Is progestin an independent risk factor for incident venous thromboembolism? A population-based case-control study

Introduction

Because the risk of venous thromboembolism (VTE) associated with progestin is uncertain, we tested oral contraceptives, estrogen and progestin as independent VTE risk factors.

Materials and Methods

Using longitudinal, population-based Rochester Epidemiology Project resources, we identified all Olmsted County, MN women with objectively-diagnosed incident VTE over the 13-year period, 1988-2000 (n = 726) and one to two Olmsted County women per case matched on age, event year and duration of prior medical history (n = 830), and reviewed their complete medical history in the community for previously-identified VTE risk factors (i.e., hospitalization with or without surgery, nursing home confinement, trauma/fracture, leg paresis, active cancer, varicose veins and pregnancy/postpartum), and oral contraceptive, oral estrogen, and oral or injectable progestin exposure. Using conditional logistic regression we tested these hormone exposures as VTE risk factors, both unadjusted and after adjusting for previously-identified VTE risk factors.

Results

In unadjusted models, oral contraceptives, progestin alone, and estrogen plus progestin were significantly associated with VTE. Individually adjusting for body mass index (BMI) and previously-identified VTE risk factors, these effects remained essentially unchanged except that progestin alone was not associated with VTE after adjusting for active cancer. Considering only case-control pairs without active cancer, progestin alone was positively but non-significantly associated with VTE (OR = 2.49; p = 0.16). Adjusting for BMI and previously-identified VTE risk factors including active cancer, oral contraceptives, estrogen alone, and progestin with or without estrogen were significantly associated with VTE.

Conclusions

Oral contraceptives, estrogen alone, estrogen plus progestin, and progestin with or without estrogen are independent VTE risk factors.     

Is idiopathic intracranial hypertension without papilledema a risk factor for migraine progression?

The association of chronic migraine (CM) with an idiopathic intracranial hypertension without papilledema (IIHWOP), although much more prevalent than expected in clinical series of CM sufferers, is not included among the risk factors for migraine progression. We discuss the available evidence supporting the existence of a pathogenetic link between CM and idiopathic intracranial hypertensive disorders and suggest a causative role for IIHWOP in migraine progression.     

Genetic risk of Parkinson’s disease in the general population

IntroductionWe investigated whether a risk score based on genetic risk variants for Parkinson’s disease (PD) is associated with the risk and improves prediction of incident PD, and whether the risk score is associated with basic activities of daily living (BADL) in healthy individuals.MethodsWithin the population-based Rotterdam Study, we genotyped 26 independent risk variants for PD and constructed a genetic risk score in 7167 participants who were free of parkinsonism and dementia at baseline (1990 or 2000). Participants were followed for a maximum of twenty years for the onset of parkinsonism, dementia or death until January 1, 2011 (median follow-up 12.1 years). We studied the relationship between the genetic risk score and incident PD with adjustment for age, sex, smoking and parental history. In an independent sample of 2997 persons free of parkinsonism and dementia, we studied whether the PD risk score was associated with impaired BADL.ResultsDuring follow-up (median 12.1 years), 99 persons were diagnosed with incident PD. The genetic risk score was associated with incident PD (hazard ratio per standard deviation risk 1.25 [95% confidence interval = 1.02; 1.55]), but did not substantially improve prediction (change in C-statistic 0.687 [0.628; 0.745] to 0.698 [0.635; 0.760], ΔC = 0.011 [−0.011; 0.033]). The genetic risk score was associated with a higher probability of any impairment in BADL (odds ratio = 1.11 [1.00; 1.23]).ConclusionGenetic variants for PD are associated with the risk of incident PD in the general population and with impairment in daily functioning in individuals without clinical parkinsonism, but do not improve the clinical prediction of PD. However, we were probably underpowered to detect a small improvement in PD prediction.     

Is there an interaction between sleep-disordered breathing, depression and apolipoprotein E phenotype?

