Trend In Odds Ratios Research Articles

Computed Tomography of the Chest in Younger Pediatric Patients with Thoracic Blunt Trauma Rarely Changes Surgical Management.

IntroductionThoracic trauma is the second leading cause of death after traumatic brain injury in children presenting with blunt chest trauma, which represents 80% of thoracic trauma in children. We hypothesized that older children undergo more clinical and surgical changes in management than younger children screened for intrathoracic injury at a single, urban, pediatric Level I trauma center.MethodsIn this retrospective observational study, we determined the frequencies and types of lesions diagnosed only by chest computed tomography (CCT) and resulting changes of clinical and surgical management among different age groups in a pediatric cohort examined for blunt trauma with chest radiograph and CCT. We used logistic regression to quantify variations in CCT diagnoses and changes in clinical and surgical management across age groups. For each age category, we determined the odds ratio for diagnosis made only on CCT and subsequent changes in all clinical management and, specifically, surgical management. We performed the test of trend to determine the relationship across age with changes in management resulting from additional diagnoses made by CCT.ResultsWe analyzed data on 1,235 patients screened for intrathoracic injury. We found the following overall clinical management and surgical management changes, respectively, per age group: 0–2 years, 5/128 (3.9) and 0/128 (0.0); 3–6 years, 11/212 (5.2) and 1/212 (0.5); 7–10 years, 16/175 (9.1) and 2/175 (1.1); 11–13 years, 17/188 (9.0) and 3/188 (1.6); 14–17 years, 58/532 (10.9) and 25/532 (4.7). There were no observed surgical management changes in the 0–2 age group and, thus, no estimated odds ratio could be calculated. The adjusted odds ratios for the occurrence of surgical change in management (14–17 age group as reference) was 0.1 (0.0–0.9) for 3–6 years, 0.3 (0.1–1.3) for 7–10 years, and 0.3 (0.1–1.1) for 11–13 years. The trend of odds ratios across ages showed that with every subsequent year of life there was a 10% increase in management change and a 30% increase in surgical management change.ConclusionChest computed tomography plays a limited role in younger children and seldom significantly changes management albeit making additional diagnoses.

Effect of time intervals in critical care provided by helicopter emergency medical services on 30-day survival after trauma

BackgroundTrauma is the leading cause of death especially in children and young adults. Prehospital care following trauma emphasizes swift transport to a hospital following initial care. Previous studies have shown conflicting results regarding the effect of time on the survival following major trauma. In our study we investigated the effect of prehospital time-intervals on 30-day mortality on trauma patients that received prehospital critical care. MethodsWe performed a retrospective study on all trauma patients encountered by helicopter emergency medical services in Finland from 2012 to 2018. Patients discharge diagnoses were classed into (1) trauma without traumatic brain injury, (2) isolated traumatic brain injury and (3) trauma with traumatic brain injury. Emergency medical services response time, helicopter emergency medical services response time, on-scene time and transport time were used as time-intervals and age, Glasgow coma scale, hypotension, need for prehospital airway intervention and ICD-10 based Injury Severity Score were used as variables in logistic regression analysis. ResultsMortality data was available for 4,803 trauma cases. The combined 30-day mortality was 12.1% (582/4,803). Patients with trauma without a traumatic brain injury had the lowest mortality, at 4.3% (111/2,605), whereas isolated traumatic brain injury had the highest, at 22.9% (435/1,903). Patients with both trauma and a traumatic brain injury had a mortality of 12.2% (36/295). Following adjustments, no association was observed between time intervals and 30-day mortality. DiscussionOur study revealed no significant association between different timespans and mortality following severe trauma in general. Trends in odds ratios can be interpreted to favor more expedited care, however, no statistical significance was observed. As trauma forms a heterogenous patient group, specific subgroups might require different approaches regarding the prehospital timeframes. Study typeprognostic/therapeutic/diagnostic test.

Association of Joint Body Weight Profile and Physical Activity with Cardiovascular Disease Risk in Montana Adults

