Practice Patterns in the Treatment of Patients With Severe Alcohol Withdrawal: A Multidisciplinary, Cross-Sectional Survey.

PURPOSE: To characterize physicians' stated practices in the treatment of patients with severe acute alcohol withdrawal syndrome (sAAWS) and to use intravenous (IV) phenobarbital as an adjuvant treatment for sAAWS. METHODS: A multidisciplinary, cross-sectional, self-administered survey at 2 large academic centers specializing in inner-city healthcare. RESULTS: We analyzed 105 of 195 questionnaires (53.8% response rate). On average, clinicians managed 32 cases of AAWS over a 6-month period, of which 7 (21.9%) were severe. Haloperidol (Haldol; 40 [39%]), clonidine (Catapres; 31 [30%]), phenobarbital (Luminal, Tedral; 29 [27%]) and propofol (Diprivan; 29 [28%]) were the most commonly used adjuvant medications for sAAWS. Sixty-three (60%) of respondents did not use phenobarbital in practice. Of phenobarbital users, 23 (55%) respondents used it early in patients who were refractory to symptom-triggered benzodiazepine treatment. Others waited until patients experienced seizures (5 [10%]) or required intensive care unit admission (8 [18%]). Respondents who used phenobarbital preferred to use the IV versus oral form (66% vs 29%, P < .001). Most respondents, however, were unfamiliar with the pharmacokinetics, side effects, contraindications, and evidence supporting phenobarbital use for sAAWS. Although many respondents (64 [61%]) expressed discomfort using phenobarbital, 87 (83%) expressed comfort or neutrality with enrolling patients in a trial to evaluate IV phenobarbital in sAAWS. CONCLUSIONS: Considerable stated practice variation exists in how clinicians treat patients with sAAWS. Our findings support conduct of a pilot trial to evaluate IV phenobarbital as an adjuvant treatment to symptom-triggered benzodiazepines for sAAWS and have informed trial design.

The efficacy and safety of pre-hospital cooling after out-of-hospital cardiac arrest: a systematic review and meta-analysis.

BACKGROUND: Mild therapeutic hypothermia (TH), or targeted temperature management, improves survival and neurological outcomes in patients after out-of-hospital cardiac arrest (OHCA). International guidelines strongly support initiating TH for all eligible individuals presenting with OHCA; however, the timing of cooling initiation remains uncertain. This systematic review and meta-analysis was conducted with all available randomised controlled trials (RCTs) included to explore the efficacy and safety of initiating pre-hospital TH in patients with OHCA. METHODS: The MEDLINE and Cochrane databases were searched from inception to October 2017. Inclusion criteria for full-text review included RCTs comparing pre-hospital TH with no pre-hospital TH after cardiac arrest, patients > 14 years of age with documented cardiac arrest from any rhythm, and outcome data that included survival to hospital discharge and temperature at hospital arrival. Results of retrieved studies were compared through meta-analysis using random effects modelling. RESULTS: A total of 10 trials comprising 4220 patients were included. There were no significant differences between the two arms for the primary outcome of neurological recovery (risk ratio [RR] 1.04, 95% CI 0.93-1.15) or the secondary outcome of survival to hospital discharge (RR 1.01, 95% CI 0.92-1.11). However, there was a significantly lower temperature at hospital arrival in patients receiving pre-hospital TH (mean difference - 0.83, 95% CI - 1.03 to - 0.63). Pre-hospital TH significantly increased the risk of re-arrest (RR 1.19, 95% CI 1.00 to 1.41). No survival differences were observed among subgroups of patients who received intra-arrest TH vs post-arrest TH or who had shockable vs non-shockable rhythms. CONCLUSIONS: Pre-hospital TH after OHCA effectively decreases body temperature at the time of hospital arrival. However, it does not improve rates of survival with good neurological outcome or overall survival and is associated with increased rates of re-arrest.

In Vitro Fertilization Success Rates after Surgically Treated Endometriosis and Effect of Time Interval between Surgery and In Vitro Fertilization.

