How does cognitive behavior therapy for dissociative seizures work? A mediation analysis of the CODES trial.

BACKGROUND: We compared dissociative seizure specific cognitive behavior therapy (DS-CBT) plus standardized medical care (SMC) to SMC alone in a randomized controlled trial. DS-CBT resulted in better outcomes on several secondary trial outcome measures at the 12-month follow-up point. The purpose of this paper is to evaluate putative treatment mechanisms. METHODS: We carried out a secondary mediation analysis of the CODES trial. 368 participants were recruited from the National Health Service in secondary / tertiary care in England, Scotland, and Wales. Sixteen mediation hypotheses corresponding to combinations of important trial outcomes and putative mediators were assessed. Twelve-month trial outcomes considered were final-month seizure frequency, Work and Social Adjustment Scale (WSAS), and the SF-12v2, a quality-of-life measure providing physical (PCS) and mental component summary (MCS) scores. Mediators chosen for analysis at six months (broadly corresponding to completion of DS-CBT) included: (a) beliefs about emotions, (b) a measure of avoidance behavior, (c) anxiety and (d) depression. RESULTS: All putative mediator variables except beliefs about emotions were found to be improved by DS-CBT. We found evidence for DS-CBT effect mediation for the outcome variables dissociative seizures (DS), WSAS and SF-12v2 MCS scores by improvements in target variables avoidance behavior, anxiety, and depression. The only variable to mediate the DS-CBT effect on the SF-12v2 PCS score was avoidance behavior. CONCLUSIONS: Our findings largely confirmed the logic model underlying the development of CBT for patients with DS. Interventions could be additionally developed to specifically address beliefs about emotions to assess whether it improves outcomes.

Moderators of cognitive behavioural therapy treatment effects and predictors of outcome in the CODES randomised controlled trial for adults with dissociative seizures.

OBJECTIVE: We explored moderators of cognitive behavioural therapy (CBT) treatment effects and predictors of outcome at 12-month follow-up in the CODES Trial (N = 368) comparing CBT plus standardised medical care (SMC) vs SMC-alone for dissociative seizures (DS). METHODS: We undertook moderator analyses of baseline characteristics to determine who had benefited from being offered CBT 12 months post-randomisation. Outcomes included: monthly DS frequency, psychosocial functioning (Work and Social Adjustment Scale - WSAS), and health-related quality of life (Mental Component Summary (MCS) and Physical Component Summary (PCS) SF-12v2 scores). When moderating effects were absent, we tested whether baseline variables predicted change irrespective of treatment allocation. RESULTS: Moderator analyses revealed greater benefits (p < 0.05) of CBT on DS frequency for participants with more (≥22) symptoms (Modified PHQ-15) or ≥ 1 current (M.I.N.I.-confirmed) comorbid psychiatric diagnosis at baseline. The effect of CBT on PCS scores was moderated by gender; women did better than men in the CBT + SMC group. Predictors of improved outcome included: not receiving disability benefits, lower anxiety and/or depression scores (PCS, MCS, WSAS); shorter duration, younger age at DS onset, employment, fewer symptoms and higher educational qualification (PCS, WSAS); stronger belief in the diagnosis and in CBT as a "logical" treatment (MCS). Some variables that clinically might be expected to moderate/predict outcome (e.g., maladaptive personality traits, confidence in treatment) were not shown to be relevant. CONCLUSION: Patient complexity interacted with treatment. CBT was more likely to reduce DS frequency in those with greater comorbidity. Other patient characteristics predicted outcome regardless of the received intervention.

Are adults just big kids? Can the newer paediatric weight estimation systems be used in adults?

