Clinical and cost-effectiveness of spironolactone in treating persistent facial acne in women: SAFA double-blinded RCT.

Background: Acne is common, can cause significant impact on quality of life and is a frequent reason for long-term antibiotic use. Spironolactone has been prescribed for acne in women for many years, but robust evidence is lacking. Objective: To evaluate whether spironolactone is clinically effective and cost-effective in treating acne in women. Design: Pragmatic, parallel, double-blind, randomised superiority trial. Setting: Primary and secondary healthcare and community settings (community and social media advertising). Participants: Women aged 18 years and older with facial acne persisting for at least 6 months, judged to potentially warrant oral antibiotic treatment. Interventions: Participants were randomised 1 : 1, using an independent web-based procedure, to either 50 mg/day spironolactone or matched placebo until week 6, increasing to 100 mg/day spironolactone or matched placebo until week 24. Participants continued usual topical treatment. Main outcome measures: Primary outcome was the adjusted mean difference in Acne-Specific Quality of Life symptom subscale score at 12 weeks. Secondary outcomes included Acne-Specific Quality of Life total and subscales; participant self-assessed improvement; Investigator's Global Assessment; Participant's Global Assessment; satisfaction; adverse effects and cost-effectiveness. Results: Of 1267 women assessed for eligibility, 410 were randomised (201 intervention, 209 control), 342 in the primary analysis (176 intervention, 166 control). Mean age was 29.2 years (standard deviation 7.2) and 7.9% (28/356) were from non-white backgrounds. At baseline, Investigator's Global Assessment classified acne as mild in 46%, moderate in 40% and severe in 13%. At baseline, 82.9% were using topical treatments. Over 95% of participants in both groups tolerated the treatment and increased their dose. Mean baseline Acne-Specific Quality of Life symptom subscale was 13.0 (standard deviation 4.7) across both groups. Mean scores at week 12 were 19.2 (standard deviation 6.1) for spironolactone and 17.8 (standard deviation 5.6) for placebo [difference favouring spironolactone 1.27 (95% confidence interval 0.07 to 2.46) adjusting for baseline variables]. Mean scores at week 24 were 21.2 (standard deviation 5.9) in spironolactone group and 17.4 (standard deviation 5.8) in placebo group [adjusted difference 3.77 (95% confidence interval 2.50 to 5.03) adjusted]. Secondary outcomes also favoured spironolactone at 12 weeks with greater differences at 24 weeks. Participants taking spironolactone were more likely than those taking placebo to report overall acne improvement at 12 weeks {72.2% vs. 67.9% [adjusted odds ratio 1.16 (95% confidence interval 0.70 to 1.91)]} and at 24 weeks {81.9% vs. 63.3% [adjusted odds ratio 2.72 (95% confidence interval 1.50 to 4.93)]}. Investigator's Global Assessment was judged successful at week 12 for 31/201 (18.5%) taking spironolactone and 9/209 (5.6%) taking placebo [adjusted odds ratio 5.18 (95% confidence interval 2.18 to 12.28)]. Satisfaction with treatment improved in 70.6% of participants taking spironolactone compared with 43.1% taking placebo [adjusted odds ratio 3.12 (95% confidence interval 1.80 to 5.41)]. Adverse reactions were similar between groups, but headaches were reported more commonly on spironolactone (20.4% vs. 12.0%). No serious adverse reactions were reported. Taking account for missing data through multiple imputation gave an incremental cost per quality-adjusted life-year of £27,879 (adjusted) compared to placebo or £2683 per quality-adjusted life-year compared to oral antibiotics. Conclusions: Spironolactone resulted in better participant-reported and investigator-reported outcomes than placebo, with greater differences at week 24 than week 12. Trial registration: This trial is registered as ISRCTN12892056 and EudraCT (2018-003630-33). Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/13/02) and is published in full in Health Technology Assessment; Vol. 28, No. 56. See the NIHR Funding and Awards website for further award information.

