Long-term impacts of forest harvesting related soil disturbance on log product yields and economic potential in a New Zealand forest

Abstract

Subclinical hyperthyroidism and the risk of coronary heart disease and mortality

Contexte L'hyperthyroïdie infra-clinique est une perturbation de la fonction thyroïdienne, définie par une thyrotropine (TSH) basse et des taux normaux de thyroxine libre (T4L) et triiodothyronine (T3). Cette dysfonction affecte de 1% à 5% des adultes de plus de 65 ans, surtout les femmes, et pourrait être associée avec les maladies cardiovasculaires, la fibrillation auriculaire et l'insuffisance cardiaque. Toutefois, les conclusions des différentes études de cohortes sont contradictoires, avec des limites méthodologiques empêchant leur comparaison de manière formelle. L'objet du travail de thèse était d'estimer le risque de mortalité de toute cause, le risque de mortalité de cause cardiovasculaire, le risque d'événements cardiovasculaires et le risque de fibrillation auriculaire associés à l'hyperthyroïdie infra-clinique dans toutes les grandes études de cohorte prospectives disponibles à ce jour. Méthode et Résultats Les données individuelles de 52'674 participants provenant de 10 études de cohorte prospectives des Etats-Unis, d'Europe, du Brésil et d'Australie ont été analysées pour évaluer les risques à long-terme de l'hyperthyroïdie infra-clinique. L'euthyroïdie était définie par une TSH entre 0.45 et 4.49 mUI/l et l'hyperthyroïdie infra-clinique par une TSH inférieure à 0.45 mUI/l avec un taux normal de T4L, après exclusion des participants prenant des médicaments pouvant perturber la thyroïde. Sur les 52'674 participants, 2188 (4.2%) avaient une hyperthyroïdie infra-clinique. Pendant un suivi de plus de 8 ans, 8527 participants sont décédés (dont 1896 de cause cardiovasculaire), 3653 sur 22'437 ont eu un événement cardiovasculaire et 785 sur 8711 ont développé une fibrillation auriculaire. Dans des analyses ajustées pour l'âge et le sexe, l'hyperthyroïdie infra-clinique était associée à une hausse de la mortalité de toute cause (hazard ratio [HR] 1.24, intervalle de confiance à 95% [IC] 1.06-1.46), de la mortalité cardiovasculaire (HR 1.29, IC 1.02-1.62), des événements cardiovasculaires (HR 1.21, IC 0.99- 1.46) ainsi qu'une hausse de l'incidence de fibrillation auriculaire (HR 1.68, IC 1.16-2.43). Les risques ne différaient pas significativement dans les analyses stratifiées selon l'âge, le sexe ou la présence de maladies cardiovasculaires préexistantes, et étaient similaires après ajustement multiple pour les facteurs de risque cardiovasculaire. Le risque de mortalité cardiovasculaire et de fibrillation auriculaire était plus élevé avec une TSH très basse (< 0.10 Ul/I) comparé à une TSH modérément abaissée (0.10-0.44 mUI/l, valeurs ρ for trend < 0.03). Conclusions et perspectives L'hyperthyroïdie infra-clinique est associée à un risque augmenté de mortalité de toute cause, de cause cardiovasculaire et de fibrillation auriculaire, avec un risque plus élevé quand la TSH est inférieure à 0.10 mUI/l. Ces résultats sont cohérents avec les dernières recommandations internationales conseillant de considérer un traitement de l'hyperthyroïdie infra-clinique pour les adultes de plus de 65 ans ou les patients avec maladie cardiaque, en particulier si la TSH est inférieure à 0.10 mUI/l. Toutefois, des études cliniques randomisées sont encore nécessaires pour prouver l'efficacité du traitement et déterminer si l'on devrait dépister les problèmes de thyroïde dans la population générale.

Exposure to radio-frequency electromagnetic fields from broadcast transmitters and risk of childhood cancer: a census-based cohort study.

