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BACKGROUND Gay and bisexual men with undiagnosed HIV contribute disproportionately to HIV transmission in Australia. METHODS In 2014 and 2018, we recruited men at gay venues and events in Sydney. Participants self-completed surveys and provided oral fluid samples for HIV testing. We calculated the prevalence of HIV and undiagnosed infection, and assessed changes in behavior, HIV testing, and the use of pre-exposure prophylaxis. We weighted the samples to adjust for differences in where participants were recruited between rounds. Two-sample tests of proportion were used to compare prevalence estimates and χ tests to assess differences between the samples. RESULTS In 2014, 944 men were recruited, and 890 men were recruited in 2018. In 2014, the weighted estimate of HIV prevalence was 6.1% [95% confidence intervals (CI): 4.6 to 7.6], of which 13.8% (95% CI: 5.0 to 22.7) was undiagnosed. In 2018, weighted HIV prevalence was 6.4% (95% CI: 4.8 to 8.0), of which 5.3% (95% CI: 0.5 to 11.1) was undiagnosed. Between 2014 and 2018 among all participants, men reporting at least 10 recent casual partners increased from 22.3% to 27.7% (P = 0.008), condomless anal intercourse with casual partners in the previous 6 months increased from 23.9% to 37.3% (P < 0.001), and sexually transmitted infection diagnoses in the previous year increased from 14.4% to 27.5% (P < 0.001). HIV testing and the use of pre-exposure prophylaxis in the previous 6 months increased from 49.6% to 56.3% (P = 0.004) and 2.0%-21.0% (P < 0.001), respectively. CONCLUSIONS Repeated, bio-behavioral surveillance suggests the prevalence of undiagnosed HIV remains low in Sydney, despite gay and bisexual men reporting more casual sex partners, condomless sex, and sexually transmitted infections.

STUDY QUESTION What is the rate of natural conception leading to ongoing pregnancy or livebirth over 6–12 months for infertile women of age ≥35 years? SUMMARY ANSWER Natural conception rates were still clinically relevant in women aged 35 years and above and were significantly higher in women with unexplained infertility compared to those with other diagnoses. WHAT IS KNOWN ALREADY In recent years, increasing numbers of women have attempted to conceive at a later age, resulting in a commensurate increase in the need for ART. However, there is a lack of data on natural fertility outcomes (i.e. no interventions) in women with increasing age. STUDY DESIGN, SIZE, DURATION A systematic review with individual participant data (IPD) meta-analysis was carried out. PubMed, MEDLINE, EMBASE, the Cochrane Library, clinicaltrials.gov were searched until 1 July 2018 including search terms ‘fertility service’, ‘waiting list’, ‘treatment-independent’ and ‘spontaneous conception’. Language restrictions were not imposed. PARTICIPANTS/MATERIALS, SETTING, METHODS Inclusion criteria were studies (at least partly) reporting on infertile couples with female partner of age ≥35 years who attended fertility services, underwent fertility workup (e.g. history, semen analysis, tubal status and ovulation status) and were exposed to natural conception (e.g. independent of treatment such as IVF, ovulation induction and tubal surgery). Studies that exclusively studied only one infertility diagnosis, without including other women presenting to infertility services for other causes of infertility, were excluded. For studies that met the inclusion criteria, study authors were contacted to provide IPD, after which fertility outcomes for women of age ≥35 years were retrieved. Time to pregnancy or livebirth and the effect of increasing age on fertility outcomes after adjustment for other prognostic factors were analysed. Quality of studies was graded with the Newcastle–Ottawa Scale (non-randomised controlled trials (RCTs)) or the Cochrane Risk of Bias tool (for RCTs). MAIN RESULTS AND THE ROLE OF CHANCE We included nine studies (seven cohort studies and two RCTs) (n = 4379 women of at least age 35 years), with the observed composite primary outcome of ongoing pregnancy or livebirth occurring in 429 women (9.8%) over a median follow-up of 5 months (25th to 75th percentile: 2.5–8.5 months). Studies were of moderate to high quality. The probability of natural conception significantly decreased with any diagnosis of infertility, when compared with unexplained infertility. We found non-linear effects of female age and duration of infertility on ongoing pregnancy and tabulated the predicted probabilities for unexplained infertile women aged 35–42 years with either primary or secondary infertility and with a duration of infertility from 1 to 6 years. For a 35-year-old woman with 2 years of primary unexplained infertility, the predicted probability of natural conception leading to ongoing pregnancy or livebirth was 0.15 (95% CI 0.11–0.19) after 6 months and 0.24 (95% CI 0.17–0.30) after 12 months. For a 42-year-old woman, this decreased to 0.08 (95% CI 0.04–0.11) after 6 months and 0.13 (95% CI 0.07–0.18) after 12 months. LIMITATIONS, REASONS FOR CAUTION In the studies selected, there were different study designs, recruitment strategies in different centres, protocols and countries and different methods of assessment of infertility. Data were limited for women above the age of 40 years. WIDER IMPLICATIONS OF THE FINDINGS Women attending fertility services should be encouraged to pursue natural conception while waiting for treatment to commence and after treatment if it is unsuccessful. Our results may aid in counselling women, and, in particular, for those with unexplained infertility. STUDY FUNDING/COMPETING INTEREST(S) S.J.C. received funding from the University of Adelaide Summer Research Scholarship. B.W.M. is supported by a NHMRC Investigator grant (GNT1176437), B.W.M. reports consultancy for ObsEva, Merck, Merck KGaA, iGenomix and Guerbet. B.W.M. reports research support by Merck and Guerbet. PROSPERO REGISTRATION NUMBER CRD42018096552.

