A review of workplace mental health interventions and their implementation in public safety organizations.

OBJECTIVE: Workplace mental health is relevant to public safety organizations due to the exposure that many public safety personnel (PSP) have to psychological trauma in the course of their daily work. While the importance of attending to PSP mental health has been established, the implementation of workplace mental health interventions is not as well understood. This scoping review describes workplace mental health interventions and their implementation in public safety organizations. METHODS: English published primary studies with any publication date up to July 3, 2020 were considered. JBI methodology and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews was followed. RESULTS: 89 citations met inclusion criteria out of the 62,299 found. Articles and reports found were largely published within the last decade, most frequently from Western nations, and most often applied to police, followed by firefighters. The focus of interventions was commonly stress management and resilience, and a frequent implementation strategy was multi-session group training. Comprehensive quality improvement initiatives, a focus on supervisors and managers, and interventions across primary, secondary, and tertiary prevention, were infrequent. CONCLUSION: Public safety organizations are frequently reporting on stress management and resilience interventions for police and firefighters, implemented through multi-session group training. A focus across a range of PSP, including paramedics, corrections officers, and emergency dispatchers, using implementation strategies beyond group training, is suggested. This area of research is currently expanding, with many studies published within the past decade; ongoing evaluation of the quality of interventions and implementation strategies is recommended.

Targeted agents or immuno-oncology therapies as first-line therapy for BRAF-mutated metastatic melanoma: a real-world study.

Aim: Targeted therapy (TT) and immuno-oncology (IO) drugs are approved for patients with BRAF mutant metastatic melanoma (MM). We compared real-world outcomes for first-line (1L) TT versus 1L IO to evaluate optimal sequencing. Materials & methods: Physicians-identified BRAF mutant MM patients initiating 1L TT or IO therapies and extracted treatment, disease and clinical outcomes including disease response which were compared between TT and IO and individual regimens. Results: 440 MM patients (TT = 283, IO = 157) were identified. A higher proportion of TT patients had liver metastases (46.3 vs 35.0%) and abnormal lactate dehydrogenase (61.1 vs 42.7%). IO-treated had a RECIST-determined response rate of 45.9 versus 60.1% for TT and time on treatment of 7.2 versus 11.4 months, respectively. There was no survival difference between cohorts. Conclusion: Despite higher risk patients, 1L TT resulted in higher response rate and longer treatment duration suggesting a preferred 1L sequence.

Comparative effectiveness of monotherapy with mood stabilizers versus second generation (atypical) antipsychotics for the treatment of bipolar disorder in children and adolescents.

OBJECTIVE: This study compared the effectiveness and safety of second generation (atypical) antipsychotic (SGA) versus traditional mood stabilizers (MS) in children and adolescents with bipolar disorder. METHODS: The study was a retrospective cohort study on 5 years (2003-2007) of Medicaid claims data from four geographically diversified states. Children and adolescents aged 6-18 years who initiated a new treatment episode for bipolar disorder on either an SGA or an MS were followed for 12 months to compare the effectiveness and safety between the two therapeutic categories for pediatric bipolar disorder (PBD). The outcome measures were psychiatric hospital admission, all cause medication discontinuation and treatment augmentation. Potential selection bias caused by unobserved confounding was addressed with instrumental variable methods, using physician prescribing preference and year of cohort entry as the instruments. Sensitivity analysis was conducted to test the robustness of findings against the uncertainties on PBD diagnosis. RESULTS: Of the 7423 bipolar children and adolescents identified, 66.60% started treatment on SGA, whereas 33.40% initiated on MS. Patients who initiated on MS and SGA had comparable risk of psychiatric hospital admission (HR=1.172, 95%CI: 0.827-1.660). However, as compared with those who initiated on MS, patients who initiated on SGA were less likely to discontinue the treatment (HR=0.634, 95%CI: 0.419-0.961) and less likely to receive treatment augmentation (HR=0.223, 95%CI: 0.103-0.484). CONCLUSION: As compared with MS monotherapy, SGA monotherapy could be a more effective and safer treatment option for PBD.

