Roseanne McNamee

Publications of Roseanne McNamee

• Increased Risk of Miscarriage and Ectopic Pregnancy Among Women With Irritable Bowel Syndrome.

  Authors: Ali S Khashan, Eamonn M M Quigley, Roseanne McNamee, Fergus P McCarthy, Fergus Shanahan, Louise C Kenny

  Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 02/2012;

  BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is the most commonly diagnosed gastrointestinal condition and is most prevalent in women of reproductive age. We investigated the effects of IBS onBACKGROUND & AIMS: Irritable bowel syndrome (IBS) is the most commonly diagnosed gastrointestinal condition and is most prevalent in women of reproductive age. We investigated the effects of IBS on risk for adverse outcomes from pregnancy. METHODS: We conducted a cohort study by using the United Kingdom General Practice Research Database. The study cohort consisted of 100,000 women selected by stratified random sampling from all women with a diagnosis of pregnancy from January 1, 1990-December 31, 2008. Those with a recorded diagnosis of IBS before pregnancy were identified (n = 26,543). Outcome measures were spontaneous miscarriage, ectopic pregnancy, preeclampsia, and stillbirth. Odds ratios (ORs) and 95% confidence intervals (CIs) for the association between IBS and pregnancy outcomes were estimated by using logistic regression adjusted for several potential confounders. RESULTS: Of women diagnosed with IBS before pregnancy, 6578 (7%) had a spontaneous miscarriage, 741 (0.74%) had an ectopic pregnancy, 425 (0.43%) developed preeclampsia, and 217 (0.22%) had a stillbirth. Maternal IBS was associated with a moderately increased risk of miscarriage (OR, 1.21; 95% CI, 1.13-1.30) and ectopic pregnancy (OR, 1.28%; 95% CI, 1.06-1.55). There did not appear to be an association between IBS and preeclampsia (OR, 1.09; 95% CI, 0.85-1.39) or stillbirth (OR, 1.00; 95% CI, 0.69-1.44). CONCLUSIONS: IBS, a common disorder in women of reproductive age, appears to increase the risk of miscarriage and ectopic pregnancy. These findings indicate the importance of prenatal care for women with IBS.

• Risk of affective disorders following prenatal exposure to severe life events: a Danish population-based cohort study.

  Authors: Ali S Khashan, Roseanne McNamee, Tine B Henriksen, Marianne G Pedersen, Louise C Kenny, Kathryn M Abel, Preben B Mortensen

  Journal of psychiatric research. 01/2011; 45(7):879-85.

  To examine the effect of prenatal exposure to severe life events on risk of affective disorders in the offspring. In a cohort of 1.1 million Danish births from May 1978 until December 1997, mothersTo examine the effect of prenatal exposure to severe life events on risk of affective disorders in the offspring. In a cohort of 1.1 million Danish births from May 1978 until December 1997, mothers were considered exposed if one (or more) of their close relatives died or was diagnosed with serious illness up to 6 months before conception or during pregnancy. Offspring were followed up from their 10th birthday until their death, migration, onset of affective disorder or 31 December 2007; hospital admissions were identified by linkage to the Central Psychiatric Register. Log-linear Poisson regression was used for data analysis. The risk of affective disorders was increased in male offspring whose mothers were exposed to severe life events during the second trimester (adjusted RR 1.55 [95% CI 1.05-2.28]). There was an increased risk of male offspring affective disorders in relation to maternal exposure to death of a relative in the second trimester (adjusted RR 1.74 [95% CI 1.06-2.84]) or serious illness in a relative before pregnancy (adjusted RR 1.44 [95% CI 1.02-2.05]). There was no evidence for an association between prenatal exposure to severe life events and risk of female offspring affective disorders. Our population-based study suggests that prenatal maternal exposure to severe life events may increase the risk of affective disorders in male offspring. These findings are consistent with studies of populations exposed to famine and earthquake disasters which indicate that prenatal environment may influence the neurodevelopment of the unborn child.

• Parental celiac disease and offspring sex ratio.

  Authors: Ali S Khashan, Tine B Henriksen, Roseanne McNamee, Preben B Mortensen, Fergus P McCarthy, Louise C Kenny

  Epidemiology (Cambridge, Mass.). 11/2010; 21(6):913-4.

