Exploring patient experiences with a telehealth approach for the PRO-ACTIVE trial intervention in head and neck cancer patients.

INTRODUCTION: Following the COVID-19 directive to cease non-essential services, a rapid shift was made in the delivery of Speech Language Pathology (SLP) dysphagia management in the 3-arm, randomized PRO-ACTIVE trial. To inform future programs, this study explored patients' experiences with telehealth when the planned in-person SLP intervention was moved to a telehealth modality. METHODS: A theory-guided qualitative descriptive approach was used. Willing participants who had received at least one telehealth swallowing therapy session participated in a one-time semi-structured interview. Interview transcripts were subjected to a standard qualitative content/theme analysis. Researchers reviewed all transcripts and used a multi-step analysis process to build a coding framework through consensus discussion. Summaries and key messages were generated for each code. RESULTS: Eleven participants recounted their telehealth experiences and reported feeling satisfied, comfortable and confident with the session(s). They identified that previous experience with teleconferencing, access to optimal technical equipment, clinician skill, and caregiver assistance facilitated their telehealth participation. Participants highlighted that telehealth was beneficial as it reduced commuting time, COVID-19 exposure and fatigue from travel; and also allowed caregiver participation particularly during COVID. In comparing their in-person SLP sessions to telehealth sessions, limitations were also identified, including: lack of previous experience with and/or poor access to technology, and less opportunity for personalization. Participants indicated that use of phone alone was less preferred than an audio/video platform. DISCUSSION: Patients reported that overall, telehealth sessions did not compromise their learning experience when compared to in-person sessions. Patients benefited from use of telehealth in several ways despite some limitations of the use of technology. Patient feedback about telehealth provides an important perspective that may be critical to inform best practices for care delivery.

Burden of Spinal Muscular Atrophy (SMA) on Patients and Caregivers in Canada.

BACKGROUND: Spinal muscular atrophy (SMA) is a rare neurodegenerative disease characterized by progressive muscular weakness, which occurs in one in 6,000 to 10,000 live births. The burden of SMA on Canadian patients and caregivers is not known. OBJECTIVE: To characterize the burden of SMA in Canada as reported by patients and caregivers, including disease and treatment impacts, indirect costs, and caregiver burden. METHODS: Surveys were distributed by Cure SMA Canada and Muscular Dystrophy Canada to individuals with SMA and their caregivers. The online surveys were anonymous and completed between January 28 and February 21, 2020. RESULTS: 965 patient and 962 caregiver responses met the eligibility criteria. Patients reported SMA subtypes as: type I (25.0%), type II (41.3%), type III (29.3%). Using the EQ-5D, patients were shown to have impaired quality of life with an average health utility index of 0.49 (SD: 0.26). The median expenditure was $4,500 CAD (IQR: $1,587 - $11,000) for assistive devices; $6,800 CAD (IQR: $3,900-$13,000) on health professional services; and $1,200 CAD (IQR: $600 -$3,100) on SMA-related travel and accommodation in the past 12 months. Caregivers reported needing respite care (45.7%), physiotherapy for an injury from a lift/transfer (45.7%), or other health impacts (63.3%). Caregivers reported changes to personal plans, sleep disturbances, and work adjustments, with a mean Caregiver Strain Index score of 7.5 [SD: 3.3]. CONCLUSION: SMA in Canada is associated with a significant burden for patients and their caregivers.

The Canadian Neuromuscular Disease Registry 2010-2019: A Decade of Facilitating Clinical Research Througha Nationwide, Pan-NeuromuscularDisease Registry.

We report the recruitment activities and outcomes of a multi-disease neuromuscular patient registry in Canada. The Canadian Neuromuscular Disease Registry (CNDR) registers individuals across Canada with a confirmed diagnosis of a neuromuscular disease. Diagnosis and contact information are collected across all diseases and detailed prospective data is collected for 5 specific diseases: Amyotrophic Lateral Sclerosis (ALS), Duchenne Muscular Dystrophy (DMD), Myotonic Dystrophy (DM), Limb Girdle Muscular Dystrophy (LGMD), and Spinal Muscular Atrophy (SMA). Since 2010, the CNDR has registered 4306 patients (1154 pediatric and 3148 adult) with 91 different neuromuscular diagnoses and has facilitated 125 projects (73 academic, 3 not-for-profit, 3 government, and 46 commercial) using registry data. In conclusion, the CNDR is an effective and productive pan-neuromuscular registry that has successfully facilitated a substantial number of studies over the past 10 years.

