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OBJECTIVE Depression and anxiety symptoms are commonly observed among clinical populations, especially among women and maltreated individuals. Few investigations have, however, assessed the existence of distinct symptoms trajectories among clinical populations and how these relate to childhood maltreatment, sex differences, and stress physiology indexed by hair cortisol concentrations (HCC). The current study (1) identified distinct depression and anxious trajectories in a sample of psychiatric inpatients followed-up prospectively from their admission to a psychiatric emergency service (PES), and (2) examined whether HCC, childhood maltreatment and sex independently and jointly predict these trajectories. METHODS Adult inpatients (N = 402, 55% women) were recruited upon admission to PES (T1) during which HCC (reflecting cortisol secretion for the last 3 months), childhood maltreatment, and depression and anxiety symptoms were assessed. Symptoms were re-evaluated when patients were discharged from the hospital (T2), admitted to outpatient clinics (T3), and 12 months later or at the end of outpatient treatment (T4). RESULTS Three trajectories were identified for depression and anxiety symptoms. Among men, higher HCC predicted higher odds of evincing chronic depressive symptoms compared to a Low Stable trajectory (OR 3.46, 95% confidence interval [CI] 1.43-8.40). Greater childhood maltreatment among men predicted higher chances of exhibiting chronic anxious symptoms than the Low Stable (OR 1.47, 95% CI 1.07-2.02) and the High Decreasing trajectories (OR .70, 95% CI .51-.95). Opposite findings were noted for women. CONCLUSIONS Childhood maltreatment and HCC should be further investigated as predictors of anxious and depressive trajectories, during which sex-specific associations ought to be considered.

The aim of this narrative review was to demonstrate how the notion of allostatic load (AL) relates directly to the mental health disparities observed between Indigenous and non-Indigenous Australians. We also endeavored to synthesize the results of the limited number of studies examining stress and AL in Indigenous Australians in order to explore the potential public health benefits of the AL concept. A range of literature examining health inequalities, psychosocial determinants of mental illness and AL was explored to demonstrate the applicability of stress biology to the significant mental health burden faced by Indigenous Australians. Furthermore, all original studies indexed in MEDLINE that provided quantitative data on primary stress biomarkers in Indigenous Australians were selected for review. Evidence of hypothalamic-pituitary-adrenal axis dysregulation and increased AL is apparent even in the handful of studies examining stress biomarkers in Indigenous Australians. Urinary, salivary, hair and fingernail cortisol, hair cortisone, urinary epinephrine, heart rate variability and the cortisol awakening response are all AL parameters which have been shown to be dysregulated in Indigenous Australian cohorts. Furthermore, associations between some of these biomarkers, self-perceived discrimination, exposure to stressful life events and symptoms of psychiatric disorders in Indigenous Australians have also been demonstrated. The continued assessment of AL biomarkers and their relationship with past traumas, lifetime stressors and socio-economic factors amongst Indigenous Australians is important to addressing the mental health this population. Measurement of AL biomarkers in a culturally appropriate manner may lead to more targeted preventative measures, interventions and policies, which mitigate the effects of stress at both the individual and societal level.

Resting-state functional connectivity has been used to study Alzheimer's disease, revealing underlying differences between groups of individuals at different levels of cognitive impairment, or groupwise changes over time. Most of these studies have employed a single scanner and/or a single scan per subject. In this study, we used data collected from a substudy to two randomized clinical trials in patients with mild-to-moderate Alzheimer's Disease to investigate the robustness of functional connectivity in a multicenter, longitudinal setting. This substudy was not powered to detect drug treatment effects. With a basic imaging charter for inter-site acquisition standardization, we found no changes to functional connectivity over time in the placebo group, despite observable changes in clinical test scores and regional brain atrophy. We infer that functional connectivity, as implemented in our study, is not sensitive enough to detect disease progression in our patients. Using an 8-week interval between scans (in both treatment and placebo groups), we found that our test-retest reproducibility was comparable with other published results. We also found that the dominant source of measurement variability was within individuals over time, compared with variability between subjects and sites. Finally, we propose a simple method of visual inspection to identify scans that should be excluded from longitudinal analysis.

En los últimos años, la concepción que se tenía de las tendinopatías ha tolerado grandes cambios. La separación de las teorías que declaran a las tendinopatías como trastornos inflamatorios, a teorías que aluden una fisiopatología de carácter continúo basado en cambios degenerativos, propició la aparición de técnicas de fisioterapia invasiva como la electrólisis percutánea, que buscan romper con este proceso de degeneración, permitiendo la recuperación del tejido. El objetivo general de esta revisión sistemática es, estudiar la eficacia y evidencia científica de la técnica del electrólisis percutánea aplicada al tratamiento de tendinopatías en la extremidad inferior, para comparar los resultados obtenidos. Para lo cual, se realizó una búsqueda sistemática de estudios en 6 bases de datos, empleando las palabras clave: patellar tendinopathy unido con electrolysis, treatment, physical therapy y rehabilitation, lo cual ofreció 28 artículos, de los cuales, 8 se emplearon en la revisión, concretamente, 5 estudios de series de casos y 2 estudios prospectivos en ratas y 1 caso clínico. La electrólisis percutánea, mostró una mejora funcional y en la sensación dolorosa, al ser combinada con terapias de ejercicios excéntricos. El tratamiento terapéutico de las tendinopatías en la extremidad inferior mediante electrólisis percutánea, brinda resultados muy promisorios, sin embargo, para establecer la consecuencia de estos resultados, requiere del aporte de una cantidad sustancialmente mayor de estudios con una metodología más sofisticada, que sustenten su evidencia científica.

Introduction: In 2019, an alarming number of cases coined as e-cigarette, or vaping, product use associated lung injury (EVALI) was described in adolescents ranging from mild respiratory distress to fulminant respiratory failure. Limited data has been published on outcomes at short term follow-up. We aimed to describe pulmonary manifestations, function and radiologic findings after corticosteroid therapy in a cohort of adolescent patients. Methods: A retrospective chart review of all patients presenting to our institution between July and December 2019 with EVALI was conducted. Patients who had pulmonary follow-up were included. Spirometry was performed prior to discharge from the hospital and during outpatient follow-up. A paired t-test was used to compare serial spirometry data between visits. Results: Eight patients (6 males) were included. Two patients required intubation with mechanical ventilation, 2 required bilevel positive airway pressure (BPAP), and 3 required oxygen supplementation. All patients received glucocorticoids (3 receiving pulse dosing). Initial spirometry revealed decreased forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) with clinically and statistically significant improvement at follow-up. Diffusing capacity of the lungs for carbon monoxide (DLCO) was decreased in 2/6 patients initially and in 4/5 at follow-up. Radiographic manifestations also improved after vaping was discontinued. Conclusion: In our cohort of patients with EVALI, at short term follow up, all normalized their spirometry parameters. However, most did not normalize their DLCO on follow up, raising concern for risk of developing chronic lung disease later in life.