This study aimed to investigate the cost-effectiveness of preimplantation genetic diagnosis (PGD) for the reproductive choices of patients with heritable retinoblastoma. The study modelled the costs of three cycles of in-vitro fertilization (IVF) and PGD across all uptake rates of PGD, number of children affected with retinoblastoma at each uptake rate and the estimated quality-adjusted life years (QALYs) gained. Cost-effectiveness analysis was conducted from the Australian public healthcare perspective. The intervention was the use of three cycles (one fresh and two frozen) of IVF and PGD with the aim of live births unaffected by the retinoblastoma phenotype. Compared with the standard care pathway (i.e. natural pregnancy), IVF and PGD resulted in a cost-saving to 18 years of age of AUD$2,747,294 for a base case of 100 couples with an uptake rate of 50%. IVF and PGD resulted in fewer affected (n = 56) and unaffected (n = 78) live births compared with standard care (71 affected and 83 unaffected live births), and an additional 0.03 QALYs per live birth. This modelling suggests that the use of IVF and PGD to achieve an unaffected child for patients with heritable retinoblastoma resulted in an overall cost-saving. There was an increase in QALYs per baby across all uptake rates. However, in total, fewer babies were born following the IVF and PGD pathway.

Objective To evaluate the clinical and cost-effectiveness of preimplantation genetic testing for aneuploidy, social freezing, donor and autologous assisted reproductive technology (ART) treatment strategies for women aged 35–45 following 6–12 months of infertility. Methods Four Markov decision-analytic models comprising: (i) Preimplantation genetic testing for aneuploidy (PGT-A); (ii) autologous ART from age 40 using oocytes cryopreserved at age 32 (social freezing); (iii) ART using donated oocytes (donor ART); (iv) standard autologous ART treatment (standard care) were developed for a hypothetical cohort of 35 to 45 years old ART naïve women with 6–12 months of infertility. Input probabilities for key parameters including live birth rates were obtained from the available literature. Deterministic and probabilistic sensitivity analyses were conducted to address uncertainty in estimating the parameters and around the model’s assumptions. Cost effectiveness was assessed from both societal and patient perspectives . Result(s) For infertile women at age 40 and above, social freezing is the most cost-saving strategy with the highest chance of a cumulative live birth at a lowest cost from a societal perspective. PGT-A and donor ART were associated with higher treatment costs and cumulative live-birth rates compared with the autologous ART. Among the four ART strategies, standard autologous ART has the lowest cumulative live birth rate of 45% at age 35 and decreasing to 1.6% by age 45 years. At a willingness-to-pay threshold of Australian dollars (A$)50,000, our model shows all alternative treatment strategies –PGT-A, social freezing and donor ART have a higher probability of being cost-effective compared to the standard autologous ART treatment. However, higher out-of-pocket expenditure may impede their access to these alternate strategies. Conclusion Given current evidence, all alternate strategies have a higher probability of being cost-effective compared to the standard autologous ART treatment. Whether this represents value for money depends on societal and individual’s willingness-to-pay for children conceived with ART treatment.

