Private practice dietetics: A scoping review of the literature.

AIM: Private practice is one of the most rapidly growing, but under-researched employment sectors for graduate dietitians in Australia, limiting evidence-based workforce development. This scoping review examines existing international literature to gain an understanding of the current private practice workforce size, distribution, demography and workforce development considerations, including competencies, supply and demand, remuneration and professional development activities. METHODS: The databases MEDLINE, EMBASE, CINAHL, EMCARE, PsycInfo (Ovid) and grey literature were systematically searched in August 2023 using key search terms to identify studies for inclusion. Articles were included if they related to private practice dietetics and described an aspect of workforce. Original research, government and organisational reports, statements of practice and websites providing governmental or organisational statistics were included. A directed content analysis and qualitative constant comparison technique were used to deductively map intelligence sources against a workforce development framework. A gap analysis was also conducted to provide a focus for future workforce development research. RESULTS: A total of 72 peer-reviewed and grey literature sources were included, with 65% of the studies being Australian-based publications. Private practice dietetics research interest has increased in the last decade. Despite a breadth of published sources, this review found little published data on workforce size, distribution, demography, supply, demand, continued professional development and remuneration, indicating a significant gap in the evidence base. Existing literature focuses on workforce challenges and barriers, the work of private practice dietitians, with limited exploration of competency requirements for graduate private practitioners. CONCLUSIONS: The literature on the private practice dietetics workforce is lacking worldwide, which constrains evidenced-based workforce development initiatives. Workforce development research across all workforce aspects is warranted to address current evidence gaps.

Association of active mobilisation variables with adverse events and mortality in patients requiring mechanical ventilation in the intensive care unit: a systematic review and meta-analysis.

BACKGROUND: Mobilisation during critical illness is now included in multiple clinical practice guidelines. However, a large, randomised trial and systematic review have recently identified an increased probability of adverse events and mortality in patients who received early active mobilisation in the intensive care unit (ICU). We aimed to determine the effects of mobilisation compared with usual care on adverse events and mortality in an acute ICU setting. In subgroup analyses, we specifically aimed to investigate possible sources of harm, including the timing and duration of mobilisation achieved, ventilation status, and admission diagnosis. METHODS: In this systematic review with frequentist and Bayesian analyses, we searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, CINAHL, SPORTDiscus, SCOPUS, Web of Science, and PEDro electronic databases, as well as clinical trial registries (ICTRP and ClinicalTrials.gov), from inception to March 16, 2023, without language restrictions. Eligible studies were randomised controlled trials that examined active mobilisation compared with either no mobilisation or mobilisation commencing later, or at a lower frequency or intensity, in adults who were critically ill during or after a period of mechanical ventilation in an acute ICU setting. Two authors independently screened reports, extracted data, and assessed the risk of bias using the Cochrane risk-of-bias tool (version 1). The primary outcome was the number of adverse events that occurred during the implementation of mobilisation, with the effect of mobilisation on mortality being the secondary outcome. Risk ratios (RRs) with 95% CIs were calculated in R (version 4.0.3) using random-effects modelling, with Bayesian analysis completed to calculate the probability of treatment harm (ie, RR >1). Subgroup analyses were completed to investigate the association of various factors of mobilisation on adverse events and mortality: duration of mobilisation (longer [≥20 min per day] vs shorter [<20 min per day]), timing of commencement (early [≤72 h from ICU admission] vs late [>72 h from ICU admission]), ventilation status at commencement (all patients mechanically ventilated vs all patients extubated), and ICU admission diagnosis (surgical vs medical). This study was registered with PROSPERO, CRD42022369272. FINDINGS: After title and abstract screening of 14 440 studies and review of 466 full texts, 67 trials with 7004 participants met inclusion criteria, with 59 trials contributing to the meta-analysis. Of the 67 included studies, 15 (22%) did not mention adverse events and 13 (19%) reported no adverse events occurring across the trial period. Overall, we found no effect of mobilisation compared with usual care on the occurrence of adverse events (RR 1·09 [95% CI 0·69-1·74], p=0·71; I2 91%; 32 731 events, 20 studies; very low certainty), with a 2·96% occurrence rate (693 events in 23 395 intervention sessions; 25 studies). Mobilisation did not have any effect on mortality (RR 0·98 [95% CI 0·87-1·12], p=0·81; I2 0%; n=6218, 58 studies; moderate certainty). Subgroup analysis was hindered by the large amount of data that could not be allocated and analysed, making the results hypothesis generating only. INTERPRETATION: Implementation of mobilisation in the ICU was associated with a less than 3% chance of an adverse event occurring and was not found to increase adverse events or mortality overall, providing reassurance for clinicians about the safety of performing this intervention. Subgroup analyses did not clearly identify any specific variable of mobilisation implementation that increased harm. FUNDING: None.

