Serum carbohydrate antigen 125 levels in nonischemic dilated cardiomyopathy: a useful biomarker for prognosis and functional mitral regurgitation

The authors investigated the prognostic relevance of serum carbohydrate antigen 125 (CA125) levels in nonischemic dilated cardiomyopathy (NICMP) and assessed whether increased levels relate to the degree of functional mitral regurgitation (FMR). Seventy-seven patients with NICMP were enrolled and followed-up for 10 ± 2 months in this prospective study. Receiver-operating characteristic analysis established a cutoff CA125 value of 25 U/mL for predicting mortality. Patients were divided into two groups according to their CA125 levels (CA125 <25 U/mL [n=58] and CA125 ≥ 25 U/mL [n=19]). Patients with high CA125 values had statistically worse functional status, higher B-type natriuretic peptide (BNP) levels, higher left ventricular volumes, lower ejection fraction, higher E/Em ratio, higher pulmonary artery systolic pressure, and more severe FMR. On the multivariate analysis, serum CA125 (P=.002) and severe FMR (P=.04) were identified as the independent predictors of mortality. Serum CA125 levels also correlated with BNP levels and FMR severity (P<.001). Serum CA125 is a powerful prognostic biomarker that is associated with the severity of heart failure, serum BNP levels and several echocardiographic parameters including left ventricular volumes, systolic and diastolic functions, pulmonary artery pressure, and the degree of FMR. Serum CA125 was also shown as an independent predictor of mortality during 10 ± 2 months of follow-up.     

Can Teenage Men Be Targeted to Prevent Teenage Pregnancy? A Feasibility Cluster Randomised Controlled Intervention Trial in Schools

The World Health Organisation advocates a direct focus on adolescent men in reducing adolescent pregnancy; however, no trials have been conducted. This trial (ISRCTN11632300; NCT02092480) determines whether a novel Relationship and Sexuality Educational intervention, If I Were Jack, is acceptable and feasible to implement in mixed sex UK classrooms. The intervention is a teacher-delivered intervention that emphasises male alongside female  responsibility in preventing unintended pregnancies and is designed to prevent unprotected sex. The trial was a parallel-group cluster randomised controlled feasibility trial with embedded process and cost evaluation in eight secondary schools (unit of randomisation) among 831 pupils (mean age 14) in Northern Ireland, alongside a qualitative evaluation of transferability in ten schools in Scotland, Wales and England. The sampling strategy was a maximum variation quota sample designed to capture a range of school management types. Four schools were randomised to each arm and the control arm continued with usual practice. Study duration was 12 months (from November 2014), with follow-up 9 months post-baseline. Results demonstrated that the intervention was acceptable to schools, pupils and teachers, and could be feasibly implemented, cost-effectively, with minor enhancements. The between-group difference in incidence of unprotected sex (primary outcome at pupil level) of 1.3% (95% CI 0.5–2.2) by 9 months demonstrated a potential effect size consistent with those reported to have had meaningful impact on teenage pregnancy. The study responds to global health policy for a paradigm shift towards inclusion of men in the achievement of sexual and reproductive health goals in a practical way by demonstrating that a gender-sensitive as well as a gender transformative intervention targeting males to prevent teenage pregnancy is acceptable to adolescent men and women and implementable in formal education structures. If I Were Jack now merits further effectiveness testing.     

Development of multi-criteria decision analysis (MCDA) framework for off-patent pharmaceuticals – an application on improving tender decision making in Indonesia

Background

Off-patent pharmaceuticals (OPPs) hold vital importance in meeting public health objectives, especially in developing countries where resources are limited. OPPs are comprised of off-patent originals, branded generics and unbranded generics; nonetheless, these products are not identical and often there are differences in their equivalence, manufacturing quality standards and reliability of supply. This necessitates reconsideration of the lowest price policy objective in pharmaceutical decision making. The aim of this study was to develop a Multi-Criteria Decision Analysis (MCDA) framework through a pilot workshop to inform the national procurement of OPPs in Indonesia.

Methods

An initial list of potentially relevant criteria was identified based on previous work and a literature review. In a 2-day pilot policy workshop, twenty local experts representing different stakeholder groups and decision-making bodies selected the final criteria, approved the scoring function for each criterion, and assigned weights to each criterion.

Results

An MCDA framework was proposed for OPP drug decision making in developing countries, which included price and 8 non-price criteria. Based on the pilot policy workshop 6?+?1 criteria were considered relevant for Indonesia: pharmaceutical price (40% weight), manufacturing quality (18.8%), equivalence with the reference product (12.2%), product stability and drug formulation (12.2%), reliability of drug supply (8.4%), real world clinical or economic outcomes, such as adherence or non-drug costs (4.2%) and pharmacovigilance (3.6%).

Conclusions

According to the pilot policy workshop, other criteria apart from price need to be strengthened in the tendering process. The introduction of additional criteria for OPP procurement in an MCDA framework creates incentives for manufacturers to invest into improved manufacturing standards, equivalence proof, product quality, reliability of supply or even additional real-world data collection, which ultimately may result in more health gain for the society.

