Clinical validation of a multi-protein, serum-based assay for disease activity assessments in multiple sclerosis.

An 18-protein multiple sclerosis (MS) disease activity (DA) test was validated based on associations between algorithm scores and clinical/radiographic assessments (N = 614 serum samples; Train [n = 426; algorithm development] and Test [n = 188; evaluation] subsets). The multi-protein model was trained based on presence/absence of gadolinium-positive (Gd+) lesions and was also strongly associated with new/enlarging T2 lesions, and active versus stable disease (composite of radiographic and clinical evidence of DA) with improved performance (p < 0.05) compared to the neurofilament light single protein model. The odds of having ≥1 Gd+ lesions with a moderate/high DA score were 4.49 times that of a low DA score, and the odds of having ≥2 Gd+ lesions with a high DA score were 20.99 times that of a low/moderate DA score. The MSDA Test was clinically validated with improved performance compared to the top-performing single-protein model and can serve as a quantitative tool to enhance the care of MS patients.

The New Zealand drug harms ranking study: A multi-criteria decision analysis.

AIMS: The harms arising from psychoactive drug use are complex, and harm reduction strategies should be informed by a detailed understanding of the extent and nature of that harm. Drug harm is also context specific, and so any comprehensive assessment of drug harm should be relevant to the characteristics of the population in question. This study aimed to evaluate and rank drug harms within Aotearoa New Zealand using a multi-criteria decision analysis (MCDA) framework, and to separately consider harm within the total population, and among youth. METHODS: Two facilitated workshops involved the separate ranking of harm for the total population, and then for youth aged 12-17, by two expert panels. In the total population workshop, 23 drugs were scored against 17 harm criteria, and those criteria were then evaluated using a swing weighting process. Scoring and weighting were subsequently updated during the youth-specific workshop. All results were recorded and analysed using specialised MCDA software. RESULTS: When considering overall harm, the MCDA modelling results indicated that alcohol, methamphetamine and synthetic cannabinoids were the most harmful to both the overall population and the youth, followed by tobacco in the total population. Alcohol remained the most harmful drug for the total population when separately considering harm to those who use it, and harm to others. CONCLUSIONS: The results provide detailed and context-specific insight into the harm associated with psychoactive drugs use within Aotearoa New Zealand. The findings also demonstrate the value of separately considering harm for different countries, and for different population subgroups.

Study rationale and baseline data for pilot trial of dronabinol adjunctive treatment of agitation in Alzheimer's dementia (THC-AD).

Agitation is a common complication of Alzheimer's dementia (Agit-AD) associated with substantial morbidity, high healthcare service utilization, and adverse emotional and physical impact on care partners. There are currently no FDA-approved pharmacological treatments for Agit-AD. We present the study design and baseline data for an ongoing multisite, three-week, double-blind, placebo-controlled, randomized clinical trial of dronabinol (synthetic tetrahydrocannabinol [THC]), titrated to a dose of 10 mg daily, in 80 participants to examine the safety and efficacy of dronabinol as an adjunctive treatment for Agit-AD. Preliminary findings for 44 participants enrolled thus far show a predominately female, white sample with advanced cognitive impairment (Mini Mental Status Examination mean 7.8) and agitation (Neuropsychiatric Inventory-Clinician Agitation subscale mean 14.1). Adjustments to study design in light of the COVID-19 pandemic are described. Findings from this study will provide guidance for the clinical utility of dronabinol for Agit-AD. ClinicalTrials.gov Identifier: NCT02792257.

Setting priorities for people with intellectual disability/intellectual developmental disorders across the lifespan: a call to action by the World Psychiatric Association.

People with DSM-5 intellectual disability/intellectual developmental disorder (ID/IDD) or ICD-11 disorders of intellectual development (DID) have multiple healthcare needs, but in many countries these needs are neither recognised nor managed effectively. This paper discusses the negative impact that stigma, discrimination and social exclusion have on the identification and care of persons with ID/IDD in low- and middle-income countries (LMICs). It also reviews different models of care for children, adolescents and adults. In discussing some initiatives in LMICs the emphasis is on early diagnosis, with success in providing locally sourced care for affected people and their families. This is where the medical, social and rights-based models of care intersect and is a premise of the person-centred biopsychosocial framework of the World Psychiatric Association's Presidential Action Plan 2020-2023. The plan invites psychiatrists to take a lead in changing the culture of care, as well as medical education, clinical training and research, with a renewed emphasis on workforce integration and service development in terms of community-based rehabilitation strategies.

