Goal-oriented cognitive rehabilitation for early-stage Alzheimer's and related dementias: the GREAT RCT

This is the author accepted manuscript. The final version is available from NIHR Journals Library via the DOI in this record.The published version is available in ORE at http://hdl.handle.net/10871/36867This study was funded by the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme; PI Professor L Clare; HTA reference 11/15/04

Understanding the impact of initial COVID-19 restrictions on physical activity, wellbeing and quality of life in shielding adults with end-stage renal disease in the United Kingdom Dialysing at home versusIn-Centre and their experiences with telemedicine

Early in the coronavirus-2019 (COVID-19) containment strategy, people with end-stage renal disease (ESRD) were identified as extremely clinically vulnerable and subsequently asked to ‘shield’ at home where possible. The aim of this study was to investigate how these restrictions and the transition to an increased reliance on telemedicine within clinical care of people living with kidney disease impacted the physical activity (PA), wellbeing and quality of life (QoL) of adults dialysing at home (HHD) or receiving in-centre haemodialysis (ICHD) in the UK. Individual semistructured telephone interviews were conducted with adults receiving HHD (n = 10) or ICHD (n = 10), were transcribed verbatim and, subsequently, thematically analysed. As result of the COVID-19 restrictions, PA, wellbeing and QoL of people with ESRD were found to have been hindered. However, widespread support for the continued use of telemedicine was strongly advocated and promoted independence and satisfaction in patient care. These findings highlight the need for more proactive care of people with ESRD if asked to shield again, as well as increased awareness of safe and appropriate PA resources to help with home-based PA and emotional wellbeing

Association between troponin level and medium-term mortality in 20 000 hospital patients.

Cardiac troponin (cTn) concentrations above the manufacturer recommended upper limit of normal (ULN) are frequently seen in hospital patients without a clinical presentation consistent with type 1 myocardial infarction, and the significance of this is uncertain. The aim of this study was to assess the relationship between medium-term mortality and cTn concentration in a large consecutive hospital population, regardless of whether there was a clinical indication for performing the test. This prospective observational study included 20 000 consecutive in-hospital and outpatient patients who had a blood test for any reason at a large teaching hospital, and in whom a hs-cTnI assay was measured, regardless of the original clinical indication. Mortality was obtained via NHS Digital. A total of 20 000 patients were included in the analysis and 18 282 of these (91.4%) did not have a clinical indication for cardiac troponin I (cTnI) testing. Overall, 2825 (14.1%) patients died at a median of 809 days. The mortality was significantly higher if the cTnI concentration was above the ULN (45.3% vs 12.3% p<0.001 log rank). Multivariable Cox analysis demonstrated that the log cTnI concentration was independently associated with mortality (HR 1.76 (95% CI 1.65 to 1.88)). Landmark analysis, excluding deaths within 30 days, showed the relationship between cTnI concentration and mortality persisted. In a large, unselected hospital population, in 91.4% of whom there was no clinical indication for testing, cTnI concentration was independently associated with medium-term cardiovascular and non-cardiovascular mortality in the statistical model tested. [Abstract copyright: © Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Heat acclimation improves sweat gland function and lowers sweat sodium concentration in an adult with cystic fibrosis

We present novel data concerning the time-course of adaptations and potential benefits of heat acclimation for people with cystic fibrosis (pwCF), who are at greater risk of exertional heat illness. A 25-year-old male (genotype: delta-F508 and RH117, forced expiratory volume in 1-second: 77% predicted and baseline sweat [Na+]: 70 mmol·L − 1), who had previously experienced muscle cramping during exercise in ambient heat, underwent 10-sessions of heat acclimation (90-min at 40°C and in 40% relative humidity). Adaptations included; lower resting core temperature (-0.40°C) and heart rate (-6 beats·min−1), plasma volume expansion (+6.0%) and, importantly, increased sweat loss (+370 mL) and sweat gland activity (+12 glands·cm2) with decreased sweat [Na+] (-18 mmol·L − 1). Adaptations were maintained for at least 7-days, with no evidence of cramping during follow-up exercise-heat stress testing. These data suggest pwCF may benefit from heat acclimation to induce sudomotor function improvements, particularly reductions in sweat [Na+], however, further research is required

Emergency care capacity in Sierra Leone: A multicentre analysis

Background: The Disease Control Priorities Project estimates that over 50 % of annual mortality in low- and middle-income countries can be addressed by improved emergency care. Sierra Leone's Ministry of Health and Sanitation has highlighted emergency care as a national priority. We conducted the first multicentre analysis of emergency care capacity in Sierra Leone, using the Hospital Emergency Unit Assessment Tool (HEAT) to analyse 14 government hospitals across the country. Methods: HEAT is a standardised assessment that is recommended in the World Health Organisation Emergency Care Toolkit. It has been used comparably elsewhere. To analyse Sierra Leone's emergency care capacity with the HEAT data, we created the HEAT-adjusted Emergency Care Capacity Score. Purposeful sampling was used to select 14 government facilities nationwide. A multidisciplinary team was interviewed over a 2-day in-person visit to each facility. Results: Human Resources was the strongest parameter, scoring 49 %. All hospitals provided emergency cover 24/7. Emergency Diagnostic Services was the most severely limited parameter, scoring 29 %. 3 hospitals had no access to basic radiography. Infrastructure scored 47 %. 2 hospitals had adequate electricity supply; 5 had adequate clean, running water. No hospitals had adequate oxygen supply. Clinical services scored 39 %. 10 hospitals had no designated Emergency Unit, only 2 triaged to stratify severity. Signal functions scored 38 %. No hospitals had reliable access to emergency drugs such as adrenaline. The total HEAT-adjusted Emergency Care Capacity Score across all hospitals was 40 %. Conclusions: These data identify gaps that have already led to local interventions, including focussing emergency resources to a resuscitation area, and training multidisciplinary teams in emergency care skills. This facility-level analysis could feed into wider assessment of Sierra Leone's emergency care systems at every level, which may help prioritise government strategy to target sustainable strengthening of national emergency care

Does routine pressure wire assessment influence management strategy at coronary angiography for diagnosis of chest pain? The RIPCORD Study

Background — The use of coronary angiography (CA) for diagnosis and management of chest pain (CP) has several flaws. The assessment of coronary artery disease using fractional flow reserve (FFR) is a well-validated technique for describing lesion-level ischemia and improves clinical outcome in the context of percutaneous coronary intervention. The impact of routine FFR at the time of diagnostic CA on patient management has not been determined.Method and Results — Two hundred patients with stable CP underwent CA for clinical indications. The supervising cardiologist (S.C.) made a management plan based on CA (optimal medical therapy alone, percutaneous coronary intervention, coronary artery bypass grafting, or more information required) and also recorded which stenoses were significant. An interventional cardiologist then measured FFR in all patent coronary arteries of stentable diameter (?2.25 mm). S.C. was then asked to make a second management plan when FFR results were disclosed. Overall, after disclosure of FFR data, management plan based on CA alone was changed in 26% of patients, and the number and localization of functional stenoses changed in 32%. Specifically, of 72 cases in which optimal medical therapy was recommended after CA, 9 (13%) were actually referred for revascularization with FFR data. By contrast, of 89 cases in whom management plan was optimal medical therapy based on FFR, revascularization would have been recommended in 25 (28%) based on CA.Conclusions — Routine measurement of FFR at CA has important influence both on which coronary arteries have significant stenoses and on patient management. These findings could have important implications for clinical practice