Do studies evaluating early-life policy interventions fully adhere to the critical conditions of difference-in-differences? A systematic review.

OBJECTIVES: To assess the reporting and methodological quality of early-life policy intervention papers that applied difference-in-differences (DiD) analysis. STUDY DESIGN: Systematic review. DATA SOURCES: Papers applying DiD of early-life policy interventions in high-income countries as identified by searching Medline, Embase and Scopus databases up to December, 2022. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS AND INTERVENTIONS: Studies evaluating policy interventions targeting expectant mothers, infants or children up to two years old and conducted in high income countries were included. We focused on seven critical conditions of DiD as proposed in a comprehensive checklist: data requirements, parallel trends, no-anticipation, standard statistical assumptions, common shocks, group composition and spillover. RESULTS: The DiD included studies (n=19) evaluating early-life policy interventions in childhood development (n=4), healthcare utilisation and providers (n=4), nutrition programmes (n=3) and economic policies such as prenatal care expansion (n=8). Although none of the included studies met all critical conditions, the most reported and adhered to critical conditions were data requirements (n=18), standard statistical assumptions (n=11) and the parallel trends assumption (n=9). No-anticipation and spillover were explicitly reported and adhered to in two studies and one study, respectively. CONCLUSIONS: This review highlights current deficiencies in the reporting and methodological quality of studies using DiD to evaluate early-life policy interventions. As the validity of study conclusions and consequent implications for policy depend on the extent to which critical conditions are met, this shortcoming is concerning. We recommend that researchers use the described checklist to improve the transparency and validity of their evaluations. The checklist should be further refined by adding order of importance or knock-out criteria and may also help facilitate uniform terminology. This will hopefully encourage reliable DiD evaluations and thus contribute to better policies relating to expectant mothers, infants and children.

Evaluation of completely online psychotherapy with app-support versus therapy as usual for clients with depression or anxiety disorder: A retrospective matched cohort study investigating the effectiveness, efficiency, client satisfaction, and costs.

INTRODUCTION: Depressive and anxiety disorders are common mental disorders ranking among the leading causes of global disease burden. Not all clients currently benefit from therapy and clients are looking for modern ways of therapy. Online psychotherapy is a promising option for better meeting clients' needs. Recently, a new psychotherapy concept has emerged that combines videoconferencing sessions with support through a mobile application. The latter allows for ecological momentary assessments and interventions, facilitates communication between patients and therapists in between sessions through chat, and allows for incorporating feedback-informed treatment principles. MATERIAL AND METHODS: The study was a retrospective observational matched cohort study, comparing online psychotherapy with Therapy As Usual (TAU) for clients with depressive or anxiety disorders. Data were obtained via questionnaires, which are part of standard clinical care. Primary outcomes included general mental functioning, and symptoms of depression and anxiety. Secondary outcomes were efficiency, client satisfaction, and therapy costs. Primary endpoints were analyzed using linear mixed models analysis, with an interaction term between time and group. Secondary outcomes were analyzed using linear regression. RESULTS: Larger improvements were observed in the online compared to the TAU group for general mental functioning and depressive disorder (i.e., General mental functioning: B = -8.50, 95 CI: -15.01 - -1.97, p = 0.011; Depressive disorder: B = - 3.66, 95 % CI: -5.79 - -1.54p < 0.01). No significant differences in change over time between the two groups were observed for anxiety disorder (B = -3.64, 95 % CI: (-13.10 - 5.82) p = 0.447). The total number of sessions was significantly higher in the online psychotherapy group than in TAU (B = 3.71, p < 0.01), although clients were matched on treatment time in weeks. Treatment session duration in minutes was comparable across the groups. DISCUSSION: Online psychotherapy with app support showed to be a promising alternative to TAU for depressive and anxiety disorders. More research is needed to evaluate the effectiveness, cost-effectiveness and client satisfaction of online psychotherapy compared to TAU, such as randomized controlled trials or studies multiple baseline series designs, and in-depth qualitative research.

Ruling out acute coronary syndrome in primary care with a clinical decision rule and a capillary, high-sensitive troponin I point of care test: study protocol of a diagnostic RCT in the Netherlands (POB HELP).

