Clinical outcome 10 years after attempted percutaneous transluminal coronary angioplasty in 856 patients.

Abstract OBJECTIVES: This study reports the 10-year outcome of 856 consecutive patients who underwent attempted coronary angioplasty at the Thoraxcenter during the years 1980 to 1985. BACKGROUND: Coronary balloon angioplasty was first performed in 1977, and this procedure was introduced into clinical practice at the Thoraxcenter in 1980. Although advances have been made, extending our knowledge of the long-term outcome in terms of survival and major cardiac events remains of interest and a valuable guide in the treatment of patients with coronary artery disease. METHODS: Details of survival, cardiac events, symptoms and medication were retrospectively obtained from the Dutch civil registry, medical records or by letter or telephone or from the patient's physician and entered into a dedicated data base. Patient survival curves were constructed, and factors influencing survival and cardiac events were identified. RESULTS: The procedural clinical success rate was 82%. Follow-up information was obtained in 837 patients (97.8%). Six hundred forty-one patients (77%) were alive, of whom 334 (53%) were symptom free, and 254 (40%) were taking no antianginal medication. The overall 5- and 10-year survival rates were 90% (95% confidence interval [CI] 87.6% to 92.4%) and 78% (95% CI 75.0% to 81.0%), respectively, and the respective freedom from significant cardiac events (death, myocardial infarction, coronary artery bypass surgery and repeat angioplasty) was 57% (95% CI 53.4% to 60.6%) and 36% (95% CI 32.4% to 39.6%). Factors that were found to adversely influence 10-year survival were age > or = 60 years (> or = 60 years [67%], 50 to 59 years [82%], or = 50% [80%]) and a history of previous myocardial infarction (previous myocardial infarction [72%], no previous infarction [83%]). These factors were also found to be independent predictors of death during the follow-up period by a multivariate stepwise logistic regression analysis. Other factors tested, with no influence on survival, were gender, procedural success and stability of angina at the time of intervention. CONCLUSIONS: The long-term prognosis of patients after coronary angioplasty is good, particularly in those <60 years old with single-vessel disease and normal left ventricular function. The majority of patients are likely to experience a further cardiac event in the 10 years after their first angioplasty procedure

Treatment of irritable bowel syndrome with diarrhoea using titrated ondansetron (TRITON): study protocol for a randomised controlled trial

Background: Irritable bowel syndrome with diarrhoea (IBS-D) affects up to 4% of the general population. Symptoms include frequent, loose, or watery stools with associated urgency, resulting in marked reduction of quality of life and loss of work productivity. Ondansetron, a 5HT3 receptor antagonist, has had an excellent safety record for over 20 years as an antiemetic, yet is not widely used in the treatment of IBS-D. It has, however, been shown to slow colonic transit and in a small randomised, placebo-controlled, cross-over pilot study, benefited patients with IBS-D. Methods: This trial is a phase III, parallel group, randomised, double-blind, multi-centre, placebo-controlled trial, with embedded mechanistic studies. Participants (n = 400) meeting Rome IV criteria for IBS-D will be recruited from outpatient and primary care clinics and by social media to receive either ondansetron (dose titrated up to 24 mg daily) or placebo for 12 weeks. Throughout the trial, participants will record their worst abdominal pain, worst urgency, stool frequency, and stool consistency on a daily basis. The primary endpoint is the proportion of “responders” in each group, using Food and Drug Administration (FDA) recommendations. Secondary endpoints include pain intensity, stool consistency, frequency, and urgency. Mood and quality of life will also be assessed. Mechanistic assessments will include whole gut transit, faecal tryptase and faecal bile acid concentrations at baseline and between weeks 8 and 11. A subgroup of participants will also undergo assessment of sensitivity (n = 80) using the barostat, and/or high-resolution colonic manometry (n = 40) to assess motor patterns in the left colon and the impact of ondansetron. Discussion: The TRITON trial aims to assess the effect of ondansetron across multiple centres. By defining ondansetron’s mechanisms of action we hope to better identify patients with IBS-D who are likely to respond

Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without D

Life after sepsis: an international survey of survivors to understand the post-sepsis syndrome.

OBJECTIVE In this study, we aim to describe the post-sepsis syndrome from the perspective of the sepsis survivors. DESIGN AND SETTING The study is a prospective, observational online international survey. PARTICIPANTS Sepsis survivors enrolled via social media from 13 September 2014 to 13 September 2016. INTERVENTIONS None. MAIN OUTCOME MEASURES Physiologic, physical and psychological function post-sepsis; and patient satisfaction with sepsis-centered care. RESULTS 1731 completed surveys from 41 countries were analyzed, with 79.9% female respondents, age 47.6 ± 14.4 years. The majority of respondents (47.8%) had sepsis within the last year. Survivors reported an increase in sensory, integumentary, digestive, breathing, chest pain, kidney and musculoskeletal problems after sepsis (all P-value <0.0001). Physical functions such as daily chores, running errands, spelling, reading and reduced libido posed increased difficulty (all P-value <0.0001). Within 7 days prior to completing the survey, the survivors reported varying degrees of anxiety, depression, fatigue and sleep disturbance. Sepsis survivors reported dissatisfaction with a number of hospital support services, with up to 29.3% of respondents stating no social services support was provided for their condition. CONCLUSIONS Sepsis survivors suffer from a myriad of physiologic, physical and psychological challenges. Survivors overall reveal dissatisfaction with sepsis-related care, suggesting areas for improvement both in-hospital and post-discharge

