Pharmacist-driven outreach initiative to increase prescribing of sodium-glucose cotransporter-2 inhibitors in eligible VHA patients with chronic kidney disease: a study protocol.

BACKGROUND: Patients with chronic kidney disease (CKD) are at increased risk for multiple adverse events, several of which have been proven to be less likely with the use of sodium-glucose cotransporter-2 inhibitors (SGLT2i). As a result, guidelines now recommend SGLT2i be given to those with mild to moderate CKD and type 2 diabetes. The objective of this study is to evaluate if a pharmacist-driven SGLT2i prescribing initiative among eligible patients with CKD and diabetes within the VA could more rapidly improve the adoption of SGLT2i via a pragmatic approach aligned with learning health systems. METHODS: Eligible patients will be identified through an established VA diabetes dashboard. Veterans with an odd social security number (SSN), which is effectively a random number, will be the intervention group. Those with even SSNs will serve as the control while awaiting a second iteration of the same interventional program. The intervention will be implemented in a rolling fashion across one Veterans Integrated Service Network. Our primary outcome is initiation of an SGLT2i. Secondary outcomes will include medication adherence and safety-related outcomes. DISCUSSION: This project tests the impact of a pharmacist-driven medication outreach initiative as a strategy to accelerate initiation of SGLT2i. The results of this work will not only illustrate the effectiveness of this strategy for SGLT2is but may also have implications for increasing other guideline-concordant care. Furthermore, the utilization of SSNs to select Veterans for the first wave of this program has created a pseudo-randomized interventional trial supporting a pragmatic learning health system approach. TRIAL REGISTRATION: ISRCTN12374636.

Clusters Based on Within-Treatment Symptom Trajectories as Predictors of Dropout in Treatment for Posttraumatic Stress Disorder and Substance Use Disorder.

Objective: Dropout rates are high in treatments for co-occurring posttraumatic stress disorder (PTSD) and substance use disorders (SUDs). We examined dropout predictors in PTSD-SUD treatment. Methods: Participants were 183 veterans receiving integrated or phased motivational enhancement therapy and prolonged exposure. Using survival models, we examined demographics and symptom trajectories as dropout predictors. Using latent trajectory analysis, we incorporated clusters based on symptom trajectories to improve dropout prediction. Results: Hispanic ethnicity (integrated arm), Black or African American race (phased arm), and younger age (phased arm) predicted dropout. Clusters based on PTSD and substance use trajectories improved dropout prediction. In integrated treatment, participants with consistently-high use and low-and-improving use had the highest dropout. In phased treatment, participants with the highest and lowest PTSD symptoms had lower dropout; participants with the lowest substance use had higher dropout. Conclusions: Identifying within-treatment symptom trajectories associated with dropout can help clinicians intervene to maximize outcomes. ClinicalTrials.gov Identifier: NCT01211106.

Bilirubin-associated single nucleotide polymorphism (SNP) and respiratory health outcomes: a mendelian randomization study.

BACKGROUND: Observational studies have shown an association between higher bilirubin levels and improved respiratory health outcomes. Targeting higher bilirubin levels has been proposed as a novel therapeutic strategy in COPD. However, bilirubin levels are influenced by multiple intrinsic and extrinsic factors, and these observational studies are prone to confounding. Genetic analyses are one approach to overcoming residual confounding in observational studies. OBJECTIVES: To test associations between a genetic determinant of bilirubin levels and respiratory health outcomes. METHODS: COPDGene participants underwent genotyping at the baseline visit. We confirmed established associations between homozygosity for rs6742078 and higher bilirubin, and between higher bilirubin and decreased risk of acute respiratory events within this cohort. For our primary analysis, we used negative binomial regression to test associations between homozygosity for rs6742078 and rate of acute respiratory events. RESULTS: 8,727 participants (n = 6,228 non-Hispanic white and 2,499 African American) were included. Higher bilirubin was associated with decreased rate of acute respiratory events [incidence rate ratio (IRR) 0.85, 95% CI 0.75 to 0.96 per SD increase in bilirubin intensity]. We did not find significant associations between homozygosity for rs6742078 and acute respiratory events (IRR 0.94, 95% CI 0.70 to 1.25 for non-Hispanic white and 1.09, 95% CI 0.91 to 1.31 for African American participants). CONCLUSIONS: A genetic determinant of higher bilirubin levels was not associated with better respiratory health outcomes. These results do not support targeting higher bilirubin levels as a therapeutic strategy in COPD.

