Comparison of an algorithm, and coding data, with traditional surveillance to identify surgical site infections in Australia: a retrospective multi-centred cohort study.

BACKGROUND: Surveillance of healthcare-associated infections (HAIs) in Australia is disparate, resource intensive, unsustainable, and provides limited information. Traditional HAI surveillance is time intensive and agreement levels between clinicians have been shown to be variable. AIM: To compare two methods: a semi-automated algorithm, and coding data, against traditional surgical site infection (SSI) surveillance methods. METHODS: This retrospective multi-centre cohort study included all patients undergoing a hip (HPRO) or knee (KPRO) prosthesis and coronary artery bypass graft (CABG) surgery during a two-year period at two large metropolitan hospitals. Routine SSI data were obtained via the infection prevention and control (IPC) team, a previously developed algorithm was applied to all patient records, and the ICD-10-AM data were searched for those categorized as having an SSI. FINDINGS: Overall, 1447, 1416, and 1026 patients who underwent HPRO, KPRO, and CABG, respectively, were included. The highest sensitivity values were generated by the algorithm: HPRO deep or organ-space (D/O) 0.87 (95% confidence interval: 0.66-0.96), CABG 0.86 (0.64-0.96), and HPRO all SSI 0.77 (0.57-89); the lowest sensitivity was Code CABG D/O 0.03 (0.00-0.21). The highest PPV values were generated by the algorithm: HPRO D/O 0.97 (0.77-0.99), CABG D/O 0.97 (0.76-0.99), and the Code HPRO D/O 0.9 (0.66-0.99). Both the algorithm and coding data resulted in a substantial reduction in the number of medical records required to review. CONCLUSION: The application of algorithms to enhance SSI surveillance demonstrates high accuracy in identifying patient records that require review by IPC teams to determine the presence of an SSI. Coding data alone should not be used to identify SSIs.

Burden of five healthcare associated infections in Australia.

BACKGROUND: Healthcare associated infections are of significant burden in Australia and globally. Previous estimates in Australia have relied on single-site studies, or combinations thereof, which have suggested the burden of these infections is high in Australia. Here, we estimate the burden of five healthcare associated infections (HAIs) in Australian public hospitals using a standard international framework, and compare these estimates to those observed in Europe. METHODS: We used data from an Australian point prevalence survey to estimate the burden of HAIs amongst adults in Australian public hospitals using an incidence-based approach, introduced by the ECDC Burden of Communicable Diseases in Europe. RESULTS: We estimate that 170,574 HAIs occur in adults admitted to public hospitals in Australia annually, resulting in 7583 deaths. Hospital acquired pneumonia is the most frequent HAI, followed by surgical site infections, and urinary tract infections. We find that blood stream infections contribute a small percentage of HAIs, but contribute the highest number of deaths (3207), more than twice that of the second largest, while pneumonia has the higher impact on years lived with disability. CONCLUSION: This study is the first time the national burden of HAIs has been estimated for Australia from point prevalence data collected using validated surveillance definitions. Per-capita, estimates are similar to that observed in Europe, but with significantly higher occurrences of bloodstream infections and healthcare-associated pneumonia, primarily amongst women. Overall, the estimated burden is high and highlights the need for continued investment in HAI prevention.

REDCap on FHIR: Clinical Data Interoperability Services.