Acne (or spots) is common and often persists into adulthood. Many people take long courses of antibiotic tablets, but concerns about antibiotic resistance mean alternatives are needed. Spironolactone is a medicine that is sometimes used for acne in women. However, we do not know whether it works. This trial aimed to answer this question. We invited women aged over 18 who had acne on their face for at least 6 months to take part via their general practitioner surgery, hospital or advertising. Women were randomly assigned to two groups: one group was given spironolactone and the other group was given identical-looking placebo ('dummy pill') daily for 24 weeks. Women in both groups could continue using acne treatments applied to the skin (gels/creams/lotions). We asked participants to rate their acne using a questionnaire called Acne-Specific Quality of Life, asked whether they felt their skin had improved and asked skin specialists to assess their skin. Four hundred and ten women took part, many of whom had had acne for a long time. Acne-Specific Quality of Life scores improved in both groups by 12 weeks but improved more in the spironolactone group at 12 and 24 weeks. When asked directly whether their skin had improved, 71% of participants in the spironolactone group said it had, compared with 43% on placebo. Skin specialists were also more likely to report that the acne had improved in the spironolactone group. Side effects were mild and similar in both groups but there were slightly more headaches on spironolactone (20% compared with 12%). Spironolactone is likely to represent value for money for the National Health Service, though this depends on a number of factors including what it is compared to. This trial suggests that spironolactone is a useful additional treatment for women with persistent acne.

Trends in organ donation in England, Scotland and Wales in the context of the COVID-19 pandemic and 'opt-out' legislation.

BACKGROUND: In May 2020, England implemented soft 'opt-out' or 'deemed consent' for deceased donation with the intention of raising consent rates. However, this coincided with the COVID-19 pandemic, making it difficult to assess the early impact of the law change. Wales and Scotland changed their organ donation legislation to implement soft opt-out systems in 2015 and 2021 respectively. This study provides a descriptive analysis of changes in consent and transplant rates for deceased organ donation in England, Scotland and Wales. METHODS: Logistic regression and descriptive trend analysis were employed to assess the probability of a patient who died in critical care becoming a donor, and to report consent rates using data, respectively, from the Intensive Care National Audit and Research Centre (ICNARC) in England from 1 April 2014 to 30 September 2021, and from the Potential Donor Audit for England, Scotland and Wales from April 2010 to June 2023. RESULTS: The number of eligible donors in April-June 2020 were 56.5%, 59.3% and 57.6% lower in England, Scotland and Wales relative to April-June 2019 (pre-pandemic). By April-June 2023, the number of eligible donors had recovered to 87.4%, 64.2% and 110.3%, respectively, of their levels in 2019. The consent rate in England, Scotland and Wales reduced from 68.3%, 63.0% and 63.6% in April-June 2019 to 63.2%, 60.5% and 56.3% in April-June 2023. CONCLUSIONS: While the UK organ donation system shows signs of recovery from the COVID-19 pandemic, the number of eligible potential donors and consent rates remain below their pre-pandemic levels.

Bladder Tumor-Focused Adaptive Radiation Therapy: Clinical Outcomes of a Phase I Dose Escalation Study.

PURPOSE: We determine the maximum tolerated tumor-focused dose (MTD) for the radical treatment of muscle invasive bladder cancer enabled by image guided adaptive radiation therapy and long-term clinical outcomes. METHODS AND MATERIALS: Fifty-nine patients with T2 to T4aN0M0 unifocal urothelial muscle invasive bladder cancer suitable for daily radical radiation therapy were recruited prospectively to an ethics-approved protocol (NCT01124682). The uninvolved bladder (PTVbladder) was planned to 52 Gy in 32 fractions. The bladder tumor (PTVtumor) was planned to an assigned dose level of 68, 70, 72, or 74 Gy. If organ at risk dose constraints were violated, then PTVtumor was planned to 64 Gy. Dose level allocation was determined by concurrent toxicity assessment of all previous patients recruited. Acute toxicity was evaluated using Common Terminology Criteria for Adverse Events v3.0; late toxicity was evaluated using Radiation Therapy Oncology Group criteria. The MTD was predefined as the highest dose level with an estimated probability of ≤ 15% ≥ G3 late toxicity and an observed rate of <50% acute G3 and <10% acute G4 toxicity. RESULTS: Twenty-six patients were assigned to 68 Gy, of whom 6 were planned to 64 Gy; 29 patients were assigned to 70 Gy of whom 1 was planned to 68 Gy, 2 patients were assigned and planned to 72 Gy; no patients were assigned to 74 Gy. Three patients did not complete the treatment as planned, of whom only 1 patient stopped treatment because dose-limiting toxicity occurred. The MTD was 70 Gy. Acute genito-urinary and gastro-intestinal G3 acute toxicity was seen in 19% and 7% of patients, respectively. No acute G4 genito-urinary or gastro-intestinal toxicity was seen. Late toxicity (any) G3 and G4 was seen in 14% and 2% of patients, respectively. The 5-year overall survival was 58% (95% CI, 44%-71%). The bladder preservation rate was 89% (95% CI, 88%-96%) with 6 patients not retaining native bladder function. CONCLUSIONS: Bladder tumor-focused dose escalation to 70 Gy using image guided adaptive radiation therapy is feasible with acceptable toxicity. This dose level has been evaluated in a phase II randomized control trial (RAIDER NCT02447549).

