Some previous studies have suggested that home pesticide exposure before birth and during a child's early years may increase the risk of childhood leukemia. To further investigate this, we pooled ...individual level data from 12 case–control studies in the Childhood Leukemia International Consortium. Exposure data were harmonized into compatible formats. Pooled analyses were undertaken using multivariable unconditional logistic regression. The odds ratio (ORs) for acute lymphoblastic leukemia (ALL) associated with any pesticide exposure shortly before conception, during pregnancy and after birth were 1.39 (95% confidence interval CI: 1.25, 1.55) (using 2,785 cases and 3,635 controls), 1.43 (95% CI: 1.32, 1.54) (5,055 cases and 7,370 controls) and 1.36 (95% CI: 1.23, 1.51) (4,162 cases and 5,179 controls), respectively. Corresponding ORs for risk of acute myeloid leukemia (AML) were 1.49 (95% CI: 1.02, 2.16) (173 cases and 1,789 controls), 1.55 (95% CI: 1.21, 1.99) (344 cases and 4,666 controls) and 1.08 (95% CI: 0.76, 1.53) (198 cases and 2,655 controls), respectively. There was little difference by type of pesticide used. The relative similarity in ORs between leukemia types, time periods and pesticide types may be explained by similar exposure patterns and effects across the time periods in ALL and AML, participants' exposure to multiple pesticides, or recall bias. Although some recall bias is likely, until a better study design can be found to investigate the associations between home pesticide use and childhood leukemia in an equally large sample, it would appear prudent to limit the use of home pesticides before and during pregnancy, and during childhood.
What's new?
Some studies have suggested that early pesticide exposure may increase the risk of childhood leukemia. In this investigation, the authors pooled individual level data from twelve previous case‐control studies to further examine this question. They found an association between home pesticide exposure before birth and during a child's early years and acute lymphoblastic leukemia (ALL) and with exposure before birth and acute myeloid leukemia (AML). These results indicate that it would be prudent for parents to limit the use of home pesticides before and after a child's birth.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Highlights • We investigated if indices of prolonged lifetime exposure to endogenous female sex hormones are associated with dementia and cognitive function. • Age at menopause is not associated with ...risk of dementia and Alzheimer’s disease. • Increasing age at menopause and reproductive period duration are possibly associated with better cognitive performance and delayed cognitive decline. • High heterogeneity indicates published literature limitations on the topic. • Independent of female hormones mechanisms potentially apply for the female preponderance in dementia.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Objectives
To determine whether albuminuria, a marker of systemic endothelial dysfunction, is associated with cerebral small vessel disease (SVD).
Design
Systematic review following the Meta‐analyses ...Of Observational Studies in Epidemiology guidelines; independent reviewers searched Pubmed/Medline and Scopus, data were extracted, studies were evaluated on quality, and random‐effects models were implemented for meta‐analysis.
Setting
Observational studies quantifying an association between albuminuria and cerebral SVD.
Participants
Adults.
Measurements
Magnetic resonance imaging–defined markers of cerebral SVD; white matter hyperintensities (WMHs), lacunar infarcts (LIs), cerebral microbleeds (CMBs), and enlarged perivascular spaces (EPVSs).
Results
Of 31 eligible studies comprising 23,056 participants identified, 27 were included in quantitative synthesis. Most of the studies were cross‐sectional and of varying quality. On meta‐analysis, albuminuria was associated with greater risk of WMHs (odds ratio (OR) = 1.70, 95% confidence interval (CI) = 1.43–2.01; 13,548 subjects, 2,665 cases; I2 = 44%), LIs (OR = 1.86, 95% CI = 1.49–2.31; 12,857 subjects, 998 cases; I2 = 27%), CMBs (OR = 1.78, 95% CI = 1.30–2.43; 7,645 subjects; 748 cases; I2 = 39%), and EPVSs in the basal ganglia (OR = 1.78, 95% CI = 1.02–3.09; 1,388 subjects, 399 cases; I2 = 37%) and centrum semiovale (OR = 3.27, 95% CI = 1.49–7.20; 1,146 subjects, 460 cases; I2 = 66%). Sensitivity analyses for high‐quality and general population studies, but also studies controlling for cardiovascular disease risk factors and renal function, confirmed the findings and resolved the moderate heterogeneity and publication bias that were evident in the overall analyses.
