Evaluation of low-dose aspirin in the prevention of recurrent spontaneous preterm labour (the APRIL study) : A multicentre, randomised, double-blinded, placebo-controlled trial

Funding: MdB, LV, TN, BM, MO and CdG received funding from ZonMw, The Dutch Organisation for Health Research and Development (grant number 836041006). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Perspectives of patients with type 1 or insulin-treated type 2 diabetes on self-monitoring of blood glucose: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Self-monitoring of blood glucose (SMBG), including self-regulation, is an important tool to achieve good glycemic control. However, many patients measure their glucose concentrations less often than is recommended. This study investigates patients' perspectives of SMBG and all relevant aspects influencing SMBG in patients with type 1 and insulin-treated type 2 diabetes.</p> <p>Methods</p> <p>In depth interviews were conducted with 13 patients with type 1 diabetes from an outpatient clinic and 15 patients with type 2 diabetes from general practices. All interviews were transcribed verbatim and analyzed using the Grounded Theory approach.</p> <p>Results</p> <p>A wide variety of SMBG was encountered. Perceptions, goals of SMBG and personal and contextual factors were identified, influencing the respondents' perspective of SMBG, and leading to this variety. Respondents experienced a discrepancy between their own and the professionals' perceptions and goals. Respondents' perception of SMBG ranged along a continuum from 'friend' to 'foe'. With respect to the goals, the respondents experienced tension between achieving good glycemic control and quality of life, and deliberately made their own choices. The performance of SMBG was tailored to their perceptions and personal goals. Personal and contextual factors such as hypo- or hyper (un)awareness, knowledge, and contact with professionals acted as either facilitating factors or as barriers to SMBG, depending on the respondents' perspective. A SMBG model was developed providing a representation of the factors and their interrelations.</p> <p>Respondents with type 1 diabetes seemed more resigned to their situation and SMBG was more integrated into their lives.</p> <p>Conclusions</p> <p>From the patients' perspective, professionals positively present SMBG as a 'friend' in order to achieve strict glycemic control. Whereas patients can also perceive SMBG as a 'foe'. They primarily seek a personal balance between achieving glycemic control and quality of life, leading them to deliberately make other choices regarding SMBG performance than was recommended. Gaining insight and discussing all factors affecting SMBG will help professionals and patients come to mutually agreed goals and to tailor the performance of SMBG to the individual patient. This should result in a more optimal use of SMBG, an improved quality of life, and improved clinical parameters.</p

A systematic review with meta-analysis of biomarkers for detection of pulmonary arterial hypertension

Rationale The blood is a rich source of potential biomarkers for the diagnosis of idiopathic and hereditary pulmonary arterial hypertension (iPAH and hPAH, referred to as “PAH”). While a lot of biomarkers have been identified for PAH, the clinical utility of these biomarkers often remains unclear. Here, we performed an unbiased meta-analysis of published biomarkers to identify biomarkers with the highest performance for detection of PAH. Methods A literature search (in PubMed, Embase.com, Clarivate Analytics/Web of Science Core Collection and Wiley/Cochrane Library) was performed up to 28 January 2021. Primary end points were blood biomarker levels in PAH versus asymptomatic controls or patients suspected of pulmonary hypertension (PH) with proven normal haemodynamic profiles. Results 149 articles were identified by the literature search. Meta-analysis of 26 biomarkers yielded 17 biomarkers that were differentially expressed in PAH and non-PH control subjects. Red cell distribution width, low density lipid-cholesterol, d-dimer, N-terminal prohormone of brain natriuretic protein (NT-proBNP), interleukin-6 (IL-6) and uric acid were biomarkers with the largest observed differences, largest sample sizes and a low risk of publication bias. Receiver operating characteristic curves and sensitivity/ specificity analyses demonstrated that NT-proBNP had a high sensitivity, but low specificity for PAH. For the other biomarkers, insufficient data on diagnostic accuracy with receiver operating characteristic curves were available for meta-analysis. Conclusion This meta-analysis validates NT-proBNP as a biomarker with high sensitivity for PAH, albeit with low specificity. The majority of biomarkers evaluated in this meta-analysis lacked either external validation or data on diagnostic accuracy. Further validation studies are required as well as studies that test combinations of biomarkers to improve specificity

Recurrent ventricular arrhythmias and mortality in cardiac arrest survivors with a reversible cause with and without an implantable cardioverter defibrillator: A systematic review

Background: Sudden cardiac arrest survivors with a reversible cause are not eligible for implantable cardioverter defibrillator (ICD) implantation. This study aims to evaluate the risk of recurrent ventricular arrhythmia in sudden cardiac arrest survivors with a reversible cause and evaluate if ICD implantation increases survival. Methods: We conducted a systematic review to identify studies evaluating ICD implantation in sudden cardiac arrest survivors with a reversible cause. Outcomes were mortality and appropriate device therapy. Sudden cardiac arrest patients were divided into 4 subgroups: due to acute myocardial infarction; due to coronary artery spasm; due to takotsubo cardiomyopathy; and studies with various reversible causes of cardiac arrest. Results: 27 studies were included, evaluating 11,402 patients. A total of 2570 patients received an ICD. Studies evaluating coronary artery spasm and with various reversible causes showed a relatively high rate of appropriate device therapy (17% and 20%) and described an increased survival in ICD patients. Takotsubo cardiomyopathy was associated with a low mortality and none of the ICD patients received appropriate device therapy. Studies evaluating acute myocardial infarction survivors reported inconsistent results, with high numbers of appropriate device therapy (12–66%), but the mortality-rate of patients with and without an ICD varied. Conclusion: This study shows that the recurrence risk of ventricular arrhythmia varies between different reversible causes of sudden cardiac arrest and should not be evaluated as one entity. Cardiac arrest survivors with a reversible cause can be at risk of recurrent ventricular arrhythmia and selected patients may benefit from ICD implantation

