Outcomes of women age 40 or more undergoing repeat cesarean or trial of labor after cesarean.

AIM: Despite the increasing trend in delayed childbirth and the known associated complications in advancing maternal age, limited information exists regarding outcomes in very advanced maternal age by delivery type. This study aims to evaluate maternal and neonatal outcomes in women age 40 or more undergoing cesarean delivery or trial of labor after cesarean delivery. MATERIALS AND METHODS: We performed a secondary analysis of the Cesarean Section Registry Maternal-Fetal Medicine Units (MFMU) Network data, which was a prospective study of women undergoing repeat cesarean delivery or trial of labor after cesarean delivery from 1 January 1999 to 31 December 2002. Women age 40 years or more at the time of delivery were compared to the control group of women less than 40 years of age. RESULTS: There were 67,389 cases identified that met inclusion criteria. 2,436 (3.6%) were age ≥40 years old, and 65,403 (97.05%) were <40 at delivery. The >40 group had a higher rate of PRBC transfusion (aRR 1.75; 95% CI 1.20-2.56), maternal ICU admission (aRR 2.02; 1.41-2.89), bowel injury (aRR 3.65; 1.43-9.31), placenta accreta (aRR 1.92; 1.09-3.38) and classical uterine incision (aRR 1.59; 1.43-9.31) compared to the control group. Maternal death rates were similar in both groups (p = .30). CONCLUSION: Women aged 40 or more undergoing repeat cesarean delivery or trial of labor after cesarean delivery are more likely to have maternal complications including intraoperative transfusion, maternal ICU admission, abnormal placentation and surgical complications in comparison to women under age 40.

Safety study of live, oral human rotavirus vaccine: A cohort study in United States health insurance plans.

As part of a regulatory commitment for post-licensure safety monitoring of live, oral human rotavirus vaccine (RV1), this study compared the incidence rates (IR) of intussusception, acute lower respiratory tract infection (LRTI) hospitalization, Kawasaki disease, convulsion, and mortality in RV1 recipients versus inactivated poliovirus vaccine (IPV) recipients in concurrent (cIPV) and recent historical (hIPV) comparison cohorts. Vaccine recipients were identified in 2 claims databases from August 2008 - June 2013 (RV1 and cIPV) and January 2004 - July 2008 (hIPV). Outcomes were identified in the 0-59 days following the first 2 vaccine doses. Intussusception, Kawasaki disease, and convulsion were confirmed via medical record review. Outcome IRs were estimated. Incidence rate ratios (IRRs) were obtained from Poisson regression models. A post-hoc self-controlled case series (SCCS) analysis compared convulsion IRs in a 0-7 day post-vaccination period to a 15-30 day post-vaccination period. We identified 57,931 RV1, 173,384 cIPV, and 159,344 hIPV recipients. No increased risks for intussusception, LRTI, Kawasaki disease, or mortality were observed. The convulsion IRRs were elevated following RV1 Dose 1 (cIPV: 2.07, 95% confidence interval [CI]: 1.27 - 3.38; hIPV: 2.05, 95% CI: 1.24 - 3.38), a finding which is inconclusive as it was observed in only one of the claims databases. The IRR following RV1 Dose 1 in the SCCS analysis lacked precision (2.40, 95% CI: 0.73 - 7.86). No increased convulsion risk was observed following RV1 Dose 2. Overall, this study supports the favorable safety profile of RV1. Continued monitoring for safety signals through routine surveillance is needed to ensure vaccine safety.

Risk of severe acute liver injury among patients with brain cancer treated with temozolomide: a nested case-control study using the healthcore integrated research database.