Survival after Stereotactic Radiosurgery in the Era of Targeted Therapy: Number of Metastases No Longer Matters.

Randomised control trial data support the use of stereotactic radiosurgery (SRS) in up to 4 brain metastases (BMs), with non-randomised prospective data complementing this for up to 10 BMs. There is debate in the neuro-oncology community as to the appropriateness of SRS in patients with >10 BMs. We present data from a large single-centre cohort, reporting survival in those with >10 BMs and in a >20 BMs subgroup. A total of 1181 patients receiving SRS for BMs were included. Data were collected prospectively from the time of SRS referral. Kaplan-Meier graphs and logrank tests were used to compare survival between groups. Multivariate analysis was performed using the Cox proportional hazards model to account for differences in group characteristics. Median survival with 1 BM (n = 379), 2-4 BMs (n = 438), 5-10 BMs (n = 236), and >10 BMs (n = 128) was 12.49, 10.22, 10.68, and 10.09 months, respectively. Using 2-4 BMs as the reference group, survival was not significantly different in those with >10 BMs in either our univariable (p = 0.6882) or multivariable analysis (p = 0.0564). In our subgroup analyses, median survival for those with >20 BMs was comparable to those with 2-4 BMs (10.09 vs. 10.22 months, p = 0.3558). This study contributes a large dataset to the existing literature on SRS for those with multi-metastases and supports growing evidence that those with >10 BMs should be considered for SRS.

Conversion of an outpatient pharmacy to a mail-order pharmacy within a health system.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: The establishment of a new outpatient pharmacy provided a strategic opportunity to repurpose and convert an existing outpatient pharmacy into a closed-door mail-order pharmacy within a health system. This article describes the steps taken to successfully make this change and evaluates the impact. SUMMARY: The mail-order pharmacy conversion project was divided into 3 phases: phase 1 (before conversion) from July through August 2022, phase 2 (conversion) from October through November 2022, and phase 3 (after conversion) from December 2022 through February 2023. Phase 1 included standardizing workflows with standard operating procedure (SOP) development, improving automation, determining staffing ratios, gathering baseline staff engagement data, and identifying primary and secondary outcomes of interest. Phase 2 encompassed SOP implementation and training of mail-order team members. Phase 3 involved evaluating available pharmacy floorspace, marketing mail-order services, and the second distribution of the staff engagement survey. The measured outcomes of this project were total prescription volumes, increase in total revenue, and staff engagement. Data collection was completed in phase 3. CONCLUSION: The existing outpatient pharmacy was successfully converted to a closed-door pharmacy, and the associated prescription volume increased. Developing a strategic action plan to establish SOPs, calculate staffing performance metrics, and identify opportunities for growth and engaging frontline team members were essential to the success of this project.

Nutritional supplementation in children with severe pneumonia in Uganda and Kenya (COAST-Nutrition): a phase 2 randomised controlled trial.