Aims This scoping review aims to: 1) examine available literature regarding the effects of power training on gait speed, power, and function in ambulatory children with CP and 2) identify the variations in exercise dosage and rehabilitation recommendations for power training and plyometrics in children with CP. Methods Four databases (PubMed, CINAHL, Embase, and Cochrane) were searched for papers including power or plyometric training with outcome measures for gait, power or functional performance. ES was calculated for RCTs. Cohorts and case series/studies were evaluated qualitatively. Results Ten articles fit search criteria: four RCTs, three cohort studies, one case series, and two case studies. Power training consistently demonstrated improvements in muscle power compared to its effects on gait and function. ES of mean MPST (W) ranged from 0.36-1.13. 1 MWT and SSGS ES were 1.31 and 1.15, respectively. TUG ES ranged from -0.33 to -2.42. ES for GMFM-66 was 0.13 and 1.11 for Dimension D and Dimension E, respectively. Conclusions There is limited, but promising evidence to support that power training may improve gait speed, power, and function in children with CP. Future, more robust research is required to examine effects in a larger, diverse population, to determine long-term effects and exercise prescription.

Background:: In 2015, New South Wales (Australia) removed patient co-payments for ART of HIV. We hypothesized the policy change would reduce overall out-of-pocket (OOP) healthcare expenditure, improve ART adherence, and better maintain HIV suppression. Methods: Using data from a national, 2-year prospective study of adults with HIV on ART (n=364) (2013-2017), we compared OOP healthcare expenditure, ART adherence, and virological failure (VF) in participants subject to the co-payment policy change with participants from other jurisdictions who never paid, and who always paid, co-payments. We used fixed effects regression models to compare outcomes, and incidence rates for VF. Results:: Although ART co-payments declined, there was no significant change in total OOP healthcare expenditure in participants ceasing co-payments compared to those who continued (adjusted coefficient 0.09, 95% CI -0.31 to 0.48). Co-payment removal did not significantly reduce suboptimal ART adherence (from 17.5% to 16.3%) or VF (from 5.0 to 3.7 episodes per-100-person-years). Participants in the lowest income group but not receiving concessional government benefits incurred a non-significant increase in total OOP healthcare expenses; while concessional participants experienced a significant increase in non-ART HIV healthcare costs after the policy changed. Conclusion:: In this population, ART co-payments represented a small proportion of OOP healthcare expenditure. Its removal did not materially impact ART adherence or VF, although the study was not powered to detect these.

Background : In 2015, New South Wales (Australia) removed patient co-payments for ART of HIV. We hypothesized the policy change would reduce overall out-of-pocket (OOP) healthcare expenditure, improve ART adherence, and better maintain HIV suppression. Methods: Using data from a national, 2-year prospective study of adults with HIV on ART (n=364) (2013-2017), we compared OOP healthcare expenditure, ART adherence, and virological failure (VF) in participants subject to the co-payment policy change with participants from other jurisdictions who never paid, and who always paid, co-payments. We used fixed effects regression models to compare outcomes, and incidence rates for VF. Results : Although ART co-payments declined, there was no significant change in total OOP healthcare expenditure in participants ceasing co-payments compared to those who continued (adjusted coefficient 0.09, 95% CI -0.31 to 0.48). Co-payment removal did not significantly reduce suboptimal ART adherence (from 17.5% to 16.3%) or VF (from 5.0 to 3.7 episodes per-100-person-years). Participants in the lowest income group but not receiving concessional government benefits incurred a non-significant increase in total OOP healthcare expenses; while concessional participants experienced a significant increase in non-ART HIV healthcare costs after the policy changed. Conclusion : In this population, ART co-payments represented a small proportion of OOP healthcare expenditure. Its removal did not materially impact ART adherence or VF, although the study was not powered to detect these.

In Australia, HIV testing services have become increasingly available in non-traditional settings such as peer-led, community-based services to expand access and increase uptake of HIV testing among gay and bisexual men (GBM). This study aimed to compare the socio-demographic and behavioural characteristics of GBM whose last HIV test was conducted at a community-based service to GBM whose last test was at a traditional clinical setting. We analysed behavioural surveillance data collected from 5988 participants in seven states and territories in the period 2016-2017. We found that non-HIV-positive GBM who attended community-based services were largely similar to men attending clinic-based settings, particularly in terms of sexual practice and risk of HIV. However, non-HIV-positive GBM who were younger, born in Asia, more socially engaged with other gay men but who had not recently used PrEP were more likely to attend community-based services for their last HIV test. This study points to the successful establishment of community-based HIV testing services in Australia as a way to attract subgroups of GBM at potentially higher risk of HIV.

