Using routine testing data to understand circulation patterns of influenza A, respiratory syncytial virus and other respiratory viruses in Victoria, Australia.

Several studies have reported evidence of interference between respiratory viruses: respiratory viruses rarely reach their epidemic peak concurrently and there appears to be a negative association between infection with one respiratory virus and co-infection with another. We used results spanning 16 years (2002-2017) of a routine diagnostic multiplex panel that tests for nine respiratory viruses to further investigate these interactions in Victoria, Australia. Time series analyses were used to plot the proportion positive for each virus. The seasonality of all viruses included was compared with respiratory syncytial virus (RSV) and influenza A virus using cross-correlations. Logistic regression was used to explore the likelihood of co-infection with one virus given infection with another. Seasonal peaks were observed each year for influenza A and RSV and less frequently for influenza B, coronavirus and parainfluenza virus. RSV circulated an average of 6 weeks before influenza A. Co-infection with another respiratory virus was less common with picornavirus, RSV or influenza A infection. Our findings provide further evidence of a temporal relationship in the circulation of respiratory viruses. A greater understanding of the interaction between respiratory viruses may enable better prediction of the timing and magnitude of respiratory virus epidemics.

Clinical purpura and elastosis and their correlation with skin tears in an aged population.

The previous research reported the results of a prospect cohort study that used logistic regression analysis to construct a risk prediction model for skin tears in individuals aged over 65 years. The model identified three baseline individual characteristics (male gender, history of STs, and history of falls) and two baseline skin manifestations (purpura and elastosis) that predicted the risk of dorsal forearm skin tears. This paper outlines the relationships between baseline skin manifestations and the risk of skin tears. Univariable logistic regression analysis was conducted of all the baseline data collected from the same-study participants to identify variables that significantly predicted purpura and elastosis at baseline. Amongst the 173 participants, 71 (41%) developed one or more skin tears, and in these participants, 52 (73.2%) displayed purpura, 41 (57.8%) had elastosis, and 30 (42.3%) exhibited both manifestations of the dorsal forearm at baseline. Four individual characteristics (age, history of skin tears, history of falls, and antiplatelet therapy) and three skin properties (pH, subepidermal low echogenicity band of the forearms, and skin thickness) were found to predict the risk of purpura. Conversely, three individual variables (age, gender, and smoking), three clinical skin variables (uneven skin pigmentation, cutis rhomboidalis nuchae, and history of actinic keratosis) and one skin property variable (collagen type IV) predicted the risk of skin elastosis. Progressive changes to the skin's structural and mechanical properties from the underlying effects of chronological ageing, and environmental and lifestyle-related influences increased the risk of purpura and elastotic skin manifestations and concomitantly increased risk of skin tears amongst participants.

A severe 2017 influenza season dominated by influenza A(H3N2), Victoria, Australia.

Surveillance for influenza-like illness (ILI) and laboratory-confirmed influenza in Victoria, Australia is undertaken jointly by the Victorian Infectious Diseases Reference Laboratory and the Victorian Government Department of Health and Human Services from May to October each year. Surveillance data comprise notifiable laboratory-confirmed influenza and ILI reporting from from two sources - a general practice sentinel surveillance programme and a locum service. The magnitude of the 2017 influenza season was high in Victoria with widespread circulation of influenza type A(H3N2), which peaked in September. A record number of laboratory-confirmed influenza cases were notified, and the proportion of ILI cases to total consultations from both the general practice and locum service were higher than previous years. Notified cases of influenza A were older than influenza B cases with 25% compared to 17% aged more than 65 years, respectively. The proportion of swabs that were positive for influenza peaked at 58%. Antigenic characterization suggested a good match between the circulating and vaccine strains of influenza A(H3N2). Most of the increases observed in notified cases of laboratory-confirmed influenza in recent years in Victoria have been attributed to increases in testing. However, that cases of ILI also increased in Victoria in 2017 is suggestive that 2017 was a relatively severe season. The dominance of influenza type A(H3N2), the extended duration of elevated activity, and a potential phylogenetic mismatch of vaccine to circulating strains are likely to have contributed to the relative severity of the 2017 season. Victoria is Australia's second most populous state and is the mainland's southernmost state. It has a temperate climate with an influenza season usually occurring in the cooler months between May and October. The Victorian Infectious Diseases Reference Laboratory (VIDRL), in partnership with the Victorian Government Department of Health and Human Services (DHHS), coordinates influenza-like illness (ILI) and laboratory-confirmed influenza surveillance in Victoria. There are three data sources included in the influenza surveillance system.

