Workplace trauma and professional quality of Life in clinical and forensic psychiatry:the CRITIC study

Background: Frontline staff in psychiatry need to perform at a very high professional level in order to ensure patient and community safety. At the same time they are exposed to high levels of stress and workplace trauma. This may have severe consequences for their professional quality of life. In addition, health care workers in general have higher incidence levels of childhood adversity than the general population. The CRITIC (CRITical Incidents and aggression in Caregivers) Study aims to improve increased understanding of the interaction between personal life history (childhood adversity and benevolence), individual capabilities, exposure to trauma and violence at work and Professional Quality of Life (ProQOL).Method: The Critic Study is a cross-sectional survey of these aspects in frontline, treatment and administrative staff in clinical and forensic psychiatry. We aim to include 360 participants. Participants will be asked to complete questionnaires on childhood adversity and childhood benevolence (assessing personal life history), professional quality of life, current trauma and violence exposure, current mental health (depression, anxiety and stress), coping, social support, work engagement and resilience. In this study we will examine the moderating role of adverse and benevolent childhood experiences in the association between workplace trauma exposure and professional quality of life. Finally, a theoretical model on the relationships between trauma, stress and coping in the context of professional functioning will be tested using structural equation modelling.Discussion: The CRITIC study examines which factors influence the complex relationship between childhood adversity and benevolence, and ProQOL in healthcare workers. It also aims to provide insight into the complex relationship between personal life history, individual characteristics, exposure to trauma and violence at work and ProQOL. The results can be used for designing interventions to increase resilience to trauma and to improve professional quality of life among health care professionals.Trial registration: The CRITIC study has been approved by the Medical Ethical Committee of the Erasmus Medical Centre, under trial registration number NL73417.078.2

Preoperative predictors of death and sustained ventricular tachycardia after pulmonary valve replacement in patients with repaired tetralogy of fallot enrolled in the INDICATOR Cohort

Background -Risk factors for adverse clinical outcomes have been identified in patients with repaired tetralogy of Fallot (rTOF) before pulmonary valve replacement (PVR). However, pre-PVR predictors for post-PVR sustained ventricular tachycardia (VT) and death have not been identified. Methods -Patients with rTOF enrolled in the INDICATOR cohort-a 4-center international cohort study- who had a comprehensive preoperative evaluation and subsequently underwent PVR were included. Pre-procedural clinical, electrocardiogram, cardiovascular magnetic resonance (CMR), and postoperative outcome data were analyzed. Cox proportional hazards multivariable regression analysis was used to evaluate factors associated with time from pre-PVR CMR until the primary outcome-death, aborted sudden cardiac death, or sustained VT. Results -Of the 452 eligible patients (median age at PVR 25.8 years), 36 (8%) reached the primary outcome (27 deaths, 2 resuscitated death, and 7 sustained VT) at a median time after PVR of 6.5 years. Cox proportional hazards regression identified pre-PVR right ventricular (RV) ejection fraction < 40% (hazard ratio [HR] 2.39; 95% confidence interval [CI] 1.18 to 4.85; P = 0.02), RV mass-to-volume ratio ≥ 0.45 g/mL (HR 4.08; 95%, CI 1.57 to 10.6; P = 0.004), and age at PVR ≥ 28 years (HR 3.10; 95% CI 1.42 to 6.78; P = 0.005) as outcome predictors. In a subgroup analysis of 230 patients with Doppler data, predicted RV systolic pressure ≥40 mm Hg was associated with the primary outcome (HR 3.42; 95% CI 1.09 to 10.7; P = 0.04). Preoperative predictors of a composite secondary outcome-postoperative arrhythmias and heart failure-included older age at PVR, pre-PVR atrial tachyarrhythmias, and a higher left ventricular end-systolic volume index. Conclusions -In this observational investigation of patients with rTOF, an older age at PVR and pre-PVR RV hypertrophy and dysfunction were predictive of shorter time to postoperative death and sustained VT. These findings may inform the timing of PVR if confirmed by prospective clinical trials

The ambiguous role of NKX2-5 mutations in thyroid dysgenesis.