Simple Bayesian models for missing binary outcomes in randomized controlled trials.

Missing outcomes are commonly encountered in randomized controlled trials (RCT) involving human subjects and present a risk for substantial bias in the results of a complete case analysis. While response rates for RCTs are typically high there is no agreed upon universal threshold under which the amount of missing data is deemed to not be a threat to inference. We focus here on binary outcomes that are possibly missing not at random, that is, the value of the outcome influences its possibility of being observed. Salient information that can assist in addressing these missing outcomes in such situations is the anticipated response rate in each study arm; these can often be anticipated based on prior research in similar populations using similar designs and outcomes. Further, in some areas of human subjects research, we are often confident or we suspect that response rates among RCT participants with successful treatment outcomes will be at least as great as those among participants without successful treatment outcomes. In other settings we may suspect the opposite relationship. This direction of the differential response between those with successful and unsuccessful outcomes can further aid in addressing the missing outcomes. We present simple Bayesian pattern-mixture models that incorporate this information on response rates to analyze the relationship between a binary outcome and an intervention while addressing the missing outcomes. We assess the performance of this method in simulation studies and apply this method to the results of an RCT of a smoking abstinence intervention.

Bayesian GWAS with Structured and Non-Local Priors.

MOTIVATION: The flexibility of a Bayesian framework is promising for GWAS, but current approaches can benefit from more informative prior models. We introduce a novel Bayesian approach to GWAS, called Structured and Non-Local Priors (SNLPs) GWAS, that improves over existing methods in two important ways. First, we describe a model that allows for a marker's gene-parent membership and other characteristics to influence its probability of association with an outcome. Second, we describe a non-local alternative model for differential minor allele rates at each marker, in which the null and alternative hypotheses have no common support. RESULTS: We employ a non-parametric model that allows for clustering of the genes in tandem with a regression model for marker-level covariates, and demonstrate how incorporating these additional characteristics can improve power. We further demonstrate that our non-local alternative model gives symmetric rates of convergence for the null and alternative hypotheses, whereas commonly used local alternative models have asymptotic rates that favor the alternative hypothesis over the null. We demonstrate the robustness and flexibility of our structured and non-local model for different data generating scenarios and signal-to-noise ratios. We apply our Bayesian GWAS method to single nucleotide polymorphisms data collected from a pool of Alzheimer's disease and cognitively normal patients from the Alzheimer's Database Neuroimaging Initiative. AVAILABILITY AND IMPLEMENTATION: R code to perform the SNLPs method is available at https://github.com/lockEF/BayesianScreening.

Batch Bayesian optimization design for optimizing a neurostimulator.

Recently, spinal epidural neurostimulation is being considered for rehabilitation of persons suffering from partial spinal-cord injury. The neurostimulator must be programmed by a neurosurgeon, yet little work has been done to develop rigorous methods for optimally programming the device. We propose an adaptive design to efficiently optimize programming of the neurostimulator based on specified interim evaluations of patient reported preferences. Preferences for the eligible device configurations are estimated after each interim analysis through a conditionally autoregressive model that assumes preference for one configuration is related to preferences for neighboring configurations. Using the adaptively updated preferences, a group of configurations is programmed into the device for the patient to evaluate during the next follow-up period. This selection is based on a balance of device exploration and preference maximization. We repeat this process until a specified stopping rule or the calibration end is reached. We show simulation studies to evaluate the overall quality of the adaptive calibration for various configuration selection strategies and the effects of stopping it early.