Prevention of postsurgical wound dehiscence after abdominal surgery with NPWT: a multicentre randomised controlled trial protocol.

OBJECTIVE: The effectiveness of negative pressure wound therapy (NPWT) in the prevention of postoperative surgical wound dehiscence (SWD) is the subject of much debate and remains to be determined. This study will identify individuals at risk of postoperative SWD and trial the use of NPWT as a prophylactic measure against the occurrence of SWD, compared with a non-NPWT standard surgical dressing (SSD). METHOD: A prospective multicentre randomised controlled trial comparing NPWT dressing against standard surgical dressings (SSD) will be conducted. An intention-to-treat (ITT) approach will be used for the trial. AIMS: The primary outcome is the prevention of postoperative SWD up to and including day 30 postoperative. Secondary outcomes are: prevention of surgical site infection (SSI) and economic analysis of treatment groups. CONCLUSION: This study will determine the effectiveness of NPWT in the prevention of postoperative abdominal SWD in a predefined level of risk population. This level 1 study will provide further data for abdominal SWD risk classification, which is anticipated to inform preventive postoperative management. The study design uses a prospective real-world scenario in order to identify clinically significant differences between the intervention and control groups. TRIAL REGISTRATION: This trial was prospectively registered on 10 December 2012 with Australian and New Zealand Clinical Trials Network (ANZCTR): 12612001275853.

Surgical wound dehiscence in an Australian community nursing service: time and cost to healing.

OBJECTIVE: Surgical wound dehiscence (SWD) increases the length of hospital stay and impacts on patient wellbeing and health-care costs. Globally, the health-care costs associated with SWD are poorly reported and those reported are frequently associated with surgical site infection (SSI), rather than dehiscence of non-microbial cause. This retrospective study describes and reports on the costs and time to healing associated with a number of surgical patients who were referred to a community nursing service for treatment of an SWD following discharge from a metropolitan hospital, in Perth, Western Australia. METHOD: Descriptive statistical analysis was carried out to describe the patient, wound and treatment characteristics. A costing analysis was conducted to investigate the cost of healing these wounds. RESULTS: Among the 70 patients referred with a SWD, 55% were treated for an infected wound dehiscence which was a significant factor (p=0.001). Overall, the cost of treating the 70 patients with a SWD in a community nursing service was in excess of $56,000 Australian dollars (AUD) (£28,705) and did not include organisational overheads or travel costs for nurse visits. The management of infection contributed to 67% of the overall cost. CONCLUSION: SWD remains an unquantified aspect of wound care from a prevalence and fiscal point of view. Further work needs to be done in the identification of SWD and which patients may be 'at risk'. DECLARATION OF INTEREST: The authors declare they have no competing interests.

Pooled influenza vaccine effectiveness estimates for Australia, 2012-2014.

