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Lake Erie supported the greatest yield of lake sturgeon within the Laurentian Great Lakes near the end of the 19th century with >2000 metric tons caught at the peak of the fishery. The fishery collapsed by the 1920s when <1% of the previous peak catch was removed. Despite closures of the fishery, lake sturgeon remain rare in Lake Erie. We applied a depletion-based stock reduction analysis (DB-SRA) to the catch of lake sturgeon from 1879 to 1929 to gain estimates of sustainable fishery reference points and the historic carrying capacity of Lake Erie for lake sturgeon. We also simulated population growth of lake sturgeon from 1929 to the present with varying assumptions of the current carrying capacity of the lake. The estimated historic carrying capacity of lake sturgeon was 22,652 metric tons. During the height of the fishery, exploitation was as high as 37% which was more than an order of magnitude greater than that required for maximum sustainable yield. Projections of the population from 1929 to 2016 suggest sufficient time has passed since the collapse of the fishery that the population should have recovered to levels that would support a fishery at maximum sustainable yield. However, lake sturgeon remain rare in Lake Erie indicating that other factors such as habitat availability may be limiting their recovery. Our estimates of carrying capacity will be informative when setting recovery targets which consider the amount of habitat loss. [ABSTRACT FROM AUTHOR]

With the legalization of non-medical cannabis in Canada, cannabis is commonly used in the community and nurses and nursing students are likely to engage in clinical practice discussions around cannabis use for both medical and non-medical purposes. However, whether having previous experience using cannabis influences nursing students' knowledge and attitudes towards cannabis remains unclear. The aim of this study was to describe nursing students' knowledge, attitudes, educational needs, and use of cannabis. Cross-sectional survey. Five academic undergraduate nursing programs in Manitoba, Canada. Nursing students in Manitoba. Students were asked about their use of cannabis, knowledge and attitudes regarding cannabis, clinical experiences and educational needs related to cannabis. Students' current knowledge was compared to their desired knowledge using paired t -tests. Using t -tests, attitudes towards cannabis were compared between students who had ever taken cannabis versus those with no experience. Descriptive statistics were utilized for all other questions. A total of 327 nursing students participated in the survey with 220 students (67.3 %) reporting they had used cannabis in the past, and 123 students (37.6 %) reporting monthly use of cannabis. Students who previously used cannabis held more positive attitudes towards both medical and non-medical cannabis use in comparison to those with no experience. Students recognised that their current knowledge around cannabis was insufficient and indicated the need for greater knowledge on both medical and non-medical cannabis-related topics. Only 37.7 % of students reported receiving any education on cannabis in their nursing program. Nearly all students (92.2 %) agreed if they had more education on medical cannabis use that they would feel more comfortable discussing this in their clinical practice. Education on both medical and non-medical cannabis is needed to support future nurses addressing cannabis use in their clinical practice. Nursing institutions must implement and evaluate curricula to ensure nursing students are adequately prepared to address cannabis use in their clinical practice and their own fitness to practice. [ABSTRACT FROM AUTHOR]

Abstract: Atrazine (ATR) is an herbicide that exerts negative reproductive effects. We examined the effects of vehicle or ATR (1, 5, 20 and 100mg/kg-d), administered to Sprague-Dawley rats on gestational days 14–21, once daily or divided into two doses per day, on female offspring reproductive indices. Offspring body weights at birth were reduced and mortality increased in the 100mg/kg-d group shortly after birth; by PND 21 there were no significant effects. Vaginal opening was delayed in this group, indicating delayed puberty. No significant differences in mammary gland development were apparent at PND 45, or estrous cyclicity through PND 272. There were no differences between dosing regimens. Lower ATR doses (0–20mg/kg-d) showed few effects in females prenatally exposed to ATR, while the high dose (100mg/kg-d) reduced offspring body weight and delayed vaginal opening. Nonetheless, it is unlikely that environmental exposure comparable to the high dose would be encountered. [Copyright &y& Elsevier]

Abstract: Pilot studies represent a fundamental phase of the research process. The purpose of conducting a pilot study is to examine the feasibility of an approach that is intended to be used in a larger scale study. The roles and limitations of pilot studies are described here using a clinical trial as an example. A pilot study can be used to evaluate the feasibility of recruitment, randomization, retention, assessment procedures, new methods, and implementation of the novel intervention. A pilot study is not a hypothesis testing study. Safety, efficacy and effectiveness are not evaluated in a pilot. Contrary to tradition, a pilot study does not provide a meaningful effect size estimate for planning subsequent studies due to the imprecision inherent in data from small samples. Feasibility results do not necessarily generalize beyond the inclusion and exclusion criteria of the pilot design. A pilot study is a requisite initial step in exploring a novel intervention or an innovative application of an intervention. Pilot results can inform feasibility and identify modifications needed in the design of a larger, ensuing hypothesis testing study. Investigators should be forthright in stating these objectives of a pilot study. Grant reviewers and other stakeholders should expect no more. [Copyright &y& Elsevier]

