Ticagrelor alone versus ticagrelor plus aspirin from month 1 to month 12 after percutaneous coronary intervention in patients with acute coronary syndromes (ULTIMATE-DAPT): a randomised, placebo-controlled, double-blind clinical trial.

BACKGROUND: Following percutaneous coronary intervention with stent placement to treat acute coronary syndromes, international clinical guidelines generally recommend dual antiplatelet therapy with aspirin plus a P2Y12 receptor inhibitor for 12 months to prevent myocardial infarction and stent thrombosis. However, data on single antiplatelet therapy with a potent P2Y12 inhibitor earlier than 12 months after percutaneous coronary intervention for patients with an acute coronary syndrome are scarce. The aim of this trial was to assess whether the use of ticagrelor alone, compared with ticagrelor plus aspirin, could reduce the incidence of clinically relevant bleeding events without an accompanying increase in major adverse cardiovascular or cerebrovascular events (MACCE). METHODS: In this randomised, placebo-controlled, double-blind clinical trial, patients aged 18 years or older with an acute coronary syndrome who completed the IVUS-ACS study and who had no major ischaemic or bleeding events after 1-month treatment with dual antiplatelet therapy were randomly assigned to receive oral ticagrelor (90 mg twice daily) plus oral aspirin (100 mg once daily) or oral ticagrelor (90 mg twice daily) plus a matching oral placebo, beginning 1 month and ending at 12 months after percutaneous coronary intervention (11 months in total). Recruitment took place at 58 centres in China, Italy, Pakistan, and the UK. Patients were required to remain event-free for 1 month on dual antiplatelet therapy following percutaneous coronary intervention with contemporary drug-eluting stents. Randomisation was done using a web-based system, stratified by acute coronary syndrome type, diabetes, IVUS-ACS randomisation, and site, using dynamic minimisation. The primary superiority endpoint was clinically relevant bleeding (Bleeding Academic Research Consortium [known as BARC] types 2, 3, or 5). The primary non-inferiority endpoint was MACCE (defined as the composite of cardiac death, myocardial infarction, ischaemic stroke, definite stent thrombosis, or clinically driven target vessel revascularisation), with an expected event rate of 6·2% in the ticagrelor plus aspirin group and an absolute non-inferiority margin of 2·5 percentage points between 1 month and 12 months after percutaneous coronary intervention. The two co-primary endpoints were tested sequentially; the primary superiority endpoint had to be met for hypothesis testing of the MACCE outcome to proceed. All principal analyses were assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03971500, and is completed. FINDINGS: Between Sept 21, 2019, and Oct 27, 2022, 3400 (97·0%) of the 3505 participants in the IVUS-ACS study were randomly assigned (1700 patients to ticagrelor plus aspirin and 1700 patients to ticagrelor plus placebo). 12-month follow-up was completed by 3399 (>99·9%) patients. Between month 1 and month 12 after percutaneous coronary intervention, clinically relevant bleeding occurred in 35 patients (2·1%) in the ticagrelor plus placebo group and in 78 patients (4·6%) in the ticagrelor plus aspirin group (hazard ratio [HR] 0·45 [95% CI 0·30 to 0·66]; p<0·0001). MACCE occurred in 61 patients (3·6%) in the ticagrelor plus placebo group and in 63 patients (3·7%) in the ticagrelor plus aspirin group (absolute difference -0·1% [95% CI -1·4% to 1·2%]; HR 0·98 [95% CI 0·69 to 1·39]; pnon-inferiority<0·0001, psuperiority=0·89). INTERPRETATION: In patients with an acute coronary syndrome who had percutaneous coronary intervention with contemporary drug-eluting stents and remained event-free for 1 month on dual antiplatelet therapy, treatment with ticagrelor alone between month 1 and month 12 after the intervention resulted in a lower rate of clinically relevant bleeding and a similar rate of MACCE compared with ticagrelor plus aspirin. Along with the results from previous studies, these findings show that most patients in this population can benefit from superior clinical outcomes with aspirin discontinuation and maintenance on ticagrelor monotherapy after 1 month of dual antiplatelet therapy. FUNDING: The Chinese Society of Cardiology, the National Natural Scientific Foundation of China, and the Jiangsu Provincial & Nanjing Municipal Clinical Trial Project. TRANSLATION: For the Mandarin translation of the abstract see Supplementary Materials section.

