Health outcomes after myocardial infarction: A population study of 56 million people in England.

BACKGROUND: The occurrence of a range of health outcomes following myocardial infarction (MI) is unknown. Therefore, this study aimed to determine the long-term risk of major health outcomes following MI and generate sociodemographic stratified risk charts in order to inform care recommendations in the post-MI period and underpin shared decision making. METHODS AND FINDINGS: This nationwide cohort study includes all individuals aged ≥18 years admitted to one of 229 National Health Service (NHS) Trusts in England between 1 January 2008 and 31 January 2017 (final follow-up 27 March 2017). We analysed 11 non-fatal health outcomes (subsequent MI and first hospitalisation for heart failure, atrial fibrillation, cerebrovascular disease, peripheral arterial disease, severe bleeding, renal failure, diabetes mellitus, dementia, depression, and cancer) and all-cause mortality. Of the 55,619,430 population of England, 34,116,257 individuals contributing to 145,912,852 hospitalisations were included (mean age 41.7 years (standard deviation [SD 26.1]); n = 14,747,198 (44.2%) male). There were 433,361 individuals with MI (mean age 67.4 years [SD 14.4)]; n = 283,742 (65.5%) male). Following MI, all-cause mortality was the most frequent event (adjusted cumulative incidence at 9 years 37.8% (95% confidence interval [CI] [37.6,37.9]), followed by heart failure (29.6%; 95% CI [29.4,29.7]), renal failure (27.2%; 95% CI [27.0,27.4]), atrial fibrillation (22.3%; 95% CI [22.2,22.5]), severe bleeding (19.0%; 95% CI [18.8,19.1]), diabetes (17.0%; 95% CI [16.9,17.1]), cancer (13.5%; 95% CI [13.3,13.6]), cerebrovascular disease (12.5%; 95% CI [12.4,12.7]), depression (8.9%; 95% CI [8.7,9.0]), dementia (7.8%; 95% CI [7.7,7.9]), subsequent MI (7.1%; 95% CI [7.0,7.2]), and peripheral arterial disease (6.5%; 95% CI [6.4,6.6]). Compared with a risk-set matched population of 2,001,310 individuals, first hospitalisation of all non-fatal health outcomes were increased after MI, except for dementia (adjusted hazard ratio [aHR] 1.01; 95% CI [0.99,1.02];p = 0.468) and cancer (aHR 0.56; 95% CI [0.56,0.57];p < 0.001). The study includes data from secondary care only-as such diagnoses made outside of secondary care may have been missed leading to the potential underestimation of the total burden of disease following MI. CONCLUSIONS: In this study, up to a third of patients with MI developed heart failure or renal failure, 7% had another MI, and 38% died within 9 years (compared with 35% deaths among matched individuals). The incidence of all health outcomes, except dementia and cancer, was higher than expected during the normal life course without MI following adjustment for age, sex, year, and socioeconomic deprivation. Efforts targeted to prevent or limit the accrual of chronic, multisystem disease states following MI are needed and should be guided by the demographic-specific risk charts derived in this study.

Establishment of standards for the referral of large nonpedunculated colorectal polyps: an international expert consensus using a modified Delphi process.

BACKGROUND AND AIMS: Resection of colorectal polyps has been shown to decrease the incidence and mortality of colorectal cancer. Large nonpedunculated colorectal polyps are often referred to expert centers for endoscopic resection, which requires relevant information to be conveyed to the therapeutic endoscopist to allow for triage and planning of resection technique. The primary objective of this study was to establish minimum expected standards for the referral of large nonpedunculated colonic polyps for potential endoscopic resection. METHODS: A Delphi method was used to establish consensus on minimum expected standards for the referral of large colorectal polyps among a panel of international endoscopy experts. The expert panel was recruited through purposive sampling, and 3 rounds of surveys were conducted to achieve consensus. Quantitative and qualitative data were analyzed for each round. RESULTS: A total of 24 international experts from diverse continents participated in the Delphi study, resulting in consensus on 19 statements related to the referral of large colorectal polyps. The identified factors, including patient demographic characteristics, relevant medications, lesion factors, photodocumentation, and the presence of a tattoo, were deemed important for conveying the necessary information to therapeutic endoscopists. The mean scores for the statements, which were scored on a scale of 1 to 10, ranged from 7.04 to 9.29, with high percentages of experts considering most statements as a very high priority. Subgroup analysis according to continent revealed some variations in consensus rates among experts from different regions. CONCLUSIONS: The identified consensus statements can aid in improving the triage and planning of resection techniques for large colorectal polyps, ultimately contributing to the reduction of colorectal cancer incidence and mortality.

Midwives and service users' perspectives on implementing a dialogue about alcohol use in antenatal care: A qualitative study.

