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    Age-dependent and sex-dependent disparity in mortality in patients with adrenal incidentalomas and autonomous cortisol secretion: an international, retrospective, cohort study.

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    BACKGROUND The association between cortisol secretion and mortality in patients with adrenal incidentalomas is controversial. We aimed to assess all-cause mortality, prevalence of comorbidities, and occurrence of cardiovascular events in uniformly stratified patients with adrenal incidentalomas and cortisol autonomy (defined as non-suppressible serum cortisol on dexamethasone suppression testing). METHODS We conducted an international, retrospective, cohort study (NAPACA Outcome) at 30 centres in 16 countries. Eligible patients were aged 18 years or older with an adrenal incidentaloma (diameter ≥1 cm) detected between Jan 1, 1996, and Dec 31, 2015, and availability of a 1 mg dexamethasone suppression test result from the time of the initial diagnosis. Patients with clinically apparent hormone excess, active malignancy, or follow-up of less than 36 months were excluded. Patients were stratified according to the 0800-0900 h serum cortisol values after an overnight 1 mg dexamethasone suppression test; less than 50 nmol/L was classed as non-functioning adenoma, 50-138 nmol/L as possible autonomous cortisol secretion, and greater than 138 nmol/L as autonomous cortisol secretion. The primary endpoint was all-cause mortality. Secondary endpoints were the prevalence of cardiometabolic comorbidities, cardiovascular events, and cause-specific mortality. The primary and secondary endpoints were assessed in all study participants. FINDINGS Of 4374 potentially eligible patients, 3656 (2089 [57·1%] with non-functioning adenoma, 1320 [36·1%] with possible autonomous cortisol secretion, and 247 [6·8%] with autonomous cortisol secretion) were included in the study cohort for mortality analysis (2350 [64·3%] women and 1306 [35·7%] men; median age 61 years [IQR 53-68]; median follow-up 7·0 years [IQR 4·7-10·2]). During follow-up, 352 (9·6%) patients died. All-cause mortality (adjusted for age, sex, comorbidities, and previous cardiovascular events) was significantly increased in patients with possible autonomous cortisol secretion (HR 1·52, 95% CI 1·19-1·94) and autonomous cortisol secretion (1·77, 1·20-2·62) compared with patients with non-functioning adenoma. In women younger than 65 years, autonomous cortisol secretion was associated with higher all-cause mortality than non-functioning adenoma (HR 4·39, 95% CI 1·93-9·96), although this was not observed in men. Cardiometabolic comorbidities were significantly less frequent with non-functioning adenoma than with possible autonomous cortisol secretion and autonomous cortisol secretion (hypertension occurred in 1186 [58·6%] of 2024 patients with non-functioning adenoma, 944 [74·0%] of 1275 with possible autonomous cortisol secretion, and 179 [75·2%] of 238 with autonomous cortisol secretion; dyslipidaemia occurred in 724 [36·2%] of 1999 patients, 547 [43·8%] of 1250, and 123 [51·9%] of 237; and any diabetes occurred in 365 [18·2%] of 2002, 288 [23·0%] of 1250, and 62 [26·7%] of 232; all p values <0·001). INTERPRETATION Cortisol autonomy is associated with increased all-cause mortality, particularly in women younger than 65 years. However, until results from randomised interventional trials are available, a conservative therapeutic approach seems to be justified in most patients with adrenal incidentaloma. FUNDING Deutsche Forschungsgemeinschaft, Associazione Italiana per la Ricerca sul Cancro, Università di Torino

    Visiting and Communication Policy in Intensive Care Units during COVID-19 Pandemic: A Cross-sectional Survey from South Asia and the Middle East.

