Abnormal Downward Gaze and Cold Caloric Examination Due to Propofol: A Case Study

Background: Adolescent patient with isolated abnormal downward gaze and oculovestibular (cold caloric) testing during propofol administration prompting concern of brainstem injury. PATIENT: An otherwise healthy 16 year old female presented after an intentional hanging. Brainstem reflexes were normal except that both eyes were in tonic downgaze on initial examination. Propofol was suspended for 30 minutes to evaluate level of responsiveness with eyes normalizing to midposition from tonic downgaze. With reinitiation of propofol, the eyes returned to the former position. C-collar stabilization prohibited oculocephalic (doll’s eyes) evaluation, and with cold caloric testing, eye movements were as follows: right sided cold water instillation resulted in right eye exodeviation to the right with minimal medial movement of the left eye to the right. Upon left sided instillation, the left eye deviated downward with minimal medial deviation of the right eye. Patient was weaned to extubation within 48 hours of admission, and off sedatives normal ocular motility returned. CONCLUSION: This patient manifested abnormal ocular motility and cold caloric exam with single-agent propofol exposure. The remainder of the cranial nerve exam was normal, and in the context of a normal brain and cervical spine MRI, the clinical picture was inconsistent with brainstem injury leading us to suspect propofol effect. This was supported by the return of normal ocular motility once propofol was discontinued. Consider pharmacologic disturbance of ocular motility and cold caloric testing in the absence of other brainstem dysfunction when concomitant propofol is administered

Suitability of external controls for drug evaluation in Duchenne muscular dystrophy

OBJECTIVE: To evaluate the suitability of real-world data (RWD) and natural history data (NHD) for use as external controls in drug evaluations for ambulatory Duchenne muscular dystrophy (DMD). METHODS: The consistency of changes in the 6-minute walk distance (Δ6MWD) was assessed across multiple clinical trial placebo arms and sources of NHD/RWD. Six placebo arms reporting 48-week Δ6MWD were identified via literature review and represented 4 sets of inclusion/exclusion criteria (n = 383 patients in total). Five sources of RWD/NHD were contributed by Universitaire Ziekenhuizen Leuven, DMD Italian Group, The Cooperative International Neuromuscular Research Group, ImagingDMD, and the PRO-DMD-01 study (n = 430 patients, in total). Mean Δ6MWD was compared between each placebo arm and RWD/NHD source after subjecting the latter to the inclusion/exclusion criteria of the trial for baseline age, ambulatory function, and steroid use. Baseline covariate adjustment was investigated in a subset of patients with available data. RESULTS: Analyses included ∼1,200 patient-years of follow-up. Differences in mean Δ6MWD between trial placebo arms and RWD/NHD cohorts ranged from -19.4 m (i.e., better outcomes in RWD/NHD) to 19.5 m (i.e., worse outcomes in RWD/NHD) and were not statistically significant before or after covariate adjustment. CONCLUSIONS: We found that Δ6MWD was consistent between placebo arms and RWD/NHD subjected to equivalent inclusion/exclusion criteria. No evidence for systematic bias was detected. These findings are encouraging for the use of RWD/NHD to augment, or possibly replace, placebo controls in DMD trials. Multi-institution collaboration through the Collaborative Trajectory Analysis Project rendered this study feasible

WSES guidelines for management of Clostridium difficile infection in surgical patients

In the last two decades there have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease in many countries worldwide. The incidence of CDI has also increased in surgical patients. Optimization of management of C difficile, has therefore become increasingly urgent. An international multidisciplinary panel of experts prepared evidenced-based World Society of Emergency Surgery (WSES) guidelines for management of CDI in surgical patients.Peer reviewe

All hands-on deck: Use of a HCW survey to identify and address barriers to hand hygiene

