Implementation of sonopartogram: multicenter feasibility study.

OBJECTIVES: Well-established clinical practice to assess progress in labor involves routine abdominal palpation and vaginal examination (VE). However, VE is subjective, poorly reproducible and painful for women. In this study, our aim is to evaluate the feasibility of systematically integrating transabdominal and transperineal ultrasound assessment of fetal position, psAOP, HPD and SCD to monitor labor progress in women undergoing induction of labor (IOL). We also aim at determining if ultrasound can reduce women's pain during examinations. METHODS: Women were recruited as they presented for IOL in three maternity units. Ultrasound assessments were performed in 100 women between 37+0 and 41+6 weeks' gestation. A baseline combined transabdominal and transperineal scan was performed, including the assessment of fetal biometry, umbilical artery and middle cerebral artery Dopplers, amniotic fluid index (AFI), fetal spine and occiput positions, psAOP, HPD, SCD, and cervical length. Intrapartum scans were performed instead of VEs according to protocol. Participants were asked to indicate their level of pain by verbally giving a pain score from 0 - 10 (with 0 representing no pain) during assessment. The repeated measures data were analyzed by mixed effect models to identify the significant factors that affected the relationship between psAOP, HPD, SCD and mode of delivery. RESULTS: 223 intrapartum ultrasound scans with a median of 2 scans per participant (interquartile range (IQR) = 1 - 3), and 151 VEs were performed with a median of 1 per participant (IQR = 0 - 2). There were no adverse fetal or maternal outcomes. After excluding those with epidural anesthesia during examination, median pain score for intrapartum scan was 0 (IQR = 0 - 1) and 3 for VE (IQR = 0 - 6). Cesarean delivery and epidural anesthesia were significantly associated with slower rate of change in psAOP, HPD and SCD. Maternal height, parity and neonatal birth weight did not affect ultrasound measurements of labor progress. CONCLUSIONS: Comprehensive transabdominal and transperineal ultrasound assessment can be successfully used to assess progress in labor and can reduce the level of pain experienced during examination. Ultrasound assessment may be able to replace some transabdominal and VE examinations during labor. This article is protected by copyright. All rights reserved.

Prediction of hospital mortality among critically ill patients in a single centre in Asia: comparison of artificial neural networks and logistic regression-based model.

INTRODUCTION: This study compared the performance of the artificial neural network (ANN) model with the Acute Physiologic and Chronic Health Evaluation (APACHE) II and IV models for predicting hospital mortality among critically ill patients in Hong Kong. METHODS: This retrospective analysis included all patients admitted to the intensive care unit of Pamela Youde Nethersole Eastern Hospital from January 2010 to December 2019. The ANN model was constructed using parameters identical to the APACHE IV model. Discrimination performance was assessed using area under the receiver operating characteristic curve (AUROC); calibration performance was evaluated using the Brier score and Hosmer-Lemeshow statistic. RESULTS: In total, 14 503 patients were included, with 10% in the validation set and 90% in the ANN model development set. The ANN model (AUROC=0.88, 95% confidence interval [CI]=0.86-0.90, Brier score=0.10; P in Hosmer-Lemeshow test=0.37) outperformed the APACHE II model (AUROC=0.85, 95% CI=0.80-0.85, Brier score=0.14; P<0.001 for both comparisons of AUROCs and Brier scores) but showed performance similar to the APACHE IV model (AUROC=0.87, 95% CI=0.85-0.89, Brier score=0.11; P=0.34 for comparison of AUROCs, and P=0.05 for comparison of Brier scores). The ANN model demonstrated better calibration than the APACHE II and APACHE IV models. CONCLUSION: Our ANN model outperformed the APACHE II model but was similar to the APACHE IV model in terms of predicting hospital mortality in Hong Kong. Artificial neural networks are valuable tools that can enhance real-time prognostic prediction.

Amniotic fluid gamma-glutamyl transferase for prediction of biliary atresia in cases of non-visualisation of the fetal gallbladder: a retrospective study using a validated analytical platform and local reference range.

