Is a randomised controlled trial of take home naloxone distributed in emergency settings likely to be feasible and acceptable? Findings from a UK qualitative study exploring perspectives of people who use opioids and emergency services staff.

OBJECTIVE: Distribution of take-home naloxone (THN) by emergency services may increase access to THN and reduce deaths and morbidity from opioid overdose. As part of a feasibility study for a randomised controlled trial (RCT) of distribution of THN kits and education within ambulance services and Emergency Departments (EDs), we used qualitative methods to explore key stakeholders' perceptions of feasibility and acceptability of delivering the trial. METHODS: We undertook semi-structured interviews and focus groups with 26 people who use opioids and with 20 paramedics and ED staff from two intervention sites between 2019 and 2021. Interviews and focus groups were recorded, transcribed verbatim and analysed using Framework Analysis. RESULTS: People using opioids reported high awareness of overdose management, including personal experience of THN use. Staff perceived emergency service provision of THN as a low-cost, low-risk intervention with potential to reduce mortality, morbidity and health service use. Staff understood the trial aims and considered it compatible with their work. All participants supported widening access to THN but reported limited trial recruitment opportunities partly due to difficulties in consenting patients during overdose. Procedural problems, restrictive recruitment protocols, limited staff buy-in and patients already owning THN limited trial recruitment. Determining trial effectiveness was challenging due to high levels of alternative community provision of THN. CONCLUSIONS: Distribution of THN in emergency settings was considered feasible and acceptable for stakeholders but an RCT to establish the effectiveness of THN delivery is unlikely to generate further useful evidence due to difficulties in recruiting patients and assessing benefits.

Take-home naloxone administered in emergency settings: feasibility of intervention implementation in a cluster randomized trial.

BACKGROUND: Opioids kill more people than any other class of drug. Naloxone is an opioid antagonist which can be distributed in kits for peer administration. We assessed the feasibility of implementing a Take-home Naloxone (THN) intervention in emergency settings, as part of designing a definitive randomised controlled trial (RCT). METHODS: We undertook a clustered RCT on sites pairing UK Emergency Departments (ED) and ambulance services. At intervention sites, we recruited emergency healthcare practitioners to supply THN to patients presenting with opioid overdose or related condition, with recruitment across 2019-2021. We assessed feasibility of intervention implementation against four predetermined progression criteria covering site sign up and staff training; identification of eligible patients; issue of THN kits and Serious Adverse Events. RESULTS: At two intervention sites, randomly selected from 4, 299/687 (43.5%) clinical staff were trained (ED1 = 107, AS1 = 121, ED2 = 25, AS2 = 46). Sixty THN kits were supplied to eligible patients (21.7%) (n: ED1 = 36, AS1 = 4, ED2 = 16, AS2 = 4). Across sites, kits were not issued to eligible patients on a further 164 occasions, with reasons reported including: staff forgot (n = 136), staff too busy (n = 15), and suspected intentional overdose (n = 3), no kit available (n = 2), already given by drugs nurse (n = 4), other (n = 4). Staff recorded 626 other patients as ineligible but considered for inclusion, with reasons listed as: patient admitted to hospital (n = 194), patient absconded (n = 161) already recruited (n = 64), uncooperative or abusive (n = 55), staff not trained (n = 43), reduced consciousness level (n = 41), lack of capacity (n = 35), patient in custody (n = 21), other (n = 12). No adverse events were reported. CONCLUSION: Staff and patient recruitment were low and varied widely by site. This feasibility study did not meet progression criteria; a fully powered RCT is not planned. TRIAL REGISTRATION: ISRCTN13232859 (Registered 16/02/2018).

Recurrent Atherosclerotic Cardiovascular Disease Events Potentially Prevented with Guideline-Recommended Cholesterol-Lowering Therapy following Myocardial Infarction.

