Early economic evaluation to identify the necessary test characteristics of a new typhoid test to be cost-effective in Ghana

Background In Ghana, there are issues with the diagnosis of typhoid fever; these include delays in diagnosis, concerns about the accuracy of current tests, and lack of availability. These issues highlight the need for the development of a rapid, accurate, and easily accessible diagnostic test. The aim of this study was to conduct an early economic analysis of a hypothetical rapid test for typhoid fever diagnosis in Ghana and identify the necessary characteristics of the test for it to be cost effective in Ghana. Methods An early cost-utility analysis was conducted using a decision tree parameterized with secondary data sources, with reasonable assumptions made for unknown parameters. The patient population considered is individuals presenting with symptoms suggestive of typhoid fever at a healthcare facility in Ghana; a time horizon of 180 days and the Ghanaian national health service perspective were adopted for the analysis. Extensive sensitivity analysis was undertaken, including headroom analysis. Results The results here show that for a hypothetical test to perform better than the existing test (Widal) in terms of QALYs gained and cost effectiveness, it is necessary for it to have a high specificity (at least 70%) and should not be priced more than US$4. The overall value of conducting research to reduce uncertainty (over 5 years) is US$3287. Conclusion The analysis shows the potential for the hypothetical test to replace the Widal test and the market potential of developing a new test in the Ghanaian setting

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Measuring the health-related Sustainable Development Goals in 188 countries : a baseline analysis from the Global Burden of Disease Study 2015

Background In September, 2015, the UN General Assembly established the Sustainable Development Goals (SDGs). The SDGs specify 17 universal goals, 169 targets, and 230 indicators leading up to 2030. We provide an analysis of 33 health-related SDG indicators based on the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015). Methods We applied statistical methods to systematically compiled data to estimate the performance of 33 health-related SDG indicators for 188 countries from 1990 to 2015. We rescaled each indicator on a scale from 0 (worst observed value between 1990 and 2015) to 100 (best observed). Indices representing all 33 health-related SDG indicators (health-related SDG index), health-related SDG indicators included in the Millennium Development Goals (MDG index), and health-related indicators not included in the MDGs (non-MDG index) were computed as the geometric mean of the rescaled indicators by SDG target. We used spline regressions to examine the relations between the Socio-demographic Index (SDI, a summary measure based on average income per person, educational attainment, and total fertility rate) and each of the health-related SDG indicators and indices. Findings In 2015, the median health-related SDG index was 59.3 (95% uncertainty interval 56.8-61.8) and varied widely by country, ranging from 85.5 (84.2-86.5) in Iceland to 20.4 (15.4-24.9) in Central African Republic. SDI was a good predictor of the health-related SDG index (r(2) = 0.88) and the MDG index (r(2) = 0.2), whereas the non-MDG index had a weaker relation with SDI (r(2) = 0.79). Between 2000 and 2015, the health-related SDG index improved by a median of 7.9 (IQR 5.0-10.4), and gains on the MDG index (a median change of 10.0 [6.7-13.1]) exceeded that of the non-MDG index (a median change of 5.5 [2.1-8.9]). Since 2000, pronounced progress occurred for indicators such as met need with modern contraception, under-5 mortality, and neonatal mortality, as well as the indicator for universal health coverage tracer interventions. Moderate improvements were found for indicators such as HIV and tuberculosis incidence, minimal changes for hepatitis B incidence took place, and childhood overweight considerably worsened. Interpretation GBD provides an independent, comparable avenue for monitoring progress towards the health-related SDGs. Our analysis not only highlights the importance of income, education, and fertility as drivers of health improvement but also emphasises that investments in these areas alone will not be sufficient. Although considerable progress on the health-related MDG indicators has been made, these gains will need to be sustained and, in many cases, accelerated to achieve the ambitious SDG targets. The minimal improvement in or worsening of health-related indicators beyond the MDGs highlight the need for additional resources to effectively address the expanded scope of the health-related SDGs.Peer reviewe

Importance of low carbohydrate diets in diabetes management

Rosemary M Hall, Amber Parry Strong, Jeremy D KrebsCentre for Endocrine, Diabetes and Obesity Research, Capital and Coast District Health Board, Wellington, New Zealand Abstract: Dietary strategies are fundamental in the management of diabetes. Historically, strict dietary control with a low carbohydrate diet was the only treatment option. With increasingly effective medications, the importance of dietary change decreased. Recommendations focused on reducing dietary fat to prevent atherosclerotic disease, with decreasing emphasis on the amount and quality of carbohydrate. As the prevalence of obesity and diabetes escalates, attention has returned to the macronutrient composition of the diet. Very low carbohydrate diets (VLCD's) have demonstrated effective initial weight loss and improvement in glycemic control, but difficult long-term acceptability and worsening lipid profile. Modifications to the very low carbohydrate (VLC) have included limiting saturated fat and increasing carbohydrate (CHO) and protein. Reducing saturated fat appears pivotal in reducing low-density lipoprotein (LDL) cholesterol and may mitigate adverse effects of traditional VLCD's. Increased dietary protein enhances satiety, reduces energy intake, and improves glycemic homeostasis, but without sustained improvements in glycemic control or cardiovascular risk over and above the effect of weight loss. Additionally, recent studies in type 1 diabetes mellitus suggest promising benefits to diabetes control with low carbohydrate diets, without concerning effects on ketosis or hypoglycemia. Dietary patterns may highlight pertinent associations. For example, Mediterranean-style and paleolithic-type diets, low in fat and carbohydrate, are associated with reduced body weight and improved glycemic and cardiovascular outcomes in type 2 diabetes mellitus (T2DM). A feature of these dietary patterns is low refined CHO and sugar and higher fiber, and it is possible that increasing sugar consumption is having a substantial effect on global escalations in obesity and T2DM. Dietary recommendations in type 1 diabetes and T2DM are changing. Dietary CHO is unquestionably important, but long-term acceptability of any diet is critical to sustain improvements in health benefits. Personalized dietary management, using a variety of dietary approaches, may be the key to optimal diabetes outcomes. Keywords: low carbohydrate diets, type 2 diabetes, dietary intervention studies, type 1 diabetes, paleo nutritio