Serum neurofilament levels and patient-reported outcomes in multiple sclerosis.

OBJECTIVE: Serum neurofilament light (sNfL) is a promising new biomarker in multiple sclerosis (MS). We explored the relationship between sNfL and health outcomes and resource use in MS patients. METHODS: MS patients with serum samples and health-outcome measurements collected longitudinally between 2011 and 2016 were analyzed. sNfL values were evaluated across age and gender. Data were analyzed using correlation with log-transformed sNfL values. RESULTS: A total of 304 MS patients with a mean age of 32.9 years, average EDSS of 1.6 (SD = 1.5) and baseline sNfL of 8.8 (range 1.23-78.3) pg/mL were studied. Baseline sNFL values increased with age and were higher in females. Baseline sNfL correlated with baseline Multiple Sclerosis Quality of Life physical composite (mean = 49.4 (9.1), P = 0.035) and baseline EDSS (P = 0.002). Other PRO measures at baseline did not show a significant relationship with baseline sNfL. Average of baseline and follow-up sNfL correlated with MSQoL physical-role limitations (mean = 48.9 (10.8), P = 0.043) and social-functioning (mean = 52.3 (7), P = 0.034) at 24-month follow-up. We found a trend for numerically higher sNfL levels in nonpersistent patients compared to those who were persistent to treatment (11.13 vs. 8.53 pg/mL, P = 0.093) measured as average of baseline and 24-month values. Baseline NfL was associated with number of intravenous steroid infusions (mean = 0.2; SD = 3.0, P = 0.013), whereas the average of baseline and 12 months NfL values related to inpatient stays at 12 months (mean = 0.2; SD = 3.0 P = 0.053). CONCLUSION: Serum NfL is a patient-centric biomarker that correlated with MS patient health-outcomes and healthcare utilization measures in a real-world cohort.

Bicycle helmet use and bicycling-related injury among young Canadians: an equity analysis.

INTRODUCTION: Cycling is a major activity for adolescents in Canada and potential differences exist in bicycling-related risk and experience of injury by population subgroup. The overall aim of this study was to inform health equity interventions by profiling stratified analytic methods and identifying potential inequities associated with bicycle-related injury and the use of bicycle helmets among Canadian youth. The two objectives of this study were: (1) To examine national patterns in bicycle ridership and also bicycle helmet use among Canadian youth in a stratified analysis by potentially vulnerable population subgroups, and (2) To examine bicycling-related injury in the same population subgroups of Canadian youth in order to identify possible health inequities. METHODS: Data for this study were obtained from the 6th cycle (2009/10) of the Health Behaviour in School-aged Children (HBSC) study, which is a general health survey that was completed by 26,078 students in grades 6-10 from 436 Canadian schools. Based on survey responses, we determined point prevalence for bicycle ridership, bicycle helmet use and relative risks for bicycling-related injury. RESULTS: Three quarters of all respondents were bicycle riders (n=19,410). Independent factors associated with bicycle ridership among students include being male, being a younger student, being more affluent, and being a resident of a small town. Among bicycle riders, 43% (95%CI ± 0.6%) reported never wearing and 32% (± 0.6%) inconsistently wearing a helmet. Only 26% (± 0.5%) of students reported always wearing a bicycle helmet. Helmets were less frequently used among older students and there were also important patterns by sex, geographic location and socioeconomic status. Adjusting for all other demographic characteristics, boys reported 2.02-fold increase (95% CI: 1.61 to 1.90) and new immigrants a 1.35-fold increase (95%CI: 1.00 to1.82) in the relative risk of bicycling-related injury in the past 12 months, as compared to girls and students born in Canada. The relative risk of injury did not vary significantly by levels of socioeconomic status. CONCLUSIONS: Troubling disparities exist in bicycle use, bicycle helmet use and bicycling-related injuries across specific population subgroups. Bicycle safety and injury prevention initiatives should be informed by disaggregated analyses and the context of bicycle-related health differences should be further examined.