INTRODUCTION: The level of amniotic fluid gamma-glutamyl transferase (AFGGT) may help identify biliary atresia (BA) in cases of non-visualisation of the fetal gallbladder (NVFGB). This study aimed to validate a serum/plasma matrix-based gamma-glutamyl transferase (GGT) assay for amniotic fluid (AF) samples, establish a local gestational age-specific AFGGT reference range, and evaluate the efficacy of AFGGT for predicting fetal BA in pregnancies with NVFGB using the constructed reference range. METHODS: The analytical performance of a serum/plasma matrix-based GGT assay on AF samples was evaluated using a Cobas c502 analyser. Amniotic fluid gamma-glutamyl transferase levels in confirmed euploid singleton pregnancies (16+0 to 22+6 weeks of gestation) were determined using the same analyser to establish a local gestational age-specific reference range (the 2.5th to 97.5th percentiles). This local reference range was used to determine the positive predictive value (PPV) and negative predictive value (NPV) of AFGGT level <2.5th percentile for identifying fetal BA in euploid pregnancies with NVFGB. RESULTS: The serum/plasma matrix-based GGT assay was able to reliably and accurately determine GGT levels in AF samples. Using the constructed local gestational age-specific AFGGT reference range, the NPV and PPV of AFGGT level <2.5th percentile for predicting fetal BA in pregnancies with NVFGB were 100% and 25% (95% confidence interval=0, 53), respectively. CONCLUSION: In pregnancies with NVFGB, AFGGT level ≥2.5th percentile likely excludes fetal BA. Although AFGGT level <2.5th percentile is not diagnostic of fetal BA, fetuses with AFGGT below this level should be referred for early postnatal investigation.

Economic and environmental analysis of processing plant interventions to reduce fluid milk waste.

With the increased awareness about the economic and environmental impact of food waste, many interventions along food supply chains have been proposed to mitigate food waste. Even though interventions used to target food waste usually revolve around logistics and operations management, we highlight a unique solution to address this issue, specifically for fluid milk. We target the intrinsic quality of fluid milk by evaluating interventions that will extend the product shelf life. We used data from a previous fluid milk spoilage simulation model, collected price and product information from retail stores, conducted an expert elicitation, and used hedonic price regressions to determine the private and social gains to the dairy processing plant when implementing 5 different interventions to extend shelf life. Our data suggest that the value of each additional day of shelf life is approximately $0.03 and indicate that increasing periodic equipment cleaning is the most cost-effective strategy for processing plants to achieve fluid milk shelf-life improvements, both from a firm's economic standpoint and from an environmental standpoint. Importantly, the approaches reported here will be valuable to help individual firms to generate customized facility and firm specific assessments that identify the most appropriate strategies for extending the shelf life of different dairy products.

Long-term trends in the incidence and management of shoulder dystocia in a tertiary obstetric unit in Hong Kong.

INTRODUCTION: Because there have been changes in the management of macrosomic pregnancies and shoulder dystocia in the past decade, this study was conducted to compare the incidences of shoulder dystocia and perinatal outcomes between the periods of 2000-2009 and 2010-2019. METHODS: This retrospective study was conducted in a tertiary obstetric unit. All cases of shoulder dystocia were identified using the hospital's electronic database. The incidences, maternal and fetal characteristics, obstetric management methods, and perinatal outcomes were compared between the two study periods. RESULTS: The overall incidence of shoulder dystocia decreased from 0.23% (134/58 326) in 2000-2009 to 0.16% (108/65 683) in 2010-2019 (P=0.009), mainly because of the overall decline in the proportion of babies with macrosomia (from 3.3% to 2.3%; P<0.001). The improved success rates of the McRoberts' manoeuvre (from 31.3% to 47.2%; P=0.012) and posterior arm extraction (from 52.9% to 92.3%; P=0.042) allowed a greater proportion of affected babies to be delivered within 2 minutes (from 59.0% to 79.6%; P=0.003). These changes led to a significant reduction in the proportion of fetuses with low Apgar scores: <5 at 1 minute of life (from 13.4% to 5.6%; P=0.042) and <7 at 5 minutes of life (from 11.9% to 4.6%; P=0.045). CONCLUSION: More proactive management of macrosomic pregnancies and enhanced training in the acute management of shoulder dystocia led to significant improvements in shoulder dystocia incidence and perinatal outcomes from 2000-2009 to 2010-2019.

