Enhanced recovery after surgery at cesarean delivery to reduce postoperative length of stay: a randomized controlled trial.

OBJECTIVE: Our objective was to determine whether an enhanced recovery after surgery pathway at the time of cesarean birth would permit a reduction in postoperative length of stay and improve postoperative patient satisfaction compared to standard perioperative care. MATERIALS AND METHODS: Patients undergoing nonemergent cesarean delivery at ≥37 weeks of gestation were randomized to enhanced recovery after surgery or standard care. Enhanced recovery after surgery involved multiple evidence-based interventions bundled into 1 protocol. The primary outcome was discharge on postoperative day 2. Secondary outcome variables included pain medication requirements, breastfeeding rates, and various measures of patient satisfaction. RESULTS: From September 27, 2017, to May 2, 2018, a total of 58 women were randomized to enhanced recovery after surgery and 60 women to standard care. The groups were similar in medical comorbidities and in demographic and perioperative characteristics. Enhanced recovery after surgery was not associated with a significantly increased rate of postoperative day 2 discharges when compared with standard care (8.6% vs 3.3%, respectively; odds ratio, 2.74; 95% confidence interval, 0.51-14.70), but it was associated with a significantly reduced postoperative length of stay when compared with standard care, with a median length of stay of 73.5 hours (interquartile range, 71.08-76.62) vs 75.5 hours (interquartile range, 72.86-76.84) from surgery, difference in median length of stay (-1.92; 95% confidence interval, -3.80 to -0.29). Enhanced recovery after surgery was not associated with a reduction in postoperative narcotic use (117.16 ± 54.17 vs 119.38 ± 47.98 morphine milligram equivalents; mean difference, -2.22; 95% confidence interval, -20.86 to 16.42). More subjects randomized to the enhanced recovery after surgery protocol reported breastfeeding at discharge (67.2% vs 48.3%; P = .046). When patients were surveyed 6 weeks postpartum, those in the enhanced recovery after surgery group were more likely to feel that their expectations were met and that they had achieved their postoperative milestones earlier, and to report continued breastfeeding. CONCLUSION: Enhanced recovery after surgery at cesarean delivery was not associated with an increase in the number of women discharged on postoperative day 2, but that may have been related to factors other than patients' medical readiness for discharge. Evidence that enhanced recovery after surgery at cesarean delivery may have the potential to improve outcomes such as day of discharge is suggested by the observed reduction in overall postoperative length of stay, improved patient satisfaction, and an increase in breastfeeding rates. Even better results may accrue with more provider and patient experience with enhanced recovery after surgery.

Prevalence and Predictors of Deep Vein Thrombosis in Critically Ill Medical Patients Who Underwent Diagnostic Duplex Ultrasonography.

INTRODUCTION: Deep vein thrombosis (DVT) is a recognized but preventable cause of morbidity and mortality in the medical intensive care unit (MICU). We examined the prevalence and risk factors for DVT in MICU patients who underwent diagnostic venous duplex ultrasonography (DUS) and the potential effect on clinical outcomes. METHODS: This is a retrospective study examining prevalence of DVT in 678 consecutive patients admitted to a tertiary care level academic MICU from July 2014 to 2015. Patients who underwent diagnostic DUS were included. Potential conditions of interest were mechanical ventilation, hemodialysis, sepsis, Sequential Organ Failure Assessment (SOFA) scores, central venous catheters, prior DVT, and malignancy. Primary outcomes were pulmonary embolism, ICU length of stay, and mortality. Additionally, means of thromboprophylaxis was compared between the groups. Multivariable logistic regression analysis was utilized to determine predictors of DVT occurrence. RESULTS: Of the 678 patients, 243 (36%) patients underwent DUS to evaluate for DVT. The prevalence of DVT was 16% (38) among tested patients, and a prior history of DVT was associated with DVT prevalence (P < .01). Between cases and controls, there were no significant differences in central venous catheters, mechanical ventilation, hemodialysis, sepsis, SOFA scores, malignancy, and recent surgery. Patients receiving chemical prophylaxis had fewer DVTs compared to persons with no prophylaxis (14% vs 29%; P = .01) and persons with dual chemical and mechanical prophylaxis (P = 0.1). Fourteen percent of patients tested had documented DVT while on chemoprophylaxis. There were no significant differences in ICU length of stay (P = .35) or mortality (P = .34). CONCLUSIONS: Despite the appropriate use of universal thromboprophylaxis, critically ill nonsurgical patients still demonstrated high rates of DVT. A history of DVT was the sole predictor for development of proximal DVT on DUS testing. Dual chemical and mechanical prophylaxis does not appear to be superior to single-chemical prophylaxis in DVT prevention in this population.

