Kaplan-Meier Life-table Analysis Research Articles

Establishing an autogenous vascular access program in a Guatemalan comprehensive pediatric nephrology center.

The Guatemalan Foundation for Children with Kidney Diseases collaborated with Bridge of Life, a not-for-profit charitable organization, to establish a vascular access program. We reviewed our experience with graded surgical responsibility and structured didactic training, creating arteriovenous fistulas (AVF) for Guatemalan children. Pediatric vascular access missions were completed from 2015 to 2023 and analyzed retrospectively. Follow-up was completed by the Guatemalan pediatric surgeons, nephrologists, and nursing staff. AVF patency and patient survival were evaluated by Kaplan-Meier life-table analysis with univariate and multivariable association between patient demographic variables by Cox proportional hazards models. Among a total of 153 vascular access operations, there were 139 new patient procedures, forming the study group for this review. The mean age was 13.6years, 42.6% were female, and the mean BMI was 17.3. Radial or ulnar artery-based direct AVFs were established in 100 patients (71.9%) and ten of the 25 transposition procedures. Brachial artery inflow was required in 29 direct AVFs (20.9%). Two patients underwent femoral vein transpositions. Access-related distal ischemia was not encountered. Seven of the AVF patients later required access banding for arm edema; all had previous dialysis catheters (mean = 9, range 4-12). Primary and cumulative patency rates were 84% and 86% at 12months and 64% and 81% at 24months, respectively. The median follow-up was 12months. Overall patient survival was 84% and 67% at 12 and 24months, respectively. There were no deaths related to AVF access. Safe and functional AVFs were established in a teaching environment within a Guatemalan comprehensive pediatric nephrology center.

Impact on early outcome after endovascular repair of type B dissection without proximal landing zone using Castor single-branched stent graft-a retrospective cohort study.

The early safety and efficacy of Castor branch stents have been demonstrated. However, the effect of aortic arch morphology on endovascular therapy remains an unresolved issue. This study aims to assess the impact of aortic arch morphology on the early outcomes of endovascular repair using Castor stent graft in patients who have acute type B aortic dissection involving the left subclavian artery (LSA). This is a retrospective cohort study. From January 2019 to December 2021, forty-one patients scheduled for thoracic endovascular aortic repair (TEVAR) of TBADs from Beijing Anzhen Hospital were enrolled in this retrospective cohort study and divided into two groups based on the length of the proximal landing zone left common carotid artery-LSA (PLZ LCCA-LSA), specifically the distance between the LCCA and the LSA (group A ≤10 mm and group B >10 mm). The study recorded technical success, mortality and aortic-related post-operative adverse events. Morphological indices were analyzed including the bird-beak configuration. The bird-beak configuration refers to the wedge-shaped gap between the undersurface of the endograft and the lesser curvature of the arch. The relationship between the risk of bird-beak configuration and PLZ was assessed with logistic regression analysis. Meanwhile, the relationship between the risk of aortic-related adverse events and bird-beak configuration was assessed with logistic regression analysis. Follow-up data were analyzed by Kaplan-Meier life table analysis. The study included 41 patients with a mean age of 63.1±9.2 years, of which 80.5% were male. 18 patients from group A and 23 patients from group B were included in the comparative analysis. There were no significant differences in aortic-related adverse events, bird-beak phenomenon and re-intervention between groups A and B in 30-day outcomes. Six-month outcomes: aortic-related adverse events and the bird-beak phenomenon were observed in 11 (26.8%) and 12 (29.3%) patients, respectively. There was a significant difference in the occurrence of aortic-related adverse events (P=0.036) and bird-beak phenomenon (P=0.002) between groups A and B. In comparison to group B, the aortic-related adverse event rate was significantly higher in group A, with event-free rates of 83.3%, 83.3%, and 72.2% at 1, 3, and 6 months, respectively (P=0.020). Multivariable logistic regression analyses revealed that PLZ LCCA-LSA length [odds ratio (OR) 0.79; 95% CI: 0.64 to 0.97; P=0.026] was significantly associated with the occurrence of the bird-beak configuration, and bird-beak (OR 17.19; 95% CI: 2.24 to 131.81; P=0.006) was a significant risk factor for aortic-related adverse events. TEVAR with LSA revascularization has good early outcomes. However, it is more susceptible to aortic adverse events when the PLZ LCCA-LSA is less than 10 mm in length. This should be carefully considered, taking into account the risks and benefits.

