Low Strength Of Evidence Research Articles

Omega-3 Fatty Acids and Maternal and Child Health: An Updated Systematic Review.

To update a prior systematic review on the effects of omega-3 fatty acids (n-3 FA) on maternal and child health and to assess the evidence for their effects on, and associations with, additional outcomes. MEDLINE®, Embase®, the Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Centre for Agriculture and Biosciences (CAB) Abstracts from 2000 to August 2015; eligible studies from the original report; and relevant systematic reviews. We included randomized controlled trials (RCTs) of any defined dose of n-3 FA (or combination) compared to placebo, any other n-3 FA, or alternative dose with an outcome of interest conducted in pregnant or breastfeeding women or neonates (preterm or term). We also included prospective observational studies that analyzed the association between baseline n-3 FA intake or biomarker level and followup outcomes. Postnatal interventions began within a week of birth for term infants and within a week of beginning enteral or oral feeding for preterm infants. Standard methods were used for data abstraction and analysis, according to the Evidence-based Practice Center Methods Guide. We identified 4,275 potentially relevant titles from our searches, of which 95 RCTs and 48 observational studies met the inclusion criteria. Risk of bias was a concern with both RCTs and observational studies. Outcomes for which evidence was sufficient to draw a conclusion are summarized here with the Strength of Evidence (SoE). (Outcomes for which the evidence was insufficient to draw a conclusion are summarized in Appendix G of the report.). Most studies in this report examined the effects of fish oil (or other combinations of DHA and EPA) supplements on pregnant or breastfeeding women or the effects of infant formula fortified with DHA plus AA. As with the original report, with the exception of small increases in birth weight and length of gestation,n-3 FA supplementation or fortification has no consistent evidence of effects on peripartum maternal or infant health outcomes. No effects of n-3 FA were seen on gestational hypertension, peripartum depression, or postnatal growth. Apparent effects of n-3 FA supplementation were inconsistent across assessment methods and followup times for outcomes related to infant visual acuity, cognitive development and prevention of allergy and asthma. Future RCTs need to assess standardized preparations of n-3 and n-6 FA, using a select group of clinically important outcomes, on populations with baseline n-3 FA intakes typical of those of most western populations.

Omega-3 Fatty Acids and Cardiovascular Disease: An Updated Systematic Review.

The effect and association of omega-3 fatty acids (n-3 FA) intake and biomarker levels with cardiovascular (CV) clinical and intermediate outcomes remains controversial. We update prior Evidence Reports of n-3 FA and clinical and intermediate CV disease (CVD) outcomes. Evaluate the effect of n-3 FA on clinical and selected intermediate CV outcomes and the association of n-3 FA intake and biomarkers with CV outcomes. The n-3 FA under review include eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), stearidonic acid (SDA), and alphalinolenic acid (ALA). MEDLINE®, Embase®, the Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and CAB Abstracts from 2000 or 2002 to June 8, 2015, and eligible studies from the original reports and relevant existing systematic reviews. We included randomized controlled trials (RCTs) of any n-3 FA intake compared to no, lower, or other n-3 FA intake with an outcome of interest conducted in healthy adults, those at risk for CVD, or those with CVD. We also included prospective observational studies of the association between baseline n-3 FA intake or biomarker level and followup outcomes. We required 1 year or more of followup for clinical outcomes and 4 weeks for intermediate outcomes (blood pressure [BP] and lipids). From 11,440 citations (from electronic literature searches and existing systematic reviews), 829 abstracts met basic eligibility criteria; 61 RCTs and 37 longitudinal observational studies (in 147 articles) were included. Most RCTs and observational studies had few risk-of-bias concerns. The 61 RCTs mostly compared marine oil supplements with placebo on CVD outcomes in populations at risk for CVD or with CVD, while the 37 observational studies mostly examined associations between various individual n-3 FA and long-term CVD events in generally healthy populations. Compared with the prior report on n-3 FA and CVD, there is more robust RCT evidence on ALA and on clinical CV outcomes; also, by design there are newly added data on associations between n-3 FA biomarkers and CV outcomes. However, conclusions regarding the effect of n-3 FA intake on CV outcomes or associations with outcomes remain substantially unchanged. Marine oils statistically significantly raise HDL-c and LDL-c by similar amounts (≤2 mg/dL), while lowering Tg in a dose-dependent manner, particularly in individuals with elevated Tg; they have no significant effect on BP. ALA has no significant effect on intermediate outcomes. Limited data were available from RCTs on the effect of n-3 FA on clinical CVD outcomes. Observational studies suggest that higher marine oil intake (including from dietary fish) is associated with lower risk of several CVD outcomes. No clear differences in effects or associations were evident based on population, demographic features, or cointerventions. Future RCTs would be needed to establish adequate evidence of the effect of n-3 FA on CVD outcomes or to clarify differential effects in different groups of people. However, future trials are unlikely to alter conclusions about the effects of n-3 FA supplementation on intermediate cardiovascular outcomes (BP, LDL-c, HDL-c, or Tg).

