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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.
To utilise a community-based participatory approach in the design and implementation of an intervention targeting diet-related health problems on Navajo Nation.
A dual strategy approach of community needs/assets assessment and engagement of cross-sectorial partners in programme design with systematic cyclical feedback for programme modifications.
Navajo Nation, USA.
Navajo families with individuals meeting criteria for programme enrolment. Participant enrolment increased with iterative cycles.
The Navajo Fruit and Vegetable Prescription (FVRx) Programme.
A broad, community-driven and culturally relevant programme design has resulted in a programme able to maintain core programmatic principles, while also allowing for flexible adaptation to changing needs.
Public awareness of ‘red flag’ symptoms for head and neck cancer is low. There is a lack of evidence regarding patient concerns and expectations in consultations for cancer assessment.
This prospective questionnaire study examined the symptoms, concerns and expectations of 250 consecutive patients attending an ‘urgent suspicion of cancer’ clinic at a tertiary referral centre.
The patients’ most frequent responses regarding their concerns were ‘no concerns’ (n = 72, 29 per cent); ‘all symptoms’ were a cause for concern (n = 65, 26 per cent) and ‘neck lump’ was a symptom causing concern (n = 37, 17 per cent). The expectations of patients attending clinic were that they would find out what was wrong with them, followed by having no expectations at all. Overall patient knowledge of red flag symptoms was lacking and their expectations were low.
Patients with non-cancer symptoms are frequently referred with suspected cancer. Patients with red flag symptoms are not aware of their significance and they have low expectations of healthcare.
To evaluate the association between novel pre- and post-operative biomarker levels and 30-day unplanned readmission or mortality after paediatric congenital heart surgery.
Children aged 18 years or younger undergoing congenital heart surgery (n = 162) at Johns Hopkins Hospital from 2010 to 2014 were enrolled in the prospective cohort. Collected novel pre- and post-operative biomarkers include soluble suppression of tumorgenicity 2, galectin-3, N-terminal prohormone of brain natriuretic peptide, and glial fibrillary acidic protein. A model based on clinical variables from the Society of Thoracic Surgery database was developed and evaluated against two augmented models.
Unplanned readmission or mortality within 30 days of cardiac surgery occurred among 21 (13%) children. The clinical model augmented with pre-operative biomarkers demonstrated a statistically significant improvement over the clinical model alone with a receiver-operating characteristics curve of 0.754 (95% confidence interval: 0.65–0.86) compared to 0.617 (95% confidence interval: 0.47–0.76; p-value: 0.012). The clinical model augmented with pre- and post-operative biomarkers demonstrated a significant improvement over the clinical model alone, with a receiver-operating characteristics curve of 0.802 (95% confidence interval: 0.72–0.89; p-value: 0.003).
Novel biomarkers add significant predictive value when assessing the likelihood of unplanned readmission or mortality after paediatric congenital heart surgery. Further exploration of the utility of these novel biomarkers during the pre- or post-operative period to identify early risk of mortality or readmission will aid in determining the clinical utility and application of these biomarkers into routine risk assessment.
The Assessing and Caring for Patients’ Expectations in Laryngology (‘ACaPELa’) questionnaire was developed to guide laryngology clinic consultations. This study aimed to audit its use, revise it depending on outcomes and validate it.
The questionnaire was completed by all new patients attending a laryngology clinic over one year. The questionnaire was refined and validated in a new cohort of patients over a six-month period.
Thirty-seven of 242 patients (15.3 per cent) incorrectly gave the same ranking to more than one question. Questions with similar content were collapsed to cover broader themes, and an outcome question was added, resulting in the five-item Assessing and Caring for Patients’ Expectations in Laryngology – Revised (‘ACaPELa-R’) questionnaire. Using this revised questionnaire, there was a significant reduction in the number of same-ranked questions (4.4 vs 15.3 per cent; p = 0.003) and high patient satisfaction post-consultation (95.7 per cent).
The Assessing and Caring for Patients' Expectations in Laryngology – Revised questionnaire makes patients’ rank ordering of questions easier. It can be used to inform how different topics should be approached during the consultation and utilised for clinician self-audit.
