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To develop updated American College of Rheumatology/American Association of Hip and Knee Surgeons guidelines for the perioperative management of disease-modifying medications for patients with rheumatic diseases, specifically those with inflammatory arthritis (IA) and those with systemic lupus erythematosus (SLE), undergoing elective total hip arthroplasty (THA) or elective total knee arthroplasty (TKA).We convened a panel of rheumatologists, orthopedic surgeons, and infectious disease specialists, updated the systematic literature review, and included currently available medications for the clinically relevant population, intervention, comparator, and outcomes (PICO) questions. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence and the strength of recommendations using a group consensus process.This guideline updates the 2017 recommendations for perioperative use of disease-modifying antirheumatic therapy, including traditional disease-modifying antirheumatic drugs, biologic agents, targeted synthetic small-molecule drugs, and glucocorticoids used for adults with rheumatic diseases, specifically for the treatment of patients with IA, including rheumatoid arthritis and spondyloarthritis, those with juvenile idiopathic arthritis, or those with SLE who are undergoing elective THA or TKA. It updates recommendations regarding when to continue, when to withhold, and when to restart these medications and the optimal perioperative dosing of glucocorticoids.This updated guideline includes recently introduced immunosuppressive medications to help decision-making by clinicians and patients regarding perioperative disease-modifying medication management for patients with IA and SLE at the time of elective THA or TKA.

Objective: To assess the accessibility, availability and utilisation of a comprehensive range of community-based healthcare services for Aboriginal people and describe contributing factors to providing effective healthcare services from the provider perspective. Setting: A remote community in New South Wales, Australia. Participants: Aboriginal and non-Aboriginal health and education professionals performing various roles in healthcare provision in the community. Design: Case study. Methodology: The study was co-designed with the community. A mixed-methods methodology was utilised. Data were gathered through structured interviews. Descriptive statistics were used to analyse the availability of 40 health services in the community, whilst quotations from the qualitative research were used to provide context for the quantitative findings. Results: Service availability was mapped for 40 primary, specialised, and allied health services. Three key themes emerged from the analysis: (1) there are instances of both underservicing and overservicing which give insight into systemic barriers to interagency cooperation; (2) nurses, community health workers, Aboriginal health workers, teachers, and administration staff have an invaluable role in healthcare and improving patient access to health services and could be better supported through further funding and opportunities for specialised training; and (3) visiting and telehealth services are critical components of the system that must be linked to existing community-led primary care services. Conclusion: The study identified factors influencing service availability, accessibility and interagency cooperation in remote healthcare services and systems that can be used to guide future service and system planning and resourcing.

Highlights • A subset of Canadian physicians, orthopedic surgeons, and plastic surgeons are using perioperative botulinum toxin (BoNT). • Forty-one percent of Canadian respondents stated that they were not notified of their patient's surgical date. • Increased collaboration between specialties and the creation of national guidelines will increase the benefits of perioperative BoNT surgical outcomes., Objective To investigate the practice patterns of Canadian physicians who use perioperative botulinum toxin (BoNT) injections to improve surgical outcomes on spastic limbs. Design A cross-sectional national survey composed of an invitation email and an 18-item questionnaire was disseminated by a national physical medicine and rehabilitation (PMR) society to 138 physician members involved in spasticity management. Setting Not applicable. Participants Twenty-five percent of the participants (N=34) fully completed the survey. Interventions Not applicable. Main Outcome Measures Participants completed an online questionnaire that examined the practice patterns and surgical outcomes associated with perioperative BoNT injections. Results The majority (n=21; 84%) of Canadian physicians who inject BoNT perioperatively to improve outcomes of surgeries performed on spastic limbs are specialists in PMR practicing in academic settings. Most respondents (74%) used BoNT injections for perioperative treatment for patients with limb spasticity undergoing surgery. Of those surveyed, 65% of physicians used BoNT preoperatively, 21% used BoNT intraoperatively, and 24% used BoNT postoperatively. Of the physicians who performed BoNT injections preoperatively, 6% performed BoNT injections 7 to 12 weeks preoperatively, 32% performed BoNT injections 4 to 6 weeks preoperatively, 47% performed BoNT injections 2 to 3 weeks preoperatively, and 15% performed BoNT injections 0 to 1 week preoperatively. The majority of physicians (85%) responded that injecting BoNT perioperatively may improve a patient's surgical outcome and all of the participants (100%) stated that BoNT did not contribute to any perioperative complications or adverse effects. Qualitative responses emphasized that successful outcomes from the perioperative BoNT were linked to enhanced collaboration with surgeons and that more research is needed to determine the optimal timing of perioperative BoNT. Conclusion Canadian physicians, mostly PMR specialists, administer perioperative BoNT to improve outcomes of surgeries performed on spastic limbs. The optimal timing for perioperative BoNT was suggested to be 2 to 3 weeks before the surgery by 47% of survey respondents. All participating physicians responded that perioperative BoNT did not contribute to any known perioperative complications or adverse events. This study highlights the importance of conducting more robust research to better understand optimal timing for perioperative BoNT injection, enhancing collaboration between physicians and surgeons, and increasing awareness of perioperative BoNT when planning for surgeries on spastic limbs.