STUDY OBJECTIVE: To evaluate the impact of endometriosis staging and endometriomas on in vitro fertilization (IVF) outcome and to assess the optimal time interval between laparoscopy and IVF. DESIGN: A retrospective clinical study (Canadian Task Force classification II1). SETTING: A university-affiliated private infertility clinic. PATIENTS: Two hundred sixteen infertile patients with endometriosis and 209 infertile patients without endometriosis. INTERVENTIONS: Laparoscopy, IVF. MEASUREMENTS AND MAIN RESULTS: Patients with endometriosis were classified according to American Society for Reproductive Medicine criteria; 58, 67, 63, and 28 patients had stages 1 through 4 disease, respectively. Patients with endometriosis had significantly lower estradiol on trigger day (9986 ± 6710 vs 12 220 ± 9414 pg/mL, respectively) and number of retrieved oocytes (12.7 ± 8.6 vs 14.0 ± 10, respectively) compared with controls. We found a consistent decline in clinical and ongoing pregnancy rates with increasing stage of endometriosis. The presence of endometrioma in patients with stages 3 and 4 endometriosis did not alter IVF outcome. Patients with a time interval of 7 to 12 and 13 to 25 months after surgery had a favorable outcome. CONCLUSION: IVF pregnancy rate was negatively correlated with endometriosis severity. The presence of endometriomas had no impact on IVF clinical outcome. The optimal time to perform IVF appears to be between 7 and 25 months after endometriosis surgery.

Phenobarbital for the management of severe acute alcohol withdrawal (the PHENOMANAL trial): a pilot randomized controlled trial.

BACKGROUND: Benzodiazepines are considered first-line treatment for patients experiencing severe acute alcohol withdrawal syndrome (sAAWS). Although several medications have been evaluated as potential adjuvant treatments for sAAWS, barbiturates show particular promise. OBJECTIVE: In the PHENOMANAL trial, we will assess the feasibility of conducting an allocation-concealed, quadruple-blinded, randomized controlled trial (RCT) comparing symptom-triggered benzodiazepine therapy with either a single dose of adjuvant intravenous (IV) phenobarbital (7.5 mg/kg of ideal body weight) or a single dose of matching IV placebo for patients with sAAWS. METHODS: We will recruit adult patients from the Emergency Department, Intensive Care Unit, or hospital wards with a Clinical Institute of Withdrawal - Adult revised (CIWA-Ar) score of 16 or more after receipt of at least 60 mg of diazepam or equivalent within 16 h of diagnosis of sAAWS, and an anticipated need for hospitalization. We will randomize participants (n=39) in a 2:1 manner to treatment and placebo groups, respectively. The primary objective of the PHENOMANAL pilot trial will be to demonstrate our ability to recruit the desired population over the trial period. As secondary objectives, we will evaluate clinician compliance with the treatment protocols, assess crossover rates from the placebo arm to the treatment arm, and obtain preliminary estimates of treatment effect. All trial participants will be followed for 7 days or until hospital discharge. RELEVANCE: The PHENOMANAL trial is novel in investigating a new treatment for a common and understudied condition, repurposing an existing medication for a novel indication, and addressing an important evidence gap. Through conduct of the multidisciplinary pilot trial, we aim to advance methodology in acute care research through the use of a hybrid consent model and inform the design of a large-scale trial. TRIAL REGISTRATION: ClinicalTrials.gov Registration NCT03586089 ; first registered July 13, 2018.

Proportion of women presenters at medical grand rounds at major academic centres in Canada: a retrospective observational study.

OBJECTIVE: To assess the proportion of women who presented research or medical grand rounds at five major academic hospitals in Canada. DESIGN: A cross-sectional study. SETTING: Five major university-affiliated hospitals in Toronto and Calgary. RESULTS: Overall, at all sites and types of academic rounds, there were an average of 17% fewer women presenting than men (P<0.001). There were an average of 32% and 21% more men presenting at the city-wide grand rounds in cities A and B, respectively (P<0.001, P=0.002). There were more male speakers at four out of five types of rounds. The proportion of women presenting on average was proportional to the Canadian workforce, but on average, below the proportion of female residents and medical students (median ratio 1.1, 0.7 and 0.8, respectively). CONCLUSION: Our study demonstrated a lower proportion of females in an important outlet for academic recognition and role modelling. This provides a possible contributing factor to the under-representation of women in academic medicine and an area that can be systematically targeted to promote equity.