Understanding barriers to optimal medication management for those requiring long-term dialysis: rationale and design for an observational study, and a quantitative description of study variables and data.

BACKGROUND: Rates of medication non-adherence in dialysis patients are high, and improving adherence is likely to improve outcomes. Few data are available regarding factors associated with medication adherence in dialysis patients, and these data are needed to inform effective intervention strategies. METHODS/DESIGN: This is an observational cross-sectional study of a multi-ethnic dialysis cohort from New Zealand, with the main data collection tool being an interviewer-assisted survey. A total of 100 participants were randomly sampled from a single centre, with selection stratified by ethnicity and dialysis modality (facility versus home). The main outcome measure is self-reported medication adherence using the Morisky 8-Item Medication Adherence Scale (MMAS-8). Study data include demographic, clinical, social and psychometric characteristics, the latter being constructs of health literacy, medication knowledge, beliefs about medications, and illness perceptions. Psychometric constructs were assessed through the following survey instruments; health literacy screening questions, the Medication Knowledge Evaluation Tool (Okuyan et al.), the Beliefs about Medication Questionnaire (Horne et al.), the Brief Illness Perception Questionnaire (Broadbent et al.). Using the study data, reliability analysis for internal consistency is satisfactory for the scales evaluating health literacy, medication knowledge, and beliefs about medications, with Chronbach's α > 0.7 for all. Reliability analysis indicated poor internal consistency for scales relating to illness perceptions. MMAS-8 and all psychometric scores are normally distributed in the study data. DISCUSSION: This study will provide important information on the factors involved in medication non-adherence in New Zealand dialysis patients. The resulting knowledge will inform long-term initiatives to reduce medication non-adherence in dialysis patients, and help ensure that they are addressing appropriate and evidence based targets for intervention.

Predictors of Place of Death for Those in Receipt of Home-Based Palliative Care Services in Ontario, Canada.

Many cancer patients die in institutional settings despite their preference to die at home. A longitudinal, prospective cohort study was conducted to comprehensively assess the determinants of home death for patients receiving home-based palliative care. Data collected from biweekly telephone interviews with caregivers (n = 302) and program databases were entered into a multivariate logistic model. Patients with high nursing costs (odds ratio [OR]: 4.3; confidence interval [CI]: 1.8-10.2) and patients with high personal support worker costs (OR: 2.3; CI: 1.1-4.5) were more likely to die at home than those with low costs. Patients who lived alone were less likely to die at home than those who cohabitated (OR: 0.4; CI: 0.2-0.8), and those with a high propensity for a home-death preference were more likely to die at home than those with a low propensity (OR: 5.8; CI: 1.1-31.3). An understanding of the predictors of place of death may contribute to the development of effective interventions that support home death.

The impact of nurse prescribing on the clinical setting.

AIM: To investigate the impact nurse prescribing has on the organisation, patient and health professional, and to identify factors associated with the growth of nurse prescribing. METHODS: Systematic search and narrative review. Data obtained through CINAHL, PubMed, Science direct, Online Computer Library Centre (OCLC), databases/websites, and hand searching. English peer-reviewed quantitative, qualitative and mixed-method articles published from September 2009 through to August 2014 exploring nurse prescribing from the perspective of the organisation, health professional and patient were included. Following a systematic selection process, studies identified were also assessed for quality by applying Cardwell's framework. RESULTS: From the initial 443 citations 37 studies were included in the review. Most studies were descriptive in nature. Commonalities addressed were stakeholders' views, prescribing in practice, jurisdiction, education and benefits/barriers. CONCLUSIONS: Prescriptive authority for nurses continues to be a positive addition to clinical practice. However, concerns have emerged regarding appropriate support, relationships and jurisdictional issues. A more comprehensive understanding of nurse and midwife prescribing workloads is required to capture the true impact and cost-effectiveness of the initiative.

Population pharmacokinetics of intravenous acetaminophen and its metabolites in major surgical patients.