Temozolomide (TMZ) is used to treat adult patients with glioblastoma multiforme (GBM). Cases of hepatotoxicity have been reported among patients using TMZ. The objective of the study was to assess the relation, if any, between exposure to TMZ and serious acute liver injury (SALI). We used the HealthCore Integrated Research Database to perform a case-control study nested within a retrospective cohort of adult patients aged 18-100 years with at least two diagnoses of brain cancer anytime between 2006 and 2014. Patients without continuous eligibility or with a SALI diagnosis within 6 months prior to the date of incident brain cancer diagnosis were excluded. Medical records were sought for potential SALI cases and reviewed by two hepatologists. Five controls were selected for each case using incidence density sampling, matched on age and calendar year of index date. The analysis included 61 confirmed SALI cases and 305 selected controls. Exposure to TMZ was classified according to dispensing date and days supply of medication dispensed. We estimated odds ratios using conditional logistic regression models. The odds ratio for any exposure to TMZ was 0.91 (95% CI 0.44-1.91), for recent exposure to TMZ was 0.62 (95% CI 0.21-1.85). There was no increased risk of SALI with increasing duration of exposure to TMZ. When patients with unconfirmed SALI were included in the analysis, results were similar (OR 1.04; 95% CI 0.70-1.54). In conclusion, this study did not find an association between TMZ and SALI risk among patients with brain cancer.

Validation of current procedural terminology codes for rotavirus vaccination among infants in two commercially insured US populations.

PURPOSE: We validated procedure codes used in health insurance claims for reimbursement of rotavirus vaccination by comparing claims for monovalent live-attenuated human rotavirus vaccine (RV1) and live, oral pentavalent rotavirus vaccine (RV5) to medical records. METHODS: Using administrative data from two commercially insured United States populations, we randomly sampled vaccination claims for RV1 and RV5 from a cohort of infants aged less than 1 year from an ongoing post-licensure safety study of rotavirus vaccines. The codes for RV1 and RV5 found in claims were confirmed through medical record review. The positive predictive value (PPV) of the Current Procedural Terminology codes for RV1 and RV5 was calculated as the number of medical record-confirmed vaccinations divided by the number of medical records obtained. RESULTS: Medical record review confirmed 92 of 104 RV1 vaccination claims (PPV: 88.5%; 95% CI: 80.7-93.9%) and 98 of 113 RV5 vaccination claims (PPV: 86.7%; 95% CI: 79.1-92.4%). Among the 217 medical records abstracted, only three (1.4%) of vaccinations were misclassified in claims-all were RV5 misclassified as RV1. The medical records corresponding to 9 RV1 and 15 RV5 claims contained insufficient information to classify the type of rotavirus vaccine. CONCLUSIONS: Misclassification of rotavirus vaccines is infrequent within claims. The PPVs reported here are conservative estimates as those with insufficient information in the medical records were assumed to be incorrectly coded in the claims. Copyright © 2016 John Wiley & Sons, Ltd.

Development and validation of an algorithm for identifying urinary retention in a cohort of patients with epilepsy in a large US administrative claims database.

PURPOSE: The aim of this study was to develop and validate an insurance claims-based algorithm for identifying urinary retention (UR) in epilepsy patients receiving antiepileptic drugs to facilitate safety monitoring. METHODS: Data from the HealthCore Integrated Research Database(SM) in 2008-2011 (retrospective) and 2012-2013 (prospective) were used to identify epilepsy patients with UR. During the retrospective phase, three algorithms identified potential UR: (i) UR diagnosis code with a catheterization procedure code; (ii) UR diagnosis code alone; or (iii) diagnosis with UR-related symptoms. Medical records for 50 randomly selected patients satisfying ≥1 algorithm were reviewed by urologists to ascertain UR status. Positive predictive value (PPV) and 95% confidence intervals (CI) were calculated for the three component algorithms and the overall algorithm (defined as satisfying ≥1 component algorithms). Algorithms were refined using urologist review notes. In the prospective phase, the UR algorithm was refined using medical records for an additional 150 cases. RESULTS: In the retrospective phase, the PPV of the overall algorithm was 72.0% (95%CI: 57.5-83.8%). Algorithm 3 performed poorly and was dropped. Algorithm 1 was unchanged; urinary incontinence and cystitis were added as exclusionary diagnoses to Algorithm 2. The PPV for the modified overall algorithm was 89.2% (74.6-97.0%). In the prospective phase, the PPV for the modified overall algorithm was 76.0% (68.4-82.6%). Upon adding overactive bladder, nocturia and urinary frequency as exclusionary diagnoses, the PPV for the final overall algorithm was 81.9% (73.7-88.4%). CONCLUSIONS: The current UR algorithm yielded a PPV > 80% and could be used for more accurate identification of UR among epilepsy patients in a large claims database.

