primary outcomes for the quantitative synthesis were emergency department (ED) or hospital visits, mortality and asthma control; we graded the main results and presented evidence in a 'Summary of findings' table. We planned a qualitative synthesis of intervention characteristics, but study authors were unable to provide the necessary information.We analysed dichotomous data as odds ratios, and continuous data as mean differences or standardised mean differences, all with a random-effects model. We assessed clinical, methodological and statistical heterogeneity when performing meta-analyses, and we narratively described skewed data.
MAIN RESULTS: Five cluster-RCTs of 111 schools met the review eligibility criteria. Investigators measured outcomes in participating staff and often in children or parents, most often at between 1 and 12 months.All interventions were educational programmes but duration, content and delivery varied; some involved elements of training for pupils or primary care providers. We noted risk of selection, performance, detection and attrition biases, although to a differing extent across studies and outcomes.Quanitative and qualitative analyses were limited. Only one study reported visits to the ED or hospital and provided data that were too skewed for analysis. No studies reported any deaths or adverse events. Studies did not report asthma control consistently, but results showed no difference between groups on the paediatric asthma quality of life questionnaire (mean difference (MD) 0.14, 95% confidence interval (CI) -0.03 to 0.31; 1005 participants; we downgraded the quality of evidence to low for risk of bias and indirectness). Data for symptom days, night-time awakenings, restricted activities of daily living and school absences were skewed or could not be analysed; some mean scores were better in the trained group, but most differences between groups were small and did not persist to 24 months.Schools that received asthma education were more adherent to asthma policies, and staff were better prepared; more schools that had received staff asthma training had written asthma policies compared with control schools, more intervention schools showed improvement in measures taken to prevent or manage exercise-induced asthma attacks and more staff at intervention schools reported that they felt able to administer salbutamol via a spacer. However, the quality of the evidence was low; results show imbalances at baseline, and confidence in the evidence was limited by risk of bias and imprecision. Staff knowledge was higher in groups that had received asthma education, although results were inconsistent and difficult to interpret owing to differences between scales (low quality).Available information about the interventions was insufficient for review authors to conduct a meaningful qualitative synthesis of the content that led to a successful intervention, or of the resources required to replicate results accurately.
AUTHORS' CONCLUSIONS: Asthma education for school staff increases asthma knowledge and preparedness, but studies vary and all available evidence is of low quality. Studies have not yet captured whether this improvement in knowledge has led to appreciable benefits over the short term or the longer term for the safety and health of children with asthma in school. Randomised evidence does not contribute to our knowledge of content or attributes of interventions that lead to the best outcomes, or of resources required for successful implementation.Complete reporting of the content and resources of educational interventions is essential for assessment of their effectiveness and feasibility for implementation. This applies to both randomised and non-randomised studies, although the latter may be better placed to observe important clinical outcomes such as exacerbations and mortality in the longer term.
BACKGROUND: Intensive Case Management (ICM) is a community-based package of care aiming to provide long-term care for severely mentally ill people who do not require immediate admission. Intensive Case Management evolved from two original community models of care, Assertive Community Treatment (ACT) and Case Management (CM), where ICM emphasises the importance of small caseload (fewer than 20) and high-intensity input.
OBJECTIVES: To assess the effects of ICM as a means of caring for severely mentally ill people in the community in comparison with non-ICM (caseload greater than 20) and with standard community care. We did not distinguish between models of ICM. In addition, to assess whether the effect of ICM on hospitalisation (mean number of days per month in hospital) is influenced by the intervention's fidelity to the ACT model and by the rate of hospital use in the setting where the trial was conducted (baseline level of hospital use).
SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Trials Register (last update search 10 April 2015).
SELECTION CRITERIA: All relevant randomised clinical trials focusing on people with severe mental illness, aged 18 to 65 years and treated in the community care setting, where ICM is compared to non-ICM or standard care.
DATA COLLECTION AND ANALYSIS: At least two review authors independently selected trials, assessed quality, and extracted data. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For continuous data, we estimated mean difference (MD) between groups and its 95% CI. We employed a random-effects model for analyses.We performed a random-effects meta-regression analysis to examine the association of the intervention's fidelity to the ACT model and the rate of hospital use in the setting where the trial was conducted with the treatment effect. We assessed overall quality for clinically important outcomes using the GRADE approach and investigated possible risk of bias within included trials.