Lactic acid bacteria feeding reversed the malformed eye structures and ameliorated gut microbiota profiles of Drosophila melanogaster Alzheimer's disease model.

AIMS: To utilize transgenic GMR-Aß42 Drosophila melanogaster as a model to evaluate potential Alzheimer's disease (AD)-reversal effects via the administration of lactic acid bacteria (LAB) strains, and associations of LAB with changes in gut microbiota profiles. METHODS AND RESULTS: Wild-type flies (Oregon-R) were crossed with glass multimer reporter-GAL4 (GMR-GAL4) to produce GMR-OreR (Control), while UAS-Aß42 (#33769) were crossed with GMR-GAL4 to produce transgenic Drosophila line that expressed Aß42 (GMR-Aß42). Feed containing seven different LAB strains (Lactobacillus paracasei 0291, Lactobacillus helveticus 1515, Lactobacillus reuteri 30242, L. reuteri 8513d, Lactobacillus fermentum 8312, Lactobacillus casei Y, Lactobacillus sakei Probio65) were given to GMR-Aß42 respectively, while feed without LAB strains were given to control and transgenic GMR-Aß42.nf Drosophila lines. The morphology of the eyes was viewed with scanning electron microscopy (SEM). The changes in gut microbiota profiles associated with LAB were analysed using 16s high throughput sequencing. Malformation of eye structures in transgenic GMR-Aß42 Drosophila were reversed upon the administration of LAB strains, with more prevalent effects from L. sakei Probio65 and L. paracasei 0291. The GMR-Aß42.nf group showed dominance of Wolbachia in the gut, a genus that was almost absent in the normal control group (P < 0·05). The administration of L. sakei Probio65 and L. paracasei 0291 reduced the abundance of Wolbachia accompanied by increased abundance of Stenotrophomonas and Acetobacter (P < 0·05), resembling the microbial profile of the control group. CONCLUSIONS: Lactobacillus sakei Probio65 and Lactobacillus paracasei 0291 have more prominent effects in reversing malformed eye of transgenic GMR-Aß42 Drosophila, and reducing the abundance of Wolbachia accompanied by an increased abundance of Stenotrophomonas and Acetobacter. SIGNIFICANCE AND IMPACT OF THE STUDY: Potentials of LAB to prevent and/or alleviate the onset and pathogenesis of neurodegenerative diseases such as AD, supporting brain health strategies along the gut-brain axis.

Development of a Monte Carlo simulation model to predict pasteurized fluid milk spoilage due to post-pasteurization contamination with gram-negative bacteria.

Psychrotolerant gram-negative bacteria introduced as post-pasteurization contamination (PPC) are a major cause of spoilage and reduced shelf life of high-temperature, short-time pasteurized fluid milk. To provide improved tools to (1) predict pasteurized fluid milk shelf life as influenced by PPC and (2) assess the effectiveness of different potential interventions that could reduce spoilage due to PPC, we developed a Monte Carlo simulation model that predicts fluid milk spoilage due to psychrotolerant gram-negative bacteria introduced as PPC. As a first step, 17 gram-negative bacterial isolates frequently associated with fluid milk spoilage were selected and used to generate growth data in skim milk broth at 6°C. The resulting growth parameters, frequency of isolation for the 17 different isolates, and initial concentration of bacteria in milk with PPC, were used to develop a Monte Carlo model to predict bacterial number at different days of shelf life based on storage temperature of milk. This model was then validated with data from d 7 and 10 of shelf life, collected from commercial operations. The validated model predicted that the parameters (1) maximum growth rate and (2) storage temperature had the greatest influence on the percentage of containers exceeding 20,000 cfu/mL standard plate count on d 7 and 10 (i.e., spoiling due to PPC), which indicates that accurate data on maximum growth rate and storage temperature are important for accurate predictions. In addition to allowing for prediction of fluid milk shelf life, the model allows for simulation of "what-if" scenarios, which allowed us to predict the effectiveness of different interventions to reduce overall fluid milk spoilage due to PPC through a set of proof-of-concept scenario (e.g., frequency of PPC in containers reduced from 100% to 10%; limiting distribution temperature to a maximum of 6°C). Combined with other models, such as previous models on fluid milk spoilage due to psychrotolerant spore-forming bacteria, the data and tools developed here will allow for rational, digitally enabled, fluid milk shelf life prediction and quality enhancement.