CRISPR/Cas9 cleavages in budding yeast reveal templated insertions and strand-specific insertion/deletion profiles.

Harnessing CRISPR-Cas9 technology provides an unprecedented ability to modify genomic loci via DNA double-strand break (DSB) induction and repair. We analyzed nonhomologous end-joining (NHEJ) repair induced by Cas9 in budding yeast and found that the orientation of binding of Cas9 and its guide RNA (gRNA) profoundly influences the pattern of insertion/deletions (indels) at the site of cleavage. A common indel created by Cas9 is a 1-bp (+1) insertion that appears to result from Cas9 creating a 1-nt 5' overhang that is filled in by a DNA polymerase and ligated. The origin of +1 insertions was investigated by using two gRNAs with PAM sequences located on opposite DNA strands but designed to cleave the same sequence. These templated +1 insertions are dependent on the X-family DNA polymerase, Pol4. Deleting Pol4 also eliminated +2 and +3 insertions, which are biased toward homonucleotide insertions. Using inverted PAM sequences, we also found significant differences in overall NHEJ efficiency and repair profiles, suggesting that the binding of the Cas9:gRNA complex influences subsequent NHEJ processing. As with events induced by the site-specific HO endonuclease, CRISPR-Cas9-mediated NHEJ repair depends on the Ku heterodimer and DNA ligase 4. Cas9 events are highly dependent on the Mre11-Rad50-Xrs2 complex, independent of Mre11's nuclease activity. Inspection of the outcomes of a large number of Cas9 cleavage events in mammalian cells reveals a similar templated origin of +1 insertions in human cells, but also a significant frequency of similarly templated +2 insertions.

Long-Term Infectious and Noninfectious Outcomes of Monthly Alemtuzumab as a Calcineurin Inhibitor- and Steroid-Free Regimen for Pancreas Transplant Recipients.

Multiple doses of alemtuzumab for immunosuppressive therapy of patients with hematologic malignancies and hematopoietic stem cell transplant have been associated with a high rate of infection. In transplantation, limited alemtuzumab dosing has been successfully used as induction immunosuppression. The effect of multiple doses of alemtuzumab, used as maintenance therapy to minimize steroid and/or calcineurin inhibitor toxicity in solid organ transplant recipients, is unknown. We evaluated the infectious and noninfectious outcomes of 179 pancreas transplant recipients treated with alemtuzumab for induction and maintenance therapy (extended alemtuzumab exposure (EAE)) from 2/28/2003 through 8/31/2005, compared with 159 pancreas transplant recipients with standard induction and maintenance (SIM) therapy performed before (1/1/2002 until 12/31/2002) and after (1/1/2006 until 12/31/2006) the implementation of EAE. EAE was associated with higher risk of overall infections (hazard ratio (HR) 1.33 (1.06-1.66), P=0.01), bacterial infections (HR 1.33 (1.05-1.67), P=0.02), fungal infections (HR 1.86 (1.28-2.71), P < 0.01), and cytomegalovirus infections (HR 2.29 (1.39-3.77), P < 0.01). In addition, EAE was associated with higher risk of acute cellular rejection (HR 2.09 (1.46-2.99), P < 0.01). In conclusion, while a limited alemtuzumab dosing is safe and effective for induction therapy in pancreas transplantation, EAE combined with steroid and calcineurin minimization is associated with a high risk of infectious complications and acute cellular rejection.

Multi-omic molecular profiling of lung cancer in COPD.

