Bcl6 is a subset-defining transcription factor of lymphoid tissue inducer-like ILC3.

Innate lymphoid cells (ILCs) are tissue-resident effector cells with roles in tissue homeostasis, protective immunity, and inflammatory disease. Group 3 ILCs (ILC3s) are classically defined by the master transcription factor RORγt. However, ILC3 can be further subdivided into subsets that share type 3 effector modules that exhibit significant ontological, transcriptional, phenotypic, and functional heterogeneity. Notably lymphoid tissue inducer (LTi)-like ILC3s mediate effector functions not typically associated with other RORγt-expressing lymphocytes, suggesting that additional transcription factors contribute to dictate ILC3 subset phenotypes. Here, we identify Bcl6 as a subset-defining transcription factor of LTi-like ILC3s in mice and humans. Deletion of Bcl6 results in dysregulation of the LTi-like ILC3 transcriptional program and markedly enhances expression of interleukin-17A (IL-17A) and IL-17F in LTi-like ILC3s in a manner in part dependent upon the commensal microbiota-and associated with worsened inflammation in a model of colitis. Together, these findings redefine our understanding of ILC3 subset biology.

Hematopoietic Cell Transplantation Trends and Outcomes in Canada: A Registry-Based Cohort Study.

Background: Hematopoietic cell transplantation (HCT) is an established therapy for hematologic malignancies and serious non-malignant blood disorders. Despite its curative potential, HCT is associated with substantial toxicity and health resource utilization. Effective delivery of HCT requires complex hospital-based care, which limits the number of HCT centres in Canada. In Canada, the quantity, indications, temporal trends, and outcomes of patients receiving HCT are not known. Methods: A retrospective cohort study of first transplants reported to the Cell Therapy Transplant Canada (CTTC) registry between 2000 and 2019. We determined overall survival (OS) and non-relapse mortality (NRM), categorizing the cohort into early (2000-2009) and later (2010-2019) eras to investigate temporal changes. Results: Of 18,046 transplants, 7571 were allogeneic and 10,475 were autologous. Comparing the two eras, allogeneic transplants increased in number by 22.3%, with greater use of matched unrelated donors in the later era. Autologous transplants increased by 10.9%. Temporal improvements in NRM were observed in children and adults. OS improved in pediatric patients and in adults receiving autologous HCT. In adults receiving allogeneic HCT, OS was stable despite the substantially older age of patients in the later era. Interpretation: HCT is an increasingly frequent procedure in Canada which has expanded to serve older adults. Noted improvements in NRM and OS reflect progress in patient and donor selection, preparation for transplant, and post-transplant supportive care. In allogeneic HCT, unrelated donors have become the most frequent donor source, highlighting the importance of the continued growth of volunteer donor registries. These results serve as a baseline measure for quality improvement and health services planning in Canada.

A Brexanolone Treatment Program at an Academic Medical Center: Patient Selection, 90-Day Posttreatment Outcomes, and Lessons Learned.

BACKGROUND: Brexanolone is the first U.S. Food and Drug Administration-approved drug for the treatment of postpartum depression. Brexanolone is a positive allosteric modulator of the GABAA receptor and is given over 60 hours by infusion in a medical setting. This drug has been shown to be effective at significantly reducing Hamilton Rating Scale for Depression scores at 60 hours and 30 days after infusion; however, data beyond 30 days have not yet been available. There have been limited clinical programs able to offer brexanolone owing to the complexity of setting up this treatment in a medical setting. PURPOSE: This study sought to obtain follow-up data from 16 patients who received a brexanolone infusion at UNC Hospitals in Chapel Hill, NC, between October 2019 and December 2020 and were beyond the 30-day postinfusion time point. We describe the methods used to successfully implement this treatment program in an academic medical center and discuss associated challenges and lessons learned with patient selection and process improvements. METHODS: Hamilton Rating Scale for Depression scores were collected before and after infusion from 16 patients who received a brexanolone infusion at UNC. Patients were subsequently contacted for a follow-up interview to obtain Hamilton Rating Scale for Depression scores and complete a semistructured interview at least 30 days past treatment end (between 3 and 16 months after infusion). RESULTS: All 16 patients had a significant reduction in Hamilton Rating Scale for Depression scores at 60 hours, scores dropping on average from 23.9 (standard deviation = 2.6) to 7.6 (standard deviation = 2.9). Eleven of 16 patients consented to provide follow-up data. Follow-up Hamilton Rating Scale for Depression scores remained lower than postinfusion at an average of 6.7 points (standard deviation = 5.1). CONCLUSION: With a strategic cross-disciplinary approach, a Clinical Brexanolone Treatment Program was established at UNC Hospitals in 2019. Sixteen patients have been treated in the program, and 11 participated in a follow-up interview. All 11 patients gave very positive feedback about their treatment. Our program has found brexanolone to be a useful clinical tool in treating women with significant symptoms of postpartum depression.

Growth perturbations from stimulant medications and inhaled corticosteroids.

