The association between placebo arm inclusion and adverse event rates in antidepressant randomized controlled trials: An examination of the Nocebo Effect.

BACKGROUND: Antidepressant efficacy is influenced by patient expectations and, in randomized controlled trials (RCTs), the probability of receiving a placebo. It is unclear whether tolerability demonstrates a similar pattern. This study aimed to determine whether study design influences adverse event (AE) rates in antidepressant trials for subjects receiving active treatment or placebo. METHODS: RCTs comparing one antidepressant to another antidepressant, placebo, or both in major depressive disorder (MDD) (1996-2018) were retrieved from Medline and PsycINFO. Clinicaltrials.gov was searched for unpublished trials. Of 1,997 studies screened, 77 trials were included. Studies were classified as drug-drug, drug-drug-placebo, or drug-placebo based on design and overall number of subjects experiencing any AE was recorded. Subgroup meta-analysis of proportions and meta-regression techniques were used to compare AE rates across study designs in patients receiving active antidepressant treatment and placebo. RESULTS: Among the actively treated, AE rates were lower in drug-drug trials (58.5%) compared to drug-drug-placebo (75.7%) and drug-placebo (76.4%) (the model reported coefficients for percent differences between AE rates of different study designs were B=17.0, p<0.001 and B=17.8, p<0.001, respectively). AE rates in patients receiving placebo were not different between study designs. LIMITATIONS: The present study is limited by the diverse range of study populations, variability in reporting of AEs, and specific antidepressants employed in the included trials. CONCLUSIONS: The inclusion of a placebo arm in the study design was unexpectedly associated with higher rates of AEs among patients receiving active medication in antidepressant trials. This observation has important implications for interpretation of trial tolerability findings.

Choosing peritoneal dialysis reduces the risk of invasive access interventions.

BACKGROUND: Patients choosing between hemodialysis (HD) and peritoneal dialysis (PD) should be well informed of the risks and benefits of each modality. Invasive access interventions are important outcomes because frequent interventions lower patient's quality of life and consume limited resources. The objective of this study was to compare the risk of access interventions between the two modalities. METHODS: Three hundred and sixty-nine incident chronic dialysis patients were prospectively enrolled at four Canadian centers that were eligible for both modalities, received at least 4 months of pre-dialysis care and started dialysis electively as an outpatient. Two hundred and twenty-four (61%) chose PD and 145 (39%) chose HD. Patients were followed for an average of 1.3 years (range 0.07-3.6 years). RESULTS: In the PD group, there were fewer access interventions (2.5 versus 3.1 interventions per patient, adjusted odds ratio of 0.79 for PD versus HD, P = 0.005) and a lower intervention rate (2.3 versus 1.9 per patient-year, adjusted rate ratio of 0.81 for PD versus HD, P = 0.04). PD catheters were less likely to experience primary failure (4.6 versus 32%, P < 0.0001), showed a trend toward lower intervention rates during use (0.8 versus 1.2 per patient-year, P = 0.06), and had equal patency compared to fistulae (1-year patency of 84 versus 88%, P = 0.48). Patients managed exclusively with HD catheters (28% of the HD group) required 1.7 interventions per patient and an intervention rate of 1.9 per patient-year. CONCLUSION: Patients who choose PD require fewer access interventions to maintain dialysis access than patients choosing HD.

Catheter patency and function after catheter sheath disruption: a pilot study.

BACKGROUND AND OBJECTIVES: Hemodialysis catheters are frequently complicated by dysfunction from fibrin sheaths. Previous studies of sheath disruption have methodologic limitations but suggest that the patency after disruption is short. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A randomized, controlled, pilot trial was conducted to investigate the impact of angioplasty sheath disruption on catheter patency and function. Forty-seven long-term hemodialysis patients with secondary, refractory catheter dysfunction underwent guidewire exchange to replace their catheters. RESULTS: Sheaths were present in 33 (70%) of the 47 patients. In 18 patients who were randomly assigned to disruption, the median time to repeat dysfunction was 373 d compared with 97.5 d in patients who did not undergo disruption (P = 0.22), and the median time to repeat catheter exchange was 411 and 198 d, respectively (P = 0.17). Mean blood flow (340 versus 329 ml/min; P < 0.001) and urea reduction ratio (72 versus 66%; P < 0.001) were higher in the disruption group. Fourteen patients had no sheaths, and their median times to repeat dysfunction and repeat exchange were 849 and 879 d, respectively. Patients with no sheaths had higher urea reduction ratio (73 versus 66%; P < 0.001) and a lower percentage of inadequate hemodialysis treatments (9.8 versus 27%; P = 0.01) and treatments that required thrombolytics (1.8 versus 5.0%; P = 0.03) than patients with sheaths that were not disrupted. CONCLUSIONS: Disrupting sheaths by angioplasty balloon results in durable catheter patency and modestly improves blood flow and clearance over the duration of catheter use.