Intravenous acetaminophen is a commonly used analgesic following surgery. The aims of this study were to determine the population pharmacokinetic profile of intravenous acetaminophen and its metabolites in adult surgical patients and to identify patient characteristics associated with acetaminophen metabolism in the postoperative period. 53 patients were included in the dataset; 28 were men, median age (range) 60 years (33-87), median weight (range) 74 kg (54-129). Patients received 1, 1.5 or 2 g of intravenous acetaminophen every 4-6 h. Plasma and urine samples were collected at various intervals for up to 6 days after surgery. Simultaneous modelling of parent acetaminophen and its metabolites was conducted in Phoenix(®) NLME™ to estimate pharmacokinetic parameters. The population mean estimate (CV%) for central (plasma) volume of distribution of parent acetaminophen (VC) was 13.9 (4.41) L, peripheral (tissue) volume of distribution (VT) was 50.9 (2.96) L, and intercompartmental clearance (Q) was 77.5 (9.29) L/h. The population mean (CV%) metabolic clearances for glucuronidation (CLPG) was 8.92 (3.25) L/h, sulfation (CLPS) was 0.903 (3.47) L/h, and oxidation (CLPO) was 0.533 (7.90) L/h. The population mean (CV%) urinary clearances of parent acetaminophen (CLRP) was 0.137 (5.46) L/h, acetaminophen glucuronide (CLRG) was 3.81 (6.71) L/h, acetaminophen sulfate (CLRS) was 3.13 (4.32) L/h, and acetaminophen cysteine + mercapturate (CLRO) was 3.51 (9.98) L/h. Age was found to be a significant covariate on the formation of acetaminophen glucuronide, and renal function (estimated as creatinine clearance) on the urinary excretion of acetaminophen glucuronide.

Nurse prescribers' experiences of recording prescribing data to the Minimum Data Set in Ireland.

This study aimed to investigate and enhance understanding of nurse prescribers' experiences of working with the Irish national data gathering system for nurse prescribing: the Minimum Data Set (MDS) in Irish clinical practice. A phenomenological research design was used, collecting data via semi-structured interviews using a purposive sample of practising nurse prescribers. The study identified three recurrent themes: communication, workload/time, and attitudes. The MDS produces only standard national reports (lists) on nurse/midwife prescribing that cannot be utilised efficiently to inform practice or understand health service needs. Nurses have reacted to this situation and evaluate the MDS in the context of their clinical setting, identifying conflicting demands and expectations and an increased workload as factors that correlated negatively with the process of collecting nurse prescribing data. Consultation and evaluation is required, particularly to analyse the nurse prescribers' views of collecting data and working with the MDS in the context of the major adjustments that the Irish health service has experienced over the past 6 years.

Structural Equation Modelling to Identify Psychometric Determinants of Medication Adherence in a Survey of Kidney Dialysis Patients.

Purpose: Medication non-adherence in dialysis patients is associated with increased mortality and higher healthcare costs. We assessed whether medication adherence is influenced by specific psychometric constructs measuring beliefs about the necessity for medication and concerns about them. We also tested whether medication knowledge, health literacy, and illness perceptions influenced this relationship. Patients and Methods: This study is based on data from a cross-sectional in-person questionnaire, administered to a random sample of all adult dialysis patients at a teaching hospital. The main outcome was self-assessed medication adherence (8-Item Morisky Medication Adherence Scale). The predictors were: concerns about medications and necessity for medication (Beliefs About Medication Questionnaire); health literacy; medication knowledge (Medication Knowledge Evaluation Tool); cognitive, emotional, and comprehensibility Illness perceptions (Brief Illness Perception Questionnaire). Path analysis was performed using structural equations in both covariance and variance-based models. Results: Necessity for medication increased (standardized path coefficient [ß] 0.30 [95% CI 0.05, 0.54]) and concerns about medication decreased (standardized ß -0.33 [-0.57, -0.09]) medication adherence, explaining most of the variance in outcome (r2=0.95). Medication knowledge and cognitive illness perceptions had no effects on medication adherence, either directly or indirectly. Higher health literacy, greater illness comprehension, and a more positive emotional view of their illness had medium-to-large sized effects in increasing medication adherence. These were indirect rather and direct effects mediated by decreases in concerns about medications (standardized ß respectively -0.40 [-0.63,-0.16], -0.60 [-0.85, -0.34], -0.33 [-0.52, -0.13]). Conclusion: Interventions that reduce patients' concerns about their medications are likely to improve adherence, rather than interventions that increase patients' perceived necessity for medication. Improving patients' general health literacy and facilitating a better understanding and more positive perception of the illness can probably achieve this. Our study is potentially limited by a lack of generalizability outside of the population and setting in which it was conducted.

Potentially inappropriate prescribing in older residents in Irish nursing homes.