BACKGROUND: The weight of a patient is an important variable that impacts on their medical care. Although some drugs are prescribed on a so-called 'adult dose' basis, we know that adults come in all shapes and sizes - a 'one-dose-fits-all' approach is not necessarily appropriate. As a measured weight may not always be available, an alternative method of accurately estimating weight is required. OBJECTIVES: To assess and compare the accuracy of weight estimations in adults by patient self-estimation, the Mercy method, Buckley method, Broca index and PAWPER XL-MAC (paediatric advanced weight prediction in the emergency room eXtra length/eXtra large mid-arm circumference) method. METHODS: This was a prospective, cross-sectional study conducted at a tertiary academic hospital in a metropolitan area of Johannesburg, South Africa. Anthropometric variables of height, abdominal circumference, thigh circumference, mid-arm circumference and humeral length were measured. These variables were then applied to the various weight estimation methods and compared with the patient's actual weight. RESULTS: There were 188 adult patients included in the study. None of the methodologies evaluated in this study achieved the recommended >70% of weight estimations within 10% of the patient's actual weight (PW10). The Mercy method was the closest to achieving greater than the recommended 95% for weight estimation falling within 20% of the patient's actual weight (PW20). The PW20 for the Mercy method was 91.5%. The PAWPER XL-MAC and patient self-estimate methods achieved a PW20 of 85.1% and 86.1%, respectively. The Broca and Buckley methods performed poorly overall. CONCLUSIONS: None of the evaluated weight estimation methodologies was accurate enough for use in adult weight estimation. The Mercy and PAWPER XL-MAC methodologies both showed significant promise for use in adult weight estimation, but need further refinement. Although patient self-estimates were similarly accurate to those found in previous studies, they were not an accurate option; self-estimations would remain the first choice if the patient was able to provide such an estimation. The Broca index and Buckley method cannot be recommended owing to their poor performance.

Emergency Medicine Society of South Africa guidelines for the training and credentialing in emergency point-of-care ultrasound.

This is the second guideline from the Emergency Medicine Society of South Africa (EMSSA) on the use of emergency point-of-care ultrasound in South Africa. It supersedes and replaces the guidelines produced in 2009. This document contains information on the changes from the 2009 guidelines and details of the training and credentialing processes recommended by EMSSA. It also contains detailed information on the curricula of the Core Emergency Point-of-Care Ultrasound and Advanced Emergency Point-of-Care Ultrasound courses.

Analysis of the airway registry from an academic emergency department in South Africa.

BACKGROUND: Airway management is an essential skill for doctors working in the emergency department (ED). Safety and efficacy are crucial to its success. Analysis of an airway registry can provide feedback that can be used for quality improvement purposes. OBJECTIVES: To examine the first airway registry from an ED in South Africa (SA), a low- to middle-income country (LMIC), and compare the findings with international data. METHODS: A retrospective analysis of 13 months' data from the airway registry of an academic ED with an annual census of 60 000 patients. Data analysed included demographics, indications for intubation, intubator training level, type of intubation device, number of attempts, adverse events, pre-oxygenation methods, and drug and intravenous fluid use. RESULTS: A total of 321 intubations were included. The majority of the patients (71.6%) had non-traumatic indications for intubation. The overall first-pass intubation success (FPS) rate for doctors was 81.8%. Although this rate is lower than the mean rate suggested in an international meta-analysis (84.1%), it is within the 95% confidence interval (80.1 - 87.4%). Overall FPS rates showed no difference between video laryngoscopy (81.7%) compared with direct laryngoscopy (73.3%) (p-value 0.079), although better glottic views were obtained with video laryngoscopy (80.5% were Cormack-Lehane grade 1). Analysis of pre-oxygenation methods found that although sicker patients had received more aggressive pre-oxygenation, e.g. with non-invasive or bag-mask ventilation techniques, they still desaturated more often (35.8% and 62.5%, respectively) than less sick patients who received simple non-rebreather facemask pre-oxygenation (4.5%). CONCLUSIONS: This analysis of the first airway registry from an SA ED highlights that airway management in an LMIC can be performed on par with accepted international standards. It serves as a good baseline for further research into airway management in other LMICs and provides useful feedback for quality improvement purposes.

Let's get physical: A prospective pedometer study of doctors working in a South African emergency department.