Chronic thromboembolic pulmonary hypertension and balloon pulmonary angioplasty - Where are we in 2024?

Pulmonary endarterectomy (PEA) is the first-line treatment for patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, some patients with CTEPH are considered inoperable, and in the last decade, balloon pulmonary angioplasty (BPA) has emerged as a viable therapeutic option for these patients with prohibitive surgical risk or recurrent pulmonary hypertension following PEA. Numerous international centers have increased their procedural volume of BPA and have reported improvements in pulmonary hemodynamics, patient functional class and right ventricular function. Randomized controlled trials have also demonstrated similar findings. Recent refinements in procedural technique, increased operator experience and advancements in procedural technology have facilitated marked reduction in the risk of complications following BPA. Current guidelines recommend BPA for patients with inoperable CTEPH and persistent pulmonary hypertension following PEA. The pulmonary arterial endothelium plays a vital role in the pathophysiologic development and progression of CTEPH.

FEM simulations for double diffusive transport mechanism hybrid nano fluid flow in corrugated enclosure by installing uniformly heated and concentrated cylinder.

Generation of fluid flow due to simultaneous occurrence of heat and mass diffusions caused by buoyancy differences is termed as double diffusion. Pervasive applications of such diffusion arise in numerous natural and scientific systems. This article investigates double diffusion in naturally convective flow of water-based fluid saturated in corrugated enclosure and containing hybrid nano particles composed of Copper (Cu) and Alumina (Al2O3). Impact of uniformly applied magnetic field is also accounted. To produce thermosolutal convective potential circular cylinder of constant radius is also adjusted by providing uniform temperature and concentration distributions. Finite element approach is capitalized to provide solution of utilized governing equations by utilizing Multiphysics COMSOL software. Wide-range of physical parameters are incorporated to depict their influence on associated distributions (velocity, temperature and concentration). Interesting physical quantities like Nusselt number, Sherwood numbers are also calculated against involved sundry parameters. It is note worthily observed that maximum strength of stream lines [Formula: see text] is 3.3 at [Formula: see text] and drops to 1.2 when [Formula: see text] is increased to 0.04. Furthermore, in the hydrodynamic case (Ha = 0), it is observed that the velocity field exhibits an increasing trend compared to the hydromagnetic case [Formula: see text] which is proved from the attained values of stream-function i.e., [Formula: see text] (in the absence of a magnetic field) and [Formula: see text] (in the presence of a magnetic field). It is revealed from the statistics of Nusselt number that increase in volume fraction of nano particles from 0 to 0.4, heat flux coefficient upsurges up to 7% approximately. Since, present work includes novel physical aspects of thermosolutal diffusion generated due to induction of hybrid nanoparticles in water contained in corrugated enclosure, so this study will provide innovative thought to the researchers to conduct research in this direction.

Intrauterine growth pattern in Butajira HDSS, Southern Ethiopia: BUNMAP pregnancy cohort.

BACKGROUND: Abnormal fetal growth pattern during pregnancy including excessive fetal size and intrauterine growth restrictions are the major determinants for perinatal outcomes and postnatal growth. Ultrasonography is a useful tool in monitoring fetal growth for appropriate care and interventions. However, there are few longitudinal studies using serial ultrasonography in low and middle-income countries. Moreover, the reference charts used for fetal growth monitoring in low-income countries comes from high income countries with distinct population features. Therefore, the purpose of this study was to evaluate the intrauterine growth pattern of the fetus using serial ultrasonography. METHODS: We conducted a prospective community-based cohort study from March 2018 to December 2019. Pregnant women with gestational age of 24 weeks or below living in the Butajira HDSS were enrolled. We followed the pregnant women until delivery. Serial ultrasound measurements were taken, and fetal weight was estimated using the Hadlock algorithm based on biparietal diameter, head circumference, abdominal circumference, and femur length. The z-scores and percentiles of biometric measurements were calculated and compared to the INTERGROWTH-21st International Standards for Fetal Growth. RESULTS: We reviewed a total of 2055 ultrasound scans and 746 women who fulfill the inclusion criteria were involved". We found similar distribution patterns of biometric measurements and estimated fetal weight compared to the previous study done in Ethiopia, the WHO and INTERGROWTH-21st references. In our study, the 5th,50th and 95th percentiles of estimated fetal weight distribution have a similar pattern to the WHO and INTERGROWTH-21st charts. The 50th and 95th percentile had also a similar distribution pattern with the previous study conducted in Ethiopia. We found that 10% of the fetus were small for gestational age (below the 10th percentile) based on the Z-score of estimated fetal weight. CONCLUSION: Our study evaluated the fetal growth patterns in rural community of Ethiopia using serial ultrasound biometric measurements. We found similar IUG patterns to the WHO and INTERGROWTH-21st reference standards as well as the previous study conducted in Ethiopia.

