The Challenges and Lessons Learned Building a New UK Infrastructure for Finding and Accessing Population-Wide COVID-19 Data for Research and Public Health Analysis: The CO-CONNECT Project.

The COVID-19-Curated and Open Analysis and Research Platform (CO-CONNECT) project worked with 22 organizations across the United Kingdom to build a federated platform, enabling researchers to instantaneously and dynamically query federated datasets to find relevant data for their study. Finding relevant data takes time and effort, reducing the efficiency of research. Although data controllers could understand the value of such a system, there were significant challenges and delays in setting up the platform in response to COVID-19.

Traumatic rhabdomyolysis: rare but morbid, potentially lethal, and inconsistently monitored.

Purpose: Although traumatic rhabdomyolysis (TR) is shown to be associated with acute kidney injury (AKI), there are no large prospective epidemiological studies, interventional trials, official guidelines outlining the appropriate investigation, monitoring, and treatment on this poorly understood condition. We aimed to establish the contemporary epidemiology and describe current practices for TR to power future higher quality studies. We hypothesised that investigation and monitoring occur in an ad hoc fashion.

How to do laparoscopic repair of perforated anterior duodenal ulcers: a 'three arches' falciform patch technique simplifies the approach.

Laparoscopic repair of perforated duodenal ulcers has proven superior results to open procedures though uptake has been poor. We describe the 'three arches' technique as a means of reducing technical difficulty and improving operative efficiency. Our case series of patients undergoing this technique for perforated peptic ulcer disease demonstrates comparable results to other methods of repair.

A Hybrid Architecture (CO-CONNECT) to Facilitate Rapid Discovery and Access to Data Across the United Kingdom in Response to the COVID-19 Pandemic: Development Study.

Background: COVID-19 data have been generated across the United Kingdom as a by-product of clinical care and public health provision, as well as numerous bespoke and repurposed research endeavors. Analysis of these data has underpinned the United Kingdom's response to the pandemic, and informed public health policies and clinical guidelines. However, these data are held by different organizations, and this fragmented landscape has presented challenges for public health agencies and researchers as they struggle to find relevant data to access and interrogate the data they need to inform the pandemic response at pace.

Life-threatening gastrointestinal haemorrhage requiring surgical resection caused by SARS-CoV-2 induced ANCA associated vasculitis: A case report.

Introduction And Importance: SARS-CoV-2 infection has been linked to the diagnosis of various autoimmune conditions as well as flares in pre-existing disease. With such high prevalence of SARS-CoV-2 in the community, it is important to consider rare manifestations of autoimmune conditions when patients present with severe symptoms. Multi-specialty care is required to ensure optimal outcomes and prompt diagnosis.

Portal vein stenting in the management of duodenal varices due to malignant obstruction: A case report and literature review.

Introduction And Importance: Ectopic varices of the small bowel are a rare complication of portal hypertension. There are various aetiologies that can cause portal vein hypertension such as portal vein obstruction. Each of these pathologies has their own management strategies.

Primary cervical screening with high risk human papillomavirus testing: observational study.

Objective: To provide the first report on the main outcomes from the prevalence and incidence rounds of a large pilot of routine primary high risk human papillomavirus (hrHPV) testing in England, compared with contemporaneous primary liquid based cytology screening.

Design: Observational study.

Setting: The English Cervical Screening Programme.

Analysis of decreases in systemic arterial pressure and heart rate in response to the hydrogen sulfide donor sodium sulfide.

The actions of hydrogen sulfide (HS) on the heart and vasculature have been extensively reported. However, the mechanisms underlying the effects of HS are unclear in the anesthetized rat. The objective of the present study was to investigate the effect of HS on the electrocardiogram and examine the relationship between HS-induced changes in heart rate (HR), mean arterial pressure (MAP), and respiratory function.

Rationale for nebivolol/valsartan combination for hypertension: review of preclinical and clinical data.

: To treat hypertension, combining two or more antihypertensive drugs from different classes is often necessary. β-Blockers and renin-angiotensin-aldosterone system inhibitors, when combined, have been deemed 'less effective' based on partially overlapping mechanisms of action and limited evidence. Recently, the single-pill combination (SPC) of nebivolol (Neb) 5 mg - a vasodilatory β1-selective antagonist/β3 agonist - and valsartan 80 mg, an angiotensin II receptor blocker, was US Food and Drug Administration-approved for hypertension.

Efficacy of nebivolol-valsartan single-pill combination in obese and nonobese patients with hypertension.

Antihypertensive efficacy of single-pill combinations (SPCs) consisting of a β -selective adrenergic blocker with vasodilatory properties via β -agonism (nebivolol) and an angiotensin II receptor blocker (valsartan) was demonstrated in an 8-week phase 3 trial (NCT01508026). In this post hoc analysis, seated blood pressure, heart rate, 24-hour ambulatory blood pressure monitoring, plasma aldosterone, estimated glomerular filtration rate, and safety measures were assessed in obese (body mass index >32 kg/m ; n=1823) and nonobese (body mass index <27 kg/m ; n=847) adults with hypertension (stage I or II) treated with nebivolol-valsartan SPCs, nebivolol or valsartan monotherapy, or placebo. At week 8, reductions from baseline in blood pressure and ambulatory blood pressure monitoring were greater with SPCs and most nebivolol and valsartan monotherapy doses vs placebo regardless of obesity status.