Off-road vehicle ridership and associated helmet use in Canadian youth: an equity analysis.

PURPOSE: In North America, the use of off-road vehicles by young people is increasing, as are related injuries and fatalities. We examined the prevalence of off-road ridership and off-road helmet use in different subgroups of Canadian youth in order to better understand possible inequities associated with these health risk behaviors. METHODS: Data came from Cycle 6 (2009-2010) of the WHO Health Behavior in School-Aged Children Study (HBSC). Participants (n = 26,078) were young people from grades 6-10 in 436 Canadian schools. Students were asked, for a 12-mo recall period, how frequently they rode off-road vehicles and how often they wore a helmet while riding. Engagement in off-road ridership and helmet use were estimated by age group, gender, urban-rural geographic location, socioeconomic status, and how long participants had lived in Canada. FINDINGS: About half of the sample reported riding off-road vehicles (12,750; 52%). Among riders, 5,691 (45%) always wore helmets. Riders were more often older students, male and born in Canada. Students in rural areas and small towns were much more likely to ride off-road vehicles than their urban peers (RR, 95% CI: 1.28 [1.23-1.33]). Helmet use was less common among females, new immigrants, older students, and those in lower socioeconomic groups. There was little reported difference in helmet use by urban-rural location. CONCLUSIONS: Risks associated with the use of off-road vehicles and with nonhelmet use are not equitably distributed across Canadian youth. Factors characterizing off-road ridership (notably urban-rural location) are distinct from factors for helmet use. Preventive interventions should target population subgroups.

Drinking, substance use and the operation of motor vehicles by young adolescents in Canada.

BACKGROUND: Impaired driving is a recognized cause of major injury. Contemporary data are lacking on exposures to impaired driving behaviours and related injury among young adolescents, as well as inequities in these youth risk behaviours. METHODS AND FINDINGS: Cycle 6 (2009/10) of the Health Behaviour in School-Aged Children survey involved 26,078 students enrolled in 436 Canadian schools. We profiled cross-sectionally the reported use of alcohol, marijuana, or other illicit drugs by on-road and off-road vehicle operators when young adolescents (mean age 13.3 (± 1.6) years) were either driving or riding as a passenger. Comparisons were made across vulnerable subgroups. Multi-level logistic regression analyses were used to quantify the effects of the driving behaviours on risks for motor vehicle-related injury. Attributable risk fractions were also estimated. A total of 10% (± 3%) of participants reported recent operation of an on-road or off-road motor vehicle after consuming alcohol, marijuana, or other illicit drugs, while 21% (± 3%) reported riding as a passenger with a driver under the same conditions. Larger proportions of youth reporting these risk behaviours were males, and from older age groups, rural communities, and socio-economically disadvantaged populations. The behaviours were consistently associated with increased risks for motor vehicle-related injury at the individual level (RR 2.35; 95% CI: 1.54 to 3.58 for frequent vs. no exposure as a driver; RR 1.68; 95% CI: 1.20 to 2.36 for frequent vs. no exposure as a passenger) and at the population level (Attributable Risk Fraction: 7.1% for drivers; 14.0% for passengers). The study was limited mainly by its reliance on self-reported data. CONCLUSION: Impaired driving is an important health priority among young adolescents in Canada. Inequities in the involvement of younger adolescents in these risk behaviours suggest the need for targeted interventions for specific subgroups such as youth from rural communities, and among socially disadvantaged populations.

Ageing and health status in adults with intellectual disabilities: results of the European POMONA II study.

