Interactions of depression, anxiety, and sleep quality with menopausal symptoms on job satisfaction among middle-aged health workers in England: a STROBE-based analysis.

BACKGROUND: This study examined the association between menopausal symptoms and job satisfaction, and ascertained whether three psychosomatic factors (e.g., anxiety, depression, and sleep quality) interact with menopausal symptoms on job satisfaction. METHODS: A cross-sectional design with sensitivity analysis was adopted. The participants of the study were clinical health workers in England. Data from 154 health workers were analyzed with the hierarchical linear regression (HLR) analysis. RESULTS: There was a negative association between menopausal symptoms and job satisfaction (ß = -0.38; t = -4.81, p < 0.001), but this relationship became non-significant after adjusting for work stress, self-reported health, job tenure, and resilience at work. An interaction between menopausal symptoms and the psychosomatic factors was found. The strength of the negative association between menopausal symptoms and job satisfaction was weakened by sleep quality (ß = 0.05; t = 0.48; p > 0.05) but was strengthened by anxiety (ß = -0.22; t = -2.28; p < 0.05) and depression (ß = -0.24; t = -2.16; p < 0.05). CONCLUSION: Menopausal symptoms can be directly associated with lower job satisfaction and indirectly associated with lower job satisfaction through its interaction with depression and anxiety. Menopausal symptoms can weaken the positive association between sleep quality and job satisfaction.

Patient voices and student insights into LGBTQ+ healthcare: a call for equitable healthcare through medical education.

PURPOSE: Lesbian, gay, bisexual, transgender, queer, and other sexual and gender diverse (LGBTQ+) individuals have health needs specific to their identities. However, they face discrimination and cis-heteronormativity in most patient-provider interactions, which often translate into poor healthcare. Evidence suggests doctors are inadequately trained to care for LGBTQ+ patients. Medical students are well-placed as the future workforce to establish affirming behaviours. This study garners LGBTQ+ patients' healthcare experiences, where limited qualitative evidence exists, and explores whether students have insight into these experiences. METHOD: Thirty LGBTQ+ patients and twenty students, evenly divided between Singapore and the United Kingdom (UK), two legally and culturally different countries, consented to semi-structured interviews in 2022 to evaluate their LGBTQ+ healthcare perceptions. Thematic analysis was conducted using a collaborative, iterative process involving five investigators, with frequent auditing of data interpretation. RESULTS: Most patients described implicit biases with a lack of support and professionalism from doctors, hindering health outcomes. Patients experienced misgendering and a lack of recognition of sexual and gender diversity; students appreciated the need to acknowledge patient identity. Although perceptions surrounding certain themes were similar between patients and students in both countries, patients' voices on the complexity and dissatisfaction of gender-diverse care contrasted with students' lack of insight on these themes. Singapore patients were more concerned with sociolegal acceptance affecting health needs, whilst UK patients noted more nuanced barriers to healthcare. Although many students were unsure about specific health needs and perceived a lack of training, they expressed willingness to create an equitable healthcare environment. CONCLUSIONS: LGBTQ+ patients provided powerful narratives on discrimination surrounding their healthcare needs. To address these, medical students must be encouraged by healthcare educators to develop identity-affirming behaviours as future change-makers and challenge cis-heteronormative views. Alongside vital institutional changes tailored to each country, patients' and students' collective action would create meaningful educational opportunities to reach culture change.

An enhanced Eco1 retron editor enables precision genome engineering in human cells from a single-copy integrated lentivirus.

Retrons are a retroelement class found in diverse prokaryotes that can be adapted to augment CRISPR-Cas9 genome engineering technology to efficiently rewrite short stretches of genetic information in bacteria and yeast; however, efficiency in human cells has been limited by unknown factors. We identified non-coding RNA (ncRNA) instability and impaired Cas9 activity as major contributors to poor retron editor efficiency. We re-engineered the Eco1 ncRNA to incorporate an exoribonuclease-resistant RNA pseudoknot from the Zika virus 3' UTR and devised an RNA processing strategy using Csy4 ribonuclease to liberate the sgRNA and ncRNA. These modifications yielded a ncRNA with 5'- and 3'-end protection and an sgRNA with minimal 5' extension. This strategy increased steady-state ncRNA levels and rescued Cas9 activity leading to enhanced efficiency of the Eco1 retron editor in human cells. The enhanced Eco1 retron editor enabled the insertion of missense mutations in human cells from a single integrated lentivirus, thereby ensuring genotype-phenotype linkage over multiple cell divisions. This work reveals a previously unappreciated role for ncRNA stability in retron editor efficiency in human cells. Here we present an enhanced Eco1 retron editor that enables efficient introduction of missense mutations in human cells from a single heritable genome copy.

