INTRODUCTION: This study estimated the costs and incremental cost per case detected of screening strategies for high-grade cervical intraepithelial neoplasia (CIN2+) in women living with HIV (WLHIV) attending HIV clinics in Burkina Faso. METHODS: The direct healthcare provider costs of screening tests (visual inspection with acetic acid (VIA), VIA combined visual inspection with Lugol's iodine (VIA/VILI), cytology and a rapid HPV DNA test (careHPV)) and confirmatory tests (colposcopy, directed biopsy and systematic four-quadrant (4Q) biopsy) were collected alongside the HPV in Africa Research Partnership (HARP) study. A model was developed for a hypothetical cohort of 1000 WLHIV using data on CIN2+ prevalence and the sensitivity of the screening tests. Costs are reported in USD (2019). RESULTS: The study enrolled 554 WLHIV with median age 36 years (inter-quartile range, 31-41) and CIN2+ prevalence of 5.8%. The average cost per screening test ranged from US$3.2 for VIA to US$24.8 for cytology. Compared to VIA alone, the incremental cost per CIN2+ case detected was US$48 for VIA/VILI and US$814 for careHPV. Despite higher costs, careHPV was more sensitive for CIN2+ cases detected compared to VIA/VILI (97% and 56%, respectively). The cost of colposcopy was US$6.6 per person while directed biopsy was US$33.0 and 4Q biopsy was US$48.0. CONCLUSION: Depending on the willingness to pay for the detection of a case of cervical cancer, decision makers in Burkina Faso can consider a variety of cervical cancer screening strategies for WLHIV. While careHPV is more costly, it has the potential to be cost-effective depending on the willingness to pay threshold. Future research should explore the lifetime costs and benefits of cervical cancer screening to enable comparisons with interventions for other diseases.

BACKGROUND: The spectrum of sexual practices that transmit Neisseria gonorrhoeae in men who have sex with men (MSM) is controversial. No studies have modelled potential Neisseria gonorrhoeae transmission when one sexual practice follows another in the same sexual encounter ('sequential sexual practices'). Our aim was to test what sequential practices were necessary to replicate the high proportion of MSM who have more than one anatomical site infected with gonorrhoea ('multisite infection'). METHODS: To test our aim, we developed eight compartmental models. We first used a baseline model (model 1) that included no sequential sexual practices. We then added three possible sequential transmission routes to model 1: (1) oral sex followed by anal sex (or vice versa) (model 2); (2) using saliva as a lubricant for penile-anal sex (model 3) and (3) oral sex followed by oral-anal sex (rimming) or vice versa (model 4). The next four models (models 5-8) used combinations of the three transmission routes. RESULTS: The baseline model could only replicate infection at the single anatomical site and underestimated multisite infection. When we added the three transmission routes to the baseline model, oral sex, followed by anal sex or vice versa, could replicate the prevalence of multisite infection. The other two transmission routes alone or together could not replicate multisite infection without the inclusion of oral sex followed by anal sex or vice versa. CONCLUSIONS: Our gonorrhoea model suggests sexual practices that involve oral followed by anal sex (or vice versa) may be important for explaining the high proportion of multisite infection.

BACKGROUND: There is limited information on risk factors for eczema in adults. Recent evidence suggests that air pollution may be associated with increased incidence of eczema in adults. We aimed to assess this possible association. METHODS: Ambient air pollution exposures (distance from a major road, nitrogen dioxide [NO2 ], fine particulate matter with an aerodynamic diameter ≤2.5 µm [PM2.5 ]) were assessed for the residential address of Tasmanian Longitudinal Health Study participants at ages 43 and 53 years. Eczema incidence (onset after age 43 years), prevalence (at 53 years), and persistence were assessed from surveys, while IgE sensitization was assessed using skin prick tests. The presence or absence of eczema and sensitization was classified into four groups: no atopy or eczema, atopy alone, non-atopic eczema, and atopic eczema. Adjusted logistic and multinomial regression models were fitted to estimate associations between ambient air pollution and eczema, and interaction by sex was assessed. RESULTS: Of 3153 participants in both follow-ups, 2369 had valid skin prick tests. For males, a 2.3 ppb increase in baselineNO2 was associated with increased odds of prevalent eczema (OR = 1.15 [95% CI 0.98-1.36]) and prevalent atopic eczema (OR = 1.26 [1.00-1.59]). These associations were not seen in females (p for interaction = 0.08, <0.01). For both sexes, a 1.6 µg/m3 increase in PM2.5 exposure at follow-up was associated with increased odds of aeroallergen sensitization (OR = 1.15 [1.03-1.30]). CONCLUSION: Increased exposure to residential ambient air pollutants was associated with an increased odds of eczema, only in males, and aeroallergen sensitization in both genders.