Stimulant medications for the treatment of attention deficit hyperactivity disorder (ADHD) and inhaled corticosteroids (ICS) for the treatment of asthma are two classes of medications that are commonly prescribed in pediatrics. Among other adverse effects of these medications, growth attenuation has long been a focus of investigation. With stimulants, growth deficits of 1-1.4 cm/year have been observed in the short term, mainly in the first 2 years of treatment, in a dose-dependent manner. Long-term studies on stimulants have reported divergent effects on growth, with many studies showing no clinically significant height deficits by adulthood. The study that followed the largest cohort of children on stimulants, however, reported an overall adult height deficit of 1.29 cm in subjects who had received stimulant medications, with mean adult height deficit of 4.7 cm among those taking the medication consistently. With ICS use, mild growth suppression is seen in the short term (particularly in the first year of therapy) with growth rates reduced by 0.4-1.5 cm/year. Available current evidence indicates that the impact of ICS use on adult height is not clinically significant, with effects limited to 1.2 cm or less. There is significant individual variability in growth suppression with ICS use, with the specific pharmacologic agent, formulation, dose exposure, age, puberty, medication adherence, and timing of administration being important modifying factors. Based on currently available evidence, the therapeutic benefits of ICS for management of asthma and stimulant medications for management of ADHD outweigh the potential risk for growth suppression. Strategies to minimize growth attenuation and other potential adverse effects of these medications include using the lowest efficacious dose, frequent assessments and dose titration. Particular vigilance is essential with concomitant use of multiple medications that can attenuate growth and to evaluate for potential adrenal insufficiency from ICS use.

Comprehensive Integrated Care Model to Improve Maternal Mental Health.

In this article, we describe an integrated care model in a perinatal psychiatry program to improve access to care for women who experience mood changes during the perinatal period. A nurse-practitioner trained in psychiatry and obstetrics is embedded in the obstetric clinic, and perinatal nurses, often the first professionals to recognize women who are experiencing mood changes, can easily refer women for follow-up. Barriers, lessons learned, and goals for implementation are described.

The association of migraine with menstrually related mood disorders and childhood sexual abuse.

BACKGROUND: Both female reproductive hormones and childhood sexual abuse (CSA) are implicated in migraine and in menstrually related mood disorders (MRMD). We examined the association of migraine, including migraine with aura (MA), and history of MRMD or CSA. METHODS: A total of 174 women (mean age 33.9 ± 7.6 years) in this cross-sectional study were evaluated for (1) current MRMD using prospective daily ratings; (2) history of CSA using structured interview; and (3) MA and migraine without aura using the International Classification of Headaches Disorders II criteria. RESULTS: Ninety-six women met MRMD criteria (21 of whom had history of CSA) and 78 women were non-MRMD controls (16 with CSA histories). Migraine with aura was more prevalent in women with MRMD when compared to non-MRMD controls (11/88 and 0/86, respectively, p=0.001). In MRMD women only, a CSA history was associated with higher MA rates (6/21 and 5/67, respectively, p=0.019). A combination of current MRMD diagnosis and a history CSA was associated with increased risk for MA, even after adjusting for potential confounders (odds ratio=12.08, 95% confidence interval 2.98-48.90, p<0.001). CONCLUSIONS: Women with MRMD may be vulnerable to the development of MA, and a history of CSA in women with a MRMD appears to increase that vulnerability. MRMDs and MA should be included among other poor mental and physical health outcomes of an abuse history. Routine screening for abuse histories would potentially improve identification of women with increased risk of experiencing abuse-related disorders.

Homicide, suicide, and unintentional firearm fatality: comparing the United States with other high-income countries, 2003.

BACKGROUND: Violent death is a major public health problem in the United States and throughout the world. METHODS: A cross-sectional analysis of the World Health Organization Mortality Database analyzes homicides and suicides (both disaggregated as firearm related and non-firearm related) and unintentional and undetermined firearm deaths from 23 populous high-income Organization for Economic Co-Operation and Development countries that provided data to the World Health Organization for 2003. RESULTS: The US homicide rates were 6.9 times higher than rates in the other high-income countries, driven by firearm homicide rates that were 19.5 times higher. For 15-year olds to 24-year olds, firearm homicide rates in the United States were 42.7 times higher than in the other countries. For US males, firearm homicide rates were 22.0 times higher, and for US females, firearm homicide rates were 11.4 times higher. The US firearm suicide rates were 5.8 times higher than in the other countries, though overall suicide rates were 30% lower. The US unintentional firearm deaths were 5.2 times higher than in the other countries. Among these 23 countries, 80% of all firearm deaths occurred in the United States, 86% of women killed by firearms were US women, and 87% of all children aged 0 to 14 killed by firearms were US children. CONCLUSIONS: The United States has far higher rates of firearm deaths-firearm homicides, firearm suicides, and unintentional firearm deaths compared with other high-income countries. The US overall suicide rate is not out of line with these countries, but the United States is an outlier in terms of our overall homicide rate.

Intimate partner violence screening and pregnant Latinas.

