Howard Weeks

Age-Specific Seroprevalence of HIV, Hepatitis B Virus, and Hepatitis C Virus Infection Among Injection Drug Users Admitted to Drug Treatment in 6 US Cities

OBJECTIVES This study measured age-specific seroprevalence of HIV, hepatitis B virus, and hepatitis C virus (HCV) infection among injection drug users (IDUs) admitted to drug treatment programs in 6 US cities. METHODS Remnant sera collected from persons entering treatment with a history of illicit drug injection were tested for antibodies to HIV, hepatitis C (anti-HCV), and hepatitis B core antigen (anti-HBc). RESULTS Prevalence of anti-HBc and anti-HCV increased with age and reached 80% to 100% among older IDUs in all 6 cities. Although overall age-specific HIV prevalence was lower than anti-HCV or anti-HBc, this prevalence was greater in the Northeast than in the Midwest and West. CONCLUSIONS The need continues for effective primary prevention programs among IDUs specifically targeting young persons who have recently started to inject drugs.

Antidepressant and Neurocognitive Effects of Isoflurane Anesthesia versus Electroconvulsive Therapy in Refractory Depression

Background Many patients have serious depression that is nonresponsive to medications, but refuse electroconvulsive therapy (ECT). Early research suggested that isoflurane anesthesia may be an effective alternative to ECT. Subsequent studies altered drug, dose or number of treatments, and failed to replicate this success, halting research on isofluranes antidepressant effects for a decade. Our aim was to re-examine whether isoflurane has antidepressant effects comparable to ECT, with less adverse effects on cognition. Method Patients with medication-refractory depression received an average of 10 treatments of bifrontal ECT (n = 20) or isoflurane (n = 8) over 3 weeks. Depression severity (Hamilton Rating Scale for Depression-24) and neurocognitive responses (anterograde and retrograde memory, processing speed and verbal fluency) were assessed at Pretreatment, Post all treatments and 4-week Follow-up. Results Both treatments produced significant reductions in depression scores at Post-treatment and 4-week Follow-up; however, ECT had modestly better antidepressant effect at follow-up in severity-matched patients. Immediately Post-treatment, ECT (but not isoflurane) patients showed declines in memory, fluency, and processing speed. At Follow-up, only autobiographical memory remained below Pretreatment level for ECT patients, but isoflurane patients had greater test-retest neurocognitive score improvement. Conclusions Our data reconfirm that isoflurane has an antidepressant effect approaching ECT with less adverse neurocognitive effects, and reinforce the need for a larger clinical trial.

Dysregulation of leukocyte gene expression in women with medication-refractory depression versus healthy non-depressed controls

BackgroundDepressive Disorders (DD) are a great financial and social burden. Females display 70% higher rate of depression than males and more than 30% of these patients do not respond to conventional medications. Thus medication-refractory female patients are a large, under-served, group where new biological targets for intervention are greatly needed.MethodsWe used real-time quantitative polymerase chain reaction (qPCR) to evaluate mRNA gene expression from peripheral blood leukocytes for 27 genes, including immune, HPA-axis, ion channels, and growth and transcription factors. Our sample included 23 females with medication refractory DD: 13 with major depressive disorder (MDD), 10 with bipolar disorder (BPD). Our comparison group was 19 healthy, non-depressed female controls. We examined differences in mRNA expression in DD vs. controls, in MDD vs. BPD, and in patients with greater vs. lesser depression severity.ResultsDD patients showed increased expression for IL-10, IL-6, OXTR, P2RX7, P2RY1, and TRPV1. BPD patients showed increased APP, CREB1, NFKB1, NR3C1, and SPARC and decreased TNF expression. Depression severity was related to increased IL-10, P2RY1, P2RX1, and TRPV4 expression.ConclusionsThese results support prior findings of dysregulation in immune genes, and provide preliminary evidence of dysregulation in purinergic and other ion channels in females with medication-refractory depression, and in transcription and growth factors in those with BPD. If replicated in future research examining protein levels as well as mRNA, these pathways could potentially be used to explore biological mechanisms of depression and to develop new drug targets.