Background: The explosion in new treatment options targeting immune checkpoints, HER signaling, DNA repair deficiency, AKT, and other pathways calls for updated breast cancer subtypes beyond HR and HER2 status to predict which patients will respond to which treatments. Here we leverage the I-SPY 2 TRIAL biomarker program over the past 8 years across 10 treatment arms to elucidate a minimal set of biomarkers that may improve response prediction in a modern treatment context, and to investigate which new patient phenotypes are identified by these response-predictive biomarkers. Methods: 986 patients were considered in this analysis. Treatments included paclitaxel alone (or with trastuzumab (H) in HER2+) or combined with investigational agents: veliparib/carboplatin (VC); neratinib; MK2206; ganitumab; ganetespib; AMG386; TDM1/pertuzumab (P); H/P; and pembrolizumab (Pembro). 24 prospectively defined, mechanism-of-action and pathway-based expression and phospho-protein signatures/biomarkers assayed from pre-treatment biopsies were previously found to be predictive in a particular agent/arm in pre-specified analysis. Here we evaluate these biomarkers in all patients. We assessed association between each biomarker and response in the population as a whole and within each arm and HR/HER2 subtype using a logistic model. To identify optimal dichotomizing thresholds for select biomarkers, 2-fold cross-validation was repeated 500 times. Our analysis is exploratory and does not adjust for multiplicities. Results: Our initial set of 24 predictive biomarkers reflects DNA repair deficiency (n=2), immune activation (n=7), ER signaling (n=2), HER2 signaling (n=4), proliferation (n=2), phospho-activation of AKT/mTOR (n=2), and ANG/TIE2 (n=1) pathways, among others. Biomarkers reflecting similar biology are correlated and cluster together. We make use of this correlation structure to reduce the dimensionality of the biomarker set to five predictive signals: proliferation, DNA repair deficiency (DRD), immune-engaged (Immune+), luminal/ER (lum), and HER2-activated. These biomarkers, when dichotomized, identify patient groups with differential predicted sensitivities to I-SPY 2 agents and are present at different proportions within receptor subtypes. For instance, in the HER2- subset, Immune+/DRD+ patients are predicted sensitive to both VC and Pembro, and account for 39% of TN, but only 12% of HR+HER2-. On the other end of the spectrum, only 17% of TN are Immune-/DRD-, compared to the majority (56%) of HR+HER2-. There are also subsets of patients positive for only one marker. For the HER2+ subset, 67% are HER2-activated+, and 25% lum+; of these HER2-activated+ patients are more likely to be Immune+ (44%), vs 23% in lum+. HER2-activated+/Immune+ patients have higher predicted sensitivity to HER2-targeted agents than lum+ or Immune- patients. In all, these molecular phenotypes predict sensitivity to one or more I-SPY 2 investigational agents for 75% of the ˜ 1000 patients. Conclusion: Molecular phenotypes reflecting proliferation, immune engagement, HER2-activation, luminal/ER-signaling, and DNA repair deficiency may provide a roadmap to guide treatment prioritization for emerging therapeutics. Citation Format: Wolf DM, Yau C, Wulfkuhle J, Petricoin E, Campbell M, Brown-Swigart L, Hirst G, Asare S, Zhu Z, Lee EP, Delson A, Pohlmann P, I-SPY 2 TRIAL Consortium, Hylton N, Liu MC, Symmans F, DeMichele A, Yee D, Berry D, Esserman L, van 't Veer L. Identifying breast cancer molecular phenotypes to predict response in a modern treatment landscape: Lessons from ˜1000 patients across 10 arms of the I-SPY 2 TRIAL [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-10-02.

