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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., (© 2023. The Author(s).)

Acute kidney injury is common in critical illness. In patients with severe acute kidney injury, renal replacement therapy is needed to prevent harm from metabolic and electrolyte disturbances and fluid overload. In the UK, continuous renal replacement therapy (CRRT) is the preferred modality, which requires anticoagulation. Over the last decade, conventional systemic heparin anticoagulation has started being replaced by regional citrate anticoagulation for CRRT, which is now used in approximately 50% of ICUs. This shift towards regional citrate anticoagulation for CRRT is occurring with little evidence of safety or longer term effectiveness. Renal replacement anticoagulant management (RRAM) is an observational comparative effectiveness study, utilising existing data sources to address the clinical and cost-effectiveness of the change to regional citrate anticoagulation for CRRT in UK ICUs. The study will use data from approximately 85,000 patients who were treated in adult, general ICUs participating in the case mix programme national clinical audit between 1 April 2009 and 31 March 2017. A survey of health service providers' anticoagulation practices will be combined with treatment and hospital outcome data from the case mix programme and linked with long-term outcomes from the Civil Registrations (deaths), Hospital Episodes Statistics for England, Patient Episodes Data for Wales, and the UK Renal Registry datasets. The primary clinical effectiveness outcome is all-cause mortality at 90-days. The study will incorporate an economic evaluation with micro-costing of both regional citrate anticoagulation and systemic heparin anticoagulation. Study registration: NCT03545750., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Intensive Care Society 2020.)

Vaccination policies have shifted dramatically during COVID-19 with the rapid emergence of population-wide vaccine mandates, domestic vaccine passports and differential restrictions based on vaccination status. While these policies have prompted ethical, scientific, practical, legal and political debate, there has been limited evaluation of their potential unintended consequences. Here, we outline a comprehensive set of hypotheses for why these policies may ultimately be counterproductive and harmful. Our framework considers four domains: (1) behavioural psychology, (2) politics and law, (3) socioeconomics, and (4) the integrity of science and public health. While current vaccines appear to have had a significant impact on decreasing COVID-19-related morbidity and mortality burdens, we argue that current mandatory vaccine policies are scientifically questionable and are likely to cause more societal harm than good. Restricting people's access to work, education, public transport and social life based on COVID-19 vaccination status impinges on human rights, promotes stigma and social polarisation, and adversely affects health and well-being. Current policies may lead to a widening of health and economic inequalities, detrimental long-term impacts on trust in government and scientific institutions, and reduce the uptake of future public health measures, including COVID-19 vaccines as well as routine immunisations. Mandating vaccination is one of the most powerful interventions in public health and should be used sparingly and carefully to uphold ethical norms and trust in institutions. We argue that current COVID-19 vaccine policies should be re-evaluated in light of the negative consequences that we outline. Leveraging empowering strategies based on trust and public consultation, and improving healthcare services and infrastructure, represent a more sustainable approach to optimising COVID-19 vaccination programmes and, more broadly, the health and well-being of the public., Competing Interests: Competing interests: Within the past 2 years, AdF was involved in Vaccine Confidence Project collaborative grants with Janssen Pharmaceutica outside of the submitted work and holds a Merck grant to investigate COVID-19 vaccine attitudes., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: This commentary explores the lessons learned during implementation of a peer-facilitated hepatitis C virus (HCV) testing and treatment access project called the Live Hep C Free (LHCF) project in contributing to micro-elimination efforts., Case Presentation: The LHCF project aims to facilitate access to on-the-spot HCV testing, treatment, and care in priority settings through partnership between a peer worker (PW) and a clinical nurse. Since the start of the project in January 2018, 4515 people were engaged about HCV and encouraged to access on-site HCV health care, and over 1000 people were screened for HCV and liver health, while almost 250 people accessed HCV treatment through the project. This commentary is intended to prompt discussion about incorporating peer-centred HCV health programs into priority sites. HCV care-delivery models such as the LHCF project can continue to contribute to micro-elimination of HCV in key settings to increase treatment uptake amongst high prevalence and/or marginalised populations and support progress toward national elimination targets., Conclusions: The LHCF project has been able to highlight the benefits of incorporating trustworthy, efficient, and convenient peer-centred health services to engage and support vulnerable populations through HCV testing and treatment, particularly individuals who have historically been disconnected from the health care system. Additional attention is needed to ensure ongoing funding support to sustain the project and deliver at scale and in expanding evaluation data to examine the operation and outcomes of the project in more detail., (© 2022. The Author(s).)

