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Objective: To compare the prevalence and clinical characteristics of early gestational diabetes (eGDM) and associated birth outcomes amongst women of different ethnic groups., Research Design and Methods: This is a secondary analysis of an international, multicentre randomized controlled trial of treating eGDM among pregnant women with GDM risk factors enrolled <20 weeks' gestation. The diagnosis of GDM was made using WHO-2013 criteria. While Europids required at least one risk factor for recruitment, for others, ethnicity itself was a risk factor., Results: Among women of Europid (n=1,567), South Asian (SA: n=971), East and South-East Asian (ESEA: n=498), Middle Eastern (ME: n=242) and Māori and Pasifika (MP: n=174) ethnicities; MP (26.4%) had the highest eGDM crude prevalence compared with Europid (20.3%), SA (24.7%), ESEA (22.3%) and ME (21.1%) (p<0.001). Compared with Europid, the highest eGDM adjusted odds ratio (aOR) was seen in SA (2.43 [95%CI 1.9-3.11]) and ESEA (aOR 2.28 [95%CI 1.68-3.08]); in late GDM, SA had the highest prevalence (20.4%: aOR 2.16 [95%CI 1.61-2.9]). Glucose patterns varied between ethnic groups and ESEA were predominantly diagnosed with eGDM through post-glucose load values, while all other ethnic groups were mainly diagnosed on fasting glucose values. There were no differences in the eGDM composite primary outcome or neonatal and pregnancy-related hypertension outcomes between the ethnic groups., Conclusions: In women with risk factors, eGDM was most prevalent in SA and ESEA women, particularly identified by the post-glucose load samples. These findings suggest an early OGTT should particularly be performed in women from these ethnic groups., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Peer support is a promising intervention to mitigate post-ICU disability, however there is a paucity of rigorously designed studies., Objectives: The objective of this study was to establish feasibility of an in-person, co-designed, peer-support model., Methods: Prospective, randomised, adaptive, single-centre pilot trial with blinded outcome assessment, conducted at a university-affiliated hospital in Melbourne, Australia. Intensive care unit survivors (and their nominated caregiver, where survivor and caregiver are referred to as a dyad), >18 years of age, able to speak and understand English and participate in phone surveys, were eligible. Participants were randomised to the peer-support model (six sessions, fortnightly) or usual care (no follow-up or targeted information). Two sequential models were piloted: 1. Early (2-3 weeks post hospital discharge) 2. Later (4-6 weeks post hospital discharge). Primary outcome was feasibility of implementation measured by recruitment, intervention attendance, and outcome completion. Secondary outcomes included post-traumatic stress and social support., Results: Of the 231 eligible patients, 80 participants were recruited. In the early model we recruited 38 participants (28 patients, 10 carers; 18 singles, 10 dyads), with an average (standard deviation) age of 60 (18) years; 55 % were female. Twenty-two participants (58 %) were randomised to intervention. Participants in the early intervention model attended a median (interquartile range) of 0 (0-1) sessions (total 24 sessions), with 53% (n = 20) completing the main secondary outcome of interest (Impact of Event Scale) at the baseline and 37 % (n = 14) at the follow-up. For the later model we recruited 42 participants (32 patients, 10 carers; 22 singles, 10 dyads), with an average (standard deviation) age of 60.4 (15.4) years; 50 % were female. Twenty-one participants (50 %) were randomised to intervention. The later intervention model attended a median (interquartile range) of 1 (0-5) sessions (total: 44 sessions), with the main secondary outcome impact of events scale (IES-R) completed by 41 (98 %) participants at baseline and 29 (69 %) at follow-up., Conclusions: In this pilot trial, a peer-support model that required in-person attendance delivered in a later posthospital phase of recovery appeared more feasible than an early model. Further research should investigate alternative modes of intervention delivery to improve feasibility (ACTRN12621000737831)., Competing Interests: Conflict of interest K Haines received a SCCM Thrive Award from SCCM to undertake this study. No conflicts of interest were declared by other authors., (Copyright © 2024 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Postpartum depression (PPD) constitutes a significant mental health disorder affecting almost one fifth of pregnancies globally. Despite extensive research, the precise etiological mechanisms underlying PPD remain elusive. However, several risk factors like genetic predisposition, hormonal fluctuations, and stress-related environmental and psychosocial triggers have been found to be implicated in its development. MAIN: Recently, an increased risk of PPD has been reported to be associated with gestational diabetes mellitus (GDM), which is characterized by the disruption of glucose metabolism, primarily attributed to the emergence of insulin resistance (IR). While IR during pregnancy seems to be an evolutionary adaptative mechanism to handle the profound metabolic alterations during pregnancy, its subsequent resolution following delivery necessitates a reconfiguration of the metabolic landscape in both peripheral tissues and the central nervous system (CNS). Considering the pivotal roles of energy metabolism, particularly glucose metabolism, in CNS functions, we propose a novel model that such pronounced changes in IR and the associated glucose metabolism seen postpartum might account for PPD development. This concept is based on the profound influences from insulin and glucose metabolism on brain functions, potentially via modulating neurotransmitter actions of dopamine and serotonin. Their sudden postpartum disruption is likely to be linked to mood changes, as observed in PPD., Conclusions: The detailed pathogenesis of PPD might be multifactorial and still remains to be fully elucidated. Nevertheless, our hypothesis might account in part for an additional etiological factor to PPD development. If our concept is validated, it can provide guidance for future PPD prevention, diagnosis, and intervention., (© 2024. The Author(s).)