The standard treatment for glioblastoma involves a combination of surgery, radiation and chemotherapy but have limited impact on survival. The exponential increase in targeted agents directed at pivotal oncogenic pathways now provide new therapeutic opportunities for this tumour type. However, lack of comprehensive precision oncology testing at diagnosis means such therapeutic opportunities are potentially overlooked.To investigate the role of semiconductor sequencing for detection of predictive biomarkers in routine glioblastoma samples we have undertaken analysis of test trending data generated by a clinically validated next generation sequencing platform designed to capture 764 of the leading anti-cancer targeted agents/combinations and immunotherapies via analysis of actionable genomic variants distributed across 505 genes. Analysis was performed across a cohort of 55 glioblastoma patients.Analysis of trending data has revealed a complex and rich actionable mutational landscape in which 166 actionable mutations were detected across 36 genes linked to 17 off label targeted therapy protocols and 111 clinical trials. The majority of patients harboured three or more actionable mutations affecting key cancer related regulatory networks including the PI3K/AKT/MTOR and RAS/RAF/MEK/MAPK signalling pathways, DNA-damage repair pathways and cell cycle checkpoints. Linkage with immunotherapy and PARP inhibitors was identified in 44% of glioblastoma patients as a consequence of alterations in DNA-damage repair genes.Taken together our data indicates that precision oncology testing utilising semiconductor sequencing can be used to identify a broad therapeutic armamentarium of targeted therapies and immunotherapies that can be potentially employed for the improved clinical management of glioblastoma patients.

IMPORTANCE: Breast cancer accounts for the largest portion of cancer-related spending in the United States. Although hypofractionated radiotherapy after breast-conserving surgery is a cost-effective and convenient treatment strategy for patients with early-stage breast cancer, less than 40% of eligible women received hypofractionated radiotherapy in 2013. OBJECTIVE: To assess the association of a large commercial payer’s utilization management policy with the use of hypofractionated radiotherapy among women with early-stage breast cancer and its associated cost. DESIGN, SETTING, AND PARTICIPANTS: A retrospective, adjusted difference-in-differences economic analysis was conducted using administrative claims data from January 1, 2012, to June 1, 2018, of women 18 years or older with early-stage breast cancer who were eligible for hypofractionated radiotherapy according to 2011 guidelines from the American Society for Radiation Oncology and were continuously enrolled in 14 geographically diverse commercial health plans covering 6.9% of US adult women. Women who received mastectomy, brachytherapy, or less than 11 or more than 40 external beam fractions of radiotherapy were excluded. A utilization management policy was used to encourage the use of hypofractionated radiotherapy among women in fully insured and Medicare Advantage (fully insured) plans. Under the new policy, claims for extended-course radiotherapy were not reimbursed for fully insured women who were eligible for hypofractionated radiotherapy. This policy did not apply to women in self-insured or Medicare supplemental insurance (self-insured) plans, allowing these groups to serve as a comparison group. MAIN OUTCOMES AND MEASURES: The primary outcome was use of hypofractionated radiotherapy, and the secondary outcome was the cost of this type of radiotherapy. RESULTS: Of 10 540 eligible women, 3619 (34.3%) were in fully insured plans and thus subject to the policy. There were no meaningful differences between the fully insured and self-insured groups in mean (SD) age at the start of radiotherapy (63.8 [8.6] vs 65.0 [8.9] years), mean (SD) Charlson Comorbidity Index score (3.0 [1.5] vs 3.2 [1.6]), or practice setting (outpatient hospital setting, 2982 of 3619 [82.4%] vs 5600 of 6921 [80.9%]). The policy was associated with an increase in use of hypofractionated radiotherapy among fully insured patients subject to the policy (adjusted percentage point difference-in-difference, 4.2%; 95% CI, 0.0%-8.4%; P = .05) and a nonsignificant decrease in radiotherapy-associated expenditures (−$2275 relative to self-insured patients; P = .09). Spillover analyses revealed a significantly higher uptake of hypofractionated radiotherapy among self-insured patients who were indirectly exposed to the policy (adjusted percentage point difference-in-difference, 8.5%; 95% CI, 3.6%-13.5%; P

Background Epigenetic clocks have been recognized for their precise prediction of chronological age, age-related diseases, and all-cause mortality. Existing epigenetic clocks are based on CpGs from the Illumina HumanMethylation450 BeadChip (450 K) which has now been replaced by the latest platform, Illumina MethylationEPIC BeadChip (EPIC). Thus, it remains unclear to what extent EPIC contributes to increased precision and accuracy in the prediction of chronological age. Results We developed three blood-based epigenetic clocks for human adults using EPIC-based DNA methylation (DNAm) data from the Norwegian Mother, Father and Child Cohort Study (MoBa) and the Gene Expression Omnibus (GEO) public repository: 1) an Adult Blood-based EPIC Clock (ABEC) trained on DNAm data from MoBa (n = 1592, age-span: 19 to 59 years), 2) an extended ABEC (eABEC) trained on DNAm data from MoBa and GEO (n = 2227, age-span: 18 to 88 years), and 3) a common ABEC (cABEC) trained on the same training set as eABEC but restricted to CpGs common to 450 K and EPIC. Our clocks showed high precision (Pearson correlation between chronological and epigenetic age (r) > 0.94) in independent cohorts, including GSE111165 (n = 15), GSE115278 (n = 108), GSE132203 (n = 795), and the Epigenetics in Pregnancy (EPIPREG) study of the STORK Groruddalen Cohort (n = 470). This high precision is unlikely due to the use of EPIC, but rather due to the large sample size of the training set. Conclusions Our ABECs predicted adults’ chronological age precisely in independent cohorts. As EPIC is now the dominant platform for measuring DNAm, these clocks will be useful in further predictions of chronological age, age-related diseases, and mortality.

Current pathophysiological models of schizophrenia suggest that stress contributes to the etiology and trajectory of the disorder. We investigated if allostatic load (AL), an integrative index of neuroendocrine, immune and metabolic dysregulation in response to chronic stress, is elevated in patients with schizophrenia (SCZ) and first-episode psychosis (FEP) and related to psychotic symptoms and social and occupational functioning. Additionally, we assessed the temporal dynamics of AL in response to treatment with second-generation antipsychotics. AL, psychotic symptoms and psychosocial functioning were assessed in a longitudinal design in patients with SCZ (n = 28), FEP (n = 28), and healthy controls (n = 53) at baseline and 6 and 12 weeks after commencement of antipsychotic therapy. AL at baseline was higher in patients with SCZ and FEP relative to controls, but not different between patients with SCZ and FEP. Adjusting for age and smoking, we found that positive symptoms were positively correlated with AL and psychosocial functioning was negatively correlated with AL at trend level. Linear mixed model analysis demonstrated that AL decreased after treatment was commenced in patients with SCZ and FEP between the baseline assessment and the 6 and 12-week follow-up. AL was not predictive of treatment response or symptomatic remission. Our data provide evidence for cumulative physiological dysregulation in patients with SCZ and FEP that is linked to the experience of current positive psychotic symptoms. AL could be a useful tool to monitor biological signatures related to chronic stress and unhealthy behaviors in schizophrenia.