Background: New-onset atrial fibrillation (NOAF) is common in patients on an intensive care unit (ICU). Evidence guiding treatments is limited, though recent reports suggest beta blocker (BB) therapy is associated with reduced mortality., Methods: We conducted a multicentre cohort study of adult patients admitted to 3 ICUs in the UK and 5 ICUs in the USA. We analysed the haemodynamic changes associated with NOAF. We analysed rate control, rhythm control, and hospital mortality associated with common NOAF treatments. We balanced admission and post-NOAF, pre-treatment covariates across treatment groups., Results: NOAF was followed by a systolic blood pressure reduction of 5 mmHg (p < 0.001). After adjustment, digoxin therapy was associated with inferior rate control versus amiodarone (adjusted hazard ratio (aHR) 0.56, [95% CI 0.34-0.92]). Calcium channel blocker (CCB) therapy was associated with inferior rhythm control versus amiodarone (aHR 0.59 (0.37-0.92). No difference was detected between BBs and amiodarone in rate control (aHR 1.15 [0.91-1.46]), rhythm control (aHR 0.85, [0.69-1.05]), or hospital mortality (aHR 1.03 [0.53-2.03])., Conclusions: NOAF in ICU patients is followed by decreases in blood pressure. BBs and amiodarone are associated with similar cardiovascular control and appear superior to digoxin and CCBs. Accounting for key confounders removes previously reported mortality benefits associated with BB treatment., Competing Interests: Declaration of Competing Interest PW worked part time for Sensyne Health and has received grant funding from National Institute for Health Research, and Sensyne Health outside the submitted work. PW was a member of the HTA EESC Methods Group 2014–2017, HTA EESC Panel 2013–2018, HTA Prioritisation Committee B (In hospital) 2018–2019 and NIHR i4i PDA A Committee 2018-. KR was a member of the DHSC/UKRI COVID-19 Rapid Response Research Initiative Member, College of Experts 2020, HS&DR Funding Committee Member 2014–2019, HS&DR Rapid Service Evaluation Themed Call Committee Member 2017, HS&DR Commissioned - Board Member 2016, and HTA Trauma Themed Call Board Member 2007–2008. DY received a salary from the University of Oxford during the duration of the work., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In the UK, 10% of admissions to intensive care units receive continuous renal replacement therapy with regional citrate anticoagulation replacing systemic heparin anticoagulation over the last decade. Regional citrate anticoagulation is now used in > 50% of intensive care units, despite little evidence of safety or effectiveness., Aim: The aim of the Renal Replacement Anticoagulant Management study was to evaluate the clinical and health economic impacts of intensive care units moving from systemic heparin anticoagulation to regional citrate anticoagulation for continuous renal replacement therapy., Design: This was an observational comparative effectiveness study., Setting: The setting was NHS adult general intensive care units in England and Wales., Participants: Participants were adults receiving continuous renal replacement therapy in an intensive care unit participating in the Intensive Care National Audit & Research Centre Case Mix Programme national clinical audit between 1 April 2009 and 31 March 2017., Interventions: Exposure - continuous renal replacement therapy in an intensive care unit after completion of transition to regional citrate anticoagulation. Comparator - continuous renal replacement therapy in an intensive care unit before starting transition to regional citrate anticoagulation or had not transitioned., Outcome Measures: Primary effectiveness - all-cause mortality at 90 days. Primary economic - incremental net monetary benefit at 1 year. Secondary outcomes - mortality at hospital discharge, 30 days and 1 year; days of renal, cardiovascular and advanced respiratory support in intensive care unit; length of stay in intensive care unit and hospital; bleeding and thromboembolic events; prevalence of end-stage renal disease at 1 year; and estimated lifetime incremental net monetary benefit., Data Sources: Individual patient data from the Intensive Care National Audit & Research Centre Case Mix Programme were linked with the UK Renal Registry, Hospital Episode Statistics (for England), Patient Episodes Data for Wales and Civil Registrations (Deaths) data sets, and combined with identified periods of systemic heparin anticoagulation and regional citrate anticoagulation (survey of intensive care units). Staff time and consumables were obtained from micro-costing. Continuous renal replacement therapy system failures were estimated from the Post-Intensive Care Risk-adjusted Alerting and Monitoring data set. EuroQol-3 Dimensions, three-level version, health-related quality of life was obtained from the Intensive Care Outcomes Network study., Results: Out of the 188 (94.9%) units that responded to the survey, 182 (96.8%) use continuous renal replacement therapy. After linkage, data were available from 69,001 patients across 181 intensive care units (60,416 during periods of systemic heparin anticoagulation use and 8585 during regional citrate anticoagulation use). The change to regional citrate anticoagulation was not associated with a step change in 90-day mortality (odds ratio 0.98, 95% confidence interval 0.89 to 1.08). Secondary outcomes showed step increases in days of renal support (difference in means 0.53 days, 95% confidence interval 0.28 to 0.79 days), advanced cardiovascular support (difference in means 0.23 days, 95% confidence interval 0.09 to 0.38 days) and advanced respiratory support (difference in means, 0.53 days, 95% CI 0.03 to 1.03 days) with a trend toward fewer bleeding episodes (odds ratio 0.90, 95% confidence interval 0.76 to 1.06) with transition to regional citrate anticoagulation. The micro-costing study indicated that regional citrate anticoagulation was more expensive and was associated with an estimated incremental net monetary loss (step change) of -£2376 (95% confidence interval -£3841 to -£911). The estimated likelihood of cost-effectiveness at 1 year was less than 0.1%., Limitations: Lack of patient-level treatment data means that the results represent average effects of changing to regional citrate anticoagulation in intensive care units. Administrative data are subject to variation in data quality over time, which may contribute to observed trends., Conclusions: The introduction of regional citrate anticoagulation has not improved outcomes for patients and is likely to have substantially increased costs. This study demonstrates the feasibility of evaluating effects of changes in practice using routinely collected data., Future Work: (1) Prioritise other changes in clinical practice for evaluation and (2) methodological research to understand potential implications of trends in data quality., Trial Registration: This trial is registered as ClinicalTrials.gov NCT03545750., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 26, No. 13. See the NIHR Journals Library website for further project information.