Background: There is much debate surrounding the fat but fit paradox, namely, questioning the extent to which physical fitness protects obese/overweight populations from premature mortality. The purpose of this study was to examine the link between joint body weight (BW) profile and physical activity (PA) (BW.PA) and cardiovascular disease (CVD) risk in adults. Methods: Data for this study came from the 2019 Montana Behavioral Risk Factor Surveillance System (BRFSS). Participants were firstly assigned to one of three BW groups (normal weight, overweight, obese) using CDC BMI criteria, secondly assigned to one of three PA groups (active, insufficiently active, inactive) using self-reported moderate-to-vigorous PA (MVPA), and finally assigned to one of the resulting nine joint BW.PA groups. Three main CVD risk factors (hypertension, hypercholesterolemia, diabetes) were used as separate and then combined outcomes. Logistic regression was employed to estimate the odds of having a CVD risk factor for each BW.PA group, relative to “normal weight and active”. Results: A direct linear trend in odds ratios (ORs) was observed across BW.PA groups for each CVD risk factor, from “normal weight and active” to “obese and inactive”. Fully adjusted regression models showed increased odds of having any of the three CVD risk factors (versus having none) for adults “overweight and active” (OR = 2.22, 95% CI: 1.73 – 2.85) and adults “obese and active” (OR = 4.03, 95% CI: 3.08 – 5.27), compared to those “normal weight and active”. Odds were also significantly (p Conclusion: This study found that BW profile was a strong and consistent predictor of three primary CVD risk factors. Obese adults were much more likely to have CVD risk, regardless of PA participation. Hence, fat but fit may not be a paradox among adults in Montana.

Withdrawal: “Meal‐specific dietary patterns and their relation to metabolic syndrome among Iranian adults” Fatemeh Mohtashaminia, Yahya Jalilpiran, Zahra Akbarzade, Mohammad Hassan Javanbakht, Sakineh Shab‐Bidar, Kurosh Djafarian

Evidence on the association between dietary patterns and metabolic syndrome (MetS) focused on habitual intake without considering dietary intake at specific eating meals. We aimed to examine the association between meal-based dietary patterns and metabolic syndrome and the odds of MetS in Iranian adults. This cross-sectional study performed on 840 healthy subjects aged 20-59 years in Tehran, Iran. Food intake was assessed by the three 24-hour recall method. Using principal component analysis (PCA), we identified three major dietary patterns per meal (breakfast, lunch, dinner). We used logistic regression analysis to compute the overall trend of odds ratios (ORs) across increasing tertiles of meal-specific pattern scores. We identified three specific patterns for meals. Our results showed an inverse association between adherence to breakfast pattern (BP) 1 (rich in bread and grains, fat, and meat products) and MetS (OR: 0.65, 95%CI: 50.46-0.93; P for trend: 0.02). Also, adherence to BP3 (rich in fruits and vegetables, egg and potato) was inversely associated with lower fasting blood sugar (OR: 1.52, 95%CI: 1.08-2.14; P for trend: 0.01) and diastolic blood pressure (OR: 0.64, 95%CI: 0.41-0.99; P for trend: 0.04). Our results also indicated that adherence to a lunch rich in fats, bread and grains, poultry associated with lower triglyceride (TG) (OR: 0.60, 95%CI: 0.41-0.88; P for trend: 0.01) and higher HDL (OR: 0.61, 95%CI: 0.42-0.87; P for trend: 0.006). Besides, it was found that LP2 (rich in egg and potato) associated with lower odds of MetS (OR: 0.61, 95%CI: 0.41-0.90; P for trend: 0.02). The results suggest that the meal-specific dietary patterns might be associated with decreased odds of MetS and its components.

Individual and additive-effect relationships of sleep problems and severe menopausal symptoms among women in menopausal transition.

Sleep problems and menopausal symptoms are both common complaints among midlife women. However, the associations of the quality and quantity of sleep problems with the severity of menopausal symptoms have not been well studied. Thus, this study aims to examine the relationships between individual sleep problems and the additive number of sleep problems with severe menopausal symptoms among women during the menopausal transition. Using the convenience sampling, a total of 848 middle-aged women in China were investigated from December 2017 to August 2018. All participants completed a questionnaire on sleep problems, Menopause Rating Scale, and the general information questionnaire. Based on the cutoff of the Menopause Rating Scale, participants were divided into the nonsevere menopausal symptom group and severe menopausal symptoms group. Propensity score matching was used to balance covariates between the two groups. Stepwise binary logistic regression and restricted cubic spline were applied to analyze the associations of individual and additive sleep problems with severe menopausal symptoms. After propensity score matching, no significant difference was observed between the nonsevere menopausal symptoms group and severe menopausal symptoms group (Ps > 0.05). Logistic regression analysis showed that five sleep problems ("feeling too hot," "having pain," "restless legs syndrome," "taking medicine to help sleep," and "having trouble staying awake") were closely associated with severe menopausal symptoms. The restricted cubic spline curve showed an upward trend in odds ratios between the number of these five sleep problems and severe menopausal symptoms, and women were more than twice as likely to suffer severe menopausal symptoms when they experienced more than three of these individual sleep problems. Both the individual and additive number of sleep problems exerted significant effects on severe menopausal symptoms. It might be useful for healthcare providers to set guidelines to support a healthy menopausal transition for midlife women.