Conclusion
Albuminuria is independently associated with cerebral SVD, indicating shared microvascular pathology in the kidney and the brain. The results suggest that peripheral systemic microvascular disease biomarkers could be useful in the evaluation of brain microvascular damage.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
In response to the ongoing debate on the long-term effects of assisted reproduction technologies, such as IVF, we systematically reviewed and meta-analyzed available evidence on the association ...between controlled ovarian hyperstimulation for IVF and risk of ovarian, endometrial and cervical cancer.
Eligible studies were identified and pooled effect estimates for relative risk (RR) were calculated by cancer type among two reference groups (general population or infertile women), through fixed- or random-effects models as appropriate.
Nine cohort studies were synthesized, corresponding to a total size of 109 969 women exposed to IVF, among whom 76 incident cases of ovarian, 18 of endometrial and 207 cases of cervical cancer were studied. The synthesis of studies with general population as the reference group pointed to a statistically significant positive association between IVF and increased risk for ovarian (RR = 1.50, 95% confidence interval (CI): 1.17-1.92) and endometrial (RR = 2.04, 95% CI: 1.22-3.43), but not cervical (RR = 0.86, 95% CI: 0.49-1.49) cancers. On the contrary, when infertile women were used as the reference group, no significant associations with ovarian, endometrial or cervical cancer types were noted (RR = 1.26, 95% CI: 0.62-2.55 RR = 0.45, 95% CI: 0.18-1.14 and RR = 5.70, 95% CI: 0.28-117.20, respectively).
IVF does not seem to be associated with elevated cervical cancer risk, nor with ovarian or endometrial cancer when the confounding effect of infertility was neutralized in studies allowing such comparisons. Of note, only one study provided follow-up longer than 10 years for the group exposed to IVF. Future cohort studies should preferably use infertile women as the reference group, rely on IVF-registered valid exposure data, adjust for a variety of meaningful confounders and adopt relatively longer follow-up periods before sound conclusions are drawn.
The effects of controlled ovarian hyperstimulation (COH) for IVF in terms of breast cancer risk remain controversial, despite the hormone-dependent nature of the latter.
Eligible studies up to 15 ...February 2013 were identified and pooled effect estimates for relative risk (RR) were calculated separately for the investigations using the general population and those using infertile women, as a reference group. Fixed- or random-effects models were implemented and subgroup analyses were performed, as appropriate.
Eight cohort studies were synthesized, yielding a total cohort size of 1,554,332 women among whom 14,961 incident breast cancer cases occurred, encompassing 576 incident breast cancer cases among women exposed to IVF. No significant association between IVF and breast cancer was observed either in the group of studies treating the general population (RR = 0.91, 95% confidence interval (CI): 0.74-1.11) or infertile women (RR = 1.02, 95% CI: 0.88-1.18), as a reference group. Of note were the marginal associations, protective for pregnant and/or parous women after IVF (pooled effect estimate = 0.86, 95% CI: 0.73-1.01) and adverse for women <30 years at first IVF treatment (pooled effect estimate = 1.64, 95% CI: 0.96-2.80).
At present, COH for IVF does not seem to impart increased breast cancer risk. Longer follow-up periods, comparisons versus infertile women, subgroup analyses aiming to trace vulnerable subgroups, adjustment for various confounders and larger informative data sets are needed before conclusive statements for the safety of the procedure are reached.
