Therapies for Clinically Localized Prostate Cancer: A Comparative Effectiveness Review.

PURPOSE: We sought to identify new information evaluating clinically localized prostate cancer therapies. MATERIALS AND METHODS: Bibliographic databases (2013-January 2020), ClinicalTrials.gov and systematic reviews were searched for controlled studies of treatments for clinically localized prostate cancer with duration ≥5 years for mortality and metastases, and ≥1 year for harms. RESULTS: We identified 67 eligible references. Among patients with clinically, rather than prostate specific antigen, detected localized prostate cancer, watchful waiting may increase mortality and metastases but decreases urinary and erectile dysfunction vs radical prostatectomy. Comparative mortality effect may vary by tumor risk and age but not by race, health status, comorbidities or prostate specific antigen. Active monitoring probably results in little to no mortality difference in prostate specific antigen detected localized prostate cancer vs radical prostatectomy or external beam radiation plus androgen deprivation regardless of tumor risk. Metastases were slightly higher with active monitoring. Harms were greater with radical prostatectomy than active monitoring and mixed between external beam radiation plus androgen deprivation vs active monitoring. 3-Dimensional conformal radiation and androgen deprivation plus low dose rate brachytherapy provided small mortality reductions vs 3-dimensional conformal radiation and androgen deprivation but little to no difference on metastases. External beam radiation plus androgen deprivation vs external beam radiation alone may result in small mortality and metastasis reductions in higher risk disease but may increase sexual harms. Few new data exist on other treatments. CONCLUSIONS: Radical prostatectomy reduces mortality vs watchful waiting in clinically detected localized prostate cancer but causes more harms. Effectiveness may be limited to younger men and those with intermediate risk disease. Active monitoring results in little to no mortality difference vs radical prostatectomy or external beam radiation plus androgen deprivation. Few new data exist on other treatments.

Benefits and Harms of Prescription Drugs and Supplements for Treatment of Clinical Alzheimer-Type Dementia.

BACKGROUND: Effects of drug treatment of clinical Alzheimer-type dementia (CATD) are uncertain. PURPOSE: To summarize evidence on the effects of prescription drugs and supplements for CATD treatment. DATA SOURCES: Electronic bibliographic databases (inception to November 2019), ClinicalTrials.gov (to November 2019), and systematic review bibliographies. STUDY SELECTION: English-language trials of prescription drug and supplement treatment in older adults with CATD that report cognition, function, global measures, behavioral and psychological symptoms of dementia (BPSD), or harms. Minimum treatment was 24 weeks (≥2 weeks for selected BPSD). DATA EXTRACTION: Studies with low or medium risk of bias (ROB) were analyzed. Two reviewers rated ROB. One reviewer extracted data; another verified extraction accuracy. DATA SYNTHESIS: Fifty-five studies reporting non-BPSD outcomes (most ≤26 weeks) and 12 reporting BPSD (most ≤12 weeks) were analyzed. Across CATD severity, mostly low-strength evidence suggested that, compared with placebo, cholinesterase inhibitors produced small average improvements in cognition (median standardized mean difference [SMD], 0.30 [range, 0.24 to 0.52]), no difference to small improvement in function (median SMD, 0.19 [range, -0.10 to 0.22]), no difference in the likelihood of at least moderate improvement in global clinical impression (median absolute risk difference, 4% [range, 2% to 4%]), and increased withdrawals due to adverse events. In adults with moderate to severe CATD receiving cholinesterase inhibitors, low- to insufficient-strength evidence suggested that, compared with placebo, add-on memantine inconsistently improved cognition and improved global clinical impression but not function. Evidence was mostly insufficient about prescription drugs for BPSD and about supplements for all outcomes. LIMITATION: Most drugs had few trials without high ROB, especially for supplements, active drug comparisons, BPSD, and longer trials. CONCLUSION: Cholinesterase inhibitors and memantine slightly reduced short-term cognitive decline, and cholinesterase inhibitors slightly reduced reported functional decline, but differences versus placebo were of uncertain clinical importance. Evidence was mostly insufficient on drug treatment of BPSD and on supplements for all outcomes. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (PROSPERO: CRD42018117897).

AHRQ EPC Series on Improving Translation of Evidence: Web-Based Interactive Presentation of Systematic Review Reports.