BACKGROUND: POMONA II was a European Commission public health-funded project. The research questions in this article focus on age-specific differences relating to environmental and lifestyle factors, and the 17 medical conditions measured by the POMONA Checklist of Health Indicators (P15). METHOD: The P15 was completed in a cross-sectional design for a stratified sample of 1,253 adults with ID across 14 European member states. RESULTS: Older people (55+) were more likely to live in larger residential homes. Rates of smoking and use of alcohol were lower than in the general population but were higher with older age. More than 60% of older adults had a sedentary lifestyle. Cataract, hearing disorder, diabetes, hypertension, osteoarthritis/arthrosis, and osteoporosis were positively associated with advancing age; allergies and epilepsy, negatively associated. CONCLUSIONS: Some evidence of health disparities was found for older people with ID, particularly in terms of underdiagnosed or inadequately managed preventable health conditions.

Implementing a collaborative protocol in a sepsis intervention program: lessons learned.

The objective of this prospective cohort study was to see the effect of the implementation of a Sepsis Intervention Program on the standard processes of patient care using a collaborative approach between the Emergency Department (ED) and Medical Intensive Care Unit (MICU). This was performed in a large urban tertiary-care hospital, with no previous experience utilizing a specific intervention program as routine care for septic shock and which has services and resources commonly available in most hospitals. The study included 106 patients who presented to the ED with severe sepsis or septic shock. Eighty-seven of those patients met the inclusion criteria for complete data analysis. The ED and MICU staff underwent a 3-month training period followed by implementation of a protocol for sepsis intervention program over 6 months. In the first 6 months of the program's implementation, 106 patients were admitted to the ED with severe sepsis and septic shock. During this time, the ED attempted to initiate the sepsis intervention protocol in 76% of the 87 septic patients who met the inclusion criteria. This was assessed by documentation of a central venous catheter insertion for continuous SvO(2) monitoring in a patient with sepsis or septic shock. However, only 48% of the eligible patients completed the early goal-directed therapy (EGDT) protocol. Our data showed that the in-hospital mortality rate was 30.5% for the 87 septic shock patients with a mean APACHE II score of 29. This was very similar to a landmark study of EGDT (30.5% mortality with mean APACHE II of 21.5). Data collected on processes of care showed improvements in time to fluid administration, central venous access insertion, antibiotic administration, vasopressor administration, and time to MICU transfer from ED arrival in our patients enrolled in the protocol versus those who were not. Further review of our performance data showed that processes of care improved steadily the longer the protocol was in effect, although this was not statistically significant. There was no improvement in secondary outcomes, including total length of hospital stay, MICU days, and mortality. Implementation of a sepsis intervention program as a standard of care in a typical hospital protocol leads to improvements in processes of care. However, despite a collaborative approach, the sepsis intervention program was underutilized with only 48% of the patients completing the sepsis intervention protocol.

Characteristics, supports, and quality of life of Irish adults with intellectual disability in life-sharing residential communities.

BACKGROUND: Few empirical studies have compared quality and outcomes for residents with intellectual disability across intentional communities such as those organised by the Camphill communities in Ireland. METHOD: Using a multi-element research protocol developed for an earlier large study, data were gathered about the characteristics of N = 29 participants living in life-sharing residences organised by Camphill, management procedures, and outcomes for residents. Comparable data were available for N = 125 adults in group homes or campus residences. RESULTS: Camphill residents reported a smaller size of household, higher staffing ratios, homely living areas, low levels of institutionalised practices such as social distance, reciprocal relationships with houseparents, and well-developed management procedures, as well as less choice, but were not found to be better on a range of other objective measures. CONCLUSION: Although modest in scale, present findings suggest that the value of applying distinctive benefits of life-sharing communities in more typical residential settings for people with intellectual disability should be investigated further to inform current policy debates.

Sampling and ethical issues in a multicenter study on health of people with intellectual disabilities.

