Group-Based Trajectory Modeling to Identify Patterns of Antipsychotic-Associated Weight Gain Among Children and Adolescents.

PURPOSE/BACKGROUND: Antipsychotic-associated weight gain (AAWG) is a common adverse effect of second-generation antipsychotic (SGA) medications among children and adolescents. This study applied group-based trajectory modeling to identify latent trajectories of AAWG among children and adolescents and associated risk factors. PROCEDURES: This was a retrospective analysis of the IQVIA Ambulatory EMR-US database from 2016 to 2021. The cohort consisted of patients aged 6 to 19 years who were SGA naive and received at least 90 days of continuous SGA prescriptions. Group-based trajectory modeling was used to identify latent trajectories of AAWG development during a 24-month period since SGA initiation, and multinomial logistic regression analysis was conducted to examine the risk factors associated with the identified AAWG trajectories. FINDINGS/RESULTS: A total of 16,262 patients were included. Group-based trajectory modeling identified the following 4 distinctive AAWG trajectories: persistent severe weight gain (4.2%), persistent moderate weight gain (20.1%), minor weight change (69.6%), and gradual weight loss (6.1%). Compared with the minor weight change group, younger age (12-17 vs 5-11: odds ratio [OR], 0.634; 95% confidence interval [CI], 0.521-0.771), lower baseline body mass index z -score (OR, 0.216; 95% CI, 0.198-0.236), and receiving olanzapine as the initial SGA (olanzapine vs aripiprazole: OR, 1.686; 95% CI, 1.673-1.699) were more likely to follow severe weight gain trajectories. The area under the receiver operating characteristic curves for comparing severe weight gain versus minor weight change groups and moderate weight vs minor weight change groups in the multinomial regression model were 0.91 and 0.8, respectively. IMPLICATIONS/CONCLUSIONS: A quarter of pediatric SGA recipients experienced persistent weight gain during the SGA treatment. The risk of having persistent AAWG can be predicted using patient characteristics collected before SGA initiation and the initial SGA agent.

Impact of geographic access to primary care providers on pediatric behavioral health screening.

Behavioral Health (BH) screening is critical for early diagnosis and treatment of pediatric mental disorders. The objective of this study was to assess the impact of geographic access to primary care providers (PCP) on pediatric BH screening in children with different race/ethnicity. A retrospective cohort study was conducted using the 2013-2016 administrative claims data from a large pediatric Medicaid Managed Care Plan that have been linked to 2010 US Census data and the 2017 National Provider Identifier (NPI) Registry. Geographic access was defined as the actual travel distance to nearest PCP and the PCP density within 10-mile travel radius from each individual's residence. Stratified multivariate logistic regression was conducted to examine the association between the geographic access to PCP and the likelihood of receiving screening for behavioral disorders within each racial/ethnic group. BH screening rate was 12.6% among 402,655 children and adolescents who met the inclusion criteria. Multivariable analysis stratified by individual race/ethnicity revealed that Hispanic and Black children were more vulnerable to the geographic access barriers than their non-Hispanic White counterparts. The increase in travel distance to the nearest PCP was negatively associated with screening uptake only among Hispanics (10-20 miles vs. 0-10 miles: OR = 0.78, 95% CI [0.71-0.86]; 20-30 miles vs. 0-10 miles: OR = 0.35, 95% CI [0.23-0.54]). In a subgroup that had access to at least one PCP within 10 miles of travel distance, the variation in PCP density had a greater impact on the screening uptake among Hispanics and Blacks than that in non-Hispanic Whites.

Systematic Review and Meta-Analysis of Bone Marrow-Derived Mononuclear Cells in Animal Models of Ischemic Stroke.