BACKGROUND: STOPP/START was formulated to identify potentially inappropriate prescribing (PIP) and potential prescribing omissions (PPOs) in older people. The purpose of this study was to determine the prevalence of PIP and PPO in older Irish patients in residential care using STOPP/START. METHODS: data were collected prospectively from seven publicly funded nursing homes within the Munster Region of Ireland over 3 weeks. Data recorded included: current medication, current medical conditions, previous medical conditions, biochemistry, sex and age. STOPP/START was applied to each patient record. RESULTS: of the 313 patients recruited, 74.4% (233) were female, mean age (± SD) 84.4 (± 7.5) years. The total number of medicines prescribed was 2,555 [range: 1-16; median: 8 (IQR 6-10 )]. STOPP identified 329 instances of PIP in 187 (59.8%) patients and START identified 199 PPOs in 132 (42.2%) patients. The number of medicines prescribed was positively associated with PIP identified by STOPP (rs = 0.303, P < 0.01). Age, sex and the number of medicines prescribed were not associated with prescribing omissions using START. CONCLUSIONS: a high proportion of patients recruited were prescribed at least one potentially inappropriate medicine, or had an omission of a clinically indicated medicine. Incorporating these tools into every-day practice could play a pivotal role in improving prescribing in this cohort.

The size, share, and predictors of publicly financed healthcare costs in the home setting over the palliative care trajectory: a prospective study.

INTRODUCTION: The increasing attention on home-based service provision for end-of-life care has resulted in greater financial demands being placed on family caregivers. The purpose of this study was to assess publicly financed costs within a home-based setting from a societal perspective. METHODS: A prospective cohort study design was employed. In all, 129 caregivers of palliative care patients were interviewed biweekly for a total of 667 interviews. Multiple regression analysis (log-linear regression and seemingly unrelated regression [SUR]) was conducted. RESULTS: While publicly financed costs accounted for 20 percent of the full economic costs and increased with proximity to death, 76.7 percent of costs were borne by patients' caregivers in the form of unpaid caregiving. The share of publicly financed healthcare costs was driven by patients' and caregivers' sociodemographic and clinical characteristics. CONCLUSION: These findings warrant affording greater attention to policies and interventions intended to reduce the economic burden on palliative patients and their caregivers.

Age-dependent B cell autoimmunity to a myelin surface antigen in pediatric multiple sclerosis.

Multiple sclerosis (MS) typically manifests in early to mid adulthood, but there is increasing recognition of pediatric-onset MS, aided by improvements in imaging techniques. The immunological mechanisms of disease are largely unexplored in pediatric-onset MS, in part because studies have historically focused on adult-onset disease. We investigated autoantibodies to myelin surface Ags in a large cohort of pediatric MS cases by flow cytometric labeling of transfectants that expressed different myelin proteins. Although Abs to native myelin oligodendrocyte glycoprotein (MOG) were uncommon among adult-onset patients, a subset of pediatric patients had serum Abs that brightly labeled the MOG transfectant. Abs to two other myelin surface Ags were largely absent. Affinity purification of MOG Abs as well as competition of binding with soluble MOG documented their binding specificity. Such affinity purified Abs labeled myelin and glial cells in human CNS white matter as well as myelinated axons in gray matter. The prevalence of such autoantibodies was highest among patients with a very early onset of MS: 38.7% of patients less than 10 years of age at disease onset had MOG Abs, compared with 14.7% of patients in the 10- to 18-year age group. B cell autoimmunity to this myelin surface Ag is therefore most common in patients with a very early onset of MS.

Evaluation of the Career Development and Compensation Program in the Department of Paediatrics at The Hospital for Sick Children.

The Career Development and Compensation Program (CDCP) was created by the Department of Paediatrics at The Hospital for Sick Children, in Toronto, Ontario, to provide clearly defined job expectations, enhance career development and assess performance through two distinct processes: the annual review and the triennial review. Staff are expected to advance the goals of the department and the hospital through activities in clinical care, education and mentorship, and research and are rewarded for excellence through compensation and career advancement. We evaluated the CDCP and conducted interviews with 27 members of the department; these formed the primary basis for our summative evaluation. The study objectives were to evaluate (1) mechanisms to recognize contributions, (2) processes used to ensure staff accountability and (3) opportunities to increase efficiencies. Interviews with members of the department resulted in a broad and comprehensive understanding of the CDCP. It is regarded as a rigorous, transparent and fair program. Concerns about the CDCP stem from the potential negative outcomes of assigning value to particular activities, the inequitable level of support provided to staff across the department and the costs of the review processes. Several recommendations were identified that serve to increase equality and strengthen supports for members of the department, to improve the ability of the CDCP to evaluate the softer aspects of clinical care and scholarship and to adopt a more holistic and integrated approach in the evaluation of staff. These re-formed arrangements build upon past modifications to the CDCP and represent natural progressions in the development of a program that has wide support from members of the department.