Sleep-disordered breathing (SDB) is widely underdiagnosed among adults. However, SDB may be considered as a public health problem because of clinical consequences for the patient: impaired awake performance, increased risk factor for cardiovascular diseases and increased prevalence of depression. Apolipoprotein E (apoE), a protein involved in lipid metabolism, has 3 major alleles e2, e3 and e4. Recently, it has been shown that apoE e4 allele, a well-known risk factor for cardiovascular diseases, was also associated with SDB. In this study, we assessed a potential interaction between SDB, depression and apoE phenotype. 92 male patients (36-79 years old, mean age 58.0 11.2) consulting in hospital for SDB were enrolled in the study. Each patient had the following exams: 1) overnight polysomnography to determine apnea/hypopnea index (AHI=average number of respiratory events 10 seconds with no breathing per hour). A moderate-to-severe SDB was defined with AHI 15. 2) a psychiatric examination to look for previous or present symptoms of depressive illness. 3) blood sampling to determine apoE genotype (using PCR-RFLP method). In our study, allele frequencies for apoE e2, e3 and e4 were similar to those reported in general population. Among 92 patients, 68 (74%) presented moderate-to-severe SDB and 28 (30%) previous or present symptoms of depressive illness. Our results indicate that: 1) apoE e4 was significantly associated with moderate-to-severe SDB (n=92, p=0.03), 2) scores of apnea-hypopnea index were significantly higher in e4-positive versus e4-negative participants (n=57, p=0,05) and 3) ApoE and depression were not linked. This study confirms a potential interaction between SDB and apoE phenotype, as recently reported. This suggests that e4 allele might be a genetic risk factor for SDB (e4 allele frequency higher in patients with moderate-to-severe SDB versus general population) and/or consequently a deleterious factor for this pathology (increased AHI in e4-positive versus e4-negative patients). Depression might be only one of clinical consequences of SDB. Thus, SDB leads to repeated hypoxemia and numerous awakenings resulting in fatigue and decreased cognitive abilities suitable to the onset of depressive illness in vulnerable persons.     

What are the contributing factors for insomnia in the general population?

Lack of a systematic assessment of insomnia has led to large variations in its reported prevalence in the general population. This study aims to provide new guidelines to assess insomnia prevalence. A cross-sectional telephone survey using the Sleep-EVAL system was done with 24,600 general population-based subjects 15 years and older representative of general populations (France, the UK, Germany, Italy, Portugal, and Spain) consisting of 251,405,391 inhabitants. The overall participation rate was 81.0%. Within the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) symptomatology for insomnia, 27.2% (95% confidence interval: 26.6–27.8%) of the sample reported difficulty initiating sleep (DIS) (10.1%) or maintaining sleep (DMS) (disrupted sleep (DS): 18.0%; early morning awakening (EMA): 10.9%) or nonrestorative sleep (NRS) (8.9%) at least three times per week; 48.5% of them were concomitantly suffering of a DSM-IV sleep/mental disorder. A factor analysis identified several variables strongly related to each of the major factors of insomnia allowing: (1) The narrowing of the definition of insomnia: the prevalence of insomnia decreased to 16.8% with 64.5% of insomnia subjects having a DSM-IV sleep/mental disorder; (2) The identification of a sleep-deprived (voluntary or not) group without insomnia symptoms, representing 2.1% (1.9–2.3%) of the sample. Interestingly, the latter group closely matched the definition of insufficient sleep syndrome as described by the International Classification of Sleep Disorders (ICSD). Using more delineated criteria to assess insomnia increases the recognition of subjects complaining about sleep. Classifications should be amended to improve the correct identification of insomnia. Sleep-deprived subjects should also not be neglected.     

Mazindol: a risk factor for pulmonary arterial hypertension?