Background. Tendinopathies are a common complaint presenting to health professionals, including osteopaths. Evidence supports the use of exercise rehabilitation, with a potential role for manual therapy. This study sought to profile the practice and clinical management characteristics of Australian osteopaths who often treat tendinopathies. Methods. The study was designed as a cross-sectional survey of Australian osteopaths. Participants were Australian osteopaths who were members of the Osteopathy Research and Innovation Network (ORION) – the Australian professions’ practice-based research network. Participants were invited to complete a 27-item practice and clinical management characteristic questionnaire. The questionnaire asked participants to identify demographic, practice and clinical management characteristics associated with their practice. Regression modelling was used to identify significant characteristics associated with often treating tendinopathies. Results. Nine hundred and eighty-nine osteopaths responded and over 41% (n = 410) reported often treating tendinopathies. This group were more likely to be female (ORa 1.5), often treat patients with chronic pain (ORa 3.8) and sports injury (ORa 2.5) and often use exercise prescription (ORa 1.6) in patient care. Conclusions. Australian osteopaths who often treat tendinopathies demonstrate different clinical practice and management characteristics compared to their colleagues who do not often treat this complaint. Research into patient outcomes and cost-effectiveness of osteopathy care for the management of tendinopathies is now required.

Objective Structured Clinical Examinations (OSCEs) are extensively used for clinical assessment in the health professions. However, current social distancing requirements (including on-campus bans) at many universities have made the co-location of participants for large cohort OSCEs impossible. While there is a developing literature on remote OSCEs, particularly in response to the COVID-19 pandemic, this is dominated by approaches dealing with small participant numbers. This paper describes our recent large scale (n = 361 candidates) implementation of a remotely delivered 2 station OSCE. The planning for this OSCE was extensive and involved comprehensive candidate, examiner and simulated patient orientation and training. Our processes were explicitly designed to develop platform familiarity for all participants and included building on remote tutorial experiences and device testing. Our remote OSCE design and logistics made use of using existing enterprise solutions including videoconferencing, survey and collaboration platforms and allowed extra time between candidates in case of technical issues. We describe our process in detail including examiner, simulated patient, and candidate perspectives to provide precise detail, hopefully assisting other institutions to understand and adopt our approach. Although logistically complex, we have demonstrated that it is possible to deliver a remote OSCE assessment involving a large student cohort with a limited number of stations using commonly available enterprise solutions. We recognise it would be ideal to sample more broadly across stations and examiners, yet given the constraints of our current COVID-19 impacted environment, we believe this to be an appropriate compromise for a non-graduating cohort at this time.

OBJECTIVE: Data errors are a well-documented part of clinical datasets as is their potential to confound downstream analysis. In this study, we explore the reliability of manually transcribed data across different pathology fields in a prostate cancer database and also measure error rates attributable to the source data. DESIGN: Descriptive study. SETTING: Specialist urology service at a single centre in metropolitan Victoria in Australia. PARTICIPANTS: Between 2004 and 2011, 1471 patients underwent radical prostatectomy at our institution. In a large proportion of these cases, clinicopathological variables were recorded by manual data-entry. In 2011, we obtained electronic versions of the same printed pathology reports for our cohort. The data were electronically imported in parallel to any existing manual entry record enabling direct comparison between them. OUTCOME MEASURES: Error rates of manually entered data compared with electronically imported data across clinicopathological fields. RESULTS: 421 patients had at least 10 comparable pathology fields between the electronic import and manual records and were selected for study. 320 patients had concordant data between manually entered and electronically populated fields in a median of 12 pathology fields (range 10-13), indicating an outright accuracy in manually entered pathology data in 76% of patients. Across all fields, the error rate was 2.8%, while individual field error ranges from 0.5% to 6.4%. Fields in text formats were significantly more error-prone than those with direct measurements or involving numerical figures (p<0.001). 971 cases were available for review of error within the source data, with figures of 0.1-0.9%. CONCLUSIONS: While the overall rate of error was low in manually entered data, individual pathology fields were variably prone to error. High-quality pathology data can be obtained for both prospective and retrospective parts of our data repository and the electronic checking of source pathology data for error is feasible.