Background: Severe pneumonia in African children results in poor long-term outcomes (deaths/readmissions) with undernutrition as a key risk factor. We hypothesised additional energy/protein-rich Ready-to-Use Therapeutic Foods (RUTF) would meet additional nutritional requirements and improve outcomes. Methods: COAST-Nutrition was an open-label Phase 2 randomised controlled trial in children (aged 6 months-12 years) hospitalised with severe pneumonia (and hypoxaemia, SpO2 <92%) in Mbale, Soroti, Jinja, Masaka Regional Referral Hospitals, Uganda and Kilifi County Hospital, Kenya (ISRCTN10829073 (registered 6th June 2018) PACTR202106635355751 (registered 2nd June 2021)). Children were randomised (ratio 1:1) to enhanced nutritional supplementation with RUTF (plus usual diet) for 56 days vs usual diet (control). The primary outcome was change in mid-upper arm circumference (MUAC) at 90 days as a composite with mortality. Secondary outcomes include anthropometric status, mortality, and readmissions at Days 28, 90 and 180. Findings: Between 12 August 2018 and 22 April 2022, 846 eligible children were randomised, 424 to RUTF and 422 to usual diet, and followed for 180-days [12 (1%) lost-to-follow-up]. RUTF supplement was initiated in 417/419 (>99%). By Day 90, there was no significant difference in the composite endpoint (probabilistic index 0.49, 95% CI 0.45-0.53, p = 0.74). Respective 90-day mortality (13/420 3.1% vs 14/421 3.3%) and MUAC increment (0.54 (SD 0.85) vs 0.55 (SD 0.81)) were similar between arms. There was no difference in any anthropometric secondary endpoints to Day 28, 90 or 180 except skinfold thickness at Day 28 and Day 90 was greater in the RUTF arm. Serious adverse events were higher in the RUTF arm (n = 164 vs 108), mainly due to hospital readmission for acute illness (54/387 (14%) vs 37/375 (10%). Interpretation: Our study suggested that nutritional supplementation with RUTF did not improve outcomes to 180 days in children with severe pneumonia. Funding: This trial is part of the EDCTP2 programme (grant number RIA-2016S-1636-COAST-Nutrition) supported by the European Union, and UK Joint Global Health Trials scheme: Medical Research Council, Department for International Development, Wellcome Trust (grant number MR/L004364/1, UK).

Vital Signs: Drowning Death Rates, Self-Reported Swimming Skill, Swimming Lesson Participation, and Recreational Water Exposure - United States, 2019-2023.

Introduction: Drowning is the cause of approximately 4,000 U.S. deaths each year and disproportionately affects some age, racial, and ethnic groups. Infrastructure disruptions during the COVID-19 pandemic, including limited access to supervised swimming settings, might have affected drowning rates and risk. Data on factors that contribute to drowning risk are limited. To assess the potential impact of the pandemic on drowning death rates, pre- and post-COVID-19 pandemic rates were compared. Methods: National Vital Statistics System data were used to compare unintentional drowning death rates in 2019 (pre-COVID-19 pandemic onset) with those in 2020, 2021, and 2022 (post-pandemic onset) by age, sex, and race and ethnicity. National probability-based online panel survey (National Center for Health Statistics Rapid Surveys System) data from October-November 2023 were used to describe adults' self-reported swimming skill, swimming lesson participation, and exposure to recreational water. Results: Unintentional drowning death rates were significantly higher during 2020, 2021, and 2022 compared with those in 2019. In all years, rates were highest among children aged 1-4 years; significant increases occurred in most age groups. The highest drowning rates were among non-Hispanic American Indian or Alaska Native and non-Hispanic Black or African American persons. Approximately one half (54.7%) of U.S. adults reported never having taken a swimming lesson. Swimming skill and swimming lesson participation differed by age, sex, and race and ethnicity. Conclusions and Implications for Public Health Practice: Recent increases in drowning rates, including those among populations already at high risk, have increased the urgency of implementing prevention strategies. Basic swimming and water safety skills training can reduce the risk for drowning. Addressing social and structural barriers that limit access to this training might reduce drowning deaths and inequities. The U.S. National Water Safety Action Plan provides recommendations and tools for communities and organizations to enhance basic swimming and water safety skills training.

Conservative versus liberal oxygenation targets in critically ill children (Oxy-PICU): a UK multicentre, open, parallel-group, randomised clinical trial.

