The same but different: a comparison of Staphylococcus aureus bloodstream infections in metropolitan and non-metropolitan hospitals (2010-2020).

BACKGROUND: Variation of infection rates between hospitals must be identified; differences may highlight opportunities for quality improvement in healthcare delivery to specific hospitals groups. AIMS: To analyse burden, time trends and risks of healthcare-associated (HA) Staphylococcus aureus bloodstream infections (SABSI) in patients admitted to Victorian metropolitan and non-metropolitan public acute care hospitals. METHODS: SABSI surveillance data submitted between 1 July 2010 and 30 June 2020 by all 118 Victorian public acute care hospitals were analysed. Aligned with the Australian Statistical Geography Standard Remoteness Structure, these hospitals were classified as metropolitan (major cities) or non-metropolitan (inner regional, outer regional, remote or very remote). RESULTS: Most SABSI were community associated: 66.9% and 75.0% of metropolitan (n = 9441) and non-metropolitan (n = 2756) hospital SABSI respectively. The overall HA-SABSI rate was statistically higher in metropolitan hospitals (1.13 per 10 000 occupied bed days (OBD)) compared with non-metropolitan hospitals (0.82 per 10 000 OBD; P < 0.001). In metropolitan and non-metropolitan hospitals, there was a statistically significant decline in the overall HA-SABSI rate (incidence rate ratio = 0.96; 95% confidence interval: 0.95-0.97; P < 0.001; and incidence rate ratio = 0.98; 95% confidence interval: 0.97-1.00; P = 0.044, respectively). In metropolitan and non-metropolitan hospitals, HA-SABSI were frequently associated with central venous (52.8%) and peripheral intravenous (62.2%) catheter use respectively. CONCLUSION: To reduce risks for SABSI and improve patient outcomes, hospital infection prevention and control programmes should be tailored according to local epidemiology. In common geographic locations, networking of hospitals should be considered as a means of strengthening delivery of these programmes.

Host immunity to Plasmodium falciparum and the assessment of emerging artemisinin resistance in a multinational cohort.

Artemisinin-resistant falciparum malaria, defined by a slow-clearance phenotype and the presence of kelch13 mutants, has emerged in the Greater Mekong Subregion. Naturally acquired immunity to malaria clears parasites independent of antimalarial drugs. We hypothesized that between- and within-population variations in host immunity influence parasite clearance after artemisinin treatment and the interpretation of emerging artemisinin resistance. Antibodies specific to 12 Plasmodium falciparum sporozoite and blood-stage antigens were determined in 959 patients (from 11 sites in Southeast Asia) participating in a multinational cohort study assessing parasite clearance half-life (PCt1/2) after artesunate treatment and kelch13 mutations. Linear mixed-effects modeling of pooled individual patient data assessed the association between antibody responses and PCt1/2.P. falciparum antibodies were lowest in areas where the prevalence of kelch13 mutations and slow PCt1/2 were highest [Spearman ρ = -0.90 (95% confidence interval, -0.97, -0.65), and Spearman ρ = -0.94 (95% confidence interval, -0.98, -0.77), respectively]. P. falciparum antibodies were associated with faster PCt1/2 (mean difference in PCt1/2 according to seropositivity, -0.16 to -0.65 h, depending on antigen); antibodies have a greater effect on the clearance of kelch13 mutant compared with wild-type parasites (mean difference in PCt1/2 according to seropositivity, -0.22 to -0.61 h faster in kelch13 mutants compared with wild-type parasites). Naturally acquired immunity accelerates the clearance of artemisinin-resistant parasites in patients with falciparum malaria and may confound the current working definition of artemisinin resistance. Immunity may also play an important role in the emergence and transmission potential of artemisinin-resistant parasites.

Compliance with follow-up Test of Cure and outcomes after treatment for high-grade cervical intraepithelial neoplasia in Victoria, Australia.