Abstract: Brooks D, Davis L, Vujovic-Zotovic N, Boulias C, Ismail F, Richardson D, Goldstein RS. Sleep-disordered breathing in patients enrolled in an inpatient stroke rehabilitation program. Objective: To report the prevalence of sleep-disordered breathing in an inpatient stroke rehabilitation unit and to explore correlations with functional status and health-related quality of life. Design: Cross-sectional study. Setting: Rehabilitation center. Participants: Consecutive patients (N=45; mean age, 67±12y) (28 men) enrolled in inpatient rehabilitation after ischemic (84%) or hemorrhagic stroke (16%). Interventions: Not applicable. Main Outcome Measures: Overnight respiratory polysomnography was performed on all subjects. Interviewer-administered scales of sleepiness (Epworth Sleepiness Scale) and functional status (FIM, Barthel Index) were completed. Health-related quality of life was assessed by using a general questionnaire (Medical Outcomes Study 36-Item Short-Form Health Survey [SF-36]). Results: Of the 45 subjects tested, only 4 (9%) had an apnea-hypopnea index of less than 10 per hour. The mean apnea-hypopnea index was 32.2 (19.4) per hour; most events were obstructive. There was no relationship between the respiratory index and the components of SF-36 (P values>.2). Conclusions: There was a dramatically high prevalence of respiratory events in patients after stroke enrolled in an inpatient stroke rehabilitation unit. The awareness of this will influence patient evaluation and management. [Copyright &y& Elsevier]

Abstract: Many patients with major depressive disorder (MDD) present with concurrent substance use disorders (SUDs), which has been thought to impair their response to antidepressants. Clinicians often delay antidepressant treatment until sustained sobriety has been established. Unfortunately, these comorbid subjects are typically excluded from depression treatment trials, leaving a gap in understanding the treatment outcomes. In the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, 2876 adult outpatients diagnosed with nonpsychotic MDD were prospectively treated with the selective serotonin-reuptake inhibitor (SSRI), citalopram, and returned for at least one post-baseline visit. Participants with SUD (29%) and without SUD (71%) were compared in regard to baseline clinical and sociodemographic features and treatment response. The group with MDD and SUD was further subdivided into those with alcohol only, drug only, and both alcohol and drug use. Despite clear sociodemographic and clinical differences, there were no significant differences between groups in the time to achieve response or rates of response to citalopram; however, those who endorsed both alcohol and drug use had significantly reduced rates of remission and significantly increased times to reach remission compared to the MDD group without SUD. In addition, subjects with MDD and SUD had higher risk of psychiatric serious adverse events (3.3% vs. 1.5%) and hospitalization (2.8% vs. 1.2%). The results indicate that first-line treatment with citalopram in depressed patients with alcohol or drug use respond as well as those without SUD. More intensive treatment is most likely needed for MDD patients with both drug and alcohol use disorders. [Copyright &y& Elsevier]

Abstract: Mozambique tilapia, (Oreochromis mossambicus), are a euryhaline teleost and an important biological model species. Captive male tilapia frequently have high levels of the estrogen-induced yolk precursor protein vitellogenin (Vg), a common indicator of exposure to estrogenic compounds. Sex steroids are found in commercial fish diets, but relatively few studies have examined the relationship between commercial diets and Vg production. In a fasting experiment to ascertain a dietary role in male Vg production, plasma Vg was reduced to negligible levels after 2weeks of fasting, while no change in estrogen receptor (ER) expression was seen. When male tilapia were fed a squid-based diet that replaced the commercial trout diet, plasma Vg was reduced to undetectable levels over 40days, concomitant with significant reductions in hepatic expression of Vgs A, B, and C, and ERβ, compared with control fish fed commercial trout diet. Female tilapia fed the squid-based for 20days had no change in these parameters. When male tilapia were fed a defined, soy-based diet, plasma Vg reduced to 20% of levels in fish given either commercial trout diet or a defined, fishmeal-based diet. Overall, results from these studies suggest that estrogens in a commercial trout diet induce vitellogenin production by increasing expression of Vg, but not ER genes in male tilapia. [Copyright &y& Elsevier]