Transitions in Labour Force Participation over the Palliative Care Trajectory.

BACKGROUND: Home-based palliative programs rely on family caregivers, who often miss time from employment. This article identified changes in caregivers' labour force participation over the palliative trajectory. METHODS: Family caregivers (n = 262) were interviewed biweekly to measure transitions across four employment categories. RESULTS: More than half of the caregivers had one employment transition and 29% had three or more. The highest proportion of transitions occurred for caregivers who were employed part-time. INTERPRETATION: Understanding these transitions is critical to the development of strategies tailored to caregivers to contain labour force losses and to support caregivers during a time of high caregiving demands.

Abnormal T-cell reactivities in childhood inflammatory demyelinating disease and type 1 diabetes.

OBJECTIVES: Pediatric-onset multiple sclerosis offers a unique window into early targets and mechanisms of immune dysregulation. It is unknown whether heightened T-cell reactivities documented in adult patients, to both target-organ and environmental antigens, emerge in parallel or develop as early or late events. Our objectives were to determine the presence, pattern, and specificity of abnormal T-cell reactivities to such antigens in the earliest stages of the multiple sclerosis process. METHODS: Peripheral T-cell proliferative responses to self-, dietary, and control antigens were blindly evaluated in a large cohort of well-characterized children (n = 172) with central nervous system (CNS) inflammatory demyelination (n = 63), recent-onset type 1 (insulin-dependent) diabetes mellitus (T1D; n = 41), nonautoimmune neurological conditions (n = 39), and healthy children (n = 29). RESULTS: Children with inflammatory demyelination, CNS injury, and T1D exhibited heightened T-cell reactivities to self-antigens, and these responses were not strictly limited to the disease target organs. Children with autoimmune disease and CNS injury also exhibited abnormal T-cell responses against multiple cow-milk proteins. Responses to specific milk epitopes distinguished T1D from inflammatory demyelination and other neurological diseases. INTERPRETATION: Abnormal T-cell reactivities to self- and environmental antigens manifest in the earliest clinical stages of inflammatory demyelination and T1D. The pattern of heightened T-cell reactivities implicates both shared and distinct mechanisms of immune dysregulation in the different autoimmune diseases. Abnormal T-cell responses in children with tissue injury challenge the prevailing view that CNS autoreactive cells inherently mediate the disease in early multiple sclerosis.

Potentially inappropriate prescribing in an Irish elderly population in primary care.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: * Potentially inappropriate prescribing in older people is a well-documented problem and has been associated with adverse drug reactions and hospitalization. * Beers' criteria, Screening Tool of Older Persons' potentially inappropriate Prescriptions (STOPP) and Screening Tool to Alert doctors to Right Treatment (START) are screening tools that have been formulated to help physicians and pharmacists identify potentially inappropriate prescribing and potential prescribing omissions. * The prevalence of potentially inappropriate prescribing and prescribing omissions in the elderly population presenting to hospital with acute illness is high according to STOPP and START criteria. WHAT THIS STUDY ADDS: * Potential errors of prescribing and of omission of medicines are prevalent among medically stable older people in primary care. * Screening tools should be incorporated into the everyday practice of primary care doctors and community pharmacists as a means of preventing potential errors of prescribing commission and prescribing omission in older people. AIMS: Screening tools have been formulated to identify potentially inappropriate prescribing (IP) in older people. Beers' criteria are the most widely used but have disadvantages when used in Europe. New IP screening tools called Screening Tool of Older Person's Prescriptions (STOPP) and Screening Tool to Alert doctors to Right Treatment (START) have been developed to identify potential IP and potential prescribing omissions (PPOs). The aim was to measure the prevalence rates of potential IP and PPOs in primary care using Beers' criteria, STOPP and START. METHODS: Case records of 1329 patients >or=65 years old from three general practices in one region of southern Ireland were studied. The mean age +/- SD of the patients was 74.9 +/- 6.4 years, 60.9% were female. Patients' current diagnoses and prescription medicines were reviewed and the Beers' criteria, STOPP and START tools applied. RESULTS: The total number of medicines prescribed was 6684; median number of medicines per patient was five (range 1-19). Overall, Beers' criteria identified 286 potentially inappropriate prescriptions in 18.3% (243) of patients, whilst the corresponding IP rate identified by STOPP was 21.4% (284), in respect of 346 potentially inappropriate prescriptions. A total of 333 PPOs were identified in 22.7% (302) of patients using the START tool. CONCLUSION: Potentially inappropriate drug prescribing and errors of drug omission are highly prevalent among older people living in the community. Prevention strategies should involve primary care doctors and community pharmacists.

