A systematic review of the methodological quality of economic evaluations in genetic screening and testing for monogenic disorders

PurposeUnderstanding the value of genetic screening and testing for monogenic disorders requires high-quality, methodologically robust economic evaluations. This systematic review sought to assess the methodological quality among such studies and examined opportunities for improvement.MethodsWe searched PubMed, Cochrane, Embase, and Web of Science for economic evaluations of genetic screening/testing (2013-2019). Methodological rigor and adherence to best practices were systematically assessed using the British Medical Journal checklist.ResultsAcross the 47 identified studies, there were substantial variations in modeling approaches, reporting detail, and sophistication. Models ranged from simple decision trees to individual-level microsimulations that compared between 2 and >20 alternative interventions. Many studies failed to report sufficient detail to enable replication or did not justify modeling assumptions, especially for costing methods and utility values. Meta-analyses, systematic reviews, or calibration were rarely used to derive parameter estimates. Nearly all studies conducted some sensitivity analysis, and more sophisticated studies implemented probabilistic sensitivity/uncertainty analysis, threshold analysis, and value of information analysis.ConclusionWe describe a heterogeneous body of work and present recommendations and exemplar studies across the methodological domains of (1) perspective, scope, and parameter selection; (2) use of uncertainty/sensitivity analyses; and (3) reporting transparency for improvement in the economic evaluation of genetic screening/testing.     

Are Medicare's Nursing Home Compare Ratings Accurate Predictors of 90-Day Complications,Readmission, and Bundle Cost for Patients Undergoing Primary Total Joint Arthroplasty?

Background

Nursing Home Compare (NHC) ratings, created and maintained by Medicare, are used by both hospitals and consumers to aid in the skilled nursing facility (SNF) selection process. To date, no studies have linked NHC ratings to actual episode-based outcomes. The purpose of this study was to evaluate whether NHC ratings are valid predictors of 90-day complications, readmission, and bundle costs for patients discharged to an SNF after primary total joint arthroplasty (TJA).

Prevalence and Correlates of Mental Health Problems in Norwegian Peacekeepers 18–38 Years Postdeployment

Peacekeeping missions involve experiences that may impact the mental health of participating soldiers. However, research on the long-term mental health consequences of peacekeeping is sparse. The present study aimed to find the prevalence of mental health problems (MHPs), possible MHP predictors, and associations between predictors and MHPs in Norwegian peacekeepers 18–38 years after deployment to a United Nations peacekeeping mission. We used data from a cross-sectional, postdeployment survey of Norwegian peacekeepers who served in Lebanon between 1978 and 1998 (N = 10,605). Participants were assessed for posttraumatic stress disorder (PTSD); anxiety; depression; insomnia; alcohol misuse; drug misuse; and exposure to pre-, peri-, and postdeployment stressors. Logistic regressions were executed to explore key variables associated with MHPs. Total MHP prevalence was 15.1%, 95% CI [14.4, 15.8]. The estimates for specific disorders were 0.1% for drug misuse, 3.4% for alcohol misuse, 4.0% for depression, 6.2% for PTSD, 6.4% for anxiety, and 9.3% for insomnia. Postdeployment stressors, OR = 1.91, 95% CI [1.79, 2.04]; employment status, OR = 1.41, 95% CI [1.33, 1.48]; and traumatic exposure during deployment, OR = 1.11, 95% CI [1.09, 1.12], were positively related to PTSD, χ2(17, N = 8,568) = 1,791.299, p < .001. Similar patterns were found for the other MHPs. Considering that most participants (84.9%) reported low symptom levels, our findings challenge the widespread public perception that most peacekeepers have MHPs. Moreover, our results indicate that future peacekeepers should be prepared for challenges they may face not only during deployment but also in the years following their homecoming.     

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.

     

Manipulation and free will in shared decision making

In recent years, there has been an increased focus on patient involvement in treatment planning in the health care system. To reduce the risk of the clinician moving towards paternalism, various methods have been introduced—shared decision making, among others. The goal of shared decision making is for the clinician and patient to share available evidence on the best treatment and to raise awareness on the needs and preferences of the patient as to make a genuinely informed choice. However, in the present article, we discuss to which degree paternalism can be avoided in light of the clinician's role as an authority with certain knowledge and expertise. Through the philosophical theory of reasons‐responsiveness, we discuss to which extend free will and control applies to the patient. Through theoretical analysis, we come to suggest that the clinician has a role as an ally rather than manipulator.     

Erythematous and reticular forms of oral lichen planus and oral lichenoid reactions differ in pathological features related to disease activity

BACKGROUND: Common clinical forms of oral lichen planus (OLP) and oral lichenoid reactions (OLR) are erythematous (ERY) or reticular (RET). The purpose of this study was to find histopathological changes that differ between these forms. METHODS: Epithelial thickness, epithelial proliferation rate, apoptosis, and HLA-DR expression were compared among 10 reticular and 12 erythematous lesions, and 11 normal oral mucosa samples (NOM). RESULTS: The epithelium in ERY was thinner than in NOM, whereas RET showed values between ERY and NOM. Cell proliferation increased significantly in ERY as compared with RET and NOM, with no difference between RET and NOM. Relative numbers of epithelial cell nuclei displaying visible chromatin condensation were reduced in ERY form. CONCLUSIONS: The markedly increased cell proliferation in ERY supports the notion that this form displays a higher disease activity as compared to RET. It can therefore be important to study each disease form separately.