PURPOSE: Many adults with atherosclerotic cardiovascular disease (ASCVD) who are recommended to take a statin, ezetimibe and/or a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) by the 2018 American Heart Association/American College of Cardiology cholesterol guideline do not receive these medications. We estimated the percentage of recurrent ASCVD events potentially prevented with guideline-recommended cholesterol-lowering therapy following a myocardial infarction (MI) hospitalization. METHODS: We conducted simulations using data from US adults with government health insurance through Medicare or commercial health insurance in the MarketScan database. We used data from patients with an MI hospitalization in 2018-2019 to estimate the percentage receiving guideline-recommended therapy. We used data from patients with an MI hospitalization in 2013-2016 to estimate the 3-year cumulative incidence of recurrent ASCVD events (i.e., MI, coronary revascularization or ischemic stroke). The low-density lipoprotein cholesterol (LDL-C) reduction with guideline-recommended therapy was derived from trials of statins, ezetimibe and PCSK9i, and the associated ASCVD risk reduction was estimated from a meta-analysis by the Cholesterol-Lowering Treatment Trialists Collaboration. RESULTS: Among 279,395 patients with an MI hospitalization in 2018-2019 (mean age 75 years, mean LDL-C 92 mg/dL), 27.3% were receiving guideline-recommended cholesterol-lowering therapy. With current cholesterol-lowering therapy use, 25.3% (95%CI: 25.2%-25.4%) of patients had an ASCVD event over 3 years. If all patients were to receive guideline-recommended therapy, 19.8% (95%CI: 19.5%-19.9%) were estimated to have an ASCVD event over 3 years, representing a 21.6% (95%CI: 20.5%-23.6%) relative risk reduction. CONCLUSION: Implementation of guideline-recommended cholesterol-lowering therapy could prevent a substantial percentage of recurrent ASCVD events.

The Socio-Demographics and Health Service Use of Opioid Overdose Decedents in Wales: A Cross-Sectional Data Linkage Study.

BACKGROUND: Fatal opioid overdose is a significant public health problem with increasing incidence in developed countries. This study aimed to describe demographic and service user characteristics of decedents of opioid overdose in Wales to identify possible targets for behaviour modification and life-saving interventions. METHODS: A retrospective cross-sectional analysis was conducted of a census sample of opioid overdose-related deaths recorded between January 01, 2012, and October 11, 2018, in Wales. UK Office for National Statistics, Welsh Demographic Service, and National Health Service datasets were linked deterministically. Decedents' circumstances of death, demographic characteristics, residency, and health service use were characterized over 3 years prior to fatal overdose using descriptive statistics. RESULTS: In total, 638 people died of opioid overdose in Wales between January 01, 2012, and October 11, 2018, with an incidence rate of 3.04 per 100,000 people per year. Decedents were predominantly male (73%) and middle aged (median age 50 years). Fatal overdoses predominantly occurred in the community (93%) secondary to heroin (30%) or oxycodone derivative use (34%). In the 3 years prior to death, decedents changed address frequently (53%) but rarely moved far geographically. The majority of decedents had recently visited the emergency department (83%) or were admitted to the hospital (64%) prior to death. Only a minority had visited specialist drug services (32%). CONCLUSIONS: Deaths from opioid overdose typically occur in middle-aged men living peripatetic lifestyles. Victims infrequently visit specialist drug services but often attend emergency medical services. Emergency department-based interventions may therefore be important in prevention of opioid overdose fatalities in the community.

The contribution of cognitive behavioural factors to social anxiety in Parkinson's disease.

BACKGROUND: Social anxiety is prevalent in idiopathic Parkinson's disease but why this is, is not yet well understood. Social cognitions, safety-seeking behaviours and internally focused attention are all known to predict social anxiety in the general population. These associated factors have not yet been explored in idiopathic Parkinson's disease, where disease severity and motor symptoms might also influence the experience of social anxiety. AIMS: This study aimed to explore the relationship between cognitive behavioural factors and social anxiety in Parkinson's disease. METHOD: Using a cross-sectional design, 124 people with Parkinson's disease completed self-report questionnaires including measures of Parkinson's disease severity, social anxiety, negative social cognitions, safety-seeking behaviours, internally focused attention, anxiety and depression. RESULTS: The final regression model accounted for 71.6% of variance in social anxiety. Cognitive behavioural variables accounted for the largest magnitude of unique variance (43.5%). Sex, anxiety and depression accounted for 23.4%, and Parkinson non-motor symptom severity for 4.7%. Negative social cognitions and safety-seeking behaviours were statistically significant predictors, while an internal focus of attention was not. CONCLUSIONS: Social anxiety in Parkinson's disease is associated with negative social cognitions and safety-seeking behaviours. Findings indicate the need for further research into cognitive behavioural approaches to social anxiety in Parkinson's disease.

Experiential avoidance in adolescents with borderline personality disorder: comparison with a non-BPD psychiatric group and healthy controls.