Background: A recently undertaken multicenter randomized controlled trial (RCT) " Treatment Of BOoking Gestational diabetes Mellitus" (TOBOGM: 2017-2022) found that the diagnosis and treatment of pregnant women with early gestational diabetes mellitus (GDM) improved pregnancy outcomes. Based on data from the trial, this study aimed to assess the cost-effectiveness of diagnosis and treatment of early GDM (from <20 weeks') among women with risk factors for hyperglycemia in pregnancy compared with usual care (no treatment until 24-28 weeks') from a healthcare perspective., Methods: Participants' healthcare resource utilization data were collected from their self-reported questionnaires and hospital records, and valued using the unit costs obtained from standard Australian national sources. Costs were reported in US dollars ($) using the purchasing power parity (PPP) estimates to facilitate comparison of costs across countries. Intention-to-treat (ITT) principle was followed. Missing cost data were replaced using multiple imputations. Bootstrapping method was used to estimate the uncertainty around mean cost difference and cost-effectiveness results. Bootstrapped cost-effect pairs were used to plot the cost-effectiveness (CE) plane and cost-effectiveness acceptability curve (CEAC)., Findings: Diagnosis and treatment of early GDM was more effective and tended to be less costly, i.e., dominant (cost-saving) [-5.6% composite adverse pregnancy outcome (95% CI: -10.1%, -1.2%), -$1373 (95% CI: -$3,749, $642)] compared with usual care. Our findings were confirmed by both the CE plane (88% of the bootstrapped cost-effect pairs fall in the south-west quadrant), and CEAC (the probability of the intervention being cost-effective ranged from 84% at a willingness-to-pay (WTP) threshold value of $10,000-99% at a WTP threshold value of $100,000 per composite adverse pregnancy outcome prevented). Sub-group analyses demonstrated that diagnosis and treatment of early GDM among women in the higher glycemic range (fasting blood glucose 95-109 mg/dl [5.3-6.0 mmol/L], 1-h blood glucose ≥191 mg/dl [10.6 mmol/L] and/or 2-h blood glucose 162-199 mg/dl [9.0-11.0 mmol/L]) was more effective and less costly (dominant) [ - 7.8% composite adverse pregnancy outcome (95% CI: -14.6%, -0.9%), -$2795 (95% CI: -$6,638, -$533)]; the intervention was more effective and tended to be less costly [ - 8.9% composite adverse pregnancy outcome (95% CI: -15.1%, -2.6%), -$5548 (95% CI: -$16,740, $1547)] among women diagnosed before 14 weeks' gestation as well., Interpretation: Our findings highlight the potential health and economic benefits from the diagnosis and treatment of early GDM among women with risk factors for hyperglycemia in pregnancy and supports its implementation. Long-term follow-up studies are recommended as a key future area of research to assess the potential long-term health benefits and economic consequences of the intervention., Funding: National Health and Medical Research Council (grants 1104231 and 2009326), Region O¨rebro Research Committee (grants Dnr OLL-970566 and OLL-942177), Medical Scientific Fund of the Mayor of Vienna (project 15,205 and project 23,026), South Western Sydney Local Health District Academic Unit (grant 2016), and Western Sydney University Ainsworth Trust Grant (2019)., Competing Interests: WHH reports participation on Merck Sharp & Dohme Board and Rivus Pharmaceuticals Board. DS reports Presidency of the Australasian Diabetes in Pregnancy Society. All otherauthor(s) have no potential conflict of interests to report., (© 2024 The Author(s).)