Recommendations for managing adults with chronic non-cancer pain in primary care: A systematic clinical guideline review.

RATIONALE: Chronic non-cancer pain (CNCP) is a leading driver of disability. Primary care clinicians treat most patients with CNCP. Yet, they are often unable to identify appropriate pain treatments, mainly due to concerns about the safety and effectiveness of available medications. Clinical practice guidelines (CPGs) can be useful tools to guide primary care clinicians in selecting pain treatments based on the best available evidence. OBJECTIVES: To undertake a systematic review of CPGs that address the management of adults with CNCP, regardless of underlying condition type, in primary care. METHOD: We systematically reviewed and synthesised current CPGs for managing adults with CNCP in primary care (2013-2023). We followed a stepwise systematic process to synthesise key CPG recommendations: extracted and analysed each recommendation, synthesised by compiling similar recommendations using a thematic analysis approach, and assessed the strength of CPG recommendations to create a final, unified set of recommendations. We focused on identifying CPGs containing recommendations on the following topics: (a) opioid pain management, (b) non-opioid pharmacological pain management, (c) non-pharmacological pain management, and (d) patient-centred communication around pain management, prevention, and organisation of care. RESULTS: We included 13 CPGs, 8 of which focused solely on use of opioids, emphasising the lack of long-term effectiveness and safety concerns, being mainly based on the expert consensus. As an exception, high-quality evidence recommended referring patients with suspected opioid use disorder to specialist addiction services for medication-assisted treatment. Recommendations for non-opioid pain management were often contradictory and based on the expert consensus. Patient-centred pain management combined with exercise-based interventions and psychological therapies are appropriate strategies for managing patients with CNCP. CONCLUSION: Most CPGs focused on opioid management, with contradictory recommendations for non-opioid management based on low-quality evidence. Additional research is needed to strengthen the evidence for using non-opioid and non-pharmacological interventions to manage patients with CNCP.

Iron Deficiency and Sleep/Wake Behaviors: A Scoping Review of Clinical Practice Guidelines-How to Overcome the Current Conundrum?

Current evidence suggests that iron deficiency (ID) plays a key role in the pathogenesis of conditions presenting with restlessness such as attention deficit hyperactivity disorder (ADHD) and restless legs syndrome (RLS). In clinical practice, ID and iron supplementation are not routinely considered in the diagnostic work-up and/or as a treatment option in such conditions. Therefore, we conducted a scoping literature review of ID guidelines. Of the 58 guidelines included, only 9 included RLS, and 3 included ADHD. Ferritin was the most frequently cited biomarker, though cutoff values varied between guidelines and depending on additional factors such as age, sex, and comorbidities. Recommendations surrounding measurable iron biomarkers and cutoff values varied between guidelines; moreover, despite capturing the role of inflammation as a concept, most guidelines often did not include recommendations for how to assess this. This lack of harmonization on the interpretation of iron and inflammation biomarkers raises questions about the applicability of current guidelines in clinical practice. Further, the majority of ID guidelines in this review did not include the ID-associated disorders, ADHD and RLS. As ID can be associated with altered movement patterns, a novel consensus is needed for investigating and interpreting iron status in the context of different clinical phenotypes.

Cost effectiveness of a GP delivered medication review to reduce polypharmacy and potentially inappropriate prescribing in older patients with multimorbidity in Irish primary care: the SPPiRE cluster randomised controlled trial.

