Ceramic-on-Ceramic Total Hip Arthroplasty Using a Double Tapered, Proximally Coated Stem: 15 to 24-year Clinical and Radiologic Follow-Up.

BACKGROUND: Total hip arthroplasty implant choice profoundly affects survivorship, complications, and failure modes. This study evaluates the long-term (average 18 year) outcomes of ceramic-on-ceramic hip arthroplasty using uncemented shells and stems. Despite an impressive 20-year cumulative percent revision of 5.9%, the hydroxyapatite proximally coated femoral components evaluated in this study have seen declining use since 2003. METHODS: A review of 349 consecutive total hip arthroplasties from 1999 to 2007 was matched to 272 cases with registry data. A survivorship analysis included 274 hips (Group A) after excluding patients lost to follow-up and navigated cases. Group B comprised 135 patients who had complete datasets spanning a minimum of 15 years. RESULTS: Kaplan-Meier analysis identified a 95.6% survivorship plateau at 16 to 24 years, with no significant impact from age, sex, component size, or original pathology. In Group B, EuroQol-5 Dimensions-5 Levels (EQ5D5L) scores indicated favorable outcomes in mobility, self-care, activities, pain/discomfort, and anxiety/depression, with an EQ5D visual analog score mean of 79.24. Functional scores, including the Harris Hip Score, Oxford Hip Score, and Forgotten Joint Score, showed positive outcomes. Radiologic assessments revealed no osteolysis or loose components, with a mean Engh score of 21.69. Dorr classification identified bone quality variations. Better Engh scores corresponded to higher levels of patient satisfaction. Age at surgery was correlated with better functional scores, while sex influenced various outcomes. CONCLUSIONS: This comprehensive study, spanning an average of 18.23 years, combined multiple patient-reported outcome measures with extensive clinical and radiologic follow-up. It reported a notably high survivorship rate for this implant combination but highlighted the declining use of the hydroxyapatite proximally coated femoral stem used in this study, potentially facing withdrawal risks in Australia. LEVEL OF EVIDENCE: Therapeutic Level IV.

School-age outcomes among IVF-conceived children: A population-wide cohort study.

BACKGROUND: In vitro fertilisation (IVF) is a common mode of conception. Understanding the long-term implications for these children is important. The aim of this study was to determine the causal effect of IVF conception on primary school-age childhood developmental and educational outcomes, compared with outcomes following spontaneous conception. METHODS AND FINDINGS: Causal inference methods were used to analyse observational data in a way that emulates a target randomised clinical trial. The study cohort comprised statewide linked maternal and childhood administrative data. Participants included singleton infants conceived spontaneously or via IVF, born in Victoria, Australia between 2005 and 2014 and who had school-age developmental and educational outcomes assessed. The exposure examined was conception via IVF, with spontaneous conception the control condition. Two outcome measures were assessed. The first, childhood developmental vulnerability at school entry (age 4 to 6), was assessed using the Australian Early Developmental Census (AEDC) (n = 173,200) and defined as scoring <10th percentile in ≥2/5 developmental domains (physical health and wellbeing, social competence, emotional maturity, language and cognitive skills, communication skills, and general knowledge). The second, educational outcome at age 7 to 9, was assessed using National Assessment Program-Literacy and Numeracy (NAPLAN) data (n = 342,311) and defined by overall z-score across 5 domains (grammar and punctuation, reading, writing, spelling, and numeracy). Inverse probability weighting with regression adjustment was used to estimate population average causal effects. The study included 412,713 children across the 2 outcome cohorts. Linked records were available for 4,697 IVF-conceived cases and 168,503 controls for AEDC, and 8,976 cases and 333,335 controls for NAPLAN. There was no causal effect of IVF-conception on the risk of developmental vulnerability at school-entry compared with spontaneously conceived children (AEDC metrics), with an adjusted risk difference of -0.3% (95% CI -3.7% to 3.1%) and an adjusted risk ratio of 0.97 (95% CI 0.77 to 1.25). At age 7 to 9 years, there was no causal effect of IVF-conception on the NAPLAN overall z-score, with an adjusted mean difference of 0.030 (95% CI -0.018 to 0.077) between IVF- and spontaneously conceived children. The models were adjusted for sex at birth, age at assessment, language background other than English, socioeconomic status, maternal age, parity, and education. Study limitations included the use of observational data, the potential for unmeasured confounding, the presence of missing data, and the necessary restriction of the cohort to children attending school. CONCLUSIONS: In this analysis, under the given causal assumptions, the school-age developmental and educational outcomes for children conceived by IVF are equivalent to those of spontaneously conceived children. These findings provide important reassurance for current and prospective parents and for clinicians.

Defining poor growth and stillbirth risk in pregnancy for infants of mothers with overweight and obesity.