This study aimed to systematically review the current literature on the economic costs of micro preemie as well as evidence on the cost-effectiveness of interventions to improve outcomes for micro preemie babies with a birth weight of ≤500 g.We searched MEDLINE, CINAHL, Scopus, ECONLIT, Business Source Premier and Cochrane Library for studies reporting costs of micro preemie from January 2000. Costs were inflated to 2019 United States dollars (US$). All full-text articles were assessed for eligibility and a quality assessment of included articles was conducted using the Drummond and the Larg and Moss checklists.The search identified three studies that met the inclusion criteria; two cost-of-illness studies and one cost-effectiveness study. Across studies, the mean healthcare spending per micro preemie survivor (in 2019 US$) ranged from US$61,310 (birth admission) to US$263,958 (inpatient and outpatient for the first six months of life). One modelling study reported exclusive human milk diet for micro preemies at birth was more cost-effective compared to the standard approach with cow milk diet from the third-party payer and societal perspectives.Despite significant advances in perinatal care and expanded access to life-saving equipment to improve survival outcomes of micro preemie, there remains a paucity of research on economic costs associated with these babies. No study has utilised quality-adjusted life-years as an outcome measure. Given the chronic conditions and long-term neurologic disability associated with micro preemie survivors, an estimate of the lifetime cost to the individual, healthcare providers and society would provide a benchmark of the potential cost-savings that could accrue from cost-effective interventions to improve the survival rate of micro preemies.

Using pre-treatment gene expression, protein/phosphoprotein and clinical data from the I-SPY2 neoadjuvant platform trial (NCT01042379), we create alternative breast cancer subtypes incorporating tumor biology beyond clinical hormone-receptor (HR) and Human Epidermal Growth Factor Receptor-2 (HER2) status to better predict drug responses. We assess predictive performance of mechanism-of-action biomarkers from ~990 patients treated with 10 regimens targeting diverse biology. We explore >11 subtyping schemas and identify treatment-subtype pairs maximizing pathologic complete response (pCR) rate over the population. The best performing schemas incorporate Immune, DNA-repair and HER2/Luminal phenotypes. Subsequent treatment allocation increases overall pCR rate to 63% from 51% using HR/HER2-based treatment selection. pCR gains from reclassification and improved patient selection are highest in HR+ subsets (>15%). As new treatments are introduced, the subtyping schema determines the minimum response needed to show efficacy. This data platform provides an unprecedented resource and supports the usage of response-based subtypes to guide future treatment prioritization.

The postpartum period is a challenging transition period with almost one in ten mothers experiencing depression after childbirth. Perceived social support is associated with mental health. Yet empirical evidence regarding the causal effects of social support on postpartum mental health remains scarce. In this paper, we used a nationally representative panel data of women to examine causality between perceived social support and postpartum mental health. We used fixed-effect method and included dependent variable lags to account for past mental health condition before birth (i.e., the pre-pregnancy and prenatal periods). The study also used an instrumental variable approach to address endogeneity. We find a declining trend in postpartum mental health between 2002 to 2018. Our study also showed that past mental health (i.e., before childbirth) is positively correlated with postpartum mental health. A universal routine mental health screening for expectant and new mothers should remain a key priority to ensure mental wellbeing for the mothers and their infants.

Background Preimplantation genetic diagnosis for aneuploidy (PGD-A) for all 24 chromosomes improves implantation and clinical pregnancy rates per single assisted reproductive technology (ART) cycle. However, there is limited data on the live-birth rate of PGD-A over repeated cycles. Aim To assess the cumulative live-birth rates (CLBR) of PGD-A compared with morphological assessment of embryos of up to three ‘complete ART cycles’ (fresh plus frozen/thaw cycles) in women aged 37 years or older. Materials and Methods A retrospective cohort study of ART treatments undertaken by ART-naive women at a large Australian fertility clinic between 2011 and 2014. Cohorts were assigned based on the embryo selection method used in their first fresh cycle [PGD-A, n = 110 women (PGD-A group); morphological assessment of embryos, n = 1983 women (control group)]. CLBR, time to clinical pregnancy and cycles needed to achieve a live birth were measured over multiple cycles. Results Compared to the control group, the PGD-A group achieved a higher per cycle live-birth rate (14.47% vs 9.12%, P

BACKGROUND: We aimed to identify preoperative psychosocial factors associated with return-to-work (RTW) and the associated cost of productivity loss due to work absenteeism following surgery. Research demonstrates a high economic burden from productivity loss after surgery, but the comparative cost of productivity loss relative to income across different operations has not been examined. MATERIALS AND METHODS: A mixed surgical cohort recruited for a randomized controlled trial were prospectively followed for up to two years following surgery with daily phone assessments to three months, weekly assessments thereafter to six months, then monthly assessments thereafter to determine RTW status, opioid use and pain. RESULTS: 183 of 207 (88.3%) patients in paid employment prior to surgery, who provided at least one day of follow-up, were included in this analysis. The average cost of productivity loss due to work absenteeism was $13 761 (median $9 064). Patients who underwent total knee replacement incurred the highest income loss. Medical claims filed before surgery were significantly associated with relative income loss (AOR 5.09;95% CI 1.73- 14.96; p

