scholarly journals Lack of association between the MTHFR C677T variant and migraine with aura in an older population: Could selective survival play a role?

Cephalalgia ◽  
2012 ◽  
Vol 33 (5) ◽  
pp. 308-315 ◽  
Author(s):  
Ann I Scher ◽  
Gudny Eiriksdottir ◽  
Melissa Garcia ◽  
Preethy Feit ◽  
Albert V Smith ◽  
...  
Keyword(s):  
Risk Factor ◽  
Migraine With Aura ◽  
Multinomial Logistic Regression ◽  
Meta Analysis ◽  
Mthfr C677t ◽  
Clinical Population ◽  
Older Population ◽  
Simple Simulation ◽  
Selective Survival ◽  
Measured Effect

Background: Several studies, but not all, of primarily middle-aged or younger adults have suggested that the common MTHFR C677T variant is a genetic risk factor for migraine with aura (MA). Here, we consider whether this variant is associated with MA risk in an older non-clinical population (AGES-Reykjavik cohort). Methods: Participants are a sub-sample ( n = 1976) of subjects from the Reykjavik Study (RS; mean age 50) and its continuation, AGES-RS (mean age 76). We estimated the relative odds of MA in TT versus CC carriers using multinomial logistic regression. As both MA and the TT genotype may be linked with modestly reduced longevity, we performed a simple simulation to illustrate the effect that selective survival may have had on our observed gene–disease association. Results: TT versus CC carriers were at marginally reduced odds of MA (ORTT 0.55 (0.3–1.0), p = 0.07), significantly for women (ORTT 0.45 (0.2–0.9), p = 0.03). Assuming the ‘true’ (e.g. mid-life) effect of the TT genotype is ORTT 1.26, from a recent meta-analysis, our simulation suggested that if 25-year mortality had been (hypothetically) 13% higher in MA subjects with the TT versus CC genotype, the measured effect of the TT genotype on MA would have been attenuated to non-significance (e.g. ORTT 1.00). Our observed protective effect was consistent with the most extreme selective mortality scenario, in which essentially all of the previously reported increased mortality in MA subjects was (hypothetically) found in CT or TT carriers. Conclusion: The MTHFR 677TT genotype was associated with marginally reduced risk of MA in our older population. Our simulation illustrated how even modest selective survival might obscure the apparent effect of a genetic or other risk factor in older populations. We speculate that some of the heterogeneity previously observed for this particular genetic variant may be due to age range differences in the studied populations.

Is Homozygosity for the MTHFR C677T Mutation a Risk Factor for Miscarriage? — Likely.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4079-4079
Author(s):  
Ivy Altomare ◽  
Louis M. Aledort
Keyword(s):  
Systematic Review ◽  
Risk Factor ◽  
Pregnancy Loss ◽  
Meta Analysis ◽  
Fetal Loss ◽  
Mthfr C677t ◽  
Early Pregnancy Loss ◽  
C677t Mutation ◽  
Recurrent Early Pregnancy Loss ◽  
In Pregnancy