Stillbirth rate in singleton pregnancies: a 20-year retrospective study from a public obstetric unit in Hong Kong.

INTRODUCTION: Although the stillbirth rate is low in Hong Kong, up to 50% of stillbirths have unclassifiable causes and up to one third of stillbirths have unexplained causes. This retrospective study investigated the underlying causes of singleton stillbirths in Hong Kong. METHODS: This study examined the prevalences and causes of stillbirths in a university tertiary obstetric unit between 2000 and 2019. Medical records were reviewed for all singleton pregnancies complicated by stillbirths. Causes of stillbirth were determined via clinical assessments and laboratory findings, then compared between 2000-09 and 2010-19. RESULTS: Overall perinatal mortality significantly decreased by 16.7%, from 5.52/1000 in 2000-09 to 4.59/1000 in 2010-19; the singleton stillbirth rate slightly decreased (from 3.27/1000 to 2.91/1000). These changes were related to early prenatal diagnostic improvements concerning congenital malformations and genetic disorders. Pre-eclampsia prevalence among singleton pregnancies increased from 1.5% to 1.7% because of increasing maternal age; the stillbirth rate among patients with pre-eclampsia decreased from 2.5% to 1.4%. Foetal growth restriction of unknown cause contributed to 16% of all stillbirths; this prevalence did not change over time. Moreover, foetal growth restriction was not diagnosed during routine antenatal care in 43.5% of patients. Thirty-six percent of all stillbirths were unexplained. The prevalences of stillbirth associated with chorioamnionitis and placental abruption did not change over time. CONCLUSIONS: Causes of stillbirth in Hong Kong have changed in the past 20 years because of altered demographic characteristics and improved prenatal testing. Further improvements should focus on early foetal growth restriction detection and preeclampsia prevention.

Perinatal mortality rate in multiple pregnancies: a 20-year retrospective study from a tertiary obstetric unit in Hong Kong.

INTRODUCTION: Multiple pregnancies have become more common, but their perinatal mortality rate remains higher than the rate among singleton pregnancies. This retrospective study investigated the prevalence and causes of perinatal mortality among multiple pregnancies in Hong Kong. METHODS: All multiple pregnancies in a university tertiary obstetric unit between 2000 and 2019 were reviewed, and the medical records of cases complicated by stillbirth and neonatal death were identified. The causes of perinatal mortality were determined based on clinical assessment and laboratory results, then compared between the first (2000-2009) and second (2010-2019) decades. RESULTS: The prevalence of multiple pregnancies increased from 1.41% in the first decade to 1.91% in the second decade (P<0.001). Compared with the first decade, the second decade had a lower stillbirth rate (14.72 vs 7.68 [both per 1000 births]; P=0.026), late neonatal death rate (4.78 vs 1.16 [both per 1000 livebirths]; P=0.030), and total mortality rate (25.32 vs 13.82 [both per 1000 births]; P=0.006). The decline in stillbirth rate was related to improvements in antenatal care and treatment. The decline in the late neonatal death rate was related to a reduction in preterm birth before 34 weeks (18.5% vs 15.2%; P=0.006), as well as an improvement in the mortality rate in the subgroup of 31-33 weeks (19.23 vs 0 [both per 1000 livebirths]; P=0.035). CONCLUSION: Although the prevalence of multiple pregnancies increased during the study period, the corresponding total perinatal mortality rate improved by 45.4%.

Neonatal mortality in singleton pregnancies: a 20-year retrospective study from a tertiary perinatal unit in Hong Kong.

