Phase Ib study of HSP90 inhibitor, onalespib (AT13387), in combination with paclitaxel in patients with advanced triple-negative breast cancer.

Background: Heat shock protein 90 (HSP90) is a molecular chaperone required for stabilization of client proteins over-activated in triple-negative breast cancer (TNBC). Over-expression of HSP90 client proteins has been implicated in paclitaxel resistance. Onalespib (AT13387) is a potent inhibitor of HSP90 that could improve paclitaxel efficacy when administered in combination. Design: This phase Ib trial administered onalespib with paclitaxel in patients with advanced TNBC to assess safety and establish a recommended phase II dose (RP2D). Objectives: The primary objectives were determining the dose-limiting toxicities and maximum tolerated dose of combination therapy. Secondary objectives included pharmacokinetic (PK) analysis and determination of overall response rate (ORR), duration of response (DOR), and progression-free survival (PFS). Methods: Patients with advanced TNBC were treated with standard dose intravenous paclitaxel in combination with intravenous onalespib at doses ranging from 120 to 260 mg/m2 administered on days 1, 8, and 15 of a 28-day cycle using a standard 3 + 3 design. A total of 15 patients were enrolled to dose expansion cohort at RP2D to confirm safety profile. Results: Thirty-one patients were enrolled in the study, of which over 90% had received prior taxane therapy. Paclitaxel was given for metastatic disease in 23% of patients. Adverse events (AEs) included anemia (grade 3: 20%), lymphopenia (grade 3: 17%), and neutropenia (grade 3: 33%, grade 4: 4%). The most frequent grade ⩾3 non-hematologic AE was diarrhea (7%). The established RP2D was 260 mg/m2 onalespib when given with paclitaxel at 80 mg/m2. PK analysis revealed a modest drug interaction profile for onalespib in the combination regimen. ORR was 20%. Three patients achieved complete responses, all of whom had received prior taxane therapy. Median DOR was 5.6 months; median PFS was 2.9 months. Conclusion: Combination treatment with onalespib and paclitaxel had an acceptable toxicity profile and RP2D was determined to be 260 mg/m2 of onalespib. Combination therapy showed antitumor activity in patients with advanced TNBC. Trial registration: Onalespib and paclitaxel in treating patients with advanced TNBC https://clinicaltrials.gov/ct2/show/NCT02474173.

Phase 1b study of HSP90 inhibitor called onalespib in combination with paclitaxel in patients with advanced triple-negative breast cancer This Phase 1b study demonstrated that treatment with a combination of onalespib and paclitaxel was reasonably well tolerated by most patients. Onalespib at 260 mg/m² given intravenously on days 1, 8 and 15 on 28-day cycles in combination with standard dose and schedule of paclitaxel was established as the recommended phase 2 dose for further clinical development. Despite minor drug-drug interactions between these 2 agents, onalespib did not alter paclitaxel exposure and paclitaxel did not affect exposure to onalespib. While onalespib with paclitaxel combination therapy did not yield durable objective responses or prolonged progression-free survival, there were several patients with long-lasting benefit from this combination including patients who previously experienced progression on taxane therapy.

Establishment of baseline urinary antimicrobial peptide levels by age: a prospective observational study.

BACKGROUND: Antimicrobial peptides (AMPs) are key effectors of urinary tract innate immunity. Identifying differences in urinary AMP levels between younger and older adults is important in understanding older adults' susceptibility and response to urinary tract infections (UTI) and AMP use as diagnostic biomarkers. We hypothesized that uninfected older adults have higher urinary human neutrophil peptides 1-3 (HNP 1-3), human alpha-defensin-5 (HD-5), and human beta-defensin-2 (hBD-2), but lower urinary cathelicidin (LL-37) than younger adults. METHODS: We conducted a cross-sectional study of patients age ≥18 years completing a family medicine clinic non-acute visit. Enzyme-linked immunosorbent assays (ELISA) were performed for AMPs. We identified associations between age and AMPs using unadjusted and multivariable linear regression models. RESULTS: Of the 308 subjects, 144 (46.8%) were ≥65 years of age. Comparing age ≥65 versus <65 years, there were no significant differences in HNP 1-3 (p=0.371), HD5 (p=0.834) or LL-37 (p=0.348) levels. Values for hBD-2 were lower in older adults versus younger (p <0.001). In multivariable analyses, older males and females had significantly lower hBD-2 levels (p<0.001 and p=0.004). Models also showed urine leukocyte esterase was associated with increased levels of HNP 1-3 and HD5; hematuria with increased hBD-2; and urine cultures with contamination with increased HNP 1-3 and hBD-2. CONCLUSIONS: Baseline urinary HNP 1-3, HD5, and LL-37 did not vary with age. Older adults had lower baseline hBD-2. This finding has implications for the potential use of urinary AMPs as diagnostic markers and will facilitate further investigation into the role of innate immunity in UTI susceptibility in older adults.