Evaluation of low-dose aspirin in the prevention of recurrent spontaneous preterm labour (the APRIL study): A multicentre, randomised, double-blinded, placebo-controlled trial

Background Preterm birth is the leading cause of neonatal morbidity and mortality. The recurrence rate of spontaneous preterm birth is high, and additional preventive measures are required. Our objective was to assess the effectiveness of low-dose aspirin compared to placebo in the prevention of preterm birth in women with a previous spontaneous preterm birth. Methods and findings We performed a parallel multicentre, randomised, double-blinded, placebo-controlled trial (the APRIL study). The study was performed in 8 tertiary and 26 secondary care hospitals in the Netherlands. We included women with a singleton pregnancy and a history of spontaneous preterm birth of a singleton between 22 and 37 weeks. Participants were randomly assigned to aspirin 80 mg daily or placebo initiated between 8 and 16 weeks of gestation and continued until 36 weeks or delivery. Randomisation was computer generated, with allocation concealment by using sequentially numbered medication containers. Participants, their healthcare providers, and researchers were blinded for treatment allocation. The primary outcome was preterm birth grade 1, intraventricular hemorrhage > grade 2, necrotising enterocolitis > stage 1, retinopathy of prematurity, culture proven sepsis, or perinatal death). Analyses were performed by intention to treat. From May 31, 2016 to June 13, 2019, 406 women were randomised to aspirin (n = 204) or placebo (n = 202). A total of 387 women (81.1% of white ethnic origin, mean age 32.5 ± SD 3.8) were included in the final analysis: 194 women were allocated to aspirin and 193 to placebo. Preterm birth <37 weeks occurred in 41 (21.2%) women in the aspirin group and 49 (25.4%) in the placebo group (relative risk (RR) 0.83, 95% confidence interval (CI) 0.58 to 1.20, p = 0.32). In women with ≥80% medication adherence, preterm birth occurred in 24 (19.2%) versus 30 (24.8%) women (RR 0.77, 95% CI 0.48 to 1.25, p = 0.29). The rate of the composite of poor neonatal outcome was 4.6% (n = 9) versus 2.6% (n = 5) (RR 1.79, 95% CI 0.61 to 5.25, p = 0.29). Among all randomised women, serious adverse events occurred in 11 out of 204 (5.4%) women allocated to aspirin and 11 out of 202 (5.4%) women allocated to placebo. None of these serious adverse events was considered to be associated with treatment allocation. The main study limitation is the underpowered sample size due to the lower than expected preterm birth rates. Conclusions In this study, we observed that low-dose aspirin did not significantly reduce the preterm birth rate in women with a previous spontaneous preterm birth. However, a modest reduction of preterm birth with aspirin cannot be ruled out. Further research is required to determine a possible beneficial effect of low-dose aspirin for women with a previous spontaneous preterm birth

Evaluation of low-dose aspirin in the prevention of recurrent spontaneous preterm labour (the APRIL study): A multicentre, randomised, double-blinded, placebo-controlled trial

Background Preterm birth is the leading cause of neonatal morbidity and mortality. The recurrence rate of spontaneous preterm birth is high, and additional preventive measures are required. Our objective was to assess the effectiveness of low-dose aspirin compared to placebo in the prevention of preterm birth in women with a previous spontaneous preterm birth. Methods and findings We performed a parallel multicentre, randomised, double-blinded, placebo-controlled trial (the APRIL study). The study was performed in 8 tertiary and 26 secondary care hospitals in the Netherlands. We included women with a singleton pregnancy and a history of spontaneous preterm birth of a singleton between 22 and 37 weeks. Participants were randomly assigned to aspirin 80 mg daily or placebo initiated between 8 and 16 weeks of gestation and continued until 36 weeks or delivery. Randomisation was computer generated, with allocation concealment by using sequentially numbered medication containers. Participants, their healthcare providers, and researchers were blinded for treatment allocation. The primary outcome was preterm birth grade 1, intraventricular hemorrhage > grade 2, necrotising enterocolitis > stage 1, retinopathy of prematurity, culture proven sepsis, or perinatal death). Analyses were performed by intention to treat. From May 31, 2016 to June 13, 2019, 406 women were randomised to aspirin (n = 204) or placebo (n = 202). A total of 387 women (81.1% of white ethnic origin, mean age 32.5 ± SD 3.8) were included in the final analysis: 194 women were allocated to aspirin and 193 to placebo. Preterm birth <37 weeks occurred in 41 (21.2%) women in the aspirin group and 49 (25.4%) in the placebo group (relative risk (RR) 0.83, 95% confidence interval (CI) 0.58 to 1.20, p = 0.32). In women with ≥80% medication adherence, preterm birth occurred in 24 (19.2%) versus 30 (24.8%) women (RR 0.77, 95% CI 0.48 to 1.25, p = 0.29). The rate of the composite of poor neonatal outcome was 4.6% (n = 9) versus 2.6% (n = 5) (RR 1.79, 95% CI 0.61 to 5.25, p = 0.29). Among all randomised women, serious adverse events occurred in 11 out of 204 (5.4%) women allocated to aspirin and 11 out of 202 (5.4%) women allocated to placebo. None of these serious adverse events was considered to be associated with treatment allocation. The main study limitation is the underpowered sample size due to the lower than expected preterm birth rates. Conclusions In this study, we observed that low-dose aspirin did not significantly reduce the preterm birth rate in women with a previous spontaneous preterm birth. However, a modest reduction of preterm birth with aspirin cannot be ruled out. Further research is required to determine a possible beneficial effect of low-dose aspirin for women with a previous spontaneous preterm birth