INTRODUCTION: The global neonatal death (NND) rate has been declining in recent decades, but there are no comprehensive data concerning the characteristics of NNDs in Hong Kong. This study investigated the trends and aetiologies of NNDs among singleton pregnancies in Hong Kong. METHODS: This study included all cases of NND from singleton pregnancies in a tertiary hospital in Hong Kong between 2000 and 2019. The rates, clinical characteristics, and aetiologies of NND were compared between the first (2000-2009) and the second (2010-2019) decades. RESULTS: The NND rate decreased from 1.66/1000 livebirths (97 cases) in the first decade to 1.32/1000 livebirths (87 cases) in the second decade. Congenital or genetic abnormalities (82 cases) caused 44.6% of all NNDs. There was a significant reduction from 0.82/1000 livebirths in the first decade to 0.52/1000 livebirths in the second decade (P=0.037). Other causes of NND were prematurity (69 cases; 37.5%), sepsis (16 cases; 8.7%), hypoxic-ischaemic encephalopathy (15 cases; 8.2%), and sudden infant death syndrome (2 cases; 1.1%). Gestational age-specific neonatal mortality for moderately preterm neonates (31-33 weeks of gestation) significantly decreased from 34.73/1000 in 2000-2009 to 8.63/1000 in 2010-2019 (P=0.001), but there were no significant changes in neonatal mortality for other gestations. CONCLUSION: The NND rate in Hong Kong is among the lowest worldwide. Neonatal deaths in our centre declined over the past two decades, mainly because of improvements in the prenatal diagnosis and treatment of congenital or genetic abnormalities, as well as an improved survival rate among moderately preterm neonates.

Transanal mesorectal excision: early outcomes in Australia and New Zealand.

BACKGROUND: Transanal total mesorectal excision (taTME) aims to overcome some of the technical challenges faced when operating on mid and low rectal cancers. Specimen quality has been confirmed previously, but recent concerns have been raised about oncological safety. This multicentre prospective study aimed to evaluate the safety of taTME among early adopters in Australia and New Zealand. METHODS: Data from all consecutive patients who had taTME for rectal cancer from July 2014 to February 2020 at six tertiary referral centres in Australasia were recorded and analysed. RESULTS: A total of 308 patients of median age of 64 years underwent taTME. Some 75.6 per cent of patients were men, and the median BMI was 26.8 kg/m2. The median distance of tumour from anal verge was 7 cm. Neoadjuvant chemoradiotherapy was administered to 57.8 per cent of patients. The anastomotic leak rate was 8.1 per cent and there was no mortality within 30 days of surgery. Pathological examination found a complete mesorectum in 295 patients (95.8 per cent), a near-complete mesorectum in seven patients (2.3 per cent), and an incomplete mesorectum in six patients (1.9 per cent). The circumferential resection margin and distal resection margin was involved in nine patients (2.9 per cent), and two patients (0.6 per cent) respectively. Over a median follow-up of 22 months, the local recurrence rate was 1.9 per cent and median time to local recurrence was 30.5 months. CONCLUSION: This study showed that, with appropriate training and supervision, skilled minimally invasive rectal cancer surgeons can perform taTME with similar pathological and oncological results to open and laparoscopic surgery.

Minimizing comprehensive geriatric assessment to identify deterioration of physical performance in a healthy community-dwelling older cohort: longitudinal data of the AEQUIPA Versa study.

BACKGROUND: It is important to identify the relevant parameters of physical performance to prevent early functional decline and to prolong independent living. The aim of this study is to describe the development of physical performance in a healthy community-dwelling older cohort aged 70+ years using comprehensive assessment over two years and to subsequently identify the most relevant predictive tests for physical decline to minimize assessment. METHODS: Physical performance was measured by comprehensive geriatric assessment. Predictors for the individual decline of physical performance by Principal Component and k-means Cluster Analysis were developed, and sensitivity and specificity determined accordingly. RESULTS: 251 subjects (Ø 75.4 years) participated in the study. Handgrip strength was low in 21.1%. The follow-up results of tests were divergent. Handgrip strength [- 16.95 (SD 11.55)] and the stair climb power test (power) [- 9.15 (SD 16.84)] yielded the highest percentage changes. Four most relevant tests (handgrip strength, stair climb power time, timed up & go and 4-m gait speed) were identified. A predictor based on baseline data was determined (sensitivity 82%, specificity 96%) to identify subjects characterized by a high degree of physical decline within two years. DISCUSSION: Although the cohort of older adults is heterogeneous, most of the individuals in the study exhibited high levels of physical performance; only a few subjects suffered a relevant decline within the 2-year follow-up. Four most relevant tests were identified to predict relevant decline of physical function. CONCLUSION: In spite of ceiling effects of the geriatric assessment in high-performers, we assume that it is possible to predict an individual's risk of physical decline within 2 years with four tests of a comprehensive geriatric assessment.

