Development and Validation of a Computerized Adaptive Assessment Tool for Discrimination and Measurement of Psychotic Symptoms

ObjectiveTime constraints limit the use of measurement-based approaches in research and routine clinical management of psychosis. Computerized adaptive testing (CAT) can reduce administration time, thus increasing measurement efficiency. This study aimed to develop and test the capacity of the CAT-Psychosis battery, both self-administered and rater-administered, to measure the severity of psychotic symptoms and discriminate psychosis from healthy controls.MethodsAn item bank was developed and calibrated. Two raters administered CAT-Psychosis for inter-rater reliability (IRR). Subjects rated themselves and were retested within 7 days for test-retest reliability. The Brief Psychiatric Rating Scale (BPRS) was administered for convergent validity and chart diagnosis, and the Structured Clinical Interview (SCID) was used to test psychosis discriminant validity.ResultsDevelopment and calibration study included 649 psychotic patients. Simulations revealed a correlation of r = .92 with the total 73-item bank score, using an average of 12 items. Validation study included 160 additional patients and 40 healthy controls. CAT-Psychosis showed convergent validity (clinician: r = 0.690; 95% confidence interval [95% CI]: 0.610–0.757; self-report: r = .690; 95% CI: 0.609–0.756), IRR (intraclass correlation coefficient [ICC] = 0.733; 95% CI: 0.611–0.828), and test-retest reliability (clinician ICC = 0.862; 95% CI: 0.767–0.922; self-report ICC = 0.815; 95%CI: 0.741–0.871). CAT-Psychosis could discriminate psychosis from healthy controls (clinician: area under the receiver operating characteristic curve [AUC] = 0.965, 95% CI: 0.945–0.984; self-report AUC = 0.850, 95% CI: 0.807–0.894). The median length of the clinician-administered assessment was 5 minutes (interquartile range [IQR]: 3:23–8:29 min) and 1 minute, 20 seconds (IQR: 0:57–2:09 min) for the self-report.ConclusionCAT-Psychosis can quickly and reliably assess the severity of psychosis and discriminate psychotic patients from healthy controls, creating an opportunity for frequent remote assessment and patient/population-level follow-up.     

Effect of cholinergic crisis on the potency of different emergency anaesthesia protocols in soman-poisoned rats

Background: In a military or terrorist scenario, combination of organophosphorus compounds (OP) poisoning with physical trauma requiring surgical treatment and thus general anaesthesia are possible. Previous in vitro studies showed an altered potency of relevant anaesthetics during cholinergic crisis. Hence, it is not clear, which anaesthetics are suitable to achieve the necessary stage of surgical anaesthesia in OP poisoning.

Methods: In the present study, different anaesthetic regimens (ketamine-midazolam, propofol-fentanyl, thiopental-fentanyl), relevant in military emergency medicine, were examined in soman-poisoned rats. Clinical signs and cardiovascular variables were recorded continuously. Blood samples for acetylcholinesterase (AChE) activity were drawn. After euthanasia or death of the animals, brain and diaphragm were collected for cholinesterase assays.

Results: Propofol-fentanyl and thiopental-fentanyl resulted in surgical anaesthesia throughout the experiments. With ketamine-midazolam, surgical anaesthesia without respiratory impairment could not be achieved in pilot experiments (no soman challenge) and was therefore not included in the study. Soman-poisoned and control animals required a comparable amount of propofol-fentanyl or thiopental-fentanyl. In combination with atropine, significantly less propofol was needed. Survival rate was higher with thiopental compared to propofol. Atropine improved survival in both groups. Blood and tissue AChE activities were strongly inhibited after soman administration with and without atropine treatment.

Discussion: The current in vivo study did not confirm concerns of altered potency of existing anaesthetic protocols for the application of propofol or thiopental with fentanyl due to soman poisoning. Despite severe cholinergic crisis, sufficient anaesthetic depth could be achieved in all animals.

Conclusion: Further experiments in in vivo models closer to human pharmaco- and toxicokinetics (e.g., swine) are required for confirmation of the initial findings and for improving extrapolation to humans.     