Assessing bias in administrative database studies of RotaTeq vaccine completion due to exclusion of subjects with incomplete follow-up.

BACKGROUND: RotaTeq® pentavalent human rotavirus vaccine (RV5) is effective against rotavirus illness and rotavirus-related hospitalizations and death. Effectiveness depends on adherence to the dosing schedule, which includes 3 doses at ages 2, 4 and 6 months. Two studies have used automated claims databases to estimate the proportion of vaccinated infants who complete the dosing schedule, but excluded from analysis vaccinated infants who were not enrolled in the database for a sufficient period to observe all 3 doses. Restricting study populations based on duration of follow-up can introduce bias if a large number of subjects are excluded due to insufficient follow-up, and if their outcomes differ from subjects who are included. To address the possibility that exclusions may have been extensive and led to biased estimates of completion rates, we conducted a claims database analysis in the HealthCore Integrated Research Database(SM) to evaluate the proportion of rotavirus vaccinated infants who completed the 3 dose series of RV5. We evaluated potential error introduced by restricting analyses to infants with complete follow-up by estimating completion rates among infants with complete follow-up, and using Kaplan-Meier analyses to estimate completion rates including infants with incomplete follow-up. RESULTS: The inclusion criterion requiring continuous enrollment for the first year of life resulted in only 108,533 (40%) of 233,143 vaccinated infants from 2006-2012 being included in the analysis. After relaxing inclusion criteria, we were able to include 86% of vaccinated infants. The estimated completion rate among infants with continuous enrollment from birth through the first year of life was 78.1% (95% confidence limits [CLs] 77.8%, 78.3%), and among the expanded population the estimated completion rate was 77.4% (95% CLs 77.2%, 77.6%). CONCLUSIONS: These results indicate that most infants were not followed in the database through the first year of life, but the impact of excluding infants with incomplete follow-up was negligible when assessing RV5 completion rates for this commercially insured population. Nonetheless, to increase the size of study populations and reduce the potential for bias, it is preferable to include subjects with incomplete follow-up in automated database analyses, and adopt more robust approaches to defining and analyzing study populations that account for missing data.

Accuracy of administrative claims data to identify dose specific rotavirus vaccination information: Implications for studies of vaccine safety.

BACKGROUND: The accuracy of vaccine administration information recorded in administrative claims databases is uncertain. METHODS: We conducted a retrospective cohort study using the HealthCore Integrated Research Database(SM) among infants who received at least 1 RotaTeq (RV5) dose during the first year of life between February 1, 2006 and November 30, 2012 and were enrolled in the health plan at birth. We reviewed medical records for a sample of infants to validate vaccine administration information. RESULTS: We identified 169,560 infants who received at least 1 RV5 dose. Medical records were obtained for 85 infants, of which 74 (PPV1 87.1%; 95% CI 78.0-93.4%) had a corresponding first RV5 vaccination in the medical record with the same or similar administration date. CONCLUSIONS: Administrative claims contained inaccuracies in dose number or administration date for 13% of RV5 first doses identified.

Validation of acute liver injury cases in a population-based cohort study of oral antimicrobial users.