Objective: Examine the feasibility and acceptability of an electrocardiogram (ECG) attached to a mobile phone (iECG) screening device for atrial fibrillation (AF) in Aboriginal Controlled Community Health Services (ACCHS) and other community settings. Methods: Semi‐structured interviews were conducted with ACCHS staff in urban, rural and remote communities in three Australian states/territories. Quantitative and qualitative questions identified the enabling factors and barriers for staff and Aboriginal patients' receptiveness to the device. Mean quantitative scores and their standard deviation were calculated in Microsoft Excel and qualitative questions were thematically analysed. Results: Eighteen interviews were conducted with 23 staff across 11 ACCHS. Quantitative data found staff were confident in providing iECG screening and managing the referral pathway, and thought the process was beneficial for patients. Qualitative data highlighted the usefulness of the device to undertake opportunistic screening and acceptability in routine practice, and provided opportunities to engage patients in education around AF. Conclusion: The iECG device was well accepted within ACCHSs and was feasible to use to screen for AF among Aboriginal patients. Implications for public health: The device can be used in clinical and community settings to screen Aboriginal people for atrial fibrillation to help reduce rates of stroke and other cardiovascular diseases.

Objective To create a consensus statement on the considerations for treatment of anticoagulated patients with botulinum toxin A (BoNTA) intramuscular injections for limb spasticity. Design We used the Delphi method. Setting A multiquestion electronic survey. Participants Canadian physicians (N=39) who use BoNTA injections for spasticity management in their practice. Interventions After the survey was sent, there were e-mail discussions to facilitate an understanding of the issues underlying the responses. Consensus for each question was reached when agreement level was ≥75%. Main Outcome Measures Not applicable. Results When injecting BoNTA in anticoagulated patients: (1) BoNTA injections should not be withheld regardless of muscles injected; (2) a 25G or smaller size needle should be used when injecting into the deep leg compartment muscles; (3) international normalized ratio (INR) level should be ≤3.5 when injecting the deep leg compartment muscles; (4) if there are clinical concerns such as history of a fluctuating INR, recent bleeding, excessive or new bruising, then an INR value on the day of injection with point-of-care testing or within the preceding 2-3 days should be taken into consideration when injecting deep compartment muscles; (5) the concern regarding bleeding when using direct oral anticoagulants (DOACs) should be the same as with warfarin (when INR is in the therapeutic range); (6) the dose and scheduling of DOACs should not be altered for the purpose of minimizing the risk of bleeding prior to BoNTA injections. Conclusions These consensus statements provide a framework for physicians to consider when injecting BoNTA for spasticity in anticoagulated patients. These consensus statements are not strict guidelines or decision-making steps, but rather an effort to generate common understanding in the absence of evidence in the literature.

Background: Australia’s healthcare system is complex and fragmented which can create challenges in healthcare, particularly in rural and remote areas. Aboriginal people experience inequalities in healthcare treatment and outcomes. This study aimed to investigate barriers and enablers to accessing healthcare services for Aboriginal people living in regional and remote Australia. Methods: Semi-structured interviews were conducted with healthcare delivery staff and stakeholders recruited through snowball sampling. Three communities were selected for their high proportion of Aboriginal people and diverse regional and remote locations. Thematic analysis identified barriers and enablers. Results: Thirty-one interviews were conducted in the three communities (n = 5 coastal, n = 13 remote, and n = 13 border) and six themes identified: (1) Improved coordination of healthcare services, (2) Better communication between services and patients, (3) Trust in services and cultural safety, (4) Importance of prioritizing health services by Aboriginal people, (5) Importance of reliable, affordable and sustainable services, (6) Distance and transport availability. These themes were often present as both barriers and enablers to healthcare access for Aboriginal people. They were also present across the healthcare system and within all three communities. Conclusions: This study describes a pathway to better healthcare outcomes for Aboriginal Australians by providing insights into ways to improve access.

INTRODUCTION: Prolonged compression is a common cause of radial neuropathy in able-bodied individuals but has not been reported in individuals with chronic SCI. This is despite the fact that individuals with SCI may be at increased risk of peripheral nerve injuries due to wheelchair mobility and baseline sensory deficits. Furthermore, diagnosis of peripheral nerve injury poses a unique challenge in this population because symptoms and signs are superimposed on pre-existing central deficits. CASE PRESENTATION: We present the case of a 48-year-old man with a C6 AIS A SCI from a motor vehicle accident 22 years earlier who had a new onset compressive radial neuropathy. At initial assessment he complained of paresthesia along his lateral right arm accompanied by new onset wrist-drop. Subsequent radial nerve conduction studies revealed severe reductions in amplitude for sensory and motor action potentials. The patient was managed with mobility exercises and vitamin B supplementation and showed full recovery of motor and sensory function to baseline levels on follow-up 4 months after the injury. DISCUSSION: The electrophysiologic profile of this patient is illustrative of severe nerve compression for an extended time period. Unlike able-bodied individuals who can reposition themselves to alleviate nerve compression, individuals with SCI may be unaware of nerve compression or unable to reposition themselves. This highlights the need for precautionary measures such as maneuvers and devices to provide trunk and limb stability along with the use of medical alert devices that allow individuals to access timely help when unattended.

