Point Estimates Of Odds Ratio Research Articles

The impact of isolated obesity compared with obesity and other risk factors on risk of stillbirth: a retrospective cohort study.

Maternal obesity is associated with stillbirth, but uncertainty persists around the effects of higher obesity classes. We sought to compare the risk of stillbirth associated with maternal obesity alone versus maternal obesity and additional or undiagnosed factors contributing to high-risk pregnancy. We conducted a retrospective cohort study using the Better Outcomes Registry and Network (BORN) for singleton hospital births in Ontario between 2012 and 2018. We used multivariable Cox proportional hazard regression and logistic regression to evaluate the relationship between prepregnancy maternal body mass index (BMI) class and stillbirth (reference was normal BMI). We treated maternal characteristics and obstetrical complications as independent covariates. We performed mediator analyses to measure the direct and indirect effects of BMI on stillbirth through major common-pathway complications. We used fully adjusted and partially adjusted models, representing the impact of maternal obesity alone and maternal obesity with other risk factors on stillbirth, respectively. We analyzed data on 681 178 births between 2012 and 2018, of which 1956 were stillbirths. Class I obesity was associated with an increased incidence of stillbirth (adjusted hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.35-1.78). This association was stronger for class III obesity (adjusted HR 1.80, 95% CI 1.44-2.24), and strongest for class II obesity (adjusted HR 2.17, 95% CI 1.83-2.57). Plotting point estimates for odds ratios, stratified by gestational age, showed a marked increase in the relative odds for stillbirth beyond 37 weeks' gestation for those with obesity with and without other risk factors, compared with those with normal BMI. The impact of potential mediators was minimal. Maternal obesity alone and obesity with other risk factors are associated with an increased risk of stillbirth. This risk increases with gestational age, especially at term.

Risk of Major Congenital Malformations Associated with the Use of Japanese Traditional (Kampo) Medicine Containing Ephedra During the First Trimester of Pregnancy.

Japanese traditional (Kampo) medicines containing ephedra may be used to treat colds during pregnancy. There are reports that ephedrine, a component of ephedra, has a risk of teratogenicity; however, the evidence remains equivocal. This study aimed to evaluate the risk of major congenital malformations (MCMs) associated with exposure to Kampo medicines containing ephedra during the first trimester of pregnancy using the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study). To 23,730 mother-infant pairs who participated in the TMM BirThree Cohort Study from July 2013 to March 2017, questionnaires in early and middle pregnancy were distributed approximately at weeks 12 and 26 of pregnancy, respectively. Infants' risk of MCMs in women who used Kampo medicines containing ephedra or acetaminophen during the first trimester was assessed, and the odds ratios (ORs) were estimated with unadjusted and adjusted analyses. Among 20,879 women, acetaminophen and Kampo medicines containing ephedra were used in 665 (3.19%) and 376 (1.80%) women, respectively, in the first trimester. Among the infants born to the mothers who used acetaminophen or Kampo medicine containing ephedra during the first trimester, 11 (1.65%) and 8 (2.13%), respectively, had overall MCMs. OR of overall MCMs was higher in women who used Kampo medicines containing ephedra than in those who used acetaminophen in the first trimester (adjusted OR, 1.45; 95% confidence interval (CIs), 0.57-3.71); however, the difference was not statistically significant. In this study, there was no statistically significant association between the use of Kampo medicines containing ephedra during the first trimester of pregnancy and the risk of MCMs. Although some point estimates of ORs exceeded 1.00, the absolute magnitude of any increased risks would be low.

MP76-17 SUCCESSFUL OUTCOMES IN ACUTE URINARY RETENTION (AUR) PATIENTS TREATED WITH THE PROSTATIC URETHRAL LIFT (PUL) ARE ASSOCIATED WITH EARLIER INTERVENTION