Fatigue and failure analysis of restored endodontically treated maxillary incisors without a dowel or ferrule

Statement of problemInformation on the survival and mode of failure of endodontically treated incisors without a ferrule and restored without dowels is lacking. PurposeThe purpose of this in vitro study was to compare the survival and failure mode of endodontically treated incisors without a ferrule and restored with bonded ceramic crowns and various composite resin foundation restorations without dowels with a control group with fiber dowels. Material and methodsForty-five decoronated endodontically treated bovine incisors without ferrule were divided into 3 experimental groups and restored with different adhesive foundation restorations without dowel: nanohybrid composite resin (Nd), bulk-fill composite resin foundation restoration (NdB), and fiber-reinforced bulk-fill composite resin (NdFR). A control group with conventional foundation restorations (glass-fiber dowel with nanohybrid composite resin foundation restoration without ferrule) (D) was included for comparison. All teeth were prepared to receive bonded lithium disilicate ceramic crowns luted with dual-polymerizing composite resin cement and were subjected to accelerated fatigue testing. Cyclic isometric loading was applied to the incisal edge at an angle of 30 degrees and a frequency of 5 Hz, beginning with a load of 100 N (5000 cycles). A 100-N load increase was applied each 15 000 cycles. Specimens were loaded until failure or to a maximum for cycles endured of 1000 N (140 000 cycles). Groups were compared by using the Kaplan-Meier survival analysis (log rank test at α=.05 and pairwise post hoc comparisons) and life table analysis for load-at-failure (followed by Wilcoxon pairwise comparison α=.05). ResultsAll the specimens failed before 140 000 load cycles. Even though no statistically significant differences were found between the experimental groups without dowel (P>.127), the fiber-reinforced foundation restoration yielded the highest mean ±standard deviation cycles to failure (46 023 ±4326) compared with Nd (38 899 ±2975) and NdB (39 751 ±2998). NdFR, however, outperformed the foundation restoration with glass-fiber dowel (35 026 ±2687) (P<.05). Most failure in groups without dowel were restorable, while 100% of catastrophic failure (unrestorable) were found in the group with dowels. ConclusionsBased on the present in vitro study, dowels did not improve the performance of the adhesive restoration of endodontically treated incisors without a ferrule. The use of a short fiber-reinforced composite resin foundation restoration without a dowel was able to not only improve the resistance of the restorations compared with adhesive foundation restorations with dowels but also minimize catastrophic failures.

Lymphoma in Miniature Dachshunds: A retrospective multicenter study of 108 cases (2006-2018) in Japan.

BackgroundMiniature Dachshunds (MD) are predisposed to lymphoma with disease onset of young age and long‐term survival.ObjectivesTo compare clinical features and survival time of lymphoma in MD and non‐MD.AnimalsOne hundred and eight MDs with lymphoma and 149 non‐MD breed dogs with lymphoma were included in the study.MethodsThis was a retrospective multicenter observational study. Lymphoma was classified based on signalment, histopathology/cytology, and anatomical site of the disease. For each type of lymphoma, median survival time was analyzed by Kaplan‐Meier estimates and life table analysis. Prognostic factors for large‐cell gastrointestinal lymphoma (LGIL) were analyzed using Cox regression.ResultsGastrointestinal lymphomas were more common in MDs (53/108) compared to non‐MDs (41/149). The multicentric lymphoma was most common in non‐MD breed dogs (74/149) compared to MDs (33/108). The median age that dog developed lymphoma in MD and non‐MD were both 10 years old; however, lymphomas were more frequently observed in younger dogs (<4 years) in MDs (20/108) compared to non‐MDs (9/149; P = .002). Seventy percent were diagnosed with B‐cell with median age of diagnosis was 3 (1‐14) years. Mott cell differentiation was observed in 6 dogs. Age <4 years and B‐cell phenotype were significant factors for longer survival time in MD with LGIL.Conclusions and Clinical ImportanceLymphomas in MDs involved gastrointestinal lesions at higher frequency compared to other dog breeds examined. B‐cell lymphoma was more common in early‐onset LGIL in MD and cases that involved Mott cell differentiation were observed. Awareness of this specific presentation of lymphoma in dogs will possibly affect the treatment decision process for the owners of MD with LGIL.

Contraceptive Effectiveness of an FDA-Cleared Birth Control App: Results from the Natural Cycles U.S. Cohort.

Background: Digital fertility awareness-based methods of birth control are an attractive alternative to hormonal or invasive birth control for modern women. They are also popular among women who may be planning a pregnancy over the coming years and wish to learn about their individual menstrual cycle. The aim of this study was to assess the effectiveness of the Natural Cycles app at preventing pregnancy for a cohort of women from the United States and to describe the key demographics of current users of the app in such a cohort. Materials and Methods: This prospective real-world cohort study included users who purchased an annual subscription to prevent pregnancy. Demographics were assessed through answers to in-app questionnaires. Birth control effectiveness estimates for the entire cohort were calculated using 1-year pearl index (PI) and 13-cycle cumulative pregnancy probability (Kaplan-Meier life table analysis). Results: The study included 5879 women who contributed an average of 10.5 months of data for a total of 5125 woman-years of exposure. The average user was 30 years old with a body mass index of 24 and reported being in a stable relationship. With typical use, the app had a 13-cycle cumulative pregnancy probability of 7.2% and a 1-year typical use PI of 6.2. When the app was used under perfect use, the PI was 2.0. Conclusions: The data presented in this study give insights into the cohort of women using this app in the United States, and provide country-specific effectiveness estimates. The contraceptive effectiveness of the app was in line with previously published figures from Natural Cycles (PI of seven for typical use and two for perfect use).