BACKGROUND: Mothers who are obese carry heavier fetuses and have lower rates of small for gestational age (<10th birthweight centile) infants. However, their infants may be growth-restricted (with an increased risk of stillbirth) at a higher birthweight centile compared with infants from healthy-weight women. OBJECTIVE: This study aimed to quantify the birthweight centile at which the risk of stillbirth in infants born to obese women equaled that of <10th-centile infants born to healthy-weight women, and clarify the relationship between maternal body mass index, infant size, and stillbirth. STUDY DESIGN: We conducted a retrospective cohort study on all infants born in Victoria, Australia, from 2009 to 2019 (754,946 cases for analysis). We applied uncustomized birthweight centiles to all infants, and stratified the maternal cohort by body mass index (<20 kg/m2, 20-25 kg/m2, 25-30 kg/m2, 30-35 kg/m2, 35-40 kg/m2, ≥40 kg/m2). For each body mass index category, we assessed proportions of infants born <10th centile and <3rd centile, stillbirth rates among infants of all sizes, and small for gestational age infants. We calculated the stillbirth rate (per 1000) and relative risk (risk of stillbirth if born <10th centile vs >10th centile) for healthy-weight women (body mass index, 20-25 kg/m2). We then determined the birthweight centile for infants born to mothers within other body mass index categories that equaled that rate or risk. RESULTS: Stillbirth rates increased with increasing maternal body mass index. Infants classified as small for gestational age (<10th centile) from mothers with high body mass index had a higher risk of stillbirth (relative risk, 3.15; 95% confidence interval, 2.22-4.47; for mothers with body mass index ≥40 kg/m2 vs healthy-weight mothers [body mass index, 20-25 kg/m2]). The stillbirth rate (stillborn infants per 1000 births) among <10th-centile infants born to healthy-weight mothers was 7.5 per 1000. The same stillbirth rate was observed at higher birthweight centiles for infants of women with higher body mass index (<18th centile for those with a body mass index of 25-30 kg/m2, <25th centile for body mass index of 30-35 kg/m2, <31st centile for body mass index of 35-40 kg/m2, <41st centile for body mass index of ≥40 kg/m2). The relative risk of stillbirth among small for gestational age infants of healthy-weight mothers was 5.46 (95% confidence interval, 4.65-6.40). The birthweight centile with a comparable relative risk of stillbirth increased with increasing body mass index (<16th centile for women with body mass index of 25-30 kg/m2, <19th centile for body mass index of 30-35 kg/m2, <28th centile for body mass index of 35-40 kg/m2, <30th centile for body mass index ≥40 kg/m2). CONCLUSION: Obesity affects the relationship between infant size and perinatal mortality. The stillbirth risk observed in <10th-centile infants from healthy-weight mothers occurs at higher birthweight centiles with overweight or obese mothers. Clinicians should be aware that the same infant risk exists at a higher birthweight centile for women with higher body mass index.

Incidence and risk factors for secondary failure after acute obstetric sphincter injury repair - an audit of 239 women.

AIM: The rate of secondary failure after obstetric sphincter injury repair is unknown, with the literature reporting rates ranging from 0.1% to 53%. We aimed to perform an audit to identify the rate and risk factors for failure of sphincter repair in a cohort of postpartum women using endoanal ultrasound (EAUS) and manometry, assessing the risk factors and impact of these events. METHOD: Prospective data were collected within a 2 year period from patients who attended the perineal clinic at Eastern Health. Variables of primary repair and presence of postpartum complications were recorded and subsequently analysed. RESULTS: Of 239 patients with obstetric anal sphincter injury (OASI) included, 100 (41.8%) had EUAS evidence of sphincter defects. Only 20% with secondary repair failure were symptomatic with faecal or flatal incontinence at a mean follow-up of 23.4 months postpartum. Patients with secondary repair failure had lower anal resting (p = 0.006) and maximum squeeze pressures compared with patients with intact repairs (p < 0.001). In terms of variables that were investigated, namely location, operator hierarchy, type of repair and material used, none had a statistically significant correlation with secondary repair failure of OASI. Postpartum complications had an overall incidence of 12.7%, and those with any complication were found to have an increased rate of secondary failure of repair (p = 0.157). CONCLUSION: Using EAUS to confirm secondary failure of repair, incidence was 41.4% in this cohort. There were no identifiable modifiable variables that reduced the risk of secondary failure of repair. Further prospective research with increased sample size and longer follow-up periods is required to assess the validity of the findings.

Defining Reference Values for the Normal Adult Lisfranc Joint Using Weightbearing Computed Tomography.

