Olaparib plus bevacizumab first-line maintenance in ovarian cancer: final overall survival results from the PAOLA-1/ENGOT-ov25 trial.

BACKGROUND: In the PAOLA-1/ENGOT-ov25 primary analysis, maintenance olaparib plus bevacizumab demonstrated a significant progression-free survival (PFS) benefit in newly diagnosed advanced ovarian cancer patients in clinical response after first-line platinum-based chemotherapy plus bevacizumab, irrespective of surgical status. Prespecified, exploratory analyses by molecular biomarker status showed substantial benefit in patients with a BRCA1/BRCA2 mutation (BRCAm) or homologous recombination deficiency (HRD; BRCAm and/or genomic instability). We report the prespecified final overall survival (OS) analysis, including analyses by HRD status. PATIENTS AND METHODS: Patients were randomized 2 : 1 to olaparib (300 mg twice daily; up to 24 months) plus bevacizumab (15 mg/kg every 3 weeks; 15 months total) or placebo plus bevacizumab. Analysis of OS, a key secondary endpoint in hierarchical testing, was planned for ∼60% maturity or 3 years after the primary analysis. RESULTS: After median follow-up of 61.7 and 61.9 months in the olaparib and placebo arms, respectively, median OS was 56.5 versus 51.6 months in the intention-to-treat population [hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.76-1.12; P = 0.4118]. Subsequent poly(ADP-ribose) polymerase inhibitor therapy was received by 105 (19.6%) olaparib patients versus 123 (45.7%) placebo patients. In the HRD-positive population, OS was longer with olaparib plus bevacizumab (HR 0.62, 95% CI 0.45-0.85; 5-year OS rate, 65.5% versus 48.4%); at 5 years, updated PFS also showed a higher proportion of olaparib plus bevacizumab patients without relapse (HR 0.41, 95% CI 0.32-0.54; 5-year PFS rate, 46.1% versus 19.2%). Myelodysplastic syndrome, acute myeloid leukemia, aplastic anemia, and new primary malignancy incidence remained low and balanced between arms. CONCLUSIONS: Olaparib plus bevacizumab provided clinically meaningful OS improvement for first-line patients with HRD-positive ovarian cancer. These prespecified exploratory analyses demonstrated improvement despite a high proportion of patients in the placebo arm receiving poly(ADP-ribose) polymerase inhibitors after progression, confirming the combination as one of the standards of care in this setting with the potential to enhance cure.

Vemurafenib in non-small-cell lung cancer patients with BRAFV600 and BRAFnonV600 mutations.

BACKGROUND: BRAF mutations occurring in 1%-5% of patients with non-small-cell lung cancer (NSCLC) are therapeutic targets for these cancers but the impact of the exact mutation on clinical activity is unclear. The French National Cancer Institute (INCA) launched the AcSé vemurafenib trial to assess the efficacy and safety of vemurafenib in cancers with various BRAF mutations. We herein report the results of the NSCLC cohort. PATIENTS AND METHODS: Tumour samples were screened for BRAF mutations in INCA-certified molecular genetic centres. Patients with BRAF-mutated tumours progressing after ≥1 line of treatment were proposed vemurafenib 960 mg twice daily. Between October 2014 and July 2018, 118 patients were enrolled in the NSCLC cohort. The primary outcome was the objective response rate (ORR) assessed every 8 weeks (RECIST v1.1). A sequential Bayesian approach was planned with an inefficacy bound of 10% for ORR. If no early stopping occurred, the treatment was of interest if the estimated ORR was ≥30% with a 90% probability. Secondary outcomes were tolerance, response duration, progression-free survival (PFS), and overall survival (OS). RESULTS: Of the 118 patients enrolled, 101 presented with a BRAFV600 mutation and 17 with BRAFnonV600 mutations; the median follow-up was 23.9 months. In the BRAFnonV600 cohort, no objective response was observed and this cohort was stopped. In the BRAFV600 cohort, 43/96 patients had objective responses. The mean Bayesian estimated success rate was 44.9% [95% confidence intervals (CI) 35.2%-54.8%]. The ORR had a 99.9% probability of being ≥30%. Median response duration was 6.4 months, median PFS was 5.2 months (95% CI 3.8-6.8), and OS was 10 months (95% CI 6.8-15.7). The vemurafenib safety profile was consistent with previous publications. CONCLUSION: Routine biomarker screening of NSCLC should include BRAFV600 mutations. Vemurafenib monotherapy is effective for treating patients with BRAFV600-mutated NSCLC but not those with BRAFnonV600 mutations. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02304809.