• Performance of statistical methods for analysing survival data in the presence of non-random compliance.

  Authors: Lang'o Odondi, Roseanne McNamee

  Statistics in medicine. 10/2010; 29(29):2994-3003.

  Noncompliance often complicates estimation of treatment efficacy from randomized trials. Under random noncompliance, per protocol analyses or even simple regression adjustments for noncompliance,Noncompliance often complicates estimation of treatment efficacy from randomized trials. Under random noncompliance, per protocol analyses or even simple regression adjustments for noncompliance, could be adequate for causal inference, but special methods are needed when noncompliance is related to risk. For survival data, Robins and Tsiatis introduced the semi-parametric structural Causal Accelerated Life Model (CALM) which allows time-dependent departures from randomized treatment in either arm and relates each observed event time to a potential event time that would have been observed if the control treatment had been given throughout the trial. Alternatively, Loeys and Goetghebeur developed a structural Proportional Hazards (C-Prophet) model for when there is all-or-nothing noncompliance in the treatment arm only. Whitebiet al. proposed a 'complier average causal effect' method for Proportional Hazards estimation which allows time-dependent departures from randomized treatment in the active arm. A time-invariant version of this estimator (CHARM) consists of a simple adjustment to the Intention-to-Treat hazard ratio estimate. We used simulation studies mimicking a randomized controlled trial of active treatment versus control with censored time-to-event data, and under both random and non-random time-dependent noncompliance, to evaluate performance of these methods in terms of 95 per cent confidence interval coverage, bias and root mean square errors (RMSE). All methods performed well in terms of bias, even the C-Prophet used after treating time-varying compliance as all-or-nothing. Coverage of the latter method, as implemented in Stata, was too low. The CALM method performed best in terms of bias and coverage but had the largest RMSE.

• Undiagnosed coeliac disease in a father does not influence birthweight and preterm birth.

  Authors: Ali S Khashan, Louise C Kenny, Roseanne McNamee, Preben B Mortensen, Marianne G Pedersen, Fergus P McCarthy, Tine B Henriksen

  Paediatric and perinatal epidemiology. 07/2010; 24(4):363-9.

  There is conflicting evidence regarding the effect of coeliac disease (CD) in the father on birthweight and preterm birth. We investigated the association between paternal CD and birthweight andThere is conflicting evidence regarding the effect of coeliac disease (CD) in the father on birthweight and preterm birth. We investigated the association between paternal CD and birthweight and preterm birth. Medical records of all singleton live-born children in Denmark between 1 January 1979 and 31 December 2004 were linked to information about parents' diseases. Fathers who were diagnosed with CD were then identified. Fathers with CD were considered treated if they were diagnosed before pregnancy and untreated if they were diagnosed after the date of conception. The outcome measures were: birthweight, small-for-gestational age (birthweight<10th centile for gestational age) and preterm birth (<37 weeks). We compared the offspring of men without CD (n = 1 472 352) and offspring of those with CD [untreated (n = 138) and treated (n = 473)]. There was no significant association between untreated CD in the father and birthweight (adjusted mean difference = -3 g; [95% CI -46, 40]) or preterm birth (adjusted odds ratio (OR) = 0.86, [95% CI 0.53, 1.37]) (compared with no CD). There was some evidence for an association between treated paternal CD and birthweight (adjusted mean difference = -81 g; [95% CI -161, -3]), but not preterm birth (adjusted OR = 1.76, [95% CI 0.95, 3.26]). Untreated paternal CD was not associated with an increased risk of reduced birthweight, or of preterm birth. There was some evidence that diagnosis and presumed treatment of paternal CD with a gluten-free diet is associated with reduced birthweight.

• Comparison of work-related ill health reporting by occupational physicians and general practitioners.

  Authors: L Hussey, S Turner, K Thorley, R McNamee, R Agius

  Occupational medicine (Oxford, England). 04/2010; 60(4):294-300.

