Systematic survey of randomized trials evaluating the impact of alternative diagnostic strategies on patient-important outcomes.

OBJECTIVES: To provide a perspective on the current practice of randomized clinical trials (RCTs) of diagnostic strategies focusing on patient-important outcomes. STUDY DESIGN AND SETTING: We conducted a comprehensive search of MEDLINE and included RCTs published in full-text reports that evaluated alternative diagnostic strategies. RESULTS: Of 56,912 unique citations, we sampled 7,500 and included 103 eligible RCTs, therefore suggesting that MEDLINE includes approximately 781 diagnostic RCTs. The 103 eligible trials reported on: mortality (n = 41; 39.8%); morbidities (n = 63; 61.2%); symptoms/quality of life/functional status (n = 14; 13.6%); and on composite end points (n = 10; 9.7%). Of the studies that reported statistically significant results (n = 12; 11.6%), we judged 7 (58.3%) as at low risk of bias with respect to missing outcome data and 4 (33.3%) as at low risk of bias regarding blinding. Of the 41 RCTs that reported on mortality, only one (2.4%) reported statistically significant results. Of 63 RCTs addressing morbidity outcomes, 11 (17.5%) reported statistically significant results, all of which reported relative effects of greater than 20%. CONCLUSION: RCTs of diagnostic tests are not uncommon, and sometimes suggest benefits on patient-important outcomes but often suffer from limitations in sample size and conduct.

Systematic reviews and meta-analyses of the accuracy of HPV tests, visual inspection with acetic acid, cytology, and colposcopy.

BACKGROUND: Cervical cancer screening is offered to women to identify and treat cervical intraepithelial neoplasia (CIN). OBJECTIVES: To support WHO guidelines, a systematic review was performed to compare test accuracy of the HPV test, cytology (cervical smear), and unaided visual inspection with acetic acid (VIA); and to determine test accuracy of HPV and colposcopy impression. SEARCH STRATEGY: Medline and Embase were searched up to September 2012, and experts were contacted for references. SELECTION CRITERIA: Studies of at least 100 nonpregnant women (aged ≥18years) not previously diagnosed with CIN were included. DATA COLLECTION AND ANALYSIS: Two investigators independently screened and collected data. Pooled sensitivity and specificity, and absolute differences were calculated, and the quality of evidence assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation). MAIN RESULTS: High to moderate quality evidence was found. The greatest difference in overtreatment occurred with VIA instead of the cervical smear (58 more per 1000 women). Differences in missed treatment ranged from 2-5 per 1000 women. For 1000 women screened positive and then sent to colposcopy, 464 would be falsely diagnosed with CIN grade 2-3 and treated. CONCLUSIONS: Although differences in sensitivity between tests could be interpreted as large, absolute differences in missed diagnoses were small. By contrast, small differences in specificity resulted in fairly large absolute differences in overtreatment.

Systematic reviews and meta-analyses of benefits and harms of cryotherapy, LEEP, and cold knife conization to treat cervical intraepithelial neoplasia.

BACKGROUND: Cervical intraepithelial neoplasia (CIN) stage 2-3 is a premalignant lesion that can progress to cervical cancer in 10-20 years if untreated. OBJECTIVES: To conduct systematic reviews of randomized and nonrandomized studies for effects of cryotherapy, loop electrosurgical excision procedure (LEEP), and cold knife conization (CKC) as treatment for CIN 2-3. SEARCH STRATEGY: Medline, Embase, and other databases were searched to February 2012 for benefits, and to July 2012 for harms. Additionally, experts were contacted. Keywords for CIN, cervical cancer, and the treatments were used. SELECTION CRITERIA: Studies of nonpregnant women 18 years or older not previously treated for CIN were included. DATA COLLECTION AND ANALYSIS: Two investigators independently screened and collected data. Relative risks and proportions were calculated and evidence assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation). MAIN RESULTS: Recurrence rate was 5.3% 12 months after cryotherapy or LEEP, and 1.4% after CKC. There seemed to be little or no differences in frequency of complications after LEEP or cryotherapy, but they occurred more often after CKC. Evidence suggests premature delivery is most common with CKC, but it also occurs after LEEP and cryotherapy. CONCLUSIONS: Despite a comprehensive search, there is very low quality evidence and often no evidence for important outcomes, including reproductive outcomes and complications. Studies assessing these outcomes are needed.

Effect of Lowering the Dialysate Temperature in Chronic Hemodialysis: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Lowering the dialysate temperature may improve outcomes for patients undergoing chronic hemodialysis. We reviewed the reported benefits and harms of lower temperature dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We searched the Cochrane Central Register, OVID MEDLINE, EMBASE, and Pubmed until April 15, 2015. We reviewed the reference lists of relevant reviews, registered trials, and relevant conference proceedings. We included all randomized, controlled trials that evaluated the effect of reduced temperature dialysis versus standard temperature dialysis in adult patients receiving chronic hemodialysis. We followed the Grading of Recommendations Assessment, Development and Evaluation approach to assess confidence in the estimates of effect (i.e., the quality of evidence). We conducted meta-analyses using random effects models. RESULTS: Twenty-six trials were included, consisting of a total of 484 patients. Compared with standard temperature dialysis, reduced temperature dialysis significantly reduced the rate of intradialytic hypotension by 70% (95% confidence interval, 49% to 89%) and significantly increased intradialytic mean arterial pressure by 12 mmHg (95% confidence interval, 8 to 16 mmHg). Symptoms of discomfort occurred 2.95 (95% confidence interval, 0.88 to 9.82) times more often with reduced temperature compared with standard temperature dialysis. The effect on dialysis adequacy was not significantly different, with a Kt/V mean difference of -0.05 (95% confidence interval, -0.09 to 0.01). Small sample sizes, loss to follow-up, and a lack of appropriate blinding in some trials reduced confidence in the estimates of effect. None of the trials reported long-term outcomes. CONCLUSIONS: In patients receiving chronic hemodialysis, reduced temperature dialysis may reduce the rate of intradialytic hypotension and increase intradialytic mean arterial pressure. High-quality, large, multicenter, randomized trials are needed to determine whether reduced temperature dialysis affects patient mortality and major adverse cardiovascular events.