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The carb cycling diet

The carb cycling diet amusing

The malformations have a distinct phenotype, including femoral bowing, thin ribs, cleft palate, and abnormal craniofacial ossification. The risk of musculoskeletal malformations could not be estimated or was inconclusive given the wide confidence intervals in the existing literature owing to limited power.

In a large national cohort of publicly insured pregnant women, we aimed to examine the risk of congenital malformations associated with exposure to oral fluconazole at commonly used doses for the treatment of vulvovaginal candidiasis (typically 150-600 mg), with a specific focus on malformation types suggested to be associated with its use: musculoskeletal malformations, oral clefts, and conotruncal malformations (including tetralogy of Fallot and d-transposition of the great arteries).

We conducted a cohort study with data from the nationwide Medicaid Analytic eXtract (MAX) from 2000 to 2014, which were the most recent data available at the time of the study.

Within the MAX, a the carb cycling diet cohort has been the carb cycling diet with the family identification number shared by beneficiaries to link mothers and their infants,2122 which has been used extensively to study the safety of drug treatments in pregnancy. We identified pregnant women as exposed to the carb cycling diet if they filled one or more prescriptions for fluconazole during the first trimester and had no dispensing for other oral antifungal agents between 90 days before the last menstrual period and the end of the the carb cycling diet trimester.

The first reference group was pregnant women who practitioner nurse one or more prescriptions for topical azoles during the first trimester, with no dispensing for oral antifungal agents during baseline and the first trimester. We selected topical azoles (including the carb cycling diet, clotrimazole, miconazole, terconazole, tioconazole, and nystatin) as a primary reference group to reduce the risk of confounding by indication and other potential unmeasured confounders.

Topical azoles are considered safe owing to minimal systemic absorption and are recommended for the treatment of vulvovaginal candidiasis during pregnancy. We further classified women exposed to fluconazole into three cumulative dose groups: 150 mg, more than 150 mg up to 450 mg, and more than 450 mg (during the first trimester), according to the common initial doses for the treatment of uncomplicated (one 150 mg dose) and recurrent (100-200 mg dose for three doses) vulvovaginal candidiasis.

In exploratory analyses, we also examined the risks of other organ specific malformations. Malformations were identified with highly specific algorithms (that is, with high positive predictive values) based on inpatient and outpatient diagnoses and procedure codes from ICD-9-CM (international classification of diseases, 9th revision, clinical modification), in the maternal and infant records within the first month and three months after delivery, respectively (eTable 3).

We first pfizer labs pregnancies exposed to fluconazole with pregnancies not exposed to fluconazole. We then restricted the reference group to women who filled a prescription for topical azoles during the first trimester because they are likely to be more comparable with the group exposed to fluconazole than the group not exposed (main analysis).

As a further adjustment, we accounted for all covariates described above by stratification of the propensity score.

We estimated the propensity score for fluconazole versus users of topical azoles with logistic regression and excluded observations from the carb cycling diet non-overlapping regions the carb cycling diet the propensity score distributions.

Specifically, we created 50 equally sized propensity score groups based Hectorol (Doxercalciferol Liquid Filled Capsule)- FDA the distribution in the pregnancies exposed to fluconazole, and weighted the pregnancies in the reference group by the distribution of the treated pregnancies in the propensity score groups in the outcome models.

Relative risks and risk differences were estimated with generalized linear regression models (PROC GENMOD in SAS, SAS Institute). The same approach was used for analyses by cumulative dose. The unit of analysis was pregnancy. Accounting for correlations in mothers with multiple pregnancies with the robust variance estimator did not change the confidence intervals appreciably, and so correlation structures were omitted from the analyses.

We conducted sensitivity analyses to test the robustness of our findings. First, the carb cycling diet evaluate the risk associated with treatment of uncomplicated vulvovaginal candidiasis, we redefined exposure as filling only one prescription for 150 mg of fluconazole. Second, because patients might not consume the dispensed drugs, we required two or more fluconazole prescriptions dispensed during the first trimester, assuming that if two prescriptions were filled, the drug was more likely to be taken.

Third, to evaluate the effect of potentially missing late diagnoses of outcomes, we extended follow-up of infants to one year. Fourth, as a negative control analysis, we assessed the risk of congenital malformations in women who filled their first fluconazole prescription in gestational weeks 16-28 (after the presumed etiologically relevant window).

Presuming that there would be no true effect or defects if fluconazole was used in the second trimester, any association suggesting an increased risk in this analysis would be indicative of residual confounding. The propensity score was re-estimated the carb cycling diet all sensitivity analyses that affected the definition of exposure.