  The provision of occupational health (OH) services to the UK population is limited and concentrated in certain industries. Occupational physicians (OPs) therefore see a different subset of theThe provision of occupational health (OH) services to the UK population is limited and concentrated in certain industries. Occupational physicians (OPs) therefore see a different subset of the population than general practitioners (GPs) and their recognition of work-related ill health may differ. To examine how reports submitted by OPs and GPs compare and to discuss how biases may affect diagnostic and demographic differences. The Health & Occupation Reporting network collects information on work-related ill health. OPs and GPs report case details, including demographic information, occupation, industry and suspected agent/task/event. Differences in reporting patterns were assessed. Musculoskeletal and mental ill-health reports made up over 80% of reports to both schemes although the likelihood ratio (LR) showed OPs were 78% more likely to report a psychological case than GPs. OPs were also more (18%) likely to report a female case. Health & social care was the industry most frequently reported by both groups; however, this was in greatly differing proportions (OPs 38%, GPs 14%). When LRs were adjusted for industry, this reduced the likelihood of an OP reporting cases of mental ill health (to 40%) and found them 10% less likely to report females than GPs. OP and GP reporting patterns highlight the variation in OH provision and its influence on the data provided. OPs are best placed to report on health and work relationships; however, as some sectors have poor access to OH services, reports from suitably trained GPs will help inform about this 'blind spot'.

• Time-sampled versus continuous-time reporting for measuring incidence.

  Authors: Roseanne McNamee, Yiqun Chen, Louise Hussey, Raymond Agius

  Epidemiology (Cambridge, Mass.). 03/2010; 21(3):376-8.

  Accuracy of incidence estimates may be affected by biases that depend on frequency of approach to reporters and reporting window length. A time-sampling strategy enables infrequent approaches withAccuracy of incidence estimates may be affected by biases that depend on frequency of approach to reporters and reporting window length. A time-sampling strategy enables infrequent approaches with short windows but has never been evaluated. A randomized crossover trial compared incidence estimates of work-related diseases using time-sampled versus continuous-time reporting. Physicians were randomly allocated either to report every month (12/12) in 2004 and for 1 randomly chosen month (1/12) in 2005, or to the reverse sequence. Numbers of new cases of work-related disease reported per reporter per month for 1/12 and 12/12 reporting periods were compared. Response rates were high (87%). Withdrawal from the study was higher under 12/12 reporting. The rate ratio for 1/12 versus 12/12 reporting was 1.26 (95% confidence interval = 1.11-1.42). Rates declined gradually in the 12/12 groups over the year, consistent with reporting fatigue. Increased frequency of data collection may reduce incidence estimates.

• Agreement in diagnosing occupational asthma by occupational and respiratory physicians who report to surveillance schemes for work-related ill-health.

  Authors: Susan Turner, Roseanne McNamee, Catherine Roberts, Lisa Bradshaw, Andrew Curran, Mandy Francis, David Fishwick, Raymond Agius

  Occupational and environmental medicine. 11/2009;

  OBJECTIVES: To assess diagnostic agreement for occupational asthma (OA) by physicians within and between clinical disciplines, and to identify case and rater characteristics associated with making anOBJECTIVES: To assess diagnostic agreement for occupational asthma (OA) by physicians within and between clinical disciplines, and to identify case and rater characteristics associated with making an OA diagnosis. METHODS: Anonymised summaries for 19 possible OA cases were sent to 51 occupational physicians (OPs) and 53 respiratory physicians (RPs). In phase 1, raters were asked to assign a likelihood score (0-100%) of OA for 4 case histories; in phase 2, raters were asked again after seeing investigative procedures/results for 2 of their cases. Interclass correlation coefficients were calculated as statistical measures of reliability for OA scores. Comparisons between mean scores for OPs and RPs were assessed for statistical significance using tests based on multilevel models. Relative risks were calculated to summarise effects of raters' demographics on OA diagnosis, and of supplying investigative procedures/results. RESULTS: OA scores from OPs and RPs were not systematically different. Mean overall OA scores from phase 1 were 52.1% (OPs) and 50.0% (RPs), the difference (OPs'-RPs'mean) was 2.1% (95%CI: -2.6,6.8 p=0.37). In phase 2, mean overall OA scores for OPs and RPs were 46.1% and 41.5%; the difference (OPs'-RPs'mean) was 4.6% (95%CI: -3.5,12.5 p=0.27). Raters with GMC registration >/=1986 were more likely to give a positive OA diagnosis, and in phase 2 males were much more likely to label a case as OA than females RR=4.5 (95%CI;3.3-6.0). CONCLUSIONS: The RR of a positive OA diagnosis was not affected by clinical specialty (OP/RP), however there was only limited agreement between physicians within each group. Further work on what triggers physicians to consider a case as OA will assist better diagnosis and prevention of this disease.

