Background Effective and safe treatments are needed for patients who have irritable bowel syndrome (IBS) with diarrhea. We conducted two phase 3 trials to assess the efficacy and safety of eluxadoline, a new oral agent with mixed opioid effects (μ- and κ-opioid receptor agonist and δ-opioid receptor antagonist), in patients with IBS with diarrhea. Methods We randomly assigned 2427 adults who had IBS with diarrhea to eluxadoline (at a dose of 75 mg or 100 mg) or placebo twice daily for 26 weeks (IBS-3002 trial) or 52 weeks (IBS-3001 trial). The primary end point was the proportion of patients who had a composite response of decrease in abdominal pain and improvement in stool consistency on the same day for at least 50% of the days from weeks 1 through 12 and from weeks 1 through 26. Results For weeks 1 through 12, more patients in the eluxadoline groups (75 mg and 100 mg) than in the placebo group reached the primary end point (IBS-3001 trial, 23.9% with the 75-mg dose and 25.1% with the 100-mg dose vs. 17.1% with placebo; P=0.01 and P=0.004, respectively; IBS-3002 trial, 28.9% and 29.6%, respectively, vs. 16.2%; P<0.001 for both comparisons). For weeks 1 through 26, the corresponding rates in IBS-3001 were 23.4% and 29.3% versus 19.0% (P=0.11 and P<0.001, respectively), and the corresponding rates in IBS-3002 were 30.4% and 32.7% versus 20.2% (P=0.001 and P<0.001, respectively). The most common adverse events associated with 75 mg of eluxadoline and 100 mg of eluxadoline, as compared with placebo, were nausea (8.1% and 7.5% vs. 5.1%), constipation (7.4% and 8.6% vs. 2.5%), and abdominal pain (5.8% and 7.2% vs. 4.1%). Pancreatitis developed in 5 (2 in the 75-mg group and 3 in the 100-mg group) of the 1666 patients in the safety population (0.3%). Conclusions Eluxadoline is a new therapeutic agent that reduced symptoms of IBS with diarrhea in men and women, with sustained efficacy over 6 months in patients who received the 100-mg dose twice daily. (Funded by Furiex Pharmaceuticals, an affiliate of Allergan; IBS-3001 and IBS-3002 ClinicalTrials.gov numbers, NCT01553591 and NCT01553747 , respectively.).
SummaryBackgroundResults of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects.MethodsFOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762.FindingsBetween Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months.InterpretationFluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function.FundingUK Stroke Association and NIHR Health Technology Assessment Programme.
Aims and objectives To determine the rate of individual and system adverse events associated with blood transfusion at home. Background Home or residential care facility based blood transfusion is beneficial for individuals requiring transfusion due to reduced disruption to daily life and the comfort of a familiar environment. However, blood transfusion may result in serious adverse events. There is a lack of research in this area, and there is a need to identify rates of adverse events and evaluate the system used for this service. Design Retrospective cohort study. Methods Existing data routinely collected for clinical care were used to determine client and system adverse events of medically stable adults with a chronic disease who underwent blood transfusion in a home setting provided by a nurse‐led service. A STROBE EQUATOR checklist was used for this study (see Appendix S1). Results There were 1790 episodes of care involving 533 participants, with 13 cases of transfusion reaction (incident rate [IR] 0.7%; 95% CI 0.43–1.25). Only five of these were severe, resulting in the cessation of the blood transfusion and further medical review or hospital admission (IR 0.28%; 95% CI 0.12–0.68). There were no cases of tampered blood packaging, expired or visually damaged blood products. There were 10 cases of incorrect paperwork (0.6%) and nine cases of incorrect temperature (0.5%). There were 153 cases of vascular access device adverse events (IR 8.5% 95% CI 7.3–9.9), most commonly, difficulty cannulating the individual (n = 82, 54%). Conclusions A nurse‐led home blood transfusion service was associated with low rates of both individual and system adverse events. Further research is needed to explore the perception of those using this service and supports required to improve the experience. Relevance to clinical practice Blood transfusions may be associated with increased risk of morbidity and mortality. This risk may be increased in a home setting due to the distance from an acute care facility. This study has demonstrated that a nurse‐led home blood transfusion service is safe (<1% adverse event rate) for those with a medically stable, chronic condition. There were few failures in the system used to provide this service. Adverse events associated with the vascular access device were the most common complication and the reason for most blood product wastage. Mainly, this was due to difficulty inserting the short‐term peripheral intravenous catheter (PIVC). RNs should consider ultrasound to aid PIVC insertion to facilitate treatment provision and enhance the experience of the individual.
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