Physical Activity and the Health of Wheelchair Users: A Systematic Review in Multiple Sclerosis, Cerebral Palsy, and Spinal Cord Injury.

OBJECTIVE: To understand the benefits and harms of physical activity in people who may require a wheelchair with a focus on people with multiple sclerosis (MS), cerebral palsy (CP), and spinal cord injury (SCI). DATA SOURCES: Searches were conducted in MEDLINE, Cumulative Index to Nursing and Allied Health, PsycINFO, Cochrane CENTRAL, and Embase (January 2008 through November 2020). STUDY SELECTION: Randomized controlled trials, nonrandomized trials, and cohort studies of observed physical activity (at least 10 sessions on 10 days) in participants with MS, CP, and SCI. DATA EXTRACTION: We conducted dual data abstraction, quality assessment, and strength of evidence. Measures of physical functioning are reported individually where sufficient data exist and grouped as "function" where data are scant. DATA SYNTHESIS: No studies provided evidence for prevention of cardiovascular conditions, development of diabetes, or obesity. Among 168 included studies, 44% enrolled participants with MS (38% CP, 18% SCI). Studies in MS found walking ability may be improved with treadmill training and multimodal exercises; function may be improved with treadmill, balance exercises, and motion gaming; balance is likely improved with balance exercises and may be improved with aquatic exercises, robot-assisted gait training (RAGT), motion gaming, and multimodal exercises; activities of daily living (ADL), female sexual function, and spasticity may be improved with aquatic therapy; sleep may be improved with aerobic exercises and aerobic fitness with multimodal exercises. In CP, balance may be improved with hippotherapy and motion gaming; function may be improved with cycling, treadmill, and hippotherapy. In SCI, ADL may be improved with RAGT. CONCLUSIONS: Depending on population and type of exercise, physical activity was associated with improvements in walking, function, balance, depression, sleep, ADL, spasticity, female sexual function, and aerobic capacity. Few harms of physical activity were reported in studies. Future studies are needed to address evidence gaps and to confirm findings.

Out-of-hospital Circulatory Measures to Identify Patients With Serious Injury: A Systematic Review.

OBJECTIVE: The objective was to systematically identify and summarize out-of-hospital measures of circulatory compromise as diagnostic predictors of serious injury, focusing on measures usable by emergency medical services to inform field triage decisions. METHODS: We searched Ovid MEDLINE, CINAHL, and the Cochrane databases from 1996 through August 2017 for published literature on individual circulatory measures in trauma. We reviewed reference lists of included articles for additional relevant citations. Measures of diagnostic accuracy included sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC). Indicators of serious injury included resource need, serious anatomic injury, and mortality. We pooled estimates when data permitted. RESULTS: We identified 114 articles, reporting results of 111 studies. Measures included systolic blood pressure (sBP), heart rate (HR), shock index (SI), lactate, base deficit, and HR variability. Pooled out-of-hospital sensitivity estimates were sBP < 90 mm Hg = 19% (95% confidence interval [CI] = 12% to 29%), HR ≥ 110 beats/min = 28% (95% CI = 20% to 37%), SI > 0.9 = 37% (95% CI = 22% to 56%), and lactate > 2.0 mmol/L = 74% (95% CI = 48% to 90%). Pooled specificity estimates were sBP < 90 mm Hg = 95% (95% CI = 91% to 97%), HR ≥ 110 beats/min = 85% (95% CI = 74% to 91%), SI > 0.9 = 85% (95% CI = 72% to 92%), and lactate > 2.0 mmol/L = 62% (95% CI = 51% to 72%). Pooled AUROCs included sBP = 0.67 (95% CI = 0.58 to 0.75), HR = 0.67 (95% CI = 0.56 to 0.79), SI = 0.72 (95% CI = 0.66 to 0.77), and lactate = 0.77 (95% CI = 0.67 to 0.82). Strength of evidence was low to moderate. CONCLUSIONS: Out-of-hospital circulatory measures are associated with poor to fair discrimination for identifying trauma patients with serious injuries. Many seriously injured patients have normal circulatory measures (low sensitivity), but when present, the measures are highly specific for identifying patients with serious injuries.