Real-World Use of FLT3-TKIs in R/R FLT3-Mutated AML in the United States

Background: Targeted inhibition of the FLT3 tyrosine kinase is a treatment strategy for patients with relapsed or refractory, FLT3 mutation-positive acute myeloid leukemia (R/R FLT3mut+ AML). While the multikinase inhibitors, sorafenib and midostaurin, were not approved specifically for R/R AML, they are used off-label as treatment. Since FDA approval on 11/28/2018, gilteritinib has become the first globally approved targeted therapy for the treatment of R/R FLT3mut+ AML in adults. This study aims to understand the treatment landscape for R/R FLT3mut+ AML patients following the introduction of a new therapeutic agent. Aim/Objective: To describe the characteristics and treatment patterns of patients initiating FLT3 tyrosine kinase inhibitors (TKIs) for R/R FLT3mut+ AML in the real-world setting. Methods: This US-based retrospective cohort study was conducted using two separate closed-claims databases (MarketScan, 1/1/2007-2/29/2020; IQVIA, 1/1/2006-4/30/2020) and a specialty-pharmacy claims database (ProMetrics, 12/6/2018-3/12/2020). Patients ≥18 years of age, with an AML diagnosis and newly initiated FLT3-TKI (ie, gilteritinib, midostaurin, or sorafenib) therapy for R/R diagnosis or episode ("R/R AML") on or after gilteritinib market availability were eligible for inclusion. Patients were indexed on the first newly initiated FLT3-TKI for R/R AML observed on or after 12/1/2018. Patients' baseline clinical and demographic characteristics, AML-related treatments preceding FLT3-TKI initiation for R/R AML, and concomitant therapies (defined as any AML-related treatment overlapping with FLT3-TKI use after R/R AML) were identified. Because individual patients could have received more than one FLT3-TKI during the study period, treatment sequencing was analyzed by FLT3-TKI-containing regimens. Given the larger sample size available within the ProMetrics Specialty Pharmacy database, gilteritinib dose patterns and treatment duration were analyzed using de-identified dispensed prescription data from a separate gilteritinib-only cohort for greater precision. Descriptive statistics were used to evaluate all study outcomes, except for treatment duration, which was estimated using Kaplan-Meier life table analysis. Results: A total of 52 and 51 patients initiating FLT3-TKIs for R/R AML were identified in the MarketScan and IQVIA databases, respectively. The mean age of patients was 53.1 (MarketScan) and 52.3 years (IQVIA); patients had a mean ± SD Quan-Charlson Comorbidity Index of 3.6 ± 2.4 (MarketScan) and 3.7 ± 2.2 (IQVIA). Most patients treated with FLT3-TKIs for R/R AML during the study period were first initiated on gilteritinib (MarketScan: n=35 [67.3%], IQVIA: n=36 [70.6%]); sorafenib was the second most common FLT3-TKI (MarketScan: n=9 [17.3%], IQVIA: n=8 [15.7%]), followed by midostaurin (MarketScan: n=8 [15.4%], IQVIA: n=7 [13.7%]). During the study period, 61 and 55 FLT3-TKI-containing regimens among 52 and 51 R/R AML patients were identified across the MarketScan and IQVIA databases, respectively. Most FLT3-TKI-containing regimens for R/R AML included gilteritinib (MarketScan: n=43 [70.5%], IQVIA: n=38 [69.1%]). Prior exposure to other FLT3-TKIs for new onset and/or R/R AML indications was observed in up to 63% of gilteritinib-, 56% of sorafenib-, and 13% of midostaurin-containing regimens (Table). Following onset of R/R AML, gilteritinib was given without concomitant chemotherapy in 47% (Marketscan: 20/43) to 55% (IQVIA: 21/38) of gilteritinib regimens; in a smaller sample of sorafenib regimens, sorafenib was given without concomitant chemotherapy in up to 56% (IQVIA: 5/9) of regimens. Of 748 patients identified in the ProMetrics database with gilteritinib claims, 714 (95%) patients were initiated on a 120-mg daily dose, with less than 5% (n=34) incurring a downward dosage titration. The median treatment duration was 150 days (95% CI: 129-172 days). Conclusions: Among FLT3-TKI-containing regimens initiated for R/R AML after gilteritinib market approval, close to 70% included gilteritinib, an agent approved for R/R FLT3mut+ AML. Sample sizes for midostaurin- and sorafenib-containing regimens limited characterization of treatment patterns. Gilteritinib was given without concomitant chemotherapy in approximately 50% of regimens prescribed; the dose and treatment durations were similar to those previously reported by the ADMIRAL trial. Disclosures Grinblatt: Astellas: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Alexion: Speakers Bureau. Pandya:Astellas Pharma, Inc.: Current Employment. Sullivan:Astellas Pharma: Current Employment. Feng:Astellas: Current Employment. Hedlund:Astellas: Current Employment.

Prosthesis Survival Rates and Prosthetic Complications of Implant-Supported Fixed Dental Prostheses in Partially Edentulous Patients.

