Knowledge and competency standards for specialized cognitive behavior therapy for adult obsessive-compulsive disorder.

Obsessive-Compulsive Disorder (OCD) is a leading cause of disability world-wide (World Health Organization, 2008). Treatment of OCD is a specialized field whose aim is recovery from illness for as many patients as possible. The evidence-based psychotherapeutic treatment for OCD is specialized cognitive behavior therapy (CBT, NICE, 2005, Koran and Simpson, 2013). However, these treatments are not accessible to many sufferers around the world. Currently available guidelines for care are deemed to be essential but insufficient because of highly variable clinician knowledge and competencies specific to OCD. The phase two mandate of the 14 nation International OCD Accreditation Task Force (ATF) created by the Canadian Institute for Obsessive Compulsive Disorders is development of knowledge and competency standards for specialized treatments for OCD through the lifespan deemed by experts to be foundational to transformative change in this field. This paper presents knowledge and competency standards for specialized CBT for adult OCD developed to inform, advance, and offer a model for clinical practice and training for OCD. During upcoming ATF phases three and four criteria and processes for training in specialized treatments for OCD through the lifespan for certification (individuals) and accreditation (sites) will be developed based on the ATF standards.

Operative tactics in floor of mouth and tongue cancer resection - the importance of imaging and planning.

Complete tumour resection (R0 margin) is an axiom of surgical oncology. Oral cancer ablation is challenging, due to anatomical, functional, and aesthetic considerations. R0 margin is strongly linked to better survival outcomes with great variation in the R0 % across units. This is commonly attributed to disease biology. Without disputing the importance of biological characteristics, we contend that image-based anatomical surgical planning has an important role to play in achieving complete resection. Here, we present our approach utilising cross-sectional imaging, anatomical characteristics and spatial awareness in planning resections for floor of mouth (FOM) and oral tongue cancers. We highlight the challenge of controlling the deep tumour margin lingual to mandible due to anterior vector constraints and emphasise the importance of resecting the genial muscles in a planned fashion and that any rim resection should be obliquely sagittal. In resecting lateral FOM tumours, assessing extension to the parapharyngeal fat is crucial; and mandibular rim resection at a sagittal plane below the mylohyoid line is often required. Assessing the proximity of the contralateral neurovascular pedicle, pre-epiglottic space and hyoid bone are crucial parameters to determine the extent of tongue tumour resection. Our cohort included 173 patients with FOM SCC and 299 patients with tongue SCC. Six patients (3.5%) from the FOM group and eight patients (3%) from the tongue group had involved (R1) margins following surgery. This was associated with local relapse (p<0.05). In conclusion, we demonstrate that image-based planning can aid achieving R0 resections and reduce disease relapse.

Intravenous omega-3 fatty acids are associated with better clinical outcome and less inflammation in patients with predicted severe acute pancreatitis: A randomised double blind controlled trial.

BACKGROUND AND AIMS: Omega-3 fatty acids (FA) can ameliorate the hyper-inflammatory response that occurs in conditions such as severe acute pancreatitis (SAP) and this may improve clinical outcome. We tested the hypothesis that parenteral omega-3 FA from a lipid emulsion that includes fish oil could be beneficial in patients with predicted SAP by reducing C-reactive protein (CRP) concentration (primary outcome), and modulating the inflammatory response and improving clinical outcome (secondary outcomes). METHODS: In a phase II randomized double-blind single-centre controlled trial, patients with predicted SAP were randomised to receive a daily infusion of fish oil containing lipid emulsion (Lipidem® 20%, BBraun) for 7 days (n = 23) or a daily infusion of a lipid emulsion without fish oil (Lipofundin® MCT 20%, BBraun) (n = 22). RESULTS: On admission, both groups had comparable pancreatitis predicted severity and APACHE II scores. Administration of fish oil resulted in lower total blood leukocyte number (P = 0.04), CRP (P = 0.013), interleukin-8 (P = 0.05) and intercellular adhesion molecule 1 (P = 0.01) concentrations, multiple organ dysfunction score, sequential organ failure assessment score (P = 0.004), early warning score (P = 0.01), and systemic inflammatory response syndrome (P = 0.03) compared to the control group. The fish oil group had fewer new organ failures (P = 0.07), lower critical care admission rate (P = 0.06), shorter critical care stay (P = 0.03) and shorter total hospital stay (P = 0.04). CONCLUSIONS: It is concluded that intravenous administration of a fish oil containing lipid emulsion, a source of omega-3 FA, improves clinical outcomes in patients with predicted SAP, benefits that may be linked to reduced inflammation. CLINICALTRIALS. GOV NUMBER: NCT01745861. EU CLINICAL TRIALS REGISTER: EudraCT (2010-018660-16).