Introduction: It is critical for planning, clinical care and resource optimization to understand patterns of emergency department (ED) utilization. Individuals who have experienced adverse childhood experiences (ACE) are known to have more unhealthy behaviors and worse health outcomes as adults and therefore may be more frequent ED users. Adverse childhood experiences include physical, sexual and emotional abuse or neglect, substance abuse in the family, witnessing violence, having a parent incarcerated or parents getting divorced or separated. To date there are few studies exploring the relationship between ACE and ED utilization. Methods: This a mixed qualitative and quantitative study. It includes analysis of data collected through a survey, a retrospective chart review and focus group discussions. The survey was administered to a convenience sample of adult patients (CTAS 2 -5) presenting to EDs in Kingston Ontario, and consisted of two validated tools that measured exposure to ACE and resiliency. Demographic data and ED utilization frequency for 12 months prior to the index visit were extracted from an electronic medical record for each patient completing the survey. A sample of participants with a high ACE burden (ACE score > 4) were invited to participate in focus groups to explore their experiences of care in the ED. Demographic, ED utilization and health status data were summarized and statistically significant patterns between high ACE and lower ACE patients were determined using Chi2t or t-tests. Transcripts from the focus groups were thematically analyzed using NVivo software by 2 independent researchers. Results: 1693 surveys were collected, 301 (18%) were deemed to have a high ACE score, data analysis is ongoing. The primary outcome is the relationship between ACE and the frequency of ED utilization among adult patients presenting to EDs in Kingston, ON. Secondary outcomes include evaluating the role of resilience as a potential mitigating factor, describing the demographics of high ACE burden frequent ED visitors, and the experiences of care for individuals with high ACE burden in the ED. These outcomes will be utilized to inform hypotheses for future studies and potential interventions aimed at optimizing ED utilization and patient care experience. Conclusion: This study provides novel insight into the relationship between ACE burden and ED utilization while also describing the demographics and experiences of care for ED patients with a high ACE score. Data analysis is on-going.
Limbic white matter pathways link emotion, cognition, and behavior and are potentially malleable to the influences of traumatic events throughout development. However, the impact of interactions between childhood and later life trauma on limbic white matter pathways has yet to be examined. Here, we examined whether childhood maltreatment moderated the effect of combat exposure on diffusion tensor imaging measures within a sample of military veterans (N = 28). We examined five limbic tracts of interest: two components of the cingulum (cingulum, cingulate gyrus, and cingulum hippocampus [CGH]), the uncinate fasciculus, the fornix/stria terminalis, and the anterior limb of the internal capsule. Using effect sizes, clinically meaningful moderator effects were found only within the CGH. Greater combat exposure was associated with decreased CGH fractional anisotropy (overall structural integrity) and increased CGH radial diffusivity (perpendicular water diffusivity) among individuals with more severe childhood maltreatment. Our findings provide preliminary evidence of the moderating effect of childhood maltreatment on the relationship between combat exposure and CGH structural integrity. These differences in CGH structural integrity could have maladaptive implications for emotion and memory, as well as provide a potential mechanism by which childhood maltreatment induces vulnerability to later life trauma exposure.
The fragmented ecosystems along the Niagara Escarpment World Biosphere Reserve provide important habitats for biota including lichens. Nonetheless, the Reserve is disturbed by dense human populations and associated air pollution. Here we investigated patterns of lichen diversity within urban and rural sites at three different locations (Niagara, Hamilton, and Owen Sound) along the Niagara Escarpment in Ontario, Canada. Our results indicate that both lichen species richness and community composition are negatively correlated with increasing human population density and air pollution. However, our quantitative analysis of community composition using canonical correspondence analysis (CCA) indicates that human population density and air pollution is more independent than might be assumed. The CCA analysis suggests that the strongest environmental gradient (CCA1) associated with lichen community composition includes regional pollution load and climatic variables; the second gradient (CCA2) is associated with local pollution load and human population density factors. These results increase the knowledge of lichen biodiversity for the Niagara Escarpment and urban and rural fragmented ecosystems as well as along gradients of human population density and air pollution; they suggest a differential influence of regional and local pollution loads and population density factors. This study provides baseline knowledge for further research and conservation initiatives along the Niagara Escarpment World Biosphere Reserve.
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. In the absence of high-level evidence base for follow-up practices, the duration and frequency are often at the discretion of local centres. By reviewing the existing literature and collating experience from varying practices across the UK, this paper provides recommendations on the work up and management of lateral skull base cancer based on the existing evidence base for this rare condition.
• Patients should be followed up to a minimum of five years with a prolonged follow-up for selected patients. (G)
• Patients should be followed up at least two monthly in the first two years and three to six monthly in the subsequent years. (G)
• Patients should be seen in dedicated multidisciplinary head and neck oncology clinics. (G)
• Patients should be followed up by dedicated multidisciplinary clinical teams. (G)
• The multidisciplinary follow-up team should include clinical nurse specialists, speech and language therapists, dietitians and other allied health professionals in the role of key workers. (G)
• Clinical assessment should include adequate clinical examination including fibre-optic rigid or flexible nasopharyngolaryngoscopy. (R)
• Magnetic resonance imaging and positron emission tomography combined with computed tomography imaging should be used when recurrence is suspected. (R)
• Narrow band imaging can be used in the follow-up in selected sites. (R)
• Second primary tumours should be part of rationale of follow-up and therefore adequate screening strategies should be used to detect them. (G)
• Patients should be educated with regard to the appearance and detection of recurrences. (G)
• Patients with persistent pain should be investigated to exclude recurrent disease. (R)
• Patients should be offered support with tobacco and alcohol cessation services. (R)
This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. It discusses the evidence base pertaining to the management of metastatic neck disease in the setting of an unknown primary and provides recommendations on the work up and management for this group of patients receiving cancer care.
