Individual and community-level determinants of knowledge of obstetric danger signs among women in Southern Ethiopia: A multi-level mixed effect negative binomial analysis.

Introduction: One of the key strategies to achieve the sustainable development goal by reducing maternal deaths below 70 per 100,000 is improving knowledge of obstetric danger signs (ODS). However, mothers' knowledge of ODS is low in general and very low in rural settings, regardless of local and national efforts in Ethiopia. Further, there is significant variation of ODS knowledge among women from region to region and urban/rural settings.

Association of overweight and obesity with gestational diabetes mellitus among pregnant women attending antenatal care clinics in Addis Ababa, Ethiopia: a case-control study.

Objective: Maternal obesity and gestational diabetes mellitus (GDM) are becoming major public health concerns in developing countries. Understanding their relationship can help in developing contextually appropriate and targeted prevention strategies and interventions to improve maternal and infant health outcomes. This study aimed to determine the association of maternal overweight and obesity with GDM among pregnant women in Ethiopia.

Mapping the membrane orientation of auxin homeostasis regulators PIN5 and PIN8 in Arabidopsis thaliana root cells reveals their divergent topology.

PIN proteins establish the auxin concentration gradient, which coordinates plant growth. PIN1-4 and 7 localized at the plasma membrane (PM) and facilitate polar auxin transport while the endoplasmic reticulum (ER) localized PIN5 and PIN8 maintain the intracellular auxin homeostasis. Although an antagonistic activity of PIN5 and PIN8 proteins in regulating the intracellular auxin homeostasis and other developmental events have been reported, the membrane topology of these proteins, which might be a basis for their antagonistic function, is poorly understood.

Emission and performance analysis of diesel engine running with CeO nanoparticle additive blended into castor oil biodiesel as a substitute fuel.

The implications of adding cerium oxide (CeO) nanoparticles as a fuel additive to a castor oil biodiesel-diesel fuel blend on engine performance and emissions in a single-cylinder four-stroke diesel engine under various speed were examined in the current study. The test fuels used were fossil diesel fuels, B5 blend biodiesel (as 5% biodiesel and 95% diesel), B10 blend biodiesel (as 10% biodiesel and 90% diesel), B15 blend biodiesel (as 15% biodiesel and 85% diesel), B20 blend biodiesel (as 20% biodiesel and 80% diesel), and B25 blend biodiesel (as 25% biodiesel and 75% diesel), with cerium oxide (CeO) nanoparticle additive (75 ppm). The result of the physio-chemical properties of the oil samples was within the limit of the ASTM standard.

Estimand in benefit-risk assessment.

ICH E9(R1) introduces the estimand framework to strengthen dialogues between sponsors and regulators during drug development. A well-structured benefit-risk assessment (BRA) framework also intends to facilitate communication among stakeholders. However, the estimand in ICH E9(R1) is written mainly from the perspective of a single measure of treatment effect in clinical trials.

Design of paediatric trials with benefit-risk endpoints using a composite score of adverse events of interest (AEI) and win-statistics.

A fundamental problem in the regulatory evaluation of a therapy is assessing whether the benefit outweighs the associated risks. This work proposes designing a trial that assesses a composite endpoint consisting of benefit and risk, hence, making the core of the design of the study, to assess benefit and risk. The proposed benefit risk measure consists of efficacy measure(s) and a risk measure that is based on a composite score obtained from pre-defined adverse events of interest (AEI).

The win odds: statistical inference and regression.

Generalized pairwise comparisons and win statistics (i.e., win ratio, win odds and net benefit) are advantageous in analyzing and interpreting a composite of multiple outcomes in clinical trials.

Win statistics (win ratio, win odds, and net benefit) can complement one another to show the strength of the treatment effect on time-to-event outcomes.

Conventional analyses of a composite of multiple time-to-event outcomes use the time to the first event. However, the first event may not be the most important outcome. To address this limitation, generalized pairwise comparisons and win statistics (win ratio, win odds, and net benefit) have become popular and have been applied to clinical trial practice.

The Magnitude and Associated Factors of Consistent Condom Utilization Among ART Users in Hawassa City, Sidama, Ethiopia.