Urine Glucose Excretion Attenuates the Association Between Lipid Accumulation Product and Serum Uric Acid in Subjects with Prediabetes.

PurposeObesity is known to be strongly associated with hyperuricemia. Moreover, the impact of urine glucose excretion (UGE) on serum uric acid (UA) levels has gained much more attention in recent years. Yet concern is raised about whether UGE influences the relationship between obesity and hyperuricemia. The aim of this study was to assess the effect of UGE on the association between lipid accumulation product (LAP), a novel marker of visceral adipose accumulation, and UA in subjects with prediabetes.Materials and MethodsData were obtained from a cross-sectional study. A total of 3645 subjects with prediabetes were included in the present study. The separate and joint associations of LAP and UGE with hyperuricemia were examined using logistic regression analyses.ResultsLAP was positively associated with UA in both genders. Subgroup analysis based on UGE revealed that the association was strongest in subjects with low UGE (r = 0.328, p < 0.001), whereas the positive association was weakened, but still remained significant in subjects with moderate and high UGE. High LAP was significantly associated with an increased odds ratio for hyperuricemia after adjustment for potential confounders in the overall population (OR = 2.07, 95% CI: 1.66–2.58, p < 0.001). However, a downward trend in odds ratios for hyperuricemia was observed across UGE categories. In addition, the joint association analysis confirmed that the relationship between LAP and hyperuricemia was attenuated by UGE.ConclusionThe positive association between LAP and UA appears to be attenuated by UGE, indicating that promoting UGE may be an effective strategy for controlling UA levels, especially for people with obesity who are at increased risk for hyperuricemia.

Promoting Adherence to Influenza Vaccination Recommendations in Pediatric Practice.

Objectives: In the United States, nonadherence to seasonal influenza vaccination guidelines for children and adolescents is common and results in unnecessary morbidity and mortality. We conducted a quality improvement project to improve vaccination rates and test effects of 2 interventions on vaccination guidelines adherence. Methods: We conducted a cluster randomized control trial with 11 primary care practices (PRACTICE) that provided care for 11 293 individual children and adolescents in a children’s health care system from September 2015 through April 2016. Practice sites (with their clinicians) were randomly assigned to 4 arms (no intervention [Control], computerized clinical decision support system [CCDSS], web-based training [WBT], or CCDSS and WBT [BOTH]). Results: During the study, 55.8% of children and adolescents received influenza vaccination, which improved modestly during the study period compared with the prior influenza season (P = .009). Actual adherence to recommendations, including dosing, timeliness, and avoidance of missed opportunities, was 46.4% of patients cared for by the PRACTICE. The WBT was most effective in promoting adherence with vaccination recommendations with an estimated average odds ratio = 1.26, P < .05, to compare between preintervention and intervention periods. Over the influenza season, there was a significantly increasing trend in odds ratio in the WBT arm (P < .05). Encouraging process improvements and providing longitudinal feedback on monthly rate of vaccination sparked some practice changes but limited impact on outcomes. Conclusions: Web-based training at the start of influenza season with monthly reports of adherence can improve correct dose and timing of influenza vaccination with modest impact on overall vaccination rate.