BACKGROUND: The positive impact of physical activity and exercise on health is well known. Individuals who walk at least 10 000 steps per day are likely to meet recommended physical activity guidelines. Very little is known about the physical activity levels of doctors at work, in particular those working in emergency departments (EDs). OBJECTIVES: To determine how many steps per shift were taken by doctors in a South African (SA) ED. Secondary objectives were to assess what factors influenced the number of steps taken. METHODS: This was a prospective observational cohort study in a tertiary academic teaching hospital ED in Johannesburg over a 1-month period. Doctors wore pedometers during their day shifts in the ED and the number of steps taken during their shifts was measured, as well as the number and triage category of patients seen and whether cardiopulmonary resuscitation (CPR) was performed. RESULTS: The median (interquartile range) number of steps taken per shift was 6 328 (4 646 - 8 409). The number of steps taken exceeded the 10 000-step target in only 11.7% of shifts. The overall mean (standard deviation (SD)) number of steps per hour was 744 (490). Factors that significantly increased the number of steps taken included shift duration, number of patients seen who were triaged yellow, and performance of CPR in a shift. Each additional hour of shift led to a mean (SD) increase of 575 (115) steps. Each additional yellow patient seen led to a mean (SD) increase of 118 (108) steps. The mean (SD) number of steps for a shift with CPR was significantly higher (8 309 (850) steps) than for a shift without CPR (6 496 (384) steps). CONCLUSIONS: Doctors working in an SA ED are not achieving the daily recommended number of steps while at work. The increased risk of ill health and burnout in an already high-risk specialty heightens the importance of exercise and physical activity that needs to be achieved outside the workplace.

A comparison of four weight estimation systems for paediatric resuscitation.

BACKGROUND: One of the most important parameters that must be obtained when resuscitating a critically ill or injured paediatric patient is their weight. The best known paediatric weight estimation system is arguably the Broselow Tape, but the tape has been shown to be very inaccurate. The aim of this study was to determine and compare the accuracy of the Broselow tape, a modified Broselow tape system, the PAWPER XL tape and the hanging leg weight technique for potential utilisation in the paediatric resuscitation setting. METHOD: A convenience sample of 200 children between the ages of 1 month and 16 years were enrolled. All the children's weights were estimated using the Broselow tape, a habitus-modified Broselow tape system, the PAWPER XL tape and the hanging leg weight technique. Overall accuracy was evaluated using the percentage of weight estimations falling within 10% of actual weight (PW10). RESULTS: The PAWPER XL tape performed the best, whilst the hanging leg weight technique performed the poorest with PW10s of 74% and 19.5%, respectively. The Broselow tape with and without habitus-modification only showed modest accuracy, with PW10s of 61.7% and 59.1% respectively. CONCLUSION: The PAWPER XL tape performed significantly better than other weight estimation systems and is most appropriate for use in South African paediatric emergencies. The habitus-modified Broselow system produced only modest improvement in overall weight estimation accuracy of the Broselow tape.

Analysis of spatial distribution of trace metals, PCB, and PAH and their potential impact on human health in Virginian Counties and independent cities, USA.

Increasing anthropogenic alteration has resulted in increased exposure to both point and nonpoint source pollution. These exposures are increasingly studied for their role in human diseases, including diseases with known genetic or lifestyle risk factors. This study analyzed associations between a variety of human diseases and trace metals, PCBs, and PAHs in soil, groundwater, sediment, and fish. Contaminant spatial data at the county level from Virginia were used in ArcGIS to identify these associations among socially vulnerable populations. The neurologic and psychiatric disorders and cognitive markers were associated with numerous metals in groundwater/soil and/or aquatic system contaminants. Cancer death rates, fetal deaths, and infant deaths were also related to multiple environmental exposures from both categories of exposure. In contrast, many of the chronic diseases which are primarily attributed to lifestyle showed little association with these exposures with the exception of COPD which did appear to be associated with multiple metal exposures. Asthma showed similar associations compared to COPD. Our data suggest that within the context of socially vulnerable populations, where disease burden is often highest, exposures to metals, PAHs, and PCBs may play a role in the development or exacerbation of several highly prevalent categories of disease. These environmental exposures likely act through a variety of pathways all generally leading to increased oxidative stress, inflammation, or interference with biological systems and a subsequent role in disease development.

The effect of different forms of heparin on point-of-care blood gas analysis.