INTRODUCTION: Chest pain is a common reason for consultation in primary care. To rule out acute coronary syndrome (ACS), general practitioners (GP) refer 40%-70% of patients with chest pain to the emergency department (ED). Only 10%-20% of those referred, are diagnosed with ACS. A clinical decision rule, including a high-sensitive cardiac troponin-I point-of-care test (hs-cTnI-POCT), may safely rule out ACS in primary care. Being able to safely rule out ACS at the GP level reduces referrals and thereby alleviates the burden on the ED. Moreover, prompt feedback to the patients may reduce anxiety and stress. METHODS AND ANALYSIS: The POB HELP study is a clustered randomised controlled diagnostic trial investigating the (cost-)effectiveness and diagnostic accuracy of a primary care decision rule for acute chest pain, consisting of the Marburg Heart Score combined with a hs-cTnI-POCT (limit of detection 1.6 ng/L, 99th percentile 23 ng/L, cut-off value between negative and positive used in this study 3.8 ng/L). General practices are 2:1 randomised to the intervention group (clinical decision rule) or control group (regular care). In total 1500 patients with acute chest pain are planned to be included by GPs in three regions in The Netherlands. Primary endpoints are the number of hospital referrals and the diagnostic accuracy of the decision rule 24 hours, 6 weeks and 6 months after inclusion. ETHICS AND DISSEMINATION: The medical ethics committee Leiden-Den Haag-Delft (the Netherlands) has approved this trial. Written informed consent will be obtained from all participating patients. The results of this trial will be disseminated in one main paper and additional papers on secondary endpoints and subgroup analyses. TRIAL REGISTRATION NUMBERS: NL9525 and NCT05827237.

Telemonitoring for Patients With COVID-19: Recommendations for Design and Implementation.

Despite significant efforts, the COVID-19 pandemic has put enormous pressure on health care systems around the world, threatening the quality of patient care. Telemonitoring offers the opportunity to carefully monitor patients with a confirmed or suspected case of COVID-19 from home and allows for the timely identification of worsening symptoms. Additionally, it may decrease the number of hospital visits and admissions, thereby reducing the use of scarce resources, optimizing health care capacity, and minimizing the risk of viral transmission. In this paper, we present a COVID-19 telemonitoring care pathway developed at a tertiary care hospital in the Netherlands, which combined the monitoring of vital parameters with video consultations for adequate clinical assessment. Additionally, we report a series of medical, scientific, organizational, and ethical recommendations that may be used as a guide for the design and implementation of telemonitoring pathways for COVID-19 and other diseases worldwide.

Evaluation of mode of birth in pregnant women with heart disease.

OBJECTIVE: Maternal heart disease (HD) complicates 1-4 % of pregnancies and is associated with adverse maternal and fetal outcomes. Although vaginal birth is generally recommended in the guidelines, cesarean section (CS) rates in women with HD are often high. Aim of the present study was to evaluate mode of birth and pregnancy outcomes in women with HD in a tertiary care hospital in the Netherlands. STUDY DESIGN: The study population consisted of 128 consecutive pregnancies in 99 women with HD, managed by a pregnancy heart team between 2012-2017 and ending in births after 24 weeks' gestation. Pregnancy risk was assessed per modified World Health Organization class. Mode of birth (planned and performed) and maternal and fetal complications (cardiovascular events, postpartum hemorrhage, prematurity, small for gestational age and death) were assessed for each pregnancy. RESULTS: Pregnancy risk was classified as modified World Health Organization class I in 23 %, class II in 50 %, class III in 21 % and class IV in 6% of pregnancies. Planned mode of birth was vaginal in 114 pregnancies (89 %) and CS in 14 (11 %; nine for obstetric and five for cardiac indication). An unplanned CS was performed in 18 pregnancies (16 %; 16 for obstetric and two for cardiac indications). Overall mode of birth was vaginal in 75 % and CS in 25 %. Twelve cardiovascular events occurred in eight pregnancies (6 %), postpartum hemorrhage in nine (7 %) and small for gestational age in 14 (11 %). No maternal or fetal deaths occurred. CONCLUSIONS: Findings of this study indicate that - given that pregnancies are managed and mode of birth is meticulously planned by a multidisciplinary pregnancy heart team - vaginal birth is a suitable option for women with HD.

Maternal mortality due to cardiac disease in low- and middle-income countries.

