Expanded carrier screening for recessively inherited disorders: economic burden and factors in decision-making when one individual in a couple is identified as a carrier.

PURPOSE: When undergoing expanded carrier screening (ECS), couples are often screened sequentially to reduce need for a second individual's test. It is unknown how often partners of individuals found to be carriers complete the recommended testing with a sequential approach and what factors contribute to decision-making regarding partner testing. Additionally, the economic burden placed on individuals by ECS testing and its effect on partner testing has not been evaluated. METHODS: In part 1, all individuals at a university-affiliated reproductive endocrinology and infertility practice identified to be carriers of a recessively inherited mutation using the Counsyl/Foresight ECS were included. Conditions were categorized by severity according to a previously described classification system. In part 2, all individuals who underwent ECS with a single test provider between September 1, 2013 and February 1, 2020 were contacted via email to complete a confidential and anonymized online survey. RESULTS: In part 1, a total of 2061 patients were screened. 36.9% were carriers of one or more recessively inherited disorders. Twenty-seven percent of positively screened individuals did not have their partner screened. Carriers of a moderate condition had a trend towards a reduced odds for having their partner screened compared to a profound condition (OR 0.36, 95% CI 0.12-1.05, p = 0.06). Number of conditions was not predictive of subsequent partner screening (OR 0.95, 95% CI 0.72-1.25, p = 0.72). In part 2, the cost of ECS was not covered by insurance for 54.5% (103/189) and most paid over $300 out-of-pocket for testing (47.6%). The most common reason for not completing partner testing was that the results would not alter their course when seeking conception (33.3%). 73.5% of patients knew that the largest benefit of ECS comes from knowing a partner's results as well as their own. CONCLUSIONS: Not all carriers of recessively inherited disorders choose to undergo partner screening. Patients found to be carrier of more debilitating genetic disorders may be more likely to screen their reproductive partners. For many, ECS testing is not covered by insurance, and this test may impose a significant economic burden. For some patients, the results of ECS would not change what they would do when seeking conception. Providers should evaluate whether a patient's ECS result would change their treatment course prior to testing.

Collection of electronic patient-reported symptoms in patients with advanced cancer using Epic MyChart surveys.

BACKGROUND: Use of electronic patient-reported outcomes (ePROs) in routine cancer care can help identify troublesome symptoms and facilitate discussions between patients and clinicians and has been shown to improve patient satisfaction, quality of life, and survival. METHODS: Eighty patients with stage IV non-hematologic malignancies on chemotherapy participated. Patient-Reported Symptom Monitoring (PRSM) surveys were sent every 14 days via the Epic MyChart system over a 12-week period. Surveys were offered via phone or paper if patients failed to complete the automated MyChart survey by day 16. Severe symptoms or concerning symptom trends were automatically highlighted in reports for clinic staff. Patients reporting severe symptoms were routed to oncology nursing triage for standard symptom care management. RESULTS: Two hundred seventy-one surveys were sent during the 12-week study period. One hundred eighty-three surveys (66%) were completed, with 68% completed electronically via MyChart, 25% by paper, and 7% by phone call from a research coordinator. At least one severe symptom was reported on 36% of all surveys. However, most severe symptoms did not result in urgent triage follow-up because they were already being addressed and/or patients felt they were manageable. Patients and clinicians generally said the ePRO was efficient and helpful for addressing distressing symptoms and would use it in routine oncology care. CONCLUSION: ePROs can be integrated into the electronic health record using the Epic MyChart system. Patients and clinicians gave positive feedback on the system. Monitoring symptoms in real time may soon become part of standard oncology practice and requires seamless methods for collection.

Impact of opioid use on health care utilization and survival in patients with newly diagnosed stage IV malignancies.