Abstract: Effects of two endocrine disruptors, o,p''-DDE and heptachlor, and 17β-estradiol (E2) on vitellogenin (Vg) and the growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis were examined in male tilapia. In the first experiment, fish were given 5 weekly injections of either E2, o,p''-DDE or heptachlor (5 μg/g). E2 treatment increased plasma Vg and hepatic expression of three Vg genes (Vgs A, B, and C) and estrogen receptor α (ERα), while reducing plasma levels of IGF-I and suppressing the expression of IGF-I, the GH receptor (GHR2) and the putative somatolactin receptor (GHR1). Neither pesticide greatly affected the other parameters examined, except for a significant reduction in expression of GHR2 and increased plasma IGF-I. In the second experiment, fish were given a single injection of o,p''-DDE or heptachlor (100 μg/g), or E2 (5 μg/g) and sacrificed 5 days post-injection. Treatment with E2 stimulated expression of all three Vg genes. Both o,p''-DDE and heptachlor increased expression of VgB, whereas only o,p''-DDE increased VgA expression. There was no effect of o,p''-DDE or heptachlor on VgC expression or plasma Vg levels. Treatment with o,p''-DDE and heptachlor as well as E2 increased ERα and ERβ transcript levels. Similarly, both pesticides increased GHR1 and IGF-I expression, whereas no significant effect of E2 was observed on GHR1, GHR2 or IGF-I expression. These results indicate that o,p''-DDE and heptachlor have varying temporal and dose effects on modulation of Vg and the GH/IGF-I axis that are distinct from E2. [Copyright &y& Elsevier]

In September 2008, an article was published in the Journal of the American Medical Directors Association criticizing current dysphagia assessment and management practices performed by speech-language pathologists in Long-Term Care (LTC) settings. In the same issue, an editorial invited dialogue on the points raised by Campbell-Taylor. We are responding to this call for dialogue. We find Campbell-Taylor''s interpretation of the literature to be incomplete and one-sided, leading to misleading and pessimistic conclusions. We offer a complementary perspective to balance this discussion on the 4 specific questions raised: (1) Is the use of videofluoroscopy warranted for evaluating dysphagia in the LTC population? (2) How effective are thickened liquids and other interventions for preventing aspiration and do they contribute to reduction of morbidity? (3) Can aspiration be prevented and is its prevention important? and (4) Is there sufficient evidence to justify dysphagia intervention by speech language pathologists? [Copyright &y& Elsevier]

Abstract: Patients with advanced cancer are often polysymptomatic. Different symptoms occur with varying frequency, intensity, and impact. Despite the high prevalence of symptoms in this population, reports of symptomatology in palliative outpatients have been limited. We report the symptom distress in metastatic cancer patients attending an outpatient palliative radiotherapy clinic. Patients referred for palliative radiotherapy for symptom control to the Rapid Response Radiotherapy Program (RRRP) were asked to rate symptom distress using the Edmonton Symptom Assessment Scale (ESAS) at the time of initial consultation. Patient demographics, cancer history, disease status, and analgesic consumption during the previous 24 hours were recorded. Between January 1999 and January 2002, 1,296 patients were seen at the RRRP and consented to participate in the study. Mean symptom distress rates ranged from 1.41 to 5.04. Fatigue, poor sense of well-being, pain, and poor appetite were the highest scored symptoms consecutively. Patients with poorer performance status (KPS ≤ 60) had significantly higher symptom distress scores for all nine symptoms (P &#60; 0.001). We conclude that the symptoms of metastatic cancer, including pain, fatigue, depression, anxiety, drowsiness, poor appetite, and sense of well-being, are common among patients attending outpatient palliative clinics. Symptom assessment tools, such as the ESAS, allow for the identification of symptoms and their severity. The appropriate regimen for management of pain and symptoms in metastatic cancer patients can then be planned. [Copyright &y& Elsevier]

Abstract: To prospectively assess patient-rated symptoms in patients with brain metastases treated with whole brain radiotherapy, these patients were asked to rate their symptoms on the Edmonton Symptom Assessment Scale (ESAS) before, and 1, 2, 4, 8, and 12 weeks following the radiation treatment. ESAS evaluates pain, fatigue, nausea, depression, anxiety, drowsiness, appetite, sense of well-being, and shortness of breath on a scale of 0–10 (0=absence of symptom and 10=worst possible symptom). Patients with a language barrier or significant cognitive impairment were excluded. The mean difference of ESAS symptoms at each follow up were compared with baseline and P &#60; 0.01 was considered statistically significant. One hundred seventy patients (102 female and 68 male) were included between January 1999 and January 2002. Their median age was 66 years (range 33–84) and the median Karnofsky performance score (KPS) at baseline was 60 (range 20–90). The most common primary cancer sites were lung (99; 58%), breast (32; 19%), gastrointestinal (16; 9%), unknown (14; 8%) and others (9; 6%). One-third had significant weight loss (≥10% over the last 6 months). All patients were prescribed dexamethasone at varying doses during radiotherapy. The dose fractionations were 20 Gy in 5 fractions, 138 (81%); 30 Gy in 10 fractions, 7 (4%); and others, 25 (15%). The baseline mean ± SD for ESAS scores were: pain 2.4 ± 2.8, fatigue 5.3 ± 2.8, nausea 1.3 ± 2.2, depression 2.8 ± 2.7, anxiety 3.6 ± 3.0, drowsiness 3.5 ± 2.9, appetite 3.0 ± 3.2, sense of well-being 3.8 ± 2.7, and shortness of breath 2.3 ± 2.5. For the entire cohort, after the delivery of palliative radiotherapy for brain metastases, there were statistically significant deteriorations in the mean differences from the baseline for the following ESAS domains: fatigue 1.0 to 1.8; drowsiness 1.2 to 1.8; and appetite 2.2 to 2.4. The data demonstrate that certain parameters of quality of life worsen after whole brain radiotherapy. [Copyright &y& Elsevier]