A phase III trial of exemestane plus bevacizumab maintenance therapy in patients with metastatic breast cancer after first-line taxane and bevacizumab: a GINECO group study.

BACKGROUND: Maintenance strategies beyond response or tumor stabilization with first-line chemotherapy in metastatic breast cancer (MBC) have not been extensively studied. Endocrine therapy combined with continued bevacizumab may be a helpful option for estrogen receptor (ER)-positive MBC. PATIENTS AND METHODS: In this prospective, open-label, phase III study, patients with histologically confirmed ER-positive, HER2-negative MBC and non-progressive disease after 16-24 weeks of taxane plus bevacizumab (T + BEV) were randomized to continuation of T + BEV or maintenance bevacizumab plus exemestane (E + BEV). The primary end point was progression-free survival (PFS) from randomization. To have 80% power to detect an improvement in the 6-month PFS rate (PFS6m) from 50% to 65%, 186 assessable patients were needed for a total of 141 PFS events. An interim analysis was planned after 40% of the required events. RESULTS: The interim analysis with 98 patients showed that the probability of reaching a statistically significant improvement in PFS by the end of the study was only 7%. This led the Independent Data and Monitoring Committee to recommend termination of patient enrollment. After a median of 21-month follow-up of all randomized patients (117 in total), PFS6m from randomization was 67.2% [95% confidence interval (CI) 53.6-77.7] with T + BEV and 55.2% (95% CI 41.5-66.9) with E + BEV [hazard ratio (HR): 1.0, 95% CI 0.7-1.5, P = 0.998]. Median PFS from BEV initiation was 12.5 and 12.3 months in the T + BEV and E + BEV arms, respectively. In the T + BEV arm, taxane was prematurely stopped for the majority of patients (94.9%), mainly due to toxicity (49.2%). Updated data after 35 months' median follow-up showed death rates of 44% and 55% in T + BEV and E + BEV arms, respectively. CONCLUSION: In this trial, maintenance therapy with E + BEV in ER-positive, HER2-negative MBC patients with no evidence of progression after first-line T + BEV did not achieve longer PFS compared with continuation of T + BEV. CLINICALTRIALSGOV: NCT01303679.

Translational studies within the TAMRAD randomized GINECO trial: evidence for mTORC1 activation marker as a predictive factor for everolimus efficacy in advanced breast cancer.

BACKGROUND: Everolimus is an agent frequently associated with specific toxicities. Predictive markers of efficacy are needed to help define which patients could benefit from it. The goal of this exploratory study was to identify potential predictive biomarkers in the mammalian target of rapamycin (mTOR) complex 1 (mTORC1) activation pathway using primary tumor samples collected during the phase II tamoxifen plus everolimus (TAMRAD) trial. PATIENTS AND METHODS: Tumor tissues were collected retrospectively from the TAMRAD trial. Immunohistochemistry was carried out using specific antibodies directed toward proteins that result in mTORC1 activation [canonical phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mTOR or alternative pathways]. DNA was extracted from the tumor tissue; mutation screening in the PIK3CA gene (exons 9 and 20) and the KRAS gene (exons 2 and 3) was first carried out using Sanger direct sequencing, and then completed by next-generation sequencing for PIK3CA. An exploratory analysis of everolimus efficacy in terms of a time-to-progression (TTP) increase was carried out in each biomarker subgroup (high versus low expression referring to the median percentage of marked cells). RESULTS: A total of 55 primary tumor samples from the TAMRAD trial­25 from the tamoxifen-alone group and 30 from the tamoxifen/everolimus group­were evaluated for biomarkers. The subgroups most likely to have an improvement in TTP with tamoxifen/everolimus therapy, compared with tamoxifen alone, were patients with high p4EBP1, low 4EBP1, low liver kinase B1, low pAkt, and low PI3K. Among the 45 samples screened for mutation status, nine samples (20%; 95% CI 9.6-34.6) had a PIK3CA mutation. KRAS mutation was observed in one patient. CONCLUSIONS: A positive correlation between late effectors of mTORC1 activation, a positive correlation between Akt-independent mTORC1 activation, and an inverse correlation between canonical PI3K/Akt/mTOR pathway and everolimus efficacy were observed in this exploratory analysis. However, these correlations need to be validated in larger studies before applying the findings to routine clinical practice.