PURPOSE: Patients with advanced cancers frequently experience pain. Opioids are commonly prescribed to treat cancer-related pain, but their use might be associated with undesirable consequences including adverse effects and tumor progression, resulting in increased heath care utilization and shorter survival. We examined these possibilities in a large cohort of patients diagnosed with ten common advanced malignancies. METHODS: We identified 1386 newly diagnosed patients with stage IV non-hematologic malignancies from 2005 to 2013 and ascertained opioid utilization within 90 days of starting anti-cancer treatment using electronic medical record and tumor registry data. Opioid utilization was stratified into low opioid (LO; < 5 mg oral morphine equivalents (OME)/day) and high opioid (HO; ≥ 5 mg OME/day). Health care utilization included tallies of emergency room, urgent care, and inpatient visits. The association of opioid use, tumor type prognosis, age, and gender with overall survival was analyzed in univariate and multivariate models. RESULTS: HO use patients (n = 624) had greater health care utilization compared to LO use patients (n = 762; p < 0.05). HO use patients also had shorter survival (median survival, 5.5 vs 12.4 months; p < 0.0001). On multivariate analysis, HO use remained associated with shorter overall survival (HR 1.4; 95% CI, 1.3-1.6; p < 0.0001) after adjusting for age, gender, and prognostic group. CONCLUSIONS: In advanced cancer patients, HO use is associated with greater health care utilization and shorter survival. Prospective studies using opioid-sparing approaches are indicated, to confirm these retrospective findings and to evaluate if these undesirable effects associated with opioid use can be mitigated.

Effect of race and ethnicity on utilization and outcomes of assisted reproductive technology in the USA.

BACKGROUND: The purpose of this study was to determine the utilization and live birth rates of assisted reproductive technology (ART) modalities among various racial and ethnic groups in recent years. METHODS: We reviewed ART data reported to the Society for Assisted Reproductive Technologies Clinic Outcome Reporting System (SART CORS) for autologous ART and third-party ART (3ART) cycles which involved donor oocytes, sperm, embryos and gestational carrier, performed in the U.S. between 2004 and 2013. To gauge demand by various racial/ethnic groups for ART services, we examined fertility rates and demographics of the entire U.S. birth cohort over the same time interval. RESULTS: Of 1,132,844 autologous ART cycles 335,462 resulted in a live birth (29.6%). An additional, 217,030 3ART cycles resulted in 86,063 live births (39.7%). Hispanic and Black women demonstrated high fertility and lower utilization rates of autologous ART and 3ART. Caucasian and Asian women exhibited lower fertility rates and higher autologous ART and 3ART utilization. Autologous ART resulted in higher live birth rates among Caucasian and Hispanic women and lower rates among Asian and especially Black women. 3ART improved live birth rates in all races/ethnicities, though Black women experienced lower live birth rates with most modalities. Spontaneous abortion rates were higher among Black women following autologous ART and some 3ART modalities than those among Caucasian women. CONCLUSION: Utilization of ART is inversely related to fertility rates. Autologous ART produces lower live birth rates among Asian and Black women. 3ART results in relatively low live birth rates among Black women. TRIAL REGISTRATION: SART CORS #57 , Registered 5/14/2015.

Utilization of third-party in vitro fertilization in the United States.

BACKGROUND: The use of in vitro fertilization that includes third-party in vitro fertilization is increasing. However, the relative contribution of third-party in vitro fertilization that includes the use of donor oocytes, sperm, or embryo and a gestational carrier to the birth cohort after in vitro fertilization is unknown. OBJECTIVE: The purpose of this study was to examine the contribution of third-party in vitro fertilization to the in vitro fertilization birth cohort over the past decade. STUDY DESIGN: This retrospective analysis investigated 1,349,874 in vitro fertilization cycles that resulted in 421,525 live births and 549,367 liveborn infants in the United States from 2004-2013. Cycles were self-reported by fertility centers to a national registry: Society for Assisted Reproductive Technologies Clinic Outcome Reporting System. RESULTS: Third-party in vitro fertilization accounted for 217,030 (16.1%) of all in vitro fertilization cycles, 86,063 (20.4%) of all live births, and 115,024 (20.9%) of all liveborn infants. Overall, 39.7% of third-party in vitro fertilization cycles resulted in a live birth, compared with 29.6% of autologous in vitro fertilization cycles. Use of third-party in vitro fertilization increased with maternal age and accounted for 42.2% of all in vitro fertilization cycles and 75.3% of all liveborn infants among women >40 years old. Oocyte donation was the most common third-party in vitro fertilization technique, followed by sperm donation. Over the study period, annual cycle volume and live birth rates gradually increased for both autologous in vitro fertilization and third-party in vitro fertilization (P<.0001 for all). Live birth rates were the highest when multiple third-party in vitro fertilization modalities were used, followed by oocyte donation. CONCLUSION: Third-party in vitro fertilization use and efficacy have increased over the past decade, now comprising >20% of the total in vitro fertilization birth cohort. In women who are >40 years old, third-party in vitro fertilization has become the dominant treatment.

