Reducing epilepsy diagnostic and treatment gaps: Standardized paediatric epilepsy training courses for health care professionals.

AIM: To evaluate improvement in knowledge and clinical behaviour among healthcare professionals after attendance at paediatric epilepsy training (PET) courses. METHOD: Since 2005, 1-day PET courses have taught evidence-based paediatric epilepsy management to doctors and nurses in low-, middle-, and high-income countries. A cohort study was performed of 7528 participants attending 252 1-day PET courses between 2005 and 2020 in 17 low-, middle-, and high-income countries, and which gathered data from participants immediately after the course and then 6 months later. Training outcomes were measured prospectively in three domains (reaction, learning, and behaviour) using a mixed-methods approach involving a feedback questionnaire, a knowledge quiz before and after the course, and a 6-month survey. RESULTS: Ninety-eight per cent (7217 of 7395) of participants rated the course as excellent or good. Participants demonstrated knowledge gain, answering a significantly higher proportion of questions correctly after the course compared to before the course (88% [47 883 of 54 196], correct answers/all quiz answers, vs 75% [40 424 of 54 196]; p < 0.001). Most survey responders reported that the course had improved their epilepsy diagnosis and management (73% [311 of 425]), clinical service (68% [290 of 427]), and local epilepsy training (68% [290 of 427]). INTERPRETATION: This was the largest evaluation of a global epilepsy training course. Participants reported high course satisfaction, showed knowledge gain, and described improvements in clinical behaviour 6 months later. PET supports the global reduction in the epilepsy 'treatment gap' as promoted by the World Health Organization.

Survivors of allogeneic bone marrow transplants in childhood report no significant long-term respiratory symptoms: A single-center analysis over 20 years.

Pulmonary toxicity is documented in long-term survivors of allogeneic BMT. No studies have specifically evaluated late pulmonary symptomatology in these patients. 85 long-term pediatric survivors were sent a validated questionnaire of pulmonary symptomatology. Demographic and clinical data were retrospectively collected from the respondents medical records. Response rate was 52.9%. Mean follow-up post-BMT of those who responded was 12.3 years. Mean pulmonary symptom scores were low (0.78). There was no significant difference in symptoms between patients who underwent MA conditioning with or without TBI. These results are reassuring that long-term survivors of pediatric BMT have few respiratory symptoms which do not impact on activities of daily living.

Concept: A randomised multicentre trial of first line chemotherapy comparing three weekly cabazitaxel versus weekly paclitaxel in HER2 negative metastatic breast cancer.

BACKGROUND: Paclitaxel is commonly used as first-line chemotherapy for HER2-negative metastatic breast cancer (MBC) patients. However, with response rates of 21.5-53.7% and significant risk of peripheral neuropathy, there is need for better chemotherapy. PATIENTS AND METHODS: This open-label phase II/III trial randomised HER2-negative MBC patients 1:1 to either 6 cycles of three-weekly cabazitaxel (25 mg/m2), or, weekly paclitaxel (80 mg/m2) over 18 weeks. The primary endpoint was progression free survival (PFS). Secondary endpoints included objective response rate (ORR), time to response (TTR), overall survival (OS), safety and tolerability and quality of life (QoL). RESULTS: 158 patients were recruited. Comparing cabazitaxel to paclitaxel, median PFS was 6.7 vs 5.8 months (HR 0.87; 80%CI 0.70-1.08, P = 0.4). There was no difference in median OS (20.6 vs 18.2 months, HR 1.00; 95%CI 0.69-1.45, P = 0.99), ORR (41.8% vs 36.7%) or TTR (HR 1.09; 95%CI 0.68-1.75, P = 0.7). Grade ≥3 adverse events occurred in 41.8% on cabazitaxel and 46.8% on paclitaxel; the most common being neutropenia (16.5%) and febrile neutropenia (12.7%) cabazitaxel and neutropenia (8.9%) and lung infection (7.6%) paclitaxel. Peripheral neuropathy of any grade occurred in 54.5% paclitaxel vs 16.5% cabazitaxel. Mean EQ-5D-5L single index utility score (+0.05; 95%CI 0.004-0.09, P = 0.03) and visual analogue scale score (+7.7; 95%CI 3.1-12.3, P = 0.001) were higher in cabazitaxel vs paclitaxel. CONCLUSIONS: Three-weekly cabazitaxel in HER2-negative MBC does not significantly improve PFS compared to weekly paclitaxel, although it has a lower risk of peripheral neuropathy with better patient reported QoL outcomes. It is well tolerated and requires fewer hospital visits.