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    Purpose The coronavirus disease-2019 (COVID-19) pandemic had affected the visiting or communicating policies for family members. We surveyed the intensive care units (ICUs) in South Asia and the Middle East to assess the impact of the COVID-19 pandemic on visiting and communication policies. Materials and method A web-based cross-sectional survey was used to collect data between March 22, 2021, and April 7, 2021, from healthcare professionals (HCP) working in COVID and non-COVID ICUs (one response per ICU). The topics of the questionnaire included current and pre-pandemic policies on visiting, communication, informed consent, and end-of-life care in ICUs. Results A total of 292 ICUs (73% of COVID ICUs) from 18 countries were included in the final analysis. Most (92%) of ICUs restricted their visiting hours, and nearly one-third (32.3%) followed a "no-visitor" policy. There was a significant change in the daily visiting duration in COVID ICUs compared to the pre-pandemic times ( = 0.011). There was also a significant change ( <0.001) in the process of informed consent and end-of-life discussions during the ongoing pandemic compared to pre-pandemic times. Conclusion Visiting and communication policies of the ICUs had significantly changed during the COVID-19 pandemic. Future studies are needed to understand the sociopsychological and medicolegal implications of revised policies. How to cite this article Chanchalani G, Arora N, Nasa P, Sodhi K, Al Bahrani MJ, Al Tayar A, . Visiting and Communication Policy in Intensive Care Units during COVID-19 Pandemic: A Cross-sectional Survey from South Asia and the Middle East. Indian J Crit Care Med 2022;26(3):268-275

    Current practice of trabeculectomy in a cohort of experienced glaucoma surgeons in Australia and New Zealand.

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    BACKGROUND/OBJECTIVES To evaluate current routine trabeculectomy technique preferences among Australian and New Zealand Glaucoma Society surgeons regularly performing trabeculectomy surgery. SUBJECTS/METHODS Survey of experienced surgeons who perform trabeculectomy. RESULTS Forty-nine surgeons (33 male:16 female) participated in the survey. Trabeculectomy was performed as day surgery (39/47, 83.0%) under local anesthesia (44/47, 93.6%). The surgical techniques most commonly used were a corneal traction suture (44/47, 93.6%), fornix-based conjunctival flap (43/47, 91.5%) and half-thickness scleral flap (38/47, 81.0%). Mitomycin C antifibrotic agent was used in routine cases by 45/46 (97.8%) surgeons. Surgeons applied the antifibrotic agent under the Tenon layer with a pledget (36/46, 78.2%) with a concentration of 0.02% (37/46, 80.4%) for 2 (11/46, 23.9%) or 3 min (30/46, 65.2%). The Kelly (26/46, 56.5%) and the Khaw Descemet (19/46, 41.3%) punches were used to perform the sclerostomy. Most surgeons performed a peripheral iridectomy in all phakic patients (46/47, 97.9%), but less commonly in pseudophakic patients (34/47, 72.3%). Techniques for closure of the limbal conjunctival edge were quite varied with a combination of suturing including purse string (21/47, 57.4%), wing (20/47, 42.6%) and horizontal mattress sutures (33/47, 70.2%). Surgeons reviewed their routine patients four times in the first month (29/47, 61.7%) and continued the postoperative topical steroids for 3-4 months (28/47, 59.6%). CONCLUSIONS Although a wide range of techniques for trabeculectomy exists among surgeons, there are consistent procedures currently in use to optimize patient outcomes. This report will assist surgeons in choosing which surgical techniques fit their best practice

    Safety and immunogenicity of the inactivated whole-virus adjuvanted vaccine VLA2001: a randomized, dose escalation, double-blind phase 1/2 clinical trial in healthy adults.

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    OBJECTIVES We aimed to evaluate the safety and optimal dose of a novel inactivated whole-virus adjuvanted vaccine against SARS-CoV-2: VLA2001. METHODS We conducted an open-label, dose-escalation study followed by a double-blind randomized trial using low, medium and high doses of VLA2001 (1:1:1). The primary safety outcome was the frequency and severity of solicited local and systemic reactions within 7 days after vaccination. The primary immunogenicity outcome was the geometric mean titre of (GMT) of neutralizing antibodies against SARS-CoV-2 two weeks after the second vaccination. The study is registered as NCT04671017. RESULTS Between December 16, 2020, and June 3, 2021, 153 healthy adults aged 18-55 years were recruited in the UK. Overall, 81.7% of the participants reported a solicited AE, with injection site tenderness (58.2%) and headache (46.4%) being the most frequent. Only 2 participants reported a severe solicited event. Up to day 106, 131 (85.6%) participants had reported any AE. All observed incidents were transient and non-life threatening in nature. Immunogenicity measured at 2 weeks after completion of the two-dose priming schedule, showed significantly higher GMTs of SARS-CoV-2 neutralising antibody titres in the highest dose group (GMT 545.6; 95% CI: 428.1, 695.4) which were similar to a panel of convalescent sera (GMT 526.9; 95% CI: 336.47, 825.06). Seroconversion rates of neutralising antibodies were also significantly higher in the high-dose group (>90%) compared to the other dose groups. In the high dose group, antigen-specific interferon-γ expressing T-cells reactive against the S, M and N proteins were observed in 76, 36 and 49%, respectively. CONCLUSIONS VLA2001 was well tolerated in all tested dose groups, and no safety signal of concern was identified. The highest dose group showed statistically significantly stronger immunogenicity with similar tolerability and safety, and was selected for phase 3 clinical development