Increased risk of stroke and mortality following new-onset atrial fibrillation during hospitalization.

AIMS: The outcome of patients who develop new-onset atrial fibrillation (AF) during hospitalization is unknown, and the management of this patient population is not specifically addressed by current guidelines. We investigated the incidence of death and inhospital stroke among a large cohort of hospitalized inpatients who developed new-onset AF. METHODS AND RESULTS: All patients ≥50 years of age admitted to a tertiary academic medical centre (20 April 2005 to 31 December 2011; n = 84 919) were studied. Demographic variables were compared among patients categorized as having new-onset, pre-existing, or no AF. A propensity-matched analysis was employed to compare outcomes by generalized estimating equations. Primary endpoints were all-cause 30-day and 1-year mortality and inhospital stroke. New-onset AF occurred in 1749 (2.1%) hospitalized patients. Among patients with new-onset AF, mortality at 30 days and 1 year was higher compared with patients without AF (at 30 days: OR 2.28, 95% CI 1.72-3.02, P < 0.0001; at 1 year: RR 1.53, 95% CI 1.36-1.73, P < 0.0001), and compared with patients with pre-existing AF at 30 days (OR 1.52, 95% CI 1.06-2.17, P = 0.02) -an effect that persisted as non-significant trend at 1 year (RR 1.14, 95% CI 0.98-1.34, P = 0.09). Risk of inhospital stroke was higher in patients with new-onset AF compared with patients without AF (OR 4.53, 95% CI 1.36-15.11, P = 0.02). Among patients with new-onset AF, the CHA2DS2-Vasc score correlated with incidence of inhospital stroke. CONCLUSION: New-onset AF among hospitalized inpatients is independently associated with an increased incidence of stroke and mortality.

Effect of Electronic Cigarette Use on the Urge-to-Cough Sensation.

INTRODUCTION: Electronic cigarettes (e-cigs) have attained common usage worldwide, yet knowledge of their physiological effects remains minimal. The aim of this study was to evaluate the effect of a single exposure to e-cig vapor on the urge-to-cough (UTC) threshold and C5. METHODS: Seventeen healthy nonsmokers underwent C5 measurement employing capsaicin cough challenge at baseline, 15 minutes, and 24 hours after e-cig exposure (30 puffs 30 seconds apart). The endpoint of cough challenge is C5, the concentration of capsaicin inducing five or more coughs. The UTC threshold (Cu) is defined as the lowest concentration of capsaicin inducing UTC without an associated motor cough. RESULTS: The Cu and C5 were significantly inhibited (Cu and C5 increased) 15 minutes after e-cig use. Mean log Cu rose from -0.035±0.08 (SEM) to 0.21±0.12 (P = .005). Mean log C5 increased from 0.60±0.11 to 0.92±0.16 (P = .001). By 24 hours after e-cig exposure, Cu and C5 had returned to baseline levels. CONCLUSIONS: A single session of e-cig use, approximating nicotine exposure of one tobacco cigarette, induces significant inhibition of the Cu, as well as C5. Previous studies implicate nicotine as the agent responsible for suppression of C5, and we hypothesize a similar role for nicotine in the suppression of the Cu. Given our observation of the effect of a single e-cig exposure, studies of the respiratory physiologic implications of repeated or chronic e-cig use are warranted. IMPLICATIONS: This is the first study to demonstrate that a single exposure to an e-cig significantly inhibits the Cu as measured by capsaicin cough challenge testing. These findings add to the growing body of evidence that e-cig vapor is not a physiologically benign substance, and support further investigation of the effects of repeated or chronic use of e-cigs on cough sensitivity and other respiratory parameters.

MEDULLARY THYROID CANCER THAT STAINS NEGATIVE FOR CA 19-9 HAS DECREASED METASTATIC POTENTIAL.