AIM: There are barriers to midwives engaging in conversations about alcohol with pregnant women. Our aim was to capture the views of midwives and service users to co-create strategies to address these barriers. DESIGN: Qualitative description. METHODS: Structured Zoom-based focus group interviews of midwives and service users where we presented known barriers and sought solutions to midwives discussing alcohol use in antenatal settings. Data collection took place between July and August 2021. RESULTS: Fourteen midwives and six service users attended five focus groups. Barriers considered were as follows: (i) lack of awareness of guidelines, (ii) poor skills in difficult conversations, (iii) lack of confidence, (iv) lack of belief in existing evidence, (v) women would not listen to their advice, and (vi) alcohol conversations were not considered part of their role. Five strategies to address barriers to midwives discussing alcohol with pregnant women were identified. These were as follows: Training that included mothers of children with Foetal Alcohol Spectrum Disorder, champion midwives, a service user questionnaire about alcohol for completion before the consultation, questions about alcohol added to the maternity data capture template and a structured appraisal to provide a means of audit and feedback on their alcohol dialogue with women. CONCLUSIONS: Co-creation involving providers and users of maternity services yielded theoretically underpinned pragmatic strategies to support midwives to ask advise assist about alcohol during antenatal care. Future research will test if the strategies can be delivered in antenatal care settings, and if they are acceptable to service providers and service users. IMPACT: If these strategies are effective in addressing barriers to midwives discussing alcohol with pregnant women, this could support women to abstain from alcohol during pregnancy, thus reducing alcohol-related maternal and infant harm. PATIENT AND PUBLIC CONTRIBUTION: Service users were involved in the design and execution of the study, considering data, supporting intervention design and delivery and dissemination.

International variation in childhood cancer mortality rates from 2001 to 2015: Comparison of trends in the International Cancer Benchmarking Partnership countries.

Despite improved survival rates, cancer remains one of the most common causes of childhood death. The International Cancer Benchmarking Partnership (ICBP) showed variation in cancer survival for adults. We aimed to assess and compare trends over time in cancer mortality between children, adolescents and young adults (AYAs) and adults in the six countries involved in the ICBP: United Kingdom, Denmark, Australia, Canada, Norway and Sweden. Trends in mortality between 2001 and 2015 in the six original ICBP countries were examined. Age standardised mortality rates (ASR per million) were calculated for all cancers, leukaemia, malignant and benign central nervous system (CNS) tumours, and non-CNS solid tumours. ASRs were reported for children (age 0-14 years), AYAs aged 15 to 39 years and adults aged 40 years and above. Average annual percentage change (AAPC) in mortality rates per country were estimated using Joinpoint regression. For all cancers combined, significant temporal reductions were observed in all countries and all age groups. However, the overall AAPC was greater for children (-2.9; 95% confidence interval = -4.0 to -1.7) compared to AYAs (-1.8; -2.1 to -1.5) and adults aged >40 years (-1.5; -1.6 to -1.4). This pattern was mirrored for leukaemia, CNS tumours and non-CNS solid tumours, with the difference being most pronounced for leukaemia: AAPC for children -4.6 (-6.1 to -3.1) vs AYAs -3.2 (-4.2 to -2.1) and over 40s -1.1 (-1.3 to -0.8). AAPCs varied between countries in children for all cancers except leukaemia, and in adults over 40 for all cancers combined, but not in subgroups. Improvements in cancer mortality rates in ICBP countries have been most marked among children aged 0 to 14 in comparison to 15 to 39 and over 40 year olds. This may reflect better care, including centralised service provision, treatment protocols and higher trial recruitment rates in children compared to older patients.

Incidence trends for twelve cancers in younger adults-a rapid review.

Many cancer referral guidelines use patient's age as a key criterium to decide who should be referred urgently. A recent rise in the incidence of colorectal cancer in younger adults has been described in high-income countries worldwide. Information on other cancers is more limited. The aim of this rapid review was to determine whether other cancers are also increasing in younger age groups, as this may have important implications for prioritising patients for investigation and referral. We searched MEDLINE, Embase and Web of Science for studies describing age-related incidence trends for colorectal, bladder, lung, oesophagus, pancreas, stomach, breast, ovarian, uterine, kidney and laryngeal cancer and myeloma. 'Younger' patients were defined based on NICE guidelines for cancer referral. Ninety-eight studies met the inclusion criteria. Findings show that the incidence of colorectal, breast, kidney, pancreas, uterine cancer is increasing in younger age groups, whilst the incidence of lung, laryngeal and bladder cancer is decreasing. Data for oesophageal, stomach, ovarian cancer and myeloma were inconclusive. Overall, this review provides evidence that some cancers are increasingly being diagnosed in younger age groups, although the mechanisms remain unclear. Cancer investigation and referral guidelines may need updating in light of these trends.