Purpose: To examine the accuracy of survival prediction by palliative radiation oncologists. Methods and materials: After consultation of cancer patients with metastatic disease for referral of palliative radiotherapy, radiation oncologists estimated the survival of the patients. These were compared with the actual dates of death obtained from the Cancer Death Registry. The time to death from all causes was the outcome. The survival times were measured from the date of the first consultation at the palliative radiotherapy clinics. Results: Six radiation oncologists provided estimates for 739 patients. Of the 739 patients, 396 were men and 343 were women (median age, 69 years). The median survival of all patients was 15.9 weeks. The mean difference between the actual survival (AS) and the clinician predicted survival (i.e., actual survival minus clinician predicted survival) was −12.3 weeks (95% confidence interval, −15.0 to −9.5) for the entire population. The mean difference was −21.9 weeks when the actual survival was ≤12 weeks, −19.2 weeks when the AS was 13–26 weeks, −9.7 weeks when the AS was 27–52 weeks, and +23.0 weeks when the AS was >52 weeks. Conclusion: In this study, the prediction of survival by radiation oncologists was inaccurate and tended to be overly optimistic. [Copyright &y& Elsevier]

Patients with major depressive disorder (MDD) often present with concurrent substance use disorders (SUD) involving alcohol and/or illicit drugs. This analysis compares the depressive symptomatic presentation and a range of clinical and demographic features of patients with MDD and concurrent SUD symptoms vs those without SUD symptoms, to clarify how these two differ and to determine whether concurrent SUD symptoms may alter the clinical presentation of MDD. The first 1500 outpatients with nonpsychotic MDD enrolled in the Sequenced Treatment Alternatives to Relieve Depression study were divided into those with and without concurrent SUD symptoms as ascertained by a self-report instrument, the Psychiatric Diagnostic Screening Questionnaire (PDSQ). Of the 1484 cases with completed baseline PDSQ, 28% (n = 419) of patients with MDD were found to endorse symptoms consistent with current SUD. Patients with symptoms consistent with SUD were more likely to be men (P < .0001), to be either divorced or never married (P = .018), to have a younger age of onset of depression (P = .014), and to have a higher rate of previous suicide attempts (P = .014) than those without SUD symptoms. Patients with major depressive disorder who have symptoms consistent with SUD endorsed greater functional impairment attributable to their illness than those without concurrent SUD symptoms (P = .0111). The presence of SUD symptoms did not alter the overall depressive symptom pattern of presentation, except that the dual-diagnosed patients had higher levels of hypersomnia (P = .006), anxious mood (P = .047), and suicidal ideation (P = .036) compared to those without SUD symptoms. In conclusion, gender, marital status, age of onset of major depression, functional impairment, and suicide risk factors differ in depressed patients with concurrent SUD symptoms compared to those without SUD comorbidity. [ABSTRACT FROM AUTHOR]

This paper will examine how listeners perceive foreignness, precision, and speaker origin in the speech of a speaker with neurogenic foreign accent syndrome, as compared to an unimpaired native speaker, an unimpaired foreign speaker, and a native speaker with ataxic dysarthria. Listeners with and without experience in speech-language pathology rated degree of foreignness and precision of speech sounds of a speaker with neurogenic foreign accent syndrome as compared to (a) an unimpaired native speaker, (b) an unimpaired foreign speaker, and (c) a native speaker with ataxic dysarthria. Listeners also attributed national origin to each speaker and rated confidence in all their attributions and ratings. Listeners rated a native speaker with foreign accent syndrome as less foreign than a true foreign speaker. They agreed less and were less accurate when attributing national origin to a speaker with foreign accent syndrome and were less confident in their attributions and ratings. Unexpectedly, listeners were equally as unsure when attributing origin to a native speaker with ataxic dysarthria as they were when attributing origin to a native speaker with foreign accent syndrome. While previous literature has characterized foreign accent syndrome as perceptually unique in comparison to true foreign accents and other motor speech disorders, our results suggest that listeners do not universally discern a clear difference between foreign accent syndrome speech and other disordered speech. This may suggest that foreign accent syndrome is not a discrete diagnosis. If it is a discrete diagnosis, these results rebut the idea that foreign accent syndrome is the only motor speech disorder in which the speaker is perceived as foreign. • Foreign accent syndrome (FAS) and ataxic dysarthria have perceptual similarities. • FAS speech rated more foreign, less precise than other speech. • Accuracy and confidence decrease when placing national origin of speakers with FAS. [ABSTRACT FROM AUTHOR]