BACKGROUND AND PURPOSE: Bone marrow-derived mononuclear cells (BMMNCs) offer the promise of augmenting poststroke recovery. There is mounting evidence of safety and efficacy of BMMNCs from preclinical studies of ischemic stroke; however, their pooled effects have not been described. METHODS: Using Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines, we conducted a systematic review of preclinical literature for intravenous use of BMMNCs followed by meta-analyses of histological and behavioral outcomes. Studies were selected based on predefined criteria. Data were abstracted by 2 independent investigators. After quality assessment, the pooled effects were generated using mixed-effect models. Impact of possible biases on estimated effect size was evaluated. RESULTS: Standardized mean difference and 95% confidence interval for reduction in lesion volume was significantly beneficial for BMMNC treatment (standardized mean difference: -3.3; 95% confidence interval, -4.3 to -2.3). n=113 each for BMMNC and controls. BMMNC-treated animals (n=161) also had improved function measured by cylinder test (standardized mean difference: -2.4; 95% confidence interval, -3.1 to -1.6), as compared with controls (n=205). A trend for benefit was observed for adhesive removal test and neurological deficit score. Study quality score (median: 6; Q1-Q3: 5-7) was correlated with year of publication. There was funnel plot asymmetry; however, the pooled effects were robust to the correction of this bias and remained significant in favor of BMMNC treatment. CONCLUSIONS: BMMNCs demonstrate beneficial effects across histological and behavioral outcomes in animal ischemic stroke models. Although study quality has improved over time, considerable degree of heterogeneity calls for standardization in the conduct and reporting of experimentation.

Adherence to Recommended Metabolic Monitoring of Children and Adolescents Taking Second-Generation Antipsychotics.

OBJECTIVE: Clinical guidelines recommend periodic monitoring for adverse metabolic effects associated with second-generation antipsychotic medications. The authors sought to evaluate adherence to the guideline-recommended metabolic monitoring schedule for children and adolescents prescribed second-generation antipsychotics. METHODS: The authors used a national electronic medical records database for a retrospective study of children and adolescents ages 1-17 years (N=9,620) who were prescribed second-generation antipsychotics in January 2010-December 2018. Adherence to guideline-recommended monitoring of body mass index (BMI), blood glucose, and cholesterol was categorized as full, partial, and no monitoring. Full monitoring of patients was defined as strict metabolic monitoring, following the guideline-recommended schedule. Patients who received any monitoring, but not meeting the full monitoring criteria, were considered partially monitored. Three multinomial logistic regression models were fitted for each metabolic parameter to identify predictors associated with monitoring status. RESULTS: BMI was the metabolic parameter with the highest adherence to guideline-recommended monitoring (full monitoring, 4.7% of patients; partial monitoring, 44.8%), followed by blood glucose (full monitoring, 6.5%; partial monitoring, 29.4%) and cholesterol (full monitoring, 0.8%; partial monitoring, 22.4%). Being Black (vs. non-Black), having a comorbid mood disorder (vs. none), receiving olanzapine as the index second-generation antipsychotic (vs. aripiprazole), and receiving an antidepressant as a concurrent medication (vs. none) were associated with a higher likelihood of receiving both full and partial monitoring of all three metabolic parameters. CONCLUSIONS: Both full and partial adherence to guideline-recommended monitoring of children and adolescents prescribed second-generation antipsychotics were poor. However, children and adolescents at increased metabolic risk tended to be more closely monitored.

Trajectories and Predictors for the Development of Clinically Significant Weight Gain in Children and Adolescents Prescribed Second-Generation Antipsychotics.