Sexual and reproductive health knowledge and behaviour of adolescent boys and girls aged 10-19 years in western Kenya: evidence from a cross-sectional pilot survey.

This paper reports findings of a pilot survey of adolescent sexual and reproductive health (ASRH) knowledge and behaviour in Homabay County of western Kenya. The study was based on a cross-sectional survey of 523 male and female adolescents aged 10-19 years from 32 Community Health Units (CHUs). Bivariate analysis of gender differences and associations between ASRH knowledge and behaviour was followed with two-level logistic regression analysis of predictors of ASRH behaviour (sexual activity, unprotected sex, HIV testing), taking individual adolescents as level-1 and CHUs as level-2. The findings reveal important gender differences in ASRH knowledge and behaviour. While male adolescents reported higher sexual activity (ever had sex, unprotected last sex), female adolescents reported higher HIV testing. Despite having lower HIV/AIDS knowledge, female adolescents were more likely to translate their SRH knowledge into appropriate behaviour. Education emerged as an important predictor of ASRH behaviour. Out-of-school adolescents had significantly higher odds of having ever had sex (aOR=3.3) or unprotected last sex (aOR=3.2) than their in-school counterparts of the same age, gender and ASRH knowledge, while those with at least secondary education had lower odds of unprotected sex (aOR=0.52) and higher odds of HIV testing (aOR=5.49) than their counterparts of the same age, gender and SRH knowledge who had primary education or lower. However, being out of school was associated with higher HIV testing (aOR=2.3); and there was no evidence of significant differences between younger (aged 10-14) and older (aged 15-19) adolescents in SRH knowledge and behaviour. Besides individual-level predictors, there were significant community variations in ASRH knowledge and behaviour, with relatively more-deprived CHUs being associated with poorer indicators. The overall findings have important policy/programme implications. There is a need for a comprehensive approach that engages schools, health providers, peers, parents/adults and the wider community in developing age-appropriate ASRH interventions for both in-school and out-of-school adolescents in western Kenya.

Preconception interventions to reduce the risk of alcohol-exposed pregnancies: A systematic review.

BACKGROUND: The preconception period provides a unique opportunity to optimize the health of women and children. High rates of alcohol use and unintended pregnancies are common across many Western societies, and alcohol-exposed pregnancies (AEPs) are a possible unintended outcome. The aim of the current study was to evaluate preconception interventions for the prevention of AEPs. METHODS: A systematic search of four electronic databases (PubMed, Embase, CINAHL, and PsycINFO) was undertaken for relevant peer-reviewed articles published from 1970 onward. Studies were included if they enrolled women and/or their support networks during the preconception period. RESULTS: Nineteen studies met the inclusion criteria. The majority of studies (n = 14) evaluated CHOICES-based interventions, which incorporate motivational interviewing approaches to change alcohol and/or contraceptive behavior. The other five interventions included a range of different approaches and modes of delivery. The majority of interventions were successful in reducing AEP risk. Changes in AEP risk were more often driven by changes in contraceptive behavior, although some approaches led to changes in both alcohol and contraceptive behavior. CONCLUSIONS: The review indicated that many interventions were efficacious at reducing AEP risk during the preconception period through preventing unplanned pregnancy. The effectiveness estimated from these clinical trials may be greater than that seen in interventions when implemented in practice where there is a lack of blinding and greater attrition of participants during follow-up. Further research investigating the real-world effectiveness of these intervention approaches implemented across a wide range of clinical settings would be beneficial.

Barriers and enablers of implementation of alcohol guidelines with pregnant women: a cross-sectional survey among UK midwives.

