Omission of Radiotherapy After Breast-Conserving Surgery for Women With Breast Cancer With Low Clinical and Genomic Risk: 5-Year Outcomes of IDEA.

PURPOSE: Multiple studies have shown a low risk of ipsilateral breast events (IBEs) or other recurrences for selected patients age 65-70 years or older with stage I breast cancers treated with breast-conserving surgery (BCS) and endocrine therapy (ET) without adjuvant radiotherapy. We sought to evaluate whether younger postmenopausal patients could also be successfully treated without radiation therapy, adding a genomic assay to classic selection factors. METHODS: Postmenopausal patients age 50-69 years with pT1N0 unifocal invasive breast cancer with margins ≥2 mm after BCS whose tumors were estrogen receptor-positive, progesterone receptor-positive, and human epidermal growth factor receptor 2-negative with Oncotype DX 21-gene recurrence score ≤18 were prospectively enrolled in a single-arm trial of radiotherapy omission if they consented to take at least 5 years of ET. The primary end point was the rate of locoregional recurrence 5 years after BCS. RESULTS: Between June 2015 and October 2018, 200 eligible patients were enrolled. Among the 186 patients with clinical follow-up of at least 56 months, overall and breast cancer-specific survival rates at 5 years were both 100%. The 5-year freedom from any recurrence was 99% (95% CI, 96 to 100). Crude rates of IBEs for the entire follow-up period for patients age 50-59 years and age 60-69 years were 3.3% (2/60) and 3.6% (5/140), respectively; crude rates of overall recurrence were 5.0% (3/60) and 3.6% (5/140), respectively. CONCLUSION: This trial achieved a very low risk of recurrence using a genomic assay in combination with classic clinical and biologic features for treatment selection, including postmenopausal patients younger than 60 years. Long-term follow-up of this trial and others will help determine whether the option of avoiding initial radiotherapy can be offered to a broader group of women than current guidelines recommend.

Investigating potential disparities in clinical trial eligibility and enrollment at an NCI-designated comprehensive cancer center.

BACKGROUND: Although barriers to trial accrual are well-reported, few studies have explored trial eligibility and trial offers as potential drivers of disparities in cancer clinical trial enrollment. METHODS: We identified patients with gastrointestinal (GI) or head/neck (HN) malignancies who were seen as new patients at the University of Michigan Health Rogel Cancer Center in 2016. By exhaustive review of the electronic medical record, we assessed the primary outcomes: (1) eligibility for, (2) documented offer of, and (3) enrollment in a clinical trial. All 41 of the clinical trials available to these patients were considered. Independent variables included clinical and non-clinical patient-related factors. We assessed associations between these variables and the primary outcomes using multivariable regression. RESULTS: Of 1446 patients, 43% were female, 15% were over age 75, 6% were Black. 305 (21%) patients were eligible for a clinical trial. Among eligible patients, 154 (50%) had documentation of a trial offer and 90 (30%) enrolled. Among the GI cohort, bivariate analyses demonstrated that older age was associated with decreased trial eligibility. Bivariate analyses also demonstrated that Black race was associated with increased trial offer. After adjustment, patients 75 or older were less likely to be eligible for a clinical trial in the GI cohort; however, we found no significant associations between race and any of the outcomes after adjustment. Among eligible GI patients, we found no significant associations between non-clinical factors and enrollment. Among the HN cohort, bivariate analyses demonstrated that female sex, older age, Black race, and unpartnered marital status were associated with decreased likelihood of trial offer; however, we found no significant associations between race, age, and marital status and any of the outcomes after adjustment. We found no significant associations between non-clinical factors and eligibility after adjustment; however, women were less likely to be offered and to enroll in a clinical trial in the HN cohort. CONCLUSION: Factors associated with eligibility, documented offer, and enrollment differed between disease site cohorts at our institution. Future work is needed to ensure the equitable inclusion of women and elderly patients in clinical trials.

Frequency and determinants of technical procedures in French general practice: a cross-sectional study.