Chronic obstructive pulmonary disease (COPD) is a known risk factor for developing lung cancer but the underlying mechanisms remain unknown. We hypothesise that the COPD stroma contains molecular mechanisms supporting tumourigenesis.We conducted an unbiased multi-omic analysis to identify gene expression patterns that distinguish COPD stroma in patients with or without lung cancer. We obtained lung tissue from patients with COPD and lung cancer (tumour and adjacent non-malignant tissue) and those with COPD without lung cancer for profiling of proteomic and mRNA (both cytoplasmic and polyribosomal). We used the Joint and Individual Variation Explained (JIVE) method to integrate and analyse across the three datasets.JIVE identified eight latent patterns that robustly distinguished and separated the three groups of tissue samples (tumour, adjacent and control). Predictive variables that associated with the tumour, compared to adjacent stroma, were mainly represented in the transcriptomic data, whereas predictive variables associated with adjacent tissue, compared to controls, were represented at the translatomic level. Pathway analysis revealed extracellular matrix and phosphatidylinositol-4,5-bisphosphate 3-kinase-protein kinase B signalling pathways as important signals in the tumour adjacent stroma.The multi-omic approach distinguishes tumour adjacent stroma in lung cancer and reveals two stromal expression patterns associated with cancer.

Handheld Magnetometer-Assisted Localization and Removal of a Foreign Body From the Chest Wall.

Foreign bodies fully embedded in soft tissues present a unique challenge to surgeons attempting excision. Small fragments can be nonpalpable, and many prove difficult to visualize intra-operatively by means of classic radiologic techniques. A 35-year-old active duty soldier presented requesting excision of ballistic fragment embedded in his chest wall that had previously failed a previous attempt at removal. The metallic foreign body was successfully localized intra-operatively using a handheld magnetometer probe and removed without complication. This case demonstrates the utility and cost-effectiveness of the handheld magnetometry for intra-operative localization of metallic foreign bodies. Metallic foreign bodies may be localized intra-operatively using inexpensive and reusable equipment that does not require radiation or bulky radiographic imaging equipment.

Clinician Burnout and Effectiveness of Guideline-Recommended Psychotherapies.

Importance: Clinician burnout has been associated with clinician outcomes, but the association with patient outcomes remains unclear. Objective: To evaluate the association between clinician burnout and the outcomes of patients receiving of guideline-recommended trauma-focused psychotherapies for posttraumatic stress disorder (PTSD). Design, Setting, and Participants: This cohort study was set at the US Veterans Affairs Health Care System and included licensed therapists who provided trauma-focused psychotherapies and responded to an online survey between May 2 and October 8, 2019, and their patients who initiated a trauma-focused therapy during the following year. Patient data were collected through December 31, 2020. Data were analyzed from May to September 2023. Exposures: Therapists completing the survey reported burnout with a 5-point validated measure taken from the Physician Worklife Study. Burnout was defined as scores of 3 or more. Main Outcomes and Measures: The primary outcome was patients' clinically meaningful improvement in PTSD symptoms according to the PTSD Checklist for the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition). Patient dropout, therapist adherence, and session spacing was assessed through electronic health records. Multivariable random-effects logistic regression examined the association of therapist burnout and clinically meaningful improvement, adjusted for case-mix. Results: In this study, 165 of 180 (91.7%) therapists (89 [53.9%] female) completed the burnout measure and provided trauma-focused psychotherapies to 1268 patients (961 [75.8%] male) with outcome data. Fifty-eight (35.2%) therapists endorsed burnout. One third of patients (431 [34.0%]) met criterion for clinically meaningful improvement. Clinically meaningful improvement in PTSD symptoms was experienced by 120 (28.3%) of the 424 patients seen by therapists who reported burnout and 311 (36.8%) of the 844 patients seen by therapists without burnout. Burnout was associated with lower odds of clinically meaningful improvement (adjusted odds ratio [OR],0.63; 95% CI, 0.48-0.85). The odds of clinically meaningful improvement were reduced for patients who dropped out (OR, 0.15; 95% CI, 0.11-0.20) and had greater session spacing (OR, 0.80; 95% CI, 0.70-0.92). Therapist adherence was not associated with therapy effectiveness. Adjusting for dropout or session spacing did not meaningfully alter the magnitude of the association between burnout and clinically meaningful improvement. Conclusions and Relevance: In this prospective cohort study, therapist burnout was associated with reduced effectiveness of trauma-focused psychotherapies. Studying when and how burnout affects patient outcomes may inform workplace interventions.

