Long-term frailty modeling using a non-proportional hazards model: Application with a melanoma dataset

2019 ◽  
Vol 29 (8) ◽  
pp. 2100-2118 ◽  
Author(s):  
Vinicius F Calsavara ◽  
Eder A Milani ◽  
Eduardo Bertolli ◽  
Vera Tomazella
Keyword(s):  
Survival Data ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Regression ◽  
Population Based ◽  
Likelihood Method ◽  
Cure Rate Models ◽  
Power Variance ◽  
Incident Cases

The semiparametric Cox regression model is often fitted in the modeling of survival data. One of its main advantages is the ease of interpretation, as long as the hazards rates for two individuals do not vary over time. In practice the proportionality assumption of the hazards may not be true in some situations. In addition, in several survival data is common a proportion of units not susceptible to the event of interest, even if, accompanied by a sufficiently large time, which is so-called immune, “cured,” or not susceptible to the event of interest. In this context, several cure rate models are available to deal with in the long term. Here, we consider the generalized time-dependent logistic (GTDL) model with a power variance function (PVF) frailty term introduced in the hazard function to control for unobservable heterogeneity in patient populations. It allows for non-proportional hazards, as well as survival data with long-term survivors. Parameter estimation was performed using the maximum likelihood method, and Monte Carlo simulation was conducted to evaluate the performance of the models. Its practice relevance is illustrated in a real medical dataset from a population-based study of incident cases of melanoma diagnosed in the state of São Paulo, Brazil.

Inter-pregnancy interval and later pediatric cardiovascular health of the offspring – a population-based cohort study

2020 ◽  
pp. 1-5
Author(s):  
Majdi Imterat ◽  
Tamar Wainstock ◽  
Eyal Sheiner ◽  
Gali Pariente
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Population Based ◽  
Cox Proportional Hazards ◽  
Cardiovascular Morbidity ◽  
Cox Proportional Hazards Model ◽  
Hazards Model ◽  
Kaplan Meier ◽  
Inter Pregnancy Interval

Abstract Recent evidence suggests that a long inter-pregnancy interval (IPI: time interval between live birth and estimated time of conception of subsequent pregnancy) poses a risk for adverse short-term perinatal outcome. We aimed to study the effect of short (<6 months) and long (>60 months) IPI on long-term cardiovascular morbidity of the offspring. A population-based cohort study was performed in which all singleton live births in parturients with at least one previous birth were included. Hospitalizations of the offspring up to the age of 18 years involving cardiovascular diseases and according to IPI length were evaluated. Intermediate interval, between 6 and 60 months, was considered the reference. Kaplan–Meier survival curves were used to compare the cumulative morbidity incidence between the groups. Cox proportional hazards model was used to control for confounders. During the study period, 161,793 deliveries met the inclusion criteria. Of them, 14.1% (n = 22,851) occurred in parturient following a short IPI, 78.6% (n = 127,146) following an intermediate IPI, and 7.3% (n = 11,796) following a long IPI. Total hospitalizations of the offspring, involving cardiovascular morbidity, were comparable between the groups. The Kaplan–Meier survival curves demonstrated similar cumulative incidences of cardiovascular morbidity in all groups. In a Cox proportional hazards model, short and long IPI did not appear as independent risk factors for later pediatric cardiovascular morbidity of the offspring (adjusted HR 0.97, 95% CI 0.80–1.18; adjusted HR 1.01, 95% CI 0.83–1.37, for short and long IPI, respectively). In our population, extreme IPIs do not appear to impact long-term cardiovascular hospitalizations of offspring.

