scholarly journals Antenatal Steroid Therapy for Fetal Lung Maturation and the Subsequent Risk of Childhood Asthma: A Longitudinal Analysis

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Jason D. Pole ◽  
Cameron A. Mustard ◽  
Teresa To ◽  
Joseph Beyene ◽  
Alexander C. Allen

This study was designed to test the hypothesis that fetal exposure to corticosteroids in the antenatal period is an independent risk factor for the development of asthma in early childhood with little or no effect in later childhood. A population-based cohort study of all pregnant women who resided in Nova Scotia, Canada, and gave birth to a singleton fetus between 1989 and 1998 was undertaken. After a priori specified exclusions, 80,448 infants were available for analysis. Using linked health care utilization records, incident asthma cases developed after 36 months of age were identified. Extended Cox proportional hazards models were used to estimate hazard ratios while controlling for confounders. Exposure to corticosteroids during pregnancy was associated with a risk of asthma in childhood between 3–5 years of age: adjusted hazard ratio of 1.19 (95% confidence interval: 1.03, 1.39), with no association noted after 5 years of age: adjusted hazard ratio for 5–7 years was 1.06 (95% confidence interval: 0.86, 1.30) and for 8 or greater years was 0.74 (95% confidence interval: 0.54, 1.03). Antenatal steroid therapy appears to be an independent risk factor for the development of asthma between 3 and 5 years of age.

2015 ◽  
Vol 22 (8) ◽  
pp. 1086-1093 ◽  
Author(s):  
Saeed Akhtar ◽  
Raed Alroughani ◽  
Samar F Ahmed ◽  
Jasem Y Al-Hashel

Background: The frequency of paediatric-onset multiple sclerosis (POMS) and the precise risk of secondary progression of disease are largely unknown in the Middle East. This cross-sectional cohort study assessed the risk and examined prognostic factors for time to onset of secondary progressive multiple sclerosis (SPMS) in a cohort of POMS patients. Methods: The Kuwait National MS Registry database was used to identify a cohort of POMS cases (diagnosed at age <18 years) from 1994 to 2013. Data were abstracted from patients’ records. A Cox proportional hazards model was used to evaluate the prognostic significance of the variables considered. Results: Of 808 multiple sclerosis (MS) patients, 127 (15.7%) were POMS cases. The median age (years) at disease onset was 16.0 (range 6.5–17.9). Of 127 POMS cases, 20 (15.8%) developed SPMS. A multivariable Cox proportional hazards model showed that at MS onset, brainstem involvement (adjusted hazard ratio 5.71; 95% confidence interval 1.53–21.30; P=0.010), and POMS patient age at MS onset (adjusted hazard ratio 1.38; 95% confidence interval 1.01–1.88; P=0.042) were significantly associated with the increased risk of a secondary progressive disease course. Conclusions: This study showed that POMS patients with brainstem/cerebellar presentation and a relatively higher age at MS onset had disposition for SPMS and warrant an aggressive therapeutic approach.


2020 ◽  
Vol 15 (6) ◽  
pp. 794-804 ◽  
Author(s):  
Abimereki D. Muzaale ◽  
Matthew Daubresse ◽  
Sunjae Bae ◽  
Nadia M. Chu ◽  
Krista L. Lentine ◽  
...  