Incidence, preventability, and impact of Adverse Drug Events (ADEs) and potential ADEs in hospitalized children in New Zealand: a prospective observational cohort study.

Adverse drug events (ADEs) are an important problem in all hospitalized patients as these events represent medication-related patient harm. Few epidemiologic data exist regarding ADEs in the pediatric inpatient setting and, in particular, the economic impact of such ADEs upon the healthcare sector. To evaluate the incidence, preventability, and seriousness of ADEs and potential ADEs occurring in hospitalized children and to examine the cost implications of these ADEs. This was a prospective observational cohort study conducted in the pediatric, neonatal intensive care unit (NICU), and postnatal wards of a university-affiliated urban general hospital in Dunedin, New Zealand (NZ). The study population was all patients admitted to these wards for >24 hours over a 12-week period from 18 March 2002 to 9 June 2002. Medication-related events were identified by chart review, attendance at multidisciplinary clinical meetings, parent/carer/child interviews, and voluntary and verbally solicited reports from staff. All suspected medication-related events were reviewed by a panel of three health professionals who independently categorized the events and rated them for seriousness, preventability, and causality, using a standardized reviewer form. Costs attributable to ADEs were calculated using both the average cost of a bed day, and specific costs for diagnostic groupings. The main outcome measures of the study were ADEs and potential ADEs. There were 495 eligible study patients, who had a total of 520 admissions and 3037 patient-days of admission, during which 3160 prescription episodes were written. There were 67 ADEs, of which 38 (56.7%) were classified as preventable, and 77 potential ADEs. ADEs occurred at a rate of 2.1 per 100 prescription episodes, 12.9 per 100 admissions, and 22.1 per 1000 patient-days. Potential ADEs occurred at a rate of 2.4 per 100 prescription episodes, 14.6 per 100 admissions, and 25 per 1000 patient-days. Although the greatest number (and rate per 100 admissions) of ADEs occurred in NICU patients, surgical pediatric ward patients had the greatest rate of ADEs per 1000 patient-days. Few events occurred in postnatal patients. Forty-six percent of ADEs were classified as being serious; 15% were deemed to result in persistent disability or were classified as life threatening. Potential ADEs were deemed more likely to be serious with 82% classified as potentially serious events; 33% were deemed as having the potential to result in persistent disability, or the potential to cause a life-threatening event. Fifteen ADEs were judged to have caused the hospital admission or to have prolonged hospital stay. The total number of days attributed to ADEs was 92 (range 1-26 days); of these, 58 were deemed preventable days and 34 non-preventable days. This extrapolates to a total annual cost of $NZ235 214 (2002 values) to the pediatric service, subdivided into $NZ148 287 for preventable ADEs and $NZ86 927 for non-preventable ADEs. ADEs and potential ADEs represent a considerable hazard for the pediatric inpatient population and ADEs represent a large cost imposition upon the healthcare sector. Over half of the ADEs were deemed preventable. This highlights the importance of developing strategies to prevent and ameliorate ADEs both to improve the quality of patient care and to reduce healthcare costs.

Assessing care-giving demands, resources and costs of family/friend caregivers for persons with mental health disorders: A scoping review.