Implementation of Routine Postpartum Depression Screening and Care Initiation Across a Multispecialty Health Care Organization: An 18-Month Retrospective Analysis.

Objectives Postpartum depression (PPD) affects approximately 10-20% of all mothers after giving birth. Adequate screening and follow-up care for the postpartum mother with depression is an essential component of quality care in this population. The purpose of this quality improvement project was to evaluate the quality and quantity of a postnatal PPD screening program and the subsequent initiation of needed PPD treatment in an integrated health system. Methods After implementing a standardized PPD screening process, we conducted an 18-month retrospective study of patient visits that required a PPD screen. Data were abstracted from medical records and analyzed to determine if postnatal PPD screening occurred, what quality of the screening was, and what follow-up measures were taken. Results Within the study timeframe, 28,389 postpartum and well-child visits were eligible for PPD screening. PPD screening occurred at 88% of eligible visits for approximately 5000 unique women. PPD was identified in 8.1% of screened women. Conclusions Of women with PPD, at least 44.8% were prescribed an SSRI and 21.4% attended a visit with a mental health professional, which is consistent with other studies. Screening can be successful through collaboration, although ongoing evaluation and process modification are necessary.

Randomized, blinded trial of vitamin D3 for treating aromatase inhibitor-associated musculoskeletal symptoms (AIMSS).

The purpose of the study was to evaluate the efficacy and safety of vitamin D3 at 4000 IU/day as a treatment option for aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) when compared with the usual care dose of 600 IU D3. We conducted a single site randomized, double-blind, phase 3 clinical trial in women with AIMSS comparing change in symptoms, reproductive hormones and AI pharmacokinetics. Postmenopausal women ≥18 years with stages I-IIIA breast cancer, taking AI and experiencing AIMSS [breast cancer prevention trial symptom scale-musculoskeletal (BCPT-MS) subscale ≥1.5] were admitted. Following randomization, 116 patients had a run-in period of 1 month on 600 IU D3, then began the randomized assignment to either 600 IU D3 (n = 56) or 4000 IU D3 (n = 57) daily for 6 months. The primary endpoint was a change in AIMSS from baseline (after 1 month run-in) on the BCPT-MS (general MS pain, joint pain, muscle stiffness, range for each question: 0 = not at all to 4 = extremely). Groups had no statistically significant differences demographically or clinically. There were no discernable differences between the randomly allocated treatment groups at 6 months in measures of AIMSS, pharmacokinetics of anastrozole and letrozole, serum levels of reproductive hormones, or adverse events. We found no significant changes in AIMSS measures between women who took 4000 IU D3 daily compared with 600 IU D3. The 4000 IU D3 did not adversely affect reproductive hormone levels or the steady state pharmacokinetics of anastrozole or letrozole. In both groups, serum 25(OH)D remained in the recommended range for bone health (≥30 ng/mL) and safety (<50 ng/mL).

Wound Care: Multicenter Feasibility Study.

OBJECTIVES: The aims of this study were to determine a sound recruitment strategy for multisite wound studies to address the rising prevalence and incidence of chronic wounds and to identify appropriate adult patient populations with wounds of interest and establish partnerships with their clinicians and clinical services as a model for a multisite wound care feasibility study. DESIGN: A pilot multisite recruitment feasibility study. SETTING: Three wound clinics located in a large, Midwestern metropolitan area. PARTICIPANTS AND INTERVENTION: A convenience sample of 3 staff and 3 patients with lower-extremity wounds from each clinic was interviewed. Medical records of all patients with lower-extremity wounds seen during 1 week at each clinic were reviewed. Outcome measures included characteristics of patients being treated at the 3 wound care clinics (patient demographics and wound characteristics) and wound treatments used. Barriers and opportunities that could be addressed in recruitment and other research strategies were identified. MAIN RESULTS: Barriers and facilitators for future research were identified and varied within and between clinics. Patients reported they were willing to participate in future research, although fewer were willing if the study was blinded. Patients received a variety of treatments within and across clinics. Medical record reviews provided further information about wound clinic patients, wound characteristics, and barriers and facilitators for future study. CONCLUSIONS: Characteristics of wound clinic patients and their wounds were found to vary by site, suggesting tailored recruitment methods by site within multisite wound care studies may be most productive. This study suggests successful recruitment strategies for future wound care intervention research.

Impact of cerebrospinal fluid matrix on the detection of Alzheimer's disease with Aß42 and influence of disease on the total-Aß42/Aß40 ratio.