Previous research has identified experiential avoidance (EA) as related to a host of adolescent internalizing and externalizing problems, as well as borderline personality disorder, suggesting that it is a crosscutting factor for adolescent psychopathology. It remains unclear whether EA differs among adolescents with BPD compared to adolescents with other psychiatric disorders and healthy adolescents. The aims of this study were to 1) examine EA in adolescents with BPD compared to non-BPD inpatient adolescents and healthy adolescents, and 2) to evaluate whether EA has a unique relationship to borderline pathology over and above internalizing and externalizing. Self-report measures of BPD features, EA, and psychopathology were completed by 692 adolescents (64.5% female, Mage= 15.20). This sample included a group of psychiatric inpatient youth (n = 197 BPD; n = 403 non-BPD) and a group of healthy adolescents (n = 92). Results revealed that EA differed significantly across all three groups, with the highest level of EA evidenced in adolescents who had BPD. Furthermore, there was a significant, unique association between BPD symptoms and EA over afnd above internalizing and externalizing pathology. These findings pinpoint EA as an important risk marker and possible target of prevention or intervention for adolescent BPD.

Racial Disparities in Sepsis-Related In-Hospital Mortality: Using a Broad Case Capture Method and Multivariate Controls for Clinical and Hospital Variables, 2004-2013.

OBJECTIVES: As sepsis hospitalizations have increased, in-hospital sepsis deaths have declined. However, reported rates may remain higher among racial/ethnic minorities. Most previous studies have adjusted primarily for age and sex. The effect of other patient and hospital characteristics on disparities in sepsis mortality is not yet well-known. Furthermore, coding practices in claims data may influence findings. The objective of this study was to use a broad method of capturing sepsis cases to estimate 2004-2013 trends in risk-adjusted in-hospital sepsis mortality rates by race/ethnicity to inform efforts to reduce disparities in sepsis deaths. DESIGN: Retrospective, repeated cross-sectional study. SETTING: Acute care hospitals in the Healthcare Cost and Utilization Project State Inpatient Databases for 18 states with consistent race/ethnicity reporting. PATIENTS: Patients diagnosed with septicemia, sepsis, organ dysfunction plus infection, severe sepsis, or septic shock. MEASUREMENTS AND MAIN RESULTS: In-hospital sepsis mortality rates adjusted for patient and hospital factors by race/ethnicity were calculated. From 2004 to 2013, sepsis hospitalizations for all racial/ethnic groups increased, and mortality rates decreased by 5-7% annually. Mortality rates adjusted for patient characteristics were higher for all minority groups than for white patients. After adjusting for hospital characteristics, sepsis mortality rates in 2013 were similar for white (92.0 per 1,000 sepsis hospitalizations), black (94.0), and Hispanic (93.5) patients but remained elevated for Asian/Pacific Islander (106.4) and "other" (104.7; p < 0.001) racial/ethnic patients. CONCLUSIONS: Our results indicate that hospital characteristics contribute to higher rates of sepsis mortality for blacks and Hispanics. These findings underscore the importance of ensuring that improved sepsis identification and management is implemented across all hospitals, especially those serving diverse populations.

The effects of multiple chronic conditions on hospitalization costs and utilization for ambulatory care sensitive conditions in the United States: a nationally representative cross-sectional study.