Delivery of a post-natal neonatal jaundice education intervention improves knowledge among mothers at Jinja Regional Referral Hospital in Uganda.

BACKGROUND: Neonatal jaundice (NNJ) is a major contributor to childhood morbidity and mortality. As many infants are discharged by 24 hours of age, mothers are key in detecting severe forms of jaundice. Mothers with limited knowledge of NNJ have a hard time identifying these infants who could go on to have the worst outcomes. This study aimed to determine the effect of a jaundice education package delivered to mothers prior to hospital discharge on maternal knowledge after discharge. METHODS: This was a before and after interventional study involving an education package delivered through a video message and informational voucher. At 10-14 days after discharge, participants were followed up via telephone to assess their post-intervention knowledge. A paired t-test was used to determine the effectiveness of the intervention on knowledge improvement. Linear regression was used to determine predictors of baseline knowledge and of change in knowledge score. RESULTS: Of the 250 mothers recruited, 188 were fit for analysis. The mean knowledge score was 10.02 before and 14.61 after the intervention, a significant difference (p<0.001). Factors determining higher baseline knowledge included attendance of 4 or more antenatal visits (p < 0.001), having heard about NNJ previously (p < 0.001), having experienced an antepartum illness (p = 0.019) and higher maternal age (p = 0.015). Participants with poor baseline knowledge (ß = 7.523) and moderate baseline knowledge (ß = 3.114) had much more to gain from the intervention relative to those with high baseline knowledge (p < 0.001). CONCLUSION: Maternal knowledge of jaundice can be increased using a simple educational intervention, especially in settings where the burden of detection often falls on the mother. Further study is needed to determine the impact of this intervention on care seeking and infant outcomes.

Consideration of comorbidity in risk stratification prior to prostate biopsy.

BACKGROUND: Previously, the patient-reported Total Illness Burden Index for Prostate Cancer (TIBI-CaP) questionnaire and/or the physician-reported Charlson Comorbidity Index (CCI) have provided assessments of competing comorbidity during treatment decisions for patients with prostate cancer. In the current study, the authors used these assessments to determine comorbidity and prognosis before prostate biopsy and the subsequent diagnosis of prostate cancer to identify those patients least likely to benefit from treatment. METHODS: A prospective observational cohort study was performed of 104 participants aged 64.0 years ± 6.5 years from 3 institutions representing different health care delivery systems. Patients were identified before undergoing transrectal ultrasound-guided prostate biopsy and followed for a median of 28 months. Associations between the comorbidity scores and nonelective hospital admissions were investigated using logistic regression and Cox proportional hazards models. RESULTS: Among the 104 patients who underwent prostate biopsy, 2 died during the follow-up period. The overall hospital admission rate was 20% (21 of 104 patients). Higher scores on both the TIBI-CaP (≥ 9) and CCI (≥ 3) were found to be significantly associated with an increased odds for hospital admission (odds ratio, 11.3 [95% confidence interval (95% CI), 2.4-53.6] and OR, 5.7 [95% CI, 1.4-22.4]) and hazards ratios (HRs) for time to hospital admission (HR, 3.8 [95% CI, 1.3-11.2] and HR, 3.2 [95% CI, 1.1-9.1]), respectively. CONCLUSIONS: TIBI-CaP and CCI scores were found to successfully predict which patients were at high risk for nonelective hospital admission. These patients are likely to have poorer health and a potentially shortened lifespan. Therefore, comorbidity analysis using these tools may help to identify those patients who are least likely to benefit from prostate cancer therapy and should avoid prostate biopsy.

Neuroimaging of nevoid basal cell carcinoma syndrome (NBCCS) in children.