OBJECTIVES: To study health inequalities in persons with intellectual disabilities, representative and unbiased samples are needed. Little is known about sample recruitment in this vulnerable group. This study aimed to determine differences in ethical procedures and sample recruitment in a multicenter research on health of persons with intellectual disabilities. Study questions regarded the practical sampling procedure, how ethical consent was obtained in each country, and which person gave informed consent for each study participant. STUDY DESIGN AND SETTING: Exploratory, as part of a multicenter study, in 14 European countries. After developing identical guidelines for all countries, partners collected data on health indicators by orally interviewing 1,269 persons with intellectual disabilities. Subsequently, semistructured interviews were carried out with partners and researchers. RESULTS: Identification of sufficient study participants proved feasible. Sampling frames differed from nationally estimated proportions of persons with intellectual disabilities living with families or in residential settings. Sometimes, people with intellectual disabilities were hard to trace. Consent procedures and legal representation varied broadly. Nonresponse data proved unavailable. CONCLUSION: To build representative unbiased samples of vulnerable groups with limited academic capacities, international consensus on respectful consent procedures and tailored patient information is necessary.

Examining the prevalence of epilepsy and delivery of epilepsy care in Ireland.

PURPOSE: To examine the prevalence of epilepsy and delivery of epilepsy care in Ireland. METHODS: A multiple case ascertainment methodology was employed examining five nationwide data sources. Data were obtained via (1) a nationwide population-based health survey, (2) secondary data analysis of all reimbursements for prescriptions of antiepilepsy medication nationwide from 2002 to 2005, (3) a nationwide survey of primary care community-based physicians, (4) a nationwide survey of specialist care hospital-based neurologists, and (5) secondary data analysis of inpatient discharges from acute hospitals nationwide for persons with a diagnosis of epilepsy between 2000 and 2005. RESULTS: The findings indicate that nationwide approximately (1) 10 per 1,000 persons (n = 31,000) 18 years and older have self-reported lifetime prevalence of epilepsy, (2) 8.3-9 per 1,000 (approximately 33,000-36,000) persons 5 years and older are being treated for epilepsy using antiepilepsy medication, (3) the typical general practitioner provides care to an average of 13 patients with active epilepsy and epilepsy in remission with treatment, (4) specialist care is provided on a weekly basis to approximately 442 persons with active epilepsy and epilepsy in remission with treatment, and (5) approximately 67 discharges for persons with a primary or secondary diagnosis of epilepsy are reported from acute hospitals weekly. DISCUSSION: This study is distinguished as the first nationwide prevalence study of epilepsy in Europe and provides previously unavailable data on this population in Ireland. Moreover, this study illustrates the merits of secondary data analysis of existing sources when access to clinical sources for the purpose of identifying epidemiologic samples is limited.

Health indicators and intellectual disability.

PURPOSE OF REVIEW: Health disparities are evident between people with intellectual disabilities and the general population. Despite the potential of indicators for measuring disparities and planning interventions to address inequalities- currently a priority health policy target- few studies have mapped the physical or mental health of people with intellectual disabilities onto the growing territory of health disparities, health information systems and health indicators. This review summarizes recent publications about the role of indicators in gathering optimal health information on behalf of this segment of the population. RECENT FINDINGS: Studies related to measures of the health of people with intellectual disabilities are presented in three sections: information captured in general population surveys; measures of health status of people with intellectual disabilities at country and regional levels; and their use of healthcare systems. The work of the Pomona group of European partners who have devised and applied a set of health indicators specifically for people with intellectual disabilities is presented. SUMMARY: Health indicators yield data to identify health conditions, plan interventions and compare populations or segments of the population. It is suggested that better definitions, measures and surveillance will yield comparable information to inform public health policy and clinical practice.

Communication among nurses and adults with severe and profound intellectual disabilities: predicted and observed strategies.

This study explored communication strategies adopted by staff nurses in a residential centre in Ireland for persons with severe and profound intellectual disabilities. Interactions between staff nurses and service users were video recorded and analysed to determine the frequencies of verbal and non-verbal communication acts. Semi-structured and focus group interviews were carried out with the 10 participating staff nurses. Participants identified staff-related factors, the communicative environment, alternative methods of communication and choice as key elements in communicating with service users. No differences were observed in the frequency of verbal and non-verbal communicative acts. There was a discrepancy between what communicative acts the participants named as their preferred strategies and those observed when they interacted with service users. Most failed to adjust their language to meet service users' needs. The findings suggest that staff nurses do not always adopt optimal strategies in everyday interactions with individuals who use non-verbal communication. Continuing education in communication is recommended.