Little is known about factors associated with health care screening of intimate partner violence (IPV) for Latinas during pregnancy. This study builds on current research examining IPV-associated outcomes among Latinas by analyzing 210 pregnant Latina responses to a patient survey. A multivariate logistic regression model examined factors associated with being screened for IPV. One-third of pregnant women reported being screened for IPV. Factors related to being screened for IPV are reported and did not match those associated with having experienced IPV. While most pregnant Latinas were not screened for IPV, having systematic processes in place for IPV screening and fostering good patient-provider communication may facilitate identification of IPV. Having a greater awareness of the risk factors associated with IPV may also provide cues for clinicians to better address the issue of IPV.

Intimate partner violence and community service needs among pregnant and postpartum Latina women.

Health care providers are advised to refer abused women to needed community services. However, little is known about abused women's perceived need for services, particularly among Latina women. We examined the relationship between intimate partner violence (IPV) and perceived needs for legal, social, and job services among a prospective cohort of 210 pregnant Latinas. IPV was associated with needing social and legal services at most time points. Women with recent IPV experiences reported greater service needs than women with more remote IPV experiences, who in turn reported greater need than women without IPV experiences. We conclude that IPV may be associated with ongoing perceived needs for social and legal services among Latina perinatal patients.

The rise and fall of the Latino dentist supply in California: implications for dental education.

The purpose of this study was to determine the number of Latino dentists in California, identify the schools and countries where they were educated, and compare Latino dentist demographics with that of the state's new demographics. From the 2000 California Department of Consumer Affairs list of 25,273 dentists, we identified Latino U.S. dental graduates (USDGs) by "heavily Hispanic" surnames and Latino international dental graduates (IDGs) by country and school of graduation. From the 2000 U.S. census Public Use Microdata Sample (PUMS), we described Latino dentist characteristics such as Spanish language capacity and practice location. The number of Latino dentists acquiring licenses to practice in California has fallen dramatically, by nearly 80 percent, between 1983 and 2000. This decline is not merely an affirmative action issue; it results in an issue of access. Latino dentists are far more likely to speak Spanish and be located in a heavily Latino area than non-Latino dentists. Currently, although the supply of Latino dentists is dwindling, the Latino population is growing rapidly. In California and out-of-state schools, first-year matriculation of Latino USDG must increase. Further, non-Latino dentists should be prepared and given incentives to learn Spanish and locate practices in areas of need. The reintroduction of IDG Latino dentists needs to be seriously considered.

Physical health burdens of women with trauma histories and co-occurring substance abuse and mental disorders.

This article documents the physical health burdens of participants in a large, federally funded cross-site study of specialized services for women with histories of trauma (physical or sexual abuse) and co-occurring substance abuse and mental health disorders. Nearly half of the 2729 women in the study (48%) reported serious physical illnesses that frequently limited their daily life activities or required them to use special equipment. Nearly half (46%) rated their health status as only fair or poor. Given the prevalence of physical illnesses in this population, behavioral service providers should discuss with clients their overall health and how it might hinder their participation in treatment for trauma, substance abuse, and mental illness, and policymakers should consider this need when designing behavioral health requirements, setting reimbursement rates, and allocating funds.

Outcomes and costs of risperidone versus olanzapine in patients with chronic schizophrenia or schizoaffective disorders: a Markov model.

OBJECTIVE: To compare expected outcomes and costs of care in patients with chronic schizophrenia or schizoaffective disorders who are treated with risperidone versus olanzapine. METHODS: A Markov model was developed to examine outcomes and costs of care in patients with chronic schizophrenia or schizoaffective disorders receiving risperidone or olanzapine. The time frame of interest was 1 year. The model focused particular attention on the likelihood of therapy switching and discontinuation as a result of treatment-emergent side effects, as the efficacy of these two agents is similar. Measures of interest included the incidence of relapse and selected side effects including extrapyramidal symptoms (EPS), prolactin-related disorders and diabetes, expected change in body weight, and the percentage of patients remaining on initial therapy at the end of 1 year. Costs of antipsychotic therapy and psychiatric and nonpsychiatric services also were examined. RESULTS: At 1 year, the rate of EPS was estimated to be slightly higher for risperidone, as was the incidence of symptomatic prolactin-related disorders. The expected incidence of diabetes mellitus, while low, was slightly higher for olanzapine. Approximately 25% and 4% of olanzapine and risperidone patients, respectively, were projected to experience an increase in body weight > or = 7%. The estimated percentage of patients remaining on initial therapy at the end of 1 year was higher for risperidone than olanzapine (76.9% vs. 45.6%, respectively). Expected mean total costs of care per month of therapy were $2163 for risperidone and $2316 for olanzapine. Results from sensitivity analyses suggest that the probability of therapy discontinuation following weight gain >5 kg would have to be lower than 0.1 for the number of patients remaining on therapy at the end of 1 year to be the same for risperidone and olanzapine. CONCLUSIONS: Compared with risperidone, treatment with olanzapine may result in greater increases in body weight, higher rates of therapy discontinuation, and higher costs of medical-care services.