The Association of Psychotherapy With Burnout, Depression, and Measures of Well-Being in Residents and Fellows: A Pilot Study.

PURPOSE: Resident physicians experience high rates of burnout and depression but rarely prioritize their well-being or seek mental health care. The Accreditation Council for Graduate Medical Education mandated that training programs prioritize resident wellness and emotional and mental health to ensure readily available and accessible mental health care. To help meet that requirement and circumvent barriers to accessing care, the University of California San Diego Healer Education Assessment & Referral (HEAR) Program offers residents and fellows short-term therapy for coping with challenges that threaten their well-being. This report describes the results of a pilot study designed to evaluate the feasibility and effectiveness of the HEAR Program's resident therapy program. METHOD: The cohort included residents and fellows who completed at least 1 postbaseline assessment from January to May 2022. Measures of fulfillment, burnout, self-compassion, quality of life, depression, and suicidal ideation were assessed and compared before and up to 12 weeks after enrollment. RESULTS: Of the 39 residents who consented to participation, 30 completed at least 1 postbaseline assessment. Most outcomes improved after therapy, with significant increases in fulfillment (mean [SE] coefficient, 0.24 [0.08]; z score, 2.86; P = .004), self-compassion (mean [SE] coefficient, 0.37 [0.07]; z score, 5.72; P < .001), and quality of life ( P < .001) and significant reductions in burnout (Stanford burnout scale: mean [SE] coefficient, -0.27 [0.07]; z score, -4.01; P < .001; single-item burnout scale: mean [SE] coefficient, -0.34 [0.08]; z score, -4.37; P < .001) and depression severity (mean [SE] coefficient, -1.08 [0.25]; z score, -4.36; P < .001). CONCLUSIONS: This pilot study noted improvements in fulfillment, compassion, quality of life, and function, as well as reductions in burnout and depression severity, among resident physicians. Future studies in larger cohorts are needed to validate these findings and inform further optimization of this program.

Loneliness Among Medical Students, Physician Trainees and Faculty Physicians.

OBJECTIVE: Aims of this study were to explore 1) how often medical students, residents, fellows, and faculty physicians who completed a suicide screening questionnaire at a large US academic medical center endorsed intense loneliness and 2) the relationships of loneliness with other negative mental health states. METHODS: Between May 2009 and September 2001, all medical students, residents, fellows, and faculty physicians were invited to complete an anonymous online questionnaire as part of a screening program to identify and engage individuals in distress with mental health support. The questionnaire assessed intense loneliness, other affective states known to be associated with suicide risk, burnout, depressive symptoms, and suicidal thoughts and behaviors. Chi-square tests, independent sample t-tests, ANOVA, and correlation analysis were used to examine relationships between loneliness and these other signals of suicide risk. RESULTS: The response rate was ~ 20%. Overall, 364 of 2016 respondents (18.1%) endorsed intense. loneliness "a lot" or "most" of the time. This included 134/641 (20.9%) medical students, 170/703 (24.2%) residents and fellows and 60/664 (9.4%) faculty physicians. A greater odds of endorsing intense loneliness was seen in those under age 40 (OR = 0.35, p < 0.001), women (OR = 1.30, p = 0.030), and non-Whites (OR = 1.70, p < 0.001); and in those with burnout (OR = 3.14, p < 0.001), depression (OR = 12.34, p < 0.001), other intense affective states (OR = 4.34-8.34, p < 0.05), and suicidal ideation (OR = 3.47-13.00, p < 0.001). CONCLUSION: Interventions to mitigate loneliness in healthcare trainees and professionals may help decrease burnout, depression, and other suicide risk factors. A limitation of the study was the use of a single item to assess loneliness.

Relationship between burnout and Major Depressive Disorder in health professionals: A HEAR report.