Background: Activin A is a potent negative regulator of muscle mass elevated in critical illness. It is unclear whether muscle strength and physical function in critically ill humans are associated with elevated activin A levels., Objectives: The objective of this study was to investigate the relationship between serum activin A levels, muscle strength, and physical function at discharge from the intensive care unit (ICU) and hospital., Methods: Thirty-six participants were recruited from two tertiary ICUs in Melbourne, Australia. Participants were included if they were mechanically ventilated for >48 h and expected to have a total ICU stay of >5 days. The primary outcome measure was the Six-Minute Walk Test distance at hospital discharge. Secondary outcome measures included handgrip strength, Medical Research Council Sum Score, Physical Function ICU Test Scored, Six-Minute Walk Test, and Timed Up and Go Test assessed throughout the hospital admission. Total serum activin A levels were measured daily in the ICU., Results: High peak activin A was associated with worse Six-Minute Walk Test distance at hospital discharge (linear regression coefficient, 95% confidence interval, p-value: -91.3, -154.2 to -28.4, p = 0.007, respectively). Peak activin A concentration was not associated with the secondary outcome measures., Conclusions: Higher peak activin A may be associated with the functional decline of critically ill patients. Further research is indicated to examine its potential as a therapeutic target and a prospective predictor for muscle wasting in critical illness., Study Registration: ACTRN12615000047594., (Copyright © 2022 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Both obesity and sleep disorders are common among women during pregnancy. Although prior research has identified a relationship between obesity and sleep disorders, those findings are from women later in pregnancy., Objective: To explore the relationships between self-reported sleep duration, insufficient sleep and snoring with body mass index (BMI) among multiethnic women at risk of gestational diabetes mellitus (GDM)in early pregnancy., Methods: Cross-sectional study of baseline data from women at risk of GDM enrolled in the Treatment of BOoking Gestational diabetes Mellitus (TOBOGM) multicentre trial across 12 Australian/Austrian sites. Participants completed a questionnaire before 20 weeks' gestation to evaluate sleep. BMI <25 kg/m 2 served as the reference group in multivariable logistic regression., Results: Among the 2865 women included, the prevalence of overweight and obesity classes I-III was 28%, 19%, 11% and 12%, respectively. There was no relationship between sleep duration and BMI. The risk of insufficient sleep >5 days/month was higher in class II and class III obesity (1.38 (1.03-1.85) and 1.34 (1.01-1.80), respectively), and the risk of snoring increased as BMI increased (1.59 (1.25-2.02), 2.68 (2.07-3.48), 4.35 (3.21-5.88) to 4.96 (3.65-6.74), respectively))., Conclusions: Obesity is associated with insufficient sleep among pregnant women at risk of GDM. Snoring is more prevalent with increasing BMI., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© 2023 The Authors. Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd.)

Objectives: To engage critical care end-users (survivors and caregivers) to describe their emotions and experiences across their recovery trajectory, and elicit their ideas and solutions for health service improvements to improve the ICU recovery experience., Design: End-user engagement as part of a qualitative design using the Framework Analysis method., Setting: The Society of Critical Care Medicine's THRIVE international collaborative sites (follow-up clinics and peer support groups)., Subjects: Patients and caregivers following critical illness and identified through the collaboratives., Interventions: None., Measurements and Main Results: Eighty-six interviews were conducted. The following themes were identified: 1) Emotions and experiences of patients-"Loss of former self; Experiences of disability and adaptation"; 2) Emotions and experiences of caregivers-"Emotional impacts, adopting new roles, and caregiver burden; Influence of gender roles; Adaptation, adjustment, recalibration"; and 3) Patient and caregiver-generated solutions to improve recovery across the arc of care-"Family-targeted education; Expectation management; Rehabilitation for patients and caregivers; Peer support groups; Reconnecting with ICU post-discharge; Access to community-based supports post-discharge; Psychological support; Education of issues of ICU survivorship for health professionals; Support across recovery trajectory." Themes were mapped to a previously published recovery framework (Timing It Right) that captures patient and caregiver experiences and their support needs across the phases of care from the event/diagnosis to adaptation post-discharge home., Conclusions: Patients and caregivers reported a range of emotions and experiences across the recovery trajectory from ICU to home. Through end-user engagement strategies many potential solutions were identified that could be implemented by health services and tested to support the delivery of higher-quality care for ICU survivors and their caregivers that extend from tertiary to primary care settings., Competing Interests: Drs. Haines’, Quasim’s, McPeake’s, and Sevin’s institutions received funding from the Society of Critical Care Medicine (SCCM). Dr. Boehm’s institution received funding from the National Heart, Lung, and Blood Institute (NHLBI); she is funded by National Institutes of Health (NIH)/NHLBI (K12 HL137943) as is Dr. Iwashyna (K12 HL138039). Drs. Boehm and Jackson received support for article research from NIH. Dr. Hope received funding from the American Association of Critical Care Nurses. Dr. Netzer received funding from UptoDate and Springer Press. Dr. Hopkins’ institution received funding from Intermountain Research and Medical Foundation. Dr. Iwashyna disclosed government work. Dr. McPeake’s institution received funding from The University of Cambridge; she is funded by a THIS Institute Post-Doctoral Fellowship (PD-2019-02-16). Dr. Sevin received support for article research from the Department of Defense. Drs. Haines, Boehm, Quasim, McPeake, and Sevin received funding from SCCM to undertake this work. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Objectives: Social determinants of health (SDoH) contribute to health outcomes. We identified SDoH that were modified by critical illness, and the effect of such modifications on recovery from critical illness., Design: In-depth semistructured interviews following hospital discharge. Interview transcripts were mapped against a pre-existing social policy framework: money and work; skills and education; housing, transport and neighbourhoods; and family, friends and social connections., Setting: 14 hospital sites in the USA, UK and Australia., Participants: Patients and caregivers, who had been admitted to critical care from three continents., Results: 86 interviews were analysed (66 patients and 20 caregivers). SDoH, both financial and non-financial in nature, could be negatively influenced by exposure to critical illness, with a direct impact on health-related outcomes at an individual level. Financial modifications included changes to employment status due to critical illness-related disability, alongside changes to income and insurance status. Negative health impacts included the inability to access essential healthcare and an increase in mental health problems., Conclusions: Critical illness appears to modify SDoH for survivors and their family members, potentially impacting recovery and health. Our findings suggest that increased attention to issues such as one's social network, economic security and access to healthcare is required following discharge from critical care., Competing Interests: Competing interests: None declared., (© 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.)