Effectiveness of Left Atrial Appendage Exclusion Procedures to Reduce the Risk of Stroke: A Systematic Review of the Evidence.

Atrial fibrillation is an important cause of cardioembolic stroke. Oral anticoagulants (OAC) reduce stroke risk but increase the risk of serious bleeding. Left atrial appendage (LAA) procedures have been developed to isolate the LAA from circulating blood flow, as an alternative to OAC. We conducted a systematic review of the benefits and harms of surgical and percutaneous LAA exclusion procedures. We searched multiple data sources, including Ovid MEDLINE, Cochrane, and Embase, through January 7, 2015. Of 2567 citations, 20 primary studies met prespecified inclusion criteria. We abstracted data on patient characteristics, stroke, mortality, and adverse effects. We assessed study quality and graded the strength of evidence using published criteria. Trials found low-strength evidence that percutaneous LAA exclusion confers similar risks of stroke and mortality as continued OAC, but this evidence was limited to the Watchman device in patients eligible for long-term OAC. Observational studies found moderate-strength evidence of serious harms with a variety of percutaneous LAA procedures. There is low-strength evidence that surgical LAA exclusion does not add significant harm during heart surgery for another indication, but evidence on stroke reduction is insufficient. There is limited evidence that the Watchman device may be noninferior to long-term OAC in selected patients. Data on effectiveness of LAA exclusion devices is lacking in patients ineligible for long-term OAC. Percutaneous LAA devices are associated with high rates of procedure-related harms. Although surgical LAA exclusion during heart surgery does not seem to add incremental harm, there is insufficient evidence of benefit.

Respiratory Syncytial Virus Hospitalizations in Healthy Preterm Infants: Systematic Review.

Background:Studies have explored the risk for and impact of respiratory syncytial virus (RSV) infection requiring hospitalization among healthy preterm infants born at 29–35 weeks of gestational age not given RSV immunoprophylaxis. We performed a systematic review and qualitative synthesis of these studies.Methods:Two experienced reviewers used prespecified inclusion/exclusion criteria to screen titles/abstracts and full-text studies using MEDLINE, Embase, BIOSIS and Cochrane Library (January 1, 1985, to November 6, 2014). We abstracted data on risk factors for RSV hospitalization, incidence and short- and long-term outcomes of RSV hospitalization. Using standard procedures, we assessed study risk of bias and graded strength of evidence (SOE).Results:We identified 4754 records and reviewed 27. Important risk factors for RSV hospitalization included young age during the RSV season, having school-age siblings and day-care attendance, with odds ratios >2.5 in at least one study (high SOE). Incidence rates for RSV hospitalizations ranged from 2.3% to 10% (low SOE). Length of hospital stays ranged from 3.8 to 6.1 days (low SOE). Recurrent wheezing rates ranged from 20.7% to 42.8% 1 to 2 years after RSV hospitalization (low SOE).Conclusions:Young chronological age and some environmental risk factors are important clinical indicators of an increased risk of RSV hospitalization in healthy preterm infants 32 to 35 weeks of gestational age. SOE was low for estimates of incidence of RSV hospitalizations, in-hospital resource use and recurrent wheezing in this population. Studies were inconsistent in study characteristics, including weeks of gestational age, age during RSV season and control for confounding factors.

The Effectiveness of Total Worker Health Interventions: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop.

The Total Worker Health (TWH) program of the National Institute for Occupational Safety and Health aims to advance worker well-being by integrating injury and illness prevention efforts with work-related safety and health hazard efforts. To evaluate evidence on the benefits and harms of integrated TWH interventions. MEDLINE, Cochrane Library, and PsycINFO (January 1990 through September 2015); clinical trial registries; and reference lists. English-language studies that enrolled employed adults and compared integrated interventions with usual work practice, no intervention, or another intervention. Dual abstraction and risk-of-bias (ROB) assessment. Ten of the 15 included studies had high ROB, primarily because of selection and attrition bias. Findings graded as having low strength of evidence (SOE) supported the effectiveness of TWH interventions for improving smoking cessation, as measured by self-reported 7-day abstinence over 22 to 26 weeks (2 randomized, controlled trials [RCTs]; n= 737), and increasing consumption of fruits and vegetables over 26 to 104 weeks (3 RCTs; n= 6056); results apply to populations of blue-collar manufacturing and construction workers. Findings graded as having low SOE supported the effectiveness of TWH interventions for reducing sedentary work behavior in office workers over 16 to 52 weeks (2 RCTs; n= 262). Evidence was insufficient or lacking for other outcomes of interest, such as rates of work injuries, quality of life, and harms. Small, diverse body of evidence with many methodological limitations; possible publication bias. Integrated TWH interventions might improve health behaviors (for example, reduce tobacco use and sedentary behavior and improve diet) of workers, but effects of these interventions on injuries and overall quality of life are not known. Agency for Healthcare Research and Quality.

