A key component of achieving universal health coverage is ensuring that all populations have access to quality health care. Examining where gains have occurred or progress has faltered across and within countries is crucial to guiding decisions and strategies for future improvement. We used the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) to assess personal health-care access and quality with the Healthcare Access and Quality (HAQ) Index for 195 countries and territories, as well as subnational locations in seven countries, from 1990 to 2016. Drawing from established methods and updated estimates from GBD 2016, we used 32 causes from which death should not occur in the presence of effective care to approximate personal health-care access and quality by location and over time. To better isolate potential effects of personal health-care access and quality from underlying risk factor patterns, we risk-standardised cause-specific deaths due to non-cancers by location-year, replacing the local joint exposure of environmental and behavioural risks with the global level of exposure. Supported by the expansion of cancer registry data in GBD 2016, we used mortality-to-incidence ratios for cancers instead of risk-standardised death rates to provide a stronger signal of the effects of personal health care and access on cancer survival. We transformed each cause to a scale of 0-100, with 0 as the first percentile (worst) observed between 1990 and 2016, and 100 as the 99th percentile (best); we set these thresholds at the country level, and then applied them to subnational locations. We applied a principal components analysis to construct the HAQ Index using all scaled cause values, providing an overall score of 0-100 of personal health-care access and quality by location over time. We then compared HAQ Index levels and trends by quintiles on the Socio-demographic Index (SDI), a summary measure of overall development. As derived from the broader GBD study and other data sources, we examined relationships between national HAQ Index scores and potential correlates of performance, such as total health spending per capita. In 2016, HAQ Index performance spanned from a high of 97·1 (95% UI 95·8-98·1) in Iceland, followed by 96·6 (94·9-97·9) in Norway and 96·1 (94·5-97·3) in the Netherlands, to values as low as 18·6 (13·1-24·4) in the Central African Republic, 19·0 (14·3-23·7) in Somalia, and 23·4 (20·2-26·8) in Guinea-Bissau. The pace of progress achieved between 1990 and 2016 varied, with markedly faster improvements occurring between 2000 and 2016 for many countries in sub-Saharan Africa and southeast Asia, whereas several countries in Latin America and elsewhere saw progress stagnate after experiencing considerable advances in the HAQ Index between 1990 and 2000. Striking subnational disparities emerged in personal health-care access and quality, with China and India having particularly large gaps between locations with the highest and lowest scores in 2016. In China, performance ranged from 91·5 (89·1-93·6) in Beijing to 48·0 (43·4-53·2) in Tibet (a 43·5-point difference), while India saw a 30·8-point disparity, from 64·8 (59·6-68·8) in Goa to 34·0 (30·3-38·1) in Assam. Japan recorded the smallest range in subnational HAQ performance in 2016 (a 4·8-point difference), whereas differences between subnational locations with the highest and lowest HAQ Index values were more than two times as high for the USA and three times as high for England. State-level gaps in the HAQ Index in Mexico somewhat narrowed from 1990 to 2016 (from a 20·9-point to 17·0-point difference), whereas in Brazil, disparities slightly increased across states during this time (a 17·2-point to 20·4-point difference). Performance on the HAQ Index showed strong linkages to overall development, with high and high-middle SDI countries generally having higher scores and faster gains for non-communicable diseases. Nonetheless, countries across the development spectrum saw substantial gains in some key health service areas from 2000 to 2016, most notably vaccine-preventable diseases. Overall, national performance on the HAQ Index was positively associated with higher levels of total health spending per capita, as well as health systems inputs, but these relationships were quite heterogeneous, particularly among low-to-middle SDI countries. GBD 2016 provides a more detailed understanding of past success and current challenges in improving personal health-care access and quality worldwide. Despite substantial gains since 2000, many low-SDI and middle-SDI countries face considerable challenges unless heightened policy action and investments focus on advancing access to and quality of health care across key health services, especially non-communicable diseases. Stagnating or minimal improvements experienced by several low-middle to high-middle SDI countries could reflect the complexities of re-orienting both primary and secondary health-care services beyond the more limited foci of the Millennium Development Goals. Alongside initiatives to strengthen public health programmes, the pursuit of universal health coverage hinges upon improving both access and quality worldwide, and thus requires adopting a more comprehensive view-and subsequent provision-of quality health care for all populations. Bill & Melinda Gates Foundation.