OBJECTIVES: To assess the frequency of maternal death (MD) due to cardiac disease in low- and middle-income countries (LMIC). METHODS: Systematic review searching Medline, EMBASE, Web of Science, Cochrane Library, Emcare, LILACS, African Index Medicus, IMEMR, IndMED, WPRIM, IMSEAR up to 01/Nov/2017. Maternal mortality reports from LMIC reviewing all MD in a given geographical area were included. Hospital-based reports or those solely based on verbal autopsies were excluded. Numbers of MD and cardiac-related deaths were extracted. We calculated cardiac disease MMR (cMMR, cardiac-related MD/100 000 live births) and proportion of cardiac-related MDs among all MDs. Frequency of cardiac MD was compared with the MMR of the country. RESULTS: Forty-seven reports were included, which reported on 38,486 maternal deaths in LMIC. Reported cMMR ranged from 0/100 000 live births (Moldova, Ghana) to 31.9/100 000 (Zimbabwe). The proportion of cardiac-related MD ranged from 0% (Moldova, Ghana) to 24.8% (Sri Lanka). In countries with a higher MMR, cMMR was also higher. However, the proportion of cardiac-related MD was higher in countries with a lower MMR. CONCLUSIONS: The burden of cardiac-related mortality is difficult to assess due limited availability of mortality reports. The proportion of cardiac deaths among all MD appeared to be higher in countries with a lower MMR. This is in line with what has been called 'obstetric transition': pre-existing medical diseases including cardiac disease are becoming relatively more important where the MMR falls.

OBJECTIFS: Evaluer la fréquence des décès maternels (DM) dus à une maladie cardiaque dans les pays à revenu faible ou intermédiaire (PRFI). MÉTHODES: Revue systématique en recherchant sur Medline, EMBASE, Web of Science, Cochrane Library, Emcare, LILACS, African Index Medicus, IMEMR, IndMED , WPRIM, IMSEAR jusqu'au 1er novembre 2017. Les reports de mortalité maternelle provenant des PRFI examinant tous les DM dans une zone géographique donnée ont été inclus. Les reports en milieu hospitalier ou ceux basés uniquement sur des autopsies verbales ont été exclus. Le nombre de DM et de décès liés à la maladie cardiaque a été extrait. Nous avons calculé le taux de mortalité maternelle par maladie cardiaque (TMMc, DM lié à un effet cardiaque/100.000 naissances vivantes) et la proportion de DM cardiaques parmi tous les DM. La fréquence des DM cardiaques a été comparée au TMM du pays. RÉSULTATS: 47 reports ont été inclus, faisant état de 38.486 décès maternels dans les PRFI. Le TMMc rapporté allait de 0/100.000 naissances vivantes (Moldavie, Ghana) à 31,9/100.000 (Zimbabwe). La proportion de DM d'origine cardiaque variait de 0% (Moldavie, Ghana) à 24,8% (Sri Lanka). Dans les pays avec un TMM plus élevé, le TMMc était également plus élevé. Cependant, la proportion de DM d'origine cardiaque était plus élevée dans les pays où le TMM était inférieur. CONCLUSIONS: La charge de la mortalité liée à une maladie cardiaque est difficile à évaluer en raison de la disponibilité limitée des rapports de mortalité. La proportion de décès cardiaques parmi tous les DM semble être plus élevée dans les pays où le TMM est plus faible. Cela correspond à ce que l'on a appelé la «transition obstétricale¼: les maladies médicales préexistantes, y compris les maladies cardiaques, deviennent relativement plus importantes là où le TMM chute.

Exercise haemodynamics after restrictive mitral annuloplasty for functional mitral regurgitation.

AIMS: Restrictive mitral annuloplasty (RMA) can provide a durable solution for functional mitral regurgitation (MR), but might result in obstruction to antegrade mitral flow. Aim of this study was to assess the magnitude of change in mitral valve area (MVA) during exercise after RMA, to relate the change in MVA to left ventricular (LV) geometry and function, and to assess its haemodynamic and clinical impact. METHODS AND RESULTS: Bicycle exercise echocardiography was performed in 32 patients after RMA. Echocardiographic data at rest and during exercise were compared with preoperative echocardiographic data. Clinical endpoints were collected following the study visit. MVA increased during exercise in 25 patients (1.6 ± 0.4 cm2 to 2.0 ± 0.6 cm2, P < 0.001), whereas MVA decreased in 7 patients (1.8 ± 0.5 cm2 to 1.5 ± 0.4 cm2, P = 0.020). Patients with an increased MVA showed a significant reduction in LV volumes at rest compared to preoperatively, and an increase in stroke volume and cardiac output (CO) during exercise. In patients with decreased MVA, LV reverse remodelling was absent and myocardial flow reserve limited. Patients with decreased exercise MVA had a higher increase in mean pulmonary artery pressure (PAP) with respect to CO and worse survival 36 months after the study visit (69±19% vs. 92±5%, P = 0.005). CONCLUSIONS: Both increased and decreased MVA were observed during exercise echocardiography after RMA for functional MR. Change in MVA was related to the extent of LV geometrical and functional changes. A decreased MVA during exercise was associated with a higher increase in mean PAP with respect to CO, and worse survival.

