A data processing pipeline for the AACR project GENIE biopharma collaborative data with the {genieBPC} R package.

MOTIVATION: Data from the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange Biopharma Collaborative (GENIE BPC) represent comprehensive clinical data linked to high-throughput sequencing data, providing a multi-institution, pan-cancer, publicly available data repository. GENIE BPC data provide detailed demographic, clinical, treatment, genomic and outcome data for patients with cancer. These data result in a unique observational database of molecularly characterized tumors with comprehensive clinical annotation that can be used for health outcomes and precision medicine research in oncology. Due to the inherently complex structure of the multiple phenomic and genomic datasets, the use of these data requires a robust process for data integration and preparation in order to build analytic models. RESULTS: We present the {genieBPC} package, a user-friendly data processing pipeline to facilitate the creation of analytic cohorts from the GENIE BPC data that are ready for clinico-genomic modeling and analyses. AVAILABILITY AND IMPLEMENTATION: {genieBPC} is available on CRAN and GitHub.

Safety and tolerability of intravenous aprepitant and fosaprepitant in children with cancer: A retrospective, single-center review.

NK-1 receptor antagonists (NK1-RA) are key agents for chemotherapy-induced nausea and vomiting (CINV) prevention in patients receiving highly emetogenic chemotherapy. Current pediatric practice guidelines recommend the use of intravenous fosaprepitant or oral aprepitant. However, there are reports of hypersensitivity reactions with fosaprepitant due to polysorbate 80. Intravenous aprepitant does not contain polysorbate 80, but its use in pediatric patients has not been described. In this retrospective, single-center study, 106 pediatric patients received either fosaprepitant or intravenous aprepitant as part of their antiemetic regimen. Intravenous aprepitant was well tolerated and did not lead to any instances of hypersensitivity reactions requiring discontinuation.

Clinical Outcomes After Definitive Treatment of Soft Tissue Sarcoma of the Hand: A Retrospective Cohort Study of 109 Patients.

PURPOSE: The purpose of this study was to provide updated data on oncologic outcomes following definitive surgical treatment of soft tissue sarcoma of the hand in a cohort of 109 patients, as well as to characterize risk factors for poor oncologic and functional outcomes. METHODS: We analyzed data from 109 consecutive patients who had definitive surgical treatment for soft tissue sarcoma of the hand performed between 1996 and 2019 by a single surgeon at a sarcoma center. Primary outcomes included functional outcome (assessed by Musculoskeletal Tumor Society scores), disease-free survival (DFS), and overall survival (OS). We compiled descriptive data and used a multivariable linear model to identify factors associated with functional outcomes. Kaplan-Meier methods were used to estimate 5- and 10-year DFS and OS. RESULTS: Patients had a median age of 36 years at presentation. Median follow-up was 6.1 years among patients alive at the end of follow-up. The median Musculoskeletal Tumor Society score was 29; functional outcome was worse among patients with high-grade tumors or complications. Among the 107 patients who became disease-free, there were four local recurrences (one with metastasis), six distant recurrences, and one death without recurrence. All local recurrences were deep tumors (two myxofibrosarcoma and two myxoinflammatory fibrosarcoma). Estimated 5- and 10-year DFS rates were 89% (95% confidence interval [CI]: 83% to 96%) and 88% (95% CI: 80% to 95%). There were seven deaths, and the estimated 5- and 10-year OS rates were 95% (95% CI: 90% to 100%) and 92% (95% CI: 84% to 100%). Larger tumor size and higher stage at diagnosis were associated with shorter DFS and OS in univariable analyses; low event rates precluded multivariable analysis of survival. CONCLUSIONS: Aggressive disease-specific surgical and multidisciplinary treatment can yield long DFS and OS, and good functional outcomes. However, complications and high-grade tumors are associated with worse functional scores. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

MRI Assessment of Extramural Venous Invasion Before and After Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer and Its Association with Disease-Free and Overall Survival.