We conducted a cohort study of acute, noninfectious liver injury among oral antimicrobial users. Potential cases were identified in the HealthCore Integrated Research Database (HIRD(SM)) population between July 1, 2001, and March 31, 2009, using ICD-9-CM codes primarily for acute and subacute necrosis of the liver, hepatic coma, and unspecified hepatitis. Liver test results were used to confirm case status according to published criteria. Two physician reviewers experienced in studying acute liver injury (blinded to study drug exposures) evaluated data abstracted from hospital and emergency department records to validate potential cases. Of 715 potential cases having claims associated with any of the primary screening codes, 312 (44%) were valid cases, 108 (15%) were not cases, and 295 (41%) were of uncertain status (records inadequate for validation). Among potential cases with adequate medical records, the PPV for presence of any of the primary codes was 74% (95% CI, 70%-78%). The highest PPV for a single code was for acute and subacute necrosis of the liver (84%; 95% CI, 77%-90%). Evaluation of cases of noninfectious liver injury using hospital and emergency department medical records continues to represent the preferred approach in studies using insurance claims data.

Risk factors for early-onset and late-onset post-transplant lymphoproliferative disorder in kidney recipients in the United States.

Solid-organ transplant recipients have an elevated risk for some malignancies because of the requirement for immunosuppression [1]. In particular, non-Hodgkin's lymphoma (NHL) is common and comprises one end of a spectrum of post-transplant lymphoproliferative disorder (PTLD) ranging from benign hyperplasia to lymphoid malignancy [2]. PTLD risk is influenced by the type of organ transplanted, the age and Epstein-Barr virus (EBV) serostatus of the transplant recipient, and the intensity of immunosuppression [3-9]. PTLD incidence is high immediately after transplantation, decreases subsequently, and then rises again 4-5 years from transplantation [10,11]. This incidence pattern suggests the presence of separate early-onset and late-onset PTLD subtypes. Early-onset PTLDs tend to be EBV-positive and, when extranodal, are more likely than late-onset PTLDs to be localized to the transplanted organ [12,13]. Late-onset PTLD is less likely to be associated with EBV and, overall, is more likely than early-onset PTLD to be extranodal [13,14]. The Scientific Registry of Transplant Recipients (SRTR) includes data on a large number of solid-organ transplant recipients in the United States and information on malignancies diagnosed post-transplantation. We used these data to conduct a retrospective cohort study among kidney transplant recipients to examine differences in risk factors between early-onset PTLD and late-onset PTLD.

Hodgkin lymphoma among US solid organ transplant recipients.

BACKGROUND: To assess the risk and identify risk factors of Hodgkin lymphoma (HL) in solid organ transplant recipients. Prior research has been limited by the rarity of HL and the requirement for extended follow-up after transplantation. METHODS: Using data from the Scientific Registry of Transplant Recipients (SRTR), we conducted a retrospective cohort study of US solid organ transplant recipients (1997-2007). We estimated hazard ratios (HRs) for HL risk factors using proportional hazards regression. Standardized incidence ratios (SIRs) compared HL risk in the transplant cohort with the general population. RESULTS: The cohort included 283,190 transplant recipients (average follow-up: 3.7 years after transplantation). Based on 73 cases, HL risk factors included male gender (HR: 2.1, 95% CI: 1.2-3.7), young age (4.0, 2.3-6.8), and Epstein-Barr virus (EBV) seronegativity at the time of transplantation (3.1, 1.2-8.1). Among tumors with EBV status information, 79% were EBV positive, including all tumors in recipients who were initially seronegative. Overall, HL risk was higher than in the general population (SIR: 2.2) and increased monotonically over time after transplantation (SIR: 4.1 at 8-10 years posttransplant). Excess HL risk was especially high after heart and/or lung transplantation (SIR: 3.2). CONCLUSION: HL is a late complication of solid organ transplantation. The high HL risk in recipients who were young or EBV seronegative at the time of transplant and the fact that most HL tumors were EBV positive highlight the role of primary EBV infection and poor immune control of this virus. The occurrence of HL may rise with improved long-term survival in transplant recipients.