DDT and Breast Cancer Trends

Cohn et al. (2008) suggested that birth cohort trends in breast cancer rates for women under 50 years of age are consistent with declining use of DDT (dichloro-diphenyltrichloroethane) after 1959. They cited Weiss (2007) in claiming that increased detection and treatment of in situ breast cancer must be considered when interpreting recent trends in breast cancer mortality rates in young women. The remarks of Weiss (2007) relate to women 40–49 years of age, and earlier detection and improved treatment of breast cancer has had a marked impact on breast cancer mortality rates in these women since 1990 (Berry et al. 2005; Chu et al. 1996). The birth cohort trends relevant to examining the possible impact of childhood DDT exposure on U.S. breast cancer rates, however, were firmly established well before 1990 in women < 40 years of age (Tarone 2007). Cohn et al. (2007) reported a large increase in breast cancer risk estimates for p,p′-DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane] exposure with successive birth cohorts after 1930. Their reported odds ratio estimates by period of birth for the highest tertile of p,p′-DDT exposure were 0.6 for women born in 1931 or earlier (i.e., ≥ 14 years of age in 1945), 3.9 for women born in 1932–1937 (i.e., 8–13 years of age in 1945), 9.6 for women born in 1938–1941 (i.e., 4–7 years of age in 1945), and 11.5 for women born in 1942 or later (i.e., 0.25), and there was a marginally significant decrease in rates for women 35–39 years of age (p = 0.04). Thus the trends in breast cancer mortality rates among women born in 1930–1945 are not consistent with the sharply increasing trend in odds ratios for childhood DDT exposure by birth period reported by Cohn et al. (2007). The most recent mortality rate contributing to the reported regression analyses (corresponding to women in the 35- to 39-year age group born in 1945) was for 1983, well before improvements in detection and treatment would have had any impact on breast cancer mortality rates. Women born after 1945 were exposed to DDT for each of the first 13 years of life (and all years thereafter). In addition, DDT exposure increased from 1945 through 1959, when DDT use peaked (with dietary exposure peaking in 1965) (Wolff et al. 2005). If DDT exposure early in life markedly increases breast cancer risk, then some evidence of the increasing DDT use after 1945 might be expected in breast cancer mortality rate trends for young women born from 1946 through 1959 (Tarone 2007). Breast cancer mortality rates decreased significantly among women 20–24 years of age (p = 0.009) and 25–29 years of age (p = 0.0002) born between 1946 and 1959 (SEER 2006; Tarone 2007). The most recent rate contributing to these regression analyses was for 1987 (corresponding to women in the 25-to 29-year age group born in 1959). Breast cancer mortality rates decreased even more markedly (p < 0.0001) for women in the 30- to 34-year and 35- to 39-year age groups born from 1946 through 1959; some of the recent rates in these latter age groups were almost certainly affected by improved breast cancer detection and treatment, although decreasing trends were apparent in both age groups for rates well before 1990 (Tarone 2007). Thus, U.S. breast cancer mortality rates in women between the ages of 20 and 39 who were born between 1930 and 1959 show no evidence of an increase in breast cancer risk associated with their marked increase in DDT exposure during childhood. The observed birth cohort trends in breast cancer rates do not refute a possible association between childhood DDT exposure and breast cancer risk, and contrary to the implication of Cohn et al. (2008), no such claim was made in my earlier letter (Tarone 2008). The regression analyses reported above suffer the weaknesses of all ecologic analyses, and in fact, the decreasing birth cohort risk of breast cancer in baby boomers has been observed in spite of trends in established risk factors (e.g., parity, age at first birth, and oral contraceptive use) that would predict increasing breast cancer rates among U.S. women born after 1945. If, as suggested by Cohn et al. (2007), the public health significance of DDT exposure early in life is large, then this would provide additional evidence that the factor or factors responsible for the paradoxical decrease in birth cohort risk of breast cancer observed among U.S. baby boomers must have a very powerful impact on breast cancer etiology, large enough to turn an expected increasing trend in breast cancer rates among baby boomers into a decreasing trend.

Smoking, Caffeine, and Nonsteroidal Anti-inflammatory Drugs in Families With Parkinson Disease

To assess associations between Parkinson disease (PD) and putatively protective factors-smoking, caffeine (coffee, tea, and soft drinks), and nonsteroidal anti-inflammatory drugs (aspirin, ibuprofen, and naproxen). Family-based case-control study. Academic medical center clinic. A total of 356 case subjects and 317 family controls who self-reported environmental exposures. Associations between PD and environmental measures (history, status, dosage, duration, and intensity) of smoking, coffee, caffeine, nonsteroidal anti-inflammatory drugs, and non-aspirin nonsteroidal anti-inflammatory drugs were examined using generalized estimating equations with an independent correlation matrix while controlling for age and sex. Individuals with PD were significantly less likely to report ever smoking (odds ratio = 0.56; 95% confidence interval, 0.41-0.78). Additional measures of smoking revealed significant inverse associations with PD (P<.05) and trends in odds ratios (P<.005). Increasing intensity of coffee drinking was inversely associated with PD (test for trend P = .05). Increasing dosage (trend P = .009) and intensity (trend P = .01) of total caffeine consumption were also inversely associated, with high dosage presenting a significant inverse association for PD (odds ratio = 0.58; 95% confidence interval, 0.34-0.99). There were no significant associations between nonsteroidal anti-inflammatory drugs and PD. Inverse associations of smoking and caffeine were corroborated using families with PD, thus emphasizing smoking and caffeine as important covariates to consider in genetic studies of PD.

Common Referent versus Shifting Referent Methods When Using Case–Control Data to Examine Patterns of Incidence Across Multiple Exposure Variables

In case-control studies, when odds ratios estimate rate ratios or risk ratios, trends in odds ratios can reflect trends in incidence in the underlying population. In this report, we use an empirical example and hypothetical data to compare two methods ("common referent" and "shifting referent") for calculating odds ratios from case-control data across multiple exposure variables. With common referent methods, a single independent variable is constructed from the joint distribution of all exposure variables. With shifting referent methods, each stratum-specific trend has its own referent. Using examples involving a single ordinal "trend" variable and a dichotomous "stratification" variable, we show that common referent odds ratios will reflect the pattern of incidence in the underlying population, whereas odds ratios calculated using shifting referent methods will not.