Defining the relationship between cellular and extracellular vesicle (EV) content in breast cancer via an integrative multi-omic analysis.

Much recent research has been dedicated to exploring the utility of extracellular vesicles (EVs) as circulating disease biomarkers. Underpinning this work is the assumption that the molecular cargo of EVs directly reflects the originating cell. Few attempts have been made, however, to empirically validate this on the -omic level. To this end, we have performed an integrative multi-omic analysis of a panel of breast cancer cell lines and corresponding EVs. Whole transcriptome analysis validated that the cellular transcriptome remained stable when cultured cells are transitioned to low serum or serum-free medium for EV collection. Transcriptomic profiling of the isolated EVs indicated a positive correlation between transcript levels in cells and EVs, including disease-associated transcripts. Analysis of the EV proteome verified that HER2 protein is present in EVs, however neither the estrogen (ER) nor progesterone (PR) receptor proteins are detected regardless of cellular expression. Using multivariate analysis, we derived an EV protein signature to infer cellular patterns of ER and HER2 expression, though the ER protein could not be directly detected. Integrative analyses affirmed that the EV proteome and transcriptome captured key phenotypic hallmarks of the originating cells, supporting the potential of EVs for non-invasive monitoring of breast cancers.

Co-producing a complex psychosocial intervention during COVID-19 with young people transitioning from adolescent secure hospitals to adult services in England: Moving Forward intervention (MFi).

BACKGROUND: Young people moving from adolescent secure hospitals to adult care present with multiple and complex needs which often remain unmet during transition periods. This paper delineates the process of developing and co-producing the moving forward intervention (MFi), which aims to address the psychosocial needs of transitioning youth who have limited access to well-researched and tailored service provisions. METHOD: An extensive search of the relevant literature was conducted to generate themes and guide the co-production phase. Fourteen Advisory Group Meetings were held virtually during COVID-19 to design the MFi module content with 17 keyworkers, 2 parents and 13 young people aged 17-18 years across six adolescent secure hospitals in England. Thematic analysis was used to reflect on the field notes discussed in the Advisory Groups. RESULTS: Co-produced themes from the literature and the Advisory Groups informed the development of the proposed intervention. Three overarching themes pertinent to expectations in adult services, improving communication gaps between services and facilitating the letting go period emerged from the co-production phase. It was suggested the MFi is co-delivered by a peer with lived experience to build trust and create hopefulness among young people. The importance of promoting graded transitions through standardised procedures was highlighted. CONCLUSIONS: The current findings promote evidence-based initiatives and build robust practice frameworks that inform treatment and policy guidelines. The young people, parents and keyworkers found the MFi supportive and valued the co-production experience. As such, co-production has been a vital tool in promoting patient engagement and empowerment, and reducing service inequalities, especially in adolescent secure hospitals.

The impact of critical illness on patients' physical function and recovery: An explanatory mixed-methods analysis.

