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Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype. Broad approval of therapy necessitates close follow-up of potential rare adverse events and effectiveness in the larger real-world population.
The Canadian Neuromuscular Disease Registry (CNDR) undertook an iterative multi-stakeholder process to expand the existing SMA dataset to capture items relevant to patient outcomes in a post-marketing environment. The CNDR SMA expanded registry is a longitudinal, prospective, observational study of patients with SMA in Canada designed to evaluate the safety and effectiveness of novel therapies and provide practical information unattainable in trials.
The consensus expanded dataset includes items that address therapy effectiveness and safety and is collected in a multicenter, prospective, observational study, including SMA patients regardless of therapeutic status. The expanded dataset is aligned with global datasets to facilitate collaboration. Additionally, consensus dataset development aimed to standardize appropriate outcome measures across the network and broader Canadian community. Prospective outcome studies, data use, and analyses are independent of the funding partner.
Prospective outcome data collected will provide results on safety and effectiveness in a post-therapy approval era. These data are essential to inform improvements in care and access to therapy for all SMA patients.
Unemployment is common in persons with severe mental illness (SMI) and more in Latino population. Department of Mental Health and Addiction Services (DMHAS) of Connecticut offers a supported employment (SE) Program to help clients get competitive work in integrated settings with nondisabled workers in the community.
Capture perspectives of key informant groups to describe barriers for linking Latinos with SMI to employment and adapt SE Services for subpopulations.
Four focus groups were conducted (employment specialists, case managers and peer support counselors/employers/two with clients-one in Spanish and other in English). They were conducted during January-February 2015, 70–90 minutes each one. A question guide was developed for each group. Participants per focus group ranged from 3–10, voluntarily. Two new questionnaires to the baseline pack were developed: challenges to Employment Assessment–provider and client version.
Thirty individuals participated. Several barriers to employment were reported. Clients and staff reported criminal record, lack of employment history and lack of motivation. Staff described client hygiene, mental status, physical health, substance abuse and discrimination. Clients, staff and employers reported language barrier for Latinos who don’t speak English. Non-adherence to medication was reported by clients and employers. About Spanish-Speaking Latinos with mental illness, medication, discrimination, previous abuse by employers, inappropriate employment, difficulties of the job interview and computer skills appeared as challenges. English-Speaking Latinos with mental illness identified transport, stability, support, keeping apartment and financial needs.
Focus groups can help in knowledge about the diversity of Latino communities to improve SE Services and outcomes for Latinos.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Introduction: Although oral rehydration therapy is recommended for children with acute gastroenteritis (AGE) with none to some dehydration, intravenous (IV) rehydration is still commonly administered to these children in high-income countries. IV rehydration is associated with pain, anxiety, and emergency department (ED) revisits in children with AGE. A better understanding of the factors associated with IV rehydration is needed to inform knowledge translation strategies. Methods: This was a planned secondary analysis of the Pediatric Emergency Research Canada (PERC) and Pediatric Emergency Care Applied Research Network (PECARN) randomized, controlled trials of oral probiotics in children with AGE-associated diarrhea. Eligible children were aged 3-48 months and reported > 3 watery stools in a 24-hour period. The primary outcome was administration of IV rehydration at the index ED visit. We used mixed-effects logistic regression model to explore univariable and multivariable relationships between IV rehydration and a priori risk factors. Results: From the parent study sample of 1848 participants, 1846 had data available for analysis: mean (SD) age of 19.1 ± 11.4 months, 45.4% females. 70.2% (1292/1840) vomited within 24 hours of the index ED visit and 34.1% (629/1846) received ondansetron in the ED. 13.0% (240/1846) were administered IV rehydration at the index ED visit, and 3.6% (67/1842) were hospitalized. Multivariable predictors of IV rehydration were Clinical Dehydration Scale (CDS) score [compared to none: mild to moderate (OR: 8.1, CI: 5.5-11.8); severe (OR: 45.9, 95% CI: 20.1-104.7), P < 0.001], ondansetron in the ED (OR: 1.8, CI: 1.2-2.6, P = 0.003), previous healthcare visit for the same illness [compared to no prior visit: prior visit with no IV (OR: 1.9, 95% CI: 1.3-2.9); prior visit with IV (OR: 10.5, 95% CI: 3.2-34.8), P < 0.001], and country [compared to Canada: US (OR: 4.1, CI: 2.3-7.4, P < 0.001]. Significantly more participants returned to the ED with symptoms of AGE within 3 days if IV fluids were administered at the index visit [30/224 (13.4%) versus 88/1453 (6.1%), P < 0.001]. Conclusion: Higher CDS scores, antiemetic use, previous healthcare visits and country were independent predictors of IV rehydration which was also associated with increased ED revisits. Knowledge translation focused on optimizing the use of antiemetics (i.e. for those with dehydration) and reducing the geographic variation in IV rehydration use may improve the ED experience and reduce ED-revisits.