A case of recurrent hepatic haemangioendothelioma.

Hepatic haemangioendothelioma is a rare (1:1,000,000) mesenchymal tumour of the liver of vascular origin. Metastatic malignancies, other primary liver tumours and cholangiocarcinomas all have significantly worse prognoses and may mimic hepatic haemangioendothelioma. Hence, careful pathological assessment with appropriate tumour markers and immunohistochemistry are essential. We present a rare case of recurrence of hepatic haemangioendothelioma after 10 years post-hemihepatectomy. Surgical approaches include liver resection, liver transplantation and ablative techniques with chemotherapy and radiotherapy reserved for patients where a surgical approach is not possible. Hepatic haemangioendothelioma has an unpredictable course that is generally indolent and it is associated with a significantly better long-term survival. Consequently, it is important that these tumours are recognised and the approach to the diagnosis should be methodical. Owing to the protracted course of the disease, a prolonged duration of surveillance and an aggressive approach towards disease recurrence are essential for long-term survival.

Imaging of cerebral venous thrombosis.

The incidence of cerebral venous thrombosis (CVT) is increasing due to the widespread use of computed tomography (CT) and magnetic resonance imaging (MRI) for investigating patients with acute headaches and new onset of seizures. Alternatively referred to as cerebral venous sinus thrombosis (CVST) or dural venous sinus thrombosis (DVST), the terms encompass a broad spectrum of neurological pathologies. These include dural venous sinus thrombosis, cortical vein thrombosis, cavernous sinus thrombosis, venous infarction/haemorrhage, and the rare sequelae of intracranial hypertension or dural arteriovenous fistula. Timely and accurate diagnosis is critical; most patients are young adults and up to 15% will die in the acute phase of the condition. Imaging diagnosis using unenhanced CT or CT venography (CTV) can be readily achieved by the general radiologist. MRI or MRI venography (MRV) are powerful techniques, provided the radiologist is aware of critical diagnostic pitfalls. In selected cases, cerebral digital subtraction angiography (DSA) can facilitate both diagnosis and anticoagulant/transcatheter thrombolytic therapy improving clinical outcome. This article will outline the condition, highlighting cerebral venous anatomy, diagnostic techniques, and pitfalls pertinent to all practising radiologists.

Over view of major traumatic injury in Australia--Implications for trauma system design.

BACKGROUND: Trauma registries are known to drive improvements and optimise trauma systems worldwide. This is the first reported comparison of the epidemiology and outcomes at major centres across Australia. METHODS: The Australian Trauma Registry was a collaboration of 26 major trauma centres across Australia at the time of this study and currently collects information on patients admitted to these centres who die after injury and/or sustain major trauma (Injury Severity Score (ISS) > 12). Data from 1 July 2016 to 30 June 2017 were analysed. Primary endpoints were risk adjusted length of stay and mortality (adjusted for age, cause of injury, arrival Glasgow coma scale (GCS), shock-index grouped in quartiles and ISS). RESULTS: There were 8423 patients from 24 centres included. The median age (IQR) was 48 (28-68) years. Median (IQR) ISS was 17 (14-25). There was a predominance of males (72%) apart from the extremes of age. Transport-related cases accounted for 45% of major trauma, followed by falls (35.1%). Patients took 1.42 (1.03-2.12) h to reach hospital and spent 7.10 (3.64-15.00) days in hospital. Risk adjusted length of stay and mortality did not differ significantly across sites. Primary endpoints across sites were also similar in paediatric and older adult (>65) age groups. CONCLUSION: Australia has the capability to identify national injury trends to target prevention and reduce the burden of injury. Quality of care following injury can now be benchmarked across Australia and with the planned enhancements to data collection and reporting, this will enable improved management of trauma victims.

A tutorial on model informed approaches to cardiovascular safety with focus on cardiac repolarisation.

Drugs can affect the cardiovascular (CV) system either as an intended treatment or as an unwanted side effect. In both cases, drug-induced cardiotoxicities such as arrhythmia and unfavourable hemodynamic effects can occur, and be described using mathematical models; such a model informed approach can provide valuable information during drug development and can aid decision-making. However, in order to develop informative models, it is vital to understand CV physiology. The aims of this tutorial are to present (1) key background biological and medical aspects of the CV system, (2) CV electrophysiology, (3) CV safety concepts, (4) practical aspects of development of CV models and (5) regulatory expectations with a focus on using model informed and quantitative approaches to support nonclinical and clinical drug development. In addition, we share several case studies to provide practical information on project strategy (planning, key questions, assumptions setting, and experimental design) and mathematical models development that support decision-making during drug discovery and development.