Nevoid basal cell carcinoma syndrome (NBCCS, Gorlin syndrome) is an autosomal dominant condition with a wide range of manifestations, including multiple basal cell carcinomas, medulloblastoma, odontogenic keratocysts (OKC) and skeletal abnormalities. Children with NBCCS also have a predisposition for secondary cancers after exposure to ionising radiation. In children undergoing imaging for posterior fossa mass and/or maxillofacial cysts, certain additional findings can raise the possibility of NBCCS. Making the diagnosis can significantly impact patient management, especially for children with medulloblastoma.

Experiencing multiple concurrent functional gastrointestinal disorders is associated with greater symptom severity and worse quality of life in chronic constipation and defecation disorders.

BACKGROUND: Recent community-based studies have demonstrated that experiencing multiple concurrent functional gastrointestinal disorders (FGIDs) is associated with increased somatization, worse quality of life (QoL), and greater health care utilization. However, the presence of multiple overlapping FGIDs is unstudied specifically in chronic constipation and functional defecation disorders (FDD). We investigated the prevalence and impact of additional nonconstipation FGIDs on constipation severity, anorectal physiology, anxiety and depression, and QoL, in patients with chronic constipation and FDD. METHODS: One-hundred and forty-six consecutive patients with functional constipation or irritable bowel syndrome (IBS-C/IBS-M) presenting to a tertiary referral Neurogastroenterology Clinic were studied. In addition, 90/146 (62%) qualified for FDD due to abnormal defecatory physiology. Patients underwent comprehensive baseline assessment comprising anorectal physiology, Bristol Stool Chart, Rome questionnaire, Knowles-Eccersley-Scott-Symptom (KESS) constipation score, Hospital Anxiety, and Depression Scale, and modified 36-Item Short Form Health Survey (SF-36) for QoL. Additional FGIDs were diagnosed using Rome III criteria. KEY RESULTS: Additional nonconstipation FGIDs occurred in 85% of patients, with a mean of 2.1 (SD 1.6) additional FGIDs. Patients with four or more additional FGIDs experienced greater constipation severity compared to those with no additional FGIDs (p = 0.004). Comorbid FGIDs were associated with worse SF-36 scores for physical functioning (p < 0.001), role-physical (p = 0.005), bodily pain (p < 0.001), vitality (p = 0.008), social functioning (p = 0.004), and mental health index (p = 0.031). CONCLUSIONS AND INFERENCES: Functional gastrointestinal disorders comorbidity is highly prevalent in chronic constipation and defecatory disorders, and this is associated with greater symptom severity and worse QoL. Multimodal treatments targeting comorbid FGIDs may lead to superior outcomes.

Use of Information and Communication Technology among Patients with Chronic Obstructive Pulmonary Disease Who Smoke: A Mixed Methods Study.

Rationale: Although overall use is on the rise, certain patient populations have persistently low technology use. Objectives: To inform the creation of a proactive tobacco treatment program, we assessed access to, use of, and barriers surrounding information and communication technology (ICT) among patients with chronic obstructive pulmonary disease (COPD) who currently smoke, examining associations between key predictors and electronic health (e-health) literacy. Methods: Single-center mixed-methods study of veterans with COPD who smoke. Eligible participants who smoked were identified by the e-health record and mailed a survey. E-health literacy was assessed by the eHEALS (Electronic Health Literacy Scale; 8-40). Low technology use was defined as no Internet-capable device and use of ICT less than monthly. Qualitative participants were purposively selected from survey respondents and interviewed using a semistructured guide. Interviews were transcribed and analyzed using directed content analysis. We used a Bayesian three-component joint model to identify predictors of low technology use and low eHEALS. Results: Participants (N = 204) were older (mean age, 65.8), primarily White (76.4%), men (87.1%), and with low income (44.9% income under $20,000). Low technology use was reported by 25.5%, and many reported low use of specific types of ICT. For example, only 36.3% had reliable in-home Internet, fewer than half (46.6%) accessed e-mail at least weekly, 58.3% texted at least weekly, and few used the secure patient portal (13.2% accessed it monthly). The mean eHEALS was 24.6 (±8.7), indicating low to moderate e-health literacy. In the Bayesian analysis, low technology use was associated with lower eHEALS (estimate: -8.5 [95% confidence interval, -12.13 to -4.81]). Attainment of at least a college graduate-level education was associated with higher eHEALS (3.83 [0.43-7.24]). Participants reported barriers to use of ICT, including struggles navigating account security, frequently lost login information, mistrust of providing personal information to the Internet, and lack of familiarity with processes. Many perceived ICT as not useful or necessary. Conclusions: Many patients with COPD who smoke report barriers to engagement with health promotion programs offered electronically, which may perpetuate health disparities. Health promotion programs must account for the low use of ICT and e-health literacy to ensure equitable access across the population.