OBJECTIVES: To determine how the perception of physical function 6-months following critical illness compares to objectively measured function, and to identify key concerns for patients during recovery from critical illness. RESEARCH METHODOLOGY AND DESIGN: A nested convergent parallel mixed methods study assessed physical function during a home visit 6-months following critical illness, with semi-structured interviews conducted at the same time. SETTING: Participants were recruited from two hospitals at one healthcare network in Melbourne, Australia from September 2017 to October 2018 with follow-up data completed in April 2019. MAIN OUTCOME MEASURES: Physical function was assessed through four objective outcomes: the functional independence measure, six-minute walk test, functional reach test, and grip strength. Semi structured interviews focused on participants function, memories of the intensive care and hospital stay, assistance required on discharge, ongoing limitations, and the recovery process. FINDINGS: Although many participants (12/20, 60%) stated they had recovered from their critical illness, 14 (70%) had function below expected population norms. Decreased function on returning home was commonly reported, although eleven participants were described as independent and safe for discharge from hospital-based staff. The importance of family and social networks to facilitate discharge was highlighted, however participants often described wanting more support and issues accessing services. The effect of critical illness on the financial well-being of the family network was confirmed, with difficulties accessing financial support identified. CONCLUSION: Survivors of critical illness perceived a better functional state than measured, but many report new limitations 6-months after critical illness. Family and friends play a crucial role in facilitating transition home and providing financial support. IMPLICATIONS FOR CLINICAL PRACTICE: Implementation of specific discharge liaison personnel to provide education, support and assist the transition from hospital-based care to home, particularly in those without stable social supports, may improve the recovery process for survivors of critical illness.

Development of a Digital Health Intervention to Support Patients on a Waitlist for Orthopedic Specialist Care: Co-Design Study.

BACKGROUND: The demand for orthopedic specialist consultations for patients with osteoarthritis in public hospitals is high and continues to grow. Lengthy waiting times are increasingly affecting patients from low socioeconomic and culturally and linguistically diverse backgrounds who are more likely to rely on public health care. OBJECTIVE: This study aimed to co-design a digital health intervention for patients with OA who are waiting for an orthopedic specialist consultation at a public health service, which is located in local government areas (LGAs) of identified social and economic disadvantage. METHODS: The stakeholders involved in the co-design process included the research team; end users (patients); clinicians; academic experts; senior hospital staff; and a research, design, and development agency. The iterative co-design process comprised several key phases, including the collation and refinement of evidence-based information by the research team, with assistance from academic experts. Structured interviews with 16 clinicians (female: n=10, 63%; male: n=6, 38%) and 11 end users (age: mean 64.3, SD 7.2 y; female: n=7, 64%; male: n=4, 36%) of 1-hour duration were completed to understand the requirements for the intervention. Weekly workshops were held with key stakeholders throughout development. A different cohort of 15 end users (age: mean 61.5, SD 9.7 y; female: n=12, 80%; male: n=3, 20%) examined the feasibility of the study during a 2-week testing period. The System Usability Scale was used as the primary measure of intervention feasibility. RESULTS: Overall, 7 content modules were developed and refined over several iterations. Key themes highlighted in the clinician and end user interviews were the diverse characteristics of patients, the hierarchical structure with which patients view health practitioners, the importance of delivering information in multiple formats (written, audio, and visual), and access to patient-centered information as early as possible in the health care journey. All content was translated into Vietnamese, the most widely spoken language following English in the local government areas included in this study. Patients with hip and knee osteoarthritis from culturally and linguistically diverse backgrounds tested the feasibility of the intervention. A mean System Usability Scale score of 82.7 (SD 16) was recorded for the intervention, placing its usability in the excellent category. CONCLUSIONS: Through the co-design process, we developed an evidence-based, holistic, and patient-centered digital health intervention. The intervention was specifically designed to be used by patients from diverse backgrounds, including those with low health, digital, and written literacy levels. The effectiveness of the intervention in improving the physical and mental health of patients will be determined by a high-quality randomized controlled trial.

The Impact of Ferric Derisomaltose on Cardiovascular and Noncardiovascular Events in Patients With Anemia, Iron Deficiency, and Heart Failure With Reduced Ejection Fraction.