Objectives: Investigate the challenges experienced by survivors of critical illness and their caregivers across the transitions of care from intensive care to community, and the potential problem-solving strategies used to navigate these challenges., Design: Qualitative design-data generation via interviews and data analysis via the framework analysis method., Setting: Patients and caregivers from three continents, identified through the Society of Critical Care Medicine's THRIVE international collaborative sites (follow-up clinics and peer support groups)., Subjects: Patients and caregivers following critical illness., Interventions: Nil., Measurements and Main Results: From 86 interviews (66 patients, 20 caregivers), we identified the following major themes: 1) Challenges for patients-interacting with the health system and gaps in care; managing others' expectations of illness and recovery. 2) Challenges for caregivers-health system shortfalls and inadequate communication; lack of support for caregivers. 3) Patient and caregiver-driven problem solving across the transitions of care-personal attributes, resources, and initiative; receiving support and helping others; and acceptance., Conclusions: Survivors and caregivers experienced a range of challenges across the transitions of care. There were distinct and contrasting themes related to the caregiver experience. Survivors and caregivers used comparable problem-solving strategies to navigate the challenges encountered across the transitions of care., Competing Interests: Drs. Haines’, Boehm’s, Quasim’s, McPeake’s, and Sevin’s institutions received funding from the Society of Critical Care Medicine. Drs. Haines, Boehm, Quasim, McPeake, and Sevin received funding from the Society of Critical Care Medicine to undertake this work. Dr. Boehm is funded by National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI) (K12 HL137943) as is Dr. Iwashyna (K12 HL138039). Drs. Boehm’s and Hope’s institutions received funding from the NHLBI. Dr. Boehm’s institution received funding from the American Association of Critical Care Nurses (AACN). Drs. Boehm and Hope received support for article research from the NIH and the AACN Impact Grant. Dr. Hope’s institution received funding from the NIH; he received funding from the AACN. Dr. Netzer received funding from UptoDate. Dr. Hopkins’ institution received funding from the Intermountain Research and Medical Foundation. Dr. Iwashyna received support for article research from the government. Dr. McPeake is funded by a THIS.Institute Post-Doctoral Fellowship (PD-2019-02-16). Dr. McPeake’s institution received funding from the THIS Institute, University of Cambridge. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Objectives: To understand the unmet needs of caregivers of ICU survivors, how they accessed support post ICU, and the key components of beneficial ICU recovery support systems as identified from a caregiver perspective., Design: International, qualitative study., Subjects: We conducted 20 semistructured interviews with a diverse group of caregivers in the United States, the United Kingdom, and Australia, 11 of whom had interacted with an ICU recovery program., Setting: Seven hospitals in the United States, United Kingdom, and Australia., Interventions: None., Measurements and Main Results: Content analysis was used to explore prevalent themes related to unmet needs, as well as perceived strategies to improve ICU outcomes. Post-ICU care was perceived to be generally inadequate. Desired caregiver support fell into two main categories: practical support and emotional support. Successful care delivery initiatives included structured programs, such as post discharge telephone calls, home health programs, post-ICU clinics, and peer support groups, and standing information resources, such as written educational materials and online resources., Conclusions: This qualitative, multicenter, international study of caregivers of critical illness survivors identified consistently unmet needs, means by which caregivers accessed support post ICU, and several care mechanisms identified by caregivers as supporting optimal ICU recovery., Competing Interests: Drs. Sevin, Boehm, Quasim, Haines, and McPeake received funding from Society of Critical Care Medicineto undertake this work. Dr. Boehm is funded by the National Institutes of Health/National Heart, Lung, and Blood Institute (K12 HL137943) as is Dr. Iwashyna (K12 HL138039). Dr. McPeake is funded by a THIS Institute Post-Doctoral Fellowship (PD-2019-02-16). The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: After critical illness, patients are often left with impairments in physical, social, emotional, and cognitive functioning. Peer support interventions have been implemented internationally to ameliorate these issues., Objective: To explore what patients believed to be the key mechanisms of effectiveness of peer support programs implemented during critical care recovery., Methods: In a secondary analysis of an international qualitative data set, 66 telephone interviews with patients were undertaken across 14 sites in Australia, the United Kingdom, and the United States to understand the effect of peer support during recovery from critical illness. Prevalent themes were documented with framework analysis., Results: Most patients who had been involved in peer support programs reported benefit. Patients described 3 primary mechanisms: (1) sharing experiences, (2) care debriefing, and (3) altruism., Conclusion: Peer support is a relatively simple intervention that could be implemented to support patients during recovery from critical illness. However, more research is required into how these programs can be implemented in a safe and sustainable way in clinical practice., (©2021 American Association of Critical-Care Nurses.)

