Cost-effectiveness frameworks for comparing genome and exome sequencing versus conventional diagnostic pathways: A scoping review and recommended methods

PurposeMethodological challenges have limited economic evaluations of genome sequencing (GS) and exome sequencing (ES). Our objective was to develop conceptual frameworks for model-based cost-effectiveness analyses (CEAs) of diagnostic GS/ES.MethodsWe conducted a scoping review of economic analyses to develop and iterate with experts a set of conceptual CEA frameworks for GS/ES for prenatal testing, early diagnosis in pediatrics, diagnosis of delayed-onset disorders in pediatrics, genetic testing in cancer, screening of newborns, and general population screening.ResultsReflecting on 57 studies meeting inclusion criteria, we recommend the following considerations for each clinical scenario. For prenatal testing, performing comparative analyses of costs of ES strategies and postpartum care, as well as genetic diagnoses and pregnancy outcomes. For early diagnosis in pediatrics, modeling quality-adjusted life years (QALYs) and costs over ≥20 years for rapid turnaround GS/ES. For hereditary cancer syndrome testing, modeling cumulative costs and QALYs for the individual tested and first/second/third-degree relatives. For tumor profiling, not restricting to treatment uptake or response and including QALYs and costs of downstream outcomes. For screening, modeling lifetime costs and QALYs and considering consequences of low penetrance and GS/ES reanalysis.ConclusionOur frameworks can guide the design of model-based CEAs and ultimately foster robust evidence for the economic value of GS/ES.     

Effect of orbital wall resection areas in the treatment of patients with endocrine orbitopathy

In patients treated by orbital wall decompression for endocrine orbitopathy (EO) there is limited evidence on the effect of orbital wall resections. Thus, the aim of this study was to evaluate the effect of one, two, and three-wall resections on orbital parameters to determine if any such correlations exist. Preoperative and postoperative data from all patients at a tertiary care centre who underwent decompression surgery from 2010 - 2020 were digitally analysed. The effect of the number and area of resected walls on orbital area, orbital volume, and Hertel value, and the effect of lateral rim advancement (LARA) were determined. A total of 131 orbital areas showed an increase from a mean (SD) preoperative area of 42.0 (4.6) cm² to 47.3 (6.1) cm² postoperatively (p<0.001). In total, the mean (SD) area of osseous wall removed in all patients was 6.2 (1.7) cm² at the lateral orbit (n = 129), 6.7 (2.3) cm² at the orbital floor (n = 123), and 5.8 (1.8) cm² at the medial orbital wall (n =30). The mean (SD) orbital volume increased by 6.0 (3.0) cm³ after decompression. There was also a significant reduction in exophthalmos of 7.3 (3.2) mm (from 25.2 (3.9) to 17.9 (3.5), p<0.001). LARA was performed in 50 patients. Changes in volume and area, and reduction in exophthalmos were not significantly different with or without LARA. The postoperative effects of orbital wall resection are predictable and exhibit a relation with six units of change. Two-wall resection is the most common intervention.     

Dietary patterns and the risk of abnormal blood lipids among young adults: A prospective cohort study

Background and aimsThe extent to which dietary patterns influence the risk of abnormal blood lipids throughout young adulthood remains unclear. The aim was to investigate whether early young adulthood dietary patterns predict the risk of abnormal blood lipids during later young adulthood.Methods and resultsWe used data from a long running birth cohort study in Australia. Western dietary pattern rich in meats, processed foods and high-fat dairy products and prudent pattern rich in fruit, vegetables, fish, nuts, whole grains and low-fat dairy products were derived using principal component analysis at the 21-year follow-up from dietary data obtained using a food frequency questionnaire. After 9-years, fasting blood samples of all participants were collected and their total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterols and triglyceride (TG) levels were measured. Abnormal blood lipids were based on clinical cut-offs for total, LDL and HDL cholesterols, and TG and relative distributions for total:HDL and TG:HDL cholesterols ratios. Log-binomial models were used to estimate risk of each outcome in relation to dietary patterns. Greater adherence to the Western pattern predicted increased risks of high LDL (RR: 1.47; 95%CI: 1.06, 2.03) and TG (1.90; 1.25, 2.86), and high ratios of total:HDL (1.48; 1.00, 2.19) and TG:HDL (1.78; 1.18, 2.70) cholesterols in fully adjusted models. Conversely, a prudent pattern predicted reduced risks of low HDL (0.58; 0.42, 0.78) and high TG (0.66; 0.47, 0.92) and high total:HDL (0.71; 0.51, 0.98) and TG:HDL (0.61; 0.45, 0.84) cholesterols ratios.ConclusionThis is the first prospective study to show greater adherence to unhealthy Western diet predicted increased risks of abnormal blood lipids, whereas healthy prudent diet predicted lower such risks in young adults. Addressing diets in early course may improve cardiovascular health of young adults.     

