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.     

Spread of an Enterococcus faecalis sequence type 6 (CC2) clone in patients undergoing selective decontamination of the digestive tract

Enterococcus faecalis (E. faecalis) is a common cause of nosocomial infection in immunocompromised patients. The presence and dissemination of high‐risk clonal complexes, such as CC2, is an ongoing problem in hospitals. The aim of this work was to characterize 24 E. faecalis isolates from ICU patients undergoing selective decontamination of the digestive tract (SDD) by phenotypical (antimicrobial susceptibility) and genotypical (presence of virulence genes, RAPD‐PCR and MLST) methods. Our results showed high prevalence of the ST6 E. faecalis clone (91.6%), especially adapted to the hospital environment, with a multidrug resistance pattern and a multitude of putative virulence genes. In addition, ST179 (4.2%) and ST191 (4.2%) were detected. By RAPD–PCR analysis, the 22 isolates identified as ST6 showed six different DNA patterns, while the two remaining isolates, ST179 and ST191, showed two additional profiles. CC2 is a known clonal complex with high adaptability to hospital environment and worldwide distribution. The high prevalence of the ST6 clone in the studied population could be related to the presence of gentamicin in the SDD mixture since most strains were gentamicin resistant. Consequently, strict surveillance should be applied for rapid detection and control of this clone to prevent future spread outside the ICU.     

Quality of Pulmonary Function Tests in Participants with Down Syndrome

IntroductionPeople with Down syndrome (DS) have high respiratory morbidity, evaluating their respiratory health with standardized, objective tests is desirable. Thus, the objective of this study was to evaluate the technical quality of Pulmonary Function Tests (PFTs) to determine which ones are most suitable for this population.MethodsParticipants included children, teenagers and adults with DS, 5 years of age or older (n = 302). The technical quality of the impulse oscillometry system (IOS), forced spirometry, lung-diffusing capacity for carbon monoxide (DL_CO), and 6-min walk test (6MWT) were analyzed by age group. Capnography and pulse oximetry were included in the study. Technical quality was determined on the basis of current international PFTs standards.ResultsFifty-one percent of participants were males. A total of 184 participants (71%) who completed the IOS fulfilled the quality criteria, while 210 (70%) completed the 6MWT. Performance on forced spirometry and DL_CO was poor. All pulse oximetries and 96% percent heart rates obtained had good quality, but exhaled carbon dioxide (PetCO₂) and respiratory rate (RR) showed deficient repeatability.ConclusionsIOS appears to be the most reliable instrument for evaluating lung mechanics in individuals with DS.     

Examining the contraceptive decisions of young,HIV-infected women: A qualitative study

This study qualitatively examined factors that influenced contraceptive choices in a sample of young, HIV-infected women. Individual qualitative interviews were conducted among 30 vertically and horizontally HIV-infected women (n = 26 African American) from the ages of 14 to 24 years (Mean age = 20.9 years). We recruited sample groups with the following characteristics: (a) current contraceptive/condom use with ≥1 child (n = 11); (b) current contraceptive/condom use with no children (n = 12); and (c) no current contraceptive/condom use with no children (n = 7). A semi-structured interview guide was used to ask participants about factors influencing past and current contraceptive choices. Individual interviews were digitally recorded and transcribed verbatim; analyses to identify core themes were informed by the Grounded Theoretical approach. Young, HIV-infected women did not identify their HIV serostatus or disease-related concerns as influential in their contraceptive decisions. However, they reported that recommendations from health-care providers and input from family and friends influenced their contraceptive choices. They also considered a particular method’s advantages (e.g., menstrual cycle improvements) and disadvantages (e.g., increased pill burden) when selecting a method. Findings suggested that HIV-infected young women’s contraceptive decisions were influenced by factors other than those related to their infection.     

Pathways in the association between sugar sweetened beverages and child asthma traits in the 2nd year of life: Findings from the BRISA cohort

Studies on the exposure of children to sugar-sweetened beverages (SSBs) at an early age may contribute to better understand the common causes and the temporal order of the relationships between obesity and asthma in early childhood. The objective of this study was to estimate the association between SSB and child asthma traits in the 2nd year of life, modeling direct and indirect pathways mediated by the highest BMI-z of the child and allergic inflammation. Data from the BRISA cohort, São Luís-MA, Brazil (n = 1140), were obtained from the baseline and from the follow-up performed at the 2nd year of life. The main explanatory variable was the calories from added sugars in SSBs as a percentage of the total daily energy intake. The outcome child asthma traits was a latent variable deduced from four indicators: medical diagnosis of asthma, wheezing, emergency visit due to intense wheezing, and medical diagnosis of rhinitis. A high percentage of daily calories from sugars added to SSBs was directly associated with higher values of child asthma traits (standardized coefficient (SC = 0.073; P = .030)). High levels of eosinophils were also directly associated with child asthma traits (SC = 0.118; P = .049). No mediation pathways were observed via greater BMI-z or eosinophil counts. Therefore, early exposure of children to SSB may contribute to increased risk of childhood asthma, preceding the link between sugar consumption and overweight/obesity, not yet evident in children in the first 2 years of life.     

Characterizing luminous efficiency functions for a simulated mesopic night driving task based on reaction time

The objective of this study is to test the luminous efficiency functions V(lambda), V'(lambda), V(10)(lambda) and their linear combinations on the basis of a data set gained from a simulated mesopic night-time driving experiment. Another aim is to provide 'real-world' data for the 'X framework' or 'linear combination model', and to find out its limits in a practical situation. Human performance was measured by the reaction time method. Results show that the single parameter of the linear combination of photopic and scotopic luminous efficiency functions can be determined analytically with little variation for a given mesopic background luminance level and a given visual target colour, but the computation leads to considerable deviations comparing all three target colours (red, green and blue) used in the experiment. The conclusion for the given experimental conditions is that the single parameter of the linear combination model has an increasing deviation for lower background luminance levels.     

Right aortic arch detected in fetal life.

OBJECTIVE: To evaluate the prenatal distribution, associated conditions and outcome of the different types of right aortic arch (RAA) detected in fetal life. METHODS: This was a retrospective review of all cases of RAA detected prenatally between 1998 and 2005 in two tertiary referral centers. RESULTS: In the study period 71 cases of RAA were detected; 26 (37%) had RAA with aberrant left subclavian artery, 23 (32%) had RAA with mirror-image branching, 20 (28%) had RAA of unknown type and two (3%) had double aortic arch. While 20/26 cases with RAA and aberrant left subclavian artery were isolated findings, all 23 cases with RAA and mirror-image branching were associated with cardiac defects, namely tetralogy of Fallot (43%) or pulmonary atresia with ventricular septal defect (22%). Of the 20 cases with RAA, 19 of unknown type were associated with heterotaxy syndromes and had additional cardiac malformations and ambiguities of the situs. The two cases with DAA were isolated findings. Seven cases in our series (10%) had a microdeletion 22q11 and these were significantly associated with extracardiac malformations. The outcome in our series depended solely on the associated cardiac and extracardiac malformations, with the exception of one infant with isolated DAA, in whom a surgical correction was warranted. CONCLUSIONS: RAA detected in fetal life is associated frequently with other cardiac/non-cardiac malformations, heterotaxy syndromes and microdeletions 22q11. The associated conditions vary depending on the branching type of the brachiocephalic vessels and the presence of extracardiac malformations.