Objectives: Improved ability to predict impairments after critical illness could guide clinical decision-making, inform trial enrollment, and facilitate comprehensive patient recovery. A systematic review of the literature was conducted to investigate whether physical, cognitive, and mental health impairments could be predicted in adult survivors of critical illness., Data Sources: A systematic search of PubMed and the Cochrane Library (Prospective Register of Systematic Reviews ID: CRD42018117255) was undertaken on December 8, 2018, and the final searches updated on January 20, 2019., Study Selection: Four independent reviewers assessed titles and abstracts against study eligibility criteria. Studies were eligible if a prediction model was developed, validated, or updated for impairments after critical illness in adult patients. Discrepancies were resolved by consensus or an independent adjudicator., Data Extraction: Data on study characteristics, timing of outcome measurement, candidate predictors, and analytic strategies used were extracted. Risk of bias was assessed using the Prediction model Risk Of Bias Assessment Tool., Data Synthesis: Of 8,549 screened studies, three studies met inclusion. All three studies focused on the development of a prediction model to predict (1) a mental health composite outcome at 3 months post discharge, (2) return-to-pre-ICU functioning and residence at 6 months post discharge, and (3) physical function 2 months post discharge. Only one model had been externally validated. All studies had a high risk of bias, primarily due to the sample size, and statistical methods used to develop and select the predictors for the prediction published model., Conclusions: We only found three studies that developed a prediction model of any post-ICU impairment. There are several opportunities for improvement for future prediction model development, including the use of standardized outcomes and time horizons, and improved study design and statistical methodology.

Many clinicians have implemented follow-up and aftercare to support patients following ICU. Some of this care is supported and facilitated by peer volunteers. There is limited contemporary work that has explicitly explored volunteer roles within ICU recovery services or the experience of volunteers undertaking these roles. We sought to explore the experience of survivors of critical illness, as volunteers, involved in ICU recovery services and understand their motivation for undertaking these roles., Design: Qualitative exploration using in-depth semistructured interviews. The study design used an inductive content analysis process. We also documented the roles that were adopted by volunteers in each site involved in the study., Setting: Patients and caregivers were sampled from seven sites across three continents., Patients and Subjects: Patients and caregivers who had adopted peer-volunteering roles were undertaken., Interventions: None., Measurements and Main Results: Twelve patient and caregiver peer volunteers were interviewed. Four key themes were identified. These themes related to the experience of volunteers within ICU recovery services and their motivation for undertaking these roles: 1) self-belief and acceptance, 2) developing peer support, 3) social roles and a sense of purpose, and 4) giving back. Overwhelmingly, participants were positive about the role of the volunteer in the critical care setting., Conclusions: Peer volunteers undertake a variety of roles in ICU recovery services and during recovery more generally. These roles appear to be of direct benefit to those in these roles. Future research is needed to develop these roles and fully understand the potential impact on the service, including the impact on other patients., Competing Interests: Drs. Quasim, Haines, Sevin, McPeake, and Boehm are currently receiving funding from Society of Critical Care Medicine to undertake this work. Dr. Meyer is funded by a THIS.Institute (University of Cambridge) Research Fellowship (PD-2019-02-16). The remaining authors have disclosed that they do not have any potential conflicts of interest.