Emergency department patient and physician survey accuracy compared to chart abstraction in patients with acute respiratory illness.

BACKGROUND: High-quality research studies in older adults are needed. Unfortunately, the accuracy of chart review data in older adult patients has been called into question by previous studies. Little is known on this topic in patients with suspected pneumonia, a disease with 500,000 annual older adult U.S. emergency department (ED) visits that presents a diagnostic challenge to ED physicians. The study objective was to compare direct interview and chart abstraction as data sources. METHODS: We present a preplanned secondary analysis of a prospective, observational cohort of ED patients ≥65 years of age with suspected pneumonia in two Midwest EDs. We describe the agreement between chart review and a criterion standard of prospective direct patient survey (symptoms) or direct physician survey (examination findings). Data were collected by chart review and from the patient and treating physician by survey. RESULTS: The larger study enrolled 135 older adults; 134 with complete symptom data and 129 with complete examination data were included in this analysis. Pneumonia symptoms (confusion, malaise, rapid breathing, any cough, new/worse cough, any sputum production, change to sputum) had agreement between patient/legally authorized representative survey and chart review ranging from 47.8% (malaise) to 80.6% (confusion). All examination findings (rales, rhonchi, wheeze) had percent agreement between physician survey and chart review of ≥80%. However, all kappas except wheezing were less than 0.60, indicating weak agreement. CONCLUSIONS: Both patient symptoms and examination findings demonstrated discrepancies between chart review and direct survey with larger discrepancies in symptoms reported. Researchers should consider these potential discrepancies during study design and data interpretation.

Risk factors influencing death prior to discharge in 302 dogs undergoing unilateral adrenalectomy for treatment of primary adrenal gland tumours.

Adrenalectomies for canine adrenal tumours are associated with peri-operative morbidity and mortality. Objectives of this study included assessing the prognostic value of tumour- or surgery-related variables in predicting peri-operative mortality and overall survival in dogs undergoing adrenalectomies for primary adrenal tumours as well as pre-treatment with phenoxybenzamine on survival to discharge with pheochromocytomas specifically. A multi-institutional retrospective cohort study was performed across nine institutions. Electronic medical record searches identified 302 dogs which met the inclusion criteria. Data collected included dog-related, tumour-related, treatment-related, surgery-related, and outcome variables. Univariate and multivariable logistic regression and cox proportional hazards models were used to identify variables associated with death prior to discharge and tumour-related survival. Overall, 87% of dogs survived to discharge with a tumour-related survival time of 3.96 years. Post-operative complications were reported in 25%. Increased surgical time (p = 0.002) and pre-surgical medical treatment other than phenoxybenzamine (p = 0.024) were significantly associated with increased peri-operative mortality while ureteronephrectomy (p = 0.021), post-operative pancreatitis (p = 0.025), and post-operative aspiration pneumonia (p < 0.001) were significantly associated with decreased overall survival. Phenoxybenzamine pretreatment had no effect on peri-operative mortality. Thirty-seven of 45 (82%) dogs with pheochromocytomas not pretreated survived to discharge, and 50 of 59 (85%) dogs with pheochromocytomas pretreated with phenoxybenzamine survived to discharge (p = 0.730). This study provides information on risk factors for death prior to discharge and tumour-related survival that may help guide clinical management and owner expectations. In addition, the study findings challenge the previously reported benefit of phenoxybenzamine for pretreatment of dogs undergoing adrenalectomies for pheochromocytomas.

Missing Components of Receptor Status Among Women With Invasive Breast Cancer.