INTRODUCTION: Technical skills have many areas of application in general practice and are a dimension of medical competence. Several studies have attempted to describe the technical procedures performed in general practice but most had limitations in the data collection process, the scope of the procedures addressed, or the healthcare actors involved. No French comparable data have been published. The aim of the present study was therefore to describe the frequency and type of technical procedures in French general practice, and to assess their determinants, in particular rurality. METHODS: The present study was ancillary to the ECOGEN (Eléments de la COnsultation en médecine GENérale) study, which was an observational cross-sectional, multicentre, nationwide study conducted in 128 French general practices. Data were collected on 20 613 patient-GP encounters, including the characteristics of GPs and encounters, as well as the health problems managed during the encounter and their associated processes of care; the latter two variables were coded according to the International Classification of Primary Care classification. The GPs' practice location was first classified as rural area, urban cluster, or urban area; the former two categories were combined for analysis. The various technical procedures were classified according to the framework of the International Classification of Process in Primary Care. The frequency of each technical procedure was compared according to GP practice location. The dependent variable analysed was the performance of at least one technical procedure per each health problem managed. Bivariate analysis was performed for all independent variables followed by multivariate analysis for key variables, using a hierarchical model including three levels: the physician, the encounter, the health problem managed. RESULTS: The data included 2202 technical procedures performed. At least one technical procedure was performed in 9.9% of encounters and for 4.6% of health problems managed. The two most frequent groups of technical procedures performed were injections (44.2% of all procedures) and clinical laboratory procedures (17.0%). The following procedures were more often performed by GPs practicing in a rural area or an urban cluster than those practicing in an urban area: injection of joints, bursae, tendons and tendon sheaths (4.1% v 1.2% of all procedures), manipulation and osteopathy (10.3% v 0.4%), excision/biopsy of superficial lesions (1.7% v 0.5%), and cryotherapy (1.7% v 0.3%). Conversely, the following procedures were more often performed by GPs practicing in urban areas: vaccine injection (46.6% v 32.1%), point-of-care testing for group A streptococci (11.8% v 7.6%), and ECG (7.6% v 4.3%). GPs practicing in a rural area or an urban cluster performed more often technical procedures than those practising in an urban area (odds ratio=1.31, 95% confidence interval 1.04-1.65), according to the multivariate model. CONCLUSION: Technical procedures were more frequently performed and more complex when they were performed in French rural and urban cluster areas. More studies are required to assess patients' needs regarding technical procedures.

Envisioning clinical trials as complex interventions.

Clinical trials are critical components of modern health care and infrastructure. Trials benefit society through scientific advancement and individual patients through trial participation. In fact, billions of dollars are spent annually in support of these benefits. Despite the massive investments, clinical trials often fail to accomplish their primary aims and trial enrollment rates remain low. Prior efforts to improve trial conduct and enrollment have had limited success, perhaps due to oversimplification of the complex, multilevel nature of trials. For these reasons, the authors propose applying implementation science to the clinical trials context. In this commentary, the authors posit clinical trials as complex, multilevel evidence-based interventions with significant societal and individual benefits yet with persistent gaps in implementation. An application of implementation science concepts to the clinical trials context as means to build common vocabulary and establish a platform for applying implementation science and practice to improve clinical trial conduct is introduced. Applying implementation science to the clinical trials context can augment improvement efforts and build capacity for better and more efficient evidence-based care for all patients and trial stakeholders throughout the clinical trials enterprise.

Efficacy of careHPV™ human papillomavirus screening versus conventional cytology tests for the detection of precancerous and cancerous cervical lesions among women living with HIV-1 in Lao People's Democratic Republic.

BACKGROUND: In the Lao People's Democratic Republic (Lao PDR), cervical cancer is the third leading cause of women cancer. AIMS: The objective of this cross-sectional study was to compare the efficacy of careHPV™ test versus conventional Pap smear or Siriraj liquid-based cytology in the detection of cervical cancer in women living with human immunodeficiency virus type 1 (HIV-1). MATERIALS & METHODS: Overall, 631 women consented to participate. Four cervical specimens were taken for the purpose of conventional Pap smear, Siriraj liquid-based cytology, careHPV™ test, and HPV-16 genotyping. The exact McNemar test was used to compare the efficacy and diagnostic performance of the tests. RESULTS: Of the 631 women with follow-up, 331 were human papillomavirus (HPV) negative. High-grade squamous intraepithelial lesions were found in 37 women, biopsy-proven high-grade cervical intraepithelial neoplasia in 50 women, and invasive carcinoma in seven women. The proportion of women with high-grade cervical lesion or carcinoma detected after abnormal careHPV™ test was higher (6.02%; 95% confidence interval [CI]: 4.4-8.1) than that detected by conventional Pap smear (4.59%; 95% CI: 3.2-6.5). careHPV™ and HPV-16 genotyping had, respectively, the highest sensitivity (80.8%; 95% CI: 67.4-89.5) and specificity (92.2%; 95% CI: 89.8-94.2). HPV-16 was the most frequently detected genotype. CONCLUSIONS: careHPV™ test represents a screening option in Lao PDR, particularly in women living with HIV-1 because of higher prevalence of chronic HPV in this population.

Trends in postmenopausal osteoporosis treatment in France during the period 2007-2016: A nationwide claims database analysis.

