Effects of valsartan vs amlodipine and achieved lower blood pressure on the incidence of end-stage kidney disease: The VALUE Trial.

Background: There is a paucity of data investigating the impact of antihypertensive drug classes and blood pressure (BP) treatment targets on the incidence of end-stage kidney disease (ESKD). In patients with high-risk hypertension aged 50-80 years or above, we aimed to, 1) compare effects of valsartan, an angiotensin receptor blocker, with amlodipine, a calcium channel blocker and, 2) assess the effect of achieving systolic BP <135 vs ≥135 mmHg on the ESKD incidence.

Methods: The VALUE Trial was a multicenter prospective double-blinded randomized clinical trial in patients with essential hypertension and high cardiovascular risk including known coronary disease, left ventricular hypertrophy and previous stroke, in which ESKD was a secondary endpoint defined as progression to kidney transplant and/or dialysis.

Supercharged Phosphotriesterase for improved Paraoxon activity.

Phosphotriesterases (PTEs) represent a class of enzymes capable of efficient neutralization of organophosphates (OPs), a dangerous class of neurotoxic chemicals. PTEs suffer from low catalytic activity, particularly at higher temperatures, due to low thermostability and low solubility. Supercharging, a protein engineering approach via selective mutation of surface residues to charged residues, has been successfully employed to generate proteins with increased solubility and thermostability by promoting charge-charge repulsion between proteins.

Effect of Therapeutic Drug Monitoring on Adherence and Blood Pressure: A Multicenter Randomized Clinical Trial.

Background: Drug concentration in blood or urine is an acknowledged method to detect nonadherence. Observational studies suggest that informing patients about low or absent serum drug levels improves blood pressure (BP). We performed a multicenter randomized clinical trial to test the hypothesis that therapeutic drug monitoring (TDM) could improve drug adherence and BP in patients with uncontrolled hypertension (HT).

Novel biomarkers in patients with uncontrolled hypertension with and without kidney damage.

Introduction: Estimated glomerular filtration rate (eGFR) and urine albumin/creatinine ratio (ACR) are insensitive biomarkers for early detection of hypertension-mediated organ damage (HMOD). In this nationwide cross-sectional study, we assessed potential biomarkers for early HMOD in healthy persons and patients with hypertension. We hypothesised that plasma levels of biomarkers: (1) are different between healthy controls and patients with hypertension, (2): can classify patients with hypertension according to the degree of hypertension severity.

Gender Differences in Cardiac Organ Damage in Arterial Hypertension: Assessing the Role of Drug Nonadherence.

Introduction: Cardiac organ damage like left ventricular (LV) hypertrophy and left atrial (LA) enlargement is more prevalent in women than men with hypertension, but the mechanisms underlying this gender difference remain unclear.

Methods: We tested the association of drug nonadherence with the presence of LV hypertrophy and LA enlargement by echocardiography in 186 women and 337 men with uncontrolled hypertension defined as daytime systolic blood pressure (BP) ≥ 135mmHg despite the prescription of at least two antihypertensive drugs. Drug adherence was assessed by measurements of serum drug concentrations interpreted by an experienced pharmacologist.

Computational Design of Phosphotriesterase Improves V-Agent Degradation Efficiency.

Organophosphates (OPs) are a class of neurotoxic acetylcholinesterase inhibitors including widely used pesticides as well as nerve agents such as VX and VR. Current treatment of these toxins relies on reactivating acetylcholinesterase, which remains ineffective. Enzymatic scavengers are of interest for their ability to degrade OPs systemically before they reach their target.

INdigenous Systems and Policies Improved and Reimagined for Ear and hearing care (INSPIRE): a multi-method study protocol.

Introduction: Otitis media (middle ear disease) severity and chronicity among Aboriginal and Torres Strait Islander people, as well as gaps in socioeconomic outcomes related to hearing loss, indicates a breakdown in the current ear and hearing care system. The ear and hearing care system spans multiple sectors due to long-term impacts of otitis media and hearing loss in health, education and employment, necessitating a multi-disciplinary cross-sectorial approach to ear and hearing care. Public policies shape the current ear and hearing care system and here it is argued that a critical public policy analysis across different sectors is needed, with strong Aboriginal and Torres Strait Islander leadership and guidance.

Ear and hearing care programs for First Nations children: a scoping review.

Background: Ear and hearing care programs are critical to early detection and management of otitis media (or middle ear disease). Otitis media and associated hearing loss disproportionately impacts First Nations children. This affects speech and language development, social and cognitive development and, in turn, education and life outcomes.

Examining relationships between parent-reported factors and recurring ear symptoms among Aboriginal and Torres Strait Islander children.

Issue Addressed: Aboriginal and Torres Strait Islander child ear health is complex and multiple. We examined relationships between parent-reported sociodemographic, child health, health service access factors and ear symptoms among Aboriginal and Torres Strait Islander children aged 3 to 7 years.