MAIN RESULTS: The 2016 update included two more studies (n = 196) and more publications with additional data for four already included studies. The updated review therefore includes 7524 participants from 40 randomised controlled trials (RCTs). We found data relevant to two comparisons: ICM versus standard care, and ICM versus non-ICM. The majority of studies had a high risk of selective reporting. No studies provided data for relapse or important improvement in mental state.1. ICM versus standard careWhen ICM was compared with standard care for the outcome service use, ICM slightly reduced the number of days in hospital per month (n = 3595, 24 RCTs, MD -0.86, 95% CI -1.37 to -0.34,low-quality evidence). Similarly, for the outcome global state, ICM reduced the number of people leaving the trial early (n = 1798, 13 RCTs, RR 0.68, 95% CI 0.58 to 0.79, low-quality evidence). For the outcome adverse events, the evidence showed that ICM may make little or no difference in reducing death by suicide (n = 1456, 9 RCTs, RR 0.68, 95% CI 0.31 to 1.51, low-quality evidence). In addition, for the outcome social functioning, there was uncertainty about the effect of ICM on unemployment due to very low-quality evidence (n = 1129, 4 RCTs, RR 0.70, 95% CI 0.49 to 1.0, very low-quality evidence).2. ICM versus non-ICMWhen ICM was compared with non-ICM for the outcome service use, there was moderate-quality evidence that ICM probably makes little or no difference in the average number of days in hospital per month (n = 2220, 21 RCTs, MD -0.08, 95% CI -0.37 to 0.21, moderate-quality evidence) or in the average number of admissions (n = 678, 1 RCT, MD -0.18, 95% CI -0.41 to 0.05, moderate-quality evidence) compared to non-ICM. Similarly, the results showed that ICM may reduce the number of participants leaving the intervention early (n = 1970, 7 RCTs, RR 0.70, 95% CI 0.52 to 0.95,low-quality evidence) and that ICM may make little or no difference in reducing death by suicide (n = 1152, 3 RCTs, RR 0.88, 95% CI 0.27 to 2.84, low-quality evidence). Finally, for the outcome social functioning, there was uncertainty about the effect of ICM on unemployment as compared to non-ICM (n = 73, 1 RCT, RR 1.46, 95% CI 0.45 to 4.74, very low-quality evidence).3. Fidelity to ACTWithin the meta-regression we found that i.) the more ICM is adherent to the ACT model, the better it is at decreasing time in hospital ('organisation fidelity' variable coefficient -0.36, 95% CI -0.66 to -0.07); and ii.) the higher the baseline hospital use in the population, the better ICM is at decreasing time in hospital ('baseline hospital use' variable coefficient -0.20, 95% CI -0.32 to -0.10). Combining both these variables within the model, 'organisation fidelity' is no longer significant, but the 'baseline hospital use' result still significantly influences time in hospital (regression coefficient -0.18, 95% CI -0.29 to -0.07, P = 0.0027).
AUTHORS' CONCLUSIONS: Based on very low- to moderate-quality evidence, ICM is effective in ameliorating many outcomes relevant to people with severe mental illness. Compared to standard care, ICM may reduce hospitalisation and increase retention in care. It also globally improved social functioning, although ICM's effect on mental state and quality of life remains unclear. Intensive Case Management is at least valuable to people with severe mental illnesses in the subgroup of those with a high level of hospitalisation (about four days per month in past two years). Intensive Case Management models with high fidelity to the original team organisation of ACT model were more effective at reducing time in hospital.However, it is unclear what overall gain ICM provides on top of a less formal non-ICM approach.We do not think that more trials comparing current ICM with standard care or non-ICM are justified, however we currently know of no review comparing non-ICM with standard care, and this should be undertaken.
OBJECTIVE: To undertake a systematic review and meta-analysis to establish the effectiveness of handwashing in reducing absence and/or the spread of respiratory tract (RT) and/or gastrointestinal (GI) infection among school-aged children and/or staff in educational settings.
DESIGN: Randomised-controlled trials (RCTs).
SETTING: Schools and other settings with a formal educational component in any country.
PATIENTS: Children aged 3-11 years, and/or staff working with them.
INTERVENTION: Interventions with a hand hygiene component.
MAIN OUTCOME MEASURES: Incidence of RT or GI infections or symptoms related to such infections; absenteeism; laboratory results of RT and/or GI infections.
RESULTS: Eighteen cluster RCTs were identified; 13 school-based, 5 in child day care facilities or preschools. Studies were heterogeneous and had significant quality issues including small numbers of clusters and participants and inadequate randomisation. Individual study results suggest interventions may reduce children's absence, RT infection incidence and symptoms, and laboratory confirmed influenza-like illness. Evidence of impact on GI infection or symptoms was equivocal.
CONCLUSIONS: Studies are generally not well executed or reported. Despite updating existing systematic reviews and identifying new studies, evidence of the effect of hand hygiene interventions on infection incidence in educational settings is mostly equivocal but they may decrease RT infection among children. These results update and add to knowledge about this crucial public health issue in key settings with a vulnerable population. More robust, well reported cluster RCTs which learn from existing studies, are required.