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

Psychological and behavioral interventions are frequently used for insomnia disorder. To assess benefits and harms of psychological and behavioral interventions for insomnia disorder in adults. Ovid MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and PsycINFO through September 2015, supplemented with hand-searching. 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 by single investigator confirmed by a second reviewer; dual investigator assessment of risk of bias; consensus determination of strength of evidence. 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. 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. 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. Agency for Healthcare Research and Quality. ( CRD42014009908).

Pharmacist-Led Chronic Disease Management: A Systematic Review of Effectiveness and Harms Compared With Usual Care.

Increased involvement of pharmacists in patient care may increase access to health care and improve patient outcomes. To determine the effectiveness and harms of pharmacist-led chronic disease management for community-dwelling adults. MEDLINE, Cochrane Library, CINAHL, and International Pharmaceutical Abstracts from 1995 through February 2016, and reference lists of systematic reviews and included studies. 65 patient populations in 63 studies conducted in the United States of any design reported outcomes of pharmacist-led chronic disease management versus a comparator for community-dwelling adults in the United States. Studies set in retail pharmacies were excluded. Data extraction done by a single investigator was confirmed by a second investigator; risk of bias was assessed by 2 investigators; and strength of evidence was determined by consensus. Pharmacist-led care was associated with similar numbers of office visits, urgent care or emergency department visits, and hospitalizations (moderate-strength evidence) and medication adherence (low-strength evidence) compared with usual care (typically continuing a prestudy visit schedule). Pharmacist-led care increased the number or dose of medications received and improved study-selected glycemic, blood pressure, and lipid goal attainment (moderate-strength evidence). Mortality and clinical events were similar (low-strength evidence). Evidence on patient satisfaction was mixed and insufficient. The reporting of harms was limited. Interventions were heterogeneous. Studies were typically short-term and designed to assess physiologic intermediate outcomes rather than clinical events. Reporting of many clinical outcomes of interest was limited, and often they were not the study-defined primary end points. Pharmacist-led chronic disease management was associated with effects similar to those of usual care for resource utilization and may improve physiologic goal attainment. Further research is needed to determine whether increased medication utilization and goal attainment improve clinical outcomes. Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Quality Enhancement Research Initiative.

Timing of Decompression in Patients with Acute Spinal Cord Injury: A Systematic Review

Introduction To perform an evidence synthesis of the literature assessing the comparative effectiveness, safety and cost effectiveness of early decompression (≤ 24 hours) versus later decompression (>24 hours) in adults with acute traumatic spinal cord injury. Material and Methods A systematic search was conducted for literature published through November 6th, 2014. Included studies were critically appraised and GRADE methods were used to determine the overall strength of evidence. Based on clinical expert opinion, an improvement of two or more grades for Frankel or ASIA grades or 5 point improvement in ASIA Motor Score was considered a priori to represent clinically meaningful improvement. Results Six studies met inclusion criteria. All but one was considered to be a moderately high risk of bias. Single studies in cervical SCI, thoracolumbar SCI, cervical and thoracolumbar SCI, acute central cord injury without instability were identified, and two studies report across SCI levels. Due to the heterogeneity across studies (injury level, measures used, and clinical characteristics), pooling of data was not done. No studies of conservative management met inclusion criteria. No full economic studies or studies of patient preferences or values were identified. Across studies and injury levels, early surgical decompression, defined as surgery ≤ 24 hours of injury, was not consistently associated statistically with clinically important improvement in neurological status. (low to very low strength of evidence) Isolated studies reported statistically significant and clinically important improvement at 6 months for cervical injury and following discharge from inpatient rehabilitation but not at other time points in a population comprised of injury at any level; another study reported a statistically significant 6 point improvement in ASIA Improvement Score only among patients with AIS B, C, or D, but not for those with AIS A. (very low strength of evidence). In one study of acute traumatic cord injury without instability, a clinically and statistically meaningful improvement in total motor scores was seen at six months but not 12 months and there were no statistical differences in ASIA Impairment Scale up to 12 months. (very low strength of evidence) Only one of three studies found a shorter length of hospital stay associated with early surgical decompression. Safety and harms were reported in only three studies; although no statistical differences between early and late decompression were seen, including for mortality, neurologic deterioration, pneumonia or pressure ulcers, studies were underpowered to detect differences particularly for rare outcomes. Conclusion The overall strength (quality) of evidence across studies was low to very low that early decompression may lead to clinically important improvement in neurologic status in some instances. For studies considering cervical SCI alone and thoracolumbar SCI alone, the overall quality (strength) of evidence was low. For studies involving a combination of cervical, thoracic and lumbar SCI the strength of the same conclusion was very low. Although no statistical or clinically significant differences were noted between early and late groups, firm conclusions regarding the safety of early versus delayed surgical decompression are difficult given small sample sizes and rare events.