Obstructive sleep apnea is a prevalent disease that is associated with significant morbidity and mortality, particularly due to cardiovascular disease. An emerging cardiovascular risk factor, ...arterial stiffness, may also be involved in the cardiovascular complications of obstructive sleep apnea. The purpose of this review was to summarize the current literature regarding the effect of obstructive sleep apnea on arterial stiffness. We conducted a systematic literature review using PubMed, Embase and the Cochrane Library. We identified 24 studies that met search criteria investigating the effect of obstructive sleep apnea on arterial stiffness. Arterial stiffness was found to be increased in obstructive sleep apnea patients compared with controls or increased in severe compared with mild sleep apnea. In some studies, a positive correlation was identified between the degree of arterial stiffness and sleep apnea severity. In the two randomized, controlled trials and the two nonrandomized trials identified, treatment of obstructive sleep apnea with continuous positive airway pressure led to significant decreases in arterial stiffness. Obstructive sleep apnea appears to have an independent effect on arterial stiffness, which may be one of the mechanisms accounting for sleep apnea-associated cardiovascular risk.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Summary Obstructive sleep apnea (OSA) is associated with increased arterial stiffness, a cumulative indicator of arterial health. Continuous positive airway pressure (CPAP) is the gold standard ...treatment for OSA. We conducted a meta-analysis of the available literature investigating the effect of CPAP on arterial stiffness in patients with OSA. Fifteen articles ( n = 615 patients) assessing indices of arterial stiffness were identified. Five different meta-analyses were performed assessing: a) all indices of arterial stiffness, b) augmentation index (AIx), c) all pulse wave velocities (PWV), d) brachial-ankle PWV and e) carotid-femoral PWV. Pooled standardized mean differences (SMDs) and weighted mean differences (WMDs) were appropriately calculated through fixed or random effects models after assessing between-study heterogeneity. A significant improvement of all indices of arterial stiffness was observed after CPAP treatment (SMD = −0.74; 95%CI: −1.08 to −0.41). AIx and PWVs were also significantly improved (WMD = −4.86; 95%CI: −7.31 to −2.41 and WMD = −0.87; 95%CI: −0.98 to −0.77, respectively), as well as brachial-ankle PWV and carotid-femoral PWV (WMD = −0.86; 95%CI: −0.97 to −0.75 and WMD = −1.21; 95%CI:−1.92 to −0.50, respectively). Neither the proportion of compliant patients nor the duration of CPAP use altered the effect of arterial stiffness reduction after CPAP treatment. In conclusion, our meta-analyses showed significant improvements in all indices of arterial stiffness after CPAP treatment in patients with OSA. As clinical use of arterial stiffness is growing in popularity, the efficacy of this useful tool in assessing cardiovascular risk reduction among patients with OSA treated with CPAP needs to be further explored.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Summary We used meta-analysis to synthesize current evidence regarding the effect of nasal continuous positive airway pressure (nCPAP) on road traffic accidents in patients with obstructive sleep ...apnea (OSA) as well as on their performance in driving simulator. The primary outcomes were real accidents, near miss accidents, and accident-related events in the driving simulator. Pooled odds ratios (ORs), incidence rate ratios (IRRs) and standardized mean differences (SMDs) were appropriately calculated through fixed or random effects models after assessing between-study heterogeneity. Furthermore, risk differences (RDs) and numbers needed to treat (NNTs) were estimated for real and near miss accidents. Meta-regression analysis was performed to examine the effect of moderator variables and publication bias was also evaluated. Ten studies on real accidents (1221 patients), five studies on near miss accidents (769 patients) and six studies on the performance in driving simulator (110 patients) were included. A statistically significant reduction in real accidents (OR = 0.21, 95% CI = 0.12–0.35, random effects model; IRR = 0.45, 95% CI = 0.34–0.59, fixed effects model) and near miss accidents (OR = 0.09, 95% CI = 0.04–0.21, random effects model; IRR = 0.23, 95% CI = 0.08–0.67, random effects model) was observed. Likewise, a significant reduction