Objective: To assess the relationship between the Screen for Cognitive Impairment in Psychiatry (SCIP) score and illness severity, subjective cognition and functioning in a cohort of major depressive disorder (MDD) patients. Methods: Patients (n = 40) diagnosed with MDD (DSM-IV-TR) completed the SCIP, a brief neuropsychological test, and a battery of self-administered questionnaires evaluating functioning (GAF, SDS, WHODAS 2.0, EDEC, PDQ-D5). Disease severity was evaluated with the Hamilton Depression Rating Scale (HDRS) and the Clinical Global Impression (CGI). Results: Age and sex were associated with performance in the SCIP. The SCIP-Global index score was associated with disease severity (r = −0.316, p r = −0.368, p r = −0.388, p r = −0.335, p F[3,34] = 4.478, p = .009; SDS, F[3,34] = 3.365, p = .030; EDEC-perceived cognitive deficits, F[3,34] = 5.216, p = .005; EDEC-perceived impacts of functional impairment, F[3,34] = 5.154, p = .005). Conclusions: This study confirms that the SCIP can be used during routine clinical evaluation of MDD, and that cognitive deficits objectively assessed in the SCIP are associated with disease severity and self-reported cognitive dysfunction and impairment in daily life.

Background Major depressive disorder (MDD) is now the first cause of disability worldwide. So far, no validated and scalable biomarker has been identified to help with response prediction to antidepressant treatment. Cardiac biomarkers such as heart rate variability (HRV) have been studied in MDD, but few studies have examined its potential use for outcome prediction to repetitive transcranial magnetic stimulation (rTMS). Objective We recorded pre-treatment HRV in MDD participants prior to an rTMS course. We hypothesized that higher pre-treatment HRV would be correlated with better clinical outcomes. Methods HRV was recorded as part of a single-arm, open-label rTMS feasibility study. Pre-treatment HRV was assessed in N = 30 MDD participants before they underwent a one-week (5 days, 8 daily sessions, 40 sessions total) accelerated rTMS (arTMS) course using a low-frequency 1 Hz course (600 pulses per session, 50-minute intersession interval) over the right dorsolateral prefrontal cortex at 120% of the resting motor threshold. Clinical outcomes were captured using the Beck Depression Inventory-II (BDI-II). We tested for an association between pre-treatment HRV and clinical outcomes on the BDI-II using a linear mixed effects model. Results Although average BDI-II score significantly changed over time, these changes were not significantly associated with pre-treatment HRV (p = 0.60). This finding remained when adjusting for age, sex, and HR, individually and collectively. Conclusion The current study did not find a relationship between pre-treatment HRV and response to low frequency rTMS. Other approaches using cardiac biomarkers may have potential for response prediction.

Background Although there has been an increase in the number of randomized controlled trials evaluating treatment efficacy for hidradenitis suppurativa (HS), instrument measurements of disease severity and quality of life (QoL) are varied, making the compilation of data and comparisons between studies a challenge for clinicians. Objective We aimed to perform a systematic literature search to examine the recent trends in the use of disease severity and QoL outcome instruments in randomized controlled trials that have been conducted on patients with HS. Methods A scoping review was conducted in February 2021. The PubMed, Embase, Web of Science, and Cochrane databases were used to identify all articles published from January 1964 to February 2021. In total, 41 articles were included in this systematic review. Results The HS Clinical Response (HiSCR) score (18/41, 44%) was the most commonly used instrument for disease severity, followed by the Sartorius and Modified Sartorius scales (combined: 16/41, 39%). The Dermatology Life Quality Index (18/41, 44%) and visual analogue pain scales (12/41, 29%) were the most commonly used QoL outcome instruments in HS research. Conclusions Randomized controlled trials conducted from 2013 onward commonly used the validated HiSCR score, while older studies were more heterogeneous and less likely to use a validated scale. A few (6/18, 33%) QoL measures were validated instruments but were not specific to HS; therefore, they may not be representative of all factors that impact patients with HS. Trial Registration National Institute of Health Research PROSPERO CRD42020209582; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020209582

Lead levels (Pb) have been linked to both hyper- and hypo-reactivity of hypothalamic-pituitary-adrenal axis (HPA) axis to acute stress in animals and humans. Similarly, allostatic load (AL), the 'wear and tear' of chronic stress, is associated with inadequate HPA axis activity. We examined whether Pb levels would be associated with altered diurnal cortisol profile, as a primary mediator of AL, during aging. Pb levels were measured from blood samples (BPb) of 126 Brazilian individuals (105 women), between 50 and 82 years old. Six neuroendocrine, metabolic, and anthropometric biomarkers were analyzed and values were transformed into an AL index using clinical reference cut-offs. Salivary samples were collected at home over 2 days at awakening, 30-min after waking, afternoon, and evening periods to determine cortisol levels. A multiple linear regression model showed a positive association between BPb as the independent continuous variable and cortisol awakening response (R2=0.128; B=0.791; p=0.005) and overall cortisol concentration (R2=0.266; B=0.889; p

Context Limited research has been done to examine osteopathic manipulative treatment (OMT) effects on modulating a compilation of allostatic load (AL) biomarkers that work to measure the body's multisystem response to homeostatic deviation. Objective To examine the efficacy of OMT on graduate students’ overall health through an objective index of representative AL biomarkers. Methods A within-subject pre- and postintervention study was conducted at Touro University College of Osteopathic Medicine in California during the fall 2017 semester. Graduate students enrolled in the Masters of Science in Medical Health Sciences program volunteered to participate in the study and received treatment by an osteopathic physician. The participants were evaluated using the following measures: Trier Inventory for the Assessment of Chronic Stress; diurnal urine cortisol and catecholamines; dried blood glycated hemoglobin, dehydroepiandrosterone, high-density lipoprotein, and high-sensitivity C-reactive protein; blood pressure, body mass index, and waist-to-hip ratio before (preintervention) and after (postintervention) OMT. Results The study consisted of 1 man (participant 1) and 1 woman (participant 2) aged 23 and 22 years, respectively. Participants were enrolled in the same academic program and received 3 OMT sessions in 7 weeks. Analysis of AL biomarkers revealed a decrease in overall AL scores from preintervention to postintervention in participant 1 (from 7 to 4) and participant 2 (from 9 to 7). Analysis of Trier Inventory for the Assessment of Chronic Stress scores revealed a decrease in self-perceived stress from preintervention to postintervention in participant 1 (from 18 to 15) and in participant 2 (from 40 to 13). Conclusion The OMT protocol used in the current study decreased measures of overall AL and self-perceived stress in both participants. This finding suggests that OMT may represent a reasonable modality to reduce AL and self-perceived stress in graduate students. Since the current study is limited by its small sample size, further research is warranted.

