Two measures of systemic inflammation are positively associated with haemoglobin levels in adolescent girls living in rural India: a cross-sectional study.

OBJECTIVE: This study tested the hypothesis that systemic inflammation is inversely associated with haemoglobin levels in adolescent girls in India. METHODS: The study population consisted of adolescent girls aged between 10 and 19 years living in a remote rural region in Maharashtra State, India. Data were collected on anthropometric measures, and a venous blood sample was taken and tested for complete blood count and C-reactive protein (CRP). RESULTS: Of 679 individuals who were invited to the research site to participate, data were available from 401 participants giving a response rate of 59%. Median blood CRP was 1.26 mg/l (Range 0.00 to 26.33), and 167 (41.6%) participants had CRP level < 1.0 mg/l. The mean haemoglobin was 12.24 g/dl (standard deviation [SD] 1.51), and the mean total white blood cells (WBC) count was 9.02 × 103 /µl (SD 2.00). With each g/dl increase in blood haemoglobin, the risk of having an elevated CRP of ≥ 1 mg/l increased with an odds ratio of 1.16 (95% CI 1.01 to 1.33, P = 0.03). Total WBC count was also positively associated with blood haemoglobin, increasing by 0.24 × 103 /µl (95% CI 0.11 to 0.37, P < 0.001) per g/dl increase in haemoglobin. Both analyses were adjusted for age. CONCLUSIONS: In this population, blood haemoglobin levels were positively associated with two measures of systemic inflammation, contrary to the primary hypothesis being tested. Other unmeasured environmental exposures may modify haemoglobin levels in this population. Understanding this observation may help design better public health interventions to improve the well-being of adolescent girls in India.

OBJECTIF: Cette étude a testé l'hypothèse selon laquelle l'inflammation systémique est inversement associée aux taux d'hémoglobine chez les adolescentes en Inde. MÉTHODES: La population étudiée était composée d'adolescentes âgées de 10 à 19 ans vivant dans une région rurale éloignée de l'Etat du Maharashtra, en Inde. Les données ont été collectées sur des mesures anthropométriques et un échantillon de sang veineux a été prélevé et testé pour la formule globulaire complète et la protéine C-réactive (CRP). RÉSULTATS: Sur 679 personnes qui ont été invitées au site de recherche à participer, des données étaient disponibles pour 401 participantes, soit un taux de réponse de 59%. La CRP sanguine médiane était de 1,26 mg/L (intervalle de 0,00 à 26,33) et 167 participantes (41,6%) avaient un taux de CRP <1,0 mg/L. L'hémoglobine moyenne était de 12,24 g/dL (écart-type [ET] 1,51), et le nombre moyen total de globules blancs (GB) était de 9,02 x103 /µL (ET 2,00). Avec chaque augmentation par g/dL de l'hémoglobine sanguine, le risque d'avoir une CRP élevée ≥1 mg/L augmentait avec un rapport de cotes de 1,16 (IC95%: 1,01 à 1,33, p = 0,03). La numération totale des GB était également positivement associée à l'hémoglobine sanguine, augmentant de 0,24 x103 /µL (IC95%: 0,11 à 0,37, p <0,001) par g/dL d'augmentation de l'hémoglobine. Les deux analyses ont été ajustées en fonction de l'âge. CONCLUSIONS: Dans cette population, les taux d'hémoglobine sanguine étaient positivement associés à deux mesures de l'inflammation systémique, contrairement à l'hypothèse principale testée. D'autres expositions environnementales non mesurées peuvent modifier les taux d'hémoglobine dans cette population. Comprendre cette observation peut aider à concevoir de meilleures interventions de santé publique pour améliorer le bien-être des adolescentes en Inde.

Access to a piped water supply is positively associated with haemoglobin levels in females living in rural Maharashtra State, India.

OBJECTIVES: There is a high prevalence of anaemia in individuals living in rural India, which may be modified by a number of environmental factors. The association between access to water, toileting facilities and healthcare services with the prevalence of anaemia was explored to determine potentially modifiable community-level risk factors. STUDY DESIGN: This was a cross-sectional survey. METHODS: Data were collected from adolescent females (aged 13-17 years) living in 34 villages in rural areas of the Maharashtra state of India on measures of sanitation facilities and access to health care along with haemoglobin measurements. Linear and logistic regression analyses were conducted to investigate associations between environmental (community) factors and adolescent haemoglobin levels and anaemia, respectively. RESULTS: Data were available from 1010 individuals, which represented a response rate of over 97% of those who were approached for the study. The prevalence of anaemia was very high (87%) when measured using haemoglobin levels. Access to a piped water supply was associated with 0.59 g/dL of increase in haemoglobin levels (95% confidence interval: 0.10-1.09). Associations between access to communal toilets, travel time to the hospital, health centres or nurses and haemoglobin levels or anaemia were not statistically significant. CONCLUSIONS: Anaemia prevalence was very high in our study population. Simple improvements such as provision of regular piped water is associated with an increase in haemoglobin levels in rural Indian females. These are consistent with the hypothesis that chronic exposure to higher levels of microbes in the living environment contributes to the risk of anaemia.