    The feasibility of conducting acute sarcopenia research in hospitalised older patients: a prospective cohort study.

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    PURPOSE To assess feasibility of conducting acute sarcopenia research in complex populations of hospitalised older adults. METHODS Patients ≥ 70 years old were recruited to three cohorts: elective colorectal surgery, emergency (abdominal) surgery, medical patients with infections. Participants were recruited to the elective cohort in preoperative assessment clinic, and acutely admitted participants from surgical and medical wards at the Queen Elizabeth Hospital Birmingham. Serial measures of muscle quantity (ultrasound quadriceps, bioelectrical impedance analysis), muscle function (hand grip strength, physical performance), and questionnaires (mini-nutritional assessment, physical function) were performed at baseline, within 7 (± 2) days of admission/surgery, and 13 (± 1) weeks post-admission/surgery. Feasibility outcomes were assessed across timepoints including recruitment and drop-out rates, and procedure completion rates. RESULTS Eighty-one participants were recruited (mean age 79, 38.3% females). Recruitment rates were higher in elective (75%, 24/32) compared to emergency surgery (37.2%, 16/43), and medical participants (45.1%, 41/91; p = 0.003). Drop-out rates varied from 8.3 to 19.5% at 7 days, and 12.5-43.9% at 13 weeks. Age and gender did not differ between patients assessed for eligibility, approached, or recruited. Completion rates were highest for ultrasound quadriceps (98.8%, 80/81 across all groups at baseline). Gait speed completion rates were lower in medical (70.7%, 29/41) compared to elective participants (100%, 24/24) at baseline. CONCLUSION Higher participation refusal and drop-out rates should be expected for research involving recruitment of participants from the acute setting. Assessment of muscle quantity/quality through ultrasound is recommended in early-stage trials in the acute setting, where completion rates of physical performance testing are expected to be lower

    A population cohort analysis of English transplant centers indicates major adverse cardiovascular events after kidney transplantation.

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    Major adverse cardiovascular event (MACE) rates immediately after kidney transplantation remain uncertain due to heterogeneous reporting in the literature. To clarify this, we retrospectively studied every eligible kidney transplant procedure performed in England between April 1, 2002 and March 31. 2018 with follow-up through August 31, 2019. The primary outcome of interest was MACE broadly defined as any hospital admission with myocardial infarction, stroke, unstable angina, heart failure, any coronary revascularisation procedure and/or any cardiovascular death. Among 30,325 kidney transplant recipients, MACE occurred in 781 within the first year after transplantation (2.6% of all kidney transplant procedures). Of these 781 events, 201 occurred during the index admission for kidney transplantation surgery representing 25.7% of all first-year MACE and 0.7% of all kidney transplant procedures. Kidney transplant recipients who suffered a non-fatal MACE within the first year had significantly decreased 1-, 3-, 5- and 10-year patient survival of 80.5%, 70.2%, 59.5% and 38.6% respectively, compared to 97.4%, 94.4%, 90.7% and 78.4% for kidney transplant recipients not developing MACE.. In an adjusted Cox proportional hazard model, non-fatal MACE within the first-year post-transplant was associated with significant long-term mortality risk (hazard ratio 2.59; 95% confidence interval 2.34-2.88). Kidney transplant recipients experiencing MACE during the index admission compared to subsequent admissions were differentiated by age, sex and previous cardiac history but had similar patient survival. These rates are significantly lower than those reported in North America. Thus, our data confirms MACE is not a benign post-transplant event and has a strong association with long-term mortality risk

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