Effectiveness of Prevention Strategies for Contrast-Induced Nephropathy: A Systematic Review and Meta-analysis.

N-acetylcysteine, sodium bicarbonate, statins, and ascorbic acid have been studied for reducing contrast-induced nephropathy (CIN). To evaluate the comparative effectiveness of interventions to reduce CIN in adults receiving contrast media. MEDLINE, EMBASE, Cochrane Library, ClinicalTrials.gov, and Scopus databases through June 2015. Risk of bias and overall strength of evidence (SOE) of studies were assessed. Randomized, controlled trials of N-acetylcysteine, sodium bicarbonate, statins, or ascorbic acid that used intravenous (IV) or intra-arterial contrast media and defined CIN with enough data for meta-analysis. Two reviewers independently extracted data and assessed study quality. Low-dose N-acetylcysteine plus IV saline compared with IV saline (risk ratio [RR], 0.75 [95% CI, 0.63 to 0.89]; low SOE), N-acetylcysteine plus IV saline compared with IV saline in patients receiving low-osmolar contrast media (RR, 0.69 [CI, 0.58 to 0.84]; moderate SOE), and statins plus N-acetylcysteine plus IV saline versus N-acetylcysteine plus IV saline (RR, 0.52 [CI, 0.29 to 0.93]; low SOE) had clinically important and statistically significant benefits. The following 3 comparisons suggested a clinically important difference that was not statistically significant: sodium bicarbonate versus IV saline in patients receiving low-osmolar contrast media (RR, 0.65 [CI, 0.33 to 1.25]; low SOE), statins plus IV saline versus IV saline (RR, 0.68 [CI, 0.39 to 1.20]; low SOE), and ascorbic acid versus IV saline (RR, 0.72 [CI, 0.48 to 1.01]; low SOE). Strength of evidence was generally insufficient for comparisons of the need for renal replacement, cardiac events, and mortality. Too few studies were done in patients receiving IV contrast media. The greatest reduction in CIN was seen with N-acetylcysteine plus IV saline in patients receiving LOCM and with statins plus N-acetylcysteine plus IV saline. Agency for Healthcare Research and Quality.

Urinary Biomarkers for Diagnosis of Bladder Cancer: A Systematic Review and Meta-analysis.

Urinary biomarkers may be a useful alternative or adjunct to cystoscopy for diagnosis of bladder cancer. To systematically review the evidence on the accuracy of urinary biomarkers for diagnosis of bladder cancer in adults who have signs or symptoms of the disease or are undergoing surveillance for recurrent disease. Ovid MEDLINE (January 1990 through June 2015), Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and reference lists. 57 studies that evaluated the diagnostic accuracy of quantitative or qualitative nuclear matrix protein 22 (NMP22), qualitative or quantitative bladder tumor antigen (BTA), fluorescence in situ hybridization (FISH), fluorescent immunohistochemistry (ImmunoCyt [Scimedx]), and Cxbladder (Pacific Edge Diagnostics USA) using cystoscopy and histopathology as the reference standard met inclusion criteria. Case-control studies were excluded. Dual extraction and quality assessment of individual studies. Overall strength of evidence (SOE) was also assessed. Across biomarkers, sensitivities ranged from 0.57 to 0.82 and specificities ranged from 0.74 to 0.88. Positive likelihood ratios ranged from 2.52 to 5.53, and negative likelihood ratios ranged from 0.21 to 0.48 (moderate SOE for quantitative NMP22, qualitative BTA, FISH, and ImmunoCyt; low SOE for others). For some biomarkers, sensitivity was higher for initial diagnosis of bladder cancer than for diagnosis of recurrence. Sensitivity increased with higher tumor stage or grade. Studies that directly compared the accuracy of quantitative NMP22 and qualitative BTA found no differences in diagnostic accuracy (moderate SOE); head-to-head studies of other biomarkers were limited. Urinary biomarkers plus cytologic evaluation were more sensitive than biomarkers alone but missed about 10% of bladder cancer cases. Restricted to English-language studies; no search for studies published only as abstracts; statistical heterogeneity present in most analyses; few studies for qualitative NMP22, quantitative BTA, and Cxbladder; and methodological shortcomings in almost all studies. Urinary biomarkers miss a substantial proportion of patients with bladder cancer and are subject to false-positive results in others. Accuracy is poor for low-stage and low-grade tumors. Agency for Healthcare Research and Quality. (PROSPERO registration number: CRD42014013284).