The 42-amino acid fragment of amyloid ß (Aß1-42) in cerebrospinal fluid has continued to be important for detecting cerebral ß-amyloidosis in Alzheimer's disease (AD). However, there are impediments to our ability to fully understand this measurement, including matrix interference and changes linked to apolipoprotein E (APOE) ε4 genotype. This study investigated matrix interference as a contributing factor for detecting AD in APOE ε4-negative patients by comparing total extractable Aß1-42 to free Aß1-42. It also examined the ratio of total Aß1-42 to Aß1-40, since changes relative to other Aß peptides may provide a measurement of cerebral ß-amyloidosis that is neutral to changes in APP metabolism. Total Aß1-42 lost the diagnostic power for detecting AD, confirming a role for matrix in the diagnostic. However, when total Aß1-42/Aß1-40 was examined, the separation between groups was reestablished. This result was confirmed in a second sample set of unknown APOE status. These results confirmed that matrix interference in some cerebrospinal fluid samples appears to contribute to identifying AD patients and this can be compensated by using a total extracted Aß1-42/Aß1-40 ratio when matrix interference is small. It may be preferable to employ a total Aß1-42/Aß1-40 measurement, since this could minimize variability because of matrix and compensate for across patient differences. Aß1-42 measurement in CSF has provided an important tool for early detection of AD. However, it appears that most assays measure a free fraction of Aß1-42. This study examined total extracted Aß1-42, since this would provide a more accurate assessment of Aß1-42 in AD CSF. Total Aß1-42 measurements alone were not good for detecting AD but total Aß1-42/Aß1-40 performed well.

Large-scale candidate gene study to identify genetic risk factors predictive of paliperidone treatment response in patients with schizophrenia.

OBJECTIVE: Clinical response to antipsychotic medications can vary markedly in patients with schizophrenia. Identifying genetic variants associated with treatment response could help optimize patient care and outcome. To this end, we carried out a large-scale candidate gene study to identify genetic risk factors predictive of paliperidone efficacy. PATIENTS AND METHODS: A central nervous system custom chip containing single nucleotide polymorphisms from 1204 candidate genes was utilized to genotype a discovery cohort of 684 schizophrenia patients from four clinical studies of paliperidone extended-release and paliperidone palmitate. Variants predictive of paliperidone efficacy were identified and further tested in four independent replication cohorts of schizophrenic patients (N=2856). RESULTS: We identified an SNP in ERBB4 that may contribute toward differential treatment response to paliperidone. The association trended in the same direction as the discovery cohort in two of the four replication cohorts, but ultimately did not survive multiple testing corrections. The association was not replicated in the other two independent cohorts. We also report several SNPs in well-known schizophrenia candidate genes that show suggestive associations with paliperidone efficacy. CONCLUSION: These preliminary findings suggest that genetic variation in the ERBB4 gene may differentially affect treatment response to paliperidone in individuals with schizophrenia. They implicate the neuregulin 1 (NRG1)-ErbB4 pathway for modulating antipsychotic response. However, these findings were not robustly reproduced in replication cohorts.

Monitoring Rates of Malnutrition Risk in Outpatient Cancer Centers Utilizing the Malnutrition Screening Tool Embedded into the Electronic Health Record.

BACKGROUND: The risk of malnutrition in patients with cancer is well documented. However, screening to identify patients at risk in ambulatory cancer centers is not standardized nor uniform. The 2-question Malnutrition Screening Tool (MST) is validated in the ambulatory oncology setting and endorsed by the Academy of Nutrition and Dietetics. OBJECTIVE: To test the feasibility of operationalizing and standardizing malnutrition risk assessment across 2 large ambulatory cancer centers by embedding the MST into the electronic health record (EHR) with the goal of identifying and quantifying the prevalence of malnutrition risk in outpatient settings. DESIGN: A Quality Assurance Performance Improvement project was conducted to evaluate malnutrition screening practices by leveraging the EHR. Work standards were developed, implemented, and evaluated to assess the feasibility of utilizing de-identified MST data, entered as discrete variables in an EHR flowsheet, to track monthly MST completion rates and to identify and quantify patients being treated for cancer scoring at risk for impaired nutritional status. PARTICIPANTS/SETTING: Data from 2 large adult ambulatory community cancer centers in the upper Midwest were collected between April 2017 and December 2018. RESULTS: Over a 20-month period, the average monthly MST completion rate was 74%. Of those with completed MST screens, the average percentage of patients identified at nutritional risk (MST score ≥2) was 5% in medical oncology and 12% in radiation oncology. CONCLUSION: It is feasible to (1) integrate and standardize data collection of the MST into existing EHR flowsheets and (2) identify and quantify patients at risk for malnutrition on a consistent basis.