BACKGROUND: Despite widespread use of electronic data capture (EDC) systems for research and electronic health records (EHR), most transfer of data between EHR and EDC systems is manual and error prone. Increased adoption of Health Level Seven Fast Healthcare Interoperability Resource (FHIR) application programming interfaces (APIs) in recent years by EHR systems has increased the availability of patient data for external applications such as REDCap. OBJECTIVE: Describe the development of the REDCap Clinical Data Interoperability Services (CDIS) module that provides seamless data exchange between the REDCap research EDC and any EHR system with a FHIR API. CDIS enables end users to independently set up their data collection projects, map EHR data to fields, and adjudicate data transfer without project-by-project involvement from Health Information Technology staff. METHODS: We identified two use cases for EHR data transfer into REDCap. Clinical Data Pull (CDP) automatically pulls EHR data into user-defined REDCap fields and replaces the workflow of having to transcribe or copy and paste data from the EHR. Clinical Data Mart (CDM) collects all specified data for a patient over a given time period and replaces the process of importing EHR data for registries from research databases. With an iterative process, we designed our access control, authentication, variable selection, and mapping interfaces in such a way that end users could easily set up and use CDIS. RESULTS: Since its release, the REDCap CDIS has been used to pull over 19.5 million data points for 82 projects at Vanderbilt University Medical Center. Software and documentation are available through the REDCap Consortium. CONCLUSIONS: The new REDCap Clinical Data and Interoperability Services (CDIS) module leverages the FHIR standard to enable real-time and direct data extraction from the EHR. Researchers can self-service the mapping and adjudication of EHR data into REDCap. The uptake of CDIS at VUMC and other REDCap consortium sites is improving the accuracy and efficiency of EHR data collection by reducing the need for manual transcription and flat file uploads.

Development and piloting of a prevention assessment and response tool for healthcare-associated Staphylococcus aureus bloodstream infection (the SAB-PART Study) using a Delphi method.

BACKGROUND: Healthcare-associated Staphylococcus aureus bloodstream infection (HA-SAB) causes preventable harm in hospitalized patients. Currently, there is no standardized method available to review HA-SAB events in order to identify and target preventable risks requiring action at an organizational level. AIM: To develop a tool to classify SAB events, and the necessary response actions, according to the degree of preventability. METHODS: Following a literature review, a tool was developed. Consensus feedback and development of the tool was sought from experts (N = 11) in healthcare-associated infection surveillance using a Delphi technique. The completed tool was retrospectively applied to HA-SAB events (N = 43) that occurred at a large healthcare organization. FINDINGS: Survey completion rates were high (91-100%). Clinicians' poor adherence to infection prevention practices and lack of engagement with feedback processes was established as the key modifiable element. A second key theme was the need for structured and detailed response actions. This feedback was incorporated into the tool and refined until consensus on all elements was achieved. Pilot application of the tool found that 56% of HA-SAB events were highly or possibly preventable; modifiable factors for HA-SAB prevention were not present in the remainder of cases. CONCLUSION: A prevention assessment and response tool was successfully developed via a consensus method to assist organizations in investigating and responding to individual cases of HA-SAB and identify future priority areas for SAB reduction strategies. Wider use of the tool with routine surveillance activities is required to evaluate impact upon infection prevention programmes and patient outcomes.

Nasopharyngeal carriage of otitis media pathogens in infants receiving 10-valent non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10), 13-valent pneumococcal conjugate vaccine (PCV13) or a mixed primary schedule of both vaccines: A randomised controlled trial.

BACKGROUND: Aboriginal children in Northern Australia have a high burden of otitis media, driven by early and persistent nasopharyngeal carriage of otopathogens, including non-typeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae (Spn). In this context, does a combined mixed primary series of Synflorix and Prevenar13 provide better protection against nasopharyngeal carriage of NTHi and Spn serotypes 3, 6A and 19A than either vaccine alone? METHODS: Aboriginal infants (n = 425) were randomised to receive Synflorix™ (S, PHiD-CV10) or Prevenar13™ (P, PCV13) at 2, 4 and 6 months (_SSS or _PPP, respectively), or a 4-dose early mixed primary series of PHiD-CV10 at 1, 2 and 4 months and PCV13 at 6 months of age (SSSP). Nasopharyngeal swabs were collected at 1, 2, 4, 6 and 7 months of age. Swabs of ear discharge were collected from tympanic membrane perforations. FINDINGS: At the primary endpoint at 7 months of age, the proportion of nasopharyngeal (Np) swabs positive for PCV13-only serotypes 3, 6A, or 19A was 0%, 0.8%, and 1.5% in the _PPP, _SSS, and SSSP groups respectively, and NTHi 55%, 52%, and 52% respectively, and no statistically significant vaccine group differences in other otopathogens at any age. The most common serotypes (in order) were 16F, 11A, 10A, 7B, 15A, 6C, 35B, 23B, 13, and 15B, accounting for 65% of carriage. Ear discharge swabs (n = 108) were culture positive for NTHi (52%), S. aureus (32%), and pneumococcus (20%). CONCLUSIONS: Aboriginal infants experience nasopharyngeal colonisation and tympanic membrane perforations associated with NTHi, non-PCV13 pneumococcal serotypes and S. aureus in the first months of life. Nasopharyngeal carriage of pneumococcus or NTHi was not significantly reduced in the early 4-dose combined SSSP group compared to standard _PPP or _SSS schedules at any time point. Current pneumococcal conjugate vaccine formulations do not offer protection from early onset NTHi and pneumococcal colonisation in this high-risk population.