To avoid methodological biases, psychoneuroendocrine studies have generally excluded psychotropic medication users. In workplace stress research, this has limited our ability to understand how psychotropic medication use affects many stress-related measures of interest. In this exploratory study, the effects of psychotropic medication use on stress physiology, occupational stress, and mental health were measured in a sample of healthy adult psychiatric hospital workers (N = 203, 70 % women). Diurnal cortisol was assessed on two non-consecutive work-days at five time-points (e.g., awakening, thirty minutes after awakening, 2 P M, 4 P M and bedtime). Cortisol reactivity was assessed by exposing participants to the Trier Social Stress Test. An allostatic load index was constructed using 19 neuroendocrine, immune, cardiovascular, and metabolic biomarkers. Occupational stress (e.g., job strain, effort-reward imbalance) and psychiatric symptoms (e.g., depression, burnout) were assessed with well-validated self-reports. Results showed that psychotropic medication use had no significant effects on diurnal cortisol profiles; however, psychotropic users had significantly decreased cortisol reactivity to the Trier Social Stress Test and higher allostatic load. Psychotropic users also had decreased effort-reward imbalance, but not job strain. Depressive symptoms did not differ between psychotropic medications users and non-users; however, burnout symptoms were higher among psychotropic medication users than non-users. Taken together, our findings do not warrant the systematic exclusion of psychotropic medication users from psychoneuroendocrine studies if insights into individual differences are sought among workers and other populations exposed to elevated stress.

BackgroundGoogle Trends is a powerful online database and analytics tool of popular Google search queries over time and has the potential to inform medical practice and priorities.ObjectiveThis review aimed to survey Google Trends literature in dermatology and elucidate its current roles and relationships with the field.MethodsA literature search was performed using PubMed to access and review relevant dermatology-related Google Trends studies published within the last 5 years.ResultsCurrent research utilizing Google Trends data provides insight related to skin cancer, pruritus, cosmetic procedures, and COVID-19. We also found that dermatology is presently the highest-searched medical specialty—among 15 medical and surgical specialties as well as general practitioners. Google searches related to dermatology demonstrate a seasonal nature for various skin conditions and sun-related topics, depending on a region’s inherent climate and hemi-sphere. In addition, celebrity social media and other viral posts have been found to potentiate Google searches about dermatology and drive public interest.ConclusionsA limited number of relevant studies may have been omitted by the simplified search strategy of this study, as well as by restriction to English language articles and articles indexed in the PubMed database. This could be expanded upon in a secondary systematic review. Future re-search is warranted to better understand how Google Trends can be utilized to improve the quality of clinic visits, drive public health campaigns, and detect disease clusters in real time.

Malignant melanoma is a common source of cutaneous metastases and can occasionally adopt a histological appearance which mimics a primary melanocytic lesion, either benign or malignant. The authors describe a case of new cutaneous deposits of metastatic melanoma in a 70-year-old woman with a prominent admixed lymphocytic infiltrate, imparting a striking resemblance to a halo nevus. The authors believe this appearance was a direct reflection of treatment with pembrolizumab, a humanized antibody against the immune checkpoint inhibitor programmed death-1. With increasing use of immune-modulating drugs, this potential histological mimic may be seen more frequently in the future.

The COVID-19 pandemic has dramatically changed the social and economic activities of the world Social distancing measures put in place by public health authorities have indirectly increased the level of stress and reduced the number and quality of social interactions maintained by individuals Because biological sex and socio-cultural gender are important determinants of health, the sexes are at risk of experiencing these COVID-19-related changes in unique ways To our knowledge, few studies have assessed how socio-political crises like that of the COVID-19 pandemic can exacerbate the mental health disparities that exist between men, women and gender diverse people In addition, very little is known about what factors can promote protection, coping, and resilience in the face of catastrophes faced during pandemics and how this may differ by sex and gender Using a cross-sectional online survey composed of 9 short questionnaires, this study aims to assess the ways in which sex and gender factors relate to stress, coping, resilience, and mental health in the current COVID-19 crisis To adequately assess sex and gender factors and maximize representation, participants (N = 3000) of different sex, gender and sexual identities from across Canada and the world will be recruited The complete protocol as well as the statistical analyses used to assess COVID-19 stress, mental health, sociodemographic factors, sex/gender factors’ association with coping and resilience, and ‘coronavirus crisis competence’ will be presented This ongoing study is funded in part by the Fonds de recherche du Quebec – Sante (FRQS)

7015 Background: While hypofractionated radiation (HFR) after breast-conserving surgery is a cost-effective, patient-centered treatment in early-stage breast cancer (ESBC), less than 40% of eligible women received it in 2013. In 2016, a large commercial payer implemented a utilization management policy to encourage HFR for eligible women through denying reimbursement for extended-course radiation. We assessed the impact of the policy on HFR use and associated spending. Methods: We conducted a retrospective, adjusted difference-in-differences analysis using administrative claims of women continuously enrolled in 14 geographically diverse commercial health plans covering 6.9% of US adult women. The study population included women aged 18 or older with ESBC who were eligible for HFR according to 2011 guidelines from the American Society for Radiation Oncology. Women who received mastectomy, brachytherapy, or < 11 or > 40 external beam fractions were excluded. We compared HFR use and associated spending between women in fully-insured and Medicare Advantage (fully-insured) plans for whom the policy applied vs. self-insured or Medicare supplemental insurance (self-insured) plans for whom the policy did not apply. We adjusted for age, comorbidity, region, Medicare enrollment, and prior chemotherapy. Results: Among 10,540 eligible women, 3,619 (34%) were in fully insured plans and thus subject to the policy. There were no meaningful differences in mean age (63.8 vs. 65.0), Charlson comorbidity index (3.0 vs. 3.2), or practice setting between the fully-insured and self-insured groups. The policy was associated with an increase in HFR (4.2 adjusted percentage point difference-in-difference [ppd], 95% CI 0.0 to 8.4, p = 0.051) and a non-significant decrease in radiotherapy-associated expenditures (-$2,275, p = 0.09). Spillover analyses revealed significantly higher uptake of HFR among self-insured patients who were indirectly exposed to the policy through seeing the providers who also treated fulled insured women (8.5 adjusted ppd, 95% CI 3.6 to 13.5, p = 0.001), compared to those who were not exposed. Conclusions: A payer’s utilization management policy was associated with direct and spillover increases in HFR use, even after accounting for a strong secular trend towards increased hypofractionation use. However, policymakers must balance the impact of this and similar policies against their additional administrative costs.