BACKGROUND: In 2016, the UK Chief Medical Officers revised their guidance on alcohol and advised women to abstain from alcohol if pregnant or planning pregnancy. Midwives have a key role in advising women about alcohol during pregnancy. The aim of this study was to investigate UK midwives' practices regarding the 2016 Chief Medical Officers Alcohol Guidelines for pregnancy, and factors influencing their implementation during antenatal appointments. METHODS: Online cross-sectional survey of a convenience sample of UK midwives recruited through professional networks and social media. Data were gathered using an anonymous online questionnaire addressing knowledge of the 2016 Alcohol Guidelines for pregnancy; practice behaviours regarding alcohol assessment and advice; and questions based on the Theoretical Domains Framework (TDF) to evaluate implementation of advising abstinence at antenatal booking and subsequent antenatal appointments. RESULTS: Of 842 questionnaire respondents, 58% were aware of the 2016 Alcohol Guidelines of whom 91% (438) cited abstinence was recommended, although 19% (93) cited recommendations from previous guidelines. Nonetheless, 97% of 842 midwives always or usually advised women to abstain from alcohol at the booking appointment, and 38% at subsequent antenatal appointments. Mean TDF domain scores (range 1-7) for advising abstinence at subsequent appointments were highest (indicative of barriers) for social influences (3.65 sd 0.84), beliefs about consequences (3.16 sd 1.13) and beliefs about capabilities (3.03 sd 073); and lowest (indicative of facilitators) for knowledge (1.35 sd 0.73) and professional role and identity (1.46 sd 0.77). Logistic regression analysis indicated that the TDF domains: beliefs about capabilities (OR = 0.71, 95% CI: 0.57, 0.88), emotion (OR = 0.78; 95%CI: 0.67, 0.90), and professional role and identity (OR = 0.69, 95%CI 0.51, 0.95) were strong predictors of midwives advising all women to abstain from alcohol at appointments other than at booking. CONCLUSIONS: Our results suggest that skill development and reinforcement of support from colleagues and the wider maternity system could support midwives' implementation of alcohol advice at each antenatal appointment, not just at booking could lead to improved outcomes for women and infants. Implementation of alcohol care pathways in maternity settings are beneficial from a lifecourse perspective for women, children, families, and the wider community.

Lifestage differences in young UK women's reasons for research participation.

Lifecourse epidemiology suggests that preconception is a valuable opportunity for health promotion with young women. Yet young women are less likely than older women to be research participants, limiting evidence about their needs and risks. Marketing data indicate that young adults are not engaged with one advertising strategy because they transition through three life stages: (i) limited independence and focus on own interests, (ii) increased independence and time with peers and (iii) establishing a home and family. The aim of this study was to explore whether these marketing lifestage categories could inform the tailoring of strategies to recruit young women. Three focus groups per lifestage category were conducted (49 women aged 16-34 years). Lifestage category (i) was represented by further education students, category (ii) by women in workplaces and (iii) by mothers. Questions explored participants' lifestyles, identity, reasons for participation in the current study and beliefs about researchers. Three major themes were identified through framework analysis: profiling how young women spend their time; facilitators of participating in research and barriers to participating. Students and women in work valued monetary remuneration whereas mothers preferred social opportunities. Participants' perceived identity influenced whether they felt useful to research. All groups expressed anxiety about participation. Altruism was limited to helping people known to participants. Therefore, the marketing categories did not map exactly to differences in young women's motivations to participate but have highlighted how one recruitment strategy may not engage all. Mass media communication could, instead, increase familiarity and reduce anxiety about participation.

Predictors of obstetric anal sphincter injury during waterbirth: a secondary analysis of a prospective observational study.

INTRODUCTION AND HYPOTHESIS: Obstetric anal sphincter injury (OASI) during childbirth is associated with urino-genital pain and dysfunction. Waterbirth is a popular birth choice for women, but controversy remains around the risk of OASI during waterbirth. This study reports on the incidence of OASI, and factors associated with OASI, for a cohort of women who gave birth in water. METHODS: This secondary analysis used prospectively collected data from 2,908 women who gave birth in water in a hospital setting. The incidence of OASI was calculated. Univariable and multivariable logistic regression analysis evaluated factors associated with OASI. RESULTS: The incidence of OASI was 1.9% (95% confidence interval (CI) 1.4, 2.4) for all women. In nulliparae it was higher (3.2%, 95% CI 2.3, 4.3) than in multiparae (0.9%, 95% CI 0.5, 1.4). In the multivariable analysis, two variables were associated with OASI; multiparity was negatively associated with OASI (adjusted odds ratio [aOR] 0.24, 95% CI 0.12, 0.50, p < 0.001), and birth weight was positively associated with OASI (aOR 1.001, 95% CI 1.000, 1.002, p = 0.02). A "hands-on" technique was used during only 13% of births. A birth position supporting a flexible sacrum did not influence OASI risk. CONCLUSIONS: A low incidence of OASI was found for this cohort of women. The low proportion of midwives using a hands-on technique suggests that it may not be required in waterbirth.

Trends in and predictors of pregnancy termination among 15-24 year-old women in Nigeria: a multi-level analysis of demographic and health surveys 2003-2018.