BACKGROUND: Burnout is a "normal" albeit concerning response to workplace stress, whereas Major Depressive Disorder (MDD) is a serious illness associated with impairment and suicide risk. Because of symptomatic overlap between the two conditions and MDD-associated stigma, individuals reporting work-related stress and depression often are "diagnosed" with burnout at the expense of recognizing and treating MDD. Our study aimed to leverage organizational implementation of the American Foundation of Suicide Prevention's Interactive Screening Program to elucidate relationships among burnout, depression, and other suicide risk factors. METHODS: 2281 of about 30,000 (~7.6 %) medical trainees, staff, and faculty responded to an anonymous online stress and depression questionnaire. Respondents were grouped into four cohorts: screened positive for burnout alone (n = 439, 19 %), depression alone (n = 268, 12 %), both conditions (n = 759, 33 %), or neither condition (n = 817, 36 %), and compared on multiple measures of distress and other suicide risk factors. RESULTS: Burnout alone and depression alone each predicted greater distress and suicide risk compared with neither condition. Depression was a stronger predictor than burnout and demonstrated a consistent association with other suicide risk factors regardless of whether burnout was present. In contrast, burnout was not consistently associated with other suicide risk factors when depression was present. LIMITATIONS: The sample was limited to one state-supported academic medical center; to individuals who elected to take the online survey; and relied on a single item, non-validated measure of burnout. CONCLUSION: When emotional distress is reported by healthcare workers, attention should not stop at "burnout," as burnout frequently comingles with clinical depression, a serious and treatable mental health condition.

A Comprehensive COVID-19 Daily News and Medical Literature Briefing to Inform Health Care and Policy in New Mexico: Implementation Study.

BACKGROUND: On March 11, 2020, the New Mexico Governor declared a public health emergency in response to the COVID-19 pandemic. The New Mexico medical advisory team contacted University of New Mexico (UNM) faculty to form a team to consolidate growing information on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its disease to facilitate New Mexico's pandemic management. Thus, faculty, physicians, staff, graduate students, and medical students created the "UNM Global Health COVID-19 Intelligence Briefing." OBJECTIVE: In this paper, we sought to (1) share how to create an informative briefing to guide public policy and medical practice and manage information overload with rapidly evolving scientific evidence; (2) determine the qualitative usefulness of the briefing to its readers; and (3) determine the qualitative effect this project has had on virtual medical education. METHODS: Microsoft Teams was used for manual and automated capture of COVID-19 articles and composition of briefings. Multilevel triaging saved impactful articles to be reviewed, and priority was placed on randomized controlled studies, meta-analyses, systematic reviews, practice guidelines, and information on health care and policy response to COVID-19. The finalized briefing was disseminated by email, a listserv, and posted on the UNM digital repository. A survey was sent to readers to determine briefing usefulness and whether it led to policy or medical practice changes. Medical students, unable to partake in direct patient care, proposed to the School of Medicine that involvement in the briefing should count as course credit, which was approved. The maintenance of medical student involvement in the briefings as well as this publication was led by medical students. RESULTS: An average of 456 articles were assessed daily. The briefings reached approximately 1000 people by email and listserv directly, with an unknown amount of forwarding. Digital repository tracking showed 5047 downloads across 116 countries as of July 5, 2020. The survey found 108 (95%) of 114 participants gained relevant knowledge, 90 (79%) believed it decreased misinformation, 27 (24%) used the briefing as their primary source of information, and 90 (79%) forwarded it to colleagues. Specific and impactful public policy decisions were informed based on the briefing. Medical students reported that the project allowed them to improve on their scientific literature assessment, stay current on the pandemic, and serve their community. CONCLUSIONS: The COVID-19 briefings succeeded in informing and guiding New Mexico policy and clinical practice. The project received positive feedback from the community and was shown to decrease information burden and misinformation. The virtual platforms allowed for the continuation of medical education. Variability in subject matter expertise was addressed with training, standardized article selection criteria, and collaborative editing led by faculty.

Preventing new episodes of bipolar disorder in adults: Systematic review and meta-analysis of randomized controlled trials.