e12562 Background: Conversion of Her-2 positive to negative after neoadjuvant treatments in Her-2 positive breast cancer has been reported. In most of these reports either chemotherapy alone or in combination with a single Her-2 agent (trastuzumab) was utilized. Use of dual anti-Her-2 agents (Pertzummab/Trastuzumab) along with chemotherapy as the neoadjuvant treatment regimen in Her-2 + breast cancer is a standard of care now. We looked at the loss of Her-2 expression after neo-adjuvant regimen consisting of dual anti-Her-2 agents and chemotherapy in locally advanced Her-2 + breast cancer. Methods: We reviewed the records of Her-2 positive patients with T2 or higher or lymph Node+ Her-2 + breast treated at our institution. Patients who had received neo-adjuvant chemotherapy and dual anti-Her-2 agents, pertuzumab and Trastuzumab were identified for this study. Clinical and pathologic data was collected. Her-2 expression was determined by IHC and FISH. Results: Between Dec 2014 and June 2019, 79 patients for identified. Median age was 47 yrs, range 31-83 yrs. All were females except one. Pre-treatment, 74 pts. were 3 + on IHC and 5 pts. were 2+ on IHC, but positive by FISH. Median Her-2/CEP 17 copy number ratio was 6.2, range 3.6-16.7. Sixty patients were ER positive and 19 were ER negative. Pertuzumab+ TCH was the most common regimen used, 91% of the patients. All patients underwent surgery. Forty five out of 79 patients, 56%, had a pCR. Thirty four pts with residual disease were re-assessed for Her-2 expression. 7/32 (20.5%) patients were Her-2 negative. 6/7 pts. were 0/1+ by IHC and 1 pt. was 2+ by IHC but negative by FISH. Five out of seven pts. (71.5%) converting to Her-2 negative were ER negative at diagnosis and 2/7 (28.5%) converting to Her-2 negative were ER + at diagnosis. All patients converting to Her-2 negative had received Pertuzumab+TCH. Conclusions: Loss of Her-2 expression is observed after neoadjuvant treatments with a dual anti-Her-2 regimen along with chemotherapy. Implications of this change on choosing adjuvant treatments in Her-2 + pts who have had neo-adjuvant therapy and effect on recurrence/survival outcomes needs to be explored in larger studies.

Few conceptual frameworks attempt to connect disaster‐associated environmental injuries to impacts on ecosystem services (the benefits humans derive from nature) and thence to both psychological and physiological human health effects. To our knowledge, this study is one of the first, if not the first, to develop a detailed conceptual model of how degraded ecosystem services affect cumulative stress impacts on the health of individual humans and communities. Our comprehensive Disaster‐Pressure State‐Ecosystem Services‐Response‐Health model demonstrates that oil spills, hurricanes, and other disasters can change key ecosystem components resulting in reductions in individual and multiple ecosystem services that support people's livelihoods, health, and way of life. Further, the model elucidates how damage to ecosystem services produces acute, chronic, and cumulative stress in humans which increases risk of adverse psychological and physiological health outcomes. While developed and initially applied within the context of the Gulf of Mexico, it should work equally well in other geographies and for many disasters that cause impairment of ecosystem services. Use of this new tool will improve planning for responses to future disasters and help society more fully account for the costs and benefits of potential management responses. The model also can be used to help direct investments in improving response capabilities of the public health community, biomedical researchers, and environmental scientists. Finally, the model illustrates why the broad range of potential human health effects of disasters should receive equal attention to that accorded environmental damages in assessing restoration and recovery costs and time frames.

Background: Despite more widely accessible combination antiretroviral therapy (cART), the human immunodeficiency virus type-1 (HIV) infection remains a global public health challenge. Even in treated and chronically HIV-infected (HIV+) individuals, neurocognitive impairment often persists, affecting quality of life. Identifying the neuroanatomical pathways associated with infection in-vivo may delineate the neuropathological processes underlying these deficits. However, to date, neuroimaging findings are inconsistent. Methods: We established the ENIGMA-HIV Working Group to retrospectively pool and harmonize heterogeneous data from 12 HIV neuroimaging studies across Africa, Asia, Australia, Europe, and North America. Volume estimates for eight subcortical brain regions were extracted from T1- weighted MRI from 1,044 HIV+ adults (aged 22-81 years; 72·4% on cART; 70·3% male; 41·6% with detectable viral load; dVL), to identify associations with plasma markers reflecting current immunosuppression (CD4+ T-cell counts) or dVL. Follow-up analyses stratified data by cART status and sex. Findings: After Bonferroni correction, lower current CD4+ counts were associated with smaller hippocampal (β=20·3 mm3 per 100 cells/mm3; p=0·0001) and thalamic volumes (β=29.3; p=0·003); in participants not on cART, they were associated with smaller putamen volumes (β=65·1; p=0·0009). dVLs were associated with smaller hippocampi (Cohen's d=0·24; p=0·0003) and amygdala (d=0·18; p=0·0058). Interpretation: In a globally representative population of HIV+ individuals, volumes of structures in the limbic system were consistently associated with current plasma markers. Deficits in these regions may represent a generalizable brain signature of HIV-infection in the cART era. Our findings support the role of viral suppression and immune restoration in maintaining brain health. Funding Statement: Funding for the ENIGMA Center for Worldwide Medicine Imaging and Genomics was provided by the NIH Big Data to Knowledge Program (BD2K; U54 EB020403). Additional funding for this work was provided by NIH grants R01AG059874 (NJ), R01MH117601 (NJ), T32AG058507 (TMN and CRKC), 5T32MH073526 (CRKC), MH083553 (CHH), MH19535 (CHH), R01HL095135 (KJK), MH095661 (TK), UL1RR033176 (TK), UL1TR000124 (TK), MH19535 (TK), NS080655 (BAN), K01AA025306 (ECP), R01HL095135 (CMS), U54MD007584 (CMS), K23MH095661 (ADT), K23AG032872 (VV), R01NS061696 (VV), K24MH098759 (VV), K01AG050707 (AJW), P01AA019072 (RAC), R01MH074368 (RAC), P30 AI042853 (RAC), and by R01MH085604 (RP). This study was also supported by the SA Medical Research Council (DJS), NHMRC APP568746 and APP1045400 (LAC), and the European Research Council Advanced Grant MedYMA 2011- 291080 (XP). Declaration of Interests: PMT, TMN, NJ, and CRKC received partial research support from Biogen, Inc., for work unrelated to the topic of this manuscript. BKN has received an honorarium from MedLink Neurology. VV has served as a consultant for Merck and ViiV Healthcare in the past 3 years, not related to this work. JA has received honoraria for participating in advisory meetings for ViiV Healthcare, Gilead, Merck, Roche and AbbVie. The remaining authors all declare no conflicts of interest. Ethics Approval Statement: Each study obtained approval from their local ethics committee or institutional review board; participants signed an informed consent form at each participating site.

