Impaired awareness of hypoglycaemia (IAH) increases the risk of severe hypoglycaemia in people with type 1 diabetes mellitus (T1DM). IAH can be reversed through meticulous avoidance of hypoglycaemia. ...Diabetic autonomic neuropathy (DAN) has been proposed as an underlying mechanism contributing to IAH; however, data are inconsistent. The aim of this study was to examine the effects of cardiac autonomic neuropathy (CAN) on IAH reversibility inT1DM.
Participants with T1DM and IAH (Gold score ≥4) recruited to the HypoCOMPaSS (24-week 2 × 2 factorial randomised controlled) trial were included. All underwent screening for cardiac autonomic function testing at baseline and received comparable education and support aimed at avoiding hypoglycaemia and improving hypoglycaemia awareness. Definite CAN was defined as the presence of ≥2 abnormal cardiac reflex tests. Participants were grouped according to their CAN status, and changes in Gold score were compared.
Eighty-three participants (52 women 62.7%) were included with mean age (SD) of 48 (12) years and mean HbA1c of 66 (13) mmol/mol (8.2 3.3 %). The mean duration of T1DM was 29 (13) years. The prevalence of CAN was low with 5/83 (6%) participants having definite autonomic neuropathy with 11 (13%) classified with possible/early neuropathy. All participants, regardless of the autonomic function status, showed a mean improvement in Gold score of ≥1 (mean improvement -1.2 95% CI -0.8, -1.6; p < 0.001).
IAH can be improved in people with T1DM, and a long duration of disease, with and without cardiac autonomic dysfunction. These data suggest that CAN is not a prime driver for modulating IAH reversibility.
BackgroundNational Early Warning Scores (NEWS2) are used to detect all-cause deterioration. While studies have looked at NEWS2, the use of virtual consultation and remote monitoring of patients with ...COVID-19 mean there is a need to know which physiological observations are important.AimTo investigate the relationship between outcome and NEWS2, change in NEWS2 and component physiology in COVID-19 inpatients.MethodsA multi-centre retrospective study of electronically recorded, routinely collected physiological measurements between March and June 2020. First and maximum NEWS2, component scores and outcomes were recorded. Areas under the curve (AUCs) for 2-day, 7-day and 30-day mortality were calculated.ResultsOf 1263 patients, 26% died, 7% were admitted to intensive care units (ICUs) before discharge and 67% were discharged without ICU. Of 1071 patients with initial NEWS2, most values were low: 50% NEWS2=0–2, 27% NEWS2=3–4, 14% NEWS2=5–6 and 9% NEWS2=7+. Maximum scores were: 14% NEWS2=0–2, 22% NEWS2=3–4, 17% NEWS2=5–6 and 47% NEWS2=7+. Higher first and maximum scores were predictive of mortality, ICU admission and longer length of stay. AUCs based on 2-day, 7-day, 30-day and any hospital mortality were 0.77 (95% CI 0.70 to 0.84), 0.70 (0.65 to 0.74), 0.65 (0.61 to 0.68) and 0.65 (0.61 to 0.68), respectively. The AUCs for 2-day mortality were 0.71 (0.65 to 0.77) for supplemental oxygen, 0.65 (0.56 to 0.73) oxygen saturation and 0.64 (0.56 to 0.73) respiratory rate.ConclusionWhile respiratory parameters were most predictive, no individual parameter was as good as a full NEWS2, which is an acceptable predictor of short-term mortality in patients with COVID-19. This supports recommendation to use NEWS2 alongside clinical judgement to assess patients with COVID-19.
Before recommending a feeding strategy for greenhouse gas (GHG) mitigation, it is important to conduct a holistic assessment of all related emissions, including from those arising from feed ...production, digestion of these feeds, managing the resulting manure, and other on-farm production processes and inputs. Using a whole-systems approach, the Holos model, and experimentally measured data, this study compares the effects of alfalfa silage- versus corn silage-based diets on GHG estimates in a simulated Canadian dairy production system. When all emissions and sources are accounted for, the differences between the two forage systems in terms of overall net GHG emissions were minimal. Utilizing the functional units of milk, meat, and total energy in food products generated by the system, the comparison demonstrates very little difference between the two silage production systems. However, the corn silage system generated 8% fewer emissions per kg of protein in food products as compared to the alfalfa silage system. Exploratory analysis of the impact of the two silage systems on soil carbon showed alfalfa silage has greater potential to store carbon in the soil. This study reinforces the need to utilize a whole-systems approach to investigate the interrelated effects of management choices. Reported GHG reduction factors cannot be simply combined additively because the interwoven effects of management choices cascade through the entire system, sometimes with counter-intuitive outcomes. It is necessary to apply this whole-systems approach before implementing changes in management intended to reduce GHG emissions and improve sustainability.
