Acute Mania in a Patient With Primary Adrenal Insufficiency Due to Autoimmune Adrenalitis: A Case Report.

We describe a rare case of acute mania in the setting of autoimmune adrenalitis. A 41-year-old male with no previous psychiatric diagnoses presented with impulsivity, grandiosity, delusions of telepathy, and hyperreligiosity following a previous hospitalization for an acute adrenal crisis and 2 subsequent days of low-dose corticosteroid treatment. Workups for encephalopathy and lupus cerebritis were negative, raising concern that this presentation might represent steroid-induced psychosis. However, discontinuation of corticosteroids for 5 days did not resolve the patient's manic episode, suggesting that his clinical presentation was more likely new onset of a primary mood disorder or a psychiatric manifestation of adrenal insufficiency itself. The decision was made to restart corticosteroid treatment for the patient's primary adrenal insufficiency (formerly known as Addison disease), coupled with administration of both risperidone and valproate for mania and psychosis. Over the following 2 weeks, the patient's manic symptoms resolved, and he was discharged home. His final diagnosis was acute mania secondary to autoimmune adrenalitis. Although acute mania in adrenal insufficiency is quite rare, clinicians should be aware of the range of psychiatric manifestations associated with Addison disease so that they can pursue the optimal course of both medical and psychiatric treatment for these patients.

Effectiveness and response differences of a multidisciplinary workplace health promotion program for healthcare workers.

Background: Workplace health promotion (WHP) in the healthcare industry is an important yet challenging issue to address, given the high workload, heterogeneity of work activities, and long work hours of healthcare workers (HCWs). This study aimed to investigate the effectiveness and response differences of a multidisciplinary WHP program conducted in HCWs. Methods: This retrospective cohort study included HCWs participating in a multidisciplinary WHP program in five healthcare facilities. The 20-week intervention included multiple easy-to-access 90-min exercise classes, one 15-min nutrition consultation, and behavioral education. Pre- and post-interventional anthropometrics, body composition, and physical fitness (PF) were compared with paired sample t-tests. Response differences across sex, age, weight status, and shiftwork status were analyzed with a generalized estimating equation. Results: A total of 302 HCWs were analyzed. The intervention effectively improved all anthropometric (body mass index, waist circumference, waist-hip ratio, and waist-to-height ratio), body composition (body fat percentage, muscle weight, visceral fat area), and PF (grip strength, high jump, sit-up, sit-and-reach, step test) parameters in all participants (all p < 0.05). Subgroup analyses revealed shift workers had a more significant mean reduction in body mass index than non-shift workers (adjusted p = 0.045). However, there was no significant response difference across sex, age, and weight subgroups. Conclusion: This study suggested that a multidisciplinary WHP program can improve anthropometric and PF profiles regardless of sex, age, and weight status for HCWs, and shifter workers might benefit more from the intervention.

A randomized controlled trial of cognitive remediation and long-acting injectable risperidone after a first episode of schizophrenia: improving cognition and work/school functioning.

BACKGROUND: Cognitive deficits at the first episode of schizophrenia are predictive of functional outcome. Interventions that improve cognitive functioning early in schizophrenia are critical if we hope to prevent or limit long-term disability in this disorder. METHODS: We completed a 12-month randomized controlled trial of cognitive remediation and of long-acting injectable (LAI) risperidone with 60 patients with a recent first episode of schizophrenia. Cognitive remediation involved programs focused on basic cognitive processes as well as more complex, life-like situations. Healthy behavior training of equal treatment time was the comparison group for cognitive remediation, while oral risperidone was the comparator for LAI risperidone in a 2 × 2 design. All patients were provided supported employment/education to encourage return to work or school. RESULTS: Both antipsychotic medication adherence and cognitive remediation contributed to cognitive improvement. Cognitive remediation was superior to healthy behavior training in the LAI medication condition but not the oral medication condition. Cognitive remediation was also superior when medication adherence and protocol completion were covaried. Both LAI antipsychotic medication and cognitive remediation led to significantly greater improvement in work/school functioning. Effect sizes were larger than in most prior studies of first-episode patients. In addition, cognitive improvement was significantly correlated with work/school functional improvement. CONCLUSIONS: These results indicate that consistent antipsychotic medication adherence and cognitive remediation can significantly improve core cognitive deficits in the initial period of schizophrenia. When combined with supported employment/education, cognitive remediation and LAI antipsychotic medication show separate significant impact on improving work/school functioning.

Depression.