Abstract TMP83: Long-term Risk of Venous Thromboembolism After Stroke

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Santosh B Murthy ◽  
Alexander E Merkler ◽  
Gino Gialdini ◽  
Abhinaba Chatterjee ◽  
Costantino Iadecola ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Venous Thromboembolism ◽  
Proportional Hazards ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
First Year ◽  
Cumulative Rate ◽  
Incident Cases

Background: There are few data on the long-term risk of venous thromboembolism (VTE) among stroke survivors. We aimed to compare the incidence of VTE amongst patients with ischemic stroke versus those with intracerebral hemorrhage (ICH). Methods: We identified all adults discharged from nonfederal acute care hospitals in CA, NY, and FL between 2005 and 2012 with previously validated ICD-9-CM codes for ischemic stroke and ICH. Our primary outcome of VTE was defined as pulmonary embolism or deep vein thrombosis. To capture incident cases of VTE, we excluded patients with a VTE prior to or during the index stroke. Kaplan-Meier survival statistics were used to calculate the cumulative rate of incident VTE. Cox regression was used to compare the risk of VTE after stroke while adjusting for demographics, vascular risk factors, and Elixhauser comorbidity index. As there was a violation of the proportional-hazards assumption, we calculated separate hazard ratios (HR) for each year of follow-up. Results: We identified 834,660 patients with stroke, of whom 712,440 (85.3%) had ischemic stroke and 112,220 (14.7%) had ICH. Over a mean follow-up of 2.8 (+/-2.4) years, 19,937 (2.4%) developed VTE. After 7 years, the cumulative rate of VTE was 4.7% (95% confidence interval [CI], 4.5-4.9%) in patients with ICH and 4.4% (95% CI, 4.3-4.5%) in patients with ischemic stroke. In multivariable analysis, VTE risk was higher in the first year after ICH compared to ischemic stroke (HR 1.51; 95% CI, 1.43-1.58). However, following the first year, the hazard of VTE was higher among patients with ischemic stroke versus those with ICH (Figure). Conclusions: The risk of VTE after stroke varies by stroke type and time. Patients with ICH have a higher risk of VTE in the first year after stroke as compared to those with ischemic stroke while patients with ischemic stroke have a higher risk beyond 1 year.

scholarly journals Maternal hepatitis B or C carrier status and long-term risk for offspring neurological morbidity: a population-based cohort study

2021 ◽  
pp. 1-5
Author(s):  
Israel Yoles ◽  
Eyal Sheiner ◽  
Naim Abu-Freha ◽  
Tamar Wainstock
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Survival Curve ◽  
Population Based ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Carrier Status ◽  
Hazards Model ◽  
Kaplan Meier

Abstract Hepatitis B and hepatitis C (HBV/HCV) are important global public health concerns. We aimed to evaluate the association between maternal HBV/HCV carrier status and long-term offspring neurological hospitalisations. A population-based cohort analysis compared the risk for long-term childhood neurological hospitalisations in offspring born to HBV/HCV carrier vs. non-carrier mothers in a large tertiary medical centre between 1991 and 2014. Childhood neurological diseases, such as cerebral palsy, movement disorders or developmental disorders, were pre-defined based on ICD-9 codes as recorded in hospital medical files. Offspring with congenital malformations and multiple gestations were excluded from the study. A Kaplan–Meier survival curve was constructed to compare cumulative neurological hospitalisations over time, and a Cox proportional hazards model was used to control for confounders. During the study period (1991–2014), 243,682 newborns met the inclusion criteria, and 777 (0.3%) newborns were born to HBV/HCV mothers. The median follow-up was 10.51 years (0–18 years). The offspring from HBV/HCV mothers had higher incidence of neurological hospitalisations (4.5 vs. 3.1%, hazard ratio (HR) = 1.91, 95% CI 1.37–2.67). Similarly, the cumulative incidence of neurological hospitalisations was higher in children born to HBV/HCV carrier mothers (Kaplan–Meier survival curve log-rank test p < 0.001). The increased risk remained significant in a Cox proportional hazards model, which adjusted for gestational age, mode of delivery and pregnancy complications (adjusted HR = 1.40, 1.01–1.95, p = 0.049). We conclude that maternal HBV or HCV carrier status is an independent risk factor for the long-term neurological hospitalisation of offspring regardless of gestational age and other adverse perinatal outcomes.