PURPOSE: To describe the trends in the pharmacological management of postmenopausal osteoporosis in France during the period 2007-2016. METHOD: This cross-sectional, yearly repeated study of patients in France used the nationwide claims database 'Échantillon Généraliste de Bénéficiaires' (EGB), covering a 1 in 97 representative sample of approximately 600,000 individuals insured by the main French public insurance scheme. For women aged 50-89 years, prescriptions for all anti-osteoporosis medications (AOMs) marketed in France during the study period (bisphosphonates alone or used in combination with calcium, selective estrogen receptor modulators, strontium ranelate, teriparatide or denosumab) were identified in each calendar year. Initiation of any AOM in a calendar year was defined by the absence of a prescription for any AOM within the 2 previous calendar years. Incidence was calculated for all AOM prescriptions and initial prescriptions for AOM. RESULTS: Marked changes were observed in the rates of women receiving any AOM, with a slight increase from 2007 to 2009 (from 10.22 to 10.42 per 100 patient-years [PY]), then a plateau in 2009-2010, followed by a rapid and more than twofold decrease until 2016 (from 10.39 to 5.02 per 100 PY). The decrease in the overall rate of women initiating an AOM showed a rapid halving from 2007 to 2012 (from 2.56 to 1.15 per 100 PY), followed by a plateau in the range of 0.90-1.0 per 100 PY during the period 2013-2016. In contrast, the use of calcium/vitamin D has been rapidly increasing as the only prevention and exclusive intervention for postmenopausal osteoporosis, from 10.6% of women in 2007 to 47.7% in 2016. The profile of patients initiating AOM changed substantially over the 10-year period. Despite a stable mean age of approximately 69 years, an increasing proportion of women with severe chronic comorbidities (from 34.9% to 43.3%), history of fractures (from 7.8% to 13.3%) or high-dose steroid use (from 2.9% to 8.4%) was observed. The decline of AOM initiation was associated with a marked reduction of prescriptions during the study period: by 64.2% for primary care physicians; by 36.7% for specialty doctors; and by 18.4% for rheumatologists. CONCLUSION: These findings suggest a general trend toward an AOM uptake that is increasingly limited to a fraction of patients who are at high risk of fractures. In the context of an aging population and declining prescription rates for AOM, these data highlight an increasing treatment gap among women in France with osteoporosis, which is similar to that seen in other European countries and in the USA.

A Randomized Trial of Fulvestrant, Everolimus, and Anastrozole for the Front-line Treatment of Patients with Advanced Hormone Receptor-positive Breast Cancer, SWOG S1222.

PURPOSE: Metastatic hormone receptor (HR)-positive, HER2-negative breast cancer is an important cause of cancer mortality. Endocrine treatment with or without additional targeted therapies has been the mainstay of treatment. This trial was designed to evaluate the combination of fulvestrant plus everolimus versus fulvestrant, everolimus, and anastrozole compared with fulvestrant alone in the first-line treatment of advanced HR-positive, HER2-negative breast cancer. PATIENTS AND METHODS: This randomized placebo-controlled trial included postmenopausal women with HR-positive, HER2-negative advanced breast cancer who had received no prior systemic therapy for metastatic disease. Participants were randomized to one of three treatment arms and the primary outcome was progression-free survival (PFS), comparing combinations of fulvestrant and everolimus with or without anastrozole with fulvestrant alone. Circulating tumor cells (CTC), as measured with two different methods, and circulating tumor DNA (ctDNA) were evaluated serially prior to treatment and the beginning of the second cycle of therapy. RESULTS: Due in part to changes in clinical practice, the study was closed after accruing only 37 participants. There was no evidence that everolimus-containing combination treatment improved PFS or overall survival relative to fulvestrant alone. When modeled continuously, an association was observed of baseline CTC and ctDNA with poorer survival. CONCLUSIONS: Although power of the study was limited, the findings were unable to support the routine use of everolimus combination endocrine therapy in the first-line treatment of advanced hormone-sensitive breast cancer. Prognostic impact of baseline ctDNA and copy-number variations in CTC was demonstrated.

21-Gene Assay to Inform Chemotherapy Benefit in Node-Positive Breast Cancer.