Council tax valuation bands, socio-economic status and health outcome: a cross-sectional analysis from the Caerphilly Health and Social Needs Study

Council tax valuation bands (CTVBs) are a categorisation of household property value in Great Britain. The aim of the study was to assess the CTVB as a measure of socio-economic status by comparing the strength of the associations between selected health and lifestyle outcomes and CTVBs with two measures of socio-economic status: the National Statistics Socio-Economic Classification (NS-SEC) and the 2001 UK census-based Townsend deprivation index.MethodsCross-sectional analysis of data on 12,092 respondents (adjusted response 62.7%) to the Caerphilly Health and Social Needs Study, a postal questionnaire survey undertaken in Caerphilly county borough, south-east Wales, UK. The CTVB was assigned to each individual by matching the sampling frame to the local authority council tax register. Crude and age-gender adjusted odds ratios for each category of CTVB, NS-SEC and fifth of the ward distribution of Townsend scores were estimated for smoking, poor diet, obesity, and limiting long-term illness using logistic regression. Mean mental (MCS) and physical (PCS) component summary scores of the Short-Form SF-36 health status questionnaire were estimated in general linear models.ResultsThere were significant trends in odds ratios across the CTVB categories for all outcomes, most marked for smoking and mental and physical health status. The adjusted odds ratio for being a smoker in the lowest versus highest CTVB category was 3.80 (95% CI: 3.06, 4.71), compared to 3.00 (95% CI: 2.30, 3.90) for the NS-SEC 'never worked and long-term unemployed' versus 'higher managerial and professional' categories, and 1.61 (95% CI: 1.42, 1.83) for the most deprived versus the least deprived Townsend fifth. The difference in adjusted mean MCS scores was 5.9 points on the scale for CTVB, 9.2 for NS-SEC and 3.2 for the Townsend score. The values for the adjusted mean PCS scores were 6.3 points for CTVB, 11.3 for NS-SEC, and 2.5 for the Townsend score.ConclusionCTVBs assigned to individuals were strongly associated with the health and lifestyle outcomes modelled in this study. CTVBs are readily available for all residential properties and deserve further consideration as a proxy for socio-economic status in epidemiological studies in Great Britain.

Birthweight and risk of type 1 diabetes in children and young adults: a population-based register study

We investigated the association between type 1 diabetes and birthweight by age at disease onset. This population-based case-referent study used data from two nationwide case registers that are linked to the Swedish Medical Birth Registry and cover incident cases of type 1 diabetes in the 0- to 14-year (since 1 July 1977) and 15- to 34-year age groups (since 1 January 1983). Of the cases linked to the Medical Birth Registry, a total of 9,283 cases with onset before 15 years of age was recorded before 1 January 2003, and 1,610 cases were recorded with onset before 30 years of age and born after 1973 (together 95% of eligible cases). Multiple births and babies of diabetic mothers were excluded. Sex-specific birthweight by gestational week is expressed as multiples of the standard deviation (SDS) and adjusted for year of birth, maternal age and parity. Cases with onset before 10 years of age (n = 5,792) showed a significant linear trend in odds ratio (OR) by SDS of adjusted birthweight (OR by SDS: 0.062; 95% CI: 0.037-0.086; p < 0.0001), while cases with onset at the age of 10-29 years showed no significant trend (OR by SDS: 0.004; 95% CI: -0.007 to 0.0014; p = 0.22). The association between type 1 diabetes risk and birthweight seems to be limited to cases with disease onset in younger years.

Interaction between common folate polymorphisms and B-vitamin nutritional status modulates homocysteine and risk for a thrombotic event