Knowledge, Attitudes, and Practices Regarding Brucellosis Among the General Population in Qassim Region, Saudi Arabia: A Cross-Sectional Study.

Background Brucellosis is an endemic infection in the Middle East. The World Health Organization has identified the illness as one of the most prevalent "neglected zoonotic diseases." Public perceptions regarding brucellosis infection vary across different regions. Thus, this study aimed to assess the knowledge, attitudes, and practices concerning brucellosis among the general population in the Qassim region of Saudi Arabia. Methods A descriptive, cross-sectional study was conducted in the Qassim region of Saudi Arabia between March 2023 and May 2023. We distributed an online questionnaire through social media platforms and received a total of 1,244 responses from different governorates in the Qassim region. Results The level of awareness of brucellosis was moderate. Out of the 1,244 participants, 706 (56.8%) were aware of the disease. Among the participants who were aware of the disease, their knowledge of brucellosis was assessed. The majority of these respondents demonstrated a good level of knowledge (70.5%). Regarding attitudes and practices toward brucellosis, no significant association was found between the participants' level of knowledge and their attitudes. Conclusion Awareness levels about brucellosis in the Qassim region vary depending on age group, area of residency, and other factors. The younger age group and certain governorates in the Qassim region showed low levels of awareness. Moreover, participants with good knowledge about the disease obtained their information from healthcare practitioners. The significant difference in our findings between Qassim's governorates demonstrates the need for more targeted awareness campaigns in areas with lower levels of awareness.

Fecal incontinence as the sole presentation of focal epilepsy; a case report.

Focal epilepsy is a surge in brain activity arising from a localised area of the cerebral cortex; it can be sub-classified in different categories including motor, sensory, autonomic and cognitive subtypes. A clinical case report of a 11-year-old girl was diagnosed with frequent fecal incontinence four or more times daily for more than two months. An electroencephalogram (EEG) study suggested a prominent interictal spike and sharp wave discharge on the left hemisphere, mainly at the frontotemporal region without loss of consciousness or even speech disruption. This could be due to the normal EEG study of the dominant hemisphere. A magnetic resonance imaging study was done to exclude space-occupying lesions or focal lesions of the left hemisphere of the brain. An impression was made with abnormal EEG showing focal epileptiform activity as a final diagnosis. The patient was treated with Leviteracetam anti-epileptic drug 250 mg twice daily with significant clinical improvement at a 3-month follow-up.

COVID-19-Related Spontaneous Aortic Arch Thrombus With Delayed Embolization.

Presentation of a 62-year-old man with baseline chronic obstructive pulmonary disease admitted to the hospital with dyspnea and newly diagnosed COVID-19 infection. CT scan of the chest was obtained to rule out pulmonary embolism. This revealed a mural thrombus of the inner curvature of the aortic arch with a floating component. Therapeutic full dose anticoagulation was initiated in combination with close clinical observation and treatment for modest hypoxia. He did well for 1 month and then returned with ischemic rest pain of the right foot. Angiography revealed thrombosis of all 3 tibial arteries in the right leg. Percutaneous mechanical thrombectomy with tissue plasminogen activator injection and angioplasty was performed with success in 1 tibial artery to achieve in line flow to the foot. After continued anticoagulation, the remainder of the tibial arteries autolysed and the aortic thrombus was noted to be resolved 4 months later. A brief pathophysiology discussion is included.