To understand from the perspective of patients who did, and did not attend ICU recovery programs, what were the most important components of successful programs and how should they be organized., Design: International, qualitative study., Setting: Fourteen hospitals in the United States, United Kingdom, and Australia., Patients: We conducted 66 semi-structured interviews with a diverse group of patients, 52 of whom had used an ICU recovery program and 14 whom had not., Interventions: None., Measurements and Main Results: Using content analysis, prevalent themes were documented to understand what improved their outcomes. Contrasting quotes from patients who had not received certain aspects of care were used to identify perceived differential effectiveness. Successful ICU recovery programs had five key components: 1) Continuity of care; 2) Improving symptom status; 3) Normalization and expectation management; 4) Internal and external validation of progress; and 5) Reducing feelings of guilt and helplessness. The delivery of care which achieved these goals was facilitated by early involvement (even before hospital discharge), direct involvement of ICU staff, and a focus on integration across traditional disease, symptom, and social welfare needs., Conclusions: In this multicenter study, conducted across three continents, patients identified specific and reproducible modes of benefit derived from ICU recovery programs, which could be the target of future intervention refinement., Competing Interests: Drs. McPeake’s, Boehm’s, Hibbert’s, Bastin’s, Johnson’s, Montgomery-Yates’s, Quasim’s, Haines’s, and Sevin’s institutions received funding from the Society of Critical Care Medicine. Dr. McPeake’s, Dr. Quasim’s, and Mrs. MacTavish’s institutions received funding from the Health Foundation (United Kingdom). Drs. Boehm’s (K12 HL137943) and Hope’s institutions received funding from the American Association of Critical-Care Nurses and the National Heart, Lung, and Blood Institute. Drs. Boehm, Hope, and Jackson received support for article research from the National Institutes of Health. Dr. Iwashyna disclosed government work (K12 HL138039). The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: Patients who survive critical illness have well-defined physical, cognitive, emotional, and familial problems. However, the impact of these problems on survivors' ability to return to work and other financial outcomes is less clear. Objectives: To determine the financial and employment consequences of an intensive care stay, we performed a systematic review and meta-analysis. Data Sources: We searched the MEDLINE, Embase, and CINAHL databases (1970-2018). All publication types except narrative reviews, case reports, case-control studies, and editorials were included. Included studies assessed financial outcomes in patients admitted to critical care and their caregivers. Data Extraction: Two reviewers independently applied eligibility criteria, assessed quality, and extracted data. The primary outcome reported was return to employment among those previously employed. We also examined financial stress and the impact financial outcomes had on quality of life and psychosocial health. Data Synthesis: Of 5,765 eligible abstracts, 51 studies were included, which provided data on 858 caregivers/family members and 7,267 patients. Forty-two papers reported patient outcomes, and 11 papers described caregivers/family members. Two papers included data from both patients and caregivers/family members. Return to employment was the most commonly reported financial outcome for critical care survivors. The pooled estimates for return to employment among those who were employed before critical illness were 33% (95% confidence interval [CI], 21-48%), 55% (95% CI, 45-64%), and 56% (95% CI, 45-66%) at 3, 6, and 12 months, respectively. Across the studies included in this review, there was a positive association with psychosocial health if patients returned to employment. This included improved health-related quality of life and fewer depressive symptoms. Regarding caregivers/family members, six studies reported changes in employment such as reduced hours and lost earnings. Conclusions: After critical illness, many patients who were previously employed do not return to work, even one year later. This new job loss is associated with worse health-related quality of life among survivors and worse psychological function among survivors and caregivers/family members. More interventional research is required to understand how best to support employability after critical illness.Registered with PROSPERO (CRD42018102360).

Objectives: Data are lacking regarding implementation of novel strategies such as follow-up clinics and peer support groups, to reduce the burden of postintensive care syndrome. We sought to discover enablers that helped hospital-based clinicians establish post-ICU clinics and peer support programs, and identify barriers that challenged them., Design: Qualitative inquiry. The Consolidated Framework for Implementation Research was used to organize and analyze data., Setting: Two learning collaboratives (ICU follow-up clinics and peer support groups), representing 21 sites, across three continents., Subjects: Clinicians from 21 sites., Measurement and Main Results: Ten enablers and nine barriers to implementation of "ICU follow-up clinics" were described. A key enabler to generate support for clinics was providing insight into the human experience of survivorship, to obtain interest from hospital administrators. Significant barriers included patient and family lack of access to clinics and clinic funding. Nine enablers and five barriers to the implementation of "peer support groups" were identified. Key enablers included developing infrastructure to support successful operationalization of this complex intervention, flexibility about when peer support should be offered, belonging to the international learning collaborative. Significant barriers related to limited attendance by patients and families due to challenges in creating awareness, and uncertainty about who might be appropriate to attend and target in advertising., Conclusions: Several enablers and barriers to implementing ICU follow-up clinics and peer support groups should be taken into account and leveraged to improve ICU recovery. Among the most important enablers are motivated clinician leaders who persist to find a path forward despite obstacles.

Objective: To identify the key mechanisms that clinicians perceive improve care in the intensive care unit (ICU), as a result of their involvement in post-ICU programs., Methods: Qualitative inquiry via focus groups and interviews with members of the Society of Critical Care Medicine's THRIVE collaborative sites (follow-up clinics and peer support). Framework analysis was used to synthesize and interpret the data., Results: Five key mechanisms were identified as drivers of improvement back into the ICU: (1) identifying otherwise unseen targets for ICU quality improvement or education programs-new ideas for quality improvement were generated and greater attention paid to detail in clinical care. (2) Creating a new role for survivors in the ICU-former patients and family members adopted an advocacy or peer volunteer role. (3) Inviting critical care providers to the post-ICU program to educate, sensitize, and motivate them-clinician peers and trainees were invited to attend as a helpful learning strategy to gain insights into post-ICU care requirements. (4) Changing clinician's own understanding of patient experience-there appeared to be a direct individual benefit from working in post-ICU programs. (5) Improving morale and meaningfulness of ICU work-this was achieved by closing the feedback loop to ICU clinicians regarding patient and family outcomes., Conclusions: The follow-up of patients and families in post-ICU care settings is perceived to improve care within the ICU via five key mechanisms. Further research is required in this novel area.