Emerging reports of rare neurological complications associated with COVID-19 infection and vaccinations are leading to regulatory, clinical and public health concerns. We undertook a self-controlled case series study to investigate hospital admissions from neurological complications in the 28 days after a first dose of ChAdOx1nCoV-19 (n = 20,417,752) or BNT162b2 (n = 12,134,782), and after a SARS-CoV-2-positive test (n = 2,005,280). There was an increased risk of Guillain-Barré syndrome (incidence rate ratio (IRR), 2.90; 95% confidence interval (CI): 2.15-3.92 at 15-21 days after vaccination) and Bell's palsy (IRR, 1.29; 95% CI: 1.08-1.56 at 15-21 days) with ChAdOx1nCoV-19. There was an increased risk of hemorrhagic stroke (IRR, 1.38; 95% CI: 1.12-1.71 at 15-21 days) with BNT162b2. An independent Scottish cohort provided further support for the association between ChAdOx1nCoV and Guillain-Barré syndrome (IRR, 2.32; 95% CI: 1.08-5.02 at 1-28 days). There was a substantially higher risk of all neurological outcomes in the 28 days after a positive SARS-CoV-2 test including Guillain-Barré syndrome (IRR, 5.25; 95% CI: 3.00-9.18). Overall, we estimated 38 excess cases of Guillain-Barré syndrome per 10 million people receiving ChAdOx1nCoV-19 and 145 excess cases per 10 million people after a positive SARS-CoV-2 test. In summary, although we find an increased risk of neurological complications in those who received COVID-19 vaccines, the risk of these complications is greater following a positive SARS-CoV-2 test., (© 2021. The Author(s).)