Background: As many as 60% of pediatric patients taking second-generation antipsychotics (SGA) experience weight gain (antipsychotic-induced weight gain). However, the subgroup that experienced substantial weight increase was poorly understood. This study aimed to identify the development and predictors of clinically significant weight gain (CSWG) among pediatric SGA recipients. Methods: A retrospective analysis of the 2016 to 2021 IQVIA Ambulatory EMR-US database was conducted. The study cohort comprised SGA-naive patients ages 5 to 19, continuously prescribed SGA for ≥90 days. CSWG was defined as a weight gain in BMI z-score >0.5. The development of CSWG was described using the group-based trajectory model approach, and multinomial logistic regression analysis was conducted to examine the risk factors associated with the CSWG trajectories. Results: Of the 16,262 SGA recipients who met the inclusion criteria, 4 distinctive CSWG trajectories were identified: (1) Rapid (14.6%), (2) Gradual (12.6%), (3) Transit (7%), and (4) no CSWG (65.8%). Factors associated with a higher likelihood of having rapid or gradual CSWG versus nonsignificant weight gain were being younger (OR [95% CI] = 12-17 vs. 5-11, Rapid, 0.727 [0.655-0.806]; Gradual, 0.776 [0.668-0.903]), male (Rapid, 1.131 [1.021-1.253]), non-Hispanic White (Black vs. White: Rapid, 0.833 [0.709-0.98]), with lower baseline BMI z-score (Rapid, 0.376 [0.361-0.392]; Gradual, 0.449 [0.424-0.476]), and receiving olanzapine as the initial SGA (Rapid, 1.38 [1.093-1.74]). The Area under the Receiver operating characteristic (ROC) Curve for the comparison of rapid and gradual CSWG with no CSWG trajectory were 0.83 and 0.80, respectively. Conclusions: SGA recipients experienced four distinctive CSWG trajectories (Rapid, Gradual, Transient, and No CSWG). The risk of CSWG could be predicted using patient characteristics at the SGA initiation. This insight highlights the importance of personalized monitoring and timely intervention strategies for at-risk individuals who experienced persistent CSWG in real practice.

Impact of the AACAP practice parameters on the metabolic adverse event monitoring for second-generation antipsychotics (SGAs) in children and adolescents.

INTRODUCTION: The objective of our study was to evaluate the impact of the publication of the American Academy of Child and Adolescent Psychiatry (AACAP) practice parameters for SGA metabolic monitoring in 2011 on SGA metabolic monitoring uptake among pediatric SGA recipients. METHODS: This was a retrospective study of children 1-17 years of age who initiated SGA treatment from Jan 2010 to December 2018 using a national Electronic Medical Records database. A segmented regression of interrupted time-series (ITS) analysis was conducted to analyze the change of metabolic monitoring rates for Body Mass Index (BMI), Blood Glucose (BG), and Total Cholesterol (CHL) 9 quarters pre- and 26 quarters post-the publication of the AACAP practice parameters. RESULTS: The analytical cohort included 9620 children and adolescents who initiated SGA treatment during the study period. The ITS results showed that the publication of the AACAP practice parameter for SGA metabolic monitoring was associated with a 12.61 percentage points (p < 0.0002) immediate increase in BMI monitoring rate, (increased from 29.10% in Q4 2011 to 40.10% in Q3 2012). There was a positive trend of BMI monitoring rate prior to the publication of AACAP practice parameters, which continued during the post-publication period. Neither immediate nor sustained changes in the association of monitoring rates for BG and CHL were observed after the issuance of the guidelines. CONCLUSION: The publication of AACAP practice parameters for SGA monitoring was associated with a significant improvement in the monitoring for BMI, but not for BG and CHL in children and adolescents.

Association Between Abnormal Metabolic Parameters and Receiving Subsequent Interventions in Children and Adolescents Initiating Second-Generation Antipsychotics.

Objectives: This study aimed to examine the association between abnormal readings of metabolic parameters detected during second-generation antipsychotic (SGA) treatment and the likelihood of receiving subsequent adverse drug event interventions. Methods: This was a nested case-control study conducted on patients 1-17 years of age with at least two prescriptions of SGAs between January 2010 and January 2019 using TriNetX EMR data. Following an incident density sampling procedure, patients who received the SGA metabolic adverse event intervention (mAEI) (case) were matched with three nonrecipients (controls). The abnormal readings of metabolic parameters within 30 days before the initiation of mAIEs were further identified. These metabolic parameters include body mass index (BMI) and laboratory parameters such as cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, blood glucose, HbA1c, thyroid hormones, liver enzymes, and prolactin. The association of abnormal metabolic parameters with subsequent mAEIs was assessed using a conditional logistic regression model, after adjusting for demographic and other clinical risk factors. Results: One thousand eight hundred eighty-four children and adolescents met the inclusion criteria and were prescribed SGA mAEIs. The most common types of mAEIs prescribed were weight management pharmacotherapy (40.6%), switching from a high or medium metabolic risk profile SGA to a low-risk one (30.9%), nonpharmacological treatment (25.4%), and switching from SGA polytherapy to monotherapy (11.7%). The conditional logistic regression analysis on matched mAEI recipients and nonrecipients showed that patients with an abnormal BMI had 43% higher odds of receiving mAEI (odds ratio [95% confidence interval]: 1.43 [1.13-1.79]). However, the presence of an abnormal laboratory reading was not associated with the initiation of mAEIs. Conclusions: The prescribing of mAEIs were associated with the presence of obesity, but not with abnormal readings of other metabolic parameters, suggesting that additional data are needed to clarify the long-term implication of SGA metabolic adverse events other than weight gain and to inform the appropriate timing for interventions.