Uncertainty remains regarding the relative efficacy of maintenance pharmacotherapy for bipolar disorder (BD), and available data require updating. The present systematic review and meta-analysis aims to consolidate the evidence from the highest quality randomized controlled trials (RCTs) published up to July 2021, overcoming the limitations of earlier reviews. The PubMed and the Cochrane Central Register of Controlled Trials were searched for double-blind RCTs involving lithium, mood stabilizing anticonvulsants (MSAs), antipsychotics, antidepressants, and other treatments. Rates of new mood episodes with test vs. reference treatments (placebo or alternative active agent) were compared by random-effects meta-analysis. Polarity index was calculated for each treatment type. Eligible trials involved ≥6 months of maintenance follow up. Of 2,158 identified reports, 22 met study eligibility criteria, and involved 7,773 subjects stabilized for 1-12 weeks and followed-up for 24-104 weeks. Psychotropic monotherapy overall (including lithium, MSAs, and second generation antipsychotics (SGA) was more effective in preventing new BD episodes than placebo (odds ratio, OR=0.42; 95% confidence interval, CI 0.34-0.51, p<0.00001). Significantly lower risk of new BD episodes was observed with the following individual drugs: aripiprazole, asenapine, lithium, olanzapine, quetiapine, and risperidone long-acting (ORs varied 0.19-0.46). Adding aripiprazole, divalproex, quetiapine, or olanzapine/risperidone to lithium or an MSA was more effective compared with lithium or MSA monotherapy (OR=0.37; 95%CI 0.25-0.55, p<0.00001). Active treatment favored prevention of mania over depression. The key limitations were "responder-enriched" design in most trials and high outcomes heterogeneity. PROSPERO registration number is CRD42020162663.

Predictors of diagnostic transition from major depressive disorder to bipolar disorder: a retrospective observational network study.

Many patients with bipolar disorder (BD) are initially misdiagnosed with major depressive disorder (MDD) and are treated with antidepressants, whose potential iatrogenic effects are widely discussed. It is unknown whether MDD is a comorbidity of BD or its earlier stage, and no consensus exists on individual conversion predictors, delaying BD's timely recognition and treatment. We aimed to build a predictive model of MDD to BD conversion and to validate it across a multi-national network of patient databases using the standardization afforded by the Observational Medical Outcomes Partnership (OMOP) common data model. Five "training" US databases were retrospectively analyzed: IBM MarketScan CCAE, MDCR, MDCD, Optum EHR, and Optum Claims. Cyclops regularized logistic regression models were developed on one-year MDD-BD conversion with all standard covariates from the HADES PatientLevelPrediction package. Time-to-conversion Kaplan-Meier analysis was performed up to a decade after MDD, stratified by model-estimated risk. External validation of the final prediction model was performed across 9 patient record databases within the Observational Health Data Sciences and Informatics (OHDSI) network internationally. The model's area under the curve (AUC) varied 0.633-0.745 (µ = 0.689) across the five US training databases. Nine variables predicted one-year MDD-BD transition. Factors that increased risk were: younger age, severe depression, psychosis, anxiety, substance misuse, self-harm thoughts/actions, and prior mental disorder. AUCs of the validation datasets ranged 0.570-0.785 (µ = 0.664). An assessment algorithm was built for MDD to BD conversion that allows distinguishing as much as 100-fold risk differences among patients and validates well across multiple international data sources.

Characteristics of Hispanics Referred to Coordinated Specialty Care for First-Episode Psychosis and Factors Associated With Enrollment.

OBJECTIVE: The primary objectives of this study were to examine referral sources and demographic, clinical, and socioenvironmental characteristics of Hispanics referred to and enrolled in a program of coordinated specialty care (Early CSC program) for first-episode psychosis, to compare them with characteristics of other referred and enrolled racial-ethnic groups, and to identify factors associated with enrollment in the program. METHODS: A retrospective review was conducted for all individuals referred to and enrolled in the Early CSC program over a 2-year period. Extracted data included referral sources and demographic and clinical characteristics. Zip code-level data from publicly available sources were cross-referenced with individual records. Nonparametric tests and appropriate secondary analysis were used to determine significant differences across racial-ethnic groups referred to (N=180) or enrolled in (N=75) the Early CSC program. A random forest model was used to determine which factors or interacting factors were associated with enrollment among the eligible referrals (N=114). RESULTS: Hispanic individuals were more likely to be referred from inpatient or outpatient mental health providers and not from other community sources. Among eligible Hispanic referrals, those who lived in areas with a lower percentage of Spanish speaking in the home were more likely to enroll in services, compared with those who lived in areas with a higher percentage of Spanish speaking. CONCLUSIONS: Continued exploration of factors associated with referral and enrollment in CSC programs for the growing Hispanic ethnic group in the United States can help determine best steps for developing these programs.

Using Machine Learning Imputed Outcomes to Assess Drug-Dependent Risk of Self-Harm in Patients with Bipolar Disorder: A Comparative Effectiveness Study.