BACKGROUND: Extramural venous invasion (EMVI) on baseline MRI is associated with poor prognosis in patients with locally advanced rectal cancer. This study investigated the association of persistent EMVI after total neoadjuvant therapy (TNT) (chemoradiotherapy and systemic chemotherapy) with survival. METHODS: Baseline MRI, post-TNT MRI, and surgical pathology data from 175 patients with locally advanced rectal cancer who underwent TNT and total mesorectal excision between 2010 and 2017 were retrospectively analyzed for evidence of EMVI. Two radiologists assessed EMVI status with disagreement adjudicated by a third. Pathologic EMVI status was assessed per departmental standards. Cox regression models evaluated the associations between EMVI and disease-free and overall survival. RESULTS: EMVI regression on both post-TNT MRI and surgical pathology was associated with disease-free survival (hazard ratio, 0.17; 95% confidence interval (CI), 0.04-0.64) and overall survival (hazard ratio, 0.11; 95% CI, 0.02-0.68). In an exploratory analysis of 35 patients with EMVI on baseline MRI, only six had EMVI on pathology compared with 18 on post-TNT MRI; these findings were not associated (p = 0.2). Longer disease-free survival was seen with regression on both modalities compared with remaining positive. Regression on pathology alone, independent of MRI EMVI status, was associated with similar improvements in survival. CONCLUSIONS: Baseline EMVI is associated with poor prognosis even after TNT. EMVI regression on surgical pathology is common even with persistent EMVI on post-TNT MRI. EMVI regression on surgical pathology is associated with improved DFS, while the utility of post-TNT MRI EMVI persistence for decision-making and prognosis remains unclear.

Clinical characteristics and outcomes of extranodal stage I diffuse large B-cell lymphoma in the rituximab era.

This retrospective study aimed to better define the characteristics and outcomes of extranodal stage I diffuse large B-cell lymphoma (DLBCL) in the rituximab era. Patients diagnosed with stage I DLBCL from 2001 to 2015 treated with rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) or R-CHOP-like regimens with or without radiation (RT) were included. We identified 1955 patients with newly diagnosed DLBCL, of whom 341 had stage I and were eligible for this analysis. Extranodal presentation was observed in 224 (66%) patients, whereas 117 (34%) had nodal involvement. The most common extranodal sites were as follows: bone, 21%; stomach, 19%; testis, 9%; intestine, 8%; breast, 8%. Overall, 69% extranodal patients and 68% nodal patients received RT. Median follow-up was 5.5 years (interquartile range, 4.3-8.2). Ten-year overall survival (OS) and disease-free survival were 77% (95% confidence interval [CI], 67%-83%) and 77% (95% CI, 68%-85%). In the multivariable analyses, extranodal involvement was associated with worse OS (hazard ratio [HR], 3.44; 95% CI, 1.05-11.30) and progression-free survival (PFS; HR, 3.25; 95% CI, 1.08-9.72) compared with nodal involvement. Consolidation RT was associated with better OS (HR, 0.26; 95% CI, 0.12-0.49) and PFS (HR, 0.35; 95% CI, 0.18-0.69) in the extranodal population; however, the benefit was no longer observed in patients that were positron emission tomography (PET) negative at the end of immunochemotherapy. Relapses occurred usually late (median, 37 months), and the most common sites were the lymph nodes (31%) and the central nervous system (27%). Extranodal stage I DLBCL had a worse outcome than nodal stage 1 DLBCL. End of immunochemotherapy PET results may help select extranodal patients for consolidation RT.

Leave it in the past - primary treatment modality for high-grade epithelial ovarian cancer is not associated with secondary cytoreduction outcomes: A Memorial Sloan Kettering Cancer Center Team Ovary study.