IntroductionEffective communication can help optimise healthcare interactions and patient outcomes. However, few interventions have been tested clinically, subjected to cost-effectiveness analysis or ...are sufficiently brief and well-described for implementation in primary care. This paper presents the protocol for determining the effectiveness and cost-effectiveness of a rigorously developed brief eLearning tool, EMPathicO, among patients with and without musculoskeletal pain.Methods and analysisA cluster randomised controlled trial in general practitioner (GP) surgeries in England and Wales serving patients from diverse geographic, socioeconomic and ethnic backgrounds. GP surgeries are randomised (1:1) to receive EMPathicO e-learning immediately, or at trial end. Eligible practitioners (eg, GPs, physiotherapists and nurse practitioners) are involved in managing primary care patients with musculoskeletal pain. Patient recruitment is managed by practice staff and researchers. Target recruitment is 840 adults with and 840 without musculoskeletal pain consulting face-to-face, by telephone or video. Patients complete web-based questionnaires at preconsultation baseline, 1 week and 1, 3 and 6 months later. There are two patient-reported primary outcomes: pain intensity and patient enablement. Cost-effectiveness is considered from the National Health Service and societal perspectives. Secondary and process measures include practitioner patterns of use of EMPathicO, practitioner-reported self-efficacy and intentions, patient-reported symptom severity, quality of life, satisfaction, perceptions of practitioner empathy and optimism, treatment expectancies, anxiety, depression and continuity of care. Purposive subsamples of patients, practitioners and practice staff take part in up to two qualitative, semistructured interviews.Ethics approval and disseminationApproved by the South Central Hampshire B Research Ethics Committee on 1 July 2022 and the Health Research Authority and Health and Care Research Wales on 6 July 2022 (REC reference 22/SC/0145; IRAS project ID 312208). Results will be disseminated via peer-reviewed academic publications, conference presentations and patient and practitioner outlets. If successful, EMPathicO could quickly be made available at a low cost to primary care practices across the country.Trial registration number ISRCTN18010240.
HLA and KIR Associations of Cervical Neoplasia Bao, Xiao; Hanson, Aimee L; Madeleine, Margaret M ...
The Journal of infectious diseases,
11/2018, Letnik:
218, Številka:
12
Journal Article
Recenzirano
Odprti dostop
Cervical cancer is the fourth most common cancer in women, and we recently reported human leukocyte antigen (HLA) alleles showing strong associations with cervical neoplasia risk and protection. HLA ...ligands are recognized by killer immunoglobulin-like receptors (KIRs) expressed on a range of immune cell subsets, governing their proinflammatory activity. We hypothesized that the inheritance of particular HLA-KIR combinations would increase cervical neoplasia risk.
Here, we used HLA and KIR dosages imputed from single-nucleotide polymorphism genotype data from 2143 cervical neoplasia cases and 13858 healthy controls of European decent.
The following 4 novel HLA alleles were identified in association with cervical neoplasia, owing to their linkage disequilibrium with known cervical neoplasia-associated HLA-DRB1 alleles: HLA-DRB3*9901 (odds ratio OR, 1.24; P = 2.49 × 10-9), HLA-DRB5*0101 (OR, 1.29; P = 2.26 × 10-8), HLA-DRB5*9901 (OR, 0.77; P = 1.90 × 10-9), and HLA-DRB3*0301 (OR, 0.63; P = 4.06 × 10-5). We also found that homozygosity of HLA-C1 group alleles is a protective factor for human papillomavirus type 16 (HPV16)-related cervical neoplasia (C1/C1; OR, 0.79; P = .005). This protective association was restricted to carriers of either KIR2DL2 (OR, 0.67; P = .00045) or KIR2DS2 (OR, 0.69; P = .0006).