Importance: There are well-known differences in patient outcomes and effective therapeutic options across subtypes of breast cancer (BC), defined by the status of estrogen receptor, progesterone receptor, and erb-B2 receptor tyrosine kinase 2 (ERBB2 [formerly HER2]) expression, making testing for these receptors part of the routine workup for all patients with a diagnosis of invasive BC. Despite its importance, this information is missing in some BC cases. Objective: To identify female patients with BC without record of testing for estrogen receptor, progesterone receptor, or ERBB2 status, defined as missing components of receptor status (MCRS). Design, Setting, and Participants: This cross-sectional study used data from National Cancer Institute's Surveillance, Epidemiology and End Results Program of 18 population-based registries from women with a diagnosis of invasive BC (excluding death certificate-only and autopsy cases) from January 2012 to December 2016. The final analyses were completed in February 2022. Main Outcome and Measure: The primary outcome was MCRS. Those with MCRS were summarized by age, race, stage at diagnosis, reporting source, primary payer, and geography. Multivariable logistic regression was used to estimate adjusted odds ratios (aORs) for MCRS. Results: Overall, 321 913 patients with invasive BC were included (1928 [1%] American Indian or Alaska Native, 28 173 [9%] Asian or Pacific Islander, 36 357 [11%] Black, and 252 447 [78%] White individuals); of these, 15 250 (4.7%) had MCRS. The multivariable model showed that the odds of MCRS were higher in women 80 years or older compared with those younger than 49 years (aOR, 1.75; 95% CI, 1.65-1.88), Black compared with White women (aOR, 1.09; 95% CI, 1.00-1.16), and those with distant stage or unknown/unstaged cancer at diagnosis compared with a local stage at diagnosis (aOR, 3.33; 95% CI, 3.17-3.50; and aOR, 19.39; 95% CI, 18.15-20.72; respectively). With hospital inpatient/outpatient or clinic as the reference group, cases reported by laboratory only, nursing/convalescent home/hospice, and a physician's office were more likely to have MCRS (aOR, 1.42; 95% CI; 1.28-1.60; aOR, 9.37; 95% CI, 6.03-14.53; and aOR, 2.32; 95% CI, 2.06-2.62; respectively). Adjusted odds of MCRS were higher for the categories of insured/no specifics and insurance status unknown compared with those who were insured. The adjusted odds of MCRS were higher in rural compared with urban areas (aOR, 1.08; 95% CI, 1.03-1.15). Conclusions and Relevance: The results of this cross-sectional study of women with a diagnosis of invasive BC suggest that despite a standard of care recommended by all expert guidelines, there needs to be greater focus on hormone receptor and ERBB2 testing in all women with invasive BC. The results of this study may help clinicians, public health practitioners, and policymakers target affected populations to minimize or eliminate this critical health disparity and help save more lives.

Kinesiophobia Is Associated With Poor Function and Modifiable Through Interventions in People With Patellofemoral Pain: A Systematic Review With Individual Participant Data Correlation Meta-Analysis.

OBJECTIVE: The aim of this systematic review and correlation meta-analysis was to identify factors associated with kinesiophobia in individuals with patellofemoral pain (PFP) and to identify interventions that may reduce kinesiophobia in individuals with PFP. METHODS: Seven databases were searched for articles including clinical factors associated with kinesiophobia or interventions that may reduce kinesiophobia in individuals with PFP. Two reviewers screened articles for inclusion, assessed risk of bias and quality, and extracted data from each study. A mixed-effects model was used to calculate correlations of function and pain with kinesiophobia using individual participant data. Meta-analyses were performed on interventional articles; Grading of Recommendations, Assessment, Development, and Evaluation was used to evaluate certainty of evidence. Results were reported narratively when pooling was not possible. RESULTS: Forty-one articles involving 2712 individuals were included. Correlation meta-analyses using individual participant data indicated a moderate association between self-reported function and kinesiophobia (n = 499; r = -0.440) and a weak association between pain and kinesiophobia (n = 644; r = 0.162). Low-certainty evidence from 2 articles indicated that passive treatment techniques were more effective than minimal intervention in reducing kinesiophobia (standardized mean difference = 1.11; 95% CI = 0.72 to 1.49). Very low-certainty evidence from 5 articles indicated that interventions to target kinesiophobia (psychobehavioral interventions, education, and self-managed exercise) were better in reducing kinesiophobia than physical therapist treatment approaches not specifically targeting kinesiophobia (standardized mean difference = 1.64; 95% CI = 0.14 to 3.15). CONCLUSION: Higher levels of kinesiophobia were moderately associated with poorer function and weakly associated with higher pain in individuals with PFP. Taping and bracing may reduce kinesiophobia immediately after use, and specific kinesiophobia-targeted interventions may reduce kinesiophobia following the full intervention; however, the certainty of evidence is very low. IMPACT: Assessment of kinesiophobia in clinical practice is recommended, on the basis of the relationships identified between kinesiophobia and other important factors that predict outcomes in individuals with PFP.