Effects of exercise vs bisphosphonates on bone mineral density in breast cancer patients receiving chemotherapy.

Chemotherapy for breast cancer causes early-onset menopause for most women older than age 40 and is associated with accelerated bone loss. The primary objective of this study was to compare the effects of intravenous (IV) zoledronic acid versus prescribed physical activity (PA) on changes in bone mineral density (BMD) for women between the ages of 40 and 55 years receiving chemotherapy for breast cancer. A randomized controlled trial of 62 patients with breast cancer during chemotherapy compared IV zoledronic acid and oral calcium/vitamin D (ZO group) versus a PA program and oral calcium/vitamin D (PA group). ZO group participants received zoledronic acid IV every 3 months for 5 treatments. PA group participants were enrolled in a home-based exercise program and received motivational counseling, pedometers, and exercise tapes. BMD measurements from dual-energy x-ray absorptiometry (DEXA) scanning were completed at baseline and at 12 months. BMD significantly decreased in the PA group but not in the ZO group. Although spine, total hip, and total body BMD increased in the ZO group by 1.6%, 0.8%, and 0.8%, respectively, BMD decreased in the PA group by 6.0%, 3.4%, and 3.3%, respectively (P values < 0.0001 for all group comparisons). Zoledronic acid protected patients with breast cancer against bone loss during initial treatment, whereas home-based PA interventions were less effective in preventing bone loss.

Comparison of 2-Hour Oral Glucose Tolerance Test and Hemoglobin A1C in the Identification of Pre-Diabetes in Women with Infertility and Recurrent Pregnancy Loss.

RESEARCH QUESTION: Does hemoglobin A1C (HbA1C) predict pre-diabetes (pre-DM) in a population of women with infertility and/or recurrent pregnancy loss (RPL), when considering the 75 g, 2-hour oral glucose tolerance test (2h GTT) as the gold standard? DESIGN: Retrospective study of 242 patients with infertility or RPL presenting to a university-affiliated reproductive endocrinology and infertility clinic between January 2012 and December 2016 who underwent screening for disorders of glucose metabolism with a 2h GTT. The prevalence of pre-DM as defined by HbA1C 5.7% to 6.4% and 2h GTT values of 140-199 mg/dL, and predictive values of HbA1C for the identification of pre-DM when compared with 2h GTT, were calculated and compared. RESULTS: Of 242 patients, 188 (77.7%) women had both HbA1C and 2h GTT performed. Of these, 89 (47.3%) tested positive for pre-DM by one or both methods. Of 89 patients, 14 (15.7%) had both an abnormal 2h GTT and an abnormal HbA1C. Only 6 out of 89 (6.7%) patients tested positive for pre-DM by an abnormal 2h GTT in the setting of a normal HbA1C result. Conversely, 69 of these 89 patients (77.5%) tested positive for pre-DM by an abnormal HbA1C in the setting of a normal 2h GTT. The prevalence of pre-DM, as defined by 2h GTT, was 10.6% (20/188) (95% CI, 6.6-16.0), compared with a prevalence of 44.1% (83/188) (95% CI, 36.9-51.6) when pre-DM was defined by HbA1C alone. When the 2h GTT was considered the gold standard for the identification of pre-DM, the negative predictive value (NPV) of HbA1C compared with 2h GTT was 94.3% (95% CI, 88.0-97.9), whereas the positive predictive value (PPV) of HbA1C compared with 2h GTT was only 16.9% (95% CI, 9.5-26.7). CONCLUSIONS: Although a normal HbA1C was highly predictive of a normal 2h GTT, the two tests demonstrate poor agreement in the identification of pre-DM in women with infertility and/or RPL. Hemoglobin A1C is superior to the 2h GTT as an initial screening test for pre-DM in this population, since it identified a substantial number of women who would otherwise remain undiagnosed in the setting for a normal 2h GTT alone. However, the long-term clinical relevance of an elevated HbA1C in this population needs to be better defined.

Vitamin D levels are not associated with ovarian reserve in a group of infertile women with a high prevalance of diminished ovarian reserve.