Abnormal Functional Connectivity Between Default and Salience Networks in Pediatric Bipolar Disorder

BACKGROUND Pediatric bipolar disorder (PBD) (occurring prior to 18 years of age) is a developmental brain disorder that is among the most severe and disabling psychiatric conditions affecting youth. Despite increasing evidence that brain connectivity is atypical in adults with bipolar disorder, it is not clear how brain connectivity may be altered in youths with PBD. METHODS This cross-sectional resting-state functional magnetic resonance imaging study included 80 participants recruited over 4 years: 32 youths with PBD, currently euthymic (13 males; 15.1 years old), and 48 healthy control (HC) subjects (27 males; 14.5 years old). Functional connectivity between eight major intrinsic connectivity networks, along with connectivity measurements between 333 brain regions, was compared between PBD and HC subjects. Additionally, connectivity differences were evaluated between PBD and HC samples in negatively correlated connections, as defined by 839 subjects of the Human Connectome Project dataset. RESULTS We found increased inter- but not intranetwork functional connectivity in PBD between the default mode and salience networks (p = .0017). Throughout the brain, atypical connections showed failure to develop anticorrelation with age during adolescence in PBD but not HC samples among connections that exhibit negative correlation in adulthood. CONCLUSIONS Youths with PBD demonstrate reduced anticorrelation between default mode and salience networks. Further evaluation of the interaction between these networks is needed in development and with other mood states such as depression and mania to clarify if this atypical connectivity is a PBD trait biomarker.

ECT for Developmental Disability and Severe Mental Illness

To THE EDITOR: Recent studies (1,2) have demonstrated the advantages of genome-wide chromosomal microarray analysis over karyotype for the prenatal detection of pathogenic copy numher variants. Chromosomal microarray analysis may soon become the standard of care in the prenatal setting (1, 2). Not discussed is the potential for later-onset phenotypes of findings identified in utero and the resultant ethical and societal challenges. For example, 22qll.2 deletions are associated with a 20%-25% risk of schizophrenia and more than 60% lifetime risk for any treatable psychiatric disorder (3). Other large (e.g., >500 kb) copy numher variants are now knovm to be enriched in diverse neuropsychiatrie diseases and are absent or very uncommon in control populations (4). To date, schizophrenia is the best studied later-onset disease for which there are replicated associations of moderate or greater effect size with specific copy number variants (5, 6). We therefore quantified the extent to which clinically significant copy number variants reported to patients in a study of prenatal chromosomal microarray analysis (1) were also known to be associated with greater risk for schizophrenia. In this largest study to date (1), established schizophrenia risk variants accounted for 49% (17of35) of the copy numher variants of definite clinical significance discovered in 3,822 karyotypically normal pregnancies. These included a Iq21.1 deletion, a 15ql3.3 deletion, four 17ql2 deletions, and 11 typical 22qll.2 deletions (6, 7). All but one were de novo mutations. Fourteen (23%) of 61 additional copy numher variants reported to patients as having the potential for clinical significance are associated with schizophrenia: three Iq21.1 duplications, one 2ql3 duplication, one 15qll-ql3 duplication, four 16pl3.11 duplications, and five atypical 22ql 1.2 deletions (5-7). Thus, at a minimum, one in every 124 prenatal samples (31/3,822) sent for clinical chromosomal microarray analysis would be reported as having a clinically significant finding that might also be considered a schizophrenia risk variant. Notably, a typical 22qll.2 deletion was found in one in every 347 prenatal samples (including one in every 1,022 samples with no anomaly on ultrasonography). The true incidence of 22qll.2 deletions in live births remains unknown (8). Analyses of data ñrom other smaller studies of prenatal chromosomal microarray analysis yielded comparable results (data not shown). Prenatal detection of copy number variants with attendant elevated risk for schizophrenia and multiple other conditions is increasingly a reality. Demand for early interventions to reduce such risks (9) is likely to increase. There are associated ethical and societal implications that have been previously considered mostly in the abstract for later-onset diseases like schizophrenia. The opinions of patients, families, psychiatrists, and other key stakeholders are largely unknown. Lessons learned from now-familiar scenarios in prenatal genetic testing, such as the association of Alzheimers disease with trisomy 21, will help guide our approach to prenatal testing using chromosomal microarray analysis. References