BACKGROUND: Test of Cure (ToC), a combination of testing for oncogenic human papillomavirus (HPV) and cytology, at 12 months post-treatment and annually thereafter, was approved in Australia in 2005 for follow-up of women treated for high-grade squamous intraepithelial lesions (HSIL) of the cervix. AIMS: To determine among women resident in Victoria, Australia, the compliance with ToC and the incidence of recurrence up to five years after successful ToC. MATERIALS AND METHODS: A retrospective analysis of women with HSIL (diagnosed at pre-treatment punch biopsy or at excision) who had excisional treatment between 1 January 2007 and 31 December 2011. De-identified data were retrieved from the Victorian Cervical Cytology Registry in Melbourne as at 24 April, 2015. Successful ToC is defined as the occurrence of two consecutive normal (negative) co-tests. Recurrence after treatment is defined by histologically detected HSIL or greater. RESULTS: There were 8478 women who had excisional treatment for HSIL, with 448 (5.5%) experiencing recurrence. Only 2253 (26.6%) women successfully completed ToC, with a decreasing likelihood of ToC completion by time since year of treatment (32.0% in 2007 compared with 20.9% in 2011). Only one (0.08%) woman had HSIL on histology after successful ToC. From the 2007 cohort, 555 (32.0%) women completed ToC successfully and no HSIL recurrence occurred thereafter (median subsequent follow-up period of 4.7 years). CONCLUSIONS: Our study confirmed that women who successfully complete ToC can be returned to five-year routine screening. However, more concerted efforts are needed to ensure that all women treated complete ToC.

Management and long-term outcomes of women with adenocarcinoma in situ of the cervix: A retrospective study.

BACKGROUND: Adenocarcinoma in situ of cervix is increasingly managed by local excision rather than hysterectomy and this study will ascertain if conservative management by excision alone is adequate. AIMS: To evaluate the long-term outcomes of conservative management of adenocarcinoma in situ of cervix, particularly in relation to excisional margin status. MATERIALS AND METHODS: Retrospective analysis of women diagnosed with adenocarcinoma in situ and their management between 1992 and 2010 retrieved from the Victorian Cervical Cytology Registry, Australia. Failure of conservative treatment is defined by histologically proven adenocarcinoma in situ or adenocarcinoma at follow-up after negative excisional margins. RESULTS: adenocarcinoma in situ of the cervix was managed primarily with cold knife cone biopsy or loop electrosurgical excision of the cervix. Most excisions were in one piece (83.4%) with average depth of 16.1 mm and 21.9% had involved excisional margins. Women with adenocarcinoma in situ on any excisional margin were more likely to have residual or recurrent disease (28.7%) compared with negative excisional margins (4.3%). Residual adenocarcinoma in situ was twice as common if adenocarcinoma in situ was present at endocervical (29.6%) and stromal (23.1%) margins compared with an ectocervical margin (13.6%). Cancer incidence at follow-up was 2.3% for women with positive excisional margins compared to 1.3% with negative margins. CONCLUSIONS: Women with adenocarcinoma in situ of cervix can be managed with local excisional procedures, best in single pieces to provide the important information on excisional margins. Adenocarcinoma in situ at endocervical and stromal excisional margins needs re-excision or where appropriate, hysterectomy, while negative excisional margins have a low rate of recurrence and can be followed up with test of cure.

Clinical Validation of the cobas HPV Test on the cobas 6800 System for the Purpose of Cervical Screening.

This study demonstrates that the clinical sensitivity, specificity, and reproducibility of the novel cobas human papillomavirus (HPV) test on the cobas 6800 system for high-risk HPV types fulfills the criteria for use in population-based cervical screening. The criteria were formulated by an international consortium, using the cobas 4800 HPV test as a validated reference assay. The cobas HPV test detected over 98% of histologically confirmed cervical intraepithelial neoplasia grade 2+ (CIN2+) lesions in women age 30 years or older, with a specificity of 98.9% compared with the reference cobas 4800 test. Both the intra- and interlaboratory agreement for the cobas HPV test were 98%. The clinical performance of the cobas HPV test is comparable to those of longitudinally validated HPV assays and fulfills the criteria for its use in primary cervical screening.

Unsupervised primaquine for the treatment of Plasmodium vivax malaria relapses in southern Papua: A hospital-based cohort study.