To determine the prevalence and distribution of prosthetic complications affecting implant-supported fixed dental prostheses (ISFDPs). Subjects previously treated with one or more ISFDP(s) were identified from an electronic health record search and recalled for comprehensive clinical examination. Past prosthesis failures and complications were identified from the patient records while any existing complications, not previously recorded, were assessed during examination. ISFDP survival and failure rates were calculated with Kaplan-Meier curves and life table analysis, while regression Poisson analysis was used to identify associations between outcomes and possible patient- and prosthesis-based risk factors. Seventy-four subjects with 107 ISFDPs were enrolled in the study with a mean time between prosthesis delivery and exam of 3.14 years (range: 1.00-9.00 years). Four prostheses failed, resulting in a cumulative prosthesis survival rate of 96.26%. Prosthetic complications affected 48.59% of ISFDPs, the majority (94.87%) of them minor complications. Only the use of a nightguard was associated with a lower prevalence of prosthetic screw loosening (HR 0.11, 95% CI 0.02-0.59, p = 0.007) while no outcome differences were noted for other variables. Patient satisfaction was high regardless of presence or number of complications. ISFDPs demonstrated a high survival rate and overall high, patient-reported satisfaction. Minor prosthetic complications were common but were only significantly associated with nightguard use.

Renal volumes and estimated glomerular filtration rate changes after fenestrated-branched endovascular aortic repair

ObjectiveTo describe changes in renal volumes (RV) and renal function after fenestrated-branched endovascular repair (F-BEVAR) for complex aortic aneurysms. MethodsThe data from patients enrolled in a physician-sponsored investigational device exemption clinical trial for endovascular treatment of complex aortic aneurysms from July 2012 to April 2017 were retrospectively analyzed. Descriptive statistics were calculated using the mean ± standard deviation. The mean estimated glomerular filtration rate (eGFR) and RV were calculated at baseline and 6, 12, and 18 months after F-BEVAR. Variable distributions were evaluated for skewness, and all models required log-transformation. Linear models using generalized estimating equations were used to assess the association between the RV and eGFR over time after adjustment for relevant covariates. We used Kaplan-Meier life-table analysis to calculate survival and branch patency. ResultsA total of 139 patients were followed up for 18 months or until death. The mean age was 71 ± 8 years (70% male). The most common risk factor was hypertension (92%). Chronic kidney disease (CKD; eGFR <60 mL/min) was present in 56 patients (40%). Thirty-one patients (22%) had ≥1 accessory renal artery. Of these 31 accessory arteries, 27 (87%) were embolized or covered. On average, the eGFR had decreased over time compared with baseline, with a median change of −4.4 mL/min (interquartile range [IQR], −11.4 to 4.9 mL/min), −2.6 mL/min (IQR, −11.9 to 6.5 mL/min), and −3.4 mL/min (IQR, −11.9 to 5.5 mL/min) at 6, 12, and 18 months postoperatively, respectively. Similarly, the RV had decreased from baseline by 8% ± 17%, 10% ± 17%, and 11% ± 22% at 6, 12, and 18 months, respectively. An increase in the baseline patient age of 5 years was estimated to be associated with a 3% (95% confidence interval [CI], 0.2%-6.0%) decrease in the mean eGFR during the follow-up period, collapsing over time. This change is similar to the natural history of renal deterioration with age. We estimated that an increase in the log-RV of 1 U would be associated with an estimated 26% (95% CI, 3%-52%) increase in the mean eGFR. Preexisting CKD did not affect the average change in RV. Of the 56 patients with previous CKD, 9 (16.1%) showed improvement in the eGFR to >60 mL/min. The median follow-up period was 17.9 months (IQR, 6.3-24.8). The Kaplan-Meier survival rate at 1 and 2 years was 84.7% (95% CI, 78.3%-91.1%) and 78.8% (95% CI, 71.0%- 86.6%), respectively. ConclusionsThe RV and eGFR decreased in patients undergoing repair at the rates expected for patients with complex aortic disease. The eGFR correlated with the RV. Most of the decline in renal function occurred within the first 6 months postoperatively, after which, the renal function had stabilized.

Short- and long-term effect of contraceptive methods on fecundity

Objective: The aim of the study was to compare the effect of previously used contraceptive methods on women’s short- and long-term fecundity. Use of hormonal contraception (HC) was compared with the use of a contraceptive mobile application (app).Methods: This real-life prospective observational study comprised 2874 women who were attempting to become pregnant using the Natural Cycles mobile app to monitor their fertility. The women registered to use the app between August 2014 and June 2016 with the intention of planning a pregnancy and had previously either used the same app to prevent pregnancy or had recently discontinued HC use. We calculated the average time to pregnancy (TTP) for all women who became pregnant during the study and performed Kaplan–Meier life-table analysis to examine the cumulative probabilities of pregnancy for all women in the study.Results: The average TTP was 2.3 (95% confidence interval [CI] 2.1, 2.4) and 3.7 (95% CI 3.4, 3.9) cycles for women who had previously used Natural Cycles and HC, respectively. The time to reach 30% pregnancy probability for women previously on HC was 1.6 (95% CI 1.5, 1.8) times longer than for women previously using Natural Cycles. There was no significant difference in the 13 cycle cumulated pregnancy probability between the two groups.Conclusion: The results show that fertility awareness-based methods of contraception increase short-term pregnancy rates relative to HC, but have no effect on long-term pregnancy rates.