Female hormonal exposures and risk of rheumatoid arthritis in the French E3N-EPIC cohort study

Rheumatology ◽  
2021 ◽  
Author(s):  
Carine Salliot ◽  
Yann Nguyen ◽  
Gaëlle Gusto ◽  
Amandine Gelot ◽  
Juliette Gambaretti ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Prospective Cohort ◽  
Regression Models ◽  
Proportional Hazards ◽  
Cox Regression ◽  
Cox Proportional Hazards ◽  
Smoking History ◽  
Nulliparous Women ◽  
Hormonal Exposures ◽  
Incident Cases

Abstract Objective To assess the relationships between female hormonal exposures and risk of rheumatoid arthritis (RA), in a prospective cohort of French women. Methods E3N is an on-going French prospective cohort that included 98 995 women aged 40–65 years in 1990. Every 2–3 years, women completed mailed questionnaires on their lifestyles, reproductive factors, and health conditions. Cox proportional-hazards regression models were used to determine factors associated with risk of incident RA, with age as the time scale, adjusted for known risk factors of RA, and considering endogenous and exogenous hormonal factors. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated. Effect modification by smoking history was investigated. Results A total of 698 incident cases of RA were ascertained among 78 452 women. In multivariable-adjusted Cox regression models, risk of RA was increased with early age at first pregnancy (&lt;22 vs ≥27 years; HR = 1.34; 95%CI 1.0–1.7) and menopause (≤45 vs ≥53 years; HR = 1.40; 95%CI 1.0–1.9). For early menopause, the association was of similar magnitude in ever and never smokers, although the association was statistically significant only in ever smokers (HR = 1.54; 95%CI 1.0–2.3). We found a decreased risk in nulliparous women never exposed to smoking (HR = 0.44; 95%CI 0.2–0.8). Risk of RA was inversely associated with exposure to progestogen only in perimenopause (&gt;24 vs 0 months; multi-adjusted HR = 0.77; 95%CI 0.6–0.9). Conclusions These results suggest an effect of both endogenous and exogenous hormonal exposures on RA risk and phenotype that deserves further investigation.

scholarly journals Effects of long-term anti-seizure medication monotherapy on all-cause death in patients with post-stroke epilepsy: a nationwide population-based study in Taiwan

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chia-Yu Hsu ◽  
Chun-Yu Cheng ◽  
Jiann-Der Lee ◽  
Meng Lee ◽  
Bruce Ovbiagele
Keyword(s):  
Valproic Acid ◽  
Ischemic Stroke ◽  
Cox Regression ◽  
Population Based ◽  
Primary Diagnosis ◽  
Research Database ◽  
Post Stroke ◽  
Risk Of Death ◽  
Index Stroke

Abstract Objective We aim to compare the effect of long-term anti-seizure medication (ASM) monotherapy on the risk of death and new ischemic stroke in patients with post-stroke epilepsy (PSE). Patients and methods We identified all hospitalized patients (≥ 20 years) with a primary diagnosis of ischemic or hemorrhagic stroke from 2001 to 2012 using the National Health Insurance Research Database in Taiwan. The PSE cohort were defined as the stroke patients (1) who had no epilepsy and no ASMs use before the index stroke, and (2) who had epilepsy and ASMs use after 14 days from the stroke onset. The patients with PSE receiving ASM monotherapy were enrolled and were categorized into phenytoin, valproic acid, carbamazepine, and new ASM groups. We employed the Cox regression model to estimate the unadjusted and adjusted hazard ratios (HRs) with 95 % confidence intervals (CIs) of death and new ischemic stroke within 5 years across all groups, using the new ASM group as the reference. Results Of 6962 patients with PSE using ASM monotherapy, 3917 (56 %) were on phenytoin, 1623 (23 %) on valproic acid, 457 (7 %) on carbamazepine, and 965 (14 %) on new ASMs. After adjusting for confounders, compared with new ASM users, phenytoin users had a higher risk of death in 5 years (HR: 1.64; 95 % CI: 1.06–2.55). On the other hand, all ASM groups showed a similar risk of new ischemic stroke in 5 years. Conclusions Among patients with PSE on first-line monotherapy, compared to new ASMs, use of phenytoin was associated with a higher risk of death in 5 years.