We have assessed the relationship between homocysteine, its thiol metabolites, specific folate coenzymes, and vitamin B 12 according to the two main functionally relevant genotype–genotype categories that maintain the balance between homocysteine transsulphuration to cysteine, and homocysteine remethylation via folate dependent methionine biosynthesis, namely 2756A → G-MS/66A → G-MSR and 677C → T-MTHFR/1298A → C-MTHFR. We examined 152 individuals who were being treated for either thromboembolic (TE) or non-thromboembolic (non-TE) events. χ 2 test for linear trend in odds ratio provides reasonable evidence for an altered risk of thromboembolism within the range of compound MS/MSR genotypes encountered (wt/wt → recessive/recessive) ( p⩽0.05), but not within the same range of MTHFR/MTHFR genotypes. Logistic regression analysis of the risk for a TE event gave OR=0.49 (95% CI, 0.26–0.92; p=0.026) for 2756A → G-MS, OR=1.08 (95% CI, 0.65–1.78) for 66A → G-MSR, OR=1.19 (95% CI, 0.69–2.06) for 677C → T-MTHFR and OR=0.98 (95% CI, 0.52–1.85) for 1298A → C-MTHFR. When genotypes were examined individually, one-way ANOVA showed only 677C → T-MTHFR ( p=0.005 [TE]) and 2756A → G-MS ( p=0.005 [non-TE] and p=0.0006 [all subjects]) influence homocysteine. One-way ANOVA also showed that MTHFR/MTHFR compound genotype significantly influences TE homocysteine distribution ( p=0.044), but no other variable. In MS/MSR, homocysteine distribution is not significantly affected in TE subjects, but approaches significance in non-TE individuals ( p=0.062). However, the increased power obtained when all subjects are analysed demonstrates a significant influence of MS/MSR upon homocysteine distribution ( p=0.008). Other significant influences of MS/MSR were on total cellular 5-methyl-H 4folate in non-TE subjects ( p=0.042) and vitamin B 12 in TE subjects ( p=0.018). Given the central role of vitamin B 12 in MS/MSR activity, 5-methyl-H 4folate and homocysteine were also looked at by vitamin B 12 quartile, independent of genotype: Vitamin B 12 quartile significantly affected homocysteine distribution in TE ( p=0.013) but not non-TE individuals, with no effect on 5-methyl-H 4folate distributions. Similarly, the prevalence of clinical phenotypes ( p=0.013) and of ‘high risk’ 2756A → G-MS wildtypes ( p=0.039) was associated with the disposition of homocysteine/B 12 in TE but not non-TE subjects. Overall, results indicate compound MS/MSR genotype is associated with risk for a TE event. This may be related to variation in activity of the functional enzymes coded for by polymorphic forms of compound MS/MSR, resulting in altered catalytic cycling of methylcobalamin/cob(I)alamin, which in turn influences Hcy (and total 5-methyl-H 4folate). The effect on vitamin B 12 is greater in TE than non-TE subjects. The compound MTHFR/MTHFR genotype also influences variation in Hcy in TE subjects, but seemingly without the same level of mediation by vitamin B 12. These results are consistent with accepted paradigms and offer a plausible explanation for the effect and interaction of specific SNPs in the TE phenotype. The biological implications of the limited number of MTHFR/MTHFR mutant alleles that can coexist, usually no more than two, may be explained by the serious consequences to folate status that these genotype combinations precipitate. We show that lowering of all folate 1-C pools occurs in the rare ct/cc compound genotype, except for the 5,10-methenyl-H 4folate pool, which expands. 5,10-methenyl-H 4folate is the immediate product of 5,10-methylene-H 4folate, which is likely diverted away from methionine biosynthesis via the aberrant MTHFR enzyme. Consequences for the methylation cycle may be severe, and in most cases lethal for the developing embryo, where methylation is required for dozens of critical processes, but particularly for maintaining DNA methylation patterns that are now known to regulate the expression of half the complement of human genes via CpG islands located in the 5 ′ promotor region, or within the first few exons of the gene.

Case-Referent Survey of Young Adults with Mesothelioma: I. Lung Fibre Analyses

Our study aimed to determine the lung tissue concentration of asbestos and other mineral fibres by type and length in persons with mesothelioma aged 50 yr or less at time of diagnosis, compared to controls of similar age and geographical region. In this age group it was thought that most, but not all, work-related exposures would have been since 1970, when the importation of crocidolite, but not amosite, was virtually eliminated. Eligible cases were sought from recent reports by chest physicians to the SWORD occupational disease surveillance scheme. Lung tissue samples were obtained at autopsy from 69 male and four female cases, and mineral fibres identified, sized and counted by electron microscopy. Fibre concentrations per microg dry tissue were compared with similar estimates from a control series of autopsies of sudden or accidental deaths. Unadjusted, and adjusted odds ratios calculated by logistic regression, assessed relative risk in relation to fibre type, length and concentration. Unadjusted and adjusted odds ratios increased steadily with concentration of crocidolite, amosite, tremolite and all amphiboles combined. There was also some increase with chrysotile, but well short of statistical significance. Incremental risk examined in a linear model was as highly significant for all amphiboles together as individually. Short, medium and long amphibole fibres were all associated with increased risk in relation to length. Mullite and iron fibres were significant predictors of mesothelioma when considered without adjustment for confounding by amphiboles, but, after adjustment, were weak and far from statistically significant. In this young age group, amosite and crocidolite fibres could account for about 80% of cases of mesothelioma, and tremolite for some 7%. The contribution of chrysotile, because of low biopersistence, cannot be reliably assessed at autopsy, but to the extent that tremolite is a valid marker, our results suggest that it was small. The steep linear trend in odds ratio shown by amphiboles combined indicates that their effects may be additive, with increased risk from the lowest detectable fibre level. Non-asbestos mineral fibres probably made no contribution to this disease. Contrary to expectation, however, some 90% of cases were in men who had started work before 1970; this was so whether or not amosite or crocidolite was found in lung tissue.