BACKGROUND: Incomplete suicidality coding in administrative claims data is a known obstacle for observational studies. With most of the negative outcomes missing from the data, it is challenging to assess the evidence on treatment strategies for the prevention of self-harm in bipolar disorder (BD), including pharmacotherapy and psychotherapy. There are conflicting data from studies on the drug-dependent risk of self-harm, and there is major uncertainty regarding the preventive effect of monotherapy and drug combinations. OBJECTIVE: The aim of this study was to compare all commonly used BD pharmacotherapies, as well as psychotherapy for the risk of self-harm, in a large population of commercially insured individuals, using self-harm imputation to overcome the known limitations of this outcome being underrecorded within US electronic health care records. METHODS: The IBM MarketScan administrative claims database was used to compare self-harm risk in patients with BD following 65 drug regimens and drug-free periods. Probable but uncoded self-harm events were imputed via machine learning, with different probability thresholds examined in a sensitivity analysis. Comparators included lithium, mood-stabilizing anticonvulsants (MSAs), second-generation antipsychotics (SGAs), first-generation antipsychotics (FGAs), and five classes of antidepressants. Cox regression models with time-varying covariates were built for individual treatment regimens and for any pharmacotherapy with or without psychosocial interventions ("psychotherapy"). RESULTS: Among 529,359 patients, 1.66% (n=8813 events) had imputed and/or coded self-harm following the exposure of interest. A higher self-harm risk was observed during adolescence. After multiple testing adjustment (P≤.012), the following six regimens had higher risk of self-harm than lithium: tri/tetracyclic antidepressants + SGA, FGA + MSA, FGA, serotonin-norepinephrine reuptake inhibitor (SNRI) + SGA, lithium + MSA, and lithium + SGA (hazard ratios [HRs] 1.44-2.29), and the following nine had lower risk: lamotrigine, valproate, risperidone, aripiprazole, SNRI, selective serotonin reuptake inhibitor (SSRI), "no drug," bupropion, and bupropion + SSRI (HRs 0.28-0.74). Psychotherapy alone (without medication) had a lower self-harm risk than no treatment (HR 0.56, 95% CI 0.52-0.60; P=8.76×10-58). The sensitivity analysis showed that the direction of drug-outcome associations did not change as a function of the self-harm probability threshold. CONCLUSIONS: Our data support evidence on the effectiveness of antidepressants, MSAs, and psychotherapy for self-harm prevention in BD. TRIAL REGISTRATION: ClinicalTrials.gov NCT02893371; https://clinicaltrials.gov/ct2/show/NCT02893371.

Imputation and characterization of uncoded self-harm in major mental illness using machine learning.

OBJECTIVE: We aimed to impute uncoded self-harm in administrative claims data of individuals with major mental illness (MMI), characterize self-harm incidence, and identify factors associated with coding bias. MATERIALS AND METHODS: The IBM MarketScan database (2003-2016) was used to analyze visit-level self-harm in 10 120 030 patients with ≥2 MMI codes. Five machine learning (ML) classifiers were tested on a balanced data subset, with XGBoost selected for the full dataset. Classification performance was validated via random data mislabeling and comparison with a clinician-derived "gold standard." The incidence of coded and imputed self-harm was characterized by year, patient age, sex, U.S. state, and MMI diagnosis. RESULTS: Imputation identified 1 592 703 self-harm events vs 83 113 coded events, with areas under the curve >0.99 for the balanced and full datasets, and 83.5% agreement with the gold standard. The overall coded and imputed self-harm incidence were 0.28% and 5.34%, respectively, varied considerably by age and sex, and was highest in individuals with multiple MMI diagnoses. Self-harm undercoding was higher in male than in female individuals and increased with age. Substance abuse, injuries, poisoning, asphyxiation, brain disorders, harmful thoughts, and psychotherapy were the main features used by ML to classify visits. DISCUSSION: Only 1 of 19 self-harm events was coded for individuals with MMI. ML demonstrated excellent performance in recovering self-harm visits. Male individuals and seniors with MMI are particularly vulnerable to self-harm undercoding and may be at risk of not getting appropriate psychiatric care. CONCLUSIONS: ML can effectively recover unrecorded self-harm in claims data and inform psychiatric epidemiological and observational studies.

Diabetes mellitus risk for 102 drugs and drug combinations used in patients with bipolar disorder.