Comparison of STEMI Door-To-Device Time During the COVID-19 Crisis in a New Jersey Inner City Community Hospital.

As the novel COVID-19 pandemic was on the rise, its impact on the healthcare system was devastating. Patients became more reluctant to present to the hospital and elective procedures were being postponed for patient safety. We wanted to assess the effects of the COVID-19 pandemic on the door-to-device time in our small community hospital in the heart of Trenton, New Jersey. We created a retrospective study that evaluated all STEMI cases that presented to our institute from January 2018 until the end of May, 2021. Our primary outcome was the door-to-device time. Secondary outcomes were the length of hospital stay, ICU admission, length of ICU stay, cardiac arrest, and death during the hospitalization. We studied 114 patients that presented with STEMI to our emergency department, 77 of these patients presented pre-COVID-19, and 37 presented during the pandemic. Our median door-to-device for STEMI cases pre-COVID-19, and during the pandemic were 70 min (IQR 84-57) and 70 min (IQR 88-59) respectively with no significant difference found (P-value 0.55, Mann Whitney Test). It is, however, interesting to note that the number of STEMI admissions significantly decreased during the pandemic era. There are limitations to our study, most noticeably the number of STEMI cases at our small community hospital which limits its generalizability. Moreover, we did not assess other comorbidities which might have confounded our outcomes and we were also unable to follow patients post-discharge to assess the long-term sequela of their STEMI admission. Therefore, more dedicated studies of this clinical conundrum are required to further assess and implement guidelines for the future.

The role of therapy delivery and clinic organizational factors in explaining therapist effects for trauma-focused psychotherapies in the Veterans Health Administration.

OBJECTIVE: This study estimated the size of therapist effects (TEs) for dropout and clinical effectiveness of two trauma-focused psychotherapies (TFPs) and evaluated whether therapy delivery and clinic organizational factors explained observed TEs. METHOD: Participants were 180 therapists (54.4% psychologists, 42.2% social workers) from 137 Veterans Health Administration facilities and 1,735 patients (24.7% women; 27.2% people of color) who completed at least two TFP sessions. Outcomes were dropout (< 8 TFP sessions) and for a subsample (n = 1,273), clinically meaningful improvement and recovery based on posttraumatic stress disorder checklist for DSM-5 (PCL-5) scores. Therapist-level predictors were ascertained through survey, manual chart review, and administrative data. Multilevel models estimated TEs. RESULTS: Over half (51.2%) of patients dropped out and those who dropped out were less likely to meet criteria for clinically meaningful improvement or recovery (ps < .001). Adjusting for case-mix and TFP type, therapists accounted for 5.812% (p < .001) of the unexplained variance in dropout. The average dropout rate for the 45 therapists in the top performing quartile was 27.0%, while the average dropout rate for the 45 therapists in the bottom performing quartile was 78.8%. Variation between therapists was reduced to 2.031% (p = .140) when therapists' mean of days between sessions, adherence, implementation climate, and caseload were added to multilevel models. TEs were nonsignificant for clinically meaningful improvement and recovery. CONCLUSIONS: Interventions targeting therapy delivery and clinic organization have the potential to reduce variation between therapists in TFP dropout, so that more patients stay engaged long enough to experience clinical benefit. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Implementation context and burnout among Department of Veterans Affairs psychotherapists prior to and during the COVID-19 pandemic.