Postoperative healing and behaviour when surgical swabs are applied to calf dehorning wounds.

OBJECTIVE: To assess the effect on healing and pain-associated behaviours of covering exposed sinuses after horn amputation under extensive production conditions in northern Australia. METHODS: Horned, weaned Brahman-cross heifers (n = 50) aged approximately 6 months were alternately allocated to have their dehorning wounds either patched with a dry, non-sterile gauze swab or left untreated. Adherence of swabs and growth rates, healing and pain-associated behaviour were monitored for 88 days post-surgery. RESULTS: Half of the patches were lost by 24 h post-surgery, with most of the rest falling off 2-6 weeks later. Patching resulted in healing 5.5 days earlier (P = 0.018). Sealing of exposed frontal sinuses occurred in most heifers within 3 weeks and full healing occurred within 13 weeks. Patching reduced haemorrhage (P < 0.01) regardless of when the patches were dislodged, prevented insect invasion of the wound and reduced the incidence of secondary infection (P < 0.01). Wound patches did not affect behaviour in the weeks following surgery. In the days after surgery, the heifers did not eat and showed a high incidence of behaviours indicating pain. Behaviour was relatively normal by 2 weeks after surgery, although the heifers avoided social interaction with other unbranded calves for 4 weeks. CONCLUSION: The application of gauze swabs to dehorning wounds advanced healing, reduced the incidence of haemorrhage and secondary infections, and may reduce deaths. Efficacy is expected to improve if high rates of 24-h retention of patches can be achieved. The prolonged time to healing and the pain-associated behaviours highlight the need for better welfare of dehorned calves through improvements in analgesia, surgical procedures and post-surgical care.

Debunking Occam's razor: Diagnosing multiple genetic diseases in families by whole-exome sequencing.

BACKGROUND: Recent clinical whole exome sequencing (WES) cohorts have identified unanticipated multiple genetic diagnoses in single patients. However, the frequency of multiple genetic diagnoses in families is largely unknown. AIMS: We set out to identify the rate of multiple genetic diagnoses in probands and their families referred for analysis in two national research programs in Canada. MATERIALS & METHODS: We retrospectively analyzed WES results for 802 undiagnosed probands referred over the past 5 years in either the FORGE or Care4Rare Canada WES initiatives. RESULTS: Of the 802 probands, 226 (28.2%) were diagnosed based on mutations in known disease genes. Eight (3.5%) had two or more genetic diagnoses explaining their clinical phenotype, a rate in keeping with the large published studies (average 4.3%; 1.4 - 7.2%). Seven of the 8 probands had family members with one or more of the molecularly diagnosed diseases. Consanguinity and multisystem disease appeared to increase the likelihood of multiple genetic diagnoses in a family. CONCLUSION: Our findings highlight the importance of comprehensive clinical phenotyping of family members to ultimately provide accurate genetic counseling.

The time to and determinants of first fractures in boys with Duchenne muscular dystrophy.

Boys with vertebral fractures (VF) identified through routine spine radiographs had milder, less symptomatic, and fewer VF compared to those diagnosed with VF following consultation for back pain. Spontaneous (i.e., medication-unassisted) reshaping of fractured vertebral bodies was absent. Long bone fractures were present even before Duchenne muscular dystrophy (DMD) diagnosis in some boys. INTRODUCTION: The objective of the study was to determine the time to and characteristics of first fractures in Duchenne muscular dystrophy. METHODS: This study was a retrospective longitudinal study of 30 boys with DMD <18 years. Boys were classified into four groups according to their first fracture: those with VF identified on routine lateral spine radiographs, those with VF diagnosed following consultation for back pain, those with long bone fractures, and those without fractures. RESULTS: Compared to boys diagnosed with VF as their initial fracture following consultation for back pain, those with VF surveillance radiographs had shorter durations of glucocorticoid (GC) therapy at the time of VF diagnosis (median 1.6 versus 5.3 years, p < 0.01), higher areal (mean ± standard deviation -1.4 ± 0.7 versus -3.1 ± 0.8, p = 0.01), and volumetric (-0.3 ± 0.5 versus -2.6 ± 0.8, p < 0.01) lumbar spine bone mineral density Z-scores, as well as fewer VF (median 1.4 versus 5.2 per person, p < 0.01) and a lower median spinal deformity index (median 1.5 versus 9.5, p < 0.01). Vertebral body reshaping following VF was not observed. Ten boys sustained a long bone fracture as their first fracture at a mean age of 8.9 ± 4.0 years; four of these boys later sustained a total of 27 incident VF. CONCLUSIONS: Routine lateral spine radiographs led to detection of VF in their earlier stages, vertebral body reshaping following VF was absent, and VF were frequent after the first long bone fracture. These results support the inclusion of a lateral spine radiograph starting at the time of GC initiation as part of routine bone health monitoring in DMD.