Background: Early in a pandemic, outcomes are biased towards patients with shorter durations of critical illness. We describe 60-day outcomes for patients critically ill with confirmed COVID-19 and explore the potential bias in the weekly reported data by ICNARC., Methods: First 200 consecutive patients with confirmed COVID-19, admitted for critical care in England, Wales and Northern Ireland, followed-up for a minimum of 60 days from admission. Outcomes included survival and duration of critical care, receipt/duration of organ support in critical care and hospital survival ., Results: Mean age was 62.6 years, 70.5% were male, 52.0% were white, 39.2% obese and 9.0% had serious comorbidities. Median APACHE II score was 16 (IQR 12, 19). After 60 days, 83 (41.5%) patients had been discharged from hospital, 15 (7.5%) had been discharged from critical care but remained in hospital, 1 (0.5%) was still receiving critical care, 90 (45.0%) had died while receiving critical care and 11 (5.5%) had died in hospital after discharge from critical care. Median duration of critical care was 14.0 days (IQR 6.1, 23.0) for survivors and 10.0 days (IQR 5.0, 16.0) for non-survivors of critical care. Overall, 158 (79.0%) patients received advanced respiratory support for a median of 13 (IQR 8, 20) calendar days. Compared with weekly reports during the pandemic, critical care mortality started higher than but then decreased below that of the first 200 consecutive patients. Duration of critical care, for both survivors and non-survivors increased over time; however, both were still lower than those for the first 200 consecutive patients. Receipt and duration of organ support increased to values similar to those for the first 200 consecutive patients., Conclusion: COVID-19 in critical care has high mortality and places a large burden on resources. Analysis of preliminary data with limited follow-up should be interpreted with caution, particularly for future planning in a pandemic., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Intensive Care Society 2020.)

Background: New-onset atrial fibrillation occurs in around 10% of adults treated in an intensive care unit. New-onset atrial fibrillation may lead to cardiovascular instability and thromboembolism, and has been independently associated with increased length of hospital stay and mortality. The long-term consequences are unclear. Current practice guidance is based on patients outside the intensive care unit; however, new-onset atrial fibrillation that develops while in an intensive care unit differs in its causes and the risks and clinical effectiveness of treatments. The lack of evidence on new-onset atrial fibrillation treatment or long-term outcomes in intensive care units means that practice varies. Identifying optimal treatment strategies and defining long-term outcomes are critical to improving care., Objectives: In patients treated in an intensive care unit, the objectives were to (1) evaluate existing evidence for the clinical effectiveness and safety of pharmacological and non-pharmacological new-onset atrial fibrillation treatments, (2) compare the use and clinical effectiveness of pharmacological and non-pharmacological new-onset atrial fibrillation treatments, and (3) determine outcomes associated with new-onset atrial fibrillation., Methods: We undertook a scoping review that included studies of interventions for treatment or prevention of new-onset atrial fibrillation involving adults in general intensive care units. To investigate the long-term outcomes associated with new-onset atrial fibrillation, we carried out a retrospective cohort study using English national intensive care audit data linked to national hospital episode and outcome data. To analyse the clinical effectiveness of different new-onset atrial fibrillation treatments, we undertook a retrospective cohort study of two large intensive care unit databases in the USA and the UK., Results: Existing evidence was generally of low quality, with limited data suggesting that beta-blockers might be more effective than amiodarone for converting new-onset atrial fibrillation to sinus rhythm and for reducing mortality. Using linked audit data, we showed that patients developing new-onset atrial fibrillation have more comorbidities than those who do not. After controlling for these differences, patients with new-onset atrial fibrillation had substantially higher mortality in hospital and during the first 90 days after discharge (adjusted odds ratio 2.32, 95% confidence interval 2.16 to 2.48; adjusted hazard ratio 1.46, 95% confidence interval 1.26 to 1.70, respectively), and higher rates of subsequent hospitalisation with atrial fibrillation, stroke and heart failure (adjusted cause-specific hazard ratio 5.86, 95% confidence interval 5.33 to 6.44; adjusted cause-specific hazard ratio 1.47, 95% confidence interval 1.12 to 1.93; and adjusted cause-specific hazard ratio 1.28, 95% confidence interval 1.14 to 1.44, respectively), than patients who did not have new-onset atrial fibrillation. From intensive care unit data, we found that new-onset atrial fibrillation occurred in 952 out of 8367 (11.4%) UK and 1065 out of 18,559 (5.7%) US intensive care unit patients in our study. The median time to onset of new-onset atrial fibrillation in patients who received treatment was 40 hours, with a median duration of 14.4 hours. The clinical characteristics of patients developing new-onset atrial fibrillation were similar in both databases. New-onset atrial fibrillation was associated with significant average reductions in systolic blood pressure of 5 mmHg, despite significant increases in vasoactive medication (vasoactive-inotropic score increase of 2.3; p  < 0.001). After adjustment, intravenous beta-blockers were not more effective than amiodarone in achieving rate control (adjusted hazard ratio 1.14, 95% confidence interval 0.91 to 1.44) or rhythm control (adjusted hazard ratio 0.86, 95% confidence interval 0.67 to 1.11). Digoxin therapy was associated with a lower probability of achieving rate control (adjusted hazard ratio 0.52, 95% confidence interval 0.32 to 0.86) and calcium channel blocker therapy was associated with a lower probability of achieving rhythm control (adjusted hazard ratio 0.56, 95% confidence interval 0.39 to 0.79) than amiodarone. Findings were consistent across both the combined and the individual database analyses., Conclusions: Existing evidence for new-onset atrial fibrillation management in intensive care unit patients is limited. New-onset atrial fibrillation in these patients is common and is associated with significant short- and long-term complications. Beta-blockers and amiodarone appear to be similarly effective in achieving cardiovascular control, but digoxin and calcium channel blockers appear to be inferior., Future Work: Our findings suggest that a randomised controlled trial of amiodarone and beta-blockers for management of new-onset atrial fibrillation in critically ill patients should be undertaken. Studies should also be undertaken to provide evidence for or against anticoagulation for patients who develop new-onset atrial fibrillation in intensive care units. Finally, given that readmission with heart failure and thromboembolism increases following an episode of new-onset atrial fibrillation while in an intensive care unit, a prospective cohort study to demonstrate the incidence of atrial fibrillation and/or left ventricular dysfunction at hospital discharge and at 3 months following the development of new-onset atrial fibrillation should be undertaken., Trial Registration: Current Controlled Trials ISRCTN13252515., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 25, No. 71. See the NIHR Journals Library website for further project information.