OBJECTIVE: Presently, no clinical tools are available to diagnose the metastatic potential of medullary thyroid cancer (MTC) at disease presentation. Surveillance with calcitonin (Ct) and carcinoembryonic antigen (CEA) is currently recommended for the observation and diagnosis of metastatic disease after initial treatment of MTC. Recently, carbohydrate antigen (CA)19-9 staining has been associated with aggressive forms of MTC and metastatic spread. This pilot study explored whether positive CA19-9 staining of MTC tissue is associated with its metastatic potential. METHODS: Sixteen cases of MTC were identified, and tissue specimens were immunostained for CA 19-9 and other MTC tumor markers. Clinical information about patients' MTC was collected through a retrospective chart review. RESULTS: Overall, 63% of the specimens stained positive for CA19-9. The median size of positively staining specimens was 2.6 cm (interquartile range [IQR] 1.2-3.2) compared to 0.7 cm (0.5-1.2) in negatively staining MTC specimens (P = .04). All specimens from patients diagnosed with stage IV MTC stained positive for CA19-9, compared to only 40% of cases that were classified as stages I to III (P = .03). Furthermore, 100% of the primary specimens that were documented to have metastatic spread stained positive for CA19-9. The sensitivity for ruling out stage IV MTC based on negative staining for CA 19-9 was 100%. CONCLUSION: Based on these results, we conclude that negative staining of MTC for CA19-9 may be associated with its decreased metastatic potential.

Novel yeast-based strategy unveils antagonist binding regions on the nuclear xenobiotic receptor PXR.

BACKGROUND: Ketoconazole binds to and antagonizes pregnane X receptor (PXR) activation. RESULTS: Yeast high throughput screens of PXR mutants define a unique region for ketoconazole binding. CONCLUSION: Ketoconazole genetically interacts with specific PXR surface residues. SIGNIFICANCE: A yeast-based genetic method to discover novel nuclear receptor interactions with ligands that associate with surface binding sites is suggested. The pregnane X receptor (PXR) is a master regulator of xenobiotic metabolism, and its activity is critical toward understanding the pathophysiology of several diseases, including inflammation, cancer, and steatosis. Previous studies have demonstrated that ketoconazole binds to ligand-activated PXR and antagonizes receptor control of gene expression. Structure-function as well as computational docking analysis suggested a putative binding region containing critical charge clamp residues Gln-272, and Phe-264 on the AF-2 surface of PXR. To define the antagonist binding surface(s) of PXR, we developed a novel assay to identify key amino acid residues on PXR based on a yeast two-hybrid screen that examined mutant forms of PXR. This screen identified multiple "gain-of-function" mutants that were "resistant" to the PXR antagonist effects of ketoconazole. We then compared our screen results identifying key PXR residues to those predicted by computational methods. Of 15 potential or putative binding residues based on docking, we identified three residues in the yeast screen that were then systematically verified to functionally interact with ketoconazole using mammalian assays. Among the residues confirmed by our study was Ser-208, which is on the opposite side of the protein from the AF-2 region critical for receptor regulation. The identification of new locations for antagonist binding on the surface or buried in PXR indicates novel aspects to the mechanism of receptor antagonism. These results significantly expand our understanding of antagonist binding sites on the surface of PXR and suggest new avenues to regulate this receptor for clinical applications.

A phase I-II study of the histone deacetylase inhibitor vorinostat plus sequential weekly paclitaxel and doxorubicin-cyclophosphamide in locally advanced breast cancer.

Histone deacetylases (HDACs) are a family of enzymes that regulate chromatin remodeling and gene transcription. Vorinostat is a panHDAC inhibitor that sensitizes breast cancer cells to taxanes and trastuzumab by suppressing HDAC6 and Hsp90 client proteins. Fifty-five patients with clinical stage IIA-IIIC breast cancer received 12 weekly doses of paclitaxel (80 mg/m(2)) plus vorinostat (200-300 mg PO BID) on days 1-3 of each paclitaxel dose plus trastuzumab (for Her2/neu positive disease only), followed by doxorubicin/cyclophosphamide (60/600 mg/m(2) every 2 weeks plus pegfilgrastim). The primary study endpoint was pathologic complete response (pCR). pCR occurred in 13 of 24 evaluable patients with Her2-positive disease (54, 95 % confidence intervals [CI] 35-72 %), which met the prespecified study endpoint. pCR occurred in 4 of 15 patients with triple negative disease (27, 95 % CI 11-52 %) and none of 12 patients with ER-positive, Her2/neu negative disease (0, 95 % CI 0-24 %), which did not meet the prespecified endpoint. ER-positive tumors exhibited lower Ki67 and higher Hsp70 expression, and HDAC6, Hsp70, p21, and p27 expression were not predictive of response. Vorinostat increased acetylation of Hsp90 and alpha tubulin, and reduced expression of Hsp90 client proteins and HDAC6 in the primary tumor. Combination of vorinostat with weekly paclitaxel plus trastuzumab followed by doxorubicin-cyclophosphamide is associated with a high pCR rate in locally advanced Her2/neu positive breast cancer. Consistent with cell line and xenograft data, vorinostat increased acetylation of Hsp90 and alpha tubulin, and decreased Hsp90 client protein and HDAC6 expression in human breast cancers in vivo.