Vertical Transmission and Discordance of Cytomegalovirus in Twin Pregnancies.

Objective: The objectives are to estimate the vertical transmission rate in twins relative to singleton pregnancies, to evaluate whether discordance within twin pairs is rare, and to characterize concordance within monozygotic and dizygotic twin pairs in relation to hereditability. Methods: We first sought to estimate the vertical transmission rate of congenital CMV infection in twins by gathering cohort-based studies of congenital CMV in which vertical transmission in both singleton and twin pregnancies was reported. This also allowed us to compare singleton and twin infection rates. From the above studies and other large cohorts of congenitally infected infants, the percentage of discordantly infected twin pairs determined whether this is a rare phenomenon. Theorizing discordance is not rare, we then analyzed data from cases with twin outcomes for congenital CMV infection, according to whether the twins were monozygotic or dizygotic, and calculated their corresponding concordance rates to estimate the broad-sense heritability. Lastly, we described other factors that might affect vertical transmission. Results: From five articles following at-risk pregnancies, the rate of vertical transmission in twin pregnancies is 58.7% (95% CI 43.3-72.3%) whereas in singleton pregnancies it is 31.4% (95% CI: 29.0-34.0%) p = 0.0002. Of ten studies of larger cohorts of infants with congenital CMV infection, 21 of 42 twin pairs with at least one twin infected were discordant for congenital CMV (50.0%, 95% CI: 34.4-65.6%) indicating discordance of congenital CMV infection in twin pairs is not rare. Of 28 studies covering 37 twin pairs where at least one twin had congenital CMV, and zygosity was known, eleven of thirteen monozygotic twin pairs (84.6%; 95% CI: 53.7-97.3%) were concordant for CMV infection, and nine of twenty-four dizygotic twin pairs (37.5%; 95% CI: 19.6-59.2%) were concordant for infection giving an estimated hereditability of 94.2%. Within these 37 twin pairs, factors such as primary or recurrent maternal infection, prematurity, growth discordance, and sex are described; however, in many of these cases these factors are unknown. Conclusion: The rate of vertical transmission of congenital CMV is higher for twins than singletons. Discordance of congenital CMV in twins is not rare and suggests a possible genetic susceptibility to congenital CMV.

Association of Primary and Behavioral Health Integrated Care Upon Pediatric Mental Disorder Treatment.

OBJECTIVE: The objective of this study was to examine whether linkage with mental health (MH) treatment differed across 3 different integrated care arrangements (ICAs), following incident attention deficit hyperactive disorder (ADHD) and major depressive disorder (MDD) diagnoses given by primary care providers (PCPs) in the pediatric setting. METHODS: Using claims linking with multiple public data sources, we examined the treatment initiation among children receiving an incident diagnosis of ADHD or MDD from PCPs working in practices with various ICAs. ICAs were categorized as PCP practiced alone (non-co-located), PCP practiced with specialist outside the practice but co-located at the practice site (co-located), and employed specialists who were co-located (co-located and co-affiliated). RESULTS: A total of 4203 incident ADHD and 298 incident MDD cases diagnosed by PCPs were identified, of which 3123 (74%) with ADHD and 200 (67%) with MDD received treatment within 90 days since the diagnosis. Children diagnosed with ADHD by co-located and co-affiliated PCPs were twice as likely to receive treatment as those diagnosed by non-co-located PCPs (odds ratio [OR] = 1.93; 95% confidence interval [CI], 1.24-2.78). Of those treated, children diagnosed by co-located and co-affiliated PCPs were 2 times more likely to receive guideline recommended psychotherapy (OR = 2.15; 95% CI, 1.35-3.44). These patients were also more likely to be treated at the diagnosing site versus elsewhere. Similar beneficial effects were not observed in those first diagnosed by co-located but non-affiliated PCPs. CONCLUSIONS: Service co-location between co-affiliated PCPs and MH specialists was associated with significant higher ADHD treatment rate and the receipt of guideline-recommended psychotherapy.