Systematic reviews are used by a diverse range of users to address an ever-expanding set of questions and needs. It is unlikely that a single static report will efficiently satisfy the different needs of diverse users. METHODS: An open-source Web-based interactive report presentation of a systematic review was developed to allow users to generate their own "reports" from the information produced by the review. Data from a broad-scope systematic review were used with network meta-analysis conducted on nonsurgical treatments of urinary incontinence (UI) in women. Stakeholders informed and piloted the tool and assessed its usefulness. RESULTS: The final tool allows users to obtain descriptive and analytic results for a network of treatment categories and various outcomes (cure, improvement, satisfaction, quality of life, adverse events) across several subgroups (all women, older women, or those with stress or urgency UI), along with study-level information, and overall conclusions. The stakeholders were satisfied with the functionality of the tool and proposed a number of improvements regarding presentation (for example, present information on numbers of trials in figures), analyses (for example, allow on-the-fly subgroup analyses, explore trade-offs between several outcomes), and information sharing (for example, provide ability to import/export data from/to other software). CONCLUSION: A prototype tool to present customized analyses from broad-scope systematic reviews is presented. Further improvements are suggested to develop a scalable tool to make systematic reviews useful to increasingly diverse user groups.

Long-Term Drug Therapy and Drug Discontinuations and Holidays for Osteoporosis Fracture Prevention: A Systematic Review.

Background: Optimal long-term osteoporosis drug treatment (ODT) is uncertain. Purpose: To summarize the effects of long-term ODT and ODT discontinuation and holidays. Data Sources: Electronic bibliographic databases (January 1995 to October 2018) and systematic review bibliographies. Study Selection: 48 studies that enrolled men or postmenopausal women aged 50 years or older who were being investigated or treated for fracture prevention, compared long-term ODT (>3 years) versus control or ODT continuation versus discontinuation, reported incident fractures (for trials) or harms (for trials and observational studies), and had low or medium risk of bias (ROB). Data Extraction: Two reviewers independently rated ROB and strength of evidence (SOE). One extracted data; another verified accuracy. Data Synthesis: Thirty-five trials (9 unique studies) and 13 observational studies (11 unique studies) had low or medium ROB. In women with osteoporosis, 4 years of alendronate reduced clinical fractures (hazard ratio [HR], 0.64 [95% CI, 0.50 to 0.82]) and radiographic vertebral fractures (both moderate SOE), whereas 4 years of raloxifene reduced vertebral but not nonvertebral fractures. In women with osteopenia or osteoporosis, 6 years of zoledronic acid reduced clinical fractures (HR, 0.73 [CI, 0.60 to 0.90]), including nonvertebral fractures (high SOE) and clinical vertebral fractures (moderate SOE). Long-term bisphosphonates increased risk for 2 rare harms: atypical femoral fractures (low SOE) and osteonecrosis of the jaw (mostly low SOE). In women with unspecified osteoporosis status, 5 to 7 years of hormone therapy reduced clinical fractures (high SOE), including hip fractures (moderate SOE), but increased serious harms. After 3 to 5 years of treatment, bisphosphonate continuation versus discontinuation reduced radiographic vertebral fractures (zoledronic acid; low SOE) and clinical vertebral fractures (alendronate; moderate SOE) but not nonvertebral fractures (low SOE). Limitation: No trials studied men, clinical fracture data were sparse, methods for estimating harms were heterogeneous, and no trials compared sequential treatments or different durations of drug holidays. Conclusion: Long-term alendronate and zoledronic acid therapies reduce fracture risk in women with osteoporosis. Long-term bisphosphonate treatment may increase risk for rare adverse events, and continuing treatment beyond 3 to 5 years may reduce risk for vertebral fractures. Long-term hormone therapy reduces hip fracture risks but has serious harms. Primary Funding Source: National Institutes of Health and Agency for Healthcare Research and Quality. (PROSPERO: CRD42018087006).

Efficacy of newer medications for lower urinary tract symptoms attributed to benign prostatic hyperplasia: a systematic review.

We conducted a systematic review to evaluate the efficacy and adverse effects of newer drugs used to treat lower urinary tract symptoms (LUTS). The drugs were either Food and Drug Administration (FDA) approved for benign prostatic hyperplasia (BPH) or not FDA approved for BPH but have been evaluated for treatment of BPH since 2008. We searched bibliographic databases through September 2017. We included randomized controlled trials (RCTs) lasting one month or longer published in English. Outcomes of interest were LUTS assessed by validated measures. Efficacy was interpreted using established thresholds indicating clinical significance that identified the minimal detectable difference. Twenty-three unique, generally short-term, RCTs evaluating over 9000 participants were identified. Alpha-blocker silodosin and phosphodiesterase type 5 inhibitor tadalafil were more effective than placebo in improving LUTS (moderate strength evidence) but these drugs had more adverse effects, including abnormal ejaculation (silodosin). Anticholinergics were only effective versus placebo when combined with an alpha-blocker. Evidence was generally low strength or insufficient for other drugs. Evidence was insufficient to assess long-term efficacy, prevention of symptom progression, need for surgical intervention, or long-term adverse effects. Longer trials are needed to assess the effect of these therapies on response rates using established minimal detectable difference thresholds, disease progression, and harms.

