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.     

The impact of different step rate threshold methods on physical activity intensity in older adults

BackgroundOlder adults benefit most from engaging in higher-intensity physical activity, which is often determined using step rate thresholds. Fixed step rate thresholds that correspond to moderate (MPA) and vigorous-intensity physical activity (VPA) have been developed for heuristic activity promotion. The activPAL monitor uses step rate thresholds to determine activity intensity. Stepping thresholds may also vary based on body mass index (BMI) or aerobic fitness level in older adults. Despite the various thresholds used in the literature, it is unclear whether they produce similar outcomes.Research QuestionHow does time spent in physical activity intensities compare between different step rate thresholds in older adults?MethodsThirty-eight participants (24♀; 67 ± 4 years; BMI: 26.6 ± 4.4 kg/m²) wore an activPAL monitor 24-hr/day for up to 7-d (total: 205-d). Aerobic fitness (V̇O₂max: 23 ± 8 ml/kg/min) was determined via indirect calorimetry during a maximal, graded cycling test. Time spent in each intensity category (light-physical-activity [LPA], MPA, VPA) was determined using the fixed (MPA/VPA) 100/130, 110/130, and activPAL step rate thresholds (74/212), as well as BMI-adjusted absolute (108.5 ± 2.5/134.0 ± 4.8) and BMI-adjusted relative (40%/60% V̇O₂max; 111.4 ± 14.7/132.0 ± 19.0) cut-offs. Times spent in each intensity category were compared between methods.ResultsThe activPAL and 100/130 thresholds yielded less LPA and more MPA than all other methods. The activPAL had no time spent in VPA at all. The BMI-adjusted absolute and relative thresholds produced statistically equivalent time in LPA and MPA (via equivalence testing), but not VPA. No two methods yielded similar time spent in LPA, MPA, or VPA.SignificanceThe choice of step rate threshold has a major impact on physical activity intensity outcomes in older adults. Inherently, strategies that adjust for older adults’ body size and/or aerobic fitness level provide a more individualized data processing strategy than fixed thresholds that assume the same threshold for all older adults     

Priorities for content for a short-course on postoperative care relevant for low- and middle-income countries: an e-Delphi process with training facilitators

Most surgical and anaesthetic mortality and morbidity occurs postoperatively, disproportionately affecting low- and middle-income countries. Various short courses have been developed to improve patient outcomes in low- and middle-income countries, but none specifically to address postoperative care and complications. We aimed to identify key features of a proposed short-course addressing this topic using a Delphi process with low- and middle-income country anaesthesia providers trained as short-course facilitators. An initial questionnaire was co-developed from literature review and exploratory workshops to include 108 potential course features. Features included content; teaching method; appropriate participants; and appropriate faculty. Over three Delphi rounds (panellists numbered 86, 64 and 35 in successive cycles), panellists indicated which features they considered most important. Responses were analysed by geographical regions: Africa, the Americas, south-east Asia and Western Pacific. Ultimately, panellists identified 60, 40 and 54 core features for the proposed course in each region, respectively. There were high levels of consensus within regions on what constituted core course content, but not between regions. All panellists preferred the small group workshop teaching method irrespective of region. All regions considered anaesthetists to be key facilitators, while all agreed that both anaesthetists and operating theatre nurses were key participants. The African and Americas regional panels recommended more multidisciplinary healthcare professionals for participant roles. Faculty from high-income countries were not considered high priority. Our study highlights variability between geographical regions as to which course features were perceived as most locally relevant, supporting regional adaptation of short-course design rather than a one-size-fits-all model.     

Contribution of different somatosensory afferent input to subcortical somatosensory evoked potentials in humans

ObjectivesTo investigate the subcortical somatosensory evoked potentials (SEPs) to electrical stimulation of either muscle or cutaneous afferents.MethodsSEPs were recorded in 6 patients suffering from Parkinson’s disease (PD) who underwent electrode implantation in the pedunculopontine (PPTg) nucleus area. We compared SEPs recorded from the scalp and from the intracranial electrode contacts to electrical stimuli applied to: 1) median nerve at the wrist, 2) abductor pollicis brevis motor point, and 3) distal phalanx of the thumb. Also the high-frequency oscillations (HFOs) were analysed.ResultsAfter median nerve and pure cutaneous (distant phalanx of the thumb) stimulation, a P1-N1 complex was recorded by the intracranial lead, while the scalp electrodes recorded the short-latency far-field responses (P14 and N18). On the contrary, motor point stimulation did not evoke any low-frequency component in the PPTg traces, nor the N18 potential on the scalp. HFOs were recorded to stimulation of all modalities by the PPTg electrode contacts.ConclusionsStimulus processing within the cuneate nucleus depends on modality, since only the cutaneous input activates the complex intranuclear network possibly generating the scalp N18 potential.SignificanceOur results shed light on the subcortical processing of the somatosensory input of different modalities.     

COVID-19 Gender Disparities and Mitigation Recommendations: A Narrative Review

The coronavirus disease 2019 (COVID-19) pandemic has rapidly created widespread impacts on global health and the economy. Data suggest that women are less susceptible to severe illness. However, sex-disaggregated data are incomplete, leaving room for misinterpretation, and focusing only on biologic sex underestimates the gendered impact of the pandemic on women. This narrative review summarizes what is known about gender disparities during the COVID-19 pandemic and the economic, domestic, and health burdens along with overlapping vulnerabilities related to the pandemic. In addition, this review outlines recommended strategies that advocacy groups, community leaders, and policymakers should implement to mitigate the widening gender disparities related to COVID-19.