Out-of-hospital Respiratory Measures to Identify Patients With Serious Injury: A Systematic Review.

OBJECTIVES: The objective was to systematically review the published literature on the diagnostic accuracy of out-of-hospital respiratory measures for identifying patients with serious injury, focusing on measures feasible for field triage by emergency medical services personnel. METHODS: We searched Ovid MEDLINE, CINAHL, and the Cochrane databases from January 1, 1996, through August 31, 2017. We included studies on the diagnostic accuracy (sensitivity, specificity, and area under the receiver operating characteristic curve [AUROC]) for all respiratory measures used to identify patients with serious injury (resource use, serious anatomic injury, and mortality). We assessed studies for risk of bias and strength of evidence (SOE). We performed meta-analysis for measures with sufficient data. RESULTS: We identified 46 articles reporting results of 44 studies. Out-of-hospital respiratory measures included respiratory rate, pulse oximetry, and airway support. Meta-analysis was only possible for respiratory rate, which demonstrated a pooled sensitivity for serious injury of 13% (95% confidence interval [CI] = 5 to 29, I2  = 97.8%), specificity of 96% (95% CI = 83 to 99, I2  = 99.6%), and AUROC of 0.70 (95% CI = 0.66 to 0.79, I2  = 16.6%). For oxygen saturation, sensitivity ranged from 13% to 63%; specificity, 85% to 99%; and AUROC, 0.53 to 0.76. Need for airway support had a sensitivity of 8% to 53% and specificity of 61% to 100%; studies did not report AUROC. Across respiratory measures, the SOE was low. Other respiratory measures (pH, end-tidal carbon dioxide [CO2 ], and sublingual partial pressure of CO2 ) were reported only in emergency department studies. CONCLUSIONS: Data on the accuracy of out-of-hospital respiratory measures for field triage are limited and of low quality. Based on available research, respiratory rate, oxygen saturation, and need for airway intervention all have low sensitivity, high specificity, and poor to fair discrimination for identifying seriously injured patients.

Predictive Utility of the Total Glasgow Coma Scale Versus the Motor Component of the Glasgow Coma Scale for Identification of Patients With Serious Traumatic Injuries.

STUDY OBJECTIVE: The motor component of the Glasgow Coma Scale (mGCS) has been proposed as an easier-to-use alternative to the total GCS (tGCS) for field assessment of trauma patients by emergency medical services. We perform a systematic review and meta-analysis to compare the predictive utility of the tGCS versus the mGCS or Simplified Motor Scale in field triage of trauma for identifying patients with adverse outcomes (inhospital mortality or severe brain injury) or who underwent procedures (neurosurgical intervention or emergency intubation) indicating need for high-level trauma care. METHODS: Ovid MEDLINE, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, Health and Psychosocial Instruments, and the Cochrane databases were searched through June 2016 for English-language cohort studies. We included studies that compared the area under the receiver operating characteristic curve (AUROC) of the tGCS versus the mGCS or Simplified Motor Scale assessed in the field or shortly after arrival in the emergency department for predicting the outcomes described above. Meta-analyses were performed with a random-effects model, and subgroup and sensitivity analyses were conducted. RESULTS: We included 18 head-to-head studies of predictive utility (n=1,703,388). For inhospital mortality, the tGCS was associated with slightly greater discrimination than the mGCS (pooled mean difference in [AUROC] 0.015; 95% confidence interval [CI] 0.009 to 0.022; I2=85%; 12 studies) or the Simplified Motor Scale (pooled mean difference in AUROC 0.030; 95% CI 0.024 to 0.036; I2=0%; 5 studies). The tGCS was also associated with greater discrimination than the mGCS or Simplified Motor Scale for nonmortality outcomes (differences in AUROC from 0.03 to 0.05). Findings were robust in subgroup and sensitivity analyses. CONCLUSION: The tGCS is associated with slightly greater discrimination than the mGCS or Simplified Motor Scale for identifying severe trauma. The small differences in discrimination are likely to be clinically unimportant and could be offset by factors such as convenience and ease of use.