Chemotherapy-induced Peripheral Neuropathy Among Paediatric Oncology Patients.

BACKGROUND: Vinca alkaloids and platinum-containing chemotherapeutic drugs have the potential to cause chemotherapy-induced peripheral neuropathy (CIPN). This study determined the frequency of CIPN among children who were treated for acute lymphoblastic leukemia (ALL), lymphoma, brain tumour or Wilms tumour. PROCEDURE: This retrospective cohort study reviewed 252 patients treated at the Children's hospital of Eastern Ontario from 2001-2011. Patients were considered to have CIPN if they developed clinical symptoms of CIPN such as limb paraesthesia, weakness and/or ataxia during chemotherapy and their treating neurologist or oncologist deemed that their symptoms were due to a peripheral cause. Patients were excluded if their treatment regime did not include chemotherapy. RESULTS: The overall frequency of CIPN was 18.3% (46/252). Tumour-specific CIPN rates were: 18.9% (29/154) for ALL; 9.4% (3/32) for lymphoma; 17.9% (5/28) for Wilms tumour; and 23.7% (9/38) for brain tumour patients. Nerve conduction studies were completed for 17% of patients (all tumour types) and were abnormal in all but one patient. Among surviving CIPN patients (41/46), 93% showed no clinical deficits at their last examination, which was on average 56 months from time of diagnosis to last follow-up visit. CONCLUSIONS: The frequency of CIPN was less than that previously reported in adults receiving chemotherapy. Children with CIPN have a favourable outcome with most showing clinical improvement during the maintenance phase of treatment or after chemotherapy completion.

Evidence for clinical, genetic and biochemical variability in spinal muscular atrophy with progressive myoclonic epilepsy.

Spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) is a recently delineated, autosomal recessive condition caused by rare mutations in the N-acylsphingosine amidohydrolase 1 (acid ceramidase) ASAH1 gene. It is characterized by motor neuron disease followed by progressive myoclonic seizures and eventual death due to respiratory insufficiency. Here we report an adolescent female who presented with atonic and absence seizures and myoclonic jerks and was later diagnosed as having myoclonic-absence seizures. An extensive genetic and metabolic work-up was unable to arrive at a molecular diagnosis. Whole exome sequencing (WES) identified two rare, deleterious mutations in the ASAH1 gene: c.850G>T;p.Gly284X and c.456A>C;p.Lys152Asn. These mutations were confirmed by Sanger sequencing in the patient and her parents. Functional studies in cultured fibroblasts showed that acid ceramidase was reduced in both overall amount and enzymatic activity. Ceramide level was doubled in the patient's fibroblasts as compared to control cells. The results of the WES and the functional studies prompted an electromyography (EMG) study that showed evidence of motor neuron disease despite only mild proximal muscle weakness. These findings expand the phenotypic spectrum of SMA-PME caused by novel mutations in ASAH1 and highlight the clinical utility of WES for rare, intractable forms of epilepsy.

The use of intravenous bisphosphonate therapy to treat vertebral fractures due to osteoporosis among boys with Duchenne muscular dystrophy.