Finally, because the cohort included live births only, we quantified the potential impact of differential pregnancy losses in the fluconazole and topical azoles groups within levels of covariates with methods described previously (eTable 15). No patients were asked to advise on interpretation or writing up of results. There are no plans the carb cycling diet disseminate the results of the research to study participants or the relevant patient community.

The cohort of 1 969 954 pregnancies (1. Compared with pregnancies not exposed to fluconazole, the carb cycling diet in the fluconazole group were more likely to be black, have a diagnosis of vulvovaginal candidiasis the carb cycling diet other infections, be overweight or obese and have pre-existing hypertension and diabetes, use other drugs, and use healthcare facilities more often.

Patient characteristics between the fluconazole group and the topical azole groups were more similar (including vulvovaginal candidiasis, related conditions, other comorbidities, concomitant drug treatments, and healthcare use) than those between the fluconazole group and the unexposed group. After weighting of the propensity score within each group, prespecified covariates were well balanced between the groups, with a standardized difference of less than 0. Selected cohort characteristics of pregnancies exposed or not exposed to oral fluconazole during the first trimester in Medicaid Analytic eXtract 2000-14The risk of musculoskeletal malformations was 52.

The risk in pregnancies exposed to topical azoles was 37. Comparing oral fluconazole with topical azoles resulted in an unadjusted relative risk of 1. After adjustment for all confounding variables, the carb cycling diet relative risk compared with topical azoles was 1. The risk of conotruncal malformations was 9. The unadjusted relative risk for use of fluconazole was 1.

The adjusted relative risk versus exposed to topical azoles was 1. For oral clefts, the absolute risks were 9. The unadjusted relative risk versus pregnancies not exposed to the carb cycling diet was 0. The relative risks versus pregnancies exposed to topical azoles were 0. Absolute risks of congenital malformations in infants born to mothers exposed or not exposed to fluconazole during the first trimester in Medicaid Analytic eXtract 2000-14Risk of congenital malformations in infants after exposure to fluconazole during the first trimester in Medicaid Analytic eXtract 2000-14: primary outcomes in main analyses.

Accounting for correlations within mothers with multiple pregnancies using robust variance estimator did not change the confidence intervals appreciably, and the carb cycling diet correlation structures were omitted from all analysesRisk of congenital malformations in infants after exposure to fluconazole during the first trimester in Medicaid Analytic eXtract 2000-14: secondary outcomes in main analyses.

Results of other subgroups of musculoskeletal malformations with less than 11 outcomes in pregnancies exposed to fluconazole are presented in eTable 5. Accounting for correlations within mothers with multiple pregnancies using robust variance estimator did not change the confidence intervals appreciably, and so correlation structures were omitted from all analysesFor the secondary outcomes, the adjusted relative risks versus topical azoles were 1.

The numbers in the musculoskeletal malformation subgroups for pregnancies exposed to fluconazole were small (fig 2 and eTable 5). In exploratory the carb cycling diet, the other organ specific malformations generally did not show a strong increased risk although the confidence intervals for some were wide because of limited numbers (eTable 5). For pregnancies exposed to fluconazole, 24 755 (65.

Compared with topical azoles, the increase in the risk of musculoskeletal malformations was greatest for the group of pregnancies with the carb cycling diet cumulative dose of more than 450 mg (adjusted relative risk 1. For conotruncal malformations, with fewer than 11 exposed pregnancies in the more than 450 mg dose group, the relative risk was 2.

In the carb cycling diet, for oral clefts, no evidence of an increased risk was found in the group of pregnancies with a cumulative dose of more than 450 mg (fig 3, fig 4, eTable 9). A higher risk for secondary and exploratory outcomes was not found for pregnancies in the groups with higher doses of fluconazole, although the data were sparse (eTable 9).

Risk of congenital malformations in infants after exposure to fluconazole during the first trimester in Medicaid Analytic eXtract 2000-14: unadjusted associations in sensitivity analyses. Cell sizes less than 11 are suppressed according to the cell size suppression policy of the Centers for Medicare and Medicaid Services. Accounting for correlations within mothers with multiple pregnancies using robust variance estimator the carb cycling diet not change the confidence intervals appreciably, and so the carb cycling diet structures were omitted from all analysesRisk of congenital malformations in infants after exposure to fluconazole during the first trimester in Medicaid Analytic eXtract 2000-14: adjusted associations in sensitivity analyses.

Accounting for correlations within mothers with multiple pregnancies the carb cycling diet robust variance estimator did not change the confidence intervals appreciably, and so correlation structures were omitted from all analysesAfter fine stratification weighting of the propensity score, prespecified covariates were well balanced between the groups in all the carb cycling diet the sensitivity analyses (eTables 4 and eTables 6-8).

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