A 1-Year Weight Management Program for Difficult-to-Treat Asthma With Obesity: A Randomized Controlled Study.

Background: Obesity-associated asthma results in increased morbidity and mortality. We report 1-year asthma outcomes with a weight management regimen, the Counterweight-Plus Programme (CWP), compared with usual care (UC) in a single-center, randomized controlled trial in patients with difficult-to-treat asthma and obesity.

Research Question: Can use of the CWP result in improved asthma control and quality of life compared with UC at 1 year in patients with difficult-to-treat asthma and obesity?

Study Design And Methods: Adults with difficult-to-treat asthma and BMI ≥ 30 kg/m were randomized (1:1 CWP:UC) to treatment.

Direct synthesis of partially ethoxylated branched polyethylenimine from ethanolamine.

We report here a method to make a branched and partially ethoxylated polyethyleneimine derivative directly from ethanolamine. The polymerization reaction is catalysed by a pincer complex of Earth-abundant metal, manganese, and produces water as the only byproduct. Industrial processes to produce polyethyleneimines involve the transformation of ethanolamine to a highly toxic chemical, aziridine, by an energy-intensive/waste-generating process followed by the ring-opening polymerization of aziridine.

De-epimerizing DyKAT of β-lactones generated by isothiourea-catalysed enantioselective [2 + 2] cycloaddition.

An enantioselective isothiourea-catalysed [2 + 2] cycloaddition of C(1)-ammonium enolates with pyrazol-4,5-diones is used to construct spirocyclic β-lactones in good yields, excellent enantioselectivity (99 : 1 er) but with modest diastereocontrol (typically 70 : 30 dr). Upon ring-opening with morpholine or alternative nucleophilic amines and alcohols β-hydroxyamide and β-hydroxyester products are generated with enhanced diastereocontrol (up to >95 : 5 dr). Control experiments show that stereoconvergence is observed in the ring-opening of diastereoisomeric β-lactones, leading to a single product (>95 : 5 dr, >99 : 1 er).

Synthesis of Tetra-Substituted 3-Hydroxyphthalide Esters by Isothiourea-Catalysed Acylative Dynamic Kinetic Resolution.

A general and highly enantioselective method for the preparation of tetra-substituted 3-hydroxyphthalide esters via isothiourea-catalysed acylative dynamic kinetic resolution (DKR) is reported. Using (2S,3R)-HyperBTM (5 mol %) as the catalyst, the scope and limitations of this methodology have been extensively probed, with high enantioselectivity and good to excellent yields observed (>40 examples, up to 99 %, 99 : 1 er). Substitution of the aromatic core within the 3-hydroxyphthalide skeleton, as well as aliphatic and aromatic substitution at C(3), is readily tolerated.

Accelerometer-derived sleep metrics in mild and difficult-to-treat asthma.

Introduction: Poor sleep health is associated with increased asthma morbidity and mortality. Accelerometers have been validated to assess sleep parameters though studies using this method in patients with asthma are sparse and none have compared mild to difficult-to-treat asthma populations.

Methods: We performed a retrospective analysis from two recent in-house trials comparing sleep metrics between patients with mild and difficult-to-treat asthma.

Understanding divergent substrate stereoselectivity in the isothiourea-catalysed conjugate addition of cyclic α-substituted β-ketoesters to α,β-unsaturated aryl esters.

The development of enantioselective synthetic methods capable of generating vicinal stereogenic centres, where one is tetrasubstituted (such as either an all-carbon quaternary centre or where one or more substituents are heteroatoms), is a recognised synthetic challenge. Herein, the enantioselective conjugate addition of a range of carbo- and heterocyclic α-substituted β-ketoesters to α,β-unsaturated aryl esters using the isothiourea HyperBTM as a Lewis base catalyst is demonstrated. Notably, divergent diastereoselectivity is observed through the use of either cyclopentanone-derived or indanone-derived substituted β-ketoesters with both generating the desired stereodefined products with high selectivity (>95 : 5 dr, up to 99 : 1 er).

Approach to Handling Atypical Field Blood Transfusion Scenarios.

Special Operations Forces (SOF) medical personnel have been at the forefront of administering blood products in the austere field medicine environment. These far-forward medical providers regularly treat patients and deliver blood transfusions in some of the world's most extreme environments with minimal resources. A multitude of questions have been raised on this topic based on the unique experiences of senior providers in this field.