BACKGROUND: Point-of-care blood gas analysis plays an integral role in the management of critically ill and injured patients presenting to the emergency department (ED). While the use of specially manufactured syringes containing electrolyte-balanced dried heparin is recommended when processing these specimens, alternatives including manually self-prepared syringes washed with liquid heparin or heparin vacutainers are still often used. OBJECTIVES: To assess the effect of two concentrations of liquid heparin and the use of heparin vacutainers on the reliability of blood gas analysis results compared with the recommended standard of dried heparin syringes in the ED setting. METHODS: Blood samples were drawn from 54 patients attending a tertiary-level hospital ED. Individual samples were distributed equally among each of four different collection devices: a dried heparin syringe, self-prepared syringes washed separately with 1 000 IU/mL and 5 000 IU/mL liquid heparin, and a heparin vacutainer. Results obtained from the standard dried heparin syringes were compared with those from the other three methods. RESULTS: For both the liquid heparin cohorts, partial pressure of carbon dioxide (pCO2), potassium (K+), sodium (Na+), ionised calcium (iCa2+) and haemoglobin had >20% of results falling beyond the total allowable error. iCa2+ and K+ results were most affected in the 5 000 IU/mL cohort and iCa2+ and Na+ in the 1 000 IU/ml cohort. pCO2, pH and iCa2+ were the most significantly affected in the heparin vacutainer cohort. CONCLUSIONS: Use of liquid heparin can result in significant negative bias in the majority of blood gas analytes, especially electrolytes. Heparin vacutainer use can result in unacceptable variations in the respiratory analytes. While standard dried heparin syringes may not always be available, it is of vital importance that practitioners be aware of these biases and limitations when using substitutes.

High positive computed tomography yields in the emergency department might not be a positive finding.

BACKGROUND: There is growing pressure to reduce unnecessary computed tomography (CT) imaging requests that the radiology department receives from the emergency department (ED); however, information on acceptable usage rates and diagnostic yields remains scanty. OBJECTIVES: To describe the indications, clinical categories and positive yield rates of patients receiving CT scans in the ED. METHODS: A retrospective record review was done of all patients who received CT scans at an urban, adult academic ED during a 4-month period. Primary outcomes were to establish CT scan usage and positive yield rates. Other outcomes included analysis of indications, demographics and anatomical areas scanned. RESULTS: Scans (n=1 010) were analysed. The median age of patients was 36 (range 4 - 93) years. Male patients received 64.3% of all scans, as well as 75.7% of the scans performed for trauma. The majority of the scans were for trauma patients. However, non-trauma patients had a higher positive yield; the non-trauma positive yield rate was 61.8% compared with the trauma positive yield rate of 47.1% (p<0.001). The majority of scans performed were of the head (58%) and neck (20%), with lowest positive yield rates of 48.9% and 17%, respectively. The overall CT scan usage rate was 4.6% and overall positive rate 53.8%. CONCLUSION: A negative CT scan does not necessarily mean that the test was not indicated. Higher positive yield rates may reflect insufficient use of CT scanning by the ED. Local guidelines should be established to ensure judicious and effective clinical use of CT scans.

A literature-based cost analysis of tissue plasminogen activator for prevention of biliary stricture in donation after circulatory death liver transplantation.

INTRODUCTION: This study sought to approximate the cost-effectiveness of tPA utilization for prevention of biliary strictures (PTBS) in donation after circulatory death liver transplantation (DCD-LT). METHODS: Previously-reported PTBS rates in DCD-LT with and without tPA were used to calculate the number needed to treat (NNT) for prevention of one PTBS. The incremental cost of PTBS was then used to determine the cost effectiveness of tPA for prevention of PTBS. RESULTS: The incidence of PTBS in the setting of tPA administration was 20%, while incidence in patients without tPA use was 43% (p < 0.001). Meta-analysis demonstrated a risk reduction of 15.7%, which translated into a NNT of 6.4. Cost associated with treating 6.4 patients was $50,353. Based on an incremental cost of $81,888 associated with PTBS management, use of tPA in DCD-LT protocols was estimated to save $31,528 per PTBS prevented. CONCLUSION: Utilization of tPA in DCD-LT protocols represents one possible cost-effective strategy for prevention of PTBS in DCD-LT.

Development and validation of a method to estimate body weight in critically ill children using length and mid-arm circumference measurements: The PAWPER XL-MAC system.