Despite a substantial decline in childhood mortality rates in South Africa (SA), progress in neonatal mortality reduction has been much slower. Severe bacterial infections remain a leading cause of neonatal morbidity and a direct cause of 13.1% of neonatal deaths among babiesgt;1 kg. The incidence of hospital-acquired infections, antimicrobial resistance and outbreaks of infections in SA neonatal units is substantial, and is possibly higher than the currently available estimates. The SA Neonatal Sepsis Task Force was launched in Port Elizabeth, SA, on 13 September 2019 to provide technical advice and guidance on surveillance for neonatal sepsis, infection prevention, case management, antimicrobial stewardship and containment of neonatal unit outbreaks.

The domestic pig (Sus scrofa) is both an economically-important livestock species and a model for biomedical research. Two highly-contiguous pig reference genomes have recently been released. To support functional annotation of the pig genomes andcomparative analysis with large human transcriptomic datasets, we aimed to create a pig gene expression atlas. To achieve thisobjective, we extended a previous approach developed for the chicken. We down-loaded RNAseq datasets from public repositories,down-sampled to a common depth and quantified expression against a reference transcriptome using the mRNA quantitation tool,Kallisto. We then used the network analysis tool, Graphia to identify clusters of transcripts that were co-expressed across themerged dataset. Consistent with the principle of guilt-by-association, we identified co-expression clusters that were highly tissueor cell-type restricted and contained transcription factors that have previously been implicated in lineage determination. Otherclusters were enriched for transcripts associated with biological processes, such as the cell cycle and oxidative phosphorylation.The same approach was used to identify co-expression clusters within RNAseq data from multiple individual liver and brainsamples, highlighting cell type, process and region-specific gene expression. Evidence of conserved expression can add confidenceto assignment of orthology between pig and human genes. Many transcripts currently identified as novel genes with ENSSSCG orLOC IDs were found to be co-expressed with annotated neighbouring transcripts in the same orientation indicating they may beproducts of the same transcriptional unit. The meta-analytic approach to utilising public RNAseq data is extendable to include newdatasets and new species and provides a framework to support the Functional Annotation of Animals Genomes (FAANG) initiative.

Background Circulatory diseases continue to be the greatest cause of mortality for Australian Aboriginal and Torres Strait Islander people, and a major cause of persistently lower life expectancy compared with non-Aboriginal Australians. The limited information that exists on atrial fibrillation (AF) prevalence in Aboriginal and Torres Strait Islander communities is mostly based on hospital admission data. This shows AF as principal or additional admission diagnosis was 1.4 times higher compared to non-Aboriginal Australians, a higher incidence of AF across the adult life span after age 20 years and a significantly higher prevalence among younger patients. Our study estimates the first national community prevalence and age distribution of AF (including paroxysmal) in Australian Aboriginal people. A handheld single-lead electrocardiograph (ECG) device (iECG), known to be acceptable in this population, was used to record participant ECGs. Methods This co-designed, descriptive cross-sectional study was conducted in partnership with 16 Aboriginal Community Controlled Health organisations at their facilities and/or with their services delivered elsewhere. The study was also conducted at one state community event. Three (3) Australian jurisdictions were involved: New South Wales, Western Australia and the Northern Territory. Study sites were located in remote, regional and urban areas. Opportunistic recruitment occurred between June 2016 and December 2017. People Results Thirty (30) of 619 Aboriginal people received a ‘Possible AF’ and 81 an ‘Unclassified’ result from a hand-held smartphone ECG device. A final diagnosis of AF was made in 29 participants (4.7%; 95%CI 3.0%–6.4%), 25 with known AF (five paroxysmal), and four with previously unknown AF. Three (3) of the four with unknown AF were aged between 55–64 years, consistent with a younger age of AF onset in Aboriginal people. Estimated AF prevalence increased with age and was higher in those aged > 55 years than the general population (7.2% compared with 5.4%). Slightly more men than women were diagnosed with AF. Conclusions This study is a significant contribution to the evidence which supports screening for AF in Aboriginal and Torres Strait Islander people commencing at a younger age than as recommended in the Australian guidelines ( > 65 years). We recommend the age of 55 years. Consideration should be given to the inclusion of AF screening in the Australian Government Department of Health annual ‘Aboriginal and Torres Strait Islander Health Assessment’. Clinical Trial Registration number ACTRN12616000459426.

Background: Data on antimicrobial use among hospitalized children in Africa are very limited due to the absence of electronic prescription tracking. Methods: This study evaluated antimicrobial consumption rates, the antimicrobial spectrum used, and the indications for therapy on a paediatric ward and in the paediatric intensive care unit (PICU) at Tygerberg Hospital, Cape Town, South Africa. Antimicrobial prescription and patient demographic data were collected prospectively from May 10, 2015 to November 11, 2015. For the same period, data on antimicrobials dispensed and costs were extracted from the pharmacy electronic medicine management system. The volume of antimicrobials dispensed (dispensing data) was compared with observed antimicrobial use (prescription data). Results: Of the 703 patients admitted, 415/451 (92%) paediatric ward admissions and 233/252 (92%) PICU admissions received ≥1 antimicrobials. On the ward, 89% of prescriptions were for community-acquired infections; 29% of PICU antimicrobials were prescribed for healthcare-associated infections. Ampicillin and third-generation cephalosporins were the most commonly prescribed agents. Antimicrobial costs were 67 541 South African Rand (ZAR) (5680 United States Dollars (USD)) on the ward and 210 484 ZAR (17 702 USD) in the PICU. Ertapenem and meropenem were the single largest contributors to antimicrobial costs on the ward (43%) and PICU (30%), respectively. The volume of antimicrobials dispensed by the pharmacy (dispensing data) differed considerably from observed antimicrobial use (prescription data). Conclusions: High rates of antimicrobial consumption were documented. Community-acquired infections were the main indication for prescription. Although pharmacy dispensing data did not closely approximate observed use, this represents a promising method for antimicrobial usage tracking in the future. Keywords: Antibiotic, Antimicrobial, Paediatric, Antibiotic stewardship, Surveillance, Prescription, Pharmacy