Systematic review and meta-analysis of pharmacological therapies for painful diabetic peripheral neuropathy.

BACKGROUND: Painful diabetic peripheral neuropathy (pDPN) is prevalent among persons with diabetes and increases over time. Published guidelines recommend a number of medications to treat this condition providing clinicians with a variety of treatment options. This study provides a comprehensive systematic review and meta-analysis of published pharmacologic therapies for pDPN. METHODS: The published literature was systematically searched to identify randomized, controlled trials of all available pharmacologic treatments for pDPN (recommended or nonrecommended) reporting predefined efficacy and safety outcomes. Bayesian fixed-effect mixed treatment comparison methods were used to assess relative therapeutic efficacy and harms. RESULTS: Data from 58 studies including 29 interventions and 11,883 patients were analyzed. Pain reduction over that of placebo on the 11-point numeric rating scale ranged from -3.29 for sodium valproate (95% credible interval [CrI] = [-4.21, -2.36]) to 1.67 for Sativex (-0.47, 0.60). Estimates for most treatments were clustered between 0 and -1.5 and were associated with more study data and smaller CrIs. Pregabalin (≥ 300 mg/day) was the most effective on the 100-point visual analog scale (-21.88; [-27.06, -16.68]); topiramate was the least (-3.09; [-3.99, -2.18]). Relative risks (RRs) of 30% pain reduction ranged from 0.78 (Sativex) to 1.84 (lidocaine 5% plaster). Analysis of the RR ratio of these 2 treatments reveals marginal significance for Sativex (3.27; [1.07, 9.81]), indicating the best treatment is only slightly better than the worst. Relative risks of 50% pain reduction ranged from 0.98 (0.56, 1.52) (amitriptyline) to 2.25 (1.51, 3.00) (alpha-lipoic acid). RR ratio for these treatments was not statistically different (3.39; [0.88, 3.34]). Fluoxetine had the lowest risk of adverse events (0.94; [0.62, 1.23]); oxycodone had the highest (1.55; [1.45, 1.64]). Discontinuation RRs were clustered around 0.8 to 1.5, with those on the extreme having greater uncertainty. CONCLUSIONS: Selecting an appropriate pDPN therapy is key given the large number of available treatments. Comparative results revealed relative equivalence among many of the studied interventions having the largest overall sample sizes and highlight the importance of standardization of methods to effectively assess pain.

Workplace mental health implementation strategies in public safety organizations: a scoping review protocol.

OBJECTIVE: This scoping review aims to map workplace mental health implementation strategies in public safety organizations and describe the characteristics, participants, and contexts of these strategies. INTRODUCTION: Workplace mental health implementation strategies are relevant to public safety organizations due to the exposure that many public safety personnel, such as firefighters, paramedics, and police officers, have to psychological trauma in the course of their daily work. While the importance of attending to public safety personnel's mental health has been established, workplace mental health implementation strategies have historically varied in public safety organizations. INCLUSION CRITERIA: This scoping review will address workplace mental health implementation strategies used in public safety organizations. It will exclude studies that do not focus on workplace mental health, do not report on the implementation strategies used, or do not take place in a public safety context. METHODS: Primary studies published in English with any publication date up to the present will be considered. JBI methodology and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) will be followed. The search will be carried out in five databases and reference lists will also be searched for additional studies. Duplicates will be removed, and two independent reviewers will screen the titles, abstracts, and full text of the selected studies. Data collection will be performed using a tool developed by the researchers, based on JBI's model instrument for extracting study details, characteristics, and results. A summary of the results will be presented in diagrams, narratives, and tables.

Real-world adverse events associated with CAR T-cell therapy among adults age ≥ 65 years.