Efficacy of the 1-year (13-cycle) segesterone acetate and ethinylestradiol contraceptive vaginal system: results of two multicentre, open-label, single-arm, phase 3 trials

SummaryBackgroundA ring-shaped, contraceptive vaginal system designed to last 1 year (13 cycles) delivers an average of 0·15 mg segesterone acetate and 0·013 mg ethinylestradiol per day. We evaluated the efficacy of this contraceptive vaginal system and return to menses or pregnancy after use.MethodsIn two identically designed, multicentre, open-label, single-arm, phase 3 trials (one at 15 US academic and community sites and one at 12 US and international academic and community sites), participants followed a 21-days-in, 7-days-out segesterone acetate and ethinylestradiol contraceptive vaginal system schedule for up to 13 cycles. Participants were healthy, sexually active, non-pregnant, non-sterilised women aged 18–40 years. Women were cautioned that any removals during the 21 days of cyclic use should not exceed 2 h, and used daily paper diaries to record vaginal system use. Consistent with regulatory requirements for contraceptives, we calculated the Pearl Index for women aged 35 years and younger, excluding adjunctive contraception cycles, as the primary efficacy outcome measure. We also did intention-to-treat Kaplan-Meier life table analyses and followed up women who did not use hormonal contraceptives or desired pregnancy after study completion for 6 months for return to menses or pregnancy. The trials are registered with ClinicalTrials.gov, numbers NCT00455156 and NCT00263341.FindingsBetween Dec 19, 2006, and Oct 9, 2009, at the 15 US sites, and between Nov 1, 2006, and July 2, 2009, at the 12 US and international sites we enrolled 2278 women. Our overall efficacy analysis included 2265 participants (1130 in the US study and 1135 in the international study) and 1303 (57·5%) participants completed up to 13 cycles. The Pearl Index for the primary efficacy group was 2·98 (95% CI 2·13–4·06) per 100 woman-years, and was well within the range indicative of efficacy for a contraceptive under a woman's control. The Kaplan-Meier analysis revealed the contraceptive vaginal system was 97·5% effective, which provided further evidence of efficacy. Pregnancy occurrence was similar across cycles. All 290 follow-up participants reported return to menses or became pregnant (24 [63%] of 38 women who desired pregnancy) within 6 months.InterpretationThe segesterone acetate and ethinylestradiol contraceptive vaginal system is an effective contraceptive for 13 consecutive cycles of use. This new product adds to the contraceptive method mix and the 1-year duration of use means that women do not need to return to the clinic or pharmacy for refills every few months.FundingEunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health, the US Agency for International Development, and the WHO Reproductive Health Research Department.

Natural history of spinal cord arteriovenous shunts: an observational study.

The natural history of intradural spinal cord arteriovenous shunts is unknown. We performed an observational study in a consecutive patient cohort with symptomatic intradural spinal cord arteriovenous shunts who were admitted to three institutes to investigate the clinical course of this complex disease, which would provide valuable evidence to inform clinical decision-making. The clinical course of patients with symptomatic intradural spinal cord arteriovenous shunts from initial presentation to occurrence of clinical deterioration, initiation of treatment, or last follow-up was analysed. Patients with at least 1 month of observation were included in this study. Clinical onset and deterioration patterns were divided into acute and gradual. Annual and cumulative rates of clinical deterioration as well as their risk factors were analysed using Kaplan-Meier life table analysis and Cox proportional hazards model. To assess risks and benefits of treatment, post-treatment clinical courses were further assessed. Four hundred and sixty-six patients with a mean observational period of 36.9 ± 58.8 months were included; 56.7% of patients presented with acute onset, of whom 77.3% experienced spontaneous recovery. Age of onset older than 28 years, initial modified Aminoff and Logue scale of >3, mid-thoracic lesions and non-ventral lesions were independent predictors of failure for spontaneous recovery. The annual risk of general, acute and gradual clinical deterioration after onset was 30.7%, 9.9% and 17.7%, respectively. Risk of deterioration was highest in the early period after initial onset. Acute onset was the only independent risk factor [hazard ratio 1.957 (95% confidence interval, CI 1.324-2.894); P = 0.0008] of acute deterioration and gradual onset was the strongest predictor [hazard ratio 2.350 (95% CI 1.711-3.229); P < 0.0001] of the gradual deterioration among all the stratifying factors. After invasive treatment, complete obliteration was achieved in 37.9% of patients (138 of 364) and improved or stable clinical status was noted in 80.8% of patients. Forty-two patients (11.5%) experienced permanent complications. Overall post-treatment deterioration rate was 8.4%/year, and 5.3%/year if permanent complications were excluded. The natural history of symptomatic spinal cord arteriovenous shunts is poor, especially in the early period after onset, and early intervention is thus recommended. Initial onset pattern significantly affects the natural history of the lesion, which prompts a differentiated treatment strategy.