ELYPSE-7: a randomized placebo-controlled phase IIa trial with CYT107 exploring the restoration of CD4+ lymphocyte count in lymphopenic metastatic breast cancer patients.

BACKGROUND: Lymphopenia is a predictive factor for hematological toxicity, progression and early death in advanced cancers including metastatic breast cancer (MBC). CYT107 is a recombinant interleukin 7 (IL-7) (Cytheris, now Revimmune), well tolerated and able to expand lymphocyte pool in humans. The aims of this study were to determine the optimal schedule to deliver CYT107 and to assess its effect on clinical end points. PATIENT AND METHODS: This placebo-controlled, double blind, phase IIa was conducted in MBC patients with <1500/µl lymphocytes treated with capecitabine. Using a 2-by-2 factorial design, 20 patients were randomly allocated to four arms to receive (i) before chemotherapy: CYT107 or placebo; then (ii) during chemotherapy: CYT107 or placebo. The primary end point was CD4+ count changes before and during chemotherapy. Secondary end points were hematological toxicity, safety, overall response, progression-free survival (PFS) and overall survival (OS). Quantification and functional competence of circulating immune cells were also assessed. RESULTS: When administered before chemotherapy, CYT107 induced a significant increase of CD4+ [+148.1% in CYT107 versus +9.9% in placebo groups, (Wilcoxon, P = 0.002)] and CD8+ T-cell counts, including both naïve and memory subsets. When CYT107 was administered during chemotherapy, the magnitude of CD4+ and CD8+ increase was less important. No modulation of immune cell functional competence was observed. CYT107 was well tolerated with no related ≥grade 3 adverse events except 1 fatal suspected unexpected serious adverse reaction (SUSAR) of uncertain relationship. Of the 12 cases evaluable for response, 6 of 7 patients (86%) receiving CYT107 before chemotherapy achieved a response or stabilization, whereas two of five patients (40%) receiving placebo achieved the same result. No significant difference was observed for PFS or OS. CONCLUSION: In lymphopenic MBC, CYT107 increases CD4+ and other T-cell subset counts without altering their function. A larger clinical trial to demonstrate its impact on clinical outcome is warranted. CLINICALTRIALSGOV IDENTIFIER: NCT01362107.

Circulating tumor cells and brain metastasis outcome in patients with HER2-positive breast cancer: the LANDSCAPE trial.

BACKGROUND: Decrease of circulating tumor cells (CTC) during treatment is an independent prognostic factor in metastatic breast cancer (MBC). We specifically evaluated the impact of CTC on brain metastasis outcome. METHODS: HER2-positive MBC with brain metastasis not previously treated with whole-brain radiotherapy received first-line combination of lapatinib and capecitabine in a phase II study. CTC were detected at baseline and day 21 (CellSearch). RESULTS: Median follow-up of the 44 analyzed patients was 21.2 months. The central nervous system objective response (CNS-OR) rate was 66%. At baseline, 20 of 41 assessable patients for CTC (49%) had ≥1 CTC (range 1-301, median 3) and 9 (22%) had ≥5 CTC. At day 21, 7 of 38 patients (18%) had ≥1 CTC (P = 0.006, versus baseline), and CTC had disappeared in 11 patients. CNS-OR rate was significantly higher in patients with no CTC at day 21 [25 of 31 (80%) versus 2 of 7 (29%), P = 0.01]. The 1-year overall survival rate was 83.9% in patients with no CTC at day 21 versus 42.9% in patients with ≥1 CTC (P = 0.02). CONCLUSIONS: This is the first report showing a correlation between CNS metastasis response, outcome and early CTC clearance under targeted treatment of HER2+ MBC. CLINICAL TRIALS NUMBER: NCT00967031.