BACKGROUND: In some countries, intravenous ferric derisomaltose (FDI) is only licensed for treating iron deficiency with anemia. Accordingly, we investigated the effects of intravenous FDI in a subgroup of patients with anemia in the IRONMAN (Effectiveness of Intravenous (IV) Iron Treatment Versus Standard Care in Patients With Heart Failure and Iron Deficiency) trial. METHOD AND RESULTS: IRONMAN enrolled patients with heart failure, a left ventricular ejection fraction of ≤45%, and iron deficiency (ferritin <100 µg/L or transferrin saturation of <20%), 771 (68%) of whom had anemia (hemoglobin <12 g/dL for women and <13 g/dL for men). Patients were randomized, open label, to FDI (n = 397) or usual care (n = 374) and followed for a median of 2.6 years. The primary end point, recurrent hospitalization for heart failure and cardiovascular death, occurred less frequently for those assigned to FDI (rate ratio 0.78, 95% confidence interval 0.61-1.01; P = .063). First event analysis for cardiovascular death or hospitalization for heart failure, less affected by the coronavirus disease 2019 pandemic, gave similar results (hazard ratio 0.77, 95% confidence interval 0.62-0.96; P = .022). Patients randomized to FDI reported a better Minnesota Living with Heart Failure quality of life, for overall (P = .013) and physical domain (P = .00093) scores at 4 months. CONCLUSIONS: In patients with iron deficiency anemia and heart failure with reduced left ventricular ejection fraction, intravenous FDI improves quality of life and may decrease cardiovascular events.

How robust are recommended waiting times to pacing after cardiac surgery that are derived from observational data?

AIMS: For bradycardic patients after cardiac surgery, it is unknown how long to wait before implanting a permanent pacemaker (PPM). Current recommendations vary and are based on observational studies. This study aims to examine why this variation may exist. METHODS AND RESULTS: We conducted first a study of patients in our institution and second a systematic review of studies examining conduction disturbance and pacing after cardiac surgery. Of 5849 operations over a 6-year period, 103 (1.8%) patients required PPM implantation. Only pacing dependence at implant and time from surgery to implant were associated with 30-day pacing dependence. The only predictor of regression of pacing dependence was time from surgery to implant. We then applied the conventional procedure of receiver operating characteristic (ROC) analysis, seeking an optimal time point for decision-making. This suggested the optimal waiting time was 12.5 days for predicting pacing dependence at 30 days for all patients (area under the ROC curve (AUC) 0.620, P = 0.031) and for predicting regression of pacing dependence in patients who were pacing-dependent at implant (AUC 0.769, P < 0.001). However, our systematic review showed that recommended optimal decision-making time points were strongly correlated with the average implant time point of those individual studies (R = 0.96, P < 0.001). We further conducted modelling which revealed that in any such study, the ROC method is strongly biased to indicate a value near to the median time to implant as optimal. CONCLUSION: When commonly used automated statistical methods are applied to observational data with the aim of defining the optimal time to pacing after cardiac surgery, the suggested answer is likely to be similar to the average time to pacing in that cohort.

Prevalence of diagnosable depression in patients awaiting orthopaedic specialist consultation: a cross-sectional analysis.

BACKGROUND: Musculoskeletal conditions, including osteoarthritis (OA), are a leading cause of disability and chronic pain, and are associated with high rates of comorbid depression. However, signs of depression are often masked by pain. The aim of this study was to determine the prevalence and severity of depression and pain in individuals awaiting specialist orthopaedic consultation. A secondary objective was to determine the relationship between pain and depression, irrespective of demographic factors and clinical diagnosis. METHODS: Cross-sectional analysis of individuals awaiting orthopaedic consultation at a public hospital in Melbourne, Australia. Relevant data were extracted from medical records and questionnaires. Descriptive statistics were used to summarise participant characteristics. The patient health questionnaire (PHQ-9) was used to assess depression and a numerical rating scale (NRS) was used to assess pain severity. Multiple linear regression analyses were used to establish the relationship between pain and depression. RESULTS: Nine hundred and eighty-six adults (mean ± standard deviation, age = 54.1 ± 15.7 years, 53.2% women) participated in the study. OA was present in 56% of the population and 34% of the entire population had moderate depression or greater, 19% of which met the criteria for major depressive disorder. Moderate-to-severe pain was present in 79% of individuals with OA and 55% of individuals with other musculoskeletal complaints. Pain was significantly associated with depression scores (ß = 0.84, adjusted R2 = 0.13, P < 0.001), and this relationship remained significant after accounting for gender, age, education and employment status, OA status, number of joints affected and waiting time (ß = 0.91, adjusted R2 = 0.19, P < 0.001). CONCLUSIONS: Depression affects one-third of individuals on an orthopaedic waitlist. A strong link between pain and depression in patients awaiting specialist orthopaedic consultation exists, indicating a need for an integrated approach in addressing pain management and depression to manage this complex and comorbid presentation.