Prevalence of healthcare-associated infections and antimicrobial use among inpatients in a tertiary hospital in Fiji: a point prevalence survey.

BACKGROUND: Healthcare-associated infections (HAIs) and antimicrobial use (AMU) are important drivers of antimicrobial resistance, yet there is minimal data from the Pacific region. We sought to determine the point prevalence of HAIs and AMU at Fiji's largest hospital, the Colonial War Memorial Hospital (CWMH) in Suva. A secondary aim was to evaluate the performance of European Centre for Diseases Prevention and Control (ECDC) HAI criteria in a resource-limited setting. METHODS: We conducted a point prevalence survey of HAIs and AMU at CWMH in October 2019. Survey methodology was adapted from the ECDC protocol. To evaluate the suitability of ECDC HAI criteria in our setting, we augmented the survey to identify patients with a clinician diagnosis of a HAI where diagnostic testing criteria were not met. We also assessed infection prevention and control (IPC) infrastructure on each ward. RESULTS: We surveyed 343 patients, with median (interquartile range) age 30 years (16-53), predominantly admitted under obstetrics/gynaecology (94, 27.4%) or paediatrics (83, 24.2%). Thirty patients had one or more HAIs, a point prevalence of 8.7% (95% CI 6.0% to 12.3%). The most common HAIs were surgical site infections (n = 13), skin and soft tissue infections (7) and neonatal clinical sepsis (6). Two additional patients were identified with physician-diagnosed HAIs that failed to meet ECDC criteria due to insufficient investigations. 206 (60.1%) patients were receiving at least one antimicrobial. Of the 325 antimicrobial prescriptions, the most common agents were ampicillin (58/325, 17.8%), cloxacillin (55/325, 16.9%) and metronidazole (53/325, 16.3%). Use of broad-spectrum agents such as piperacillin/tazobactam (n = 6) and meropenem (1) was low. The majority of prescriptions for surgical prophylaxis were for more than 1 day (45/76, 59.2%). Although the number of handwashing basins throughout the hospital exceeded World Health Organization recommendations, availability of alcohol-based handrub was limited and most concentrated within high-risk wards. CONCLUSIONS: The prevalence of HAIs in Fiji was similar to neighbouring high-income countries, but may have been reduced by the high proportion of paediatric and obstetrics patients, or by lower rates of inpatient investigations. AMU was very high, with duration of surgical prophylaxis an important target for future antimicrobial stewardship initiatives.

Increased fluid intake for the prevention of urinary tract infection in adults and children in all settings: a systematic review.

BACKGROUND: Non-antibiotic interventions for urinary tract infection (UTI) prevention have been investigated as a strategy to reduce antibiotic prescribing for UTI and subsequent antibiotic resistance. Increased hydration is widely advocated for preventing UTI; however, evidence for its effectiveness is unknown. AIM: To systematically review the published literature on the effectiveness of increased fluid intake as a preventive intervention for UTI in adults and children in any setting. METHODS: Five electronic databases were searched from inception to February 2019 to identify published randomized controlled trials (RCTs) and quasi-experimental studies evaluating the effectiveness of high (≥1.5 L/24 h) versus normal/low (<1.5 L/24 h) fluid intake for UTI prevention. The outcome was UTI incidence. Risk of bias was assessed using the Cochrane Collaboration's tool. Due to the small number of studies identified, meta-analysis was not possible. Hence a narrative synthesis was undertaken. FINDINGS: Of the 2822 potentially relevant papers, two were eligible for inclusion: an RCT (individual randomization) and a cluster-RCT. Both studies differed regarding participants, setting, sample size, UTI definition, and intervention. The RCT was assessed as having a low risk of bias whereas the cluster-RCT had a high risk of bias. Only the RCT, which included healthy premenopausal women visiting primary care clinics, demonstrated statistical significance for the effect of high fluid intake for UTI prevention. CONCLUSION: The lack of enough adequately powered and robust RCTs highlights the need for further research on the effectiveness of this intervention for UTI prevention.