Background: We can improve healthcare services by better understanding current provision. One way to understand this is by linking data sets from clinical and national audits, national registries and other National Health Service (NHS) encounter data. However, getting to the point of having linked national data sets is challenging., Objective: We describe our experience of the data application and linkage process for our study 'LAUNCHES QI', and the time, processes and resource requirements involved. To help others planning similar projects, we highlight challenges encountered and advice for applications in the current system as well as suggestions for system improvements., Findings: The study set up for LAUNCHES QI began in March 2018, and the process through to data acquisition took 2.5 years. Several challenges were encountered, including the amount of information required (often duplicate information in different formats across applications), lack of clarity on processes, resource constraints that limit an audit's capacity to fulfil requests and the unexpected amount of time required from the study team. It is incredibly difficult to estimate the resources needed ahead of time, and yet necessary to do so as early on as funding applications. Early decisions can have a significant impact during latter stages and be hard to change, yet it is difficult to get specific information at the beginning of the process., Conclusions: The current system is incredibly complex, arduous and slow, stifling innovation and delaying scientific progress. NHS data can inform and improve health services and we believe there is an ethical responsibility to use it to do so. Streamlining the number of applications required for accessing data for health services research and providing clarity to data controllers could facilitate the maintenance of stringent governance, while accelerating scientific studies and progress, leading to swifter application of findings and improvements in healthcare., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: New-onset atrial fibrillation (NOAF) in patients treated on an intensive care unit (ICU) is common and associated with significant morbidity and mortality. We undertook a systematic scoping review to summarise comparative evidence to inform NOAF management for patients admitted to ICU., Methods: We searched MEDLINE, EMBASE, CINAHL, Web of Science, OpenGrey, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, ISRCTN, ClinicalTrials.gov, EU Clinical Trials register, additional WHO ICTRP trial databases, and NIHR Clinical Trials Gateway in March 2019. We included studies evaluating treatment or prevention strategies for NOAF or acute anticoagulation in general medical, surgical or mixed adult ICUs. We extracted study details, population characteristics, intervention and comparator(s), methods addressing confounding, results, and recommendations for future research onto study-specific forms., Results: Of 3,651 citations, 42 articles were eligible: 25 primary studies, 12 review articles and 5 surveys/opinion papers. Definitions of NOAF varied between NOAF lasting 30 s to NOAF lasting > 24 h. Only one comparative study investigated effects of anticoagulation. Evidence from small RCTs suggests calcium channel blockers (CCBs) result in slower rhythm control than beta blockers (1 study), and more cardiovascular instability than amiodarone (1 study). Evidence from 4 non-randomised studies suggests beta blocker and amiodarone therapy may be equivalent in respect to rhythm control. Beta blockers may be associated with improved survival compared to amiodarone, CCBs, and digoxin, though supporting evidence is subject to confounding. Currently, the limited evidence does not support therapeutic anticoagulation during ICU admission., Conclusions: From the limited evidence available beta blockers or amiodarone may be superior to CCBs as first line therapy in undifferentiated patients in ICU. The little evidence available does not support therapeutic anticoagulation for NOAF whilst patients are critically ill. Consensus definitions for NOAF, rate and rhythm control are needed., (© 2021. The Author(s).)