Factors Related to Human Papillomavirus Positivity among Oral Cavity and Pharynx Cancers from Surveillance, Epidemiology and End Results (SEER) Program Data.

BACKGROUND: As human papillomavirus positive (HPV+) oral cavity and pharynx cancer (OCPC) incidence increases significantly, our objective was to determine whether selected sociodemographic and clinical factors were associated with HPV+ OCPCs overall and by oropharyngeal and non-oropharyngeal sites. METHODS: Surveillance, Epidemiology and End Results (SEER) Program data were used in this study. Specifically, univariate and logistic regression models were used to examine the relationships between HPV+ and HPV- OCPC cases and age, sex, race, ethnicity, marital status, factors of neighborhood socioeconomic status (i.e., nSES/Yost index) and rurality/urbanity, first malignancy status, histology, reporting source, stage at diagnosis, and OCPC anatomic site. The same approach was used to identify risk factors for HPV positivity for oropharyngeal and non-oropharyngeal OCPCs separately. RESULTS: In all OCPCs, cases that were male, <80 years old, lived in the four highest nSES categories, diagnosed with a non-"gum and other mouth" OCPC (ref = hypopharynx), not locally staged at diagnosis, and a first malignancy had higher odds of being HPV+. Cases that were American Indian/Alaska Native and Asian or Pacific Islander (ref = White), Spanish-Hispanic-Latino ethnicity, non-married/partnered, and not reported by a hospital/clinic had lower odds of being HPV+. Associations were maintained in oropharyngeal OCPCs and only age and race remained significant for non-oropharyngeal OCPCs. CONCLUSIONS: Sociodemographic and clinical differences in HPV+ and HPV- OCPC, overall and for (non)oropharyngeal, cases exist. IMPACT: Identification of OCPC and (non)oropharyngeal risk factors for HPV positivity may assist in discovering high-risk groups that should receive enhanced public health efforts to reduce the U.S. OCPC burden.

Long-Term Follow-Up of Fractional CO2 Laser Therapy for Genitourinary Syndrome of Menopause in Breast Cancer Survivors.

(1) Background: The objective of this study was to determine the long-term efficacy of fractional CO2 laser therapy in breast cancer survivors. (2) Methods: This was a single-arm study of breast cancer survivors. Participants received three treatments of fractional CO2 laser therapy and returned for a 4 week follow-up. Participants were contacted for follow-up at annual intervals. The Vaginal Assessment Scale (VAS), the Female Sexual Function Index (FSFI), the Female Sexual Distress Scare Revised (FSDS-R), the Urinary Distress Inventory (UDI), and adverse events were collected and reported for the two-year follow-up. The changes in scores were compared between the four-week and two-year and the one-year and two-year follow-ups using paired t-tests. (3) Results: In total, 67 BC survivors were enrolled, 59 completed treatments and the four week follow-up, 39 participated in the one-year follow-up, and 33 participated in the two-year follow-up. After initial improvement in the VAS from baseline to the four week follow-up, there was no statistically significant difference in the VAS score (mean Δ 0.23; 95% CI [-0.05, 0.51], p = 0.150) between the four week follow-up and the two-year follow-up. At the two-year follow-up, the FSFI and FSDS-R scores remained improved from baseline and there was no statistically significant change in the FSFI score (mean Δ -0.83; 95% CI [-3.07, 2.38] p = 0.794) or the FSDS-R score (mean Δ -2.85; 95% CI [-1.88, 7.59] p = 0.227) from the one to two-year follow-up. The UDI scores approached baseline at the two-year follow-up; however, the change between the one- and two-year follow-ups was not statistically significant (mean Δ 4.76; 95% CI [-1.89, 11.41], p = 0.15). (4) Conclusions: Breast cancer survivors treated with fractional CO2 laser therapy have sustained improvement in sexual function two years after treatment completion, suggesting potential long-term benefit.

An implementation science approach to geriatric screening in an emergency department.