Challenging immunodominance of influenza-specific CD8+ T cell responses restricted by the risk-associated HLA-A*68:01 allomorph.

Although influenza viruses lead to severe illness in high-risk populations, host genetic factors associated with severe disease are largely unknown. As the HLA-A*68:01 allele can be linked to severe pandemic 2009-H1N1 disease, we investigate a potential impairment of HLA-A*68:01-restricted CD8+ T cells to mount robust responses. We elucidate the HLA-A*68:01+CD8+ T cell response directed toward an extended influenza-derived nucleoprotein (NP) peptide and show that only ~35% individuals have immunodominant A68/NP145+CD8+ T cell responses. Dissecting A68/NP145+CD8+ T cells in low vs. medium/high responders reveals that high responding donors have A68/NP145+CD8+ memory T cells with clonally expanded TCRαßs, while low-responders display A68/NP145+CD8+ T cells with predominantly naïve phenotypes and non-expanded TCRαßs. Single-cell index sorting and TCRαß analyses link expansion of A68/NP145+CD8+ T cells to their memory potential. Our study demonstrates the immunodominance potential of influenza-specific CD8+ T cells presented by a risk HLA-A*68:01 molecule and advocates for priming CD8+ T cell compartments in HLA-A*68:01-expressing individuals for establishment of pre-existing protective memory T cell pools.

Associations of clinical and dosimetric parameters with late rectal toxicities after radical intensity-modulated radiation therapy for prostate cancer: a single-centre retrospective study.

INTRODUCTION: This study assessed the incidence of late rectal toxicities and evaluated potential predictive factors for late proctitis in patients treated with prostate-specific intensity-modulated radiotherapy in Hong Kong. METHODS: This retrospective longitudinal observational study included patients with localised prostate cancer who were treated with intensity-modulated radiation therapy in an oncology unit in Hong Kong between January 2007 and December 2011, and who had >1 year of follow-up. Clinical, pharmacological, and radiation parameters were recorded. Toxicities were measured by Common Terminology Criteria for Adverse Events version 4. RESULTS: In total, 232 patients were included in this analysis. The mean follow-up time was 7.3 ± 2.1 years and 46.5% of the patients had late rectal toxicities. Late proctitis occurred in 30.5% of patients; 25% of the patients with late proctitis exhibited grade ≥2 toxicity. Median onset times for late proctitis and rectal bleeding were 15 and 18.4 months, respectively. Multivariable regression showed increased odds for the occurrence of late proctitis in patients with older age (odds ratio [OR]=1.11, 95% confidence interval [CI]=1.04-1.19, P=0.003), higher V70 (OR=1.08, 95% CI=1.01-1.15, P=0.027), and presence of acute rectal toxicities (OR=4.47, 95% CI=2.37-8.43, P<0.001). Antiplatelet use was not significantly associated with the occurrence of late proctitis (OR=1.98, 95% CI=0.95-4.14, P=0.07). CONCLUSIONS: The incidence of late rectal toxicities was considerable among patients in this study. Clinicians should consider the possibility of late proctitis for patients with older age, acute rectal toxicities, and higher V70. High doses to rectal volumes should be limited because of the significant association with V70.

Chlorhexidine-alcohol versus iodine-alcohol for surgical site skin preparation in an elective arthroplasty (ACAISA) study: a cluster randomized controlled trial.