Laryngotracheal Stenosis in Early vs Late Tracheostomy: A Systematic Review.

OBJECTIVE: For critically ill patients undergoing long-term mechanical ventilation, to determine whether early conversion from endotracheal intubation to tracheostomy reduces the incidence of laryngotracheal stenosis. DATA SOURCES: MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and the Cumulative Index to Nursing and Allied Health Literature. REVIEW METHODS: A systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and an assessment of bias were performed. Included studies reported outcomes of patients who were converted from endotracheal intubation to tracheostomy, compared early vs late tracheostomy, and reported the incidence of laryngotracheal stenosis and details of postoperative surveillance. Data were also collected for intensive care setting, method of tracheostomy, and timing of tracheostomy. RESULTS: Seven articles met inclusion criteria: 2 randomized trials, 2 quasi-randomized trials, 1 prospective cohort, and 2 retrospective cohorts. A total of 966 patients were included in this analysis (496 in the early tracheostomy group and 470 in the late tracheostomy group). The mean incidence of laryngotracheal stenosis was 8.9% (range, 0%-20.8%), with a mean incidence of 8.1% in early tracheostomy groups and 10.9% in late tracheostomy groups. In studies with the least risk of bias, there were no differences in the incidence of laryngotracheal stenosis in patients who underwent early vs late tracheostomy. CONCLUSION: In critically ill patients undergoing long-term mechanical ventilation, early conversion to tracheostomy within 7 days of intubation does not significantly decrease the risk of laryngotracheal stenosis compared to later conversion as defined by the included studies.

The association between geographic access to providers and the treatment quality of pediatric depression.

OBJECTIVE: To examine the association of geographic access to providers with racial/ethnic variations in treatment quality among youth with depression. METHODS: The geographic access to providers who initiated the depression treatment was measured using the travel distance estimated based on Google Maps® and the provider density within a 5-mile radius of each patient residence. Depression treatment quality was measured as treatment engagement, defined as having ≥2 prescriptions or psychotherapy with 2-month following a new depression diagnosis, and treatment completion defined as having ≥8 sessions of psychotherapy within 12 weeks or received ≥84 days of continuous treatment with antidepressants within 114 days following the treatment initiation. RESULTS: The results of multivariate logistic regression analysis have demonstrated that the travel distance to provider was only negatively associated with the treatment engagement of Hispanics (5.0 - 14.9 vs ≤ 4.9 miles: OR=0.74, 95% CI [0.54-0.88]; ≥15 vs ≤ 4.9 miles: OR=0.82, 95% CI [0.56-0.97]), while a higher mental health specialist density was only positively associated with the treatment engagement of Blacks (1.00-1.99 vs < 1.00: OR=1.63, 95% CI [1.03-4.51]; 2.00-4.99 vs < 1.0: OR=2.28, 95% CI [1.21-7.11]). Among those who have engaged in the treatment, travel distance was associated with a lower likelihood of treatment completion in all racial/ethnic groups. LIMITATIONS: The study did not account for types of transportation used by patients. CONCLUSION: Geographic access barriers had a negative association with treatment quality of pediatric depression. Minority children were more sensitive to the barriers than Whites.

Integrating behavioral health and primary care: the Harris County Community Behavioral Health Program.