Physical Activity Interventions in Preventing Cognitive Decline and Alzheimer-Type Dementia: A Systematic Review.

Background: The prevalence of cognitive impairment and dementia is expected to increase dramatically as the population ages, creating burdens on families and health care systems. Purpose: To assess the effectiveness of physical activity interventions in slowing cognitive decline and delaying the onset of cognitive impairment and dementia in adults without diagnosed cognitive impairments. Data Sources: Several electronic databases from January 2009 to July 2017 and bibliographies of systematic reviews. Study Selection: Trials published in English that lasted 6 months or longer, enrolled adults without clinically diagnosed cognitive impairments, and compared cognitive and dementia outcomes between physical activity interventions and inactive controls. Data Extraction: Extraction by 1 reviewer and confirmed by a second; dual-reviewer assessment of risk of bias; consensus determination of strength of evidence. Data Synthesis: Of 32 eligible trials, 16 with low to moderate risk of bias compared a physical activity intervention with an inactive control. Most trials had 6-month follow-up; a few had 1- or 2-year follow-up. Evidence was insufficient to draw conclusions about the effectiveness of aerobic training, resistance training, or tai chi for improving cognition. Low-strength evidence showed that multicomponent physical activity interventions had no effect on cognitive function. Low-strength evidence showed that a multidomain intervention comprising physical activity, diet, and cognitive training improved several cognitive outcomes. Evidence regarding effects on dementia prevention was insufficient for all physical activity interventions. Limitation: Heterogeneous interventions and cognitive test measures, small and underpowered studies, and inability to assess the clinical significance of cognitive test outcomes. Conclusion: Evidence that short-term, single-component physical activity interventions promote cognitive function and prevent cognitive decline or dementia in older adults is largely insufficient. A multidomain intervention showed a delay in cognitive decline (low-strength evidence). Primary Funding Source: Agency for Healthcare Research and Quality.

Does Cognitive Training Prevent Cognitive Decline?: A Systematic Review.

Background: Structured activities to stimulate brain function-that is, cognitive training exercises-are promoted to slow or prevent cognitive decline, including dementia, but their effectiveness is highly debated. Purpose: To summarize evidence on the effects of cognitive training on cognitive performance and incident dementia outcomes for adults with normal cognition or mild cognitive impairment (MCI). Data Sources: Ovid MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and PsycINFO through July 2017, supplemented by hand-searches. Study Selection: Trials (published in English) lasting at least 6 months that compared cognitive training with usual care, waitlist, information, or attention controls in adults without dementia. Data Extraction: Single-reviewer extraction of study characteristics confirmed by a second reviewer; dual-reviewer risk-of-bias assessment; consensus determination of strength of evidence. Only studies with low or medium risk of bias were analyzed. Data Synthesis: Of 11 trials with low or medium risk of bias, 6 enrolled healthy adults with normal cognition and 5 enrolled adults with MCI. Trainings for healthy older adults were mostly computer based; those for adults with MCI were mostly held in group sessions. The MCI trials used attention controls more often than trials with healthy populations. For healthy older adults, training improved cognitive performance in the domain trained but not in other domains (moderate-strength evidence). Results for populations with MCI suggested no effect of training on performance (low-strength and insufficient evidence). Evidence for prevention of cognitive decline or dementia was insufficient. Adverse events were not reported. Limitation: Heterogeneous interventions and outcome measures; outcomes that mostly assessed test performance rather than global function or dementia diagnosis; potential publication bias. Conclusion: In older adults with normal cognition, training improves cognitive performance in the domain trained. Evidence regarding prevention or delay of cognitive decline or dementia is insufficient. Primary Funding Source: Agency for Healthcare Research and Quality.

Pharmacologic Interventions to Prevent Cognitive Decline, Mild Cognitive Impairment, and Clinical Alzheimer-Type Dementia: A Systematic Review.