Help-seeking for Intimate Partner Violence and Abuse: Experiences of Serving and Ex-serving UK Military Personnel.

Purpose: Intimate Partner Violence and Abuse (IPVA) is as a major health concern globally. The prevalence of IPVA perpetration and victimisation has been found to be higher in military compared to civilian populations. Of concern, help-seeking for other psychosocial difficulties among military communities has been shown to be both limited and challenging, and military personnel could face additional or amplified barriers to help-seeking for IPVA than their civilian counterparts. This study aimed to use qualitative methods to explore the experiences of, and barriers to, help-seeking for IPVA victimisation and perpetration among UK military personnel. Methods: Thematic analysis was conducted on 40 one-to-one semi-structured interviews with military personnel (29 male, 11 female). Results: Four superordinate themes were derived, thematically organised according to different levels of the social ecological model: Military cultural factors; Support service factors; Interpersonal factors; and Individual factors. At a military cultural level, participants described difficulties in help-seeking for IPVA resulting from widespread stigma and hypermasculine attitudes in military communities, minimisation of violence, perceived pressure from chain of command, and fear of consequences of reporting. At a support-service level, participants' negative views or experiences and lack of awareness of services were also significant in deterring help-seeking. At an interpersonal level, participants recounted how relationships with military colleagues, their partner and their family could be both instrumental or a hindrance to help-seeking for IPVA. At an individual level, lack of insight into IPVA and different forms of abuse were suggested through minimisation of violence and described to contribute to delay in help-seeking. Shame, compounded by multi-layered stigma present at each social ecological model level, was a key reason for delaying or avoiding help-seeking. Conclusions: The findings indicate the added challenges in help-seeking for IPVA experienced by military personnel and highlight a need for a whole systems approach to improve the provision of support for IPVA in the military serving and ex-serving community to instil meaningful change.

Differential roles of CTP synthetases CTPS1 and CTPS2 in cell proliferation.

The CTP nucleotide is a key precursor of nucleic acids metabolism essential for DNA replication. De novo CTP production relies on CTP synthetases 1 and 2 (CTPS1 and CTPS2) that catalyze the conversion of UTP into CTP. CTP synthetase activity is high in proliferating cells including cancer cells; however, the respective roles of CTPS1 and CTPS2 in cell proliferation are not known. By inactivation of CTPS1 and/or CTPS2 and complementation experiments, we showed that both CTPS1 and CTPS2 are differentially required for cell proliferation. CTPS1 was more efficient in promoting proliferation than CTPS2, in association with a higher intrinsic enzymatic activity that was more resistant to inhibition by 3-deaza-uridine, an UTP analog. The contribution of CTPS2 to cell proliferation was modest when CTPS1 was expressed but essential in absence of CTPS1. Public databases analysis of more than 1,000 inactivated cancer cell lines for CTPS1 or CTPS2 confirmed that cell growth is highly dependent of CTPS1 but less or not of CTPS2. Therefore, our results demonstrate that CTPS1 is the main contributor to cell proliferation.

CTP Synthase 1 Is a Novel Therapeutic Target in Lymphoma.

