residual confounding
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2022 ◽  
Vol 160 ◽  
pp. 107010
Author(s):  
Jos H. Verbeek ◽  
Paul Whaley ◽  
Rebecca L. Morgan ◽  
Kyla W. Taylor ◽  
Andrew A. Rooney ◽  
...  

2022 ◽  
Vol 14 (1) ◽  
Author(s):  
Tosca O. E. de Crom ◽  
Sanne S. Mooldijk ◽  
M. Kamran Ikram ◽  
M. Arfan Ikram ◽  
Trudy Voortman

Abstract Background Adherence to the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet has been linked to a decreased risk of dementia, but reverse causality and residual confounding by lifestyle may partly account for this link. We aimed to address these issues by studying the associations over cumulative time periods, which may provide insight into possible reverse causality, and by using both historical and more contemporary dietary data as this could give insight into confounding since historical data may be less affected by lifestyle factors. Methods In the population-based Rotterdam Study, dietary intake was assessed using validated food frequency questionnaires in 5375 participants between 1989 and 1993 (baseline I) and in a largely non-overlapping sample in 2861 participants between 2009 and 2013 (baseline II). We calculated the MIND diet score and studied its association with the risk of all-cause dementia, using Cox models. Incident all-cause dementia was recorded until 2018. Results During a mean follow-up of 15.6 years from baseline I, 1188 participants developed dementia. A higher MIND diet score at baseline I was associated with a lower risk of dementia over the first 7 years of follow-up (hazard ratio (HR) [95% confidence interval (CI)] per standard deviation (SD) increase, 0.85 [0.74, 0.98]), but associations disappeared over longer follow-up intervals. The mean follow-up from baseline II was 5.9 years during which 248 participants developed dementia. A higher MIND diet score at baseline II was associated with a lower risk of dementia over every follow-up interval, but associations slightly attenuated over time (HR [95% CI] for 7 years follow-up per SD increase, 0.76 [0.66, 0.87]). The MIND diet score at baseline II was more strongly associated with the risk of dementia than the MIND diet score at baseline I. Conclusion Better adherence to the MIND diet is associated with a decreased risk of dementia within the first years of follow-up, but this may in part be explained by reverse causality and residual confounding by lifestyle. Further research is needed to unravel to which extent the MIND diet may affect the risk of dementia.


2022 ◽  
Author(s):  
Jacob Wallace ◽  
J. Michael McWilliams ◽  
Anthony Lollo ◽  
Janet Eaton ◽  
Chima D. Ndumele

2021 ◽  
Vol 157 ◽  
pp. 106868
Author(s):  
Jos H. Verbeek ◽  
Paul Whaley ◽  
Rebecca L. Morgan ◽  
Kyla W. Taylor ◽  
Andrew A. Rooney ◽  
...  

2021 ◽  
Author(s):  
Qui-Yi Lim ◽  
Kurt Taylor ◽  
Tom Dudding

Objectives: (1) To explore the associations between modifiable maternal pregnancy exposures: pre-pregnancy body mass index (BMI), pregnancy smoking and alcohol consumption with offspring molar-incisor hypomineralisation (MIH). (2) To explore for the presence of residual confounding using negative control analyses. Methods: This study used data from Avon Longitudinal Study of Parents and Children (ALSPAC), a UK prospective birth cohort. We defined offspring MIH using prospectively collected questionnaire data. We used logistic regression to explore confounder adjusted associations between maternal pre-pregnancy BMI and smoking and alcohol consumption during pregnancy with MIH. We included negative control exposure (paternal BMI, smoking and alcohol around the time of pregnancy) and outcome (offspring dental trauma) analyses to explore for the presence of residual confounding. Results: 5536 mother/offspring pairs were included (297 MIH cases [5.4%]). We found a positive association between maternal mean BMI and offspring MIH (OR per 1‐kg/m2 difference in maternal BMI: 1.04, 95% CI: 1.00, 1.08). In subsequent analyses, we found evidence that this effect was non-linear and being driven by women in the highest BMI quintiles. In negative control analyses, we found no evidence of association between paternal BMI and offspring MIH (OR: 0.94, 95% CI: 0.89, 1.00) and maternal BMI and offspring dental trauma (OR: 0.99, 95% CI: 0.96, 1.02). There was no clear evidence of an association for maternal pregnancy smoking (OR: 0.76, 95%CI: 0.46, 1.22) and alcohol consumption (OR: 0.79, 95% CI: 0.56, 1.21) with offspring MIH with results imprecisely estimated. Conclusion: In summary we found evidence of a possible intrauterine effect of high maternal pre-pregnancy BMI on offspring MIH. We did not find robust evidence for an intrauterine effect of maternal pregnancy smoking or alcohol consumption on offspring MIH. Our findings provide further support for women of reproductive age to maintain a healthy weight. Future studies are warranted to explore possible mechanisms on how the pregnancy environment may relate to offspring MIH.