The uninjured contralateral feet of consecutive patients undergoing cone-beam weightbearing computed tomography for acute Lisfranc injury between July 2017 and October 2019 were retrospectively analyzed. Of these, any cases with history or radiological evidence of trauma to the Lisfranc interval were excluded. The area of the non-weightbearing (NWBA) and weightbearing (WBA) Lisfranc joint was calculated (in mm2) using a novel technique. Area difference (AD) was calculated as WBA-NWBA. Area ratio (AR) was calculated as WBA/NWBA. A subset of cases was double-measured by 2 technologists to evaluate inter- and intraobserver variability. A total of 91 patients aged 15 to 74 years were included in the study. The measurement technique was reproducible with excellent intraobserver correlation (intraclass correlation coefficient [ICC]: 0.998, 95% confidence interval [CI]: 0.996-0.999) and high interobserver correlation (ICC: 0.964, CI: 0.939-0.979). The median NWBA was 83 (range 52-171) and median WBA was 86 (range 52-171). Median AD was 1 mm2 (range -3 to 10) and median AR was 1.01 (range 0.96-1.11). No significant difference was identified in AD or AR when adjusted for age, gender, patient-weight or weight put through the foot. Both AD and AR distributions were highly skewed toward 0 and 1, respectively. Based on 95% CI, normal reference range for AD is -1 to 7 mm2 and for AR is 0.98 to 1.09. Absolute area of the Lisfranc joint is highly variable between individuals. The Lisfranc joint is rigid with little to no physiologic widening in most subjects. The normal upper limit of widening of the Lisfranc area on weightbearing was 9%. Differences in age, sex, patient-weight or weight put through the foot were not significantly associated with the extent of joint widening.

Risk of obstetric anal sphincter injury among women who birth vaginally after a prior caesarean section: A state-wide cohort study.

OBJECTIVE: Vaginal birth after caesarean (VBAC) has been suggested to be associated with an increased risk of obstetric anal sphincter injury (compared with primiparous women who birth vaginally). However, prior studies have been small or have used outdated methodology. We set out to validate whether the risk of obstetric anal sphincter injury among women having their first VBAC is greater than that among primiparous women having a vaginal birth. DESIGN: State-wide retrospective cohort study. SETTING: Victoria, Australia. POPULATION: All births (455 000) between 2009 and 2014. METHODS: The risk of severe perineal injury between the first vaginal birth and the first VBAC was compared, after adjustment for potential confounding variables. Covariates were examined using logistic regression for categorical data and the Wilcoxon rank-sum test for continuous data. Missing data were handled using multiple imputation; the analysis was performed using regression adjustment and stata 16 multiple imputation and suite of effects commands. RESULTS: Women having a VBAC (n = 5429) were significantly more likely than primiparous women (n = 123 353) to sustain a third- or fourth-degree tear during vaginal birth (7.1 versus 5.7%, p < 0.001). After adjustment for mode of birth, body mass index, maternal age, infant birthweight, episiotomy and epidural, there was a 21% increased risk of severe perineal injury (RR 1.21, 95% CI 1.07-1.38). CONCLUSIONS: Women having their first VBAC have a significantly increased risk of sustaining a third- or fourth-degree tear, compared with primiparous women having a vaginal birth. Patient counselling and professional guidelines should reflect this increased risk.

Efficacy of dexamethasone in the management of malignant small bowel obstruction in advanced epithelial ovarian cancer.

INTRODUCTION: Malignant small bowel obstruction (MSBO) occurs in up to 50% of women with advanced epithelial ovarian cancer (EOC) causing symptom burden and distress to women and their families, particularly in the terminal stages of the disease. Corticosteroids are used to promote symptom resolution in malignant small bowel obstruction (MSBO) related to EOC, with little published data on their efficacy, optimal dosing and duration of treatment. OBJECTIVE: To evaluate the efficacy of dexamethasone in achieving symptom control in women with advanced EOC presenting with MSBO, assess dexamethasone dosing and efficacy over subsequent presentations, and examine differences in dexamethasone responsiveness between platinum-resistant and platinum-sensitive patient. METHODS: This is a retrospective cohort study of women presenting with MSBO due to advanced EOC over a 12-year period from January 2005 to December 2016 in a single tertiary hospital. RESULTS: Ninety-one women with MSBO were administered dexamethasone over 154 admissions with 89% of women initially achieving partial or complete symptom control. Dexamethasone responsiveness did not change with recurrent admissions, and platinum responsive patients were more likely to respond to dexamethasone than platinum-resistant patients (OR 3.6 [95%CI 1.1 to 12.2, p = 0.04]). A total of 15.6% of patients required additional measures to control symptoms of MSBO, and 44.8% had adequate symptom resolution to allow them to remain on or commence further treatment for EOC. CONCLUSION: Dexamethasone therapy is a useful adjunctive therapy in the management of symptoms associated with MSBO in women with EOC.

Hysteroscopic management of retained products of conception: A systematic review.