scholarly journals 1388. Dose Discrimination for ASN100: Bridging from Rabbit Survival Data to Predicted Activity in Humans Using a Minimal Physiologically Based Pharmacokinetic (mPBPK) Model

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S426-S426
Author(s):  
Christopher M Rubino ◽  
Lukas Stulik ◽  
Harald Rouha ◽  
Zehra Visram ◽  
Adriana Badarau ◽  
...  
Keyword(s):  
Survival Data ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Model ◽  
Virulent Strain ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Simulated Patients ◽  
Research Support ◽  
Mpbpk Model

Abstract Background ASN100 is a combination of two co-administered fully human monoclonal antibodies (mAbs), ASN-1 and ASN-2, that together neutralize the six cytotoxins critical to S. aureus pneumonia pathogenesis. ASN100 is in development for prevention of S. aureus pneumonia in mechanically ventilated patients. A pharmacometric approach to dose discrimination in humans was taken in order to bridge from dose-ranging, survival studies in rabbits to anticipated human exposures using a mPBPK model derived from data from rabbits (infected and noninfected) and noninfected humans [IDWeek 2017, Poster 1849]. Survival in rabbits was assumed to be indicative of a protective effect through ASN100 neutralization of S. aureus toxins. Methods Data from studies in rabbits (placebo through 20 mg/kg single doses of ASN100, four strains representing MRSA and MSSA isolates with different toxin profiles) were pooled with data from a PK and efficacy study in infected rabbits (placebo and 40 mg/kg ASN100) [IDWeek 2017, Poster 1844]. A Cox proportional hazards model was used to relate survival to both strain and mAb exposure. Monte Carlo simulation was then applied to generate ASN100 exposures for simulated patients given a range of ASN100 doses and infection with each strain (n = 500 per scenario) using a mPBPK model. Using the Cox model, the probability of full protection from toxins (i.e., predicted survival) was estimated for each simulated patient. Results Cox models showed that survival in rabbits is dependent on both strain and ASN100 exposure in lung epithelial lining fluid (ELF). At human doses simulated (360–10,000 mg of ASN100), full or substantial protection is expected for all four strains tested. For the most virulent strain tested in the rabbit pneumonia study (a PVL-negative MSSA, Figure 1), the clinical dose of 3,600 mg of ASN100 provides substantially higher predicted effect relative to lower doses, while doses above 3,600 mg are not predicted to provide significant additional protection. Conclusion A pharmacometric approach allowed for the translation of rabbit survival data to infected patients as well as discrimination of potential clinical doses. These results support the ASN100 dose of 3,600 mg currently being evaluated in a Phase 2 S. aureus pneumonia prevention trial. Disclosures C. M. Rubino, Arsanis, Inc.: Research Contractor, Research support. L. Stulik, Arsanis Biosciences GmbH: Employee, Salary. H. Rouha, 3Arsanis Biosciences GmbH: Employee, Salary. Z. Visram, Arsanis Biosciences GmbH: Employee, Salary. A. Badarau, Arsanis Biosciences GmbH: Employee, Salary. S. A. Van Wart, Arsanis, Inc.: Research Contractor, Research support. P. G. Ambrose, Arsanis, Inc.: Research Contractor, Research support. M. M. Goodwin, Arsanis, Inc.: Employee, Salary. E. Nagy, Arsanis Biosciences GmbH: Employee, Salary.

scholarly journals Tigecycline Therapy for Infections Caused by Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae in Critically Ill Patients

Antibiotics ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 231
Author(s):  
Wen-Liang Yu ◽  
Nan-Yao Lee ◽  
Jann-Tay Wang ◽  
Wen-Chien Ko ◽  
Chung-Han Ho ◽  
...  
Keyword(s):  
Sofa Score ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Regression ◽  
Clinical Success ◽  
Clinical Success Rate ◽  
Clinical Effectiveness ◽  
E Coli ◽  
Extended Spectrum ◽  
Complicated Skin