OBJECTIVES: Surgical site skin preparation is an effective method to prevent wound complications. The optimal agent has not been established, and guidelines contain conflicting recommendations. METHODS: The aim of alcoholic chlorhexidine or alcoholic iodine skin antisepsis (ACAISA) was to assess the efficacy of surgical site skin preparation with 0.5% chlorhexidine gluconate (w/v) in 70% ethanol (v/v) to 1% iodine (w/v) in 70% ethanol (v/v). This was a cluster randomized, controlled, single-centre, assessor-blinded, superiority trial in patients undergoing elective hip or knee arthroplasty. Each surgeon had a set operating day and the unit of randomization was the day of surgery. The primary outcome was superficial wound complication, defined as a composite endpoint of superficial incisional surgical site infection and/or clinically significant wound ooze in the 30 days following arthroplasty. The secondary outcome was any surgical site infection, including prosthetic joint infection. Outcome ascertainment was undertaken by an independent verification panel. The primary analysis was intention-to-treat, performed at the individual level. Taking into account the clustering effect, analysis of primary and secondary outcomes was undertaken at the level of the surgeon. RESULTS: A total of 780 participants were included; 390 participants were allocated chlorhexidine-alcohol and 390 participants were allocated iodine-alcohol. There was no difference in superficial wound complications: 19 (4.9%) versus 15 (3.8%) respectively (OR 1.28; 95%CI 0.62, 2.63; p 0.50). There was an increased odds of surgical site infection in the chlorhexidine-alcohol group compared to iodine-alcohol: 12 (3.1%) versus four (1.0%) respectively (OR 3.06; 95%CI 1.26, 7.46; p 0.014). The odds of prosthetic joint infection were also increased in the chlorhexidine-alcohol arm compared with iodine-alcohol: seven (1.8%) versus two (0.5%) respectively (OR 3.55; 95%CI 1.20, 10.44; p 0.022). CONCLUSIONS: No difference was observed in the primary outcome of superficial wound complications when chlorhexidine-alcohol and iodine-alcohol were compared. However, on a secondary analysis, iodine-alcohol had greater efficacy than chlorhexidine-alcohol for preventing surgical site infection. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12614000177651.

Do concordances of social support and relationship quality predict psychological distress and well-being of cancer patients and caregivers?

This study examined concordances of cancer patients' received and caregivers' provided support and dyadic relationship quality, and their predictive utility in prospective psychological distress and well-being. A total of 83 Chinese cancer patient-caregiver dyads were recruited in two government-funded hospitals in Hong Kong. Participants reported received (patient)/provided (caregiver) emotional and instrumental support and dyadic relationship quality within 6 months after diagnosis (T1), and anxiety and depressive symptoms, positive affect and life satisfaction at both T1 and 6-month follow-up (T2). We hypothesised that concordances at T1 would predict lower psychological distress and higher psychological well-being among both patients and caregivers at T2. Concordances were indicated by Gwet's AC2 scores (possible range = -1.00 to 1.00) and as follows: emotional support: M = 0.92, SD = 0.12, range = 0.25-1.00; instrumental support: M = 0.92, SD = 0.16, range = 0.08-1.00; and relationship quality: M = 0.63, SD = 0.27, range = -0.31 to 1.00. Hierarchical multiple regressions revealed that T1 concordances of perceived emotional and instrumental support and dyadic relationship quality positively predicted T2 anxiety symptoms [F(9, 74) = 6.725, ∆R2  = .031, p < .001)] and state positive affect [F(9, 74) = 3.436, ∆R2  = .042, p = .001)], whereas inversely predicted T2 depressive symptoms [F(9, 74) = 4.189, ∆R2  = .042, p < .01)]. Significant associations were found only among caregivers, but not patients.

What risk of endocarditis is low enough to justify the omission of transoesophageal echocardiography in Staphylococcus aureus bacteraemia? A narrative review.