Background We investigated the effect of crenezumab, a humanized anti-amyloid-beta (Aβ) immunoglobulin (Ig)G4 monoclonal antibody, on biomarkers of amyloid pathology, neurodegeneration, and disease progression in patients with mild-to-moderate Alzheimer’s disease (AD). Methods This double-blind, placebo-controlled, randomized phase II study enrolled patients with mild-to-moderate AD and a Mini-Mental State Examination (MMSE) score of 18–26. In part 1 of the study, patients were 2:1 randomized to receive low-dose subcutaneous (SC) 300 mg crenezumab every 2 weeks (q2w) or placebo for 68 weeks; in part 2, patients were 2:1 randomized to receive high-dose intravenous (IV) 15 mg/kg crenezumab every 4 weeks (q4w) or placebo for 68 weeks. The primary endpoint was change in amyloid burden from baseline to week 69 assessed by florbetapir positron emission tomography (PET) in the modified intent-to-treat population. Secondary endpoints were change from baseline to week 69 in cerebrospinal fluid (CSF) biomarkers and fluorodeoxyglucose PET, and change from baseline to week 73 in 12-point Alzheimer’s Disease Assessment Scale cognitive subscale (ADAS-Cog12) and Clinical Dementia Rating Sum of Boxes (CDR-SB). Safety was assessed in patients who received at least one dose of study treatment. Results From August 2011 to September 2012, 91 patients were enrolled and randomized (low-dose SC cohort: crenezumab (n = 26) or placebo (n = 13); high-dose IV cohort: crenezumab (n = 36) or placebo (n = 16)). The primary endpoint was not met using a prespecified cerebellar reference region to calculate standard uptake value ratios (SUVRs) from florbetapir PET. Exploratory analyses using subcortical white matter reference regions showed nonsignificant trends toward slower accumulation of plaque amyloid in the high-dose IV cohort. In both cohorts, a significant mean increase from baseline in CSF Aβ(1–42) levels versus placebo was observed. Nonsignificant trends toward ADAS-Cog12 and CDR-SB benefits were identified in a mild (MMSE 20–26) subset of the high-dose IV cohort. No amyloid-related imaging abnormalities due to edema/effusion were observed. Conclusion The primary endpoint was not met. Exploratory findings suggest potential Aβ target engagement with crenezumab and possible slower accumulation of plaque amyloid. Studies investigating the effects of higher doses of crenezumab on amyloid load and disease progression are ongoing. Trial registration ClinicalTrials.gov, NCT01397578. Registered on 18 July 2011.

Objective Individuals requiring psychiatric emergency services are often highly distressed and intoxicated. To provide an objective and comprehensive measure of their stress-related physiological dysregulations, we indexed allostatic load with 14 biomarkers collected within 24 h of patients' admission to the largest psychiatric hospital in the Canadian province of Quebec. Methods This study (N = 278) combines data for emergency patients (n = 76; 65.8% women; M age = 44.97, SE = 1.6) and hospital workers who served as sex- and age-matched controls (n = 202; 70.8% women; M age = 40.10, SE = 0.83). Sex-specific allostatic load indices summarized neuroendocrine (cortisol), immune (tumor necrosis factor-α, interleukin-6, c-reactive protein), metabolic (insulin, glycosylated hemoglobin, total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, body mass index), and cardiovascular (heart rate, systolic and diastolic blood pressure) functioning. Well-validated questionnaires assessed substance (ab)use. Results Individuals presenting at psychiatric emergency showed elevated allostatic load, drug abuse, and tobacco use compared to controls. Elevated allostatic load in emergency patients was driven by elevated cortisol, interleukin-6, systolic blood pressure, and heart rate; however, allostatic load was not explained by substance (ab)use or demographic variables. Sub-group analyses revealed that emergency patients primarily diagnosed with bipolar, depressive, or anxiety disorders showed higher allostatic load than those diagnosed with personality disorder(s). Conclusions This study demonstrates that individuals presenting at psychiatric emergency services show physiological dysregulations associated with chronic stress. Future research should explore the clinical utility of allostatic load in predicting comorbidities among psychiatric patients.

Perceptions of past, present, and future events may be related to stress pathophysiology. We assessed whether Time Perspective (TP) is associated with cortisol dynamics among healthy adults (N = 61, Ages = 18–35, M = 22.9, SD = 4.1) exposed to the Trier Social Stress Test (TSST). TP was measured according to two profiles: maladaptive Deviation from Balanced TP (DBTP) and adaptive Deviation from Negative TP (DNTP). Eight salivary cortisol samples were analyzed using area under the curve with respect to ground (AUCg) and to increase (AUCi). Statistic analyses involved partial correlations controlling for depressive symptoms. Results for both sexes showed that higher DBTP scores were associated with lower cortisol AUCg scores, while higher DNTP scores were associated with higher cortisol AUCg scores. These novel findings suggest that maladaptive TP profiles influence hypocortisolism, whereas adaptive TP profiles influence hypercortisolism. Thus, TP profiles may impact conditions characterized by altered cortisol concentrations.

Objective Failure to adhere to treatment with antipsychotic medication is the most common cause of relapse among patients with schizophrenia. A novel multifamily group (MFG) intervention, informed by the Theory of Planned Behavior (TPB), demonstrated efficacy in increasing medication adherence and decreasing rehospitalizations in schizophrenia patients. This report explores the hypothesis that the improved outcomes obtained through the MFG approach were mediated by changes in the patients' attitudes toward medications, subjective norms-social influences, and perceived behavioral control of resources. Method Data from a recently completed, randomized controlled trial of MFG was used to test the hypothesis that the improvement in adherence was mediated by the 3 TPB factors. Subjects were 174 Mexican American adults with schizophrenia-spectrum disorder who had participated in a study of MFG focused on improving medication adherence. Assessments occurred at baseline and at 4, 8, 12, 18, and 24 months. Results Path analysis revealed that the increased adherence associated with MFG was mediated by improvements in subjective norms but not attitudes toward medications nor perceived behavioral control. Conclusion An MFG treatment specifically tailored to increase medication adherence among Mexican Americans with schizophrenia achieved its benefits by leveraging social influences through teaching family members how to support medication adherence in their ill relatives.

