Are sample sizes clear and justified in RCTs published in dental journals?

Sample size calculations are advocated by the CONSORT group to justify sample sizes in randomized controlled trials (RCTs). The aim of this study was primarily to evaluate the reporting of sample size calculations, to establish the accuracy of these calculations in dental RCTs and to explore potential predictors associated with adequate reporting. Electronic searching was undertaken in eight leading specific and general dental journals. Replication of sample size calculations was undertaken where possible. Assumed variances or odds for control and intervention groups were also compared against those observed. The relationship between parameters including journal type, number of authors, trial design, involvement of methodologist, single-/multi-center study and region and year of publication, and the accuracy of sample size reporting was assessed using univariable and multivariable logistic regression. Of 413 RCTs identified, sufficient information to allow replication of sample size calculations was provided in only 121 studies (29.3%). Recalculations demonstrated an overall median overestimation of sample size of 15.2% after provisions for losses to follow-up. There was evidence that journal, methodologist involvement (OR = 1.97, CI: 1.10, 3.53), multi-center settings (OR = 1.86, CI: 1.01, 3.43) and time since publication (OR = 1.24, CI: 1.12, 1.38) were significant predictors of adequate description of sample size assumptions. Among journals JCP had the highest odds of adequately reporting sufficient data to permit sample size recalculation, followed by AJODO and JDR, with 61% (OR = 0.39, CI: 0.19, 0.80) and 66% (OR = 0.34, CI: 0.15, 0.75) lower odds, respectively. Both assumed variances and odds were found to underestimate the observed values. Presentation of sample size calculations in the dental literature is suboptimal; incorrect assumptions may have a bearing on the power of RCTs.

Impact of IL28B genotype on first-week response to telaprevir-based therapy in HIV-HCV coinfection

BACKGROUND IL28B genotype predicts response to treatment against hepatitis C virus (HCV) with pegylated interferon/ribavirin (PR) and impacts on the outcome of therapy including telaprevir (TVR). This study aimed to determine the influence of the favorable IL28B genotype on early viral kinetics during therapy with TVR/PR in HIV/HCV-coinfected patients. METHODS All HIV/HCV genotype 1-coinfected subjects who received TVR/PR for at least 4 weeks were included from populations prospectively followed in 22 centers throughout Germany, Switzerland and Spain. RESULTS Of the 129 subjects included, 38 (29.5%) presented with IL28B genotype CC and 94 (72.9%) were treatment-experienced. Ninety-six (73.8%) patients showed undetectable plasma HCV-RNA at treatment week (W) 4: 30 (78.9%) of the IL28B-CC carriers and 65 (71.4%) of the non-CC carriers (p=0.377). Among treatment-naïve patients, proportions of undetectable HCV-RNA among IL28B-CC versus non-CC carriers were 8/9 (88.9%) versus 3/9 (33.3%, p=0.016) and 14/17 (82.4%) versus 11/18 (61.1%, p=0.164) at W2 and W4. The decrease of HCV-RNA at W2 and W4 was similar among the IL28B carriers. CONCLUSIONS IL28B genotype does not predict W4 response to TVR/PR in HIV/HCV-coinfected patients, regardless of their treatment history. However, there is evidence of an impact on response during the first weeks in treatment-naïve patients.

Relationship between survival and increased radiation dose to subventricular zone in glioblastoma is controversial.