BACKGROUND: The Geriatric Emergency Department (ED) Guidelines recommend screening older adults during their ED visit for delirium, fall risk/safe mobility, and home safety needs. We used the Consolidated Framework for Implementation Research (CFIR) and the Expert Recommendations for Implementation Change (ERIC) tool for preimplementation planning. METHODS: The cross-sectional survey was conducted among ED nurses at an academic medical center. The survey was adapted from the CFIR Interview Guide Tool and consisted of 21 Likert scale questions based on four CFIR domains. Potential barriers identified by the survey were mapped to identify recommended implementation strategies using ERIC. RESULTS: Forty-six of 160 potential participants (29%) responded. Intervention Characteristics: Nurses felt geriatric screening should be standard practice for all EDs (76.1% agreed some/very much) and that there was good evidence (67.4% agreed some/very much). Outer setting: The national and regional practices such as the existence of guidelines or similar practices in other hospitals were unknown to many (20.0%). Nurses did agree some/very much (64.4%) that the intervention was good for the hospital/health system. Inner Setting: 67.4% felt more staff or infrastructure and 63.0% felt more equipment were needed for the intervention. When asked to pick from a list of potential barriers, the most commonly chosen were motivational (I often do not remember (n = 27, 58.7%) and It is not a priority (n = 14, 30.4%)). The identified barriers were mapped using the ERIC tool to rate potential implementation strategies. Strategies to target culture change were identifying champions, improve adaptability, facilitate the nurses performing the intervention, and increase demand for the intervention. CONCLUSION: CFIR domains and ERIC tools are applicable to an ED intervention for older adults. This preimplementation process could be replicated in other EDs considering implementing geriatric screening.

Emergency department disposition of non-neutropenic febrile patients with cancer.

OBJECTIVES: National data reveal that 60% of the 4.5 million annual emergency department (ED) visits by patients with cancer result in admission. Many of these visits are due to a febrile illness. Current literature provides limited guidance on how to treat non-neutropenic febrile ED patients. This study characterizes clinical outcomes of non-neutropenic febrile patients with cancer presenting to an academic, Comprehensive Cancer Center affiliated ED. METHODS: Retrospective chart review of 101 randomly selected adult patients with active cancer presenting with a chief complaint of fever or a documented fever in the ED and an absolute neutrophil count above 1000 between October 2015 and September 2016. Descriptive statistics were calculated. RESULTS: The primary malignancies represented were hematologic (24%), gastrointestinal (13%), head and neck (13%), and genitourinary (8%). Sixty-two percent were on chemotherapy, 15% on radiation therapy, and 12% were on targeted therapy. Severe illness outcomes occurred in 39% and 83% were admitted with a median length of stay of 4 days. Among admitted patients, 24% experienced a length of stay ≤2 days. A return visit to the ED or an in-system hospitalization within 7 days of the index visit occurred in 10% and death occurred within 7 days of the index visit in 4%. CONCLUSION: A majority of patients presenting to the ED with non-neutropenic fever are admitted (83%), of whom nearly a quarter experience a length of stay of ≤2 days with infrequent serious illness outcomes. Future efforts should focus on the development of risk stratification tools in this population to avoid potentially unnecessary hospitalizations.

Assessment of Leptomeningeal Carcinomatosis Diagnosis, Management and Outcomes in Patients with Solid Tumors Over a Decade of Experience.

OBJECTIVE: Leptomeningeal carcinomatosis (LMC), a common complication of advanced malignancies, is associated with high morbidity and mortality, yet diagnosis and treatment decisions remain challenging. This study describes the diagnostic and treatment modalities for LMC and identifies factors associated with overall survival (OS). MATERIALS AND METHODS: We performed a single-institution retrospective study (registration #: OSU2016C0053) of 153 patients diagnosed with LMC treated at The Ohio State University, Comprehensive Cancer Center, (OSUCCC)-James between January 1, 2010 and December 31, 2015. RESULTS: Median age at diagnosis was 55.7 years, and 61% had Eastern Cooperative Oncology Group baseline performance status ≤1. Most common primary tumors were breast (43%), lung (26%), and cutaneous melanoma (10%). At presentation, most patients were stage III-IV (71%) with higher grade tumors (grade III: 46%). Metastases to bone (36%), brain (33%), and lung (12%) were the most common sites with a median of 0.5 years (range, 0-14.9 years) between the diagnosis of first metastasis and of LMC. 153 (100%) patients had MRI evidence of LMC. Of the 67 (44%) who underwent lumbar puncture (LP), 33 (22%) had positive cerebrospinal fluid (CSF) cytology. Most patients received radiotherapy for LMC (60%) and chemotherapy (93%) for either the primary disease or LMC. 28 patients received intrathecal chemotherapy, 22 of whom had a primary diagnosis of breast cancer. 98% died with median OS of all patients was 1.9 months (95% CI: 1.3-2.5 months). CONCLUSION: Despite improved treatments and targeted therapies, outcomes of LMC remain extremely poor. Positive CSF cytology was associated with lower OS in patients who had cytology assessed and specifically in patients with breast cancer. CSF cytology serves as an important indicator for prognosis and helps aid in developing individualized therapeutic strategies for patients with LMC.