Effectiveness of Biologic Agents Among Hispanic Patients With Metastatic Colorectal Cancer.

BACKGROUND: Randomized clinical trials have defined the survival advantage with the addition of biologic drugs to chemotherapy in patients with metastatic colorectal cancer (mCRC). Under representation of Hispanics contributes to poorly defined outcomes in this group. We aim to determine whether the real-world benefit of biologics extends to Hispanics using a comparative effectiveness research approach. METHODS: This retrospective cohort study included all treatment centers contributing to SEER registry with available claims in the SEER-Medicare linked database (2001-2011) and 2 hospitals (2004-2016) catering to minorities. Metastatic CRC patients were classified as receiving chemotherapy or biochemotherapy (CT plus biologics; if initiated within 3 months of chemotherapy). The primary outcome was overall survival (OS) among the Hispanic patients calculated from time of administration of first dose of chemotherapy to death or last follow-up. A weighted Cox regression model was used to assess differences in survival. RESULTS: We identified 182 Hispanic patients with mCRC from the Patient Entitlement and Diagnosis Summary (PEDSF) file (n = 101) and hospital database (n = 81). Overall, 52% were women and 72% received biologics. The median OS was 11.3 and 17.0 months in chemotherapy and biochemotherapy group, respectively. Biochemotherapy offered a survival benefit compared with chemotherapy alone, with an average hazard rate reduction of 39% (95% CI 6%-60%, p = .0236) using inverse probability of treatment weighting (IPTW) based analysis. CONCLUSION: In this cohort of Hispanic patients with mCRC, biochemotherapy was associated with longer survival. Clinicians may offer biochemotherapy therapy to all patients regardless of race/ethnicity to maximize clinical benefit.

Investigation of the urge-to-cough sensation in healthy volunteers.

BACKGROUND AND OBJECTIVE: Recently, there has been interest in the sensation of irritation that precedes the motor act of coughing, which has been termed the urge-to-cough (UTC). The aim of this study was to perform the largest evaluation to date of the UTC threshold (C(u)) in a healthy population. The specific aims were to investigate the relationship between C(u) and cough reflex sensitivity, to evaluate gender differences in the UTC and to assess the reproducibility of measurements of C(u). METHODS: Standard capsaicin cough challenge methodology was employed to measure cough reflex sensitivity in 100 healthy adult non-smokers (50 females) with the additional measurement of C(u). A subgroup of 40 subjects (20 males) underwent repeat cough challenges after 1 week to examine the reproducibility of the measurements. RESULTS: All 100 subjects demonstrated motor cough in response to capsaicin. Twenty-one subjects (10 females) did not show a discernible C(u), as the motor cough event preceded a UTC sensation unaccompanied by cough. Although cough reflex sensitivity, as measured by the concentration of capsaicin inducing five or more coughs (C(5)), was enhanced in women, there was no gender difference in C(u). Similar to standard cough reflex sensitivity measurements, the measurement of C(u) was highly reproducible. CONCLUSIONS: These results demonstrate that the UTC threshold can be effectively and reproducibly measured using a modification of standard cough challenge methodology. Given its clinical significance as a prevalent symptom, UTC, as measured by C(u), represents an additional relevant end point for studies investigating the effects of pharmacological and other interventions in cough and cough reflex sensitivity.

Comparative Effectiveness of Biologic Agents Among Black and White Medicare Patients in the US With Metastatic Colorectal Cancer.