Knowledge and Attitude of the Public Toward Bariatric Weight Loss Surgery and Its Impact on Candidates and Patients in the Al-Qassim Region, Saudi Arabia.

Background Obesity is defined as abnormal or excessive fat accumulation that presents a serious health risk and is a major public health concern. Obesity prevention and management require evidence-based strategies that emphasize diet and physical activity. Bariatric surgery is also a life-changing procedure that can improve physical and mental health, but the stigma associated with it can prevent people from seeking treatment and affect their lives adversely. Studies have shown that bariatric surgery patients face discrimination from the public and healthcare professionals, which can lead to adverse psychological outcomes and hinder access to quality care. Goals and methods This study intends to explore the stigma related to bariatric surgery in Al-Qassim Region, Saudi Arabia, because it is crucial to understand its prevalence among the public and the influence it has on both those who have undergone the surgery and those who are considering it as an option. The participants had to complete an online questionnaire, comprised a general section and other sections based on whether or not the individual has, has not, or is considering bariatric surgery. Results A total of 988 individuals, 605 of whom were female (61.2%), agreed to participate in the study. The most common body mass index (BMI) category was 18.5-24.9 (43.5%, n=414). The majority of the participants had either agreed or strongly agreed that obesity is a disease (87.8%, n=867) and that genetic factors play a role in causing it (38.8%, n=383). The factors selected most commonly that increase the risk of obesity were "idle and lazy life" (76.5%, n=756) and "eating too much" (75.6%, n=747). Fewer than half of the participants (44.43%, n=439) reported that they had never thought about treating obesity through surgical operations, 9.62% (n=95) had considered it, and 3.74% (n=37) had actually undergone the surgery. Among those who underwent weight loss surgery (n=37), 43.20% (n=16) reported that they received critical comments or poor treatment from the community, 35.10% (n=13) felt ashamed or embarrassed to disclose their surgery, and 37.80% (n=14) avoided social situations or events because of those comments or poor treatment. The comments reported most often were "You have taken the easy way out instead of adopting a healthy lifestyle" (51.40%, n=19) and "Why didn't you try to go on a diet?" (51.40%, n=19). Among those who have intentions to undergo weight loss surgery (n=95), a significant proportion of the participants (43%, n=40) agreed or strongly agreed that concerns about public opinion or community treatment could affect their decision to undergo weight loss surgery. Moreover, 32.6% (n=31) of them agreed or strongly agreed that society has a negative attitude toward individuals who have undergone obesity treatment. When asked whether they had ever avoided telling people that they were considering surgery because of potential adverse reactions, 42.10% (n=40) of the participants responded that they had. Conclusion This study helped bring attention to, and prove, the stigma related to bariatric surgery in Al-Qassim Region. Such stigma has prevented patients from seeking or undergoing a surgical option to manage their weight, even if it is the option recommended for them. As such, public education and awareness campaigns are encouraged to help reduce the stigma, as well as improve access to bariatric surgery for those who need it.

Chronic aflatoxin exposure during pregnancy is associated with lower fetal growth trajectories: a prospective cohort from the Butajira Nutrition, Mental Health, and Pregnancy (BUNMAP) Study in rural Ethiopia.