OBJECTIVES: To compare outcomes of patients with high-grade epithelial ovarian cancer (EOC) who underwent secondary cytoreduction surgery (SCS) after up-front treatment with neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) versus primary debulking surgery (PDS). METHODS: Patients with high-grade EOC who underwent SCS from 2/1/2004-10/31/2021 were classified by up-front treatment. Clinical and treatment characteristics were compared between cohorts. Progression-free survival (PFS2) and overall survival (OS2) following SCS were compared using a Cox model adjusted for stage, age at SCS, and number of years between end of chemotherapy and SCS. RESULTS: Of 374 patients, 62 (17%) underwent NACT-IDS and 312 (83%) PDS. Justification for NACT was disease extent (n = 57, 92%), comorbidities (n = 3, 5%), and thromboembolism (n = 2, 3%). The NACT-IDS cohort had a higher median age at SCS (64 years [IQR: 56-70] vs 59 years [IQR: 53-66]; P = .03), higher proportion of stage III/IV disease (100% vs 81%; P < .001), and shorter median interval between end of chemotherapy and SCS (1.5 years [IQR: 1.1-2.3] vs 1.9 years [IQR: 1.3-3.1]; P = .01). Achievement of complete gross resection at SCS did not differ between NACT-IDS and PDS (84% vs 88%; P = .18). PFS2 (HR: 1.19, 95% CI: 0.83-1.71) and OS2 (HR: 0.96, 95% CI: 0.57-1.63) did not vary by primary treatment modality after adjusting for clinically relevant covariates. CONCLUSIONS: Despite more extensive disease at presentation, patients with high-grade EOC who recur after NACT-IDS seem to have similar surgical and survival outcomes after SCS compared to patients who recur after PDS, suggesting that prior NACT-IDS should not preclude SCS.

Second cancer risk in childhood cancer survivors treated with intensity-modulated radiation therapy: An updated analysis of more than 10 years of follow-up.

BACKGROUND: It is unclear how intensity-modulated radiation therapy (IMRT) impacts long-term risk of second malignant neoplasms (SMNs) in childhood cancer patients. PROCEDURE: Patients aged ≤21 years treated with IMRT between 1998 and 2009 and who survived ≥5 years after IMRT were included. SMN site in relation to isodose level (IDL) of IMRT was evaluated. Standardized incidence ratios (SIR) and excess absolute risks (EAR) were calculated. Cumulative incidences were estimated with death as a competing risk. RESULTS: Three-hundred twenty-five patients were included with median follow-up of 11.2 years from IMRT (interquartile range: 9.4-14.0) among patients alive at the end of follow-up. Two hundred (62%) patients had ≥10 years of follow-up and 284 (87%) patients were alive at the time of analysis. Fifteen patients developed SMNs (11 solid, four hematologic). Median time from IMRT to solid SMN was 11.0 years (range: 6.8-19.2) with 10- and 15-year cumulative incidences 1.8% (95% CI: 0.7-3.9) and 3.5% (95% CI: 1.4-7.5), respectively; SIR was 13.7 (95% CI: 6.9-24.6) and EAR was 2.8 per 1000 person-years (95% CI: 1.0-4.6). Eight solid SMNs developed within the IMRT field (100% IDL [n = 5], 80% IDL [n = 1], 50% IDL [n = 1], 40% IDL [n = 1]), one within the 70%-80% IDL of a conventional field, one was out-of-field, and one could not be determined. CONCLUSIONS: With median follow-up of >10 years, many solid SMNs after IMRT in childhood cancer survivors develop in the high-dose region. These data serve as a foundation for comparison with other modalities of radiation treatment (e.g., proton therapy).

TOXICITY AND EFFICACY OF INTRAVITREAL MELPHALAN FOR RETINOBLASTOMA: 25 µg Versus 30 µg.

PURPOSE: To compare retinal toxicity as measured by electroretinogram, ocular, and patient survival in retinoblastoma treated with intravitreal melphalan at two concentrations (25 vs. 30 µg). METHODS: Single-center, retrospective analysis of retinoblastoma eyes receiving 25-µg or 30-µg intravitreal melphalan from September 2012 to January 2019. Ocular toxicity was measured by electroretinogram of evaluable injections in 449 injections in 136 eyes. A repeated-measures linear mixed model with a random intercept and slope was applied to account for repeated measures for each eye. RESULTS: Average decline in electroretinogram after each additional injection was -4.9 µV (95% confidence interval -6.3 to -3.4); electroretinogram declined by -4.6 µV (95% confidence interval -7.0 to -2.2) after 25-µg injections and -5.2 µV (95% confidence interval -6.6 to -3.8) after 30-µg injections (P = 0.66). Injection at a new clock site hour was associated with a -3.91-µV lower average (95% confidence interval -7.8 to -0.04). CONCLUSION: Electroretinogram-measured toxicity in retinoblastoma eyes treated with intravitreal injections was not found to be different across 25-µg and 30-µg injections. There were no cases of extraocular extension or metastatic deaths in our patient population.