As mental health (MH) care has shifted from institutional settings to the community, families and friends are responsible for providing the majority of the care at home. The substantial literature on the adverse effects experienced by caregivers has focused mainly on psychological morbidity. Less attention has been paid to how caregivers for persons with MH disorders interact with larger social systems and the impacts of factors such as financial strain, lost time from leisure activities, and the availability of health and social services. We conducted a scoping review of MH and other caregiver questionnaires published between 1990 and 2016 to determine whether they addressed four key domains: caregiver work demands, resource needs, resource utilisation and costs. A range of health and social care databases were searched, including MEDLINE and Health and Psychosocial Instruments. After screening for relevance and quality, our search identified 14 instruments addressing elements related to one or more of our domains. Because these instruments covered only a small portion of our domains, we conducted a second targeted search of the general care-giving literature and consulted with experts, identifying an additional 18 instruments. A total of 32 questionnaires were reviewed, 14 specific to care-giving for mental health problems and 18 for other health conditions. Our search identified instruments or items within instruments that assess constructs in each of our domains, but no one instrument covered them completely. Additionally, some constructs were evaluated in detail and others only addressed by single items. While these instruments are helpful for moving measurement beyond the psychological impacts of care-giving, our results serve only as an initial guide. Additional methodological work is needed to more comprehensively measure the impact of care-giving for individuals with MH disorders and to contribute to the development of more meaningful and effective policies and programmes.

Training: improving antenatal detection and outcomes of congenital heart disease.

OBJECTIVES: This study describes the design, delivery and efficacy of a regional fetal cardiac ultrasound training programme. This programme aimed to improve the antenatal detection of congenital heart disease (CHD) and its effect on fetal and postnatal outcomes. DESIGN SETTING AND PARTICIPANTS: This was a prospective study that compared antenatal CHD detection rates by professionals from 13 hospitals in Wales before and after engaging in our 'skills development programme'. Existing fetal cardiac practice and perinatal outcomes were continuously audited and progressive targets were set. The work was undertaken by the Welsh Fetal Cardiovascular Network, Antenatal Screening Wales (ASW), a superintendent sonographer and a fetal cardiologist. INTERVENTIONS: A core professional network was established, engaging all stakeholders (including patients, health boards, specialist commissioners, ASW, ultrasonographers, radiologists, obstetricians, midwives and paediatricians). A cardiac educational lead (midwife, superintendent sonographer, radiologist, obstetrician, or a fetal medicine specialist) was established in each hospital. A new cardiac anomaly screening protocol ('outflow tract view') was created and training on the new protocol was systematically delivered at each centre. Data were prospectively collected and outcomes were continuously audited: locally by the lead fetal cardiologist; regionally by the Congenital Anomaly Register and Information Service in Wales; and nationally by the National Institute for Cardiac Outcomes and Research (NICOR) in the UK. MAIN OUTCOME MEASURES: Patient satisfaction; improvements in individual sonographer skills, confidence and competency; true positive referral rate; local hospital detection rate; national detection rate of CHD; clinical outcomes of selected cardiac abnormalities; reduction of geographical health inequality; cost efficacy. RESULTS: High levels of patient satisfaction were demonstrated and the professional skill mix in each centre was improved. The confidence and competency of sonographers was enhanced. Each centre demonstrated a reduction in the false-positive referral rate and a significant increase in cardiac anomaly detection rate. According to the latest NICOR data, since implementing the new training programme Wales has sustained its status as UK lead for CHD detection. Health outcomes of children with CHD have improved, especially in cases of transposition of the great arteries (for which no perinatal mortality has been reported since 2008). Standardised care led to reduction of geographical health inequalities with substantial cost saving to the National Health Service due to reduced false-positive referral rates. Our successful model has been adopted by other fetal anomaly screening programmes in the UK. CONCLUSIONS: Antenatal cardiac ultrasound mass training programmes can be delivered effectively with minimal impact on finite healthcare resources. Sustainably high CHD detection rates can only be achieved by empowering the regional screening workforce through continuous investment in lifelong learning activities. These should be underpinned by high quality service standards, effective care pathways, and robust clinical governance and audit practices.

Clinical features and viral serologies in children with multiple sclerosis: a multinational observational study.