Long term activity of vemurafenib in cancers with BRAF mutations: the ACSE basket study for advanced cancers other than BRAFV600-mutated melanoma.

BACKGROUND: BRAF inhibitors are approved in BRAFV600-mutated metastatic melanoma, non-small-cell lung cancer (NSCLC), Erdheim-Chester disease (ECD), and thyroid cancer. We report here the efficacy, safety, and long-term results of single-agent vemurafenib given in the AcSé vemurafenib basket study to patients with various BRAF-mutated advanced tumours other than BRAFV600-mutated melanoma and NSCLC. PATIENTS AND METHODS: Patients with advanced tumours other than BRAFV600E melanoma and progressing after standard treatment were eligible for inclusion in nine cohorts (including a miscellaneous cohort) and received oral vemurafenib 960 mg two times daily. The primary endpoint was the objective response rate (ORR) estimated with a Bayesian design. The secondary outcomes were disease control rate, duration of response, progression-free survival (PFS), overall survival (OS), and vemurafenib safety. RESULTS: A total of 98 advanced patients with various solid or haematological cancers, 88 with BRAFV600 mutations and 10 with BRAFnonV600 mutations, were included. The median follow-up duration was 47.7 months. The Bayesian estimate of ORR was 89.7% in hairy cell leukaemias (HCLs), 33.3% in the glioblastomas cohort, 18.2% in cholangiocarcinomas, 80.0% in ECD, 50.0% in ovarian cancers, 50.0% in xanthoastrocytomas, 66.7% in gangliogliomas, and 60.0% in sarcomas. The median PFS of the whole series was 8.8 months. The 12-, 24-, and 36-month PFS rates were 42.2%, 23.8%, and 17.9%, respectively. Overall, 54 patients died with a median OS of 25.9 months, with a projected 4-year OS of 40%. Adverse events were similar to those previously reported with vemurafenib. CONCLUSION: Responses and prolonged PFS were observed in many tumours with BRAF mutations, including HCL, ECD, ovarian carcinoma, gliomas, ganglioglioma, and sarcomas. Although not all cancer types responded, vemurafenib is an agnostic oncogene therapy of cancers.

The PhaSeal® system: impact of its use on workplace contamination and duration of chemotherapy preparation.

PURPOSE: The primary objective of this study was to compare the levels of environmental contamination before and after the introduction of PhaSeal® (closed-system drug transfer device) in two hospital pharmacies. Our secondary objective was to assess the impact of the device on the duration of drug preparation compared to procedures involving the use of needles and syringes. METHODS: The study involved two French hospitals, which prepared antineoplastic chemotherapy using a biological safety cabinet and an isolator. Five skilled pharmacy technicians at each hospital prepared a total of 100 chemotherapy preparations using the standard procedure and 100 using the PhaSeal® system. To control for possible contamination occurring in the course of the procedure, we used fluorescein which becomes fluorescent when exposed to UV light. To reply the second objective, we timed the duration of the different steps of the manipulation. RESULTS: Our findings showed a major reduction in the contamination of the work environment when using the PhaSeal® system for drug preparation. Reduction rates higher than 93% were obtained, whatever the type of protection used. On the duration of preparation, our results indicate that this duration would be approximately 1 h longer for the preparation of 100 samples. CONCLUSION: In conclusion, this study clearly establishes the benefit of using PhaSeal® for protecting the staff members who work with hazardous agents. It also indicates that the duration of drug preparation is not impacted by the use of the system.

MOVIE: a phase I, open-label, multicenter study to evaluate the safety and tolerability of metronomic vinorelbine combined with durvalumab plus tremelimumab in patients with advanced solid tumors.