Cognitive impairments constitute a core feature of attention deficit and hyperactivity disorders (ADHD), but are infrequently assessed in the clinical setting. We have previously demonstrated the ability of an objective cognitive battery, the Screen for Cognitive Impairment in Psychiatry (SCIP), to differentiate adult ADHD patients from healthy controls in five cognitive domains. Here, we further characterize these subtle cognitive deficits by conducting additional univariate analyses on our ADHD dataset to assess the contributions of various demographic characteristics on SCIP performance and to determine correlations between SCIP scores and scores on other measures evaluating illness severity, perceived cognitive deficits, and overall functioning. Age and years of education were moderately associated with performance on the SCIP and/or its subscales in our ADHD cohort. The SCIP global index score was moderately correlated with clinician-rated measures of illness severity and weakly associated with clinician-rated overall functional status. Intriguingly, overall SCIP performance was only weakly associated with patient self-reported measures of cognitive functioning. Of practical importance, small-to-moderate associations were consistently observed between performances on two subscales of the SCIP and the other measures evaluating illness severity, overall functioning, and patient self-reported cognitive functioning (the working memory and visuomotor tracking subscales). Thus, these data demonstrate that the SCIP, particularly the working memory and visuomotor tracking subscales, is sensitive enough to detect cognitive deficits in adult patients with ADHD, and that these deficits are correlated with functional impairments. Furthermore, these data highlight the importance of integrating both objective and subjective evaluations of cognition in adult ADHD.

Background: Foreign body aspiration (FBA) is the 4th leading cause of death in children between the ages 1-5. Although direct laryngoscopy and bronchoscopy (DL&B) is the reference standard for diagnosis of pediatric airway foreign bodies, there is a high negative bronchoscopy rate, exposing patients to unnecessary operative and anesthetic risks and costs. Methods: A clinical care protocol entailing the selective use of low-dose non-contrast airway computed tomography (CT) for children with an intermediate risk for FBA on the basis of clinical exam and chest radiography was implemented to decrease the negative DL&B rate. A retrospective review was conducted to compare negative bronchoscopy rates before and after implementation of the new protocol and the diagnostic performance characteristics of airway CT for airway foreign bodies were analyzed. Results: After implementation of the airway FB clinical care protocol entailing selective airway CT, the overall negative bronchoscopy rate decreased from an institutional historical rate of 37% (54/145) to 17% (10/56) (p = .06). The overall sensitivity, specificity, and positive and negative predictive value of airway CT for FB was 91%, 100%, 100%, and 97% respectively. Conclusions: Low-dose non-contrast airway CT is highly sensitive and specific for airway foreign bodies, and its selective use in a clinical care protocol for children with suspected foreign body aspiration could greatly reduce the negative bronchoscopy rate, thereby decreasing operative risks and costs.

ObjectiveTo evaluate the safety and efficacy of crenezumab in patients with mild to moderate Alzheimer disease (AD).MethodsIn this phase 2 trial, 431 patients with mild to moderate AD 50 to 80 years of age were randomized 2:1 (crenezumab:placebo). Patients received low-dose subcutaneous crenezumab 300 mg or placebo every 2 weeks (n = 184) or high-dose intravenous crenezumab 15 mg/kg or placebo every 4 weeks (n = 247) for 68 weeks. Primary outcome measures were change in Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS-Cog12) and Clinical Dementia Rating–Sum of Boxes scores from baseline to week 73.ResultsThe primary and secondary endpoints were not met. In an exploratory post hoc analysis, a reduction in decline on the ADAS-Cog12 was observed in the high-dose group. Separation from the placebo group on the ADAS-Cog12 was greatest in the milder subsets of AD patients and reached statistical significance in the group with Mini-Mental State Examination scores of 22 to 26. In both groups, there was a significant increase in CSF β-amyloid1-42 levels that correlated with crenezumab CSF levels. The overall rate of adverse events was balanced between groups. One case of amyloid-related imaging abnormalities indicative of vasogenic edema or effusions was reported.ConclusionsAlthough prespecified criteria for testing treatment effects were not met, these data suggest a potential treatment effect in patients with mild AD treated with high-dose crenezumab. Together with the safety profile for crenezumab, these data support the exploration of crenezumab treatment at even higher doses in patients with early AD.Clinicaltrials.gov identifierNCT 01343966.Classification of evidenceThis study provides Class II evidence that, for people with AD, crenezumab does not significantly improve cognition or function at 18 months. The study is rated Class II because

Background: Current pathophysiological models of schizophrenia suggest that stress contributes to the etiology and trajectory of the disorder. We investigated whether cumulative exposure to stress, quantified by allostatic load (AL), an integrative index of immune, metabolic, and neuroendocrine dysregulation, is elevated in patients with schizophrenia (SCZ) and first-episode psychosis (FEP) and related to psychotic symptoms and social and occupational functioning and assessed the temporal dynamics of AL in response to treatment with second-generation antipsychotics. Methods: We assessed AL in a naturalistic study of unmedicated patients with SCZ (n = 28), FEP (n = 28), and healthy controls matched for age and gender (n = 53) at baseline and 6 and 12 weeks after commencement of antipsychotic therapy. Biomarkers for the AL index were selected based on (1) representation of several physiological systems including the cardiovascular, neuroendocrine, immune, and metabolic systems; (2) use in previous AL research; and (3) associations with disease risk. We adopted a scaled AL algorithm whereby each marker proportionally contributes to the overall AL index. Unadjusted and adjusted differences between patients with SCZ, FEP, and controls in AL were tested with ANCOVA, and partial correlations were used to test associations of AL with psychometric variables. Results: AL was higher in patients with SCZ compared to controls (4.91 ± 1.89 vs. 2.87 ± 1.62, P < .001), patients with FEP compared to controls (3.80 ± 1.66 vs. 2.87 ± 1.62, P = .020) but not different between patients with SCZ and patients with FEP (P = .302). Adjusting for age and smoking, we found that positive symptoms were positively correlated with AL across all patients with a psychotic disorder (adjusted R = .520, P < .001) and Global Assessment of Functioning (GAF) scores were negatively correlated with AL at trend level (adjusted R = −.251, P = .070). No significant associations were found for negative symptoms (P = .582). AL decreased after treatment with olanzapine, risperidone, or quetiapine was commenced in patients with SCZ and FEP between the baseline assessment and the 6- and 12-week follow-up. Conclusion: Our data provide evidence for cumulative physiological dysregulation in patients with SCZ and FEP that is linked to the experience of current positive psychotic symptoms. AL could be a useful model that takes stress, long-term adaptation, and its failures into account to further understand the pathophysiology of schizophrenia.