BACKGROUND: Primaquine is the only licensed drug for eradicating Plasmodium vivax hypnozoites and, therefore, preventing relapses of vivax malaria. It is a vital component of global malaria elimination efforts. Primaquine is efficacious when supervised in clinical trials, but its effectiveness in real-world settings is unknown. We aimed to determine whether unsupervised primaquine was effective for preventing re-presentation to hospital with vivax malaria in southern Papua, Indonesia. METHODS AND FINDINGS: Routinely-collected hospital surveillance data were used to undertake a pragmatic comparison of the risk of re-presentation to hospital with vivax malaria in patients prescribed dihydroartemisinin-piperaquine (DHP) combined with primaquine versus those patients prescribed DHP alone. The omission of primaquine was predominantly due to 3 stock outages. Individual clinical, pharmacy, and laboratory data were merged using individual hospital identification numbers and the date of presentation to hospital. Between April 2004 and December 2013, there were 86,797 documented episodes of vivax malaria, of which 62,492 (72.0%) were included in the analysis. The risk of re-presentation with vivax malaria within 1 year was 33.8% (95% confidence Interval [CI] 33.1%-34.5%) after initial monoinfection with P. vivax and 29.2% (95% CI 28.1%-30.4%) after mixed-species infection. The risk of re-presentation with P. vivax malaria was higher in children 1 to <5 years of age (49.6% [95% CI 48.4%-50.9%]) compared to patients 15 years of age or older (24.2% [95% CI 23.4-24.9%]); Adjusted Hazard Ratio (AHR) = 2.23 (95% CI 2.15-2.31), p < 0.001. Overall, the risk of re-presentation was 37.2% (95% CI 35.6%-38.8%) in patients who were prescribed no primaquine compared to 31.6% (95% CI 30.9%-32.3%) in those prescribed either a low (≥1.5 mg/kg and <5 mg/kg) or high (≥5 mg/kg) dose of primaquine (AHR = 0.90 [95% CI 0.86-0.95, p < 0.001]). Limiting the comparison to high dose versus no primaquine in the period during and 12 months before and after a large stock outage resulted in minimal change in the estimated clinical effectiveness of primaquine (AHR 0.91, 95% CI 0.85-0.97, p = 0.003). Our pragmatic study avoided the clinical influences associated with prospective study involvement but was subject to attrition bias caused by passive follow-up. CONCLUSIONS: Unsupervised primaquine for vivax malaria, prescribed according to the current World Health Organization guidelines, was associated with a minimal reduction in the risk of clinical recurrence within 1 year in Papua, Indonesia. New strategies for the effective radical cure of vivax malaria are needed in resource-poor settings.

Acute Pancreatitis Associated With Antipsychotic Medication: Evaluation of Clinical Features, Treatment, and Polypharmacy in a Series of Cases.

BACKGROUND: Antipsychotic-associated acute pancreatitis presents like pancreatitis from other causes, requiring clinical judgment, tests, and decision support to establish the diagnosis. Many new cases of atypical antipsychotic pancreatitis have been established, and current decision supports are out of date as antipsychotic polypharmacy is being recognized. Given the population frequency of psychosis and frequency of antipsychotic prescribing, we reviewed published cases summarizing common clinical findings and antipsychotics associated with acute pancreatitis to updating earlier decision support. METHODS: Case reports of antipsychotic pancreatitis from 1990 to 2015 were reviewed and abstracted by independent reviewers. Demographic, clinical features, management, and Naranjo and probability scores were abstracted and reviewed for associations. Appropriate statistical tests were selected for normally and non-normally distributed data. RESULTS: We summarized 41 cases of acute pancreatitis associated with antipsychotics, and cases were younger men (59%) (mean age, 39 years). Alcohol, diabetes, and previous lithiasis appeared in 27%; polypharmacy was associated with 53% of cases, and 80% had concomitant use of other medication linked to pancreatitis.The median lipase, amylase, and alkaline phosphate during acute presentation were 1210 IU/L (range, 243-5482 IU/L), 492 IU/L (range, 3-2916 IU/L), and 152 IU/L (range, 119-367 IU/L), respectively. Median exposure to antipsychotics were 49 days (range, 5-3,650 days); most were mild (63%, n = 26), several severe (27%, n = 11), and few fatal (10%, n = 4). DISCUSSION: We identified 41 reports of antipsychotic-related acute pancreatitis, many associated with antipsychotic polypharmacy. Olanzapine, risperidone, quetiapine, aripiprazole, and ziprasidone are associated with acute pancreatitis and often in combination with mood stabilizers.