Unmasking leading to a healthcare worker Mycobacterium tuberculosis transmission.

BACKGROUND: Mycobacterium tuberculosis is a major health burden worldwide. The disease may present as an individual case, community outbreak, or more rarely as a nosocomial outbreak. Even in countries with a low prevalence such as the UK, tuberculosis (TB) presents a risk to healthcare workers (HCWs). AIM: To report an outbreak which manifested 12 months after a patient with pulmonary tuberculosis was admitted to Queen Elizabeth Hospital Birmingham. METHODS: We present the epidemiological and outbreak investigations; the role of whole genome sequencing (WGS) in identifying the outbreak and control measures to prevent further outbreaks. FINDINGS: Subsequent to a diagnosis of open TB in a patient, transmission was confirmed in one HCW who had active TB; HCWs with latent TB infection (LTBI) were also identified among seven HCW contacts of the index patient. Of note, all the LBTI patients had other risk factors for TB. Routine use of WGS identified the outbreak link between the index patient and the HCW with active TB disease, and informed our investigations. CONCLUSION: Exposure most likely occurred during an aerosol-generating procedure (AGP) which was done in accordance with national guidance at that time without using respiratory protection. Enhanced control measures were implemented following the outbreak.

What are the position and power of supermarkets in the Australian food system, and the implications for public health? A systematic scoping review.

Supermarkets have been described as having unprecedented and disproportionate power in the food system. This scoping review synthesized the literature that describes the position and power of supermarkets in the Australian food system, and the implications for public health. A systematic search of peer-reviewed and grey literature identified 68 documents that described supermarket power. Implications for public health were also recorded. Data revealed that supermarkets hold a powerful position in the Australian food system, acting as the primary gatekeepers. Supermarkets have obtained instrumental, structural and discursive power from many sources that overlap and reinforce each other. Few positive public health impacts of supermarket power were identified, providing many opportunities for improvement in the domains of food governance, the food system and public health nutrition. There is very little public health research examining the impact of supermarket power in Australia. More research is needed, and examination of supermarket own brands is of particular importance owing to their pivotal role as a source of power and their potential to improve public health outcomes, such as obesity.

Mental Health Screening in a Bosnian Refugee Population Using the Primary Care Behavioral Health Screener-Bosnian Translation.

This study assesses the utility of the primary care behavioral health screener (PCBHS), which the authors have adapted and translated for adult Bosnian refugees (PCBHS-B) living in the Midwest area of the United States, who utilized primary care services within a private physician clinic and a federally qualified health center. The study was conducted from March 2012-April 2013 and included 131 Bosnian respondents, 24% of whom were receiving behavioral health services. Similar to a non-Bosnian U.S. sample, one-third (34.4%) of the respondents experienced clinically significant symptoms. Results suggest that the PCBHS-B can be a useful and acceptable instrument for identifying behavioral health problems in Bosnian primary care patients.

Patient-reported outcome measure for neuromyelitis optica: pretesting of preliminary instrument and protocol for further development in accordance with international guidelines.

OBJECTIVE: This study outlines the development of a patient-reported outcome measure (PROM), an instrument to obtain self-reported health status for neuromyeltis optica (NMO), a disabling neurological condition. DESIGN: Development was conducted in accordance with international guidance for PROMs including systematic review of existing literature, item generation guided by qualitative interviews, health-related quality of life conceptual framework and clinical expert panel and cognitive interviews with NMO patients. SETTING: Participants were identified through a national NMO clinic in a tertiary NHS neurosciences service. PARTICIPANTS: 15 individuals with NMO participated in cognitive interviews requiring review and ranking of proposed PROM items and qualitative feedback on content, layout and response options. RESULTS: Participants endorsed the draft instrument as reflecting their experience of the condition and as being easy to understand. Rating and ranking of item relevance and importance reduced the draft instrument from 106 to 48 items. Participant feedback on overlapping items eliminated a further 2 items and resulted in a preliminary instrument of 46 items. As a direct result of participant feedback ordering of the 10 domains was revised, a 4 option Likert scale was employed and a 4-week recall period for impact of symptoms was selected. CONCLUSIONS: A 46-item instrument developed in accordance with international PROM development guidelines through literature review, developed by subject matter experts and refined through pretesting examining content validity provides a preliminary measure for assessing patient-report of health status in NMO. Further evaluation is proposed including sensitivity to clinical change, and international contributions to evaluating the measure are encouraged.