BACKGROUND: The optimal target for systemic oxygenation in critically ill children is unknown. Liberal oxygenation is widely practiced, but has been associated with harm in paediatric patients. We aimed to evaluate whether conservative oxygenation would reduce duration of organ support or incidence of death compared to standard care. METHODS: Oxy-PICU was a pragmatic, multicentre, open-label, randomised controlled trial in 15 UK paediatric intensive care units (PICUs). Children admitted as an emergency, who were older than 38 weeks corrected gestational age and younger than 16 years receiving invasive ventilation and supplemental oxygen were randomly allocated in a 1:1 ratio via a concealed, central, web-based randomisation system to conservative peripheral oxygen saturations ([SpO2] 88-92%) or liberal (SpO2 >94%) targets. The primary outcome was the duration of organ support at 30 days following random allocation, a rank-based endpoint with death either on or before day 30 as the worst outcome (a score equating to 31 days of organ support), with survivors assigned a score between 1 and 30 depending on the number of calendar days of organ support received. The primary effect estimate was the probabilistic index, a value greater than 0·5 indicating more than 50% probability that conservative oxygenation is superior to liberal oxygenation for a randomly selected patient. All participants in whom consent was available were included in the intention-to-treat analysis. The completed study was registered with the ISRCTN registry (ISRCTN92103439). FINDINGS: Between Sept 1, 2020, and May 15, 2022, 2040 children were randomly allocated to conservative or liberal oxygenation groups. Consent was available for 1872 (92%) of 2040 children. The conservative oxygenation group comprised 939 children (528 [57%] of 927 were female and 399 [43%] of 927 were male) and the liberal oxygenation group included 933 children (511 [56%] of 920 were female and 409 [45%] of 920 were male). Duration of organ support or death in the first 30 days was significantly lower in the conservative oxygenation group (probabilistic index 0·53, 95% CI 0·50-0·55; p=0·04 Wilcoxon rank-sum test, adjusted odds ratio 0·84 [95% CI 0·72-0·99]). Prespecified adverse events were reported in 24 (3%) of 939 patients in the conservative oxygenation group and 36 (4%) of 933 patients in the liberal oxygenation group. INTERPRETATION: Among invasively ventilated children who were admitted as an emergency to a PICU receiving supplemental oxygen, a conservative oxygenation target resulted in a small, but significant, greater probability of a better outcome in terms of duration of organ support at 30 days or death when compared with a liberal oxygenation target. Widespread adoption of a conservative oxygenation saturation target (SpO2 88-92%) could help improve outcomes and reduce costs for the sickest children admitted to PICUs. FUNDING: UK National Institute for Health and Care Research Health Technology Assessment Programme.

An aromatherapy massage intervention on sleep in the ICU: A randomized controlled feasibility study.

We conducted a feasibility randomized controlled trial exploring the effect of aromatherapy massage on sleep in critically ill patients. Patients were randomized to receive aromatherapy massage or usual care, and feasibility of recruitment and outcome data completion was captured. Sleep (depth) was assessed through Bispectral Index monitoring and self/nurse-reported Richards-Campbell Sleep Questionnaires, and the Sleep in the ICU Questionnaire. Thirty-four patients participated: 17 were randomized to aromatherapy massage and 17 to control. Five participants who received the intervention completed outcomes for analysis (alongside eight controls). A larger study was deemed unfeasible in this population, highlighting the value of testing feasibility of complex interventions, such as massage for sleep in ICU.

Cost-effectiveness of Spironolactone for Adult Female Acne (SAFA): economic evaluation alongside a randomised controlled trial.

OBJECTIVE: This study aims to estimate the cost-effectiveness of oral spironolactone plus routine topical treatment compared with routine topical treatment alone for persistent acne in adult women from a British NHS perspective over 24 weeks. DESIGN: Economic evaluation undertaken alongside a pragmatic, parallel, double-blind, randomised trial. SETTING: Primary and secondary healthcare, community and social media advertising. PARTICIPANTS: Women ≥18 years with persistent facial acne judged to warrant oral antibiotic treatment. INTERVENTIONS: Participants were randomised 1:1 to 50 mg/day spironolactone (increasing to 100 mg/day after 6 weeks) or matched placebo until week 24. Participants in both groups could continue topical treatment. MAIN OUTCOME MEASURES: Cost-utility analysis assessed incremental cost per quality-adjusted life year (QALY) using the EQ-5D-5L. Cost-effectiveness analysis estimated incremental cost per unit change on the Acne-QoL symptom subscale. Adjusted analysis included randomisation stratification variables (centre, baseline severity (investigator's global assessment, IGA <3 vs ≥3)) and baseline variables (Acne-QoL symptom subscale score, resource use costs, EQ-5D score and use of topical treatments). RESULTS: Spironolactone did not appear cost-effective in the complete case analysis (n=126 spironolactone, n=109 control), compared with no active systemic treatment (adjusted incremental cost per QALY £67 191; unadjusted £34 770). Incremental cost per QALY was £27 879 (adjusted), just below the upper National Institute for Health and Care Excellence's threshold value of £30 000, where multiple imputation took account of missing data. Incremental cost per QALY for other sensitivity analyses varied around the base-case, highlighting the degree of uncertainty. The adjusted incremental cost per point change on the Acne-QoL symptom subscale for spironolactone compared with no active systemic treatment was £38.21 (complete case analysis). CONCLUSIONS: The results demonstrate a high level of uncertainty, particularly with respect to estimates of incremental QALYs. Compared with no active systemic treatment, spironolactone was estimated to be marginally cost-effective where multiple imputation was performed but was not cost-effective in complete case analysis. TRIAL REGISTRATION NUMBER: ISRCTN registry (ISRCTN12892056).