BACKGROUND: The full spectrum of clinical manifestations and outcome, and the potential importance of regional or demographic features or viral triggers in paediatric multiple sclerosis (MS), has yet to be fully characterised. Our aim was to determine some of these characteristics in children with MS. METHODS: 137 children with MS and 96 control participants matched by age and geographical region were recruited in a multinational study. They underwent structured clinical-demographic interviews, review of academic performance, physical examination, disability assessment (MS patients only), and standardised assays for IgG antibodies directed against Epstein-Barr virus, cytomegalovirus, parvovirus B19, varicella zoster virus, and herpes simplex virus. FINDINGS: MS was relapsing-remitting at diagnosis in 136 (99%) children. The first MS attack resembled acute disseminated encephalomyelitis (ADEM) in 22 (16%) of the children, most under 10 years old (mean age 7.4 [SD 4.2] years). Children with ADEM-like presentations were significantly younger than were children with polyfocal (11.2 [4.5] years; p<0.0001) or monofocal (12.0 [3.8] years; p=0.0005) presentations. Permanent physical disability (EDSS>or=4.0) developed within 5 years in 15 (13%) of the 120 children for whom EDSS score was available. 23 (17%) had impaired academic performance, which was associated with increasing disease duration (p=0.02). Over 108 (86%) of the children with MS, irrespective of geographical residence, were seropositive for remote EBV infection, compared with only 61 (64%) of matched controls (p=0.025, adjusted for multiple comparisons). Children with MS did not differ from controls in seroprevalence of the other childhood viruses studied, nor with respect to month of birth, sibling number, sibling rank, or exposure to young siblings. INTERPRETATION: Paediatric MS is a relapsing-remitting disease, with presenting features that vary by age at onset. MS in children might be associated with exposure to EBV, suggesting a possible role for EBV in MS pathobiology.

Taking the lead from our colleagues in medical education: the use of images of the in-vivo setting in teaching concepts of pharmaceutical science.

Despite pharmaceutical sciences being a core component of pharmacy curricula, few published studies have focussed on innovative methodologies to teach the content. This commentary identifies imaging techniques which can visualise oral dosage forms in-vivo and observe formulation disintegration in order to achieve a better understanding of in-vivo performance. Images formed through these techniques can provide students with a deeper appreciation of the fate of oral formulations in the body compared to standard disintegration and dissolution testing, which is conducted in-vitro. Such images which represent the in-vivo setting can be used in teaching to give context to both theory and experimental work, thereby increasing student understanding and enabling teaching of pharmaceutical sciences supporting students to correlate in-vitro and in-vivo processes.

Magnetic Resonance Imaging to Visualize Disintegration of Oral Formulations.

This article demonstrates that magnetic resonance imaging can visualize the disintegration of a variety of paracetamol containing oral formulations in an in vitro setting and in vivo in the human stomach. The different formulations had unique disintegration profiles which could be imaged both in vitro and in vivo. No special formulation approaches or other contrast agents were required. These data demonstrate the potential for further use of magnetic resonance imaging to investigate and understand the disintegration behavior of different formulation types in vivo, and could potentially be used as a teaching tool in pharmaceutical and medical curricula.

Multi-Centre Clinical Evaluation of Photothermal Radiometry and Luminescence Correlated with International Benchmarks for Caries Detection.

INTRODUCTION: A clinical study was initiated to investigate a caries detection device (The Canary System (CS)), based on photothermal radiometry and modulated luminescence (PTR-LUM). The primary objective of this study was to determine if PTR-LUM values (in the form of Canary Numbers; CN) correlate with International Caries Diagnostic and Assessment System (ICDAS II) scores and clinical situations. The secondary objectives of this study were to monitor the safety of PTR-LUM, and collect data to determine how CN values could be used to differentiate healthy from decayed tooth surfaces on a normalized scale. METHODS: The trial was a four site, non-blinded study. Data was collected from 92 patients, resulting in 842 scanned tooth surfaces over multiple appointments. Surfaces were assessed according to ICDAS II, and further stratified into five clinical situation categories: 1) healthy surface, 2) non-cavitated white and/or brown spots; 3) caries lesions; 4) cavitation and 5) teeth undergoing remineralization therapy.CN data was analyzed separately for smooth and occlusal surfaces. Using a semi-logarithmic graph to plot raw CN (rCN) and normalized (CN) values, rCN data was normalized into a scale of 0-100. RESULTS: Linear correlations (R2) between CN and ICDAS II groupings for smooth and occlusal surfaces were calculated as 0.9759 and 0.9267, respectively. The mean CN values derived from smooth (20.2±0.6) and occlusal (19±1.0) surfaces identified as healthy had significantly lower CN values (P<0.05) compared with the values from the other clinical situation categories. No adverse events were reported. CONCLUSION: The present study demonstrated the safety of PTR-LUM for clinical application and its ability to distinguish sound from carious tooth surfaces. A clear shift from the baseline in both PTR and LUM in carious enamel was observed depending on the type and nature of the lesion, and correlated to ICDAS II classification codes, which enabled the preliminary development of a Canary Scale.