We conducted this systematic review to support the U.S. Preventive Services Task Force in updating its 2014 recommendation on screening for cognitive impairment in older adults. Our review addressed the direct evidence on the benefits and harms of screening for cognitive impairment versus no screening, the test accuracy of screening instruments to detect mild cognitive impairment (MCI) and dementia, and the benefits and harms of treatment for MCI and mild to moderate dementia among community-dwelling older adults age 65 years and older.
DATA SOURCES:
We performed an updated search of MEDLINE, PubMed Publisher-Supplied, PsycINFO, and the Cochrane Central Register of Controlled Trials for studies published through January 2019. We supplemented searches by examining reference lists from related articles and expert recommendations and searched federal and international trial registries for ongoing trials.
STUDY SELECTION:
Two researchers reviewed 11,644 titles and abstracts and 966 full-text articles against prespecified inclusion criteria. We included test accuracy studies that included screening instruments that could be delivered in primary care in 10 minutes or less by a clinician or self-administered in 20 minutes or less compared with a reference standard. We included trials of major pharmacologic and nonpharmacologic interventions in persons with MCI or mild to moderate dementia and large, observational studies examining adverse effects of these interventions. We conducted dual, independent critical appraisal of all provisionally included studies and abstracted all important study details and results from all studies rated fair or good quality. Data were abstracted by one reviewer and confirmed by another.
DATA ANALYSIS:
We synthesized data separately for each key question and within subcategories of screening instruments and treatments. For diagnostic accuracy studies, we focused on sensitivity and specificity of instruments that were evaluated in more than one study. We conducted a qualitative synthesis of results using summary tables and figures to capture key study characteristics, sources of clinical heterogeneity, and overall results of each study. Quantitative synthesis was limited to test performance of the Mini Mental State Examination (MMSE) (due to insufficient number of homogeneous studies for other instruments) and U.S. Food and Drug Administration (FDA)–approved medications to treat Alzheimer’s Disease on global cognitive outcomes, global function, and harms; nonpharmacologic interventions aimed at the patient on global cognitive outcomes; and caregiver and caregiver-patient dyad interventions on caregiver burden and depression outcomes. We ran random-effects meta-analyses using the DerSimonian and Laird method and sensitivity analyses using a Restricted Likelihood Estimation Model with the Knapp-Hartung correction to calculate the pooled differences in mean changes (for continuous data) and pooled risk ratio (for binary data). We used meta-regression to explore potential effect modification by various study, population, and intervention characteristics in cases where 10 or more studies were pooled. We generated funnel plots and conducted tests for small-study effects for all pooled analyses. Using established methods, we assessed the strength of evidence for each question.
RESULTS:
Screening (Key Questions 1–3): Only one trial was identified that examined the direct effect of screening for cognitive impairment on important patient outcomes, including potential harms. In that trial, at 12 months, there was no difference in health-related quality of life between those who were screened vs. not screened. Symptoms of depression and anxiety were also similar between groups at 1, 6, and 12 months as was health care utilization and advance care planning. We identified 59 studies that addressed the diagnostic accuracy of 49 screening instruments to detect cognitive impairment. Most instruments were only studied in a handful of well-designed diagnostic accuracy studies in primary care–relevant populations. The MMSE, a brief test taking 7 to 10 minutes to complete, remains the most thoroughly studied instrument. The pooled estimate across 15 studies (n=12,796) resulted in 89 percent sensitivity (95% CI, 0.85 to 0.92) and 89 percent specificity (95% CI, 0.85 to 0.93) to detect dementia at a cutoff of 23 or less or 24 or less. Other screening instruments evaluated in more than one study included the very brief instruments (≤5 minutes) of the CDT, MIS, MSQ, Mini-Cog, Lawton IADL, VF, AD8, and FAQ and the brief instruments (6 to 10 minutes) of the 7MS, AMT, MoCA, SLUMS, and TICS with sensitivity to detect dementia usually at 0.75 or higher and specificity at 0.80 or higher for all instruments. For self-administered, longer tests (>10 minutes), only the IQCODE was assessed in more than one study, with sensitivity to detect dementia ranging from 0.80 to 0.88 and specificity ranging from 0.51 to 0.91. Across all instruments, test performance was generally higher in the detection of dementia vs. mild cognitive impairment, although confidence intervals overlapped. No studies directly addressed the adverse psychological effects of screening or adverse effects from false-positive or false-negative testing. Treatment (Key Questions 4 and 5): We identified 224 trials and 3 observational studies representing more than 240,000 patients and/or caregivers that addressed the treatment or management of MCI or mild to moderate dementia. None of the treatment trials were linked with a screening program; in all cases, trial participants were persons with known MCI or dementia. Pharmacologic