BACKGROUND: The presence of multiple chronic conditions (MCCs) complicates inpatient hospital care, leading to higher costs and utilization. Multimorbidity also complicates primary care, increasing the likelihood of hospitalization for ambulatory care sensitive conditions. The purpose of this study was to evaluate how MCCs relate to inpatient hospitalization costs and utilization for ambulatory care sensitive conditions. METHODS: The 2012 Agency for Healthcare Research and Quality (AHRQ) Healthcare Cost and Utilization Project (HCUP) State Inpatient Databases (SID) provided data to carry out a cross-sectional analysis of 1.43 million claims related to potentially preventable hospitalizations classified by the AHRQ Prevention Quality Indicator (PQI) composites. Categories of MCCs (0-1, 2-3, 4-5, and 6+) were examined in sets of acute, chronic, and overall PQIs. Multivariate models determined associations between categories of MCCs and 1) inpatient costs per stay, 2) inpatient costs per day, and 3) length of inpatient hospitalization. Negative binomial was used to model costs per stay and costs per day. RESULTS: The most common category observed was 2 or 3 chronic conditions (37.8 % of patients), followed by 4 or 5 chronic conditions (30.1 % of patients) and by 6+ chronic conditions (10.1 %). Compared with costs for patients with 0 or 1 chronic condition, hospitalization costs per stay for overall ambulatory care sensitive conditions were 19 % higher for those with 2 or 3 (95 % confidence interval [CI] 1.19-1.20), 32 % higher for those with 4 or 5 (95 % CI 1.31-1.32), and 31 % higher (95 % CI 1.30-3.32) for those with 6+ conditions. Acute condition stays were 11 % longer when 2 or 3 chronic conditions were present (95 % CI 1.11-1.12), 21 % longer when 4 or 5 were present (95 % CI 1.20-1.22), and 27 % longer when 6+ were present (95 % CI 1.26-1.28) compared with those with 0 or 1 chronic condition. Similar results were seen within chronic conditions. Associations between MCCs and total costs were driven by longer stays among those with more chronic conditions rather than by higher costs per day. CONCLUSIONS: The presence of MCCs increased inpatient costs for ambulatory care sensitive conditions via longer hospital stays.

The efficacy and safety of intravenous hydralazine for the treatment of hypertension in the hospitalized child.

BACKGROUND: Intravenous (IV) hydralazine is frequently used for the treatment of elevated blood pressure (BP) in hospitalized children. Its safety and efficacy have not been examined. METHODS: This is a retrospective chart review of IV hydralazine use in hospitalized children (birth to 17 years) over a 3-year period. Demographic data and data on adverse effects (AE), BP, and heart rate (HR) prior to and after each first dose were collected. RESULTS: The patient cohort comprised 110 children admitted to the hospital during the study period, of whom 77 received the recommended dose. Mean age of the children was 8.5 ± 5.4 years; 33 % were male, and 32.5 % were white. Pre-dose systolic and diastolic BP indexes were 1.3 and 1.2, respectively. The median reduction in systolic and diastolic BP was 8.5 and 11.5 %, respectively. Sixteen (21 %) children achieved a 25 % reduction in systolic or diastolic BP, and BP increased in 30 % of patients; 10 % of children had a BP of <95th percentile for age, sex, and height after one dose. Seven (9 %) children had a documented AE. HR increased by a median of 3.5 %. In the multivariable models examining percentage change in systolic and diastolic BP, male gender was significantly associated with a change in systolic BP. CONCLUSIONS: In hospitalized children, IV hydralazine was well tolerated, BP response was variable, and 21 % of the patients achieved a ≥25 % reduction of systolic or diastolic BP. Further studies are needed to compare the safety and efficacy of IV hydralazine to other short-acting antihypertensive agents.

Decreased heart rate variability is associated with increased transcranial Doppler velocities in children with sickle cell disease.

OBJECTIVE: To explore the relationship between 24-hour blood pressure (BP) variability, heart rate (HR) variability, and transcranial Doppler velocity (TCDV) in a cohort of pediatric sickle cell disease (SCD) patients. DESIGN, SETTING, AND PARTICIPANTS: This is a retrospective study of 11 children aged 8-18 years with SCD who previously underwent 24-hour ambulatory BP monitoring and TCDV measurements. INTERVENTIONS: Medical records were reviewed for TCDV and 24-hour ABP data. TCDV in the right and left middle cerebral artery were examined, and the highest velocity was recorded. HR and BP standard deviations were used as markers of variability. The relationships between daytime, nighttime, and 24-hour blood pressures and heart rate variability were determined. RESULTS: Mean age, body mass index and hemoglobin levels were 11.2 ± 3.0 years, 18.7 ± 3.4 kg/m2, and 9.1 ± 1.7 g/dL, respectively. Median transcranial Doppler velocity was 136cm/s (125-142). Decreased day, night, and 24-hour heart rate variability were significantly associated with increased transcranial Doppler velocity (R = -.69, P = .02; R = -.82 P =.002; R = -.66, P = .03, respectively). BP variability did not correlate with TCDV. Nighttime BP indexes were higher than daytime. CONCLUSIONS: In this small cohort, decreased heart rate variability assessed by the standard deviation of HR was associated with increased transcranial Doppler velocities in children with SCD. No correlation between measurements of BP variability and TCDV was found. Our study provides new information on heart rate and blood pressure variability and TCDV; a surrogate marker of stroke risk in sickle cell disease. Larger multicenter studies are needed to confirm our findings.