基于临床观察文本解析痛经辨治规律研究

目的:研究痛经的中医药辨治规律。方法:检索国家知识基础设施数据库(CNKI)1988—2019年应用中药治疗痛经的相关文献,采用Medcase Ver38诊籍中医师工作室-名老中医经验传承辅助平台,运用文本解析对临床医案进行研究。结果:研究文献131篇,医案104则,涉及病例128次,332诊次,涉及症状92条,病机33条,舌象27条,脉象17条,药物249种。结论:中医药治疗痛经的特异症状为“经行腹痛”,可见症为“夹血块、月经色暗、手足冰冷、经期腰酸”,相关舌脉为“舌质暗红,苔薄白”“脉沉细弦”,核心病机为“瘀血阻滞”,常用治法为“行气化瘀,活血止痛”,常用药物为“当归、白芍、甘草、延胡索、川芎”。     

A discourse analysis of health provider interactions with parents who are reluctant to vaccinate

ObjectiveVaccine hesitancy is a persistent barrier to vaccination uptake, and health professionals report interactions with such parents to be difficult. Using discourse analytic techniques, we examine the foundation of a therapeutic relationship: the display of empathy and attempts to build rapport, in consultations between immunisation specialists and vaccine reluctant parents.MethodsConsultations between consenting clinicians and parents in two Specialist Immunisation Clinics in Australia were recorded. Twelve conversations between the clinicians and parents were analysed using interactional sociolinguistic (IS) discourse analytic methods.ResultsThis paper takes a case study approach by citing two interactions that exemplify the interactional work of the consultants as they strive to engender mutual understanding and goodwill, noting examples of discursive choices that demonstrate empathy and the building of rapport.ConclusionAwareness of discourse strategies that interweave relational and clinical goals enable a more nuanced understanding of communication skills that support a guiding partnership in vaccine related decisions with parents.Practical implicationsThrough highlighting the strategic interactional work that displays empathy and builds rapport, we can inform educational approaches and build a repertoire of communication choices that strengthen the communication skills of health professionals.     

Key Social Determinants to Narrow the Gap between Health-adjusted Life Expectancy and Life Expectancy in Megacities

ObjectiveImprovement in the quality of life is reflected in the narrowing of the gap between health-adjusted life expectancy (HALE) and life expectancy (LE). The effect of megacity expansion on narrowing the gap is rarely reported. This study aimed to disclose this potential relationship.MethodsAnnual life tables were constructed from identified death records and population counts from multiple administrative sources in Guangzhou, China, from 2010 to 2020. Joinpoint regression was used to evaluate the temporal trend. Generalized principal component analysis and multilevel models were applied to examine the county-level association between the gap and social determinants.ResultsAlthough LE and HALE in megacities are increasing steadily, their gap is widening. Socio-economic and health services are guaranteed to narrow this gap. Increasing personal wealth, a growing number of newborns and healthy immigrants, high urbanization, and healthy aging have helped in narrowing this gap.ConclusionIn megacities, parallel LE and HALE growth should be highly considered to narrow their gap. Multiple social determinants need to be integrated as a whole to formulate public health plans.     

Hepatitis B virus DNA in the fingernails and hair of children with acute hepatitis B

Hepatitis B virus (HBV) DNA is detectable in the nails and hair of patients with chronic HBV infection. However, it remains unclear whether HBV DNA can be detectable in the nails and hair of patients with acute HBV infection. We encountered two cases of children with acute HBV infection. HBV DNA in the nails and hair from the two children was evaluated by real-time PCR. To clarify the characteristics of HBV DNA, full-length HBV genome sequencing and phylogenetic tree analysis were performed. The levels of serum HBV DNA in children of cases 1 and 2 at day 0 were 7.6 Log IU/mL and 7.4 Log IU/mL, respectively. Nail HBV DNA was detected in both children (case 1: 4.6 Log IU/mL at day 0, case 2: 5.5 Log IU/mL at day 14). Moreover, hair HBV DNA was detectable in case 2 (4.0 Log IU/mL at day 14). Serum HBV DNA became undetectable within approximately 3–4 months after the first hospital visit. After the resolution of HBV viremia, nail and hair HBV DNA became undetectable. The sequence analysis of serum, nail and hair HBV DNA showed the same HBV genotype in each case (case1: genotype C, case 2: genotype A). In case 1, 3 nucleotides were different in the full-genome HBV sequence between the serum and nails. In case 2, the full-genome HBV sequences were identical among the serum, nails and hair. In conclusion, HBV DNA was detectable in nails and hair of children with acute HBV infection.     

Immunogenicity and protective efficacy of adenoviral and subunit RSV vaccines based on stabilized prefusion F protein in pre-clinical models

Respiratory Syncytial Virus (RSV) remains a leading cause of severe respiratory disease for which no licensed vaccine is available. We have previously described the derivation of an RSV Fusion protein (F) stabilized in its prefusion conformation (preF) as vaccine immunogen and demonstrated superior immunogenicity in naive mice of preF versus wild type RSV F protein, both as protein and when expressed from an Ad26 vaccine vector. Here we address the question if there are qualitative differences between the two vaccine platforms for induction of protective immunity. In naïve mice, both Ad26.RSV.preF and preF protein induced humoral responses, whereas cellular responses were only elicited by Ad26.RSV.preF. In RSV pre-exposed mice, a single dose of either vaccine induced cellular responses and strong humoral responses. Ad26-induced RSV-specific cellular immune responses were detected systemically and locally in the lungs. Both vaccines showed protective efficacy in the cotton rat model, but Ad26.RSV.preF conferred protection at lower virus neutralizing titers in comparison to RSV preF protein. Factors that may contribute to the protective capacity of Ad26.RSV.preF elicited immunity are the induced IgG2a antibodies that are able to engage Fcγ receptors mediating Antibody Dependent Cellular Cytotoxicity (ADCC), and the induction of systemic and lung resident RSV specific CD8 + T cells. These data demonstrate qualitative improvement of immune responses elicited by an adenoviral vector based vaccine encoding the RSV preF antigen compared to the subunit vaccine in small animal models which may inform RSV vaccine development.