We investigated the association between exposure to radio-frequency electromagnetic fields (RF-EMFs) from broadcast transmitters and childhood cancer. First, we conducted a time-to-event analysis including children under age 16 years living in Switzerland on December 5, 2000. Follow-up lasted until December 31, 2008. Second, all children living in Switzerland for some time between 1985 and 2008 were included in an incidence density cohort. RF-EMF exposure from broadcast transmitters was modeled. Based on 997 cancer cases, adjusted hazard ratios in the time-to-event analysis for the highest exposure category (>0.2 V/m) as compared with the reference category (<0.05 V/m) were 1.03 (95% confidence interval (CI): 0.74, 1.43) for all cancers, 0.55 (95% CI: 0.26, 1.19) for childhood leukemia, and 1.68 (95% CI: 0.98, 2.91) for childhood central nervous system (CNS) tumors. Results of the incidence density analysis, based on 4,246 cancer cases, were similar for all types of cancer and leukemia but did not indicate a CNS tumor risk (incidence rate ratio = 1.03, 95% CI: 0.73, 1.46). This large census-based cohort study did not suggest an association between predicted RF-EMF exposure from broadcasting and childhood leukemia. Results for CNS tumors were less consistent, but the most comprehensive analysis did not suggest an association.

Early pregnancy sex steroids and maternal risk of epithelial ovarian cancer.

Well-established associations between reproductive characteristics and epithelial ovarian cancer (EOC) support an involvement of sex steroid hormones in the etiology of EOC. Limited previous studies have evaluated circulating androgens and the risk of EOC, and estrogens and progesterone have been investigated in only one of the previous studies. Furthermore, there is little data on potential heterogeneity in the association between circulating hormones and EOC by histological subgroup. Therefore, we conducted a nested case-control study within the Finnish Maternity Cohort and the Northern Sweden Maternity Cohort to investigate the associations between circulating pre-diagnostic sex steroid concentrations and the histological subtypes of EOC. We identified 1052 EOC cases among cohort members diagnosed after recruitment (1975-2008) and before March 2011. Up to three controls were individually matched to each case (n=2694). Testosterone, androstenedione, 17-hydroxyprogesterone (17-OHP), progesterone, estradiol (E2), and sex hormone-binding globulin levels were measured in serum samples collected during the last pregnancy before EOC diagnosis. We used conditional logistic regression to estimate odds ratios (ORs) and 95% CIs. Associations between hormones and EOC differed with respect to tumor histology and invasiveness. Sex steroid concentrations were not associated with invasive serous tumors; however, doubling of testosterone and 17-OHP concentration was associated with approximately 40% increased risk of borderline serous tumors. A doubling of androgen concentrations was associated with a 50% increased risk of mucinous tumors. The risk of endometrioid tumors increased with higher E2 concentrations (OR: 1.89 (1.20-2.98)). This large prospective study in pregnant women supports a role of sex steroid hormones in the etiology of EOC arising in the ovaries.

Missed appointments in an outpatient clinic for adolescents, an approach to predict the risk of missing.

PURPOSE: To predict the risk of an adolescent patient to miss an appointment, based on the previous appointments and on the characteristics of the patient and the appointment. METHODS: Two thousand one hundred ninety-three (1873 females) patients aged 12 to 20 years having scheduled at least four appointments were included. We assessed the rate of missed nonexcused appointments of each patient. Second, a Markovian multilevel model was used to predict the risk of defaulting. RESULTS: Forty-five percent of the patients have not missed even once, and 14% of females and 17% of males have missed &gt;25% of their appointments. Females show two types of behaviors (an abstract concept that groups individuals based on a combination of their appointment-keeping and their recorded type of healthcare need) depending on the diagnosis. Somatic, gynecology, violence, and counseling diagnoses are mostly grouped together. In this group, having already missed and having an appointment with a paramedical provider increases the risk of missing. In the second group (eating disorders and psychiatric diagnoses) having already missed and a longer delay between appointments influence the risk of missing, although the risk is lower for this latter group. Males only show one type of behavior regarding missed appointments. Having missed a previous appointment, being older, having cancelled the next to last appointment and the type of diagnosis explain the risk of missing. CONCLUSIONS: Patients who have already defaulted have a higher risk of defaulting again. Means of control regarding missed appointments should consequently focus on defaulters, to decrease the associated workload. Reminders could be a solution for the follow-up appointments scheduled with a long delay.

Family history of cancer and the risk of cancer: a network of case-control studies.