• Work-related mental ill-health and 'stress' in the UK (2002-05).

  Authors: Melanie Carder, Susan Turner, Roseanne McNamee, Raymond Agius

  Occupational medicine (Oxford, England). 09/2009;

  BACKGROUND: There is concern about the frequency of work-related mental ill-health and 'stress' within the UK. AIMS: To provide a measure of the incidence of work-related mental ill-health reportedBACKGROUND: There is concern about the frequency of work-related mental ill-health and 'stress' within the UK. AIMS: To provide a measure of the incidence of work-related mental ill-health reported by specialist psychiatrists and occupational physicians to UK voluntary reporting schemes during the period 2002-05. Additionally, an investigation of determinants, notably factors identified by reporters as precipitants in cases of work-related mental ill-health was undertaken. METHODS: The study used data collected by The Health and Occupation Reporting Network (THOR) from 2002 to 2005. Cases were analysed by age, gender, industry and precipitating event. RESULTS: Estimated annual average incidence rates and 95% confidence intervals of work-related mental ill-health diagnoses reported to THOR between 2002 and 2005 by psychiatrists were 89 (78, 101) per million and by occupational physicians were 1589 (1443, 1735) per million. For both groups of reporters, anxiety and depression continued to make up the largest proportion of diagnoses. The majority of cases were attributed to factors such as workload and difficulties with other workers. There was some suggestion that the type of factors associated with the mental ill-health case reports varied between industrial sectors. CONCLUSIONS: Work-related anxiety and depression and stress continue to constitute a significant proportion of all work-related mental ill-health diagnoses in the UK, with workload and interpersonal relationships reported as significant risk factors. Further investigations may determine whether guidance for employers and employees on work-related mental ill-health would benefit from being more industry specific.

• Does socio-economic status modify the effect of particulate air pollution on cardiorespiratory mortality?

  Authors: Melanie Carder, Roseanne McNamee, Iain Beverland, Robert A Elton, Geoff Cohen, James Boyd, Martie van van Tongeren, Raymond M Agius

  Occupational and environmental medicine. 09/2009;

  OBJECTIVES: To investigate whether deprivation index modifies the acute effect of black smoke on cardiorespiratory mortality. METHODS: Generalised linear Poisson regression models were used toOBJECTIVES: To investigate whether deprivation index modifies the acute effect of black smoke on cardiorespiratory mortality. METHODS: Generalised linear Poisson regression models were used to investigate whether deprivation index (as measured by the Carstairs deprivation index) modified the acute effect of black smoke on mortality in the two largest Scottish cities (Glasgow and Edinburgh) between January 1981 and December 2001. Lag periods of up to one month were assumed for the effects of black smoke. RESULTS: Deprivation index significantly modified the effect of black smoke on mortality with black smoke effects generally increasing as level of deprivation increased. The interaction coefficient from a parametric model assuming a linear interaction between black smoke (microgm-3) and deprivation in their effect on mortality - equivalent to a test of 'linear trend' across Carstairs Categories - was significant for all mortality outcomes. In a model where black smoke effects were estimated independently for each deprivation category, the estimated increase in respiratory mortality over the ensuing one-month period associated with a 10microgm-3 increase in the mean black smoke concentration was 8.0 percent (95% CI: 5.1, 10.9) for subjects residing in the 'most' deprived category (Carstairs category 7) compared to 3.7 percent (95% CI: -0.7, 8.4) for subjects residing in the 'least' deprived category (Carstairs category 1). CONCLUSIONS: The results suggest a stronger effect of black smoke on mortality among people living in more deprived areas. The effect was greatest for respiratory mortality although significant trends were also seen for other groups. If corroborated, these findings could have important public health implications.

• Intention to treat, per protocol, as treated and instrumental variable estimators given non-compliance and effect heterogeneity.