Safety concerns persist for long-term pediatric fluoroquinolone use. Seventy children (median age, 2.1 years) treated with levofloxacin 10–20 mg/kg once daily for multidrug-resistant tuberculosis (median observation time, 11.8 months) had few musculoskeletal events, no levofloxacin-attributed serious adverse events, and no Fridericia-corrected QT interval >450 ms. Long-term levofloxacin was safe and well tolerated.

Objective(s) To systematically review the association between ulnar nerve hypermobility at the elbow and ulnar neuropathy. Data Sources We searched the CINAHL, Embase, and Medline databases to July 4, 2020 for studies that evaluated the prevalence of ulnar nerve hypermobility in those with and without ulnar neuropathy. Study Selection Our inclusion criteria were: ulnar nerve hypermobility presence or absence determined by ulnar nerve examination at the elbow either A) under ultrasound or B) by clinical examination; ulnar neuropathy at the elbow presence or absence determined by either eletrophysiological or ultrasound measurements in addition to a physical examination and history; English language; case-control, cohort, or randomized controlled studies. 20 of 654 studies identified met inclusion criteria. Data Extraction We pooled data for ulnar nerve hypermobility subjects based on method of diagnosis and presence or absence of UNE. We reviewed these studies for ulnar nerve cross-sectional area measurements, and pooled data for cross sectional areas based on presence or absence of ulnar neuropathy at the elbow and ulnar nerve hypermobility. Data Synthesis The meta-analysis pooled rate of ulnar nerve hypermobility was 0.37 (95% CI: 0.20, 0.57) for those without ulnar neuropathy at the elbow and 0.33 (95% CI: 0.23, 0.45) for those with ulnar neuropathy at the elbow, which was not significantly different (p=0.73). We repeated the analysis for nerves examined under ultrasound, again, there was no significant difference between the pooled rates of ulnar nerve hypermobility between those with and without ulnar neuropathy at the elbow (p=0.80). Conclusions The clinical finding of ulnar nerve hypermobility is unhelpful when assessing for ulnar neuropathy at the elbow, as the presence of ulnar nerve hypermobility does not make the diagnosis of ulnar neuropathy at the elbow more likely. Author(s) Disclosures None

Background Critical illness polyneuromyopathy (CIPNM) increasingly is recognized as a source of disability in patients requiring intensive care unit (ICU) admission. The prevalence and impact of CIPNM on patients in the rehabilitation setting has not been established. Objectives To determine the proportion of at-risk rehabilitation inpatients with evidence of CIPNM and the functional sequelae of this disorder. Design Prospective observational study. Setting Tertiary academic rehabilitation hospital. Patients Rehabilitation inpatients with a history of ICU admission for at least 72 hours. Methods Electrodiagnostic studies were performed to evaluate for axonal neuropathy and/or myopathy in at least one upper and one lower limb. Main Outcome Measurements The primary outcome was prevalence of CIPNM. Secondary outcomes included Functional Independence Measure (FIM) scores, rehabilitation length of stay (RLOS), and discharge disposition. Results A total of 33 participants were enrolled; 70% had evidence of CIPNM. Admission FIM score, discharge FIM, FIM gain, and FIM efficiency were 64.1, 89.9, 25.5, and 0.31 in those with CIPNM versus 78.4, 94.6, 16.1, and 0.33 in those without CIPNM, respectively. Average RLOS was 123 days versus 76 days and discharge to home was 57% versus 90% in the CIPNM and non-CIPNM groups, respectively. Conclusions CIPNM is very common in rehabilitation inpatients with a history of ICU admission. It was associated with a lower functional status at rehabilitation admission, but functional improvement was at a similar rate to those without CIPNM. Longer RLOS stay may be required to achieve the same functional level. Level of Evidence III

OBJECTIVES: To determine the Canadian age-adjusted incidence rates of lower limb amputation (LLA) by province, sex, level, and cause of amputation. METHODS: Data on all hospital discharges associated with LLA from April 1, 2006, to March 31, 2012, were obtained from the Canadian Institute for Health Information’s Discharge Abstract Database. National and provincial age-adjusted rates were calculated per 100 000 individuals by sex, level, and cause of LLA using the direct method of standardization. The relative risk of LLA in people with diabetes was calculated. RESULTS: There were a total of 44 430 LLAs performed in Canada over the study years. The number of LLAs increased from 7331 in 2006 to 7708 in 2011. Mean (SD) age was 65.7 (16.6) years, and 68.8% were males. Sixty-five percent of the LLA cases were due to diabetes. The average age-adjusted rate of LLA in Canada was 22.9 per 100 000 individuals. The age-adjusted rates declined over the study years. The relative risk of diabetes-related LLAs was 28.9. CONCLUSION: This study provided the first Canadian national and provincial age-adjusted incidence rates of LLA and a baseline for monitoring and evaluation in the future. Understanding the incidence of LLA is essential to managing preventive and rehabilitation services for this population. Although the age-adjusted LLA incidence rates have decreased, the number of new LLAs has increased. The increase in the number of LLAs has important implications for social and health care costs.