BACKGROUND: The risk of many cancers is higher in subjects with a family history (FH) of cancer at a concordant site. However, few studies investigated FH of cancer at discordant sites. PATIENTS AND METHODS: This study is based on a network of Italian and Swiss case-control studies on 13 cancer sites conducted between 1991 and 2009, and including more than 12 000 cases and 11 000 controls. We collected information on history of any cancer in first degree relatives, and age at diagnosis. Odds ratios (ORs) for FH were calculated by multiple logistic regression models, adjusted for major confounding factors. RESULTS: All sites showed an excess risk in relation to FH of cancer at the same site. Increased risks were also found for oral and pharyngeal cancer and FH of laryngeal cancer (OR = 3.3), esophageal cancer and FH of oral and pharyngeal cancer (OR = 4.1), breast cancer and FH of colorectal cancer (OR = 1.5) and of hemolymphopoietic cancers (OR = 1.7), ovarian cancer and FH of breast cancer (OR = 2.3), and prostate cancer and FH of bladder cancer (OR = 3.4). For most cancer sites, the association with FH was stronger when the proband was affected at age <60 years. CONCLUSIONS: Our results point to several potential cancer syndromes that appear among close relatives and may indicate the presence of genetic factors influencing multiple cancer sites.

Subclinical Thyroid Dysfunction and the Risk of Heart Failure in Older Persons at High Cardiovascular Risk.

Context: Subclinical thyroid dysfunction is common in older people. However, its clinical importance is uncertain. Objective: Our objective was to determine the extent to which subclinical hyperthyroidism and hypothyroidism influence the risk of heart failure and cardiovascular diseases in older people. Setting and Design: The Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) is an prospective cohort study. Patients: Patients included men and women aged 70-82 yr (n = 5316) with known cardiovascular risk factors or previous cardiovascular disease. Main Outcome Measures: Incidence rate of heart failure hospitalization, atrial fibrillation, and cardiovascular events and mortality according to baseline thyroid status were evaluated. Euthyroid participants (TSH =0.45-4.5 mIU/liter) were compared with those with subclinical hyperthyroidism (TSH <0.45 mIU/liter) and those with subclinical hypothyroidism (TSH ≥4.5 mIU/liter, both with normal free T(4)). Results: Subclinical hyperthyroidism was present in 71 participants and subclinical hypothyroidism in 199 participants. Over 3.2 yr follow-up, the rate of heart failure was higher for subclinical hyperthyroidism compared with euthyroidism [age- and sex-adjusted hazard ratio (HR) = 2.93, 95% confidence interval (CI) = 1.37-6.24, P = 0.005; multivariate-adjusted HR = 3.27, 95% CI = 1.52-7.02, P = 0.002). Subclinical hypothyroidism (only at threshold >10 mIU/liter) was associated with heart failure (age- and sex-adjusted HR = 3.01, 95% CI = 1.12-8.11, P = 0.029; multivariate HR = 2.28, 95% CI = 0.84-6.23). There were no strong evidence of an association between subclinical thyroid dysfunction and cardiovascular events or mortality, except in those with TSH below 0.1 or over 10 mIU/liter and not taking pravastatin. Conclusion: Older people at high cardiovascular risk with low or very high TSH along with normal free T(4) appear at increased risk of incident heart failure.

Effect of white-matter lesions on the risk of periprocedural stroke after carotid artery stenting versus endarterectomy in the International Carotid Stenting Study (ICSS): a prespecified analysis of data from a randomised trial.

BACKGROUND: Findings from randomised trials have shown a higher early risk of stroke after carotid artery stenting than after carotid endarterectomy. We assessed whether white-matter lesions affect the perioperative risk of stroke in patients treated with carotid artery stenting versus carotid endarterectomy. METHODS: Patients with symptomatic carotid artery stenosis included in the International Carotid Stenting Study (ICSS) were randomly allocated to receive carotid artery stenting or carotid endarterectomy. Copies of baseline brain imaging were analysed by two investigators, who were masked to treatment, for the severity of white-matter lesions using the age-related white-matter changes (ARWMC) score. Randomisation was done with a computer-generated sequence (1:1). Patients were divided into two groups using the median ARWMC. We analysed the risk of stroke within 30 days of revascularisation using a per-protocol analysis. ICSS is registered with controlled-trials.com, number ISRCTN 25337470. FINDINGS: 1036 patients (536 randomly allocated to carotid artery stenting, 500 to carotid endarterectomy) had baseline imaging available. Median ARWMC score was 7, and patients were dichotomised into those with a score of 7 or more and those with a score of less than 7. In patients treated with carotid artery stenting, those with an ARWMC score of 7 or more had an increased risk of stroke compared with those with a score of less than 7 (HR for any stroke 2·76, 95% CI 1·17-6·51; p=0·021; HR for non-disabling stroke 3·00, 1·10-8·36; p=0·031), but we did not see a similar association in patients treated with carotid endarterectomy (HR for any stroke 1·18, 0·40-3·55; p=0·76; HR for disabling or fatal stroke 1·41, 0·38-5·26; p=0·607). Carotid artery stenting was associated with a higher risk of stroke compared with carotid endarterectomy in patients with an ARWMC score of 7 or more (HR for any stroke 2·98, 1·29-6·93; p=0·011; HR for non-disabling stroke 6·34, 1·45-27·71; p=0·014), but there was no risk difference in patients with an ARWMC score of less than 7. INTERPRETATION: The presence of white-matter lesions on brain imaging should be taken into account when selecting patients for carotid revascularisation. Carotid artery stenting should be avoided in patients with more extensive white-matter lesions, but might be an acceptable alternative to carotid endarterectomy in patients with less extensive lesions. FUNDING: Medical Research Council, the Stroke Association, Sanofi-Synthélabo, the European Union Research Framework Programme 5.