A Total Diet Replacement Weight Management Program for Difficult-to-Treat Asthma Associated With Obesity: A Randomized Controlled Feasibility Trial.

Background: Obesity is often associated with uncontrolled, difficult-to-treat asthma and increased morbidity and mortality. Previous studies suggest that weight loss may improve asthma outcomes, but with heterogenous asthma populations studied and unclear consensus on the optimal method of weight management. The Counterweight-Plus Programme (CWP) for weight management is an evidence-based, dietitian-led total diet replacement (TDR) program.

Assessing medication use patterns in patients hospitalised with COVID-19: a retrospective study.

Objective: To describe patterns of medication use-that is, dexamethasone; remdesivir; and tocilizumab-in the management of patients hospitalised with COVID-19.

Design And Setting: Retrospective observational study, using routinely collected, linked electronic data from clinical practice in Scotland. Data on drug exposure in secondary care has been obtained from the Hospital Electronic Prescribing and Medicines Administration System.

Rational Design of a Facially Coordinating P,N,N Ligand for Manganese-Catalysed Enantioselective Hydrogenation of Cyclic Ketones.

DFT calculations on the full catalytic cycle for manganese catalysed enantioselective hydrogenation of a selection of ketones have been carried out at the PBE0-D3 //RI-BP86 level. Mn complexes of an enantiomerically pure chiral P,N,N ligand have been found to be most reactive when adopting a facial coordination mode. The use of a new ligand with an ortho-substituted dimethylamino-pyridine motif has been calculated to completely transform the levels of enantioselectivity possible for the hydrogenation of cyclic ketones relative to the first-generation Mn catalysts.

A pragmatic randomised controlled trial of tailored pulmonary rehabilitation in participants with difficult-to-control asthma and elevated body mass index.

Background: Difficult-to-control asthma associated with elevated body mass index (BMI) is challenging with limited treatment options. The effects of pulmonary rehabilitation (PR) in this population are uncertain.

Methods: This is a randomised controlled trial of an eight-week asthma-tailored PR programme versus usual care (UC) in participants with difficult-to-control asthma and BMI ≥ 25 kg/m.

Obesity affects type 2 biomarker levels in asthma.

Objective: Type 2 (T2) inflammation offers a therapeutic target for biologics. Previous trials suggest obesity influences T2-biomarker levels in asthma, though have not accounted for key variables, e.g.

Hydricity of 3d Transition Metal Complexes from Density Functional Theory: A Benchmarking Study.

A range of modern density functional theory (DFT) functionals have been benchmarked against experimentally determined metal hydride bond strengths for three first-row TM hydride complexes. Geometries were found to be produced sufficiently accurately with RI-BP86-D3(PCM)/def2-SVP and further single-point calculations with PBE0-D3(PCM)/def2-TZVP were found to reproduce the experimental hydricity accurately, with a mean absolute deviation of 1.4 kcal/mol for the complexes studied.

Induction of labour: Experiences of care and decision-making of women and clinicians.

Background: There has been a rise in induction of labour over recent decades. There is some tension in the literature in relation to when induction is warranted and when not, with variability between guidelines and practice. Given these tensions, the importance of shared decision-making between clinicians and women is increasingly highlighted as paramount, but it remains unclear to what extent this occurs in routine care.

They Didn't Believe Her Pain: My Education in Interpersonal Violence.

In my first year of medical school, I began to care for patients who were survivors of interpersonal violence. As I transitioned from didactics to clinical experiences, I was struck by how common the hidden threads of physical and sexual violence were in my patients' stories of chronic pain, depression, and poor health outcomes. Their symptoms often seemed intangible and challenging to treat, unable to fit neatly into typical diagnostic and therapeutic algorithms.

Prevalence of Sexual Violence and its Association with Depression among Male and Female Patients with Risky Drug Use in Urban Federally Qualified Health Centers.

Sexual violence (SV) is common; however, the prevalence of SV and its long term sequela vary geographically and among subpopulations within the USA. As such, the aims of this study are the following: (1) to determine the prevalence of SV, (2) to identify correlates of SV, and (3) to determine if SV is associated with depression among male and female risky drug users in urban Federally Qualified Health Centers (FQHCs) in Los Angeles. This study includes adult patients of five urban FQHCs who self-reported risky drug use.