NKX2-5 is a homeodomain-containing transcription factor implied in both heart and thyroid development. Numerous mutations in NKX2-5 have been reported in individuals with congenital heart disease (CHD), but recently a select few have been associated with thyroid dysgenesis, among which the p.A119S variation. We sequenced NKX2-5 in 303 sporadic CHD patients and 38 families with at least two individuals with CHD. The p.A119S variation was identified in two unrelated patients: one was found in the proband of a family with four affected individuals with CHD and the other in a sporadic CHD patient. Clinical evaluation of heart and thyroid showed that the mutation did not segregate with CHD in the familial case, nor did any of the seven mutation carriers have thyroid abnormalities. We tested the functional consequences of the p.A119S variation in a cellular context by performing transactivation assays with promoters relevant for both heart and thyroid development in rat heart derived H10 cells and HELA cells. There was no difference between wildtype NKX2-5 and p.A119S NKX2-5 in activation of the investigated promoters in both cell lines. Additionally, we reviewed the current literature on the topic, showing that there is no clear evidence for a major pathogenic role of NKX2-5 mutations in thyroid dysgenesis. In conclusion, our study demonstrates that p.A119S does not cause CHD or TD and that it is a rare variation that behaves equal to wildtype NKX2-5. Furthermore, given the wealth of published evidence, we suggest that NKX2-5 mutations do not play a major pathogenic role in thyroid dysgenesis, and that genetic testing of NKX2-5 in TD is not warranted

Anti-nausea effects and pharmacokinetics of ondansetron, maropitant and metoclopramide in a low-dose cisplatin model of nausea and vomiting in the dog: a blinded crossover study

Nausea is a subjective sensation which is difficult to measure in non-verbal species. The aims of this study were to determine the efficacy of three classes of antiemetic drugs in a novel low dose cisplatin model of nausea and vomiting and measure change in potential nausea biomarkers arginine vasopressin (AVP) and cortisol. A four period cross-over blinded study was conducted in eight healthy beagle dogs of both genders. Dogs were administered 18 mg/m2 cisplatin intravenously, followed 45 min later by a 15 min infusion of either placebo (saline) or antiemetic treatment with ondansetron (0.5 mg/kg; 5-HT3 antagonist), maropitant (1 mg/kg; NK1 antagonist) or metoclopramide (0.5 mg/kg; D2 antagonist). The number of vomits and nausea associated behaviours, scored on a visual analogue scale, were recorded every 15 min for 8 h following cisplatin administration. Plasma samples were collected to measure AVP, cortisol and antiemetic drug concentrations

6-thioguanine treatment in inflammatory bowel disease: A critical appraisal by a European 6-TG working party

Recently, the suggestion to use 6-thioguanine (6-TG) as an alternative thiopurine in patients with inflammatory bowel disease (IBD) has been discarded due to reports about possible (hepato) toxicity. During meetings arranged in Vienna and Prague in 2004, European experts applying 6-TG further on in IBD patients presented data on safety and efficacy of 6-TG. After thorough evaluation of its risk-benefit ratio, the group consented that 6-TG may still be considered as a rescue drug in stringently defined indications in IBD, albeit restricted to a clinical research setting. As a potential indication for administering 6-TG, we delineated the requirement for maintenance therapy as well as intolerance and/or resistance to aminosalicylates, azathioprine, 6-mercaptopurine, methotrexate and infliximab. Furthermore, indications are preferred in which surgery is thought to be inappropriate. The standard 6-TG dosage should not exceed 25 mg daily. Routine laboratory controls are mandatory in short intervals. Liver biopsies should be performed after 6-12 months, three years and then three-yearly accompanied by gastroduodenoscopy, to monitor for potential hepatotoxicity, including nodular regenerative hyperplasia (NRH) and veno-occlusive disease (VOD). Treatment with 6-TG must be discontinued in case of overt or histologically proven hepatotoxicity. Copyright (c) 2006 S. Karger AG, Basel