Case-referent survey of young adults with mesothelioma: I. lung fibre analyses

Objectives: Our study aimed to determine the lung tissue concentration of asbestos and other mineral fibres by type and length in persons with mesothelioma aged 50 yr or less at time of diagnosis, compared to controls of similar age and geographical region. In this age group it was thought that most, but not all, work-related exposures would have been since 1970, when the importation of crocidolite, but not amosite, was virtually eliminated.Methods: Eligible cases were sought from recent reports by chest physicians to the SWORD occupational disease surveillance scheme. Lung tissue samples were obtained at autopsy from 69 male and four female cases, and mineral fibres identified, sized and counted by electron microscopy. Fibre concentrations per μg dry tissue were compared with similar estimates from a control series of autopsies of sudden or accidental deaths. Unadjusted, and adjusted odds ratios calculated by logistic regression, assessed relative risk in relation to fibre type, length and concentration.Results: Unadjusted and adjusted odds ratios increased steadily with concentration of crocidolite, amosite, tremolite and all amphiboles combined. There was also some increase with chrysotile, but well short of statistical significance. Incremental risk examined in a linear model was as highly significant for all amphiboles together as individually. Short, medium and long amphibole fibres were all associated with increased risk in relation to length. Mullite and iron fibres were significant predictors of mesothelioma when considered without adjustment for confounding by amphiboles, but, after adjustment, were weak and far from statistically significant.Conclusion: In this young age group, amosite and crocidolite fibres could account for about 80% of cases of mesothelioma, and tremolite for some 7%. The contribution of chrysotile, because of low biopersistence, cannot be reliably assessed at autopsy, but to the extent that tremolite is a valid marker, our results suggest that it was small. The steep linear trend in odds ratio shown by amphiboles combined indicates that their effects may be additive, with increased risk from the lowest detectable fibre level. Non-asbestos mineral fibres probably made no contribution to this disease. Contrary to expectation, however, some 90% of cases were in men who had started work before 1970; this was so whether or not amosite or crocidolite was found in lung tissue.

Increasing Use of Inhaled Steroids Associated with Declining Asthma Mortality

Increasing worldwide asthma prevalence and mortality has led to greater advocacy of inhaled agents, especially steroids. To determine whether corresponding drug usage trends had ensued locally, wholesale data (expressed as defined daily doses (DDDs)/1000 inhabitants/day) were compared for inclusive periods 1984–1986 and 1992–1994. Whereas absolute usage of anti-asthmatics increased by 79%, proportional inhaled usage increased markedly, especially of steroids (571%) and in hospitals. An odds ratio trend analysis revealed asthma mortality from 1992 onward had declined, particularly in males (p < 0.001). In Hong Kong, despite increasing asthma prevalence, more intensive use of anti-asthmatic drugs (especially inhaled steroids) was associated with declining asthma mortality.

Effect of age on the relationship between gastric cancer and Helicobacter pylori. Tokyo Research Group of Prevention for Gastric Cancer.

Helicobacter pylori is thought to be involved in the pathogenesis of gastric cancer, but the time point at which it produces its effects (critical time) is unknown. We measured the serum level of H. pylori antibody in 787 gastric cancer patients and 1007 controls aged 20 to 69. Odds ratios for different gastric cancer types and stages were determined for each 10‐year age class. The overall odds ratio for gastric cancer decreased with age, being 7.0 for those aged 20–29, 14.5 for those aged 30–39, 9.1 for those aged 40–49, 3.5 for those aged 50–59, and 1.5 for those aged 60–69 (trend in odds ratios: P < 0.01). However, there was no such age‐dependent trend for early diffuse‐type cancer; the odds ratios were 12.6, 4.0, 7.2, 6.5, and 18.5 respectively (P=0.29). Early cancer tended to show higher seroprevalence than advanced cancer, especially in older subjects. No significant difference in seroprevalence was observed between diffuse and intestinal cancers within each age‐class. Seroreversion must have occurred in the time interval between the critical time and the diagnosis of the cancer, especially in older patients. The age‐dependent relationship between H. pylori and gastric cancer may be due to seroreversion, which itself may be independent of age. This age‐independence indicates that prolonged exposure to H. pylori does not increase the magnitude of its influence on gastric carcinogenesis. Possible mechanisms through which H. pylori exerts pathogenic effects are continuous inflammation in adulthood and/or irreversible damage to gastric mucosa in childhood or the teenage years.