Behavioral Programs for Type 1 Diabetes Mellitus: A Systematic Review and Meta-analysis.

Whether behavioral approaches for self-management programs benefit individuals with type 1 diabetes mellitus is unclear. To determine the effects of behavioral programs for patients with type 1 diabetes on behavioral, clinical, and health outcomes and to investigate factors that might moderate effect. 6 electronic databases (1993 to June 2015), trial registries and conference proceedings (2011 to 2014), and reference lists. 36 prospective, controlled studies involving participants of any age group that compared behavioral programs with usual care, active controls, or other programs. One reviewer extracted and another verified data. Two reviewers assessed quality and strength of evidence (SOE). Moderate SOE showed reduction in glycated hemoglobin (HbA1c) at 6 months after the intervention compared with usual care (mean difference, -0.29 [95% CI, -0.45 to -0.13] percentage points) and compared with active controls (-0.44 [CI, -0.69 to -0.19] percentage points). At the end of the intervention and 12-month follow-up or longer, there were no statistically significant differences in HbA1c (low SOE) for comparisons with usual care or active control. Compared with usual care, generic quality of life at program completion did not differ (moderate SOE). Other outcomes had low or insufficient SOE. Adults appeared to benefit more for glycemic control at program completion (-0.28 [CI, -0.57 to 0.01] percentage points) than did youth (-0.12 [CI, -0.43 to 0.19] percentage points). Program intensity appeared not to influence effectiveness; some individual delivery appears beneficial. All studies had medium or high risk of bias. There was scarce evidence for many outcomes. Behavioral programs for type 1 diabetes offer some benefit for glycemic control, at least at short-term follow-up, but improvement for other outcomes has not been shown. (PROSPERO registration number: CRD42014010515). Agency for Healthcare Research and Quality. (PROSPERD registration number: CRD42014010515).

Intermediate- and Long-Term Cognitive Outcomes After Cardiovascular Procedures in Older Adults: A Systematic Review.

Risks for intermediate- and long-term cognitive impairment after cardiovascular procedures in older adults are poorly understood. To summarize evidence about cognitive outcomes in adults aged 65 years or older at least 3 months after coronary or carotid revascularization, cardiac valve procedures, or ablation for atrial fibrillation. MEDLINE, Cochrane, and Scopus databases from 1990 to January 2015; ClinicalTrials.gov; and bibliographies of reviews and eligible studies. English-language trials and prospective cohort studies. One reviewer extracted data, a second checked accuracy, and 2 independently rated quality and strength of evidence (SOE). 17 trials and 4 cohort studies were included; 80% of patients were men, and mean age was 68 years. Cognitive function did not differ after the procedure between on- and off-pump coronary artery bypass grafting (CABG) (n=6; low SOE), hypothermic and normothermic CABG (n=3; moderate to low SOE), or CABG and medical management (n=1; insufficient SOE). One trial reported lower risk for incident cognitive impairment with minimal versus conventional extracorporeal CABG (risk ratio, 0.34 [95% CI, 0.16 to 0.73]; low SOE). Two trials found no difference between surgical carotid revascularization and carotid stenting or angioplasty (low and insufficient SOE, respectively). One cohort study reported increased cognitive decline after transcatheter versus surgical aortic valve replacement but had large selection and outcome measurement biases (insufficient SOE). Mostly low to insufficient SOE; no pertinent data for ablation; limited generalizability to the most elderly patients, women, and persons with substantial baseline cognitive impairment; and possible selective reporting and publication bias. Intermediate- and long-term cognitive impairment in older adults attributable to the studied cardiovascular procedures may be uncommon. Nevertheless, clinicians counseling patients before these procedures should discuss the uncertainty in their risk for adverse cognitive outcomes. Agency for Healthcare Research and Quality.

Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop.

Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is a debilitating multisystem condition affecting more than 1 million adults in the United States. To determine benefits and harms of treatments for adults with ME/CFS and identify future research needs. MEDLINE, PsycINFO, and Cochrane databases (January 1988 to September 2014); clinical trial registries; reference lists; and manufacturer information. English-language randomized trials of the effectiveness and adverse effects of ME/CFS treatments. Data on participants, study design, analysis, follow-up, and results were extracted and confirmed. Study quality was dual-rated by using prespecified criteria; discrepancies were resolved through consensus. Among 35 treatment trials enrolling participants primarily meeting the 1994 Centers for Disease Control and Prevention and Oxford case definitions of CFS, the immune modulator rintatolimod improved some measures of exercise performance compared with placebo in 2 trials (low strength of evidence). Trials of galantamine, hydrocortisone, IgG, valganciclovir, isoprinosine, fluoxetine, and various complementary medicines were inconclusive (insufficient evidence). Counseling therapies and graded exercise therapy compared with no treatment, relaxation, or support improved fatigue, function, global improvement, and work impairment in some trials; counseling therapies also improved quality of life (low to moderate strength of evidence). Harms were rarely reported across studies (insufficient evidence). Trials were heterogeneous and were limited by size, number, duration, applicability, and methodological quality. Trials of rintatolimod, counseling therapies, and graded exercise therapy suggest benefit for some patients meeting case definitions for CFS, whereas evidence for other treatments and harms is insufficient. More definitive studies comparing participants meeting different case definitions, including ME, and providing subgroup analysis are needed to fill research gaps.