BACKGROUND: Aflatoxins are toxic secondary metabolites produced by Aspergillus fungi, which are ubiquitously present in the food supplies of low- and middle-income countries. Studies of maternal aflatoxin exposure and fetal outcomes are mainly focused on size at birth and the effect on intrauterine fetal growth has not been assessed. OBJECTIVES: In the present study, we examined the association between chronic aflatoxin exposure during pregnancy and fetal growth trajectories in a rural setting in Ethiopia. METHODS: In a prospective cohort study, we enrolled 492 pregnant females, with a singleton pregnancy and before 28 wk of gestation. Serum aflatoxin B1-lysine concentration was measured using LC-tandem MS. Three rounds of ultrasound measurements were conducted to estimate fetal weight at mean ± SD gestational age weeks of 19.1 ± 3.71, 28.5 ± 3.51, and 34.5 ± 2.44. Estimated fetal weight was expressed in centiles using the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st) reference. We fitted a multivariable linear mixed-effects model to estimate the rate of fetal growth between aflatoxin-exposed (i.e., aflatoxin B1-lysine concentration above or equal to the limit of detection) and unexposed mothers in the study. RESULTS: Mothers had a mean ± SD age of 26.0 ± 4.58 y. The median (25th, 75th percentile) serum aflatoxin B1-lysine concentration was 12.6 (0.93, 96.9) pg/mg albumin, and aflatoxin exposure was observed in 86.6% of maternal blood samples. Eighty-five percent of the females enrolled provided at least 2 ultrasound measurements for analysis. On average, the aflatoxin-exposed group had a significantly lower change over time in fetal weight-for-gestational-age centile than the unexposed group (ß = -0.92; 95% CI: -1.77, -0.06 centiles/week; P = 0.037). CONCLUSIONS: Chronic maternal aflatoxin exposure is associated with lower fetal growth over time. Our findings emphasize the importance of nutrition-sensitive strategies to mitigate dietary aflatoxin exposure and adopting food safety measures in low-income settings, in particular during the fetal period of development.

Sleep quality in COVID-19 recovered patients.

Objective: Novel coronavirus disease 2019 is known to have poor impacts on health with health systems facing serious challenges. Limited information is available on health issues for patients who have recovered from the disease. Our study aims to investigate the extent of sleep disorders in patients who have recovered from the coronavirus disease. Material and Methods: A casecontrol study with 256 patients who had recovered from coronavirus disease 2019 was carried out, with 491 patients enrolled as the control. All participants were 18 years or older, and sleep quality was assessed using the Pittsburgh sleep quality index. Furthermore, sleep latency and hours needed for sleep were calculated. Chi-square and t-test statistical methods were used to analyze the variables. Results: A total of 215 (84%) recovered patients were associated with poor sleep quality, with 384 patients (78%) in the control group. The PSQI values for recovered and control groups were 8.77±3.7591 and 8.139±3.068, respectively, with a significant p-value of 0.014. Average hours needed for sleep were 6.899±3.7869 and 6.44±1.477 for recovered and control patients, respectively, with a significant p-value of 0.01. The difference in sleep latency was non-significant (p=0.374), with 29.01±39.3702 and 33.520±38.208 minutes for recovered and control patients, respectively. Conclusion: Sleep disorders were more prevalent among patients who had recovered from COVID-19 than the control group.

Significance of induced hybridized metallic and non-metallic nanoparticles in single-phase nano liquid flow between permeable disks by analyzing shape factor.

The current communication is designed by keeping in the mind high heat transfer capabilities of nanoliquids with the dispersion of diversified-natured nanoparticles in poorly conducting base liquids. Here, an amalgamation of metallic (Cu) and hybridization of metallic and non-metallic oxide (Cu-TiO2) nanoparticles to uplift thermophysical attributes of water is deliberated. The magnetically affected flow between rotating disks under the impact and permeability aspect is assumed. Empirical relations for effective dynamic viscosity, density, and heat capacitance to show mesmerizing features of obliged nanoparticles are also expressed. In addition, mathematical relations also depend on morphological factors like shape, size, and diameter of inducted nanoparticles. The mathematical formulation of the problem is conceded in the form of a system of ODEs after using similarity transformation on dimensional PDEs. Simulations of the complex coupled differential structure are solved by using a numerical approach by employing shooting and Runge-Kutta procedures jointly. The impact of flow concerning variables on associated distributions is revealed through tabular and graphical manner. Quantities of engineering interest associated with work like wall friction and thermal flux coefficients at walls of the disk are also calculated. It is deduced from an examination that the addition of metallic particles raises heat transfer more than non-metallic particles. A significant impression of magnetic field on shear stress is executed by hybrid nanoparticles along the surface of disks. In addition, elevation in Nusselt number and depreciation in skin friction coefficient is revealed against increasing magnitude of nanoparticle volume fraction. A positive trend in skin friction coefficient is manifested against the increasing magnitude of Reynold number. It is also observed that by increasing the size and shape of hybrid nanoparticles thermal conductivity and viscosity of the base fluid increases.