A case-control study of employment status and mortality in a cohort of Australian youth

Recent studies have demonstrated a link in young populations between unemployment and ill health. The purpose of this study is to correlate mortality with employment status in two cohorts of young Australian males, aged 17–25 years, from 1984 to 1988. Two youth cohorts consisting of an initially unemployed sample ( n=1424 males) and a population sample ( n=4573 males), were surveyed annually throughout the study period. Those lost to follow-up during the survey period were matched with death registries across Australia. Employment status was determined from weekly diaries and death certificates and was designated as: employed or student; unemployed; not in the work force (excluding students). Conditional logistic regression, using age- and cohort- matched cases (deaths) and controls (alive), was used to estimate the odds ratio (OR) of dying with regard to employment status, taking into account potential confounders such as ethnicity, aboriginality, educational attainment, pre-existing health problems, socio-economic status of parents, and other factors. Twenty three male survey respondents were positively matched to death registry records. Compared to those employed or students (referent group), significantly elevated ORs were found to be associated with neither being in the workforce nor a student for all cause, external cause, and external cause mortality other than suicide. Odds ratios were adjusted for age, survey cohort, ethnicity, pre-existing physical and mental health status, education level, and socio-economic status of parent(s). A statistically significant increasing linear trend in odds ratios of male mortality for most cause groups was found across the employment categories, from those employed or student (lowest ORs), through those unemployed, to those not in the workforce (highest ORs). Suicide was higher, but not statistically significantly, in those unemployed or not in the workforce. Suicide also was associated, though not significantly, with the respondent not living with their parents when they were 14 years of age. No association was found between mortality and past unemployment experience, as measured by length of time spent unemployed, or the number of spells of unemployment experienced during the survey. The results of this study underscore the elevated risk to survival in young males as a consequence of being neither employed nor a student.

Testing for or against a trend in odds ratios

Consider data arranged into k × 2 × 2 contingency tables. The principal result of this paper is the derivation of the likelihood ratio test and its asymptotic distribution for testing for or against an order restriction placed upon the odds ratios. We will show that the limiting distributions are of chi-bar square type and give the expression of the weighting values.

Risk of venous thromboembolism in users of hormone replacement therapy

The association between current use of oral contraceptives and increased risk of venous thromboembolism (VTE) has been firmly established. Although data-sheets for hormone replacement therapy (HRT) carry similar warnings as regards VTE, evidence of an association is inconclusive. We carried out a hospital-based case-control study to investigate whether current use of HRT is associated with VTE. We screened all women aged 45-64 years admitted to hospitals in the area of the Oxford Regional Health Authority with a suspected diagnosis of VTE between February, 1993, and December, 1994. We recruited 81 cases of idiopathic VTE and 146 hospital controls with disorders of eyes, skin, ears, respiratory and alimentary tracts, kidneys, bones, and joints, and trauma; controls were matched to cases for age-group and date and district of admission. To increase the study power, an additional 22 cases of idiopathic VTE and 32 hospital controls admitted before February, 1993, were recruited retrospectively. Participants were questioned about medical and gynaecological history, use of oral contraceptives and HRT, use of other drugs within the previous 3 months, and lifestyle and socioeconomic characteristics. Detailed diagnostic data were extracted from the notes of eligible cases. Matched analyses, adjusted for body-mass Index, socioeconomic group, and history of varicose veins, were undertaken by conditional logistic regression. 44 (42.7%) cases and 44 (24.7%) controls were current users of HRT. The adjusted odds ratio for VTE in current users of HRT compared with non-users (never-users and past users combined) was 3.5 (95% CI 1.8-7.0; p < 0.001). No association was found with past use, and risk appeared to be highest among short-term current users (adjusted likelihood ratio test of trend in odds ratios across different durations of current use, p = 0.011). Current HRT use is associated with risk of VTE. The increased risk may be concentrated in new users. The number of extra cases appears to be only about one in 5000 users per year. These findings need to be weighed against the probable benefits of long-term treatment, including reductions in risks of osteoporotic fracture and coronary heart disease, and the probable modest increase in risk of breast cancer.