Feasibility of early waking cardiac arrest patients whilst receiving therapeutic hypothermia: The therapeutic hypothermia and early waking (THAW) trial.

AIM: To determine the safety and feasibility of an early (12 h) waking and extubation protocol for out-of-hospital cardiac arrest (OHCA) patients receiving targeted temperature management (TTM). METHODS: This was a single-centre, prospective, non-randomised, observational, safety and feasibility pilot study which included successfully resuscitated OHCA patients, of presumed cardiac cause. Inclusion criteria were: OHCA patients aged over 18 years with a return of spontaneous circulation, who were going to receive TTM33 (TTM at 33 °C for 24 h and prevention of hyperthermia for 72 h) as part of their post cardiac arrest care. Clinical stability was measured against physiological and neurological parameters as well as clinical assessment. RESULTS: 50 consecutive patients were included (median age 65.5 years, 82% male) in the study. Four (8%) patients died within the first twelve hours and were excluded from the final cohort (n = 46). Twenty-three patients (46%) were considered clinically stable and suitable for early waking based on the intention to treat analysis; 12 patients were extubated early based on a variety of clinical factors (21.4 ± 8.6 h) whilst continuing to receive TTM33 with a mean core temperature of 34.2 °C when extubated. Of these, five patients were discharged from the intensive care unit (ICU) <48 h after admission with a mean ICU length of stay 1.8 ± 0.4 days. Twenty-eight patients (56%) were discharged from the ICU with a modified Rankin Score of 0-2. The overall intra-hospital mortality was 50% (n = 25). CONCLUSIONS: It is safe and feasible to wake selected comatose OHCA patients at 12 h, allowing for earlier positive neuro-prognostication and reduced ICU stay.

Postoperative weightbearing following ankle arthrodesis: a systematic review.

AIMS: Postoperative rehabilitation regimens following ankle arthrodesis vary considerably. A systematic review was conducted to determine the evidence for weightbearing recommendations following ankle arthrodesis, and to compare outcomes between different regimens. PATIENTS AND METHODS: MEDLINE, Web of Science, Embase, and Scopus databases were searched for studies reporting outcomes following ankle arthrodesis, in which standardized postoperative rehabilitation regimens were employed. Eligible studies were grouped according to duration of postoperative nonweightbearing: zero to one weeks (group A), two to three weeks (group B), four to five weeks (group C), or six weeks or more (group D). Outcome data were pooled and compared between groups. Outcomes analyzed included union rates, time to union, clinical scores, and complication rates. RESULTS: A total of 60 studies (2426 ankles) were included. Mean union rates for groups A to D were 93.2%, 95.5%, 93.0%, and 93.0%, respectively. Mean time to union was 10.4 weeks, 14.5 weeks, 12.4 weeks, and 14.4 weeks for groups A to D, respectively. Mean complication rates were 22.3%, 23.0%, 27.1%, and 28.7% for groups A to D, respectively. Reporting of outcome scores was insufficient to conduct meaningful analysis. CONCLUSION: Outcomes following ankle arthrodesis appear to be similar regardless of the duration of postoperative nonweightbearing, although the existing literature is insufficient to make definitive conclusions. Cite this article: Bone Joint J 2019;101-B:1256-1262.

Is It Feasible and Safe to Wake Cardiac Arrest Patients Receiving Mild Therapeutic Hypothermia After 12 Hours to Enable Early Neuro-Prognostication? The Therapeutic Hypothermia and Early Waking Trial Protocol.

Mild therapeutic hypothermia (MTH 33°C) post out-of-hospital cardiac arrest (OHCA) is widely accepted as standard of care. However, uncertainty remains around the dose and therapy duration. OHCA patients are usually kept sedated±paralyzed and ventilated for the first 24-36 hours, which allows for targeted temperature management, but makes neurological prognostication challenging. The aim of this study is to investigate the feasibility and safety of assessing the unconscious OHCA patient after 12 hours for early waking/extubation while continuing to provide MTH for 24 hours, and fever prevention for 72 hours by using an intravenous temperature management (IVTM) system and established conscious MTH anti-shiver regimens. This is a single-center, prospective, non-randomized observational study that will compare the results of early awakening (at 12 hours) with historical controls. A total of 50 consecutive unconscious survivors of OHCA, treated with MTH, who meet the Therapeutic Hypothermia and eArly Waking (THAW) inclusion criteria will be enrolled. The patient will receive MTH by using IVTM. After 12 hours of MTH, patients will be assessed by using strict clinical criteria to determine suitability for early waking and extubation. Once awake and extubated, MTH will continue for 24 hours with skin counter-warming and anti-shiver regimen followed fever prevention up to 72 hours. All patients will have serial electroencephalogram (EEG), somatic sensory potential, and neuro-biomarkers performed on admission to intensive care unit, 6 and 12 hours, then every 24 hours until 72 hours. The study has been approved by the National Research Ethics Service, Health Research Authority.

Preparative chromatographic resolution of racemates using HPLC and SFC in a pharmaceutical discovery environment.

The preparative chromatographic resolution of racemates has become a standard approach for the generation of enantiomers in pharmaceutical discovery laboratories. This paper will discuss the use of preparative HPLC and SFC to generate individual enantiomers for discovery activities. Analytical HPLC and SFC method development to rapidly screen chiral stationary phases and solvent combinations will be presented. The usefulness of preparative chromatographic resolution of racemates will be demonstrated through the presentation of numerous non-routine case studies from the laboratories at Amgen.