Background: Optimal treatment to prevent or delay cognitive decline, mild cognitive impairment (MCI), or dementia is uncertain. Purpose: To summarize current evidence on the efficacy and harms of pharmacologic interventions to prevent or delay cognitive decline, MCI, or dementia in adults with normal cognition or MCI. Data Sources: Several electronic databases from January 2009 to July 2017, bibliographies, and expert recommendations. Study Selection: English-language trials of at least 6 months' duration enrolling adults without dementia and comparing pharmacologic interventions with placebo, usual care, or active control on cognitive outcomes. Data Extraction: Two reviewers independently rated risk of bias and strength of evidence; 1 extracted data, and a second checked accuracy. Data Synthesis: Fifty-one unique trials were rated as having low to moderate risk of bias (including 3 that studied dementia medications, 16 antihypertensives, 4 diabetes medications, 2 nonsteroidal anti-inflammatory drugs [NSAIDs] or aspirin, 17 hormones, and 7 lipid-lowering agents). In persons with normal cognition, estrogen and estrogen-progestin increased risk for dementia or a combined outcome of MCI or dementia (1 trial, low strength of evidence); high-dose raloxifene decreased risk for MCI but not for dementia (1 trial, low strength of evidence); and antihypertensives (4 trials), NSAIDs (1 trial), and statins (1 trial) did not alter dementia risk (low to insufficient strength of evidence). In persons with MCI, cholinesterase inhibitors did not reduce dementia risk (1 trial, low strength of evidence). In persons with normal cognition and those with MCI, these pharmacologic treatments neither improved nor slowed decline in cognitive test performance (low to insufficient strength of evidence). Adverse events were inconsistently reported but were increased for estrogen (stroke), estrogen-progestin (stroke, coronary heart disease, invasive breast cancer, and pulmonary embolism), and raloxifene (venous thromboembolism). Limitation: High attrition, short follow-up, inconsistent cognitive outcomes, and possible selective reporting and publication. Conclusion: Evidence does not support use of the studied pharmacologic treatments for cognitive protection in persons with normal cognition or MCI. Primary Funding Source: Agency for Healthcare Research and Quality.

Over-the-Counter Supplement Interventions to Prevent Cognitive Decline, Mild Cognitive Impairment, and Clinical Alzheimer-Type Dementia: A Systematic Review.

Background: Optimal interventions to prevent or delay cognitive decline, mild cognitive impairment (MCI), or dementia are uncertain. Purpose: To summarize the evidence on efficacy and harms of over-the-counter (OTC) supplements to prevent or delay cognitive decline, MCI, or clinical Alzheimer-type dementia in adults with normal cognition or MCI but no dementia diagnosis. Data Sources: Multiple electronic databases from 2009 to July 2017 and bibliographies of systematic reviews. Study Selection: English-language trials of at least 6 months' duration that enrolled adults without dementia and compared cognitive outcomes with an OTC supplement versus placebo or active controls. Data Extraction: Extraction performed by a single reviewer and confirmed by a second reviewer; dual-reviewer assessment of risk of bias; consensus determination of strength of evidence. Data Synthesis: Thirty-eight trials with low to medium risk of bias compared ω-3 fatty acids, soy, ginkgo biloba, B vitamins, vitamin D plus calcium, vitamin C or ß-carotene, multi-ingredient supplements, or other OTC interventions with placebo or other supplements. Few studies examined effects on clinical Alzheimer-type dementia or MCI, and those that did suggested no benefit. Daily folic acid plus vitamin B12 was associated with improvements in performance on some objectively measured memory tests that were statistically significant but of questionable clinical significance. Moderate-strength evidence showed that vitamin E had no benefit on cognition. Evidence about effects of ω-3 fatty acids, soy, ginkgo biloba, folic acid alone or with other B vitamins, ß-carotene, vitamin C, vitamin D plus calcium, and multivitamins or multi-ingredient supplements was either insufficient or low-strength, suggesting that these supplements did not reduce risk for cognitive decline. Adverse events were rarely reported. Limitation: Studies had high attrition and short follow-up and used a highly variable set of cognitive outcome measures. Conclusion: Evidence is insufficient to recommend any OTC supplement for cognitive protection in adults with normal cognition or MCI. Primary Funding Source: Agency for Healthcare Research and Quality.

Comparative Effectiveness of Newer Medications for Lower Urinary Tract Symptoms Attributed to Benign Prostatic Hyperplasia: A Systematic Review and Meta-analysis.

CONTEXT: Alpha-blockers (ABs) and 5-alpha reductase inhibitors have an established role in treating male lower urinary tract symptoms (LUTS) attributed to benign prostatic hyperplasia (BPH). Recently, newer drugs have shown promise for this indication. OBJECTIVE: To assess the comparative effectiveness and adverse effects (AEs) of newer drugs to treat LUTS attributed to BPH through a systematic review and meta-analysis. EVIDENCE ACQUISITION: Ovid MEDLINE, the Cochrane Central Register of Controlled Trials, and Ovid Embase bibliographic databases (through June 2016) were hand searches for references of relevant studies. Eligible studies included randomized controlled trials published in English of newer ABs, antimuscarinics, a beta-3 adrenoceptor agonist, phosphodiesterase type-5 inhibitors, or combination therapy with one of these medications as an active comparator. Observational studies of the same agents with a duration ≥1 yr that reported AEs were also included. EVIDENCE SYNTHESIS: We synthesized evidence from 43 randomized controlled trials as well as five observational studies. Based on improvement of mean International Prostate Symptom Score and quality of life scores, the effectiveness of the newer ABs was not different from the older ABs (moderate strength of evidence [SOE]), but had more AEs (low SOE). Antimuscarinics/AB combination therapy had similar outcomes as AB monotherapy (all moderate SOE), but often had more AEs. Phosphodiesterase type-5 inhibitors alone or in combination with ABs had similar or inferior outcomes than ABs alone. Evidence was insufficient for the beta-3 adrenoceptor agonist. For all newer agents, the evidence was generally insufficient to assess long-term efficacy, prevention of symptom progression, or AEs. CONCLUSIONS: None of the drugs or drug combinations newly used to treat LUTS attributed to BPH showed outcomes superior to traditional AB treatment. Given the lack of superior outcomes, the studies' short time-horizon, and less assurance of their safety, their current value in treating LUTS attributable to BPH appears low. PATIENT SUMMARY: In this paper, we reviewed the evidence of newer drugs to treat men with urinary problems attributable to an enlarged prostate. We found none of the new drugs to be better but there was more concern about side effects.