Long-term safety in patients with recurrent ovarian cancer treated with niraparib versus placebo: Results from the phase III ENGOT-OV16/NOVA trial.

OBJECTIVE: Niraparib is a poly(ADP-ribose) polymerase (PARP) inhibitor approved for use in heavily pretreated patients and as maintenance treatment in patients with newly-diagnosed or recurrent ovarian cancer following a response to platinum-based chemotherapy. We present long-term safety data for niraparib from the ENGOT-OV16/NOVA trial. METHODS: This multicenter, double-blind, randomized, controlled phase III trial evaluated the efficacy and safety of niraparib for the treatment of recurrent ovarian cancer. Patients were randomly assigned 2:1 to receive either once-daily niraparib 300 mg or placebo. Two independent cohorts were enrolled based on germline BRCA mutation status. The primary endpoint was progression-free survival, reported previously. Long-term safety data were from the most recent data cutoff (September 2017). RESULTS: Overall, 367 patients received niraparib 300 mg once daily. Dose reductions due to TEAEs were highest in month 1 (34%) and declined every month thereafter. Incidence of any-grade and grade ≥ 3 hematologic and symptomatic TEAEs was also highest in month 1 and subsequently declined. Incidence of grade ≥ 3 thrombocytopenia decreased from 28% (month 1) to 9% and 5% (months 2 and 3, respectively), with protocol-directed dose interruptions and/or reductions. Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) were reported in 2 and 6 niraparib-treated patients, respectively, and in 1 placebo patient each. Treatment discontinuations due to TEAEs were <5% in each month and time interval measured. CONCLUSION: These data demonstrate the importance of appropriate dose reduction according to toxicity criteria and support the safe long-term use of niraparib for maintenance treatment in patients with recurrent ovarian cancer. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01847274.

Singaporean nursing students' perceptions of a career in community nursing.

BACKGROUND: The ageing population and the changing disease profile have been driving the demand for community nurses. However, few nursing students in Singapore aspire to have a career in community nursing following graduation. OBJECTIVES: To explore undergraduate nursing students' perceptions of a career in community nursing and to identify strategies to promote community nursing among nursing students. METHODS: An exploratory qualitative design was used. Four focus group discussions were conducted with a purposive sample of 24 undergraduate nursing students from a university. Interview transcripts were analysed using thematic analysis. FINDINGS: Four key themes emerged as follows: 'mid-life career', 'limited career progression', 'a difficult transition' and 'international nurses-dominated workforce'. DISCUSSION: While most participants rejected a career in community nursing immediately after graduation, they planned to join it at the later stages of their lives to accommodate changing life priorities. Limited career progression and increased difficulty in career transition from community nursing to acute care nursing were identified as deterrent factors in the participants' choices of community nursing as a career. Feelings of marginalization and a lack of role models in community nursing were perceived to be the result of the international nurses-dominated community workforce. CONCLUSION: Community nursing remains an underrated career. There is a need to foster an optimistic career outlook and mobility in community nursing to entice nursing students into this career track. IMPLICATIONS FOR NURSING POLICY: Strategies to enhance community nursing recruitment should focus on providing more quality and diverse community placement opportunities in various community care settings, implementing a clearly defined career developmental plan to elucidate the role of community nurses, and improving community care and cultural competencies to develop a skilled and diverse community nursing workforce.

OV21/PETROC: a randomized Gynecologic Cancer Intergroup phase II study of intraperitoneal versus intravenous chemotherapy following neoadjuvant chemotherapy and optimal debulking surgery in epithelial ovarian cancer.