This column describes and evaluates the Harris County Community Behavioral Health Program, a new integrated care program operating in community health centers serving low-income uninsured residents in Houston, Texas. Patient service data, provider satisfaction, patient outcome data, and appointment waiting periods were obtained to evaluate the initial operation of the program. The integrated care program has been successfully implemented on a large scale at an annual cost of about dollars 800,000, or dollars 268 per patient served. About 3,000 patients were treated for behavioral problems by behavioral health staff during the first 11 months of the program. In addition, efforts were made to expand the scope of behavioral health interventions provided by primary care physicians. Providers were satisfied with the program, improvement was detected among patients treated, and there was an increase in the average number of community-based behavioral health services received per patient since the program was implemented.

Updating the evidence on physical activity and health in women.

OBJECTIVE: This narrative review updates evidence from the last 10 years on physical activity (PA) and the primary prevention of cardiovascular disease, diabetes, and cancer in women. METHODS: A literature search was conducted to identify prospective cohort studies published from January 1997 to February 2006. RESULTS: There were significant reductions in risk in 12 of 17 studies of cardiovascular outcomes (risk reductions ranging from 28% to 58%), in seven of eight studies of diabetes (14% to 46%), in seven of ten studies of breast cancer (11% to 67%), in two of two studies of endometrial cancer (68% to 90%), and in one of three studies of colorectal cancer (31% to 46%). There was mixed evidence for PA preventing gestational diabetes (three studies) and a range of other cancers (13 studies). Protective benefits for cardiovascular disease and diabetes were reported with as little as 60 minutes of moderate-intensity physical activity per week (240 Metabolic Equivalent (MET) minutes or 4 MET hours), with walking and moderate-intensity physical activity providing risk reductions comparable to those for the equivalent energy expenditure from more vigorous-intensity physical activity. CONCLUSIONS: There is strong evidence of a role for PA in the primary prevention of cardiovascular disease, diabetes, and some cancers in women. There was no evidence of additional health benefits from vigorous-intensity PA, over and above those achieved from walking or moderate-intensity PA. This may be because, in most studies, there was limited reporting of vigorous PA by women. For some health outcomes, the amount of PA required for health benefits in middle-aged and older women might be lower than current national recommendations.

Evaluating reactivity to ecological momentary assessment during smoking cessation.

Ecological momentary assessment (EMA) consists of assessing phenomena in real time in the natural environment. EMA allows for more fine-grained analyses of addictive behavior and minimizes threats to internal validity, such as recall biases and errors. However, because of the intensive monitoring involved in EMA, measurement reactivity is a concern. To test whether EMA with palmtop personal computers induces reactivity, the authors compared smoking-related outcomes between smokers using EMA and those not using EMA during a quit attempt. The use of no-EMA control groups has been rare in reactivity investigations to date. The EMA protocol included event-contingent assessments (smoking episodes, urge episodes) and random assessments. Outcomes included biologically confirmed abstinence and self-report measures of withdrawal, self-efficacy, motivation, affect, and temptations. Participants were smokers motivated to quit (N = 96). They were randomized to 1 of 3 groups: EMA for the week preceding a planned quit date, EMA for the week following the quit date, and no EMA. Abstinence rates did not differ between the groups at Day 7 or at Day 28 postcessation. For the 20 subscales assessed at each of 3 assessment times, there were significant differences between participants with and without EMA experience for 3 subscales at the 1st of 3 assessment times, and significant differences for 3 different subscales at the 3rd assessment time. These differences suggest some reactivity to EMA, although the inconsistent pattern across time indicates that further research is needed to definitively conclude that EMA induces reactivity.

Constraints on gene patent protection fuel secrecy concerns: a qualitative study.