BACKGROUND: Evidence on the cost effectiveness of deprescribing in multimorbidity is limited. OBJECTIVE: To investigate the cost effectiveness of a general practitioner (GP) delivered, individualised medication review to reduce polypharmacy and potentially inappropriate prescribing in older patients with multimorbidity in Irish primary care. METHODS: Within trial economic evaluation, from a healthcare perspective and based on a cluster randomised controlled trial with a 6 month follow up and 403 patients (208 Intervention and 195 Control) recruited between April 2017 and December 2019. Intervention GPs used the SPPiRE website which contained educational materials and a template to support a web-based individualised medication review. Control GPs delivered usual care. Incremental costs, quality adjusted life years (QALYs) generated using the EQ-5D-5L instrument, and expected cost effectiveness were estimated using multilevel modelling and multiple imputation techniques. Uncertainty was explored using parametric, deterministic and probabilistic methods. RESULTS: On average, the SPPiRE intervention was dominant over usual care, with non-statistically significant mean cost savings of €410 (95% confidence interval (CI): - 2211, 1409) and mean health gains of 0.014 QALYs (95% CI - 0.011, 0.039). At cost effectiveness threshold values of €20,000 and €45,000 per QALY, the probability of SPPiRE being cost effective was 0.993 and 0.988. Results were sensitive to missing data and data collection period. CONCLUSIONS: The study observed a pattern towards dominance for the SPPiRE intervention, with high expected cost effectiveness. Notably, observed differences in costs and outcomes were consistent with chance, and missing data and related uncertainty was non trivial. The cost effectiveness evidence may be considered promising but equivocal. TRIAL REGISTRATION: ISRCTN: 12752680, 20th October 2016.

Alcohol induces p53-mediated apoptosis in neural crest by stimulating an AMPK-mediated suppression of TORC1, p70/S6K, and ribosomal biogenesis.

Prenatal alcohol exposure is a leading cause of permanent neurodevelopmental disability and can feature distinctive craniofacial deficits that partly originate from the apoptotic deletion of craniofacial progenitors, a stem cell lineage called the neural crest (NC). We recently demonstrated that alcohol causes nucleolar stress in NC through its suppression of ribosome biogenesis (RBG) and this suppression is causative in their p53/MDM2-mediated apoptosis. Here, we show that this nucleolar stress originates from alcohol's activation of AMPK, which suppresses TORC1 and the p70/S6K-mediated stimulation of RBG. Alcohol-exposed cells of the pluripotent, primary cranial NC line O9-1 were evaluated with respect to their p70/S6K, TORC1, and AMPK activity. The functional impact of these signals with respect to RBG, p53, and apoptosis were assessed using gain-of-function constructs and small molecule mediators. Alcohol rapidly (<2hr) increased pAMPK, pTSC2, pRaptor, p-mTOR(S2446), and reduced both total and p-p70/S6K in NC cells. These changes persisted for at least 12hr to 18hr following alcohol exposure. Attenuation of these signals via gain- or loss-of-function approaches that targeted AMPK, p70/S6K, or TORC1 prevented alcohol's suppression of rRNA synthesis and the induction of p53-stimulated apoptosis. We conclude that alcohol induces ribosome dysbiogenesis and activates their p53/MDM2-mediated apoptosis via its activation of pAMPK, which in turn activates TSC2 and Raptor to suppress the TORC1-p70/S6K-mediated promotion of ribosome biogenesis. This represents a novel mechanism underlying alcohol's neurotoxicity and is consistent with findings that TORC1-p70/S6K networks are critical for cranial NC survival.

Association of latent class analysis-derived multimorbidity clusters with adverse health outcomes in patients with multiple long-term conditions: comparative results across three UK cohorts.

Background: It remains unclear how to meaningfully classify people living with multimorbidity (multiple long-term conditions (MLTCs)), beyond counting the number of conditions. This paper aims to identify clusters of MLTCs in different age groups and associated risks of adverse health outcomes and service use. Methods: Latent class analysis was used to identify MLTCs clusters in different age groups in three cohorts: Secure Anonymised Information Linkage Databank (SAIL) (n = 1,825,289), UK Biobank (n = 502,363), and the UK Household Longitudinal Study (UKHLS) (n = 49,186). Incidence rate ratios (IRR) for MLTC clusters were computed for: all-cause mortality, hospitalisations, and general practice (GP) use over 10 years, using <2 MLTCs as reference. Information on health outcomes and service use were extracted for a ten year follow up period (between 01st Jan 2010 and 31st Dec 2019 for UK Biobank and UKHLS, and between 01st Jan 2011 and 31st Dec 2020 for SAIL). Findings: Clustering MLTCs produced largely similar results across different age groups and cohorts. MLTC clusters had distinct associations with health outcomes and service use after accounting for LTC counts, in fully adjusted models. The largest associations with mortality, hospitalisations and GP use in SAIL were observed for the "Pain+" cluster in the age-group 18-36 years (mortality IRR = 4.47, hospitalisation IRR = 1.84; GP use IRR = 2.87) and the "Hypertension, Diabetes & Heart disease" cluster in the age-group 37-54 years (mortality IRR = 4.52, hospitalisation IRR = 1.53, GP use IRR = 2.36). In UK Biobank, the "Cancer, Thyroid disease & Rheumatoid arthritis" cluster in the age group 37-54 years had the largest association with mortality (IRR = 2.47). Cardiometabolic clusters across all age groups, pain/mental health clusters in younger groups, and cancer and pulmonary related clusters in older age groups had higher risk for all outcomes. In UKHLS, MLTC clusters were not significantly associated with higher risk of adverse outcomes, except for the hospitalisation in the age-group 18-36 years. Interpretation: Personalising care around MLTC clusters that have higher risk of adverse outcomes may have important implications for practice (in relation to secondary prevention), policy (with allocation of health care resources), and research (intervention development and targeting), for people living with MLTCs. Funding: This study was funded by the National Institute for Health and Care Research (NIHR; Personalised Exercise-Rehabilitation FOR people with Multiple long-term conditions (multimorbidity)-NIHR202020).