BACKGROUND: The management of retained products of conception (RPOC) is not well standardised due to a lack of evidence-based guidelines. Hysteroscopic resection has been proven to be safe and is hypothesised to have lower risk than dilation and curettage, but data comparing the two directly are limited. AIM: The aim of this study is to evaluate the outcomes for hysteroscopic resection for the management of RPOC in comparison to current standard management techniques. METHODS: A literature search was conducted in September 2019 using MEDLINE, Scopus, The Cochrane Library and Web of Science. The key search terms were 'hysteroscopy'/'hysteroscopic resection' and 'retained products of conception'/'RPOC'. Both prospective and retrospective studies were included. A total of 19 studies were included (n = 2314). Due to a critical risk of bias in all studies with a comparison arm, a meta-analysis was not performed. Meta-analysis techniques were still used to provide summary estimates for primary and secondary outcomes, including conception rate, time to conception, live birth rate, intrauterine adhesions (IUAs), surgical complications and future pregnancy complications. RESULTS: The overall conception rate for hysteroscopic resection was 81.1% (live birth rate 87.3%) compared to 65.4% for non-hysteroscopic management (live birth rate 93.8%). After hysteroscopic resection the overall complication rate was 1.9% and the IUA rate was 6.8%. CONCLUSIONS: Due to the poor quality and overall scarcity of comparative data, the question whether hysteroscopic resection is superior to traditional curettage for the management of RPOC remains unanswered. This review provides summary data, which will enable the design of adequately powered future studies.

We live in a virtual world: Training the trainee using an integrated visual reality simulator curriculum.

BACKGROUND: Gynaecology trainees struggle to obtain adequate procedural experience. Training programs integrating virtual reality simulators (VRS) have been suggested as a solution. AIMS: The study aimed to assess if a VRS training program (LapSim® , Surgical Sciences, Göteborg, 2017) improved live operating performance at six months for novice and experienced trainees. Additional outcomes included the association between LapSim® logged time and live operating performance at six months, LapSim® scores and live operating performance at zero and sixmonths and the difference in benefit for novice and experienced gynaecology trainees. METHODS: A prospective intervention study was conducted. Novice and experienced trainees were enrolled, and comparisons made at zero- and six-month time points. The intervention groups were provided with a laparoscopic gynaecology curriculum incorporating VRS. Controls underwent routine training only. Assessment of live operating performance was conducted after six months training. RESULTS: Thirty-five trainees participated, and 25 had access to the VRS curriculum (17 novice and eight experienced trainees). Access to the VRS curriculum and time spent training on the LapSim® made no difference to live operating ability for either intervention group (P > 0.05). The median (interquartile range) hours of VRS usage were 7.9 (4.5-10.8) and 6.0 (4.0-6.8) for novice and experienced trainees respectively. The intervention group provided positive feedback on the utility of VRS in their laparoscopic skill development. CONCLUSION: Optimal utilisation of VRS in Australian training paradigms remains incompletely understood. Further research is required to establish the most effective integration of VRS into training models to ensure uptake and transferability to the operating theatre.

Maternal lithium use and the risk of adverse pregnancy and neonatal outcomes: a Swedish population-based cohort study.

BACKGROUND: Lithium is prescribed during pregnancy, but there is limited information about pregnancy and neonatal outcomes following in utero exposure. Thus, this study aimed to investigate the associations between lithium use and adverse pregnancy and neonatal outcomes. METHODS: This population-based cohort study examined associations between maternal lithium use and major adverse pregnancy and neonatal outcomes via inverse probability weighted propensity score regression models. RESULTS: Of 854,017 women included in this study, 434 (0.05%) used lithium during pregnancy. Among pre-specified primary outcomes, lithium use during pregnancy was associated with an increased risk of spontaneous preterm birth (8.7% vs 3.0%; adjusted relative risk [aRR] 2.64 95% CI 1.82, 3.82) and birth of a large for gestational age infant (9.0% vs 3.5%; aRR 2.64 95% CI 1.91, 3.66), but not preeclampsia nor birth of a small for gestational age infant. Among secondary outcomes, lithium use was associated with an increased risk of cardiac malformations (2.1% vs 0.8%; aRR 3.17 95% CI 1.64, 6.13). In an analysis restricted to pregnant women with a diagnosed psychiatric illness (n=9552), associations remained between lithium and spontaneous preterm birth, birth of a large for gestational age infant, and cardiovascular malformations; and a positive association with neonatal hypoglycaemia was also found. These associations were also apparent in a further analysis comparing women who continued lithium treatment during pregnancy to those who discontinued prior to pregnancy. CONCLUSIONS: Lithium use during pregnancy is associated with an increased risk of spontaneous preterm birth and other adverse neonatal outcomes. These potential risks must be balanced against the important benefit of treatment and should be used to guide shared decision-making.

Risk of major labour-related complications for pregnancies progressing to 42 weeks or beyond.