BACKGROUND: The recurrence score based on the 21-gene breast-cancer assay has been clinically useful in predicting a chemotherapy benefit in hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, axillary lymph-node-negative breast cancer. In women with positive lymph-node disease, the role of the recurrence score with respect to predicting a benefit of adjuvant chemotherapy is unclear. METHODS: In a prospective trial, we randomly assigned women with hormone-receptor-positive, HER2-negative breast cancer, one to three positive axillary lymph nodes, and a recurrence score of 25 or lower (scores range from 0 to 100, with higher scores indicating a worse prognosis) to endocrine therapy only or to chemotherapy plus endocrine (chemoendocrine) therapy. The primary objective was to determine the effect of chemotherapy on invasive disease-free survival and whether the effect was influenced by the recurrence score. Secondary end points included distant relapse-free survival. RESULTS: A total of 5083 women (33.2% premenopausal and 66.8% postmenopausal) underwent randomization, and 5018 participated in the trial. At the prespecified third interim analysis, the chemotherapy benefit with respect to increasing invasive disease-free survival differed according to menopausal status (P = 0.008 for the comparison of chemotherapy benefit in premenopausal and postmenopausal participants), and separate prespecified analyses were conducted. Among postmenopausal women, invasive disease-free survival at 5 years was 91.9% in the endocrine-only group and 91.3% in the chemoendocrine group, with no chemotherapy benefit (hazard ratio for invasive disease recurrence, new primary cancer [breast cancer or another type], or death, 1.02; 95% confidence interval [CI], 0.82 to 1.26; P = 0.89). Among premenopausal women, invasive disease-free survival at 5 years was 89.0% with endocrine-only therapy and 93.9% with chemoendocrine therapy (hazard ratio, 0.60; 95% CI, 0.43 to 0.83; P = 0.002), with a similar increase in distant relapse-free survival (hazard ratio, 0.58; 95% CI, 0.39 to 0.87; P = 0.009). The relative chemotherapy benefit did not increase as the recurrence score increased. CONCLUSIONS: Among premenopausal women with one to three positive lymph nodes and a recurrence score of 25 or lower, those who received chemoendocrine therapy had longer invasive disease-free survival and distant relapse-free survival than those who received endocrine-only therapy, whereas postmenopausal women with similar characteristics did not benefit from adjuvant chemotherapy. (Funded by the National Cancer Institute and others; RxPONDER ClinicalTrials.gov number, NCT01272037.).

Impact of a health literacy intervention combining general practitioner training and a consumer facing intervention to improve colorectal cancer screening in underserved areas: protocol for a multicentric cluster randomized controlled trial.

BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer burden worldwide. In France, it is the second most common cause of cancer death after lung cancer. Systematic uptake of CRC screening can improve survival rates. However, people with limited health literacy (HL) and lower socioeconomic position rarely participate. Our aim is to assess the impact of an intervention combining HL and CRC screening training for general practitioners (GPs) with a pictorial brochure and video targeting eligible patients, to increase CRC screening and other secondary outcomes, after 1 year, in several underserved geographic areas in France. METHODS: We will use a two-arm multicentric randomized controlled cluster trial with 32 GPs primarily serving underserved populations across four regions in France with 1024 patients recruited. GPs practicing in underserved areas (identified using the European Deprivation Index) will be block-randomized to: 1) a combined intervention (HL and CRC training + brochure and video for eligible patients), or 2) usual care. Patients will be included if they are between 50 and 74 years old, eligible for CRC screening, and present to recruited GPs. The primary outcome is CRC screening uptake after 1 year. Secondary outcomes include increasing knowledge and patient activation. After trial recruitment, we will conduct semi-structured interviews with up to 24 GPs (up to 8 in each region) and up to 48 patients (6 to 12 per region) based on data saturation. We will explore strategies that promote the intervention's sustained use and rapid implementation using Normalization Process Theory. We will follow a community-based participatory research approach throughout the trial. For the analyses, we will adopt a regression framework for all quantitative data. We will also use exploratory mediation analyses. We will analyze all qualitative data using a framework analysis guided by Normalization Process Theory. DISCUSSION: Limited HL and its impact on the general population is a growing public health and policy challenge worldwide. It has received limited attention in France. A combined HL intervention could reduce disparities in CRC screening, increase screening rates among the most vulnerable populations, and increase knowledge and activation (beneficial in the context of repeated screening). TRIAL REGISTRATION: Registry: ClinicalTrials.gov. TRIAL REGISTRATION NUMBER: 2020-A01687-32 . Date of registration: 17th November 2020.

A randomized, placebo-controlled phase 2 study of paclitaxel in combination with reparixin compared to paclitaxel alone as front-line therapy for metastatic triple-negative breast cancer (fRida).

PURPOSE: CXCR1, one of the receptors for CXCL8, has been identified as a druggable target on breast cancer cancer stem cells (CSC). Reparixin (R), an investigational oral inhibitor of CXCR1, was safely administered to metastatic breast cancer patients in combination with paclitaxel (P) and appeared to reduce CSC in a window-of-opportunity trial in operable breast cancer. The fRida trial (NCT02370238) evaluated the addition of R to weekly as first-line therapy for metastatic (m) TNBC. SUBJECTS AND METHODS: Subjects with untreated mTNBC were randomized 1:1 to R or placebo days 1-21 in combination with weekly P 80 mg/m2 on days 1, 8, 15 of 28-day cycles. The primary endpoint was PFS by central review. RESULTS: 123 subjects were randomized (62 to R + P and 61 to placebo + P). PFS was not different between the 2 groups (median 5.5 and 5.6 months for R + P and placebo + P, respectively; HR 1.13, p = 0.5996). ALDH+ and CD24-/CD44+ CSC centrally evaluated by IHC were found in 16 and 34 of the 54 subjects who provided a metastatic tissue biopsy at study entry. Serious adverse events (21.3 and 20% of subjects) and grade ≥ 3 adverse reactions (ADR) (9.1 and 6.3% of all ADRs) occurred at similar frequency in both groups. CONCLUSION: fRida is the first randomized, double-blind clinical trial of a CSC-targeting agent in combination with chemotherapy in breast cancer. The primary endpoint of prolonged PFS was not met. CLINICAL TRIAL REGISTRATION/DATE OF REGISTRATION: NCT01861054/February 24, 2015.