Objectives: Nationally accredited simulation courses such as advance pediatric life support and pediatric advance life support are recommended for health care professionals (HCPs) at two yearly intervals as a minimum requirement, despite literature evidence suggesting rapid decline in knowledge shortly after course completion. The objective of this study was to evaluate an observation-based, educational intervention program aimed at improving previously acquired knowledge and confidence in managing critical illnesses., Methods: A prospective cohort longitudinal study was conducted over a 6-month period. Participants were assessed with a knowledge based questionnaire immediately prior to and after observing 12 fortnightly critical illness scenario demonstrations (CISDs). The outcome measure was performance on questionnaires. Regression analysis was used to adjust for potential confounders. Questionnaire practice effect was evaluated on 30 independent HCPs not exposed to the CISDs., Results: Fifty-four HCPs (40 doctors and 14 nurses) participated in the study. All participants had previously attended nationally accredited simulation courses with a mean time since last attendance of 1.8 ± 0.4 years. The median number of attendances at CISD was 6 (2-12). The mean questionnaire scores at baseline (17.2/25) were significantly lower than the mean post intervention questionnaire scores (20.3/25), p = 0.003. The HCPs self-rated confidence in managing CISD was 6.5 times higher at the end of the program in the intervention group (p = 0.002) than at baseline. There was no practice effect for questionnaires demonstrated in the independent sample., Conclusion: The educational intervention program significantly improved the knowledge and confidence of the participants in managing pediatric critical illnesses. The CISD program provides an inexpensive, practical, and time effective method of facilitating knowledge acquisition and retention. Despite the distinctively different approach, this study has shown the effectiveness of the participant being an observer to enhance pediatric resuscitation skills.

Glulisine (Apidra(®)) is a rapid-acting human insulin analog approved for use in children with diabetes mellitus ≥4 years of age. Management of children with type 1 diabetes has seen a shift in favor of mimicking normal physiological insulin responses with multiple daily injections or continuous subcutaneous insulin infusions (CSII). Few studies have compared the rapid-acting insulin analogs in this population but limited data indicate that glulisine is as effective as lispro when used in a basal-bolus regimen. This review appraises the current available studies and reviews on insulin glulisine in children. An extensive keyword search of 'insulin glulisine', 'insulin analogs', and 'Apidra' in the pediatric population was performed. These studies have suggested that glulisine is safe, well tolerated, and is an effective option in the diabetes armamentarium. Further studies are needed to determine its safety for use in CSII pumps in the pediatric population.

Objective: This prospective study was performed on patients aged >65 years commencing therapy with venlafaxine, in order to determine the incidence of hyponatraemia induced by the drug, to investigate the underlying pathophysiological mechanisms, and to evaluate a simple approach to management of this condition., Method: All patients aged >65 years seen by one author (MR) from all referral sources were entered into the study. Baseline biochemical tests were ordered, and if hyponatraemia developed (plasma Na <130 mmol L(-1)) additional tests were performed to ascertain the mechanism, while the patient continued on venlafaxine and fluid restriction was instituted., Results: A total of 58 patients were seen, of whom 10 developed hyponatraemia, giving an incidence of 17.2%. Of these 10 patients, five were excluded from prolonged observation because of either severe medical illness, side-effects from the antidepressant or being lost to follow up. When hyponatraemia developed, it invariably did so within a few days of starting venlafaxine, and was associated with non-suppression of antidiuretic hormone in the face of a low serum osmolality. Fluid restriction (800 mL day(-1)) was effective in raising the plasma sodium to the normal range within 2 weeks, after which the fluid restriction could be relaxed without relapse occurring. These patients remained well for the follow-up period of up to 6 months., Conclusions: Patients >65 years of age should have their electrolytes measured 3-5 days after starting venlafaxine therapy. If hyponatraemia develops, it can be managed with modest fluid restriction without discontinuing drug treatment, subject to close continued clinical observation and biochemical monitoring.

Background: Increased vitamin D intake may preserve or increase bone mineral density (BMD) in older persons., Objective: A 2-y double-blind study was undertaken to determine whether weekly administration of 10 000 units of vitamin D(2) maintained or increased BMD in younger postmenopausal women more efficiently than did calcium supplements alone., Design: One hundred eighty-seven women who were >or= 1 y postmenopausal were randomly assigned to take either 1000 mg Ca/d after the evening meal or 1000 mg Ca/d plus 10 000 U vitamin D(2)/wk in a double-blind, placebo-controlled format. The BMD of the proximal forearm, lumbar spine, femoral neck, Ward's triangle, and femoral trochanter was measured at 6-mo intervals by osteodensitometry., Results: During the 2-y period, there was no significant difference in the change in BMD at any site between the subjects taking calcium supplements and those taking calcium plus vitamin D(2). Both groups significantly (P < 0.005) gained BMD in Ward's triangle and the femoral trochanter but significantly (P < 0.005) lost bone in the proximal radius. There was no significant change in the lumbar spine or femoral neck BMD., Conclusion: In younger postmenopausal women ( age: 56 y) whose average baseline serum 25-hydroxyvitamin D concentration was well within the normal range, the addition of 10 000 U vitamin D(2)/wk to calcium supplementation at 1000 mg/d did not confer benefits on BMD beyond those achieved with calcium supplementation alone.