To test the hypothesis on prolonged survival in glioblastoma cases with increased subventricular zone (SVZ) radiation dose. Sixty glioblastoma cases were previously treated with adjuvant radiotherapy and Temozolamide. Ipsilateral, contralateral and bilateral SVZs were contoured and their doses were retrospectively evaluated. Median follow-up, progression free survival (PFS) and overall survival (OS) were 24.5, 8.5 and 19.3 months respectively. Log-rank tests showed a statistically significant correlation between contralateral SVZ (cSVZ) dose > 59.2 Gy (75th percentile) and poor median PFS (10.37 [95% CI 8.37-13.53] vs 7.1 [95% CI 3.5-8.97] months, p = 0.009). cSVZ dose > 59.2 Gy was associated with poor OS in the subgroup with subtotal resection/biopsy (HR: 4.83 [95% CI 1.71-13.97], p = 0.004). High ipsilateral SVZ dose of > 62.25 Gy (75th percentile) was associated with poor PFS in both subgroups of high performance status (HR: 2.58 [95% CI 1.03-6.05], p = 0.044) and SVZ without tumoral contact (HR: 10.57 [95% CI 2.04-49], p = 0.008). The effect of high cSVZ dose on PFS lost its statistical significance in multivariate Cox regression analysis. We report contradictory results compared to previous publications. Changing the clinical practice based on retrospective studies which even do not indicate consistent results among each other will be dangerous. We need carefully designed prospective randomized studies to evaluate any impact of radiation to SVZ in glioblastoma.

Impact of early-onset seizures on grading and outcome in patients with subarachnoid hemorrhage

OBJECT After subarachnoid hemorrhage (SAH), seizure occurs in up to 26% of patients. The impact of seizure on outcome has been studied, yet its impact on grading is unknown. The authors evaluated the impact of early-onset seizures (EOS) on grading of spontaneous SAH and on outcome. METHODS This retrospective analysis included consecutive patients with SAH who were treated at the NeuroCenter, Inselspital, University Hospital Bern, Switzerland, between January 2005 and December 2010. Demographic data, clinical data, and reports of EOS were recorded. The EOS were defined as seizures occurring within 24 hours after ictus. Patients were graded according to the World Federation of Neurosurgical Societies (WFNS) scale pre- and postresuscitation and dichotomized into good (WFNS I-III) and poor (WFNS IV-V) grades. Outcome was assessed at 6 months by using the modified Rankin Scale (mRS); an mRS score of 0-3 was considered a good outcome and an mRS score of 4-6 was considered a poor outcome. RESULTS Forty-one of 425 patients with SAH had EOS. Twenty-seven of those 41 patients (65.9%) had a poor WFNS grade. Twenty-eight (68.3%) achieved a good outcome, 11 (26.8%) had a poor outcome, and 2 (4.9%) were lost to followup. Early-onset seizures were proven in 9 of 16 electroencephalograms. The EOS were associated with poor WFNS grade (OR 2.81, 97.5% CI 1.14-7.46; p = 0.03) and good outcome (OR 4.01, 97.5% CI 1.63-10.53; p = 0.03). Increasing age, hydrocephalus, intracerebral hemorrhage, and intraventricular hemorrhage were associated with poor WFNS grade, whereas only age, intracerebral hemorrhage (p < 0.001), and poor WFNS grade (p < 0.001) were associated with poor outcome. CONCLUSIONS Patients with EOS were classified significantly more often in a poor grade initially, but then they significantly more often achieved a good outcome. The authors conclude that EOS can negatively influence grading. This might influence decision making for the care of patients with SAH, so grading of patients with EOS should be interpreted with caution.