Our findings suggest that HLA-C1 group alleles play a role in protecting against HPV16-related cervical neoplasia, mainly through a KIR-mediated mechanism.
People living with cancer and haematological malignancies are at an increased risk of hospitalisation and death following infection with acute respiratory syndrome coronavirus 2. Coronavirus third ...dose vaccine boosters are proposed to boost waning immune responses in immunocompromised individuals and increase coronavirus protection; however, their effectiveness has not yet been systematically evaluated.
This study is a population-scale real-world evaluation of the United Kingdom’s third dose vaccine booster programme for cancer patients from 8th December 2020 to 7th December 2021. The cancer cohort comprises individuals from Public Health England’s national cancer dataset, excluding individuals less than 18 years. A test-negative case-control design was used to assess the third dose booster vaccine effectiveness. Multivariable logistic regression models were fitted to compare risk in the cancer cohort relative to the general population.
The cancer cohort comprised of 2,258,553 tests from 361,098 individuals. Third dose boosters were evaluated by reference to 87,039,743 polymerase chain reaction coronavirus tests. Vaccine effectiveness against breakthrough infections, symptomatic infections, coronavirus hospitalisation and death in cancer patients were 59.1%, 62.8%, 80.5% and 94.5%, respectively. Lower vaccine effectiveness was associated with a cancer diagnosis within 12 months, lymphoma, recent systemic anti-cancer therapy (SACT) or radiotherapy. Patients with lymphoma had low levels of protection from symptomatic disease. In spite of third dose boosters, following multivariable adjustment, individuals with cancer remain at an increased risk of coronavirus hospitalisation and death compared to the population control (OR 3.38, 3.01, respectively. p < 0.001 for both).
Third dose boosters are effective for most individuals with cancer, increasing protection from coronavirus. However, their effectiveness is heterogenous and lower than the general population. Many patients with cancer will remain at the increased risk of coronavirus infections even after 3 doses. In the case of patients with lymphoma, there is a particularly strong disparity of vaccine effectiveness against breakthrough infection and severe disease. Breakthrough infections will disrupt cancer care and treatment with potentially adverse consequences on survival outcomes. The data support the role of vaccine boosters in preventing severe disease, and further pharmacological intervention to prevent transmission and aid viral clearance to limit the disruption of cancer care as the delivery of care continues to evolve during the coronavirus pandemic.
•Largest population evaluation of third dose SARS-CoV-2 disease (COVID-19) vaccination in patients with cancer.•Vaccine effectiveness against COVID-19 infections, hospitalisation and death assessed.•Lower vaccine effectiveness associated with recent systemic anti-cancer therapy.•Patients with lymphoma had low levels of vaccine protection from symptomatic COVID-19.•Patients with cancer remain at a higher risk of severe COVID-19 hospitalisation and death.
An electrochemical approach for the preparation of copper(I) N-heterocyclic carbene complexes has been developed to include a diverse range of ligand precursors. Importantly, the method is effective ...for a ligand precursor that contains several acidic protons and for which traditional methods of carbene formation are not suitable.
The HypoCOMPaSS study was designed to test the hypothesis that successful avoidance of biochemical hypoglycemia without compromising overall glycemic control would restore sufficient hypoglycemia ...awareness to prevent recurrent severe hypoglycemia in the majority of participants with established type 1 diabetes. Before starting the study, we planned to investigate associations between baseline characteristics and recurrent severe hypoglycemia over 2 years' follow-up.
A total of 96 adults with type 1 diabetes and impaired awareness of hypoglycemia participated in a 24-week 2 × 2 factorial randomized controlled trial comparing insulin delivery and glucose monitoring modalities, with the goal of rigorous biochemical hypoglycemia avoidance. The analysis included 71 participants who had experienced severe hypoglycemia in the 12-month prestudy with confirmed absence (complete responder) or presence (incomplete responder) of severe hypoglycemia over 24 months' follow-up.