Effectiveness of spironolactone for women with acne vulgaris (SAFA) in England and Wales: pragmatic, multicentre, phase 3, double blind, randomised controlled trial.

OBJECTIVE: To assess the effectiveness of oral spironolactone for acne vulgaris in adult women. DESIGN: Pragmatic, multicentre, phase 3, double blind, randomised controlled trial. SETTING: Primary and secondary healthcare, and advertising in the community and on social media in England and Wales. PARTICIPANTS: Women (≥18 years) with facial acne for at least six months, judged to warrant oral antibiotics. INTERVENTIONS: Participants were randomly assigned (1:1) to either 50 mg/day spironolactone or matched placebo until week six, increasing to 100 mg/day spironolactone or placebo until week 24. Participants could continue using topical treatment. MAIN OUTCOME MEASURES: Primary outcome was Acne-Specific Quality of Life (Acne-QoL) symptom subscale score at week 12 (range 0-30, where higher scores reflect improved QoL). Secondary outcomes were Acne-QoL at week 24, participant self-assessed improvement; investigator's global assessment (IGA) for treatment success; and adverse reactions. RESULTS: From 5 June 2019 to 31 August 2021, 1267 women were assessed for eligibility, 410 were randomly assigned to the intervention (n=201) or control group (n=209) and 342 were included in the primary analysis (n=176 in the intervention group and n=166 in the control group). Baseline mean age was 29.2 years (standard deviation 7.2), 28 (7%) of 389 were from ethnicities other than white, with 46% mild, 40% moderate, and 13% severe acne. Mean Acne-QoL symptom scores at baseline were 13.2 (standard deviation 4.9) and at week 12 were 19.2 (6.1) for spironolactone and 12.9 (4.5) and 17.8 (5.6) for placebo (difference favouring spironolactone 1.27 (95% confidence interval 0.07 to 2.46), adjusted for baseline variables). Scores at week 24 were 21.2 (5.9) for spironolactone and 17.4 (5.8) for placebo (difference 3.45 (95% confidence interval 2.16 to 4.75), adjusted). More participants in the spironolactone group reported acne improvement than in the placebo group: no significant difference was reported at week 12 (72% v 68%, odds ratio 1.16 (95% confidence interval 0.70 to 1.91)) but significant difference was noted at week 24 (82% v 63%, 2.72 (1.50 to 4.93)). Treatment success (IGA classified) at week 12 was 31 (19%) of 168 given spironolactone and nine (6%) of 160 given placebo (5.18 (2.18 to 12.28)). Adverse reactions were slightly more common in the spironolactone group with more headaches reported (20% v 12%; p=0.02). No serious adverse reactions were reported. CONCLUSIONS: Spironolactone improved outcomes compared with placebo, with greater differences at week 24 than week 12. Spironolactone is a useful alternative to oral antibiotics for women with acne. TRIAL REGISTRATION: ISRCTN12892056.

The effect of blood pressure on mortality following out-of-hospital cardiac arrest: a retrospective cohort study of the United Kingdom Intensive Care National Audit and Research Centre database.

BACKGROUND: Hypotension following out-of-hospital cardiac arrest (OHCA) may cause secondary brain injury and increase mortality rates. Current guidelines recommend avoiding hypotension. However, the optimal blood pressure following OHCA is unknown. We hypothesised that exposure to hypotension and hypertension in the first 24 h in ICU would be associated with mortality following OHCA. METHODS: We conducted a retrospective analysis of OHCA patients included in the Intensive Care National Audit and Research Centre Case Mix Programme from 1 January 2010 to 31 December 2019. Restricted cubic splines were created following adjustment for important prognostic variables. We report the adjusted odds ratio for associations between lowest and highest mean arterial pressure (MAP) and systolic blood pressure (SBP) in the first 24 h of ICU care and hospital mortality. RESULTS: A total of 32,349 patients were included in the analysis. Hospital mortality was 56.2%. The median lowest and highest MAP and SBP were similar in survivors and non-survivors. Both hypotension and hypertension were associated with increased mortality. Patients who had a lowest recorded MAP in the range 60-63 mmHg had the lowest associated mortality. Patients who had a highest recorded MAP in the range 95-104 mmHg had the lowest associated mortality. The association between SBP and mortality followed a similar pattern to MAP. CONCLUSIONS: We found an association between hypotension and hypertension in the first 24 h in ICU and mortality following OHCA. The inability to distinguish between the median blood pressure of survivors and non-survivors indicates the need for research into individualised blood pressure targets for survivors following OHCA.

