Carla Marienfeld

Translational Regulation of X-Linked Inhibitor of Apoptosis Protein by Interleukin-6 A Novel Mechanism of Tumor Cell Survival

Interleukin-6 (IL-6) is a pleiotropic cytokine with diverse biological effects. IL-6 has been implicated in autocrine signaling pathways promoting tumor progression and chemoresistance in some human tumors. However, the mechanisms by which IL-6 modulates these responses are unknown. Aberrant apoptosis has been implicated as a fundamental mechanism of chemotherapeutic resistance. Thus, we investigated whether IL-6 alters the expression of apoptosis regulatory proteins as a mechanism of drug resistance. We provide evidence that IL-6 rapidly phosphorylates the translation initiation factor eukaryotic initiation factor-4E and triggers antiapoptotic responses in cholangiocarcinoma cells. Reduction of cellular eukaryotic initiation factor-4E by RNA interference decreases IL-6-induced effects on cytotoxic drug-induced caspase activation and apoptosis. Furthermore, IL-6 increases expression of the endogenous X-linked inhibitor of apoptosis protein expression by translation at an internal ribosome entry site. Our findings that IL-6 translationally regulates X-linked inhibitor of apoptosis protein expression reveal a novel mechanism by which IL-6 mediates tumor cell survival that may be targeted therapeutically to decrease tumor progression and chemoresistance.

Attitudes Toward Mental Illness and Changes Associated with a Brief Educational Intervention for Medical and Nursing Students in Nigeria

ObjectiveThis study assessed beliefs about mental disorders and changes in those beliefs following an educational intervention for a convenience sample of Nigerian medical and nursing students.MethodsA 43-item questionnaire was used to assess perceptions regarding mental disorders and attitudes toward people with mental illness before and after a 4-day educational intervention.ResultsFactor analysis identified four domains: (1) socializing with people with mental illness, (2) belief in witchcraft or curses as causes of mental illness, (3) favorable attitudes toward normalization of the lives of people with mental illness, and (4) biopsychosocial approaches to mental illness. The greatest changes were in attitudes favoring normalization of the lives of people with mental illness (p = 0.0002), socializing with the mentally ill (p = 0.01), and biopsychosocial perspectives on mental illness (p = 0.01).ConclusionBrief educational interventions may alter some stigmatizing negative attitudes toward mental illness in healthcare trainees in low- and middle-income countries.

Impulsivity, cognitive function, and their relationship in heroin-dependent individuals.

There is mixed evidence concerning cognitive function and heroin dependence. In this study, abstinent heroin-dependent individuals (n = 86) and age- and sex-matched non-drug-using controls (n = 88) were compared on self-report measures of impulsivity and computerized assessments of cognitive function. Abstinent heroin-dependent individuals reported greater motor impulsivity and experience seeking and showed functional weaknesses in cognitive ability, including impulsivity and distractibility (d = 0.28 to 0.49), but not decision making or working memory. Self-reported impulsivity was uncorrelated with cognitive function. These results suggest underlying brain-related factors in heroin dependence and have implications for therapeutic intervention.

Use of naltrexone for alcohol use disorders in the Veterans’ Health Administration: A national study

BACKGROUND This study aimed to determine the proportion of patients with alcohol use disorders who were prescribed naltrexone in Veterans Administration (VA) Healthcare system for fiscal year (FY) 2010 and socio-demographic and clinical factors associated with its use. METHODS VA national administrative data were used to identify all veterans who had an alcohol use disorder diagnosis (ICD-9-CM codes 303.9x or305.0x) in fiscal year (FY 2010) and were not prescribed any opioids (n=224,319). Patients in this group who filled a naltrexone prescription during this period were identified. Bivariate analysis was used to evaluate differences between veterans who received naltrexone prescription and those who did not on baseline characteristics and diagnoses. Multivariate logistic regression analysis identified measures that were independently related to receipt of naltrexone. RESULTS 6172 (2.75%) of the 224,319 patients with a diagnosis of alcohol use disorder who did not receive a prescription for opioid medications received naltrexone prescription. Bivariate analyses showed that patients taking naltrexone were 69 times more likely to have a co-morbid axis I diagnosis. Multivariate logistic regression analysis showed that a history of any substance abuse outpatient visit, any psychiatric outpatient visit or any mental health inpatient hospitalization, were significantly related to filling a prescription for naltrexone. CONCLUSIONS The rate of use of naltrexone by clinicians and patients remains low and having a co-morbid axis I diagnosis and receiving specialty mental health care were strong predictors of receiving a naltrexone prescription. Understanding the reasons for these findings may further naltrexones clinical usefulness.

Evaluation of an implementation of methadone maintenance treatment in China.