BACKGROUND: Three-quarters of pregnancy terminations in Africa are carried out in unsafe conditions. Unsafe abortion is the leading cause of maternal mortality among 15-24 year-old women in Sub-Saharan Africa. Greater understanding of the wider determinants of pregnancy termination in 15-24 year-olds could inform the design and development of interventions to mitigate the harm. Previous research has described the trends in and factors associated with termination of pregnancy for women of reproductive age in Nigeria. However, the wider determinants of pregnancy termination have not been ascertained, and data for all women have been aggregated which may obscure differences by age groups. Therefore, we examined the trends in and individual and contextual-level predictors of pregnancy termination among 15-24 year-old women in Nigeria. METHODS: We analysed data from the 2003, 2008, 2013 and 2018 Nigerian Demographic and Health Surveys (NDHS) comprising 45,793 women aged 15-24 years. Trends in pregnancy termination across the four survey datasets were examined using bivariate analysis. Individual and contextual predictors of pregnancy termination were analysed using a three-level binary logistic regression analysis and are reported as adjusted odds ratios (aOR) with 95% confidence intervals (CI). RESULTS: Trends in pregnancy termination declined from 5.8% in 2003 to 4.2% in 2013 then reversed to 4.9% in 2018. The declining trend was greater for 15-24 year-old women with higher socioeconomic status. Around 17% of the total variation in pregnancy termination was attributable to community factors, and 7% to state-level factors. Of all contextual variables considered, only contraceptive prevalence (proxy for reproductive health service access by young women) at community level was significant. Living in communities with higher contraceptive prevalence increased odds of termination compared with communities with lower contraceptive prevalence (aOR = 4.2; 95% CI 2.7-6.6). At the individual-level, sexual activity before age 15 increased odds of termination (aOR = 2.3; 95% CI 1.9-2.8) compared with women who initiated sexual activity at age 18 years or older, and married women had increased odds compared with never married women (aOR = 3.0; 95% CI 2.5-3.7). CONCLUSION: Our findings highlight the importance of disaggregating data for women across the reproductive lifecourse, and indicates where tailored interventions could be targeted to address factors associated with pregnancy termination among young women in Nigeria.

Retrospective analysis of complications associated with retrobulbar bupivacaine in dogs undergoing enucleation surgery.

OBJECTIVE: To investigate complications associated with, and without, bupivacaine retrobulbar local anesthesia in dogs undergoing unilateral enucleation surgery. STUDY DESIGN: Retrospective, observational study. ANIMALS: A total of 167 dogs underwent unilateral enucleation surgery via a transpalpebral approach. METHODS: Records from 167 dogs that underwent unilateral enucleation surgery that did (RB) or did not (NB) include retrobulbar bupivacaine anesthesia were reviewed, including anesthetic record, daily physical examination records, surgery report, patient discharge report and patient notes within 14 days of the surgery. Specific complications and severity were compared between RB and NB using the Wilcoxon rank-sum test. A 'complication burden' (0-5) comprising five prespecified complications was assigned and tested using rank-sum procedures. Statistical significance was set to 0.05. RESULTS: Group RB included 97 dogs and group NB 70 dogs. Dogs in NB had a 17.0 percentage points (points) greater risk for a postoperative recovery complication (38.6% versus 21.6%; 95% confidence interval: 3.0-30.6 points; p = 0.017). There was inconclusive evidence that dogs in group RB had a lower risk of requiring perioperative anticholinergic administration (12.4% versus 22.9%; 10.5 points; p = 0.073). Other complications were similar between groups RB and NB with risks that differed by <10 points. The risk of hemorrhage was similar between groups RB (22.7%) and NB (20.0%) with no significant difference in the level of severity (p = 0.664). CONCLUSIONS AND CLINICAL RELEVANCE: In this retrospective study, the use of retrobulbar bupivacaine for enucleation surgery in dogs was not associated with an increased risk of major or minor complications.

Respiratory morbidity in young people surviving cancer: Population-based study of hospital admissions, treatment-related risk factors and subsequent mortality.

Respiratory diseases are a major cause of late morbidity and mortality amongst childhood cancer survivors. This population-based study investigates respiratory hospital admissions in long-term survivors of cancers diagnosed in young people to identify specific respiratory morbidities, treatment-related risks and their relationship to subsequent morbidity and mortality. Population-based cancer registrations in Yorkshire, England, diagnosed between 1990 and 2011 aged 0-29 years, were linked to inpatient Hospital Episode Statistics (HES) for admissions up to 2017. All 5-year survivors were included in analysis (n = 4235). Admission rates were compared to age- and sex- matched general population rates. Competing risk regression models were used to assess associations between treatment exposures and risk of admission. Risk of death after admission was calculated using Cox regression. By age 40, cumulative incidence for an admission for any type of respiratory condition was 49%. Respiratory admission rates were 1.86 times higher in cancer survivors than in the general population (95% Confidence Interval (CI) 1.73-2.01), and varied by respiratory condition and age at diagnosis. Treatment with chemotherapy with known lung toxicity increased the risk of admission for all respiratory conditions (subdistribution Hazard ratio (sHR) = 1.26, 95%CI 1.03-1.53) and pneumonia (sHR = 1.48, 95%CI 1.01-2.17). Subsequent mortality was highest in those admitted for pneumonia compared to other respiratory conditions (28% and 15% respectively). Survivors of childhood and young adult cancer remain at significantly increased risk of respiratory complications several decades after treatment, emphasising the importance for clinical initiatives for prevention, early detection and treatment.