MIS lateral spine surgery: a systematic literature review of complications, outcomes, and economics.

Over the past decade, the minimally disruptive lateral transpsoas approach for lumbar interbody fusion (MI-LIF) is increasingly being used as an alternative to conventional surgical approaches. The purpose of this review was to evaluate four primary questions as they relate to MI-LIF: (1) Is there an anatomical justification for MI-LIF at L4-5? (2) What are the complication and outcome profiles of MI-LIF and are they acceptable with respect to conventional approaches? (3) Given technical and neuromonitoring differences between various MI-LIF procedures, are there any published clinical differences? And, (4) are modern minimally disruptive procedures (e.g., MI-LIF) economically viable? Through a MEDLINE and Google Scholar search, a total of 237 articles that discussed MI-LIF were identified. Of those, topical areas included anatomy (22), biomechanics/testing (17), technical descriptions (11), case reports (40), complications (30), clinical and radiographic outcomes (43), deformity (23), trauma or thoracic applications (10), and review articles (41). In answer to the questions posed, (1) there is a high strength of evidence showing MI-LIF to be anatomically justified at all levels of the lumbar spine from L1-2 to L4-5. The evidence also supports the use of advanced neuromonitoring modalities. (2) There is moderate strength evidence in support of reproducible and reasonable complication, side effect, and outcome profiles following MI-LIF which may be technique dependent. (3) There is low-strength evidence that shows elevated neural complication rates in non-traditional (e.g., shallow-docking approaches and/or those without specialized neuromonitoring) MI-LIF, and (4) there is low- to moderate-strength evidence that modern minimally disruptive surgical approaches are cost-effective. There is considerable published evidence to support MI-LIF in spinal fusion and advanced applications, though the results of some reports, especially concerning complications, vary greatly depending on technique and instrumentation used. Additional cost-effectiveness analyses would assist in fully understanding the long-term implications of MI-LIF.

The efficacy and safety of heparin in patients with sepsis: a systematic review and metaanalysis.

To evaluate the efficacy and safety of heparin in patients with sepsis, septic shock, or disseminated intravascular coagulation associated with infection. Systematic review and metaanalysis. Randomized controlled trials from MEDLINE, EMBASE, CENTRAL, Global Health, Scopus, Web of Science, the International Clinical Trials Registry Platform (inception to April 2014), conference proceedings, and reference lists of relevant articles. Two reviewers independently identified and extracted trial-level data from randomized trials investigating unfractionated or low molecular heparin administered to patients with sepsis, severe sepsis, septic shock, or disseminated intravascular coagulation associated with infection. Internal validity was assessed in duplicate using the Risk of Bias tool. The strength of evidence was assessed in duplicate using Grading of Recommendations Assessment, Development, and Evaluation methodology. Our primary outcome was mortality. Safety outcomes included hemorrhage, transfusion, and thrombocytopenia. We included nine trials enrolling 2,637 patients. Eight trials were of unclear risk of bias and one was classified as having low risk of bias. In trials comparing heparin to placebo or usual care, the risk ratio for death associated with heparin was 0.88 (95% CI, 0.77-1.00; I2 = 0%; 2,477 patients; six trials; moderate strength of evidence). In trials comparing heparin to other anticoagulants, the risk ratio for death was 1.30 (95% CI, 0.78-2.18; I2 = 0%; 160 patients; three trials; low strength of evidence). In trials comparing heparin to placebo or usual care, major hemorrhage was not statistically significantly increased (risk ratio, 0.79; 95% CI, 0.53-1.17; I2 = 0%; 2,392 patients; three trials). In one small trial of heparin compared with other anticoagulants, the risk of major hemorrhage was significantly increased (2.14; 95% CI, 1.07-4.30; 48 patients). Important secondary and safety outcomes, including minor bleeding, were sparsely reported. Heparin in patients with sepsis, septic shock, and disseminated intravascular coagulation associated with infection may be associated with decreased mortality; however, the overall impact remains uncertain. Safety outcomes have been underreported and require further study. Increased major bleeding with heparin administration cannot be excluded. Large rigorous randomized trials are needed to evaluate more carefully the efficacy and safety of heparin in patients with sepsis, severe sepsis, and septic shock.