Data were pooled from three Australian sentinel general practice influenza surveillance networks to estimate Australia-wide influenza vaccine coverage and effectiveness against community presentations for laboratory-confirmed influenza for the 2012, 2013 and 2014 seasons. Patients presenting with influenza-like illness at participating GP practices were swabbed and tested for influenza. The vaccination odds of patients testing positive were compared with patients testing negative to estimate influenza vaccine effectiveness (VE) by logistic regression, adjusting for age group, week of presentation and network. Pooling of data across Australia increased the sample size for estimation from a minimum of 684 to 3,683 in 2012, from 314 to 2,042 in 2013 and from 497 to 3,074 in 2014. Overall VE was 38% [95% confidence interval (CI) 24-49] in 2012, 60% (95% CI 45-70) in 2013 and 44% (95% CI 31-55) in 2014. For A(H1N1)pdm09 VE was 54% (95% CI-28 to 83) in 2012, 59% (95% CI 33-74) in 2013 and 55% (95% CI 39-67) in 2014. For A(H3N2), VE was 30% (95% CI 14-44) in 2012, 67% (95% CI 39-82) in 2013 and 26% (95% CI 1-45) in 2014. For influenza B, VE was stable across years at 56% (95% CI 37-70) in 2012, 57% (95% CI 30-73) in 2013 and 54% (95% CI 21-73) in 2014. Overall VE against influenza was low in 2012 and 2014 when A(H3N2) was the dominant strain and the vaccine was poorly matched. In contrast, overall VE was higher in 2013 when A(H1N1)pdm09 dominated and the vaccine was a better match. Pooling data can increase the sample available and enable more precise subtype- and age group-specific estimates, but limitations remain.

Seasonal influenza vaccine effectiveness estimates: Development of a parsimonious case test negative model using a causal approach.

BACKGROUND: Influenza vaccine effectiveness (VE) is increasingly estimated using the case-test negative study design. Cases have a symptom complex consistent with influenza and test positive for influenza, while non-cases have the same symptom complex but test negative. We aimed to determine a parsimonious logistic regression model for this study design when applied to patients in the community. METHODS: To determine the minimum covariate set required, we used a previously published systematic review to find covariates and restriction criteria commonly included in case-test negative logistic regression models. Covariates were assessed for inclusion using a directed acyclic graph. We used data from the Victorian Influenza Sentinel Practice Network from 2007 to 2013, excluding the pandemic year of 2009, to test the model. VE was estimated as (1-adjusted OR) * 100%. Changes in model fit from addition of specified covariates were examined. Restriction criteria were examined using change in VE estimate. VE was estimated for each year, all years aggregated, and for influenza type and sub-type. RESULTS: Using publicly available software, the directed acyclic graph indicated that covariates specifying age, time within the influenza season, immunocompromising comorbid conditions and year or study site, where applicable, were required for closure. The inclusion of sex was not required. Inclusions and exclusions were validated when testing the variables (when collected) with our data. Restriction by time between onset and swab was supported by the data. VE for all years aggregated was estimated as 53% (95%CI 38, 64). VE was estimated as 42% (95%CI 19, 59) for H3N2, 75% (95%CI 51, 88) for H1N1pdm09 and 63% (95%CI 38, 79) for influenza B. CONCLUSION: Theoretical covariates specified by the directed acyclic graph were validated when tested against surveillance data. A parsimonious model using the case test negative design allows regular estimates of VE and aggregated estimates by year.

A review of patient and skin characteristics associated with skin tears.

OBJECTIVE: Skin tears are the most common wound among the elderly and have the potential to cause infection, form chronic wounds, reduce quality of life and increase health-care costs. Our aim was to identify studies that reviewed patient and skin characteristics associated with skin tears. METHOD: A review of skin tear studies reported in the English literature between 1980 and 2013 was undertaken using the following electronic databases: PubMed, Medline, CINAHL, Embase, Scopus, Evidence Based and Medicine Reviews (EBM). Search terms included aged, skin, tears or lacerations, skin tearing, geri tear, epidermal tear and prevalence. RESULTS: There were 343 articles found with using the search terms. After abstract review nine were found to be relevant to the search. The principle findings from these eight published articles and one unpublished study revealed that the most common patient characteristics were a history of skin tears, impaired mobility and impaired cognition. Skin characteristics associated with skin tears included senile purpura, ecchymosis and oedema. CONCLUSION: This review provides an overview of identified patient and skin characteristics that predispose the elderly to skin tears and exposes the lack of research within this domain. DECLARATION OF INTEREST: R. Rayner is a recipient of a 2013 Australian Postgraduate Award, Curtin University Postgraduate Scholarship and a Wound Management Cooperative Research Centre (CRC) PhD stipend. The School of Nursing, Midwifery and Paramedicine, Curtin University and the Silver Chain Group, Western Australia are participants in the Wound Management Innovation CRC. No conflict of interest exists among the authors.