BACKGROUND: Post-term gestation beyond 41+6 completed weeks of gestation is known to be associated with a sharp increase in the risk of stillbirth and perinatal mortality. However, the risk of common adverse outcomes related to labour, such as shoulder dystocia and post-partum haemorrhage for those delivering at this advanced gestation, remains poorly characterised. The objective of this study was to examine the risk of adverse, labour-related outcomes for women progressing to 42 weeks gestation or beyond, compared with those giving birth at 39 completed weeks. METHODS: We performed a state-wide cohort study using routinely collected perinatal data in Australia. Comparing the two gestation cohorts, we examined the adjusted relative risk of clinically significant labour-related adverse outcomes, including macrosomia (≥ 4500 at birth), post-partum haemorrhage (≥1000 ml), shoulder dystocia, 3rd or 4th degree perineal tear and unplanned caesarean section. Parity, maternal age and mode of birth were adjusted for using logistic regression. RESULTS: The study cohort included 91,314 women who birthed at 39 completed weeks and 4317 at ≥42 completed weeks. Compared to 39 weeks gestation, those giving birth ≥42 weeks gestation had an adjusted relative risk (aRR) of 1.85 (95% CI 1.55-2.20) for post-partum haemorrhage following vaginal birth, 2.29 (95% CI 1.89-2.78) following instrumental birth and 1.44 (95% CI 1.17-1.78) following emergency caesarean section; 1.43 (95% CI 1.16-1.77) for shoulder dystocia (for non-macrosomic babies); and 1.22 (95% CI 1.03-1.45) for 3rd or 4th degree perineal tear (all women). The adjusted relative risk of giving birth to a macrosomic baby was 10.19 (95% CI 8.26-12.57) among nulliparous women and 4.71 (95% CI 3.90-5.68) among multiparous women. The risk of unplanned caesarean section was 1.96 (95% CI 1.86-2.06) following any labour and 1.47 (95% CI 1.38-1.56) following induction of labour. CONCLUSIONS: Giving birth at ≥42 weeks gestation may be an under-recognised risk factor for several important, labour-related adverse outcomes. Clinicians should be aware that labour at this advanced gestation incurs a higher risk of adverse outcomes. In addition to known perinatal risks, the risk of obstetric complications should be considered in the counselling of women labouring at post-term gestation.

Botulinum toxin A (Botox) injection into muscles of pelvic floor as a treatment for persistent pelvic pain secondary to pelvic floor muscular spasm: A pilot study.

BACKGROUND: Persistent pelvic pain (PPP) remains an important cause of morbidity. Pelvic floor muscle spasm is an important contributor to PPP. AIMS: The study's primary aim was to assess if botulinum toxin (BoNT) injection to pelvic floor muscles altered pain scores or quality of life (QoL) at six, 12 and 26 weeks. Secondary aims included investigating the impact of BoNT on opiate usage, examining the role of pain catastrophising, and assessing for complications. MATERIALS AND METHODS: A single-centre prospective cohort study enrolled 21 patients with PPP who had failed physiotherapy techniques. Each participant underwent BoNT injection to muscles of the pelvic floor and pudendal nerve block. Questionnaires and digital vaginal examinations were conducted at baseline, six, 12 and 26 weeks. Pain score quantification used visual analogue scales (VAS) and numerical rating scales (NRS). Other outcome assessments included The World Health Organization Quality of Life instrument (WHOQoL-BREF), Pain Catastrophising Scale (PCS), and modified Australian Pelvic Floor Questionnaire (APFQ). ACTRN12620000067976. RESULTS: Following BoNT injection, median VAS scores decreased for all domains at six and 12 weeks, with VAS for dyspareunia significant at six weeks (P = 0.026). Scores returned to baseline by 26 weeks. Opiate usage was significantly less following BoNT injection, with a percentage reduction of 23.8% (95% CI -48.3 to 0.7, P = 0.06). Sexual function improved significantly (P < 0.01), and at six months, four previously apareunic participants reported successful penetrative vaginal intercourse. Health-related QoL and PCS demonstrated sustained improvement (P = 0.02-0.05). NRS for muscle tenderness decreased for all assessed muscle groups (P < 0.001). CONCLUSIONS: BoNT requires further assessment as a treatment modality for select women with PPP.

Possible high-grade squamous intraepithelial lesion (pHSIL) in the new cervical screening paradigm: The outcomes and the role of clinicopathological review.

BACKGROUND: A renewed National Cervical Screening Program (NCSP) was introduced in Australia in December 2017. Under the renewed NCSP, there are limited data to guide the management of discordant colposcopy and biopsy results after a liquid-based cytology (LBC) finding of 'possible high-grade squamous intraepithelial lesion' (pHSIL). AIMS: This study aims to determine the proportion of women referred with pHSIL who are found to have HSIL, identify influencing factors of women most at risk, and examine the role that cytopathology review plays in management decisions. MATERIALS AND METHODS: Two-hundred and thirty-two women presenting to a tertiary women's hospital in Australia with pHSIL since December 2017 were identified. Women with HSIL following colposcopy directed biopsy were referred for treatment. When HSIL was not identified, these patients were referred for multidisciplinary clinicopathological review. Pathological outcomes and treatment recommendations are included. MAIN OUTCOME MEASURES: The primary outcome of the study was histological confirmation of HSIL. RESULTS: Primary outcome data were available for 182 women (78.5%); 62 (34.1%) had HSIL on histology, three (1.7%) had adenocarcinoma in situ (AIS) and one (1%) had cervical squamous cell carcinoma (SCC). There was no association between age and the presence of HSIL. The presence of human papillomavirus 16 and/or 18 increased the likelihood of HSIL on histology (relative risk 1.9; 95% CI 1.27-2.80, P = 0.002). Fifty-nine (25.4%) women were referred for observation who had low-grade squamous intraepithelial lesion/no dysplasia. CONCLUSIONS: Clinicopathological review optimises management and triage of patients with pHSIL on referral cytology. Understanding outcomes in these patients informs counselling and management.