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

BACKGROUND: The diagnosis of myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is based on clinical criteria, yet there has been no consensus regarding which set of criteria best identifies patients with the condition. The Institute of Medicine has recently proposed a new case definition and diagnostic algorithm. PURPOSE: To review methods to diagnose ME/CFS in adults and identify research gaps and needs for future research. DATA SOURCES: MEDLINE, PsycINFO, and Cochrane databases (January 1988 to September 2014); clinical trial registries; and reference lists. STUDY SELECTION: English-language studies describing methods of diagnosis of ME/CFS and their accuracy. DATA EXTRACTION: Data on participants, study design, analysis, follow-up, and results were extracted and confirmed. Study quality was dual-rated by using prespecified criteria, and discrepancies were resolved through consensus. DATA SYNTHESIS: Forty-four studies met inclusion criteria. Eight case definitions have been used to define ME/CFS; a ninth, recently proposed by the Institute of Medicine, includes principal elements of previous definitions. Patients meeting criteria for ME represent a more symptomatic subset of the broader ME/CFS population. Scales rating self-reported symptoms differentiate patients with ME/CFS from healthy controls under study conditions but have not been evaluated in clinically undiagnosed patients to determine validity and generalizability. LIMITATIONS: Studies were heterogeneous and were limited by size, number, applicability, and methodological quality. Most methods were tested in highly selected patient populations. CONCLUSION: Nine sets of clinical criteria are available to define ME/CFS, yet none of the current diagnostic methods have been adequately tested to identify patients with ME/CFS when diagnostic uncertainty exists. More definitive studies in broader populations are needed to address these research gaps.

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

BACKGROUND: Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is a debilitating multisystem condition affecting more than 1 million adults in the United States. PURPOSE: To determine benefits and harms of treatments for adults with ME/CFS and identify future research needs. DATA SOURCES: MEDLINE, PsycINFO, and Cochrane databases (January 1988 to September 2014); clinical trial registries; reference lists; and manufacturer information. STUDY SELECTION: English-language randomized trials of the effectiveness and adverse effects of ME/CFS treatments. DATA EXTRACTION: 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. DATA SYNTHESIS: 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). LIMITATION: Trials were heterogeneous and were limited by size, number, duration, applicability, and methodological quality. CONCLUSION: 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.

Imaging Techniques for the Diagnosis of Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

BACKGROUND: Several imaging modalities are available for diagnosis of hepatocellular carcinoma (HCC). PURPOSE: To evaluate the test performance of imaging modalities for HCC. DATA SOURCES: MEDLINE (1998 to December 2014), the Cochrane Library Database, Scopus, and reference lists. STUDY SELECTION: Studies on test performance of ultrasonography, computed tomography (CT), or magnetic resonance imaging (MRI). DATA EXTRACTION: One investigator abstracted data, and a second investigator confirmed them; 2 investigators independently assessed study quality and strength of evidence. DATA SYNTHESIS: Few studies have evaluated imaging for HCC in surveillance settings. In nonsurveillance settings, sensitivity for detection of HCC lesions was lower for ultrasonography without contrast than for CT or MRI (pooled difference based on direct comparisons, 0.11 to 0.22), and MRI was associated with higher sensitivity than CT (pooled difference, 0.09 [95% CI, 0.07 to 12]). For evaluation of focal liver lesions, there were no clear differences in sensitivity among ultrasonography with contrast, CT, and MRI. Specificity was generally 0.85 or higher across imaging modalities, but this item was not reported in many studies. Factors associated with lower sensitivity included use of an explanted liver reference standard, and smaller or more well-differentiated HCC lesions. For MRI, sensitivity was slightly higher for hepatic-specific than nonspecific contrast agents. LIMITATIONS: Only English-language articles were included, there was statistical heterogeneity in pooled analyses, and costs were not assessed. Most studies were conducted in Asia and had methodological limitations. CONCLUSION: CT and MRI are associated with higher sensitivity than ultrasonography without contrast for detection of HCC; sensitivity was higher for MRI than CT. For evaluation of focal liver lesions, the sensitivities of ultrasonography with contrast, CT, and MRI for HCC are similar. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. ( PROSPERO: CRD42014007016).