Risk of ovarian cancer in women treated with ovarian stimulating drugs for infertility.

BACKGROUND: This is an updated version of the original Cochrane Review published in the Cochrane Library in 2013 (Issue 8) on the risk of ovarian cancer in women using infertility drugs when compared to the general population or to infertile women not treated. The link between fertility drugs and ovarian cancer remains controversial. OBJECTIVES: To evaluate the risk of invasive ovarian cancer and borderline ovarian tumours in women treated with ovarian stimulating drugs for subfertility. SEARCH METHODS: The original review included published and unpublished observational studies from 1990 to February 2013. For this update, we extended the searches from February 2013 to November 2018; we evaluated the quality of the included studies and judged the certainty of evidence by using the GRADE approach. We have reported the results in a Summary of findings table to present effect sizes across all outcome types. SELECTION CRITERIA: In the original review and in this update, we searched for randomised controlled trials (RCTs) and non-randomised studies and case series including more than 30 participants. DATA COLLECTION AND ANALYSIS: At least two review authors independently conducted eligibility and 'Risk of bias' assessments and extracted data. We grouped studies based on the fertility drug used for two outcomes: borderline ovarian tumours and invasive ovarian cancer. We conducted no meta-analyses due to expected methodological and clinical heterogeneity. MAIN RESULTS: We included 13 case-control and 24 cohort studies (an additional nine new cohort and two case-control studies), which included a total of 4,684,724 women.Two cohort studies reported an increased incidence of invasive ovarian cancer in exposed subfertile women compared with unexposed women. One reported a standardised incidence ratio (SIR) of 1.19 (95% confidence interval (CI) 0.54 to 2.25) based on 17 cancer cases. The other cohort study reported a hazard ratio (HR) of 1.93 (95% CI 1.18 to 3.18), and this risk was increased in women remaining nulligravid after using clomiphene citrate (HR 2.49, 95% CI 1.30 to 4.78) versus multiparous women (HR 1.52, 95% CI 0.67 to 3.42) (very low-certainty evidence). The slight increase in ovarian cancer risk among women having between one and three cycles of in vitro fertilisation (IVF) was reported, but this was not clinically significant (P = 0.18). There was no increase in risk of invasive ovarian cancer after use of infertility drugs in women with the BRCA mutation according to one cohort and one case-control study. The certainty of evidence as assessed using GRADE was very low.For borderline ovarian tumours, one cohort study reported increased risk in exposed women with an SIR of 3.61 (95% CI 1.45 to 7.44), and this risk was greater after treatment with clomiphene citrate (SIR 7.47, 95% CI 1.54 to 21.83) based on 12 cases. In another cohort study, the risk of a borderline ovarian tumour was increased, with an HR of 4.23 (95% CI 1.25 to 14.33), for subfertile women treated with IVF compared with a non-IVF-treated group with more than one year of follow-up. A large cohort reported increased risk of borderline ovarian tumours, with HR of 2.46 (95% CI 1.20 to 5.04), and this was based on 17 cases. A significant increase in serous borderline ovarian tumours was reported in one cohort study after the use of progesterone for more than four cycles (risk ratio (RR) 2.63, 95% CI 1.04 to 6.64). A case-control study reported increased risk after clomiphene citrate was taken, with an SIR of 2.5 (95% CI 1.3 to 4.5) based on 11 cases, and another reported an increase especially after human menopausal gonadotrophin was taken (odds ratio (OR) 9.38, 95% CI 1.66 to 52.08). Another study estimated an increased risk of borderline ovarian tumour, but this estimation was based on four cases with no control reporting use of fertility drugs. The certainty of evidence as assessed using GRADE was very low.However, although some studies suggested a slight increase in risks of ovarian cancer and borderline ovarian tumour, none provided moderate- or high-certainty evidence, as summarised in the GRADE tables. AUTHORS' CONCLUSIONS: Since the last version of this review, only a few new relevant studies have provided additional findings with supporting evidence to suggest that infertility drugs may increase the risk of ovarian cancer slightly in subfertile women treated with infertility drugs when compared to the general population or to subfertile women not treated. The risk is slightly higher in nulliparous than in multiparous women treated with infertility drugs, and for borderline ovarian tumours. However, few studies have been conducted, the number of cancers is very small, and information on the dose or type of fertility drugs used is insufficient.

Association of maternal exposures with adiposity at age 4/5 years in white British and Pakistani children: findings from the Born in Bradford study.