Reduced growth velocity from the mid-trimester is associated with placental insufficiency in fetuses born at a normal birthweight.

BACKGROUND: Fetal growth restriction (FGR) due to placental insufficiency is a major risk factor for stillbirth. While small-for-gestational-age (SGA; weight < 10th centile) is a commonly used proxy for FGR, detection of FGR among appropriate-for-gestational-age (AGA; weight ≥ 10th centile) fetuses remains an unmet need in clinical care. We aimed to determine whether reduced antenatal growth velocity from the time of routine mid-trimester ultrasound is associated with antenatal, intrapartum and postnatal indicators of placental insufficiency among term AGA infants. METHODS: Three hundred and five women had biometry measurements recorded from their routine mid-trimester (20-week) ultrasound, at 28 and 36 weeks' gestation, and delivered an AGA infant. Mid-trimester, 28- and 36-week estimated fetal weight (EFW) and abdominal circumference (AC) centiles were calculated. The EFW and AC growth velocities between 20 and 28 weeks, and 20-36 weeks, were examined as predictors of four clinical indicators of placental insufficiency: (i) low 36-week cerebroplacental ratio (CPR; CPR < 5th centile reflects cerebral redistribution-a fetal adaptation to hypoxia), (ii) neonatal acidosis (umbilical artery pH < 7.15) after the hypoxic challenge of labour, (iii) low neonatal body fat percentage (BF%) reflecting reduced nutritional reserve and (iv) placental weight < 10th centile. RESULTS: Declining 20-36-week fetal growth velocity was associated with all indicators of placental insufficiency. Each one centile reduction in EFW between 20 and 36 weeks increased the odds of cerebral redistribution by 2.5% (odds ratio (OR) = 1.025, P = 0.001), the odds of neonatal acidosis by 2.7% (OR = 1.027, P = 0.002) and the odds of a < 10th centile placenta by 3.0% (OR = 1.030, P < 0.0001). Each one centile reduction in AC between 20 and 36 weeks increased the odds of neonatal acidosis by 3.1% (OR = 1.031, P = 0.0005), the odds of low neonatal BF% by 2.8% (OR = 1.028, P = 0.04) and the odds of placenta < 10th centile by 2.1% (OR = 1.021, P = 0.0004). Falls in EFW or AC of > 30 centiles between 20 and 36 weeks were associated with two-threefold increased relative risks of these indicators of placental insufficiency, while low 20-28-week growth velocities were not. CONCLUSIONS: Reduced growth velocity between 20 and 36 weeks among AGA fetuses is associated with antenatal, intrapartum and postnatal indicators of placental insufficiency. These fetuses potentially represent an important, under-recognised cohort at increased risk of stillbirth. Encouragingly, this novel fetal assessment would require only one additional ultrasound to current routine care, and adds to the potential benefits of routine 36-week ultrasound.

Circulating mRNAs are differentially expressed in pregnancies with severe placental insufficiency and at high risk of stillbirth.

BACKGROUND: Fetuses affected by placental insufficiency do not receive adequate nutrients and oxygenation, become growth restricted and acidemic, and can demise. Preterm fetal growth restriction is a severe form of placental insufficiency with a high risk of stillbirth. We set out to identify maternal circulating mRNA transcripts that are differentially expressed in preterm pregnancies complicated by very severe placental insufficiency, in utero fetal acidemia, and are at very high risk of stillbirth. METHODS: We performed a cohort study across six hospitals in Australia and New Zealand, prospectively collecting blood from 128 pregnancies complicated by preterm fetal growth restriction (delivery < 34 weeks' gestation) and 42 controls. RNA-sequencing was done on all samples to discover circulating mRNAs associated with preterm fetal growth restriction and fetal acidemia in utero. We used RT-PCR to validate the associations between five lead candidate biomarkers of placental insufficiency in an independent cohort from Europe (46 with preterm fetal growth restriction) and in a third cohort of pregnancies ending in stillbirth. RESULTS: In the Australia and New Zealand cohort, we identified five mRNAs that were highly differentially expressed among pregnancies with preterm fetal growth restriction: NR4A2, EMP1, PGM5, SKIL, and UGT2B1. Combining three yielded an area under the receiver operative curve (AUC) of 0.95. Circulating NR4A2 and RCBTB2 in the maternal blood were dysregulated in the presence of fetal acidemia in utero. We validated the association between preterm fetal growth restriction and circulating EMP1, NR4A2, and PGM5 mRNA in a cohort from Europe. Combining EMP1 and PGM5 identified fetal growth restriction with an AUC of 0.92. Several of these genes were differentially expressed in the presence of ultrasound parameters that reflect placental insufficiency. Circulating NR4A2, EMP1, and RCBTB2 mRNA were differentially regulated in another cohort destined for stillbirth, compared to ongoing pregnancies. EMP1 mRNA appeared to have the most consistent association with placental insufficiency in all cohorts. CONCLUSIONS: Measuring circulating mRNA offers potential as a test to identify pregnancies with severe placental insufficiency and at very high risk of stillbirth. Circulating mRNA EMP1 may be promising as a biomarker of severe placental insufficiency.