Plating Versus Intramedullary Nailing of OTA/AO 43C1 and C2 Intra-articular Distal Tibia Fractures: A Propensity Score and Multivariate Analysis.

OBJECTIVE: To compare rates of reduction loss, nonunion, and infection in intra-articular distal tibia fractures (IADTF) treated with limited open reduction internal fixation and intramedullary nailing (IMN) as compared to open reduction internal fixation with plate and screws (plate fixation [PF]). DESIGN: Retrospective review. SETTING: Level-I academic trauma center. PATIENT SELECTION CRITERIA: Patients age ≥ 18 with OTA/AO 43C1 and C2 IADTF treated with IMN or PF between 2013-2021. OUTCOME MEASURES AND COMPARISONS: Loss of reduction, surgical site infection (SSI), nonunion, and patient-reported outcomes (PROs) were compared for IMN versus PF treatments. RESULTS: One hundred ten patients met the inclusion criteria (IMN 33 and PF 77). There was no loss of reduction found. Seventeen nonunions (15% overall; IMN 4/33 and PF 13/77) and 13 SSIs (12% overall; IMN 2/33 and PF11/77) were identified. Despite several risk factors being identified for nonunion and SSI in bivariate analysis, only open fracture remained significant as a risk factor for both nonunion (odds ratio 0.09 for closed fracture, 95% confidence interval, 0.02-0.56, P = 0.009) and SSI (odds ratio 0.07 for closed fracture, 95% confidence interval, 0.06-0.26, P = 0.012) in the multivariate model. Propensity scoring based on presurgical variables was significantly different between patients who received IMN versus PF ( P = 0.03); however, logistic regression incorporating the propensity score revealed no significant association with nonunion and SSI. Adjusting for the propensity score, there remained no association comparing IMN versus PF with nonunion and SSI ( P = 0.54 and P = 0.17, respectively). There was also no difference in PROs between IMN and PF (physical function: P = 0.25 and pain interference: P = 0.21). CONCLUSIONS: Overall nonunion and SSI prevalence was 15% and 12%, respectively, in operatively treated OTA/AO 43C1 and C2 IADTF. An open fracture was a significant risk factor for nonunion and SSI. Metaphyseal fixation through IMN or PF did not affect loss of reduction, nonunion, SSI, or PROs. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

LOGAN-CV: A Prospective Study of a Multifaceted Intervention Targeting United States Clinicians to Improve Guideline-Based Management of Lipid-Lowering Therapy.

INTRODUCTION: The 2018 American Heart Association (AHA)/American College of Cardiology (ACC)/Multisociety blood cholesterol guidelines recommend clinicians consider adding non-statin therapy for patients with very high-risk (VHR) atherosclerotic cardiovascular disease (ASCVD) and low-density lipoprotein cholesterol (LDL-C) ≥ 70 mg/dl while receiving maximally tolerated statins. However, according to a recent study, only 17.1% of patients with established ASCVD received appropriate lipid-lowering therapy (LLT) intensification. Here, we describe the design of a prospective, 12-month study (LOGAN-CV) evaluating a multifaceted site-level intervention to enhance clinicians' adherence to guidelines to improve LDL-C levels for patients with VHR ASCVD. METHODS: Clinicians from up to ten research sites are eligible if they care for adult patients with ASCVD. Interventions include educational modules, a cloud-based performance platform providing clinicians a tailored summary of their LDL-C management performance, newsletters, periodic peer-to-peer calls, and pre- and post-intervention surveys evaluating knowledge, attitudes, and beliefs around LDL-C management, with additional interventions for clinicians demonstrating a lower readiness to make treatment decisions based on guideline recommendations. Patients with VHR ASCVD, defined as having recent myocardial infarction and LDL-C ≥ 70 mg/dl despite statin treatment, will be included in the study. Patient data will be collected from electronic medical records from baseline (clinician enrollment) through the 12-month intervention. The study started in October 2022, with anticipated completion in March 2024. PLANNED OUTCOMES: The change in proportion of patients with LDL-C < 70 mg/dl achieved at any time during the 12-month intervention (primary); LLT intensification, changes in guideline-aligned LDL-C testing and LLT titration over 12 months, and change in overall clinicians' knowledge, attitudes, and beliefs are key outcomes of interest. The LOGAN-CV study addresses a critical unmet need in LDL-C control in patients with VHR ASCVD and evaluates the effect of a multifaceted intervention targeting clinicians to improve their adherence to guidelines and consequently improve clinical outcomes for patients.