Vasoplegia After Restrictive Mitral Annuloplasty for Functional Mitral Regurgitation in Patients With Heart Failure.

OBJECTIVES: Patients undergoing heart failure surgery are at risk for developing postoperative vasoplegia. The aim of this study was to determine the incidence, survival, and predictors of vasoplegia in heart failure patients undergoing mitral valve repair for functional mitral regurgitation and to evaluate the effect of ischemic versus non-ischemic etiology. DESIGN: Retrospective. SETTING: University medical center, single institutional. PARTICIPANTS: Heart failure patients with functional mitral regurgitation who underwent restrictive mitral annuloplasty (2006-2015). MEASUREMENTS AND MAIN RESULTS: One hundred twenty-two patients were included (48% ischemic etiology). The incidence of vasoplegia was 19% and was not influenced by mitral regurgitation etiology. Ninety-day survival rate was decreased in vasoplegic compared with non-vasoplegic patients (65% v 93%, p < 0.001). After adjusting for age, gender, and heart failure etiology, prior hypertension (odds ratio [OR] 0.28; 95% confidence interval [CI] 0.08-0.91; p = 0.034), higher creatinine clearance (OR 0.97; 95% CI 0.95-0.99; p = 0.009), and beta-blocker use (OR 0.25; 95% CI 0.09-0.73; p = 0.011) decreased the risk of vasoplegia. Anemia (OR 3.00; 95% CI 1.10-8.20; p = 0.032) and longer cross clamp (OR 1.03; 95% CI 1.01-1.04; p = 0.001), cardiopulmonary bypass (OR 1.01; 95% CI 1.00-1.02; p = 0.003), and procedure times (OR 1.01; 95% CI 1.00-1.02, p = 0.002) increased the risk of vasoplegia. CONCLUSIONS: Vasoplegia occurs in 19% of heart failure patients undergoing mitral valve repair for functional mitral regurgitation. It is associated with a poor early outcome. Prior hypertension, a higher creatinine clearance, and beta-blocker use were associated with a decreased risk of vasoplegia, whereas anemia and longer procedure times were associated with an increased risk of vasoplegia, independent of heart failure etiology.

Impact of recurrent mitral regurgitation after mitral valve repair for functional mitral regurgitation: long-term analysis of competing outcomes.

AIMS: Recurrent mitral regurgitation (MR) has been reported after mitral valve repair for functional MR. However, the impact of recurrent MR on long-term survival remains poorly defined. In the present study, mortality-adjusted recurrent MR rates, the clinical impact of recurrent MR and its determinants were studied in patients after mitral valve repair with revascularization for functional MR in the setting of ischaemic heart disease. METHODS AND RESULTS: Long-term clinical and echocardiographic outcome was evaluated in 261 consecutive patients after restrictive mitral annuloplasty and revascularization for moderate to severe functional MR, between 2000 and 2014. The cumulative incidence of recurrent MR ≥ Grade 2, assessed by competing risk analysis, was 9.6 ± 1.8% at 1-year, 20.3 ± 2.5% at 5-year, and 27.6 ± 2.9% at 10-year follow-up. Cumulative survival was 85.8% [95% confidence interval (CI) 81.0-90.0] at 1-year, 67.3% (95% CI 61.1-72.6%) at 5-year, and 46.1% (95% CI 39.4-52.6%) at 10-year follow-up. Age, preoperative New York Heart Association Class III or IV, a history of renal failure, and recurrence of MR expressed as a time-dependent variable [HR 3.28 (1.87-5.75), P < 0.001], were independently associated with an increased mortality risk. Female gender, a history of ST-elevation myocardial infarction, a preoperative QRS duration ≥120 ms, a higher preoperative MR grade, and a higher indexed left ventricular end-systolic volume were independently associated with an increased likelihood of recurrent MR. CONCLUSION: Mitral valve repair for functional ischaemic MR resulted in a low incidence of recurrent MR with favourable clinical outcome up to 10 years after surgery. Presence of recurrent MR at any moment after surgery proved to be independently associated with an increased risk for mortality.