Childhood adversity and mental health admission patterns prior to young person suicide (CHASE): a case-control 36 year linked hospital data study, Scotland UK 1981-2017.

BACKGROUND: Childhood adversity is associated with increased later mental health problems and suicidal behaviour. Opportunities for earlier healthcare identification and intervention are needed. AIM: To determine associations between hospital admissions for childhood adversity and mental health in children who later die by suicide. METHOD: Population-based longitudinal case-control study. Scottish in-patient general and psychiatric records were summarised for individuals born 1981 or later who died by suicide between 1991 and 2017 (cases), and matched controls (1:10), for childhood adversity and mental health (broadly defined as psychiatric diagnoses and general hospital admissions for self-harm and substance use). RESULTS: Records were extracted for 2477 'cases' and 24 777 'controls'; 2106 cases (85%) and 13 589 controls (55%) had lifespan hospitalisations. Mean age at death was 23.7; 75.9% were male. Maltreatment or violence-related childhood adversity codes were recorded for 7.6% cases aged 10-17 (160/2106) versus 2.7% controls (371/13 589), odds ratio = 2.9 (95% CI, 2.4-3.6); mental health-related admissions were recorded for 21.7% cases (458/2106), versus 4.1% controls (560/13 589), odds ratio = 6.5 (95% CI, 5.7-7.4); 80% of mental health admissions were in general hospitals. Using conditional logistic models, we found a dose-response effect of mental health admissions <18y, with highest adjusted odds ratio (aOR) for three or more mental health admissions: aORmale = 8.17 (95% CI, 5.02-13.29), aORfemale = 15.08 (95% CI, 8.07-28.17). We estimated that each type of childhood adversity multiplied odds of suicide by aORmale = 1.90 (95% CI, 1.64-2.21), aORfemale = 2.65 (95% CI, 1.94-3.62), and each mental health admission by aORmale = 2.06 (95% CI, 1.81-2.34), aORfemale = 1.78 (95% CI, 1.50-2.10). CONCLUSIONS: Our lifespan study found that experiencing childhood adversity (primarily maltreatment or violence-related admissions) or mental health admissions increased odds of young person suicide, with highest odds for those experiencing both. Healthcare practitioners should identify and flag potential 'at-risk' adolescents to prevent future suicidal acts, especially those in general hospitals.

Revision of an Adult Burn Center's Resuscitation Guideline Leads to Lower Resuscitation Requirements.

In 2018, the institutional burn resuscitation guideline was updated to remove the use of high-dose ascorbic acid (HDAA) therapy, to lower 24-hour resuscitation fluid estimations from 4 to 2 mL/kg/TBSA, and to optimize guidance around appropriate colloid resuscitation. This retrospective study compared the incidence of a composite safety outcome (acute kidney injury, or intra-abdominal hypertension requiring intervention) between the pre-guideline update to post-guideline update. Secondarily, 24-hour resuscitation volumes, hourly urine output, vasopressor use, and mechanical ventilation duration were compared as well. The composite safety outcome was similar between the 2 groups (40% vs 29%; p=0.27), but the post-group showed significantly lower 24-hour resuscitation volumes (3.74 mL/kg/TBSA vs 2.94 mL/kg/TBSA; p<0.01), as well as lower urine output (1.26 mL/kg/hr vs 0.75 mL/kg/hr; p<0.01). There was no difference between the groups with respect to vasopressor use, mechanical ventilation duration, or mortality. This study suggests that a simplified resuscitation protocol without HDAA, combined with a lower starting fluid rate led to significantly lower 24-hour resuscitation volumes without an increase in adverse safety events.