Low-Density Lipoprotein Cholesterol Testing Following Myocardial Infarction Hospitalization Among Medicare Beneficiaries.

Background: Low-density lipoprotein cholesterol (LDL-C) is used to guide lipid-lowering therapy after a myocardial infarction (MI). Lack of LDL-C testing represents a missed opportunity for optimizing therapy and reducing cardiovascular risk. Objectives: The purpose of this study was to estimate the proportion of Medicare beneficiaries who had their LDL-C measured within 90 days following MI hospital discharge. Methods: We conducted a retrospective cohort study of Medicare beneficiaries ≥66 years of age with an MI hospitalization between 2016 and 2020. The primary analysis used data from all beneficiaries with fee-for-service coverage and pharmacy benefits (532,767 MI hospitalizations). In secondary analyses, we used data from a 5% random sample of beneficiaries with fee-for-service coverage without pharmacy benefits (10,394 MI hospitalizations), and from beneficiaries with Medicare Advantage (176,268 MI hospitalizations). The proportion of beneficiaries who had their LDL-C measured following MI hospital discharge was estimated accounting for the competing risk of death. Results: In the primary analysis (mean age 76.9 years, 84.4% non-Hispanic White), 29.9% of beneficiaries had their LDL-C measured within 90 days following MI hospital discharge. Among Hispanic, Asian, non-Hispanic White, and non-Hispanic Black beneficiaries, the 90-day postdischarge LDL-C testing was 33.8%, 32.5%, 30.0%, and 26.0%, respectively. Postdischarge LDL-C testing within 90 days was highest in the Middle Atlantic (36.4%) and lowest in the West North Central (23.4%) U.S. regions. In secondary analyses, the 90-day postdischarge LDL-C testing was 26.9% among beneficiaries with fee-for-service coverage without pharmacy benefits, and 28.6% among beneficiaries with Medicare Advantage coverage. Conclusions: LDL-C testing following MI hospital discharge among Medicare beneficiaries was low.

Neurocognitive risk phenotyping to predict mood symptoms in adolescence.

Predicting mood disorders in adolescence is a challenge that motivates research to identify neurocognitive predictors of symptom expression and clinical profiles. This study used machine learning to test whether neurocognitive variables predicted future manic or anhedonic symptoms in two adolescent samples risk-enriched for lifetime mood disorders (Sample 1, n = 73, ages = 13-25, M [SD] = 19.22 [2.49] years, 68% lifetime mood disorder) or familial mood disorders (Sample 2, n = 154, ages = 13-21, M [SD] = 16.46 [1.95] years, 62% first-degree family history of mood disorder). Participants completed cognitive testing and functional magnetic resonance imaging at baseline, for behavioral and neural measures of reward processing and executive functioning. Next, participants completed a daily diary procedure for 8-16 weeks. Penalized mixed-effects models identified neurocognitive predictors of future mood symptoms and stress-reactive changes in mood symptoms. Results included the following. In both samples, adolescents showing ventral corticostriatal reward hyposensitivity and lower reward performance reported more severe stress-reactive anhedonia. Poorer executive functioning behavior was associated with heightened anhedonia overall in Sample 1, but lower stress-reactive anhedonia in both samples. In Sample 1, adolescents showing ventral corticostriatal reward hypersensitivity and poorer executive functioning reported more severe stress-reactive manic symptoms. Clustering analyses identified, and replicated, five neurocognitive subgroups. Adolescents characterized by neural or behavioral reward hyposensitivities together with average-to-poor executive functioning reported unipolar symptom profiles. Adolescents showing neural reward hypersensitivity together with poor behavioral executive functioning reported a bipolar symptom profile (Sample 1 only). Together, neurocognitive phenotypes may hold value for predicting symptom expression and profiles of mood pathology. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Emergency admission predictive risk stratification models: assessment of implementation consequences (PRISMATIC 2): protocol for a mixed methods study.