Development and Validation of a Predictive Model of Hypovitaminosis D in General Adult Population: SCOPYD Study.

The worldwide global increase in serum 25-hydroxyvitamin D (25(OH)D) measurements has led some countries to restrict reimbursement for certain clinical situations only. Another approach could consist in providing physicians with screening tools in order to better target blood test prescription. The objective of the SCOPYD study was to identify the best combination of predictors of serum VitD concentration among adults aged 18-70 years. Potential risk factors for VitD deficiency were collected using a comprehensive self-administered questionnaire. A multivariable linear regression was used to build a predictive model of serum 25(OH)D concentration. Among 2488 participants, 1080 (43.4%) had VitD deficiency (<50 nmol/L) and 195 (7.8%) had severe deficiency (<25 nmol/L). The final model included sunlight exposure in the preceding week and during the last holidays, month of blood sampling, age, sex, body mass index, skin phototype, employment, smoking, sport practice, latitude, and VitD supplementation in preceding year. The area under the curve was 0.82 (95% CI (0.78; 0.85)) for severe deficiency. The model predicted severe deficiency with a sensitivity of 77.9% (95% CI (69.1; 85.7)) and a specificity of 68.3% (95% CI (64.8; 71.9)). We identified a set of predictors of severe VitD deficiency that are easy to collect in routine that may help to better target patients for serum 25(OH)D concentration determination.

Improving the delivery of team-based survivorship care after primary breast cancer treatment through a multi-level intervention: a pilot randomized controlled trial.

PURPOSE: We developed and tested a multi-level intervention, ConnectedCancerCare (CCC), which includes a tailored website and appointment reminder system for women with early-stage breast cancer and a provider summary letter sent to their medical oncologist and primary care provider to improve the delivery of team-based survivorship care. METHODS: We conducted a pilot randomized controlled trial to establish the feasibility and acceptability of CCC. Women diagnosed with stages 0-II breast cancer within one year of completing primary treatment were randomized to CCC (intervention) or a static online survivorship care plan (control). Participants completed baseline and 3-month follow-up surveys online. Post-trial interviews with 5 PCPs, 6 oncology providers, and 8 intervention patients were conducted. RESULTS: Of the 160 eligible women invited to participate, 66 completed the baseline survey and were randomized (41%) and 54 completed a follow-up survey (83%). Participants in the intervention arm found the CCC content to be acceptable, with 82% reporting it was easy to use and 86% reporting they would recommend it to other patients. Women randomized to CCC (vs. control) more often reported scheduling a PCP follow-up visit (64% vs. 42%), communicating with their PCP about provider roles (67% vs. 18%), and higher mean team-based cancer care knowledge scores (3.7 vs. 3.4). CONCLUSION: Deploying CCC in medical oncology practices was feasible, and the intervention content was acceptable. CCC shows promise for improving patient knowledge and patient-provider communication about provider roles in team-based cancer care and encouraging patients to engage with their PCP early in the survivorship period.

Assessment of Clinical Benefit of Integrative Genomic Profiling in Advanced Solid Tumors.