Consistency of dementia caregiver intervention classification: an evidence-based synthesis.

BACKGROUND: There are many systematic reviews and meta-analyses (SRs) of interventions for family caregivers of persons with Alzheimer's disease or a related dementia. A challenge when synthesizing the efficacy of dementia caregiver interventions is the potential discrepancy in how they are categorized. The objective of this study was to systematically examine inconsistencies in how dementia caregiver interventions are classified. METHODS: We searched Ovid Medline®, Ovid PsycINFO®, Ovid Embase®, and the Cochrane Library to identify previous SRs published and indexed in bibliographic databases through January 2015. Following a graphical network analysis, open-coding of classification definitions was conducted. A descriptive analysis was then completed to examine classification consistency of individual interventions across SR grouping labels. RESULTS: Twenty-three SRs were identified. A graphical network analysis revealed a significant amount of overlap in individual studies included across SRs, but stark differences in how reviews labeled or categorized them. The qualitative content analysis identified seven themes; one of these, content of the intervention, was used to compare classification consistency. When subjecting the classification of interventions to descriptive empirical analysis, extensive inconsistency was apparent. CONCLUSIONS: The substantial inconsistency in how dementia caregiver interventions are classified across SRs has hindered the science and practice of dementia caregiver interventions. Specifically, accurate reporting of intervention components and SRs would allow for more precise assessments of efficacy as well as a fuller determination of how caregiver interventions can best yield benefits for caregivers and persons with dementia.

Pharmacologic Treatment of Insomnia Disorder: An Evidence Report for a Clinical Practice Guideline by the American College of Physicians.

BACKGROUND: Pharmacologic interventions are often prescribed for insomnia disorder. PURPOSE: To assess the benefits, harms, and comparative effectiveness of pharmacologic treatments for adults with insomnia disorder. DATA SOURCES: Several electronic databases (2004-September 2015), reference lists, and U.S. Food and Drug Administration (FDA) documents. STUDY SELECTION: 35 randomized, controlled trials of at least 4 weeks' duration that evaluated pharmacotherapies available in the United States and that reported global or sleep outcomes; 11 long-term observational studies that reported harm information; FDA review data for nonbenzodiazepine hypnotics and orexin receptor antagonists; and product labels for all agents. DATA EXTRACTION: Data extraction by single investigator confirmed by a second reviewer; dual-investigator assessment of risk of bias; consensus determination of strength of evidence. DATA SYNTHESIS: Eszopiclone, zolpidem, and suvorexant improved short-term global and sleep outcomes compared with placebo, although absolute effect sizes were small (low- to moderate-strength evidence). Evidence for benzodiazepine hypnotics, melatonin agonists, and antidepressants, and for most pharmacologic interventions in older adults, was insufficient or low strength. Evidence was also insufficient to compare efficacy within or across pharmacotherapy classes or versus behavioral therapy. Harms evidence reported in trials was judged insufficient or low strength; observational studies suggested that use of hypnotics for insomnia was associated with increased risk for dementia, fractures, and major injury. The FDA documents reported that most pharmacotherapies had risks for cognitive and behavioral changes, including driving impairment, and other adverse effects, and they advised dose reduction in women and in older adults. LIMITATIONS: Most trials were small and short term and enrolled individuals meeting stringent criteria. Minimum important differences in outcomes were often not established or reported. Data were scant for many treatments. CONCLUSION: Eszopiclone, zolpidem, and suvorexant may improve short-term global and sleep outcomes for adults with insomnia disorder, but the comparative effectiveness and long-term efficacy of pharmacotherapies for insomnia are not known. Pharmacotherapies for insomnia may cause cognitive and behavioral changes and may be associated with infrequent but serious harms. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. ( PROSPERO: CRD42014009908).

Psychological and Behavioral Interventions for Managing Insomnia Disorder: An Evidence Report for a Clinical Practice Guideline by the American College of Physicians.