Background and objectivesMortality from benzodiazepine/opioid interactions is a growing concern in light of the opioid epidemic. Patients on hemodialysis suffer from a high burden of physical/psychiatric conditions, which are treated with benzodiazepines, and they are three times more likely to be prescribed opioids than the general population. Therefore, we studied mortality risk associated with short- and long-acting benzodiazepines and their interaction with opioids among adults initiating hemodialysis.Design, setting, participants, & measurementsThe cohort of 69,368 adults initiating hemodialysis (January 2013 to December 2014) was assembled by linking US Renal Data System records to Medicare claims. Medicare claims were used to identify dispensed benzodiazepines and opioids. Using adjusted Cox proportional hazards models, we estimated the mortality risk associated with benzodiazepines (time varying) and tested whether the benzodiazepine-related mortality risk differed by opioid codispensing.ResultsWithin 1 year of hemodialysis initiation, 10,854 (16%) patients were dispensed a short-acting benzodiazepine, and 3262 (5%) patients were dispensed a long-acting benzodiazepine. Among those who were dispensed a benzodiazepine during follow-up, codispensing of opioids and short-acting benzodiazepines occurred among 3819 (26%) patients, and codispensing of opioids and long-acting benzodiazepines occurred among 1238 (8%) patients. Patients with an opioid prescription were more likely to be subsequently dispensed a short-acting benzodiazepine (adjusted hazard ratio, 1.66; 95% confidence interval, 1.59 to 1.74) or a long-acting benzodiazepine (adjusted hazard ratio, 1.11; 95% confidence interval, 1.03 to 1.20). Patients dispensed a short-acting benzodiazepine were at a 1.45-fold (95% confidence interval, 1.35 to 1.56) higher mortality risk compared with those without a short-acting benzodiazepine; among those with opioid codispensing, this risk was 1.90-fold (95% confidence interval, 1.65 to 2.18; Pinteraction<0.001). In contrast, long-acting benzodiazepine dispensing was inversely associated with mortality (adjusted hazard ratio, 0.84; 95% confidence interval, 0.72 to 0.99) compared with no dispensing of long-acting benzodiazepine; there was no differential risk by opioid dispensing (Pinteraction=0.72).ConclusionsCodispensing of opioids and short-acting benzodiazepines is common among patients on dialysis, and it is associated with higher risk of death.


2021 ◽  
pp. 000486742110096
Author(s):  
Oleguer Plana-Ripoll ◽  
Patsy Di Prinzio ◽  
John J McGrath ◽  
Preben B Mortensen ◽  
Vera A Morgan

Introduction: An association between schizophrenia and urbanicity has long been observed, with studies in many countries, including several from Denmark, reporting that individuals born/raised in densely populated urban settings have an increased risk of developing schizophrenia compared to those born/raised in rural settings. However, these findings have not been replicated in all studies. In particular, a Western Australian study showed a gradient in the opposite direction which disappeared after adjustment for covariates. Given the different findings for Denmark and Western Australia, our aim was to investigate the relationship between schizophrenia and urbanicity in these two regions to determine which factors may be influencing the relationship. Methods: We used population-based cohorts of children born alive between 1980 and 2001 in Western Australia ( N = 428,784) and Denmark ( N = 1,357,874). Children were categorised according to the level of urbanicity of their mother’s residence at time of birth and followed-up through to 30 June 2015. Linkage to State-based registers provided information on schizophrenia diagnosis and a range of covariates. Rates of being diagnosed with schizophrenia for each category of urbanicity were estimated using Cox proportional hazards models adjusted for covariates. Results: During follow-up, 1618 (0.4%) children in Western Australia and 11,875 (0.9%) children in Denmark were diagnosed with schizophrenia. In Western Australia, those born in the most remote areas did not experience lower rates of schizophrenia than those born in the most urban areas (hazard ratio = 1.02 [95% confidence interval: 0.81, 1.29]), unlike their Danish counterparts (hazard ratio = 0.62 [95% confidence interval: 0.58, 0.66]). However, when the Western Australian cohort was restricted to children of non-Aboriginal Indigenous status, results were consistent with Danish findings (hazard ratio = 0.46 [95% confidence interval: 0.29, 0.72]). Discussion: Our study highlights the potential for disadvantaged subgroups to mask the contribution of urban-related risk factors to risk of schizophrenia and the importance of stratified analysis in such cases.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Siqing Wang ◽  
Aiya Qin ◽  
Gaiqin Pei ◽  
Zheng Jiang ◽  
Lingqiu Dong ◽  
...  

Abstract Background Whether cigarette smoking is associated with the progression of immunoglobulin A nephropathy (IgAN) remains uncertain; therefore, we aimed to evaluate the effect of cigarette smoking on the prognosis of IgAN. Methods We divided 1239 IgAN patients from West China Hospital of Sichuan University who met the inclusion criteria into smoker (current or former) and non-smoker groups. The endpoint was end-stage renal disease (ESRD: eGFR < 15 mL/min/1.73 m2 or undergoing renal replacement treatment) and/or eGFR decreased by > 50%. Kaplan–Meier, correlation, logistic regression and Cox proportional hazards analyses were performed. The association between cigarette smoking and IgAN was further verified by propensity-score-matched cohort analysis. Results During the mean follow-up period of 61 months, 19% (40/209) of the smoker group and 11% (110/1030) of the non-smoker group reached the study endpoint (p < 0.001). Multivariate Cox regression analysis revealed that cigarette smoking (hazard ratio (HR) = 1.58; p = 0.043) was an independent risk factor predicting poor renal progression in IgAN, and that IgAN patients with chronic kidney disease (CKD) stage 3–4 were more susceptible to cigarette smoking (p < 0.001). After propensity score matching (PSM), a significant correlation between cigarette smoking and renal outcomes in IgAN patients was seen. Furthermore, Spearman’s correlation test revealed that smoking dose was negatively correlated with eGFR (r = 0.141; p < 0.001) and positively related with proteinuria (r = 0.096; p = 0.001). Conclusions Cigarette smoking is an independent risk factor for IgAN progression, especially for advanced patients.


Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Yilong Wang ◽  
Xiaomeng Yang ◽  
Jing Jing ◽  
Xingquan Zhao ◽  
Liping Liu ◽  
...  

Objective: We aim to investigate the effects and safety of clopidogrel plus aspirin in patients with different types of single small subcortical infarction(SSSI) in the Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial. Methods: In this subgroup analysis, SSSI was defined as single DWI lesion of ≤2.0 cm and SSSI with stenosis of any degree of the parent artery was regarded as a SSSI+PAD. We assessed the interaction of the treatment effects of clopidogrel plus aspirin versus aspirin alone among patients with and without PAD. Efficacy was assessed by intention to treat analysis and safety was assessed in the on-treatment population. Results: A total of 338 patients with SSSI were included in the final analysis,105 with SSSI+PAD and 233 SSSI-PAD. In SSSI+PAD patients, 10.9% (5/46) had recurrent stroke in the clopidogrel-aspirin group as compared to 13.6% (8/59) in the aspirin group (adjusted hazard ratio, 0.66; 95% confidence interval, 0.20-2.20; P=0.50). In SSSI-PAD patients, 8.9% (11/124) had recurrent stroke in the clopidogrel-aspirin group as compared 7.3% (8/109) in the aspirin group (adjusted hazard ratio, 1.64; 95% confidence interval, 0.61- 4.38; P=0.32). The number of bleeding events was similar between the clopidogrel-aspirin group and aspirin group regardless of SSSI+PAD or SSSI-PAD. Conclusions: Although dual antiplatelet therapy did not significantly reduce the risk of recurrent stroke than aspirin alone in patients with SSSI. It was potentially beneficial to the patients with SSSI+PAD. Dual antiplatelet treatment did not increase the risk of bleeding in patients with any kind of SSSI.


2019 ◽  
Author(s):  
Inger van Heijl ◽  
Valentijn A. Schweitzer ◽  
C.H. Edwin Boel ◽  
Jan Jelrik Oosterheert ◽  
Susanne M. Huijts ◽  
...  

BackgroundObservational studies have demonstrated that de-escalation of antimicrobial therapy is independently associated with lower mortality. This most probably results from confounding by indication. Reaching clinical stability is associated with the decision to de-escalate and with survival. However, studies rarely adjust for this confounder. We quantified the potential confounding effect of clinical stability on the estimated impact of de-escalation on mortality in patients with community-acquired pneumonia.MethodsData were used from the Community-Acquired Pneumonia immunization Trial in Adults (CAPiTA). The primary outcome was 30-day mortality. We performed Cox proportional-hazards regression with de-escalation as time-dependent variable and adjusted for baseline characteristics using propensity scores. The potential impact of unmeasured confounding was quantified through simulating a variable representing clinical stability on day three, using data on prevalence and associations with mortality from the literature.ResultsOf 1,536 included patients, 257 (16.7%) were de-escalated, 123 (8.0%) were escalated and in 1156 (75.3%) the antibiotic spectrum remained unchanged. The adjusted hazard ratio of de-escalation for 30-day mortality (compared to patients with unchanged coverage), without adjustment for clinical stability, was 0.36 (95%CI: 0.18-0.73). If 90% to 100% of de-escalated patients were clinically stable on day three, the fully adjusted hazard ratio would be 0.53 (95%CI: 0.26-1.08) to 0.90 (95%CI: 0.42-1.91), respectively. The simulated confounder was substantially stronger than any of the baseline confounders in our dataset.ConclusionsWith plausible, literature-based assumptions, clinical stability is a very strong confounder for the effects of de-escalation. Quantification of effects of de-escalation on patient outcomes without proper adjustment for clinical stability results in strong negative bias. As a result, the safety of de-escalation remains to be determined.