Decreased varicella and increased herpes zoster incidence at a sentinel medical deputising service in a setting of increasing varicella vaccine coverage in Victoria, Australia, 1998 to 2012.

We performed an ecological study using sentinel consultation data from a medical deputising service to assess the impact of increasing coverage with childhood varicella vaccine on the incidence risk of varicella and zoster in the population served by the deputising service in Victoria, Australia from 1998 to 2012. Following a successful vaccination programme, the incidence of varicella in Australia was modelled to decrease and the incidence of zoster to increase, based on a theoretical decrease in boosting of zoster immunity following a decrease in wild varicella virus circulation due to vaccination. Incidence risks (consultation proportions for varicella and zoster) were directly age-standardised to the Melbourne population in 2000, when varicella vaccine was first available. Age-standardised varicella incidence risk peaked in 2000 and halved by 2012. Age-standardised zoster incidence risk remained constant from 1998 to 2002, but had almost doubled by 2012. The increase in zoster consultations largely reflected increases in people younger than 50 years-old. Although causality cannot be inferred from ecological studies, it is generally agreed that the decrease in varicella incidence is due to increasing varicella vaccine coverage. The possible indirect effect of the vaccine on zoster incidence is less clear and ongoing monitoring of zoster is required.

Predicting concordance with multilayer compression bandaging.

OBJECTIVE: To examine the relationship between concordance with multilayer compression bandaging and a number of client and wound characteristics, including wound severity, health status and client independence with respect to activities of daily living. METHOD: Using data gathered for a randomised controlled trial that compared two types of antimicrobial dressings on infected or critically colonised lower leg ulcers, we explored the level of concordance with compression therapy by patients with wounds that had an ankle brachial pressure index of between 0.8 and 1.2. RESULTS: A logistic regression analysis found that increased pain and wound size, older age and shallow wound depth were all significant predictors of non-concordance with multilayer compression bandaging. CONCLUSION: Although the results suggest that pain, wound size, age and wound depth are all significant predictors of non-concordance with multilayer bandaging, the generalisability of these results is limited, given that data were gathered in the context of a RCT. Further studies are required to explore the relative contribution of predictors of concordance with compression therapy, in order to help inform strategies that promote it and, thereby, optimise healing. CONFLICT OF INTEREST: None.

Challenges faced in implementation of a telehealth enabled chronic wound care system.

INTRODUCTION: In the rural Midwest region of Western Australia (WA), wound care is a major burden on the healthcare system. Optimal wound care was found to be impeded by issues that included the involvement of multiple healthcare providers, incomplete and inconsistent documentation, and limited access to expert review. A telehealth solution was trailed in 2007. OBJECTIVE: To describe the systemic barriers encountered in implementing a telehealth program in rural WA and to provide recommendations for future telehealth initiatives. METHODS: This study trialled the use of a shared electronic wound imaging and reporting system in combination with an expert remote wound consultation service for the management of patients with chronic wounds in the Midwest of WA. The trial sites included rural hospital out-patient clinics, a private domiciliary nursing service, residential aged care facilities, general practices and a podiatry clinic. The implementation conformed to accepted best practice in introducing telehealth initiatives. RESULTS: During the trial 12 sites had the relevant software installed and were able to access a central server. Although a total of 41 patients with chronic wounds were enrolled, four sites did not enroll any patients and only two sites successfully incorporated the system into regular practice. Major obstacles were workforce issues and significant delays in installing the software at some sites. Only 47% of the healthcare providers trained to use the software at the beginning of the trial were still employed when the trial ended. Prolonged periods of vacant positions at one remote clinic and an aged care facility made it impossible for the remaining providers to allocate time for using the wound care software. CONCLUSION: The disease burden of the patient group, funding models and workforce shortages frustrated the successful adoption of an evidence based strategy that was known to improve health outcomes.