Identification of the optimal growth charts for use in a preterm population: An Australian state-wide retrospective cohort study.

BACKGROUND: Preterm infants are a group at high risk of having experienced placental insufficiency. It is unclear which growth charts perform best in identifying infants at increased risk of stillbirth and other adverse perinatal outcomes. We compared 2 birthweight charts (population centiles and INTERGROWTH-21st birthweight centiles) and 3 fetal growth charts (INTERGROWTH-21st fetal growth charts, World Health Organization fetal growth charts, and Gestation Related Optimal Weight [GROW] customised growth charts) to identify which chart performed best in identifying infants at increased risk of adverse perinatal outcome in a preterm population. METHODS AND FINDINGS: We conducted a retrospective cohort study of all preterm infants born at 24.0 to 36.9 weeks gestation in Victoria, Australia, from 2005 to 2015 (28,968 records available for analysis). All above growth charts were applied to the population. Proportions classified as <5th centile and <10th centile by each chart were compared, as were proportions of stillborn infants considered small for gestational age (SGA, <10th centile) by each chart. We then compared the relative performance of non-overlapping SGA cohorts by each chart to our low-risk reference population (infants born appropriate size for gestational age [>10th and <90th centile] by all intrauterine charts [AGAall]) for the following perinatal outcomes: stillbirth, perinatal mortality (stillbirth or neonatal death), Apgar <4 or <7 at 5 minutes, neonatal intensive care unit admissions, suspicion of poor fetal growth leading to expedited delivery, and cesarean section. All intrauterine charts classified a greater proportion of infants as <5th or <10th centile than birthweight charts. The magnitude of the difference between birthweight and fetal charts was greater at more preterm gestations. Of the fetal charts, GROW customised charts classified the greatest number of infants as SGA (22.3%) and the greatest number of stillborn infants as SGA (57%). INTERGROWTH classified almost no additional infants as SGA that were not already considered SGA on GROW or WHO charts; however, those infants classified as SGA by INTERGROWTH had the greatest risk of both stillbirth and total perinatal mortality. GROW customised charts classified a larger proportion of infants as SGA, and these infants were still at increased risk of mortality and adverse perinatal outcomes compared to the AGAall population. Consistent with similar studies in this field, our study was limited in comparing growth charts by the degree of overlap, with many infants classified as SGA by multiple charts. We attempted to overcome this by examining and comparing sub-populations classified as SGA by only 1 growth chart. CONCLUSIONS: In this study, fetal charts classified greater proportions of preterm and stillborn infants as SGA, which more accurately reflected true fetal growth restriction. Of the intrauterine charts, INTERGROWTH classified the smallest number of preterm infants as SGA, although it identified a particularly high-risk cohort, and GROW customised charts classified the greatest number at increased risk of perinatal mortality.

Characteristics of patients with cancer who die by suicide: Coronial case series in an Australian state.

OBJECTIVE: Suicide rates are elevated in epidemiological studies, but extrapolating population level data to the individual patient cancer is difficult, and there is a dearth of studies examining how suicidality might be linked to the cancer experience. We examine the cancer-suicide correlates to explore clinical implications and future research directions. METHOD: We used a novel database to examine all suicide deaths reported to the Coroners Court of Victoria between 2009 and 2013 in individuals with active, diagnosed cancer. Cases were classified in relation to whether cancer had been a probable, possible, or unlikely influence on suicidal ideation. Sociodemographic, clinical, health service contacts, and suicide method data were analysed to describe the characteristics of individuals with cancer at the time of their suicide. RESULTS: There were 2870 suicide deaths, and 118 cases met inclusion criteria. Clinically distinct patient subgroups emerged through a contrast between those cases where the data suggested a correlate between cancer and suicide, and those where the data did not. The former group had many more cancer-related health problems than the latter group, who had a higher burden of psychiatric illness that predated their cancer diagnosis. The intent to suicide was known to most clinicians. CONCLUSIONS: All clinicians working with cancer patients should be prepared to explore suicidal ideation. Understanding how the patient conceptualises suicidality with respect to cancer experience and mental health may be of central importance in determining whether mental health care is best provided as part of cancer care, or through a separate mental health service.

Timing of palliative care referral and aggressive cancer care toward the end-of-life in pancreatic cancer: a retrospective, single-center observational study.