Transforming the Model T: random effects meta-analysis with stable weights.

Standard meta-analytic theory assumes that study outcomes are normally distributed with known variances. However, methods derived from this theory are often applied to effect sizes having skewed distributions with estimated variances. Both shortcomings can be largely overcome by first applying a variance stabilizing transformation. Here we concentrate on study outcomes with Student t-distributions and show that we can better estimate parameters of fixed or random effects models with confidence intervals using stable weights or with profile approximate likelihood intervals following stabilization. We achieve even better coverage with a finite sample bias correction. Further, a simple t-interval provides very good coverage of an overall effect size without estimation of the inter-study variance. We illustrate the methodology on two meta-analytic studies from the medical literature, the effect of salt reduction on systolic blood pressure and the effect of opioids for the relief of breathlessness. Substantial simulation studies compare traditional methods with those newly proposed. We can apply the theoretical results to other study outcomes for which an effective variance stabilizer is available.

An evaluation of influenza, pneumococcal and herpes zoster vaccination coverage in Australian aged care residents, 2018 to 2022.

BACKGROUND: For older persons, vaccination mitigates the harmful impact of vaccine preventable infections. Our study objectives were to evaluate in the Victorian public sector residential aged care services (PSRACS) (1) the existence of local vaccination policies and admission assessment practices, (2) the current documented status of resident influenza, pneumococcal and herpes zoster vaccination uptake and (3) changes in documented resident vaccination uptake over time. METHODS: Standardised data were annually reported by all PSRACS between 2018 and 2022. The influenza, pneumococcal and herpes zoster vaccination status of each resident was classified as vaccinated, declined, contraindicated or unknown. Annual trends in vaccination status were assessed using Spearman's correlation. RESULTS: In 2022, most PSRACS reported an influenza immunisation policy existed (87.1%) and new residents were assessed for their influenza vaccination status (97.2%); fewer PSRACS reported the same for pneumococcal disease (73.1% and 78.9%) and herpes zoster (69.3% and 75.6%). The median resident influenza, pneumococcal and herpes zoster (70-79 years old) vaccination uptake was 86.8%, 32.8% and 19.3% respectively. The median unknown status was 6.9%, 63.0% and 76.0% respectively. Statistical evidence of an increase in annual uptake was observed for the herpes zoster (all resident) surveillance module (rs = 0.900, p = 0.037). CONCLUSIONS: Our study showed local influenza vaccination policies and practices exist and influenza vaccination uptake was consistently high. Pneumococcal and herpes zoster vaccination uptake were lower. Quality improvement strategies that at least determine the status of those residents classified as unknown are required.

Applying the standardized infection ratio for reporting surgical site infections in Australian healthcare facilities.

Objective: We explored the utility of the standardized infection ratio (SIR) for surgical site infection (SSI) reporting in an Australian jurisdiction. Design: Retrospective chart review. Setting: Statewide SSI surveillance data from 2013 to 2019. Patients: Individuals who had cardiac bypass surgery (CABG), colorectal surgery (COLO), cesarean section (CSEC), hip prosthesis (HPRO), or knee prosthesis (KPRO) procedures. Methods: The SIR was calculated by dividing the number of observed infections by the number of predicted infections as determined using the National Healthcare Safety Network procedure-specific risk models. In line with a minimum precision criterion, an SIR was not calculated if the number of predicted infections was <1. Results: A SIR >0 (≥1 observed SSI, predicted number of SSI ≥1, no missing covariates) could be calculated for a median of 89.3% of reporting quarters for CABG, 75.0% for COLO, 69.0% for CSEC, 0% for HPRO, and 7.1% for KPRO. In total, 80.6% of the reporting quarters, when the SIR was not calculated, were due to no observed infections or predicted infections <1, and 19.4% were due to missing covariates alone. Within hospitals, the median percentage of quarters during which zero infections were observed was 8.9% for CABG, 20.0% for COLO, 25.4% for CSEC, 67.3% for HPRO, and 71.4% for KPRO. Conclusions: Calculating an SIR for SSIs is challenging for hospitals in our regional network, primarily because of low event numbers and many facilities with predicted infections <1. Our SSI reporting will continue to use risk-indexed rates, in tandem with SIR values when predicted number of SSI ≥1.