Diagnosis and Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

OBJECTIVES: 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. DATA SOURCES: 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. REVIEW METHODS: 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. RESULTS: 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.Of the 35 trials of treatment, rintatolimod compared with placebo improved measures of exercise performance; counseling therapies and graded exercise treatment (GET) compared with no treatment, relaxation, or support improved fatigue, function, and quality of life, and counseling therapies also improved employment outcomes. Other treatments either provided no benefit or results were insufficient to draw conclusions. GET was associated with higher numbers of reported adverse events compared with counseling therapies or controls. Harms were generally inadequately reported across trials. LIMITATIONS: Diagnostic methods were studied only in highly selected patient populations. Treatment trials were limited in number and had small sample sizes and methodological shortcomings. CONCLUSIONS: 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.

Pressure ulcer treatment strategies: a systematic comparative effectiveness review.

BACKGROUND: Pressure ulcers affect as many as 3 million Americans and are major sources of morbidity, mortality, and health care costs. PURPOSE: To summarize evidence comparing the effectiveness and safety of treatment strategies for adults with pressure ulcers. DATA SOURCES: MEDLINE, EMBASE, CINAHL, Evidence-Based Medicine Reviews, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, and Health Technology Assessment Database for English- or foreign-language studies; reference lists; gray literature; and individual product packets from manufacturers (January 1985 to October 2012). STUDY SELECTION: Randomized trials and comparative observational studies of treatments for pressure ulcers in adults and noncomparative intervention series (n > 50) for surgical interventions and evaluation of harms. DATA EXTRACTION: Data were extracted and evaluated for accuracy of the extraction, quality of included studies, and strength of evidence. DATA SYNTHESIS: 174 studies met inclusion criteria and 92 evaluated complete wound healing. In comparison with standard care, placebo, or sham interventions, moderate-strength evidence showed that air-fluidized beds (5 studies [n = 908]; high consistency), protein-containing nutritional supplements (12 studies [n = 562]; high consistency), radiant heat dressings (4 studies [n = 160]; moderate consistency), and electrical stimulation (9 studies [n = 397]; moderate consistency) improved healing of pressure ulcers. Low-strength evidence showed that alternating-pressure surfaces, hydrocolloid dressings, platelet-derived growth factor, and light therapy improved healing of pressure ulcers. The evidence about harms was limited. LIMITATION: Applicability of results is limited by study quality, heterogeneity in methods and outcomes, and inadequate duration to assess complete wound healing. CONCLUSION: Moderate-strength evidence shows that healing of pressure ulcers in adults is improved with the use of air-fluidized beds, protein supplementation, radiant heat dressings, and electrical stimulation.

Blood tests to diagnose fibrosis or cirrhosis in patients with chronic hepatitis C virus infection: a systematic review.

BACKGROUND: Many blood tests have been proposed as alternatives to liver biopsy for identifying fibrosis or cirrhosis. PURPOSE: To evaluate the diagnostic accuracy of blood tests to identify fibrosis or cirrhosis in patients with hepatitis C virus (HCV) infection. DATA SOURCES: MEDLINE (1947 to January 2013), the Cochrane Library, and reference lists. STUDY SELECTION: Studies that compared the diagnostic accuracy of blood tests with that of liver biopsy. DATA EXTRACTION: Investigators abstracted and checked study details and quality by using predefined criteria. DATA SYNTHESIS: 172 studies evaluated diagnostic accuracy. For identifying clinically significant fibrosis, the platelet count, age-platelet index, aspartate aminotransferase-platelet ratio index (APRI), FibroIndex, FibroTest, and Forns index had median positive likelihood ratios of 5 to 10 at commonly used cutoffs and areas under the receiver-operating characteristic curve (AUROCs) of 0.70 or greater (range, 0.71 to 0.86). For identifying cirrhosis, the platelet count, age-platelet index, APRI, and Hepascore had median positive likelihood ratios of 5 to 10 and AUROCs of 0.80 or greater (range, 0.80 to 0.91). The Göteborg University Cirrhosis Index and the Lok index had slightly lower positive likelihood ratios (4.8 and 4.4, respectively). In direct comparisons, the APRI was associated with a slightly lower AUROC than the FibroTest for identifying fibrosis and a substantially higher AUROC than the aspartate aminotransferase-alanine aminotransferase ratio for identifying fibrosis or cirrhosis. LIMITATION: Only English-language articles were included, and most studies had methodological limitations, including failure to describe blinded interpretation of liver biopsy specimens and inadequate description of enrollment methods. CONCLUSION: Many blood tests are moderately useful for identifying clinically significant fibrosis or cirrhosis in HCV-infected patients. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Reducing risk for mother-to-infant transmission of hepatitis C virus: a systematic review for the U.S. Preventive Services Task Force.