Background: Antiretroviral therapy (ART) introduction has sharply decreased mortality and morbidity rates among HIV-infected patients and resulted in longer and healthier lives among people living with HIV. Hence, the aim of this study is to determine the level of consistent condom use and associated factors among ART users in Hawassa City.

Methods: Cross-sectional study design triangulated with qualitative phenomenology was used.

Prevalence and Associated Factors of Diabetes Mellitus Among Adult Population in Hawassa Zuria Woreda, Sidama Region, Ethiopia.

Background: Diabetes mellitus (DM) is one of the main health problems in unindustrialized countries. According to the International Diabetes Federation report, adults living with diabetes were growing from time to time globally. Worldwide, diabetes mellitus accounts for 8.

Real-World Evidence Utilization in Clinical Development Reflected by US Product Labeling: Statistical Review.

The US Food and Drug Administration (FDA) has shown scientific discretion in interpreting the substantial evidence requirement for the approval of new drugs with its considerations on the use of single controlled or uncontrolled trials (Federal Food, Drug, and Cosmetic Act § 505(d), 21 USC 355(d), 1962). With the passage of the 21st Centuries Cures Act (21st Century Cures-patients. House, Energy and Commerce Committee, Washington, DC, 2019 available at: https://energycommerce.

Randomized, assessor-blinded trial comparing highly purified human menotropin and recombinant follicle-stimulating hormone in high responders undergoing intracytoplasmic sperm injection.

Objective: To evaluate the efficacy and safety of highly purified human menotropin (HP-hMG) and recombinant follicle-stimulating hormone (rFSH) for controlled ovarian stimulation in a population of patients predicted to be high responders.

Design: Randomized, open-label, assessor-blinded, parallel-group, noninferiority trial.

Setting: Fertility centers.

The win ratio: Impact of censoring and follow-up time and use with nonproportional hazards.

The win ratio has been studied methodologically and applied in data analysis and in designing clinical trials. Researchers have pointed out that the results depend on follow-up time and censoring time, which are sometimes used interchangeably. In this article, we distinguish between follow-up time and censoring time, show theoretically the impact of censoring on the win ratio, and illustrate the impact of follow-up time.

The Nuts and Bolts of PIN Auxin Efflux Carriers.

The plant-specific proteins named PIN-FORMED (PIN) efflux carriers facilitate the direction of auxin flow and thus play a vital role in the establishment of local auxin maxima within plant tissues that subsequently guide plant ontogenesis. They are membrane integral proteins with two hydrophobic regions consisting of alpha-helices linked with a hydrophilic loop, which is usually longer for the plasma membrane-localized PINs. The hydrophilic loop harbors molecular cues important for the subcellular localization and thus auxin efflux function of those transporters.

Efficacy and safety of a ready-to-drink bowel preparation for colonoscopy: a randomized, controlled, non-inferiority trial.

Background: We performed a randomized, controlled, assessor-blinded, multicenter, non-inferiority (NI) study to compare the safety and efficacy of a ready-to-drink formulation of sodium picosulfate, magnesium oxide, and citric acid (SPMC oral solution) with a powder formulation (P/MC powder) for oral solution.

Methods: Eligible participants (adults undergoing elective colonoscopy) were randomized 1:1 to split-dose SPMC oral solution or P/MC powder. The primary efficacy endpoint assessed overall colon-cleansing quality with the Aronchick Scale (AS), and the key secondary efficacy endpoint rated quality of right colon cleansing with the Boston Bowel Preparation Scale (BBPS).

Statistical Monitoring in Clinical Trials: Best Practices for Detecting Data Anomalies Suggestive of Fabrication or Misconduct.

Background: Traditional site-monitoring techniques are not optimal in finding data fabrication and other nonrandom data distributions with the greatest potential for jeopardizing the validity of study results. TransCelerate BioPharma conducted an experiment testing the utility of statistical methods for detecting implanted fabricated data and other signals of noncompliance.

Methods: TransCelerate tested statistical monitoring on a data set from a chronic obstructive pulmonary disease (COPD) clinical study with 178 sites and 1554 subjects.

Nonparametric multivariate inference on shift parameters.