Improvements in glucose metabolism and insulin sensitivity with a low-carbohydrate diet in obese patients with type 2 diabetes

Objective: The optimal diet for weight loss in type 2 diabetes remains controversial. This study examined a low-carbohydrate, high-fat diet with detailed physiological assessments of insulin sensitivity, glycemic control, and risk factors for cardiovascular disease. Methods: Fourteen obese patients (body mass index [BMI] 40.6 ± 4.9 kg/m2) with type 2 diabetes were recruited for an “Atkins”-type low-carbohydrate diet. Measurements were made at 0, 12, and 24 weeks of weight, insulin sensitivity, HbA1c, lipids, and blood pressure. Results: Twelve completers lost a mean of 9.7 ± 1.8 kg over 24 weeks attributable to a major reduction in carbohydrates and resultant reduction in total energy intake. Glycemic control significantly improved (HbA1c -1.1 ± 0.25%) with reductions in hypoglycemic medication. Fasting glucose, homeostasis model assessment (HOMA), and area under the curve (AUC) glucose (intravenous glucose tolerance test [IVGTT]) were significantly reduced by week 12 ( p < 0.05). There were nonsignificant improvements in insulin sensitivity (SI) at week 12 ( p = 0.19) and week 24 ( p = 0.31). Systolic blood pressure was reduced (mean -10.0 mmHg between weeks 0 and 24, p = 0.13). Mean high-density lipoprotein (HDL), low-density lipoprotein (LDL), and total cholesterol all increased. The ratio of total: HDL cholesterol and triglycerides was reduced. Conclusion: A low-carbohydrate diet was well tolerated and achieved weight loss over 24 weeks in subjects with diabetes. Glycemic control improved with a reduction in requirements for hypoglycemic agents

Short Telomeres are Sufficient to Cause the Degenerative Defects Associated with Aging

Telomerase function is critical for telomere maintenance. Mutations in telomerase components lead to telomere shortening and progressive bone marrow failure in the premature aging syndrome dyskeratosis congenita. Short telomeres are also acquired with aging, yet the role that they play in mediating age-related disease is not fully known. We generated wild-type mice that have short telomeres. In these mice, we identified hematopoietic and immune defects that resembled those present in dyskeratosis congenita patients. When mice with short telomeres were interbred, telomere length was only incrementally restored, and even several generations later, wild-type mice with short telomeres still displayed degenerative defects. Our findings implicate telomere length as a unique heritable trait that, when short, is sufficient to mediate the degenerative defects of aging, even when telomerase is wild-type

A pilot investigation of the hypoalgesic effects of transcutaneous electrical nerve stimulation upon low back pain in people with multiple sclerosis

Objective: To investigate the hypoalgesic effects of transcutaneous electrical nerve stimulation (TENS) upon low back pain (LBP) in people with multiple sclerosis (MS). Design: A randomized double-blind placebo controlled clinical pilot study. Subjects and setting: Fifteen people with MS were recruited and randomly allocated to one of the following groups under double blind conditions (n = 5 per group): TENS 1 (4 Hz, 200 μs), TENS 2 (110 Hz, 200 μs), placebo TENS. Interventions: Treatment was applied for 45 minutes three times a week for six weeks with a four-week follow-up. Outcome measures: The following outcome measures were taken at weeks 1, 6, and 10: visual analogue scale (VAS) (for current LBP, right leg pain, left leg pain); Leeds Multiple Sclerosis Quality of Life Questionnaire; Roland Morris Disability Questionnaire; Short Form-36 (SF-36) Version 1; and the McGill Pain Questionnaire (MPQ). VAS for current LBP, right and left leg pain were also taken before and after treatment, and once a week during the follow-up period. Results: Analysis showed no statistically significant effects for any of the data. However, both active treatment groups showed a trend of improvement in the majority of the outcome measures. Conclusion: Active TENS was more effective than placebo TENS in decreasing VAS scores following each treatment although results were not statistically significant. Further work in this area is warranted and should include a larger number of participants in the form of a randomized controlled clinical trial to determine the efficacy of this modality