Psychological interventions for acute pain after open heart surgery

BACKGROUND Acute postoperative pain is one of the most disturbing complaints in open heart surgery, and is associated with a risk of negative consequences. Several trials investigated the effects of psychological interventions to reduce acute postoperative pain and improve the course of physical and psychological recovery of participants undergoing open heart surgery. OBJECTIVES To compare the efficacy of psychological interventions as an adjunct to standard care versus standard care alone or standard care plus attention in adults undergoing open heart surgery on pain, pain medication, mental distress, mobility, and time to extubation. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 8), MEDLINE (1946 to September 2013), EMBASE (1980 to September 2013), Web of Science (all years to September 2013), and PsycINFO (all years to September 2013) for eligible studies. We used the 'related articles' and 'cited by' options of eligible studies to identify additional relevant studies. We also checked lists of references of relevant articles and previous reviews. We also searched the ProQuest Dissertations and Theses Full Text Database (all years to September 2013) and contacted the authors of primary studies to identify any unpublished material. SELECTION CRITERIA Randomised controlled trials comparing psychological interventions as an adjunct to standard care versus standard care alone or standard care plus attention in adults undergoing open heart surgery. DATA COLLECTION AND ANALYSIS Two review authors (SK and JR) independently assessed trials for eligibility, estimated the risk of bias and extracted all data. We calculated effect sizes for each comparison (Hedges' g) and meta-analysed data using a random-effects model. MAIN RESULTS Nineteen trials were included (2164 participants).No study reported data on the number of participants with pain intensity reduction of at least 50% from baseline. Only one study reported data on the number of participants below 30/100 mm on the Visual Analogue Scale (VAS) in pain intensity. Psychological interventions have no beneficial effects in reducing pain intensity measured with continuous scales in the medium-term interval (g -0.02, 95% CI -0.24 to 0.20, 4 studies, 413 participants, moderate quality evidence) nor in the long-term interval (g 0.12, 95% CI -0.09 to 0.33, 3 studies, 280 participants, low quality evidence).No study reported data on median time to remedication or on number of participants remedicated. Only one study provided data on postoperative analgesic use. Studies reporting data on mental distress in the medium-term interval revealed a small beneficial effect of psychological interventions (g 0.36, 95% CI 0.10 to 0.62, 12 studies, 1144 participants, low quality evidence). Likewise, a small beneficial effect of psychological interventions on mental distress was obtained in the long-term interval (g 0.28, 95% CI 0.05 to 0.51, 11 studies, 1320 participants, low quality evidence). There were no beneficial effects of psychological interventions on mobility in the medium-term interval (g 0.23, 95% CI -0.22 to 0.67, 3 studies, 444 participants, low quality evidence) nor in the long-term interval (g 0.29, 95% CI -0.14 to 0.71, 4 studies, 423 participants, low quality evidence). Only one study reported data on time to extubation. AUTHORS' CONCLUSIONS For the majority of outcomes (two-thirds) we could not perform a meta-analysis since outcomes were not measured, or data were provided by one trial only. Psychological interventions have no beneficial effects on reducing postoperative pain intensity or enhancing mobility. There is low quality evidence that psychological interventions reduce postoperative mental distress. Due to limitations in methodological quality, a small number of studies, and large heterogeneity, we rated the quality of the body of evidence as low. Future trials should measure crucial outcomes (e.g. number of participants with pain intensity reduction of at least 50% from baseline) and should focus to enhance the quality of the body of evidence in general. Altogether, the current evidence does not clearly support the use of psychological interventions to reduce pain in participants undergoing open heart surgery.

Polypharmacy is Associated with an Increased Risk of Bleeding in Elderly Patients with Venous Thromboembolism.

BACKGROUND Polypharmacy, defined as the concomitant use of multiple medications, is very common in the elderly and may trigger drug-drug interactions and increase the risk of falls in patients receiving vitamin K antagonists. OBJECTIVE To examine whether polypharmacy increases the risk of bleeding in elderly patients who receive vitamin K antagonists for acute venous thromboembolism (VTE). DESIGN We used a prospective cohort study. PARTICIPANTS In a multicenter Swiss cohort, we studied 830 patients aged ≥ 65 years with VTE. MAIN MEASURES We defined polypharmacy as the prescription of more than four different drugs. We assessed the association between polypharmacy and the time to a first major and clinically relevant non-major bleeding, accounting for the competing risk of death. We adjusted for known bleeding risk factors (age, gender, pulmonary embolism, active cancer, arterial hypertension, cardiac disease, cerebrovascular disease, chronic liver and renal disease, diabetes mellitus, history of major bleeding, recent surgery, anemia, thrombocytopenia) and periods of vitamin K antagonist treatment as a time-varying covariate. KEY RESULTS Overall, 413 (49.8 %) patients had polypharmacy. The mean follow-up duration was 17.8 months. Patients with polypharmacy had a significantly higher incidence of major (9.0 vs. 4.1 events/100 patient-years; incidence rate ratio [IRR] 2.18, 95 % confidence interval [CI] 1.32-3.68) and clinically relevant non-major bleeding (14.8 vs. 8.0 events/100 patient-years; IRR 1.85, 95 % CI 1.27-2.71) than patients without polypharmacy. After adjustment, polypharmacy was significantly associated with major (sub-hazard ratio [SHR] 1.83, 95 % CI 1.03-3.25) and clinically relevant non-major bleeding (SHR 1.60, 95 % CI 1.06-2.42). CONCLUSIONS Polypharmacy is associated with an increased risk of both major and clinically relevant non-major bleeding in elderly patients receiving vitamin K antagonists for VTE.