A Cardiac Rehabilitation Program for Breast Cancer Survivors: A Feasibility Study.

PURPOSE: The purpose of this study was to determine the feasibility and preliminary efficacy of a cardiac rehabilitation (CR) intervention in the breast cancer population. METHODS: This single-arm feasibility study evaluated a 14-week CR intervention program in breast cancer survivors. Feasibility was defined as completion of at least 30/36 sessions of the program without serious adverse events (SAE) in 80% of patients. Secondary endpoints included the change in VO2 max, cardiovascular disease (CVD) risk factors, Duke Activity Secondary Index (DASI), Brief Fatigue Inventory (BFI), and QLQ-C30. All outcomes were reported as mean change and compared using paired t-tests. RESULTS: A total of 25 patients were enrolled in the study. 18 patients of the 25 enrolled (72%) completed the 14 weeks program without SAE. The overall adherence to the study protocol was 60%. Of the 18 participants who did not withdraw from the program, 15 (83%) adhered to the study protocol and completed 30 or more sessions. There was a nonsignificant improvement in VO2 max (mean Δ0.5, p=0.6). The scores for DASI, BFI, and QLQ-C30 improved from baseline to posttreatment. CONCLUSION: A CR intervention in breast cancer survivors had high adherence in those who were able to complete the 14-week program. The program significantly improved patient reported physical activity, fatigue, and quality of life (QoL), without significant improvement in CVD risk factors. Implications for cancer patients are that early implementation of a CR program should be considered by practitioners as it improves QoL and exercise tolerance in breast cancer survivors.

Patient-reported sexual function of breast cancer survivors with genitourinary syndrome of menopause after fractional CO2 laser therapy.

OBJECTIVE: The objective of this pilot study was to evaluate the change in sexual function following treatment with fractional CO2 laser therapy in breast cancer (BC) survivors with genitourinary syndrome of menopause (GSM). METHODS: A single-arm feasibility study of BC survivors with symptoms of GSM, including dyspareunia and/or vaginal dryness, was conducted. Participants who received three treatments with fractional CO2 laser and 4-week follow-up were contacted for patient-reported outcomes and adverse events at 12 months. Sexual function was measured using the Female Sexual Function Index (FSFI) and Female Sexual Distress Scale Revised (FSDS-R). Descriptive statistics were calculated for patient demographics and disease characteristics for the set of participants who agreed to long-term follow-up and those who were lost to follow-up. FSFI and FSDS-R scores were summarized at baseline, 4 weeks and 12 months, as well as the change from baseline, and were compared using a Wilcoxon signed rank test. RESULTS: A total of 67 BC survivors enrolled, 59 completed treatments and 4-week follow-up; 39 participated in the 12 month follow-up. The overall FSFI score improved from baseline to 4-week follow-up (median Δ 8.8 [Q1, Q3] (QS) (2.2, 16.7)], P < 0.001). There were improvements at 4 weeks in all domains of the FSFI (P < 0.001 for each) including desire (median Δ 1.2; QS [0.6, 1.8]), arousal (median Δ 1.2; QS [0.3, 2.7]), lubrication (median Δ 1.8 (0, 3.3), orgasm (median Δ 1.2; QS [0, 3.6]), satisfaction (median Δ 1.6 (0.4, 3.2)), and pain (median Δ 1.6 (0, 3.6). The FSDS-R score also improved from baseline to 4-week follow-up (median Δ -10.0; QS [-16, -5] P < 0.001) indicating less sexually related distress. The scores of the FSFI and FSDS-R remained improved at 12 months and there were no serious adverse events reported. CONCLUSIONS: In BC survivors with GSM, the total and individual domain scores of the FSFI and the FSDS-R improved after fractional CO2 laser therapy.