Exposure to Violence and Mental Health Outcomes Among Pre-schoolers in a South African Birth Cohort.

Little is known about the relationship between violence exposure and mental health in preschoolers living in low- and middle-income countries (LMICs). Multiple regression analyses investigated associations between violence exposure and mental health in the Drakenstein Child Health Study (N = 978), a South African birth cohort. Lifetime violence exposure was assessed at age 4.5 years using the parent-report Child Exposure to Community Violence Checklist (CECV). Mental health was assessed at age 5 years using the Child Behaviour Checklist (CBCL 1.5-5). Eighty-three percent of the children were exposed to some form of violence. Internalising and externalising behaviours were positively associated with overall violence exposure (ß per one unit change in the overall score = 0.55 [0.16, 0.94] and ß = 0.53 [0.23, 0.84], respectively), domestic victimisation (ß per one unit change in the subscore = 1.28 [0.28, 2.27]; ß = 1.14 [0.37, 1.90]) and witnessing community violence (ß = 0.77 [0.15, 1.39]; ß = 0.68 [0.19, 1.18]). There was a positive association between polyvictimisation and externalising (ß = 1.02 [0.30, 1.73]) but not internalising (ß = 0.87 [-0.06, 1.80]) behaviour problems. Evidence for an association of witnessing domestic violence with internalising (ß = 0.63 [-0.97, 2.24]) or externalising (ß = 1.23 [-0.04, 2.50]) behaviours was less robust. There was no association between community victimisation and internalising or externalising behaviours (ß = 0.72 [-1.52, 2.97; ß = 0.68 [ -1.06, 2.41]). Observations highlight the risk for mental health problems among preschoolers living in high-violence contexts and emphasize the need for early interventions.

Critical care pharmacist perspectives on optimal practice models and prioritization of professional activities: A cross-sectional survey.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Critical care pharmacists (CCPs) are essential members of the multidisciplinary critical care team. Professional activities of the CCP are outlined in a 2020 position paper on critical care pharmacy services. This study looks to characterize CCP perspectives for priorities in optimizing pharmacy practice models and professional activities. METHODS: This was a cross-sectional survey conducted from July 24 to September 20, 2023. A 41-question survey instrument was developed to assess 7 domains: demographics, CCP resource utilization, patient care, quality improvement, research and scholarship, training and education, and professional development. This voluntary survey was sent to members of the American College of Clinical Pharmacy's Critical Care Practice and Research Network. The survey was open for a total of 6 weeks. RESULTS: There was a response rate of 20.7% (332 of 1,605 invitees), with 66.6% of respondents (n = 221) completing at least 90% of the survey questions. Most respondents were clinical specialists (58.2%) and/or practiced at an academic medical center (58.5%). Direct patient care, quality improvement and medication safety, and teaching and precepting were identified as the CCP activities of highest importance to CCPs. The CCP-to-patient ratios considered ideal were 1:11-15 (selected by 49.8% of respondents) and 1:16-20 (33.9% of respondents). The ideal percentage of time dedicated to direct patient care activities, as identified by survey respondents, was 50% (interquartile range, 40-50). CONCLUSION: These findings highlight the professional activities viewed as having the highest priority by CCPs. Future research is needed to define optimal CCP practice models for the delivery of patient care in real-world settings.

Deprescribing interventions in older adults: An overview of systematic reviews.

OBJECTIVE: The growing deprescribing field is challenged by a lack of consensus around evidence and knowledge gaps. The objective of this overview of systematic reviews was to summarize the review evidence for deprescribing interventions in older adults. METHODS: 11 databases were searched from 1st January 2005 to 16th March 2023 to identify systematic reviews. We summarized and synthesized the results in two steps. Step 1 summarized results reported by the included reviews (including meta-analyses). Step 2 involved a narrative synthesis of review results by outcome. Outcomes included medication-related outcomes (e.g., medication reduction, medication appropriateness) or twelve other outcomes (e.g., mortality, adverse events). We summarized outcomes according to subgroups (patient characteristics, intervention type and setting) when direct comparisons were available within the reviews. The quality of included reviews was assessed using A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR 2). RESULTS: We retrieved 3,228 unique citations and assessed 135 full-text articles for eligibility. Forty-eight reviews (encompassing 17 meta-analyses) were included. Thirty-one of the 48 reviews had a general deprescribing focus, 16 focused on specific medication classes or therapeutic categories and one included both. Twelve of 17 reviews meta-analyzed medication-related outcomes (33 outcomes: 25 favored the intervention, 7 found no difference, 1 favored the comparison). The narrative synthesis indicated that most interventions resulted in some evidence of medication reduction while for other outcomes we found primarily no evidence of an effect. Results were mixed for adverse events and few reviews reported adverse drug withdrawal events. Limited information was available for people with dementia, frailty and multimorbidity. All but one review scored low or critically low on quality assessment. CONCLUSION: Deprescribing interventions likely resulted in medication reduction but evidence on other outcomes, in particular relating to adverse events, or in vulnerable subgroups or settings was limited. Future research should focus on designing studies powered to examine harms, patient-reported outcomes, and effects on vulnerable subgroups. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020178860.