Importance: Randomized clinical trials have defined the survival benefit provided by the addition of biologic drugs to chemotherapy in patients with metastatic colorectal cancer (mCRC). However, Black patients may be underrepresented in trial populations, and outcomes in this group remain poorly defined. Objective: To determine whether the real-world benefit of biologic drugs in Black patients is consistent with the real-world benefit of biologic drugs in White patients using a comparative effectiveness research approach. Design, Setting, and Participants: Population-based retrospective comparative effectiveness analysis of a cohort of patients aged 65 years or older with mCRC diagnosed between 2004 and 2011 who had received at least 1 dose of chemotherapy and had complete Medicare claims data using the Surveillance, Epidemiology, and End Result (SEER)-Medicare linked database. Data were analyzed from August 1, 2020, to March 31, 2021. Interventions: Patient data were classified according to whether patients received chemotherapy (oxaliplatin, irinotecan, and 5-fluorouracil or capecitabine) or biochemotherapy (bevacizumab, cetuximab, panitumumab, ramucirumab, or aflibercept, started within 3 months of chemotherapy). Main Outcomes and Measures: Overall survival (OS) defined as the time from starting chemotherapy to death or last follow-up. A weighted Cox regression model was used to assess differences in survival. Results: A total of 5617 patients with mCRC were identified in the SEER-Medicare linked database, and 4542 patients were included in the main analysis. Of the 5617 patients, 3969 (70.7%) received biologic agents at any point between 2004 and 2011; biologic agent therapy was started within 3 months of chemotherapy in 2894 patients (72.9%). Among 4542 patients with data on race and ethnicity, the median age was 72 years (IQR, 68-78 years), 2365 (52.0%) were female, 3445 (75.8%) had colon as the primary site, 552 (12.2%) were Black patients, and 3990 (87.8%) were White patients. There was no difference in the receipt of 1 (76.7% and 74.8%) vs 2 or more (23.3% and 25.2%: P = .92) lines of therapy, and in the receipt of biologic agents (63.6% vs 64.3% P = .33), among White patients and Black patients, respectively. Biochemotherapy was associated with a significant survival benefit compared with chemotherapy alone in the overall population (biochemotherapy median OS, 17.9 [95% CI, 17.3-18.7] months vs chemotherapy median OS, 8.3 [95% CI, 9.1-9.9] months; P < .001). The survival benefit was similar among White patients (17.8 vs 9 months; average hazard ratio, 0.59; 95% CI, 0.55-0.64; P < .001) and Black patients (18.6 vs 9.9; average hazard ratio, 0.58; 95% CI, 0.47-0.71; P < .001). Conclusions and Relevance: In this comparative effectiveness analysis of a cohort of Medicare recipients with mCRC, biochemotherapy was associated with an improvement in OS with a similar rate of reduction in mortality among Black and White patients. Clinicians may offer biochemotherapy therapy to all patients to maximize clinical benefit, factoring in clinical variables, but not their race.

Prediction Model Using Machine Learning for Mortality in Patients with Heart Failure.

Heart Failure (HF) is a major cause of morbidity and mortality in the US. With aging of the US population, the public health burden of HF is enormous. We aimed to develop an ensemble prediction model for 30-day mortality after discharge using machine learning. Using an electronic medical records (EMR) database, all patients with a non-elective HF admission over 10 years (January 2001 - December 2010) within the Montefiore Medical Center (MMC) health system, in the Bronx, New York, were included. We developed an ensemble model for 30-day mortality after discharge and employed discrimination, range of prediction, Brier index and explained variance as metrics in assessing model performance. A total of 7,516 patients were included. The discrimination achieved by the ensemble model was higher 0.83 (95% CI: 0.80 to 0.87) compared to the benchmark model 0.79 (95% CI: 0.75 to 0.84). The ensemble model also exhibited a better range of prediction as well as a favorable profile with respect to the other metrics employed. In conclusion, an ensemble machine learning approach exhibited an improvement in performance compared to the benchmark logistic model in predicting all-cause mortality among HF patients within 30-days of discharge. Machine learning is a promising alternative approach for risk profiling of HF patients, and it enhances individualized patient management.

Racial Diversity Among Histology of Renal Cell Carcinoma at an Urban Medical Center.