Efficacy and Safety of a 1-Year Segesterone Acetate and Ethinyl Estradiol Contraceptive Vaginal System

To report the efficacy and safety of a ring-shaped, 1-year (13 cycles) contraceptive vaginal system (CVS) releasing systemically a daily mean of segesterone acetate 150 mcg and ethinyl estradiol 13 mcg. Efficacy and safety are reported from two multicenter, 1-year, open-label, Phase 3 trials (one U.S., one international); a 1-year pharmacokinetic study; and three safety substudies from a Phase 3 study. Twenty-seven clinical study sites inside and outside of the United States. Women ages 18–40 years who were sexually active and had regular menstrual cycles. Participants were instructed to use the CVS on a 21/7-day, in–out continuous schedule and to not remove the CVS for more than 2 hours during the ring-in period. The primary efficacy outcome was the Pearl Index (PI) for women 35 years old or younger. The intention-to-treat Kaplan–Meier life-table analysis was a secondary outcome. Safety was assessed by adverse events (AEs) and substudy data evaluating endometrial, vaginal microbiology, and liver protein changes. A total of 2,265 participants’ data were analyzed for efficacy and 2,308 for safety. The primary PI of 2.98, 95% CI [2.13, 4.06], indicated excellent efficacy. Women who followed use instructions had greater efficacy, PI = 2.10, 95% CI [1.37, 3.06], than those who removed the CVS for more than 2 hours, PI = 5.89, 95% CI [3.46, 9.27], p = .0024. The CVS was 97.3% effective in life-table analyses. Most women were satisfied/very satisfied with the CVS (91%), found it easy to use (91%), and would recommend it to a friend (84%). Treatment-related AEs most frequently reported included headache (n = 601, 26%), nausea (n = 420, 18%), vaginal discharge–vulvovaginal mycotic infection (n = 242, 10%), and abdominal pain (n = 225, 10%). Discontinuations for these complaints were low (<1.5%). Four (0.2%) women experienced venous thromboembolism, 3 of whom had thrombosis risk factors. Substudies revealed no unexpected safety signals. The segesterone acetate and ethinyl estradiol CVS, recently approved by the U.S. Food & Drug Administration, is an effective, 1-year, procedure-free, user-controlled contraceptive that women found acceptable. Efficacy was lower for those who removed the CVS for more than 2 hours during the ring-in period, an important topic for nurses to emphasize when counseling their patients. The CVS also has a safety profile in line with other ethinyl estradiol–based hormonal contraceptives.

Elevated pretreatment serum IL-8 and PD-L1 and overall survival in a phase III randomized advanced pancreatic cancer clinical trial.

4131 Background: We previously reported the prognostic and predictive utility of pretreatment serum PD-L1 in the CCTG MA.31 serum bank (SABCS 2018, abstr PD3-10). IL-8 (CXCL8) is a pro-inflammatory cytokine that binds to CXCR1 and CXCR2 and promotes tumor immune escape and progression. High serum IL-8 levels are associated with poor prognosis in many cancers, and have recently been reported to predict for reduced OS to nivolumab in lung cancer and melanoma (ASCO 2018, abstr #3025). In this study, we retrospectively evaluated combined pretreatment serum IL-8 and PD-L1 on overall survival (OS) from a phase III randomized pancreatic cancer trial of first-line therapy (octreotide + 5-FU vs. 5-FU) that had reported no significant OS difference between treatment arms. Methods: This study had 147 patients with serum available for this retrospective biomarker analysis from an advanced pancreatic cancer phase III clinical trial.TheELLA immunoassay platform (ProteinSimple, San Jose, CA) was utilized to quantitate serum levels of IL-8 and PD-L1. Kaplan-Meier life table analysis was used to correlate serum biomarkers with overall survival (OS). Results: In univariate analysis, pretreatment serum IL-8 was a significant biomarker as a continuous variable (HR = 1.004; p = 0.012) and trended significant at the median cutpoint (HR = 1.379; p = 0.098) for OS, however serum PD-L1 was not significant at any cutpoint. When serum PD-L1 and IL-8 levels were analyzed as combined biomarkers (median cutpoints), the serum IL-8 high / PD-L1 high cohort had a significantly shorter OS vs the serum IL-8 low / PD-L1 low cohort (HR = 1.816; p = 0.017). Conclusions: In this phase III randomized clinical trial in advanced pancreatic cancer, pretreatment serum IL-8 was a significant biomarker for OS, but serum PD-L1 was not. Higher combined pretreatment serum levels of PD-L1 and IL-8 (both biomarkers high vs. both low) were prognostic for reduced OS in this phase III pancreatic cancer trial. Further study of circulating IL-8 and PD-L1 is warranted in pancreatic cancer for evaluation of targeted and investigational therapies, including the immune checkpoint inhibitors and anti-IL8 therapy.