OBJECTIVE: To compare the largest set of bipolar disorder pharmacotherapies to date (102 drugs and drug combinations) for risk of diabetes mellitus (DM). METHODS: The IBM MarketScan® database was used to retrospectively analyze data on 565,253 adults with bipolar disorder without prior glucose metabolism-related diagnoses. The pharmacotherapies compared were lithium, mood-stabilizing anticonvulsants, antipsychotics, and antidepressants (monotherapy and multi-class polypharmacy). Cox regression modeling included fixed pre-treatment covariates and time-varying drug exposure covariates to estimate the hazard ratio (HR) of each treatment versus "No drug". RESULTS: The annual incidence of new-onset diabetes during the exposure period was 3.09 % (22,951 patients). The HR of drug-dependent DM ranged from 0.79 to 2.37. One-third of the studied pharmacotherapies, including most of the antipsychotic-containing regimens, had a significantly higher risk of DM compared to "No drug". A significantly lower DM risk was associated with lithium, lamotrigine, oxcarbazepine and bupropion monotherapies, selective serotonin reuptake inhibitors (SSRI) mono-class therapy and several drug combinations containing bupropion and an SSRI. As additional drugs were combined in more complex polypharmacy, higher HRs were consistently observed. CONCLUSIONS: There is an increased risk of diabetes mellitus associated with antipsychotic and psychotropic polypharmacy use in bipolar disorder. The evidence of a lower-than-baseline risk of DM with lamotrigine, oxcarbazepine, lithium, and bupropion monotherapy should be further investigated.

Preferences of Information Dissemination on Treatment for Bipolar Disorder: Patient-Centered Focus Group Study.

BACKGROUND: Patient education has taken center stage in successfully shared decision making between patients and health care providers. However, little is known about how patients with bipolar disorder typically obtain information on their illness and the treatment options available to them. OBJECTIVE: This study aimed to obtain the perspectives of patients with bipolar disorder and their family members on the preferred and most effectively used information channels on bipolar disorder and the available treatment options. METHODS: We conducted nine focus groups in Montana, New Mexico, and California, in which we surveyed 84 individuals including patients with bipolar disorder and family members of patients with bipolar disorder. The participants were recruited using National Alliance on Mental Illness mailing lists and websites. Written verbatim responses to semistructured questionnaires were analyzed using summative content analysis based on grounded theory. Two annotators coded and analyzed the data on the sentence or phrase level to create themes. Relationships between demographics and information channel were also examined using the Chi-square and Fisher exact tests. RESULTS: The focus group participants mentioned a broad range of information channels that were successfully used in the past and could be recommended for future information dissemination. The majority of participants used providers (74%) and internet-based resources (75%) as their main information sources. There was no association between internet use and basic demographics such as age or geographical region of the focus groups. Patients considered time constraints and the fast pace in which an overwhelming amount of information is often presented by the provider as major barriers to successful provider-patient interactions. If Web-based channels were used, the participants perceived information obtained through Web-based channels as more helpful than information received in the provider's office (P<.05). CONCLUSIONS: Web-based resources are increasingly used by patients with bipolar disorder and their family members to educate themselves about the disease and its treatment. Although provider-patient interactions are frequently perceived to be burdened with time constraints, Web-based information sources are considered reliable and helpful. Future research should explore how high-quality websites could be used to empower patients and improve provider-patient interactions with the goal of enhancing shared decision making between patients and providers.

Comparison of 71 bipolar disorder pharmacotherapies for kidney disorder risk: The potential hazards of polypharmacy.

BACKGROUND: This study compared the largest set of bipolar disorder pharmacotherapies to date (71 drugs and drug combinations) for risk of kidney disorders (KDs). METHODS: This retrospective observational study used the IBM MarketScan® database to analyze data on 591,052 adults with bipolar disorder without prior nephropathy, for onset of KDs (of "moderate" or "high" severity) following psychopharmacotherapy (lithium, mood stabilizing anticonvulsants [MSAs], antipsychotics, antidepressants), or "No drug". Cox regression models included fixed pre-treatment covariates and time-varying drug exposure covariates to estimate the hazard ratio (HR) of each treatment versus "No drug". RESULTS: Newly observed KD occurred in 14,713 patients. No regimen had significantly lower risk of KDs than "No drug". The HR estimates ranged 0.86-2.66 for "all" KDs and 0.87-5.30 for "severe" KDs. As additional drugs were combined to compare more complex polypharmacies, higher HRs were consistently observed. Most regimens containing lithium, MSAs, or antipsychotics had a higher risk than "No drug" (p < 0.05). The risk for "all" and "severe" KDs was highest respectively on monoamine oxidase inhibitors (MAOIs) (HR = 2.66, p = 5.73 × 10-5), and a lithium-containing four-class combination (HR = 5.30, p = 2.46 × 10-9). The HR for lithium monotherapy was 1.82 (p = 4.73 × 10-17) for "severe" KDs. LIMITATIONS: The limitations inherent for an observational study were non-randomized assignment of patients to treatment groups, non-standardization of diagnostic decisions, and non-uniform quality of data collection. No correction was made for medication dosage. CONCLUSIONS: The findings support literature concerns about lithium nephrotoxicity and highlight the potential risks of MAOIs, MSAs, antipsychotics and psychotropic polypharmacy.