Concern is mounting that innovators are responding to recent changes in patent eligibility by increasingly choosing to protect their discoveries as trade secrets. Due to the clandestine nature of trade secrets, it is impossible to quantify the extent to which innovators actually elect to protect their inventions as trade secrets rather than patents. Nevertheless, interest in each strategy may be gauged through qualitative means. We conducted semi-structured interviews of legal and scientific experts (n = 30) to understand the effect of recent patent eligibility changes on interest in patenting and trade secrecy of genetic innovations. Interview data indicate that secrecy may have increased in strategic appeal relative to patent protection in some areas of genetic innovation, although the actual election of secrecy strategies is often limited as a practical matter. The data also suggest that the burden of navigating the new intellectual property landscape may be falling disproportionately on those who translate gene-based discoveries into clinical applications. Some interviewees expressed concern about the normative implications of secrecy on advancements in and access to genetic medicine. Our findings are potentially relevant to policy proposals intended to restore some of the legal protection that was lost as a result of recent changes to patent eligibility, including amending the federal patent statute and expanding regulatory exclusivities for some genetic technologies.

Depressive symptoms have an independent, gradient risk for coronary heart disease incidence in a random, population-based sample.

PURPOSE: Depression is a risk factor for incident coronary heart disease (CHD), and predicts poor prognosis for patients post-myocardial infarction (MI). Few population-based, prospective studies have tested a gradient risk for depressive symptoms on CHD incidence. METHODS: The sample (n=1302) was derived from the Nova Scotia Health Survey-1995 (NSHS95), an age- and sex-stratified, random, population-based health survey. All subjects were 45 years or older, free of overt CHD at baseline, and completed the Center for Epidemiological Studies-Depression (CES-D) scale. Covariates included age, sex, body mass index, physical activity level, family history of premature CHD, diastolic blood pressure, lipids, smoking, alcohol use, diabetes, and education level. For the 4 years following NSHS95, MI-related hospitalizations (ICD-9-CM code 410) and CHD-related deaths (ICD-9-CM codes 410-414) were extracted from the provincial, universal healthcare registry. RESULTS: Fifty-two participants experienced a CHD event. A one standard-deviation increase in CES-D score was associated with a 1.32 hazard risk (confidence interval, 1.01-1.71) of CHD events, controlling for established CHD risk factors. CONCLUSIONS: An independent, gradient association between depression and incident CHD was detected in a population-based sample with complete 4-year CHD data. This evidence supports the value of investigating mechanisms linking depression and CHD.

What psychiatric screening and monitoring might be needed with the new generation of hepatitis C treatments?

Psychiatric difficulties, including depression and alcohol use disorders, pose a challenge to treatment decision-making for chronic hepatitis C. This is especially made worse because interferon-alpha, as part of the standard of care, may exacerbate depressive symptoms and cause suicidal symptoms to appear. This requires a treatment setting that has the capacity to carry out psychiatric assessment and monitoring, and the capability to deliver patient education regarding these aspects of care. Psychiatric comorbidities create a challenging decision-making situation, especially since success rates for the most common hepatitis C genotype, genotype 1, hover around 40%. In recent years, new treatments have emerged. These significantly boost the likelihood of sustained viral response, including for genotype 1, and do not seem to have the side effects of interferon-alpha or ribavirin. Relevant data are reviewed to assess the degree that these new treatments might reduce the portion not eligible for treatment due to psychiatric comorbidities, and might reduce the emergence of psychiatric symptoms during treatment. Several organizations have recently released evidence-based treatment recommendation guidelines. It is apparent that interferon-alpha continues to be a standard of care, with the new drugs added to this recognized regimen in order to shorten treatment and to boost efficacy. Clinical settings must continue to assess appropriateness for treatment, including current or recent psychiatric comorbidities, and must continue to closely monitor patients for the emergence of psychiatric side effects. The newly developed hepatitis C treatments may affect the metabolism of several categories of psychiatric drugs, and so drug-drug interactions must also be considered and monitored. With many promising drugs under development, an all-pill regimen, with no interferon-alpha and no ribavirin, may emerge in the near future. This will greatly change the challenge of treatment decision-making, and should expand the portion of patients able to successfully complete a treatment regimen.

Psychosocial assessment and monitoring in the new era of non-interferon-alpha hepatitis C virus treatments.