There were 43 (61%) complete responders and 28 (39%) incomplete responders experiencing mean ± SD 1.5 ± 1.0 severe hypoglycemia events/person-year. At 24 months, incomplete responders spent no more time with glucose ≤3 mmol/L (1.4 ± 2.1% vs. 3.0 ± 4.8% for complete responders;
= 0.26), with lower total daily insulin dose (0.45 vs. 0.58 units/24 h;
= 0.01) and greater impairment of hypoglycemia awareness (Clarke score: 3.8 ± 2.2 vs. 2.0 ± 1.9;
= 0.01). Baseline severe hypoglycemia rate (16.9 ± 16.3 vs. 6.4 ± 10.8 events/person-year;
= 0.002) and fear of hypoglycemia were higher in incomplete responders. Peripheral neuropathy was more prevalent in incomplete responders (11 39% vs. 2 4.7%;
< 0.001) with a trend toward increased autonomic neuropathy.
Recurrent severe hypoglycemia was associated with higher preintervention severe hypoglycemia rate, fear of hypoglycemia, and concomitant neuropathy.
This paper describes a rural immersive attachment program for allied health students at an Australian University Department of Rural Health and its workforce outcomes. A mixed methods longitudinal ...cohort study, with data collected via end-of-placement and post-graduation surveys. Over 13 years, 311 allied health ‘year-long’ immersive rural attachments, as well as short-term placements, were supported. Pre- and post-placement rural practice intention ratings were paired (from 572 end of placement surveys) for 553 (96.7%) students. Students from metropolitan (49.4%, n = 273, p < 0.001), and rural origin (50.6%, n = 280, p < 0.001) showed a significant increase in rural practice intention. At 1 year post-graduation, 40.3% (n = 145) of graduates had worked in a rural or remote location in Australia, 39.9% at 3 years (n = 87) and 36.5% (n = 42) at 5 years. Longer-term rural attachments were found to be associated with rural practice location, independent of rural background. Those who had undertaken a longer rural attachment (≥18-weeks) were twice as likely to be working in a rural or remote area than those <18 weeks at 1 year (OR 2.018 95% CI 1.204–3.382) and 2.7 times as likely at 3 years (OR 2.727, 95% CI (1.325–5.614). Supporting students to undertake rural immersive attachments appears to be associated with greater rural practice intention and later rural practice.
Impaired awareness of hypoglycemia (IAH) and defective counterregulation significantly increase severe hypoglycemia risk in type 1 diabetes (T1D). We evaluated restoration of IAH/defective ...counterregulation by a treatment strategy targeted at hypoglycemia avoidance in adults with T1D with IAH (Gold score ≥4) participating in the U.K.-based multicenter HypoCOMPaSS randomized controlled trial.
Eighteen subjects with T1D and IAH (mean ± SD age 50 ± 9 years, T1D duration 35 ± 10 years, HbA1c 8.1 ± 1.0% 65 ± 10.9 mmol/mol) underwent stepped hyperinsulinemic-hypoglycemic clamp studies before and after a 6-month intervention. The intervention comprised the HypoCOMPaSS education tool in all and randomized allocation, in a 2 × 2 factorial study design, to multiple daily insulin analog injections or continuous subcutaneous insulin infusion therapy and conventional glucose monitoring or real-time continuous glucose monitoring. Symptoms, cognitive function, and counterregulatory hormones were measured at each glucose plateau (5.0, 3.8, 3.4, 2.8, and 2.4 mmol/L), with each step lasting 40 min with subjects kept blinded to their actual glucose value throughout clamp studies.
After intervention, glucose concentrations at which subjects first felt hypoglycemic increased (mean ± SE from 2.6 ± 0.1 to 3.1 ± 0.2 mmol/L, P = 0.02), and symptom and plasma metanephrine responses to hypoglycemia were higher (median area under curve for symptoms, 580 interquartile range {IQR} 420-780 vs. 710 460-1,260, P = 0.02; metanephrine, 2,412 -3,026 to 7,279 vs. 5,180 -771 to 11,513, P = 0.01). Glycemic threshold for deterioration of cognitive function measured by four-choice reaction time was unchanged, while the color-word Stroop test showed a degree of adaptation.
Even in long-standing T1D, IAH and defective counterregulation may be improved by a clinical strategy aimed at hypoglycemia avoidance.
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