Determination of the time-dependent association between ciprofloxacin consumption and ciprofloxacin resistance using a weighted cumulative exposure model compared with standard models

2020 ◽  
Author(s):  
Rolina D van Gaalen ◽  
Wieke Altorf-van der Kuil ◽  
Marjolijn C A Wegdam-Blans ◽  
Jessica M Aguilar Diaz ◽  
Marie-Eve Beauchamp ◽  
...  
Keyword(s):  
Conditional Logistic Regression ◽  
Time Windows ◽  
Cumulative Effect ◽  
Time Dependent ◽  
Cumulative Exposure ◽  
Exposure Model ◽  
Repeated Treatment ◽  
Antibiotic Susceptibility Test ◽  
Ciprofloxacin Resistance ◽  
Nested Case Control

Abstract Objectives To obtain comprehensive insight into the association of ciprofloxacin use at different times in the past with the current risk of detecting resistance. Methods This retrospective nested case–control study of ciprofloxacin users used Dutch data from the PHARMO Database Network and one laboratory for the period 2003–14. Cases and controls were selected as patients with an antibiotic susceptibility test (AST) indicating ciprofloxacin resistance or susceptibility, respectively. We performed univariable and multivariable conditional logistic regression analyses, defining time-dependent exposure using standard definitions (current ciprofloxacin use, used 0–30, 31–90, 91–180 and 181–360 days ago) and a flexible weighted cumulative effect (WCE) model with four alternative time windows of past doses (0–30, 0–90, 0–180 and 0–360 days). Results The study population consisted of 230 cases and 909 controls. Under the standard exposure definitions, the association of ciprofloxacin use with resistance decreased with time [current use: adjusted OR 6.8 (95% CI 3.6–12.4); used 181–360 days ago: 1.3 (0.8–1.9)]. Under the 90 day WCE model (best-fitting model), more recent doses were more strongly associated with resistance than past doses, as was longer or repeated treatment. The 180 day WCE model, which fitted the data equally well, suggested that doses taken 91–180 days ago were also significantly associated with resistance. Conclusions The estimates for the association between ciprofloxacin use at different times and resistance show that ciprofloxacin prescribers should consider ciprofloxacin use 0–180 days ago to ensure that patients receive suitable treatment. The OR of ciprofloxacin resistance could be reduced by eliminating repeated ciprofloxacin prescription within 180 days and by treating for no longer than necessary.

Assessing the cumulative effects of exposure to selected benzodiazepines on the risk of fall-related injuries in the elderly

2011 ◽  
Vol 24 (4) ◽  
pp. 577-586 ◽  
Author(s):  
Marie-Pierre Sylvestre ◽  
Michal Abrahamowicz ◽  
Radan Čapek ◽  
Robyn Tamblyn
Keyword(s):  
Cumulative Effect ◽  
The Elderly ◽  
Cumulative Effects ◽  
Cumulative Exposure ◽  
Exposure Model ◽  
Administrative Database ◽  
The Past ◽  
Increased Risk ◽  
Benzodiazepine Use ◽  
Risk Of Fall

ABSTRACTBackground: The use of benzodiazepines is associated with increased risk of fall-related injuries in the elderly. However, it is unclear if the risks vary across the products and how they depend on the pattern of use and dosage. Specifically, the possibility of cumulative effects of past benzodiazepine use has not been thoroughly investigated.Methods: We used the administrative database for a cohort of 23,765 new users of benzodiazepines, aged 65 years and older, in Quebec, Canada, between 1990 and 1994. The associations between the use of seven benzodiazepines and the risk of fall-related injuries were assessed using several statistical models, including a novel weighted cumulative exposure model. That model assigns to each dose taken in the past a weight that represents the importance of that dose in explaining the current risk of fall.Results: For flurazepam, the best-fitting model indicated a cumulative effect of doses taken in the last two weeks. Uninterrupted use of flurazepam in the past months was associated with a highly significant increase in the risk of fall-related injuries (HR = 2.83, 95% CI: 1.45–4.34). The cumulative effect of a 30-day exposure to alprazolam was 1.27 (1.13–1.42). For temazepam, the results suggested a potential withdrawal effect.Conclusions: Mechanisms affecting the risk of falls differ across benzodiazepines, and may include cumulative effects of use in the previous few weeks. Thus, benzodiazepine-specific analyses that account for individual patterns of use should be preferred over simpler analyses that group different benzodiazepines together and limit exposure to current use or current dose.