BACKGROUND: Emergency admissions are costly, increasingly numerous, and associated with adverse patient outcomes. Policy responses have included the widespread introduction of emergency admission risk stratification (EARS) tools in primary care. These tools generate scores that predict patients' risk of emergency hospital admission and can be used to support targeted approaches to improve care and reduce admissions. However, the impact of EARS is poorly understood and there may be unintended consequences. AIM: To assess effects, mechanisms, costs, and patient and healthcare professionals' views related to the introduction of EARS tools in England. DESIGN & SETTING: Quasi-experimental mixed methods design using anonymised routine data and qualitative methods. METHOD: We will apply multiple interrupted time series analysis to data, aggregated at former Clinical Commissioning Group level, to look at changes in emergency admission and other healthcare use following EARS introduction across England. We will investigate GP decision-making at practice level using linked general practice and secondary care data to compare case-mix, demographics, indicators of condition severity and frailty associated with emergency admissions before and after EARS introduction. We will undertake interviews (n~48) with GPs and healthcare staff to understand how patient care may have changed. We will conduct focus groups (n=2) and interviews (n~16) with patients to explore how they perceive that communication of individual risk scores might affect their experiences and health seeking behaviours. CONCLUSION: Findings will provide policymakers, healthcare professionals, and patients, with a better understanding of the effects, costs and stakeholder perspectives related to the introduction of EARS tools.

Persistence and Adherence to PCSK9 Inhibitor Monoclonal Antibodies Versus Ezetimibe in Real-World Settings.

INTRODUCTION: The cardiovascular disease risk reduction benefits of proprotein convertase subtilisin/kexin type 9 inhibitor monoclonal antibodies (PCSK9i mAb) and ezetimibe are dependent on remaining on treatment and being persistent and adherent. We estimated the percentage of patients on therapy, persistent and adherent at 182 and 365 days among US adults with health insurance who initiated a PCSK9i mAb (n = 16,588) or ezetimibe (n = 83,086) between July 2015 and December 2019. METHODS: Using pharmacy fill claims, being on therapy was defined as having a day of medication supply in the last 60 of 182 and 365 days following treatment initiation, being persistent was defined as not having a gap of 60 days or more between the last day of supply from one prescription fill and the next fill, and being adherent was defined by having medication available to take on ≥ 80% of the 182 and 365 days following treatment initiation. We estimated multivariable-adjusted risk ratios for being persistent and adherent comparing patients initiating PCSK9i mAb versus ezetimibe using Poisson regression. RESULTS: At 182 days following initiation, 80% and 68% were on therapy and 76% and 64% were persistent among patients who initiated a PCSK9i mAb and ezetimibe, respectively. Among patients who were on therapy and persistent at 182 days following initiation, 88% and 81% of those who initiated a PCSK9i mAb and ezetimibe, respectively, were on therapy at 365 days. Among those on therapy and persistent at 182 days following initiation, being persistent and being adherent at 365 days were each more common among PCSK9i mAb versus ezetimibe initiators (persistent: 82% versus 76%, multivariable-adjusted risk ratio 1.07; 95% confidence interval [CI] 1.06-1.08; adherent: 74% versus 71%, multivariable-adjusted risk ratio 1.02; 95% CI 1.01-1.03). CONCLUSIONS: These data suggest approaches to increase persistence and adherence to PCSK9i mAb and ezetimibe should be implemented prior to or within 182 days following treatment initiation.

The coding of telephone consultations in UK primary care databases: are we picking up all the calls?

OBJECTIVES: To examine the use of two coding systems used in the THIN UK primary care research database for the coding of telephone encounters between patient and healthcare professional in primary care. This is relevant to other research databases built on GP clinical systems. Consideration of telephone consultations was particularly important during the COVID-19 pandemic as remote interactions between patient and GP are more numerous than before and are likely to remain at a higher frequency. RESULTS: Telephone encounters could either be indicated by a consultation-type code or by a Read code. All three possible combinations (coded by one method, the other method and both) were in use. In 2014, 30% were coded by the consultation-type, 55% by Read codes and 15% by both. In contrast, in 2000, 77% were coded by the consultation-type, 21% by Read codes and 2% by both. This has important implications because national and regional consultation rates by GPs are often estimated from these research databases by looking only at the consultation-type codes and consequently many encounters will not be detected.

Unpacking reappraisal: a systematic review of fMRI studies of distancing and reinterpretation.