HBV or HCV coinfections and risk of myocardial infarction in HIV-infected individuals: the D:A:D Cohort Study.

BACKGROUND: Data on a link between HCV or HBV infection and the development of cardiovascular disease among HIV-negative and HIV-positive individuals are conflicting. We sought to investigate the association between HBV or HCV infection and myocardial infarction in HIV-infected individuals. METHODS: The prospective observational database of the D:A:D collaboration of 11 cohorts of HIV-infected individuals, including 212 clinics in Europe, the United States and Australia was used. Multivariate Poisson regression was used to assess the effect of HCV or HBV infection on the development of myocardial infarction after adjustment for potential confounders, including cardiovascular risk factors, diabetes mellitus and exposure to antiretroviral therapy. RESULTS: Of 33,347 individuals, 517 developed a myocardial infarction over 157,912 person-years, with an event rate of 3.3 events/1,000 person-years (95% confidence interval [CI] 3.0-3.6). Event rates (95% CIs) per 1,000 person-years in those who were HCV-seronegative and HCV-seropositive were 3.3 (3.0-3.7) and 2.7 (2.2-3.3), respectively, and for those who were HBV-seronegative, had inactive infection or had active infection were 3.2 (2.8-3.5), 4.2 (3.1-5.2) and 2.8 (1.8-3.9), respectively. After adjustment, there was no association between HCV seropositivity (rate ratio 0.86 [95% CI 0.62-1.19]), inactive HBV infection (rate ratio 1.07 [95% CI 0.79-1.43]) or active HBV infection (rate ratio 0.78 [95% CI 0.52-1.15]) and the development of myocardial infarction. CONCLUSIONS: We found no association between HBV or HCV coinfection and the development of myocardial infarction among HIV-infected individuals.

Canakinumab reduces the risk of acute gouty arthritis flares during initiation of allopurinol treatment: results of a double-blind, randomised study.

Objective This study assessed the efficacy and safety of canakinumab, a fully human anti-interleukin 1 beta monoclonal antibody, for prophylaxis against acute gouty arthritis flares in patients initiating urate-lowering treatment.Methods In this double-blind, double-dummy, dose-ranging study, 432 patients with gouty arthritis initiating allopurinol treatment were randomised 1:1:1:1:1:1:2 to receive: a single dose of canakinumab, 25, 50, 100, 200, or 300 mg subcutaneously; 4 x 4-weekly doses of canakinumab (50 + 50 + 25 + 25 mg subcutaneously); or daily colchicine 0.5 mg orally for 16 weeks. Patients recorded details of flares in diaries. The study aimed to determine the canakinumab dose having equivalent efficacy to colchicine 0.5 mg at 16 weeks.Results A dose-response for canakinumab was not apparent with any of the four predefined dose-response models. The estimated canakinumab dose with equivalent efficacy to colchicine was below the range of doses tested. At 16 weeks, there was a 62% to 72% reduction in the mean number of flares per patient for canakinumab doses >= 50 mg versus colchicine based on a negative binomial model (rate ratio: 0.28-0.38, p <= 0.0083), and the percentage of patients experiencing >= 1 flare was significantly lower for all canakinumab doses (15% to 27%) versus colchicine (44%, p<0.05). There was a 64% to 72% reduction in the risk of experiencing >= 1 flare for canakinumab doses >= 50 mg versus colchicine at 16 weeks (hazard ratio (HR): 0.28-0.36, p <= 0.05). The incidence of adverse events was similar across treatment groups.Conclusions Single canakinumab doses >= 50 mg or four 4-weekly doses provided superior prophylaxis against flares compared with daily colchicine 0.5 mg.