Video Summary:http://links.lww.com/MENO/A711 .

Cervical Cancer Among Older Women: Analyses of Surveillance, Epidemiology and End Results Program Data.

OBJECTIVE: To describe age-specific cervical cancer incidence rates based on demographic and clinical characteristics. METHODS: Women with cervical cancer in the SEER program were grouped into 3 age categories. Demographics, clinical characteristics, and incidence rates were obtained for each age group. RESULTS: Older women (≥65 years) had higher incidence rates of cervical cancer than women <65 years with the highest rates in black women ≥75 years. Older black women had more adverse factors at diagnosis than similarly aged white and younger black women. There was a higher incidence rate of cervical cancer in women with lower socioeconomic status (SES), with the highest rates in older black women. However, the incidence rates were similar for older black women regardless of SES. CONCLUSION: Older black have the highest cervical cancer incidence rates, regardless of SES, suggesting an age and race disparity when compared to younger and white women.

Study protocol for IMAGE: implementing multidisciplinary assessments for geriatric patients in an emergency department observation unit, a hybrid effectiveness/implementation study using the Consolidated Framework for Implementation Research.

BACKGROUND: Older adults in the emergency department (ED) are at high risk for functional decline, unrecognized delirium, falls, and medication interactions. Holistic assessment by a multidisciplinary team in the ED decreases these adverse outcomes and decreases admissions, but there are many barriers to incorporating this type of care during the ED visit. METHODS: This is a hybrid type II effectiveness-implementation study using a pre-/post-cohort design (n = 380) at a tertiary care academic ED with an ED observation unit (Obs Unit). The intervention is a two-step protocol of (step 1) ED nurses screening adult patients ≥ 65 years old for geriatric needs using the Delirium Triage Screen, 4-Stage Balance Test, and the Identifying Seniors at Risk score. Patients who have geriatric needs identified by this screening but who do not meet hospital admission criteria will (step 2) be placed in the Obs Unit for multidisciplinary geriatric assessment by the hospital's geriatric consultation team, physical therapists, occupational therapists, pharmacists, and/or case managers. Not all patients may require all elements of the multidisciplinary geriatric assessment. The Consolidated Framework for Implementation Research: Care Transitions Framework was used to identify barriers to implementation. Lean Six Sigma processes will be used to overcome these identified barriers with the goal of achieving geriatric screening rates of > 80%. Implementation success and associated factors will be reported. For the effectiveness aim, pre-/post-cohorts of adults ≥ 65 years old cared for in the Obs Unit will be followed for 90 days post-ED visit (n = 150 pre and 230 post). The primary outcome is the prevention of functional decline. Secondary outcomes include health-related quality of life, new geriatric syndromes identified, new services provided, and Obs Unit metrics such as length of stay and admission rates. DISCUSSION: A protocol for implementing integrated multidisciplinary geriatric assessment into the ED setting has the potential to improve patient functional status by identifying and addressing geriatric issues and needs prior to discharge from the ED. Using validated frameworks and implementation strategies will increase our understanding of how to improve the quality of ED care for older adults in the acute care setting. TRIAL REGISTRATION: ClinicalTrials.gov Identifier, NCT04068311, registered 28 August 2019.

The impact of granulocyte colony-stimulating factor use in patients with metastatic breast cancer treated with palliative chemotherapy: a single-institution retrospective review.