The Garamantes were the earliest urbanised population in the Central Sahara, and their socio-political and economic histories have been the subject of extensive study.However, little is known about their biological origins. Building on the results obtained in the Desert Migrations Project, the biocultural theme within the Trans-SAHARA Project has sought to answer two main questions relating to human migration in the Central Sahara. First, it aimed to determine what (if any) biological and cultural links can be established between the historical kingdom of the Garamantes and the preceding late Neolithic (Pastoral) and contemporary peoples in the surrounding Saharan, Sahelian, Nilotic and Mediterranean regions. Second, the project aimed to investigate aspects of the diet and individual mobility of the people who were buried in the Garamantian cemeteries of the Wadi al-Ajal, in direct comparison with results from the analysis of people from the surrounding regions.
People with pancreatic cancer have poor survival, and management is challenging. Pancreatic cancer patients' perceptions of their care coordination and its association with their outcomes have not been well-studied. Our objective was to determine if perception of care coordination is associated with patient-reported outcomes or survival.
People with pancreatic cancer who were 1–8 months postdiagnosis (52 with completed resection and 58 with no resection) completed a patient-reported questionnaire that assessed their perceptions of care coordination, quality of life, anxiety, and depression using validated instruments. Mean scores for 15 care-coordination items were calculated and then ranked from highest (best experience) to lowest (worst experience). Associations between care-coordination scores (including communication and navigation domains) and patient-reported outcomes and survival were investigated using general linear regression and Cox regression, respectively. All analyses were stratified by whether or not the tumor had been resected.
In both groups, the highest-ranked care-coordination items were: knowing who was responsible for coordinating care, health professionals being informed about their history, and waiting times. The worst-ranked items related to: how often patients were asked about visits with other health professionals and how well they and their family were coping, knowing the symptoms they should monitor, having sufficient emotional help from staff, and access to additional specialist services. For people who had a resection, better communication and navigation scores were significantly associated with higher quality of life and less anxiety and depression. However, these associations were not statistically significant for those with no resection. Perception of cancer care coordination was not associated with survival in either group.
Significance of results:
Our results suggest that, while many core clinical aspects of care are perceived to be done well for pancreatic cancer patients, improvements in emotional support, referral to specialist services, and self-management education may improve patient-reported outcomes.
To achieve their conservation goals individuals, communities and organizations need to acquire a diversity of skills, knowledge and information (i.e. capacity). Despite current efforts to build and maintain appropriate levels of conservation capacity, it has been recognized that there will need to be a significant scaling-up of these activities in sub-Saharan Africa. This is because of the rapid increase in the number and extent of environmental problems in the region. We present a range of socio-economic contexts relevant to four key areas of African conservation capacity building: protected area management, community engagement, effective leadership, and professional e-learning. Under these core themes, 39 specific recommendations are presented. These were derived from multi-stakeholder workshop discussions at an international conference held in Nairobi, Kenya, in 2015. At the meeting 185 delegates (practitioners, scientists, community groups and government agencies) represented 105 organizations from 24 African nations and eight non-African nations. The 39 recommendations constituted six broad types of suggested action: (1) the development of new methods, (2) the provision of capacity building resources (e.g. information or data), (3) the communication of ideas or examples of successful initiatives, (4) the implementation of new research or gap analyses, (5) the establishment of new structures within and between organizations, and (6) the development of new partnerships. A number of cross-cutting issues also emerged from the discussions: the need for a greater sense of urgency in developing capacity building activities; the need to develop novel capacity building methodologies; and the need to move away from one-size-fits-all approaches.