Abstract Various hereditary thrombophilias such as activated protein C resistance, the factor V leiden mutation, the prothrombin G20210A mutation, protein S deficiency, hyperhomocysteinemia, or combinations of the above disorders have been linked to pregnancy loss at varying stages of gestation (Robertson L, et al. Thrombophilia in pregnancy: a systematic review. Br J Haematol2006;132(2):171–96; Seligsohn U, et al. Genetic susceptibility to venous thrombosis. N Engl J Med2001;344(16):1222–31). The literature regarding methylenetetrahydrofolate reductase (MTHFR) mutations is confusing. Much of the evidence supporting a causal relationship between MTHFR mutations and early fetal loss comes from individual case reports with little outcome data. Three recent meta-analyses of thrombophilia in pregnancy concluded that although there may be a trend toward higher risk, the relationship between MTHFR mutations and spontaneous abortions is not truly significant (Robertson L, et al. Thrombophilia in pregnancy: a systematic review. Br J Haematol2006;132(2):171–96; Nelen WL, et al. Hyperhomocysteinemia and recurrent early pregnancy loss: a meta-analysis. Fertil Steril2000;74(6):1196–9; Rey E, et al. Thrombophilic disorders and fetal loss: a meta-analysis. Lancet2003;361(9361):901–8). In contrast, a study supporting the role of MTHFR mutations in recurrent unexplained abortions found a 2–3 fold increased risk of early fetal loss among Caucasian females homozygous for the C677T mutation versus normal controls (Nelen WL, et al. Genetic risk factor for unexplained recurrent early pregnancy loss. Lancet1997;350(9081):861). We present 5 patients with this genetic defect who presented consecutively to our clinic for decision making for future pregnancies. Each had strong histories of miscarriages after the 8th week of gestation. The clinical features of these patients are reported in the table below. Each woman is Caucasian, and is homozygous for the MTHFR C677T mutation with no other acquired or hereditary thrombophilias. Homocysteine levels were also in normal range for each patient. Our case series of 5 Caucasian women gives support to the theory of a causal relationship between MTHFR mutations and fetal loss. We recommended anticoagulation with low-molecular weight or unfractionated heparin for each patient as a therapeutic intervention to reduce the risk of recurrent abortion in future pregnancies.

scholarly journals Sleep apnoea is a risk factor for severe COVID-19

2021 ◽  
Vol 8 (1) ◽  
pp. e000845
Author(s):  
Satu Strausz ◽  
Tuomo Kiiskinen ◽  
Martin Broberg ◽  
Sanni Ruotsalainen ◽  
Jukka Koskela ◽  
...  
Keyword(s):  
Risk Factor ◽  
Independent Risk Factor ◽  
Causes Of Death ◽  
Meta Analysis ◽  
Sleep Apnoea ◽  
Male Gender ◽  
Multivariate Logistic Regression Model ◽  
Multivariate Logistic Regression ◽  
Obstructive Sleep ◽  
Positive Controls

BackgroundObstructive sleep apnoea (OSA) is associated with higher body mass index (BMI), diabetes, older age and male gender, which are all risk factors for severe COVID-19.We aimed to study if OSA is an independent risk factor for COVID-19 infection or for severe COVID-19.MethodsOSA diagnosis and COVID-19 infection were extracted from the hospital discharge, causes of death and infectious diseases registries in individuals who participated in the FinnGen study (n=260 405). Severe COVID-19 was defined as COVID-19 requiring hospitalisation. Multivariate logistic regression model was used to examine association. Comorbidities for either COVID-19 or OSA were selected as covariates. We performed a meta-analysis with previous studies.ResultsWe identified 445 individuals with COVID-19, and 38 (8.5%) of them with OSA of whom 19 out of 91 (20.9%) were hospitalised. OSA associated with COVID-19 hospitalisation independent from age, sex, BMI and comorbidities (p-unadjusted=5.13×10−5, OR-adjusted=2.93 (95% CI 1.02 to 8.39), p-adjusted=0.045). OSA was not associated with the risk of contracting COVID-19 (p=0.25). A meta-analysis of OSA and severe COVID-19 showed association across 15 835 COVID-19 positive controls, and n=1294 patients with OSA with severe COVID-19 (OR=2.37 (95% 1.14 to 4.95), p=0.021).ConclusionRisk for contracting COVID-19 was the same for patients with OSA and those without OSA. In contrast, among COVID-19 positive patients, OSA was associated with higher risk for hospitalisation. Our findings are in line with earlier works and suggest OSA as an independent risk factor for severe COVID-19.

scholarly journals Incidence and risk factors of delirium after percutaneous coronary intervention in individuals hospitalised for acute myocardial infarction: protocol for a systematic review and meta-analysis

BMJ Open ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. e044564
Author(s):  
Kaizhuang Huang ◽  
Jiaying Lu ◽  
Yaoli Zhu ◽  
Tao Cheng ◽  
Dahao Du ◽  
...  
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Systematic Review ◽  
Acute Myocardial Infarction ◽  
Percutaneous Coronary Intervention ◽  
Risk Factor ◽  
Meta Analysis ◽  
Coronary Intervention ◽  
Cochrane Library ◽  
Percutaneous Coronary