Antimicrobial stewardship in outpatient settings: a systematic review.

Evaluate the effect of outpatient antimicrobial stewardship programs on prescribing, patient, microbial outcomes, and costs. Systematic review Search of MEDLINE (2000 through November 2013), Cochrane Library, and reference lists of relevant studies. We included English language studies with patient populations relevant to the United States (eg, infectious conditions, prescription services) evaluating stewardship programs in outpatient settings and reporting outcomes of interest. Data regarding study characteristics and outcomes were extracted and organized by intervention type. We identified 50 studies eligible for inclusion, with most (29 of 50; 58%) reporting on respiratory tract infections, followed by multiple/unspecified infections (17 of 50; 34%). We found medium-strength evidence that stewardship programs incorporating communication skills training and laboratory testing are associated with reductions in antimicrobial use, and low-strength evidence that other stewardship interventions are associated with improved prescribing. Patient-centered outcomes, which were infrequently reported, were not adversely affected. Medication costs were generally lower with stewardship interventions, but overall program costs were rarely reported. No studies reported microbial outcomes, and data regarding outpatient settings other than primary care clinics are limited. Low- to moderate-strength evidence suggests that antimicrobial stewardship programs in outpatient settings improve antimicrobial prescribing without adversely effecting patient outcomes. Effectiveness depends on program type. Most studies were not designed to measure patient or resistance outcomes. Data regarding sustainability and scalability of interventions are limited.

Diagnosis and Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

This systematic review summarizes research on methods of diagnosing myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and benefits and harms of multiple medical and nonmedical treatments. It identifies evidence gaps and limitations to inform future research. Searches of electronic databases included MEDLINE® (1988 to September 2014), PsycINFO® (1988 to September 2014), and the Cochrane Library (through the third quarter of 2014). The searches were supplemented by reviewing reference lists, seeking suggestions from reviewers, and requesting scientific information from drug and device manufacturers. Two investigators reviewed abstracts and full-text articles for inclusion based on predefined criteria. Discrepancies were resolved through discussion and consensus, with a third investigator making the final decision. A total of 6,175 potentially relevant articles were identified, 1,069 were selected for full-text review, and 71 studies in 81 publications were included (36 observational studies on diagnosis and 35 trials of treatments). Eight case definitions have been used to define ME/CFS; those for ME, requiring the presence of postexertional malaise, represent a more symptomatic subset of the broader ME/CFS population. Researchers are unable to determine differences in accuracy between case definitions because there is no universally accepted reference standard for diagnosing ME/CFS. The Oxford criteria are the least restrictive and include patients who would not otherwise meet criteria for ME/CFS. Self-reported symptom scales may differentiate ME/CFS patients from healthy controls but have not been adequately evaluated to determine validity and generalizability in large populations with diagnostic uncertainty. Fourteen studies reported the consequences of diagnosis, including perceived stigma and the burden of misdiagnosis, as well as feelings of legitimacy upon receiving the diagnosis of ME/CFS. Diagnostic methods were studied only in highly selected patient populations. Treatment trials were limited in number and had small sample sizes and methodological shortcomings. None of the current diagnostic methods have been adequately tested to identify patients with ME/CFS when diagnostic uncertainty exists. Rintatolimod improves exercise performance in some patients (low strength of evidence), while counseling therapies and GET have broader benefit but have not been adequately tested in more disabled populations (low to moderate strength of evidence). Other treatments and harms have been inadequately studied (insufficient evidence). More definitive studies are needed to fill the many research gaps in diagnosing and treating ME/CFS.