Internationally distributed frozen oyster meat causing multiple outbreaks of norovirus infection in Australia.

BACKGROUND: Between November 2003 and January 2004, outbreaks of norovirus in 3 Australian jurisdictions involving 83 cases of illness were associated with imported oyster meat. METHODS: Cohort studies were conducted in 2 jurisdictions to identify relative risks of illness for the consumption of oysters. A case series was conducted in the third jurisdiction. RESULTS: The cohort studies conducted in the first 2 jurisdictions identified relative risks of illness of 17 (95% confidence interval, 5-51) and 35 (95% confidence interval, 5-243), respectively, for the consumption of oysters. Multiple strains of norovirus were detected in fecal specimens from 8 of 14 patients and in 1 of the 3 batches of implicated oyster meat using seminested reverse-transcriptase polymerase chain reaction methods. Traceback investigations revealed that all oyster meat was harvested from the same estuary system in Japan within the same month. CONCLUSIONS: These outbreaks demonstrate the potential of foodborne disease to spread internationally and the need for national and international collaboration to investigate such outbreaks. Foodborne illness related to norovirus is underestimated because of underreporting of human cases and challenges in laboratory detection of viruses in foods, both of which can delay public health action.

Evaluation of a short interspersed nucleotide element in the 3' untranslated region of the defective dystrophin gene of dogs with muscular dystrophy.

OBJECTIVES: To determine the distribution of a 231-base pair (bp) element in the dystrophin gene 3' untranslated region (UTR) in a colony of Golden Retrievers with muscular dystrophy and other unrelated dogs and to estimate the frequency of recombination for the canine dystrophin gene. ANIMALS: 77 dogs from the Golden Retriever Muscular Dystrophy (GRMD) colony at the Murdoch Veterinary School and 30 unrelated dogs from the Murdoch University Veterinary Clinic. PROCEDURE: Samples of blood or hair from dogs were used for amplification of DNA, using primers to the canine dystrophin 3' UTR. RESULTS: The DNA from affected dogs generated a larger PCR product than that obtained from clinically normal dogs. Products were cloned and sequenced, and the difference in size was found to be attributable to a 231-bp short interspersed nucleotide element (SINE). The SINE was found in all affected dogs in the colony but not in most unaffected puppies in the colony. Eighteen of 19 dogs in the colony were heterozygous for the GRMD mutation, and 7 of 30 unrelated dogs also were heterozygous for the SINE. CONCLUSION AND CLINICAL RELEVANCE: Evidence of recombination between the GRMD mutation and the SINE was observed in only 4 dogs (2 sets of littermates) in the GRMD colony. Incidence of this SINE in a few unrelated dogs suggests that this particular insertion into the dystrophin gene may have been a recent event. The SINE in the dystrophin 3' UTR did not have an apparent influence on dystrophin mRNA concentrations.

Specific removal of the nonsense mutation from the mdx dystrophin mRNA using antisense oligonucleotides.