BACKGROUND: Mother-to-infant transmission is the leading cause of childhood hepatitis C virus (HCV) infection, with up to 4000 new cases each year in the United States. PURPOSE: To evaluate effects of mode of delivery, labor management strategies, and breastfeeding practices on risk for mother-to-infant transmission of HCV. DATA SOURCES: MEDLINE (1947 to May 2012), the Cochrane Library Database, clinical trial registries, and reference lists. STUDY SELECTION: Randomized trials and observational studies on mode of delivery, labor management strategies, and breastfeeding practices and risk for mother-to-infant transmission of HCV. DATA EXTRACTION: Investigators abstracted and reviewed study details and quality using predefined criteria. DATA SYNTHESIS: Eighteen observational studies evaluated the association between mode of delivery, labor management strategies, or breastfeeding practices and risk for mother-to-infant HCV transmission. Fourteen studies (2 good-quality, 4 fair-quality, and 8 poor-quality studies) found no clear association between mode of delivery (vaginal versus cesarean delivery) and risk for transmission. Two studies (1 good-quality and 1 poor-quality study) reported an association between prolonged duration of ruptured membranes and increased risk for transmission. Fourteen studies (2 good-quality, 2 fair-quality, and 10 poor-quality studies) found no association between breastfeeding and risk for transmission. LIMITATIONS: Only English-language articles were included. Studies were observational, and most had important methodological shortcomings, including failure to adjust for potential confounders and small sample sizes. CONCLUSION: No intervention has been clearly demonstrated to reduce the risk for mother-to-infant HCV transmission. Avoidance of breastfeeding does not seem to be indicated for reducing transmission risk. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Comparative effectiveness of antiviral treatment for hepatitis C virus infection in adults: a systematic review.

BACKGROUND: Multiple treatments are available for chronic hepatitis C virus (HCV) infection. PURPOSE: To compare benefits and harms of antiviral regimens for chronic HCV infection in treatment-naive adults. DATA SOURCES: English-language literature from MEDLINE (1947 to August 2012), the Cochrane Library Database, Embase, Scopus, PsychINFO, and clinical trial registries. STUDY SELECTION: Randomized trials of antiviral treatments and cohort studies examining associations between sustained virologic response (SVR) after therapy and clinical outcomes. DATA EXTRACTION: Several investigators abstracted study details and quality by using predefined criteria. DATA SYNTHESIS: No trial evaluated effectiveness of treatment on long-term clinical outcomes. Dual therapy with pegylated interferon alfa-2b plus ribavirin was associated with a lower likelihood of SVR than was pegylated interferon alfa-2a plus ribavirin (absolute difference, 8 percentage points [95% CI, 3 to 14 percentage points]) on the basis of 7 poor- to fair-quality trials. For genotype 2 or 3 infection, dual therapy for 12 to 16 weeks was associated with a lower likelihood of SVR than was therapy for 24 weeks, and lower doses of pegylated interferon alfa-2b were less effective than standard doses (2 to 4 fair-quality trials). For genotype 1 infection, fair-quality trials found that triple therapy with pegylated interferon, ribavirin, and either boceprevir (2 trials) or telaprevir (4 trials) was associated with a higher likelihood of SVR than was dual therapy (absolute difference, 22 to 31 percentage points). Compared with dual therapy, boceprevir triple therapy increased risk for hematologic adverse events and telaprevir triple therapy increased risk for anemia and rash. A large well-designed cohort study and 18 smaller cohort studies found that an SVR after antiviral therapy was associated with lower risk for all-cause mortality than was no SVR. LIMITATIONS: Trials involved highly selected populations. Observational studies did not always adequately control for confounders. CONCLUSION: SVR rates for genotype 1 infection are higher with triple therapy that includes a protease inhibitor than with standard dual therapy. An SVR after antiviral therapy appears associated with improved clinical outcomes. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Screening for hepatitis C virus infection in adults: a systematic review for the U.S. Preventive Services Task Force.