The experience of financial toxicity among advanced melanoma patients treated with immunotherapy.

Purpose To measure financial toxicity and explore its association with quality of life (QOL) in an emerging population of survivors: advanced melanoma patients treated with immunotherapy. Design Cross-sectional survey and medical record review. Sample 106 survivors (39% response). Median time since start of immunotherapy was 36.4 months (range: 14.2-133.9). Methods The Comprehensive Score for Financial Toxicity measured financial toxicity, and the EORTC-QLQ30 assessed QOL and functioning across five domains. Data were collected online, by phone, or in clinic. Findings: Younger patients (<65 years) reported higher financial toxicity (p < .001) than older patients. Controlling for age, financial toxicity was correlated with QOL (p < .001), financial difficulties (p < .001), and EORTC-QLQ30 functioning subscales. Conclusions Given the demonstrated association between financial toxicity and QOL, our study highlights the importance of addressing financial toxicity, particularly among patients receiving high-cost treatments. Implications for Psychosocial Providers: Providers should educate patients and their caregivers about cost-management techniques, link them with available resources, and provide psychosocial counseling to alleviate related distress.

Impact of provider volume on front-line chemotherapy guideline compliance and overall survival in elderly patients with advanced ovarian cancer.

PURPOSE: We sought to evaluate whether provider volume or other factors are associated with chemotherapy guideline compliance in elderly patients with epithelial ovarian cancer (EOC). METHODS: We queried the SEER-Medicare database for patients ≥66 years, diagnosed with FIGO stage II-IV EOC from 2004 to 2013 who underwent surgery and received chemotherapy within 7 months of diagnosis. We compared NCCN guideline compliance (6 cycles of platinum-based doublet) and chemotherapy-related toxicities across provider volume tertiles. Factors associated with guideline compliance and chemotherapy-related toxicities were assessed using logistic regression. Overall survival (OS) was compared across volume tertiles and Cox proportional-hazards model was created to adjust for case-mix. RESULTS: 1924 patients met inclusion criteria. The overall rate of guideline compliance was 70.3% with a significant association between provider volume and compliance (64.5% for low-volume, 72.2% for medium-volume, 71.7% for high-volume, p = .02). In the multivariate model, treatment by low-volume providers and patient age ≥ 80 years were independently associated with worse chemotherapy-guideline compliance. In the survival analysis, there was a significant difference in median OS across provider volume tertiles with median survival of 32.8 months (95%CI 29.6, 36.4) low-volume, 41.9 months (95%CI 37.5, 46.7) medium-volume, 42.1 months (95%CI 38.8, 44.2) high-volume providers, respectively (p < .01). After adjusting for case-mix, low-volume providers were independently associated with higher rates of mortality (aHR 1.25, 95%CI: 1.08, 1.43). CONCLUSIONS: In a modern cohort of elderly Medicare patients with advanced EOC, we found higher rates of non-compliant care and worse survival associated with treatment by low-volume Medicare providers. Urgent efforts are needed to address this volume-outcomes disparity.

Inpatient folate testing at an academic cancer center: single-year experience.