Preexisting Neuropsychiatric Conditions and Associated Risk of Severe COVID-19 Infection and Other Acute Respiratory Infections.

Importance: Evidence indicates that preexisting neuropsychiatric conditions confer increased risks of severe outcomes from COVID-19 infection. It is unclear how this increased risk compares with risks associated with other severe acute respiratory infections (SARIs). Objective: To determine whether preexisting diagnosis of and/or treatment for a neuropsychiatric condition is associated with severe outcomes from COVID-19 infection and other SARIs and whether any observed association is similar between the 2 outcomes. Design, Setting, and Participants: Prepandemic (2015-2020) and contemporary (2020-2021) longitudinal cohorts were derived from the QResearch database of English primary care records. Adjusted hazard ratios (HRs) with 99% CIs were estimated in April 2022 using flexible parametric survival models clustered by primary care clinic. This study included a population-based sample, including all adults in the database who had been registered with a primary care clinic for at least 1 year. Analysis of routinely collected primary care electronic medical records was performed. Exposures: Diagnosis of and/or medication for anxiety, mood, or psychotic disorders and diagnosis of dementia, depression, schizophrenia, or bipolar disorder. Main Outcomes and Measures: COVID-19-related mortality, or hospital or intensive care unit admission; SARI-related mortality, or hospital or intensive care unit admission. Results: The prepandemic cohort comprised 11 134 789 adults (223 569 SARI cases [2.0%]) with a median (IQR) age of 42 (29-58) years, of which 5 644 525 (50.7%) were female. The contemporary cohort comprised 8 388 956 adults (58 203 severe COVID-19 cases [0.7%]) with a median (IQR) age of 48 (34-63) years, of which 4 207 192 were male (50.2%). Diagnosis and/or treatment for neuropsychiatric conditions other than dementia was associated with an increased likelihood of a severe outcome from SARI (anxiety diagnosis: HR, 1.16; 99% CI, 1.13-1.18; psychotic disorder diagnosis and treatment: HR, 2.56; 99% CI, 2.40-2.72) and COVID-19 (anxiety diagnosis: HR, 1.16; 99% CI, 1.12-1.20; psychotic disorder treatment: HR, 2.37; 99% CI, 2.20-2.55). The effect estimate for severe outcome with dementia was higher for those with COVID-19 than SARI (HR, 2.85; 99% CI, 2.71-3.00 vs HR, 2.13; 99% CI, 2.07-2.19). Conclusions and Relevance: In this longitudinal cohort study, UK patients with preexisting neuropsychiatric conditions and treatments were associated with similarly increased risks of severe outcome from COVID-19 infection and SARIs, except for dementia.

Hip Fracture-Related Emergency Department Visits, Hospitalizations and Deaths by Mechanism of Injury among Adults Aged 65 and Older, United States 2019.

OBJECTIVE: Describe rates of hip fracture-related emergency department (ED) visits, hospitalizations, and deaths among older adults (aged ≥65 years) in the United States. METHODS: Data from the 2019 Healthcare Cost and Utilization Project and National Vital Statistics System were used to calculate rates of hip fracture-related ED visits, hospitalizations, and deaths among older adults by select characteristics and mechanism of injury. RESULTS: In 2019, there were 318,797 ED visits, 290,130 hospitalizations, and 7731 deaths related to hip fractures among older adults. About 88% of ED visits and hospitalizations and approximately 83% of deaths related to hip fractures were caused by falls. Rates were highest among older adults living in rural areas and among those aged ≥85 years. DISCUSSION: Most hip fractures among older adults are fall-related. Healthcare providers can prevent falls among their older patients by screening for fall risk, assessing modifiable risk factors, and offering evidence-based interventions.

Method comparison for Japanese encephalitis virus detection in samples collected from the Indo-Pacific region.