BACKGROUND: Recent criteria which can identify patients with Staphylococcus aureus bacteraemia (SAB) who are at very low risk of endocarditis raise the question of whether transoesophageal echocardiography (TOE) is appropriate for these patients. AIMS: To estimate the probability of occult endocarditis complicating SAB below which a TOE-guided treatment strategy no longer offers the best 180-day survival, and to examine the key uncertainties affecting this result. SOURCES: Estimates of the parameters required to calculate the Pauker-Kassirer testing threshold were identified from studies published prior to 1 June 2017 using a composite search strategy that involved a systematic search for relevant controlled trials and guidelines, followed by a non-systematic iterative search of the observational literature. CONTENT: Estimates of the necessary parameters were generally consistent across the literature with the exception of the procedural mortality of TOE. In our base-case scenario (TOE mortality 0.1%), the testing threshold for TOE in apparently uncomplicated SAB was a 1.1% probability of occult endocarditis. Sensitivity analyses revealed that the procedural mortality of TOE was a key uncertainty affecting estimates of the testing threshold. IMPLICATIONS: None of the available clinical tools can place patients with SAB below this probability of endocarditis with 95% confidence. Future work in this area should concentrate on improving the precision of these tools and on exploring the value of alternative echocardiography strategies. In addition, a better understanding of the harms of TOE is required to ensure that recommendations regarding the role of this investigation in the management of patients with SAB are appropriate.

Risk factors for infectiousness of patients with tuberculosis: a systematic review and meta-analysis.

We performed a systematic review and meta-analyses of studies assessing tuberculosis (TB) patient-related risk factors for transmission of Mycobacterium tuberculosis infection. Meta-analyses were conducted for sputum smear-positivity, lung cavitation and HIV seropositivity of index patients with both crude and adjusted odds ratios (AORs) pooled using random effect models. Thirty-seven studies were included in the review. We found that demographic characteristics such as age and sex were not significant risk factors, while behaviours such as smoking and alcohol intake were associated with infectiousness although inconsistently. Treatment delay of >28 days was a significant predictor of greater infectiousness. Contacts of sputum smear-positive index patients were found to be more likely to be infected than contacts of sputum smear-negative patients, with a pooled AOR of 2.15 (95% confidence interval (CI) 1.47-3.17, I 2 = 38%). Similarly, contacts of patients with the cavitary disease were around twice as likely to be infected as contacts of patients without cavitation (pooled AOR 1.9, 95% CI 1.26-2.84, I 2 = 63%). In contrast, HIV seropositive patients were associated with few contact infections than HIV seronegative patients (AOR 0.45, 95% CI 0.26-0.80, I 2 = 52%). In conclusion, behavioural and clinical characteristics of TB patients can be used to identify highly infectious patients for targeted interventions.

Central line-associated bloodstream infections in Australian ICUs: evaluating modifiable and non-modifiable risks in Victorian healthcare facilities.

Central line-associated bloodstream infections (CLABSIs) in intensive care units (ICUs) result in poor clinical outcomes and increased costs. Although frequently regarded as preventable, infection risk may be influenced by non-modifiable factors. The objectives of this study were to evaluate organisational factors associated with CLABSI in Victorian ICUs to determine the nature and relative contribution of modifiable and non-modifiable risk factors. Data captured by the Australian and New Zealand Intensive Care Society regarding ICU-admitted patients and resources were linked to CLABSI surveillance data collated by the Victorian Healthcare Associated Infection Surveillance System between 1 January 2010 and 31 December 2013. Accepted CLABSI surveillance methods were applied and hospital/patient characteristics were classified as 'modifiable' and 'non-modifiable', enabling longitudinal Poisson regression modelling of CLABSI risk. In total, 26 ICUs were studied. Annual CLABSI rates were 1·72, 1·37, 1·00 and 0·93/1000 CVC days for 2010-2013. Of non-modifiable factors, the number of non-invasively ventilated patients standardised to total ICU bed days was found to be independently associated with infection (RR 1·07; 95% CI 1·01-1·13; P = 0·030). Modelling of modifiable risk factors demonstrated the existence of a policy for mandatory ultrasound guidance for central venous catheter (CVC) localisation (RR 0·51; 95% CI 0·37-0·70; P < 0·001) and increased number of sessional specialist full-time equivalents (RR 0·52; 95% CI 0·29-0·93; P = 0·027) to be independently associated with protection against infection. Modifiable factors associated with reduced CLABSI risk include ultrasound guidance for CVC localisation and increased availability of sessional medical specialists.