scholarly journals A systematic assessment of the association between frequently prescribed medicines and the risk of common cancers: a series of nested case-control studies

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
R. D. McDowell ◽  
C. Hughes ◽  
P. Murchie ◽  
C. Cardwell
Keyword(s):  
Cancer Risk ◽  
Conditional Logistic Regression ◽  
Exposure Dose ◽  
Case Control ◽  
Case Control Studies ◽  
Systematic Assessment ◽  
Exposure Response ◽  
Prescribed Medicines ◽  
Nested Case Control ◽  
Novel Associations

Abstract Background Studies systematically screening medications have successfully identified prescription medicines associated with cancer risk. However, adjustment for confounding factors in these studies has been limited. We therefore investigated the association between frequently prescribed medicines and the risk of common cancers adjusting for a range of confounders. Methods A series of nested case-control studies were undertaken using the Primary Care Clinical Informatics Unit Research (PCCIUR) database containing general practice (GP) records from Scotland. Cancer cases at 22 cancer sites, diagnosed between 1999 and 2011, were identified from GP records and matched with up to five controls (based on age, gender, GP practice and date of registration). Odds ratios (OR) and 95% confidence intervals (CI) comparing any versus no prescriptions for each of the most commonly prescribed medicines, identified from prescription records, were calculated using conditional logistic regression, adjusting for comorbidities. Additional analyses adjusted for smoking use. An association was considered a signal based upon the magnitude of its adjusted OR, p-value and evidence of an exposure-response relationship. Supplementary analyses were undertaken comparing 6 or more prescriptions versus less than 6 for each medicine. Results Overall, 62,109 cases and 276,580 controls were included in the analyses and a total of 5622 medication-cancer associations were studied across the 22 cancer sites. After adjusting for comorbidities 2060 medicine-cancer associations for any prescription had adjusted ORs greater than 1.25 (or less than 0.8), 214 had a corresponding p-value less than or equal to 0.01 and 118 had evidence of an exposure-dose relationship hence meeting the criteria for a signal. Seventy-seven signals were identified after additionally adjusting for smoking. Based upon an exposure of 6 or more prescriptions, there were 118 signals after adjusting for comorbidities and 82 after additionally adjusting for smoking. Conclusions In this study a number of novel associations between medicine and cancer were identified which require further clinical and epidemiological investigation. The majority of medicines were not associated with an altered cancer risk and many identified signals reflected known associations between medicine and cancer.

scholarly journals Association of Mesothelioma Deaths With Cumulated Neighborhood Exposures Due to a Large-Scale Asbestos Cement Plant in Amagasaki City, Japan: A Nested Case-control Study

2021 ◽  
Author(s):  
Yuri Kitamura ◽  
Ling Zha ◽  
Rong Liu ◽  
Masayuki Shima ◽  
Tomoki Nakaya ◽  
...  
Keyword(s):  
Occupational Exposure ◽  
Large Scale ◽  
Case Control Study ◽  
Conditional Logistic Regression ◽  
Asbestos Exposure ◽  
Case Control ◽  
Asbestos Cement ◽  
Nested Case Control ◽  
Dose Dependent ◽  
Control Study