Importance: Child maltreatment is a prominent public health concern affecting 20% to 50% of children worldwide. Consequences for mental and physical health have been reported, but population-level estimates of risk of death during childhood that are adjusted for confounders have not been published to date., Objective: To estimate the association of documented child protection concerns regarding maltreatment with risk of death from infancy to 16 years of age., Design, Setting, and Participants: This case-control study was nested in a population birth cohort of 608 547 persons born in South Australia, Australia. Case children were those who died between 1 month and 16 years of age (with the death registered by May 31, 2019). Control children were randomly selected individuals from the same population who were alive at the age at which the case child died, matched 5:1 for age, sex, and Aboriginal status. Data were analyzed from January 2019 to March 2021., Exposure: Children were assigned to 1 of 4 child protection concern categories (child protection system notification[s] only, investigation[s] [not substantiated], substantiated maltreatment, and ever placed in out-of-home care) based on administrative data from the South Australia Department for Child Protection or were classified as unexposed., Main Outcomes and Measures: Mortality rate ratios for death before 16 years of age, by child protection concern category, were estimated using conditional logistic regression, adjusted for birth outcomes, maternal attributes, and area-based socioeconomic status. Patterns of cause of death were compared for children with vs without child protection concerns., Results: Of 606 665 children included in the study, 1635 were case children (57.9% male [when sex was known]; mean [SD] age, 3.59 [4.56] years) and 8175 were control children (57.7% male; mean [SD] age, 3.59 [4.56] years [age censored at the time of death of the matched control child]). Compared with children with no child protection system contact, adjusted mortality rate ratios among children who died before 16 years of age were 2.69 (95% CI, 2.05-3.54) for children with child protection system notification(s) only; 3.16 (95% CI, 2.25-4.43) for children with investigation(s) (not substantiated); 2.93 (95% CI, 1.95-4.40) with substantiated maltreatment; and 3.79 (95% CI, 2.46-5.85) for children ever placed in out-of-home care. External causes represented 136 of 314 deaths (43.3%) among children with a documented child protection concern and 288 of 1306 deaths (22.1%) among other children. Deaths from assault or self-harm were most overrepresented, accounting for 11.1% of deaths in children with child protection concerns but just 0.8% of deaths among other children., Conclusions and Relevance: In this case-control study, children with documented child protection concerns, who were known to child protection agencies and were typically seen by clinicians and other service providers, had a higher risk of death compared with children with no child protection service contact. These findings suggest the need for a more comprehensive service response for children with protection concerns.