Long-term changes of salivary exoglycosidases and their applicability as chronic alcohol-drinking and dependence markers.

OBJECTIVES: Investigation of long-term dynamic changes of salivary activity/output of exoglycosidases, deglycosylation processes and their applicability as alcohol markers. METHODS: Exoglycosidase (α-fucosidase (FUC), ß-galactosidase (GAL), ß-glucuronidase (GLU), ß-hexosaminidase (HEX, HEX A and HEX B isoenzymes) and α-mannosidase (MAN)) activities were measured in the saliva of healthy social drinking controls (C), alcohol-dependent non-smokers (ANS) and alcohol-dependent smokers (AS) at the 1st, 15th, 30th and 50th day of abstinence after chronic alcohol drinking. RESULTS: The activity of exoglycosidases was 2-3-fold (MAN), 2-6 fold (FUC), 8-25-fold (HEX A) and 19-40-fold (GLU) higher in the ANS and AS groups than in controls, and had good/excellent sensitivity, specificity and accuracy. The higher outputs of exoglycosidases were in the AS and ANS groups than in controls at the 1st day (GLU, HEX A) and at the 50th day (GLU, FUC, MAN) of abstinence. We found numerous correlations between alcohol-drinking days with GLU and HEX A, alcohol amounts with HEX A and duration of alcohol dependence with FUC and MAN activity/output. CONCLUSIONS: Salivary exoglycosidases/deglycosylation processes were still very high up to 50 days after the end of alcohol consumption. We found markers of chronic alcohol consumption (HEX A), alcohol dependence (FUC and MAN) and chronic alcohol consumption and dependence (GLU).

Neurobiological Effects of Binge Drinking Help in Its Detection and Differential Diagnosis from Alcohol Dependence.

The prevalence of binge drinking in the general population is 3-4 times higher than that of alcohol dependence. Neuroimaging studies show that binge drinking in adolescence impairs brain development and white matter integrity. Regions with reduced functional activity include the limbic system, ventral diencephalon, frontal lobe, and middle and inferior temporal lobes, whereas the right superior frontal and parietal lobes are typically hyperactivated. The observed activation of the frontoparietal areas might reflect the alternative memory system operating, whereas the reduced occipito-hippocampal response is associated with impaired visual and linguistic processing/learning. Some other findings from literature research include a decrease of N-acetylaspartate (NAA) in the frontal lobe and its increase in the parietal lobes, as well as the reduced components of event-related potentials, reflecting deficit in attention, working memory, inhibition, and executive functioning. Animal studies show that even a single day of binge drinking results in a neurodegeneration and reactive gliosis in the limbic cortex as well as in gene expression dysregulation and histone acetylation. Another biological evidence on binge drinking effect include inflammatory response, oxidative stress, formation of toxic ceramides, activation of caspase 3, and secretion of corticoliberin. Some of the binge drinking-induced cognitive abnormalities can be reversible after three weeks of abstinence. Although binge drinkers have a similar pattern of neuropsychological deficits with chronic alcohol consumers (mainly memory deficits), binge drinkers have prominent impairment of inhibitory control, which may be a marker of binge pattern of alcohol drinking. The optimal therapeutic strategies should target the inhibitory control processes to facilitate discontinuation of alcohol consumption and to block its possible progression to the alcohol dependence syndrome.

Trends in patient procurement of postoperative opioids and route of hysterectomy in the United States from 2004 through 2014.