Complementary integrative medicine, such as mindfulness-based interventions, (MBI) have demonstrated efficacy in the treatment of depression, anxiety, substance use disorders (SUDs), and pain. Mindfulness-based relapse prevention (MBRP) is an aftercare intervention targeting SUD relapse that integrates cognitive-behavioral relapse prevention and mindfulness meditation practices, raising awareness of substance use triggers and reactive behavioral patterns. This study evaluated the efficacy of MBRP in reducing relapse in veterans following completion of an SUD treatment program. This study was a two-site, randomized controlled trial comparing MBRP to 12-step facilitation (TSF) aftercare in military veterans following completion of intensive treatment for SUDs. The 8 weeks of 90-minute, group-based MBRP or TSF sessions were followed by 3-, 6- and 10-month follow-up periods with assessments of alcohol/substance use and secondary outcomes of depression, anxiety, and mindfulness. Forty-seven percent of veterans attended ≥75 % of sessions. Veterans in both the MBRP and TSF aftercare groups maintained reductions in alcohol and illicit substance use during the aftercare treatment. Nineteen participants (11 %; 19/174) reported returning to alcohol use during the study treatment period and the study found no difference between study groups [MBRP: 9 % vs. TSF 13 %; p = 0.42]. Thirteen participants (7.5 %; 13/174) reported a return to illicit substance use during study treatment [MBRP: 5.4 % vs. TSF 10.3 % p = 0.34]. The number of days of drinking and illicit substance use was not different between groups (alcohol, p = 0.53; illicit substance use, p = 0.28). Although retention in treatment limits interpretation of the findings, both MBRP and TSF were effective in maintenance of treatment gains following an intensive treatment program for veterans with SUDs. Future studies should focus on strategies to improve treatment participation. • Veterans receiving aftercare MBRP or TSF were less likely to use alcohol or illicit substances as before intensive treatment. • Veterans receiving aftercare MBRP or TSF had fewer days of alcohol and illicit substance use. • Veterans receiving aftercare MBRP or TSF maintained reductions in drinking and substance use at 10-month follow-up. [ABSTRACT FROM AUTHOR]

Abstract: The Sequenced Treatment Alternatives to Relieve Depression (STAR⁎D) trial is a multi-site effectiveness study funded by the National Institute of Mental Health (NIMH) with the aim of identifying successful, acceptable and cost-effective treatment strategies for outpatients with unremitted depression. With enrollment of 4041 adults with major depressive disorder (MDD), it is the largest controlled psychiatric treatment study ever undertaken. In the course of developing procedures to ensure that ambitious enrollment goals were met, a number of ethical and practical issues became apparent that underscore the conflicts between effectiveness research and human subject protections. These are delineated as they relate to study design; eligibility criteria; incentives to subjects; investigators and clinical sites; the complementary roles of clinical research coordinators (CRCs) and study clinicians; and recruitment and consent procedures. The STAR⁎D trial exemplifies the interplay and tension between those strategies that integrate research and clinical aims and roles in the service of enhancing external validity, site participation, and recruitment and retention versus those strategies that differentiate research and clinical treatment in the service of research integrity and human subject protections. We hope that a discussion of these key challenges and dilemmas and how they have been addressed will help inform future discussions concerning design and conduct of ethical effectiveness trials designed to optimize care in real world clinical settings. [Copyright &y& Elsevier]

Abstract: Background and purpose: To examine the incidence of pain flare following external beam radiotherapy and to determine what constitutes a meaningful change in pain scores in the treatment of bone metastases. Patients and methods: Patients with bone metastases treated with external beam radiotherapy were asked to score their pain on a scale of 0–10 before the treatment (baseline), daily during the treatment and for 10 days after completion of external beam radiation. Pain flare was defined as a two-point increase from baseline pain in the pain scale of 0–10 with no decrease in analgesic intake or a 25% increase in analgesic intake employing daily oral morphine equivalent with no decrease in pain score. To distinguish pain flare from progression of pain, we required the pain score and analgesic intake to return back to baseline levels after the increase/flare. They were also asked to indicate if their pain changed during that time compared to pre-treatment level. The change in pain score was compared with patient perception. Results: Eighty-eight patients were evaluated in this study. There were 49 male and 39 female patients with the median age of 70 years. Twelve of 88 patients (14%) had pain flare on day 1. The overall incidence of pain flare during the study period ranged from 2 to 16%. A total of 797 pain scorings were obtained. Patients perceived an improvement in pain when their self-reported pain score decreased by at least two points. Conclusions: Our study confirms the occurrence of pain flare following the external beam radiotherapy in the treatment of bone metastases. Further studies are required to predict who are at risk for flare. Appropriate measures can be taken to alleviate the pain flare. The finding in the meaningful change in pain scores supports the investigator-defined partial response used in some clinical trials. [Copyright &y& Elsevier]