This study assessed the economic evidence on the pharmacological and non-pharmacological management of infants with neonatal opioid withdrawal syndrome (NOWS). Six databases were searched up to October 2020 for peer-reviewed studies. After titles and abstracts were screened, 79 studies remained for full-text review, and finally, 8 studies were eligible for inclusion in the review. The methodological quality of included studies was assessed using the Drummond checklist. The review showed significant limitations in these studies, with one study being rated as good and the remaining seven studies as of poor quality. There are methodological issues that require addressing, including a lack of detail on cost categories, a robust investigation of uncertainty, and extending the time horizon to consider longer-term outcomes beyond the initial birth hospitalization. Despite these limitations, existing evidence suggests non-pharmacological strategies such as rooming-in were associated with a shorter hospital stay and a decreased need for pharmacological treatment, thereby lowering hospitalization costs. The review highlights the paucity of high-quality studies assessing the cost-effectiveness of intervention strategies for NOWS. There is also a lack of evidence on long-term outcomes associated with NOWS and the treatment of NOWS. The inclusion of economic analyses in future studies will provide evidence to inform policymakers on resource allocation decisions for this patient population.

Using repeated, cross-sectional behavioural surveillance data from Australia, we assessed trends in relationship agreements and casual sex among HIV-negative and untested gay and bisexual men who had regular partners during 2013–2018. We conducted three analyses: (i) trends in relationship agreements and casual sex over time; (ii) bivariate comparisons of PrEP users and non-PrEP-users to identify factors associated with PrEP use; and (iii) multivariate logistic regression to identify factors independently associated with PrEP use. The analysis of trends over time included 21,593 men, from which a sub-sample (n = 3764) was used to compare PrEP users and non-PrEP-users. We found a large increase in agreements that allowed condomless sex with casual partners, particularly by PrEP users in relationships (nearly 40% of whom had such an agreement). A further 34% of PrEP users reported having casual condomless sex without an agreement that permitted that behaviour, while 13% of non-PrEP-users also reported condomless sex with casual partners without an agreement. PrEP use was independently associated with having agreements permitting condomless sex with casual partners, recent condomless sex with casual partners, having greater numbers of male partners, recent post-exposure prophylaxis use, having an HIV-positive regular male partner, and recent condomless sex with regular male partners. Our findings show a shift away from relationship agreements in which condomless sex was only sanctioned between regular partners.

Chorioangioma or chorangioma is a benign placental tumour which occurs in 1% of the pregnancies. Large lesions of more than 4–5 cm in size, also known as giant chorangiomas, are rare with the incidence of 1:3500 and 1:9000 birth. Unlike small tumours, the giant chorangiomas are highly associated with pregnancy complications. We report a case of multiple large chorangiomas resulting in an extremely preterm delivery. A 24-year-old primigravida presented at 25 weeks of gestation for threatened preterm labour. Transabdominal ultrasound revealed an echogenic mass on the placenta measuring 8.7 × 4.4 cm. Following a successful tocolysis and administration of a course of antenatal corticosteroids, she was discharged home. At 27 weeks of gestation, she developed a second episode of preterm contractions. Besides, the foetus was found to be small for gestational age. In the second episode of preterm contractions, intravenous magnesium sulfate infusion was commenced for foetal neuroprotection. Tocolysis was commenced for severe prematurity. She went into spontaneous preterm labour. Placenta examination revealed multiple solid masses with fleshy and congested dark red surface. A histopathological examination of the placenta confirmed the diagnosis of chorangiomas. The baby was discharged in good condition at 5 months of age. Placental chorangiomas, notably when they are multiple and large in size, are associated with adverse pregnancy outcomes. Therefore, close antenatal surveillance is necessary to allow timely recognition and intervention of pregnancy complications. Our case portrays an unexpected favourable neonatal outcome associated with a giant chorangiomas.