2021 ◽  
Author(s):  
Luke A McGuinness ◽  
Julian PT Higgins ◽  
Venexia M Walker ◽  
Neil M Davies ◽  
Richard M Martin ◽  
...  

Background: There is some evidence that circulating blood lipids play a role in the development of Alzheimer's disease (AD) and dementia. These modifiable risk factors could be targeted by existing lipid-regulating agents, including statins, for dementia prevention. Here, we test the association between lipid-regulating agents and incidence of dementia and related conditions in the Clinical Practice Research Datalink (CPRD), an United Kingdom-based electronic health record database. Methods: A retrospective cohort study was performed using routinely collected CPRD data (January 1995 and March 2016). Multivariable Cox proportional hazard models, allowing for a time-varying treatment indicator, were used to estimate the association between seven lipid-regulating drug classes (vs. no drug) and five dementia outcomes (all-cause, vascular and other dementias, and probable and possible Alzheimer's disease). Results: We analyzed 1,684,564 participants with a total follow-up of 10,835,685 patient-years (median: 5.9 years (IQR:2.7-9.7)). We found little evidence that lipid-regulating agents were associated with incidence of Alzheimer's disease (probable HR:0.98, 95%CI:0.94-1.01; possible HR:0.97, 95%CI:0.93-1.01), but there was evidence of an increased risk of all-cause (HR:1.17, 95%CI:1.14-1.19), vascular (HR:1.81, 95%CI:1.73-1.89) and other dementias (HR:1.19, 95%CI:1.15-1.24). Evidence from a number of control outcomes indicated the presence of substantial residual confounding by indication (ischaemic heart disease HR: 1.62, 95%CI: 1.59-1.64; backpain HR: 1.04, 95%CI: 1.03-1.05; and Type 2 diabetes HR: 1.50, 95%CI: 1.48-1.51). Conclusion: Lipid-regulating agents were not associated with reduced Alzheimer's disease risk. There was some evidence of an increased the risk of all-cause, vascular and other dementias, likely due to residual confounding by indication.


2021 ◽  
pp. 1-25
Author(s):  
L.E.T. Vissers ◽  
I. Sluijs ◽  
S. Burgess ◽  
N.G. Forouhi ◽  
H. Freisling ◽  
...  

Abstract Higher milk intake has been associated with a lower stroke risk, but not with risk of coronary heart disease (CHD). Residual confounding or reverse causation cannot be excluded. Therefore, we estimated the causal association of milk consumption with stroke and CHD risk through instrumental variable (IV) and gene-outcome analyses. IV analysis included 29,328 participants (4,611 stroke; 9,828 CHD) of the EPIC-CVD (8 European countries) and EPIC-NL case-cohort studies. rs4988235, a lactase persistence (LP) single nucleotide polymorphism which enables digestion of lactose in adulthood was used as genetic instrument. Intake of milk was first regressed on rs4988235 in a linear regression model. Next, associations of genetically predicted milk consumption with stroke and CHD were estimated using Prentice-weighted Cox regression. Gene-outcome analysis included 777,024 participants (50,804 cases) from MEGASTROKE (including EPIC-CVD), UK Biobank and EPIC-NL for stroke, and 483,966 participants (61,612 cases) from CARDIoGRAM, UK Biobank and EPIC-CVD and EPIC-NL for CHD. In IV analyses, each additional LP allele was associated with a higher intake of milk in EPIC-CVD (β=13.7 g/day; 95%CI: 8.4-19.1) and EPIC-NL (36.8 g/day; 20.0-53.5). Genetically predicted milk intake was not associated with stroke (HR per 25 g/day 1.05; 95%CI: 0.94-1.16) or CHD (1.02; 0.96-1.08). In gene-outcome analyses, there was no association of rs4988235 with risk of stroke (odds ratios 1.02; 0.99-1.05) or CHD (0.99; 0.95-1.03). Current Mendelian Randomization analysis does not provide evidence for a causal inverse relationship between milk consumption and stroke or CHD risk.