  Authors: Roseanne McNamee

  Statistics in medicine. 08/2009;

  We consider the behaviour of three approaches to efficacy estimation-using so-called 'as treated' (AT), 'per protocol' (PP) and 'instrumental variable' (IV) analyses-and of the Intention to TreatWe consider the behaviour of three approaches to efficacy estimation-using so-called 'as treated' (AT), 'per protocol' (PP) and 'instrumental variable' (IV) analyses-and of the Intention to Treat estimator, in a two-arm randomized treatment trial with a Normally distributed outcome when there is treatment effect heterogeneity and non-random compliance with assigned treatment. Formulae are derived for the bias of estimators when used either to estimate average treatment effect (ACE) or to estimate complier average treatment effect (CACE) under several models for the relationship between compliance and potential outcomes. These enable the expected values of AT, PP and IV estimators to be ranked in relation to ACE, and show that AT and PP estimators are generally biased for both ACE and CACE even under homogeneity. However, we show that the difference between any pair of (AT, PP, IV) estimates can be used to estimate the correlation between the latent variable determining compliance behaviour and one potential outcome. In the absence of measures that predict compliance, bounds for ACE can only be set given strong assumptions. Regarding the Intention to Treat estimator, while this is 'biased towards the null' if viewed as a measure of CACE, we show that it is not always so in relation to ACE. Finally we discuss the behaviour of the estimators under weak and strong null hypotheses. Copyright (c) 2009 John Wiley & Sons, Ltd.

• Work-related ill health in general practice, as reported to a UK-wide surveillance scheme.

  Authors: Louise Hussey, Susan Turner, Kevan Thorley, Roseanne McNamee, Raymond Agius

  The British journal of general practice : the journal of the Royal College of General Practitioners. 10/2008; 58(554):637-40.

  GPs with training in occupational medicine report cases of work-related ill health and sickness absence to The Health and Occupation Reporting network in General Practice (THOR-GP) using an onlineGPs with training in occupational medicine report cases of work-related ill health and sickness absence to The Health and Occupation Reporting network in General Practice (THOR-GP) using an online webform. This report describes the data reported in 2006 and 2007. GPs mainly reported musculoskeletal disorders and mental ill-health. A much larger proportion of the mental ill-health cases were sickness-absence certified, making up 55.9% of the total days certified. Musculoskeletal disorders are the most frequently reported diagnoses of work-related ill health, but mental ill-health is responsible for most work-related sickness absence.

• Reduced infant birthweight consequent upon maternal exposure to severe life events.

  Authors: Ali S Khashan, Roseanne McNamee, Kathryn M Abel, Marianne G Pedersen, Roger T Webb, Louise C Kenny, Preben Bo Mortensen, Philip N Baker

  Psychosomatic medicine. 08/2008; 70(6):688-94.

  OBJECTIVE: To investigate the association between maternal exposure to severe life events and fetal growth (birthweight and small for gestational age). Stress has been associated with adverseOBJECTIVE: To investigate the association between maternal exposure to severe life events and fetal growth (birthweight and small for gestational age). Stress has been associated with adverse pregnancy outcome. METHODS: Mothers of 1.38 million singleton live births in Denmark between January 1, 1979 and December 31, 2002 were linked to information on their spouses, parents, siblings, and older children. Exposure was defined as death or serious illness in a relative during pregnancy or in the 6 months before conception. Linear regression was used to examine the effect of exposure on birthweight. Log-linear binomial regression was used to assess the effect of exposure on small for gestational age. RESULTS: Death of a relative during pregnancy or in the 6 months before conception reduced birthweight by 27 g (adjusted estimate -27 g, 95% Confidence Interval (CI) = -33, -22). There was a significant association between maternal exposure to death of a relative and risk of a baby weighing below the 10th percentile (adjusted relative risk (RR) = 1.17, 95% CI = 1.13, 1.22) and 5th percentile (adjusted RR = 1.22, 95% CI = 1.15, 1.29). CONCLUSIONS: Mothers exposed to severe life events before conception or during pregnancy have babies with significantly lower birthweight. If this association is causal, the potential mechanisms of stress-related effects on birthweight include changes in lifestyle due to the exposure and stress-related dysregulation of the hypothalamic-pituitary-adrenal axis during pregnancy.

• Bias in frequently reported analyses of subfertility trials.