Examine how specific types of childhood adversity are associated with clinical features and treatment in adults with Major Depressive Disorder (MDD). This is a secondary analysis of the 35-site VA Augmentation and Switching Treatments for Improving Depression Outcomes study. A 10-item Adverse Childhood Events (ACE) survey was administered at baseline. 83% experienced at least one of the 10 ACEs and 20.7% experienced 6 or more. Participants with childhood adversities were more likely to be younger, female, unemployed, single or divorced, and to have had more severe depression and anxiety, more lifetime episodes, a younger age of first diagnosed MDD, more comorbid PTSD, worse quality of life, and more suicidal ideation than those no or fewer adversities. Neither the overall number nor any of the specific types of adversities were associated with lower remission rates after administration of standard "next-step" treatment strategies, while histories of different specific types were associated with lower depression severity, better quality of life, and less suicidal ideation post-treatment. Attention to different forms of childhood adversity and to diverse clinical outcomes beyond remission and relapse are important considerations when treating individuals with MDD with histories of childhood maltreatment. ClinicalTrials.gov identifier: NCT01421342. • Histories of adverse childhood life events are common in outpatients with major depressive disorder. • Childhood adversity is associated with a younger age of first diagnosis of major depression, lifetime suicidal thoughts, severe depression and PTSD. • Childhood adversity does not predict remission or response to "next-step" treatments for major depressive disorder. • Different types of childhood adversities are associated with distinct treatment outcomes. • Sustained clinical attention to ongoing suicide risk and focused interventions are needed for patients with MDD and histories of childhood adversity. [ABSTRACT FROM AUTHOR]

Because two-thirds of patients with Major Depressive Disorder do not achieve remission with their first antidepressant, we designed a trial of three “next-step” strategies: switching to another antidepressant (bupropion-SR) or augmenting the current antidepressant with either another antidepressant (bupropion-SR) or with an atypical antipsychotic (aripiprazole). The study will compare 12-week remission rates and, among those who have at least a partial response, relapse rates for up to 6 months of additional treatment. We review seven key efficacy/effectiveness design decisions in this mixed “efficacy-effectiveness” trial. [ABSTRACT FROM AUTHOR]

Abstract: Few studies have investigated the long-term effects of atrazine (ATR) following in utero exposure. We evaluated the effects of gestational exposure of Sprague Dawley dams to ATR (0, 1, 5, 20, or 100mg/kg-d) on the reproductive development of male offspring. We also quantified the distribution of ATR and its chlorinated metabolites in maternal, fetal, and neonatal fluid and tissue samples following gestational and/or lactational exposure. Dose-dependent levels of chlorotriazines, primarily diamino-s-chlorotriazine, were present in most samples analyzed, including fetal tissue. In utero exposure to 1–20mg/kg-d ATR did not alter testosterone production, the timing of puberty, play behavior, or other androgen-dependent endpoints of male offspring. Significant maternal toxicity and postnatal mortality were observed at 100mg/kg-d. We conclude that, although levels of chlorotriazines within the fetus were considerable, gestational exposures of 1–20mg/kg-d do not lead to alterations in the measures of male development examined in this study. [Copyright &y& Elsevier]

Purpose: Hemibody irradiation has been shown to relieve bony metastatic pain within 24–48 hours of treatment, whereas for local external beam radiation, onset of pain relief is 1–4 weeks after radiation. The primary objective of this study is to examine whether there is a relationship between the areas of radiation treatment and onset of pain relief. Methods and Materials: From Jan 1999 to Jan 2002, a total of 653 patients with symptomatic bone metastases were treated with external beam radiation. Pain scores and analgesic consumption were recorded at baseline and Weeks 1, 2, 4, 8, and 12. The areas of radiation treatment for all patients were calculated, then correlated with the response and analyzed in various ways. We first compared pain score alone with mean radiation field size. Second, we combined pain score and analgesic consumption. Last, we implemented the International Consensus end points for pain score and analgesic intake. Results: Assessment of 653 patients showed no significant correlation comparing pain scores alone with radiation field area, with the exception of Week 4 for partial responders. Again, no significant correlation was found when combining both analgesic intake and pain score against radiation field size. Even when implementing the International Consensus end point definitions for radiation response, the only significant correlation between radiation field size and response was observed in Week 2 for partial response. Conclusion: There was no statistical significance between mean areas of radiation treatment with the onset of pain relief. [Copyright &y& Elsevier]