BACKGROUND: Identification of hepatitis C virus (HCV)-infected persons through screening could lead to interventions that improve clinical outcomes. PURPOSE: To review evidence about potential benefits and harms of HCV screening in asymptomatic adults without known liver enzyme abnormalities. DATA SOURCES: English-language publications identified from MEDLINE (1947 to May 2012), the Cochrane Library Database, clinical trial registries, and reference lists. STUDY SELECTION: Randomized trials and cohort, case-control, and cross-sectional studies that assessed yield or clinical outcomes of screening; studies reporting harms from HCV screening; and large series reporting harms of diagnostic liver biopsies. DATA EXTRACTION: Multiple investigators abstracted and checked study details and quality by using predefined criteria. DATA SYNTHESIS: No study evaluated clinical outcomes associated with screening compared with no screening or of different risk- or prevalence-based strategies. Three cross-sectional studies in higher prevalence populations found that screening strategies that targeted multiple risk factors were associated with sensitivities greater than 90% and numbers needed to screen to identify 1 case of HCV infection of less than 20. Data on direct harms of screening were sparse. A large study of percutaneous liver biopsies (n = 2740) in HCV-infected patients with compensated cirrhosis reported no deaths and a 1.1% rate of serious adverse events (primarily bleeding and severe pain). LIMITATIONS: Modeling studies were not examined. High or unreported proportions of potentially eligible patients in the observational studies were not included in calculations of screening yield because of unknown HCV status. CONCLUSION: Although screening tests can accurately identify adults with chronic HCV infection, targeted screening strategies based on the presence of risk factors misses some patients with HCV infection. Well-designed prospective studies are needed to better understand the effects of different HCV screening strategies on diagnostic yield and clinical outcomes. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

"Serious skin & soft tissue infections in rheumatoid arthritis patients taking anti-tumor necrosis factor alpha drugs: a nested case-control study".

BACKGROUND: Anti-tumor necrosis factor alpha (anti-TNF) drugs are very effective for the treatment of rheumatoid arthritis but may increase the risk of serious bacterial infections. We assessed the association between the risk of serious skin and soft tissue infections (SSSTI) and the use of these agents in rheumatoid arthritis patients (RA). METHODS: We conducted a nested case-control study among rheumatoid arthritis patients in the Veterans Integrated Service Network 20 from 2000-2008. We identified rheumatoid arthritis patients with SSSTI, matched them to three sets of RA controls and used conditional logistic regression to compare the risk of SSSTI between patients treated and those not treated with an anti-TNF drug, after adjusting for known confounders and important covariates. Limited by the design, we could not assess (absolute) risk but only relative risk in terms of association. RESULTS: Among the 97 cases and 291 controls, 90 percent were male, 62 percent white, with a mean age of 63 years. Twenty percent received anti-TNF drugs during the study period. Thirty-nine percent of cases and 15 percent of controls died, (OR 3.5, 95% CI: 2.033, 6.11, p <0.01). Diabetes mellitus (37%), kidney disease (16%) and a history of skin infections (27%) were common among cases. Based on conditional logistic regression, anti-TNF use was not significantly associated with skin and soft tissue infections (OR 1.1, 95% CI: 0.61-2.03, p = 0.92). However, patients with diabetes mellitus (OR 2.5, 95% CI: 1.53-4.13, p = 0.01) or a prior history of skin infection (OR 5.7, 95% CI: 2.87-11.43, p <0.01) were more likely to have skin and soft tissue infections. CONCLUSION: Use of anti-TNF therapy among RA patients was not associated with an increased risk of SSSTI, but patients with diabetes mellitus and those with a history of prior skin infection were significantly more likely to have SSSTI and mortality was higher among cases than controls in this veteran cohort.