PURPOSE: The value of testing for folate deficiency has been scrutinized recently given low prevalence of deficiency with widespread dietary fortification. Numerous studies have shown folate testing to be low yield overall. However, the value of such testing in the inpatient cancer population has not been defined. METHODS: We queried all folate tests performed during 2017 at our center on admitted cancer patients. We used diagnosis codes and manual chart review to assess risk factors for folate deficiency. Descriptive statistics were used to summarize characteristics of patients undergoing folate testing, the frequency of vitamin B12 co-testing, and repeat folate testing. Fisher's exact test was used to compare the proportion of deficient vs. not deficient tests based on the presence of risk factors. A Cox proportional hazards model was fit to examine the association between folate deficiency and survival. RESULTS: In total, 937 patients had 1065 tests performed during 2017. Among all tests, 7.0% indicated folate deficiency. In patients who underwent two folate tests in a single hospitalization, 89% were deficient neither instance. Risk factors for folate deficiency were equally common in instances with deficient compared with replete testing (25.3 vs. 20.4%, P = 0.334). Folate deficiency was associated with higher risk for death (HR 1.49, 95% CI 1.10-2.03, P = 0.01). CONCLUSION: Folate deficiency was present in 7% of hospitalized cancer patients and associated with shorter overall survival. Repeat testing in the same patient over time was low yield. Traditional risk factors for folate deficiency do not appear to apply in this patient population.

Implementing Obstetric Venous Thromboembolism Protocols on a Statewide Basis: Results from New York State's Safe Motherhood Initiative.

OBJECTIVE: To determine whether a state-level initiative to reduce obstetric venous thromboembolism (VTE) risk affected outcomes and process measures. METHODS: In 2013, the Safe Motherhood Initiative (SMI) developed a VTE safety bundle to reduce obstetric VTE risk. A total of 117 of 124 hospitals providing obstetrical services in New York participated in SMI. Data evaluating thromboembolism events (deep vein thrombosis and pulmonary embolism) and thromboprophylaxis process measures were collected from March through November 2015. RESULTS: A total of 107 hospitals, in any individual quarter, reported data on each of the VTE bundle outcomes and measures. Centers that provided low-risk care (Level 1 centers) reported the lowest rate of bundle implementation at the end of the study period (55.6%). Mechanical prophylaxis for a cesarean was common at all centers. Hospitals that adopted the bundle were more likely to provide routine pharmacologic prophylaxis for women undergoing cesarean. The risk of VTE did not differ by bundle implementation. CONCLUSION: While adoption of the SMI VTE bundle occurred at a majority of centers across New York, uptake was less likely at low-acuity centers. Bundle adoption was associated with implementation of recommended practices. The rare nature of VTE events underscores the need for large data samples to determine the best prophylaxis strategies.

The New York State Safe Motherhood Initiative: Early Impact of Obstetric Hemorrhage Bundle Implementation.

OBJECTIVE: To determine the effects of the Safe Motherhood Initiative's (SMI) obstetric hemorrhage bundle in New York State (NYS). STUDY DESIGN: In 2013, the SMI convened interprofessional workgroups on hemorrhage, venous thromboembolism, and hypertension tasked with developing evidence-based care bundles. Participating hospitals submitted data measured before, during, and after implementation of the hemorrhage bundle: maternal mortality, intensive care unit (ICU) admission, cardiovascular collapse, hysterectomy, and transfusion of ≥4 units of red blood cells (RBCs). Data were analyzed for trends stratified by implementation status. RESULTS: Of the 123 maternity hospitals in NYS, 117 participated, of which 113 submitted data. Of 250,719 births, transfusion of ≥4 units RBCs (1.8 per 1,000) and ICU admissions (1.1 per 1,000) were the most common morbidities. Four hemorrhage-related maternal deaths (1.6 per 100,000) and 10 cases of cardiovascular collapse requiring cardiopulmonary resuscitation (4.0 per 100,000) occurred. Hemorrhage morbidity did not change over the five quarters studied. Risks were similar across hospital level of care and implementation status. CONCLUSION: Statewide implementation of bundles is feasible with resources critical to success. The low hemorrhage-related maternal death rate makes changes in mortality risk difficult to detect over short time intervals. Long-term and timely data collection with individual expert case review will be required.

Primary and Repeat Cesarean Deliveries: A Population-based Study in the United States, 1979-2010.