Clinical management of nausea and vomiting in pregnancy and hyperemesis gravidarum across primary and secondary care: a population-based study.

OBJECTIVES: To assess how nausea and vomiting in pregnancy (NVP) and hyperemesis gravidarum (HG) are managed and treated across primary and secondary care. DESIGN: Population-based pregnancy cohort. SETTING: Medical records (CPRD-GOLD) from England. POPULATION: 417 028 pregnancies during 1998-2014. METHODS: Proportions of pregnancies with recorded NVP/HG diagnoses, primary care treatment, and hospital admissions were calculated. Multinomial logistic regression was employed to estimate adjusted relative risk ratios (aRRRs) with 99% confidence intervals (CIs) for the association between NVP/HG management paths and maternal characteristics. MAIN OUTCOME MEASURES: NVP/HG diagnoses, treatments, and hospital admissions. RESULTS: Overall prevalence of clinically recorded NVP/HG was 9.1%: 2.1% had hospital admissions, 3.4% were treated with antiemetics in primary care only, and 3.6% had only recorded diagnoses. Hospital admissions and antiemetic prescribing increased continuously during 1998-2013 (trend P < 0.001). Younger age, deprivation, Black/Asian/mixed ethnicity, and multiple pregnancy were associated with NVP/HG generally across all levels, but associations were strongest for hospital admissions. Most comorbidities had patterns of association with NVP/HG levels. Among women with NVP/HG who had no hospital admissions, 49% were prescribed antiemetics, mainly from first-line treatment (21% prochlorperazine, 15% promethazine, 13% cyclizine) and metoclopramide (10%). Of those admitted, 38% had prior antiemetic prescriptions (34% first-line, 9% second-line, 1% third-line treatment). CONCLUSION: Previous focus on hospital admissions has greatly underestimated the NVP/HG burden. Although primary care prescribing has increased, most women admitted to hospital have no antiemetics prescribed before this. An urgent call is made to assess whether admissions could be prevented with better primary care recognition and timely treatment. TWEETABLE ABSTRACT: The NVP/HG burden is increasing over time and management optimisation should be high priority to help reduce hospital admissions.

Peripartum hysterectomy: an economic analysis of direct healthcare costs using routinely collected data.

OBJECTIVE: To estimate resource use and costs associated with peripartum hysterectomy for the English National Health Service. DESIGN/SETTING: Analysis of linked Clinical Practice Research Datalink and Hospital Episodes Statistics (CPRD-HES) data. POPULATION: Women undergoing peripartum hysterectomy between 1997 and 2013 and matched controls. METHODS: Inverse probability weighted generalised estimating equations were used to model the non-linear trend in healthcare service use and costs over time, accounting for missing data, adjusting for maternal age, body mass index, delivery year, smoking and socio-economic indicators. MAIN OUTCOME MEASURES: Primary care, hospital outpatient and inpatient attendances and costs (UK 2015 prices). RESULTS: The study sample included 1362 women (192 cases and 1170 controls) who gave birth between 1997 and 2013; 1088 (153 cases and 935 controls) of these were deliveries between 2003 and 2013 when all categories of hospital resource use were available. Based on the 2003-2013 delivery cohort, peripartum hysterectomy was associated with a mean adjusted additional total cost of £5380 (95% CI £4436-6687) and a cost ratio of 1.76 (95% CI 1.61-1.98) over 5 years of follow up compared with controls. Inpatient costs, mostly incurred during the first year following surgery, accounted for 78% excluding or 92% including delivery-related costs. CONCLUSION: Peripartum hysterectomy is associated with increased healthcare costs driven largely by increased post-surgery hospitalisation rates. To reduce healthcare costs and improve outcomes for women who undergo hysterectomy, interventions that reduce avoidable repeat hospitalisations following surgery such as providing active follow up, treatment and support in the community should be considered. TWEETABLE ABSTRACT: A large amount of NHS data on peripartum hysterectomy suggests active community follow up could reduce costs, #HealthEconomics.

Risk factors for maternal anaemia and low birth weight in pregnant women living in rural India: a prospective cohort study.

OBJECTIVE: The aim of this prospective study was to estimate the prevalence and risk factors for maternal anaemia and low birth weight (LBW) in pregnant women living in Maharashtra state, India. STUDY DESIGN: This is a prospective study. METHODS: Women between 3 and 5 months of pregnancy were recruited from 34 villages based in Maharashtra state. Baseline data collection, anthropometric measurements and blood investigations were performed. Participants were followed-up to record birth weight. RESULTS: In total, 303 women were eligible, and 287 (95%) provided data. 77% were anaemic, defined as haemoglobin less than 11.0 g/dl at the time of recruitment, with a mean corpuscular volume of 80.5 fl/cell (standard deviation: 7.22, range: 53.4-93.8). The increased risk of anaemia was seen in women with consanguineous marriages (odds ratio [OR]: 2.41, 95% confidence interval [CI]: 1.16-5.01, P = 0.01) after adjustment for potential confounding factors. Postdelivery data from full-term singleton live births demonstrated a 7% prevalence of LBW. Consanguineous marriage was a major risk factor for LBW (OR: 4.10, 95% CI: 1.25-13.41, P = 0.02). The presence of maternal anaemia during 3-5 months of pregnancy was associated with lower risk of LBW (unadjusted OR: 0.34, 95% CI: 0.13-0.92, P = 0.03). CONCLUSION: About 30% of our study participants were in a consanguineous marriage, which was identified as a potentially avoidable risk factor for both anaemia and LBW.