Introduction: Japanese encephalitis virus (JEV) is a mosquito-borne viral pathogen, which is becoming a growing public health concern throughout the Indo-Pacific. Five genotypes of JEV have been identified. Current vaccines are based on genotype III and provide a high degree of protection for four of the five known genotypes. Methods: RT-PCR, Magpix, Twist Biosciences Comprehensive Viral Research Panel (CVRP), and SISPA methods were used to detect JEV from mosquito samples collected in South Korea during 2021. These methods were compared to determine which method would be most effective for biosurveillance in the Indo-Pacific region. Results: Our data showed that RT-PCR, Twist CVRP, and SISPA methods were all able to detect JEV genotype I, however, the proprietary Magpix panel was only able to detect JEV genotype III. Use of minION sequencing for pathogen detection in arthropod samples will require further method development. Conclusion: Biosurveillance of vectorborne pathogens remains an area of concern throughout the Indo-Pacific. RT-PCR was the most cost effective method used in the study, but TWIST CVRP allows for the identification of over 3,100 viral genomes. Further research and comparisons will be conducted to ensure optimal methods are used for large scale biosurveillance.

Prevalence and Implications of Low Reticulocyte-Hemoglobin Levels among Extreme Preterm Neonates: A Single-Center Retrospective Study.

This retrospective cohort study aims to determine the epidemiology of iron deficiency among extreme preterm neonates and the association of iron-deficient status during the NICU stay with neurodevelopmental outcomes at 18−24 months. Neonates ≤29 weeks gestational age (GA) born between June 2016 and December 2019, who received routine iron supplementation were enrolled. Iron deficiency was defined as reticulocyte−hemoglobin (Ret-Hb) levels ≤ 29 pg at 36 weeks corrected age. A subcohort of neonates completed standardized developmental assessment at 18−24 months corrected age. Significant neurodevelopmental impairment (sNDI) was defined as either Bayley Scales of Infant Development score < 70 or cerebral palsy or blindness or hearing aided. Among a cohort of 215 neonates [GA 25.8 (1.7) weeks, birthweight 885 (232) g], prevalence of iron deficiency was 55%, 21%, 26%, and 13%, in neonates <24 weeks, 24−25 + 6 weeks, 26−27 + 6 weeks, and ≥ 28 weeks GA, respectively. Male sex and receipt of corticosteroid therapy were associated with iron-deficiency. In the subcohort analysis (n = 69), there was no statistically significant association between Ret-Hb levels at 36 weeks corrected age and the risk of sNDI [OR 0.99 (95% CI 0.85−1.2)]. Male infants and those who received postnatal corticosteroids are likely to have iron-limited erythropoiesis at corrected term despite routine iron-supplementation; however, low Ret-Hb levels during the neonatal period were not associated with significant neurological disability in early childhood.

Disparities in traumatic brain injury-related deaths-United States, 2020.

INTRODUCTION: Traumatic brain injury (TBI) affects how the brain functions and remains a prominent cause of death in the United States. Although preventable, anyone can experience a TBI and epidemiological research suggests some groups have worse health outcomes following the injury. METHODS: We analyzed 2020 multiple-cause-of-death data from the National Vital Statistics System to describe TBI mortality by geography, sociodemographic characteristics, mechanism of injury (MOI), and injury intent. Deaths were included if they listed an injury International Classification of Diseases, Tenth Revision (ICD-10) underlying cause of death code and a TBI-related ICD-10 code in one of the multiple-cause-of-death fields. RESULTS: During 2020, 64,362 TBI-related deaths occurred and age-adjusted rates, per 100,000 population, were highest among persons residing in the South (20.2). Older adults (≥75) displayed the highest number and rate of TBI-related deaths compared with other age groups and unintentional falls and suicide were the leading external causes among this older age group. The age-adjusted rate of TBI-related deaths in males was more than three times the rate of females (28.3 versus 8.4, respectively); further, males displayed higher numbers and age-adjusted rates compared with females for all the principal MOIs that contributed to a TBI-related death. American Indian or Alaska Native, Non-Hispanic (AI/AN) persons had the highest age-adjusted rate (29.0) of TBI-related deaths when compared with other racial and ethnic groups. Suicide was the leading external cause of injury contributing to a TBI-related death among AI/AN persons. PRACTICAL APPLICATION: Prevention efforts targeting older adult falls and suicide are warranted to reduce disparities in TBI mortality among older adults and AI/AN persons. Effective strategies are described in CDC's Stopping Elderly Accidents, Deaths, & Injuries (STEADI) initiative to reduce older adult falls and CDC's Preventing Suicide: A Technical Package of Policy, Programs, and Practices for the best available evidence in suicide prevention.