Development and validation of food frequency questionnaire for food and nutrient intakes of adults in Butajira, Southern Ethiopia.

We developed a culturally-specific Food Frequency Questionnaire (FFQ) to the Ethiopian context and evaluate its validity in comparison to two 24-h dietary recalls (24-HRs) of food and nutrient intake. To evaluate the validity of a culturally-specific FFQ against two 24-HRs, we used a paired t-test, Wilcoxon-signed-rank test, Correlation coefficients, cross-classification, κ and Bland-Altman analysis. The FFQ was obtained 15 d after the second 24-HR was completed. A total of 105 adults, of which 43 (41 %) were men and 62 (59 %) women, aged 20-65 years participated in this present study. Mean energy and macronutrient intake obtained from the FFQ were significantly higher than those obtained from the mean of two 24-HRs. For energy and nutrient intakes, the crude correlation ranged from 0⋅05 (total fat) to 0⋅49 (vitamin B1). The de-attenuated correlation ranged from to 0⋅10 (total fat) to 0⋅80 (vitamin A). For the majority of food groups, no significant difference was observed in the median intake of food and nutrients. Crude correlation for food groups ranged from 0⋅12 (egg) to 0⋅78 (legumes). The de-attenuated correlation ranged from 0⋅24 (egg) to 1⋅00 (meat/poultry/fish and dairy). The FFQ is valid to assess and rank individuals in terms of intake of most food groups according to high and low intake categories.

Inadequacy of nutrient intake among adolescent girls in south central Ethiopia.

Adolescent undernutrition is a major public health problem in Ethiopia. Inadequate dietary intake of nutrients is the major determinants of undernutrition. However, the adequacy of dietary intake among adolescents was not sufficiently explored. The present study aims to estimate the inadequacy of nutrient intake among adolescent girls in south central Ethiopia. A community-based cross-sectional study was conducted. We assess food and nutrient intake using repeated multiple-pass 24-h dietary recall. The study was conducted in Damot Gale district, Woliyta zone, Southern Ethiopia. Data were collected from 288 female adolescents. The majority of adolescent girls consumed cereals (96⋅9 %) and roots/tubers (75⋅3 %). However, only less than 1 % of them consumed flesh food. The mean energy, carbohydrate, protein and dietary fibre intake of the adolescent girls per day was 1452⋅7 ± 356⋅3 kcal, 305⋅6 ± 72⋅4 g, 35⋅7 ± 13⋅3 g and 18⋅6 ± 8⋅4 g, respectively. The median fat intake was 13⋅3 g (IQR 8⋅8, 19⋅8). The contribution of carbohydrate, protein and fat for the total energy was 80, 10 and 8 %, respectively. The prevalence of inadequate intake of protein was 60⋅9 %. The prevalence of inadequate intake of iron for early adolescents and late adolescents was 82 and 53 %, respectively. The prevalence of inadequate intake of folate was 83⋅9 % and zinc was 58 %. The prevalence of inadequate intake was greater than 90 % for vitamin B12, vitamin C and calcium. The present study found an alarmingly high prevalence of inadequate intake of some nutrients among adolescent girls of Damot Gale district.

Dispersion of metallic/ceramic matrix nanocomposite material through porous surfaces in magnetized hybrid nanofluids flow with shape and size effects.