BACKGROUND: Despite the temporal increase in cesarean deliveries, the extent to which maternal age, period, and maternal birth cohorts may have contributed to these trends remains unknown. METHODS: We performed an analysis of 123 million singleton deliveries in the United States (1979-2010). We estimated rate ratio (RR) with 95% confidence interval (CI) for primary and repeat cesarean deliveries. We examined changes in cesarean rates with weighted Poisson regression models across three time-scales: maternal age, year of delivery, and birth cohort (mother's birth year). RESULTS: The primary cesarean rate increased by 68% (95% confidence interval [CI]: 67%, 69%) between 1979 (11.0%) and 2010 (18.5%). Repeat cesarean deliveries increased by 178% (95% CI: 176, 179) from 5.2% in 1979 to 14.4% in 2010. Cesarean rates increased with advancing age. Compared with 1979, the RR for the period effect in primary and repeat cesarean deliveries increased up to 1990, fell to a nadir at 1993, and began to rise thereafter. A small birth cohort effect was evident, with women born before 1950 at increased risk of primary cesarean; no cohort effect was seen for repeat cesarean deliveries. Adjustment for maternal BMI had a small effect on these findings. Period effects in primary cesarean were explained by a combination of trends in obesity and chronic hypertension, as well as demographic shifts over time. CONCLUSIONS: Maternal age and period appear to have important contributions to the temporal increase in the cesarean rates, although the effect of parity on these associations remains undetermined.

Incidence and Risk Factors for Blood Transfusion in Total Joint Arthroplasty: Analysis of a Statewide Database.

BACKGROUND: Significant attempts have been made to adopt practices to minimize blood transfusion after total joint arthroplasty (TJA) because of transfusion cost and potential negative clinical consequences including allergic reactions, transfusion-related lung injuries, and immunomodulatory effects. We aimed to evaluate risk factors for blood transfusion in a large cohort of TJA patients. METHODS: We used the all-payer California Healthcare Cost and Utilization Project data from 2006 to 2011 to examine the trends in utilization of blood transfusion among arthroplasty patients (n = 320,746). We performed descriptive analyses and multivariate logistic regression clustered by hospital, controlling for Deyo-Charlson comorbidity index, age, insurance type (Medicaid vs others), gender, procedure year, and race/ethnicity. RESULTS: Eighteen percent (n = 59,038) of TJA patients underwent blood transfusion during their surgery, from 15% with single knee to 45% for bilateral hip arthroplasty. Multivariate analysis indicated that compared with the referent category of single knee arthroplasty, single hip had a significantly higher odds of blood transfusion (odds ratio [OR], 1.76; 95% confidence interval [CI], 1.68-1.83), as did bilateral knee (OR, 3.57; 95% CI, 3.20-3.98) and bilateral hip arthroplasty (OR, 6.17; 95% CI, 4.85-7.85). Increasing age (eg, age ≥80 years; OR, 2.99; 95% CI, 2.82-3.17), Medicaid insurance (OR, 1.36; 95% CI, 1.27-1.45), higher comorbidity index (eg, score of ≥3; OR, 2.33; 95% CI, 2.22-2.45), and females (OR, 1.75; 95% CI, 1.70-1.80) all had significantly higher odds of blood transfusion after TJA. CONCLUSION: Primary hip arthroplasties have significantly greater risk of transfusion than knee arthroplasties, and bilateral procedures have even greater risk, especially for hips. These factors should be considered when evaluating the risk for blood transfusions.

Cervical ripening agents in the second trimester of pregnancy in women with a scarred uterus: a systematic review and metaanalysis of observational studies.