Most psychiatric care is delivered in primary care settings, where depression is the most common presenting psychiatric symptom. Given the high prevalence of depression worldwide and the well-established consequences of untreated depression, the ability of primary care clinicians to effectively diagnose and treat it is critically important. This article offers up-to-date guidance for the diagnosis and treatment of major depressive disorder, including practical considerations for delivering optimal and efficient care for these patients.

Psychiatric Clinics: Computer-Based Teaching.

Learning is no longer constrained to the classroom or lecture hall. Today's students expect teaching to be available 24/7 and on whatever device they own and to be interactive and engaging. Educators need to become familiar with computer-based teaching tools and learn how to implement them or risk losing their audience. Use of these tools is not merely converting the medium, say from a VHS (video home system) tape to a YouTube stream, but incorporating the features of the educational tools to facilitate active learning. Social media has become a force in the educational arena, providing a foundational framework.

A Framework for Competencies for the Use of Mobile Technologies in Psychiatry and Medicine: Scoping Review.

BACKGROUND: To ensure quality care, clinicians need skills, knowledge, and attitudes related to technology that can be measured. OBJECTIVE: This paper sought out competencies for mobile technologies and/or an approach to define them. METHODS: A scoping review was conducted to answer the following research question, "What skills are needed for clinicians and trainees to provide quality care via mHealth, have they been published, and how can they be made measurable and reproducible to teach and assess them?" The review was conducted in accordance with the 6-stage scoping review process starting with a keyword search in PubMed/Medical Literature Analysis and Retrieval System Online, APA PsycNET, Cochrane, EMBASE, PsycINFO, Web of Science, and Scopus. The literature search focused on keywords in 4 concept areas: (1) competencies, (2) mobile technologies, (3) telemedicine mode, and (4) health. Moreover, 2 authors independently, in parallel, screened the search results for potentially relevant studies based on titles and abstracts. The authors reviewed the full-text articles for final inclusion based on inclusion/exclusion criteria. Inclusion criteria were keywords used from concept area 1 (competencies) and 2 (mobile technologies) and either 3 (telemedicine mode) or 4 (health). Exclusion criteria included, but were not limited to, keywords used from a concept area in isolation, discussion of skills abstractly, outline or listing of what clinicians need without detail, and listing immeasurable behaviors. RESULTS: From a total of 1232 results, the authors found 78 papers eligible for a full-text review and found 14 papers directly relevant to the 4 key concepts. Although few studies specifically discussed skills, the majority were clinical studies, and the literature included no lists of measurable behaviors or competency sets for mobile technology. Therefore, a framework for mobile technology competencies was built according to the review, expert consensus, and recommendations of the Institute of Medicine's Health Professions Education Summit and Accreditation Council of Graduate Medical Education framework. This framework borrows from existing competency framework domains in telepsychiatry and social media (patient care, medical knowledge, practice-based learning and improvement, systems-based practice, professionalism, and interpersonal skills and communication) and added domains of mHealth clinical decision support, device/technology assessment/selection, and information flow management across an electronic health record platform. mHealth Asynchronous components require additional traditional learning, teaching, supervisory and evaluation practices. Interactive curricula with case-, problem-, and system-based teaching may help faculty focus on decision making and shape skills and attitudes to complement clinical exposure. CONCLUSIONS: Research is needed on how to customize implementation and evaluation of mHealth competencies and to ensure skill development is linked to the quality of care. This will require the management of organizational change with technology and the creation of a positive electronic culture in a complex policy and regulatory environment.

A Guide for the 21st Century Psychiatrist to Managing Your Online Reputation, Your Privacy, and Professional Use of Social Media.

The Internet is a vast expanse of information; however, search engines have made finding the proverbial needle in a haystack a simple matter. Although insurance provider databases and referrals may dominate how patients find their doctor today, one's online reputation and reviews on physician ratings sites will increasingly play a role in how prospective patients find their next provider. Social media plays a dominant role as the medium where people place and find information, blurring the boundary of professional and personal use. Privacy online has become an endangered species, requiring active strategies to keep it from going extinct.

Mobile Health, Smartphone/Device, and Apps for Psychiatry and Medicine: Competencies, Training, and Faculty Development Issues.

Faculty and trainees need clinical skills, knowledge, and attitudes to ensure quality care using technology. Clinical faculty teach, supervise, and role model skills for trainees and interprofessional team members. Mobile health, smartphone/device, and app competencies may be situated within the graduate medical education milestone domains. This article outlines these competencies and aligns them with clinical care, teaching methods, and evaluation. These competencies have similarities and differences from in-person and telepsychiatric care and additional dimensions like clinical decision support, technology selection, and information flow management across an e-platform. Health systems must integrate in-person and technology-based care, while maintaining the therapeutic relationship.