Evaluating peripheral intravascular catheter insertion, maintenance and removal practices in small hospitals using a standardized audit tool.

AIM: The aim of this study was to evaluate clinical practice about peripheral intravenous catheter (PIVC) insertion, maintenance and removal in a cohort of Victorian hospitals. DESIGN: A standardized PIVC audit tool was developed, and results from point prevalent surveys were conducted. METHODS: Hospitalized patients requiring a PIVC insertion were eligible for audit. Audit data submitted between 2015 and 2019 were extracted for the current study. RESULTS: 3566 PIVC insertions in 15 Victorian public hospitals were evaluated. 57.6% of PIVCs were inserted in wards, 18.7% in operating theatres and 11.6% in Emergency Departments (ED). 45.2% were inserted by nurses and 38.2% by medical staff. The preferred site for insertion was the dorsum of the hand and forearm (58.8%). 22.6% did not report a visual infusion phlebitis score at least daily, and 48% did not document a daily dressing assessment. Reasons for PIVC removal included no longer required (63%) and phlebitis (4.8%). No bloodstream infections were reported.

Prophylactic Antimicrobial Prescribing in Australian Residential Aged-Care Facilities: Improvement is Required.

BACKGROUND AND OBJECTIVE: Inappropriate antimicrobial use can lead to adverse consequences, including antimicrobial resistance. The objective of our study was to describe patterns of prophylactic antimicrobial prescribing in Australian residential aged-care facilities and thereby provide insight into antimicrobial stewardship strategies that might be required. METHODS: Annual point prevalence data submitted by participating residential aged-care facilities as part of the Aged Care National Antimicrobial Prescribing Survey between 2016 and 2020 were extracted. All antimicrobials except anti-virals were counted; methenamine hippurate was classified as an antibacterial agent. RESULTS: The overall prevalence of residents prescribed one or more prophylactic antimicrobial on the survey day was 3.7% (n = 4643, 95% confidence interval 3.6-3.8). Of all prescribed antimicrobials (n = 15,831), 27.1% (n = 4871) were for prophylactic use. Of these prophylactic antimicrobials, 87.8% were anti-bacterials and 11.4% antifungals; most frequently, cefalexin (28.7%), methenamine hippurate (20.1%) and clotrimazole (8.8%). When compared with prescribing of all antimicrobial agents, prophylactic antimicrobials were less commonly prescribed for pro re nata administration (7.0% vs 20.3%) and more commonly prescribed greater than 6 months (52.9% vs 34.1%). The indication and review or stop date was less frequently documented (67.5% vs 73.8% and 20.9% vs 40.7%, respectively). The most common body system for which a prophylactic antimicrobial was prescribed was the urinary tract (54.3%). Of all urinary tract indications (n = 2575), about two thirds (n = 1681, 65.3%) were for cystitis and 10.6% were for asymptomatic bacteriuria. CONCLUSIONS: Our results clearly identified immediate antimicrobial stewardship strategies that aim to improve prophylactic antimicrobial prescribing in Australian residential-aged care facilities are required.

Topical antimicrobial prescribing patterns in residents of Australian aged-care facilities: use of a national point prevalence survey to identify opportunities for quality improvement.

