Background Cannabis use is associated with increased risk of later psychotic disorder but whether it affects incidence of the disorder remains unclear. We aimed to identify patterns of cannabis use with the strongest effect on odds of psychotic disorder across Europe and explore whether differences in such patterns contribute to variations in the incidence rates of psychotic disorder. Methods We included patients aged 18-64 years who presented to psychiatric services in 11 sites across Europe and Brazil with first-episode psychosis and recruited controls representative of the local populations. We applied adjusted logistic regression models to the data to estimate which patterns of cannabis use carried the highest odds for psychotic disorder. Using Europe-wide and national data on the expected concentration of Δ⁹-tetrahydrocannabinol (THC) in the different types of cannabis available across the sites, we divided the types of cannabis used by participants into two categories: low potency (THC <10%) and high potency (THC ≥10%). Assuming causality, we calculated the population attributable fractions (PAFs) for the patterns of cannabis use associated with the highest odds of psychosis and the correlation between such patterns and the incidence rates for psychotic disorder across the study sites. Findings Between May 1, 2010, and April 1, 2015, we obtained data from 901 patients with first-episode psychosis across 11 sites and 1237 population controls from those same sites. Daily cannabis use was associated with increased odds of psychotic disorder compared with never users (adjusted odds ratio [OR] 3•2, 95% CI 2•2-4•1), increasing to nearly five-times increased odds for daily use of high-potency types of cannabis (4•8, 2•5-6•3). The PAFs calculated indicated that if high-potency cannabis were no longer available, 12•2% (95% CI 3•0-16•1) of cases of first-episode psychosis could be prevented across the 11 sites, rising to 30•3% (15•2-40•0) in London and 50•3% (27•4-66•0) in Amsterdam. The adjusted incident rates for psychotic disorder were positively correlated with the prevalence in controls across the 11 sites of use of high-potency cannabis (r = 0•7; p=0•0286) and daily use (r = 0•8; p=0•0109). Interpretation Differences in frequency of daily cannabis use and in use of high-potency cannabis contributed to the striking variation in the incidence of psychotic disorder across the 11 studied sites. Given the increasing availability of high-potency cannabis, this has important implications for public health.

Abstract.A high delivered Kt/V urea (dKt/V urea ) is advocated in the U.S. National Kidney Foundation Dialysis Outcomes Quality Initiative guidelines on hemodialysis (HD) adequacy, irrespective of the presence of residual renal function. The contribution of treatment adequacy and residual renal function to patient survival was investigated. The Netherlands Cooperative Study on the Adequacy of Dialysis is a prospective multicenter study that includes incident ESRD patients older than 18 yr. The longitudinal data on residual renal function and dialysis adequacy of patients who were treated with HD 3 mo after the initiation of dialysis (n ϭ 740) were analyzed. The mean renal Kt/V urea (rKt/V urea ) at 3 mo was 0.7/wk (SD 0.6) and the dKt/V urea at 3 mo was 2.7/wk (SD 0.8). Both components of urea clearance were associated with a better survival (for each increase of 1/wk in rKt/V urea , relative risk of death ϭ 0.44 [P Ͻ 0.0001]; dKt/V urea , relative risk of death ϭ 0.76 [P Ͻ 0.01]). However, the effect of dKt/V urea on mortality was strongly dependent on the presence of rKt/V urea , low values for dKt/ V urea of Ͻ2.9/wk being associated with a significantly higher mortality in anuric patients only. Furthermore, an excess of ultrafiltration in relation to interdialytic weight gain was associated with an increase in mortality independent of dKt/V urea . In conclusion, residual renal clearance seems to be an important predictor of survival in HD patients, and the dKt/V urea should be tuned appropriately to the presence of renal function. Further studies are required to substantiate the important role of fluid balance in HD adequacy.

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This study demonstrates that thalidomide improves the response rate and VGPR in elderly patients with newly diagnosed MM. MP-T also results in a better EFS, PFS, and OS.

Various studies indicate that fair comparisons of mortality rates between hemodialysis (HD) patients and peritoneal dialysis (PD) patients are difficult because of differences in patient characteristics, because of nonconstant relative risks of death (RR), and because the survival times of patients who switch treatment modalities can be censored in different ways. The differences in mortality rates between HD and PD patients were investigated in an analysis in which these potential sources of bias were taken into account. The Netherlands Cooperative Study on the Adequacy of Dialysis is a multicenter, prospective, observational, cohort study in which new patients with ESRD are monitored until transplantation or death. A multivariate Cox regression analysis was used to analyze the mortality data according to treatment modality (HD, n = 742; PD, n = 480). No statistically significant differences in adjusted mortality rates between HD and PD patients were observed during the first 2 yr of dialysis. In the years thereafter, increases in mortality rates for PD patients and resulting decreases in RR in favor of HD were observed (e.g., months 24 to 36, adjusted RR, 0.53; 95% confidence interval, 0.31 to 0.91). This tendency was observed especially among patients >/=60 yr of age and was not influenced by the censoring strategy. These results suggest that long-term use of PD, especially among elderly patients, is associated with increases in mortality rates. Further analyses are required to determine the potential role of dialysis adequacy in the observed long-term differences in mortality rates between HD and PD patients and to establish the possible survival benefits for PD patients who switch to HD in time.

The role of thalidomide for previously untreated elderly patients with multiple myeloma remains unclear. Six randomized controlled trials, launched in or after 2000, compared melphalan and prednisone alone (MP) and with thalidomide (MPT). The effect on overall survival (OS) varied across trials. We carried out a meta-analysis of the 1685 individual patients in these trials. The primary endpoint was OS, and progression-free survival (PFS) and 1-year response rates were secondary endpoints. There was a highly significant benefit to OS from adding thalidomide to MP (hazard ratio ‫؍‬ 0.83; 95% confidence interval 0.73-0.94, P ‫؍‬ .004), representing increased median OS time of 6.6 months, from 32.7 months (MP) to 39.3 months (MPT). The thalidomide regimen was also associated with superior PFS (hazard ratio ‫؍‬ 0.68, 95% confidence interval 0.61-0.76, P < .0001) and better 1-year response rates (partial response or better was 59% on MPT and 37% on MP). Although the trials differed in terms of patient baseline characteristics and thalidomide regimens, there was no evidence that treatment affected OS differently according to levels of the prognostic factors. We conclude that thalidomide added to MP improves OS and PFS in previously untreated elderly patients with multiple myeloma, extending the median survival time by on average 20%. (Blood.

The survival of anuric peritoneal dialysis patients is in line with expectations based on the duration of dialysis. The risk factors for death are the same as in the dialysis population as a whole. Besides an association with ultrafiltration, our study enabled us to define the lower limits of adequate peritoneal dialysis, that is Kt/V(urea) <1.5 per week and creatinine clearance <40 L/week/1.73 m2.

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