Efficacy of the 1-Year Segesterone Acetate/Ethinyl Estradiol Contraceptive Vaginal System [21OP

INTRODUCTION: A novel, ring-shaped, contraceptive vaginal system (CVS) containing segesterone acetate (SA), also known as Nestorone®, and ethinyl estradiol (EE) is designed to last 1 year (13 cycles), delivering an average of SA 0.15/EE 0.013 mg/day. Efficacy was evaluated in 2 multicenter, 1-year, open-label studies (one at 15 US sites; one at 5 US/7 international sites). METHODS: Women (18-40 yrs) used the CVS for 21 days/cycle followed by having it out for 7 days. Women were not to remove the CVS for >2 hours during the 21 days of use. The primary efficacy outcome was the Pearl Index (PI) for women ≤35 years of age, excluding cycles with adjunctive contraception. Secondary outcomes included the PI for subgroups and intention-to-treat Kaplan-Meier life-table analyses. RESULTS: Of 2265 participants analyzed, 1303 (57.5%) completed. The primary PI was 2.98 (95% CI [2.13-4.06]). The PI was 2.10 (95% CI [1.37-3.06]) in women who followed use instructions versus 5.89 (95% CI [3.46-9.27]) for women who documented removals >2 hours (P=0.0024). Significantly higher PIs were also observed in subgroups by age (18-19 yrs vs ≥36yrs), parity (≥1 vs 0), race (Black vs white), ethnicity (Hispanic vs non-Hispanic), and site (non-Europe vs Europe), but not by BMI. Life-table analyses revealed the CVS is 97.3% effective in preventing pregnancy. Pregnancies did not increase across cycles. CONCLUSION: The SA/EE CVS is an effective 1-year, procedure-free contraceptive controlled by women that can help address an unmet worldwide contraceptive need. Counseling to ensure correct use is essential for optimizing efficacy.

Occult HBV infection may negatively impact on drug survival in patients with rheumatoid arthritis on treatment with a first biologic drug. An appraisal from the Biologic Apulian Registry (BIOPURE).

We performed a retrospective analysis to evaluate the survival on first line biologic drug of rheumatoid arthritis (RA) patients with potential occult HBV infection (pOBI). We analysed longitudinal data of 486 consecutive RA patients starting a first biological drug in a time frame from 1st January 2008 to 31st December 2014. Demographic and disease related characteristics were collected at baseline and at the last observation visit. Baseline serological markers of HBV infection and causes of treatment discontinuation were also recorded. Primary endpoint was the influence of pOBI on drug survival, estimated by Kaplan-Meier life table analysis. Estimates hazard ratios (HRs) of drug discontinuation, adjusted for disease characteristics, biological drug class and HBcAb status were computed by Cox-regression models. The retention rate was significantly lower in pOBI positive patients (58.2%) when compared to pOBI negative ones (67.8%) and this data was confirmed also when only discontinuation due to ineffectiveness was considered (pOBI positive 66.4% vs pOBI negative 75.3%, long rank 7.93, p=0.005). Cox regression models showed a significant association between HBcAb-neg (HR 0.58, 0.41-0.84), higher ESR-DAS28 at baseline (HR 1.07, 1.03-1.11) or RF/ACPA-neg (HR 1.46, 1.04-2.06) and drug discontinuation. Occult HBV infection seems to influence negatively the effectiveness of biological therapies in RA patients.

Validating the Newly Reported ASA Score

Purpose The ASA score (Age > 60 yo, serum sodium Methods We reviewed records of patients discharged on palliative inotropes who were not candidates for LVAD or heart transplant and calculated their ASA ‘point’ score. The effect of ASA score on survival was estimated and tested for statistical significance using a Cox proportional hazards regression model. In addition, Kaplan-Meier lifetable analysis was used to generate the figure and the log-rank p-value. Results A total of 72 patients from 2009 - 2017 met the inclusion criteria. (75% male, mean age 64, 75% white.) A point was assigned for each of the three components of the ASA score and each patient was scored from 0 to 3. As seen on the figure below, this score provides highly significant discrimination between patients with excellent survival at one year and those with progressively worse survival. (p=0.002) Conclusion The ASA score is a simple three component score that stratifies patients that are at low, medium and high risk for death on chronic inotropic therapy. Our analysis suggests that this score is a reliable way to assess mortality in patients receiving palliative inotropic therapy. However, further research is necessary to independently validate the score in a larger population.

Prognostic factors in endometrial cancer Stages III and IV: a single academic institution experience of 49 patients

Background: To evaluate the clinical and pathologic factors associated with survival in patients with advanced staged endometrial carcinoma. Matreials and Methods: Between 2005 and 2017 all patients with endometrial carcinoma type I were identified from tumor registry databases at this Academic hospital. The impact of clinical and pathologic risk factors on the survival of patients with endometrial carcinoma was evaluated using Kaplan-Meier life table analyses and log-rank tests. Results: Forty-nine patients with advanced endometrial cancer were collected. The median progression-free survival (PFS) for all patients was 42 months whereas the median overall survival (OS) was 69 months for all patients. Univariate analysis was extended to all prognostic factors for all stages showed as statistically significant positive cytology and cervical invasion, whereas for Stage III only cervical invasion. For Stage IIIA the prognostic factors statistically significant were cervical invasion and lymphovascular space invasion (LVSI). Furthermore, prognosis was worse in tumors belonging to Stage IV with positive cytology. Conclusion: Prognostic factors related to a lower survival rate in advanced stages of endometrial cancer are represented by cervical invasion, LVSI, and positive peritoneal cytology. These factors with respect to LVSI and positive peritoneal cytology should be included in FIGO 2009 surgical staging system because associated to a poor prognosis.