In recent decades, a substantial volume of work has examined the neural mechanisms of cognitive reappraisal. Distancing and reinterpretation are two frequently used tactics through which reappraisal can be implemented. Theoretical frameworks and prior evidence have suggested that the specific tactic through which one employs reappraisal entails differential neural and psychological mechanisms. Thus, we were motivated to assess the neural mechanisms of this distinction by examining the overlap and differentiation exhibited by the neural correlates of distancing (specifically via objective appraisal) and reinterpretation. We analyzed 32 published functional magnetic resonance imaging (fMRI) studies in healthy adults using multilevel kernel density analysis. Results showed that distancing relative to reinterpretation uniquely recruited right bilateral dorsolateral PFC (DLPFC) and left posterior parietal cortex, previously associated with mentalizing, selective attention and working memory. Reinterpretation relative to distancing uniquely recruited left bilateral ventrolateral PFC (VLPFC), previously associated with response selection and inhibition. Further, distancing relative to reinterpretation was associated with greater prevalence of bilateral amygdala attenuation during reappraisal. Finally, a behavioral meta-analysis showed efficacy for both reappraisal tactics. These results are consistent with prior theoretical models for the functional neural architecture of reappraisal via distancing and reinterpretation and suggest potential future applications in region-of-interest specification and neural network analysis in studies focusing on specific reappraisal tactics.

Amygdala and nucleus accumbens activation during reward anticipation moderates the association between life stressor frequency and depressive symptoms.

BACKGROUND: Life stressors confer risk for depressive symptoms, but individuals vary in the extent of their sensitivity to life stressors. One protective factor may be an individual's level of reward sensitivity, e.g., a stronger neurobiological response to environmental rewards may mitigate emotional responses to stressors. However, the nature of neurobiological reward sensitivity that corresponds with stress resilience is unknown. Further, this model is untested in adolescence, when life stressor frequency and depression increase. METHODS: We tested the hypothesis that stronger reward-related activation in the left and right nucleus accumbens (NAc), amygdala, and medial prefrontal cortex (mPFC) attenuates the strength of the stress-depression relation. We measured BOLD activation throughout Win and Lose blocks of a monetary reward task, as well as during anticipation and outcome phases of the task. Participants (N = 151, ages 13-19) were recruited to be stratified on risk for mood disorders to enhance variance in depressive symptoms. RESULTS: Activation during anticipation of rewards in the bilateral amygdala and NAc, but not mPFC, buffered the association between life stressors and depressive symptoms. This buffering effect was not found for reward outcome activation or activation across Win blocks. CONCLUSIONS: Results highlight the importance of reward anticipation activation of subcortical structures in attenuating the stress-depression link, suggesting that reward motivation may be a cognitive mechanism through which this stress buffering occurs.

High Nonunion and Amputations Rates With Either Early Intramedullary Nail Removal or Retention for Tibial Shaft Fracture-Related Infections.

OBJECTIVES: To compare debridement, antibiotics, and implant retention (DAIR) and intramedullary nail (IMN) removal with subsequent strategy for fracture stabilization in the treatment of tibia fracture-related infections (FRIs) occurring within 90 days of initial IMN placement. DESIGN: Retrospective case-control. SETTING: Four academic, Level 1 trauma centers. PATIENTS: Sixty-six patients who subsequently received unplanned operative treatment for FRI diagnosed within 90 days of initial tibia IMN. INTERVENTION: DAIR versus IMN removal pathways. MAIN OUTCOME MEASUREMENTS: Fracture union. RESULTS: Twenty-eight patients (42.4%) were treated with DAIR and 38 (57.6%) via IMN removal with subsequent strategy for fracture stabilization. Mean follow-up was 16.3 months. At final follow-up, ultimate bone healing was achieved in 75.8% (47/62), whereas 24.2% (15/62) had persistent nonunion or amputation. No significant difference was observed in ultimate bone healing ( P = 0.216) comparing DAIR and IMN removal. Factors associated with persistent nonunion or amputation were time from injury to initial IMN ( P < 0.001), McPherson systemic host grade B ( P = 0.046), and increasing open-fracture grade, with Gustilo-Anderson IIIB/IIIC fractures being the worst ( P = 0.009). Fewer surgeries after initial FRI treatment were positively associated with ultimate bone healing ( P = 0.029). CONCLUSIONS: Treatment of FRI within 90 days of tibial IMN with DAIR or IMN removal with subsequent strategy for fracture stabilization results in a high rate, nearly 1 in 4, of persistent nonunion or amputation, with neither appearing superior for improving bone healing outcomes. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.