Rationale And Objectives: Consider a study evaluating the prognostic value of prostate-specific antigen (PSA), in the presence of Gleason score, in differentiating between early and advanced prostate cancer. This data set features subjects divided into two groups (early versus advanced cancer), with one manifest variable (PSA), one covariate (Gleason score), and one stratification variable (hospital, taking three values). We present a nonparametric method for estimating a shift in median PSA score between the two groups, after adjusting for differences in Gleason score and stratifying on hospital.

Time-to-effect with darifenacin in overactive bladder: a pooled analysis.

Introduction And Hypothesis: This study was conducted to assess time-to-effect with darifenacin in patients with overactive bladder (OAB).

Methods: Efficacy and safety data were pooled from 1,059 patients (19-88 years, 85% women) randomized to darifenacin 7.5 or 15 mg once daily or matched placebo in three double-blind 12-week studies.

Moderate versus intensive treatment of hypertension with amlodipine/valsartan for patients uncontrolled on angiotensin receptor blocker monotherapy.

Objectives: Many angiotensin receptor blocker (ARB) monotherapy patients need at least two agents to control blood pressure (BP). We investigated whether initiating intensive treatment with combination amlodipine/valsartan was superior to moderate treatment with amlodipine/valsartan in patients previously uncontrolled on ARB monotherapy.

Methods: In this 12-week study, patients aged at least 18 years on ARB (other than valsartan) for at least 28 days (with treatment-naïve patients or those not controlled on agents other than an ARB treated with open-label olmesartan 20 or 40 mg, respectively, for 28 days) and with uncontrolled mean sitting systolic blood pressure (MSSBP; ≥ 150-<200 mmHg) were randomized to amlodipine/valsartan 5/320 mg (n = 369) or 5/160 mg (n = 359).

Effect of intensive versus standard blood pressure lowering on diastolic function in patients with uncontrolled hypertension and diastolic dysfunction.

Diastolic dysfunction may precede development of heart failure in hypertensive patients. We randomized 228 patients with uncontrolled hypertension, preserved ejection fraction, and diastolic dysfunction to 2 targeted treatment strategies: intensive, with a systolic blood pressure target of <130 mm Hg, or standard, with a systolic blood pressure target of <140 mm Hg, using a combination of valsartan, either 160 or 320 mg, plus amlodipine, either 5 or 10 mg, with other antihypertensive medications as needed. Echocardiographic assessment of diastolic function was performed at baseline and after 24 weeks in a prospective, open-label, blinded end point design.

EXCEED: Exforge-intensive control of hypertension to evaluate efficacy in diastolic dysfunction: study rationale, design, and participant characteristics.

Background: Both diastolic dysfunction and increased vascular stiffness represent important measures of target-organ damage in hypertension. Whether intensive blood pressure (BP) control can further improve these measures remains unknown.

Methods: EXCEED is a prospective, randomized open-label blinded endpoint trial (PROBE) design, aiming to test the hypothesis that more aggressive BP lowering would result in greater improvement in diastolic function among patients with stage II hypertension, evidence of diastolic dysfunction and preserved systolic function (EF > or = 50%).

Initial combination therapy compared with monotherapy in diabetic hypertensive patients.

Subgroup analyses were performed for the diabetic and nondiabetic cohorts from 3 randomized clinical trials that had evaluated the systolic blood pressure (SBP)-lowering efficacy and tolerability of an angiotensin receptor blocker, valsartan, alone or in combination with hydrochlorothiazide to determine when and how to initiate combination therapy in hypertensive patients with diabetes. Blood pressure reductions achieved with monotherapy were compared with combination therapy in the diabetic and nondiabetic cohorts. In addition, multivariate models were developed to predict the likelihood of the goal SBP of < 130 mm Hg being reached in a diabetic patient with monotherapy or combination therapy across the range of baseline SBP values.

Long-term administration of enteric-coated mycophenolate sodium (EC-MPS; myfortic) is safe in kidney transplant patients.

Background: To date, there are no data on long-term use of enteric-coated mycophenolate sodium (EC-MPS; myfortic) from time of renal transplantation. We report the first long-term safety and efficacy data on EC-MPS when administered for up to 3 years post transplant.

Methods: De novo renal transplant recipients completing 1 year of treatment in a multicenter, randomized, double-blind trial of EC-MPS versus mycophenolate mofetil (MMF) were invited to take part in an open-label extension during which all patients received EC-MPS 720 mg b.