Outliers from national audits: their analysis and use by the Care Quality Commission in quality assurance and regulation of healthcare services in England.

The Care Quality Commission (CQC) is the independent regulator of health and adult social care in England. As part of the intelligence-driven approach to regulation, the CQC works closely with national clinical audit bodies to identify key metrics which reflect quality of care and track the performance of providers against these metrics. Where outliers on national audits are identified that may reflect risks to patients, the CQC encourages the hospital to identify any learning points and implement changes to improve patient care.In this article, we describe the role of national audit outcomes in the regulatory process and how providers can use national audits to inform both quality assurance and quality improvement processes, with two illustrative case studies. We discuss the ongoing challenges with using audit data in the regulatory process and how these could be addressed.

Indigenous fathers' involvement in reconstituting "circles of care".

This qualitative study, part of a Canadian national study of fathers' involvement, opened up First Nations and Métis fathering as a new area of inquiry. Conversational interviews with 80 Indigenous fathers illuminated the socio-historical conditions that have shaped Indigenous men's experiences of learning to be a father and becoming a man in the context of changing gender relationships and the regeneration of circles of care. Indigenous fathers' experiences unfold in a socio-historical context fraught with difficulties. However, the study findings suggest cultural strengths and sources of resilience unseen in research and community programs driven by Euro-western perspectives. This research can inform efforts to reduce systemic barriers and reconstitute positive father involvement following disrupted intergenerational transmission of fathering in Canada and elsewhere.

Respiratory viral panels and pediatric airway evaluation: The role of testing for upper respiratory infections to stratify perioperative risk.

OBJECTIVES: Children admitted with stridor and respiratory distress comprise a complex patient group that requires the otolaryngologist to decide when to assess and intervene with direct laryngoscopy and bronchoscopy (DLB). Historically, the diagnosis of viral upper respiratory tract infection (URTI) can lead to postponement of surgery due to concerns of perioperative complications related to acute illness. Respiratory viral panels (RVP) are often used to confirm the presence of recent or active viral infection and can affect the differential diagnosis of upper airway obstruction. This study examined whether positive RVP testing is associated with perioperative complications and operative findings in pediatric patients undergoing inpatient DLB. METHODS: A retrospective chart review of 132 pediatric patient encounters was performed. Viral testing results, DLB indication, DLB findings, and perioperative complications were compared. RESULTS: Sixty encounters (45.5%) involved a positive RVP, and 72 (54.5%) involved a negative RVP. Those with positive RVP were less likely to have a preoperative structural airway diagnosis (P =.0250) and more likely to have a history of recurrent upper respiratory infections (P =.0464). The most common reason for DLB was the need to assess the airway due to concern for structural pathology. Anatomic abnormalities were seen in a majority of encounters (77.3%) Laryngospasm occurred in 1 (1.7%) RVP positive and 1 (1.4%) RVP negative encounter, and 2 (2.8%) RVP negative encounters required reintubation. No other major complications were observed. No association was noted between RVP results and incidence of major or minor complication. CONCLUSIONS: Major perioperative complications after surgical intervention with DLB for the management of complex, inpatient children with stridor and respiratory distress are rare. RVP positivity, specific pathogens identified on RVP, and presence of URI symptoms were not associated with perioperative complications.

Lumbosacral transitional vertebrae in cats and its relationship to lumbosacral vertebral canal stenosis.

