Bayesian analysis, hierarchical models, response time, MCMC, Weibull distribution,

No abstract

BackgroundFew controlled clinical trials exist to support oral combination therapy in pulmonary arterial hypertension (PAH).MethodsPatients with PAH (idiopathic [IPAH] or associated with connective tissue disease [APAH-CTD]) taking bosentan (62.5 or 125 mg twice daily at a stable dose for ≥3 months) were randomized (1:1) to sildenafil (20 mg, 3 times daily; n = 50) or placebo (n = 53). The primary endpoint was change from baseline in 6-min walk distance (6MWD) at week 12, assessed using analysis of covariance. Patients could continue in a 52-week extension study. An analysis of covariance main-effects model was used, which included categorical terms for treatment, baseline 6MWD (<325 m; ≥325 m), and baseline aetiology; sensitivity analyses were subsequently performed.ResultsIn sildenafil versus placebo arms, week-12 6MWD increases were similar (least squares mean difference [sildenafil–placebo], −2.4 m [90% CI: –21.8 to 17.1 m]; P = 0.6); mean ± SD changes from baseline were 26.4 ± 45.7 versus 11.8 ± 57.4 m, respectively, in IPAH (65% of population) and −18.3 ± 82.0 versus 17.5 ± 59.1 m in APAH-CTD (35% of population). One-year survival was 96%; patients maintained modest 6MWD improvements. Changes in WHO functional class and Borg dyspnoea score and incidence of clinical worsening did not differ. Headache, diarrhoea, and flushing were more common with sildenafil.ConclusionsSildenafil, in addition to stable (≥3 months) bosentan therapy, had no benefit over placebo for 12-week change from baseline in 6MWD. The influence of PAH aetiology warrants future study.Trial registrationClinicalTrials.gov NCT00323297 (registration date: May 5, 2006).Electronic supplementary materialThe online version of this article (10.1186/s12872-017-0674-3) contains supplementary material, which is available to authorized users.

In HFpEF patients, treatment with a selective ETA receptor antagonist increased exercise tolerance but did not improve any of the secondary endpoints such as left ventricular mass or diastolic function. Further studies will be necessary to determine whether ETA receptor antagonists may be useful in the treatment of HFpEF. (A Study of the Effectiveness of Sitaxsentan Sodium in Patients With Diastolic Heart Failure; NCT00303498).

ObjectiveTo compare the efficacy and tolerability of celecoxib and ibuprofen for the treatment of knee osteoarthritis symptoms.MethodIn this 6-week, multicentre, double-blind, non-inferiority trial, patients were randomized to 200 mg celecoxib once daily, 800 mg ibuprofen three times daily or placebo. The primary outcome was non-inferiority of celecoxib to ibuprofen in Patient’s Assessment of Arthritis Pain (scored 0–100). Secondary outcomes included the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index, Pain Satisfaction Scale, and upper gastrointestinal tolerability.ResultsA total of 388 patients were treated (celecoxib n = 153; ibuprofen n = 156; placebo n = 79). Mean difference (95% confidence interval) between celecoxib and ibuprofen in the Patient’s Assessment of Arthritis Pain was 2.76 (−3.38, 8.90). As the lower bound was greater than −10, celecoxib was non-inferior to ibuprofen. The WOMAC total score was significantly improved with celecoxib and ibuprofen, versus placebo. Patients receiving celecoxib were significantly more satisfied (versus placebo) in 10 of 11 measures on the Pain Satisfaction Scale versus three measures with ibuprofen. Upper gastrointestinal events were less frequent with celecoxib (1.3%) than ibuprofen (5.1%) or placebo (2.5%).ConclusionCelecoxib was well tolerated and as effective as ibuprofen for symptoms associated with knee osteoarthritis.ClinicalTrials.gov identifierNCT00630929

PurposeThis study was performed to understand the practice patterns of ophthalmologists administering intravitreal (IVT) injections in Europe after the procedure became routine.MethodsAs part of a prospective, multinational, non-interventional cohort study in 13 countries in Europe between 2006 and 2012, ophthalmologists completed the Baseline Questionnaire and the Follow-up Questionnaire 1 year after baseline.Results and discussionOf the 125 ophthalmologists who participated in the study, 113 (90.4%) completed the Baseline Questionnaire. Most of these ophthalmologists were medical retina specialists (43.0%). The median number of IVT injections that the ophthalmologists performed per month during the year prior to completing the Baseline Questionnaire was 20.0. The majority of the ophthalmologists had performed their last IVT injection prior to completing the questionnaire in an operating room or theater (68.4%). When performing IVT injections, a majority of the ophthalmologists reported applying povidone–iodine (90.4%) before IVT injections and topical antibiotics right after IVT injections (89.5%). In addition, 81.6% of the ophthalmologists reported using a sterile adhesive eye drape and 80.7% reported using an eyelid speculum. In all, 95 ophthalmologists (76%) completed the Follow-up Questionnaire. The median number of IVT injections performed per month during the year prior to completing the Follow-up Questionnaire by these ophthalmologists was increased to 35. The results of the Follow-up Questionnaire on administering IVT injections were similar to those of the Baseline Questionnaire. A majority of the ophthalmologists reported applying povidone–iodine (87.4%) before IVT injections, topical antibiotics right after IVT injections (89.5%), and an eyelid speculum (85.3%).ConclusionThe results of this study indicated a good adherence to all aspects of the guidelines on IVT injections. It seemed that ophthalmologists were more experienced in IVT injections after they became a routine treatment procedure.

In patients receiving ICDs, the automatic templates were successfully created during a 6-month follow-up period, and consistently matched the patients' intrinsic rhythm at the nominal match threshold. Both early (<1 month postimplant) and late (1- to 3-month follow-up period) changes in electrogram morphology were identified, confirming the need for automatic template updating.

Background/Aims: To investigate the impact of kidney function (using estimated glomerular filtration rate, [eGFR]) on blood pressure variability (BPV) via a retrospective post hoc analysis of patients with hypertension enrolled in two large clinical trials. Methods: Subject-level data were extracted from ASCOT (N=18,852) and ALLHAT (N=26,441) databases; both were randomized, active controlled studies, with treatment duration for hypertension ≥4 years. Visit-to-visit BPV was assessed using the square root of the coefficient of variation of systolic blood pressure (SBP) across visits from 12 weeks onwards. Baseline GFR, estimated by the simplified Modification of Diet in Renal Disease equation, was stratified into ≤60, 61-90, and >90 mL/min/1.73 m². The relationship between baseline eGFR and systolic BPV was analyzed using an analysis of covariance, with baseline factors considered as covariates. Studies were pooled and analyzed individually. Results: Patient characteristics were largely consistent between studies. In the pooled population (n=38,133) there were 19.1%, 62.9%, and 18.0% patients, with eGFR ≤60, 61-90, and > 90 mL/min/1.73 m², respectively. Patients with lower baseline eGFR had higher systolic BPV, in the pooled population and the individual analyses. Other baseline predictors of high systolic BPV included high SBP and age, being male, and a smoker. An amlodipine-based regimen was a negative predictor of high systolic BPV, vs. other antihypertensives, regardless of eGFR. Conclusions: Patients with declining renal function tended to have higher systolic BPV vs. those without, even after adjusting for risk factors. Amlodipine-based therapy reduced BPV more than other antihypertensive agents, regardless of level of eGFR.