AIMS/HYPOTHESIS: There is evidence that, from birth, South Asians are fatter, for a given body mass, than Europeans. The role of developmental overnutrition related to maternal adiposity and circulating glucose in these ethnic differences is unclear. Our aim was to compare associations of maternal gestational adiposity and glucose with adiposity at age 4/5 years in white British and Pakistani children. METHODS: Born in Bradford is a prospective study of children born between 2007 and 2010 in Bradford, UK. Mothers completed an OGTT at 27-28 weeks of gestation. We examined associations between maternal gestational BMI, fasting glucose, post-load glucose and diabetes (GDM) and offspring height, weight, BMI and subscapular skinfold (SSF) and triceps skinfold (TSF) thickness at age 4/5 years, using data from 6060 mother-offspring pairs (2717 [44.8%] white British and 3343 [55.2%] Pakistani). RESULTS: Pakistani mothers had lower BMI and higher fasting and post-load glucose and were twice as likely to have GDM (defined using modified WHO criteria) than white British women (15.8% vs 6.9%). Pakistani children were taller and had lower BMI than white British children; they had similar SSF and lower TSF. Maternal BMI was positively associated with the adiposity of offspring in both ethnic groups, with some evidence of stronger associations in Pakistani mother-offspring pairs. For example, the difference in adjusted mean BMI per 1 kg/m2 greater maternal BMI was 0.07 kg/m2 (95% CI 0.05, 0.08) and 0.10 kg/m2 (95% CI 0.09. 0.11) in white British and Pakistani children, respectively, with equivalent results for SSF being 0.07 mm (95% CI 0.05, 0.08) and 0.09 mm (95% CI 0.08. 0.11) (p for ethnic difference < 0.03 for both). There was no strong evidence of association of fasting and post-load glucose, or GDM, with outcomes in either group. CONCLUSIONS/INTERPRETATION: At age 4/5 years, Pakistani children are taller and lighter than white British children. While maternal BMI is positively associated with offspring adiposity, gestational glycaemia is not clearly related to offspring adiposity in either ethnic group.

Long-term survival after childhood acute lymphoblastic leukaemia: population-based trends in cure and relapse by clinical characteristics.

'Cure models' offer additional information to traditional epidemiological approaches to assess survival for cancer patients by simultaneously estimating the proportion cured and the survival of those 'uncured'. The proportion cured is a summary of long-term survival while the median survival time of the uncured provides important information on those who are not long-term survivors. Population-based trends in the cure proportion and survival of the uncured for childhood acute lymphoblastic leukaemia (ALL) by clinical prognostic risk factors were estimated using flexible parametric cure models, based on overall survival and event-free survival. Children aged 1-17 years diagnosed between 1990 and 2011 in Yorkshire, UK, were included (n = 492). The percentage cured increased from 77% (95% confidence interval 70-84%) in 1990-1997 to 89% (84-93%) in 2003-2011, while the median survival time of the uncured decreased from 3·2 years (2·2-4·1 years) to 0·7 years (0-1·5 years). Models based on event-free survival showed a similar trend. The 5-year cumulative incidence of relapse substantially decreased from 35% in 1990-97 to 9% in 2003-2011. These results show selective improvement in survival between 1990 and 2011 with a significant reduction in the risk of relapse alongside a reduced absolute duration of survival for those destined to be uncured.

Do Maternal Dietary Antioxidants Modify the Relationship Between Binge Drinking and Small for Gestational Age? Findings from a Longitudinal Cohort Study.

BACKGROUND: Vitamin C, vitamin E, and carotenoids are potent dietary antioxidants that have been shown to attenuate ethanol-induced harm in animal models of fetal alcohol spectrum disorders. A diet low in antioxidant-rich foods may induce a state of oxidative stress in the context of maternal alcohol consumption during pregnancy, potentially causing growth restriction in the developing fetus. METHODS: We conducted a secondary analysis of a longitudinal U.K. birth cohort. The sample comprised 9,699 women and their babies in Avon, U.K., with an estimated delivery date between April 1, 1991 and December 31, 1992. Alcohol consumption data were self-reported at 18 weeks' gestation via a postal questionnaire. Women reported any binge drinking (≥4 U.K. units/occasion) during the past month. Dietary data were self-reported at 32 weeks' gestation using a food frequency questionnaire. Estimated intakes of vitamins C and E and carotenoids were categorized into quartiles. Logistic regression models with interaction terms were used to investigate relationships between maternal binge drinking, dietary antioxidants, and fetal growth. Models were adjusted for maternal sociodemographic and lifestyle characteristics. Small for gestational age (SGA; <10th percentile) was defined using customized birth centiles. RESULTS: In the unadjusted models, binge drinking was associated with higher risk of SGA birth (odds ratio [OR] 1.38, 95% confidence interval [CI] 1.10, 1.72, p = 0.005), and higher maternal intakes of vitamin C (OR = 0.90, 95% CI 0.84, 0.96, p = 0.002) and vitamin E (OR = 0.90, 95% CI 0.84, 0.95, p < 0.0001) were associated with lower risk of SGA birth. However, addition of potentially confounding variables attenuated these relationships. Likelihood ratio tests indicated that interaction terms were not significant for vitamin C (p = 0.116), vitamin E (p = 0.059), or carotenoid intakes (p = 0.174). CONCLUSIONS: There was no evidence of maternal intake of dietary antioxidants modifying the relationship between maternal binge drinking and SGA birth.