Diagnostic Accuracy of 18F-Prostate Specific Membrane Antigen (PSMA) PET/CT Radiotracers in Staging and Restaging of Patients With High-Risk Prostate Cancer or Biochemical Recurrence: An Overview of Reviews.

The aim of this overview was to consolidate existing evidence syntheses and provide a comprehensive overview of the evidence for 18F-prostate specific membrane antigen (PSMA) PET/CT in the staging of high-risk prostate cancer and restaging after biochemical recurrence. An overview of reviews was performed and reported in line with the preferred reporting items for overview of reviews (PRIOR) statement and synthesis without meta-analysis (SWiM) reporting guidelines. A comprehensive database and grey literature search were conducted up to July 18, 2023. Systematic reviews were assessed using the risk of bias in systematic reviews (ROBIS) tool. The certainty of the evidence was assessed using grading of recommendations, assessment, development and evaluations (GRADE). 11 systematic reviews were identified; 10 were at high or unclear risk of bias. Evidence reported on a per-patient, per-lymph node, and per-lesion basis for sensitivity, specificity and overall accuracy was identified. There was a lack of data on dose, adverse events and evidence directly comparing 18F-PSMA PET/CT to other imaging modalities. Evidence with moderate to very low certainty indicated high sensitivity, specificity and accuracy of 18F-PSMA PET/CT in patients with high-risk prostate cancer and biochemical recurrence. There was considerably lower certainty evidence and greater variability in effect estimates for outcomes for the combined intermediate/high-risk cohort. While evidence gaps remain for some outcomes, and most systematic reviews were at high or unclear risk of bias, the current evidence base is broadly supportive of 18F-PSMA PET/CT imaging in the staging and restaging of patients with high-risk prostate cancer and biochemical recurrence.

An exploratory randomised trial investigating feasibility, potential impact and cost effectiveness of link workers for people living with multimorbidity attending general practices in deprived urban communities.

BACKGROUND: Social prescribing link workers are non-health or social care professionals who connect people with psychosocial needs to non-clinical community supports. They are being implemented widely, but there is limited evidence for appropriate target populations or cost effectiveness. This study aimed to explore the feasibility, potential impact on health outcomes and cost effectiveness of practice-based link workers for people with multimorbidity living in deprived urban communities. METHODS: A pragmatic exploratory randomised trial with wait-list usual care control and blinding at analysis was conducted during the COVID 19 pandemic (July 2020 to January 2021). Participants had two or more ongoing health conditions, attended a general practitioner (GP) serving a deprived urban community who felt they may benefit from a one-month practice-based social prescribing link worker intervention.. Feasibility measures were recruitment and retention of participants, practices and link workers, and completion of outcome data. Primary outcomes at one month were health-related quality of life (EQ-5D-5L) and mental health (HADS). Potential cost effectiveness from the health service perspective was evaluated using quality adjusted life years (QALYs), based on conversion of the EQ-5D-5L and ICECAP-A capability index to utility scoring. RESULTS: From a target of 600, 251 patients were recruited across 13 general practices. Randomisation to intervention (n = 123) and control (n = 117) was after baseline data collection. Participant retention at one month was 80%. All practices and link workers (n = 10) were retained for the trial period. Data completion for primary outcomes was 75%. There were no significant differences identified using mixed effects regression analysis in EQ-5D-5L (MD 0.01, 95% CI -0.07 to 0.09) or HADS (MD 0.05, 95% CI -0.63 to 0.73), and no cost effectiveness advantages. A sensitivity analysis that considered link workers operating at full capacity in a non-pandemic setting, indicated the probability of effectiveness at the €45,000 ICER threshold value for Ireland was 0.787 using the ICECAP-A capability index. CONCLUSIONS: While the trial under-recruited participants mainly due to COVID-19 restrictions, it demonstrates that robust evaluations and cost utility analyses are possible. Further evaluations are required to establish cost effectiveness and should consider using the ICE-CAP-A wellbeing measure for cost utility analysis. REGISTRATION: This trial is registered on ISRCTN. TITLE: Use of link workers to provide social prescribing and health and social care coordination for people with complex multimorbidity in socially deprived areas. TRIAL ID: ISRCTN10287737. Date registered 10/12/2019. Link: https://www.isrctn.com/ISRCTN10287737.