IntroductionDelirium in the postoperative period is a wide-reaching problem that affects important clinical outcomes. The incidence and risk factors of delirium in individuals with acute myocardial infarction (AMI) after primary percutaneous coronary intervention (PCI) has not been completely determined and no relevant systematic review and meta-analysis of incidence or risk factors exists. Hence, we aim to conduct a systematic review and meta-analysis to ascertain the incidence and risk factors of delirium among AMI patients undergoing PCI.Methods and analysesWe will undertake a comprehensive literature search among PubMed, EMBASE, Cochrane Library, PsycINFO, CINAHL and Google Scholar from their inception to the search date. Prospective cohort and cross-sectional studies that described the incidence or at least one risk factor of delirium will be eligible for inclusion. The primary outcome will be the incidence of postoperative delirium. The quality of included studies will be assessed using a risk of bias tool for prevalence studies and the Cochrane guidelines. Heterogeneity of the estimates across studies will be assessed. Incidence and risk factors associated with delirium will be extracted. Incidence data will be pooled. Each risk factor reported in the included studies will be recorded together with its statistical significance; narrative and meta-analytical approaches will be employed. The systematic review and meta-analysis will be presented according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.Ethics and disseminationThis proposed systematic review and meta-analysis is based on published data, and thus there is no requirement for ethics approval. The study will provide an up to date and accurate incidence and risk factors of delirium after PCI among patients with AMI, which is necessary for future research in this area. The findings of this study will be disseminated through publication in a peer-reviewed journal.PROSPERO registration numberCRD42020184388.

Association of infrapopliteal medial arterial calcification with lower-limb amputations in high-risk patients: A systematic review and meta-analysis

2020 ◽  
pp. 1358863X2097973
Author(s):  
Fabrizio Losurdo ◽  
Roberto Ferraresi ◽  
Alessandro Ucci ◽  
Anna Zanetti ◽  
Giacomo Clerici ◽  
...  
Keyword(s):  
Risk Factor ◽  
High Risk ◽  
Lower Limb ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Arterial Calcification ◽  
High Risk Patients ◽  
Patients With Diabetes ◽  
Risk Patients ◽  
Medial Arterial Calcification

Medial arterial calcification (MAC) is a known risk factor for cardiovascular morbidity. The association between vascular calcifications and poor outcome in several vascular districts suggest that infrapopliteal MAC could be a risk factor for lower-limb amputation (LLA). This study’s objective is to review the available literature focusing on the association between infrapopliteal MAC and LLA in high-risk patients. The PubMed and Embase databases were systematically searched. We selected original studies reporting the association between infrapopliteal MAC and LLAs in patients with diabetes and/or peripheral artery disease (PAD). Estimates were pooled using either a fixed-effects or a random-effects model meta-analysis. Heterogeneity was evaluated using the Q and I2 statistics. Publication bias was investigated with a funnel plot and Egger test. The trim-and-fill method was designed to estimate the possibly missing studies. Influence analysis was conducted to search studies influencing the final result. Test of moderators was used to compare estimates in good versus non-good-quality studies. Fifteen articles satisfied the selection criteria ( n = 6489; median follow-up: 36 months). MAC was significantly associated with LLAs (pooled adjusted risk ratio (RR): 2.27; 95% CI: 1.89–2.74; I2 = 25.3%, Q-test: p = 0.17). This association was kept in the subgroup of patients with diabetes (RR: 2.37; 95% CI: 1.76–3.20) and patients with PAD (RR: 2.48; 95% CI: 1.72–3.58). The association was maintained if considering as outcome only major amputations (RR: 2.11; 95% CI: 1.46–3.06). Our results show that infrapopliteal MAC is associated with LLAs, thus suggesting MAC as a possible new marker of the at-risk limb.

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