BACKGROUND: Australian residential aged care facilities (RACFs) are encouraged to participate in an annual Aged Care National Antimicrobial Prescribing Survey. This data source was analysed to describe patterns of topical antimicrobial prescribing and thereby provide insight into antimicrobial stewardship (AMS) changes that might be required. METHODS: 2018 and 2019 survey data was analysed. RESULTS: The overall prevalence of the 52,431 audited residents (629 facilities) who were prescribed 1 or more topical antimicrobials was 2.9%. Of all prescribed antimicrobials (n=4899), 33.0% were for topical application. Most frequently prescribed topical antifungals were clotrimazole (85.3%) and miconazole (9.1%), and antibacterials chloramphenicol (64.1%) and mupirocin (21.8%). Tinea (38.3%) and conjunctivitis (23.8%) were the 2 most common indications. Topical antimicrobials were sometimes prescribed for pro re nata administration (38.8%) and greater than 6 months (11.3%). The review or stop date was not always documented (38.7%). CONCLUSIONS: To reduce the possibility of adverse consequences associated with antimicrobial use, antimicrobial stewardship programs in Australian residential aged care facilities should at least ensure mupirocin is appropriately used, first line antimicrobial therapy is prescribed for tinea, chloramphenicol is prescribed for conjunctivitis only if necessary, pro re nata orders for prescriptions are discouraged and to avoid prolonged duration of prescriptions, review or stop dates are always documented.

Determination of postexcitation thresholds for single ultrasound contrast agent microbubbles using double passive cavitation detection.

This work presents experimental responses of single ultrasound contrast agents to short, large amplitude pulses, characterized using double passive cavitation detection. In this technique, two matched, focused receive transducers were aligned orthogonally to capture the acoustic response of a microbubble from within the overlapping confocal region. The microbubbles were categorized according to a classification scheme based on the presence or absence of postexcitation signals, which are secondary broadband spikes following the principle oscillatory response of the ultrasound contrast agent and are indicative of the transient collapse of the microbubble. Experiments were conducted varying insonifying frequencies (0.9, 2.8, 4.6, and 7.1 MHz) and peak rarefactional pressures (200 kPa to 6.2 MPa) for two types of contrast agents (Definity and Optison). Results were fit using logistic regression analysis to define pressure thresholds where at least 5% and 50% of the microbubble populations collapsed for each frequency. These thresholds were found to occur at lower pressures for Definity than for Optison over the range of frequencies studied; additionally, the thresholds occurred at lower pressures with lower frequencies for both microbubble types in most cases, though this trend did not follow a mechanical index scaling.

Understanding the participation of breast screening among women born in predominantly Muslim countries living in Victoria, Australia from record-linkage data.

BACKGROUND: Early detection of breast cancer can improve survival rates and decrease mortality rates. This study investigates whether there are significant differences in participation in breast screening among women born in Muslim countries compared to women born in Non-Muslim countries and Australia. METHODS: Screening data from January 1st, 2000 to December 31st, 2013 from the Breast Screen Victoria Registry (BSV) was linked with hospital records from the Victorian Admitted Episodes Dataset (VAED). Countries having more than 50% of their population as Muslim were categorised as Muslim countries. Age adjusted rates were calculated for women born in Muslim and Non-Muslim countries and compared with the Australian age adjusted rates. Logistic regression assessed the association between screening status and other factors which include country of birth, marital status, age and socio-economic status. RESULTS: Women born in Muslim countries (Odds Ratio (OR) = 0.70, 95%CI = 0.68-0.72) and in other Non-Muslim countries (OR = 0.87, 95%CI = 0.86-0.88) had lower odds of participation in breast screening than Australian born women. Women aged 60-64 years (OR = 1.42, 95%CI = 1.40-1.44) had higher odds of participation in the BreastScreen program than 50-54 age group. CONCLUSION: This study provides valuable insights to understanding breast screening participation among women born in Muslim countries residing in Victoria. This population level study contributes to the broader knowledge of screening participation of women born in Muslim countries, an understudied population group in Australia and across the world. This study has implications for breast screening programs as it highlights the need for culturally sensitive approaches to support breast screening participation among women born in Muslim countries.

Measles immunisation status of healthcare workers in smaller Victorian hospitals: can we do better?