2019 ◽  
Author(s):  
Nicolai A Lund-Blix ◽  
German Tapia ◽  
Karl Mårild ◽  
Anne Lise Brantsaeter ◽  
Pål R Njølstad ◽  
...  

ABSTRACTOBJECTIVETo examine the association between maternal and child gluten intake and risk of type 1 diabetes in children.DESIGNPregnancy cohortSETTINGPopulation-based, nation-wide study in NorwayPARTICIPANTS86,306 children in The Norwegian Mother and Child Cohort Study born from 1999 through 2009, followed to April 15, 2018.MAIN OUTCOME MEASURESClinical type 1 diabetes, ascertained in a nation-wide childhood diabetes registry. Hazard ratios were estimated using Cox regression for the exposures maternal gluten intake up to week 22 of pregnancy and child’s gluten intake when the child was 18 months old.RESULTSDuring a mean follow-up of 12.3 years (range 0.7-16.0), 346 children (0.4%) developed type 1 diabetes (incidence rate 32.6 per 100,000 person-years). The average gluten intake was 13.6 grams/day for mothers during pregnancy, and 8.8 grams/day for the child at 18 months of age. Maternal gluten intake in mid-pregnancy was not associated with the development of type 1 diabetes in the child (adjusted hazard ratio 1.02 (95% confidence interval 0.73 to 1.43) per 10 grams/day increase in gluten intake). However, the child’s gluten intake at 18 months of age was associated with an increased risk of later developing type 1 diabetes (adjusted hazard ratio 1.46 (95% confidence interval 1.06 to 2.01) per 10 grams/day increase in gluten intake).CONCLUSIONSThis study suggests that the child’s gluten intake at 18 months of age, and not the maternal intake during pregnancy, could increase the risk of type 1 diabetes in the child.WHAT IS ALREADY KNOWN ON THIS TOPICA national prospective cohort study from Denmark found that a high maternal gluten intake during pregnancy could increase the risk of type 1 diabetes in the offspring (adjusted hazard ratio 1.31 (95% confidence interval 1.001 to 1.72) per 10 grams/day increase in gluten intake). No studies have investigated the relation between the amount of gluten intake by both the mother during pregnancy and the child in early life and risk of developing type 1 diabetes in childhood.WHAT THIS STUDY ADDSIn this prospective population-based pregnancy cohort with 86,306 children of whom 346 developed type 1 diabetes we found that the child’s gluten intake at 18 months of age was associated with the risk of type 1 diabetes (adjusted hazard ratio 1.46 (95% confidence interval 1.06 to 2.01) per 10 grams/day increase in gluten intake). This study suggests that the child’s gluten intake at 18 months of age, and not the maternal intake during pregnancy, could increase the child’s risk of type 1 diabetes.


Neurosurgery ◽  
2015 ◽  
Vol 77 (6) ◽  
pp. 880-887 ◽  
Author(s):  
Eric J. Heyer ◽  
Joanna L. Mergeche ◽  
Shuang Wang ◽  
John G. Gaudet ◽  
E. Sander Connolly

BACKGROUND: Early cognitive dysfunction (eCD) is a subtle form of neurological injury observed in ∼25% of carotid endarterectomy (CEA) patients. Statin use is associated with a lower incidence of eCD in asymptomatic patients having CEA. OBJECTIVE: To determine whether eCD status is associated with worse long-term survival in patients taking and not taking statins. METHODS: This is a post hoc analysis of a prospective observational study of 585 CEA patients. Patients were evaluated with a battery of neuropsychometric tests before and after surgery. Survival was compared for patients with and without eCD stratifying by statin use. At enrollment, 366 patients were on statins and 219 were not. Survival was assessed by using Kaplan-Meier methods and multivariable Cox proportional hazards models. RESULTS: Age ≥75 years (P = .003), diabetes mellitus (P &lt; .001), cardiac disease (P = .02), and statin use (P = .014) are significantly associated with survival univariately (P &lt; .05) by use of the log-rank test. By Cox proportional hazards model, eCD status and survival adjusting for univariate factors within statin and nonstatin use groups suggested a significant effect by association of eCD on survival within patients not taking statin (hazard ratio, 1.61; 95% confidence interval, 1.09–2.40; P = .018), and no significant effect of eCD on survival within patients taking statin (hazard ratio, 0.98; 95% confidence interval, 0.59–1.66; P = .95). CONCLUSION: eCD is associated with shorter survival in patients not taking statins. This finding validates eCD as an important neurological outcome and suggests that eCD is a surrogate measure for overall health, comorbidity, and vulnerability to neurological insult.