With an aging population on the rise, there is a projected exponential expansion in the prevalence of dementia, particularly Alzheimer's disease (AD). AD is the most common form of dementia, characterized by senile plaques and tangles in the brain. Although the pathophysiology and clinical symptoms are well described, the etiology and pathogenesis of the disease are still unknown. Over the past few decades, research has shown that a number of hormones and their respective systems are dysregulated in the course of cognitive aging and AD. This chapter summarizes some of the implicated hormones, including gonadal hormones, adrenal hormones, insulin, and melatonin. Finally, the chapter ends with a brief summary of some of the genetic variants that have been found to modulate the aforementioned hormones in relation to pathological cognitive decline.

Objectives: Lesbian, gay, and bisexual (LGB) individualsVparticularly those who have not disclosed their sexual orientationVare believed to experience increased chronic stress in comparison with heterosexuals. This interdisciplinary study assessed whether psychiatric symptoms (self-rated anxiety, depression, and burnout), stress hormone profiles (diurnal cortisol), and physiological dysregulations (allostatic load [AL]) would differ for a) LGBs versus heterosexuals and b) disclosed LGBs versus nondisclosed LGBs. Methods: The study included 87 healthy participants (mean [SD] age = 24.6 [0.6] years; LGB n = 46, 43% women; and heterosexual n = 41, 49% women). Diurnal cortisol sampled at five time points was averaged for 2 days. AL indices were based on an algorithm incorporating 21 biomarkers representing neuroendocrine, immune/inflammatory, metabolic, and cardiovascular functioning. Psychological measures were assessed with well-validated questionnaires. Results: Between-group results revealed no significant differences in symptoms of anxiety and burnout, nor among diurnal cortisol levels between sexual orientations. By contrast, gay/bisexual men unexpectedly had lower depressive symptoms (p = .003) and AL levels (p = .043) compared with heterosexual men. Within-group results revealed that disclosed LGBs had fewer psychiatric symptoms (p values G 0.01) and lower cortisol levels +30 minutes upon awakening (p = .004) compared with nondisclosed LGBs. Disclosure was not significantly related to AL levels. Conclusions: LGBs did not manifest more stress-related problems than did heterosexuals. Life transitions like disclosing to one’s family and friends may be protective against psychopathologies and hyperactive cortisol awakening responses. Our novel findings underline the roles disclosure processes have on positive health and well-being for sexual minorities. Key words: sexual minority stress, disclosure, allostatic load, diurnal cortisol, mental health, sexual orientation, stigma. AL = allostatic load; ANCOVA = analysis of covariance; CAR = cortisol awakening response; HPA = hypothalamic-pituitary-adrenal; IOM = Institute of Medicine; LGB = lesbian, gay, bisexual.

Self-rated health (SRH)—a person’s subjective evaluation of his general health—is a more valid and powerful predictor of morbidity and mortality than any other combination of objective and self-reported measures. However, current theoretical frameworks fail to explain this association. Here, we sought to investigate SRH in relation to health outcomes from a transdisciplinary perspective. Using a selective review of epidemiological, clinical and qualitative SRH literature, we analyzed the relationships between this global subjective self-perception of health (the whole) and its directly measurable constituents (the parts). Although SRH often predicts major health outcomes, its underpinnings vary from person to person. Factors influencing individual’s health interact in complex ways evade reductionist methods assessing the parts, and may be best captured by global self-perceptions of health. The study of SRH from a transdisciplinary perspective exemplifies the notion that the whole is greater than the sum of its parts. Insight into individual’s experience of “health”, their association with physiological processes, and impact on the health/disease continuum may contribute to the development of individualized strategies for health care and promotion with aging. In particular, this should be most valuable for addressing non-communicable health conditions where cross-talk between health domains (biological, psychological, social, behavioral, spiritual) may significantly contribute to pathophysiology.

Objective To examine whether the challenges of a cross-national adaptation of an American, evidence-based, illness self-management module for people with serious mental illnesses could be met. The UCLA Medication Management Module was adapted for use in Japan with individuals experiencing short-stay, acute care in an inpatient setting. Method Two evaluations were conducted with 37 and 63 persons diagnosed as having schizophrenia and bipolar disorder, respectively, to test the feasibility and impact of the module as an intervention for illness self- management in an academic, Japanese psychiatric unit. Results The short-term feasibility was demonstrated by consumers' enhanced comprehension of the value and benefits of antipsychotic medication as well as their gaining positive, therapeutic attitudes toward use of medication. A second evaluation of the module revealed that consumers who participated in the skills training developed better understanding of the purposes of medication, more positive attitudes toward medication, and superior coping skills in dealing with medication side effects than their counterparts who received standard treatment. The greater benefits achieved from participating in the module persisted for 7 months postdischarge. Conclusions and implications for practice While preliminary, these studies suggest the applicability of the Medication Management Module for illness management for Japanese hospital practice.

INTRODUCTION AND OBJECTIVES: Anastrozole, an aromatase inhibitor, is used in the empiric treatment of subfertile males to increase endogenous testosterone levels, elevate testosterone-toestradiol ratios and improve semen parameters. However, controversy exists in regard to the effect on prostate specific antigen (PSA) levels by pharmacological agents which increase testosterone levels. In addition, the effects of anastrozole on the prostate and PSA are unknown. Therefore, we sought to study the effect of the increased endogenous testosterone levels seen with anastrozole, on serum PSA levels in subfertile men. METHODS: Patients presenting with infertility and diagnosed with hypogonadism were treated with anastrozole for a minimum of three months. Serum follicle stimulating hormone (FSH), luteinizing hormone (LH), total testosterone (T), estradiol (E), testosterone-toestradiol ratio (T/E), bioavailable testosterone (BT) and PSA levels were recorded at baseline and measured at 3 months and at 5 months during therapy when available. Paired t-test was used to compare baseline and post-treatment laboratory parameters. RESULTS: A total of 50 male patients were included in the study, mean age 35.9 1.0 (SEM). Mean baseline testosterone was 270.2 11.7 ng/dl, mean T/E ratio was 10.5 0.9 and mean baseline PSA was 0.69 0.07 ng/ml. LH, T/E ratios, total testosterone and bioavailable testosterone levels increased significantly on anastrozole therapy. Slight but insignificant increase in PSA values was observed at 3 months of anastrozole treatment (0.78 0.07, p1⁄40.35). For 33 men, follow up laboratory evaluation was obtained at 5 months of anastrozole therapy and no significant change in PSA levels was observed (0.80 0.89, p 1⁄4 0.47). No patient had a signi?cant increase in PSA velocity or change in digital rectal examination requiring prostate biopsy. CONCLUSIONS: The increase in testosterone levels and improved T/E ratios observed with the use of anastrozole in the treatment of hypogonadal, subfertile males does not result in significant increases in PSA levels at 5 months of therapy. Although there does not appear to be any short term adverse effects, further study of the long-term effects of anastrozole on serum PSA is warranted. Source of Funding: none