An understanding of the trends in tuberculosis incidence, prevalence, and mortality is crucial to tracking of the success of tuberculosis control programmes and identification of remaining challenges. We assessed trends in the fatal and non-fatal burden of tuberculosis over the past 25 years for 195 countries and territories. We analysed 10 691 site-years of vital registration data, 768 site-years of verbal autopsy data, and 361 site-years of mortality surveillance data using the Cause of Death Ensemble model to estimate tuberculosis mortality rates. We analysed all available age-specific and sex-specific data sources, including annual case notifications, prevalence surveys, and estimated cause-specific mortality, to generate internally consistent estimates of incidence, prevalence, and mortality using DisMod-MR 2.1, a Bayesian meta-regression tool. We assessed how observed tuberculosis incidence, prevalence, and mortality differed from expected trends as predicted by the Socio-demographic Index (SDI), a composite indicator based on income per capita, average years of schooling, and total fertility rate. We also estimated tuberculosis mortality and disability-adjusted life-years attributable to the independent effects of risk factors including smoking, alcohol use, and diabetes. Globally, in 2015, the number of tuberculosis incident cases (including new and relapse cases) was 10·2 million (95% uncertainty interval 9·2 million to 11·5 million), the number of prevalent cases was 10·1 million (9·2 million to 11·1 million), and the number of deaths was 1·3 million (1·1 million to 1·6 million). Among individuals who were HIV negative, the number of incident cases was 8·8 million (8·0 million to 9·9 million), the number of prevalent cases was 8·9 million (8·1 million to 9·7 million), and the number of deaths was 1·1 million (0·9 million to 1·4 million). Annualised rates of change from 2005 to 2015 showed a faster decline in mortality (-4·1% [-5·0 to -3·4]) than in incidence (-1·6% [-1·9 to -1·2]) and prevalence (-0·7% [-1·0 to -0·5]) among HIV-negative individuals. The SDI was inversely associated with HIV-negative mortality rates but did not show a clear gradient for incidence and prevalence. Most of Asia, eastern Europe, and sub-Saharan Africa had higher rates of HIV-negative tuberculosis burden than expected given their SDI. Alcohol use accounted for 11·4% (9·3-13·0) of global tuberculosis deaths among HIV-negative individuals in 2015, diabetes accounted for 10·6% (6·8-14·8), and smoking accounted for 7·8% (3·8-12·0). Despite a concerted global effort to reduce the burden of tuberculosis, it still causes a large disease burden globally. Strengthening of health systems for early detection of tuberculosis and improvement of the quality of tuberculosis care, including prompt and accurate diagnosis, early initiation of treatment, and regular follow-up, are priorities. Countries with higher than expected tuberculosis rates for their level of sociodemographic development should investigate the reasons for lagging behind and take remedial action. Efforts to prevent smoking, alcohol use, and diabetes could also substantially reduce the burden of tuberculosis. Bill & Melinda Gates Foundation.

Renin Angiotensin System (RAS) is a hormonal system that regulates blood pressure and fluid balance through a coordinated action of renal, cardiovascular, and central nervous systems. In addition to its hemodynamic regulatory role, RAS involves in many brain activities, including memory acquisition and consolidation. This review has summarized the involvement of RAS in the pathology of Alzheimer’s disease (AD), and the outcomes of treatment with RAS inhibitors. We have discussed the effect of brain RAS in the amyloid plaque (Aβ) deposition, oxidative stress, neuroinflammation, and vascular pathology which are directly and indirectly associated with AD. Angiotensin II (AngII) via AT1 receptor is reported to increase brain Aβ level via different mechanisms including increasing amyloid precursor protein (APP) mRNA, β-secretase activity, and presenilin expression. Similarly, it was associated with tau phosphorylation, and reactive oxygen species generation. However, these effects are counterbalanced by Ang II mediated AT2 signaling. The protective effect observed with angiotensin receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs) could be as the result of inhibition of Ang II signaling. ARBs also offer additional benefit by shifting the effect of Ang II toward AT2 receptor. To conclude, targeting RAS in the brain may benefit patients with AD though it still requires further in depth understanding.