10-Year Outcomes After Left Ventricular Reconstruction: Rethinking the Impact of Mitral Regurgitation.

BACKGROUND: Heart failure with reduced ejection fraction due to a post-infarction anteroseptal aneurysm carries a poor prognosis. Patients with refractory heart failure may be considered for advanced surgery, including left ventricular assist device implantation, heart transplantation and left ventricular reconstruction. The aim of this study was to evaluate outcomes after an integrated approach of left ventricular reconstruction with concomitant procedures (mitral/tricuspid valve repair, coronary revascularization), and assess risk factors for event-free survival, focusing on left ventricular geometry/function and presence of functional mitral regurgitation (MR). METHODS: A total of 159 consecutive heart failure patients who underwent left ventricular reconstruction between 2002 and 2011 were included. Mid-term echocardiographic and long-term clinical outcomes were evaluated. Preoperative risk factors were correlated to event-free survival (freedom from mortality, left ventricular assist device implantation, and heart transplantation). RESULTS: Mid-term echocardiography demonstrated decreased indexed left ventricular end-systolic volumes (89 ± 42 mL/m2 preoperatively; 51 ± 18 at mid-term, p < 0.001), and absence of MR ≥ grade 2. Event-free survival was 83% ± 3% at 1-year, 68% ± 4% at 5-year, and 46% ± 4% at 10-year follow-up. Preoperative wall motion score index (WMSI; hazard ratio [HR] 3.1, 95% confidence interval [CI] 1.7-5.8, p < 0.001) and presence of MR ≥ grade 2 (HR 1.9, 95% CI 1.1-3.1, p = 0.014) were independently associated with adverse event-free survival. CONCLUSIONS: Event-free survival is favorable in patients with WMSI < 2.5 and significantly worse when WMSI is ≥ 2.5. In both groups, the presence of preoperative MR ≥ grade 2 negatively affects event-free survival, despite successful correction of MR. Risk stratification by preoperative WMSI and MR grade supports the Heart team in choosing the optimal surgical strategy for patients with refractory heart failure.

Prognostic value of left ventricular reverse remodelling and recurrent mitral regurgitation after personalized surgical treatment of patients with non-ischaemic cardiomyopathy and functional mitral regurgitation.

OBJECTIVES: The aim of this study was to determine the prevalence of left ventricular reverse remodelling (LVRR) and recurrent mitral regurgitation (MR) at mid-term follow-up (1-2 years after surgery) in patients after personalized surgical treatment of heart failure and functional MR due to non-ischaemic cardiomyopathy and to assess their prognostic impact on long-term clinical outcomes. METHODS: Consecutive patients with refractory heart failure and non-ischaemic MR, who underwent mitral valve surgery with or without additional procedures, were identified. Patients with complete preoperative and mid-term echocardiographic data were included. LVRR (≥15% decrease in indexed left ventricular end-systolic volume) and recurrent MR (≥ Grade 2) were echocardiographically assessed at mid-term follow-up, and the primary end point was a composite of all-cause mortality and heart transplantation (HTx-free survival). RESULTS: The prevalence of LVRR was 38%, and the prevalence of recurrent MR was 20% at mid-term follow-up. The absence of LVRR and the presence of recurrent MR-which were highly correlated-were significantly associated with worse HTx-free survival. HTx-free survival 1 and 3 years after mid-term follow-up were 100% and 88 ± 6% in patients with LVRR (n = 29), 82 ± 7% and 68 ± 8% in patients without LVRR and without recurrent MR (n = 34), and 49 ± 14% and 33 ± 13% in patients without LVRR and with recurrent MR (n = 14). CONCLUSIONS: Patients with LVRR at mid-term follow-up showed favourable HTx-free survival, whereas HTx-free survival was significantly worse in patients without LVRR and without recurrent MR and extremely poor in patients without LVRR and with recurrent MR. Close echocardiographic monitoring is warranted for timely identification of this latter subgroup of patients, in order to re-evaluate additional treatment options and improve their prognosis.