2018 ◽  
Vol 29 (6) ◽  
pp. 1761-1770 ◽  
Author(s):  
Sarah B. See ◽  
Olivier Aubert ◽  
Alexandre Loupy ◽  
Yokarla Veras ◽  
Xavier Lebreton ◽  
...  

Background The development of antibodies specific to HLA expressed on donor tissue (donor-specific antibodies [DSAs]) is a prominent risk factor for kidney graft loss. Non-HLA antibodies with pathogenic potential have also been described, including natural antibodies (Nabs). These IgG Nabs bind to immunogenic self-determinants, including oxidation-related antigens.Methods To examine the relationship of Nabs with graft outcomes, we assessed Nabs in blinded serum specimens collected from a retrospective cohort of 635 patients who received a transplant between 2005 and 2010 at Necker Hospital in Paris, France. Serum samples were obtained immediately before transplant and at the time of biopsy-proven rejection within the first year or 1 year after transplant. Nabs were detected by ELISA through reactivity to the generic oxidized epitope malondialdehyde.Results Univariate Cox regression analysis identified the development of post-transplant Nabs (defined as 50% increase in reactivity to malondialdehyde) as a significant risk factor for graft loss (hazard ratio, 2.68; 95% confidence interval, 1.49 to 4.82; P=0.001). Post-transplant Nabs also correlated with increased mean Banff scores for histologic signs of graft injury in post-transplant biopsy specimens. Multivariable Cox analyses confirmed Nabs development as a risk factor independent from anti-HLA DSAs (hazard ratio, 2.07; 95% confidence interval, 1.03 to 4.17; P=0.04). Moreover, patients with Nabs and DSAs had a further increased risk of kidney graft loss.Conclusions These findings reveal an association between Nabs, kidney graft injury, and eventual graft failure, suggesting the involvement of Nabs in immune mechanisms of rejection.


BMJ ◽  
2018 ◽  
pp. k3547 ◽  
Author(s):  
Julie C Antvorskov ◽  
Thorhallur I Halldorsson ◽  
Knud Josefsen ◽  
Jannet Svensson ◽  
Charlotta Granström ◽  
...  

Abstract Objective To examine the association between prenatal gluten exposure and offspring risk of type 1 diabetes in humans. Design National prospective cohort study. Setting National health information registries in Denmark. Participants Pregnant Danish women enrolled into the Danish National Birth Cohort, between January 1996 and October 2002, Main outcome measures Maternal gluten intake, based on maternal consumption of gluten containing foods, was reported in a 360 item food frequency questionnaire at week 25 of pregnancy. Information on type 1 diabetes occurrence in the participants’ children, from 1 January 1996 to 31 May 2016, were obtained through registry linkage to the Danish Registry of Childhood and Adolescent Diabetes. Results The study comprised 101 042 pregnancies in 91 745 women, of whom 70 188 filled out the food frequency questionnaire. After correcting for multiple pregnancies, pregnancies ending in abortions, stillbirths, lack of information regarding the pregnancy, and pregnancies with implausibly high or low energy intake, 67 565 pregnancies (63 529 women) were included. The average gluten intake was 13.0 g/day, ranging from less than 7 g/day to more than 20 g/day. The incidence of type 1 diabetes among children in the cohort was 0.37% (n=247) with a mean follow-up period of 15.6 years (standard deviation 1.4). Risk of type 1 diabetes in offspring increased proportionally with maternal gluten intake during pregnancy (adjusted hazard ratio 1.31 (95% confidence interval 1.001 to 1.72) per 10 g/day increase of gluten). Women with the highest gluten intake versus those with the lowest gluten intake (≥20 v <7 g/day) had double the risk of type 1 diabetes development in their offspring (adjusted hazard ratio 2.00 (95% confidence interval 1.02 to 4.00)). Conclusions High gluten intake by mothers during pregnancy could increase the risk of their children developing type 1 diabetes. However, confirmation of these findings are warranted, preferably in an intervention setting.


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