OBJECTIVE: To determine whether a relationship exists between vitamin D (25OH-D) levels and ovarian reserve parameters (antimüllerian hormone [AMH] and FSH levels) in a large cohort of infertile women with a high prevalence of diminished ovarian reserve. DESIGN: Retrospective cohort study. SETTING: Academically affiliated private fertility center. PATIENT(S): A total of 457 infertile women 21-50 years of age who had baseline hormone measurements. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Statistical analyses to determine whether a relationship exists between AMH, FSH, and serum 25OH-D levels. RESULT(S): As defined by 25OH-D <20.0 ng/mL, 74/457 patients (16.2%) had vitamin D deficiency. AMH and FSH levels did not vary between women with vitamin D deficiency and those with normal levels (0.8 ± 3.0 vs. 0.5 ± 1.6 ng/mL [P=.18] and 9.4 ± 7.2 vs. 9.2 ± 9.5 mIU/mL [P=.54], respectively). Multivariate linear regression analysis of log-transformed AMH and FSH with 25OH-D levels adjusted for age, body mass index, and seasonal variation confirmed lack of association. Receiver operating characteristic (ROC) analysis to determine if 25OH-D levels are predictive of AMH showed areas under the ROC curves (AUCs) for women <38 years of age to be 0.501, 0.554, and 0.511 for AMH threshold values of 0.5 ng/mL, 1.0 ng/mL, and 5.0 ng/mL, respectively. For women ≥38 years respective AUC values were 0.549, 0.545, and 0.557 ng/mL. CONCLUSION(S): Vitamin D levels were not associated with ovarian reserve in a large group of infertile women with a high prevalence of diminished ovarian reserve. Previously reported vitamin D-associated outcomes in infertility patients may, therefore, be mediated by factors other than ovarian reserve.

Interventions to prevent loss of bone mineral density in women receiving chemotherapy for breast cancer.

Loss of bone mineral density (BMD) is a significant problem for women receiving breast cancer treatment. The purpose of this article is to present the state of the knowledge on BMD loss and analyze interventions to prevent BMD loss in women receiving breast cancer treatment. The data sources include primary research reports, review articles, and book chapters. With increased numbers of breast cancer survivors, BMD loss experienced with treatment is a significanthealth concern because of risks of osteoporosis and bone fractures. These long-term treatment effects may significantly impact patients' long-term morbitity and mortality. BMD screening as well as an assessment of physical activity and dietary history should be conducted with women undergoing breast cancer treatment. Bisphosphonates are effective in preventing BMD loss, and other interventions such as physical activity and dietary interventions need further testing. Oncology nurses are ideal candidates for implementing interventions to prevent BMD loss because of their understanding of cancer treatments, knowledge of health-related behaviors, and ability to teach patients about the positive health benefits of lifestyle changes.

Identification of tools to measure changes in musculoskeletal symptoms and physical functioning in women with breast cancer receiving aromatase inhibitors.

PURPOSE/OBJECTIVES: To estimate and compare responsiveness of standardized self-reported measures of musculoskeletal symptoms (MSSs) and physical functioning (PF) during treatment with aromatase inhibitors (AIs). DESIGN: Prospective, longitudinal study. SETTING: Park Nicollet Institute and North Memorial Cancer Center, both in Minneapolis, MN. SAMPLE: 122 postmenopausal women with hormone receptor-positive breast cancer. METHODS: MSSs and PF were assessed before starting AIs and at one, three, and six months using six self-reported MSSs measures and two PF tests. MAIN RESEARCH VARIABLES: MSSs and PF changes from baseline to six months. FINDINGS: Using the Breast Cancer Prevention Trial-Musculoskeletal Symptom (BCPT-MS) subscale, 54% of participants reported MSSs by six months. Scores from the BCPT-MS subscale and the physical function subscales of the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) and Western Ontario and McMaster Osteoarthritis Index (WOMAC) were most responsive to changes over six months. CONCLUSIONS: BCPT-MS, AUSCAN, and WOMAC were the most responsive instruments for measuring AI-associated MSSs. IMPLICATIONS FOR NURSING: Assessment and management of MSSs are important aspects of oncology care because MSSs can affect functional ability and AI adherence. KNOWLEDGE TRANSLATION: The three measures with the greatest sensitivity were the BCPT-MS, AUSCAN, and WOMAC questionnaires. These measures will be useful when conducting research on change in MSSs associated with AI treatment in women with breast cancer.