IMPORTANCE: Use of next-generation sequencing (NGS) to identify clinically actionable genomic targets has been incorporated into routine clinical practice in the management of advanced solid tumors; however, the clinical utility of this testing remains uncertain. OBJECTIVE: To determine which patients derived the greatest degree of clinical benefit from NGS profiling. DESIGN, SETTING, AND PARTICIPANTS: Patients in this cohort study underwent fresh tumor biopsy and blood sample collection for genomic profiling of paired tumor and normal DNA (whole-exome or targeted-exome capture with analysis of 1700 genes) and tumor transcriptome (RNA) sequencing. Somatic and germline genomic alterations were annotated and classified according to degree of clinical actionability. Results were returned to treating oncologists. Data were collected from May 1, 2011, to February 28, 2018, and analyzed from May 1, 2011, to April 30, 2020. MAIN OUTCOMES AND MEASURES: Patients' subsequent therapy and treatment response were extracted from the medical record to determine clinical benefit rate from NGS-directed therapy at 6 months and exceptional responses lasting 12 months or longer. RESULTS: During the study period, NGS was attempted on tumors from 1138 patients and was successful in 1015 (89.2%) (MET1000 cohort) (538 men [53.0%]; mean [SD] age, 57.7 [13.3] years). Potentially clinically actionable genomic alterations were discovered in 817 patients (80.5%). Of these, 132 patients (16.2%) received sequencing-directed therapy, and 49 had clinical benefit (37.1%). Exceptional responses were observed in 26 patients (19.7% of treated patients). Pathogenic germline variants (PGVs) were identified in 160 patients (15.8% of cohort), including 49 PGVs (4.8% of cohort) with therapeutic relevance. For 55 patients with carcinoma of unknown primary origin, NGS identified the primary site in 28 (50.9%), and sequencing-directed therapy in 13 patients resulted in clinical benefit in 7 instances (53.8%), including 5 exceptional responses. CONCLUSIONS AND RELEVANCE: The high rate of therapeutically relevant PGVs identified across diverse cancer types supports a recommendation for directed germline testing in all patients with advanced cancer. The high frequency of therapeutically relevant somatic and germline findings in patients with carcinoma of unknown primary origin and other rare cancers supports the use of comprehensive NGS profiling as a component of standard of care for these disease entities.

Diagnostic yield of esophagogastroduodenoscopy in France.

BACKGROUND AND STUDY AIMS: Large scale data on esophagogastroduodenoscopy (EGD) in Western countries are scarce. We conducted a prospective study on the diagnostic yield of upper gastrointestinal endoscopy in France. PATIENTS AND METHODS: An online questionnaire was sent to all French gastroenterologists practicing endoscopy. Data from EGDs performed during one week were collected. A statistical extrapolation of the results to a whole year was performed. RESULTS: 342 gastrointestinal endoscopists, representative of the population of French gastroenterologists, provided data on 2735 EGDs, corresponding to 1 006 316 (95%CI=937 080-1 075 552) procedures for the entire year. 1770 (64.7%) EGDs were performed under sedation or general anesthesia, and 930 (34%) were associated with a colonoscopy. 896 (32.8%) EGDs were normal. Hiatal hernia and esophagitis were the most frequent esophageal diagnoses, in 496 (18.1%) and 374 (13.7%) cases, respectively. Barrett's esophagus was diagnosed in 109 (4%) patients. Among gastric lesions, endoscopic gastritis was reported in 572 (20.9%) patients; ulcer, polyps, and suspected malignancy in 78 (2.9%), 62 (2.3%), and 19 (0.7%), respectively. 1597 (58.4%) EGDs included mucosal biopsies, and 141 (5.1%) were associated with a therapeutic procedure. CONCLUSIONS: We report nationwide prospective data on upper gastrointestinal endoscopy practice in France. Our data suggest that about 300 000 normal EGDs each year in France could potentially be avoided by a diagnostic strategy relying on upper GI capsule endoscopy, providing significant relief on healthcare practitioners.

The Effects of Foot Reflexology on Chemotherapy-Induced Nausea and Vomiting in Patients with Digestive System or Lung Cancer: Protocol for a Randomized Controlled Trial.

BACKGROUND: The side effects of chemotherapy, specifically chemotherapy-induced nausea and vomiting, are a concern for patients. To relieve these side effects, antiemetic drugs are recommended. However, some patients report that these drugs are not sufficiently effective. Moreover, patients with chronic disease, including cancer, are increasingly interested in complementary and alternative medicines, and express the desire for nonpharmacological treatments to be used in hospitals. Foot reflexology is a holistic approach that is reported to significantly reduce the severity of chemotherapy-induced nausea and vomiting in patients with breast cancer. Some of the chemotherapy treatments for patients with lung and digestive system cancer are moderately or highly emetic. OBJECTIVE: The primary objective of this study is to assess the benefits of foot reflexology, together with conventional treatments, on the severity and frequency of chemotherapy-induced nausea and vomiting in patients with lung or digestive system cancer. The secondary objectives to be assessed are quality of life, anxiety, and self-esteem. METHODS: This study is an open-label randomized controlled trial conducted over 22 months (18 months intervention and 4 months follow-up). Eligible participants are patients with a lung or digestive system cancer with an indication for platinum-based chemotherapy. Participants are randomized into two groups: conventional care with foot reflexology and conventional care without foot reflexology. Foot reflexology sessions (30 minutes) are performed on an outpatient or inpatient basis. It was estimated that 40 participants per group will be required. The benefits of foot reflexology will be assessed by comparing the relative change in the severity of nausea and vomiting, as assessed by a visual analogue scale, and the frequency of these side effects between the two groups. The secondary objectives will be assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire; Hospital and Anxiety Depression Scale; and Body Image Questionnaire. RESULTS: This study was approved by the regional ethics committee (Île de France X CPP) on April 3, 2018 (No. ID RCB 2018-A00571-54). Enrollment started in June 2018. Data analysis will be performed during the second quarter of 2020 and results will be published in the last quarter of 2020. CONCLUSIONS: The lack of knowledge regarding the efficacy and safety of foot reflexology limits oncologists to recommend it for this use. This study will provide evidence of the benefits of foot reflexology. If efficacy is confirmed, foot reflexology may be a promising complement to conventional antiemetic drugs. TRIAL REGISTRATION: Clinicaltrials.gov NCT03508180; https://www.clinicaltrials.gov/ct2/show/NCT03508180. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/17232.