Propofol for Treatment-Resistant Depression: A Pilot Study

Abstract Background We hypothesized that propofol, a unique general anesthetic that engages N-methyl-D-aspartate and gamma-aminobutyric acid receptors, has antidepressant properties. This open-label trial was designed to collect preliminary data regarding the feasibility, tolerability, and efficacy of deep propofol anesthesia for treatment-resistant depression. Methods Ten participants with moderate-to-severe medication-resistant depression (age 18–45 years and otherwise healthy) each received a series of 10 propofol infusions. Propofol was dosed to strongly suppress electroencephalographic activity for 15 minutes. The primary depression outcome was the 24-item Hamilton Depression Rating Scale. Self-rated depression scores were compared with a group of 20 patients who received electroconvulsive therapy. Results Propofol treatments were well tolerated by all subjects. No serious adverse events occurred. Montreal Cognitive Assessment scores remained stable. Hamilton scores decreased by a mean of 20 points (range 0–45 points), corresponding to a mean 58% improvement from baseline (range 0–100%). Six of the 10 subjects met the criteria for response (>50% improvement). Self-rated depression improved similarly in the propofol group and electroconvulsive therapy group. Five of the 6 propofol responders remained well for at least 3 months. In posthoc analyses, electroencephalographic measures predicted clinical response to propofol. Conclusions These findings demonstrate that high-dose propofol treatment is feasible and well tolerated by individuals with treatment-resistant depression who are otherwise healthy. Propofol may trigger rapid, durable antidepressant effects similar to electroconvulsive therapy but with fewer side effects. Controlled studies are warranted to further evaluate propofol’s antidepressant efficacy and mechanisms of action. ClinicalTrials.gov: NCT02935647.

Patient reported outcomes – experiences with implementation in a University Health Care setting

AimPatient-reported outcomes (PROs) have traditionally been implemented through a manual process of paper and pencil with little standardization throughout a Healthcare System. Each practice has asked patients specific questions to understand the patient’s health as it pertains to their specialty. These data were rarely shared and there has not been a comparison of patient’s health across different specialty domains. We sought to leverage interoperable electronic systems to provide a standardization of PRO assessments across sites of care.MethodsUniversity of Utah Health is comprised of four hospitals, 12 community clinics, over 400,000 unique annual patients, and more than 5000 providers. The enterprise wide implementation of PROs started in November of 2015. Patients can complete an assessment at home via email, or within the clinic on a tablet. Each specialty has the opportunity to add additional specialty-specific instruments. We customized the interval with which the patient answers the assessments based on specialty preference in order to minimize patient burden, while maximizing relevant data for clinicians.ResultsBarriers and facilitators were identified in three phases: Pre-implementation, Implementation, and Post-implementation. Each phase was further broken down into technical challenges, content inclusion and exclusion, and organizational strategy. These phases are unique and require collaboration between several groups throughout the organization with support from executive leadership.DiscussionWe are deploying system-wide standard and customized PRO collection with the goals of providing better patient care, improving physician-patient communication, and ultimately improving the value of the care given. Standardized assessment provides any clinician with information to quickly evaluate the overall, physical and mental health of a patient. This information is available real time to aid in patient communication for the clinician.