Interventions: Based on 45 trials (n=22,431) and three observational studies (n=190,076) that evaluated acetylcholinesterase inhibitors (AChEIs) (i.e., donepezil, galantamine, rivastigmine) and memantine, these medications may improve measures of global cognitive function in the short term, but the magnitude of change is small. In meta-analyses, the differences in changes between those on AChEIs or memantine compared with those on placebo ranged from approximately 1 to 2.5 points on the ADAS-Cog-11 and 0.5 to 1 point on the MMSE over 3 months to 3 years of followup. AChEIs and memantine appeared to increase the likelihood of improving or maintaining patients’ global function by 15 percent (for memantine) to 50 percent (for rivastigmine) in the short term (pooled 95% confidence interval range, 0.49 to 2.69). Other outcome measures were inconsistently reported. Total adverse events and discontinuation due to adverse events were more common with AChEIs, but not memantine, compared with placebo. Rates of serious adverse events overall were not higher among those taking medications vs. placebo, but individual studies noted increased rates of serious adverse events. Trials evaluating other medications or dietary supplements (k=29; n=6,489), including discontinuing antihypertensives, 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors (atorvastatin and simvastatin), nonsteroidal anti-inflammatory drugs (ibuprofen, naproxen, indomethacin, and celecoxib), gonadal steroids (estrogen [plus or minus progesterone] and testosterone), and dietary supplements and vitamins (multivitamins, B vitamins, vitamin E, and omega-3 fatty acids) showed no benefit on global cognitive or physical function in persons with mild to moderate dementia or MCI. Nonpharmacologic Interventions: We identified 61 trials (n=7,847) that evaluated nonpharmacologic patient-level interventions, including cognitive-focused, exercise, and multicomponent and other interventions. Among all interventions, there was no clear benefit on global or domain-specific measures of cognitive function compared with control conditions at 3 months to 2 years followup. Effect estimates generally favored the intervention groups over control groups, but the magnitude of effect was inconsistent across trials and represented very wide confidence intervals (ranging from no effect to a large effect). Physical function outcomes, including change in activities of daily living and independent activities of daily living, as well as quality of life and mental and neuropsychiatric symptoms, were inconsistently reported. There was, however, a pattern of effect for exercise interventions, with small improvements seen in measures of physical function and symptoms for intervention groups, whereas control groups reported worsening function. Caregiver and caregiver-patient dyad interventions including psychoeducation for the caregiver and care and case management interventions, reported in 88 trials (n=14,880), resulted in a consistent benefit on caregiver burden and depression outcomes. Effect sizes were mostly small, however, and were of unclear clinical significance. Little harm was evident in the few nonpharmacologic intervention trials that reported harms.
LIMITATIONS:
There is a lack of evidence around how screening for and treating MCI and early-stage dementia affects decision making outcomes. Furthermore, there has been little reproducibility in testing specific screening instruments in primary care populations. The treatment literature is limited by a lack of consistency in the specific outcomes reported and short followup duration. It is difficult to interpret the clinical importance of the small average effects seen among treatment trials, and many measures likely have limited responsiveness for patients with less pronounced cognitive impairment. Consistent and standardized reporting of results according to meaningful thresholds of clinical significance would be helpful in interpreting the small average effects on continuous outcome measures. Other important measures such as quality of life, physical function, and institutionalization, were inconsistently reported.
CONCLUSIONS:
Several brief screening instruments can adequately detect cognitive impairment, especially in populations with a higher prevalence of underlying dementia. There is no empiric evidence, however, that screening for cognitive impairment or early diagnosis of cognitive impairment improves patient, caregiver, family, or clinician decision making or other important outcomes nor causes harm. In general, there is support that AChEIs and memantine and interventions that support caregivers, including those that help coordinate care for patients and caregivers, can result in small improvements in the short term. Unfortunately, the average effects of these benefits are quite small and likely not of clinical significance. Any benefits are further limited by the commonly experienced side effects of medications and the limited availability of complex caregiver interventions. Cognitive stimulation and training, exercise interventions, and other medications and supplements showed some favorable effects on patients’ cognitive and physical function, but trial evidence lacked consistency and the estimates of benefit were imprecise. There is less evidence related to screening for and treating MCI. The test performance of the few instruments evaluated to detect MCI was lower than the sensitivity and specificity to detect dementia and there is little evidence for any pharmacologic or nonpharmacologic interventions to preserve or improve patient functioning in persons with MCI.