BACKGROUND: The opioid epidemic in the United States is a public health emergency. Minimally invasive surgical technology has decreased length of hospital stay, improved postoperative recovery, and decreased postoperative pain. Hysterectomy is one of the most commonly performed surgeries in the United States. Increasing trends in minimally invasive gynecologic surgery are expected to reduce patients' postoperative pain. It is unclear whether this assumption has resulted in decreasing postoperative opioid prescriptions or patient need for these prescriptions, as prescribing patterns may be contributing to the current opioid public health emergency. OBJECTIVE: We sought to describe opioid prescribing and patient procurement practices for postoperative pain at time of discharge for benign hysterectomy from 2004 through 2014 using the Truven Health Analytics MarketScan Research Database. The trends of the route of hysterectomy over this time period were concomitantly described to reflect the movement toward more minimally invasive approaches. STUDY DESIGN: The Truven Health Analytics MarketScan Research Database including the Commercial Claims and Encounters Database, and the Medicare Supplemental and Coordination of Benefits Database were utilized. Current Procedural Terminology, 4th Edition, and International Classification of Diseases, Ninth Revision, codes identified all patients who underwent a hysterectomy for benign indications from 2004 through 2014. Hysterectomy routes were categorized into abdominal, laparoscopic, and vaginal. The MarketScan database captures prescriptions filled at a retail or mail-order pharmacy and does not capture prescriptions filled within the inpatient, hospital facility. The days of opioids procured by patients at the time of discharge were identified for each encounter. Descriptive statistics were used to summarize data within the entire study period. Although this article is purely descriptive, further analyses were conducted for exploratory purposes only. analysis of variance and χ2 analyses were used for continuous and categorical variables, respectively. Multiple linear regression models were used to describe associations between variables of interest and postoperative opioid prescriptions. RESULTS: We identified 793,016 patients who underwent a hysterectomy for benign indications from 2004 through 2014. Of these, 96% were identified from the Commercial Claims and Encounters Database. During the study period, the overall route of hysterectomy was categorized into 40.5% abdominal, 42.0% laparoscopic, and 17.5% vaginal hysterectomy. The route of hysterectomy changed from 60.2-25.6% (a decrease of Δ = 34.58; 95% confidence interval, 33.96-35.20) for abdominal, 17.0-61.9% (an increase of Δ = 44.83; 95% confidence interval, 44.21-45.44) for laparoscopic, and 22.8-12.6% (a decrease of Δ = 10.25; 95% confidence interval, 9.77-10.73) for vaginal. At discharge, the percentage of patients who were prescribed opioids and filled them increased from 25.6-82.1% (an increase of Δ = 56.50; 95% confidence interval, 55.88-57.13 with P < .001) from 2004 through 2014 for all hysterectomy routes. Additionally, the quantity of opioids prescribed also increased. CONCLUSION: Opioid prescriptions filled for postoperative pain after hysterectomy substantially increased from 2004 through 2014. Opioid prescription procurement has increased despite a concomitant increase in minimally invasive hysterectomy routes. In light of the current opioid epidemic, physicians must recognize that postoperative prescribing practices may contribute to chronic opioid use. Heightened awareness of opioid prescribing practices following surgery is critically important to decrease risk of development of chronic opioid dependence.

Association of MIR137 With Symptom Severity and Cognitive Functioning in Belarusian Schizophrenia Patients.

MicroRNA-137 (miRNA-137; miR-137) is one of the important post-transcriptional regulators of the nervous system development, and its MIR137 gene rs1625579 polymorphism was reported to be a potential regulator for schizophrenia susceptibility. However, schizophrenia characteristics controlled by MIR137 rs1625579 polymorphism are still insufficiently understood. There were 3 groups included in the study: (a) subjects with diagnosis of schizophrenia (n = 150; 81-females, 69-males), (b) mentally healthy people (control group; n = 102; 66-females, 36-males) and (c) Belarusian indigenous male group (n = 295). Associations of rs1625579 with schizophrenia, symptom's severity and cognitive performance [by using Positive and Negative Syndrome Scale (PANSS) and Wisconsin Card Sorting Test (WCST), respectively] were studied, when compared to controls. Allele and genotype frequencies were investigated in Belarusian indigenous males. Rs1625579 displayed no association with schizophrenia in Belarusian population. Significant "symptom severity-genotype" interactions were revealed for schizophrenia patients. Patients with T/G genotype displayed lower severity of positive symptoms and general psychopathology compared to homozygous subjects. T/T genotype was associated with the highest symptom's severity. The negative symptom scores and the total PANSS-score were significantly higher in females carrying genotype T/T vs. T/G+G/G; no significant gene-phenotype associations were found in males. WCST parameters did not show any association with rs1625579 polymorphism. MIR137 rs1625579 polymorphism might be an important sex-dependent factor influencing severity of schizophrenia psychopathological manifestations. These findings also contribute to the knowledge on candidate gene effects on characteristics related to schizophrenia phenotype. As miR 137 is considered to be cancer therapeutic target, miR-137 may also explain the lower incidence of cancer in schizophrenia patients. Further studies with larger sample size are needed to confirm these novel findings.