Immunohistochemistry for c-myc and bcl-2 overexpression improves risk stratification in primary central nervous system lymphoma

Overexpression of bcl-2 and c-myc are defining features of double-expressor-lymphoma (DEL) but may also occur separately in patients with primary central nervous system lymphoma (PCNSL). Despite all progress in optimizing treatment regimen, there is lack of sufficient risk stratification models. Here, we first describe the relationship between DEL biology, the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI), treatment response, disease progression, and mortality in PCNSL. In this study, we determined c-myc and bcl-2 status immunohistochemically in samples of 48 patients with newly diagnosed PCNSL and followed these patients for a median interval of 6.2 years. Twelve, 18, and 17 patients harbored none, one, or both DEL features. Corresponding overall response rates after first-line therapy were strongly associated with DEL biology (100%, 42%, and 44% in patients with 0, 1, or 2 DEL features). Patients with one or both DEL features had a 5-fold and 13-fold higher 5-year risk of progression and/or death than patients without DEL features. These associations prevailed after adjusting for the NCCN-IPI. DEL improved the discriminatory capability of the NCCN-IPI (P = .0001). Furthermore, we could show that addition of DEL biology to the NCCN-IPI significantly improved the score's discriminatory potential both toward progression-free survival (increase in Harell's c = 0.15, P = .005) and overall survival (increase in Harell's c = 0.11, P = .029). In conclusion, DEL biology is a strong and simple-to-use predictor of adverse outcome in PCNSL. Addition of DEL to the NCCN-IPI improves its prognostic potential. Disease progression from PCNSL harboring both DEL features is invariably fatal. This defines a novel PCNSL patient subset with a great unmet need for improved therapy.     

Extensive endometriosis surgery: rASRM and Enzian score independently relate to post-operative complication grade

Archives of Gynecology and Obstetrics - We aimed to assess post-operative complications based on the Clavien–Dindo classification system following routine laparoscopic treatment of all stages...     

Low-dose hydrocortisone in patients with COVID-19 and severe hypoxia (COVID STEROID) trial—Protocol and statistical analysis plan

Introduction

Severe acute respiratory syndrome coronavirus-2 has caused a pandemic of coronavirus disease (COVID-19) with many patients developing hypoxic respiratory failure. Corticosteroids reduce the time on mechanical ventilation, length of stay in the intensive care unit and potentially also mortality in similar patient populations. However, corticosteroids have undesirable effects, including longer time to viral clearance. Clinical equipoise on the use of corticosteroids for COVID-19 exists.

Methods

The COVID STEROID trial is an international, randomised, stratified, blinded clinical trial. We will allocate 1000 adult patients with COVID-19 receiving ≥10 L/min of oxygen or on mechanical ventilation to intravenous hydrocortisone 200 mg daily vs placebo (0.9% saline) for 7 days. The primary outcome is days alive without life support (ie mechanical ventilation, circulatory support, and renal replacement therapy) at day 28. Secondary outcomes are serious adverse reactions at day 14; days alive without life support at day 90; days alive and out of hospital at day 90; all-cause mortality at day 28, day 90, and 1 year; and health-related quality of life at 1 year. We will conduct the statistical analyses according to this protocol, including interim analyses for every 250 patients followed for 28 days. The primary outcome will be compared using the Kryger Jensen and Lange test in the intention to treat population and reported as differences in means and medians with 95% confidence intervals.

Discussion

The COVID STEROID trial will provide important evidence to guide the use of corticosteroids in COVID-19 and severe hypoxia.

     

Cardiac Strain in a Swine Model of Regional Hibernating Myocardium: Effects of CoQ10 on Contractile Reserve Following Bypass Surgery

There is conflicting clinical evidence whether administration of coenzyme Q10 (CoQ10) improves function following coronary artery bypass graft surgery (CABG). Using a swine model of hibernating myocardium, we tested whether daily CoQ10 would improve contractile function by MRI at 4-week post-CABG. Twelve pigs underwent a thoracotomy and had a constrictor placed on the left anterior descending (LAD). At 12 weeks, they underwent off-pump bypass and received daily dietary supplements of either CoQ10 (10 mg/kg/day) or placebo. At 4-week post-CABG, circumferential strain measurements in the hibernating LAD region from placebo and CoQ10 groups were not different and increased to a similar extent with dobutamine (?14.7?±?0.6 versus ?14.8?±?0.1, respectively (NS)). Post-sacrifice, oxidant stress markers were obtained in the mitochondrial isolates and protein carbonyl in the placebo, and CoQ10 groups were 6.14?±?0.36 and 5.05?±?0.32 nmol/mg, respectively (NS). In summary, CoQ10 did not improve contractile reserve or reduce oxidant stress at 4-week post-CABG.