OBJECTIVE: The aim of this systematic review and metaanalysis was to determine the efficacy and safety of cervical ripening agents in the second trimester of pregnancy in patients with previous cesarean delivery. STUDY DESIGN: Data sources were PubMed, EMBASE, CINAHL, LILACS, Google Scholar, and clinicaltrials.gov (1983 through 2015). Eligibility criteria were cohort or cross-sectional studies that reported on efficacy and safety of cervical ripening agents in patients with previous cesarean delivery. Efficacy was determined based on the proportion of patients achieving vaginal delivery and vaginal delivery within 24 hours following administration of a cervical ripening agent. Safety was assessed by the risk of uterine rupture and complications such as retained placental products, blood transfusion requirement, and endometritis, when available, as secondary outcomes. Of the 176 studies identified, 38 met the inclusion criteria. Of these, 17 studies were descriptive and 21 studies compared the efficacy and safety of cervical ripening agents between patients with previous cesarean and those with no previous cesarean. From included studies, we abstracted data on cervical ripening agents and estimated the pooled risk differences and risk ratios with 95% confidence intervals. To account for between-study heterogeneity, we estimated risk ratios based on underlying random effects analyses. Publication bias was assessed via funnel plots and across-study heterogeneity was assessed based on the I(2) measure. RESULTS: The most commonly used agent was PGE1. In descriptive studies, PGE1 was associated with a vaginal delivery rate of 96.8%, of which 76.3% occurred within 24 hours, uterine rupture in 0.8%, retained placenta in 10.8%, and endometritis in 3.9% in patients with ≥1 cesarean. In comparative studies, the use of PGE1, PGE2, and mechanical methods (laminaria and dilation and curettage) were equally efficacious in achieving vaginal delivery between patients with and without prior cesarean (risk ratio, 0.99, and 95% confidence interval, 0.98-1.00; risk ratio, 1.00, and 95% confidence interval, 0.98-1.02; and risk ratio, 1.00, and 95% confidence interval, 0.98-1.01; respectively). In patients with history of ≥1 cesarean the use of PGE1 was associated with higher risk of uterine rupture (risk ratio, 6.57; 95% confidence interval, 2.21-19.52) and retained placenta (risk ratio, 1.21; 95% confidence interval, 1.03-1.43) compared to women without a prior cesarean. However, the risk of uterine rupture among women with history of only 1 cesarean (0.47%) was not statistically significant (risk ratio, 2.36; 95% confidence interval, 0.39-14.32), whereas among those with history of ≥2 cesareans (2.5%) was increased as compared to those with no previous cesarean (0.08%) (risk ratio, 17.55; 95% confidence interval, 3.00-102.8). Funnel plots did not demonstrate any clear evidence of publication bias. Across-study heterogeneity ranged from 0-81%. CONCLUSION: This systematic review and metaanalysis provides evidence that PGE1, PGE2, and mechanical methods are efficacious for achieving vaginal delivery in women with previous cesarean delivery. The use of prostaglandin PGE1 in the second trimester was not associated with significantly increased risk for uterine rupture among women with only 1 cesarean; however, this risk was substantially increased among women with ≥2 cesareans although the absolute risk appeared to be relatively small.

Temporal trends in obstetric trauma and inpatient surgery for pelvic organ prolapse: an age-period-cohort analysis.

BACKGROUND: The rates of cesarean delivery have increased over time in industrialized countries, while the rates of instrumental vaginal delivery have declined. Instrumental vaginal delivery and obstetric trauma are risk factors for pelvic floor disorders. OBJECTIVE: We carried out a population-based study to quantify the association between temporal changes in obstetric trauma during childbirth and temporal changes in surgery for pelvic organ prolapse. STUDY DESIGN: We designed a retrospective analysis to examine age-specific trends in vaginal and cesarean delivery, obstetric trauma, and surgery for pelvic organ prolapse among all women (pregnant and nonpregnant) in Washington State, from 1987 through 2009. Cases of obstetric trauma (including severe perineal tears and high vaginal lacerations) and inpatient surgery for pelvic organ prolapse were identified among all hospitalizations. Temporal trends and age-period-cohort regression analyses were used to quantify the time period, age, and birth cohort effects among women born from 1920 through 1980. RESULTS: From 1987 through 2009, cesarean delivery rates among women aged 15-44 years increased from 12.7-18.1 per 1000 women, vaginal delivery rates remained stable, and instrumental vaginal delivery rates declined from 6.3-3.9 per 1000 women. Obstetric trauma decreased from 6.7 in 1987 to 2.5 per 1000 women aged 15-44 years in 2009. Surgery for pelvic organ prolapse decreased from 2.1 in 1987 to 1.4 per 1000 women aged 20-84 years in 2009. Obstetric trauma rates in 1987 through 1999 among women 15-44 years old were strongly correlated with the rates of surgery for pelvic organ prolapse among women 25-54 years of age 10 years later in 1997 through 2009 (correlation coefficient 0.87, P < .001). Similarly, rates of midpelvic forceps delivery in 1987 through 1999 were correlated with the rates of surgery for pelvic organ prolapse 10 years later (correlation coefficient 0.72, P < .01). Regression analyses showed a strong effect of age on surgery for prolapse, temporal decline in surgery, and an effect of birth cohort, as younger cohorts (women born in ≥1965 vs 1940) had lower rates of surgery for pelvic organ prolapse. CONCLUSION: Temporal decline in instrumental vaginal delivery and obstetric trauma may have contributed to the reduction in surgery for pelvic organ prolapse.