Comparison of caloric reactivity between migraineurs and non-migraineurs.

OBJECTIVE: To demonstrate that the elevated prevalence of migraine in patients with vertigo disorders is due to enhanced sensitivity to dizziness, which could cause migraineurs to seek more, or earlier, medical care for vertigo disorders, confounding the ability to show causation. METHODS: This case-control study investigated whether migraineurs perceive dizziness more intensely than non-migraineurs by comparing caloric responses in migraineurs, non-migraineurs and possible migraineurs. The summed caloric responses in the best responding ear were reviewed. RESULTS: The migraine group had higher caloric response values, with a mean of 37.97 degrees per second, which was statistically significant when compared to the values for the possible migraine group (30.74 degrees per second (p < 0.05)) and the non-migraine group (30.70 degrees per second (p < 0.001)). CONCLUSION: The findings suggest that migraineurs experience vestibular stimuli more intensely compared to non-migraineurs, which might explain the association of migraine with vestibular disorders in general.

Elicitation of health state utilities associated with varying severities of flares in Systemic Lupus Erythematosus.

BACKGROUND: Systemic Lupus Erythematosus (SLE) is characterised by fluctuating periods of minimal disease activity and 'flare'. Flare is an important outcome variable impacting the disease burden associated with SLE. The objective of this study was to obtain population-based utility values for varying severities of flare to measure the impact on health-related quality of life (HRQoL) in Australia, Canada, France, Japan, Spain and the UK. METHODS: Six health states (HS) for varying severities of flare were developed based on literature, patient blogs, and interviews with patients (n = 12), rheumatologists (n = 7) and nurses (n = 2). HS were validated by independent clinical experts (n = 6) and pilot interviews (n = 10, UK). HS were evaluated using the time-trade-off (TTO) method during face-to-face interviews with a minimum representative sample (n = 100) of the general population, per-country. Visual Analog Scale (VAS) scores were obtained to validate TTO scores. TTO scores were converted into utility values. RESULTS: The highest mean TTO utility scores were observed for the anchor HS (minimal disease activity) across all countries; means ranged from 0.66 in Japan to 0.82 in UK. All flare HS were associated with a disutility compared with the anchor HS (p < 0.001), means ranged across countries: mild flare HS: 0.55-0.71, moderate flare HS: 0.38-0.53, severe renal flare HS: 0.33-0.45, severe central nervous system (CNS) flare HS: 0.30-0.45 and severe generalised flare HS: 0.19-0.33. Mean VAS scores followed the same trend. CONCLUSIONS: These results show increasing severity of flare has a detrimental impact on HRQoL. The severe generalised flare HS received the lowest mean utility score suggesting that the perceived day-to-day impact of a severe generalised flare was greater than a severe CNS or severe renal flare. This is, to the best of our knowledge, the first utility study to assess varying severities of flare in SLE across six different countries.

Pharmacological and electrophysiological characterization of AZSMO-23, an activator of the hERG K(+) channel.

BACKGROUND AND PURPOSE: We aimed to characterize the pharmacology and electrophysiology of N-[3-(1H-benzimidazol-2-yl)-4-chloro-phenyl]pyridine-3-carboxamide (AZSMO-23), an activator of the human ether-a-go-go-related gene (hERG)-encoded K(+) channel (Kv 11.1). EXPERIMENTAL APPROACH: Automated electrophysiology was used to study the pharmacology of AZSMO-23 on wild-type (WT), Y652A, F656T or G628C/S631C hERG, and on other cardiac ion channels. Its mechanism of action was characterized with conventional electrophysiology. KEY RESULTS: AZSMO-23 activated WT hERG pre-pulse and tail current with EC50 values of 28.6 and 11.2 µM respectively. At 100 µM, pre-pulse current at +40 mV was increased by 952 ± 41% and tail current at -30 mV by 238 ± 13% compared with vehicle values. The primary mechanism for this effect was a 74.5 mV depolarizing shift in the voltage dependence of inactivation, without any shift in the voltage dependence of activation. Structure-activity relationships for this effect were remarkably subtle, with close analogues of AZSMO-23 acting as hERG inhibitors. AZSMO-23 blocked the mutant channel, hERG Y652A, but against another mutant channel, hERG F656T, its activator activity was enhanced. It inhibited activity of the G628C/S631C non-inactivating hERG mutant channel. AZSMO-23 was not hERG selective, as it blocked hKv 4.3-hKChIP2.2, hCav 3.2 and hKv 1.5 and activated hCav 1.2/ß2/α2δ channels. CONCLUSION AND IMPLICATIONS: The activity of AZSMO-23 and those of its close analogues suggest these compounds may be of value to elucidate the mechanism of type 2 hERG activators to better understand the pharmacology of this area from both a safety perspective and in relation to treatment of congenital long QT syndrome.