Parenteral opioids for maternal pain management in labour.

BACKGROUND: Parenteral opioids (intramuscular and intravenous drugs including patient-controlled analgesia) are used for pain relief in labour in many countries throughout the world. This review is an update of a review first published in 2010. OBJECTIVES: To assess the effectiveness, safety and acceptability to women of different types, doses and modes of administration of parenteral opioid analgesia in labour. A second objective is to assess the effects of opioids in labour on the baby in terms of safety, condition at birth and early feeding. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (11 May 2017) and reference lists of retrieved studies. SELECTION CRITERIA: We included randomised controlled trials examining the use of intramuscular or intravenous opioids (including patient-controlled analgesia) for women in labour. Cluster-randomised trials were also eligible for inclusion, although none were identified. We did not include quasi-randomised trials. We looked at studies comparing an opioid with another opioid, placebo, no treatment, other non-pharmacological interventions (transcutaneous electrical nerve stimulation (TENS)) or inhaled analgesia. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We assessed the quality of each evidence synthesis using the GRADE approach. MAIN RESULTS: We included 70 studies that compared an opioid with placebo or no treatment, another opioid administered intramuscularly or intravenously or compared with TENS applied to the back. Sixty-one studies involving more than 8000 women contributed data to the review and these studies reported on 34 different comparisons; for many comparisons and outcomes only one study contributed data. All of the studies were conducted in hospital settings, on healthy women with uncomplicated pregnancies at 37 to 42 weeks' gestation. We excluded studies focusing on women with pre-eclampsia or pre-existing conditions or with a compromised fetus. Overall, the evidence was graded as low- or very low-quality regarding the analgesic effect of opioids and satisfaction with analgesia; evidence was downgraded because of study design limitations, and many of the studies were underpowered to detect differences between groups and so effect estimates were imprecise. Due to the large number of different comparisons, it was not possible to present GRADE findings for every comparison.For the comparison of intramuscular pethidine (50 mg/100 mg) versus placebo, no clear differences were found in maternal satisfaction with analgesia measured during labour (number of women satisfied or very satisfied after 30 minutes: 50 women; 1 trial; risk ratio (RR) 7.00, 95% confidence interval (CI) 0.38 to 128.87, very low-quality evidence), or number of women requesting an epidural (50 women; 1 trial; RR 0.50, 95% CI 0.14 to 1.78; very low-quality evidence). Pain scores (reduction in visual analogue scale (VAS) score of at least 40 mm: 50 women; 1 trial; RR 25, 95% CI 1.56 to 400, low-quality evidence) and pain measured in labour (women reporting pain relief to be "good" or "fair" within one hour of administration: 116 women; 1 trial; RR 1.75, 95% CI 1.24 to 2.47, low-quality evidence) were both reduced in the pethidine group, and fewer women requested any additional analgesia (50 women; 1 trial; RR 0.71, 95% CI 0.54 to 0.94, low-quality evidence).There was limited information on adverse effects and harm to women and babies. There were few results that clearly showed that one opioid was more effective than another. Overall, findings indicated that parenteral opioids provided some pain relief and moderate satisfaction with analgesia in labour. Opioid drugs were associated with maternal nausea, vomiting and drowsiness, although different opioid drugs were associated with different adverse effects. There was no clear evidence of adverse effects of opioids on the newborn. We did not have sufficient evidence to assess which opioid drug provided the best pain relief with the least adverse effects. AUTHORS' CONCLUSIONS: Though most evidence is of low- or very-low quality, for healthy women with an uncomplicated pregnancy who are giving birth at 37 to 42 weeks, parenteral opioids appear to provide some relief from pain in labour but are associated with drowsiness, nausea, and vomiting in the woman. Effects on the newborn are unclear. Maternal satisfaction with opioid analgesia was largely unreported. The review needs to be examined alongside related Cochrane reviews. More research is needed to determine which analgesic intervention is most effective, and provides greatest satisfaction to women with acceptable adverse effects for mothers and their newborn.