A case of haemolytic disease of the fetus and newborn attributed to a novel antigen in the RHAG blood group system.

BACKGROUND AND OBJECTIVES: A newborn presented with jaundice in Thailand. The cord red cells tested positive by direct antiglobulin test (DAT) for an unknown maternal red cell antibody. Initial blood group sequencing suggested that the infant carried a novel variant RHAG c.140T>C, responsible for a low-prevalence antigen in the RHAG blood group system (ISBT 030). We report here on testing of samples from the infant's parents and older sibling to define a new antigen in the RHAG system. MATERIALS AND METHODS: Massive parallel sequencing (MPS) using a custom-designed panel was performed on all four family members. Extended serological testing was also performed to determine whether family members with the same variant as the infant showed reactivity with the antibody in the maternal plasma. RESULTS: We identified a novel single nucleotide variant (SNV) (RHAG c.140T>C, p.[Phe47Ser]) in samples from three of the four family members tested (the infant, the older sibling and the father). The variant was not detected in the mother's sample. Maternal plasma showed positive agglutination with all family members tested; however, when tested with routine panel cells, no reactivity was observed. CONCLUSION: This case study showed that the presence of the novel variant (RHAG c.140T>C), encoding a p.(Phe47Ser) change in the RhAG glycoprotein, was the apparent cause of incompatibility between maternal plasma and that of red cells from the proband, father and older sibling of the proband. We propose this variant to be a new low-prevalence antigen in the RHAG blood group system.

Childhood overweight and obesity abatement policies in Europe.

Over the past two decades, a concerted effort to combat the rising tide of childhood overweight and obesity has taken shape. The World Health Organization (WHO) Commission on Ending Childhood Obesity (ECHO) provides recommendations for six priority areas of action, including the promotion of healthy food consumption, promotion of physical activity, preconception and pregnancy care, early childhood diet and physical activity, healthy nutrition and physical activity for school-aged children, and community-based weight management. This paper provides a snapshot of policies and measures aligned to these areas of action within the WHO European Region in order to encourage other countries to make similar efforts. Examples are drawn from Portugal (sugar-sweetened beverage tax, integrated nutrition strategy), the United Kingdom (soft drink levy, active commuting programs, urban design principles), Lithuania (prohibition of energy drinks), Norway (industry and government partnerships to promote healthier foods, nutrition education curriculum for schools), Hungary (tax subsidies to promote healthy diets), the European Union (cross-border marketing regulations, preconception and pregnancy care), Slovenia (food marketing restrictions), Spain (marketing restrictions within educational settings), Poland (investing in sports infrastructure), Russia (increasing sports participation), Estonia (redevelopment of the physical education curriculum), Netherlands (preconception and pregnancy care), Croatia (conditions to support breastfeeding), Austria (perinatal and early childhood nutrition), Czechia (life-course strategy), San Marino (nutrition and physical activity for school-aged children), Ukraine (potable water for schools), Ireland and Italy (community-based weight management approaches). Our findings suggest that a large disparity exists among the type and breadth of policies adopted by Member States, with a mix of single-issue policy responses and more cohesive strategies. The role of data, implementation research, and ongoing surveillance of country-level progress related to childhood overweight and obesity policies are discussed as an essential part of the iterative process of policy development. Additional work to systematically gather context-specific information on policy development, implementation, and reach according to ECHO's six areas of action by WHO European Region countries will inform future policy paradigms within the region.

Childhood overweight and obesity in Europe: Changes from 2007 to 2017.