Behavior Change Content, Understandability, and Actionability of Chronic Condition Self-Management Apps Available in France: Systematic Search and Evaluation.

BACKGROUND: The quality of life of people living with chronic conditions is highly dependent on self-management behaviors. Mobile health (mHealth) apps could facilitate self-management and thus help improve population health. To achieve their potential, apps need to target specific behaviors with appropriate techniques that support change and do so in a way that allows users to understand and act upon the content with which they interact. OBJECTIVE: Our objective was to identify apps targeted toward the self-management of chronic conditions and that are available in France. We aimed to examine what target behaviors and behavior change techniques (BCTs) they include, their level of understandability and actionability, and the associations between these characteristics. METHODS: We extracted data from the Google Play store on apps labelled as Top in the Medicine category. We also extracted data on apps that were found through 12 popular terms (ie, keywords) for the four most common chronic condition groups-cardiovascular diseases, cancers, respiratory diseases, and diabetes-along with apps identified through a literature search. We selected and downloaded native Android apps available in French for the self-management of any chronic condition in one of the four groups and extracted background characteristics (eg, stars and number of ratings), coded the presence of target behaviors and BCTs using the BCT taxonomy, and coded the understandability and actionability of apps using the Patient Education Material Assessment Tool for audiovisual materials (PEMAT-A/V). We performed descriptive statistics and bivariate statistical tests. RESULTS: A total of 44 distinct native apps were available for download in France and in French: 39 (89%) were found via the Google Play store and 5 (11%) were found via literature search. A total of 19 (43%) apps were for diabetes, 10 for cardiovascular diseases (23%), 8 for more than one condition in the four groups (18%), 6 for respiratory diseases (14%), and 1 for cancer (2%). The median number of target behaviors per app was 2 (range 0-7) and of BCTs per app was 3 (range 0-12). The most common BCT was self-monitoring of outcome(s) of behavior (31 apps), while the most common target behavior was tracking symptoms (30 apps). The median level of understandability was 42% and of actionability was 0%. Apps with more target behaviors and more BCTs were also more understandable (ρ=.31, P=.04 and ρ=.35, P=.02, respectively), but were not significantly more actionable (ρ=.24, P=.12 and ρ=.29, P=.054, respectively). CONCLUSIONS: These apps target few behaviors and include few BCTs, limiting their potential for behavior change. While content is moderately understandable, clear instructions on when and how to act are uncommon. Developers need to work closely with health professionals, users, and behavior change experts to improve content and format so apps can better support patients in coping with chronic conditions. Developers may use these criteria for assessing content and format to guide app development and evaluation of app performance. TRIAL REGISTRATION: PROSPERO CRD42018094012; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=94012.

The international St-aging system as a prognostic marker in general senior population: Findings from the EPIDOS cohort study.

The International Staging System (ISS) -calculated from serum albumin and beta-2 microglobulin (ß2m)- is an established prognostic marker in multiple myeloma (MM), which has also been suggested to account for survival among general senior population. Our objective was to examine long-term survival of older women free of MM according to baseline ISS. The study included 230 community-dwelling healthy older women without known MM from the EPIDOS cohort (mean ±â€¯SD, 80.4 ±â€¯3.4 years). Serum albumin and ß2m were measured at baseline, and used to calculate the ISS a posteriori. Abnormal ISS was defined as ISS = 2 or ISS = 3, although ISS = 1 was considered normal. The vital status was sought after a mean follow-up of 17.6 ±â€¯0.2 years (range, 16.8-18.3). Age, body mass index, mean arterial pressure, diabetes mellitus, hypertension, coronary heart disease, stroke, use corticosteroids, number of drugs daily taken, smoking, physical activity, fall history, bone mineral density, and creatinine clearance were used as potential confounders. All participants died during the 17-year follow-up. Compared to women with normal ISS, those with abnormal ISS (n = 24) had shorter survival time (4.9 ±â€¯4.3 versus 8.7 ±â€¯5.2 years, P = .001) and died earlier (85.6 ±â€¯4.8 versus 89.1 ±â€¯5.6 years old, P = .003). Survival time after blood test correlated with both serum albumin (r = 0.16, P = .015) and ß2m (r = -0.27, P < .001). Cox regression revealed that abnormal ISS was associated with mortality (adjusted HR = 3.03, P < .001). Kaplan-Meier distributions showed that participants with abnormal ISS died earlier than those with normal ISS (log-rank P < .001). In conclusion, community-dwelling older women with abnormal ISS had shorter survival time than the others, suggesting that ISS could be considered as a universal prognostic "aging system" rather than a specific MM "staging system".