Medication Therapy Management Interventions in Outpatient Settings

ImportanceMedication therapy management (MTM) services (also called clinical pharmacy services) aim to reduce medication-related problems and their downstream outcomes.ObjectiveTo assess the effect of MTM interventions among outpatients with chronic illnesses.Data SourcesMEDLINE, Cochrane Library, and International Pharmaceutical s through January 9, 2014.Study SelectionTwo reviewers selected studies with comparators and eligible outcomes of ambulatory adults.Data Extraction and SynthesisDual review of titles, abstracts, full-text, extractions, risk of bias, and strength of evidence grading. We conducted meta-analyses using random-effects models.Main Outcomes and MeasuresMedication-related problems, morbidity, mortality, quality of life, health care use, costs, and harms.ResultsForty-four studies met the inclusion criteria. The evidence was insufficient to determine the effect of MTM interventions on most evaluated outcomes (eg, drug therapy problems, adverse drug events, disease-specific morbidity, disease-specific or all-cause mortality, and harms). The interventions improved a few measures of medication-related problems and health care use and costs (low strength of evidence) when compared with usual care. Specifically, MTM interventions improved medication appropriateness (4.9 vs 0.9 points on the medication appropriateness index, P < .001), adherence (approximately 4.6%), and percentage of patients achieving a threshold adherence level (odds ratios [ORs] ranged from 0.99 to 5.98) and reduced medication dosing (mean difference, −2.2 doses; 95% CI, −3.738 to −0.662). Medication therapy management interventions reduced health plan expenditures on medication costs, although the studies reported wide CIs. For patients with diabetes mellitus or heart failure, MTM interventions lowered the odds of hospitalization (diabetes: OR, 0.91 to 0.93 based on type of insurance; adjusted hazard rate for heart failure: 0.55; 95% CI, 0.39 to 0.77) and hospitalization costs (mean differences ranged from −$363.45 to −$398.98). The interventions conferred no benefit for patient satisfaction and most measures of health-related quality of life (low strength).Conclusions and RelevanceWe graded the evidence as insufficient for most outcomes because of inconsistency and imprecision that stem in part from underlying heterogeneity in populations and interventions. Medication therapy management interventions may reduce the frequency of some medication-related problems, including nonadherence, and lower some health care use and costs, but the evidence is insufficient with respect to improvement in health outcomes.

Role of troponin in patients with chronic kidney disease and suspected acute coronary syndrome: a systematic review.

Patients with chronic kidney disease (CKD) have high prevalence of elevated serum troponin levels, which makes diagnosis of acute coronary syndrome (ACS) challenging. To evaluate the utility of troponin in ACS diagnosis, treatment, and prognosis among patients with CKD. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through May 2014. Studies examining elevated versus normal troponin levels in terms of their diagnostic performance in detection of ACS, effect on ACS management strategies, and prognostic value for mortality or cardiovascular events after ACS among patients with CKD. Paired reviewers selected articles for inclusion, extracted data, and graded strength of evidence (SOE). Twenty-three studies met inclusion criteria. The sensitivity of troponin T for ACS diagnosis ranged from 71% to 100%, and specificity ranged from 31% to 86% (6 studies; low SOE). The sensitivity and specificity of troponin I ranged from 43% to 94% and from 48% to 100%, respectively (8 studies; low SOE). No studies examined how troponin levels affect management strategies. Twelve studies analyzed prognostic value. Elevated levels of troponin I or troponin T were associated with higher risk for short-term death and cardiac events (low SOE). A similar trend was observed for long-term mortality with troponin I (low SOE), but less evidence was found for long-term cardiac events for troponin I and long-term outcomes for troponin T (insufficient SOE). Patients with advanced CKD tended to have worse prognoses with elevated troponin I levels than those without them (moderate SOE). Studies were heterogeneous in design and in ACS definitions and adjudication methods. In patients with CKD and suspected ACS, troponin levels can aid in identifying those with a poor prognosis, but the diagnostic utility is limited by varying estimates of sensitivity and specificity. Agency for Healthcare Research and Quality.

Depression drug treatment outcomes in pregnancy and the postpartum period: a systematic review and meta-analysis.

To evaluate the comparative benefits and harms in both mother and child of antidepressant treatment for depression in pregnant or postpartum women. MEDLINE, the Cochrane Library, CINAHL, Scopus, ClinicalTrials.gov (inception to July 2013), manufacturers, and reference lists. Two reviewers independently selected studies of pregnant women with depression comparing antidepressants with each other, placebo or no treatment, or nondrug treatments. Studies making comparisons among women taking antidepressants for any reason and those not taking antidepressants (depression status unknown) were used to fill gaps in the evidence. Dual study data extraction and quality assessment were used. Six randomized controlled trials and 15 observational studies provided evidence. Low-strength evidence suggested neonates of pregnant women with depression taking selective serotonin reuptake inhibitors had higher risk of respiratory distress than did neonates of untreated women (13.9% compared with 7.8%; P<.001) but no difference in risk of neonatal convulsions (0.14% compared with 0.11%; P=.64) or preterm birth (17% compared with 10%; P=.07). Indirect evidence from studies of pregnant women receiving antidepressants for mixed or unreported reasons compared with pregnant women not taking antidepressants (depression status unknown) suggested future research should focus on congenital anomalies and autism spectrum and attention deficit disorders in the child. In postpartum depression, low-strength evidence suggested symptom response was not improved when sertraline was added to psychotherapy or when cognitive-behavioral therapy was added to paroxetine. Evidence was insufficient for other outcomes, including depression symptoms, functional capacity, breastfeeding, and infant and child development. A serious limitation is the lack of study populations of exclusively depressed pregnant and postpartum women. Evidence about the comparative benefits and harms of pharmacologic treatment of depression in pregnant and postpartum women was largely inadequate to allow informed decisions about treatment. Considering the prevalence of depression, filling this gap is essential.