BACKGROUND: Psychological and behavioral interventions are frequently used for insomnia disorder. PURPOSE: To assess benefits and harms of psychological and behavioral interventions for insomnia disorder in adults. DATA SOURCES: Ovid MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and PsycINFO through September 2015, supplemented with hand-searching. STUDY SELECTION: Randomized, controlled trials of psychological or behavioral interventions that were published in English and enrolled adults with insomnia disorder lasting 4 or more weeks. DATA EXTRACTION: Data extraction by single investigator confirmed by a second reviewer; dual investigator assessment of risk of bias; consensus determination of strength of evidence. DATA SYNTHESIS: Sixty trials with low to moderate risk of bias compared psychological and behavioral interventions with inactive controls or other psychological and behavioral interventions. Cognitive behavioral therapy for insomnia (CBT-I) improved posttreatment global and most sleep outcomes, often compared with information or waitlist controls (moderate-strength evidence). Use of CBT-I improved several sleep outcomes in older adults (low- to moderate-strength evidence). Multicomponent behavioral therapy improved several sleep outcomes in older adults (low- to moderate-strength evidence). Stimulus control improved 1 or 2 sleep outcomes (low-strength evidence). Evidence for other comparisons and for harms was insufficient to permit conclusions. LIMITATIONS: A wide variety of comparisons limited the ability to pool data. Trials did not always report global outcomes and infrequently conducted remitter or responder analysis. Comparisons were often information or waitlist groups, and publication bias was possible. CONCLUSION: Use of CBT-I improves most outcomes compared with inactive controls. Multicomponent behavioral therapy and stimulus control may improve some sleep outcomes. Evidence on other outcomes, comparisons, and long-term efficacy were limited. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. ( PROSPERO: CRD42014009908).

Care-Delivery Interventions to Manage Agitation and Aggression in Dementia Nursing Home and Assisted Living Residents: A Systematic Review and Meta-analysis.

OBJECTIVES: To evaluate the efficacy of nonpharmacological care-delivery interventions (staff training, care-delivery models, changes to the environment) to reduce and manage agitation and aggression in nursing home and assisted living residents. DESIGN: Three bibliographic databases, references of systematic reviews, ClincalTrials.gov, and the International Controlled Trials Registry Platform were systematically searched for randomized controlled trials reporting behavioral outcomes for nonpharmacological care-delivery interventions in nursing homes and assisted living facilities. Five investigators independently assessed study eligibility, extracted data, rated risk of bias, and graded strength of evidence. Inclusion was limited to studies with low to moderate risk of bias. SETTING: Nursing homes and assisted living facilities. PARTICIPANTS: Facility caregiving staff. MEASUREMENTS: Agitation, aggression, antipsychotic and other psychotropic use, general behavior. RESULTS: Nineteen unique studies met entry criteria, addressing several categories of facility caregiver training interventions: dementia care mapping (DCM; n = 3), person-centered care (PCC; n = 3), clinical protocols to reduce the use of antipsychotic and other psychotropic drugs (n = 3), and emotion-oriented care (n = 2). Eleven additional studies evaluated other unique interventions. Results were pooled for the effect of each type of intervention on agitation and aggression: DCM (standardized mean difference -0.12, 95% confidence interval (CI) = -0.66 to 0.42), PCC (standardized mean difference -0.15, 95% CI = -0.67 to 0.38), and protocols to reduce antipsychotic and other psychotropic use (Cohen-Mansfield Agitation Inventory mean difference -4.5, 95% C = -38.84 to 29.93). Strength of evidence was generally insufficient to draw conclusions regarding efficacy or comparative effectiveness. CONCLUSION: Evidence was insufficient regarding the efficacy of nonpharmacological care-delivery interventions to reduce agitation or aggression in nursing home and assisted living facility residents with dementia.

Long-term Outcomes of Living Kidney Donation.

BACKGROUND: In an effort to improve outcomes associated with living kidney donation, the Kidney Diseases Improving Global Outcomes (KDIGO) assembled a Work Group to develop comprehensive guidelines addressing the evaluation and care of living kidney donors. We conducted this systematic review to inform guideline development. METHODS: We searched Ovid Medline, Ovid Embase, and the Cochrane Library to identify systematic reviews, randomized controlled trials, and observational studies published through September of 2014 and consulted the KDIGO Expert Work Group. We extracted data from systematic reviews and observational studies with sample size over 100 and mean follow-up time of at least 5 years. Studies had to have an adequate comparison group that excludes subjects with contraindications to kidney donation. RESULTS: For the long-term donor outcomes, we extracted 5 systematic reviews and 40 observational studies. Moderate grade evidence reveals an association between living kidney donation and greater risk of end-stage renal disease. This association is true for donors of all races with African American donors sustaining the greatest increase in absolute risk. We found very low grade evidence that kidney donation is associated with lower kidney function, proteinuria, hypertension, and psychosocial outcomes. Consistent evidence from 3 studies reveals that donors are at higher risk for preeclampsia and gestational hypertension with postdonation pregnancies and compared with healthy matched nondonors. CONCLUSIONS: Living kidney donation appears to be associated with a small absolute increase in risk of end-stage renal disease, hypertension, and pregnancy complications, such as preeclampsia and gestational hypertension.