Inkunabelkatalog der Stadt- und Universitätsbibliothek und anderer öffentlicher Sammlungen in Frankfurt am Main

bearb. von Kurt Ohly und Vera Sack

The effect of cumulating exposure to abacavir on the risk of cardiovascular disease events in patients from the Swiss HIV Cohort Study.

BACKGROUND Patients with HIV exposed to the antiretroviral drug abacavir may have an increased risk of cardiovascular disease (CVD). There is concern that this association arises because of a channelling bias. Even if exposure is a risk, it is not clear how that risk changes as exposure cumulates. METHODS We assess the effect of exposure to abacavir on the risk of CVD events in the Swiss HIV Cohort Study. We use a new marginal structural Cox model to estimate the effect of abacavir as a flexible function of past exposures while accounting for risk factors that potentially lie on a causal pathway between exposure to abacavir and CVD. RESULTS 11,856 patients were followed for a median of 6.6 years; 365 patients had a CVD event (4.6 events per 1000 patient years). In a conventional Cox model, recent - but not cumulative - exposure to abacavir increased the risk of a CVD event. In the new marginal structural Cox model, continued exposure to abacavir during the past four years increased the risk of a CVD event (hazard ratio 2.06, 95% confidence interval 1.43-2.98). The estimated function for the effect of past exposures suggests that exposure during the past 6 to 36 months caused the greatest increase in risk. CONCLUSIONS Abacavir increases the risk of a CVD event: the effect of exposure is not immediate, rather the risk increases as exposure cumulates over the past few years. This gradual increase in risk is not consistent with a rapidly acting mechanism, such as acute inflammation.

36Cl production rate from K-spallation in the European Alps (Chironico landslide, Switzerland)

The abundant production of in situ cosmogenic 36Cl from potassium renders 36Cl measurements in K-rich rocks or minerals, such as K-feldspars, potentially useful for precisely dating rock surfaces, either in single-nuclide or in multi-nuclide studies, for example combined with 10Be measurements in quartz. However, significant discrepancies in experimentally calibrated 36Cl production rates from spallation of potassium (36PK-sp), referenced to sea-level/high-latitude (SLHL), limit the accuracy of 36Cl dating from K-rich lithologies. We present a new 36Cl calibration using K-feldspars, in which K-spallation is the most dominant 36Cl production pathway (>92% of total 36Cl), thus minimizing uncertainties from the complex multi-pathway 36Cl production systematics. The samples are derived from boulders of an ∼13.4 ka-old landslide in the Swiss Alps (∼820 m, 46.43°N, 8.85°E). We obtain a local 36PK-sp of 306 ± 16 atoms 36Cl (g K)−1 a−1 and an SLHL 36PK-sp of 145.5 ± 7.7 atoms 36Cl (g K)−1 a−1, when scaled with a standard scaling protocol (‘Lm’). Applying this SLHL 36PK-sp to determine 36Cl exposure ages of K-feldspars from 10Be-dated moraine boulders yields excellent agreement, confirming the validity of the new SLHL 36PK-sp for surface exposure studies, involving 36Cl in K-feldspars, in the Alps.