Adherence to antihypertensive medications is a key component to control blood pressure levels. Poor adherence to these medications leads to the development of hypertensive complications and increase risk of cardiovascular events which in turn reduces the ultimate clinical outcome. The purpose of this study was to assess antihypertensive medication adherence and associated factors among adult hypertensive patients. A hospital-based cross-sectional study among adult hypertensive patients was conducted at hypertensive follow-up clinic of Jimma University Specialized Hospital from March 4, 2015 to April 3, 2015. A simple random sampling technique was used to select the study participants from the study population. The study patients were interviewed and their medical charts were reviewed using a pretested structured questionnaire. Adherence was assessed using Morisky Medication Adherence Scale-8 (MMAS-8) and MMAS-8 score less than 6 was considered as non-adherent and MMAS-8 score was ≥ 6 was declared as adherence. Factors associated with adherence were identified using binary and multivariate logistic regression analysis. Crude odds ratio, adjusted odds ratio (AOR) and 95% confidence interval of the odds ratio were calculated using SPSS version 21. Variables with p-value less than 0.05 were assumed as statistically significant factors. Among 280 hypertensive patients, 61.8% of the study participants were found to be adherent. More than half (53.2%) of the participants were males and the mean age of the participants was 55.0 ± 12.7 years. Co-morbidity (AOR = 0.083, 95% CI = 0.033–0.207, p < 0.001), alcohol intake (AOR = 0.011, 95% CI = 0.002–0.079, p < 0.001), getting medications freely (AOR = 0.020, 95% CI = 0.003–0.117, p < 0.001), and combination of antihypertensive medications (AOR = 0.32, 95% CI = 0.144–0.712, p < 0.005) were inversely associated with antihypertensive medication adherence. The adherence level to the prescribed antihypertensive medications was found to be sub-optimal according to the MMAS-8, and influenced by co morbidity, alcohol intake, self-purchasing of the medications and combination of antihypertensive medications.

Neuroactive steroids are naturally occurring steroids, which are synthesized centrally as de novo from cholesterol and are classified as pregnane, androstane, and sulfated neurosteroids. Neuroactive steroids modulate many processes via interacting with gamma-aminobutyric acid (GABA), N-methyl-D-aspartate, serotonin, voltage-gated calcium channels, voltage-dependent anion channels, α-adrenoreceptors, X-receptors of the liver, transient receptor potential channels, microtubule-associated protein 2, neurotrophin nerve growth factor, and σ1 receptors. Among these, neurosteroids (especially allopregnanolone) have high potency and extensive GABA-A receptors and hence demonstrate anticonvulsant, anesthetic, central cytoprotectant and baroreflex inhibitory effects. Neurosteroids are also involved in mood and learning via serotonin and anti-nociceptive activity via T-type voltage-gated Ca2+ channels. Moreover, they are modulators of mitochondrial function, synaptic plasticity, or regulators of apoptosis, which have a role in neuroprotective via voltage- dependent anion channels receptors. For proper functioning, neuroactive steroids need to be in their normal level whereas excess and deficiency may lead to abnormalities. When they are below the normal, neurosteroids could have a part in development of depression, neuro-inflammation, multiple sclerosis, experimental autoimmune encephalitis (EAE), epilepsy, and schizophrenia. On the other hand, stress and attention deficit disorder could occur during excessive level. Overall, neuroactive steroids are very important molecules with major neuropsychiatric activity.

Epilepsy is a major public health problem worldwide. Despite multiple drug therapies, people with epilepsy continue to have frequent seizures. There is a dearth of data on epilepsy treatment outcome and associated factors in our setting. Therefore, the aim of this was to assess treatment outcome and associated factors among epileptic patients on follow up at the neurologic clinic of Ayder comprehensive specialized hospital, Ethiopia. A cross-sectional study was conducted on randomly selected epileptic patients. Data were collected through patient interview and review of medical records. Epilepsy treatment outcome was evaluated in terms of seizure control status in the last one year follow up period. Binary logistic regression analysis was performed to identify predictors of treatment outcome. A total of 270 patients were included. Of whom, 46.6% had controlled seizures. Whereas, 38.5%, 8.8%, and 5.9% had experienced seizure attacks 1–5 times, 6–10 times, and greater than 10 times, respectively. Alcohol consumption [adjusted odds ratio [(AOR): 14.87, 95% confidence interval (CI): 3.25–68.11], negative medication belief [AOR: 3.0, 95%CI: 1.31–6.71], low medication adherence [AOR:11.52, 95%CI: 3.25–40.82], and presence of comorbidities [AOR: 10.35, 95%CI: 4.40–24.40] were predictors of uncontrolled seizure. Our finding revealed that more than half of the epileptic patients had uncontrolled seizure. Epileptic patients with a negative medication belief, comorbidities, low medication adherence, and those who consume alcohol were more likely to have uncontrolled seizure. Therefore, more emphasis should be given to these patients.