2 Minute Medicine Rewind April 23, 2018

Effect of Uterosacral Ligament Suspension vs Sacrospinous Ligament Fixation With or Without Perioperative Behavioral Therapy for Pelvic Organ Vaginal Prolapse on Surgical Outcomes and Prolapse Symptoms at 5 Years in the OPTIMAL Randomized Clinical Trial

Pelvic organ prolapse (POP) is the downward descent of the female bladder, uterus, small or large bowel, resulting in protrusion of the vagina, uterus, or both. Uterosacral ligament suspension (ULS) and sacrospinous ligament fixation (SSLF) are procedures commonly performed as part of the definitive management of POP. Long-term efficacy data, however, has not been reported. In this this randomized controlled trial, 309 patients who had been previously randomized to undergo ULS or SSLF were followed up 5 years after their index surgery to compare the efficacy of these procedures. As part of the original trial, women were also randomized to receive perioperative behavioural therapy with pelvic floor muscle training (BPMT) or usual care. The primary surgical outcome was time to surgical failure, defined as apical descent greater than one third of total vaginal length, anterior or posterior vaginal wall beyond the hymen, or bothersome bulge symptoms. Researchers found that by year 5 there was no significant difference in groups in terms of surgical failure rate, where the failure rate in the ULS group was 61.5% compared to 70.3% in the SSLF group (adjusted difference -8.8%, 95% Cl -24.2% to 6.6%). Researchers also found that there was no significant difference in anatomic failure rate between the BPMT and usual care groups (adjusted difference -1.6%, 95% Cl -21.2% to 17.9%). Researchers therefore concluded that in women who had undergone surgery for apical pelvic organ vaginal prolapse, there was no significant difference between ULS and SSLF in rates of surgical failure at 5 years of follow-up. Researchers also concluded that there was no significant difference between perioperative behavioral muscle training and usual care on rates of anatomic success and symptom scores.

Safety and efficacy of eculizumab in Guillain-Barré syndrome: a multicentre, double-blind, randomised phase 2 trial 

Guillain-Barré syndrome (GBS) is an immune-mediated neuropathy and the most common cause of acute flaccid tetraplegia worldwide. Plasma exchange and intravenous immunoglobulin are the standard treatments for this syndrome, shown to improve recovery in the acute and subacute phases of the disease. Despite this, however, many patients do not recover completely. In this multicenter randomized controlled trial, 34 patients with GBS, unable to walk independently, were randomized to receive 4 weeks of intravenous immunoglobulin plus either 900 mg eculizumab, a humanized monoclonal antibody, or placebo to investigate the safety and efficacy of eculizumab against the complement protein C5 in patients with severe GBS. Efficacy was measured as the proportion of patients with restored ability to walk independently (functional grade £2), with a predefined response rate threshold of the lower 90% CI boundary exceeding 50%. Researchers found that at 4 weeks of follow-up, the proportion of patients able to walk independently was not significantly greater in the group treated with eculizumab at 61% (90% Cl 42% to 78%) compared to the group treated with placebo at 45% (90% Cl 20% to 73%). In terms of serious adverse events, one patient in the eculizumab group experienced anaphylaxis and intracranial hemorrhage, while another patient developed an abscess. Overall, as the primary outcome measure did not reach the predefined response rate, investigators were unable to conclude whether eculizumab is efficacious in the management of severe GBS. As a major limitation of this study was in its small size, this underlines the need for larger studies in evaluating the efficacy and safety of eculizumab in patients with severe GBS.

Effect of a Digital Health Intervention on Receipt of Colorectal Cancer Screening in Vulnerable Patients: A Randomized Controlled Trial

It has been established that screening reduces colorectal cancer (CRC) incidence and mortality. However, more than a third of age-eligible Americans do not participate in screening. This randomized controlled trial aimed to examine the effect of a digital health intervention in 6 community-based primary care practices. Patients (n=450) were randomly assigned to receive the digital health intervention or usual care. The digital health intervention consisted of an iPad application that displays a CRC screening decision aid, allowing patients to order their own screening tests and send automated follow-up electronic messages as part of patient support. The primary outcome was chart-verified completion of CRC screening within 24 weeks of the intervention. Researchers found that screening was higher among participants that received the digital health intervention at 30% as compared to the usual care group, where screening was completed by 15% of participants (OR 2.5, 95% CI 1.6 to 4.0). Researchers also found that, compared with usual care, more digital health intervention patients could state a screening preference, planned to be screened within 6 months, discussed screening with their provider and had a screening test ordered. Investigators therefore concluded that patients that used the digital health intervention were more likely to complete CRC screening compared to patients who received usual care. This highlights the role of digital health interventions that allow patients to self-order tests in keeping with current practice guidelines.