You have accessJournal of UrologyCME1 Apr 2023MP76-17 SUCCESSFUL OUTCOMES IN ACUTE URINARY RETENTION (AUR) PATIENTS TREATED WITH THE PROSTATIC URETHRAL LIFT (PUL) ARE ASSOCIATED WITH EARLIER INTERVENTION Oliver (Olly) Kayes, Neil Barber, Rajesh Kavia, Toby Page, Nikesh Thiruchelvam, Gregg Eure, and Mark Rochester Oliver (Olly) KayesOliver (Olly) Kayes More articles by this author , Neil BarberNeil Barber More articles by this author , Rajesh KaviaRajesh Kavia More articles by this author , Toby PageToby Page More articles by this author , Nikesh ThiruchelvamNikesh Thiruchelvam More articles by this author , Gregg EureGregg Eure More articles by this author , and Mark RochesterMark Rochester More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003350.17AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: AUR represents a subset of difficult patients with BPH-LUTS who require rapid restoration of voiding. Shifting to a day case procedure such as PUL with demonstrated safety and efficacy in AUR patients, may accelerate treatment pathways without compromising patient outcomes. As such, appropriate selection criteria are desired to help urologists better gauge how AUR patients may respond to PUL. Here, we examine patient and procedural characteristics that underpin treatment success in AUR patients who underwent PUL. METHODS: A logistical regression model was constructed to evaluate factors associated with outcomes predicting success following PUL (i.e., catheter and surgery free at 12 months). Covariates for subjects in the PULSAR study (single arm PUL in AUR; n=51) as well as retention patients in the real-world registry (RWRr; n=388) included age, prostate volume, proxies of BPH disease severity (IPSS, IPSS QoL, Qmax, PSA, PVR), medical history (duration of catheterization), and procedural details (implants placed, procedure time, voiding efficiency). Results were reported as odds ratio point estimates with statistical significance quantified using chi-squared tests. RESULTS: After PUL, 73% of PULSAR subjects were catheter and surgery free at 12 months with success associated with higher voiding efficiency during the perioperative period. Slightly higher catheter-free rates (80%) were seen in RWRr patients and variables that influenced success encompassed age <70 years at procedure, lower baseline PSA, lower baseline PVR, and shorter pre-procedural catheter duration. Logistic regression for the combined PULSAR and RWRr retention groups revealed success associated with procedural age <70 yr and higher voiding efficiency. Stepwise multivariate regression analysis did not reveal any significant associations (Table 1). CONCLUSIONS: Advanced age, higher baseline PSA and PVR, and longer pre-procedure catheter durations drive suboptimal PUL outcomes in AUR patients. Voiding efficiencies following PUL may also help to ascertain long-term response after treatment. In men deemed suitable for PUL treatment, these new selection criteria may provide more men in AUR with earlier access to safe and effective BPH surgery. Source of Funding: Teleflex, Inc © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1098 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Oliver (Olly) Kayes More articles by this author Neil Barber More articles by this author Rajesh Kavia More articles by this author Toby Page More articles by this author Nikesh Thiruchelvam More articles by this author Gregg Eure More articles by this author Mark Rochester More articles by this author Expand All Advertisement PDF downloadLoading ...

Prevalence of heart failure phenotypes and current use of therapies in primary care: results from a nationwide study.

Heart failure (HF) is an increasing concern worldwide. A rising HF burden is expected due to the prospected future demographic changes with aging populations. Consequently, the long-term follow-up and treatment will be performed increasingly by primary care physicians in the future. Contemporary data on HF patients in primary care are needed to plan and ensure an effective and safe follow-up of future patients. The electronic patient journals of 148 primary care clinics in Denmark were searched in a standardized manner to identify patients with HF [code K77 of the International Classification of Primary Care, Second Edition]. Prespecified variables including demographic information, clinical variables, co-morbidities, prescribed medications, and setting of follow-up were recorded. In total, 1111 patients were included in the study. The mean timepoint for the HF diagnosis was August 2018. In 95% of cases, the diagnosis of HF was made in a specialized setting. The echocardiogram data used for phenotyping were available in 1042 (94%) of the 1111 patients. HF with reduced ejection fraction (HFrEF) was present in 43%, recovered HFrEF in 31%, and HF with mildly reduced (HFmrEF) or preserved ejection fraction (HFpEF) in 26%. In patients with HFrEF or recovered HFrEF, fundamental treatments were prescribed in 86% for angiotensin converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), or angiotensin receptor neprilysin inhibitor (ARNI), in 82% for beta-blocker, in 38% for mineralocorticoid receptor antagonist (MRA), and in 12% for sodium-glucose co-transporter-2 inhibitor (SGLT2i). Older patients were treated to a significantly lesser extent than young patients for all drug classes [odds ratio (OR) point estimates 0.50 to 0.69, all P-values<0.05]. In patients with HFmrEF or HFpEF, an ACEI, ARB, or ARNI was prescribed in 67%, beta-blocker in 67%, MRA in 22%, and SGLT2i in 7.4% with significantly lower probability of treatment compared to patients with HFrEF or recovered HFrEF [OR point estimates 0.33 to 0.57, all P-values<0.05]. The setting of follow-up was available in 96% of patients. Irrespective of HF phenotype, follow-up was performed solely in primary care in 64%. These patients were generally treated to a lesser extent with HF therapies compared with patients where follow-up included specialized care, yet differences were generally small. HFrEF is the most common phenotype of HF in primary care followed by recovered HFrEF and fundamental therapies are markedly underutilized. Initiatives to increase the use of recommended therapies are needed to improve the future care of patients with HF.