BACKGROUND: Hand hygiene (HH) is considered the most effective method for preventing healthcare-associated infections (HAIs); however, healthcare worker (HCW) compliance rates remain low nationwide. Some hospitals did report an initial increase in HH compliance during the COVID-19 pandemic however these increases were difficult to sustain. To develop targeted interventions to improve HH rates in a post-COVID-19 world, a three-hospital network developed a HCW survey assessing current practices and perceived barriers to HH compliance. METHODS: A 14-item anonymous survey composed of Likert, Yes/No and open-ended questions was developed by an Infection Prevention and Quality team from across the network. Items assessed included clarity of HH education received, perceived HH effectiveness, willingness to provide and/or receive real-time feedback, assessment of potential perceived barriers and evaluation of effectiveness of potential targeted interventions. The survey was developed in Microsoft Forms and distributed via email in July 2021. Staff were given 2-weeks to complete the survey. Data analysis was completed in Microsoft Excel. RESULTS: 1,001 HCWs completed the survey. 89% of respondents indicated that HH instructions received in the past year were extremely clear. 92% indicated that they perceived HH as very effective at preventing patients and self from acquiring an HAI. 93% indicated they would be receptive to someone asking them to perform HH if not seen not doing so, however only 45% indicated they always remind colleagues to perform HH. 57% identified availability of alcohol-based hand rub (ABHR) to be a significant barrier to performing HH. 79% ranked supplementing the existing secret shopper HH auditing program with real time feedback and coaching as an effective method to improve HH rates. CONCLUSIONS: Survey results suggest that interventions aimed at improving the availability of ABHR, encouraging peer-to-peer reminders, and supplementing existing auditing processes with real time feedback and coaching may have greater impact on HH compliance than education

<i>Pik3ca</i>^<i>d/d</i> mice have impaired implantation.

<p>(A) Gross anatomy of implantation sites in both the control (a) and <i>Pik3ca</i>^<i>d/d</i> uterus (b) at GD 7.5. (B) The number of implantation sites were recorded in the uteri. (C) The size of implantation sites were measured. (D) The proliferative cells were assessed in control and <i>Pik3ca</i>^<i>d/d</i> uterus at GD 7.5 by immunohistochemical staining using anti-Ki67 antibody. Arrow indicates the blastocyst. The data represents the mean ± SEM. ***, p < 0.001; **, p < 0.01.</p

<i>Pik3ca</i>^<i>d/d</i> mice were subfertile.

<p><i>Pik3ca</i>^<i>d/d</i> mice were subfertile.</p

The defect of gland formation in <i>Pik3ca</i>^<i>d/d</i> mice.

<p>(A) Gross anatomy of 8-week-old control (a) and <i>Pik3ca</i>^<i>d/d</i> (b) mice. (B) There was a significant decrease in the ratio of uterine weight in <i>Pik3ca</i>^<i>d/d</i> mice. (C) Histology of the uterus of control (a) and <i>Pik3ca</i>^<i>d/d</i> (b) mice. The expression of FOXA2 in the uterus of control (c) and <i>Pik3ca</i>^<i>d/d</i> (d) mouse. (D) Quantification of FOXA2 positive endometrial glands in mouse uteri. The results represent the mean ± SEM. *, p < 0.05; ***, p < 0.001.</p

A defect of uterine gland development in <i>Pik3ca</i>^<i>d/d</i> mice at 20 days of age.

<p>(A) The expression of PIK3CA was examined during uterine development. Immunohistochemical staining of PIK3CA in the uterus of PD 14 (a), PD 20 (b), and PD 28 (c). The uterus of GD 3.5 was used a positive control (d). (B) Gross anatomy of control (a) and <i>Pik3ca</i>^<i>d/d</i> (b) mice at PD 20. (C) The weight of uteri was not different between control and <i>Pik3ca</i>^<i>d/d</i> mice. (D) Immunohistochemical staining of FOXA2 in control (a and c) and <i>Pik3ca</i>^<i>d/d</i> (b and d) mice. (E) Quantification of FOXA2 positive endometrial glands in uteri of control and <i>Pik3ca</i>^<i>d/d</i> mice at PD 20. (F) The expression of <i>Foxa2</i> and <i>Spink3</i> in the uteri of control and <i>Pik3ca</i>^<i>d/d</i> mice. The results represent the mean ± SEM. ***, p < 0.001; **, p < 0.01.</p