Prevalence of iron-deficiency anaemia and risk factors in 1010 adolescent girls from rural Maharashtra, India: a cross-sectional survey.

OBJECTIVE: Iron-deficiency anaemia (IDA) is the most common nutritional disorder observed in adolescent girls in India. Our aim was to investigate the prevalence and risk factors associated with IDA in rural Maharashtra, India, to address current evidence gaps. STUDY DESIGN: Cross-sectional survey. METHODS: The study recruited 13- to 17-year-old adolescent girls living in 34 villages of Osmanabad district. Data were collected on individual health, dietary, sociodemographic factors, and anthropometric measurements were taken. Haemoglobin (Hb) levels were measured using Sahli's haemometer. Logistic and linear regressions were used to identify risk factors associated with IDA and Hb levels, respectively. RESULTS: Among 1010 adolescent girls (response rate 97.5%), the mean Hb was 10.1 g/dl (standard deviation = 1.3), and 87% had anaemia (Hb < 12 g/dl). The prevalence of mild (11.0-11.9 g/dl), moderate (8.0-10.9 g/dl) and severe (Hb ≤ 7.9 g/dl) anaemia was 17%, 65% and 5%, respectively. Anaemia likelihood increased significantly with age (odds ratio (OR): 1.41 per year, 95% confidence interval (CI): 1.17-1.70). Factors associated with decreased anaemia risk were mid-upper arm circumference (MUAC) ≥22 cm (OR: 0.51, 95% CI: 0.31-0.82), ≥3 days/week consumption of fruit (OR: 0.35, 95% CI: 0.23-0.54) or rice (OR: 0.39, 95% CI: 0.17-0.91), and incomplete schooling (OR: 0.47, 95% CI: 0.24-0.91). In the final model lower age, MUAC and fruit consumption were significantly associated with Hb level. CONCLUSION: Anaemia prevalence was extremely high among adolescent girls in rural areas of Maharashtra. Whilst we identified risk factors that could be used for targeting interventions, there is urgent need of comprehensive preventative interventions for the whole adolescent girl population.

Hospital admission for hyperemesis gravidarum: a nationwide study of occurrence, reoccurrence and risk factors among 8.2 million pregnancies.

STUDY QUESTION: What are the maternal risk factors for hyperemesis gravidarum (HG) hospital admission, readmission and reoccurrence in a following pregnancy? SUMMARY ANSWER: Young age, less socioeconomic deprivation, nulliparity, Asian or Black ethnicity, female fetus, multiple pregnancy, history of HG in a previous pregnancy, thyroid and parathyroid dysfunction, hypercholesterolemia and Type 1 diabetes are all risk factors for HG. WHAT IS KNOWN ALREADY: Women with Black or Asian ethnicity, of young age, carrying multiple babies or singleton females, with Type 1 diabetes or with a history of HG were previously reported to be at higher risk of developing HG; however, most evidence is from small studies. Little is known about associations with other comorbidities and there is controversy over other risk factors such as parity. Estimates of HG prevalence vary and there is a little understanding of the risks of HG readmission in a current pregnancy and reoccurrence rates in subsequent pregnancies, all of which are needed for planning measures to reduce onset or worsening of the condition. STUDY DESIGN, SIZE, DURATION: We performed a population-based cohort study of pregnancies ending in live births and stillbirths using prospectively recorded secondary care records (Hospital Episode Statistics) from England. We analysed those computerized and anonymized clinical records from over 5.3 million women who had one or more pregnancies between 1997 and 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS: We obtained 8 215 538 pregnancies from 5 329 101 women of reproductive age, with a total of 186 800 HG admissions occurring during 121 885 pregnancies. Multivariate logistic regression with generalized estimating equations was employed to estimate odds ratios (aOR) to assess sociodemographic, pregnancy and comorbidity risk factors for HG onset, HG readmission within a pregnancy and reoccurrence in a subsequent pregnancy. MAIN RESULTS AND THE ROLE OF CHANCE: Being younger, from a less socioeconomically deprived status, of Asian or Black ethnicity, carrying a female fetus or having a multiple pregnancy all significantly increased HG and readmission risk but only ethnicity increased reoccurrence. Comorbidities most strongly associated with HG were parathyroid dysfunction (aOR = 3.83, 95% confidence interval 2.28-6.44), hypercholesterolemia (aOR = 2.54, 1.88-3.44), Type 1 diabetes (aOR = 1.95, 1.82-2.09), and thyroid dysfunction (aOR = 1.85, 1.74-1.96). History of HG was the strongest independent risk factor (aOR = 4.74, 4.46-5.05). Women with higher parity had a lower risk of HG compared with nulliparous women (aOR = 0.90, 0.89-0.91), which was not explained by women with HG curtailing further pregnancies. LIMITATIONS, REASONS FOR CAUTION: Although this represents the largest population-based study worldwide on the topic, the results could have been biased by residual and unmeasured confounding considering that some potential important risk factors such as smoking, BMI or prenatal care could not be measured with these data. Underestimation of non-routinely screened comorbidities such as hypercholesterolemia or thyroid dysfunction could also be a cause of selection bias. WIDER IMPLICATIONS OF THE FINDINGS: The estimated prevalence of 1.5% from our study was similar to the average prevalence reported in the literature and the representativeness of our data has been validated by comparison to national statistics. Also the prevalence of comorbidities was mostly similar to other studies estimating these in the UK and other developed countries. Women with Black or Asian ethnicity, of young age, carrying multiple babies or singleton females, with Type 1 diabetes or with history of HG were confirmed to be at higher risk of HG with an unprecedented higher statistical power. We showed for the first time that socioeconomic status interacts with maternal age, that hypercholesterolemia is a potential risk factor for HG and that carrying multiple females increases risk of hyperemesis compared with multiple males. We also provided robust evidence for the association of parity with HG. Earlier recognition and management of symptoms via gynaecology day-case units or general practitioner services can inform prevention and control of consequent hospital admissions. STUDY FUNDING/COMPETING INTERESTS: The work was founded by The Rosetrees Trust and the Stoneygate Trust. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. C.N.-P. reports personal fees from Sanofi Aventis, Warner Chilcott, Leo Pharma, UCB and Falk, outside the submitted work and she is one of the co-developers of the RCOG Green Top Guideline on HG; all other authors did not report any potential conflicts of interest. TRIAL REGISTRATION NUMBER: Not applicable.