Male patients with paranoid schizophrenia have greater ACTH and cortisol secretion in response to metoclopramide-induced AVP release.

Dynamic testing of the hypothalamic-pituitary-adrenal axis in schizophrenia has yielded conflicting results, which may be related to patient selection and previous exposure to psychotropic medication. The objective of this study was to determine the pattern of corticotropin (ACTH) and cortisol release in response to metoclopramide (a dopamine antagonist), which appears to be unique in its ability to release vasopressin (AVP), in drug naive patients with schizophrenia experiencing their first episode of psychosis. In this study, we examined AVP, ACTH and cortisol release in response to metoclopramide in 10 drug-naive, first-episode male patients with a DSM IV diagnosis of paranoid schizophrenia and compared them to healthy control subjects matched for age, sex and smoking status. Patients, as compared to controls had higher levels of baseline plasma cortisol (375.5+/-47.4/l vs. 273.8+/-42.2 nmol/l, respectively; t=2.48, df=9, p< 0.02) and plasma ACTH (14.9+/-0.85 vs. 11.3+/-0.57 pg/ml, respectively; t=4.29, df=9, p<0.001). AVP levels were lower in patients though this did not reach statistical significance (0.89+/-0.09 vs. 1.3+/-0.08 pmol/l, respectively; t=1.97, df=9, p<0.07). A repeated measures 2-way ANOVA to compare responses to metoclopramide over time between the two groups yielded a significant group by time interaction for cortisol (F=11.3, df=6, 108, p<0.001) and ACTH (F=15.65, df=6, 108, p<0.002). Post hoc Tukey's test revealed significant differences between the two groups at +30, +45, +60, +90 and +120 min for cortisol (p<0.01) and at +30, +45, +60 and +90 min for ACTH (p<0.01). The group by time interactions continued to remain significant when cortisol (F=10.9, df=6, 107, p<0.001) and ACTH (F=13.04, df=6, 108, p<0.002) were entered as co-variates. There was a significant positive correlation between AVP and cortisol responses in patients (r=0.65, df=8, p<0.01). Male patients with paranoid schizophrenia release greater amounts of ACTH and cortisol in responses to metoclopramide-induced AVP secretion than control subjects.

Ageing and health issues in intellectual disabilities.

PURPOSE OF REVIEW: This review summarizes recent research and evidence-based practice and policy guidelines from 31 articles or books focused on the health of ageing individuals with intellectual disabilities. RECENT FINDINGS: Findings are presented under four headings that correspond to categories of health measures applied in recent EU evidence-based public health documents. Large group studies, notably longitudinal studies, have advanced knowledge of the health-related attributes of the population of older adults with intellectual disabilities and their distinctive health risks, including those linked to aetiologies. Empirical studies applying various research designs and literature reviews presented findings about weight and levels of physical activity, prevalent health problems (e.g. high levels of sensory impairment, risk factors for coronary artery disease) and other aspects of the health status of this population. Efforts to improve assessment methods for dementia continue. Evidence from small group studies in Israel and the USA suggests that interventions to increase physical activity and functioning of older adults may be beneficial. Pharmacological studies consider treatments for dementia as well as widespread prescription of medications to manage challenging behaviours. Health system issues include access to health care, training for health professionals, support for family care givers, end of life care and more cohesive national health policies. SUMMARY: Health-related research in older people with intellectual disabilities has extended our understanding of the characteristics of this population relative to other groups of older individuals and to national populations in terms of health status, determinants of health and priorities for policy and practice.

Retreat and resilience: life experiences of older women with intellectual disabilities.

Older women with intellectual disabilities remain the least studied and understood members of the disability population, and yet they often live well into late adulthood. In this exploratory study we used extensive interviews to examine the demographics, economic and personal safety nets, health, social roles, and well-being of 29 Irish and American older women with intellectual disabilities. Results suggest that these women have very limited resources, social networks, and opportunities. All the women were poor and most lived in group residences, with paid staff as their main allies and careproviders. They reported that their health was good, though it often limited their activities. Despite their societal limitations, these women reported this is the happiest period of their lives.