Prespecified candidate biomarkers identify follicular lymphoma patients who achieved longer progression-free survival with bortezomib-rituximab versus rituximab.

PURPOSE: Identify subgroups of patients with relapsed/refractory follicular lymphoma deriving substantial progression-free survival (PFS) benefit with bortezomib-rituximab versus rituximab in the phase III LYM-3001 study. EXPERIMENTAL DESIGN: A total of 676 patients were randomized to five 5-week cycles of bortezomib-rituximab or rituximab. The primary end point was PFS; this prespecified analysis of candidate protein biomarkers and genes was an exploratory objective. Archived tumor tissue and whole blood samples were collected at baseline. Immunohistochemistry and genetic analyses were completed for 4 proteins and 8 genes. RESULTS: In initial pairwise analyses, using individual single-nucleotide polymorphism genotypes, one biomarker pair (PSMB1 P11A C/G heterozygote, low CD68 expression) was associated with a significant PFS benefit with bortezomib-rituximab versus rituximab, controlling for multiple comparison corrections. The pair was analyzed under dominant, recessive, and additive genetic models, with significant association with PFS seen under the dominant model (G/G+C/G). In patients carrying this biomarker pair [PSMB1 P11A G allele, low CD68 expression (≤50 CD68-positive cells), population frequency: 43.6%], median PFS was 14.2 months with bortezomib-rituximab versus 9.1 months with rituximab (HR 0.47, P < 0.0001), and there was a significant overall survival benefit (HR 0.49, P = 0.0461). Response rates were higher and time to next antilymphoma therapy was longer in the bortezomib-rituximab group. In biomarker-negative patients, no significant efficacy differences were seen between treatment groups. Similar proportions of patients had high-risk features in the biomarker-positive and biomarker-negative subsets. CONCLUSIONS: Patients with PSMB1 P11A (G allele) and low CD68 expression seemed to have significantly longer PFS and greater clinical benefit with bortezomib-rituximab versus rituximab.

Changes in weight and body composition in women receiving chemotherapy for breast cancer.

PURPOSE: This study aimed to identify predictors of changes in weight and body composition among women receiving chemotherapy for breast cancer. PATIENTS AND METHODS: Data were from 49 women age 40-54 receiving chemotherapy for breast cancer. Weight, height, and body composition measurements from dual-energy x-ray absorptiometry (DEXA) scanning were completed at baseline (within 1 month of beginning chemotherapy) and 12 months. Caloric intake was assessed from food diaries at baseline, 6 and 12 months, and physical activity was measured by questionnaire at baseline, 3, 6, 9, and 12 months. RESULTS: Baseline body mass index (BMI) was inversely associated with gains in weight (P = .01) and fat mass in torso (P = .006). Women of normal weight gained an average of 4.3 pounds and increased fat mass in torso and arms. Overweight women lost 3.0 pounds, and obese women lost 4.1 pounds, and neither group increased body fat. Decreased physical activity was associated with weight gain (P = .047). Additional predictors of increased fat mass in torso were younger age (P = .023) and treatment with tamoxifen (P = .015). Predictors of loss of bone mineral content included older age (P = .004) and treatment with aromatase inhibitor (P = .024), whereas treatment with bisphosphonate prevented bone loss (P < .0001). CONCLUSION: Women receiving chemotherapy for breast cancer who are of normal weight at the time of breast cancer diagnosis are more likely to gain weight and body fat during the following year than overweight or obese women.

The effects of pregnancy on memory: recall is worse but recognition is not.

Women who are pregnant frequently complain of memory problems. Past research suggests that pregnancy is associated with a measurable decline when memory is tested using free recall but not when memory is tested using recognition. However, no prior studies on recognition memory tested performance across two time periods (e.g., pregnant vs. postpartum). A repeated measures design has greater power than a between-subject design to detect any difference in recognition memory performance that might exist. We administered a standardized memory test to 37 women during pregnancy and then again during the postpartum period 3 to 12 months later. Our results show that during pregnancy free-recall performance was somewhat worse (in agreement with prior research) than postpartum but that recognition performance was not worse and was, if anything, slightly enhanced. These results weigh against a purely biological explanation of the memory difficulties associated with pregnancy and instead point to a strategic explanation. In particular, the results suggest that when women are pregnant they rely more on item-specific processing (which can enhance recognition) but when they are no longer pregnant they rely more on relational processing (which enhances recall).