Blood transfusions and the subsequent risk of hematologic malignancies.

BACKGROUND: Blood transfusions are associated with viral transmission and immunomodulation, perhaps increasing subsequent risk of hematologic malignancies (HMs). Prior studies of transfusion recipients have lacked details on specific HM subtypes. STUDY DESIGN AND METHODS: Risk of HM after blood transfusion was evaluated in a US population-based case-control study (77,488 elderly HM cases identified through cancer registries, 154,509 controls). Transfusions were identified using linked Medicare hospitalization claims. Polytomous logistic regression was used to calculate odds ratios (ORs) associating transfusion and HM subtypes by features suggestive of a causal relationship. RESULTS: A history of transfusion was present in 7.9% of HM cases versus 5.9% of controls. Associations for most HM subtypes suggested reverse causality: ORs were elevated only during the shortest latency periods; ORs for unspecified anemia and gastrointestinal bleeding, which may be related to undiagnosed HM, were stronger than for surgeries, which are unlikely to be related to HM; and/or there was no dose response. In contrast, risk for lymphoplasmacytic lymphoma (1397 cases) was elevated at long latency (OR, 1.56 at 10+ years after transfusion), after transfusions related to surgeries (OR, 1.22-1.47), and in a dose-response relationship with number of transfusion-related hospitalizations (OR, 1.53 with one hospitalization; OR, 1.80 with two or more hospitalizations, p trend < 0.0001). Risk for marginal zone lymphoma (1915 cases) was also elevated at 10+ years after transfusion (OR, 1.80). CONCLUSION: Consistent with prior studies, blood transfusions did not increase risk of most HM subtypes. Patterns of elevated risk for lymphoplasmacytic and marginal zone lymphomas suggest an etiologic role for transfusion.

Increased risk for lymphoid and myeloid neoplasms in elderly solid-organ transplant recipients.

BACKGROUND: By assessing the spectrum of hematologic malignancies associated with solid-organ transplantation in the elderly, we provide information on the pathogenesis of lymphoid and myeloid neoplasms and the clinical manifestations of immunosuppression. METHODS: Using data from the U.S. Surveillance, Epidemiology, and End Results Medicare database, we identified 83,016 cases with a hematologic malignancy (age 66-99 years) and 166,057 population-based controls matched to cases by age, sex, and calendar year. Medicare claims were used to identify a history of solid-organ transplantation. We used polytomous logistic regression to calculate odds ratios (OR) comparing transplantation history among cases with various hematologic malignancy subtypes and controls, adjusting for the matching factors and race. RESULTS: A prior solid-organ transplant was identified in 216 (0.26%) cases and 204 (0.12%) controls. Transplantation was associated with increased risk for non-Hodgkin lymphomas [OR, 2.13; 95% confidence interval (95% CI), 1.67-2.72], especially diffuse large B-cell lymphoma (OR, 3.29; 95% CI, 2.28-4.76), marginal zone lymphoma (OR, 2.48; 95% CI, 1.17-5.22), lymphoplasmacytic lymphoma (OR, 3.32; 95% CI, 1.41-7.81), and T-cell lymphoma (OR, 3.07; 95% CI, 1.56-6.06). Transplantation was also associated with elevated risk of Hodgkin lymphoma (OR, 2.53; 95% CI, 1.01-6.35) and plasma cell neoplasms (OR, 1.91; 95% CI, 1.24-2.93). Risks for myeloid neoplasms were also elevated (OR, 1.99; 95% CI, 1.41-2.81). CONCLUSION: Solid-organ transplantation is associated with a wide spectrum of hematologic malignancies in the elderly. Risk was increased for four specific non-Hodgkin lymphoma subtypes for which a viral agent has been implicated, supporting an added role for immunosuppression. IMPACT: Our results support monitoring for a wide spectrum of hematologic malignancies following solid-organ transplant.