OBJECTIVE: To determine the proportion of healthcare workers (HCWs) in smaller Victorian public healthcare facilities with documented evidence of measles immunity. METHODS: A cross-sectional survey, developed by the Victorian Healthcare Associated Surveillance System Coordinating Centre, was completed by all eligible facilities. HCWs were reported as having evidence or no evidence of measles immunity. Those without evidence of immunity were sub-classified as incomplete, declined or unknown status. RESULTS: Seventy-five facilities reported measles immunity status of 17,522 employed HCWs. Of these, 11,751 (67.1%) had documented evidence of immunity. The proportion with evidence of immunity was lowest (45.6%) in facilities with ≤50 HCWs. The majority of HCWs without evidence of immunity (88.2%) had 'unknown' status. Declination or incomplete status comprised very low overall proportions (0.3% and 3.6%, respectively). CONCLUSIONS: Reported evidence of HCW measles immunity was moderate in surveyed facilities, with a large proportion having unknown status. HCW immunisation programs in some facilities require refinement to appropriately support public health responses to measles cases and prevention of occupational acquisition of measles. Implications for public health: Non-immune HCWs are at increased risk for acquiring and transmitting measles. Timely access to accurate HCW immunisation records is required to ensure that public health responses are effective.

Implementation of Australia's renewed cervical screening program: Preparedness of general practitioners and nurses.

The National Cervical Screening Program (NCSP) in Australia underwent major changes on December 1st, 2017. The program changed from 2-yearly Pap testing for women aged 18-69 years to 5-yearly HPV testing for women aged 25-74 years including differential management pathways for oncogenic HPV 16/18 positive versus HPV non16/18 positive test results and the option of self-collection for under-screened women. We conducted a survey among cervical screening providers in primary care to assess their level of preparedness in undertaking cervical screening before (pre-renewal) and after (post-renewal) the new program was implemented. Surveys were conducted between 14th August and 30th November 2017 (pre-renewal) and 9th February and 26th October 2018 (post-renewal) among cervical screening providers who attended education sessions related to the new guidelines. Preparedness was assessed in three areas: 1) level of comfort implementing the new guidelines (7 questions), 2) level of confidence in their ability to convey information about the new guidelines (9 questions) and 3) level of agreement regarding access to resources to support implementation (11 questions). Proportions were calculated for each question response and pre- and post-renewal periods compared using generalised linear models. Open-ended questions related to anticipated barriers and ways to overcome barriers were also included in the questionnaires. Compared to the pre-renewal period, a higher proportion of practitioners in the post-renewal period were more comfortable offering routine screening to women ≥25 years (p = 0.005) and more confident explaining the rationale for not screening before 25 years (p = 0.015); confident explaining a positive HPV 16/18 (p = 0.04) and HPV non 16/18(p = 0.013) test result and were comfortable with not referring women with a positive HPV non 16/18 test result and low grade/negative cytology for colposcopy (p = 0.01). A higher proportion of Victorian practitioners in the post-renewal period sample were also comfortable (p = 0.04) and confident (p = 0.015) recommending self-collection to under-screened women and agreed that self-collection is a reliable test (p = 0.003). The most commonly reported suggestion was to provide information, education and communication materials to both patients and practitioners. Compared to the pre-renewal period, practitioners in the post-renewal period were better prepared to implement the renewed screening program. Healthcare providers require further support to implement the self-collection pathway.

HPV16/18 prevalence in high-grade cervical lesions in an Australian population offered catch-up HPV vaccination.

OBJECTIVES: Using laser capture microdissection (LCM) and sensitive human papillomavirus (HPV) genotyping, we aimed to determine the distribution of vaccine-preventable types in cervical intraepithelial neoplasia grade 3 (CIN3) lesions and adenocarcinoma in situ (AIS) in young women in Victoria, Australia, offered catch-up HPV vaccination, as a baseline for ongoing vaccine impact monitoring. We also compared findings with available pre-vaccination estimates from women with HPV detected on concurrently-collected cytology samples. METHODS: Consecutive histologically-confirmed CIN3/AIS biopsies were collected between May 2011 and December 2014 from vaccine-eligible women (born after 30th June 1981). Genotypes present in whole tissue sections (WTS) were determined by a sensitive reverse hybridisation assay; RHA kit HPV SPF10-LiPA25, v1 (Labo Bio-medical Products). Where multiple genotypes were detected, lesions were isolated using LCM and genotyped. Cervical cytology samples from a pre-vaccine cohort had been previously collected and genotyped using HPV Linear Array HPV Genotyping Test (Roche Diagnostics). Mixed-genotype detections in this cohort were resolved to single-lesion-attributable genotypes using hierarchical attribution. RESULTS: Overall, 213 and 530 cases were included from pre- and post-vaccine time-periods, respectively. In 18-25 year-olds, the proportion of HPV16/18-positive CIN3/AIS decreased significantly over time from 69% in 2001-2005 (pre-vaccine), to 62% in 2011-2012 (post-vaccine), to 47% in 2013-2014 (p-trend = 0.004). There was no significant change in HPV16/18 in 26-32 year-olds (p-trend = 0.15). In 2013/14, nonavalent vaccine types accounted for 80% of CIN3/AIS in 18-25 year old women and 90% in 26-32 year old women. CONCLUSION: Four to 8 years following implementation of HPV vaccination in Australia, approximately 70% of CIN3/AIS in young women was due to HPV16/18. Our data, despite some limitations due to change in methods between pre- and post-vaccine periods, suggests that for vaccine-eligible women aged 18-25 at the time of biopsy, the proportion of HPV16/18-attributable CIN3/AIS lesions is significantly declining post-vaccination.