Lymphoma is the most common hematological malignancy and is among the 10 most prevalent cancers worldwide. Although survival has been improved by modern immunochemotherapeutic regimens, there remains a significant need for novel targeted agents to treat both B-cell and T-cell malignancies. Cytidine triphosphate synthase 1 (CTPS1), which catalyzes the rate-limiting step in pyrimidine synthesis, plays an essential and nonredundant role in B-cell and T-cell proliferation but is complemented by the homologous CTPS2 isoform outside the hemopoietic system. This report describes the identification and characterization of CTPS1 as a novel target in B- and T-cell cancers. A series of small molecules have been developed which show potent and highly selective inhibition of CTPS1. Site-directed mutagenesis studies identified the adenosine triphosphate pocket of CTPS1 as the binding site for this small molecule series. In preclinical studies, a potent and highly selective small molecule inhibitor of CTPS1 blocked the in vitro proliferation of human neoplastic cells, showing the highest potency against lymphoid neoplasms. Importantly, pharmacological CTPS1 inhibition induced cell death by apoptosis in the majority of lymphoid cell lines tested, thus demonstrating a cytotoxic mechanism of action. Selective CTPS1 inhibition also inhibited the growth of neoplastic human B- and T- cells in vivo. These findings identify CTPS1 as a novel therapeutic target in lymphoid malignancy. A compound from this series is in phase 1/2 clinical studies for the treatment of relapsed/refractory B- and T-cell lymphoma (NCT05463263).

Variation in optimal hemodynamic atrio-ventricular delay of biventricular pacing with different endocardial left ventricular lead locations using precision hemodynamics.

INTRODUCTION: It is not known whether the optimal atrioventricular (AVopt ) delay varies between left ventricular (LV) pacing site during endocardial biventricular pacing (BiVP) and may therefore needs consideration. METHODS: We assessed the hemodynamic AVopt in patients with chronic heart failure undergoing endocardial LV lead implantation. AVopt was assessed during atrio-BiVP with a "roving LV lead." Up to four locations were studied: mid-lateral wall, mid-septum (or a close alternative), site of greatest hemodynamic improvement, and LV lead implant site. The AVopt was compared to a fixed AV delay of 180 ms. RESULTS: Seventeen patients were included (12 male, aged 66.5 ± 12.8 years, ejection fraction 26 ± 7%, 16 left bundle branch block or high percentage of right ventricular pacing [RVP], QRS duration 167 ± 27 ms). In most locations (62/63), AVopt increased systolic blood pressure during BiVP compared with RVP (relative improvement 6 mmHg, interquartile range [IQR] 4-9 mmHg). Compared to a fixed AV delay, the hemodynamic improvement at AVopt was higher (1 mmHg, IQR 0.2-2.6 mmHg, p < .001). Within most patients (16/17), we observed a difference in AVopt between pacing sites (median paced AVopt 209 ms, IQR 117-250). Within this range, the hemodynamic impact of these differences was small (median loss 0.6 mmHg, IQR 0.1-2.6 mmHg). CONCLUSION: Within a patient, different endocardial LV lead locations have slightly different hemodynamic AVopt which are superior to a fixed AV delay. The hemodynamic consequence of applying an optimum from a different lead location is small.

Isolated subcutaneous implantable cardioverter-defibrillator generator displacement causing inappropriate shocks despite preserved lead tip and coil position: a case report.

Background: Subcutaneous implantable cardioverter-defibrillators (S-ICDs) are increasingly used in patients without a pacing indication, and may reduce venous complications, endocarditis and extraction morbidity. Subcutaneous implantable cardioverter-defibrillator displacements may be less obvious than their transvenous counterparts. Case summary: A 59-year-old man was found to have dilated cardiomyopathy associated with heavy alcohol intake following investigation for a stroke. Despite 2 years of alcohol cessation and optimal drug therapy, his ejection fraction remained severely impaired, and he received an S-ICD using the manufacturer recommended screening and implant method, and by an experienced operator. Ten months later, inappropriate shocks were delivered despite optimal programming. Device displacement was demonstrated by lateral chest radiography on the second instance of inappropriate therapy. On the first admission, a lateral film was not performed, and simple device programming was undertaken which failed to prevent the second occurrence. The patient requested an explant; as ventricular function had improved following initiation of sacubutril/valsartan, the clinical team opted to remove the device. Discussion: Careful inspection of lateral chest films and review of device indication are needed to reduce the risk of inappropriate shocks. This is the first description of inappropriate device activity following lone generator displacement-lead displacement is well described.