Mazindol is an imidazo-isoindole derivative, a tricyclic compound and a non-amphetamine central nervous system stimulant that blocks dopamine and norepinephrine reuptake. Mazindol was withdrawn from the US and European markets in 1999 for reasons unrelated to its efficacy or safety around a time when other anorexic drugs were found to be associated with the development of pulmonary arterial hypertension (PAH). Despite the use of mazindol for decades, reports of PAH due to mazindol intake have been extremely rare. Recent interest on mazindol has emerged for the treatment of narcolepsy and attention-deficit/hyperactivity disorder. Therefore, an updated understanding of the potential benefits and risks of mazindol in these patient populations is warranted.     

Who is at risk for having persistent insomnia symptoms? A longitudinal study in the general population in Korea

ObjectivesOur study had three goals: (1) to investigate the longitudinal course of insomnia symptoms over 4 years (3 time points) by analyzing the trajectory of insomnia symptoms for all participants, (2) to compare persistent insomnia symptom to nonpersistent insomnia symptom groups on mental health and quality of life (QoL), and (3) to conduct exploratory analyses on the relative contribution of multiple factors to persistence of insomnia symptoms.MethodsOur population-based longitudinal study utilized a community-based sample from the Korean Genome and Epidemiology study (KoGES). Participants were 1247 individuals (40.1% men; mean age, 54.3 ± 7.1 years). Insomnia, QoL (measured by 12-item Short-Form health survey [SF-12]), sleep-interfering behaviors, and depression (measured by the Beck Depression Inventory [BDI]) were followed with biennial examinations at 3 data points spaced 2 years apart (baseline, time 1, and time 2).ResultsAmong individuals experiencing insomnia symptoms at baseline, the most common trajectory was to experience persistent nocturnal insomnia symptoms across all 3 time points. Those with persistent insomnia symptoms had significantly lower physical and mental QoL (measured by SF-12) and higher depression (measured by BDI) at time points compared to those without persistent nocturnal insomnia symptoms. A follow-up exploratory receiver operating characteristic curve (ROC) analysis identified poor sleep quality, frequent sleep-interfering behaviors, and low mental health QoL as the strongest predictors of persistent insomnia symptoms above other well-known risk factors.ConclusionsIn particular, an interaction between poor sleep quality, sleep-interfering behaviors, and mental health QoL appeared to be the strongest risk factor for persistent insomnia symptoms.     

Bullying in the school environment: an injury risk factor?

OBJECTIVE: To describe a research project assessing the role of bullying at school as an injury trigger and the modification effect of the socio-economic environment of the victims. Preliminary results are also presented. METHOD: A case-crossover and a case-referent design were combined. The study base consisted of all children aged 10-15 years residing in the Stockholm county in 2000-02. Cases were recruited at the county's children hospital and interviewed shortly after the injury, using a specially designed questionnaire. RESULTS: Preliminary analyses (261 interviews) reveal that about two injured children out of 10 reported having been bullied during the school term. Also, one out of 10 had been bullied shortly enough before the injury for bullying to be considered as a trigger. The circumstances of occurrence of those injuries varied. CONCLUSION: Bullying, apart from being frequent in the school environment, is quite likely to act as an injury trigger.     

Angiogenin gene polymorphism A risk factor for diabetic peripheral neuropathy in the northern Chinese Han population ？

Angiogenin is associated with the pathogenesis of diabetic peripheral neuropathy. Here, we se- quenced the coding region of the angiogenin gene in genomic DNA from 207 patients with type 2 diabetes mellitus （129 diabetic peripheral neuropathy patients and 78 diabetic non-neuropathy pa- tients） and 268 healthy controls. All subjects were from the Han population of northern China. No mutations were found. We then compared the genotype and allele frequencies of the angiogenin synonymous single nucleotide polymorphism rs11701 between the diabetic peripheral neuropathy patients and controls, and between the diabetic neuropathy and non-neuropathy patients, using a case-control design. We detected no statistically significant genetic associations. Angiogenin may not be associated with genetic susceptibility to diabetic peripheral neuropathy in the Han population of northern China.