Incidence and Complications of Atrial Fibrillation in a Low Socioeconomic and High Disability United States (US) Population: A Combined Statistical and Machine Learning Approach.

Background Poor socioeconomic status coupled with individual disability is significantly associated with incident atrial fibrillation (AF) and AF-related adverse outcomes, with the information currently lacking for US cohorts. We examined AF incidence/complications and the dynamic nature of associated risk factors in a large socially disadvantaged US population. Methods A large population representing a combined poor socioeconomic status/disability (Medicaid program) was examined from diverse geographical regions across the US continent. The target population was extracted from administrative databases with patients possessing medical/pharmacy benefits. This retrospective cohort study was conducted from Jan 1, 2016, to Sep 30, 2021, and was limited to 18- to 80-year age group drawn from the Medicaid program. Descriptive and inferential statistics (parametric: logistic regression and neural network) were applied to all computations using a combined statistical and machine learning (ML) approach. Results A total of 617413 individuals participated in the study, with mean age of 41.7 years (standard deviation “SD” 15.2) and 65.6% female patients. Seven distinct groups were identified with different combinations of low socioeconomic status and disability constraints. The overall crude AF incidence rate was 0.49 cases/100 person-years (95% confidence limit “CI” 0.40–0.58), with the lowest rate for the younger group (temporary assistance for needy family “TANF”) (0.20, 95%CI 0.18–0.21), the highest rates for the older groups (age, blindness, or disability “ABD” duals—1.51, 95% CI 1.31–1.58; long-term services and support “LTSS” duals—1.45, 95% CI 1.31–1.58), and the remaining four other groups in between the lower and upper rates. Based on independent effects after accounting for confounders in main effect modeling, the point estimates of odds ratios for AF status with various clinical outcomes were as follows: stroke (2.69, 95% CI 2.53–2.85); heart failure (6.18, 95% CI 5.86–6.52); myocardial infarction (3.71, 95% CI 3.49–3.94); major bleeding (2.26, 95% CI 2.14–2.38); and cognitive impairment (1.74, 95% CI 1.59–1.91). A logistic regression-based ML model produced excellent discriminant validity for high-risk AF outcomes (c “concordance” index based on training data 0.91, 95%CI 0.891–0.929), together with similar measures for external validity, calibration, and clinical utility. The performance measures for the ML models predicting associated complications with high-risk AF cases were good to excellent. Conclusions A combination of low socioeconomic status and disability contributes to AF incidence and complications, elevating risks to higher levels relative to the general population. ML algorithms can be used to identify AF patients at high risk of clinical events. While further research is definitely in need on this socially important issue, the reported investigation is unique in which it integrates the general case about the subject due to the different ethnic groups around the world under a unified culture stemming from residing in the US.

Examination of Correlates of OUD Outcomes in Young Adults: Secondary Analysis From the XBOT Trial.

Opioid use disorder (OUD) treatment outcomes are poorer for young adults than older adults. Developmental differences are broadly implicated, but particular vulnerability factor interactions are poorly understood. This study sought to identify moderators of OUD relapse between age groups. This secondary analysis compared young adults (18-25) to older adults (26+) from a comparative effectiveness trial ("XBOT") that randomized (N = 570) participants to extended-release naltrexone or sublingual buprenorphine-naloxone. We explored the relationship between 25 prespecified patient baseline characteristics and relapse to regular opioid use by age group and treatment condition, using logistic regression. Young adults (n = 111) had higher rates of 24-week relapse than older adults (n = 459) (70.3% vs 58.8%) and differed on a number of specific characteristics, including more smokers, more intravenous opioid use, and more cannabis use. No significant moderators predicted relapse, in either three-way or two-way interactions. No baseline factors were identified as moderating the relationship between age group and opioid relapse, nor any interactions between baseline characteristics, age group, and treatment condition to predict opioid relapse. Poorer treatment outcomes for young adults are likely associated with multiple developmental vulnerabilities rather than any single predominant factor. Although not reaching significance, several characteristics (using heroin, smoking tobacco, high levels of depression/anxiety, or treatment because of family/friends) showed higher odds ratio point estimates for relapse in young adults than older adults. This is the first study to explore moderators of worse OUD treatment outcomes in young adults, highlighting the need to identify predictor variables that could inform treatment enhancements. (Am J Addict 2021;00:1-12).