2021 ◽  
pp. 089686082110515
Author(s):  
Takeshi Hasegawa ◽  
Hisashi Noma ◽  
Takayuki Hamano ◽  
Masanori Abe ◽  
Atsushi Wada ◽  
...  

Background: The use of exchange devices for peritoneal dialysis (PD) fluids is a common practice in Japan. Evidence on the effectiveness of exchange devices in preventing PD-related peritonitis is scarce. We evaluated the association between the use of exchange devices for PD fluids and peritonitis incidence. Methods: We retrospectively enrolled 3845 patients, aged ≥20 years, receiving PD for ≥3 months, with available data on the exchange procedure for PD fluids and peritonitis incidence that was obtained from the Japan Renal Data Registry, a nationwide annual survey. The patients were grouped according to whether the manual or device PD fluid exchange method was used. The onset of peritonitis was defined as a leukocyte count of >100/µL (neutrophils ≥50%) in PD effluents. We applied quasi-Poisson regression analyses to estimate the incidence rate ratio (IRR). Age, sex, PD vintage, body mass index, automated PD use, residual kidney function, comorbidities, haemoglobin and serum albumin were adjusted as potential confounders. Results: Older age, automated PD use, diabetes as comorbidity and lower haemoglobin levels were associated with the use of exchange devices for PD fluids. Patients using devices for PD fluid exchange (69.2%) had an increased risk of peritonitis of 37% (IRR: 1.37, 95% confidence interval (CI): 1.07–1.75) and 28% (IRR: 1.28, 95% CI: 1.00–1.63) in the crude and multivariate adjustment models, respectively. Conclusions: The use of exchange devices for PD fluids and peritonitis incidence showed no favourable association. There may remain possible residual confounding by indication.


2021 ◽  
Vol 5 (1) ◽  
pp. e001207
Author(s):  
Ashish KC ◽  
Shyam Sundar Budhathoki ◽  
Jeevan Thapa ◽  
Susan Niermeyer ◽  
Rejina Gurung ◽  
...  

BackgroundStimulation of non-crying neonates after birth can help transition to spontaneous breathing. In this study, we aim to assess the impact of intact versus clamped umbilical cord on spontaneous breathing after stimulation of non-crying neonates.MethodsThis is an observational study among non-crying neonates (n=3073) born in hospitals of Nepal. Non-crying neonates born vaginally at gestational age ≥34 weeks were observed for their response to stimulation with the cord intact or clamped. Obstetric characteristics of the neonates were analysed. Association of spontaneous breathing with cord management was assessed using logistic regression.ResultsAmong non-crying neonates, 2563 received stimulation. Of these, a higher proportion of the neonates were breathing in the group with cord intact as compared with the group cord clamped (81.1% vs 68.9%, p<0.0001). The use of bag-and-mask ventilation was lower among those who were stimulated with the cord intact than those who were stimulated with cord clamped (18.0% vs 32.4%, p<0.0001). The proportion of neonates with Apgar Score ≤3 at 1 min was lower with the cord intact than with cord clamped (7.6% vs 11.5%, p=0.001). In multivariate analysis, neonates with intact cord had 84% increased odds of spontaneous breathing (adjusted OR, 1.84; 95% CI: 1.48 to 2.29) compared with those with cord clamped.ConclusionsStimulation of non-crying neonates with intact cord was associated with more spontaneous breathing than among infants who were stimulated with cord clamped. Intact cord stimulation may help establish spontaneous breathing in apnoeic neonates, but residual confounding variables may be contributing to the findings. This study provides evidence for further controlled research to evaluate the effect of initial steps of resuscitation with cord intact.


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