BACKGROUND: Non-Hispanic blacks (NHB) with renal cell carcinoma (RCC) are more likely to have papillary RCC (pRCC) than non-Hispanic whites (NHW). Data on histologic subtypes in RCC in Hispanics (H) are also sparse. Previous studies have shown that pRCC is more prevalent in NHB than in NHW, but they analyzed predominantly NHW populations. The Montefiore-Einstein Center for Cancer Care (MECC) serves a predominantly NHB and H population in the Bronx, NY. We investigated histologic subtype specific associations with established RCC risk factors in this population. PATIENTS AND METHODS: The MECC tumor registry was used to identify patients ≥ 18 years of age treated with partial or radical nephrectomy between January 2000 and December 2015. An institutional software program and individual chart review were used to obtain demographic data (including self-reported race, age, and sex), pathology data, and RCC risk factors (hypertension, diabetes, renal function, weight). Data were modeled by multinomial logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A total of 1010 RCC cases were identified. Of these, 232 (23.0%) occurred in NHW, 383 (37.9%) NHB, 181 (17.9%) H, and 214 (21.2%) other. A total of 530 cases (52.5%) were clear cell (ccRCC) histology, 257 (25.4%) pRCC, 100 (9.9%) chromophobe (cRCC), and 123 (12.2%) other. Individuals with pRCC compared to ccRCC were more likely to be NHB than NHW (OR, 4.41; 95% CI, 2.81-6.93) but were less likely to be female (OR, 0.50; 95% CI, 0.35-0.72). Individuals with pRCC were also less likely to be H than NHW (OR, 0.52; 95% CI, 0.27-0.99). Patients with cRCC were also more likely to be NHB than NHW (OR, 2.23; 95% CI, 1.06-4.67). CONCLUSION: In the MECC data set, histology of RCC varies by race, confirming earlier reports that non-ccRCC is more common in NHB than NHW. We also report that pRCC is less common in H than NHW.

Noninvasive monitoring of uterine electrical activity among patients with obesity: a new external monitoring device.

BACKGROUND: Tocodynamometry is a common, noninvasive tool used to measure contraction frequency; however, its utility is often limited in patients with obesity. An intrauterine pressure catheter provides a more accurate measurement of uterine contractions but requires ruptured membranes, limiting its utility during early latent labor. Electrical uterine myography has shown promise as a noninvasive contraction monitor with efficacy similar to that of the intrauterine pressure catheter; however, its efficacy has not been widely studied in the obese population. OBJECTIVE: This study aimed to validate the accuracy of electrical uterine myography by comparing it with tocodynamometry and intrauterine pressure catheters among laboring patients with obesity. STUDY DESIGN: This was a prospective observational study from February 2017 to April 2018 of patients with obesity, aged 18 years or older, who were admitted to the labor unit with viable singleton pregnancies and no contraindications for electromyography. Patients were monitored simultaneously with electrical myography and tocodynamometry or intrauterine catheter for more than 30 minutes. Two blinded obstetricians reviewed the tracings. The outcomes of interest were continuous and interpretable tracing, number of contractions, and timing and duration of contractions, interpreted as point estimates and associated 95% confidence intervals. RESULTS: A total of 110 patients were enrolled (65 tocodynamometry, 55 intrauterine catheter). Electrical myography was significantly more interpretable during a 30-minute tracing (P=.001) and detected 39% more contractions than tocodynamometry (P<.0001; 95% confidence interval, 23%-57%), whereas there was no difference in the interpretability of tracings or number of contractions between electrical myography and an intrauterine catheter (P=.16; 95% confidence interval, -0.19 to 1.19). Patients who underwent simultaneous monitoring preferred the electrical myography device over tocodynamometry. CONCLUSION: Electrical uterine myography is superior to tocodynamometry in the detection of intrapartum uterine contraction monitoring and comparable with internal contraction monitoring.

A multi-center prospective cohort study of benign breast disease and risk of subsequent breast cancer.

OBJECTIVE: We used a nested case-control design within a large, multi-center cohort of women who underwent a biopsy for benign breast disease (BBD) to assess the association of broad histologic groupings and specific histologic entities with risk of breast cancer. METHODS: Cases were all women who had a biopsy for BBD and who subsequently developed breast cancer; controls were individually matched to cases and were women with a biopsy for BBD who did not develop breast cancer in the same follow-up interval as that for the cases. After exclusions, 1,239 records (615 cases and 624 controls) were available for analysis. We used conditional logistic regression to estimate odds ratios and 95% confidence intervals (CIs). RESULTS: Relative to non-proliferative BBD/normal pathology, the multivariable-adjusted odds ratio for proliferative lesions without atypia was 1.45 (95% CI 1.10-1.90), and that for atypical hyperplasia was 5.27 (95% CI 2.29-12.15). The presence of multiple foci of columnar cell hyperplasia and of complex fibroadenoma without atypia was associated with a non-significantly increased risk of breast cancer, whereas sclerosing adenosis, radial scar, and papilloma showed no association with risk. CONCLUSION: Our results indicate that, compared to women with normal pathology/non-proliferative disease, women with proliferative disease without atypia have a modestly increased risk of breast cancer, whereas women with atypical hyperplasia have a substantially increased risk.