Effects of haemodynamically atrio-ventricular optimized His bundle pacing on heart failure symptoms and exercise capacity: the His Optimized Pacing Evaluated for Heart Failure (HOPE-HF) randomized, double-blind, cross-over trial.

AIMS: Excessive prolongation of PR interval impairs coupling of atrio-ventricular (AV) contraction, which reduces left ventricular pre-load and stroke volume, and worsens symptoms. His bundle pacing allows AV delay shortening while maintaining normal ventricular activation. HOPE-HF evaluated whether AV optimized His pacing is preferable to no-pacing, in a double-blind cross-over fashion, in patients with heart failure, left ventricular ejection fraction (LVEF) ≤40%, PR interval ≥200 ms and either QRS ≤140 ms or right bundle branch block. METHODS AND RESULTS: Patients had atrial and His bundle leads implanted (and an implantable cardioverter-defibrillator lead if clinically indicated) and were randomized to 6 months of pacing and 6 months of no-pacing utilizing a cross-over design. The primary outcome was peak oxygen uptake during symptom-limited exercise. Quality of life, LVEF and patients' holistic symptomatic preference between arms were secondary outcomes. Overall, 167 patients were randomized: 90% men, 69 ± 10 years, QRS duration 124 ± 26 ms, PR interval 249 ± 59 ms, LVEF 33 ± 9%. Neither peak oxygen uptake (+0.25 ml/kg/min, 95% confidence interval [CI] -0.23 to +0.73, p = 0.3) nor LVEF (+0.5%, 95% CI -0.7 to 1.6, p = 0.4) changed with pacing but Minnesota Living with Heart Failure quality of life improved significantly (-3.7, 95% CI -7.1 to -0.3, p = 0.03). Seventy-six percent of patients preferred His bundle pacing-on and 24% pacing-off (p < 0.0001). CONCLUSION: His bundle pacing did not increase peak oxygen uptake but, under double-blind conditions, significantly improved quality of life and was symptomatically preferred by the clear majority of patients. Ventricular pacing delivered via the His bundle did not adversely impact ventricular function during the 6 months.

Correlation of patient-reported outcome measures to performance-based function in critical care survivors: PREDICTABLE.

BACKGROUND: Establishing sequela following critical illness is a public health priority; however, recruitment and retention of this cohort make assessing functional outcomes difficult. Completing patient-reported outcome measures (PROMs) via telephone may improve participant and researcher involvement; however, there is little evidence regarding the correlation of PROMs to performance-based outcome measures in critical care survivors. OBJECTIVES: The objective of this study was to assess the relationship between self-reported and performance-based measures of function in survivors of critical illness. METHODS: This was a nested cohort study of patients enrolled within a previously published study determining predictors of disability-free survival. Spearman's correlation (rs) was calculated between four performance-based outcomes (the Functional Independence Measure [FIM], 6-min walk distance [6MWD], Functional Reach Test [FRT], and grip strength) that were collected during a home visit 6 months following their intensive care unit admission, with two commonly used PROMs (World Health Organization Disability Assessment Scale 2.0 12 Level [WHODAS 2.0] and EuroQol-5 Dimension-5 Level [EQ-5D-5L]) obtained via phone interview (via the PREDICT study) at the same time point. RESULTS: There were 38 PROMs obtained from 40 recruited patients (mean age = 59.8 ± 16 yrs, M:F = 24:16). All 40 completed the FIM and grip strength, 37 the 6MWD, and 39 the FRT. A strong correlation was found between the primary outcome of the WHODAS 2.0 with all performance-based outcomes apart from grip strength where a moderate correlation was identified. Although strong correlations were also established between the EQ-5D-5L utility score and the FIM, 6MWD, and FRT, it only correlated weakly with grip strength. The EQ-5D overall global health rating only had very weak to moderate correlations with the performance-based outcomes. CONCLUSION: The WHODAS 2.0 correlated stronger across multiple performance-based outcome measures of functional recovery and is recommended for use in survivors of critical illness.

