A randomized, double-blind, placebo-controlled, phase 3 trial to evaluate the efficacy, safety, and tolerability of prucalopride in men with chronic constipation.

OBJECTIVES: Prucalopride is effective at alleviating symptoms of chronic constipation in women. The aim of this study was to assess the efficacy of 12 weeks of prucalopride treatment compared with placebo in men with chronic constipation. METHODS: This was a multicenter, stratified, randomized, parallel-group, double-blind, placebo-controlled, phase 3 study (ClinicalTrials.gov identifier: NCT01147926). The primary end point was the proportion of patients with a mean of three or more spontaneous complete bowel movements (SCBMs) per week across the treatment period. Efficacy end points were assessed using daily electronic diaries, global assessment of the severity of constipation and efficacy of treatment, and Patient Assessment of Constipation-Symptoms (PAC-SYM) and Patient Assessment of Constipation-Quality of Life (PAC-QOL) questionnaires. RESULTS: In total, 374 patients were enrolled in the study. Significantly more patients achieved a mean of three or more SCBMs per week in the prucalopride group (37.9%) than in the placebo group (17.7%, P<0.0001). The proportion of patients rating their constipation treatment as "quite a bit" to "extremely" effective at the final on-treatment visit was 46.7 and 30.4% in the prucalopride and placebo groups, respectively. The difference between treatment groups was statistically significant (P<0.0001). The proportion of patients with an improvement of at least 1 point in PAC-QOL satisfaction subscale score was 52.7 and 38.8% in the prucalopride and placebo groups, respectively (P=0.0035). Prucalopride had a good safety profile and was well tolerated. CONCLUSIONS: Prucalopride is effective, has a good safety profile, and is well tolerated for the treatment of men with chronic constipation.

A single-centre observational cohort study to evaluate volume and severity of emergency general surgery admissions during the COVID-19 pandemic: Is there a "lockdown" effect?

INTRODUCTION: The COVID-19 pandemic has led to changes in NHS surgical service provision, including reduced elective surgical and endoscopic activity, with only essential emergency surgery being undertaken. This, combined with the government-imposed lockdown, may have impacted on patient attendance, severity of surgical disease, and outcomes. The aim of this study was to investigate a possible 'lockdown' effect on the volume and severity of surgical admissions and their outcomes. METHODS: Two separate cohorts of adult emergency general surgery inpatient admissions 30 days immediately before (February 16, 2020 to March 15, 2020), and after UK government advice (March 16, 2020 to April 15, 2020). Data were collected relating to patient characteristics, severity of disease, clinical outcomes, and compared between these groups. RESULTS: Following lockdown, a significant reduction in median daily admissions from 7 to 3 per day (p < 0.001) was observed. Post-lockdown patients were significantly older, frailer with higher inflammatory indices and rates of acute kidney injury, and also were significantly more likely to present with gastrointestinal cancer, obstruction, and perforation. Patients had significantly higher rates of Clavien-Dindo Grade ≥3 complications (p = 0.001), all cause 30-day mortality (8.5% vs. 2.9%, p = 0.028), but no significant difference was observed in operative 30-day mortality. CONCLUSION: There appears to be a "lockdown" effect on general surgical admissions with a profound impact; fewer surgical admissions, more acutely unwell surgical patients, and an increase in all cause 30-day mortality. Patients should be advised to present promptly with gastrointestinal symptoms, and this should be reinforced for future lockdowns during the pandemic.

A randomized double-blinded sham-controlled cross-over trial of tined-lead sacral nerve stimulation testing for chronic constipation.

OBJECTIVES: Sacral nerve stimulation (SNS) may provide long-term symptom relief to patients suffering from chronic constipation. Patients are currently selected for SNS using a 2-week peripheral nerve evaluation (PNE) comprising stimulation by temporary leads. However, only 40% of test responders receive long-term benefit from treatment meaning that healthcare costs per successfully treated patient are too high. The primary objective was to assess tined-lead testing to predict benefit from SNS for chronic constipation. PATIENTS AND METHODS: A randomized double-blind sham-controlled cross-over design evaluated enhanced PNE (ePNE) using tined quadripolar electrode leads over 6 weeks. The design differentiated between patients with discriminate and indiscriminate responses to testing. A score improvement of 25% or more was considered to be a positive response within a stimulation period. The primary outcome was the proportion of patients showing a reduction of at least 0.5 in constipation symptom score at 6 months. RESULTS: A total of 45 patients were randomized, of whom 29 (64.4%) were test-phase responders. Of these, 27 were implanted providing permanent SNS. During ePNE, seven (18%) were discriminate responders, 22 (56%) were indiscriminate responders and 10 (26%) were nonresponders. Six patients were withdrawn during the test phase because of infection or noncompliance. At 6 months, there was no significant difference in primary outcome between discriminate and indiscriminate responders (60 vs. 57%, P=0.76). The study was terminated prematurely because of a persistent infection rate of 10 (22%) during ePNE of which nine (20%) were severe. CONCLUSION: ePNE is a poor predictor of treatment response at 6 months. This suggests a strong and persistent placebo response during both SNS PNE and treatment. An extended 6-week PNE poses a high risk of infection.