The Childhood Obesity Surveillance Initiative (COSI) routinely measures height and weight of primary school children aged 6-9 years and calculates overweight and obesity prevalence within the World Health Organization (WHO) European Region using a standard methodology. This study examines the trends in the prevalence of overweight and obesity from the first round of COSI carried out in 2007/2008 to the latest of 2015/2017 in 11 European countries in which data were collected for at least three rounds. In total 303,155 children were measured. In general, the prevalence of overweight and obesity among boys and girls decreased in countries with high prevalence (Southern Europe) and remained stable or slightly increased in Northern European and Eastern European countries included in the analysis. Among boys, the highest decrease in overweight (including obesity) was observed in Portugal (from 40.5% in 2007/2008 to 28.4 in 2015/2017) and in Greece for obesity (from 30.5% in 2009/2010 to 21.7% in 2015/2017). Lithuania recorded the strongest increase in the proportion of boys with overweight (from 24.8% to 28.5%) and obesity (from 9.4% to 12.2%). The trends were similar for boys and girls in most countries. Several countries in Europe have successfully implemented policies and interventions to counteract the increase of overweight and obesity, but there is still much to be done.

Anti-phospholipid syndrome leading to digital ischaemia and rare organ complications in systemic sclerosis and related disorders.

Antiphospholipid syndrome (APS) is an acquired, autoimmune thrombophilia that can occur as a primary disorder (with no associated disease) or secondary to infection, medication usage and autoimmune rheumatic diseases (ARDs). The association between APS and systemic lupus erythematosus (SLE) is well established, and practicing rheumatologists check for APS antibodies in the routine assessment of SLE, particularly if clinical features such as thrombotic events or pregnancy loss are present. APS secondary to systemic sclerosis (SSc)-related disorders is less widely recognised and easily overlooked. We describe 5 cases that highlight the varied breadth of clinical manifestations of APS in the context of SSc and related disorders. These cases range from uncomplicated Raynaud's phenomenon, digital ulceration/necrosis, critical digital ischaemia/gangrene and rare internal organ complications of APS in SSc-spectrum disorders. To our knowledge, our cases include the first reported case of secondary APS contributing to digital necrosis in the context of RACAND syndrome (Raynaud's phenomenon, anti-centromere antibodies and necrosis of the digits) and the first reported case of secondary APS in SSc causing posterior reversible encephalopathy syndrome (PRES). The case series is accompanied by a comprehensive review of the literature relevant to each case. Rheumatologists should be alert to the possibility of APS in SSc-spectrum disorders and should routinely check APS antibodies in all patients at diagnosis, and again later in the disease course if new features emerge that could indicate the presence of thrombotic events or other recognised APS manifestations. Key points • APS should be considered in all patients with digital ischaemic symptoms. • APS may be an important driver of SSc-related digital ulceration/necrosis. • Identification of SSc-associated APS opens up new therapeutic options for acute management and secondary prevention.

Type 2 Diabetes as a Risk Factor for Dementia in Women Compared With Men: A Pooled Analysis of 2.3 Million People Comprising More Than 100,000 Cases of Dementia.

OBJECTIVE: Type 2 diabetes confers a greater excess risk of cardiovascular disease in women than in men. Diabetes is also a risk factor for dementia, but whether the association is similar in women and men remains unknown. We performed a meta-analysis of unpublished data to estimate the sex-specific relationship between women and men with diabetes with incident dementia. RESEARCH DESIGN AND METHODS: A systematic search identified studies published prior to November 2014 that had reported on the prospective association between diabetes and dementia. Study authors contributed unpublished sex-specific relative risks (RRs) and 95% CIs on the association between diabetes and all dementia and its subtypes. Sex-specific RRs and the women-to-men ratio of RRs (RRRs) were pooled using random-effects meta-analyses. RESULTS: Study-level data from 14 studies, 2,310,330 individuals, and 102,174 dementia case patients were included. In multiple-adjusted analyses, diabetes was associated with a 60% increased risk of any dementia in both sexes (women: pooled RR 1.62 [95% CI 1.45-1.80]; men: pooled RR 1.58 [95% CI 1.38-1.81]). The diabetes-associated RRs for vascular dementia were 2.34 (95% CI 1.86-2.94) in women and 1.73 (95% CI 1.61-1.85) in men, and for nonvascular dementia, the RRs were 1.53 (95% CI 1.35-1.73) in women and 1.49 (95% CI 1.31-1.69) in men. Overall, women with diabetes had a 19% greater risk for the development of vascular dementia than men (multiple-adjusted RRR 1.19 [95% CI 1.08-1.30]; P < 0.001). CONCLUSIONS: Individuals with type 2 diabetes are at ∼60% greater risk for the development of dementia compared with those without diabetes. For vascular dementia, but not for nonvascular dementia, the additional risk is greater in women.