Background: Child maltreatment (CM) is a global public health issue, with reported impacts on health and social outcomes. Evidence on mortality is lacking. In this study, we aimed to estimate the impact of CM on death rates in persons 16 to 33 years., Methods: A retrospective cohort study of all persons born in South Australia 1986 to 2003 using linked administrative data. CM exposure was based on child protection service (CPS) contact: unexposed, no CPS contact before 16 years, and 7 exposed groups. Deaths were observed until May 31, 2019 and plotted from 16 years. Adjusted hazard ratios (aHRs) by CPS category were estimated using Cox proportional hazards models, adjusting for child and maternal characteristics. Incident rate ratios (IRRs) were derived for major causes of death, with and without CPS contact., Results: The cohort included 331 254 persons, 20% with CPS contact. Persons with a child protection matter notification and nonsubstantiated or substantiated investigation had more than twice the death rate compared with persons with no CPS contact: aHR = 2.09 (95% confidence interval [CI] = 1.62-2.70) to aHR = 2.61 (95% CI = 1.99-3.43). Relative to no CPS contact, persons ever placed in out-of-home care had the highest mortality if first placed in care aged ≥3 years (aHR = 4.67 [95% CI = 3.52-6.20]); aHR was 1.75(95% CI = 0.98-3.14) if first placed in care aged <3 years. The largest differential cause-specific mortality (any contact versus no CPS contact) was death from poisonings, alcohol, and/or other substances (IRR = 4.82 [95% CI = 3.31-7.01]) and from suicide (IRR = 2.82 [95% CI = 2.15-3.68])., Conclusions: CM is a major underlying cause of potentially avoidable deaths in early adulthood. Clinical and family-based support for children and families in which CM is occurring must be a priority to protect children from imminent risk of harm and early death as young adults., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Objectives: To identify characteristics that predict 30-day mortality among patients critically ill with coronavirus disease 2019 in England, Wales, and Northern Ireland., Design: Observational cohort study., Setting: A total of 258 adult critical care units., Patients: A total of 10,362 patients with confirmed coronavirus disease 2019 with a start of critical care between March 1, 2020, and June 22, 2020, of whom 9,990 were eligible (excluding patients with a duration of critical care less than 24 hr or missing core variables)., Measurements and Main Results: The main outcome measure was time to death within 30 days of the start of critical care. Of 9,990 eligible patients (median age 60 yr, 70% male), 3,933 died within 30 days of the start of critical care. As of July 22, 2020, 189 patients were still receiving critical care and a further 446 were still in acute hospital. Data were missing for between 0.1% and 7.2% of patients across prognostic factors. We imputed missing data ten-fold, using fully conditional specification and continuous variables were modeled using restricted cubic splines. Associations between the candidate prognostic factors and time to death within 30 days of the start of critical care were determined after adjustment for multiple variables with Cox proportional hazards modeling. Significant associations were identified for age, ethnicity, deprivation, body mass index, prior dependency, immunocompromise, lowest systolic blood pressure, highest heart rate, highest respiratory rate, Pao2/Fio2 ratio (and interaction with mechanical ventilation), highest blood lactate concentration, highest serum urea, and lowest platelet count over the first 24 hours of critical care. Nonsignificant associations were found for sex, sedation, highest temperature, and lowest hemoglobin concentration., Conclusions: We identified patient characteristics that predict an increased likelihood of death within 30 days of the start of critical care for patients with coronavirus disease 2019. These findings may support development of a prediction model for benchmarking critical care providers., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2020 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Introduction: Disease registers and electronic health records are valuable resources for disease surveillance and research but can be limited by variation in data quality over time. Quality may be limited in terms of the accuracy of clinical information, of the internal linkage that supports person-based analysis of most administrative datasets, or by errors in linkage between multiple datasets., Objectives: By linking the National Down Syndrome Cytogenetic Register (NDSCR) to Hospital Episode Statistics for England (HES), we aimed to assess the quality of each and establish a consistent approach for analysis of trends in prevalence of Down's syndrome among live births in England., Methods: Probabilistic record linkage of NDSCR to HES for the period 1998-2013 was supported by linkage of babies to mothers within HES. Comparison of prevalence estimates in England were made using NDSCR only, HES data only, and linked data. Capture-recapture analysis and quantitative bias analysis were used to account for potential errors, including false positive diagnostic codes, unrecorded diagnoses, and linkage error., Results: Analyses of single-source data indicated increasing live birth prevalence of Down's Syndrome, particularly in the analysis of HES. Linked data indicated a contrastingly stable prevalence of 12.3 (plausible range: 11.6-12.7) cases per 10 000 live births., Conclusion: Case ascertainment in NDSCR improved slightly over time, creating a picture of slowly increasing prevalence. The emerging epidemic suggested by HES primarily reflects improving linkage within HES (assignment of unique patient identifiers to hospital episodes). Administrative data are valuable but trends should be interpreted with caution, and with assessment of data quality over time. Data linkage with quantitative bias analysis can provide more robust estimation and, in this case, stronger evidence that prevalence is not increasing. Routine linkage of administrative and register data can enhance the value of each., Competing Interests: Conflict of interest statement JM was Director of the National Downs Syndrome Cytogenetic Register at Queen Mary University of London until its integration into the National Congenital Anomaly and Rare Disease Registration Service at Public Health England in 2014. SS was the Registry Lead for the National Congenital Anomaly and Rare Disease Registration Service at the time of writing.

Myofascial trigger points are not an isolated neuromusculoskeletal phenomenon and have been implicated in systemic, visceral, and metabolic pathology, as a side effect of some medications and in the presence of psychological risk factors. This complexity can complicate adequate screening of patients prior to choosing dry needling as a treatment intervention. Regardless of whether clinicians practice in a direct access setting, they should be cognizant of medical conditions, comorbidities, and risk factors that will influence clinical decisions for dry-needling appropriateness, technique chosen, and potential adverse responses to treatment. Of primary concern are conditions that can either manifest with myalgia and/or myopathy or masquerade as a more common musculoskeletal condition. This clinical commentary reviews system-specific considerations and other common disorders that should be screened for and discusses not only whether dry needling is appropriate but comments on technique and dosage considerations when initiating dry needling.