Efficacy and tolerability of triple drug therapy with albendazole, pyrantel pamoate, and oxantel pamoate compared with albendazole plus oxantel pamoate, pyrantel pamoate plus oxantel pamoate, and mebendazole plus pyrantel pamoate and oxantel pamoate against hookworm infections in school-aged children in Laos: a randomised, single-blind trial

More than 1.5 billion people are infected with one of the three soil transmitted helminths (STHs). This resulted in more than 3 million disability-adjusted life years in 2016. Albendazole and mebendazole are commonly used in controlling hookworm, however, the efficacy of these medications has decreased over time. In this randomized controlled trial, 533 hookworm-positive children were randomly assigned (2:2:1:1) to receive triple drug therapy (TDT) with albendazole, pyrantel pamoate, and oxantel pamoate; albendazole plus oxantel pamoate; pyrantel pamoate plus oxantel pamoate; or mebendazole with pyrantel pamoate and oxantel pamoate. The aim of this study was to investigate whether TDT with albendazole, pyrantel pamoate and oxantel pamoate is more effective than the standard co-administration of two drugs for the treatment of hookworm infection. The primary outcome studied was the proportion of hookworm egg-negative children at follow-up. Researchers found that the cure rate was higher in children that received TDT with a cure rate of 84%, compared to 53% in children that received albendazole and oxantel pamoate (OR 4.7, 95% Cl 2.7 to 8.3, p<0.0001) and 52% in children that received pyrantel pamoate and oxantel pamoate (OR 4.8, 95% Cl 2.5 to 9.3, p<0.0001). Adverse events were reported in 1% of children but without any significant difference across treatment groups. Researchers therefore concluded that the administration of TDT with albendazole, pyrantel pamoate, and oxantel pamoate is more efficacious in soil-transmitted helminth elimination compared to dual drug therapy.

Comparative risk of major congenital malformations with eight different antiepileptic drugs: a prospective cohort study of the EURAP registry

A number of teratogenic risks are associated with the use of antiepileptic medications. In this prospective cohort study, based on the EURAP international registry, 7555 pregnancies exposed to one of eight commonly used antiepileptic drugs in monotherapy were followed up to compare the risk of major congenital malformations as assessed at 1 year after birth. The eight commonly used antiepileptic drugs included carbamazepine, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, topiramate, and valproate. Researchers found that the prevalence of congenital malformations was 10.3% in pregnancies exposed to valproate, 6.5% for phenobarbital, 6.4% for phenytoin, 5.5% for carbamazepine, 3.9% for topiramate, 3.0% for oxcarbazepine, 2.9% for lamotrigine, and 2.8% for levetiracetam. The prevalence of major congenital malformations increased with dose at the time of conception for carbamazepine (p=0.0140), lamotrigine (p=0.0145), phenobarbital (p=0.0390), and valproate (p<0.0001). Multivariable analysis also showed that the prevalence of major congenital malformations was significantly higher for all doses of carbamazepine, valproate and phenobarbital at doses of more than 80 mg/day when compared to lamotrigine at doses of 325 mg/day or less, which was associated with the lowest frequency of major congenital malformations. Valproate at doses of 650 mg/day or less was also associated with an increased risk of major congenital malformations when compared to levetiracetam at doses of 250-4000 mg/day (OR 2.43, 95% CI 1.30 to 4.55, p=0·0069). Similarly, carbamazepine at doses of more than 700 mg/day was associated with an increased risk of major congenital malformations compared to levetiracetam at doses of 250-4000 mg/day (OR 2.41, 95% CI 1.33 to 4.38, p=0·0055) and oxcarbazepine at doses of 75-4500 mg/day (OR 2.37, 95% CI 1.17 to 4.80; p=0·0169). This study therefore demonstrates a spectrum in terms of the teratogenic risks associated with various antiepileptic medications, with valproate, phenobarbital and carbamazepine conferring the greatest risks. Data for topiramate and phenytoin should be interpreted with caution, as there were few exposed pregnancies in this study.

Image: PD

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