1038-P: Insulin Glargine 300 U/ml (Gla-300) vs. First-Generation Standard-of-Care Basal Insulin Analogs (SOC-BI) in Insulin-Naïve Patients with Type 2 Diabetes (T2D): Impact of Renal Function on the Outcomes of the Randomized Pragmatic Real-Life Achieve Control S

In the 12-month ACHIEVE Control study, significantly more insulin-naive patients with T2D treated with Gla-300 vs. SOC-BI (glargine 100 U/mL or detemir) achieved the primary composite endpoint of individualized HEDIS A1c target attainment at 6 months without documented symptomatic (≤70 mg/dL) or severe hypoglycemia. This post-hoc analysis explored outcomes in subgroups with estimated glomerular filtration rate (eGFR) of &amp;lt;60, 60 to &amp;lt;90, and ≥90 mL/min/1.73 m2. Patients with eGFR &amp;lt;60 mL/min/1.73 m2 were older and had longer T2D duration. Within each eGFR subgroup, baseline characteristics were generally balanced between treatment groups. Within subgroups, odds ratios for clinical outcomes generally showed trends favoring Gla-300 vs. SOC-BI, consistent with the overall study population (Figure). In patients with eGFR &amp;lt;60 mL/min/1.73 m2, the odds ratio point estimates for absence of documented symptomatic (≤70 mg/dL and &amp;lt;54 mg/dL) or severe hypoglycemia at 6 and 12 months strongly favored Gla-300 (&amp;gt;1.40). The results suggest a potential benefit of Gla-300 vs. SOC-BI for avoiding hypoglycemia in patients with compromised renal function that warrants further evaluation in prospective studies. Disclosure L. Meneghini: Advisory Panel; Self; Novo Nordisk Inc., Sanofi US. Consultant; Self; Applied Therapeutics, Sanofi US. A. Cheng: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Boehringer Ingelheim International GmbH, Eli Lilly and Company, HLS Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Medtronic, Merck &amp; Co., Inc., Novo Nordisk A/S, Sanofi. Research Support; Self; Applied Therapeutics, Sanofi. Speaker’s Bureau; Self; Abbott, AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Boehringer Ingelheim International GmbH, Eli Lilly and Company, Insulet Corporation, Janssen Pharmaceuticals, Inc., mdBriefCase, Medtronic, Merck &amp; Co., Inc., Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Sanofi. P. Evenou: Employee; Self; Sanofi. J. Gill: Other Relationship; Self; Sanofi US. A. Mohamed: None. G.E. Umpierrez: None. Funding Sanofi US

Modification of the impact of access to water on childhood diarrhoea by socioeconomic status in the Gaza Strip from 2000 to 2014: a cross-sectional study

BackgroundAccess to unsafe water is a concern in the Gaza Strip, where water supplies continue to degrade owing to regional sanctions, bombardment, and mismanagement. Our previous study found that decreased access to public water networks was associated with increased diarrhoea prevalence in children younger than 5 years in the Gaza Strip. This study examined the role of socioeconomic status as an effect modifier in this association. MethodsWe used data from five consecutive demographic health surveys and multiple indicator cluster surveys conducted by the Palestinian Central Bureau of Statistics in 2000, 2004, 2006/2007 (December, 2006, to March, 2007), 2010, and 2014. Multivariable logistic regression models were applied to pooled data with prevalence of diarrhoea as the outcome and access to water as the main exposure of interest, with adjustment for age, sex, governorate, and survey year (to adjust for the seasons or other administrative conditions, for each survey). Access to water was characterised by the type of source, namely piped, other improved (eg, public standpipe, borehole, protected dug well, protected spring, and rainwater collection), or unimproved, as defined by the WHO. We defined socioeconomic status in the analysis using maternal education, refugee status, and locality type (urban, rural, or camp). FindingsThe odds ratio (OR) of diarrhoea for children with access to unimproved water sources was higher than for those with access to piped water sources when mothers had only primary education (OR 1·35; 95% CI 1·07–1·71) than when mothers also had secondary or higher education (1·09; 0·93–1·27). The OR for children in camps was 1·32 (1·10–1·57) compared with 1·19 in urban areas (1·05–1·36). Point estimates of ORs suggested strong effect modification by refugee status, although with wider CIs for non-registered refugee children (4·95; 1·58–15·55) than for registered refugees (1·35; 1·18–1·53) or non-refugees (1·18; 1·07–1·43). InterpretationOur results suggest that, in the Gaza strip, children with lower socioeconomic status experience a greater burden of diarrhoea morbidity risk than children with higher socioeconomic status, even when using the same type of water source. Changes to policy are required to address such disproportionate burden of diarrhoea risk in the occupied Palestinian territory. FundingNone.