Medical management to prevent recurrent nephrolithiasis in adults: a systematic review for an American College of Physicians Clinical Guideline.

BACKGROUND: Optimum management to prevent recurrent kidney stones is uncertain. PURPOSE: To evaluate the benefits and harms of interventions to prevent recurrent kidney stones. DATA SOURCES: MEDLINE, Cochrane, and other databases through September 2012 and reference lists of systematic reviews and randomized, controlled trials (RCTs). STUDY SELECTION: 28 English-language RCTs that studied treatments to prevent recurrent kidney stones and reported stone outcomes. DATA EXTRACTION: One reviewer extracted data, a second checked accuracy, and 2 independently rated quality and graded strength of evidence. DATA SYNTHESIS: In patients with 1 past calcium stone, low-strength evidence showed that increased fluid intake halved recurrent composite stone risk compared with no treatment (relative risk [RR], 0.45 [95% CI, 0.24 to 0.84]). Low-strength evidence showed that reducing soft-drink consumption decreased recurrent symptomatic stone risk (RR, 0.83 [CI, 0.71 to 0.98]). In patients with multiple past calcium stones, most of whom were receiving increased fluid intake, moderate-strength evidence showed that thiazides (RR, 0.52 [CI, 0.39 to 0.69]), citrates (RR, 0.25 [CI, 0.14 to 0.44]), and allopurinol (RR, 0.59 [CI, 0.42 to 0.84]) each further reduced composite stone recurrence risk compared with placebo or control, although the benefit from allopurinol seemed limited to patients with baseline hyperuricemia or hyperuricosuria. Other baseline biochemistry measures did not allow prediction of treatment efficacy. Low-strength evidence showed that neither citrate nor allopurinol combined with thiazide was superior to thiazide alone. There were few withdrawals among patients with increased fluid intake, many among those with other dietary interventions and more among those who received thiazide and citrate than among control patients. Reporting of adverse events was poor. LIMITATIONS: Most trial participants had idiopathic calcium stones. Nearly all studies reported a composite (including asymptomatic) stone recurrence outcome. CONCLUSION: In patients with 1 past calcium stone, increased fluid intake reduced recurrence risk. In patients with multiple past calcium stones, addition of thiazide, citrate, or allopurinol further reduced risk. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Participation after multidisciplinary rehabilitation for moderate to severe traumatic brain injury in adults: a systematic review.

OBJECTIVE: To determine the effectiveness and comparative effectiveness of multidisciplinary rehabilitation programs for moderate to severe traumatic brain injury (TBI) in improving participation-related outcomes in adults. This article presents results of select key questions from a recent Agency for Healthcare Quality and Research comparative effectiveness review. DATA SOURCES: MEDLINE, Cochrane Central Register of Controlled Trials, and PsycINFO; hand searches of previous relevant reviews. STUDY SELECTION: We included prospective controlled studies that evaluated the effectiveness or comparative effectiveness of multidisciplinary rehabilitation programs delivered to adults with moderate to severe TBI on their participation in life and community. DATA EXTRACTION: We extracted data, assessed risk of bias, and evaluated strength of evidence. Participation was selected as our primary outcome and included measures of productivity (eg, return to employment or military service) and select scales measuring community integration. Only data from studies with a low or moderate risk of bias were synthesized. DATA SYNTHESIS: Twelve studies met our inclusion criteria; of these, 8 were of low or moderate risk of bias (4 randomized controlled trials of 680 patients and 4 cohort studies of 190 patients, sample size 36-366). Heterogeneous populations, interventions, and outcomes precluded pooled analysis. Evidence was insufficient to draw conclusions about effectiveness. Evidence on comparative effectiveness often demonstrated that improvements were not different between groups; however, this evidence was low strength and may have limited generalizability. CONCLUSIONS: Our review used a rigorous systematic review methodology and focused on participation after multidisciplinary rehabilitation programs for impairments from moderate to severe TBI. The available evidence did not demonstrate the superiority of one approach over another. This conclusion is consistent with previous reviews that examined other patient-centered outcomes. While these findings will have little clinical impact, they do point out the limited evidence available to assess effectiveness and comparative effectiveness while highlighting important issues to consider in future comparative effectiveness research on this topic.

Wheeled mobility (wheelchair) service delivery: scope of the evidence.