Background The domestic pig (Sus scrofa) is important both as a food source and as a biomedical model given its similarity in size, anatomy, physiology, metabolism, pathology, and pharmacology to humans. The draft reference genome (Sscrofa10.2) of a purebred Duroc female pig established using older clone-based sequencing methods was incomplete, and unresolved redundancies, short-range order and orientation errors, and associated misassembled genes limited its utility. Results We present 2 annotated highly contiguous chromosome-level genome assemblies created with more recent long-read technologies and a whole-genome shotgun strategy, 1 for the same Duroc female (Sscrofa11.1) and 1 for an outbred, composite-breed male (USMARCv1.0). Both assemblies are of substantially higher (>90-fold) continuity and accuracy than Sscrofa10.2. Conclusions These highly contiguous assemblies plus annotation of a further 11 short-read assemblies provide an unprecedented view of the genetic make-up of this important agricultural and biomedical model species. We propose that the improved Duroc assembly (Sscrofa11.1) become the reference genome for genomic research in pigs.

Purpose: This study describes prosthetic rehabilitation services provided to individuals who have had a lower limb amputation in Canada. Method: This cross-sectional survey study used an online survey to collect data from facilities that provide lower limb prosthetic rehabilitation; it included questions about approaches and types of service, therapies, focus of service, and health care providers. One representative from each facility was asked to complete the survey. Results: Of the 65 identified eligible facilities, 59 completed the survey (response rate = 90.8%). The majority of facilities ( n = 39; 66.1%) indicated that they provided both in-patient and outpatient prosthetic rehabilitation services. All facilities provided balance, coordination, and gait training as well as prosthetic fit education. Most facilities indicated that they had a physical therapist ( n = 58; 93.8%), an occupational therapist ( n = 52; 88.1%), and a prosthetist ( n = 52; 88.1%) on their team. Conclusions: The majority of the facilities surveyed provided both in-patient and outpatient services and had specialized health care provider teams. Future surveys are required to collect more specific information about prosthetic rehabilitation in Canada.

Background. Ampicillin to treat Listeria monocytogenes (LM) infection is empirically added to the treatment of infants (

Objective: To assess the feasibility of Wii.n.Walk for improving walking capacity in older adults with lower limb amputation. Design: A parallel, evaluator-blind randomized controlled feasibility trial. Setting: Community-living. Participants: Individuals who were ⩾50 years old with a unilateral lower limb amputation. Intervention: Wii.n.Walk consisted of Wii Fit training, 3x/week (40 minute sessions), for 4 weeks. Training started in the clinic in groups of 3 and graduated to unsupervised home training. Control group were trained using cognitive games. Main Measures: Feasibility indicators: trial process (recruitment, retention, participants’ perceived benefit from the Wii.n.Walk intervention measured by exit questionnaire), resources (adherence), management (participant processing, blinding), and treatment (adverse event, and Cohen’s d effect size and variance). Primary clinical outcome: walking capacity measured using the 2 Minute Walk Test at baseline, end of treatment, and 3-week retention. Results: Of 28 randomized participants, 24 completed the trial (12/arm). Median (range) age was 62.0 (50-78) years. Mean (SD) score for perceived benefit from the Wii.n.Walk intervention was 38.9/45 (6.8). Adherence was 83.4%. The effect sizes for the 2 Minute Walk Test were 0.5 (end of treatment) and 0.6 (3-week retention) based on intention to treat with imputed data; and 0.9 (end of treatment) and 1.2 (3-week retention) based on per protocol analysis. The required sample size for a future larger RCT was deemed to be 72 (36 per arm). Conclusions: The results suggested the feasibility of the Wii.n.Walk with a medium effect size for improving walking capacity. Future larger randomized controlled trials investigating efficacy are warranted.

The expression patterns of secreted (MUC2 and MUC5AC) and membrane-tethered (MUC1, MUC4, MUC12 and MUC13) mucins were monitored in healthy pigs and pigs challenged orally with Lawsonia intracellularis. These results showed that the regulation of mucin gene expression is distinctive along the GI tract of the healthy pig, and may reflect an association between the function of the mucin subtypes and different physiological demands at various sites. We identified a specific depletion of secreted MUC2 from goblet cells in infected pigs that correlated with the increased level of intracellular bacteria in crypt cells. We concluded that L. intracellularis may influence MUC2 production, thereby altering the mucus barrier and enabling cellular invasion.