Comprehensive comparison of monotherapies for psychiatric hospitalization risk in bipolar disorders.

OBJECTIVES: This study compared 29 drugs for risk of psychiatric hospitalization in bipolar disorders, addressing the evidence gap on the >50 drugs used by US patients for treatment. METHODS: The Truven Health Analytics MarketScan® database was used to identify 190 894 individuals with bipolar or schizoaffective disorder who filled a prescription for one of 29 drugs of interest: lithium, first- or second-generation antipsychotics, mood-stabilizing anticonvulsants, and antidepressants. Competing risks regression survival analysis was used to compare drugs for risk of psychiatric hospitalization, adjusting for patient age, sex, comorbidities, and pretreatment medications. Other competing risks were ending monotherapy and non-psychiatric hospitalization. RESULTS: Three drugs were associated with significantly lower risk of psychiatric hospitalization than lithium: valproate (relative risk [RR] = 0.80, P = 3.20 × 10-4 ), aripiprazole (RR = 0.80, P = 3.50 × 10-4 ), and bupropion (RR = 0.80, P = 2.80 × 10-4 ). Eight drugs were associated with significantly higher risk of psychiatric hospitalization: haloperidol (RR = 1.57, P = 9.40 × 10-4 ), clozapine (RR = 1.52, P = .017), fluoxetine (RR = 1.17, P = 3.70 × 10-3 ), sertraline (RR = 1.17, P = 3.20 × 10-3 ), citalopram (RR = 1.14, P = .013), duloxetine (RR = 1.24, P = 5.10 × 10-4 ), venlafaxine (RR = 1.33; P = 1.00 × 10-6 ), and ziprasidone (RR = 1.25; P = 6.20 × 10-3 ). CONCLUSIONS: This largest reported retrospective observational study on bipolar disorders pharmacotherapy to date demonstrates that the majority of patients end monotherapy within 2 months after treatment start. The risk of psychiatric hospitalization varied almost two-fold across individual medications. The data add to the evidence favoring lithium and mood stabilizer use in short-term bipolar disorder management. The findings that the dopaminergic drugs aripiprazole and bupropion had better outcomes than other members of their respective classes and that antidepressant outcomes may vary by baseline mood polarity merit further investigation.

Systemic challenges in bipolar disorder management: A patient-centered approach.

OBJECTIVES: As part of a series of Patient-Centered Outcomes Research Institute-funded large-scale retrospective observational studies on bipolar disorder (BD) treatments and outcomes, we sought the input of patients with BD and their family members to develop research questions. We aimed to identify systemic root causes of patient-reported challenges with BD management in order to guide subsequent studies and initiatives. METHODS: Three focus groups were conducted where patients and their family members (total n = 34) formulated questions around the central theme, "What do you wish you had known in advance or over the course of treatment for BD?" In an affinity mapping exercise, participants clustered their questions and ranked the resulting categories by importance. The research team and members of our patient partner advisory council further rated the questions by expected impact on patients. Using a Theory of Constraints systems thinking approach, several causal models of BD management challenges and their potential solution were developed with patients using the focus group data. RESULTS: A total of 369 research questions were mapped to 33 categories revealing 10 broad themes. The top priorities for patient stakeholders involved pharmacotherapy and treatment alternatives. Analysis of causal relationships underlying 47 patient concerns revealed two core conflicts: for patients, whether or not to take pharmacotherapy, and for mental health services, the dilemma of care quality vs quantity. CONCLUSIONS: To alleviate the core conflicts identified, BD management requires a coordinated multidisciplinary approach including: improved access to mental health services, objective diagnostics, sufficient provider visit time, evidence-based individualized treatment, and psychosocial support.