  Authors: Sofia Dias, Roseanne McNamee, Andy Vail

  Statistics in medicine. 08/2008;

  Randomized controlled trials in subfertility are often designed so that participants in each trial arm are offered the randomized treatment for up to k cycles, until success occurs. In clinicalRandomized controlled trials in subfertility are often designed so that participants in each trial arm are offered the randomized treatment for up to k cycles, until success occurs. In clinical journals, success probabilities are often reported 'per cycle' and inferential procedures carried out as if all cycles were independent. However, this assumption does not hold. In this paper we consider the implications of such an assumption when we have a heterogeneous (Beta) patient population. We conducted a simulation study to assess the bias of estimates of the risk difference, risk ratio and odds ratio calculated using the total number of randomized women or the total number of treatment cycles as the unit of analysis, as well as the coverage of their confidence intervals (CIs). We found that the commonly reported 'per cycle' analyses are more biased and have poorer coverage of the CIs than the analyses based on the total number of women, in heterogeneous populations. Such information will help researchers who wish to interpret publications when the number of randomized participants is not extractable. Copyright (c) 2008 John Wiley & Sons, Ltd.

• Measurement of trends in incidence of work-related skin and respiratory diseases, UK 1996-2005.

  Authors: Roseanne McNamee, Melanie Carder, Yiqun Chen, Raymond Agius

  Occupational and environmental medicine. 05/2008;

  ABSTRACT OBJECTIVES: The ability to measure temporal trends in disease incidence is important but valid methods are needed. We investigated UK trends during 1996-2005 in work-related skin andABSTRACT OBJECTIVES: The ability to measure temporal trends in disease incidence is important but valid methods are needed. We investigated UK trends during 1996-2005 in work-related skin and respiratory diseases including non-malignant pleural disease, asthma, mesothelioma and pneumoconiosis and the potential for bias when using surveillance systems for this purpose. METHODS: The volunteer reporters in three surveillance schemes were specialist physicians for skin diseases, respiratory diseases and occupational physicians respectively, who provided monthly reports of new cases of disease which they considered work-related. Poisson regression models were used to investigate variation by calendar year (trend), season and reporter characteristics. Separately, temporal patterns in the probabilities of non-response and zero reports were investigated. Annual changes in disease incidences were compared between reporter groups. RESULTS: There was little evidence of change in incidences of non-malignant pleural disease, mesothelioma, skin neoplasia and urticaria but falls were seen for contact dermatitis and pneumoconiosis. Although the direction of changes were similar across reporter groups, the magnitude of annual change in incidence was often not consistent: for occupational asthma, it was -1.9% (95% CI: -5.2,1.4) and -12.1% (95% CI:-19.5,-4.1) using respiratory and occupational physician reports respectively. Response rates were high (~85%) but non-response increased slightly with membership time, as did the probability of a zero return in some groups. Adjustment of results for presumed reporting fatigue led to an upward correction in some calendar trends. CONCLUSIONS: Some estimated changes in incidence based on volunteer reporting may be biased by reporting fatigue; therefore apparent downward trends need to be interpreted cautiously. Differences in the population bases of the surveillance schemes and UK health service capacity constraints may also explain differences in trends found here. (277 words).

• Occupation and male infertility: glycol ethers and other exposures.

  Authors: Nicola Cherry, Harry Moore, Roseanne McNamee, Allan Pacey, Gary Burgess, Julie-Ann Clyma, Martin Dippnall, Helen Baillie, Andrew Povey

  Occupational and environmental medicine. 04/2008;