OBJECTIVES: Although a clear relationship has been demonstrated between the presence of lumbosacral transitional vertebrae and the development of lumbosacral stenosis in dogs, this relationship has not been evaluated in cats. The aim of this study was to investigate the relationship between the presence of lumbosacral transitional vertebrae and lumbosacral stenosis in cats. METHODS: The medical records and diagnostic imaging studies of 13 cats diagnosed with lumbosacral stenosis were retrospectively reviewed for lumbosacral abnormalities and compared with findings of 405 cats that underwent CT for reasons unrelated to spinal disease. RESULTS: Clinical signs associated with lumbosacral stenosis included lumbosacral pain, low tail carriage, difficulty jumping, and urinary or faecal incontinence. Neurological signs included proprioceptive deficits, ambulatory paraparesis, pelvic limb ataxia, reduced spinal reflexes and reduced perianal reflex. Duration of clinical signs ranged from 1 day to 10 months (mean 3 months). Of the 13 cats with lumbosacral stenosis, seven (53.8%) were diagnosed with lumbosacral transitional vertebrae. In the control population of 405 cats, 24 (5.9%) were diagnosed with lumbosacral transitional vertebrae. Results indicated that lumbosacral transitional vertebrae were significantly ( P <0.0001) more prevalent in cats with lumbosacral stenosis compared with the control feline population (odds ratio 18.52, 95% confidence interval 6.1-62.1). Development of clinical signs of lumbosacral stenosis in cats with lumbosacral transitional vertebrae (mean 10.8 years) was not significantly different from that of cats without lumbosacral transitional vertebrae (mean 12.7 years). Likewise, there was no significant influence of breed ( P >0.99) or sex ( P = 0.29) on the occurrence of lumbosacral transitional vertebrae. CONCLUSIONS AND RELEVANCE: Despite lumbosacral stenosis being a rare spinal condition in cats, lumbosacral transitional vertebrae can be considered a risk factor for its development.

A direct comparison of porcine (Strattice™) and bovine (Surgimend™) acellular dermal matrices in implant-based immediate breast reconstruction.

INTRODUCTION: Acellular dermal matrix (ADM) assisted implant-based breast reconstruction (IBBR) has grown in popularity over traditional submuscular techniques. Numerous human, bovine or porcine derived ADMs are available with the type used varying considerably worldwide. Yet, comparative evidence for the efficacy of different ADMs particularly xenogenic is limited. This study directly compares early outcomes of porcine (Strattice™) and bovine (Surgimend™) ADMs in IBBR. METHOD: Retrospective study of sequential experience of immediate IBBR using Strattice or Surgimend ADM. Data was collected for patients undergoing ADM assisted IBBR after prophylactic or therapeutic mastectomy in Cambridge (October 2011-March 2016). Patient demographics, adjuvant and neoadjuvant therapies, operative details, postoperative management and outcomes were analysed. KEY RESULTS: Total of 81 patients underwent IBBR with ADM; 38 bilateral and 43 unilateral (n = 119 breasts). Strattice was used in 30 breasts (25%) and Surgimend in 89 (75%). Analysis of patient specific variables showed statistical significance only for higher mastectomy weight in the Strattice group (367.1 ± 159.3 g versus 296.3 ± 133.4 g; P = 0.0379). Strattice was associated with higher rates of skin erythema post-operatively (16.7% versus 4.5%; P = 0.044). Analysed per woman or per breast, there was no statistically significant difference in rates of haematoma, infection, wound dehiscence, skin necrosis or seroma, although there was a trend towards more complications with Strattice. CONCLUSION: This study found significantly higher rates of skin erythema and a trend towards higher complication rates with Strattice in IBBR. Randomised controlled trials comparing different ADM outcomes are needed to inform best practice.

The biofilm matrix destabilizers, EDTA and DNaseI, enhance the susceptibility of nontypeable Hemophilus influenzae biofilms to treatment with ampicillin and ciprofloxacin.