BACKGROUND: Pancreatic cancer is noted for its late presentation at diagnosis, limited prognosis and physical and psychosocial symptom burden. This study examined associations between timing of palliative care referral (PCR) and aggressive cancer care received by pancreatic cancer patients in the last 30 days of life through a single health service. METHOD: A retrospective cohort analysis of end-of-life (EOL) care outcomes of patients with pancreatic cancer who died between 2012 and 2016. Key indicators of aggressive cancer care in the last 30 days of life used were: ≥1 emergency department (ED) presentations, acute inpatient/intensive care unit (ICU) admission, and chemotherapy use. We examined time from PCR to death and place of death. Early and late PCR were defined as > 90 and ≤ 90 days before death respectively. RESULTS: Out of the 278 eligible deaths, 187 (67.3%) were categorized as receiving a late PCR and 91 (32.7%) an early PCR. The median time between referral and death was 48 days. Compared to those receiving early PCR, those with late PCR had: 18.1% (95% CI 6.8-29.4%) more ED presentations; 12.5% (95% CI 1.7-24.8%) more acute hospital admissions; with no differences in ICU admissions. Pain and complications of cancer accounted for the majority of overall ED presentations. Of the 166 patients who received chemotherapy within 30 days of death, 23 (24.5%) had a late PCR and 12 (16.7%) an early PCR, with no association of PCR status either unadjusted or adjusted for age or gender. The majority of patients (55.8%) died at the inpatient palliative care unit. CONCLUSION: Our findings reaffirm the benefits of early PCR for pancreatic cancer patients to avoid inappropriate care toward the EOL. We suggest that in modern cancer care, there can sometimes be a need to reconsider the use of the term 'aggressive cancer care' at the EOL when the care is appropriately based on an individual patient's presenting physical and psychosocial needs. Pancreatic cancer patients warrant early PCR but the debate must thus continue as to how we best achieve and benchmark outcomes that are compatible with patient and family needs and healthcare priorities.

Estimating success of vaginal birth after caesarean section in a regional Australian population: Validation of a prediction model.

BACKGROUND: Following a primary caesarean section (CS), women must decide between attempted vaginal birth after caesarean (VBAC) and elective repeat caesarean section (ERCS) in subsequent pregnancies. Both options carry potential morbidity and mortality for mother and child, with the most feared being uterine rupture and its consequences. In attempts to reduce morbidity, several predictive nomograms have been developed to assist in delivery mode decisions. AIM: To assess the validity of the predictive nomogram developed by Grobman et al. in our regional Australian population. MATERIALS AND METHODS: In our retrospective analysis, patients at term, with one previous CS who had a trial of labour were assigned a 'Grobman score' based on antenatal details. Outcomes were noted and patient groups analysed according to percentage deciles of estimated VBAC success, compared with actual VBAC success rates. RESULTS: A total of 395 women underwent trial of labour after a single prior CS, with a VBAC success rate of 83%. The Grobman model displayed adequate calibration and the re-calibrated model good calibration with the slope coefficient of 0.87 (95% CI 0.54-1.19) and intercept 0.19 (95% CI -0.34-0.72). Discrimination was moderate with receiver operating characteristic area of 0.71 (95% CI 0.67-0.76). CONCLUSION: This analysis supports further validation studies in larger Australian settings, and suggests that use of the original Grobman predictive nomogram may be appropriate in Australia.

Customised growth charts in large-for-gestational-age infants and the association with emergency caesarean section rate.

BACKGROUND AND AIM: Large-for-gestational-age (LGA) infants are at increased risk of intrapartum complications. However, some infants classified as LGA may be appropriate-for-gestational-age (AGA) if adjusted for maternal stature. We determined whether customisation of birthweight centiles by maternal height, or height and weight, improves the detection of LGA infants at risk of complications. METHODS: We conducted a retrospective analysis of 38 246 term, singleton nulliparous women. We compared population birthweight centiles to those customised by height, or height and weight for complications including intrapartum caesarean section, instrumental delivery, postpartum haemorrhage, anal sphincter injury and neonatal outcomes. RESULTS: Those considered LGA when customised for height but AGA by population centiles (LGA-ht-only) were at increased risk of intrapartum emergency caesarean section compared with infants AGA on all charts (AGA-all); odds ratio (OR) 4.64, 95% CI 3.22-6.76. In contrast, infants considered LGA on population charts, but AGA when customised by height (LGA-pop-only) were not at increased risk compared to the AGA-all group (OR 1.43, 95% CI 0.70-1.88). Infants classified as LGA-ht-only compared to LGA-pop-only remained at significantly higher risk after adjustment for potential confounders (aOR 3.27; 95% CI 2.02-5.31). No difference was seen for any other outcomes. No benefit was seen with customisation by both maternal height and weight. CONCLUSION: Women with an infant classified as AGA on population centiles but LGA when customised for height are at increased risk of intrapartum caesarean section. This is a population unrecognised in current practice. Fetal growth should be customised for maternal height when making assessments regarding the LGA infant.