Background. A countrywide epidemic of Listeria monocytogenes (LM) in South Africa began in the first quarter of 2017, rapidly becoming the world’s largest LM outbreak to date. Methods. We describe the clinical course of neonates with culture-confirmed LM infection admitted to a tertiary neonatal unit at Tygerberg Hospital, Cape Town (1 January 2017 - 31 January 2018). Current epidemic LM cases were compared with a historical cohort of sporadic neonatal LM cases at our institution (2006 - 2016). The global literature on epidemic neonatal LM outbreaks (1 January 1978 - 31 December 2017) was reviewed. Results. Twelve neonates (median gestational age 35 weeks, median birth weight 2 020 g) were treated for confirmed LM bacteraemia in 2017/18, presenting at a median age of 0.5 days. In 5 cases, neurolisteriosis was suspected. Three neonates died (25.0%) v. 8/13 neonatal deaths (61.6%) in the sporadic listeriosis cohort (2006 - 2016) ( p =0.075). The institution’s neonatal LM infection incidence increased significantly in 2017 from a historical rate of 0.17/1 000 live births to 1.4/1 000 ( p

Balancing selection provides a plausible explanation for the maintenance of deleterious alleles at moderate frequency in livestock, including lethal recessives exhibiting heterozygous advantage in carriers. In the current study, a leg weakness syndrome causing mortality of piglets in a commercial line showed monogenic recessive inheritance, and a region on chromosome 15 associated with the syndrome was identified by homozygosity mapping. Whole genome resequencing of cases and controls identified a mutation coding for a premature stop codon within exon 3 of the porcineMyostatin (MSTN)gene, similar to those causing a double-muscling phenotype observed in several mammalian species. TheMSTNmutation was in Hardy-Weinberg equilibrium in the population at birth, but significantly distorted amongst animals still in the herd at 110 kg, due to an absence of homozygous mutant genotypes. In heterozygous form, theMSTNmutation was associated with a major increase in muscle depth and decrease in fat depth, suggesting that the deleterious allele was maintained at moderate frequency due to heterozygous advantage. Knockout of the porcineMSTNby gene editing has previously been linked to problems of low piglet survival and lameness. ThisMSTNmutation is an example of putative balancing selection in livestock, providing a plausible explanation for the lack of disrupting MSTN mutations in pigs despite many generations of selection for lean growth.

BACKGROUND Primary, specialist, and allied health services can assist in providing equitable access in rural and remote areas, where higher proportions of Aboriginal and Torres Strait Islander people (Aboriginal Australians) reside, to overcome the high rates of chronic diseases experienced by this population group. Little is currently known about the location and frequency of services and the extent to which providers believe delivery is occurring in a sustained and coordinated manner. OBJECTIVE The objective of this study will be to determine the availability, accessibility, and level of coordination of a range of community-based health care services to Aboriginal people and identify potential barriers in accessing health care services from the perspectives of the health service providers. METHODS This mixed-methods study will take place in 3 deidentified communities in New South Wales selected for their high population of Aboriginal people and geographical representation of location type (coastal, rural, and border). The study is designed and will be conducted in collaboration with the communities, Aboriginal Community Controlled Health Services (ACCHSs), and other local health services. Data collection will involve face-to-face and telephone interviews with participants who are health and community professionals and stakeholders. Participants will be recruited through snowball sampling and will answer structured, quantitative questions about the availability and accessibility of primary health care, specialist medical and allied health services and qualitative questions about accessing services. Quantitative data analysis will determine the frequency and accessibility of specific services across each community. Thematic and content analysis will identify issues relating to availability, accessibility, and coordination arising from the qualitative data. We will then combine the quantitative and qualitative data using a health ecosystems approach. RESULTS We identified 28 stakeholder participants across the ACCHSs for recruitment through snowball sampling (coastal, n=4; rural, n=12; and border, n=12) for data collection. The project was funded in 2017, and enrolment was completed in 2017. Data analysis is currently under way, and the first results are expected to be submitted for publication in 2019. CONCLUSIONS The study will give an indication of the scope and level of coordination of primary, specialist, and allied health services in rural communities with high Aboriginal populations from the perspectives of service providers from those communities. Identification of factors affecting the availability, accessibility, and coordination of services can assist ways of developing and implementing culturally sensitive service delivery. These findings could inform recommendations for the provision of health services for Aboriginal people in rural and remote settings. The study will also contribute to the broader literature of rural and remote health service provision. INTERNATIONAL REGISTERED REPOR DERR1-10.2196/11471

Despite the popularity of commercial games in lower limb prosthetic rehabilitation, data about their prevalence of use as well as therapists' perspectives about these games are still lacking.To learn about the prevalence of use of commercial games in lower limb prosthetic rehabilitation and therapists' perspectives about these games.Cross-sectional.An online survey was sent to physical and occupational therapists across prosthetic rehabilitation facilities in Canada. The survey had questions about the use of commercial games and therapists' perspectives.Data were collected from 82 therapists. Overall, 46.3% (38/82) reported that they use commercial games; of those, 94.7% (36/38) used the Nintendo Wii Fit. The most reported perceived benefits were the Wii Fit helping to improve weight shifting ( n = 76/82, 92.7%) and balance ( n = 75/82, 91.5%), and being motivating and complementing traditional therapy ( n = 75/82, 91.5%). The most reported perceived barriers/challenges were lack of time and familiarity with the games ( n = 58/82, 70.7%).Commercial games, particularly the Wii Fit, are commonly used in lower prosthetic rehabilitation in Canada. Most of the queried therapists view the Wii Fit positively. Knowledge translation activities and developing standard treatment protocols would be helpful in minimizing the barriers identified in this study. Clinical relevance The Wii Fit is prevalent in lower limb prosthetic rehabilitation in Canada and it is viewed positively by therapists as having the potential to improve balance and weight bearing, making rehabilitation more motivating, and complementing traditional therapy. Future studies should investigate the efficacy of the Wii Fit in prosthetic rehabilitation.