Strength of the association between antibiotic use and hemolytic uremic syndrome following Escherichia coli O157:H7 infection varies with case definition

BackgroundThe veracity of the association between antibiotic use and hemolytic uremic syndrome (HUS) caused by Escherichia coli O157:H7 has been a topic of debate. We postulated that criteria used to define HUS affect this association. MethodsWe reviewed 471 hospitalized E. coli O157:H7 cases reported in Washington State, 2005–2014, to determine HUS status by various case definitions and antibiotic treatment. We used age-adjusted logistic regression models to estimate the effect of treatment on HUS status according to four common, but heterogeneous, definitions: the Council of State and Territorial Epidemiologists (CSTE) definition, hematology-focused and age-focused definitions from the literature, and hospital diagnosis. ResultsInter-annual variation in antibiotic use was high, but no meaningful change in antibiotic use was observed over this ten-year period. Thirteen percent of cases <18 years-old received antibiotics, compared to 54% of cases ≥18 years-old. The CSTE, hematology-focused, age-focused, and hospital diagnosis definitions identified 149, 57, 74, and 89 cases of HUS, respectively. The association between antibiotic treatment and HUS varied by definition: CSTE odds ratio (OR) 1.57 [95% confidence interval (CI) 0.98, 2.55]; hematology-focused OR 1.73 (95% CI 0.83, 3.54); age-focused OR 2.29 (95% CI 1.20, 4.39); and hospital diagnosis OR 1.94 (95% CI 1.01, 3.72). ConclusionsEach definition yielded an estimate of the association in the direction of increased risk of HUS with antibiotics. While the range of OR point estimates was relatively small, confidence intervals for two HUS definitions crossed the null and two did not, potentially altering the inference an investigator makes. Discrepant reports of the association between antibiotic use and HUS in the literature might be due in part to the choice of HUS definition, and a consistent definition of HUS should be adopted for research and public health purposes.

Talking on a Wireless Cellular Device While Driving: Improving the Validity of Crash Odds Ratio Estimates in the SHRP 2 Naturalistic Driving Study

Dingus and colleagues (Proc. Nat. Acad. Sci. U.S.A. 2016, 113, 2636–2641) reported a crash odds ratio (OR) estimate of 2.2 with a 95% confidence interval (CI) from 1.6 to 3.1 for hand-held cell phone conversation (hereafter, “Talk”) in the SHRP 2 naturalistic driving database. This estimate is substantially higher than the effect sizes near one in prior real-world and naturalistic driving studies of conversation on wireless cellular devices (whether hand-held, hands-free portable, or hands-free integrated). Two upward biases were discovered in the Dingus study. First, it selected many Talk-exposed drivers who simultaneously performed additional secondary tasks besides Talk but selected Talk-unexposed drivers with no secondary tasks. This “selection bias” was removed by: (1) filtering out records with additional tasks from the Talk-exposed group; or (2) adding records with other tasks to the Talk-unexposed group. Second, it included records with driver behavior errors, a confounding bias that was also removed by filtering out such records. After removing both biases, the Talk OR point estimates declined to below 1, now consistent with prior studies. Pooling the adjusted SHRP 2 Talk OR estimates with prior study effect size estimates to improve precision, the population effect size for wireless cellular conversation while driving is estimated as 0.72 (CI 0.60–0.88).

Individual risk alleles of susceptibility to schizophrenia are associated with poor clinical and social outcomes

Many patients with schizophrenia have poor clinical and social outcomes. Some risk alleles closely related to the onset of schizophrenia have been reported to be associated with their clinical phenotypes, but the direct relationship between genetic vulnerability to schizophrenia and clinical/social outcomes of schizophrenia, as evaluated by both practical clinical scales and 'real-world' function, has not been investigated. We evaluated the clinical and social outcomes of 455 Japanese patients with schizophrenia by severity of illness according to the Clinical Global Impression-Severity Scale (CGI-S) and social outcomes by social adjustment/maladjustment at 5 years after the first visit. We examined whether 46 single nucleotide polymorphisms (SNPs) selected from a Japanese genome-wide association study of susceptibility to schizophrenia were associated with clinical and social outcomes. We also investigated the polygenic risk scores of 46 SNPs. Allele-wise association analysis detected three SNPs, including rs2623659 in the CUB and Sushi multiple domains-1 (CSMD1) gene, associated with severity of illness at end point. The severity of illness at end point was associated with treatment response, but not with the severity of illness at baseline. Three SNPs, including rs2294424 in the C6orf105 gene, were associated with social outcomes. Point estimates of odds ratios showed positive relationships between polygenic risk scores and clinical/social outcomes; however, the results were not statistically significant. Because these results are exploratory, we need to replicate them with a larger sample in a future study.