Alcohol exposure suppresses ribosome biogenesis and causes nucleolar stress in cranial neural crest cells.

Prenatal alcohol exposure (PAE) causes cognitive impairment and a distinctive craniofacial dysmorphology, due in part to apoptotic losses of the pluripotent cranial neural crest cells (CNCs) that form facial bones and cartilage. We previously reported that PAE rapidly represses expression of >70 ribosomal proteins (padj = 10-E47). Ribosome dysbiogenesis causes nucleolar stress and activates p53-MDM2-mediated apoptosis. Using primary avian CNCs and the murine CNC line O9-1, we tested whether nucleolar stress and p53-MDM2 signaling mediates this apoptosis. We further tested whether haploinsufficiency in genes that govern ribosome biogenesis, using a blocking morpholino approach, synergizes with alcohol to worsen craniofacial outcomes in a zebrafish model. In both avian and murine CNCs, pharmacologically relevant alcohol exposure (20mM, 2hr) causes the dissolution of nucleolar structures and the loss of rRNA synthesis; this nucleolar stress persisted for 18-24hr. This was followed by reduced proliferation, stabilization of nuclear p53, and apoptosis that was prevented by overexpression of MDM2 or dominant-negative p53. In zebrafish embryos, low-dose alcohol or morpholinos directed against ribosomal proteins Rpl5a, Rpl11, and Rps3a, the Tcof homolog Nolc1, or mdm2 separately caused modest craniofacial malformations, whereas these blocking morpholinos synergized with low-dose alcohol to reduce and even eliminate facial elements. Similar results were obtained using a small molecule inhibitor of RNA Polymerase 1, CX5461, whereas p53-blocking morpholinos normalized craniofacial outcomes under high-dose alcohol. Transcriptome analysis affirmed that alcohol suppressed the expression of >150 genes essential for ribosome biogenesis. We conclude that alcohol causes the apoptosis of CNCs, at least in part, by suppressing ribosome biogenesis and invoking a nucleolar stress that initiates their p53-MDM2 mediated apoptosis. We further note that the facial deficits that typify PAE and some ribosomopathies share features including reduced philtrum, upper lip, and epicanthal distance, suggesting the facial deficits of PAE represent, in part, a ribosomopathy.

Defining the "ideal state": A primer on critical care pharmacy practice models.

PURPOSE: Critical care pharmacists (CCPs) have been clearly established as value-added members of the interprofessional team, and their contributions positively impact patient outcomes in the intensive care unit (ICU). Despite this, not every critically ill patient in the US receives care from a CCP and the model through which CCPs practice is variable, which has important implications. The purpose of this primer is to review current CCP models and discuss elements of the optimal CCP practice model. SUMMARY: Current CCP practice models are defined, including the drug processing and dispensing model, clinical pharmacy specialist model, integrated pharmacy generalist model, and hybrid model, as well as unit-based vs service-based models. The optimal CCP practice model considers the Triple Domain of CCP workload, which includes direct patient care, indirect patient care, and professional service. Elements of the ideal CCP practice model including 24/7/365 CCP services, unit- vs service-based models, prescriptive authority, operational support, and CCP-to-patient ratio are discussed. Other vital elements include dedicated offline time, use of appropriate workload metrics, development of career ladders, opportunities for professional development, and providing wellness resources. The ideal CCP practice model must also be considered through the lens of the patient and medical team, the CCP, the institution, and professional organizations. Strategies for optimizing current CCP practice models are provided, and application of optimal CCP practice model elements is explored through 5 case studies. CONCLUSION: The optimal CCP practice model includes multiple elements and incorporates the viewpoints of patients, providers, CCPs, institutions, and professional organizations; this model will increase access of all ICU patients to CCPs, enhance the scope of CCP cognitive services, and ensure the economic sustainability of CCP practice while establishing CCP involvement in activities outside of patient care and in professional service.