This was a cross-over efficacy study design. To determine spasticity differences between static and dynamic standing training in individuals with spinal cord injury (SCI). Vancouver, Canada. Ten individuals with SCI who could stand with or without bracing or supports participated in both dynamic and static standing training (one session each, 2 days apart) using a Segway. The primary outcome was spasticity as measured by Visual Analog Scale (VAS), Modified Ashworth Scale (MAS) and electromyography (EMG) of the quadriceps, hamstrings, adductors and gastrocnemius. There was no statistically detectable difference in spasticity between dynamic and static standing training in individuals with SCI as measured by VAS, MAS or EMG, although there was a trend towards decreased spasticity after the dynamic training. There is no significant difference in spasticity outcomes between static and dynamic standing training on a Segway for individuals with SCI. This research was funded by Natural Sciences and Engineering Research Council of Canada and International Collaboration on Repair Discoveries.

Background. High antenatal human immunodeficiency virus (HIV) seroprevalence rates (∼30%) with low perinatal HIV transmission rates (2.5%), due to HIV prevention of mother-to-child transmission program improvements in South Africa, has resulted in increasing numbers of HIV-exposed but uninfected (HEU) children. We aimed to describe the epidemiology of invasive pneumococcal disease (IPD) in HEU infants. Methods. We conducted a cross-sectional study of infants aged

Female reproductive performance traits in pigs have low heritabilities thus limiting improvement through traditional selective breeding programmes. However, there is substantial genetic variation found between pig breeds with the Chinese Meishan being one of the most prolific pig breeds known. In this study, three cohorts of Large White × Meishan F2 cross-bred pigs were analysed to identify quantitative trait loci (QTL) with effects on reproductive traits, including ovulation rate, teat number, litter size, total born alive and prenatal survival. A total of 307 individuals were genotyped for 174 genetic markers across the genome. The genome-wide analysis of the trait-recorded F2 gilts in their first parity/litter revealed one QTL for teat number significant at the genome level and a total of 12 QTL, which are significant at the chromosome-wide level, for: litter size (three QTL), total born alive (two QTL), ovulation rate (four QTL), prenatal survival (one QTL) and teat number (two QTL). Further support for eight of these QTL is provided by results from other studies. Four of these 12 QTL were mapped for the first time in this study: on SSC15 for ovulation rate and on SSC18 for teat number, ovulation rate and litter size.

Introduction There is a 10-year gap in life expectancy between Aboriginal and non-Aboriginal Australians. The leading cause of death for Aboriginal Australians is cardiovascular disease, including myocardial infarction and stroke. Although atrial fibrillation (AF) is a known precursor to stroke there are no published studies about the prevalence of AF for Aboriginal people and limited evidence about AF in indigenous populations globally. Methods and analysis This mixed methods study will recruit and train Aboriginal health workers to use an iECG device attached to a smartphone to consecutively screen 1500 Aboriginal people aged 45 years and older. The study will quantify the proportion of people who presented for follow-up assessment and/or treatment following a non-normal screening and then estimate the prevalence and age distribution of AF of the Australian Aboriginal population. The study includes semistructured interviews with the Aboriginal health workers about the effectiveness of the iECG device in their practice as well as their perceptions of the acceptability of the device for their patients. Thematic analysis will be undertaken on the qualitative data collected in the study. If the device and approach are acceptable to the Aboriginal people and widely adopted, it may help prevent the effects of untreated AF including ischaemic stroke and early deaths or impairment in Aboriginal people. Ethics and dissemination This mixed methods study received ethics approval from the Aboriginal Health and Medical Research Council (1135/15) and the Australian Health Council of Western Australia (HREC706). Ethics approval is being sought in the Northern Territory. The findings of this study will be shared with Aboriginal communities, in peer reviewed publications and at conferences. There are Aboriginal investigators in each state/territory where the study is being conducted who have been actively involved in the study. They will also be involved in data analysis, dissemination and research translation. Trial registration number ACTRN12616000459426.

Objective: To systematically review randomized controlled trials of botulinum neurotoxin for limb spasticity to determine whether different injection techniques affect spasticity outcomes. Methods: MEDLINE, EMBASE, CINAHL, and Cochrane Central Register of Controlled Trials electronic databases were searched for English language human randomized controlled trials from 1990 to 13 May 2016. Studies were assessed in duplicate for data extraction and risk of bias using the Physiotherapy Evidence Database scale and graded according to Sackett’s levels of evidence. Results: Nine of 347 studies screened met selection criteria. Four categories of botulinum neurotoxin injection techniques were identified: (1) injection localization technique; (2) injection site selection; (3) injectate volume; (4) injection volume and site selection. There is level 1 evidence that: ultrasound, electromyography, and electrostimulation are superior to manual needle placement; endplate injections improve outcomes vs. multisite quadrant injections; motor point injections are equivalent to multisite injections; high volume injections are similar to low volume injections; and high volume injections distant from the endplate are more efficacious than low volumes closer to the endplate. Conclusion: Level 1 evidence exists for differences in treatment outcomes using specific botulinum neurotoxin injection techniques. Findings are based on single studies that require independent replication and further study.