PURPOSE: The goal of chemotherapy for metastatic breast cancer (MBC) is palliation of symptoms while minimizing treatment-related toxicities. It remains unclear whether use of granulocyte colony-stimulating factor (G-CSF) to maintain relative dose intensity of chemotherapy for MBC is associated with improved clinical outcomes. METHODS: The medical records of MBC patients treated with chemotherapy in 1st-3rd-line settings between May 2010 and April 2014 were reviewed. Time to progression (TTP), progression-free survival (PFS), and overall survival (OS) were compared between patients who received G-CSF and those who did not. Antibiotic use, total clinic visits, and pre- and post-treatment Eastern Cooperative Oncology Group (ECOG) performance status were also compared between the groups. RESULTS: Of the 169 patients included, 55 (32.5%) received > 1 G-CSF dose and 114 (67.5%) did not receive any G-CSF. The median TTP was similar between the two groups (5.0 months (95% CI 3.4-7.1) vs. 5.2 months (95% CI 4.8-6.2) respectively; p = 0.998). The median PFS (p = 0.955; 5.0 months (95% CI 3.4-5.9) vs. 5.2 months (95% CI 4.7-6.0), respectively) and OS (14.6 (95% CI 9.0-26.6) vs. 18.5 months (95% CI 15.2-22.0) in G-CSF and non-G-CSF groups, respectively; p = 0.628) were also similar between groups. No significant between-group differences were noted in rate of decline in ECOG performance status, antibiotic use, and number of clinic visits and hospitalizations. CONCLUSION: This retrospective analysis did not find any evidence that the use of G-CSF to maintain chemotherapy dose intensity for the treatment of MBC improves TTP, PFS, and OS or results in improved ECOG performance status compared with lack of G-CSF use in patients with MBC treated in 1st to 3rd-line settings.

Incorporation of a patient navigator into a secondary fracture prevention program identifies barriers to patient care.

INTRODUCTION: Patient navigation improves outcomes in various clinical contexts, but has not been evaluated in secondary fracture prevention. METHODS: We retrospectively reviewed charts of patients, age 50 + from April to October, 2016 hospitalized with fragility fracture contacted by a patient navigator. Patients were identified using an electronic tool extracting data from electronic medical records which alerted the patient navigator to contact patients by phone post-discharge to schedule appointments to "High-Risk Osteoporosis Clinic" (HiROC) and Dual-energy X-ray Absorptiometry (DXA) scan. Primary outcome was transition from hospital to HiROC. We also compared completion of DXA, five osteoporosis-associated in-hospital laboratory tests (calcium, 25-hydroxy vitamin D, complete blood count, renal, and liver function), osteoporosis medication prescription and adherence, and other patient characteristics to historical controls (2014-2015) without patient navigation. Comparisons were made using Chi-square, Fisher's Exact, two-sample t test or Wilcoxon Rank Sum test, as appropriate. RESULTS: The proportion of patients transitioning to HiROC with and without patient navigation was not different (53% vs. 48%, p = 0.483), but DXA scan completion was higher (90% vs. 67%, p = 0.006). No difference in medication initiation within 3 months post discharge (73% vs. 65%, p = 0.387) or adherence at 6 months (68% vs. 71%, p = 0.777) was found. Patients attending HiROC lived closer (11 vs. 43 miles, p < 0.001) and more likely to follow-up in surgery clinic (95% vs. 61%, p < 0.001). CONCLUSION: Patient navigation did not improve transition to HiROC. Longer travel distance may be a barrier-unaffected by patient navigation. Identifying barriers may inform best practices for Fracture Liaison Service programs.

Efficacy of different dosing schedules of capecitabine for metastatic breast cancer: a single-institution experience.

Purpose Capecitabine is widely used as a single agent on a 21-day cycle in the management of metastatic breast cancer (MBC). Our primary objective was to compare the standard dosing of capecitabine (Arm A: days 1-14 on 21-day cycle) to biweekly dosing (Arm B: days 1-7 and 15-21 on 28-day cycle) using retrospective data analysis. Methods 166 patients with MBC treated with single agent capecitabine at The Ohio State University from 2002 to 2014 were considered eligible. Median time to treatment failure (TTF) and overall survival (OS) were estimated using Kaplan-Meier (KM) methods. KM curves were compared using log-rank tests with Holm's correction for multiplicity. Results Patients were grouped by dose schedule into one of three arms: Arm A (21-day cycle; capecitabine given at 1000 mg/m2 orally, twice daily on days 1-14 of 21-day cycle); Arm B (28-day cycle; capecitabine given at 1000 mg/m2 orally, twice daily on days 1-7 and 15-21 of 28-day cycle); and Arm C (changeover regimen where patients started on the 21-day cycle, but changed to a 28-day cycle for tolerability). No difference was found in TTF or OS for patients with MBC between those who received capecitabine on either standard dosing (Arm A) and those on a biweekly cycle (Arm B or C). Overall, 41% of patients required dose reduction. Conclusions Our single institution experience showed that alternate dosing of capecitabine (biweekly, 28-day cycle) may be a reasonable alternative to standard 21-day cycle with similar efficacy and fewer dose reductions.