Screening for sickle cell disease in newborns: a systematic review.

BACKGROUND: Sickle cell disease (SCD) is an inherited autosomal recessive disorder caused by the replacement of normal haemoglobin (HbA) by mutant Hb (sickle Hb, HbS). The sickle-shaped red blood cells lead to haemolysis and vaso-occlusion. Especially in the first years of life, patients with SCD are at high risk of life-threatening complications. SCD prevalence shows large regional variations; the disease predominantly occurs in sub-Saharan Africa. We aimed to systematically assess the evidence on the benefit of newborn screening for SCD followed by an earlier treatment start. METHODS: We systematically searched bibliographic databases (MEDLINE, EMBASE, Cochrane Databases, and the Health Technology Assessment Database), trial registries, and other sources to identify systematic reviews and randomised controlled trials (RCTs) or non-randomised trials on newborn screening for SCD. The last search was in 07/2020. Two reviewers independently reviewed abstracts and full-text articles and assessed the risk of bias of the studies included. Data were extracted by one person and checked by another. As meta-analyses were not possible, a qualitative summary of results was performed. RESULTS: We identified 1 eligible study with direct evidence: a Jamaican retrospective study evaluating newborn screening for SCD followed by preventive measures (prevention of infections and education of parents). The study included 500 patients with SCD (intervention group, 395; historical control group, 105). Although the results showed a high risk of bias, the difference between the intervention and the control group was very large: mortality in children decreased by a factor of about 10 in the first 5 years of life (0.02% in the intervention group vs. 0.19% in the control group, odds ratio 0.09; 95% confidence interval [0.04; 0.22], p < 0.001). CONCLUSION: The results are based on a single retrospective study including historical controls. However, the decrease of mortality by a factor of 10 is unlikely to be explained by bias alone. Therefore, in terms of mortality, data from this single retrospective study included in our systematic review suggest a benefit of newborn screening for SCD (followed by preventive measures) versus no newborn screening for SCD (weak certainty of conclusions).

[GRADE: Evidence to Decision (EtD) framework for coverage decisions]. / GRADE: Von der Evidenz zur Empfehlung oder Entscheidung ­ Entscheidungen zur Kostenerstattung.

BACKGROUND: Coverage decisions are decisions by third party payers about whether and how much to pay for technologies or services, and under what conditions. Given their complexity, a systematic and transparent approach is needed. The DECIDE project, a GRADE working group initiative funded by the European Union, has developed GRADE Evidence to Decision (EtD) frameworks for different types of decisions, including coverage ones. METHODS: We used an iterative approach, including brainstorming to generate ideas, consultation with stakeholders, user testing, and pilot testing of the framework. RESULTS: The general structure of the EtD includes formulation of the question, an assessment using 12 criteria, and conclusions. Criteria that are relevant for coverage decisions are similar to those for clinical recommendations from a population perspective. Important differences between the two include the decision-making processes, accountability, and the nature of the judgments that need to be made for some criteria. Although cost-effectiveness is a key consideration when making coverage decisions, it may not be the determining factor. Strength of recommendation is not directly linked to the type of coverage decisions, but when there are important uncertainties, it may be possible to cover an intervention for a subgroup, in the context of research, with price negotiation, or with restrictions. CONCLUSION: The EtD provides a systematic and transparent approach for making coverage decisions. It helps ensure consideration of key criteria that determine whether a technology or service should be covered and that judgments are informed by the best available evidence.

Benefits and harms of screening for and treatment of asymptomatic bacteriuria in pregnancy: a systematic review.

BACKGROUND: Most European and North American clinical practice guidelines recommend screening for asymptomatic bacteriuria (ASB) as a routine pregnancy test. Antibiotic treatment of ASB in pregnant women is supposed to reduce maternal upper urinary tract infections (upper UTIs) and preterm labour. However, most studies supporting the treatment of ASB were conducted in the 1950s to 1980s. Because of subsequent changes in treatment options for ASB and UTI, the applicability of findings from these studies has come into question. Our systematic review had three objectives: firstly, to assess the patient-relevant benefits and harms of screening for ASB versus no screening; secondly, to compare the benefits and harms of different screening strategies; and thirdly, in case no reliable evidence on the overarching screening question was identified, to determine the benefits and harms of treatment of ASB. METHODS: We systematically searched several bibliographic databases, trial registries, and other sources (up to 02/2016) for randomised controlled trials (RCTs) and prospective non-randomised trials. Two authors independently reviewed abstracts and full-text articles and assessed the risk of bias of the studies included. As meta-analyses were not possible, we summarised the results qualitatively. RESULTS: We did not identify any eligible studies that investigated the benefits and harms of screening for ASB versus no screening or that compared different screening strategies. We identified four RCTs comparing antibiotics with no treatment or placebo in 454 pregnant women with ASB. The results of 2 studies published in the 1960s showed a statistically significant reduction in rates of pyelonephritis (odds ratio [OR] = 0.21, 95 % confidence interval [CI] 0.07-0.59) and lower UTI (OR = 0.10, 95 % CI 0.03-0.35) in women treated with antibiotics. By contrast, event rates reported by a recent study were not statistically significantly different, neither regarding pyelonephritis (0 % vs. 2.2 %; OR = 0.37, CI 0.01-9.25, p = 0.515) nor regarding lower UTI during pregnancy (10 % vs. 18 %; Peto odds ratio [POR] = 0.53, CI 0.16-1.79, p = 0.357). Data were insufficient to determine the risk of harms. As three of the four studies were conducted several decades ago and have serious methodological shortcomings, the applicability of their findings to current health care settings is likely to be low. The recent high-quality RCT was stopped early due to a very low number of primary outcome events, a composite of preterm delivery and pyelonephritis. Therefore, the results did not show a benefit of treating ASB. CONCLUSIONS: To date, no reliable evidence supports routine screening for ASB in pregnant women.