Matrix nanocomposites are high performance materials possessing unusual features along with unique design possibilities. Due to extraordinary thermophysical characteristic contained by these matrix nanocomposites materials they are useful in several areas ranging from packaging to biomedical applications. Being an environment friendly, utilization of nanocomposites offer new technological opportunities for several sectors of aerospace, automotive, electronics and biotechnology. In this regards, current pagination is devoted to analyze thermal features of viscous fluid flow between orthogonally rotating disks with inclusion of metallic matrix nanocomposite (MMNC) and ceramic matrix nanocomposites (CMNC) materials. Morphological aspects of these nanomaterials on flow and heat transfer characteristics has been investigated on hybrid viscous fluid flow. Mathematical structuring of problem along with empirical relations for nanocomposites materials are formulated in the form of partial differential equations and later on converted into ordinary differential expressions by using suitable variables. Solution of constructed coupled differential system is found by collaboration of Runge-Kutta and shooting methods. Variation in skin friction coefficient at lower and upper walls of disks along with measurement about heat transfer rate are calculated against governing physical parameters. Impact of flow concerning variables on axial, radial components of velocity and temperature distribution are also evaluated. Contour plots are also drawn to explore heat and thermal profiles. Comparison and critical analysis of MMNc and CMNc have been presented at lower and upper porous disks. Our computed analysis indicates that hybrid nanofluids show significant influence as compared to simple nanofluids with the permutation of the different shape factors.

RAS inhibition in resident fibroblast biology.

Angiotensin II (Ang II) is a primary mediator of profibrotic signaling in the heart and more specifically, the cardiac fibroblast. Ang II-mediated cardiomyocyte hypertrophy in combination with cardiac fibroblast proliferation, activation, and extracellular matrix production compromise cardiac function and increase mortality in humans. Profibrotic actions of Ang II are mediated by increasing production of fibrogenic mediators (e.g. transforming growth factor beta, scleraxis, osteopontin, and periostin), recruitment of immune cells, and via increased reactive oxygen species generation. Drugs that inhibit Ang II production or action, collectively referred to as renin angiotensin system (RAS) inhibitors, are first line therapeutics for heart failure. Moreover, transient RAS inhibition has been found to persistently alter hypertensive cardiac fibroblast responses to injury providing a useful tool to identify novel therapeutic targets. This review summarizes the profibrotic actions of Ang II and the known impact of RAS inhibition on cardiac fibroblast phenotype and cardiac remodeling.

Drivers of stunting reduction in Ethiopia: a country case study.

BACKGROUND: Chronic undernutrition in children continues to be a global public health concern. Ethiopia has documented a significant decline in the prevalence of childhood stunting, a measure of chronic undernutrition, over the last 20 y. OBJECTIVES: The aim of this research was to conduct a systematic assessment of the determinants that have driven child stunting reduction in Ethiopia from 2000 to 2016, focused on the national, community, household, and individual level. METHODS: This study employed both quantitative and qualitative methods. Specifically, a systematic literature review, retrospective quantitative data analysis using Demographic and Health Surveys from 2000-2016, qualitative data collection and analysis, and analyses of key nutrition-specific and -sensitive policies and programs were undertaken. RESULTS: National stunting prevalence improved from 51% in 2000 to 32% in 2016. Regional variations exist, as do pro-rich, pro-urban, and pro-educated inequalities. Child height-for-age z score (HAZ) decomposition explained >100% of predicted change in mean HAZ between 2000 and 2016, with key factors including increases in total consumable crop yield (32% of change), increased number of health workers (28%), reduction in open defecation (13%), parental education (10%), maternal nutrition (5%), economic improvement (4%), and reduced diarrhea incidence (4%). Policies and programs that were key to stunting decline focused on promoting rural agriculture to improve food security; decentralization of the health system, incorporating health extension workers to improve rural access to health services and reduce open defecation; multisectoral poverty reduction strategies; and a commitment to improving girls' education. Interviews with national and regional stakeholders and mothers in communities presented improvements in health service access, women and girls' education, improved agricultural production, and improved sanitation and child care practices as drivers of stunting reduction. CONCLUSIONS: Ethiopia's stunting decline was driven by both nutrition-specific and -sensitive sectors, with particular focus on the agriculture sector, health care access, sanitation, and education.

Development and Validation of a Risk Score to Predict Low Birthweight Using Characteristics of the Mother: Analysis from BUNMAP Cohort in Ethiopia.