Introduction: Analysis of linked health data can generate important, even life-saving, insights into population health. Yet obstacles both legal and organisational in nature can impede this work., Approach: We focus on three UK infrastructures set up to link and share data for research: the Administrative Data Research Network, NHS Digital, and the Secure Anonymised Information Linkage Databank. Bringing an interdisciplinary perspective, we identify key issues underpinning their challenges and successes in linking health data for research., Results: We identify examples of uncertainty surrounding legal powers to share and link data, and around data protection obligations, as well as systemic delays and historic public backlash. These issues require updated official guidance on the relevant law, approaches to linkage which are planned for impact and ongoing utility, greater transparency between data providers and researchers, and engagement with the patient population which is both high-profile and carefully considered., Conclusions: Health data linkage for research presents varied challenges, to which there can be no single solution. Our recommendations would require action from a number of data providers and regulators to be meaningfully advanced. This illustrates the scale and complexity of the challenge of health data linkage, in the UK and beyond: a challenge which our case studies suggest no single organisation can combat alone. Planned programmes of linkage are critical because they allow time for organisations to address these challenges without adversely affecting the feasibility of individual research projects., Competing Interests: Statement on conflicts of interest: The authors declare they have no conflict of interest.

Many of the distinctions made between probabilistic and deterministic linkage are misleading. While these two approaches to record linkage operate in different ways and can produce different outputs, the distinctions between them are more a result of how they are implemented than because of any intrinsic differences. In the way they are generally applied, probabilistic and deterministic procedures can be little more than alternative means to similar ends-or they can arrive at very different ends depending on choices that are made during implementation. Misconceptions about probabilistic linkage contribute to reluctance for implementing it and mistrust of its outputs. We aim to explain how the outputs of either approach can be tailored to suit the intended application, but also to highlight the ways in which probabilistic linkage is generally more flexible, more powerful and more informed by the data. This is accomplished by examining common misconceptions about probabilistic linkage and its difference from deterministic linkage, highlighting the potential impact of design choices on the outputs of either approach. We hope that better understanding of linkage designs will help to allay concerns about probabilistic linkage, and help data linkers to select and tailor procedures to produce outputs that are appropriate for their intended use.

In antral mucosa of the mouse stomach, the volume of mucus in mucous cells was measured morphometrically to determine whether this value changes during cell migration from the base of the pit to the surface. Both the volume density of mucous granules (the fraction of cell volume occupied by the granules) and the volume of intracellular mucus were reduced to about half in surface cells compared with those of upper pit cells. This indicates that mucus secretion is substantial during the later part of the lifespan of these cells, and is not due simply to the shedding of senescent cells.

A study of the actions of adrenergic and non-adrenergic nerves which affect mammalian airways was carried out. The preparations studied included strips of lung from guinea-pig, rat, rabbit, monkey and human, tracheal strips from the first 4 animals and bronchial strips from the last 3. Relaxations to field stimulation of sympathetic nerves were found in the guinea-pig trachea only. Functional nonadrenergic inhibitory nerves were found in the larger airways of all species except rat. Lung strips from all the mammals failed to respond to sympathetic or nonadrenergic inhibitory nerve stimulation suggesting a lack of functional inhibitory nerves of either type in the fine airways. Studies on the distribution of adrenergic nerves showed that primary target of the nerves in all species appeared to be the vasculature, especially in lung. Occasional fibres were seen entering the smooth muscle of the fine airways in guinea-pig, rabbit, and rat, but not in monkey or human lung or in monkey trachea or bronchus or human bronchus. Guinea-pig and rabbit trachealis muscles received a significant innervation but only the guinea-pig tissue responded to sympathetic stimulation. Inhibitory beta-adrenoceptors were demonstrated in the proximal airways of all species except rabbit. The fine airways of rat, monkey and human contained a mixed population of alpha-excitatory and beta-inhibitory adrenoceptors only were found in guinea-pig lung and alpha-adrenoceptors only in rabbit lung.

Do comprehensive community mental health services reduce admissions to state hospital? A recent Nader report says no. Surprisingly few studies have documented the success of comprehensive community mental health programs. Wyoming had four unique characteristics that aided in evaluating the impact of centers on hospital admissions. The results of this study indicated that community-based comprehensive mental health services do, in fact, reduce psychiatric hospitalization.