Limited risks of major congenital anomalies in children of mothers with coeliac disease: a population-based cohort study.

OBJECTIVE: To examine major congenital anomaly (CA) risks in children of mothers with coeliac disease (CD) compared with mothers without CD. DESIGN: Population-based cohort study. SETTING: Linked maternal-child medical records from a large primary care database from the UK. POPULATION: A total of 562,332 live singletons of mothers with and without CD in 1990-2013. METHODS: We calculated the absolute major CA risks in children whose mothers had CD, and whether this was diagnosed or undiagnosed before childbirth. Logistic regression with a generalised estimating equation was used to estimate adjusted odds ratios (aORs) with 95% confidence intervals (95% CIs) for CAs associated with CD. MAIN OUTCOME MEASURES: Fourteen system-specific major CA groups classified according to the European Surveillance of Congenital Anomalies and neural tube defects (NTDs). RESULTS: Major CA risk in 1880 children of mothers with CD was 293 per 10,000 liveborn singletons, similar to the risk in those without CD (282; aOR 0.98, 95% CI 0.74-1.30). The risk was slightly higher in 971 children, whose mothers were undiagnosed (350; aOR 1.14, 95% CI 0.79-1.64), than in 909 children whose mothers were diagnosed (231; aOR 0.80, 95% CI 0.52-1.24). There was a three-fold increase in nervous system anomalies in the children of mothers with undiagnosed CD (aOR 2.98, 95% CI 1.06-8.33, based on five exposed cases and one had an NTD), and these women were all diagnosed with CD at least 4 years after their children were born. CONCLUSIONS: There was no statistically significant increase in risk of major CAs in children of mothers with coeliac disease overall, compared with the general population.

Treatment decisions and survival for people with small-cell lung cancer.

BACKGROUND: Chemotherapy improves survival for many patients with SCLC, and hence it is important to understand variations in practice and outcomes for this treatment strategy. METHODS: We used the National Lung Cancer Audit and Hospital Episodes Statistics to determine the proportion of patients who received chemotherapy for SCLC, and assess the effects of patient and organisational factors on the odds of receiving chemotherapy and of completing four cycles. We calculated median survival and used Cox regression to determine factors that predicted survival. RESULTS: Of 15 091 cases of SCLC, 70% received at least one cycle of chemotherapy. More deprived people were less likely to receive chemotherapy, but patients were more likely to receive chemotherapy, and to complete ≥ four cycles, if they were referred to the lung cancer team by their GP. Median survival for those treated with chemotherapy was 12.9 months for limited and 7.3 months for extensive stage disease. CONCLUSIONS: The Linked NLCA and HES data provide real-life measures of survival in people treated with chemotherapy and show how this is influenced by patient and tumour characteristics. These data show the characteristics of patients who are less likely to complete a full course of treatment, an adverse predictor of survival.

Maternal depression, antidepressant prescriptions, and congenital anomaly risk in offspring: a population-based cohort study.