Laboratory tasks to delineate anxiety disorder features are used to refine classification and inform our understanding of etiological mechanisms. The present study examines laboratory measures of response inhibition, specifically the inhibition of a pre-potent motor response, in clinical anxiety. Data on associations between anxiety and response inhibition remain inconsistent, perhaps because of dissociable effects of clinical anxiety and experimentally manipulated state anxiety. Few studies directly assess the independent and interacting effects of these two anxiety types (state v. disorder) on response inhibition. The current study accomplished this goal, by manipulating state anxiety in healthy and clinically anxious individuals while they complete a response inhibition task.
The study employs the threat-of-shock paradigm, one of the best-established manipulations for robustly increasing state anxiety. Participants included 82 adults (41 healthy; 41 patients with an anxiety disorder). A go/nogo task with highly frequent go trials was administered during alternating periods of safety and shock threat. Signal detection theory was used to quantify response bias and signal-detection sensitivity.
There were independent effects of anxiety and clinical anxiety on response inhibition. In both groups, heightened anxiety facilitated response inhibition, leading to reduced nogo commission errors. Compared with the healthy group, clinical anxiety was associated with excessive response inhibition and increased go omission errors in both the safe and threat conditions.
Response inhibition and its impact on go omission errors appear to be a promising behavioral marker of clinical anxiety. These results have implications for a dimensional view of clinical anxiety.
Many medications administered to patients with schizophrenia possess anticholinergic properties. When aggregated, pharmacological treatments may result in a considerable anticholinergic burden. The extent to which anticholinergic burden has a deleterious effect on cognition and impairs ability to participate in and benefit from psychosocial treatments is unknown.
Seventy patients were followed for approximately 3 years. The MATRICS consensus cognitive battery (MCCB) was administered at baseline. Anticholinergic burden was measured with the Anticholinergic Cognitive Burden (ACB) scale. Ability to benefit from psychosocial programmes was measured using the DUNDRUM-3 Programme Completion Scale (D-3) at baseline and follow-up. Psychiatric symptoms were measured using the PANSS. Total antipsychotic dose was measured using chlorpromazine equivalents. Functioning was measured using the Social and Occupational Functioning Assessment Scale (SOFAS).
Mediation analysis found that the influence of anticholinergic burden on ability to participate and benefit from psychosocial programmes was completely mediated by the MCCB. For every 1-unit increase on the ACB scale, change scores for DUNDRUM-3 decreased by −0.27 points. This relationship appears specific to anticholinergic burden and not total antipsychotic dose. Moreover, mediation appears to be specific to cognition and not psychopathology. Baseline functioning also acted as mediator but only when MCCB was not controlled for.
Anticholinergic burden has a significant impact on patients’ ability to participate in and benefit from psychosocial treatment programmes. Physicians need to be mindful of the cumulative effect that medications can have on patient cognition, functional capacity and ability to benefit from psychosocial treatments.
Patient registries represent an important method of organizing “real world” patient information for clinical and research purposes. Registries can facilitate clinical trial planning and recruitment and are particularly useful in this regard for uncommon and rare diseases. Neuromuscular diseases (NMDs) are individually rare but in aggregate have a significant prevalence. In Canada, information on NMDs is lacking. Barriers to performing Canadian multicentre NMD research exist which can be overcome by a comprehensive and collaborative NMD registry.
We describe the objectives, design, feasibility and initial recruitment results for the Canadian Neuromuscular Disease Registry (CNDR).
The CNDR is a clinic-based registry which launched nationally in June 2011, incorporates paediatric and adult neuromuscular clinics in British Columbia, Alberta, Ontario, Quebec, New Brunswick and Nova Scotia and, as of December 2012, has recruited 1161 patients from 12 provinces and territories. Complete medical datasets have been captured on 460 “index disease” patients. Another 618 “non-index” patients have been recruited with capture of physician-confirmed diagnosis and contact information. We have demonstrated the feasibility of blended clinic and central office-based recruitment. “Index disease” patients recruited at the time of writing include 253 with Duchenne and Becker muscular dystrophy, 161 with myotonic dystrophy, and 71 with ALS.