Amniotic fluid phthalate levels and male fetal gonad function.

Prenatal exposure to phthalates may pose a threat to human male reproduction. However, additional knowledge about the in vivo effect in humans is needed, and reported associations with genital abnormalities are inconclusive. We aimed to study prenatal di(2-ethylhexyl) phthalate (DEHP) and diisononyl phthalate (DiNP) exposure in relation to cryptorchidism, hypospadias, and human fetal Leydig cell function. We studied 270 cryptorchidism cases, 75 hypospadias cases, and 300 controls. Second-trimester amniotic fluid samples were available from a Danish pregnancy-screening biobank (n = 25,105) covering 1980-1996. We assayed metabolites of DEHP and DiNP (n = 645) and steroid hormones (n = 545) by mass spectrometry. We assayed insulin-like factor 3 by immunoassay (n = 475) and analyzed data using linear or logistic regression. Mono(2-ethyl-5-carboxypentyl) phthalate (5cx-MEPP, DEHP metabolite) was not consistently associated with cryptorchidism or hypospadias. However, we observed an 18% higher (95% confidence interval [CI] = 5%-33%) testosterone level, and a 41% lower (-56% to -21%) insulin-like factor 3 level in the highest 5cx-MEPP tertile compared with the lowest. Mono(4-methyl-7-carboxyheptyl) phthalate (7cx-MMeHP, DiNP metabolite) showed elevated odds ratio point estimates for having cryptorchidism (odds ratio = 1.28 [95% CI = 0.80 to 2.01]) and hypospadias (1.69 [0.78 to 3.67]), but was not consistently associated with the steroid hormones or insulin-like factor 3. Data on the DEHP metabolite indicate possible interference with human male fetal gonadal function. Considering the DiNP metabolite, we cannot exclude (nor statistically confirm) an association with hypospadias and, less strongly, with cryptorchidism.

Pilot randomized controlled trial of an internet-based smoking cessation intervention for pregnant smokers (‘MumsQuit’)

BackgroundInternet-based Smoking Cessation Interventions could help pregnant women quit smoking, especially those who do not wish to, or cannot, access face-to-face or telephone support. This study aimed to preliminarily evaluate the effectiveness and usage of a fully automated smoking cessation website targeted to pregnancy, ‘MumsQuit’, and obtain an initial effect-size estimate for a full scale trial. MethodsWe recruited 200 UK-based pregnant adult smokers online to a two-arm double-blind pilot RCT assessing the effectiveness of MumsQuit compared with an information-only website. MumsQuit was adapted from a generic internet smoking cessation intervention, ‘StopAdvisor’. The primary outcome was self-reported continuous 4-week abstinence assessed at 8 weeks post-baseline. Secondary outcomes were automatically collected data on intervention usage. ResultsParticipants smoked 15 cigarettes per day on average, 73% were in the first trimester of their pregnancy, 48% were from lower socioeconomic backgrounds, and 43% had never used evidence-based cessation support. The point estimate of odds ratio for the primary outcome was 1.5 (95% CI=0.8–2.9; 28% vs. 21%). Compared with control participants, those in the MumsQuit group logged in more often (3.5 vs. 1.3, p<0.001), viewed more pages (67.4 vs. 5.7, p<0.001) and spent more time browsing the website (21.3min vs. 1.0min, p<0.001). ConclusionsMumsQuit is an engaging and potentially helpful form of support for pregnant women who seek cessation support online, and merits further development and evaluation in a full-scale RCT.

Comparison of statistical models in a meta-analysis of fungicide treatments for the control of citrus black spot caused by Phyllosticta citricarpa

Meta-analysis has been recognised as a powerful method to synthetize existing published data from different studies through a formal statistical analysis. Several statistical models have been proposed to evaluate the effectiveness of treatments against plant diseases using meta-analysis, but the sensitivity of the estimated treatment effects to the model chosen has not been investigated in detail in the context of plant pathology. In this paper, four different statistical models were defined to analyse fungicide control trials with binary outcomes. These models were used to conduct a meta-analysis on the effectiveness of fungicide treatments against citrus black spot, a fungal disease caused by the quarantine pathogen Phyllosticta citricarpa. The models differed in the assumption made on the variability of the treatment effect (constant or variable between experimental plots) and in the method used for parameter estimation (classical or Bayesian). Odds ratios were estimated for two groups of fungicides, copper compounds and dithiocarbamates, widely applied for CBS control using each model in turn. Classical and Bayesian statistical models led to similar results, but the estimated treatment effectiveness and their associated levels of uncertainty were sensitive to the assumption made about the variability of the treatment effect. Estimated odds ratios were different depending on whether the treatment effect was assumed to be constant or variable between experimental plots. The size of the confidence intervals was underestimated when the treatment effect was assumed constant while it was variable in reality. Because of the strong between-plot variability, the 90 % percentiles of the odds ratios were much higher than the point estimates, and this result revealed that, in some plots, treatment effectiveness could be much lower than expected. Based on our results, we conclude that it is not sufficient to calculate point estimates of odds ratio when the between-plot variability of the treatment effect is strong and that, in such case, it is recommended to compute the predictive distributions of the odds ratio.