Phase II trial of tipifarnib plus neoadjuvant doxorubicin-cyclophosphamide in patients with clinical stage IIB-IIIC breast cancer.

PURPOSE: Tipifarnib is a farnesyl transferase (FTase) inhibitor that has activity in metastatic breast cancer and enhances the efficacy of cytotoxic agents in preclinical models. We evaluated the biological effects of tipifarnib in primary breast cancers in vivo, whether adding tipifarnib to preoperative chemotherapy increased the pathologic complete response rate (pCR) at surgery, and determined whether biomarkers predictive of pCR could be identified. EXPERIMENTAL DESIGN: Forty-four patients with stage IIB-IIIC breast cancer received up to four cycles of neoadjuvant doxorubicin-cyclophosphamide (AC) every 2 weeks plus tipifarnib and filgrastim followed by surgery. Enzymatic assays measuring FTase activity and Western blotting for phospho (p)-signal transducer and activator of transcription 3 (STAT3), phospho-extracellular signal-regulated kinase, p-AKT, and p27 were done in 11 patients who agreed to optional tissue biopsies before therapy and 2 hours after the final dose of tipifarnib during the first cycle, and predictive biomarkers were evaluated by immunohistochemistry in 33 patients. The trial was powered to detect an improvement in breast pCR rate of 10% or less expected for AC alone to 25% for AC-tipifarnib (alpha = 0.05, beta = 0.10). RESULTS: Eleven patients had a breast pCR (25%; 95% confidence interval, 13-40%). FTase enzyme activity decreased in all patients (median, 91%; range, 24-100%) and p-STAT3 expression decreased in 7 of 9 (77%) patients. Low tumor Ki-67 expression (below the median of 60%) at baseline was significantly associated with resistance to therapy (P = 0.01). CONCLUSION: Tipifarnib inhibits FTase activity in human breast tumors in vivo, is associated with down-regulation of p-STAT3, and enhances the breast pCR rate, thus meriting further evaluation.

Associations between immediate postpartum long-acting reversible contraception and short interpregnancy intervals.

OBJECTIVE: We aimed to evaluate the rates of short interpregnancy interval pregnancies and deliveries among women who receive immediate postpartum LARC. STUDY DESIGN: We conducted a retrospective cohort study of all women who delivered at Montefiore Medical Center between January 2015 and June 2016 (N = 9561). In this cohort, we identified all repeat deliveries and pregnancies within 18 months of the initial delivery. Using logistic regression models, we compared rates of short interpregnancy interval delivery and pregnancy among recipients of an immediate postpartum IUD, immediate postpartum implant, and no immediate postpartum LARC, adjusting for covariates including patient age, mode of delivery, socioeconomic status, and race. RESULTS: In our cohort, 12.9% of patients received immediate postpartum LARC. The rates of short interpregnancy interval delivery were 3.3% (N = 259/7833) among patients who did not receive immediate postpartum LARC, 1% (N = 6/595) among immediate postpartum IUD recipients, and 0.4% (N = 2/562) among immediate postpartum implant recipients. The rates of short interpregnancy interval pregnancy were 13.8% (N = 1082/7833) among patients who did not receive immediate postpartum LARC, 7.4% (N = 44/595) among immediate postpartum IUD recipients, and 5.2% (N = 29/562) among immediate postpartum implant recipients. Both recipients of immediate postpartum IUDs and immediate postpartum implants had lower rates of short interpregnancy interval delivery and pregnancy compared to patients who did not receive immediate postpartum LARC. CONCLUSIONS: This study confirms that women who received immediate postpartum IUDs and implants have lower rates of short interpregnancy interval pregnancies. IMPLICATIONS: Making immediate postpartum LARC widely available is a promising public health approach to help women achieve a longer interpregnancy interval.

The impact of menstrual hygiene management on adolescent health: The effect of Go! pads on rate of urinary tract infection in adolescent females in Kibogora, Rwanda.

