Ethnicity and Observed Oxygen Saturations, Fraction of Inspired Oxygen, and Clinical Outcomes: A Post Hoc Analysis of the Oxy-PICU Trial of Conservative Oxygenation.

OBJECTIVES: A conservative oxygenation strategy, targeting peripheral oxygen saturations (Spo2) between 88% and 92% in mechanically ventilated children in PICU, was associated with a shorter duration of organ support and greater survival compared with Spo2 greater than 94% in our recent Oxy-PICU trial. Spo2 monitors may overestimate arterial oxygen saturation (Sao2) in patients with higher levels of skin pigmentation compared with those with less skin pigmentation. We investigated if ethnicity was associated with changes in distributions of Spo2 and Fio2 and outcome. DESIGN: Post hoc analysis of a pragmatic, open-label, multicenter randomized controlled trial. SETTING: Fifteen PICUs across the United Kingdom and Scotland. PATIENTS: Children aged 38 weeks corrected gestational age to 15 years accepted to a participating PICU as an unplanned admission and receiving invasive mechanical ventilation with supplemental oxygen for abnormal gas exchange. METHODS: Hierarchical regression models for Spo2 and Fio2, and ordinal models for the primary trial outcome of a composite of the duration of organ support at 30 days and death, were used to examine the effects of ethnicity, accounting for baseline Spo2, Fio2, and mean airway pressure and trial allocation. MEASUREMENTS AND MAIN RESULTS: Ethnicity data were available for 1577 of 1986 eligible children, 1408 (89.3%) of which were White, Asian, or Black. Spo2 and Fio2 distributions did not vary according to Black or Asian ethnicity compared with White children. The trial primary outcome measure also did not vary significantly with ethnicity. The point estimate for the treatment effect of conservative oxygenation in Black children was 0.64 (95% CI, 0.33-1.25) compared with 0.84 (0.68-1.04) in the overall trial population. CONCLUSIONS: These data do not suggest that the association between improved outcomes and conservative oxygenation strategy in mechanically ventilated children in PICU is modified by ethnicity.

Access to personalised dementia care planning in primary care: a mixed methods evaluation of the PriDem intervention.

OBJECTIVES: Provision of personalised care planning is a national priority for people with dementia. Research suggests a lack of quality and consistency of care plans and reviews. The PriDem model of care was developed to deliver feasible and acceptable primary care-based postdiagnostic dementia care. We aimed to increase the adoption of personalised care planning for people with dementia, exploring implementation facilitators and barriers. DESIGN: Mixed-method feasibility and implementation study. SETTING: Seven general practices from four primary care networks (PCNs) in the Northeast and Southeast of England. PARTICIPANTS: A medical records audit collected data on 179 community-dwelling people with dementia preintervention, and 215 during the intervention year. The qualitative study recruited 26 health and social care professionals, 14 people with dementia and 16 carers linked to participating practices. INTERVENTION: Clinical dementia leads (CDL) delivered a 12-month, systems-level intervention in participating PCNs, to develop care systems, build staff capacity and capability, and deliver tailored care and support to people with dementia and their carers. PRIMARY AND SECONDARY OUTCOME MEASURES: Adoption of personalised care planning was assessed through a preintervention and postintervention audit of medical records. Implementation barriers and facilitators were explored through semistructured qualitative interviews and non-participant observation, analysed using codebook thematic analysis informed by Normalisation Process Theory. RESULTS: The proportion of personalised care plans increased from 37.4% (95% CI 30.3% to 44.5%) preintervention to 64.7% (95% CI 58.3% to 71.0%) in the intervention year. Qualitative findings suggest that the flexible nature of the PriDem intervention enabled staff to overcome contextual barriers through harnessing the skills of the wider multidisciplinary team, delivering increasingly holistic care to patients. CONCLUSIONS: Meaningful personalised care planning can be achieved through a team-based approach. Although improved guidelines for care planning are required, commissioners should consider the benefits of a CDL-led approach. TRIAL REGISTRATION NUMBER: ISRCTN11677384.