BACKGROUND Methadone maintenance treatment (MMT) reduces the harms of opioid use disorder and is being rapidly scaled-up in China. This study evaluated the real-world implementation of MMT system in Wuhan, China. METHODS Data extracted from electronic medical records collected in 2010 on 8811 patients were used to compute for each patient indices of the prescribed and consumed daily methadone doses, an adherence index, dose adjustments following missed doses, the rates of opiate positive urine tests, self-reported drug use, injection drug use (IDU), and the duration of MMT exposure. FINDINGS The modal daily doses prescribed were 60 mg and above for 68.5% of patients. Adherence was variable: 51% of patients attended less than 60% and 26% attended 80-100% of their treatment days; and patients with long MMT exposure had significantly higher adherence rates than patients with short MMT exposure. The differences between doses dispensed immediately before and after the interruption in dosing days ranged from 0 to 7 mg, independently of the length of the interruption or the prescribed dosing level. The overall rate of opiate positive tests was 20%; 45% of patients had at least one opiate positive test; 29% reported past month drug use and 53% of them reported past month IDU. Adherence and MMT exposure duration correlated significantly with the proportion of opiate negative urine tests (r=0.355, p<0.001; r=0.351, p<0.001, respectively). Treatment for males and females was comparable. CONCLUSIONS Provision of safe methadone dosing after absences and improving daily attendance are identified as priority improvement areas.

Impact of a Global Mental Health Program on a Residency Training Program

Interest in global health education has grown among medical students and residents, and medical schools and residencies have responded with both increased coursework and international experiences. In a study from 2008, 59% of medical schools offered international clinical elective rotations for residents; 45% offered opportunities for clinical research abroad for medical students; 32% offered research opportunities for residents; and 11% had formal global health track options for students (1). Several reports have described the demand and successful techniques for structuring global health-related medical student experiences in both the United States and Canada (2–7).

Betel quid chewing alters functional connectivity in frontal and default networks: A resting‐state fMRI study

To explore the acute effect of betel quid (BQ) use on functional network connectivity by comparing the global functional brain networks and their subsets before and immediately after BQ chewing.

Long-acting injectable depot naltrexone use in the Veterans' Health Administration: A national study

INTRODUCTION Alcohol use disorders affect millions, but few utilize medications. This paper examines factors contributing to the use of long-acting injectable depot naltrexone (LADN) in a large patient population. METHODS Bivariate analysis, stepwise multivariate logistic regression, and multivariate logistic regression analysis were used. RESULTS The sample had 101,026 patients of whom 3180 (3.1%) received any form of naltrexone and 240 (0.24%) received LADN. Of those who received naltrexone, only 7.5% (240/3180) received LADN. The LADN group was more likely to have outpatient mental health service use and a mental health inpatient admission. The LADN group was more likely to have a co-morbid Axis 1 psychiatric disorder and to fill a psychotropic prescription. CONCLUSION In order to better serve and understand the implications of LADN treatment for the patient population that uses and may benefit from it, more research is needed on the effectiveness of this medication in the dually-diagnosed and high service use population.

Psychiatric Services and Prescription Fills Among Veterans With Serious Mental Illness in Methadone Maintenance Treatment

Objective: Comorbidity and co-prescription patterns of people with serious mental illness in methadone maintenance may complicate their treatment and have not been studied. The goal of this study was to examine the care and characteristics of people with serious mental illness in methadone maintenance treatment nationally in the Veterans Health Administration (VHA). Methods: Using national VHA data from FY2012, bivariate and multiple logistic regression analyses were used to compare veterans in methadone maintenance treatment wo had a serious mental illness (schizophrenia, bipolar disorder, or major affective disorder) to patients in methadone maintenance treatment without serious mental illness and patients with serious mental illness who were not in methadone maintenance treatment. Results: Only a small fraction of patients with serious mental illness were receiving methadone maintenance treatment (0.65%), but a relatively large proportion in methadone maintenance treatment had a serious mental illness (33.2%). Compared to patients without serious mental illness, patients with serious mental illness in methadone maintenance treatment were more likely to have been homeless, to have had a recent psychiatric hospitalization, to be over 50% disabled, and to have had more fills for more classes of psychotropic drugs. Compared to other patients with serious mental illness, patients with serious mental illness in methadone maintenance treatment were more likely to have a drug abuse diagnosis and to reside in large urban areas. Conclusions: One-third of patients in methadone maintenance treatment have serious mental illness and more frequent psychiatric comorbidity, and they are more likely to use psychiatric and general health services and fill more types of psychiatric prescriptions. Further study and clinical awareness of potential drug-drug interactions in this high medication and service using population are needed.

National psychotropic prescription dispensation among dually diagnosed patients

Purpose – The purpose of this paper is to determine if dually diagnosed (DDx) patients with severe mental illnesses such as bipolar disorder and schizophrenia are at higher risk of not obtaining prescribed medication.Design/methodology/approach – National Veterans Health Administration records from 2010 identified all DDx patients with Bipolar (BP) spectrum (n=98,894) and Schizophrenia (SZ) spectrum (n=80,654) disorders. Pharmacy records identified the total number of prescriptions dispensed per veteran for antidepressants, antipsychotics, sedative‐hypnotics and anxiolytics, mood stabilizers (anti‐convulsants), and lithium. To identify potential sociodemographic and clinical confounders, bivariate analyses compared four groups: BP and SZ with and without DDx. Analysis of covariance (ANCOVA) was used to determine the association of DDx with the number of dispensed prescriptions, and interaction analysis was used to determine whether any “dual‐diagnosis effect” was greater between BP or SZ. Further ANCOVA e...