The CNDR is a new nationwide registry of patients with NMDs that represents an important advance in Canadian neuromuscular disease research capacity. It provides an innovative platform for organizing patient information to facilitate clinical research and to expedite translation of recent laboratory findings into human studies.
We summarise recent progress in understanding the star formation activity in early-type galaxies (ETGs), using recent studies that leverage photometry in the rest-frame ultraviolet (UV) wavelengths. While classically thought to be old, passively-evolving systems, recent UV studies have revealed widespread star formation in ETGs, with ~20% of the stellar mass in today's ETGs forming at late epochs (z < 1). A strong correlation is found between the presence of morphological disturbances and blue UV colours, suggesting that the star formation is merger-driven. However, the major merger rate at late epochs is far too low to satisfy the number of disturbed ETGs, indicating that minor mergers drive the star formation in these galaxies over the latter half of cosmic time. Together with the recent literature which suggests that minor mergers may drive the size evolution of massive ETGs, these results highlight the significant role of minor mergers in driving the evolution of massive galaxies in the low and intermediate-redshift Universe.
Although Lyme borreliosis is increasingly diagnosed in the United Kingdom, few systematic studies have been performed there. UK data suggest that the commonest complications are neurological, but inadequate information exists about their nature and the incidence of late neuroborreliosis. Local data are necessary because clinical presentations may show geographical variation. This study aimed to provide data on clinical manifestations in an area of South West England and to estimate treatment delay. We reviewed clinical records of 88 patients in the Royal Devon and Exeter Hospital catchment area who had positive Borrelia antibody tests during a 5-year period. Fifty-six (64%) reported tick bites. The commonest presentations were erythema migrans (65%) and arthralgia/myalgia (27%). However, 22 patients (25%) had neurological symptoms other than headache alone. Fourteen had facial palsy, eight had confusion/drowsiness, four had meningism, five had radiculopathy, two had sixth nerve palsies, and two had peripheral neuropathies. No late, progressive or atypical neurological syndromes were found. Neurological manifestations were generally predictable and usually included either (or all) of meningoencephalitis, facial palsy or radiculopathy.
Changes in physical body size during gestation were monitored using 529 sets of sow measurements. All sows were from the same herd and production system with a range in parity from 1 to 8. Sows were individually weighed, P2 backfat thickness was determined by ultrasound and morphometric measurements of body size were taken five times during gestation: day 0 (at service), day 25, day 50, day 80 and day 110. The morphometric measurements included sow height (from floor to last rib at the midline, from floor to ventral surface and from floor to hip), heart girth, depth of last rib, length (from snout to tail and from anterior scapula to tail) and width (at ham, at last rib and at shoulder). Regression analyses were used to model the relationship between day of gestation or parity number and morphometric measurements of body size. Regression equations were also developed to estimate sow weight from physical measurements, day of gestation and parity. As expected, sow dimensions, in general, increased as pregnancy progressed and also with increasing parity number. The relationships between day of gestation and body dimensions were described by linear and quadratic regression models, which had a range of adjusted R2 values up to 0.99. Similar relationships to parity number had a range of R2 values between 0.51 and 0.96. Sow depth, which can be used as an estimate of the width of the sow when lying, equalled the maximum width of the gestation stall (650 mm) at day 103 of gestation. However, by day 40 of gestation, predicted mean sow depth (570 mm) equalled the width at the rear of the crate. The implication of this is that after day 40 of gestation, the average sow was too wide for the rear of the crate when lying in a recumbent position. On day 110 of gestation, 95% of the mean sow body depths would be accommodated in stalls that were 674 mm wide; however, the range in body sizes with increasing parity number suggests the use of more than one stall width would be appropriate. Sow weight could be estimated with an adjusted R2 value of 0.81 and with a residual standard deviation (r.s.d.) of 16.5 kg using heart girth alone, or more accurately using a model with parity, day of gestation, P2 backfat depth and heart girth as the parameters (R2 = 0.89, r.s.d. 12.4 kg).