Evaluating a model of best practice in primary care led post-diagnostic dementia care: feasibility and acceptability findings from the PriDem study.

OBJECTIVES: To evaluate the feasibility and acceptability of a primary care-based intervention for improving post-diagnostic dementia care and support (PriDem), and implementation study procedures. DESIGN: A non-randomised, mixed methods, feasibility study. SETTING: Seven general practices from four primary care networks (PCNs) in the Northeast and Southeast of England. PARTICIPANTS: We aimed to recruit 80 people with dementia (PWD) and 66 carers INTERVENTION: Clinical Dementia Leads delivered a 12-month intervention in participating PCNs, to develop care systems, build staff capacity and capability, and deliver tailored care and support to PWD and carers. OUTCOMES: Recruitment and retention rates were measured. A mixed methods process evaluation evaluated feasibility and acceptability of the intervention and study procedures. Using electronic care records, researchers extracted service use data and undertook a dementia care plan audit, preintervention and postintervention, assessing feasibility of measuring the primary implementation outcome: adoption of personalised care planning by participating general practices. Participants completed quality of life, and service use measures at baseline, 4 and 9 months. RESULTS: 60 PWD (75% of recruitment target) and 51 carers (77% of recruitment target) were recruited from seven general practices across four PCNs. Retention rate at 9 months was 70.0% of PWD and 76.5% of carers. The recruitment approach showed potential for including under-represented groups within dementia. Despite implementation challenges, the intervention was feasible and acceptable, and showed early signs of sustainability. Study procedures were feasible and accessible, although researcher capacity was crucial. Participants needed time and support to engage with the study. Care plan audit procedures were feasible and acceptable. CONCLUSIONS: The PriDem model is an acceptable and feasible intervention. A definitive study is warranted to fully inform dementia care policy and personalised dementia care planning guidance. Successful strategies to support inclusion of PWD and their carers in future research were developed. TRIAL REGISTRATION NUMBER: ISRCTN11677384.

Adapted problem adaptation therapy for depression in mild to moderate Alzheimer's disease dementia: A randomized controlled trial.

INTRODUCTION: Trials of effectiveness of treatment options for depression in dementia are an important priority. METHODS: Randomized controlled trial to assess adapted Problem Adaptation Therapy (PATH) for depression in mild/moderate dementia caused by Alzheimer's disease. RESULTS: Three hundred thirty-six participants with mild or moderate dementia, >7 on Cornell Scale for Depression in Dementia (CSDD), randomized to adapted PATH or treatment as usual. Mean age 77.0 years, 39.0% males, mean Mini-Mental State Examination 21.6, mean CSDD 12.9. For primary outcome (CSDD at 6 months), no statistically significant benefit with adapted PATH on the CSDD (6 months: -0.58; 95% CI -1.71 to 0.54). The CSDD at 3 months showed a small benefit with adapted PATH (-1.38; 95% CI -2.54 to -0.21) as did the EQ-5D (-4.97; 95% CI -9.46 to -0.48). DISCUSSION: An eight-session course of adapted PATH plus two booster sessions administered within NHS dementia services was not effective treatment for depression in people with mild and moderate dementia. Future studies should examine the effect of more intensive and longer-term therapy.

Unquantifiably low aldosterone concentrations are prevalent in hospitalised COVID-19 patients but may not be revealed by chemiluminescent immunoassay.

