Effectiveness of preconceptional and prenatal cystic fibrosis carrier screening: a systematic review

BACKGROUND: genetic testing for cystic fibrosis (CF) has been offered to people with higher risk of being carrier. OBJECTIVES: to assess the effectiveness of population-based CF carrier screening for adults of reproductive age and its optimal organizational features. DESIGN: systematic review. SETTING AND PARTICIPANTS: MedLine, Embase, Cochrane Library, CINAHL and LILACS (1990-2022) were searched to retrieve primary and secondary studies on adults (16 years and older), with no clinical indication or genetic risk, eligible for genetic testing for CF carrier status. MAIN OUTCOMES MEASURES: attitude to screening, uptake of screening offered, informed reproductive choices. RESULTS: a total of 3,326 records were screened and 292 potentially eligible full-text publications assessed. The review included 71 publications, corresponding to 3 reviews, 40 cohort studies (11 comparative, 29 single-arm), and 6 model studies, published between 1992 and 2021 (median 1998). Only one study compared screening or no screening. This study suggested an association between carrier screening and a lower incidence of CF. Comparative studies examined different approaches for invitation and testing, i.e., settings, target population (individuals/couples, prenatal/preconceptional), how invitations are organized (primary care/maternal hospitals), and format and content of the pre-test information. However, no firm conclusions can be drawn on the impact of these features on informed reproductive choices, uptake, and attitude, because of the limitations of the evidence collected. CONCLUSIONS: the broad heterogeneity of the studies, methodological weaknesses, and the limited transferability of the results mean there is still uncertainty about the effectiveness of preconceptional and prenatal CF carrier screening in the general population.

Adherence of systematic reviews to Cochrane RoB2 guidance was frequently poor: a meta epidemiological study.

OBJECTIVES: To assess whether the use of the revised Cochrane risk of bias tool for randomized trials (RoB2) in systematic reviews (SRs) adheres to RoB2 guidance. METHODS: We searched MEDLINE, Embase, Cochrane Library from 2019 to May 2021 to identify SRs using RoB2. We analyzed methods and results sections to see whether risk of bias was assessed at outcome measure level and applied to primary outcomes of the SR as per RoB2 guidance. The relation between SR characteristics and adequacy of RoB2 use was examined by logistic regression analysis. RESULTS: Two hundred-eight SRs were included. We could assess adherence in 137 SRs as 12 declared using RoB2 but actually used RoB1 and 59 did not report the number of primary outcomes. The tool usage was adherent in 69.3% SRs. Considering SRs with multiple primary outcomes, adherence dropped to 28.8%. We found a positive association between RoB2 guidance adherence and the methodological quality of the reviews assessed by AMSTAR2 (p-for-trend 0.007). Multivariable regression analysis suggested journal impact factor [first quartile vs. other quartiles] was associated with RoB2 adherence (OR 0.34; 95% CI: 0.16-0.72). CONCLUSIONS: Many SRs did not adhere to RoB2 guidance as they applied the tool at the study level rather than at the outcome measure level. Lack of adherence was more likely among low and very low quality reviews.

Characteristics and outcomes of vaccinated and nonvaccinated patients hospitalized in a single Italian hub for COVID-19 during the Delta and Omicron waves in Northern Italy.

OBJECTIVE: We compared the characteristics and outcomes of vaccinated and nonvaccinated patients hospitalized with COVID-19. DESIGN: We analyzed patients hospitalized in a COVID hub during three one-month periods: (i) October 15, 2020-November 15, 2020 (prevaccination peak); (ii) October 15, 2021-November 15, 2021 (Delta wave); (iii) December 15, 2021-January 15, 2022 (Omicron wave). To define the epidemiologic context, SARS-CoV-2 infection in healthcare workers was analyzed. RESULTS: SARS-CoV-2 infection incidence in healthcare workers was 146 cases per 1000 persons in 2020 (prevaccination) and 67 in 2021 (postvaccination, when the Omicron variant caused most infections). There were 420 hospitalized patients in the prevaccination period, 51 during the Delta wave (52.1% vaccinated) and 165 during the Omicron wave (52.9% vaccinated). During the Delta wave, a significantly higher number of nonvaccinated (29.2%) than vaccinated patients (3.7%) were admitted to the intensive care unit (ICU) (p = 0.019). Nonvaccinated patients were younger and had a lower rate of concomitant medical conditions (53.2% vs 83.7%; p < 0.001) during the Omicron wave when 80% of patients admitted to ICU and all those who died were still infected by the Delta variant. CONCLUSIONS: Vaccine effectiveness in fragile individuals appears to be lower because of a faster immunity decline. However, the Omicron variant seems to cause less severe COVID-19.