BACKGROUND: Erroneous weight estimation during the management of emergency presentations in children may contribute to patient harm and poor outcomes. The PAWPER (Paediatric Advanced Weight Prediction in the Emergency Room) XL tape is an accurate length-based, habitus-modified weight estimation device, but is vulnerable to errors if subjective visual assessments of children's body habitus are incorrect or erratic. OBJECTIVE: Mid-arm circumference (MAC) has previously been used as a surrogate indicator of habitus, and the objective of this study was to determine whether MAC cut-off values could be used to predict habitus scores (HSs) to create an objective and standardised weight estimation methodology, the PAWPER XL-MAC method. METHODS: The PAWPER XL-MAC model was developed by creating MAC ranges for each HS in each weight segment of the tape. This model was validated against two samples, the National Health and Nutrition Examination Survey datasets and data from two previous PAWPER tape studies. The primary outcome measure was to achieve >70% of estimations within 10% of measured weight (PW10 >70%) and >95% within 20% of measured weight (PW20 >95%) for children aged 0 - 18 years. RESULTS: The PAWPER XL-MAC model achieved very high accuracy in the three validation datasets (PW10 79.2%, 79.0% and 81.9%) and a very low critical error rate (PW20 98.5%, 96.0% and 98.0%). This accuracy was maintained across all ages and in all habitus types, except for the severely obese. CONCLUSIONS: The PAWPER XL-MAC model proved to be a very accurate, fully objective, standardised system in this study. It has the potential to be accurate across a wide variety of populations, even when used by those not experienced in visual assessment of habitus.

Implementation fidelity of a self-management course for epilepsy: method and assessment.

BACKGROUND: Complex interventions such as self-management courses are difficult to evaluate due to the many interacting components. The way complex interventions are delivered can influence the effect they have for patients, and can impact the interpretation of outcomes of clinical trials. Implementation fidelity evaluates whether complex interventions are delivered according to protocol. Such assessments have been used for one-to-one psychological interventions; however, the science is still developing for group interventions. METHODS: We developed and tested an instrument to measure implementation fidelity of a two-day self-management course for people with epilepsy, SMILE(UK). Using audio recordings, we looked at adherence and competence of course facilitators. Adherence was assessed by checklists. Competence was measured by scoring group interaction, an overall impression score and facilitator "didacticism". To measure "didacticism", we developed a novel way to calculate facilitator speech using computer software. Using this new instrument, implementation fidelity of SMILE(UK) was assessed on three modules of the course, for 28% of all courses delivered. RESULTS: Using the instrument for adherence, scores from two independent raters showed substantial agreement with weighted Kappa of 0.67 and high percent agreement of 81.2%. For didacticism, the results from both raters were highly correlated with an intraclass coefficient of 0.97 (p < 0.0001). We found that the courses were delivered with a good level of adherence (> 50% of scored items received the maximum of 2 points) and high competence. Groups were interactive (mean score: 1.9-2.0 out of 2) and the overall impression was on average assessed as "good". Didacticism varied from 42% to 93% of total module time and was not associated with the other competence scores. CONCLUSION: The instrument devised to measure implementation fidelity was reproducible and easy to use. The courses for the SMILE(UK) study were delivered with a good level of adherence to protocol while not compromising facilitator competence. TRIAL REGISTRATION: ISRCTN57937389 .

The accuracy of nurse performance of the triage process in a tertiary hospital emergency department in Gauteng Province, South Africa.

BACKGROUND: Triage in the emergency department (ED) is necessary to prioritise management according to the severity of a patient's condition.The South African Triage Scale (SATS) is a hospital-based triage tool that has been adopted by numerous EDs countrywide.Many factors can influence the outcome of a patient's triage result, and evaluation of performance is therefore pivotal. OBJECTIVES: To determine how often patients were allocated to the correct triage category and the extent to which they were incorrectly promoted or demoted, and to determine the main reasons for errors in a nurse-led triage system. METHODS: Triage forms from a tertiary hospital ED in Gauteng Province, South Africa, were collected over a 1-week period and reviewed retrospectively. RESULTS: A total of 1 091 triage forms were reviewed. Triage category allocations were correct 68.3% of the time. Of the incorrect category assignments, 44.4% of patients were promoted and 55.6% demoted. Patients in the green category were most commonly promoted (29.4%) and patients who should have been in orange were most commonly demoted (35.0%). Trauma patients were more likely to be incorrectly promoted and non-trauma patients to be incorrectly demoted. Mistakes were mainly due to discriminator errors (57.8%), followed by numerical miscalculations (21.5%). The leading omitted discriminators were 'abdominal pain', 'chest pain' and 'shortness of breath'. CONCLUSIONS: Mis-triaging using the SATS can be attributed to incorrect or lack of discriminator use, numerical miscalculations and other human errors. Quality control and quality assurance measures must target training in these areas to minimise mis-triage in the ED.