INTRODUCTION: Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment for relapsed or refractory large B-cell lymphoma (LBCL) with the Food and Drug Administration (FDA) approvals of axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tis-cel). Although the incidence of LBCL is highest among patients age ≥ 65, clinical trials supporting approval of these 2 products primarily enrolled younger patients. Safety data for axi-cel and tis-cel in older patients is limited. METHODS: In this analysis, we queried the FDA Adverse Events Reporting System (FAERS) database for cases associated with axi-cel or tis-cel from the FDA approval dates for the LBCL indication for each product through December 31, 2019, and compared adverse events (AEs) reported for cases involving patients aged <65 and ≥ 65. RESULTS: A total of 804 cases were retrieved, with 333 (41%) involving patients age ≥ 65. Cytokine release syndrome (CRS) was the most common AE reported in both age groups. Cases involving older patients had a significantly higher proportion of neurological AEs, including CAR T-cell-related encephalopathy syndrome (8% vs. 4%, p = 0.03). Some individual clinical features of CRS were significantly more common among younger age group cases, including pyrexia (33% vs. 23%, p < 0.01), tachycardia (10% vs. 5%, p < 0.01), and thrombocytopenia (4% vs. 2%, p = 0.03). DISCUSSION: In this age-based analysis of FAERS reports for patients treated with axi-cel or tis-cel, we identified differences in patterns of AEs experienced. This large-scale post-marketing study complements clinical trial safety data and may help inform clinicians' decision making when treating adult patients with CAR-T cell therapy.

Neurological adverse events following CAR T-cell therapy: a real-world analysis.

Aim: To characterize real-world neurological adverse events (AEs) associated with chimeric antigen receptor T-cell therapies in patients with refractory/relapsed large B-cell lymphomas. Materials & methods: Postmarketing case reports from the US FDA AEs reporting system involving axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) for large B-cell lymphomas were analyzed. Results: Of 804 AE cases identified (637 axi-cel, 167 tisa-cel), 428 (67%) of axi-cel cases and 43 (26%) of tisa-cel cases reported neurological AEs. Compared with cases without neurological AEs, significant associations were observed between neurological AEs and use of axi-cel, age ≥65 years, and the outcome of hospitalization. Conclusion: Neurological AEs were common with chimeric antigen receptor T-cell therapy in the real world and largely reflected those reported in clinical trials.

Frequency and Causes of Burnout in US Community Oncologists in the Era of Electronic Health Records.

BACKGROUND: Physician burnout, characterized by exhaustion of physical or emotional strength, cynicism, and lack of achievement, has become a worsening phenomenon in medicine, contributing to higher health care costs and patient/physician dissatisfaction. How burnout has affected hematologists and oncologists is not well studied. METHODS: US community oncologists/hematologists were queried via a Web-based survey from September-November 2018. Physicians were asked about frequency of burnout symptoms, drivers of work-related stress, and their perceptions on management of workload. RESULTS: Among the 163 physicians surveyed, 46% felt a substantial amount of stress at work. Most physicians felt emotionally (85%) and physically (87%) exhausted. A majority of physicians felt lethargic (67%), ineffective (64%), and/or detached (63%). In a typical workweek, 93% needed time beyond time allocated to clinical care to complete work responsibilities. Electronic health record (EHR) responsibilities caused moderate to excessive stress at work for 67% of physicians; 79% of physicians worked on EHRs outside of clinic hours. Other sources of excessive stress were changing reimbursement models (33%), interactions with payers (31%), and increasing patient and caregiver demands (31%). A third of physicians have considered retiring early or changing their career path to cope. To combat burnout, physicians' practices have used advanced practice providers, invested in information technology, and/or hired additional administrative staff. However, the majority of physicians stated they had optimal or good control over their workload. CONCLUSION: Most oncologists experience burnout symptoms and require additional time beyond that allocated to clinical care to complete their workload. The discordance between oncologists' admission of stress and exhaustion while claiming good control over those same burdens warrants exploration in future research.

Treatment patterns, symptom reduction, quality of life, and resource use associated with lubiprostone in irritable bowel syndrome constipation subtype.