The mdx mouse, which carries a nonsense mutation in exon 23 of the dystrophin gene, has been used as an animal model of Duchenne muscular dystrophy to evaluate cell or gene replacement therapies. Despite the mdx mutation, which should preclude the synthesis of a functional dystrophin protein, rare, naturally occurring dystrophin-positive fibres have been observed in mdx muscle tissue. These dystrophin-positive fibres are thought to have arisen from an exon-skipping mechanism, either somatic mutations or alternative splicing. Increasing the frequency of these fibres may offer another therapeutic approach to reduce the severity of Duchenne muscular dystrophy. Antisense oligonucleotides have been shown to block aberrant splicing in the human beta-globin gene. We wished to use a similar approach to re-direct normal processing of the dystrophin pre-mRNA and induce specific exon skipping. Antisense 2'-O-methyl-oligoribonucleotides, directed to the 3' and 5' splice sites of introns 22 and 23, respectively in the mdx pre-mRNA, were used to transfect myoblast cultures. The 5' antisense oligonucleotide appeared to efficiently displace factors normally involved in the removal of intron 23 so that exon 23 was also removed during the splicing of the dystrophin pre-mRNA. Approximately 50% of the dystrophin gene mRNAs were missing this exon 6 h after transfection of primary mdx myotubes, with all transcripts showing skipping of exon 23 after 24 h. Deletion of exon 23 does not disrupt the reading frame and should allow the synthesis of a shorter but presumably functional Becker-like dystrophin. Molecular intervention at dystrophin pre-mRNA splicing has the potential to reduce the severity of a Duchenne mutation to the milder Becker phenotype.

Development of a snapback method of single-strand conformation polymorphism analysis for genotyping Golden Retrievers for the X-linked muscular dystrophy allele.

OBJECTIVE: To develop a snapback method of single-strand conformation polymorphism (SSCP) analysis for genotyping Golden Retrievers for the X-linked muscular dystrophy allele. ANIMALS: 20 Golden Retriever puppies from a colony with X-linked muscular dystrophy. PROCEDURE: DNA spanning the canine dystrophin mutation was amplified by means of a polymerase chain reaction (PCR), using a primer modified to have an additional sequence at the 5' terminus. The primer was designed so that 1 terminus of the single-stranded PCR product could anneal to the normal sequence flanking the region of the mutation in the allele but not in the mutant allele. True disease status of the dogs was determined by means of a PCR and restriction digest protocol. RESULTS: Snapback SSCP analysis allowed for accurate and unambiguous genotyping of unaffected, carrier, and affected dogs, whereas conventional SSCP analysis, using the unmodified primer, did not. Creatine kinase activities measured within 24 hours after birth were not consistent with genotype. CONCLUSION AND CLINICAL RELEVANCE: Snapback SSCP analysis provided a simple, fast, and accurate method for genotyping Golden Retrievers for the mutation known to cause X-linked muscular dystrophy.

The -308 tumor necrosis factor-alpha promoter polymorphism effects transcription.

Since the tumor necrosis factor alpha (TNF-alpha) gene was found to be located in the central major histocompatibility complex (MHC) there has been much speculation concerning a genetic association between particular TNF alleles and disease susceptibility. A relationship between the MHC haplotype A1, B8, DR3, TNF-alpha expression levels and susceptibility to autoimmune disease has been suggested by several groups. The identification of the -308 polymorphism and its association with the HLA A1, B8, DR3 haplotype have led to speculation that the polymorphism may play a role in the altered expression of TNF-alpha. We have demonstrated that the region (-323 to -285) encompassing -308 in the TNF2 allele binds nuclear factors differently to the same region in the promoter of the more common TNF1 allele. The G/A -308 polymorphism affected the affinity of factor binding and resulted in a factor binding to TNF2 but not TNF1. The observed differential binding was shown to be functional, with the 38bp region from TNF2 causing a two-fold greater activity of a heterologous promoter over that due to the same region in TNF1. To further substantiate the functional consequences of the TNF-alpha -308 polymorphism, we analysed both allelic forms of the TNF-alpha promoter region (-993 to +110) in a transient transfection assay, using luciferase as a reporter gene. The results showed that when present with the 3'UTR the -308A allelic form gave a two-fold greater level of transcription than the 308G form in PMA-stimulated Jurkat and U937 cells. This suggests that the -308 G/A polymorphism may play a role in the altered TNF-alpha gene expression observed in individuals with the HLA A1, B8, DR3 haplotype.