OBJECTIVE: To estimate risks of major congenital anomaly (MCA) among children of mothers prescribed antidepressants during early pregnancy or diagnosed with depression but without antidepressant prescriptions. DESIGN: Population-based cohort study. SETTING: Linked UK maternal-child primary care records. POPULATION: A total of 349,127 singletons liveborn between 1990 and 2009. METHODS: Odds ratios adjusted for maternal sociodemographics and comorbidities (aORs) were calculated for MCAs, comparing women with first-trimester selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants (TCAs) and women with diagnosed but unmedicated depression, or women without diagnosed depression. MAIN OUTCOME MEASURES: Fourteen system-specific MCA groups classified according to the European Surveillance of Congenital Anomalies and five specific heart anomaly groups. RESULTS: Absolute risks of MCA were 2.7% (95% confidence interval, 95% CI, 2.6-2.8%) in children of mothers without diagnosed depression, 2.8% (95% CI 2.5-3.2%) in children of mothers with unmedicated depression, and 2.7% (95% CI 2.2-3.2%) and 3.1% (95% CI 2.2-4.1%) in children of mothers with SSRIs or TCAs, respectively. Compared with women without depression, MCA overall was not associated with unmedicated depression (aOR 1.07, 95% CI 0.96-1.18), SSRIs (aOR 1.01, 95% CI 0.88-1.17), or TCAs (aOR 1.09, 95% CI 0.87-1.38). Paroxetine was associated with increased heart anomalies (absolute risk 1.4% in the exposed group compared with 0.8% in women without depression; aOR 1.78, 95% CI 1.09-2.88), which decreased marginally when compared with women with diagnosed but unmedicated depression (aOR 1.67, 95% CI 1.00-2.80). CONCLUSIONS: Overall MCA risk did not increase with maternal depression or with antidepressant prescriptions. Paroxetine was associated with increases of heart anomalies, although this could represent a chance finding from a large number of comparisons undertaken.

Lung cancer survival in England: trends in non-small-cell lung cancer survival over the duration of the National Lung Cancer Audit.

BACKGROUND: In comparison with other European and North American countries, England has poor survival figures for lung cancer. Our aim was to evaluate the changes in survival since the introduction of the National Lung Cancer Audit (NLCA). METHODS: We used data from the NLCA to identify people with non-small-cell lung cancer (NSCLC) and stratified people according to their performance status (PS) and clinical stage. Using Cox regression, we calculated hazard ratios (HRs) for death according to the year of diagnosis from 2004/2005 to 2010; adjusted for patient features including age, sex and co-morbidity. We also assessed whether any changes in survival were explained by the changes in surgical resection rates or histological subtype. RESULTS: In this cohort of 120,745 patients, the overall median survival did not change; but there was a 1% annual improvement in survival over the study period (adjusted HR 0.99, 95% confidence interval (CI) 0.98-0.99). Survival improvement was only seen in patients with good PS and early stage (adjusted HR 0.97, 95% CI 0.95-0.99) and this was partly accounted for by changes in resection rates. CONCLUSION: Survival has only improved for a limited group of people with NSCLC and increasing surgical resection rates appeared to explain some of this improvement.

Occurrence of fertility problems presenting to primary care: population-level estimates of clinical burden and socioeconomic inequalities across the UK.

STUDY QUESTION: What are the age-specific incident rates of clinically recorded fertility problems in women aged 15-49 years and how do they vary by socioeconomic group and geographic area. SUMMARY ANSWER: The incident rate of recorded fertility problems was highest in women age 30-34 years: about 1% of women per annum. Overall rates did not vary by socioeconomic group; however, age-specific rates varied substantially by socioeconomic deprivation quintile; among younger women, deprivation was associated with higher infertility rates. WHAT IS KNOWN ALREADY AND WHAT THIS PAPER ADDS: The rates of infertility in the UK range from 2 to 26%. Infertility definitions and denominators vary widely, and most current evidence is based on questionnaire studies that are subject to recall, reporting and selection bias. The current paper presents population-based estimates of clinically recorded fertility problems in women of reproductive age and the variation by age and socioeconomic deprivation quintile across different regions of the UK, using a nationally representative cohort of women that is larger than any previous study. Although infertility overall does not vary by socioeconomic status, consultation for fertility problems is closely related to socioeconomic patterns of women's age at first conception, demonstrating that many couples have pre-existing, rather than specifically age-related, infertility. STUDY DESIGN, SIZE, DURATION: This cohort study used data from The Health Improvement Network, a computerized primary care database of anonymized patient records from general practices across the UK, with prospective health records on over 1.7 million women between 1990 and 2010. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Our cohort included 1,776,746 women of reproductive age (age 15-49 years) who contributed one or more years of active general practice registration. We estimated rates of new clinically recorded fertility problems in these women using medical records and medications exclusively used to treat infertility. We assessed variation in age-specific incidence by socioeconomic deprivation quintile and geographic area using Poisson regression. MAIN RESULTS AND THE ROLE OF CHANCE: The rate of incident recorded fertility problems was highest in women in the 30-34 year age group (10.9 per 1000 person-years), which equates to approximately 1% of women per annum in this age group. Lowest rates were in women in the 15-19 and 45-49 year age groups (0.7 and 0.4 per 1000 person-years, respectively). Overall rates did not vary by socioeconomic group, measured using quintiles of the Townsend index. Age-specific rates, however, varied substantially with socioeconomic deprivation quintile (P-value for interaction < 0.0001) such that up to age 25, women with more deprivation had more recorded fertility problems [rate ratio (RR) comparing most to least deprived 5.6, 95% confidence interval (CI) 4.4-7.2 at 15-20 years of age]. This reversed from age 25 to 39, when women with more deprivation had fewer recorded fertility problems (RR 0.6 95% CI 0.5-0.6 at age 30-34). After age 40, there was no socioeconomic gradient in absolute rates. LIMITATIONS, REASONS FOR CAUTION: This is by far the largest population-based study to estimate clinically recorded fertility problems in women and the first in the UK to assess variation across such a broad age group from 15 to 49 years. Our data, however, did not capture women who experience difficulty in conceiving, but do not consult their general practitioner (GP) regarding fertility problems. WIDER IMPLICATIONS OF THE FINDINGS: Compared with existing estimates, our measures of the extent and distribution of recorded fertility problems in primary care are more useful for GPs, primary care trusts and policy makers for the planning and delivery of fertility services. We have shown a high burden of infertility with little geographic variation; however, the significant burden in young, more deprived women needs recognition in light of age restrictions for treatment availability for infertility in the UK. Not only does treatment access need to be universal and more equitably allocated across socioeconomic groups, but also more resources are required to reduce fertility problems by targeting modifiable risk factors. STUDY FUNDING/COMPETING INTEREST(S): There was no direct source of funding for this research work. N.N.D. completed the work as part of an M.Sc., which was funded by Developing Solutions Scholarship provided by the International Office, University of Nottingham. J.W. is supported by a University of Nottingham/National Institute for Health Research (NIHR) Senior Clinical Research Fellowship. TRIAL REGISTRATION NUMBER: Not applicable.