     

Bypass procedures in the management of juxtarenal aortic occlusion

Juxtarenal aortic occlusion is one of the most important though less frequent atherosclerotic lesions. The indications for surgical treatment using bypass techniques, are well known. However, controversy remains about the pathogenesis of the lesion; from either a thrombosis developing on an atherosclerotic lesion of the terminal aorta, or a primary atherosclerosis of the subrenal aorta. In our series of 1,180 patients submitted to surgery for aorto-iliac occlusive disease, we encountered 91 cases (7.7%) of juxtarenal occlusion. Apart from the different angiographic pictures, the patients were grouped on the operative finding of either thrombosis or atheroma. An aortobifemoral bypass graft was implanted on all but three of the cases; in these three we performed an axillo-bifemoral bypass. A different technique was used, for juxtarenal disobliteration, using a different (end-to-end, or end-to-side) suture of the proximal anastomosis. The operative indications and results are discussed.     

Mothers’ Selection of Future Primary Caregivers in Rural West Java,Indonesia

This study analyzes mothers’ preference of a future primary caregiver by using within-family analysis approach in the context of Sundanese population in rural West Java, Indonesia. This is a cross-sectional study involving healthy mothers (60–69 years old) with a perfect score of Instrumental Activity of Daily Living (IADL), and who had at least two living children. The within-family analysis of a selection of future caregivers was conducted based on the report from 177 mothers of their 904 children using multilevel modeling with binomial outcome. Being a daughter, older, emotionally the closest to the mother, having supported the mother in the past, being perceived as future bequest receiver, and being geographically closer to mother increased the chance of being selected as preferred future primary caregivers. There were also cross-level effects of socioeconomic status (SES) on the selection of future primary caregivers by mothers, where poor mothers tend to pick poor children as their future primary caregivers. The results were contrasted to the findings from a similar study conducted in the United States. In addition, the importance of knowledge about future care preference and its implications for intervention is discussed.     

Accommodation of additional non-randomly sampled cases in a study of Helicobacter pylori infection in families

Epidemiological studies with two-stage designs typically gather information about some covariates from all study subjects in the first sampling stage, while additional data from only a subset of the subjects are collected in the second sampling stage. Appropriate analysis of two-stage studies maintains validity and can also improve precision. We describe an application of a weighted likelihood method, mean-score logistic regression, to accommodate data from a cross-sectional study of Helicobacter pylori infection in children, where the study sample was enriched with additional non-randomly sampled cases. The present work exemplifies how careful analysis of epidemiological data from complex sampling schemes can adjust for potential selection bias, improve precision and enable a more complete investigation of factors of interest. Our results highlight the importance of H. pylori infected mothers and siblings as risk factors for the infection in children in Sweden.     

A perspective on protein profiling of blood

Protein profiling of blood is going to lead to huge changes in the development of biomarkers and perhaps also in producing targets for the medical treatment of cancer. Experts in this field from Los Angeles have written an outstanding mini‐review about this topic. Renal cancer has been an area of interest to all of those involved in urological oncology, particularly from the point of view of adjuvant medical treatment either to prevent metastatic disease or to treat it. Authors from Los Angeles have produced a review of great interest on this subject. There are three other reviews on important issues. Authors from Paris have written about microsatellite instability and TCC of the upper urinary tract, and authors from Bristol have written a mini‐review about the options available when considering orthotopic bladder reconstruction. Finally, authors from Dublin have written about a significant problem in renal transplantation, delayed graft function.     

Protein synthesis and translation initiation factor activation in neonatal pigs fed increasing levels of dietary protein

Limited data suggest that the growth of low-birth-weight infants is enhanced by feeding a high-protein diet; however, the mechanisms involved in the effect have not been delineated. To identify these mechanisms, 34 pigs were fed from 2 to 7 d of age [60 g dry matter/(kg body weight . d)] isocaloric milk diets that contained levels of dietary protein that were marginal, adequate, and in excess of the piglets protein requirement (21, 33, and 45% of dry matter, respectively). Dietary protein replaced lactose and fat on an isocaloric basis. Fractional protein synthesis rates, various biomarkers of translational regulation, and plasma glucose and insulin levels were measured in overnight food-deprived and fed pigs. Mean daily weight gain of pigs fed the 33 and 45% protein diets was greater than that of pigs fed the 21% protein diet (P < 0.01). Plasma glucose (P = 0.07) and insulin (P < 0.01) levels decreased as dietary protein increased 60 min after feeding. Protein synthesis rates in longissimus dorsi, gastrocnemius, masseter, heart, liver, kidney, jejunum, and pancreas were greater in the fed than in the food-deprived state (P < 0.01). Protein synthesis in skeletal muscle did not change with protein intake in the fed state, but decreased quadratically (P < 0.01) with increasing dietary protein in the food-deprived state. Protein kinase B, ribosomal protein S6 kinase 1(S6K1), and eukaryotic initiation factor (eIF) 4E binding protein-1 (4E-BP1) were more phosphorylated, and assembly of the inactive eukaryotic initiation factor 4E . 4E-BP1 complex in muscle and liver was reduced in the fed state (P < 0.001) and were not consistently affected by dietary protein level. The results suggest that feeding stimulates protein synthesis, and this is modulated by the activation of initiation factors that regulate mRNA binding to the ribosomal complex. However, the provision of a high-protein diet that exceeds the protein requirement does not further enhance protein synthesis or translation initiation factor activation.