Dissociation in patients with dissociative seizures: relationships with trauma and seizure symptoms.

BACKGROUND: This study aimed to extend the current understanding of dissociative symptoms experienced by patients with dissociative (psychogenic, non-epileptic) seizures (DS), including psychological and somatoform types of symptomatology. An additional aim was to assess possible relationships between dissociation, traumatic experiences, post-traumatic symptoms and seizure manifestations in this group. METHOD: A total of 40 patients with DS were compared with a healthy control group (n = 43), matched on relevant demographic characteristics. Participants completed several self-report questionnaires, including the Multiscale Dissociation Inventory (MDI), Somatoform Dissociation Questionnaire-20, Traumatic Experiences Checklist and the Post-Traumatic Diagnostic Scale. Measures of seizure symptoms and current emotional distress (Hospital Anxiety and Depression Scale) were also administered. RESULTS: The clinical group reported significantly more psychological and somatoform dissociative symptoms, trauma, perceived impact of trauma, and post-traumatic symptoms than controls. Some dissociative symptoms (i.e. MDI disengagement, MDI depersonalization, MDI derealization, MDI memory disturbance, and somatoform dissociation scores) were elevated even after controlling for emotional distress; MDI depersonalization scores correlated positively with trauma scores while seizure symptoms correlated with MDI depersonalization, derealization and identity dissociation scores. Exploratory analyses indicated that somatoform dissociation specifically mediated the relationship between reported sexual abuse and DS diagnosis, along with depressive symptoms. CONCLUSIONS: A range of psychological and somatoform dissociative symptoms, traumatic experiences and post-traumatic symptoms are elevated in patients with DS relative to healthy controls, and seem related to seizure manifestations. Further studies are needed to explore peri-ictal dissociative experiences in more detail.

Psychologic treatment of functional neurologic disorders.

The management of patients with functional neurologic disorders poses many challenges. Psychologic treatments may well start at the point of delivery of the diagnosis, when careful explanations about the nature of the disorder have to be given to the patient and possibly also relatives/carers. Different conceptual models may assist in explaining the factors underlying the presentation, two of which (functional and dissociative) are briefly outlined here. The challenges for neurologists and psychiatrists of delivering a psychologic formulation as part of the diagnosis delivery are considered, along with the importance of clear communication between professionals involved in the patient's care. Existing literature on treatments incorporating psychologic components suggests that, despite limitations in the study designs and the potential bias in some outcome evaluations, there is evidence to support the use of psychologic interventions for at least some functional neurologic disorders, although larger and better-designed studies are required in this area.

A pilot study of cognitive behavioural therapy and relaxation for migraine headache: a randomised controlled trial.

Headache is being viewed more commonly in a biopsychosocial framework, which introduces the possible utilisation of psychological treatment options, such as cognitive behavioural therapy and relaxation. No such treatments have been trialled in the UK. We conducted a randomised controlled pilot trial, comparing a brief guided self-help CBT and relaxation treatment with standard medical care (SMC), in a UK NHS setting. Participants were recruited from specialist headache clinics across London. Participants were randomised to receive either treatment or standard medical care. Our objective was to provide design information necessary for a future definitive trial of the SHE treatment, including, recruitment/retention rates, acceptability of randomisation, treatment fidelity and estimations of mean and variances of outcome measures. From the initial 275 patients identified, 73 were randomised. There was no difference in drop-out rates between SMC and treatment groups. Of the 36 participants randomised to receive treatment, 72% attended all sessions. Findings show that a future definitive trial of the SHE treatment is feasible, with small modifications of protocol, within a UK NHS context.