This study sought to identify variables associated with functional impairment in persons exposed to terrorism. A sample of adults who sought treatment for psychological distress related to the 2001 World Trade Center attack completed standardized self-report measures of PTSD symptoms, expectancies of ability to regulate negative moods, inter- personal problems, and social-occupational impairment. A multiple regression analysis found that PTSD numbing symptoms, beliefs about the ability to regulate negative moods, feelings of social discomfort and expectations of being disliked, income level, and relationship status significantly predicted 58% of the variance in social-occupational impairment. The results suggest that treatments targeting PTSD numbing symptoms as well as maladaptive expectations about social interactions and one's ability to manage negative affect may have utility for persons adversely affected by mass violence. [ABSTRACT FROM AUTHOR]

Abstract: Background: Depressed patients often present with comorbid anxiety and/or substance use disorder. This report compares the four groups defined by the disorders (anxiety disorder, substance use disorder, both, and neither) in terms of baseline clinical and sociodemographic features, and in terms of outcomes following treatment with citalopram (a selective serotonin reuptake inhibitor). Methods: The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial enrolled 2838 outpatients with non-psychotic major depressive disorder (MDD) from 18 primary and 23 psychiatric care clinics. Clinical and sociodemographic features were assessed at baseline. These baseline features and the treatment outcomes following treatment with citalopram were compared among the four groups. Results: Participants with non-psychotic MDD and comorbid anxiety and/or substance use disorder showed several distinctive baseline sociodemographic and clinical features. They also showed greater depression severity; length of illness; likelihood of anxious, atypical or melancholic features; more intolerance/attrition; and worse remission/response outcomes with treatment. Participants with either anxiety or substance use disorder showed outcomes generally intermediate between those with both and those with neither. Conclusions: Comorbid anxiety and/or substance use disorder are clinically identifiable, and their presence may define distinct MDD subgroups that have more problems and worse pharmacological treatment outcomes. They may benefit from more aggressive, multi-faceted treatment and psychosocial rehabilitation targeted at reducing their psychological comorbidity and functional impairment. [Copyright &y& Elsevier]

Abstract: Background: Pain complaints commonly accompany major depressive disorder (MDD). However, whether patients with MDD and pain complaints differ from those without pain complaints is not well studied. Objective: The objective of this study was to compare depressed outpatients with and those without current pain complaints in terms of sociodemographic, clinical, and presenting symptom features. Methods: The baseline clinical and sociodemographic data of a large representative outpatient sample with nonpsychotic MDD (n=3745) enrolled in the STAR*D (Sequenced Treatment Alternatives to Relieve Depression) study were collected. Baseline information on pain complaints was based on Item No. 25 (somatic pain) of the 30-item Inventory of Depressive Symptomatology–Clinician Rating (IDS-C30). Results: After adjusting for sex, depression severity (IDS-C30 less Item No. 25), and general medical comorbidities (as measured by the Cumulative Illness Rating Scale total score), we found clinically meaningful differences between patients with and those without pain complaints. Younger, African American, Hispanic, and less educated patients were more likely to report pain complaints. In addition, those with pain complaints were more likely to report anxious features with irritable mood, sympathetic nervous system arousal, and gastrointestinal problems as well as poorer quality of life. Neither a more chronic course of illness nor suicidal ideation was associated with pain. Conclusions: Pain complaints are common among outpatients with MDD and are associated with certain symptom features and poorer quality of life. However, the findings of this study suggest that depression accompanied by pain complaints does not increase the clinical psychiatric burden or chronicity of depression. [Copyright &y& Elsevier]

Abstract: The purpose of this treatment effectiveness study was to evaluate the flexible application of a manualized cognitive behavioral treatment (CBT) for PTSD and related symptoms in survivors of the 9/11 terrorist attack on the World Trade Center. Treatment delivery ranged from 12 to 25 sessions; therapist experience ranged from no prior training to extensive training in CBT; and training and supervision of clinicians in the treatment manual was considerably less than that required in a randomized clinical trial (RCT). Paired t-tests demonstrated significant pre–post reductions in symptoms of PTSD and depression for the flexible application of the treatment. A benchmarking analysis revealed that the moderate-to-large effect sizes found for these variables were similar to those obtained in an RCT of the same treatment. Furthermore, effect sizes on measures of outcomes particularly relevant to this population of mass violence survivors such as functional impairment, use of alcohol and drugs to cope, and use of social support to cope, were also medium to large. [Copyright &y& Elsevier]