How do patient and hospital features influence outcomes in small-cell lung cancer in England?

BACKGROUND: Our aim was to systematically determine how features of patients and hospitals influence access to chemotherapy and survival for people with small-cell lung cancer in England. METHODS: We linked the National Lung Cancer Audit and Hospital Episode Statistics and used multiple logistic and Cox regression analyses to assess the influence of patient and hospital features on small-cell lung cancer outcomes. RESULTS: There were 7845 patients with histologically proven small-cell lung cancer. Sixty-one percent (4820) of the patients received chemotherapy. Increasing age, worsening performance status, extensive stage and greater comorbidity all reduced the likelihood of receiving chemotherapy. There was wide variation in access to chemotherapy between hospitals in general and patients first seen in centres with a strong interest in clinical trials had a higher odds of receiving chemotherapy (adjusted odds ratio 1.42, 95% confidence interval (CI) 1.06, 1.90). Chemotherapy was associated with a lower mortality rate (adjusted hazard ratio 0.51, 95% CI 0.46, 0.56). CONCLUSION: Patients first seen at a hospital with a keen interest in clinical trials are more likely to receive chemotherapy, and chemotherapy was associated with improved survival.

Effect of maternal asthma, exacerbations and asthma medication use on congenital malformations in offspring: a UK population-based study.

BACKGROUND: Clinical advice to pregnant women with asthma is to maintain optimal therapeutic management; however, potential adverse effects of asthma treatments on fetal development remain uncertain. A study was undertaken to assess the association between maternal asthma and gestational exposure to asthma medications with risk of congenital malformation in offspring. METHODS: A matched case-control study was performed using The Health Improvement Network primary care database. Children with malformations were matched to control children on birth year, general practice and singleton or twin delivery. RESULTS: 5124 cases of liveborn children with major congenital malformations and 30,053 controls were included in the study. The risk of any malformation in children born to women with asthma was marginally higher than that in children born to women without asthma (adjusted OR 1.10, 95% CI 1.01 to 1.20). However, no association was present in children born to mothers receiving asthma treatment in the year before or during pregnancy (OR 1.06, 95% CI 0.94 to 1.20). In assessing teratogenicity of medications, no increased risk of malformation was found with gestational exposures to short- or long-acting beta agonists, inhaled corticosteroids, oral corticosteroids, other bronchodilators or cromones. These findings were similar for each of 11 system-specific malformation groups, except for an increase in musculo-skeletal system malformation associated with cromone exposure. CONCLUSIONS: Gestational exposure to commonly used asthma medications was found to be safe overall, although a moderate teratogenic risk of cromones cannot be excluded. There was some evidence of a small increased risk of congenital malformation in children born to women with asthma, but this was not explained by gestational exposure to asthma drugs.

The risk of community-acquired pneumonia among 9803 patients with coeliac disease compared to the general population: a cohort study.

