Objective
The severe forms of hypertriglyceridaemia (HTG) are caused by mutations in genes that lead to loss of function of lipoprotein lipase (LPL). In most patients with severe HTG (TG >10 mmol/L) it is a challenge to define the underlying cause. We investigated the molecular basis of severe HTG in patients referred to the Lipid Clinic at the Academic Medical Center Amsterdam.
Methods
The coding regions of LPL, APOC2, APOA5 and two novel genes, lipase maturation factor 1 (LMF1) and GPI-anchored HDL-binding protein 1 (GPIHBP1), were sequenced in 86 patients with type 1 and type 5 HTG and 327 controls.
Results
In 46 patients (54%) rare DNA sequence variants were identified, comprising variants in LPL (n=19), APOC2 (n=1), APOA5 (n=2), GPIHBP1 (n=3) and LMF1 (n=8). In 22 patients (26%) only common variants in LPL (p.Asp36Asn, p.Asn318Ser and p.Ser474Ter) and APOA5 (p.Ser19Trp) could be identified, whereas no mutations were found in 18 patients (21%). In vitro validation revealed that the mutations in LMF1 were not associated with compromised LPL function. Consistent with this, five of the eight LMF1 variants were also found in controls and therefore cannot account for the observed phenotype.
Conclusion
The prevalence of mutations in LPL was 34% and mostly restricted to patients with type 1 HTG. Mutations in GPIHBP1 (n=3), APOC2 (n=1) and APOA5 (n=2) were rare but the associated clinical phenotype was severe. Routine sequencing of candidate genes in severe HTG has improved our understanding of the molecular basis of this phenotype associated with acute pancreatitis, and may help to guide future individualized therapeutic strategies.
Background
: Namibia, a middle-income country in sub-Saharan Africa (SSA), plans to use the Maternal Near Miss (MNM) approach. Adaptations of the World Health Organization (WHO) MNM defining criteria (‘WHO MNM criteria’) were previously proposed for low-income settings in sub-Saharan Africa (‘SSA MNM criteria’), but whether these adaptations are required in middle-income settings is unknown.
Objective
: To establish MNM criteria suitable for use in Namibia, a middle-income country in SSA.
Methods
: Cross-sectional study from 1 March 2018 to 31 May 2018 in four Namibian hospitals. Pregnant women or within 42 days of termination of pregnancy or birth, fulfilling at least one WHO or SSA MNM criterion were included. Records of women identified by either only WHO criteria or only SSA criteria were assessed in detail.
Results
: 194 Women fulfilled any MNM criterion. WHO criteria identified 61 MNM, the SSA criteria 184 MNM. Of women who only fulfilled any of the unique SSA MNM criteria, 18 fulfilled the criterion ‘eclampsia’, one ‘uterine rupture’ and five ‘laparotomy’. These women were assessed to be MNM. Thresholds for blood transfusion to define MNM due to haemorrhage were two units in the SSA and five in WHO set. Two or three units were given to 95 women for mild/moderate haemorrhage or chronic anaemia who did not fulfil any WHO criterion and were not considered MNM. Fourteen women who were assessed to be MNM from severe haemorrhage received four units.
Conclusions
: WHO MNM criteria may underestimate and SSA MNM criteria overestimate the prevalence of MNM in a middle-income country such as Namibia, where MNM criteria ‘in between’ may be more appropriate. Namibia opts to apply a modification of the WHO criteria, including eclampsia, uterine rupture, laparotomy and a lower threshold of four units of blood to define MNM. We recommend that other middle-income countries validate our criteria for their setting.
Despite high ANC coverage, opportunities for repeat HIV testing were missed in almost half of all women who delivered in this hospital in a high-prevalence HIV setting.
Abstractobjective WHO uses the Caesarean section (CS) rate to monitor implementation of emergency obstetric care (EmOC). Although CS rates are rising in sub-Saharan Africa, maternal outcome has not improved. We audited indications for CS and related complications among women with severe maternal morbidity and mortality in a referral hospital in rural Tanzania.methods Cross-sectional study was from November 2009 to November 2011. Women with severe maternal morbidity and mortality were identified and those with CS were included in this audit. Audit criteria were developed based on the literature review and (inter)national guidelines. Tanzanian and Dutch doctors reviewed hospital notes. The main outcome measured was prevalence of substandard quality of care leading to unnecessary CS and delay in performing interventions to prevent CS.results A total of 216 maternal near misses and 32 pregnancy-related deaths were identified, of which 82 (33.1%) had a CS. Indication for CS was in accordance with audit criteria for 36 of 82 (44.0%) cases without delay. In 20 of 82 (24.4%) cases, the indication was correct; however, there was significant delay in providing standard obstetric care. In 16 of 82 (19.5%) cases, the indication for CS was not in accordance with audit criteria. During office hours, CS was more often correctly indicated than outside office hours (60.0% vs. 36.0%, P < 0.05).discussion Caesarean section rate is not an useful indicator to monitor quality of EmOC as a high rate of unnecessary and potentially preventable CS was identified in this audit.keywords Caesarean section, quality of health care, medical audit, maternal mortality, unnecessary surgery
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