Background: Bipolar disorder has been linked to alterations in the multifunctional enzyme glycogen synthase kinase-3β (GSK3β). The mood stabilizer lithium inhibits GSK3β in vitro and in mouse brain, and this is currently the strongest known potential therapeutic target of lithium. We tested whether lithium modified GSK3β in vivo or in vitro in peripheral blood mononuclear cells (PBMCs) from healthy control and bipolar disorder subjects. Methods: The PBMCs were obtained from 23 healthy control subjects, 9 bipolar subjects currently treated with lithium, and 13 lithium-free bipolar subjects. Immunoblot analyses were used to measure the inhibited, serine9-phosphorylated GSK3β. Results: The level of phospho-Ser9-GSK3β in PBMCs was regulated by agents that modified kinases and phosphatases acting on GSK3β and was increased by in vitro lithium treatment. More important, phospho-Ser9-GSK3β levels were eightfold higher in PBMCs from lithium-treated bipolar than healthy control subjects. Conclusions: Signaling pathways regulating serine9-phosphorylation of GSK3β can be studied in human PBMCs. Both in vitro and in vivo therapeutic lithium treatment is associated with a large increase in phospho-Ser9-GSK3β in PBMCs. Therefore, the inhibitory serine9-phosphorylation of GSK3β in human PBMCs may provide a biochemical marker to evaluate the association between GSK3β inhibition and therapeutic responses to lithium treatment. [Copyright &y& Elsevier]

Abstract: Although posttraumatic stress disorder (PTSD) is relatively common in community epidemiologic surveys (5–6% for men, 10–12% for women), and psychiatric patients with PTSD are known to have poor functioning and high levels of psychiatric comorbidity, there are no studies that address PTSD prevalence, functioning, and burden in primary care settings. This article reports on (1) the prevalence of PTSD using Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition diagnostic criteria in Veterans Affairs (VA) primary care settings, (2) associated sociodemographic characteristics and comorbidities, (3) functional status related to PTSD, (4) the extent to which PTSD was recognized by providers and (5) health services use patterns (including specialty mental health) of PTSD patients. Patients were randomly selected from those who had an outpatient visit in FY 1999 at one of four VA hospitals; 888 patients consented (74.1% of 1198 contacted); 746 patients (84.0% of consenting patients; 62.3% of contacted patients) were reached for telephone diagnostic interviews. Diagnostic interviews with the Clinician Administered PTSD Scale yielded estimates of current PTSD prevalence of 11.5%. At statistically significant levels, PTSD was positively associated with a variety of comorbid psychiatric disorders, war zone service, age &#60;65 years, not working, less formal education and decreased functioning. Of patients diagnosed with PTSD by study procedures, 12-month medical record review indicated that providers identified only 46.5% and only 47.7% had used mental health specialty services. PTSD-positive [PTSD(+)] patients who used mental health care in the past 12 months were more apt to be identified as having PTSD than nonmental health service users (78.0% vs. 17.8%). Although PTSD(+) patients had more medical record diagnoses than PTSD-negative [PTSD(−)] patients (6.28 vs. 4.95), their use of primary care, urgent care and inpatient care was not different from PTSD(−) patients. [Copyright &y& Elsevier]

There are currently no validated pharmacotherapies for posttraumatic stress disorder (PTSD)-related insomnia. The purpose of the National Adaptive Trial for PTSD-Related Insomnia (NAP Study) is to efficiently compare to placebo the effects of three insomnia medications with different mechanisms of action that are already prescribed widely to veterans diagnosed with PTSD within U.S. Department of Veterans Affairs (VA) Medical Centers. This study plans to enroll 1224 patients from 34 VA Medical Centers into a 12- week prospective, randomized placebo-controlled clinical trial comparing trazodone, eszopiclone, and gabapentin. The primary outcome measure is insomnia, assessed with the Insomnia Severity Index. A novel aspect of this study is its adaptive design. At the recruitment midpoint, an interim analysis will be conducted to inform a decision to close recruitment to any "futile" arms (i.e. arms where further recruitment is very unlikely to yield a significant result) while maintaining the overall study recruitment target. This step could result in the enrichment of the remaining study arms, enhancing statistical power for the remaining comparisons to placebo. This study will also explore clinical, actigraphic, and biochemical predictors of treatment response that may guide future biomarker development. Lastly, due to the COVID-19 pandemic, this study will allow the consenting process and follow-up visits to be conducted via video or phone contact if in-person meetings are not possible. Overall, this study aims to identify at least one effective pharmacotherapy for PTSD-related insomnia, and, perhaps, to generate definitive negative data to reduce the use of ineffective insomnia medications. NCT03668041 [ABSTRACT FROM AUTHOR]