Traditional birth attendants lack basic information on HIV and safe delivery practices in rural Mysore, India

<p>Abstract</p> <p>Background</p> <p>There is little research on HIV awareness and practices of traditional birth attendants (TBA) in India. This study investigated knowledge and attitudes among rural TBA in Karnataka as part of a project examining how traditional birth attendants could be integrated into prevention-of-mother-to-child transmission of HIV (PMTCT) programs in India.</p> <p>Methods</p> <p>A cross-sectional survey was conducted between March 2008 and January 2009 among TBA in 144 villages in Mysore <it>Taluk</it>, Karnataka. Following informed consent, TBA underwent an interviewer-administered questionnaire in the local language of <it>Kannada </it>on practices and knowledge around birthing and HIV/PMTCT.</p> <p>Results</p> <p>Of the 417 TBA surveyed, the median age was 52 years and 96% were Hindus. A majority (324, 77.7%) had no formal schooling, 88 (21.1%) had up to 7 years and 5 (1%) had more than 7 yrs of education. Only 51 of the 417 TBA (12%) reported hearing about HIV/AIDS. Of those who had heard about HIV/AIDS, only 36 (72%) correctly reported that the virus could be spread from mother to child; 37 (74%) identified unprotected sex as a mode of transmission; and 26 (51%) correctly said healthy looking people could spread HIV. Just 22 (44%) knew that infected mothers could lower the risk of transmitting the virus to their infants. An overwhelming majority of TBA (401, 96.2%) did not provide antenatal care to their clients. Over half (254, 61%) said they would refer the woman to a hospital if she bled before delivery, and only 53 (13%) felt referral was necessary if excessive bleeding occurred after birth.</p> <p>Conclusions</p> <p>Traditional birth attendants will continue to play an important role in maternal child health in India for the foreseeable future. This study demonstrates that a majority of TBA lack basic information about HIV/AIDS and safe delivery practices. Given the ongoing shortage of skilled birth attendance in rural areas, more studies are needed to examine whether TBA should be trained and integrated into PMTCT and maternal child health programs in India.</p

Expression Levels of a Kinesin-13 Microtubule Depolymerase Modulates the Effectiveness of Anti-Microtubule Agents

Chemotherapeutic drugs often target the microtubule cytoskeleton as a means to disrupt cancer cell mitosis and proliferation. Anti-microtubule drugs inhibit microtubule dynamics, thereby triggering apoptosis when dividing cells activate the mitotic checkpoint. Microtubule dynamics are regulated by microtubule-associated proteins (MAPs); however, we lack a comprehensive understanding about how anti-microtubule agents functionally interact with MAPs. In this report, we test the hypothesis that the cellular levels of microtubule depolymerases, in this case kinesin-13 s, modulate the effectiveness of the microtubule disrupting drug colchicine.We used a combination of RNA interference (RNAi), high-throughput microscopy, and time-lapse video microscopy in Drosophila S2 cells to identify a specific MAP, kinesin-like protein 10A (KLP10A), that contributes to the efficacy of the anti-microtubule drug colchicine. KLP10A is an essential microtubule depolymerase throughout the cell cycle. We find that depletion of KLP10A in S2 cells confers resistance to colchicine-induced microtubule depolymerization to a much greater extent than depletion of several other destabilizing MAPs. Using image-based assays, we determined that control cells retained 58% (+/-2%SEM) of microtubule polymer when after treatment with 2 microM colchicine for 1 hour, while cells depleted of KLP10A by RNAi retained 74% (+/-1%SEM). Likewise, overexpression of KLP10A-GFP results in increased susceptibility to microtubule depolymerization by colchicine.Our results demonstrate that the efficacy of microtubule destabilization by a pharmacological agent is dependent upon the cellular expression of a microtubule depolymerase. These findings suggest that expression levels of Kif2A, the human kinesin-13 family member, may be an attractive biomarker to assess the effectiveness of anti-microtubule chemotherapies. Knowledge of how MAP expression levels affect the action of anti-microtubule drugs may prove useful for evaluating possible modes of cancer treatment