Methodological evaluation of the noninvasive estimation of central systolic blood pressure in nontreated patients: the Bogalusa Heart Study.

Objectives: This study sought to compare the estimation of central systolic blood pressure (cSBP) obtained by two different noninvasive devices, in addition to its comparisons with measured peripheral systolic blood pressure (pSBP), in a biracial (Black/White) community-based cohort.

Participants And Methods: Estimations of cSBP by applanation tonometry were obtained in 586 participants of the Bogalusa Heart Study (mean age: 43.5 years; 69% White, 54% women) using two different commonly used instruments: Omron HEM-9000AI and SphygmoCor CPV.

A mathematical algorithm for quantification of CT image noise.

Quantification of computed tomography (CT) noise helps in determination of radiation dosage requirements for adequate image quality. Clinical methods used include calculation of the standard deviation (SD) of a selected region of interest (ROI). In industry, wavelet decomposition has been used for image compression while removing high-frequency noise.

Fixed-dose combination therapy of nebivolol and valsartan for the treatment of hypertension.

Recent large clinical trials have refuted earlier suggestions from the Joint National Committee 8 committee that less aggressive targets for blood pressure control were all that could be justified in most hypertensive patients. It now does appear that in fact "lower is better," with blood pressure targets < 120/80 mm Hg appropriate for many hypertensive patients. Two drug combinations are often indicated as initial therapy if a 20/10 mm Hg or greater blood pressure reduction is necessary to reach target.

Prehypertension: Defining the Transitional Phenotype.

More than a simple "transitional stage" defined by covenanted cut points of systolic pressure from 120 to 139 mm of mercury (mm Hg) or a diastolic pressure from 80 to 89 mm Hg, prehypertension should be referred to as a categorical term that defines a specific phenotype in the progression from the "absence of disease" to clinically overt disease. While the currently utilized definition of prehypertension stresses the use of blood pressure cut points to establish the diagnosis, it is of relevance to direct our attention to the structural and functional hemodynamic alterations that occur in response to the two cardinal abnormalities in the development of prehypertension and hypertension: autonomic dysfunction and arterial remodeling. Our current review addresses these aspects of the pathophysiology or prehypertension on its progression to hypertension and suggests a new approach to its classification.

Correlations of plasma renin activity and aldosterone concentration with ambulatory blood pressure responses to nebivolol and valsartan, alone and in combination, in hypertension.

After demonstration of the antihypertensive efficacy of the combination of the beta-blocker nebivolol and the angiotensin receptor blocker valsartan in an 8-week, randomized, placebo-controlled trial (N = 4161), we now report the effects of this treatment on the renin-angiotensin-aldosterone system in a substudy (n = 805). Plasma renin activity increased with valsartan (54%-73%) and decreased with nebivolol (51%-65%) and the combination treatment (17%-39%). Plasma aldosterone decreased with individual treatments (valsartan, 11%-22%; nebivolol, 20%-26%), with the largest reduction (35%) observed with maximum combination dose (20 mg nebivolol/320 mg valsartan).

The 'W' prawn-trawl with emphasised drag-force transfer to its centre line to reduce overall system drag.

For prawn trawling systems, drag reduction is a high priority as the trawling process is energy intensive. Large benefits have occurred through the use of multiple-net rigs and thin twine in the netting. An additional positive effect of these successful twine-area reduction strategies is the reduced amount of otter board area required to spread the trawl systems, which leads to further drag reduction.

Nebivolol and valsartan as a fixed-dose combination for the treatment of hypertension.

Introduction: The fixed-dose combination of nebivolol and valsartan drug has been clinically evaluated and demonstrated to represent a unique combination of nebivolol, a selective β1-adrenoceptor antagonist and a β3-adrenoceptor agonist; β3 receptor activation increases endothelial nitric oxide and produces vasodilation. Valsartan is highly selective angiotensin AT1 receptor blocker and exerts its major pharmacological effect by decreasing angiotensin II-induced vasoconstriction and production of aldosterone. The addition of nebivolol counteracts the effects of increased angiotensin II concentrations resulting from potent AT1 blockade.

Digital plethysmography and arginine metabolism in prehypertension: effect of nebivolol therapy.

Prehypertension is an important phenotype for cardiovascular risk and development of established hypertension. To better understand the early circulatory changes in this group, the authors studied 34 patients with prehypertension (blood pressure 120-139/80-89 mm Hg) using digital plethysmography for measurement of blood flow and reactive hyperemic index (RHI). Arterial augmentation index (AI) was also measured.