Transanal Irrigation for Refractory Chronic Idiopathic Constipation: Patients Perceive a Safe and Effective Therapy.

Background. Transanal irrigation (TAI) can successfully treat neurogenic bowel dysfunction (NBD), but patient perception of its use in chronic idiopathic constipation (CIC) is unknown. Objective. To evaluate patient perceptions of the efficacy and safety of TAI for CIC and whether there are predictive factors of perceived treatment response. Methods. Prospective data collection of baseline physiology and symptom severity; retrospective evaluation of efficacy and safety perceptions using a snapshot survey. All patients fulfilling the Rome III criteria for functional constipation with chronic idiopathic aetiology were included. The main outcome measure was the duration of patients' usage of TAI. Results. 102 patients reported 21,476 irrigations over 119 patient years, with a mean duration of therapy use of 60.5 weeks [SD 73.2 : SE 7.3]. Overall symptom improvement included general well-being (65%), rectal clearance (63%), bloating (49%), abdominal pain (48%), and bowel frequency (42%). 68 patients (67%) were "moderately better" or "very much better" on a satisfaction question. Reported complications were minor. No correlation was demonstrated between duration of therapy use and baseline measures. Conclusion. A significant proportion of CIC sufferers use TAI as a long-term or bridging therapy and perceive it as safe. This therapy demands a prospective investigation of efficacy and safety.

A National Biofeedback Practitioners Service Evaluation: Focus on Chronic Idiopathic Constipation.

INTRODUCTION: Within the UK, there is anecdotal evidence of disparity in the training, practice, supervision and perception of efficacy among practitioners of biofeedback therapy for chronic constipation. AIMS: To establish the current knowledge, practice and opinions of UK practitioners. METHODS: Between October 2012 and October 2013, a prospective service evaluation was distributed to biofeedback practitioners in the UK through academic conferences or by invitation to complete an on-line assessment form. RESULTS: 76 practitioners responded, consisting of nurses (47%), physiotherapists (35%), physiologists (12%) and others (7%). Only 45% described 'biofeedback' consistent with an accepted definition. 86% use equipment to provide sensory feedback. Methods of biofeedback varied: balloon catheter (54%), brace pump technique (78%), urge resistance (83%), irrigation (16%) and relaxation (12%). Only 65% of practitioners had attended formal training courses, and 52% considered themselves to be self-taught. 36% receive formal supervision and only 38% of those by a senior. Regular audit of outcomes is undertaken by 67%. UK-wide perception of treatment response for chronic constipation is markedly variable (mean response=57% (IQR 50-75%, SD 23%)); there were no differences in perception of treatment response between nurses or physiotherapists. Practitioners' free responses demonstrated strong positive themes of a holistic approach and an overall perception of effectiveness. Negative themes included service restrictions. CONCLUSIONS: There is marked variation in practice, training and supervision of biofeedback therapists throughout the UK. Perceptions of efficacy vary greatly. Development of training and supervision standards is a priority as well as a consensus to standardise therapy.

Value of triple H therapy in a patient with an ischemic penumbra following subarachnoid hemorrhage: a case study.

We report the case of a 43-year-old patient with delayed ischemic neurological deficit and an ischemic penumbra, reversed with triple H therapy (hypertension, hypervolemia, and hemodilution). The patient presented with subarachnoid hemorrhage caused by an aneurysm of the anterior communicating artery. He underwent surgical clipping and developed cerebral ischemia due to vasospasm. Permanent damage to the area of ischemic brain was prevented by institution of the triple H therapy. He recovered and was discharged with no subsequent neurological deficits.