Accepting or declining non-invasive ventilation or gastrostomy in amyotrophic lateral sclerosis: patients' perspectives.

The objective was to identify factors associated with decisions made by patients with amyotrophic lateral sclerosis (ALS) to accept or decline non-invasive ventilation (NIV) and/or gastrostomy in a prospective population-based study. Twenty-one people with ALS, recruited from the South-East ALS Register who made an intervention decision during the study timeframe underwent a face-to-face in-depth interview, with or without their informal caregiver present. Sixteen had accepted an intervention (11 accepted gastrostomy, four accepted NIV and one accepted both interventions). Five patients had declined gastrostomy. Thematic analysis revealed three main themes: (1) patient-centric factors (including perceptions of control, acceptance and need, and aspects of fear); (2) external factors (including roles played by healthcare professionals, family, and information provision); and (3) the concept of time (including living in the moment and the notion of 'right thing, right time'). Many aspects of these factors were inter-related. Decision-making processes for the patients were found to be complex and multifaceted and reinforce arguments for individualised (rather than 'algorithm-based') approaches to facilitating decision-making by people with ALS who require palliative interventions.

Real-time assessment of relapse risk based on the WT1 marker in acute leukemia and myelodysplastic syndrome patients after hematopoietic cell transplantation.

Relapse is the major cause of treatment failure after allogeneic hematopoietic cell transplantation (alloHCT) for acute leukemia and myelodysplastic syndrome (MDS). Wilms' tumor Ag (WT1) is overexpressed in the majority of acute leukemia and MDS patients and has been proposed as a universal diagnostic marker for detection of impending relapse. Comprehensive studies have shown that WT1 transcript levels have predictive value in acute leukemia patients in CR after chemotherapy. However, the focus of this study is the period after alloHCT for predicting relapse onset. We analyzed the accumulation of WT1 mRNA transcripts in PB of 82 leukemia and MDS patients and defined specific molecular ratios for relapse prediction. The extensively validated WT1/c-ABL ratio was used to normalize increases in WT1 transcript levels. The observed lead time of crossing or exceeding set WT1 levels is presented along with linear interpolation to estimate the calculated day the WT1 thresholds were crossed. The WT1/c-ABL transcript ratio of 50 or above yielded 100% specificity and 75% sensitivity reliably predicting future relapse with an observed average of 29.4 days (s.d.=19.8) and a calculated average of 63 days (s.d.=29.3) lead time before morphologic confirmation. A lower ratio of 20 or above gave lower specificity, but higher sensitivity (84.8% and 87.5%, respectively) identified more patients who relapsed, at earlier times, providing an earlier warning with actual average lead time of 49.1 days (s.d.=30.8) and calculated average of 78 days (s.d.=28.8). WT1 transcript levels serve as a diagnostic relapse test with greater sensitivity than the morphologic approach used in the clinic as a readout.

Global epidemiology of amyotrophic lateral sclerosis: a systematic review of the published literature.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is relatively rare, yet the economic and social burden is substantial. Having accurate incidence and prevalence estimates would facilitate efficient allocation of healthcare resources. OBJECTIVE: To provide a comprehensive and critical review of the epidemiological literature on ALS. METHODS: MEDLINE and EMBASE (1995-2011) databases of population-based studies on ALS incidence and prevalence reporting quantitative data were analyzed. Data extracted included study location and time, design and data sources, case ascertainment methods and incidence and/or prevalence rates. Medians and interquartile ranges (IQRs) were calculated, and ALS case estimates were derived using 2010 population estimates. RESULTS: In all, 37 articles met the inclusion criteria. In Europe, the median incidence rate (/100,000 population) was 2.08 (IQR 1.47-2.43), corresponding to an estimated 15,355 (10,852-17,938) cases. Median prevalence (/100,000 population) was 5.40 (IQR 4.06-7.89), or 39,863 (29,971-58,244) prevalent cases. CONCLUSIONS: Disparity in rates among ALS incidence and prevalence studies may be due to differences in study design or true variations in population demographics such as age and geography, including environmental factors and genetic predisposition. Additional large-scale studies that use standardized case ascertainment methods are needed to more accurately assess the true global burden of ALS.