Help-seeking for Intimate Partner Violence and Abuse: Experiences of Civilian Partners of UK Military Personnel.

There is evidence that Intimate Partner Violence and Abuse (IPVA) is more prevalent among military populations compared with civilian populations. However, there has been limited research into the help-seeking experiences of civilian victim-survivors who have experienced IPVA within relationships with military personnel. This qualitative study aimed to explore the experiences of, and barriers to, help-seeking for IPVA victimisation among civilian partners of military personnel in order to identify strategies to improve the management of IPVA both within the military and civilian sectors. The study adopted a descriptive cross-sectional study design and used qualitative research methods. One-to-one telephone interviews were conducted with civilian victim-survivors (n = 25) between January and August 2018. Interview transcripts were analysed using thematic analysis. Three superordinate themes were derived: (1) Drivers to help-seeking; (2) Barriers to help-seeking; and (3) Experiences of services. The findings indicate difficulties in help-seeking for IPVA among civilian partners of military personnel due to stigma, fear, dependency, poor understanding of IPVA, lack of appropriate and timely support, and a perceived lack of victim support. Difficulties in help-seeking were perceived by participants to be amplified by military culture, public perceptions of the military, military protection of personnel and the lack of coordination between civilian and military judicial services. This study reinforces the need for a military specific Domestic Abuse strategy, identifies vulnerable groups and highlights a need for both increased awareness and understanding of IPVA within civilian and military services in order to provide adequate victim protection.

Characteristics of young people accessing recently implemented Community Forensic Child and Adolescent Mental Health Services (F:CAMHS) in England: insights from national service activity data.

Children and young people in contact with forensic child and adolescent mental health services present with more complex needs than young people in the general population. Recent policy in child and adolescent mental health has led to the implementation of new workstreams and programmes to improve service provision. This research examines the characteristics of children and young people referred to recently commissioned Community Forensic Child and Adolescent Services (F:CAMHS) and service activity during the first 24 months of service. The study is a national cohort study to describe the population and investigate service provision and access across England. Secondary data on 1311 advice cases and 1406 referrals are included in analysis. Findings show that 71.9% of the sample had accessed mainstream CAMHS before their referral, 50.9% had experienced/witnessed multiple traumatic events and 58.4% of young people presented with multiple difficulties. The results of the study highlight the complexity of the cohort and a need for interagency trauma-informed working. This is the first study to describe the characteristics of children and young people referred to Community F:CAMHS and provides valuable information on pathways and needs to inform service policy and provision.

The Effect of Mobilization at 6 Months after Critical Illness - Meta-Analysis.

Mobilization at 6 Months After Critical IllnessThis report was a systemic review and meta-analysis of early mobilization in the intensive care unit. The authors found no significant effect on days alive and out of hospital; however, they report the possibility that it might increase mortality and adverse events.

Discovery and Optimization of Potent and Orally Available CTP Synthetase Inhibitors for Use in Treatment of Diseases Driven by Aberrant Immune Cell Proliferation.

Herein, we report the discovery of a first-in-class chemotype 2-(alkylsulfonamido)thiazol-4-yl)acetamides that act as pan-selective inhibitors of cytidine 5'-triphosphate synthetase (CTPS1/2), critical enzymes in the de novo pyrimidine synthesis pathway. Weak inhibitors identified from a high-throughput screening of 240K compounds have been optimized to a potent, orally active agent, compound 27, which has shown significant pharmacological responses at 10 mg/kg dose BID in a well-established animal model of inflammation.