Linaclotide in Chronic Idiopathic Constipation Patients with Moderate to Severe Abdominal Bloating: A Randomized, Controlled Trial

<div><p>Background</p><p>Abdominal bloating is a common and bothersome symptom of chronic idiopathic constipation. The objective of this trial was to evaluate the efficacy and safety of linaclotide in patients with chronic idiopathic constipation and concomitant moderate-to-severe abdominal bloating.</p><p>Methods</p><p>This Phase 3b, randomized, double-blind, placebo-controlled clinical trial randomized patients to oral linaclotide (145 or 290 μg) or placebo once daily for 12 weeks. Eligible patients met Rome II criteria for chronic constipation upon entry with an average abdominal bloating score ≥5 (self-assessment: 0 10-point numerical rating scale) during the 14-day baseline period. Patients reported abdominal symptoms (including bloating) and bowel symptoms daily; adverse events were monitored. The primary responder endpoint required patients to have ≥3 complete spontaneous bowel movements/week with an increase of ≥1 from baseline, for ≥9 of 12 weeks. The primary endpoint compared linaclotide 145 μg vs. placebo.</p><p>Results</p><p>The intent-to-treat population included 483 patients (mean age=47.3 years, female=91.5%, white=67.7%). The primary endpoint was met by 15.7% of linaclotide 145 μg patients vs. 7.6% of placebo patients (<i>P</i><0.05). Both linaclotide doses significantly improved abdominal bloating vs. placebo (<i>P</i><0.05 for all secondary endpoints, controlling for multiplicity). Approximately one-third of linaclotide patients (each group) had ≥50% mean decrease from baseline in abdominal bloating vs. 18% of placebo patients (<i>P</i><0.01). Diarrhea was reported in 6% and 17% of linaclotide 145 and 290 μg patients, respectively, and 2% of placebo patients. AEs resulted in premature discontinuation of 5% and 9% of linaclotide 145 μg and 290 μg patients, respectively, and 6% of placebo patients.</p><p>Conclusions</p><p>Once-daily linaclotide (145 and 290 μg) significantly improved bowel and abdominal symptoms in chronic idiopathic constipation patients with moderate-to-severe baseline abdominal bloating; in particular, linaclotide significantly improved abdominal bloating compared to placebo, an important finding given the lack of agents available to treat abdominal bloating in chronic idiopathic constipation patients.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT01642914?term=NCT01642914&rank=1" target="_blank">NCT01642914</a></p></div

Incremental Percent Improvement in Abdominal Bloating at Week 12.

<p>Intent-to-treat Population; % improvement in abdominal bloating at week 12 (end of the treatment period). Note: The distribution of % improvement in abdominal bloating at week 12 was a secondary endpoint for both linaclotide dose groups. (<i>P</i> < 0.01 for both linaclotide groups vs. placebo; <i>P</i> values were obtained from a Kolmogorov-Smirnov test for equality of distribution.)</p

Primary Endpoint.

<p>Intent-to-treat Population; Responder = patient who had ≥ 3 CSBMs and an increase of ≥ 1 CSBM from baseline, in the same week, for at least 9 of the 12 treatment-period weeks. Note: Primary endpoint for linaclotide 145 μg vs. placebo; secondary endpoint for linaclotide 290 μg vs. placebo. CSBM = complete spontaneous bowel movement; ITT = intent to treat; Lin = linaclotide; n = number of patients meeting the responder endpoint; N = number of patients in the ITT population. * P < 0.05; P values were obtained from a Cochran-Mantel-Haenszel test controlling for geographic region, comparing each linaclotide dose vs. placebo in a pairwise manner.</p

Percent Change from Baseline in Abdominal Bloating by Week.

<p>Intent-to-treat Population; % change from baseline in abdominal bloating during each week of the treatment period. % changes from baseline are the least-squares means from an analysis of covariance (ANCOVA) model. Note: % change from baseline in abdominal bloating at each treatment period week was an additional endpoint for both linaclotide dose groups vs. placebo. Both linaclotide doses are associated with greater improvement than placebo at all individual treatment weeks (all reported individual <i>P</i> values < 0.05 for both linaclotide groups vs. placebo; <i>P</i> values were obtained from an ANCOVA model with treatment group and geographic region as factors and baseline abdominal bloating score as a covariate).</p