Does less frequent routine monitoring of patients on a stable, fully suppressed cART regimen lead to an increased risk of treatment failure?

OBJECTIVE: To investigate whether HIV-infected patients on a stable and fully suppressive combination antiretroviral therapy (cART) regimen could safely be monitored less often than the current recommendations of every 3 months. DESIGN: Two thousand two hundred and forty patients from the EuroSIDA study who maintained a stable and fully suppressed cART regimen for 1 year were included in the analysis. METHODS: Risk of treatment failure, defined by viral rebound, fall in CD4 cell count, development of new AIDS-defining illness, serious opportunistic infection or death, in the 12 months following a year of a stable and fully suppressed regimen was assessed. RESULTS: One hundred thirty-one (6%) patients experienced treatment failure in the 12 months following a year of stable therapy, viral rebound occurred in 99 (4.6%) patients. After 3, 6 and 12 months, patients had a 0.3% [95% confidence interval (CI) 0.1-0.5], 2.2% (95% CI 1.6-2.8) and 6.0% (95% CI 5.0-7.0) risk of treatment failure, respectively. Patients who spent more than 80% of their time on cART with fully suppressed viraemia prior to baseline had a 38% reduced risk of treatment failure, hazard ratio 0.62 (95% CI 0.42-0.90, P = 0.01). CONCLUSION: Patients who have responded well to cART and are on a well tolerated and durably fully suppressive cART regimen have a low chance of experiencing treatment failure in the next 3-6 months. Therefore, in this subgroup of otherwise healthy patients, it maybe reasonable to extend visit intervals to 6 months, with cost and time savings to both the treating clinics and the patients.

Subclinical hypothyroidism and the risk of coronary heart disease: a meta-analysis.

PURPOSE: Subclinical hypothyroidism has been associated with elevated cholesterol and increased risk for atherosclerosis, but data on the risk of coronary heart disease (CHD) are conflicting. We performed a systematic review to determine whether subclinical hypothyroidism is associated with CHD in adults. METHODS: We searched MEDLINE from 1966 to April 2005, and the bibliographies of key articles to identify studies that provided risk estimates for CHD or cardiovascular mortality associated with subclinical hypothyroidism. Two authors independently reviewed each potential study for eligibility, assessed methodologic quality, and extracted the data. RESULTS: We identified 14 observational studies that met eligibility criteria. Subclinical hypothyroidism increased the risk of CHD (summary odds ratio [OR]: 1.65, 95% confidence interval [CI], 1.28-2.12). The summary OR for CHD was 1.81 (CI, 1.38-2.39) in 9 studies adjusted or matched for demographic characteristics, and 2.38 (CI, 1.53-3.69) after pooling the studies that adjusted for most cardiovascular risk factors. Sensitivity analyses including only population-based studies and those with formal outcome adjudication procedures yielded similar results. Subgroup analyses by type of study design showed a similar trend, but lower risk, in the 5 prospective cohort studies (OR 1.42, CI, 0.91-2.21), compared with the case-control and cross-sectional studies (OR 1.72, CI, 1.25-2.38). CONCLUSION: Our systematic review indicates that subclinical hypothyroidism is associated with an increased risk of CHD. Clinical trials are needed to assess whether thyroxine replacement reduces the risk of CHD in subjects with subclinical hypothyroidism.

Economic grand rounds: financial burden of medical care and risk of forgoing care among Europeans with depressive symptoms

Little is known about the financial burden of individuals with depressive symptoms. This study explored that burden, using data from the Survey of Health, Ageing, and Retirement in Europe. To assess the association between depressive symptoms and the individuals' financial burden for medical care and whether they forwent medical care because of costs, logistic regressions were performed that adjusted for age, gender, marital status, education, and chronic diseases. A total of 16,696 noninstitutionalized individuals aged 50-79 years were included in the study. Individuals with depressive symptoms and those without such symptoms bore a similar financial burden. However, individuals with depressive symptoms were at increased risk of forgoing care because of costs, which may worsen their health and financial situation