A new tool to assess Clinical Diversity In Meta-analyses (CDIM) of interventions.

OBJECTIVE: To develop and validate Clinical Diversity In Meta-analyses (CDIM), a new tool for assessing clinical diversity between trials in meta-analyses of interventions. STUDY DESIGN AND SETTING: The development of CDIM was based on consensus work informed by empirical literature and expertise. We drafted the CDIM tool, refined it, and validated CDIM for interrater scale reliability and agreement in three groups. RESULTS: CDIM measures clinical diversity on a scale that includes four domains with 11 items overall: setting (time of conduct/country development status/units type); population (age, sex, patient inclusion criteria/baseline disease severity, comorbidities); interventions (intervention intensity/strength/duration of intervention, timing, control intervention, cointerventions); and outcome (definition of outcome, timing of outcome assessment). The CDIM is completed in two steps: first two authors independently assess clinical diversity in the four domains. Second, after agreeing upon scores of individual items a consensus score is achieved. Interrater scale reliability and agreement ranged from moderate to almost perfect depending on the type of raters. CONCLUSION: CDIM is the first tool developed for assessing clinical diversity in meta-analyses of interventions. We found CDIM to be a reliable tool for assessing clinical diversity among trials in meta-analysis.

Antioxidant treatment to reduce mortality and serious adverse events in adult surgical patients: A systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: Hyperoxia during anesthesia can increase cellular oxidative stress, and perioperative antioxidant treatment may reduce the resulting damage. The aim of this review was to evaluate risks and benefits of antioxidant treatment in surgical patients. We hypothesized that antioxidant treatment reduced mortality compared to placebo/no intervention. METHODS: This systematic review with meta-analyses and trial sequential analysis (TSA) was conducted using Cochrane standards and GRADE methodology. Randomized clinical trials comparing perioperative antioxidant treatment vs. placebo/no intervention in adults were included. Primary outcome was mortality at longest follow-up. RESULTS: Ninety-seven trials with 8156 patients were included. The most common interventions were N-Acetylcysteine (36 trials) and vitamin C (29 trials). Trials were primarily performed during cardiac surgery (53 trials). Fifty-six trials with 4890 patients reported information on mortality (243 events). The meta-analysis of mortality at longest follow-up showed a reduced mortality in antioxidant treated patients (RR 0.74, 95% CI 0.59; 0.94, I2 0%), however, TSA-adjusted CI was broadened (0.55-1.02) and only 31% of the required information size was reached. Furthermore, in the subgroup of three trials with overall low risk of bias the RR for mortality was 1.18 (95% CI 0.39, 3.63). Based on GRADE, our findings are of low quality of evidence due to high risk of bias, imprecision, and indirectness. CONCLUSION: We found a 26% relative risk reduction of mortality in surgical patients treated with antioxidants but the quality of evidence supporting our findings is low and influenced by clinical heterogeneity and high risk of systematic- and random errors.

Sphenopalatine ganglion block for the treatment of postdural puncture headache: a randomised, blinded, clinical trial.

BACKGROUND: Current treatment of postdural puncture headache includes epidural blood patch (EBP), which is invasive and may result in rare but severe complications. Sphenopalatine ganglion block is suggested as a simple, minimally invasive treatment for postdural puncture headache. We aimed to investigate the analgesic effect of a transnasal sphenopalatine ganglion block with local anaesthetic vs saline. METHODS: We conducted a blinded, randomised clinical trial including adults fulfilling the criteria for EBP. Participants received a sphenopalatine ganglion block bilaterally with 1 ml of either local anaesthetic (lidocaine 4% and ropivacaine 0.5%) or placebo (saline). Primary outcome was pain in upright position 30 min post-block, measured on a 0-100 mm VAS. RESULTS: We randomised 40 patients with an upright median pain intensity of 74 and 84 mm in the local anaesthetic and placebo groups at baseline, respectively. At 30 min after sphenopalatine ganglion block, the median pain intensity in upright position was 26 mm in the local anaesthetic group vs 37 mm in the placebo group (estimated median difference: 5 mm; 95% confidence interval: -14 to 21; P=0.53). In the local anaesthetic group, 50% required an EBP compared with 45% in the placebo group (P=0.76). CONCLUSIONS: Administration of a sphenopalatine ganglion block with local anaesthetic had no statistically significant effect on pain intensity after 30 min compared with placebo. However, pain was reduced and EBP was avoided in half the patients of both groups, which suggests a major effect not necessarily attributable to local anaesthetics. CLINICAL TRIAL REGISTRATION: NCT03652714.

Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis.

BACKGROUND: Hydroxyethyl starch (HES) [corrected] is widely used for fluid resuscitation in intensive care units (ICUs), but its safety and efficacy have not been established in patients with severe sepsis. METHODS: In this multicenter, parallel-group, blinded trial, we randomly assigned patients with severe sepsis to fluid resuscitation in the ICU with either 6% HES 130/0.42 (Tetraspan) or Ringer's acetate at a dose of up to 33 ml per kilogram of ideal body weight per day. The primary outcome measure was either death or end-stage kidney failure (dependence on dialysis) at 90 days after randomization. RESULTS: Of the 804 patients who underwent randomization, 798 were included in the modified intention-to-treat population. The two intervention groups had similar baseline characteristics. At 90 days after randomization, 201 of 398 patients (51%) assigned to HES 130/0.42 had died, as compared with 172 of 400 patients (43%) assigned to Ringer's acetate (relative risk, 1.17; 95% confidence interval [CI], 1.01 to 1.36; P=0.03); 1 patient in each group had end-stage kidney failure. In the 90-day period, 87 patients (22%) assigned to HES 130/0.42 were treated with renal-replacement therapy versus 65 patients (16%) assigned to Ringer's acetate (relative risk, 1.35; 95% CI, 1.01 to 1.80; P=0.04), and 38 patients (10%) and 25 patients (6%), respectively, had severe bleeding (relative risk, 1.52; 95% CI, 0.94 to 2.48; P=0.09). The results were supported by multivariate analyses, with adjustment for known risk factors for death or acute kidney injury at baseline. CONCLUSIONS: Patients with severe sepsis assigned to fluid resuscitation with HES 130/0.42 had an increased risk of death at day 90 and were more likely to require renal-replacement therapy, as compared with those receiving Ringer's acetate. (Funded by the Danish Research Council and others; 6S ClinicalTrials.gov number, NCT00962156.).