Background: The purpose of this multistage, adaptively, designed randomized phase II study was to evaluate the role of intraperitoneal (i.p.) chemotherapy following neoadjuvant chemotherapy (NACT) and optimal debulking surgery in women with epithelial ovarian cancer (EOC). Patients and methods: We carried out a multicenter, two-stage, phase II trial. Eligible patients with stage IIB-IVA EOC treated with platinum-based intravenous (i.v.) NACT followed by optimal (<1 cm) debulking surgery were randomized to one of the three treatment arms: (i) i.v. carboplatin/paclitaxel, (ii) i.p. cisplatin plus i.v./i.p. paclitaxel, or (iii) i.p. carboplatin plus i.v./i.p. paclitaxel. The primary end point was 9-month progressive disease rate (PD9). Secondary end points included progression-free survival (PFS), overall survival (OS), toxicity, and quality of life (QOL). Results: Between 2009 and 2015, 275 patients were randomized; i.p. cisplatin containing arm did not progress beyond the first stage of the study after failing to meet the pre-set superiority rule. The final analysis compared i.v. carboplatin/paclitaxel (n = 101) with i.p. carboplatin, i.v./i.p. paclitaxel (n = 102). The intention to treat PD9 was lower in the i.p. carboplatin arm compared with the i.v. carboplatin arm: 24.5% (95% CI 16.2% to 32.9%) versus 38.6% (95% CI 29.1% to 48.1%) P = 0.065. The study was underpowered to detect differences in PFS: HR PFS 0.82 (95% CI 0.57-1.17); P = 0.27 and OS HR 0.80 (95% CI 0.47-1.35) P = 0.40. The i.p. carboplatin-based regimen was well tolerated with no reduction in QOL or increase in toxicity compared with i.v. administration alone. Conclusion: In women with stage IIIC or IVA EOC treated with NACT and optimal debulking surgery, i.p. carboplatin-based chemotherapy is well tolerated and associated with an improved PD9 compared with i.v. carboplatin-based chemotherapy. Clinical trial number: clinicaltrials.gov, NCT01622543.

Evolution of the IgE and IgG repertoire to a comprehensive array of allergen molecules in the first decade of life.

BACKGROUND: In early childhood, the allergen-specific IgG repertoire is mainly directed to animal and vegetable food molecules and infrequently to airborne molecules. It is unknown whether this early pattern is maintained throughout childhood. OBJECTIVE: To investigate the evolution of IgG and IgE responses to a broad panel of allergenic molecules from birth to age 10 years. METHODS: We examined the sera collected between birth and age 10 years from participants in the German Multicentre Allergy Study, a birth cohort born in 1990. The IgE (cutoff ≥0.30 ISU) and IgG (cutoff ≥0.10 ISU) responses to 35 genuine allergenic molecules were measured with a multiplex microarray approach (ImmunoCAP ISAC™). RESULTS: IgE responses were mostly directed against a restricted group of airborne molecules, with a sequence and prevalence hierarchy (Phl p 1> Bet v 1> Fel d 1> Phl p 5> Der p 2> Der p 1) largely maintained over time. Conversely, the IgG repertoire was much broader, starting with animal foodborne, then spreading to vegetable foodborne and finally to airborne molecules. A strong and persistent IgG response to a given airborne molecule almost invariably preceded or accompanied an IgE response to that molecule. CONCLUSIONS: The evolution of IgG and IgE responses throughout childhood differs widely at population level. IgG responses are mostly directed to animal food allergens, while IgE responses are dominated by airborne allergens. However, a strong IgG response almost invariably precedes or accompanies the appearance of IgE to the same molecule in specifically sensitized subjects.

The sex-shift in single disease and multimorbid asthma and rhinitis during puberty - a study by MeDALL.