: We aimed to evaluate tigecycline on the clinical effectiveness in treating complicated skin and soft tissue infections (cSSTI), complicated intra-abdominal infections (cIAI), and pneumonia, caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, as data are limited. From three medical centers in Taiwan, we retrospectively studied the cSSTI, cIAI, and/or pneumonia caused by ESBL-producing Enterobacteriaceae. Among the 71 patients, including 39 patients infected with Klebsiella pneumoniae, 30 infected with Escherichia coli and others, the clinical success rate of tigecycline-based therapy was 80%–90% for pneumonia and cSSTI caused by E. coli and 50%–60% for cIAI caused by K. pneumoniae and E. coli. Microbiological and clinical outcome of pneumonia caused by carbapenem-resistant K. pneumoniae was poor. Univariate Cox analysis showed that dyspnea, SOFA score, septic shock, thrombocytopenia, prolonged prothrombin time, and lesser microbiological eradication were significant factors associated with 30-day mortality after the end of therapy. Cox regression proportional hazards model revealed dyspnea and a SOFA score > 8 to be independently associated with time to death. For ESBL producers, tigecycline showed good effects for cSSTI and pneumonia by E. coli, ordinary for cIAI, but ineffective for pneumonia by K. pneumoniae. Dyspnea and a high SOFA score predict a poor outcome.

scholarly journals Comorbidities and Outcome of Alcoholic and Non-Alcoholic Liver Cirrhosis in Taiwan: A Population-Based Study

2020 ◽  
Vol 17 (8) ◽  
pp. 2825
Author(s):  
Tzu-Wei Yang ◽  
Chi-Chih Wang ◽  
Ming-Chang Tsai ◽  
Yao-Tung Wang ◽  
Ming-Hseng Tseng ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Survival Rates ◽  
Study Groups ◽  
Population Based ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Study Cohort ◽  
Hazards Model

The prognosis of different etiologies of liver cirrhosis (LC) is not well understood. Previous studies performed on alcoholic LC-dominated cohorts have demonstrated a few conflicting results. We aimed to compare the outcome and the effect of comorbidities on survival between alcoholic and non-alcoholic LC in a viral hepatitis-dominated LC cohort. We identified newly diagnosed alcoholic and non-alcoholic LC patients, aged ≥40 years old, between 2006 and 2011, by using the Longitudinal Health Insurance Database. The hazard ratios (HRs) were calculated using the Cox proportional hazards model and the Kaplan–Meier method. A total of 472 alcoholic LC and 4313 non-alcoholic LC patients were identified in our study cohort. We found that alcoholic LC patients were predominantly male (94.7% of alcoholic LC and 62.6% of non-alcoholic LC patients were male) and younger (78.8% of alcoholic LC and 37.4% of non-alcoholic LC patients were less than 60 years old) compared with non-alcoholic LC patients. Non-alcoholic LC patients had a higher rate of concomitant comorbidities than alcoholic LC patients (79.6% vs. 68.6%, p < 0.001). LC patients with chronic kidney disease demonstrated the highest adjusted HRs of 2.762 in alcoholic LC and 1.751 in non-alcoholic LC (all p < 0.001). In contrast, LC patients with hypertension and hyperlipidemia had a decreased risk of mortality. The six-year survival rates showed no difference between both study groups (p = 0.312). In conclusion, alcoholic LC patients were younger and had lower rates of concomitant comorbidities compared with non-alcoholic LC patients. However, all-cause mortality was not different between alcoholic and non-alcoholic LC patients.

scholarly journals 1402. Long-Term Mortality and Epilepsy in Patients After Brain Abscess: A Nationwide Population-based Matched Cohort Study

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S510-S510
Author(s):  
Jacob Bodilsen ◽  
Michael Dalager-Pedersen ◽  
Diederik van de Beek ◽  
Matthijs C Brouwer ◽  
Henrik Nielsen
Keyword(s):  
Cohort Study ◽  
Brain Abscess ◽  
Cox Regression ◽  
Population Based ◽  
Matched Cohort ◽  
Matched Cohort Study ◽  
Population Controls ◽  
New Onset