A Hierarchical Framework for Evaluation and Informed Decision Making Regarding Smartphone Apps for Clinical Care.

With thousands of smartphone apps targeting mental health, it is difficult to ignore the rapidly expanding use of apps in the treatment of psychiatric disorders. Patients with psychiatric conditions are interested in mental health apps and have begun to use them. That does not mean that clinicians must support, endorse, or even adopt the use of apps, but they should be prepared to answer patients' questions about apps and facilitate shared decision making around app use. This column describes an evaluation framework designed by the American Psychiatric Association to guide informed decision making around the use of smartphone apps in clinical care.

Stem cell-derived exosomes: a novel vector for tissue repair and diabetic therapy.

Exosomes are extracellular vesicles (EVs) secreted from a majority of cell types. Exosomes play a role in healthy and pathogenic intercellular interactions via the transfer of proteins, lipids and RNA. The contents and effects of exosomes vary depending on the properties of the originating cell. Exosomes secreted from some cell types, including stem cells, carry biological factors implicated in the protection, regeneration and angiogenesis of damaged tissues. Due to these properties, exosomes have attracted attention as a novel vector for regenerative therapies. Exosomes as a therapeutic tool could have applications for the treatment of many disorders characterized by chronic tissue damage. Exosomes derived from stem cells could be applied to repair or prevent damage from the complications of diabetes mellitus. The immunomodulatory and reparative properties of stem cell-derived exosomes could protect or even restore an early-stage type 1 diabetic patient's original islets from autoimmune destruction. Exosomes could also possibly suppress graft rejection of pancreatic islet transplants. Therefore, it is our recommendation that the treatment of diabetes mellitus using exosome-based therapies be further explored. Development of novel therapies using exosomes is slowed by a limited understanding of their mechanisms. This hurdle must be overcome to pave the way for clinical trials and ultimately the adaptation of exosomes as a therapeutic vector.

Effects of bone marrow on the microenvironment of the human pancreatic islet: A Protein Profile Approach.

Stem cells are a new therapeutic modality that may support the viability and function of human organs and tissue. Our previous studies have revealed that human allogeneic bone marrow (BM) sustains pancreatic ß cell function and survival. This paper examines whether BM creates a microenvironment that supports human pancreatic islets in vitro by evaluating 107 proteins in culture media from BM, islet, and islet/bone marrow (IB) with mass spectrometry. Proteins were considered up- or down-regulated if p-values < 0.05 and fold change was greater than 2 fold I VS. IB. In addition, proteins identified that were uniquely found in islets co-cultured with bone marrow, but not in islets or bone marrow. A 95% protein probability was used as a threshold. Twenty three proteins were upregulated, and sixteen proteins were downregulated. The function of each protein is listed based on the protein database, which include structural proteins (9 upregulated, 4 downregulated); anti-protease and anti-endopeptidase enzymes (8 upregulated); cation binding proteins (6 up-regulated). Six proteins were uniquely identified in islet co-cultured with bone marrow. Three are anti-proteases or anti-endopeptidases, and 1 is a structural protein. These findings suggest that BM, by changing culture media proteins, may be one of mechanisms to maintain human islet function and survival.

EFFECTS OF GINSENG AND ITS FOUR PURIFED GINSENOSIDES (Rb2, Re, Rg1, Rd) ON HUMAN PANCREATIC ISLET ß CELL IN VITRO.

Ginseng has attracted interest because of its potential therapeutic role in diabetes therapy. No direct evidence has shown the effects of ginseng and its components, ginsenosides, on human islet ß cell. In this study, we evaluated ginseng extract and ginsenosides (Rb2, Re, Rg1, Rd) on human pancreatic ß cell function. The results provide direct evidence that ginseng extract promotes human pancreatic ß cell function. Ginsenoside Rb2 increased islet ß cell insulin release and promoted ß cell migration. Ginsenoside Re had some impact on cell migration, but had no effect on islet function by evaluating insulin release. The other ginsenosides had no effect on insulin release and islet migration. To date, this is the first study that examines the impact of ginsenosides on human pancreatic islets in vitro.

A framework for telepsychiatric training and e-health: Competency-based education, evaluation and implications.