Abstract BackgroundAlthough a causal relationship between mesothelioma and asbestos exposure is well known, few studies have shown a relationship to non-occupational exposure, including neighborhood exposure, most likely because of the large effect size of occupational exposure. The aim of this study was to quantify the risk of malignant mesothelioma death associated with neighborhood asbestos exposure due to a large-scale asbestos-cement (AC) plant in Amagasaki, Japan, by properly adjusting for occupational exposure. MethodsThis was a nested case-control study in which a fixed population of 143,929 residents who had been living in Amagasaki City between 1975 and 2002 were followed from 2002 to 2015. All 133 cases and 403 matched controls were interviewed about their occupational, domestic, household, and neighborhood asbestos exposures. Odds ratios (ORs) for mesothelioma death associated with neighborhood exposure were estimated by a conditional logistic-regression model that adjusted for other asbestos exposures. We adopted cumulative indices that considered residence-specific asbestos (crocidolite) concentrations and durations during the potential exposure period of 1957-1975 to evaluate individual neighborhood exposures.ResultsThere was an increasing, dose-dependent risk of mesothelioma death associated with neighborhood exposure, demonstrated by ORs in the highest quintile category that were 21.4 (95%CI: 5.8 to 79.2) for all, 23.7 (95% CI: 3.8-147.2) for males and 26.0 (95% CI: 2.8-237.5) for females, compared to the lowest quintile, respectively. These results clearly demonstrated no substantial differences between males and females in relation to the magnitude of risk from neighborhood exposure.Our findings suggest that the risk of mesothelioma death associated with neighborhood exposure persists and will not be diminished for many years, even though it has been decades since the AC plant closed. ConclusionsBy adjusting for occupational and other asbestos exposures, a dose-dependent relationship was demonstrated between mesothelioma death and neighborhood asbestos exposure from a large-scale AC plant.

scholarly journals Maternal Transfer of Environmentally Relevant Polybrominated Diphenyl Ethers (PBDEs) Produces a Diabetic Phenotype and Disrupts Glucoregulatory Hormones and Hepatic Endocannabinoids in Adult Mouse Female Offspring

2020 ◽  
Author(s):  
Elena V. Kozlova ◽  
Bhuvaneswari D. Chinthirla ◽  
Pedro A. Pérez ◽  
Nicholas V. DiPatrizio ◽  
Donovan A. Argueta ◽  
...  
Keyword(s):  
Polybrominated Diphenyl Ethers ◽  
Ex Vivo ◽  
Time Windows ◽  
Female Offspring ◽  
Exposure Model ◽  
Maternal Transfer ◽  
Tissue Mass ◽  
Brown Adipose ◽  
Diphenyl Ethers

AbstractPolybrominated diphenyl ethers (PBDEs) are brominated flame retardant chemicals and environmental contaminants with endocrine-disrupting properties that are associated with diabetes and metabolic syndrome in humans. However, their diabetogenic actions are not completely characterized or understood. In this study, we investigated the effects of DE-71, a commercial penta-mixture of PBDEs, on glucose regulatory parameters in a perinatal exposure model using female C57Bl/6 mice. Results from in vivo glucose and insulin tolerance tests and ex vivo analyses showed that DE-71 produced fasting hyperglycemia, glucose intolerance, reduced sensitivity and delayed glucose clearance after insulin challenge, and exaggerated hepatic endocannabinoid tone in F1 offspring exposed to 0.1 mg/kg DE-71 relative to control. DE-71 effects on F0 dams were more limited indicating that indirect exposure to developing offspring is more detrimental. Other ex vivo glycemic correlates occur more generally in exposed F0 and F1, i.e., reduced plasma insulin and altered glucoregulatory endocrines, exaggerated sympathoadrenal activity, decreased thermogenic brown adipose tissue mass and reduced hepatic glutamate dehydrogenase enzymatic activity. Hepatic PBDE congener analysis indicated maternal transfer of BDE-28 and −153 to F1 at a collective level of 200 ng/g lipid, in range with maximum values detected in serum of human females. Given the persistent diabetogenic phenotype, especially pronounced in female offspring after developmental exposure to environmentally relevant levels of DE-71, additional animal studies should be conducted that further characterize PBDE-induced diabetic pathophysiology and identify critical developmental time windows of susceptibility. Longitudinal human studies should also be conducted to determine the risk of long-lasting metabolic consequences after maternal transfer of PBDEs during early-life development.

scholarly journals Nested Case-Control Studies With Multiple Measurements: Estimating Marginal Relationships