OBJECTIVE: To determine the rates of urinary tract infection (UTI) in adolescent users of menstrual pads versus non-users in a rural area of Rwanda. METHODS: An interventional prospective cohort study was conducted at four secondary schools in the Western Province of Rwanda from May 12, 2017 to October 20, 2017. Inclusion criteria were female students aged 18-24 who were menstruating and volunteered to participate in the study. In total, 240 adolescent participants were assigned to two cohorts; 120 received menstrual pads for 6 months and the other 120 did not use pads. Baseline symptoms and urine cultures were obtained. Symptoms and methods of menstrual hygiene management were assessed and urine cultures were obtained every 2 months. The primary outcome was the presence of UTI diagnosed by positive urine culture. Secondary outcomes were symptoms of UTI, vulvovaginal symptoms, sexual activity, dyspareunia, and self-reported sexually transmitted infection. Generalized estimating equations with nesting were used to assess associations of pad use with study outcomes. RESULTS: A total of 209 participants completed the study. There was no difference in rates of positive urine culture. A decreased odds of vulvovaginal symptoms was found in self-reported "always" versus "never" pad users (odds ratio [OR] 0.64, 95% confidence interval [CI] 0.43-0.96; P=0.031). CONCLUSIONS: Despite not finding any difference in rates of UTI, the present study showed a decreased rate of vulvovaginal symptoms in users of menstrual pads. Further research investigating rates of genital infections in this population is thus necessary.

The Neutrophil-to-Lymphocyte Ratio is a Prognostic Biomarker in An Ethnically Diverse Patient Population with Advanced Pancreatic Cancer.

PURPOSE: The neutrophil-to-lymphocyte ratio (NLR) is associated with decreased overall survival in patients with pancreatic adenocarcinoma (PAC) in studies including few minority patients. We investigated the association between NLR and survival in patients with advanced PAC in an ethnically diverse population. METHODS: We retrospectively evaluated 226 patients with advanced PAC treated at Montefiore Medical Center between 2006 and 2015. Adjusted Cox proportion hazard regression models were utilized to derive effect estimates for survival duration. RESULTS: Patients with a NLR ≤ 5 (126 patients, median age 66 years) were more likely to be non-Hispanic Black (30.8% vs. 20%), while patients with a NLR > 5 (70 patients, median age 66 years) were more likely to be non-Hispanic White (21.4% vs. 12.2%) or Hispanic (44.3% vs. 34%). A NLR > 5 compared with a NLR ≤ 5 was significantly associated with a worse overall survival when adjusted for a priori and exploratory variables from the univariate analysis (median survival 7.4 vs. 12 months, HR 1.650, 95% CI 1.139, 2.390). CONCLUSIONS: In an ethnically diverse population, elevated NLR is an independent marker of poor prognosis and a potentially valuable factor in driving therapeutic decisions and defining prognosis for patients in the locally advanced or metastatic for PAC setting, meriting investigation in prospective clinical trials.

A randomized controlled trial of calcium plus vitamin D supplementation and risk of benign proliferative breast disease.

Experimental evidence provides strong support for anti-carcinogenic effects of calcium and vitamin D with respect to breast cancer. Observational epidemiologic data also provide some support for inverse associations with risk. We tested the effect of calcium plus vitamin D supplementation on risk of benign proliferative breast disease, a condition which is associated with increased risk of breast cancer. We used the Women's Health Initiative randomized controlled trial. The 36,282 participants were randomized either to 500 mg of elemental calcium as calcium carbonate plus 200 IU of vitamin D(3) (GlaxoSmithKline) twice daily (n = 18,176) or to placebo (n = 18,106). Regular mammograms and clinical breast exams were performed. We identified women who had had a biopsy for benign breast disease and subjected histologic sections from the biopsies to standardized review. After an average follow-up period of 6.8 years, 915 incident cases of benign proliferative breast disease had been ascertained, with 450 in the intervention group and 465 in the placebo group. Calcium plus vitamin D supplementation was not associated with altered risk of benign proliferative breast disease overall (hazard ratio = 0.99, 95% confidence interval = 0.86-1.13), or by histologic subtype. Risk varied significantly by levels of age at baseline, but not by levels of other variables. Daily use of 1,000 mg of elemental calcium as calcium carbonate plus 400 IU of vitamin D(3) for almost 7 years by postmenopausal women did not alter the overall risk of benign proliferative breast disease.