Exploring social media influences on vaccine decision-making in parents: a netnography.

Background: Immunization is one of the most significant health initiatives of recent times. Despite this, vaccine hesitancy is increasing and was listed as one of the top 10 threats to global health by the World Health Organization in 2019. A major factor associated with vaccine hesitancy is thought to be the viral spread of misinformation by a small but active anti-vaccination movement. Objectives: The purpose of this study was to explore the influences of social media on vaccine decision-making in parents. Design: This study is part of a larger body of research that explored vaccine decision-making in parents. Other methods included were an online survey and semi-structured interviews. This study investigated the influence of cyberculture on parents in an online environment. Method: This study employed netnography, a form of qualitative inquiry with its roots in ethnography as methodology and a purpose-designed Facebook page as the means of exploring a purpose-designed online community with a particular focus on the culture, belief systems and influences present. Both manual and computer-assisted thematic analyses were used to analyse the data obtained. Results: Three key themes were identified in this study. These included vaccine safety concerns, the emotional debate and COVID-19-specific issues. The results indicated the presence of strong anti-vaccination sentiment combined with an 'infodemic' of conspiracy theories, misinformation and vitriol with the potential to negatively impact parents seeking immunization information. Conclusion: Given the popularity and accessibility of social media and the ready access to misinformation present online, it is evident that parental vaccine decision-making may be impacted adversely. Therefore, it is important that healthcare professionals are aware of this and provide adequate and timely education prior to parents seeking information on social media.

Exploring the influence of social media on vaccine decision-making in parents: a netnography This research explored the impact of Facebook interactions on the vaccine decision-making of parents.

A common data model for the standardization of intensive care unit medication features.

Objective: Common data models provide a standard means of describing data for artificial intelligence (AI) applications, but this process has never been undertaken for medications used in the intensive care unit (ICU). We sought to develop a common data model (CDM) for ICU medications to standardize the medication features needed to support future ICU AI efforts. Materials and Methods: A 9-member, multi-professional team of ICU clinicians and AI experts conducted a 5-round modified Delphi process employing conference calls, web-based communication, and electronic surveys to define the most important medication features for AI efforts. Candidate ICU medication features were generated through group discussion and then independently scored by each team member based on relevance to ICU clinical decision-making and feasibility for collection and coding. A key consideration was to ensure the final ontology both distinguished unique medications and met Findable, Accessible, Interoperable, and Reusable (FAIR) guiding principles. Results: Using a list of 889 ICU medications, the team initially generated 106 different medication features, and 71 were ranked as being core features for the CDM. Through this process, 106 medication features were assigned to 2 key feature domains: drug product-related (n = 43) and clinical practice-related (n = 63). Each feature included a standardized definition and suggested response values housed in the electronic data library. This CDM for ICU medications is available online. Conclusion: The CDM for ICU medications represents an important first step for the research community focused on exploring how AI can improve patient outcomes and will require ongoing engagement and refinement.

Meeting the need for effective and standardized neonatology training: a pan-European Master's Curriculum.

Neonatology is a pediatric sub-discipline focused on providing care for newborn infants, including healthy newborns, those born prematurely, and those who present with illnesses or malformations requiring medical care. The European Training Requirements (ETR) in Neonatology provide a framework for standardized quality and recognition of equality of training throughout Europe. The latest ETR version was approved by the Union of European Medical Specialists (UEMS) in April 2021. Here, we present the curriculum of the European School of Neonatology Master of Advanced Studies (ESN MAS), which is based on the ETR in Neonatology and aims to provide a model for effective and standardized training and education in neonatal medicine. We review the history and theory that form the foundation of contemporary medical education and training, provide a literature review on best practices for medical training, pediatric training, and neonatology training specifically, including educational frameworks and evidence-based systems of evaluation. The ESN MAS Curriculum is then evaluated in light of these best practices to define its role in meeting the need for a standardized empirically supported neonatology training curriculum for physicians, and in the future for nurses, to improve the quality of neonatal care for all infants. IMPACT STATEMENT: A review of the neonatology training literature was conducted, which concluded that there is a need for standardized neonatology training across international contexts to keep pace with growth in the field and rapidly advancing technology. This article presents the European School of Neonatology Master of Advanced Studies in Neonatology, which is intended to provide a standardized training curriculum for pediatricians and nurses seeking sub-specialization in neonatology. The curriculum is evaluated in light of best practices in medical education, neonatology training, and adult learning theory.