  OBJECTIVES: To investigate the relation between male infertility and occupational exposures, particularly glycol ethers. METHODS: A case-referent study was designed in which men attending 14OBJECTIVES: To investigate the relation between male infertility and occupational exposures, particularly glycol ethers. METHODS: A case-referent study was designed in which men attending 14 fertility clinics in 11 centres across the United Kingdom in 1999-2002 were recruited following 12 months of unprotected intercourse and without a previous semen analysis. Cases were those with low motile sperm concentration (MSC) relative to the time since their last ejaculation (MSC<12x 106 for 3 days of abstinence). Referents were other men attending these clinics and meeting the inclusion criteria. A single semen sample was collected at the clinic and analysed at the andrology laboratory serving each hospital. Concentration was determined manually with motility assessed centrally from video recordings. Exposures and confounding factors were assessed from self completed and nurse-interviewer questionnaires, completed prior to the results of the semen analysis. The occupational histories were assessed for exposures relative to UK norms by a team of occupational hygienists blind to case status. RESULTS: Of 2118 men in employment at the time of the interview, 874 (41.3%) were cases. Work with organic solvents, particularly glycol ethers, in the 3 months before the first clinic visit was associated with the likelihood of low motile sperm count. Unadjusted odds ratios (OR) for moderate and high glycol ether exposure (compared with none) were 1.70 (95%CI 1.11-2.61) and 2.54 (95%CI 1.24 - 5.21). Adjustment for potential confounders (surgery to the testes, previous conception, wearing boxer shorts, drinking alcohol, employed in manual work) reduced the risk associated with glycol ether exposure: moderate OR=1.46 (95%CI 0.93-2.28) high OR=2.25 (95%CI 1.08-4.69). No other occupational risk factor was identified. CONCLUSIONS: Glycol ether exposure was related to low motile sperm count in men attending fertility clinics. This suggests that, at the time of the study, glycol ethers continued to be a hazard for male fertility.

• Higher risk of offspring schizophrenia following antenatal maternal exposure to severe adverse life events.

  Authors: Ali S Khashan, Kathryn M Abel, Roseanne McNamee, Marianne G Pedersen, Roger T Webb, Philip N Baker, Louise C Kenny, Preben Bo Mortensen

  Archives of general psychiatry. 03/2008; 65(2):146-52.

  CONTEXT: Most societies believe that a mother's psychological state can influence her unborn baby. Severe adverse life events during pregnancy have been consistently associated with an elevated riskCONTEXT: Most societies believe that a mother's psychological state can influence her unborn baby. Severe adverse life events during pregnancy have been consistently associated with an elevated risk of low birth weight and prematurity. Such events during the first trimester have also been associated with risk of congenital malformations. OBJECTIVE: To assess the effect in offspring of antenatal maternal exposure to an objective measure of stress on risk of adverse neurodevelopment, specifically schizophrenia. We hypothesized that the strongest relationship would be to maternal exposures during the first trimester. DESIGN: Population-based study. SETTING: Denmark. PARTICIPANTS: In a cohort of 1.38 million Danish births from 1973 to 1995, mothers were considered exposed if 1 (or more) of their close relatives died or was diagnosed with cancer, acute myocardial infarction, or stroke syndrome up to 6 months before conception or during pregnancy. Offspring were followed up from their 10th birthday until their death, migration, onset of schizophrenia, or June 30, 2005; admissions were identified by linkage to the Central Psychiatric Register. Main Outcome Measure Schizophrenia. RESULTS: The risk of schizophrenia and related disorders was raised in offspring whose mothers were exposed to death of a relative during the first trimester (adjusted relative risk, 1.67 [95% confidence interval, 1.02-2.73]). Death of a relative during other trimesters or up to 6 months before pregnancy were not linked with a higher risk of schizophrenia. CONCLUSIONS: Our population-based study suggests that severe stress to a mother during the first trimester may alter the risk of schizophrenia in offspring. This finding is consistent with ecological evidence from whole populations exposed to severe stressors and suggests that environment may influence neurodevelopment at the feto-placental-maternal interface.

• Instrumental Variables vs. Grouping Approach for Reducing Bias Due to Measurement Error

  Authors: Evridiki Batistatou, Roseanne McNamee

  International Journal of Biostatistics. 02/2008; 4(1).