Background: Little is known about patterns of clinical skills acquisition among junior doctors undertaking clinical training in the early postgraduate period. A better understanding would assist in the design of effective educational interventions for this group., Methods: We conducted a cross-sectional survey of the levels of confidence and experience with a broad raft of clinical skills among early PGY1 trainees (interns), PGY2s and PGY3s within a university teaching hospital network in Sydney at the beginning of the clinical year in 1999. The instrument was a new validated 69 item questionnaire. A total of 92 respondents took part, representing 100% of the PGY1 (n=36), PGY2 (n=31) and PGY3 (n=25) cohorts., Results: Commencing interns reported high confidence levels with a small group of practical skills but less confidence with clinical management skills. Significant positive differences were found for confidence with all skill areas between early PGY1 and PGY3. We identified three patterns for skills acquisition. Pattern A was the most common, with a significant difference in levels of confidence and experience between PGY1 and PGY2 but not between PGY2 and PGY3 (e.g. suturing a simple laceration). In Pattern B, significant differences were found in levels of confidence and experience between PGY1 and PGY2 as well as between PGY2 and PGY3 (e.g. cardiopulmonary resuscitation). In Pattern C, significant differences were found in levels of experience between PGY2 and PGY3 but not between PGY1 and PGY2 (e.g. endotracheal intubation). There was a significant correlation between reported confidence and experience for all skill areas., Conclusions: Early postgraduate medical trainees in a Sydney teaching hospital acquire high levels of confidence and experience in most skill areas after two years of training. The first postgraduate year is particularly significant for the development of clinical skills.

Holins are small hydrophobic proteins causing non-specific membrane lesions at the end of bacteriophage multiplication, to promote access of the murein hydrolase to their substrate. We have established a lambdaDeltaS genetic system, which enables functional expression of holins from various phages in an isogenic phage lambda background, and allows qualitative evaluation of their ability to support lysis of Escherichia coli cells. Synthesis of Holins is under control of native lambda transcription and translation initiation signals, and the temperature-sensitive CIts857 repressor. A number of different holins were tested in this study. The opposing action of phage lambda S105 and S107 holin variants in lysis timing could be confirmed, whereas we found evidence for a functionally non-homologous dual translational start motif in the Listeria phage Hol500 holin, i.e., the Hol500-96 polypeptide starting at Met-1 revealed a more distinct lytic activity as compared to the shorter product Hol500-93. The largest holin known, HolTW from a Staphylococcus aureus phage, revealed an early lysis phenotype in the lambdaDeltaSthf background, which conferred a plaque forming defect due to premature lysis. Mutant analysis revealed that an altered C-terminus and/or a V52L substitution were sufficient to delay lysis and enable plaque formation. These results suggest that the extensively charged HolTW C-terminus may be important in regulation of lysis timing. The gene 17.5 product of E. coli phage T7 was found to support sudden, saltatory cell lysis in the lambdaDeltaSthf background, which clearly confirms its holin character. In conclusion, lambdaDeltaSthf offers a useful genetic tool for studying the structure-function relationship of the extremely heterogeneous group of holin protein orthologs.

Background: A 41-year-old premenopausal woman with newly diagnosed haemochromatosis was found to have osteopenia on screening bone mineral densitometry., Methods and Results: Liver biopsy showed grade 3 haemochromatosis with an hepatic iron index of 4. Investigation for secondary factors for osteopenia revealed no cause. The patient was clinically and biochemically eugonadal. Following venesection of 8 L blood (4 g iron) over 17 months and calcium supplementation, her bone density rose significantly. Neck of femur bone density increased by 6.0% over 13 months and lumbar vertebral bone density increased by 7.2%. There are no previous reports of response of bone density to venesection in eugonadal patients or in women with haemochromatosis.

The largest documented case of a double parathyroid adenoma is reported. The patient presented in hypercalcaemic crisis with a large intrathoracic mass. After removal of a massive cystic parathyroid adenoma from the right superior mediastinum, a second very large parathyroid adenoma was found on the contralateral side adjacent to the left thyroid lobe. This case illustrates the importance of the cervical approach, as well as routine bilateral neck exploration, for all cases of primary hyperparathyroidism.

To test the association of hyperpyrexia (temperature greater than or equal to 41.1 degrees C) with increased rates of bacteremia and serious bacterial illness in young children, we performed a retrospective case-control study. Seventy-six hyperpyrexic children and an equal number of control cases with temperatures of 39.1-40 degrees C and 40.1-41.0 degrees C were identified. A significantly larger number of diagnostic procedures including blood cultures, urine cultures, chest x-rays and white blood cell counts were performed in the hyperpyrexic children (P less than 0.05). The frequency of serious bacterial infections and bacteremia did not differ among the groups (P greater than 0.05). Hyperpyrexic children need to be evaluated as thoroughly and carefully as any other febrile child but do not merit special consideration.