Summary Background The 13-valent pneumococcal conjugate vaccine (PCV13) was designed to include disease-causing serotypes that are important in low-income and middle-income countries. Vaccine effectiveness estimates are scarce in these settings. South Africa replaced PCV7 with PCV13 in 2011 using a 2 + 1 schedule. We aimed to assess the effectiveness of two or more doses of PCV13 against invasive pneumococcal disease in children with HIV infection and in those not infected with HIV. Methods Cases of invasive pneumococcal disease in children aged 5 years or younger were identified through national laboratory-based surveillance. Isolates were serotyped with the Quellung reaction or PCR. We sought in-hospital controls for every case, matched for age, HIV status, and study site. We aimed to enrol four controls for every case not infected with HIV and six controls for every case with HIV infection (case-control sets). With conditional logistic regression, we calculated vaccine effectiveness as a percentage, with the equation 1 – [adjusted odds ratio for vaccination] × 100. We included data from an earlier investigation of PCV7 to assess vaccine effectiveness in children exposed to but not infected with HIV and in malnourished children not infected with HIV. Findings Between January, 2012, and December, 2014, we enrolled children aged 16 weeks or older to our study: 240 were cases not infected with HIV, 75 were cases with HIV infection, 1118 were controls not infected with HIV, and 283 were controls with HIV infection. The effectiveness of two or more doses of PCV13 against PCV13-serotype invasive pneumococcal disease was 85% (95% CI 37 to 96) among 11 case-control sets of children not infected with HIV and 91% (−35 to 100) among three case-control sets of children with HIV infection. PCV13 effectiveness among 26 case-control sets of children not infected with HIV was 52% (95% CI −12 to 79) against all-serotype invasive pneumococcal disease and 94% (44 to 100) for serotype 19A. Vaccine effectiveness against PCV7-serotype invasive pneumococcal disease was 87% (95% CI 38 to 97) in children exposed to HIV but uninfected and 90% (53 to 98) in malnourished children not infected with HIV. Interpretation Our results indicate that PCV13 in a 2 + 1 schedule is effective for preventing vaccine-type pneumococcal infections in young children not infected with HIV, including those who are malnourished or who have been exposed to HIV. Although the point estimate for PCV13 vaccine effectiveness in children infected with HIV was high, it did not reach significance, possibly because of the small sample size. These findings support recommendations for widespread use of pneumococcal conjugate vaccine in low-income and middle-income countries. Funding Gavi, The Vaccine Alliance.

Interferon regulatory factor 7 (IRF7), as a key regulator of type I interferon response, plays an important role during innate response against viral infection. Although well conserved across species, the structure of IRF7 and its function during parasite infection are not well documented in farm animals, such as the pig. To bridge this gap, we have determined the porcine IRF7 gene structure and identified two intronic single nucleotide polymorphisms (SNPs), SNP g.748G>C and SNP g.761A>G, in commercial pig breeds. The distribution of SNP g.761A>G in multiple breeds suggested that it was in Hardy-Weinberg equilibrium and allowed us to map it at the top of SSC2. We found that during Sarcocystis miescheriana infection, the G allele was associated with high lymphocyte levels (P G enhances the transactivation activity of IRF7, possibly by improving IRF7 transcript splicing of intron-3. These findings would suggest that IRF7, as a transcriptional regulator, is involved in the defence mechanism against a larger spectrum of pathogens, and in more host species, than initially anticipated.

This paper describes our experience of the novel H1N1 pandemic at Tygerberg Children’s Hospital. Twenty-six children with polymerase chain reaction (PCR)-confrmed H1N1 infection were hospitalised between 1 July 2009 and 30 September 2009. Seventy-three per cent (19/26) had underlying co-morbidities. Cough and/or dyspnoea (92%) and fever (54%) were the main presenting features. Seven children (27%) required intensive care management, with one death. Nosocomial transmission was suspected in 6/26 (23%) children. The H1N1 pandemic caused morbidity especially among low birthweight, premature infants. There is a need for continued vigilance, improved isolation facilities and appropriate immunisation.

Sequences from 20 amplicons representing nine different loci and 11369bp from the short arm of the pig Y chromosome were compared using pools of DNA from different European and Chinese breeds. A total of 33 polymorphic sites were identified, including five indels and 28 single nucleotide polymorphisms (SNPs). Three high frequency SNPs within the coding regions of SRY were further analysed across 889 males representing 25 European and 25 Asian breeds or Lines, plus a European Line of Meishan. Two haplotypes seen to be associated with 'European' or 'Chinese' origin in the initial SNP discovery phase were found to be the most common in their respective groups of breeds in a more detailed genotyping study. Two further SRY haplotypes are relatively rare. One was found exclusively within Tamworth, at low frequency in Retinto, and in three Chinese breeds (Huai, Sahwutou and Xiaomeishan). The other uncommon haplotype is found exclusively in Bamajiang, two further Chinese breeds (Hangjiang Black and Longling) and two European rare breeds (Mangalica and Linderodssvin), but appears based on comparison with other suids to represent an ancestral sequence.