Cardiovascular safety of tocilizumab: A systematic review and network meta-analysis.

OBJECTIVES: Our objective was to compare the cardiovascular safety of tocilizumab and other biological disease-modifying antirheumatic drugs (bDMARD) in rheumatoid arthritis using a network meta-analysis (NMA). METHODS: A systematic literature search through May 2018 identified randomized controlled trials (RCT) or observational studies (cohort only) reporting cardiovascular outcomes of tocilizumab (TCZ) and/or abatacept (ABA) and/or rituximab (RTX) and/or tumor necrosis factor inhibitors (TNFi) in rheumatoid arthritis patients. The composite primary outcome was the rate of major adverse cardiovascular outcomes (MACE, myocardial infarction (MI), peripheral artery disease (PAD) and cardiac heart failure (CHF)). RESULTS: 19 studies were included in the NMA, including 11 RCTs and 8 cohort studies. We found less events with RTX (5.41 [1.70;17.26]. We found no difference between TCZ and other treatments. Concerning MI, we found no difference between TCZ and csDMARD (4.23 [0.22;80.64]), no difference between TCZ and TNFi (2.00 [0.18;21.84]). There was no difference between TCZ and csDMARD (1.51[0.02;103.50] and between TCZ and TNFi (1.00 [0.06;15.85]) for stroke event. With cohorts and RCT NMA, we found no difference between TCZ and other treatments for MACE (0.66 [0.42;1.03] with ABA, 1.04 [0.60;1.81] with RTX, 0.78[0.53;1.16] and 0.91 [0.54;1.51] with csDMARD), but the risk of myocardial infarction was lower with TCZ compared to ABA (0.67 [0.47;0.97]). We lacked data to compare TCZ and other bDMARD for stoke and MI. Not enough data was available to perform a NMA for CHF and PAD. CONCLUSIONS: Despite an increase in cholesterol levels, TCZ has safe cardiovascular outcomes compared to other bDMARD.

Inequalities in Financial Distress, Symptoms, and Quality of Life Among Patients with Advanced Cancer in France and the U.S.

BACKGROUND: Financial distress (FD) is common among patients with advanced cancer. Our purpose was to compare the frequency and intensity of FD and its associations with symptom distress and quality of life (QOL) in these patients in France and the U.S. MATERIALS AND METHODS: In this secondary analysis of two cross-sectional studies, we assessed data on 292 patients who received cancer care at a public hospital or a comprehensive cancer center in France (143 patients) or the U.S. (149 patients). Outpatients and hospitalized patients over 18 years of age with advanced lung or breast or colorectal or prostate cancer were included. Diagnosed cognitive disorder was considered a noninclusion criterion. Advanced cancer included relapse or metastasis or locally advanced cancer or at least a second-line chemotherapy regimen. Patients self-rated FD and assessed symptoms, psychosocial distress, and QOL on validated questionnaires. RESULTS: The average patient age was 59 years, and 144 (49%) were female. FD and high intensity were reported more frequently in U.S. patients than in French (respectively 129 [88%] vs. 74 [52%], p < .001; 100 [98%] vs. 48 [34%], p < .001,). QOL was rated higher by the U.S. patients than by the French (69 [SD, 18] vs. 63 [SD, 18], p = .003). French patients had more psychological symptoms such as anxiety (8 [SD, 4] vs. 6 [SD, 5], p = .008). Associations were found between FD and U.S. residence, FD and single status (0.907, p = .023), and FD and metastasis (1.538, p = .036). In contrast, negative associations were found between FD and older age (-0.052, p = .003) and FD and France residence (-3.376, p = .001). CONCLUSION: Regardless of health care system, FD is frequent in patients with advanced cancer. U.S. patients were more likely to have FD than French patients but reported better QOL. Further research should focus on factors contributing to FD and opportunities for remediation. IMPLICATIONS FOR PRACTICE: Suffering is experienced in any component of the lives of patients with a life-threatening illness. Financial distress (FD) is one of the least explored cancer-related symptoms, and there are limited studies describing its impact on this frail population. This study highlights the high frequency and severity of FD in patients with advanced cancer in the U.S. and France as well as its impact on their physical and emotional symptoms and their quality of life in these different health care systems. It is necessary for all health care providers to explore and evaluate the presence of FD in patients living with life-threatening illnesses.