Chronic hepatitis C virus (HCV) is a global concern. With the 2014 Food and Drug Administration approvals of two direct-acting antiviral (DAA) regimens, ledipasvir/sofosbuvir regimen and the ombitasvir/paritaprevir/ritonavir and dasabuvir regimen, we may now be in the era of all-pill regimens for HCV. Until this development, interferon-alpha along with Ribavirin has remained part of the standard of care for HCV patients. That regimen necessitates psychosocial assessment of factors affecting treatment eligibility, including interferon-alpha-related depressive symptoms, confounding psychiatric conditions, and social aspects such as homelessness affecting treatment eligibility. These factors have delayed as much as 70% of otherwise eligible candidates from interferon-based treatment, and have required treating physicians to monitor psychiatric as well as medical side effects throughout treatment. All-pill DAA regimens with the efficaciousness that would preclude reliance upon interferon-alpha or ribavirin have been anticipated for years. Efficacy studies for these recently approved DAA regimens provide evidence to assess the degree that psychosocial assessment and monitoring will be required. With shorter treatment timelines, greatly reduced side effect profiles, and easier regimens, psychosocial contraindications are greatly reduced. However, current or recent psychiatric comorbidity, and drug-drug interactions with psychiatric drugs, will require some level of clinical attention. Evidence from these efficacy studies tentatively demonstrate that the era of needing significant psychosocial assessment and monitoring may be at an end, as long as a manageable handful of clinical issues are managed.

State mandates regarding postpartum depression.

OBJECTIVE: Postpartum depression continues to be undertreated. This project identified state policies that have been enacted regarding peripartum mental health and assessed how effective they might be. METHODS: A systematic search strategy was used to detect state-level legislative initiatives. Legislative tracking resources were used to determine which were enacted. Policies were sorted into categories. Related evidence was reviewed to gauge the impact of each category. RESULTS: Thirteen states have enacted one or more state-level peripartum mental health policies. Categories include patient education mandates, depression screening mandates, mandated task force, and public awareness campaigns. Those mandating screening include Illinois, Massachusetts, New Jersey, and West Virginia. Related outcomes evidence suggests a very limited impact. CONCLUSIONS: Several states have enacted policies addressing peripartum mental health, but these are probably not influencing clinical outcomes. Home visits with a mental health component are effective for postpartum depression; state policies could support home visits.

Does prophylactic antidepressant treatment boost interferon-alpha treatment completion in HCV?

Depression is often a side effect of interferon-alpha treatment for hepatitis C, and is recognized as a cause for treatment discontinuation. When detected, antidepressant treatment begins promptly. In contrast to this rescue approach, prophylactic antidepressant treatment has been considered as a superior approach. While studies indicate that depression is lower with prophylaxis, no study has prospectively evaluated the degree that treatment completion might be boosted by the prophylactic strategy. A structured literature search was conducted to discover all trials of antidepressant prophylaxis for patients undergoing antiviral treatment for chronic hepatitis C. Selection criteria included: antidepressant prophylaxis study; report of depression treatment outcome; report of numbers discontinuing and reason for discontinuation (including any of the following: discontinuation data for medical side effects (i.e., thrombocytopenia); discontinuation due to lack of antiviral response; discontinuation due to lack of antidepressant effect; discontinuation due to antidepressant side effects; discontinuation due to patient preference; discontinuation due to loss to follow-up; or unspecified discontinuation). Across the studies, total enrollees were determined for the prophylaxis arms and the rescue arms, and then, again across studies, those discontinuing for reasons other than lack of antiviral response or medical side effect were summed for each of these two arms. Twelve studies were discovered. One was a retrospective chart review, one was an uncontrolled trial, and ten were controlled trials. Discontinuation of antiviral therapy was not less common in the prophylaxis arms: of the 396 patients treated by the prophylaxis strategy, 47 (11.9%) discontinued; of the 380 patients in the rescue strategy, 45 (11.8%) discontinued. While the prophylaxis strategy seems to manage depression symptoms, it does not seem to boost treatment completion. Rescue was a very successful strategy when indicated. While antidepressant prophylaxis has benefit in antiviral treatment, it should not generally be valued for boosting the likelihood of treatment completion.