Precision medicine aims to use patient genomic, epigenomic, specific drug dose, and other data to define disease patterns that may potentially lead to an improved treatment outcome. Personalized dosing regimens based on tumor drug penetration can play a critical role in this approach. State-of-the-art techniques to measure tumor drug penetration focus on systemic exposure, tissue penetration, cellular or molecular engagement, and expression of pharmacological activity. Using in silico methods, this information can be integrated to bridge the gap between the therapeutic regimen and the pharmacological link with clinical outcome. These methodologies are described, and challenges ahead are discussed. Supported by many examples, this review shows how the combination of these techniques provides enhanced patient-specific information on drug accessibility at the tumor tissue level, target binding, and downstream pharmacology. Our vision of how to apply tumor drug penetration measurements offers a roadmap for the clinical implementation of precision dosing., SCOPUS: re.j, info:eu-repo/semantics/published

Phosphorylation networks intimately regulate mechanisms of response to therapies. Mapping the phospho-catalytic profile of kinases in cells or tissues remains a challenge. Here, we introduce a practical high-throughput system to measure the enzymatic activity of kinases using biological peptide targets as phospho-sensors to reveal kinase dependencies in tumour biopsies and cell lines. A 228-peptide screen was developed to detect the activity of >60 kinases, including ABLs, AKTs, CDKs and MAPKs. Focusing on BRAF(V600E) tumours, we found mechanisms of intrinsic resistance to BRAFV(600E)-targeted therapy in colorectal cancer, including targetable parallel activation of PDPK1 and PRKCA. Furthermore, mapping the phospho-catalytic signatures of melanoma specimens identifies RPS6KB1 and PIM1 as emerging druggable vulnerabilities predictive of poor outcome in BRAF(V600E) patients. The results show that therapeutic resistance can be caused by the concerted upregulation of interdependent pathways. Our kinase activity-mapping system is a versatile strategy that innovates the exploration of actionable kinases for precision medicine.

BACKGROUND Current evidence suggests that preimplantation genetic testing for aneuploidy (PGT-A) used during assisted reproductive technology improves per-cycle live-birth rates but cumulative live-birth rate (CLBR) was similar to a strategy of morphological assessment (MA) of embryos. No study has assessed the cost-effectiveness of repeated cycles with PGT-A using longitudinal patient-level data. AIM To assess the cost-effectiveness of repeated cycles with PGT-A compared to MA of embryos in older women. MATERIALS AND METHODS Micro-costing methods were used to value direct resource consumption of 2093 assisted reproductive technology-naive women aged ≥37 years undergoing up to three 'complete assisted reproductive technology cycles' (fresh plus cryopreserved embryos) with either PGT-A or MA in an Australian clinic between 2011 and 2014. Incremental cost-effective ratios were calculated from healthcare and patient perspectives with uncertainty assessed using non-parametric bootstrap methods. Cost-effectiveness acceptability curves were constructed to evaluate the probability of PGT-A being cost-effective over a range of willingness-to-pay thresholds. RESULTS The CLBR and mean healthcare costs per patient were 30.90% and $22 962 for the PGT-A group, and 26.77% and $21 801 for the MA group, yielding an incremental cost-effective ratio of $28 103 for an additional live birth with PGT-A. At a willingness-to-pay threshold of $50 000 and above, there is more than an 80% probability of PGT-A being cost-effective from the healthcare perspective and a 50% likelihood from a patient perspective. CONCLUSION This is the first study to use real-world patient-level data to assess the cost-effectiveness of PGT-A in older women from the healthcare and patient perspectives. The findings contribute to the ongoing debate on the role of PGT-A in clinical practice.

BACKGROUND: HIV prevention cascades can assist in monitoring the implementation of prevention methods like preexposure prophylaxis (PrEP). We developed 2 PrEP cascades for Australia's primary HIV-affected population, gay and bisexual men. METHODS: Data were drawn from 2 national, repeated, cross-sectional surveys (the Gay Community Periodic Surveys and PrEPARE Project). One cascade had 3 steps, and the other had 7 steps. Trends over time were assessed using logistic regression. For the most recent year, we identified the biggest drop between steps in each cascade and compared the characteristics of men between the 2 steps using multivariate logistic regression. RESULTS: Thirty-nine thousand six hundred and seventy non-HIV-positive men participated in the Periodic Surveys during 2014-2018. PrEP eligibility increased from 28.1% (1901/6762) in 2014 to 37.3% (2935/7878) in 2018 (P