Objectives Real-world patient outcomes data is scarce concerning the high disease burden of IBS-C. The aim of this study was to compare patient-reported symptom control, health-related quality of life (HRQoL), resource utilization, and treatment satisfaction of lubiprostone vs non-lubiprostone treatment for irritable bowel syndrome-constipation (IBS-C). Research design and methods An observational, retrospective US chart review and computer-assisted telephone patient survey was conducted March to August 2013 recruiting women over 18 years old with physician-confirmed IBS-C who had initiated new treatment from inadequate relief of previous treatments and who had been on the new treatment ≥3 months. Multiple IBS-C treatments were permitted. IBS-C severity, time since diagnosis, age, and race were controlled using inverse probability of treatment weighting. Weighted outcomes were compared using t-tests (continuous outcomes) and chi-squared tests (categorical outcomes). Main outcomes measures Instruments included Patient Assessment of Constipation Symptoms (PAC-SYM) and IBS quality of life (IBS-QoL). A single item assessed current treatment satisfaction. Results Of 162 patients (mean age 45.9 [SD 15.3] years old, 71% white, 61.1% with moderate IBS-C), 76 switched to lubiprostone and 86 to non-lubiprostone. Groups were similar in clinical and demographic characteristics and previous 30 day IBS-C treatment. After weighting, all PAC-SYM scores were lower for lubiprostone (P < 0.05). All IBS-QoL subscales were higher for lubiprostone including overall, dysphoria, social reaction, sexual, and relationship scores (P < 0.05.) More lubiprostone patients reported positive treatment satisfaction (92.3% vs 71.0%, P < 0.001). Conclusions In IBS-C patients with inadequate response to previous therapies, lubiprostone improved patient-reported symptom control, treatment satisfaction, and HRQoL. Key limitations include lack of measurement of patient-reported outcomes at treatment start and potential data gaps in chart documentation.

A Mammalian enhancer trap resource for discovering and manipulating neuronal cell types.

There is a continuing need for driver strains to enable cell-type-specific manipulation in the nervous system. Each cell type expresses a unique set of genes, and recapitulating expression of marker genes by BAC transgenesis or knock-in has generated useful transgenic mouse lines. However, since genes are often expressed in many cell types, many of these lines have relatively broad expression patterns. We report an alternative transgenic approach capturing distal enhancers for more focused expression. We identified an enhancer trap probe often producing restricted reporter expression and developed efficient enhancer trap screening with the PiggyBac transposon. We established more than 200 lines and found many lines that label small subsets of neurons in brain substructures, including known and novel cell types. Images and other information about each line are available online (enhancertrap.bio.brandeis.edu).

Indirect costs associated with metastatic breast cancer.

OBJECTIVE: To compare the indirect costs of productivity loss between metastatic breast cancer (MBC) and early stage breast cancer (EBC) patients, as well as their respective family members. METHODS: The MarketScan Health and Productivity Management database (2005-2009) was used. Adult BC patients eligible for employee benefits of sick leave and/or short-term disability were identified with ICD-9 codes. Difference in sick leave and short-term disability days was calculated between MBC patients and their propensity score matched EBC cohort and general population (controls) during a 12-month follow-up period. Generalized linear models were used to examine the impact of MBC on indirect costs to patients and their families. RESULTS: A total of 139 MBC, 432 EBC, and 820 controls were eligible for sick leave and 432 MBC, 1552 EBC, and 4682 controls were eligible for short-term disability (not mutually exclusive). After matching, no statistical difference was found in sick leave days and the associated costs between MBC and EBC cohorts. However, MBC patients had significantly higher short-term disability costs than EBC patients and controls (MBC: $6166 ± $9194 vs. EBC: $3690 ± $6673 vs. CONTROLS: $558 ± $2487, both p < 0.001). MBC patients had more sick leave cost than controls ($2383 ± $5539 vs. $1282 ± $2083, p < 0.05). Controlling for covariates, MBC patients incurred 47% more short-term disability costs vs EBC patients (p = 0.009). Older patients (p = 0.002), non-HMO payers (p < 0.05), or patients not receiving chemotherapy during follow-up (p < 0.001) were associated with lower short-term disability costs. MBC patients' families incurred 39.7% (p = 0.06) higher indirect costs compared to EBC patients' families after controlling for key covariates. CONCLUSION: Productivity loss and associated costs in MBC patients are substantially higher than EBC patients or the general population. These findings underscore the economic burden of MBC from a US societal perspective. Various treatment regimens should be evaluated to identify opportunities to reduce the disease burden from the societal perspective.