in accident-related events was observed in the driving simulator (SMD = −1.20, 95% CI = −1.75 to −0.64, random effects). The RD for real accidents was −0.22 (95% CI = −0.32 to −0.13, random effects), with NNT equal to five patients (95% CI = 3–8), whereas for near miss accidents the RD was −0.47 (95% CI = −0.69 to −0.25, random effects), with NNT equal to two patients (95% CI = 1–4). For near miss accidents, meta-regression analysis suggested that nCPAP seemed more effective among patients entering the studies with higher baseline accident rates. In conclusion, all three meta-analyses demonstrated a sizeable protective effect of nCPAP on road traffic accidents, both in real life and virtual environment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Gliomatosis cerebri (GC) comprises a rare widespread infiltrating growth pattern of diffuse gliomas. We explored the incidence patterns and survival rates of GC in a population-based registration ...sample from the Surveillance, Epidemiology and End, Results database (1973–2012). GC cases (n = 176) were identified based on their International Classification of Diseases in Oncology (ICD-O-3) morphology code (9381). We calculated age-adjusted incidence rates (AIR) and evaluated temporal trends. Survival was assessed with Kaplan–Meier curves and Cox regression models. The annual AIR of GC was 0.1/million. We noted increasing trends in the preceding registration years (1973–2002; annually, + 7%) and a tendency of clinical/radiological approaches to substitute the gold-standard histological assessment for diagnosis. GC was diagnosed in the entire age spectrum (range 1–98 years), but higher incidence rates (0.43/million) were noted among the elderly (≥ 65 years). A slight male preponderance was identified (male-to-female ratio: 1.4). Median overall survival was 9 months with a 5 year survival rate of 18%. Increasing age, primary tumor location not restricted to the cerebral hemispheres and rural residence at diagnosis were identified as negative prognostic factors, whereas receipt of radiotherapy, surgical treatment, race and method of diagnosis were not associated with outcome. This first comprehensive overview of GC epidemiology exemplifies the rarity of the disease, provides evidence for male preponderance and increased incidence among the elderly and shows lower survival rates compared to the published single center reports. Expansion of registration to histological and molecular characteristics would allow emergence of clinical prognostic factors at the population level.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Introduction
Gliomatosis cerebri (GC) is a rare fatal widespread infiltrating CNS tumor. As consistent disease features have not been established, the tumor comprises a diagnostic challenge.
Methods
...We conducted a systematic literature search for published case reports and case series on patients with histologically confirmed GC. Clinical, diagnostic, neuroimaging, histopathological, and molecular data on individual or summary patient level were extracted and analyzed.
Results
A total of 274 studies were identified, including 866 patients with individual-level data and 782 patients with summary data (58.9% males, mean age 43.6 years). Seizures (49.8%) were the most common presenting symptom followed by headache (35.9%), cognitive decline (32.2%), and focal motor deficits (32%). Imaging studies showed bilateral hemisphere involvement in 65%, infratentorial infiltration in 29.9% and a focal contrast-enhanced mass (type II GC) in 31.1% of cases. MRI (extensive hyperintensities in T2/FLAIR sequences) and MR spectroscopy (elevated choline, creatinine, and myoinositol levels; decreased NAA levels) showed highly consistent findings across GC patients. Low-grade and anaplastic astrocytoma were the most prevalent diagnostic categories, albeit features of any histology (astrocytic, oligodendroglial, oligoastrocytic) and grade (II–IV) were also reported. Among molecular aberrations, IDH1 mutation and MGMT promoter methylation were the most commonly reported. Increasing time elapsed from symptom onset to diagnosis comprised the only independent determinant of the extent of CNS infiltration.
Conclusion
A distinct clinical, neuroimaging, histopathological, or molecular GC phenotype is not supported by current evidence. MRI and MR spectroscopy are important tools for the diagnosis of the tumor before confirmation with biopsy.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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