Telepsychiatry (TP; video; synchronous) is effective, well received and a standard way to practice. Best practices in TP education, but not its desired outcomes, have been published. This paper proposes competencies for trainees and clinicians, with TP situated within the broader landscape of e-mental health (e-MH) care. TP competencies are organized using the US Accreditation Council of Graduate Medical Education framework, with input from the CanMEDS framework. Teaching and assessment methods are aligned with target competencies, learning contexts, and evaluation options. Case examples help to apply concepts to clinical and institutional contexts. Competencies can be identified, measured and evaluated. Novice or advanced beginner, competent/proficient, and expert levels were outlined. Andragogical (i.e. pedagogical) methods are used in clinical care, seminar, and other educational contexts. Cross-sectional and longitudinal evaluation using quantitative and qualitative measures promotes skills development via iterative feedback from patients, trainees, and faculty staff. TP and e-MH care significantly overlap, such that institutional leaders may use a common approach for change management and an e-platform to prioritize resources. TP training and assessment methods need to be implemented and evaluated. Institutional approaches to patient care, education, faculty development, and funding also need to be studied.

Anti-apoptotic Effects of Bone Marrow on Human Islets: A Preliminary Report.

Apoptosis is one of the major factors contributing to the failure of human islet transplantation. Contributors to islet apoptosis exist in both the pre-transplantation and post transplantation stages. Factors include the islet isolation process, deterioration in vitro prior to transplantation, and immune rejection post transplantation. Previous studies have demonstrated that co-cultured bone marrow cells with human islets not only significantly enhanced the longevity of human islets but also maintained function. We hypothesized that the protective effects of bone marrow cells on human islets are through mechanisms related to preventing apoptosis. This study observed the levels of inflammatory factors such as interleukin-1ß (IL-1ß), the release of extracellular ATP in vitro, and expression levels of P2X7 ATP receptor (P2X7R), all of which lead to the occurrence of apoptosis in human islets. When human islets were co-cultured with human bone marrow, there was a reduction in the rate of apoptosis correlated with the reduction in inflammatory factors, extra cellular ATP accumulation, and ATP receptor P2X7R expression versus human islets cultured alone. These results suggest that co-culturing bone marrow cells with human islets inhibits inflammation and reduces apoptosis, thus protecting islets from self-deterioration.

Long-Acting Injectable Risperidone for Relapse Prevention and Control of Breakthrough Symptoms After a Recent First Episode of Schizophrenia. A Randomized Clinical Trial.

IMPORTANCE: Long-acting, injectable, second-generation antipsychotic medication has tremendous potential to bring clinical stability to persons with schizophrenia. However, long-acting medications are rarely used following a first episode of schizophrenia. OBJECTIVE: To compare the clinical efficacy of the long-acting injectable formulation of risperidone with the oral formulation in the early course of schizophrenia. DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial performed at a university-based research clinic, between 2005 and 2012. Eighty-six patients with recent onset of schizophrenia were randomized to receive long-acting injectable risperidone or oral risperidone. Half of each group was simultaneously randomized to receive cognitive remediation to improve cognitive functioning or healthy-behaviors training to improve lifestyle habits and well-being. An intent-to-treat analysis was performed between October 4, 2012, and November 12, 2014. INTERVENTIONS: A 12-month trial comparing the long-acting injectable vs oral risperidone and cognitive remediation vs healthy-behaviors training. MAIN OUTCOMES AND MEASURES: Psychotic relapse and control of breakthrough psychotic symptoms. RESULTS: Of the 86 patients randomized, 3 refused treatment in the long-acting injectable risperidone group. The psychotic exacerbation and/or relapse rate was lower for the long-acting risperidone group compared with the oral group (5% vs 33%; χ21 = 11.1; P < .001; relative risk reduction, 84.7%). Long-acting injectable risperidone better controlled mean levels of hallucinations and delusions throughout follow-up (ß = -0.30; t68 = -2.6, P = .01). The cognitive remediation and healthy-behaviors training groups did not differ significantly regarding psychotic relapse, psychotic symptom control, or hospitalization rates, and there were no significant interactions between the 2 medications and the 2 psychosocial treatments. Discontinuations owing to inadequate clinical response were more common in the oral group than in the long-acting risperidone group (χ21 = 6.1; P = .01). Adherence to oral risperidone did not appear to differ before randomization but was better for the long-acting risperidone group compared with the oral group (t80 = 5.3; P < .001). Medication adherence was associated with prevention of exacerbation and/or relapse (χ21 =11.1; P = .003) and control of breakthrough psychotic symptoms (ß = 0.2; t79 = 2.1; P = .04). CONCLUSIONS AND RELEVANCE: The use of long-acting injectable risperidone after a first episode of schizophrenia has notable advantages for clinical outcomes. The key clinical advantages are apparently owing to the more consistent administration of the long-acting injectable. Such formulations should be offered earlier in the course of illness. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00333177.

Human Bone Marrow Subpopulations Sustain Human Islet Function and Viability In vitro.

