The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin–Siris syndrome

Purpose: Pathogenic variants in ARID1B are one of the most frequent causes of intellectual disability (ID) as determined by large-scale exome sequencing studies. Most studies published thus far describe clinically diagnosed Coffin–Siris patients (ARID1B-CSS) and it is unclear whether these data are representative for patients identified through sequencing of unbiased ID cohorts (ARID1B-ID). We therefore sought to determine genotypic and phenotypic differences between ARID1B-ID and ARID1B-CSS. In parallel, we investigated the effect of different methods of phenotype reporting. Methods: Clinicians entered clinical data in an extensive web-based survey. Results: 79 ARID1B-CSS and 64 ARID1B-ID patients were included. CSS-associated dysmorphic features, such as thick eyebrows, long eyelashes, thick alae nasi, long and/or broad philtrum, small nails and small or absent fifth distal phalanx and hypertrichosis, were observed significantly more often (p < 0.001) in ARID1B-CSS patients. No other significant differences were identified. Conclusion: There are only minor differences between ARID1B-ID and ARID1B-CSS patients. ARID1B-related disorders seem to consist of a spectrum, and patients should be managed similarly. We demonstrated that data collection methods without an explicit option to report the absence of a feature (such as most Human Phenotype Ontology-based methods) tended to underestimate gene-related features

Too busy to care?: Analysing the impact of system-related factors on maternal mortality in Zanzibar's Referral Hospital

This study analyses the contribution of system-related factors to maternal mortality in the low-resource setting of Mnazi Mmoja Hospital in Zanzibar, Tanzania. It is a retrospective cohort study including all maternal deaths (MD, n = 139) and maternal near-misses (MNM, n = 122) in Mnazi Mmoja Hospital with sufficient documentation during 2015 to 2018 (MD) and 2017 to 2018 (MNM). The number of admissions and surgical interventions per health care provider on the day of admission and the number of times vital signs were monitored per day were compared between MNM and MD cases using logistic regression. The mean number of times vital signs were monitored per day was associated with reduced odds of mortality (aOR 0.75, 95% CI 0.64–0.89), after adjustment for confounding factors such as severity of illness. The numbers of admissions or surgical procedures per health care provider were not associated with mortality. Concluding, the degree of monitoring of patients with life-threatening complications of pregnancy or childbirth is associated with the risk of mortality independent of the degree of severity. Preventing maternal mortality requires going beyond availability of essential interventions to tackle system-related factors that have a direct impact on the capacity to provide comprehensive care.Impact StatementWhat is already known on this subject? Root cause analyses of maternal deaths have identified many system-related factors, such as availability of health care providers, adequate training, and motivation to sustain high intensity monitoring (Madzimbamuto et al. 2014; Mahmood et al. 2018). What do the results of this study add? This is the first study to attempt to quantify the contribution of these system-related factors by comparing cases of maternal death with cases of maternal near-miss. We show that the degree of monitoring of patients with life-threatening complications is associated with the odds of mortality independent of the degree of severity. Even though this relation should not be regarded as causative, monitoring of vital signs can be seen as reflective of many system-related factors which hamper or facilitate comprehensive care. What are the implications of these findings for clinical practice and/or further research? This study helps increase general understanding of the factors leading to progression from severe disease to death in a high-volume low-income setting

De prevalentie van huiselijk geweld en kindermishandeling in Nederland

In dit rapport is verslag gedaan van een prevalentieonderzoek naar huiselijk geweld en kindermishandeling in Nederland en van de ontwikkeling daarin sinds de vorige rapportages over huiselijk geweld (Van der Veen & Bogaerts, 2010; Van Dijk et al., 2010; Van der Heijden, Cruyff & Van Gils, 2009) en over kindermishandeling (Alink et al., 2011). Het onderzoek bestaat uit verschillende studies en is op verzoek van het ministerie van Volksgezondheid, Welzijn en Sport en het ministerie van Justitie en Veiligheid door diverse onderzoeksteams uitgevoerd, onder regie van het WODC. De vergelijkbaarheid met de eerdere prevalentiestudies is zo groot mogelijk gehouden. Aanvullend op de prevalentieschattingen is voor het eerst de mate van samenloop tussen huiselijk geweld en kindermishandeling in gezinnen onderzocht. Verder is in het onderzoek meer dan voorheen aandacht geweest voor de vraag wat slachtofferschap van huiselijk geweld, in het bijzonder (ex-)partnergeweld, voor vrouwen en mannen inhoudt. In het rapport wordt ook de context waarin huiselijk geweld en kindermishandeling plaatsvinden uitgebreid beschreven, onder andere met behulp van een zogenoemd ecologisch model. De centrale probleemstelling van deze synthese luidt: Wat is de aard en omvang van huiselijk geweld en kindermishandeling in Nederland, welke ontwikkeling heeft hierin plaatsgevonden en in welke mate is sprake van samenloop van beide vormen van geweld binnen gezinnen? Het volledige onderzoek bestond, naast een drietal voorstudies, uit vijf empirische studies. Twee studies waren primair gericht op het schatten van de omvang van huiselijk geweld onder volwassenen (Van Eijkern et al., 2018; Van der Heijden et al., 2019), twee studies op het schatten van de omvang van kindermishandeling (Schellingerhout & Ramakers, 2017; Alink et al., 2018) en een studie betrof een verdiepend onderzoek onder plegers van partnergeweld en kindermishandeling (Woicik et al., 2018). Deze synthese gaat alleen over de prevalentie van huiselijk geweld en kindermishandeling