BACKGROUND: Patients with coeliac disease are considered as individuals for whom pneumococcal vaccination is advocated. AIM: To quantify the risk of community-acquired pneumonia among patients with coeliac disease, assessing whether vaccination against streptococcal pneumonia modified this risk. METHODS: We identified all patients with coeliac disease within the Clinical Practice Research Datalink linked with English Hospital Episodes Statistics between April 1997 and March 2011 and up to 10 controls per patient with coeliac disease frequency matched in 10-year age bands. Absolute rates of community-acquired pneumonia were calculated for patients with coeliac disease compared to controls stratified by vaccination status and time of diagnosis using Cox regression in terms of adjusted hazard ratios (HR). RESULTS: Among 9803 patients with coeliac disease and 101 755 controls, respectively, there were 179 and 1864 first community-acquired pneumonia events. Overall absolute rate of pneumonia was similar in patients with coeliac disease and controls: 3.42 and 3.12 per 1000 person-years respectively (HR 1.07, 95% CI 0.91-1.24). However, we found a 28% increased risk of pneumonia in coeliac disease unvaccinated subjects compared to unvaccinated controls (HR 1.28, 95% CI 1.02-1.60). This increased risk was limited to those younger than 65, was highest around the time of diagnosis and was maintained for more than 5 years after diagnosis. Only 26.6% underwent vaccination after their coeliac disease diagnosis. CONCLUSIONS: Unvaccinated patients with coeliac disease under the age of 65 have an excess risk of community-acquired pneumonia that was not found in vaccinated patients with coeliac disease. As only a minority of patients with coeliac disease are being vaccinated there is a missed opportunity to intervene to protect these patients from pneumonia.

Does concurrent prescription of selective serotonin reuptake inhibitors and non-steroidal anti-inflammatory drugs substantially increase the risk of upper gastrointestinal bleeding?

BACKGROUND: A 15-fold increased risk of gastrointestinal bleeding has been reported with concurrent use of selective serotonin reuptake inhibitors and non-steroidal anti-inflammatory drugs. Recent guidance cautions against concurrent prescription, particularly in older people. AIM: To quantify the risk of gastrointestinal bleeding associated with current exposure to non-steroidal anti-inflammatory drugs, selective serotonin reuptake inhibitors, and both drugs concurrently. METHODS: We conducted a case-control analysis of 11,261 cases with upper gastrointestinal bleeding and 53,156 controls matched by gender, age and general practice from computerized primary care data. We coupled this with self-controlled case series analysis. RESULTS: Both drugs were associated with a twofold increased risk of gastrointestinal bleeding (odds ratio =2.38, 95% confidence interval 2.08-2.72 for selective serotonin reuptake inhibitors and odds ratio = 2.15, 95% confidence interval 2.02-2.28 for non-steroidal anti-inflammatory drugs). This increased risk was marginally higher for concurrent prescription (odds ratio = 2.93, 95% confidence interval 2.25-3.82). The self-controlled analysis showed a greater incidence rate ratio for gastrointestinal bleeding with non-steroidal anti-inflammatory drugs (2.71, 95% confidence interval 2.51-2.91) and lower incidence rate ratio with selective serotonin reuptake inhibitors (1.71, 95% confidence interval 1.48-1.98). The incidence rate ratio when both drugs were combined was 3.25, 95% confidence interval 1.95-5.42. Estimates were similar after restricting to people over 80 years of age. Increased risk of gastrointestinal bleeding was not specifically related to class of non-steroidal anti-inflammatory drugs and was similar when we looked at tricyclic anti-depressants. CONCLUSIONS: Our study suggests that the risk of gastrointestinal bleeding is not substantially increased when non-steroidal anti-inflammatory drugs and selective serotonin reuptake inhibitors are prescribed together, compared with their use alone.

Decreased fertility rates in 9639 women diagnosed with inflammatory bowel disease: a United Kingdom population-based cohort study.

BACKGROUND: Clinical studies have reported reduced fertility in women with inflammatory bowel disease (IBD). AIM: To compare fertility rates in women with IBD to those in women without IBD and assess whether the relative fertility differed following IBD diagnosis, flares and surgery. METHODS: Women aged 15-44 years in 1990-2010 were identified from a UK primary care database. We estimated overall and age-specific fertility rates by 5-year age bands for women with and without IBD. We used Poisson regression to calculate adjusted fertility rate ratios (AFRR), adjusted for age, smoking and socioeconomic deprivation. RESULTS: There were 46.2 live births per 1000 person-years [95% confidence interval (95% CI); 44.6-47.9] in 9639 women with IBD and 49.3 (95% CI 49.2-49.5) in 2 131 864 without (AFRR: 0.93; 95% CI: 0.89-0.96). Excluding periods of contraception use, the AFRR was 0.99 (95% CI: 0.95-1.03). Before diagnosis, the AFRR for women with ulcerative colitis (UC) was 1.07 (95% CI: 0.99-1.16) and was 0.88 (95% CI: 0.81-0.97) for women with CD. After diagnosis, AFRRs were 0.87 (95% CI: 0.82-0.94) for CD and 0.92 (95% CI: 0.86-1.00) for UC. The fertility rate was lower following flares (AFRR: 0.70; 95% CI: 0.59-0.82) or surgery (AFRR: 0.84; 95% CI: 0.77-0.92). Women with pouch and non-pouch surgery had similar overall fertility though the reduction after surgery was greater for pouches (AFRR: 0.48; 95% CI: 0.23-0.99). CONCLUSIONS: Women with Crohn's disease have marginally lower fertility rates. These rates decreased following flares and surgical interventions. Fertility rates returned almost to normal when women were not prescribed contraception but the reduction following surgical intervention remained. As the lifetime effect of pouch vs. nonpouch surgery on fertility is small, the reduction post-pouch surgery should be interpreted with caution.