AIMS: Allogeneic bone marrow (BM) has been shown to support human islet survival and function in long-term culture by initiating human islet vascularization and ß-cell regeneration. Various BM subpopulations may play different roles in human islet functions and survival. In this paper we investigated the effects of BM and its subpopulations, endothelial progenitor cells (E) and mesenchymal (M) cells on human islet's ß-cell function and regeneration. STUDY DESIGN: Isolation and identification of subpopulations from human bone marrow and culture with allogeneic human islet to investigate effects of different cell population on human islet function and regeneration. PLACE AND DURATION OF STUDY: Department of Medicine, Center for Stem Cell & Diabetes Research, RWMC, Providence, RI, USA, between 2010 - 2014. METHODOLOGY: Human islets were distributed from Integrated Islet Distribution Program (IIDP) and human bone marrow (BM) was harvested by Bone marrow transplantation center at Roger Williams Hospital. BM subpopulation was identified cell surface markers through Fluorescence-activated cell sorting, applied in flow cytometry (FACS), islet function was evaluated by human ELISA kit and ß cell regeneration was evaluated by three methods of Cre-Loxp cell tracing, ß cell sorting and RT-PCR for gene expression. RESULTS: Four different BM and seven different islet donates contributed human tissues. We observed islet ß-cell having self regeneration capability in short term culture (3∼5 days) using a Cre-Loxp cell tracing. BM and its subtype E, M have similar benefits on ß cell function during co-culture with human islet comparison to islet only. However, only whole BM enables to sustain the capability of islet ß-cell self regeneration resulting in increasing ß cell population while single E and M individual do not significantly affect on that. Mechanism approach to explore ß-cell self regeneration by evaluating transcription factor expressions, we found that BM significantly increases the activations of ß-cell regeneration relative transcription factors, the LIM homeodomain protein (Isl1), homologue to zebrafish somite MAF1 (MAFa), the NK-homeodomain factor 6.1 (NKX6.1), the paired box family factors 6 (PAX6), insulin promoter factor 1 (IPF1) and kinesin family member 4A (KIF4a). CONCLUSION: These results suggest that BM and its derived M and E cells enable to support human islet ß-cell function. However, only BM can sustain the capability of ß-cell self regeneration through initiating ß-cell transcriptional factors but not individual E and M cells suggesting pure E and M cells less supportive for islet long-term survival in vitro.

The Biochemical Cascades of the Human Pancreatic ß-Cells: The Role of MicroRNAs.

Diabetes mellitus is a disease that poses a burden to the health care system due to its prevalence and chronic nature. Understanding ß cell pathophysiology may lead to future therapeutic options for diabetes mellitus type 1 and 2. MicroRNAs (MiR) fine-tune ß cell biochemical cascades through specific protein targets. This review argues that miRs may play a critical role in human islet ß cell biology and are potential candidates for a new pharmacological strategy. We have reviewed and presented how miRs fine tune four biochemical cascades in islet ß cells: glucose stimulated insulin secretion, ß cell replication, apoptosis, and development. Only studies that examine human pancreatic islets either in vitro or in vivo are included. The unveiling role of miR pathways in regulating human islet ß cell biology could open the door for diagnostic and therapeutic methods for diabetes mellitus prevention and therapy.

The impact of second-generation antipsychotic adherence on positive and negative symptoms in recent-onset schizophrenia.

OBJECTIVE: The aim of the study was to explore the extent to which initial severity of positive or negative symptoms in patients with recent-onset schizophrenia is related to medication nonadherence during the first outpatient year. METHODS: The study involved 64 first-episode schizophrenia patients treated with the second-generation oral antipsychotic medication, risperidone, for 12 months. Symptoms were evaluated using the SANS and SAPS completed every 3 months. Pearson correlations between medication adherence and symptoms were examined over each 3-month interval during 12 months of follow-through treatment. Possible causality was inferred from cross-lagged panel analyses. RESULTS: As expected, higher levels of adherence with antipsychotic medication were generally associated with lower levels of concurrent reality distortion (mean of SAPS delusions and hallucinations). Greater adherence during the 3-month baseline interval was generally associated with lower levels of avolition-apathy as well as alogia throughout the first outpatient year. However, medication adherence was not significantly associated with decreases in avolition-apathy or alogia over time. Cross-lagged panel analyses based on correlation coefficients are consistent with a causal relationship between initial medication adherence and lower levels of alogia. A test of mediation confirmed that an indirect path through reality distortion mediated the relationship between medication nonadherence and alogia. CONCLUSIONS: The associations between greater medication adherence and lower levels of negative symptoms appeared to be accounted for by the relationship of both variables to positive psychotic symptoms. The findings suggest that the impact of second-generation antipsychotic medication on suppression of negative symptoms might be mediated via a reduction in positive symptoms.