UNLABELLED: The impact of intravenous bisphosphonate treatment to treat painful vertebral fractures in boys with DMD has not been documented. In this retrospective observational study of seven boys, 2 years of intravenous bisphosphonate therapy was associated with back pain improvement and stabilization or increases in the height ratios of fractured vertebrae. INTRODUCTION: Boys with Duchenne muscular dystrophy (DMD) are at risk for vertebral fractures. We studied the impact of intravenous bisphosphonate therapy for the treatment of painful vertebral fractures in DMD. METHODS: This was a retrospective observational study in seven boys with DMD (median 11.6 years, range 8.5 to 14.3) treated with intravenous pamidronate (9 mg/kg/year) or zoledronic acid (0.1 mg/kg/year) for painful vertebral fractures. RESULTS: At baseline, 27 vertebral fractures were evident in the seven boys. After 2 years of bisphosphonate therapy, 17 of the fractures had an increase in the most severely affected vertebral height ratio, 10 vertebrae stabilized, and none showed a decrease in height ratio. Back pain resolved completely (N = 3) or improved (N = 4). The median change in lumbar spine volumetric bone mineral density Z-score was 0.5 standard deviations (interquartile range, -0.3 to 1.7). Two boys had three incident vertebral fractures in previously normal vertebral bodies that developed over the observation period. There was a decline in the trabecular bone formation rate on trans-iliac bone biopsy but no evidence of osteomalacia. First-dose side effects included fever and malaise (N = 4), hypocalcemia (N = 2), and vomiting (N = 1); there were no side effects with subsequent infusions. CONCLUSIONS: Intravenous bisphosphonate therapy was associated with improvements in back pain and stabilization to improvement in vertebral height ratios of previously fractured vertebral bodies. At the same time, such therapy does not appear to completely prevent the development of new vertebral fractures in this context.

An observational cohort study of triage for critical care provision during pandemic influenza: 'clipboard physicians' or 'evidenced based medicine'?

We assessed the impact of a United Kingdom government-recommended triage process, designed to guide the decision to admit patients to intensive care during an influenza pandemic, on patients in a teaching hospital intensive care unit. We found that applying the triage criteria to a current case-mix would result in 116 of the 255 patients (46%) admitted during the study period being denied intensive care treatment they would have otherwise received, of which 45 (39%) survived to hospital discharge. In turn, 69% of those categorised as too ill to warrant admission according to the criteria survived. The sensitivity and specificity of the triage category at ICU admission predicting mortality was 0.29 and 0.84, respectively. If the need for intensive care beds is estimated to be 275 patients per week, the triage criteria would not exclude enough patients to prevent the need for further rationing. We conclude that the proposed triage tool failed adequately to prioritise patients who would benefit from intensive care.

Effects of copper and the sea lice treatment Slice on nutrient release from marine sediments.

Copper-based antifoulant paints and the sea lice treatment Slice are widely used, and often detectable in the sediments beneath farms where they are administered. Ten-day, whole sediment mesocosm experiments were conducted to examine how increasing sediment concentrations of copper or Slice influenced final water column concentrations of ammonium-nitrogen (NH(4)-N), nitrate+nitrite-nitrogen (NO(X)-N) and phosphate-phosphorus (PO(4)-P) in the presence of the non-target, benthic organisms Corophium volutator and Hediste diversicolor. Nominal sediment concentrations of copper and Slice had significant effects on the resulting concentrations of almost all nutrients examined. The overall trends in nutrient concentrations at the end of the 10-day incubations were highly similar between the trials with either copper or Slice, irrespective of the invertebrate species present. This suggests that nutrient exchange from the experimental sediments was primarily influenced by the direct effect of copper/Slice dose on the sediment microbial community, rather than the indirect effect of reduced bioturbation/irrigation due to increased macrofaunal mortality.

Brainstem compression: a predictor of postoperative cerebellar mutism.

PURPOSE: Cerebellar mutism is a common complication of posterior fossa tumor resection. We observed marked, preoperative brainstem compression on MR imaging, among patients who developed postoperative mutism. This study was designed to investigate if an association was indeed present. MATERIALS AND METHODS: Patients (18 months-18 years) undergoing resection of a midline, posterior fossa tumor were retrospectively reviewed. Demographic data, tumor pathology, mutism onset and duration, and postoperative complications were obtained from hospital records. Pre- and postoperative MR images were studied to assess tumor size and the severity of pons compression (an estimate of the mechanical and distortional forces imparted by the tumor). RESULTS: Patients with mutism showed greater preoperative pons compression and a greater increase in postoperative pons diameter. CONCLUSION: We predict that brainstem compression may represent white-matter injury from (1) surgical manipulation and traction, and (2) axonal damage caused by the release of the tumor's compressive force and ensuing axon distortion and dysfunction. The results provide support that mutism may be largely caused by white-matter damage disrupted axon integrity and function.

Ophthalmoplegic migraine: inflammatory neuropathy with secondary migraine?