BACKGROUND AND PURPOSE: Individuals born very preterm (before 33 weeks of gestation, VPT) are at risk of damage to developing white matter, which may affect later cognition and behaviour. METHODS: We used diffusion tensor MRI (DT-MRI) to assess white matter microstructure (fractional anisotropy; FA) in 80 VPT and 41 term-born individuals (mean age 19.1 years, range 17-22, and 18.5 years, range 17-22 years, respectively). VPT individuals were part of a 1982-1984 birth cohort which had been followed up since birth; term individuals were recruited by local press advertisement. General intellectual function, executive function and memory were assessed. RESULTS: The VPT group had reduced FA in four clusters, and increased FA in four clusters relative to the Term group, involving several association tracts of both hemispheres. Clusters of increased FA were associated with more severe neonatal brain injury in the VPT group. Clusters of reduced FA were associated with lower birth weight and perinatal hypoxia, and with reduced adult cognitive performance in the VPT group only. CONCLUSIONS: Alterations of white matter microstructure persist into adulthood in VPT individuals and are associated with cognitive function.

AIM: Activation of the master energy-regulator AMP-activated protein kinase (AMPK) in the heart reduces the severity of ischemia-reperfusion injury (IRI) but the role of AMPK in renal IRI is not known. The aim of this study was to determine whether activation of AMPK by acute renal ischemia influences the severity of renal IRI. METHODS: AMPK expression and activation and the severity of renal IRI was studied in mice lacking the AMPK β1 subunit and compared to wild type (WT) mice. RESULTS: Basal expression of activated AMPK, phosphorylayed at αThr¹⁷², was markedly reduced by 96% in AMPK-β1⁻/⁻ mice. Acute renal ischaemia caused a 3.2-fold increase in α1-AMPK activity and a 2.5-fold increase in α2-AMPK activity (P<0.001) that was associated with an increase in AMPK phosphorylation of the AMPK-α subunit at Thr¹⁷² and Ser⁴⁸⁵, and increased inhibitory phosphorylation of the AMPK substrate acetyl-CoA carboxylase. After acute renal ischemia AMPK activity was reduced by 66% in AMPK-β1⁻/⁻ mice compared with WT. There was no difference, however, in the severity of renal IRI at 24-hours between AMPK-β1⁻/⁻ and WT mice, as measured by serum urea and creatinine and histological injury score. In the heart, macrophage migration inhibitory factor (MIF) released during IRI contributes to AMPK activation and protects from injury. In the kidney, however, no difference in AMPK activation by acute ischemia was observed between MIF⁻/⁻ and WT mice. Compared with the heart, expression of the MIF receptor CD74 was found to be reduced in the kidney. CONCLUSION: The failure of AMPK activation to influence the outcome of IRI in the kidney contrasts with what is reported in the heart. This difference might be due to a lack of effect of MIF on AMPK activation and lower CD74 expression in the kidney.

OBJECTIVE: The objective of this study is to determine whether obstructive sleep apnea (OSA) is associated with reduced fetal growth, and whether nocturnal oxygen desaturation precipitates acute fetal heart rate changes. STUDY DESIGN: We performed a prospective observational study, screening 371 women in the second trimester for OSA symptoms. 41 subsequently underwent overnight sleep studies to diagnose OSA. Third trimester fetal growth was assessed using ultrasound. Fetal heart rate monitoring accompanied the sleep study. Cord blood was taken at delivery, to measure key regulators of fetal growth. RESULTS: Of 371 women screened, 108 (29%) were high risk for OSA. 26 high risk and 15 low risk women completed the longitudinal study; 14 had confirmed OSA (cases), and 27 were controls. The median (interquartile range) respiratory disturbance index (number of apnoeas, hypopnoeas or respiratory related arousals/hour of sleep) was 7.9 (6.1-13.8) for cases and 2.2 (1.3-3.5) for controls (p<0.001). Impaired fetal growth was observed in 43% (6/14) of cases, vs 11% (3/27) of controls (RR 2.67; 1.25-5.7; p = 0.04). Using logistic regression, only OSA (OR 6; 1.2-29.7, p = 0.03) and body mass index (OR 2.52; 1.09-5.80, p = 0.03) were significantly associated with impaired fetal growth. After adjusting for body mass index on multivariate analysis, the association between OSA and impaired fetal growth was not appreciably altered (OR 5.3; 0.93-30.34, p = 0.06), although just failed to achieve statistical significance. Prolonged fetal heart rate decelerations accompanied nocturnal oxygen desaturation in one fetus, subsequently found to be severely growth restricted. Fetal growth regulators showed changes in the expected direction- with IGF-1 lower, and IGFBP-1 and IGFBP-2 higher- in the cord blood of infants of cases vs controls, although were not significantly different. CONCLUSION: OSA may be associated with reduced fetal growth in late pregnancy. Further evaluation is warranted to establish whether OSA may be an important contributor to adverse perinatal outcome, including stillbirth.