Identifying the appropriate wheelchair for a person who needs one has implications for both disabled persons and society. For someone with severe locomotive problems, the right wheelchair can affect mobility and quality of life. However, policymakers are concerned about the increasing demand for unnecessarily elaborate chairs. The Office of Inspector General, U.S. Department of Health and Human Services, issued 4 reports between 2009 and 2011 detailing fraud and misapplication of Medicare funds for powered wheelchairs, more than a decade after similar concerns were first raised by 4 contractors who process claims for durable medical equipment. Subsequent concerns have arisen about whether some impaired persons who need wheeled mobility devices may now be inappropriately denied coverage. A transparent, evidence-based approach to wheeled mobility service delivery (the matching of mobility-impaired persons to appropriate devices and supporting services) might lessen these concerns. This review describes the process of wheeled mobility service delivery for long-term wheelchair users with complex rehabilitation needs and presents findings from a survey of the literature (published and gray) and interviews with key informants. Recommended steps in the delivery process were identified in textbooks, guidelines, and published literature. Delivery processes shared many commonalities; however, no research supports the recommended approaches. A search of bibliographic databases through March 2011 identified 24 studies that evaluated aspects of wheeled mobility service delivery. Most were observational, exploratory studies designed to determine consumer use of and satisfaction with the process. The evidence base for the effectiveness of approaches to wheeled mobility service delivery is insufficient, and additional research is needed to develop standards and guidelines.

Health literacy interventions and outcomes: an updated systematic review.

OBJECTIVES: To update a 2004 systematic review of health care service use and health outcomes related to differences in health literacy level and interventions designed to improve these outcomes for individuals with low health literacy. Disparities in health outcomes and effectiveness of interventions among different sociodemographic groups were also examined. DATA SOURCES: We searched MEDLINE®, the Cumulative Index to Nursing and Allied Health Literature, the Cochrane Library, PsychINFO, and the Educational Resources Information Center. For health literacy, we searched using a variety of terms, limited to English and studies published from 2003 to May 25, 2010. For numeracy, we searched from 1966 to May 25, 2010. REVIEW METHODS: We used standard Evidence-based Practice Center methods of dual review of abstracts, full-text articles, abstractions, quality ratings, and strength of evidence grading. We resolved disagreements by consensus. We evaluated whether newer literature was available for answering key questions, so we broadened our definition of health literacy to include numeracy and oral (spoken) health literacy. We excluded intervention studies that did not measure health literacy directly and updated our approach to evaluate individual study risk of bias and to grade strength of evidence. RESULTS: We included good- and fair-quality studies: 81 studies addressing health outcomes (reported in 95 articles including 86 measuring health literacy and 16 measuring numeracy, of which 7 measure both) and 42 studies (reported in 45 articles) addressing interventions. Differences in health literacy level were consistently associated with increased hospitalizations, greater emergency care use, lower use of mammography, lower receipt of influenza vaccine, poorer ability to demonstrate taking medications appropriately, poorer ability to interpret labels and health messages, and, among seniors, poorer overall health status and higher mortality. Health literacy level potentially mediates disparities between blacks and whites. The strength of evidence of numeracy studies was insufficient to low, limiting conclusions about the influence of numeracy on health care service use or health outcomes. Two studies suggested numeracy may mediate the effect of disparities on health outcomes. We found no evidence concerning oral health literacy and outcomes. Among intervention studies (27 randomized controlled trials [RCTs], 2 cluster RCTs, and 13 quasi-experimental designs), the strength of evidence for specific design features was low or insufficient. However, several specific features seemed to improve comprehension in one or a few studies. The strength of evidence was moderate for the effect of mixed interventions on health care service use; the effect of intensive self-management inventions on behavior; and the effect of disease-management interventions on disease prevalence/severity. The effects of other mixed interventions on other health outcomes, including knowledge, self-efficacy, adherence, and quality of life, and costs were mixed; thus, the strength of evidence was insufficient. CONCLUSIONS: The field of health literacy has advanced since the 2004 report. Future research priorities include justifying appropriate cutoffs for health literacy levels prior to conducting studies; developing tools that measure additional related skills, particularly oral (spoken) health literacy; and examining mediators and moderators of the effect of health literacy. Priorities in advancing the design features of interventions include testing novel approaches to increase motivation, techniques for delivering information orally or numerically, "work around" interventions such as patient advocates; determining the effective components of already-tested interventions; determining the cost-effectiveness of programs; and determining the effect of policy and practice interventions.

Consumer health information and local health resources: MedlinePlus and My Health Minnesota --> Go Local Outreach Efforts.

The University of Minnesota Health Sciences Libraries and an NLM Public Health Informationist Fellow are designing, implementing and evaluating outreach and training related to the My Health Minnesota --> Go Local project. The goal is to enhance the skills of public health and community based organizations in assisting community members with health information needs. Ultimately, this project seeks to improve health literacy among Minnesota citizens.