COMPARING AUTOMATED MENTAL HEALTH SCREENING TO MANUAL PROCESSES IN A HEALTH CARE SYSTEM

Statement of the Problem: If following a medication prescription is a complex task for standard adults, it is often a too complex task for many older adults. Because they are generally prone to complex polypharmacy, may suffer from cognitive, motor, or sensorial decline, and are faced with a standard prescriber-patient communication, elderly people encounter supplementary difficulties. These factors could partially explain why they are frequently non-adherent. Specific tools are needed to analyze the exact nature of these difficulties. Our objective is to present such a tool, that we are developing in a multidisciplinary project, the CONSIGNELA project.A the central nervous system controls whole-body motion, which involves multi-joint movement, certain problems regarding the number of variables controlled by the central nervous system arise (i.e., the “degree of freedom problem”). The central nervous system solves these problems, not by controlling joint movements, but rather by controlling only the task-dependent center of mass (COM) position of the whole body. Although uncontrolled joint movement should be organized in a coordinate manner to form the task-dependent COM position, it is unclear how the law joint coordination is organized. In the present study, we aimed to clarify the shape of joint coordination by elucidating the mutual relationship between the COM trajectory and joint movement during whole body motion. Downward squatting motions with five trunk angles were recorded by using a 3-D motion analysis system in eight healthy men. The trunk, thigh, and shank angles relative to the vertical line were calculated. Furthermore, the COM coordination in the sagittal plane was calculated using those angles. The COM trajectory showed an approximately vertical path in all trunk conditions, suggesting that the form of the COM trajectory depends on a motor-task. In addition, the COM vertical path suggests that the COM trajectory is constrained by biomechanical dynamics and minimum muscle torques. The shank angle decreased with an increase in the trunk angle, whereas the thigh showed a constant angle. This result suggests that the shank and trunk angles form the COM vertical path and the thigh angle adjusts the COM height. These findings demonstrate that the joints are organized into a lawful coordinative structure to make up the task-dependent COM trajectory. The present findings can contribute to improving motor abilities in healthcare activity and effectiveness of activity of daily living.Generally, TQM (Total Quality Management) is used worldwide and recognized. However, contents of activity are various, and it is very difficult for organization to define the whole assessment scope of TQM. On the other hand, we have participated in the development of international standard for supporting the quality requirements and evaluation of system in ISO/IECJTC1/SC7. In the previous study, we suggested the concept of TQM matrix and the view point of Three Dimensional Unification Value Models for evaluating system. Based on the previous study, in this paper, we would like to propose the common process management based on the consideration of TQM matrix and view point of three dimensional integrated value models.Objective: The use of Patient Reported Outcomes (PROs) to screen for mental health has traditionally been implemented through a manual process of paper and pencil with little standardization throughout a Healthcare System. Patients are typically screened when the provider identifies them as having a need; many patients are not screened. As we move forward into an era of health technology we can leverage this capability to provide a standardized health outcomes assessment using PROs for mental health screening to all patients. We investigate the rate of identification of depressive symptoms in patients before and after deployment of a standard technology-based screening.Introduction: The rising trend of non-communicable diseases (NCDs) has led to a “dual burden” in low and middle-income (LAMI) countries like India which are still battling with high prevalence of communicable diseases. Insufficient physical activity is one of the behavioural risk factors responsible for development of NCDs. Mobile phone technology is viewed as a promising communication channel that offers the potential to promote behaviour change among vulnerable populations. An advantage of mHealth interventions is that they can be delivered to many individuals in a cost-effective manner and in a shorter time.

Single-reviewer electronic phenotyping validation in operational settings

OBJECTIVE Develop evidence-based recommendations for single-reviewer validation of electronic phenotyping results in operational settings. MATERIAL AND METHODS We conducted a randomized controlled study to evaluate whether electronic phenotyping results should be used to support manual chart review during single-reviewer electronic phenotyping validation (N=3104). We evaluated the accuracy, duration and cost of manual chart review with and without the availability of electronic phenotyping results, including relevant patient-specific details. The cost of identification of an erroneous electronic phenotyping result was calculated based on the personnel time required for the initial chart review and subsequent adjudication of discrepancies between manual chart review results and electronic phenotype determinations. RESULTS Providing electronic phenotyping results (vs not providing those results) was associated with improved overall accuracy of manual chart review (98.90% vs 92.46%, p<0.001), decreased review duration per test case (62.43 vs 76.78s, p<0.001), and insignificantly reduced estimated marginal costs of identification of an erroneous electronic phenotyping result (

Where Is the "Top of License" for the Psychiatrist?

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