Non-small cell lung cancer in young adults: presentation and survival in the English National Lung Cancer Audit.

BACKGROUND: Non-small cell lung cancer (NSCLC) in young adults is a rare but devastating illness with significant socioeconomic implications, and studies of this patient subgroup are limited. AIM: This study employed the National Lung Cancer Audit to compare the clinical features and survival of young adults with NSCLC with the older age groups. DESIGN: A retrospective cohort review using a validated national audit dataset. METHODS: Data were analysed for the period between 1 January 2004 and 31 December 2011. Young adults were defined as between 18 and 39 years, and all others were divided into decade age groups, up to the 80 years and above group. We performed logistic and Cox regression analyses to assess clinical outcomes. RESULTS: Of a total of 1 46 422 patients, 651 (0.5%) were young adults, of whom a higher proportion had adenocarcinoma (48%) than in any other age group. Stage distribution of NSCLC was similar across the age groups and 71% of young patients had stage IIIb/IV. Performance status (PS) was 0-1 for 85%. Young adults were more likely to have surgery and chemotherapy compared with the older age groups and had better overall and post-operative survival. The proportion with adenocarcinoma, better PS and that receiving surgery or chemotherapy diminished progressively with advancing decade age groups. CONCLUSION: In our cohort of young adults with NSCLC, the majority had good PS despite the same late-stage disease as older patients. They were more likely to have treatment and survive longer than older patients.

Patients' attitudes to risk in lung cancer surgery: A qualitative study.

OBJECTIVES: Lung cancer surgery leads to long term survival for some patients but little is known about how patients decide whether to accept the associated surgical risks. The objective of this qualitative study was to explore patients' attitudes to the risks associated with lung cancer surgery. METHODS: Fifteen patients with resectable lung cancer, recruited via multi-disciplinary team meetings at an English tertiary referral centre, participated in semi-structured interviews to explore their attitudes to the morbidity and mortality risks associated with lung cancer surgery. Transcripts were analysed using the framework method. RESULTS: Participants reported being 'pleased' to hear that they were suitable for surgery and felt that surgery was not a treatment to be turned down because they did not see any alternatives. Participants had some knowledge of perioperative risks, including mortality estimates; however, many voiced a preference not to know these risks and to let the medical team decide their treatment plan. Some found it difficult to relate the potential risks and complications of surgery to their own situation and appeared willing to accept high perioperative mortality risks. Generally, participants were willing to accept quite severe long-term postoperative breathlessness; however, it was apparent that many actually found this possibility difficult to imagine. CONCLUSION: Patients do not necessarily wish to know details of risks associated with lung cancer surgery and may wish to defer decisions about treatment to their medical team. Investment in the doctor-patient relationship, particularly for the surgeon, is therefore important in the management of patients with lung cancer.

Risk factors and survival outcome for non-elective referral in non-small cell lung cancer patients--analysis based on the National Lung Cancer Audit.

INTRODUCTION: Survival after diagnosis of lung cancer is poor and seemingly lower in the UK than other Western countries, due in large part to late presentation with advanced disease precluding curative treatment. Recent research suggests that around one-third of lung cancer patients reach specialist care after emergency presentation and have a worse survival outcome. Confirmation of these data and understanding which patients are affected may allow a targeted approach to improving outcomes. METHODS: We used data from the UK National Lung Cancer Audit in a multivariate logistic regression model to quantify the association of non-elective referral in non-small cell lung cancer patients with covariates including age, sex, stage, performance status, co-morbidity and socioeconomic status and used the Kaplan-Meier method and Cox proportional hazards model to quantify survival by source of referral. RESULTS: In an analysis of 133,530 cases of NSCLC who presented 2006-2011, 19% of patients were referred non-electively (following an emergency admission to hospital or following an emergency presentation to A&E). This route of referral was strongly associated with more advanced disease stage (e.g. in Stage IV - OR: 2.34, 95% CI: 2.14-2.57, p<0.001) and worse performance status (e.g. in PS 4 - OR: 7.28, 95% CI: 6.75-7.86, p<0.001), but was also independently associated with worse socioeconomic status, and extremes of age. These patients were more likely to have died within 1 year of diagnosis (hazard ratio of 1.51 (95% CI: 1.49-1.54) after adjustment for key clinical variables. CONCLUSION: Our data confirm and quantify poorer survival in lung cancer patients who are referred non-electively to specialist care, which is more common in patients with poorer performance status, higher disease stage and less advantaged socioeconomic status. Work to tackle this late presentation should be urgently accelerated, since its realisation holds the promise of improved outcomes and better healthcare resource utilisation.