Abstract Background The long-term outcome of brain abscess is unclear. Methods We used medical registries to conduct a nationwide population-based matched cohort study to examine the long-term risks of mortality and new-onset epilepsy in patients hospitalized with brain abscess in Denmark from 1982 through 2016. Comparison cohorts from the same population individually matched on age, sex, and residence were identified, as were siblings of all study participants (Figure 1). We computed cumulative incidences and hazard rate ratios (HRRs) for mortality and new-onset epilepsy among brain abscess patients, comparison cohorts and siblings. Population and appendicitis controls had similar characteristics and prognosis why only comparisons between brain abscess patients and population controls are detailed here. Results We identified 1,384 brain abscess patients with a median follow-up time of 5.9 years (IQR 1.1–14.2). The 1-year, 2–5 year, and 6–30-year mortality of patients after brain abscess was 21%, 16% and 27% when compared with 1%, 6% and 20% for matched population controls (Figure 2). Cox regression analyses adjusted for Charlson comorbidity index score showed 1-year, 2–5 year, and 6- to 30-year HRRs of 17.5 (95% CI 13.9–22.2), 2.61 (95% CI 2.16–3.16) and 1.94 (95% CI 1.62–2.31). The mortality in brain abscess patients compared with population controls was significantly increased regardless of sex or age group except among subjects 80 years or older, and in both previously healthy individuals and immuno-compromised persons. Among the 30-day survivors of brain abscess (median follow-up 7.6 years [IQR 2.2–15.5]), new-onset epilepsy occurred in 32% compared with 2% in matched population controls. Cause-specific Cox regression analysis adjusted for stroke, head trauma, alcohol abuse, and cancer showed 1-year, 2–5-year, and 6–30-year HRRs for new-onset epilepsy of 155 (95% CI 78.8–304), 37.7 (95% CI 23.0–59.9), and 8.93 (95% CI 5.62–14.2) (Figure 3). Comparisons between sibling cohorts suggested no substantial effect of family-related factors on the long-term risk of death or epilepsy after brain abscess (Figure 4). Conclusion Brain abscess is associated with an increased long-term risk of mortality and new-onset epilepsy for several years after the acute infection. Disclosures All authors: No reported disclosures.

scholarly journals Maternal Hepatitis B Virus or Hepatitis C Virus Carrier Status and Long-Term Endocrine Morbidity of the Offspring—A Population-Based Cohort Study

2020 ◽  
Vol 9 (3) ◽  
pp. 796 ◽  
Author(s):  
Naim Abu Freha ◽  
Tamar Wainstock ◽  
Tzvi Najman Menachem ◽  
Eyal Sheiner
Keyword(s):  
Cohort Study ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Cox Regression ◽  
Population Based ◽  
Carrier Status ◽  
B Virus

This study aimed to investigate the long-term effect of maternal hepatitis B virus (HBV) or hepatitis C virus (HCV) carrier status on offspring endocrine morbidity. A population-based cohort study included all singleton deliveries between the years 1991–2014 at the Soroka University Medical Center, Beer-Sheva, Southern Israel. The mothers were subdivided into three groups, HBV carriers, HCV carriers and non-carriers. Data regarding the long-term endocrine morbidity of their offspring were compared between the groups. The study included 242,905 (99.7%) non-carrying mothers, 591 (0.2%) mothers who were carriers for HBV and 186 (0.1%) mothers who were carriers for HCV. The Kaplan–Meier’s survival curve demonstrated a significantly higher cumulative endocrine morbidity in children born to mothers with HCV (log-rank test, p = 0.002). Specifically, higher rates of hypoglycemia were noted among the offspring born to mothers who were carriers of HCV (1.1%; p = 0.001) compared with the offspring of mothers who were either carriers of HBV (0.2%) or non-carriers (0.1%). A Cox regression model controlled for maternal age, gestational age, maternal diabetes, hypertensive disorders of pregnancy, found maternal HCV carrier status to be independently associated with pediatric endocrine morbidity in the offspring (adjusted hazard ratio = 5.05, 95% CI: 1.625–15.695, p = 0.005). Maternal HCV carrier status is an independent risk factor for long-term endocrine morbidity.

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