  Attenuation of the exposure-response relationship due to exposure measurement error is often encountered in epidemiology. Given that error cannot be totally eliminated, bias correction methods ofAttenuation of the exposure-response relationship due to exposure measurement error is often encountered in epidemiology. Given that error cannot be totally eliminated, bias correction methods of analysis are needed. Many methods require more than one exposure measurement per person to be made, but the `group mean OLS method,' in which subjects are grouped into several a priori defined groups followed by ordinary least squares (OLS) regression on the group means, can be applied with one measurement. An alternative approach is to use an instrumental variable (IV) method in which both the single error-prone measure and an IV are used in IV analysis. In this paper we show that the `group mean OLS' estimator is equal to an IV estimator with the group mean used as IV, but that the variance estimators for the two methods are different. We derive a simple expression for the bias in the common estimator which is a simple function of group size, reliability and contrast of exposure between groups, and show that the bias can be very small when group size is large. We compare this method with a new proposal (group mean ranking method), also applicable with a single exposure measurement, in which the IV is the rank of the group means. When there are two independent exposure measurements per subject, we propose a new IV method (EVROS IV) and compare it with Carroll and Stefanski's (CS IV) proposal in which the second measure is used as an IV; the new IV estimator combines aspects of the `group mean' and `CS' strategies. All methods are evaluated in terms of bias, precision and root mean square error via simulations and a dataset from occupational epidemiology. The `group mean ranking method' does not offer much improvement over the `group mean method.' Compared with the `CS' method, the `EVROS' method is less affected by low reliability of exposure. We conclude that the group IV methods we propose may provide a useful way to handle mismeasured exposures in epidemiology with or without replicate measurements. Our finding may also have implications for the use of aggregate variables in epidemiology to control for unmeasured confounding.

• Evidence of improving quality of reporting of randomized controlled trials in subfertility.

  Authors: Sofia Dias, Roseanne McNamee, Andy Vail

  Human reproduction (Oxford, England). 11/2006; 21(10):2617-27.

  BACKGROUND: The quality of randomized controlled trials (RCTs) in subfertility and their suitability for inclusion in meta-analyses have been assessed in the past and found to be insufficient. OurBACKGROUND: The quality of randomized controlled trials (RCTs) in subfertility and their suitability for inclusion in meta-analyses have been assessed in the past and found to be insufficient. Our aim was to assess whether this quality has improved over time, particularly since the publication of the Consolidated Standards of Reporting Trials (CONSORT) statement, and to assess what proportion of trials could be included in the meta-analyses of pregnancy outcomes such as those included in Cochrane Reviews. METHODS: A selection of subfertility trials published in 1990, 1996 and 2002 was collected from the Cochrane Menstrual Disorder and Subfertility Group (MDSG) database. Only trials published in English as full journal articles, claiming to be randomized and reporting on pregnancy outcomes, were included. RESULTS: One hundred and sixty-four trials met our inclusion criteria. Twenty-four (15%) were found not to be randomized, despite claims, and only 10 trials (6%) provided adequate details on the methods of randomization and allocation concealment. Of these, only three had sufficient details extractable to allow for an intention-to-treat analysis of the outcome 'live birth'. CONCLUSIONS: Although an improvement in some subfertility-specific issues was observed, the quality of reporting of RCTs still needs to improve to make them suitable for inclusion in meta-analyses such as those in the Cochrane Library.

• Assessing the reliability of ordered categorical scales using kappa-type statistics.

  Authors: Chris Roberts, Roseanne McNamee

  Statistical methods in medical research. 11/2005; 14(5):493-514.

  Methods for the analysis of reliability of ordered categorical scales are discussed, focussing on the limitation of the single summary-weighted kappa coefficients. A symmetric matrix of kappa-typeMethods for the analysis of reliability of ordered categorical scales are discussed, focussing on the limitation of the single summary-weighted kappa coefficients. A symmetric matrix of kappa-type coefficients is suggested as an alternative. The method is proposed as being suitable for ordinal scale where there is no underlying continuum. Their application is illustrated using two data sets from reliability studies. If, instead, distances between categories can be specified, a weighted mean of the matrix terms can be used as a summary measure. This is equal to a weighted kappa coefficient with squared weights, provided distances between adjacent categories are equal. When a study design corresponds to a one-way random effects model, estimates of precision of kappa-type coefficient, including the coefficients described here, can be obtained using the delta-method, bootstrap resampling by subjects or jack-knifing by subjects. In the case of interobserver reliability studies, where there may be systematic differences between observers, the investigator may wish to generalise to a population of observers and subjects. In this case, jack-knifing by observer and subject is suggested. Empirical comparisons are made between standard error estimates based on the delta-method, on jack-knifing by subjects and a two-way jack-knife by subjects and observers. The results suggest that standard errors based on the delta-method or jack-knifing by subject alone may be overly precise.