NAMPT (visfatin) and AKT1 genetic variants associate with myocardial infarction

BackgroundHigh plasma levels of the adipokine NAMPT (or visfatin) have been associated with cardiovascular disease. However experimental data suggest that NAMPT, via Akt signaling, protects the myocardium against hypoxic insults. We studied whether the NAMPT rs1319501, AKT1 rs3730358, p53 rs1042522, Mdm2 rs2279744 or eNOS rs1799983 SNP:s linked to NAMPT and Akt signaling associate with risk of myocardial infarction (MI). MethodsCases were 828 men and 346 women aged 45–70 who had suffered a first MI. Control individuals, 1062 men and 513 women, were randomly chosen from the study base. We employed unconditional logistic regression analysis. ResultsThe rs1319501 minor allele associated with MI among women aged 45–60; odds ratio (OR) under a recessive model of inheritance: 2.96 (95% confidence interval [CI] 1.06–8.29). Replication analysis in an independent material yielded OR point estimates in the same direction. The rs3730358 minor allele associated with low MI risk in men aged 45–60 (OR dominant model: 0.72, 95% CI 0.53–0.97), an association completely attenuated by adjusting for inflammatory markers. ConclusionsThe NAMPT rs1319501 minor allele associates with increased MI risk in young women. In young men a protective effect of the AKT1 rs3730358 minor allele was suggested, possibly related to an attenuated inflammation.

Association between obesity and the risk of malignant lymphoma in Japanese: a case–control study

Although marked differences in anthropometric characteristics and malignant lymphoma (ML) incidence suggest that the association between obesity and ML risk in Asian and non-Asian populations may differ, few studies have investigated this association in Asian populations. Here, we conducted a sex- and age-matched case-control study in a Japanese population using 782 cases and 3,910 noncancer controls in the hospital-based Epidemiological Research Program at Aichi Cancer Center Hospital. Odds ratios (ORs) and 95% confidence intervals (CIs) for anthropometric characteristics were estimated using a conditional logistic regression model that incorporated smoking and alcohol intake. Recent body weight and body mass index (BMI) showed marginally significant association with ML risk (ORs [95% CIs] per 5-unit increase in recent weight and BMI; 1.04 [0.99-1.09] and 1.11 [0.98-1.27], respectively). On the other hand, weight and BMI in early adulthood exhibited a strong association with ML risk (ORs [95% CIs] per 5-unit increase in early adulthood weight and BMI; 1.11 [1.05-1.18] and 1.33 [1.13-1.55], respectively). Further, in women, a BMI of 25.0-29.9 kg/m(2), defined as obesity in Asian populations, during early adulthood was significantly associated with ML risk compared to the normal range of 18.5-22.9 kg/m(2). By histological ML subtype, the point estimates of ORs for obesity relative to normal weight in early adulthood were over unity for non-Hodgkin lymphoma (NHL) as a whole and significant for diffuse large B-cell lymphoma (DLBCL). In conclusion, our study in Japanese subjects suggested that early adulthood obesity is associated with the risk of NHL, particularly DLBCL.

Association of Alcohol Intake and Smoking with Malignant Lymphoma Risk in Japanese: A Hospital-Based Case-Control Study at Aichi Cancer Center