• All patients presenting with confirmed cervical lymph node metastatic squamous cell carcinoma and no apparent primary site should undergo:
Over the last decade, we have observed an escalating trend in the number of laryngeal biopsies performed, despite the incidence of laryngeal cancer remaining constant. This study aimed to quantify the rate of laryngeal biopsies and record the indications.
A retrospective analysis of laryngeal biopsies performed in North Glasgow, Scotland, UK, between 2001 and 2010, was conducted.
From 2001 to 2010, 3902 laryngeal biopsies were carried out in North Glasgow. Histopathological results indicated the following diagnoses: squamous cell carcinoma, in 889 cases (23 per cent); dysplasia, in 986 cases (25 per cent); ‘no tumour’, in 913 cases (23 per cent); and benign pathology, in the remaining 1084 cases (28 per cent). There has been a significant increase in the number of biopsies performed after 2004, with the incidence of squamous cell carcinoma and benign disease remaining relatively static.
It is hypothesised that organ preservation strategies, endoscopic resection in early stage laryngeal cancer and chemoradiotherapy in advanced head and neck cancer are responsible for the increase in laryngeal biopsies.
During the period from 1995 to 2011, radiocarbon measurements from the coast around Hartlepool in NE England have revealed anomalous enrichments in seawater, sediment, and marine biota. These cannot be explained on the basis of atomic weapons testing or authorized nuclear industry discharges, including those from the nearby advanced gas-cooled reactor. Enhanced 14C-specific activities have also been observed since 2005 in biota during routine monitoring at Hartlepool by the Food Standards Agency, but are reported as “likely” originating from a “nearby non-nuclear source.” Studies undertaken in Hartlepool and Teesmouth during 2005 and 2011 suggest that the 14C discharges are in the vicinity of Greatham Creek, with activity levels in biota analogous to those measured at Sellafield, which discharges TBq activities of 14C per annum. However, if the discharges are into Greatham Creek or even the River Tees, it is proposed that they would be much smaller than those at Sellafield and the high specific activities would be due to much smaller dilution factors. The discharge form of the 14C remains unclear. The activity patterns in biota are similar to those at Sellafield, suggesting that initial inputs are dissolved inorganic carbon (DI14C). However, the mussel/seaweed ratios are more akin to those found around Amersham International, Cardiff, which is known to discharge 14C in an organic form. 14C analysis of a sediment core from Seal Sands demonstrated excess 14C to the base of the core (43–44 cm). 210Pb dating of the core (0–32 cm) produced an accumulation rate of 0.7 g cm−2 yr−1, implying that 14C discharges have occurred from the 1960s until the present day.
From 1994 onwards, radiocarbon discharges from the Sellafield nuclear fuel reprocessing plant have been made largely to the northeast Irish Sea. They represent the largest contributor to UK and European populations of the collective dose commitment derived from the entire nuclear industry discharges. Consequently, it is important to understand the long-term fate of 14C in the marine environment. Research undertaken in 2000 suggested that the carbonate component of northeast Irish Sea sediments would increase in 14C activity as mollusk shells, which have become enriched in Sellafield-derived 14C, are broken down by physical processes including wave action and incorporated into intertidal and subtidal sediments. The current study, undertaken in 2011, tested this hypothesis. The results demonstrate significant increases in 14C enrichments found in whole mussel shells compared to those measured in 2000. Additionally, in 2000, there was an enrichment above ambient background within only the largest size fraction (>500 μm) of the intertidal inorganic sediment at Nethertown and Flimby (north of Sellafield). In comparison, the present study has demonstrated 14C enrichments above ambient background in most size fractions at sites up to 40 km north of Sellafield, confirming the hypothesis set out more than a decade ago.
Traditionally, parasitology has been concerned with the harmful effects of parasitic organisms; it is basically an applied science. Since its founding in the field of medicine, and later in veterinary medicine, parasitology has been mainly devoted to generating knowledge, which is applicable to parasite control and management, and eventually to their eradication. However, the complexity of parasitism, as revealed over recent decades by workers in various specialisms of parasitology, makes the application of management and control measures very difficult in natural environments. This is particularly true in the marine realm, where however some applied aspects of parasitology, other than those devoted to control and management of parasites, have been shown to be of great importance for fisheries, human health, biological control of introduced species and environmental sciences (Rohde, 2002). The relationship of parasitology with mariculture practices, which are carried out mostly on artificial and controlled systems, follows a more classical approach, focusing on the development of strategies of prevention, management and control of pathogens.