Predicting changes in cardiac myocyte contractility during early drug discovery with in vitro assays.

Cardiovascular-related adverse drug effects are a major concern for the pharmaceutical industry. Activity of an investigational drug at the L-type calcium channel could manifest in a number of ways, including changes in cardiac contractility. The aim of this study was to define which of the two assay technologies - radioligand-binding or automated electrophysiology - was most predictive of contractility effects in an in vitro myocyte contractility assay. The activity of reference and proprietary compounds at the L-type calcium channel was measured by radioligand-binding assays, conventional patch-clamp, automated electrophysiology, and by measurement of contractility in canine isolated cardiac myocytes. Activity in the radioligand-binding assay at the L-type Ca channel phenylalkylamine binding site was most predictive of an inotropic effect in the canine cardiac myocyte assay. The sensitivity was 73%, specificity 83% and predictivity 78%. The radioligand-binding assay may be run at a single test concentration and potency estimated. The least predictive assay was automated electrophysiology which showed a significant bias when compared with other assay formats. Given the importance of the L-type calcium channel, not just in cardiac function, but also in other organ systems, a screening strategy emerges whereby single concentration ligand-binding can be performed early in the discovery process with sufficient predictivity, throughput and turnaround time to influence chemical design and address a significant safety-related liability, at relatively low cost.

Investigation of connexin 43 uncoupling and prolongation of the cardiac QRS complex in preclinical and marketed drugs.

BACKGROUND AND PURPOSE: Prolongation of the cardiac QRS complex is linked to increased mortality and may result from drug-induced inhibition of cardiac sodium channels (hNaV 1.5). There has been no systematic evaluation of preclinical and marketed drugs for their additional potential to cause QRS prolongation via gap junction uncoupling. EXPERIMENTAL APPROACH: Using the human cardiac gap junction connexin 43 (hCx43), a dye transfer 'parachute' assay to determine IC50 values for compound ranking was validated with compounds known to uncouple gap junctions. Uncoupling activity (and hNaV 1.5 inhibition by automated patch clamp) was determined in a set of marketed drugs and preclinical candidate drugs, each with information regarding propensity to prolong QRS. KEY RESULTS: The potency of known gap junction uncouplers to uncouple hCx43 was ranked (according to IC50 ) as phorbol ester>digoxin>meclofenamic acid>carbenoxolone>heptanol. Among the drugs associated with QRS prolongation, 29% were found to uncouple hCx43 (IC50 < 50 µM), whereas no uncoupling activity was observed in drugs not associated with QRS prolongation. In preclinical candidate drugs, hCx43 and hNaV 1.5 IC50 values were similar (within threefold). No consistent margin over preclinical Cmax (free) was apparent for QRS prolongation associated with Cx43 inhibition. However, instances were found of QRS prolonging compounds that uncoupled hCx43 with significantly less activity at hNaV 1.5. CONCLUSION AND IMPLICATIONS: These results demonstrate that off-target uncoupling activity is apparent in drug and drug-like molecules. Although the full ramifications of Cx inhibition remain to be established, screening for hCx43 off-target activity could reduce the likelihood of developing candidate drugs with a risk of causing QRS prolongation.

Transporting integrated primary care to the private sector: addressing the business challenges.

The primary care literature provides some useful information and several project examples for clinicians attempting to develop an integrated care practice, but prior discussion has been based largely on projects developed in government-funded or HMO systems. The current paper focuses on the business challenges of establishing an integrated care practice in a private, fee-for-service setting. Despite increasing commitment to the concept of the medical home, which embraces behavioral health care, physicians in the private sector remain cautious about proposed practice changes such as integrated care. There are additional obstacles that can impede successful implementation of integrated primary care in the private sector. The authors identify five major challenges and suggest potential strategies to address these challenges, drawing, in part, on their experience with a 4-year integrated primary care demonstration project.