BACKGROUND: The first goal of this study was to assess longitudinal changes in burnout among psychotherapists prior to (T1) and during the COVID-19 pandemic (T2). The second objective was to assess the effects of job demands, job resources (including organizational support for evidence-based psychotherapies, or EBPs) and pandemic-related stress (T2 only) on burnout. METHOD: Psychotherapists providing EBPs for posttraumatic stress disorder in U.S. Department of Veterans Affairs (VA) facilities completed surveys assessing burnout, job resources, and job demands prior to (T1; n = 346) and during (T2; n = 193) the COVID-19 pandemic. RESULTS: Burnout prevalence increased from 40 % at T1 to 56 % at T2 (p < .001). At T1, stronger implementation climate and implementation leadership (p < .001) and provision of only cognitive processing therapy (rather than use of prolonged exposure therapy or both treatments; p < .05) reduced burnout risk. Risk factors for burnout at T2 included T1 burnout, pandemic-related stress, less control over when and how to deliver EBPs, being female, and being a psychologist rather than social worker (p < .02). Implementation leadership did not reduce risk of burnout at T2. LIMITATIONS: This study involved staff not directly involved in treating COVID-19, in a healthcare system poised to transition to telehealth delivery. CONCLUSION: Organizational support for using EBPs reduced burnout risk prior to but not during the pandemic. Pandemic related stress rather than increased work demands contributed to elevated burnout during the pandemic. A comprehensive approach to reducing burnout must address the effects of both work demands and personal stressors.

Novel TSHB variant (c.217A>C) causing severe central hypothyroidism and pituitary hyperplasia.

Summary: Biallelic pathological variants in the thyroid stimulating hormone (TSH) subunit ß gene (TSHB) result in isolated TSH deficiency and secondary hypothyroidism, a rare form of central congenital hypothyroidism (CCH), with an estimated incidence of 1 in 65 000 births. It is characterised by low levels of free thyroxine and inappropriately low serum TSH and may therefore be missed on routine neonatal screening for hypothyroidism, which relies on elevated TSH. We describe a patient with CCH who developed recurrence of pituitary hyperplasia and symptomatic hypothyroidism due to poor compliance with thyroxine replacement. She was diagnosed with CCH as a neonate and had previously required trans-sphenoidal hypophysectomy surgery for pituitary hyperplasia associated with threatened chiasmal compression at 17 years of age due to variable adherence to thyroxine replacement. Genetic testing of TSHB identified compound heterozygosity with novel variant c.217A>C, p.(Thr73Pro), and a previously reported variant c.373delT, p.(Cys125Valfs*10). Continued variable adherence to treatment as an adult resulted in recurrence of significant pituitary hyperplasia, which subsequently resolved with improved compliance without the need for additional medications or repeat surgery. This case describes a novel TSHB variant associated with CCH and demonstrates the importance of consistent compliance with thyroxine replacement to treat hypothyroidism and prevent pituitary hyperplasia in central hypothyroidism. Learning points: Pathogenic variants in the TSH subunit ß gene (TSHB) are rare causes of central congenital hypothyroidism (CCH). c.217A>C, p.(Thr73Pro), is a novel TSHB variant, presented in association with CCH in this case report. Thyroxine replacement is critical to prevent clinical hypothyroidism and pituitary hyperplasia. Pituitary hyperplasia can recur post-surgery if adherence to thyroxine replacement is not maintained. Pituitary hyperplasia can dramatically reverse if compliance with thyroxine replacement is improved to maintain free thyroxine (FT4) levels in the middle-to-upper normal range, without the need for additional medications or surgeries.