At least one ultrasound is recommended to predict fetal growth restriction and low birthweight earlier in pregnancy. However, in low-income countries, imaging equipment and trained manpower are scarce. Hence, we developed and validated a model and risk score to predict low birthweight using maternal characteristics during pregnancy, for use in resource limited settings. We developed the model using a prospective cohort of 379 pregnant women in South Ethiopia. A stepwise multivariable analysis was done to develop the prediction model. To improve the clinical utility, we developed a simplified risk score to classify pregnant women at high- or low-risk of low birthweight. The accuracy of the model was evaluated using the area under the receiver operating characteristic curve (AUC) and calibration plot. All accuracy measures were internally validated using the bootstrapping technique. We evaluated the clinical impact of the model using a decision curve analysis across various threshold probabilities. Age at pregnancy, underweight, anemia, height, gravidity, and presence of comorbidity remained in the final multivariable prediction model. The AUC of the model was 0.83 (95% confidence interval: 0.78 to 0.88). The decision curve analysis indicated the model provides a higher net benefit across ranges of threshold probabilities. In general, this study showed the possibility of predicting low birthweight using maternal characteristics during pregnancy. The model could help to identify pregnant women at higher risk of having a low birthweight baby. This feasible prediction model would offer an opportunity to reduce obstetric-related complications, thus improving the overall maternal and child healthcare in low- and middle-income countries.

Application of Clinical Pharmacology Principles in Drug Development of Modified-Release Products: Leveraging Exposure-Response Information to Support Approval.

The development of modified-release (MR) drug products aims to address a clinical need such as improving patient compliance. There are multiple pathways and development strategies for the registration and approval of MR products. The development strategy of an MR product is usually dependent on the availability and pharmacokinetic/pharmacodynamics (PK/PD) characteristics of the reference drug product, that is, an immediate-release (IR) product or a reference MR. Compared with a reference IR product, an MR product is likely to have a different PK profile over the least common dosing time due to unequal dosing intervals. In case of differences in PK profiles between the MR product and the reference product, confirmatory efficacy and safety studies may be needed to support registration. In some cases, however, a thorough clinical PK/PD characterization may provide sufficient basis to support the approval of the proposed MR product without the need for additional safety and efficacy studies. This article summarizes the US Food and Drug Administration experience and the regulatory considerations supporting the approval of MR products in the past 6 years and discusses cases in which clinical pharmacology and PK/PD information were leveraged to support approval without the need for additional clinical studies. Details of all these cases are available in the public domain. In 2 cases a well-characterized exposure-response relationship provided sufficient justification that differences in the shape of the PK profiles were not clinically relevant. In the remaining 3 cases a thorough characterization of the PK profile along with a risk-based approach provided bases for approval.

Unhealthy weight control behaviors among Ethiopian female adolescents.

BACKGROUND: Unhealthy weight control behaviors are a serious concern, impairing the quality of life in adolescents. Although recent epidemiological studies indicate a high level of disordered eating in developing countries, such data in Ethiopia are scarce. Thus, this study aimed to determine the extent of unhealthy weight control behaviors (i.e., purging and nonpurging) and corresponding associated factors among urban Ethiopian adolescents. METHOD: A cross-sectional study using self-administered questionnaires was applied to 690 randomly selected female high school adolescents in Addis Ababa, Ethiopia in 2017. Measures included unhealthy weight control behaviors, body mass index, subjective perception of body weight, appearance satisfaction, depressive symptoms, and socio-demographic factors. Logistic regression was applied for data analyses, that is, adjusted odds ratio (aOR) with 95% confidence interval (CI). RESULTS: The level of unhealthy weight control behaviors (i.e., a score of at least once a week in the last 1 month) was 30.7% (N = 208). Specifically, the extent of purging and nonpurging weight control behaviors was 1.5% (N = 10) and 29.8% (N = 202), respectively. Factors that were significantly associated with unhealthy weight control behaviors were perception of being overweight [aOR = 3.01; 95%CI: 1.11-8.11], being overweight [aOR = 3.28; 95%CI: 1.54-7.01], severe depression [aOR = 4.09; 95%CI: 1.73-9.96], and high socio-economic status [aOR = 2.07; 95%CI: 1.30-2.80]. CONCLUSION: This study reveals a considerable level of unhealthy weight control behaviors among female adolescents in an urban setting in Ethiopia. Researchers and policy makers should focus their attention upon this emerging public health challenge and develop associated strategies.