Assessment of attribution algorithms for resolving CIN3-related HPV genotype prevalence in mixed-genotype biopsy specimens using laser capture microdissection as the reference standard.

To make accurate determinations regarding potential and actual impact of HPV vaccine programs, precise estimates of genotype-specific contributions to disease are required for pre- and post-vaccine populations. Definitive determination of lesion-specific genotypes, particularly where multiple genotypes are detected in a sample, can be technically demanding and resource intensive; therefore, most prevalence studies use mathematical algorithms to adjust for multiple genotype detections. There are currently several algorithms, which can produce genotype estimates within a wide range of variability. The use of these for cervical cytology samples has recently been assessed for accuracy against a definitive reference standard, but none have yet been assessed for multiple-genotype-containing whole biopsy specimens. Using laser capture microdissection (LCM) on biopsy samples, lesion-specific genotype prevalence data were generated for a cohort of 516 young Australian women (aged 18-32 years) with cervical intraepithelial neoplasia grade 3 or adenocarcinoma in situ. Using whole tissue section genotype data from the same cohort, including 71 (13.7%) with multiple genotypes, lesion-associated genotype prevalence was estimated using four different attribution algorithms. The proportion of lesions attributable to HPV16 and HPV18 by LCM were 58.4% and 5%, respectively; hierarchical, proportional, single type/minimum and any type/maximum attribution estimates were comparable across genotypes. For analyses utilising whole tissue biopsy cervical specimens, attribution estimates are appropriate for estimating the proportional contribution of individual genotypes to lesions in a population.

Increased risk of cervical dysplasia in females with autoimmune conditions-Results from an Australia database linkage study.

BACKGROUND: Autoimmune conditions (AICs) and/or their treatment may alter risk of human papilloma virus (HPV) infection and females with AICs are therefore at an increased risk of cervical dysplasia. However, inclusion of these at-risk populations in cervical cancer screening and HPV-vaccination guidelines, are mostly lacking. This study aimed to determine the prevalence of cervical dysplasia in a wide range of AICs and compare that to HIV and immunocompetent controls to support the optimisation of cervical cancer preventive health measures. METHODS: Data linkage was used to match cervical screening episodes to emergency department records of females with AICs or HIV to immunocompetent controls over a 14-year period. The primary outcome was histologically confirmed high-grade cervical disease. Results, measured as rates by cytology and histology classification per 1,000 females screened, were analysed per disease group, and intergroup comparisons were performed. RESULTS: Females with inflammatory bowel disease (2,683), psoriatic and enteropathic arthropathies (1,848), multiple sclerosis (MS) (1,426), rheumatoid arthritis (1,246), systemic lupus erythematosus and/or mixed connective tissue disease (SLE/MCTD) (702), HIV (44), and 985,383 immunocompetent controls were included. SLE/MCTD and HIV groups had greater rates of high-grade histological and cytological abnormalities compared to controls. Increased rates of low-grade cytological abnormalities were detected in all females with AICs, with the exception of the MS group. CONCLUSIONS: Females with SLE/MCTD or HIV have increased rates of high-grade cervical abnormalities. The increased low-grade dysplasia rate seen in most females with AICs is consistent with increased HPV infection. These findings support expansion of cervical cancer preventative programs to include these at-risk females.