Given the lower incidence and differences in distribution of malignant lymphoma in Asian than western populations, the association of alcohol intake and smoking with malignant lymphoma risk in Asian populations merits investigation. Here, we conducted a sex- and age-matched case-control study of a Japanese population using two data sets, the first and second versions of the Hospital-based Epidemiological Research Program at Aichi Cancer Center Hospital (HERPACC-I and HERPACC-II, respectively), in 452 and 330 cases of histologically diagnosed malignant lymphoma and 2,260 and 1,650 noncancer controls, respectively. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using a conditional logistic regression model that incorporated smoking exposure and alcohol intake. Compared with nondrinking, consumption of >or=50 g/d by frequent drinkers was associated with significantly decreased risk in both data sets [OR (95% CI), 0.70 (0.53-0.93) for HERPACC-I and 0.40 (0.23-0.68) for HERPACC-II]. Given similar findings among groups, we used pooled data sets in subsequent analyses. For any alcohol intake versus nondrinking, point estimates of OR were less than unity for all four malignant lymphoma subtypes. In contrast, pack-years of smoking were associated with increased malignant lymphoma risk: relative to the reference (0-4 pack-years), OR (95% CI) were 1.32 (1.02-1.71), 1.39 (1.07-1.80), and 1.48 (1.12-1.95) for 5 to 19, 20 to 39, and >or=40 pack-years, respectively. This association with smoking was less apparent for all subtypes, except Hodgkin's lymphoma. In conclusion, we found that alcohol had an inverse association with malignant lymphoma risk across all malignant lymphoma subtypes in our Japanese subjects. Smoking appeared to be positively associated with malignant lymphoma risk, but this finding may vary by subtype.

New Drugs for the Treatment of Diabetes Mellitus

The cardiovascular disease (CVD) risk associated with diabetes mellitus (DM) has become increasingly evident, accounting for ≈80% of deaths among patients with this disease1 and making CVD risk modification a key therapeutic objective in diabetic patients. Indeed, in some clinical contexts, DM has been elevated to a coronary heart disease risk equivalent for risk reduction strategies.1–4 The rapidly increasing global burden of DM,5 coupled with the associated CVD risk, underscores the imperative for continued generation and application of evidence-based therapies to reduce CVD risk in this high-risk cohort. In this 2-part series, we first review the CVD effects of the thiazolidinedione medications, the most broadly investigated class of antihyperglycemic drugs evaluated in the context of CVD risk. In the second part, we review the modulators of the incretin axis that have most recently achieved US Food and Drug Administration approval, with a focus on CVD considerations; introduce selected drugs in advanced development; summarize glucose control strategies for cardiovascular patients; and discuss the regulatory review of glucose-lowering medications. Ciglitazone, the first thiazolidinedione, was discovered in a compound-screening program for lipid-lowering agents and serendipitously observed to lower glucose in experimental animals, but it failed in clinical testing as a result of toxicities.6 Troglitazone became the first thiazolidinedione approved to treat type 2 DM (T2DM) in 1997, with little understanding of its mechanism of action. Subsequently, the peroxisome proliferator–activated (PPAR)-γ receptor, a nuclear receptor that regulates gene transcription, was identified as the thiazolidinedione target of action.7 PPAR-γ is a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors8 that, when activated, dimerizes with the retinoid X receptor and binds to DNA (PPAR-response element) to regulate gene transcription through coordinate transactivation and transrepression.9 PPAR-γ is expressed most prominently in adipocytes, regulating adipogenesis10 and glucose …

Association between endometriosis stage, lesion type, patient characteristics and severity of pelvic pain symptoms: a multivariate analysis of over 1000 patients

The association between lesion type, disease stage and severity of pain was studied in a large group of women with endometriosis to verify whether endometrial implants at different sites determine specific complaints and to evaluate the validity of the current classification system in women with symptomatic disease. A total of 1054 consecutive women with endometriosis undergoing first-line conservative or definitive surgery were included. Data on age at surgery, disease stage according to the revised American Fertility Society (AFS) classification, anatomical characteristics of endometriotic lesions, and type and severity of pain symptoms were collected and analysed by multiple logistic regression. Minimal endometriosis was present in 319 patients, mild in 139, moderate in 292 and severe in 304. A significant inverse relationship was demonstrated between age at surgery and moderate-to-severe dysmenorrhoea, dyspareunia and non-menstrual pain. A strong association was found between posterior cul-de-sac lesions and pain at intercourse [Wald chi (2) = 17.00, P = 0.0001; odds ratio (OR) = 2.64, 95% confidence interval (CI) = 1.68-4.24]. A correlation between endometriosis stage and severity of symptoms was observed only for dysmenorrhoea (Wald chi (2) = 5.14, P = 0.02) and non-menstrual pain (Wald chi (2) = 5.63, P = 0.018). However, the point estimates of ORs were very close to unity (respectively, 1.33, 95% CI = 1.04-1.71, and 1.01, 95% CI = 1.00-1.03). The association between endometriosis stage and severity of pelvic symptoms was marginal and inconsistent and could be demonstrated only with a major increase in study power.

Estimation of the relative risk of developing clinical scrapie: the role of prion protein (PrP) genotype and selection bias

Prion protein (PrP) genotype data from statutory confirmed cases and from three non-case datasets have been used to calculate the odds ratio (OR) for the development of clinical scrapie for...