Influenza hospitalizations in Australian children.

Australia's National Immunisation Program (NIP) provides free influenza vaccination for children at high risk of severe influenza; a pilot-funded programme for vaccine in all children aged 6 months to <5 years in one of eight states, has seen poor vaccine impact, related to recent vaccine safety concerns. This retrospective review examined influenza hospitalizations in children aged <16 years from three seasons (2011-2013) at two paediatric hospitals on opposite sides of the country. Comparisons of this cohort were made with state-based data on influenza-coded hospitalizations and national immunization register data on population-level immunization coverage. Of 740 hospitalizations, the majority were aged <5 years (476/740, 64%), and a substantial proportion (57%) involved healthy children, not currently funded for influenza vaccine. Intensive care unit admission occurred in 8·5%, and 1·5% of all children developed encephalitis. Use of antiviral therapy was uncommon (20·5%) and decreasing. Of those hospitalized, only 5·0% of at-risk children, who are currently eligible for free vaccine, and 0·7% of healthy children were vaccinated prior to hospitalization. This was consistent with low population-wide estimates of influenza vaccine uptake. It highlights the need to examine alternative strategies, such as universally funded paediatric influenza vaccination, to address disease burden in Australian children.

Australia's National Notifiable Diseases Surveillance System 1991-2011: expanding, adapting and improving.

We reviewed key attributes (flexibility, data quality and timeliness) of Australia's National Notifiable Diseases Surveillance System (NNDSS) over its first 21 years. Cases notified to NNDSS from 1991 to 2011 were examined by jurisdiction (six states and two territories) and sub-period to describe changes in the number of notifiable diseases, proportion of cases diagnosed using PCR tests, data quality (focusing on data completeness), and notification delays. The number of notifiable diseases increased from 37 to 65. The proportion of cases diagnosed by PCR increased from 1% (1991-1997) to 49% (2005-2011). Indigenous status was complete for only 44% notifications (jurisdictional range 19-87%). Vaccination status was complete for 62% (jurisdictional range 32-100%) and country of acquisition for 24% of relevant cases. Data completeness improved over the study period with the exception of onset date. Median time to notification was 8 days (interquartile range 4-17 days, jurisdictional range 5-15 days); this decreased from 11 days (1991-1997) to 5 days (2005-2011). NNDSS expanded during the study period. Data completeness and timeliness improved, likely related to mandatory laboratory reporting and electronic data transfer. A nationally integrated electronic surveillance system, including electronic laboratory reporting, would further improve infectious disease surveillance in Australia.

Proposed primary endpoints for use in clinical trials that compare treatment options for bloodstream infection in adults: a consensus definition.

OBJECTIVES: To define standardized endpoints to aid the design of trials that compare antibiotic therapies for bloodstream infections (BSI). METHODS: Prospective studies, randomized trials or registered protocols comparing antibiotic therapies for BSI, published from 2005 to 2016, were reviewed. Consensus endpoints for BSI studies were defined using a modified Delphi process. RESULTS: Different primary and secondary endpoints were defined for pilot (small-scale studies designed to evaluate protocol design, feasibility and implementation) and definitive trials (larger-scale studies designed to test hypotheses and influence clinical practice), as well as for Staphylococcus aureus and Gram-negative BSI. For pilot studies of S. aureus BSI, a primary outcome of success at day 7 was defined by: survival, resolution of fever, stable/improved Sequential Organ Failure Assessment (SOFA) score and clearance of blood cultures, with no microbiologically confirmed failure up to 90 days. For definitive S. aureus BSI studies, a primary outcome of success at 90 days was defined by survival and no microbiologically confirmed failure. For pilot studies of Gram-negative BSI, a primary outcome of success at day 7 was defined by: survival, resolution of fever and symptoms related to BSI source, stable or improved SOFA score and negative blood cultures. For definitive Gram-negative BSI studies, a primary outcome of survival at 90 days supported by a secondary outcome of success at day 7 (as previously defined) was agreed. CONCLUSIONS: These endpoints provide a framework to aid future trial design. Further work will be required to validate these endpoints with respect to patient-centred clinical outcomes.