BACKGROUND: This critical review provides a summary of the clinical presentation, neuroimaging, treatment and prognosis in pediatric ophthalmoplegic migraine (OM). The features of OM are not in keeping with its classification as a migraine-variant. METHOD: We review 3 new and 37 reported pediatric OM cases. RESULTS: Headache was an inconsistent feature, with 25% patients showing no evidence of pain at the initial OM episode. Patients demonstrated: 1) prolonged time for symptom resolution to occur (median time 3 weeks); 2) tendency for recurrent episodes to have more severe and persistent nerve involvement; 3) evidence of permanent neurological sequelae with recurrent episodes (30% of patients); 4) rapid improvement and shortened duration with corticosteroid therapy and; 5) transient, reversible MRI contrast enhancement of the affected cranial nerve (86% of patients). These features would not be expected in primary migraine headache. CONCLUSION: A detailed understanding of the natural history of OM is essential for the clinical. This review provides support that OM may result from cranial nerve inflammation with headache a secondary and later feature of this condition.

Maternal folate status and neural tube defects in Ireland: the need for a national food fortification program.

To determine the present risk of a Neural Tube Defect [NTD] pregnancy in the caucasian primigravid population in Dublin by comparing the serum folate and red cell folate status of primigravid patients attending the first prenatal booking clinic with data from the late 80's. This Cross-sectional population study looking at blood folate status of over 400 sequential primigravid caucasian women with a singleton pregnancy, booking at less than or equal to 20 weeks gestation. All patients were attending a prenatal booking clinic at the Rotunda Hospital in Dublin during 2003-2004. Comparing serum and red cell folate values in 454 primigravid patients in 2003-4 to values to in a large case-control study based on over 56,000 women attending maternity hospitals in Dublin from 1986 to 1990. Just 13.9% of our patients took periconceptual folate, 33.5% of patients took folate in the first 20 weeks of pregnancy and 58.8% of mothers were taking no folate supplement. Overall, 30% of mothers had RCF levels below 400 ug/L--a level recommended as the minimum value required for protection. NTD risk occurred most frequently amongst patients with RCF levels between 300 and 400 ng/mL.

Screening for Chlamydia trachomatis in asymptomatic women attending outpatient clinics in a large maternity hospital in Dublin, Ireland.

BACKGROUND: Chlamydia trachomatis can cause a sexually transmitted infection, which, untreated, may result in considerable morbidity. METHODS: A prevalence study was conducted for C trachomatis using nucleic acid amplification technology in asymptomatic women, and certain risk factors that may be used to direct future screening strategies were assessed. RESULTS: The study population comprised 945 asymptomatic women, of whom 783 were attending antenatal clinics, 91 were attending infertility clinics and 71 were attending family planning clinics. An overall C trachomatis prevalence of 3.7% (35/945) was found, with the highest prevalence of 11.2% (22/196) in Irish single women aged <25 years. Logistic regression analysis showed that single status and age <25 years were independent, statistically significant predictors of C trachomatis infection. CONCLUSION: These results support routine screening of asymptomatic women who are sexually active and aged <25 years. An opportunist active screening of all sexually active women independent of age should be additionally considered if resources permit.

Divergent reproductive endocrinology of the estrous cycle and pregnancy in dwarf hamsters (phodopus).

Progesterone (P4) and prolactin (PRL) in peripheral circulation of Siberian hamsters (Phodopus sungorus) throughout an estrous cycle and pregnancy were determined by repeated, small volume sampling from individuals housed in modified home cages. As predicted, the endocrinology of P. sungorus reproduction is similar to the rat, mouse and golden hamster and shows none of the eight distinctive features known for Djungarian hamsters (Phodopus campbelli). Specifically, in P. sungorus there is no evidence for resumption of pituitary PRL surges in late pregnancy, P4 concentrations during the differentiation of the corpus luteum on day 2 of pregnancy are higher (as opposed to lower) than concentrations on the comparable day of an unmated estrous cycle (diestrus 1), P4 concentrations increase throughout pregnancy, PRL surges are common during the estrous cycle, including a reliable surge on proestrus, and P4 plays an important role in facilitating the expression of behavioral receptivity. We conclude that 'novel' P. campbelli reproductive endocrinology has evolved since a common ancestor was shared with P. sungorus. With a time frame (the available time since the divergence of the two species) and an ecological context (known niches and behavior in the wild) these species offer the opportunity to study endocrinological evolution in progress.