Improving preconception health and care: a situation analysis.

Background: The purpose of this situation analysis was to explore the views of health and non-health professionals working with women of childbearing age on current and future delivery of preconception care in one National Health Service (NHS) Board area in Scotland.

Methods: The situation analysis was undertaken using a mixed methods approach. Six focus groups were conducted organised by profession - general practitioners (GPs), practice nurses, health visitors, family nurses, guidance teachers and youth workers.

Predictors of Primary Care Physician Practice Location in Underserved Urban or Rural Areas in the United States: A Systematic Literature Review.

Purpose: The authors conducted a systematic review of the medical literature to determine the factors most strongly associated with localizing primary care physicians (PCPs) in underserved urban or rural areas of the United States.

Method: In November 2015, the authors searched databases (MEDLINE, ERIC, SCOPUS) and Google Scholar to identify published peer-reviewed studies that focused on PCPs and reported practice location outcomes that included U.S.

The Truth about Sugar.

Sugars are used by the industry to enhance the attractiveness of foods and drinks. These added sugars, or 'free sugars', are not easily identified in food or drink labels. Certain manufactured foods and drinks with 'safe' names, such as dried fruit and fruit juice, still contain free sugars and can be confusing.

Improvement in iodine status of pregnant Australian women 3 years after introduction of a mandatory iodine fortification programme.

Introduction: In order to address population-level mild iodine deficiency in Australia, a mandatory iodine fortification programme of salt used in bread was introduced in late 2009.

Methods: A before-after study was conducted to assess changes in median urinary iodine concentration (MUIC) measurements, according to supplement use, in convenience samples of pregnant women attending a public antenatal clinic in a regional area of New South Wales, Australia in 2008 (n=139), 2011 (n=147) and 2012 (n=114). Knowledge and practices related to iodine nutrition were investigated in 2012, using self-administered questionnaires.

Poor knowledge and practices related to iodine nutrition during pregnancy and lactation in Australian women: pre- and post-iodine fortification.

A before-after review was undertaken to assess whether knowledge and practices related to iodine nutrition, supplementation and fortification has improved in Australian women since the introduction of mandatory iodine fortification in 2009. Surveys of pregnant (n = 139) and non-pregnant (n = 75) women in 2007-2008 are compared with surveys of pregnant (n = 147) and lactating women (n = 60) one to two years post-fortification in a regional area of New South Wales, Australia. A self-administered questionnaire was completed and dietary intake of iodine was assessed using a validated food frequency questionnaire.

Utility of an interferon-gamma release assay for latent tuberculosis diagnosis in a case of bullous pemphigoid.

Background: With increasing use of immunosuppressive therapy, including tumor necrosis factor alpha inhibitors, there is concern about infectious complications, including reactivation of latent Mycobacterium tuberculosis infection. Routine testing prior to administration of systemic immunosuppression includes the tuberculin skin test, which lacks sensitivity and specificity and may be difficult to interpret in the presence of extensive cutaneous disease. Treatment of individuals with latent tuberculosis infection is recommended when immunosuppressive medications are to be employed.

Willingness to pay to assess patient preferences for therapy in a Canadian setting.

Background: Adult outpatient parenteral antibiotic therapy (OPAT) programs have been reported in the literature for over 20 years, however there are no published reports quantifying preference for treatment location of patients referred to an OPAT program. The purpose of this study was to elicit treatment location preferences and willingness to pay (WTP) from patients referred to an OPAT program.

Methods: A multidisciplinary, single centre, prospective study at a 1000-bed Canadian adult tertiary care teaching hospital.

Distinct endocytic pathways regulate TGF-beta receptor signalling and turnover.

Endocytosis of cell surface receptors is an important regulatory event in signal transduction. The transforming growth factor beta (TGF-beta) superfamily signals to the Smad pathway through heteromeric Ser-Thr kinase receptors that are rapidly internalized and then downregulated in a ubiquitin-dependent manner. Here we demonstrate that TGF-beta receptors internalize into both caveolin- and EEA1-positive vesicles and reside in both lipid raft and non-raft membrane domains.