Extending endovascular aneurysm repair to more patients without better outcomes

ObjectiveThis study quantifies the survival and outcomes associated with endovascular aneurysm repair (EVAR) patients treated in two eras. We hypothesized that both end points will improve over time. MethodsPatients receiving EVAR between January 2003 and May 2017 contained within the Vascular Quality Initiative data set were examined. Those patients treated between January 2003 and December 2007 were included in the early era, and those treated between January 2012 and December 2015 were considered late era. Baseline demographics, technical variables, and outcomes were compared with appropriate statistical tests. Survival was estimated with Kaplan-Meier life-table analysis. Cox proportional hazards modeling analyzed the relationship between repair era and survival; the repair era's significance was further examined in matched cohorts generated by coarsened exact matching and propensity scoring. ResultsEarly era (n = 787) patients demonstrate decreased estimated survival in comparison to those treated in the late era (n = 20,066; log-rank, P < .001). Repair in the late era was not an independent predictor of survival in the Cox model (hazard ratio, 1.06; 95% confidence interval, 0.23-4.95; P = .94). Three different matching methods confirmed a nonsignificant contribution of treatment era to survival suggested by the initial Cox model (all P > .05). Total hospital stays were longer in the late era (3.1 vs 4.2 days; P < .001). Postoperative myocardial infarction and surgical site infections decreased in frequency in the late group, although postoperative vasopressor use became more frequent (all P < .05). Operations became 20% faster, required 27% less contrast material and 29% less crystalloid, and lost 30% less blood over time (all P < .05). ConclusionsAlthough EVAR volume increased significantly over time, post-EVAR outcomes of patients do not differ between the early era, 2003 to 2007, and the late era, 2012 to 2015. Aspects of surgical performance improved, but this did not translate into a measurable benefit to patients. Length of hospital stay unexpectedly increased over time.

Minimally Invasive Aortobiilliofemoral Endarterectomy for Aortoiliac Occlusive Disease Is a Compelling Alternative to Bypass.

Aortobifemoral bypass is a time-honored, durable surgery allowing restoration of lower extremity blood. However, the potential for significant complications exists, impacting mortality, morbidity, and quality of life. Minimally invasive aortobiiliofemoral endarterectomy offers an alternative to prosthetic bypass and its associated complications. Here, we present a case series using remote endarterectomy for aortoiliac occlusive disease. Nine patients with aortoiliac occlusive disease were treated at a single institution, by a single surgeon, with direct and remote endarterectomy combination. Standard femoral access approach was used. A limited longitudinal distal aorta arteriotomy into the right common iliac artery to the hypogastric bifurcation was made. Then, an open thromboendarterectomy was performed. Circumferential common femoral endarterectomies were performed bilaterally and the plaque transected, allowing manually controlled Vollmar ring passage proximally to the iliac bifurcation on the right and the aortic bifurcation on the left. Aortoiliac arteriotomy was closed, followed by the femoral arteriotomies. Morbidity, secondary interventions, recurrent stenosis (adjacent segment velocity ratios ≥2), ankle-brachial index (ABI), and patency rates were tracked postoperatively for 6 years. Kaplan-Meier life-table analysis was used to determine patency rates per the criteria of SVS and ISCS. The average age was 59.1 years (54-87 years), and 88% were male. Comorbidities included hypertension (75%), former/current smokers (100%), and prior PAD surgical intervention (38%). Revascularization of 100% was achieved, with average ABI improving from 0.42 preoperatively to 0.92 postoperatively (0.91 at 8-month follow-up). Six-year patency rate was 100% without reintervention. Incidence of myocardial infarction, stroke, death, amputation, intestinal ischemia, sexual dysfunction, and aneurysmal degeneration was zero after 6 years of follow-up. Minimally invasive aortobiiliofemoral endarterectomy is a viable alternative to aortobifemoral bypass for the treatment of aortoiliac occlusive disease, allowing reestablishment of normal anatomic anatomy while avoiding the use of prosthetic material. Patency rates in this series was 100% at 6 years, with minimal postoperative complications or morbidity.

360-degree suture trabeculotomy ab interno with phacoemulsification in open-angle glaucoma and coexisting cataract: a pilot study

ObjectiveWe performed a pilot trial to evaluate the 24-month safety and efficacy of 360-degree suture trabeculotomy ab interno with phacoemulsification used to treat mild to moderate open-angle glaucoma coexisting with...