Antibiograms have effectively improved antibiotic prescribing in acute-care settings; however, their effectiveness in skilled nursing facilities (SNFs) is currently unknown.
To develop SNF-specific antibiograms and identify opportunities to improve antibiotic prescribing.
Design and Setting.
Cross-sectional and pretest-posttest study among residents of 3 Maryland SNFs.
Antibiograms were created using clinical culture data from a 6-month period in each SNF. We also used admission clinical culture data from the acute care facility primarily associated with each SNF for transferred residents. We manually collected all data from medical charts, and antibiograms were created using WHONET software. We then used a pretest-posttest study to evaluate the effectiveness of an antibiogram on changing antibiotic prescribing practices in a single SNF. Appropriate empirical antibiotic therapy was defined as an empirical antibiotic choice that sufficiently covered the infecting organism, considering antibiotic susceptibilities.
We reviewed 839 patient charts from SNF and acute care facilities. During the initial assessment period, 85% of initial antibiotic use in the SNFs was empirical, and thus only 15% of initial antibiotics were based on culture results. Fluoroquinolones were the most frequently used empirical antibiotics, accounting for 54.5% of initial prescribing instances. Among patients with available culture data, only 35% of empirical antibiotic prescribing was determined to be appropriate. In the single SNF in which we evaluated antibiogram effectiveness, prevalence of appropriate antibiotic prescribing increased from 32% to 45% after antibiogram implementation; however, this was not statistically significant (P = .32).
Implementation of antibiograms may be effective in improving empirical antibiotic prescribing in SNFs.
Myxosporeans are among the most common parasites of marine fish. Their economic importance is mainly as pathogens of both wild and farmed fish, but they have also been used as biological tags in population studies of their fish hosts. Here we review the literature and show the distribution of different families of Myxosporea infecting marine fishes in the world's oceans – the North Atlantic, South Atlantic, North Pacific, South Pacific and Indian. We also analyse their distribution in different orders of marine fishes. New families, genera and species of marine Myxosporea are continually being described and many more await description. Some regions, in particular the North Atlantic, have been more thoroughly investigated than others, so the analyses we present may not reflect the true distributions and we acknowledge that these may change considerably as other regions are investigated more fully. The distribution of myxosporean families in different taxonomic groups of marine fishes can indicate phylogenetic relationships between parasite and host and suggest the origins of different myxosporean taxa. We present some examples, while recognizing that new molecular information on phylogenetic relationships within the Myxozoa will lead to major changes in classification.
Mariculture is a rapidly developing industrial sector. Generally, fish are maintained in net cages with high density. Cage culture systems allow uncontrolled flow of sea water containing potentially infectious stages of fish parasites. In such culture conditions, prevention of such parasitic infections is difficult for parasites with life cycles that complete within culture sites, among which monogeneans and blood flukes are the most important platyhelminthes. Intense monogenean infections induce respiratory and osmo-regulatory dysfunctions. A variety of control measures have been developed, including freshwater bath treatment and chemotherapy. The potential to control monogenean infections through selective breeding, modified culture techniques to avoid infection, and general fish health management are discussed. It should be noted that mariculture conditions have provided some host-specific monogeneans with a chance to expand their host ranges. Blood flukes sometimes induce mass mortality among farmed fish. In-feed administration of praziquantel is the best solution to treat infected fish. Some cases are described that show how international trade in marine fish has resulted in the spread of hitherto unknown parasites into indigenous farmed and wild fish.
Studies of the use of parasites as biological tags for stock identification and to follow migrations of marine fish, mammals and invertebrates in European Atlantic waters are critically reviewed and evaluated. The region covered includes the North, Baltic, Barents and White Seas plus Icelandic waters, but excludes the Mediterranean and Black Seas. Each fish species or ecological group of species is treated separately. More parasite tag studies have been carried out on Atlantic herring Clupea harengus than on any other species, while cod Gadus morhua have also been the subject of many studies. Other species that have been the subjects of more than one study are: blue whiting Micromesistius poutassou, whiting Merlangius merlangus, haddock Melanogrammus aeglefinus, Norway pout Trisopterus esmarkii, horse mackerel Trachurus trachurus and mackerel Scomber scombrus. Other species are dealt with under the general headings redfishes, flatfish, tunas, anadromous fish, elasmobranchs, marine mammals and invertebrates. A final section highlights how parasites can be, and have been, misused as biological tags, and how this can be avoided. It also reviews recent developments in methodology and parasite genetics, considers the potential effects of climate change on the distributions of both hosts and parasites, and suggests host-parasite systems that should reward further research.
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.