BACKGROUND: Anti-programmed cell death protein 1 (PD1)/programmed death-ligand 1 (PD-L1) agents have only moderate antitumor activity in some advanced solid tumors (AST), including breast cancer (BC), prostate cancer (PC), cervical cancer (CC), and head and neck cancer (HNC). Combining anti-PD-L1 with anti-cytotoxic T-lymphocyte-associated protein (CTLA) and chemotherapy may significantly improve efficacy. PATIENTS AND METHODS: MOVIE is a multicohort phase I/II study examining the combination of anti-PD-L1 durvalumab (Durv; 1500 mg IV Q4W) plus anti-CTLA tremelimumab (Trem; 75 mg IV Q4W) with metronomic vinorelbine (MVino; 20-40 mg orally daily) in various AST resistant to conventional therapies. The primary objective of the phase I part was to determine the maximum tolerated dose (MTD) and recommended dose for phase II (RP2D). RESULTS: Among the 14 patients enrolled during phase I, including 13 women and 1 man, 9 had BC, 1 PC, 2 CC, and 2 miscellaneous cancers with high mutational loads. Median age was 53 years. A total of 12 patients were assessable for the dose-escalation part in which only one dose-limiting toxicity (DLT) was observed [one neutropenia without fever, grade (G) 4]. Two (14.3%), four (28.6%), and four (28.6%) patients had G ≥3 adverse events (AEs) related to MVino, Durv, and Trem, respectively. Treatment-related events included mostly clinical AEs with asthenia (eight G2; three G3), colitis (one G2, one G3), diarrhea (one G3), nausea (two G2), dry skin (two G2), maculopapular rash (one G3), and hyperthyroidism (three G2). No toxic death was reported. Preliminary data showed one patient (CC) who presented a complete response and four patients with stable disease (SD). CONCLUSIONS: MTD was not reached and dose level 2 (MVino 40 mg, Durv 1500 mg, Trem 75 mg) was selected as RP2D. The safety profile of the combination was manageable and consistent with previous reports of Trem + Durv or MVino. Phase II is currently ongoing in BC, PC, CC, HNC, and miscellaneous cohorts.

When local phytotherapies meet biomedicine. Cross-sectional study of knowledge and intercultural practices against malaria in Eastern French Guiana.

ETHNOPHARMACOLOGICAL RELEVANCE: In French Guiana, traditional phytotherapies are an important part of self-healthcare, however, a precise understanding of the interactions between local phytotherapies and biomedicine is lacking. Malaria is still endemic in the transition area between French Guiana and Brazil, and practices of self-treatment, although difficult to detect, have possible consequences on the outcome of public health policies. AIM OF THE STUDY: The objectives of this research were 1) to document occurences of co-medication (interactions between biomedicine and local phytotherapies) against malaria around Saint-Georges de l'Oyapock (SGO), 2) to quantify and to qualify plant uses against malaria, 3) and to discuss potential effects of such co-medications, in order to improve synergy between community efforts and public health programs in SGO particularly, and in Amazonia more broadly. MATERIALS AND METHODS: This cross-sectional study was conducted in 2017 in SGO. Inhabitants of any age and nationality were interviewed using a questionnaire (122 questions) about their knowledge and habits regarding malaria, and their use of plants to prevent and treat it. They were invited to show their potential responses on a poster illustrating the most common antimalarial plants used in the area. In order to correlate plant uses and malaria epidemiology, all participants subsequently received a medical examination, and malaria detection was performed by Rapid Diagnostic Test (RDT) and Polymerase Chain Reaction (PCR). RESULTS: A total of 1566 inhabitants were included in the study. Forty-six percent of them declared that they had been infected by malaria at least once, and this rate increased with age. Every person who reported that they had had malaria also indicated that they had taken antimalarial drugs (at least for the last episode), and self-medication against malaria with pharmaceuticals was reported in 142 cases. A total of 550 plant users was recorded (35.1% of the interviewed population). Among them 95.5% associated pharmaceuticals to plants. All plants reported to treat malaria were shared by every cultural group around SGO, but three plants were primarily used by the Palikur: Cymbopogon citratus, Citrus aurantifolia and Siparuna guianensis. Two plants stand out among those used by Creoles: Eryngium foetidum and Quassia amara, although the latter is used by all groups and is by far the most cited plant by every cultural group. Cultivated species accounts for 91.3% of the use reports, while wild taxa account for only 18.4%. CONCLUSIONS: This study showed that residents of SGO in French Guiana are relying on both traditional phytotherapies and pharmaceutical drugs to treat malaria. This medical pluralism is to be understood as a form of pragmatism: people are collecting or cultivating plants for medicinal purposes, which is probably more congruent with their respective cultures and highlights the wish for a certain independence of the care process. A better consideration of these practices is thus necessary to improve public health response to malaria.