Pre-exposure prophylaxis (PrEP) has been rapidly rolled out in large, publicly funded implementation projects in Victoria and New South Wales, Australia. Using behavioural surveillance of gay and bisexual men, we analysed the uptake and effect of PrEP, particularly on condom use by gay and bisexual men not using PrEP.We collected data from the Melbourne and Sydney Gay Community Periodic Surveys (GCPS), cross-sectional surveys of adult gay and bisexual men in Melbourne, VIC, and Sydney, NSW. Recruitment occurred at gay venues or events and online. Eligible participants were 18 years or older (face-to-face recruitment) or 16 years or older (online recruitment), identified as male (including transgender participants who identified as male); and having had sex with a man in the past 5 years or identified as gay or bisexual, or both. Using multivariate logistic regression, we assessed trends in condom use, condomless anal intercourse with casual partners (CAIC), and PrEP use by gay and bisexual men, controlling for sample variation over time.Between Jan 1, 2013, and March 31, 2017, 27 011 participants completed questionnaires in the Melbourne (n=13 051) and Sydney (n=13 960) GCPS. 16 827 reported sex with casual male partners in the 6 months before survey and were included in these analyses. In 2013, 26 (1%) of 2692 men reported CAIC and were HIV-negative and using PrEP, compared with 167 (5%) of 3660 men in 2016 and 652 (16%) of 4018 men in 2017 (p0·0001). Consistent condom use was reported by 1360 (46%) of 2692 men in 2013, 1523 (42%) of 3660 men in 2016, and 1229 (31%) of 4018 men in 2017 (p0·0001). In 2013, 800 (30%) of 2692 men who were HIV-negative or untested and not on PrEP reported CAIC, compared with 1118 (31%) of 3660 men in 2016, and 1166 (29%) of 4018 in 2017 (non-significant trend).A rapid increase in PrEP use by gay and bisexual men in Melbourne and Sydney was accompanied by an equally rapid decrease in consistent condom use. Other jurisdictions should consider the potential for community-level increases in CAIC when modelling the introduction of PrEP and in monitoring its effect.Australian Government Department of Health, Victorian Department of Health and Human Services, and New South Wales Ministry of Health.

Background: Triple-negative breast cancer (TNBC) accounts for approximately 10 to 15% of all breast cancer cases. The management of TNBC cases will significantly improve once molecular mechanisms specific to TNBC cells will be identified and treated accordingly. Evidence suggests that TNBC cells display deregulated kinase-dependent signaling cascades that differ from non-triple-negative breast cancer cells. We hypothesized that uniquely divergent phospho-circuits could be distinguished between TNBC and non-TNBC cell lines. By revealing such unique, dysfunctional phospho-signaling network, our long-term objective is to identify kinases that underpin triple-negative breast cancer development, and can be inhibited using targeted therapy. Methods: The kinome activity of TNBC and non-TNBC cell lines was identified (HCC70, MDA-MB-231, MDA-MB-436 compared to AU565, MCF-7, T47D). The functional phospho-signature of each breast cancer cell was analyzed using a high throughput experimental platform that monitors the level of activity of myriad kinases at once. This technique uses 242 phospho-sensing probes and 78 controls in an aqueous-based assay to simultaneously and directly measure the phospho-catalytic activity of phosphorylating enzymes in cell lysates. We mapped the most significantly deranged phospho-signaling cascades and the related kinases. Results: Using 6 cell lines tested under various conditions, we generated 72 phospho-signatures, out of a total of 23,040 data points. After validating the repeatability and robustness of the assay, the kinase activity signature of each breast cancer cell line was analyzed and compared to each other using unsupervised hierarchical clustering. The phospho-sensing assay revealed the heterogeneity of kinase activity networks among breast cancer cells. These data also established that phospho-signaling cascades related to AKT, ERK, and SRC kinases were differentially altered in TNBC and non-TNBC cell lines. Conclusions: We successfully identified unique phospho-circuits of TNBC and non-TNBC cell lines. Our goal is now to test whether specific kinase inhibitors can efficiently kill or prevent the growth of TNBC cell lines in culture and animal models. We will expand our approach into a high-content, functional kinome-screening platform to characterize the phospho-fingerprint of breast cancer cells and tissues, and explore the druggable, kinase-dependent mechanisms critical to triple-negative breast tumors. Citation Format: Bo Pan, Miki Mori, Pei Rong Evelyn Lee, Marij Hartog, Qiang Sun, Laura van 't Veer, Jean-Philippe Coppe. Functional mapping of the oncogenic kinome activity of triple-negative breast cancer cells [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-05-09.