2021 ◽  
Author(s):  
Joshua N. Sampson ◽  
Paul S. Albert ◽  
Mark P. Purdue
Keyword(s):  
Conditional Logistic Regression ◽  
Case Control ◽  
Case Control Studies ◽  
Robust Variance ◽  
Non Hodgkin Lymphoma ◽  
Multiple Measurements ◽  
Matched Case ◽  
Nested Case Control ◽  
Standard Software ◽  
Single Time Point

Abstract Background: We consider the analysis of nested, matched, case-control studies that have multiple biomarker measurements per individual. We propose a simple approach for estimating the marginal relationship between a biomarker measured at a single time point and the risk of an event. We know of no other standard software package that can perform such analyses while explicitly accounting for the matching. Results: We propose an application of conditional logistic regression (CLR) that can include all measurements and uses a robust variance estimator. We compare our approach to other methods such as performing CLR with only the first measurement, CLR with an average of all measurements, and Generalized Estimating Equations. In simulations, our approach is significantly more powerful than CLR with one measurement or an average of all measurements, and has similar to power to GEE but correctly accounts for the matching. We then apply our approach to the CLUE cohort to show that an increased level of the immune marker sCD27 is associated with non‐Hodgkin lymphoma (NHL) and, by evaluating the strength of the association as a function of time until diagnosis, that the an increased level is likely an effect of the disease as opposed to a cause of the disease. The approach can be implemented by the R function clogitRV available at https://github.com/sampsonj74/clogitRV.Conclusion: We offered an approach and software for analyzing matched case-control studies with multiple measurements. We demonstrated that these methods are accurate, precise, and statistically powerful.

scholarly journals Time-Varying Associations Between an Exposure History and a Subsequent Health Outcome: A landmark Approach to Identify Critical Windows.

2021 ◽  
Author(s):  
Maude Wagner ◽  
Francine Grodstein ◽  
Karen Leffondre ◽  
Cécilia Samieri ◽  
Cécile Proust-Lima
Keyword(s):  
Risk Factors ◽  
Health Outcome ◽  
Measurement Errors ◽  
Mixed Model ◽  
Time Window ◽  
Time Windows ◽  
Critical Time ◽  
Cumulative Exposure ◽  
Exposure Measurement ◽  
Exposure History

Abstract Background: Long-term behavioral and health risk factors constitute a primary focus of research on the etiology of chronic diseases. Yet, identifying critical time-windows during which risk factors have the strongest impact on disease risk is challenging. To assess the trajectory of association of an exposure history with an outcome, the weighted cumulative exposure index (WCIE) has been proposed, with weights reflecting the relative importance of exposures at different times. However, WCIE is restricted to a complete observed error-free exposure whereas exposures are often measured with intermittent missingness and error. Moreover, it rarely explores exposure history that is very distant from the outcome as usually sought in life-course epidemiology.Methods: We extend the WCIE methodology to (i) exposures that are intermittently measured with error, and (ii) contexts where the exposure time-window precedes the outcome time-window using a landmark approach. First, the individual exposure history up to the landmark time is estimated using a mixed model that handles missing data and error in exposure measurement, and the predicted complete error-free exposure history is derived. Then the WCIE methodology is applied to assess the trajectory of association between the predicted exposure history and the health outcome collected after the landmark time. In our context, the health outcome is a longitudinal marker analyzed using a mixed model.Results: A simulation study first demonstrates the correct inference obtained with this approach. Then, applied to the Nurses’ Health Study (19,415 women) to investigate the association between body mass index history (collected from midlife) and subsequent cognitive decline (evaluated after age 70), the method identified two major critical windows of association: long before the first cognitive evaluation (roughly 24 to 12 years), higher levels of BMI were associated with poorer cognition. In contrast, adjusted for the whole history, higher levels of BMI became associated with better cognition in the last years prior to the first cognitive interview, thus reflecting reverse causation (changes in exposure due to underlying disease).Conclusions: This approach, easy to implement, provides a flexible tool for studying complex dynamic relationships and identifying critical time windows while accounting for exposure measurement errors.

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