BACKGROUND: Cross-sectional studies suggested that allergy prevalence in childhood is higher in boys compared to girls, but it remains unclear whether this inequality changes after puberty. We examined the sex-specific prevalence of asthma and rhinitis as single and as multimorbid diseases before and after puberty onset in longitudinal cohort data. METHODS: In six European population-based birth cohorts of MeDALL, we assessed the outcomes: current rhinitis, current asthma, current allergic multimorbidity (ie, concurrent asthma and rhinitis), puberty status and allergic sensitization by specific serum antibodies (immunoglobulin E) against aero-allergens. With generalized estimating equations, we analysed the effects of sex, age, puberty (yes/no) and possible confounders on the prevalence of asthma and rhinitis, and allergic multimorbidity in each cohort separately and performed individual participant data meta-analysis. FINDINGS: We included data from 19 013 participants from birth to age 14-20 years. Current rhinitis only affected girls less often than boys before and after puberty onset: adjusted odds ratio for females vs males 0.79 (95%-confidence interval 0.73-0.86) and 0.86 (0.79-0.94), respectively (sex-puberty interaction P = .089). Similarly, for current asthma only, females were less often affected than boys both before and after puberty onset: 0.71, 0.63-0.81 and 0.81, 0.64-1.02, respectively (sex-puberty interaction P = .327). The prevalence of allergic multimorbidity showed the strongest sex effect before puberty onset (female-male-OR 0.55, 0.46-0.64) and a considerable shift towards a sex-balanced prevalence after puberty onset (0.89, 0.74-1.04); sex-puberty interaction: P < .001. INTERPRETATION: The male predominance in prevalence before puberty and the "sex-shift" towards females after puberty onset were strongest in multimorbid patients who had asthma and rhinitis concurrently.

Challenges in the implementation of the EAACI AIT guidelines: A situational analysis of current provision of allergen immunotherapy.

PURPOSE: The European Academy of Allergy and Clinical Immunology (EAACI) has produced Guidelines on Allergen Immunotherapy (AIT). We sought to gauge the preparedness of primary care to participate in the delivery of AIT in Europe. METHODS: We undertook a mixed-methods, situational analysis. This involved a purposeful literature search and two surveys: one to primary care clinicians and the other to a wider group of stakeholders across Europe. RESULTS: The 10 papers identified all pointed out gaps or deficiencies in allergy care provision in primary care. The surveys also highlighted similar concerns, particularly in relation to concerns about lack of knowledge, skills, infrastructural weaknesses, reimbursement policies and communication with specialists as barriers to evidence-based care. Almost all countries (92%) reported the availability of AIT. In spite of that, only 28% and 44% of the countries reported the availability of guidelines for primary care physicians and specialists, respectively. Agreed pathways between specialists and primary care physicians were reported as existing in 32%-48% of countries. Reimbursement appeared to be an important barrier as AIT was only fully reimbursed in 32% of countries. Additionally, 44% of respondents considered accessibility to AIT and 36% stating patient costs were barriers. CONCLUSIONS: Successful working with primary care providers is essential to scaling-up AIT provision in Europe, but to achieve this, the identified barriers must be overcome. Development of primary care interpretation of guidelines to aid patient selection, establishment of disease management pathways and collaboration with specialist groups are required as a matter of urgency.

Challenges in the implementation of EAACI guidelines on allergen immunotherapy: A global perspective on the regulation of allergen products.

Regulatory approaches for allergen immunotherapy (AIT) products and the availability of high-quality AIT products are inherently linked to each other. While allergen products are available in many countries across the globe, their regulation is very heterogeneous. First, we describe the regulatory systems applicable for AIT products in the European Union (EU) and in the United States (US). For Europe, a depiction of the different types of relevant procedures, as well as the committees involved, is provided and the fundamental role of national agencies of the EU member states in this complex and unique network is highlighted. Furthermore, the regulatory agencies from Australia, Canada, Japan, Russia, and Switzerland provided information on the system implemented in their countries for the regulation of allergen products. While AIT products are commonly classified as biological medicinal products, they are made available by varying types of procedures, most commonly either by obtaining a marketing authorization or by being distributed as named patient products. Exemptions from marketing authorizations in exceptional cases, as well as import of allergen products from other countries, are additional tools applied by countries to ensure availability of needed AIT products. Several challenges for AIT products are apparent from this analysis and will require further consideration.