Nontypeable Hemophilus influenzae (NTHi) is a Gram-negative bacterial pathogen that causes chronic biofilm infections of the ears and airways. The biofilm matrix provides structural integrity to the biofilm and protects biofilm cells from antibiotic exposure by reducing penetration of antimicrobial compounds into the biofilm. Extracellular DNA (eDNA) has been found to be a major matrix component of biofilms formed by many species of Gram-positive and Gram-negative bacteria, including NTHi. Interestingly, the cation chelator ethylenediaminetetra-acetic acid (EDTA) has been shown to reduce the matrix strength of biofilms of several bacterial species as well as to have bactericidal activity against various pathogens. EDTA exerts its antimicrobial activity by chelating divalent cations necessary for growth and membrane stability and by destabilizing the matrix thus enhancing the detachment of bacterial cells from the biofilm. In this study, we have explored the role of divalent cations in NTHi biofilm development and stability. We have utilized in vitro static and continuous flow models of biofilm development by NTHi to demonstrate that magnesium cations enhance biofilm formation by NTHi. We found that the divalent cation chelator EDTA is effective at both preventing NTHi biofilm formation and at treating established NTHi biofilms. Furthermore, we found that the matrix destablilizers EDTA and DNaseI increase the susceptibility of NTHi biofilms to ampicillin and ciprofloxacin. Our observations indicate that DNaseI and EDTA enhance the efficacy of antibiotic treatment of NTHi biofilms. These observations may lead to new strategies that will improve the treatment options available to patients with chronic NTHi infections.

Enacting research ethics in partnerships with indigenous communities in Canada: "Do it in a good way".

Two studies conducted through community-campus partnerships demonstrated emerging frameworks for ethical conduct of research involving Indigenous peoples in Canada. Both projects involved multiple Indigenous community partners whose interests in promoting children's development and fathers' involvement motivated the projects. The Indigenous projects were conceived within a broader social agenda of restorative justice and self-determination of Indigenous peoples in Canada following centuries of colonial government interventions. Guiding principles included community relevance, community participation, mutual capacity building, and benefit to Indigenous communities. Memoranda of Understanding negotiated with each community partner specified the roles of community and university partners and research team members in each phase of the research. Testimonials obtained from community representatives before and after the research projects indicated the success of the projects in yielding benefits to the communities in the form of substantive knowledge and strengthened capacities to engage in collaborative research through community-campus partnerships. The larger collaborative research projects in which these two Indigenous projects were embedded created challenges and opportunities due to varying recognition within these networks of the primacy of relationships as a foundation for research and the indeterminacy of outcomes when ownership of data and control over dissemination is in the hands of community partners.

First Nations English dialects in Canada: implications for speech-language pathology.

The current study reports preliminary information gathered about First Nations English dialects in Canada and considers implications for speech-language pathology practice. Information was gathered from literature searches and forums of First Nations and non-First Nations speech-language pathologists, developmentalists, and linguists. The exploratory findings suggest that First Nations English dialects are shaped both by transference of features from the ancestral languages and by cultural patterns of communication. The dialects likely represent late stages of depidginization and decreolization. Examples of phonological and syntactic dialectal features illustrate the importance of recognizing non-standard varieties of English when assessing speakers of First Nations communities and setting up goals and strategies for treatment. Research is urgently needed to identify features of First Nations English dialects both for linguistic documentation and to help speech-language pathologists and other educators to distinguish between language impairments and dialect differences and to develop culturally relevant assessment and intervention practices.

The quorum sensing negative regulators EsaR and ExpR(Ecc), homologues within the LuxR family, retain the ability to function as activators of transcription.

Most LuxR homologues function as activators of transcription during the process of quorum sensing, but a few, including EsaR and ExpR(Ecc), negatively impact gene expression. The LuxR-activated luxI promoter and LuxR binding site, the lux box, were used in artificial contexts to assess the potential for transcriptional activation and DNA binding by EsaR and ExpR(Ecc). Although the acyl-homoserine lactone responsiveness of both proteins is the opposite of that shown by most LuxR family members, EsaR and ExpR(Ecc) have preserved the ability to interact with RNA polymerase and activate transcription despite their low affinity for the lux box DNA.