Objective: Previous studies have reported conflicting findings regarding aldosterone levels in patients hospitalised with COVID-19. We therefore used the gold-standard technique of liquid chromatography-tandem mass spectrometry (LCMSMS) to address this uncertainty. Design: All patients admitted to Cambridge University Hospitals with COVID-19 between 10 March 2020 and 13 May 2021, and in whom a stored blood sample was available for analysis, were eligible for inclusion. Methods: Aldosterone was measured by LCMSMS and by immunoassay; cortisol and renin were determined by immunoassay. Results: Using LCMSMS, aldosterone was below the limit of detection (<70 pmol/L) in 74 (58.7%) patients. Importantly, this finding was discordant with results obtained using a commonly employed clinical immunoassay (Diasorin LIAISON®), which over-estimated aldosterone compared to the LCMSMS assay (intercept 14.1 (95% CI -34.4 to 54.1) + slope 3.16 (95% CI 2.09-4.15) pmol/L). The magnitude of this discrepancy did not clearly correlate with markers of kidney or liver function. Solvent extraction prior to immunoassay improved the agreement between methods (intercept -14.9 (95% CI -31.9 to -4.3) and slope 1.0 (95% CI 0.89-1.02) pmol/L) suggesting the presence of a water-soluble metabolite causing interference in the direct immunoassay. We also replicated a previous finding that blood cortisol concentrations were often increased, with increased mortality in the group with serum cortisol levels > 744 nmol/L (P = 0.005). Conclusion: When measured by LCMSMS, aldosterone was found to be profoundly low in a significant proportion of patients with COVID-19 at the time of hospital admission. This has likely not been detected previously due to high levels of interference with immunoassays in patients with COVID-19, and this merits further prospective investigation.

Statistical modeling of annual highest monthly rainfall in Zimbabwe.

The first statistical analysis of maximum rainfall in Zimbabwe is provided. The data are from 103 stations spread across the different climatic regions of Zimbabwe. More than 90% of the stations had at least 50 years of data. The generalized extreme value distribution was fitted to maximum rainfall by the method of maximum likelihood. Probability plots, quantile plots and Kolmogorov-Smirnov tests showed that the generalized extreme value distribution provided an adequate fit for all stations. The vast majority of stations do not exhibit significant trends in rainfall. Twelve of the stations exhibit negative trends and three of the stations exhibit positive trends in rainfall. Estimates of return levels are given for 2, 5, 10, 20, 50 and 100 years.

Development and validation of a dynamic 48-hour in-hospital mortality risk stratification for COVID-19 in a UK teaching hospital: a retrospective cohort study.

OBJECTIVES: To develop a disease stratification model for COVID-19 that updates according to changes in a patient's condition while in hospital to facilitate patient management and resource allocation. DESIGN: In this retrospective cohort study, we adopted a landmarking approach to dynamic prediction of all-cause in-hospital mortality over the next 48 hours. We accounted for informative predictor missingness and selected predictors using penalised regression. SETTING: All data used in this study were obtained from a single UK teaching hospital. PARTICIPANTS: We developed the model using 473 consecutive patients with COVID-19 presenting to a UK hospital between 1 March 2020 and 12 September 2020; and temporally validated using data on 1119 patients presenting between 13 September 2020 and 17 March 2021. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome is all-cause in-hospital mortality within 48 hours of the prediction time. We accounted for the competing risks of discharge from hospital alive and transfer to a tertiary intensive care unit for extracorporeal membrane oxygenation. RESULTS: Our final model includes age, Clinical Frailty Scale score, heart rate, respiratory rate, oxygen saturation/fractional inspired oxygen ratio, white cell count, presence of acidosis (pH <7.35) and interleukin-6. Internal validation achieved an area under the receiver operating characteristic (AUROC) of 0.90 (95% CI 0.87 to 0.93) and temporal validation gave an AUROC of 0.86 (95% CI 0.83 to 0.88). CONCLUSIONS: Our model incorporates both static risk factors (eg, age) and evolving clinical and laboratory data, to provide a dynamic risk prediction model that adapts to both sudden and gradual changes in an individual patient's clinical condition. On successful external validation, the model has the potential to be a powerful clinical risk assessment tool. TRIAL REGISTRATION: The study is registered as 'researchregistry5464' on the Research Registry (www.researchregistry.com).