BACKGROUND: High purity of tumour samples is a necessity for accurate genetic and expression analysis and is usually achieved by positive selection in chronic lymphocytic leukaemia (CLL). RESULTS: We adapted a bifunctional rosette-based antibody cocktail for negative selection of B-cells for isolating CLL cells from peripheral blood (PB). PB samples from CLL patients were split into aliquots. One aliquot of each sample was enriched by density gradient centrifugation (DGC), while the other aliquot of each sample was incubated with an antibody cocktail for B-cell enrichment prior to DGC (RS+DGC). The purity of CLL cells after DGC averaged 74.1% (range: 15.9 - 97.4%). Using RS+DGC, the purity averaged 93.8% (range: 80.4 - 99.4%) with 23 of 29 (79%) samples showing CLL purities above 90%. RNA extracted from enriched CLL cells was of appropriately high quality for microarray analysis. CONCLUSION: This study confirms the use of a bifunctional rosette-based antibody cocktail as an effective method for the purification of CLL cells from peripheral blood.

Autism spectrum disorder (ASD) depends on a clinical interview with no biomarkers to aid diagnosis. The current investigation interrogated single-nucleotide polymorphisms (SNPs) of individuals with ASD from the Autism Genetic Resource Exchange (AGRE) database. SNPs were mapped to Kyoto Encyclopedia of Genes and Genomes (KEGG)-derived pathways to identify affected cellular processes and develop a diagnostic test. This test was then applied to two independent samples from the Simons Foundation Autism Research Initiative (SFARI) and Wellcome Trust 1958 normal birth cohort (WTBC) for validation. Using AGRE SNP data from a Central European (CEU) cohort, we created a genetic diagnostic classifier consisting of 237 SNPs in 146 genes that correctly predicted ASD diagnosis in 85.6% of CEU cases. This classifier also predicted 84.3% of cases in an ethnically related Tuscan cohort; however, prediction was less accurate (56.4%) in a genetically dissimilar Han Chinese cohort (HAN). Eight SNPs in three genes (KCNMB4, GNAO1, GRM5) had the largest effect in the classifier with some acting as vulnerability SNPs, whereas others were protective. Prediction accuracy diminished as the number of SNPs analyzed in the model was decreased. Our diagnostic classifier correctly predicted ASD diagnosis with an accuracy of 71.7% in CEU individuals from the SFARI (ASD) and WTBC (controls) validation data sets. In conclusion, we have developed an accurate diagnostic test for a genetically homogeneous group to aid in early detection of ASD. While SNPs differ across ethnic groups, our pathway approach identified cellular processes common to ASD across ethnicities. Our results have wide implications for detection, intervention and prevention of ASD.

BACKGROUND: Unintended pregnancy (mistimed or unwanted) remains an important health issue for women. The purpose of this study was to determine the prevalence of and factors associated with risk of unintended pregnancy in a sample of Victorian women attending family planning clinics. METHODS: This cross-sectional survey of three Family Planning Victoria Clinics from April to July 2011 recruited women aged 16-50 years with a male sexual partner in the last 3 months, and not intending to conceive. The questionnaire asked about contraceptive behaviours and important factors that influence contraception use (identified from a systematic literature review). Univariate analysis was calculated for the variables of interest for associations with contraceptive use. An overall multivariate model for being at risk for unintended pregnancy (due to inconsistent or ineffective contraceptive use or non-use) was calculated through backward elimination with statistical significance set at <0.05. RESULTS: 1006 surveys were analyzed with 96% of women reporting contraception use in the last 3 months. 37% of women were at risk for unintended pregnancy due to imperfect use (61% inconsistent users; 31% ineffective methods) or never using contraception (8%). On multivariate analysis, women at risk for unintended pregnancy compared with women not at risk were <25 years old (OR 1.8, 95% CI 1.2-2.7); had no university/postgraduate degree (OR 1.7, 95% CI 1.2-2.4); and had >1 partner in the last 3 months (OR 3.2, 95% CI 2.3-4.6). These women were dissatisfied with current contraception (OR 2.5, 95% 1.8-3.5); felt "vulnerable" to pregnancy (OR 2.1, 95% CI 1.6-3.0); were not confident in contraceptive knowledge (OR 2.6, 95% CI 1.5-4.8); were unable to stop to use contraception when aroused (OR 2.1, 95% CI 1.5-2.9) but were comfortable in speaking to a doctor about contraception (OR 2.3, 95% CI 1.1-4.1). CONCLUSION: Despite reported high contraceptive usage, nearly 40% of women were at risk for unintended pregnancy primarily due to inconsistent contraceptive use and use of ineffective contraception. Strategies for improving consistency of effective contraception use or greater emphasis on long-acting contraception may be needed for certain subpopulations at higher risk for unintended pregnancy.