Methods: The Longitudinal Study of Indigenous Children is a large child cohort study with annual parent-reported data collection.

Culturally safe speech-language supports for First Nations children: Achieving Sustainable Development Goals 3, 4, 8 and 10.

Purpose: Self-determination is foundational to health and well-being for First Nations people. Colonisation has undermined self-determination and widespread effects are observed as disparities in health and well-being. Chronic middle ear disease is more highly prevalent in First Nations children, is associated with delays in speech and language and lower levels of educational readiness.

Nonadherence by Serum Drug Analyses in Resistant Hypertension: 7-Year Follow-Up of Patients Considered Adherent by Directly Observed Therapy.

Background Measurement of serum concentrations of drugs is a novelty found useful in detecting poor drug adherence in patients taking ≥2 antihypertensive agents. Regarding patients with treatment-resistant hypertension, we previously based our assessment on directly observed therapy. The present study aimed to investigate whether serum drug measurements in patients with resistant hypertension offer additional information regarding drug adherence, beyond that of initial assessment with directly observed therapy.

Leveraging artificial intelligence and data science techniques in harmonizing, sharing, accessing and analyzing SARS-COV-2/COVID-19 data in Rwanda (LAISDAR Project): study design and rationale.

Background: Since the outbreak of COVID-19 pandemic in Rwanda, a vast amount of SARS-COV-2/COVID-19-related data have been collected including COVID-19 testing and hospital routine care data. Unfortunately, those data are fragmented in silos with different data structures or formats and cannot be used to improve understanding of the disease, monitor its progress, and generate evidence to guide prevention measures. The objective of this project is to leverage the artificial intelligence (AI) and data science techniques in harmonizing datasets to support Rwandan government needs in monitoring and predicting the COVID-19 burden, including the hospital admissions and overall infection rates.

Development of UHPLC-MS/MS methods to quantify 25 antihypertensive drugs in serum in a cohort of patients treated for hypertension.

We developed three ultra-high pressure liquid chromatography coupled to mass spectrometry detection (UHPLC-MS/MS) methods to quantify 25 antihypertensive drugs in serum samples. Patient-reported drug lists were collected, and drug concentrations were analysed in samples from 547 patients, half with uncontrolled hypertension, and all treated with ≥ 2 antihypertensive drugs. For sample preparation, serum was mixed with deuterated internal standards and acetonitrile and precipitated.

Detection of Nonadherence to Antihypertensive Treatment by Measurements of Serum Drug Concentrations.

[Figure: see text].

The randomised Oslo study of renal denervation Antihypertensive drug adjustments: efficacy and safety through 7 years of follow-up.

Purpose: The blood pressure (BP) lowering effect of renal sympathetic denervation (RDN) in treatment-resistant hypertension shows variation amongst the existing randomised studies. The long-term efficacy and safety of RDN require further investigation. For the first time, we report BP changes and safety up to 7 years after RDN, compared to drug adjustment in the randomised Oslo RDN study.

Impact of phenylalanines outside the dimer interface on phosphotriesterase stability and function.

We explore the significance of phenylalanine outside of the phosphotriesterase (PTE) dimer interface through mutagenesis studies and computational modeling. Previous studies have demonstrated that the residue-specific incorporation of para-fluorophenylalanine (pFF) into PTE improves stability, suggesting the importance of phenylalanines in stabilization of the dimer. However, this comes at a cost of decreased solubility due to pFF incorporation into other parts of the protein.

Implantation and persistence of yeast inoculum in Pinot noir fermentations at three Canadian wineries.

Inoculated fermentations are practiced in most wine regions of the world. This type of fermentation involves adding a commercial Saccharomyces cerevisiae strain as an inoculant. It is often assumed that the inoculant maintains dominance throughout the fermentation; however, sometimes commercial or indigenous yeasts, which were not intentionally added, end up as the dominant yeast in the winery fermentation.

Giving birth with rape in one's past: a qualitative study.

Background: Rape is one of the most traumatizing violations a woman can be subjected to, and leads to extensive health problems, predominantly psychological ones. A large proportion of women develop a form of posttraumatic stress termed Rape Trauma Syndrome. A previous study by our research group has shown that women with a history of rape far more often had an operative delivery in their first birth and those who gave birth vaginally had second stages twice as long as women with no history of sexual assault.

Image diagnosis: Spontaneous hematoma from scurvy.

A 58-year-old alcoholic man presents with pain, swelling, and bruising of his right leg, without history of trauma or injury. He had had frequent spontaneous hematomas in his legs. This patient drank a 1.

Different labour outcomes in primiparous women that have been subjected to childhood sexual abuse or rape in adulthood: a case-control study in a clinical cohort.

Objective: To compare the duration and outcome of the first labour in women who have been subjected to childhood sexual abuse (CSA) and women who have been raped in adulthood (RA).

Design: Case-control study in a clinical cohort.

Setting: University Hospital of North Norway.