Platinum versus non-platinum chemotherapy regimens for small cell lung cancer.

BACKGROUND: Small cell lung cancer (SCLC) is a very fast growing form of cancer and is characterised by early metastasis. As a result, chemotherapy is the mainstay of treatment. A number of different platinum-based chemotherapy regimens and non-platinum-based chemotherapy regimens have been used for the treatment of SCLC, with varying results. This review was conducted to analyse the data from these studies in order to compare their effectiveness. OBJECTIVES: To determine the effectiveness of platinum chemotherapy regimens compared with non-platinum chemotherapy regimens in the treatment of SCLC with respect to survival, tumour response, toxicity and quality of life. SEARCH METHODS: We searched the biomedical literature databases CENTRAL (TheCochrane Library 2014, Issue 7), MEDLINE, EMBASE and CINAHL from 1966 to August 2014. In addition, we handsearched reference lists from relevant resources. SELECTION CRITERIA: All randomised controlled trials involving patients with pathologically confirmed SCLC (including both limited-stage disease and extensive-stage disease) and the use of a platinum-based chemotherapy regimen in at least one treatment arm and a non-platinum-based chemotherapy regimen in a separate arm. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by the Cochrane Collaboration. Two authors independently assessed search results. We assessed included studies for methodological quality and recorded the following outcome data: survival, tumour response, toxicity and quality of life. We combined the results of the survival, tumour response and toxicity data in a meta-analysis. Quality-of-life data were analysed individually. MAIN RESULTS: A total of 32 studies involving 6075 patients with SCLC were included in this systematic review. The majority of studies were multi-centre randomised controlled trials conducted throughout Europe, North America and Asia with the earliest study publishing data in 1981 and the latest in 2014. The duration of studies ranged from 12 to 72 months with a median of 32 months. The median age of patients in the vast majority of studies was between 60 and 65 years of age. Eighteen studies presented data on extensive-stage disease. Nine studies presented data on limited-stage disease. Eleven studies did not present data based on the disease stage. These data were analysed separately in subgroup analyses. Sixteen (50%) studies were of good quality with a low risk of bias and the data from these studies were analysed separately in a heterogeneity analysis.There was no statistically significant difference between treatment groups in terms of survival at 6 months, 12 months and 24 months. There was also no statistically significant difference in terms of overall tumour response. However, platinum-based treatment regimens did have a significantly higher rate of complete response. Platinum-based chemotherapy regimens had significantly higher rates of nausea and vomiting and thrombocytopenia toxicity. Four trials presented quality-of-life data, but, due to the different systems used to measure quality of life this data could not be combined in a meta-analysis. AUTHORS' CONCLUSIONS: Platinum-based chemotherapy regimens did not offer a statistically significant benefit in survival or overall tumour response compared with non-platinum-based regimens. However, platinum-based chemotherapy regimens did increase complete response rates, at the cost of higher adverse events including nausea and vomiting, anaemia and thrombocytopenia toxicity. These data suggest non-platinum chemotherapy regimens have a more advantageous risk-benefit profile. This systematic review highlights the lack of quality-of-life data in trials involving chemotherapy treatment for SCLC. With poor long-term survival associated with both treatment groups, the issue of the quality of the survival period takes on even more significance. It would be beneficial for future trials in this area to include a quality-of-life assessment.