Severe placental abruption: clinical definition and associations with maternal complications.

BACKGROUND: Placental abruption traditionally is defined as the premature separation of the implanted placenta before the delivery of the fetus. The existing clinical criteria of severity rely exclusively on fetal (fetal distress or fetal death) and maternal complications without consideration of neonatal or preterm delivery-related complications. However, two-thirds of abruption cases are accompanied by fetal or neonatal complications, including preterm delivery. A clinically meaningful classification for abruption therefore should include not only maternal complications but also adverse fetal and neonatal outcomes that include intrauterine growth restriction and preterm delivery. OBJECTIVES: The purpose of this study was to define severe placental abruption and to compare serious maternal morbidity profiles of such cases with all other cases of abruption (ie, mild abruption) and nonabruption cases. STUDY DESIGN: We performed a retrospective cohort analysis using the Premier database of hospitalizations that resulted in singleton births in the United States between 2006 and 2012 (n = 27,796,465). Severe abruption was defined as abruption accompanied by at least 1 of the following events: maternal (disseminated intravascular coagulation, hypovolemic shock, blood transfusion, hysterectomy, renal failure, or in-hospital death), fetal (nonreassuring fetal status, intrauterine growth restriction, or fetal death), or neonatal (neonatal death, preterm delivery or small for gestational age) complications. Abruption cases that did not qualify as being severe were classified as mild abruption cases. The morbidity profile included amniotic fluid embolism, pulmonary edema, acute respiratory or heart failure, acute myocardial infarction, cardiomyopathy, puerperal cerebrovascular disorders, or coma. Associations were expressed as rate ratios with 95% confidence intervals that were derived from fitting log-linear Poisson regression models. RESULTS: The overall prevalence rate of abruption was 9.6 per 1000, of which two-thirds of cases were classified as being severe (6.5 per 1000). Serious maternal complications occurred in 15.4, 33.3, and 141.7 per 10,000 among nonabruption cases and mild and severe abruption cases, respectively. In comparison with no abruption, the rate ratio for serious maternal complications were 1.52 (95% confidence interval, 1.35-1.72) and 4.29 (95% confidence interval, 4.11-4.47) in women with mild and severe placental abruption, respectively. Rate ratios for the individual complications were 2- to 7-fold higher among severe abruption cases. Furthermore, the rate ratios for serious maternal complications among severe abruption cases compared with mild abruption cases was 3.47 (95% confidence interval, 3.05-3.95). This association was considerably stronger for virtually all maternal complications among cases with severe abruption compared with mild abruption. Annual rates of mild and severe abruption were fairly constant during the study period. Although the maternal complication rate among non-abruption births was stable from 2006-2012, the rate of complications among mild abruption cases dropped from 2006-2008 and then leveled off thereafter. In contrast, the rate of serious complications among severe abruption cases remained fairly stable from 2006-2010 and increased sharply thereafter. CONCLUSIONS: Severe abruption was associated with a distinctively higher morbidity risk profile compared with the other 2 groups. The clinical characteristics and morbidity profile of mild abruption were more similar to those of women without an abruption. These findings suggest that the definition of severe placental abruption based on the proposed specific criteria is clinically relevant and may facilitate epidemiologic and genetic research.