Delayed care for patients with newly diagnosed cancer due to COVID-19 and estimated impact on cancer mortality in France.

BACKGROUND: The impact of the first coronavirus disease 2019 (COVID-19) wave on cancer patient management was measured within the nationwide network of the Unicancer comprehensive cancer centers in France. PATIENTS AND METHODS: The number of patients diagnosed and treated within 17 of the 18 Unicancer centers was collected in 2020 and compared with that during the same periods between 2016 and 2019. Unicancer centers treat close to 20% of cancer patients in France yearly. The reduction in the number of patients attending the Unicancer centers was analyzed per regions and cancer types. The impact of delayed care on cancer-related deaths was calculated based on different hypotheses. RESULTS: A 6.8% decrease in patients managed within Unicancer in the first 7 months of 2020 versus 2019 was observed. This reduction reached 21% during April and May, and was not compensated in June and July, nor later until November 2020. This reduction was observed only for newly diagnosed patients, while the clinical activity for previously diagnosed patients increased by 4% similar to previous years. The reduction was more pronounced in women, in breast and prostate cancers, and for patients without metastasis. Using an estimated hazard ratio of 1.06 per month of delay in diagnosis and treatment of new patients, we calculated that the delays observed in the 5-month period from March to July 2020 may result in an excess mortality due to cancer of 1000-6000 patients in coming years. CONCLUSIONS: In this study, the delays in cancer patient management were observed only for newly diagnosed patients, more frequently in women, for breast cancer, prostate cancer, and nonmetastatic cancers. These delays may result is an excess risk of cancer-related deaths in the coming years.

Resource use associated with type 2 diabetes in Asia, Latin America, the Middle East and Africa: results from the International Diabetes Management Practices Study (IDMPS).

AIMS: To estimate diabetes-related resource use and investigate its predictors among individuals with type 2 diabetes in 24 countries in Asia, Latin America, the Middle East and Africa. METHODS: Cross-sectional observational data on diabetes-related resource use were collected from 15,016 individuals with type 2 diabetes within the second wave of International Diabetes Management Practices Study. Mean (SD) annual quantities were determined and predictors of diabetes-related hospitalisations, inpatient days, emergency room visits and absenteeism were investigated using negative binomial regression. RESULTS: Patients in Asia (n = 4678), Latin America (n = 6090) and the Middle East and Africa (n = 4248) made a mean (SD) of 3.4 (6.9), 5.4 (6.7) and 2.5 (4.4) General Practitioner visits per year. The mean (SD) number of inpatient days amounted to 3.8 (18.1), 2.2 (13.9) and 2.6 (13.5) per year. Results of the regression analysis showed the major influence of diabetes-related complications and inadequate glycaemic control on resource use. The expected annual rate of hospitalisation of patients with macrovascular complications compared with those without was 4.7 times greater in Asia [incidence rate ratio (IRR) = 4.7, 95% CI: 2.8-7.8, n = 2551], 5.4 times greater in Latin America (IRR = 5.4, 95% CI: 3.0-9.8, n = 3228) and 4.4 times greater in the Middle East and Africa (IRR = 4.4, 95% CI: 2.8-6.9, n = 2630). CONCLUSIONS: Micro- and macrovascular complications and inadequate glycaemic control are significant predictors of resource use in people with type 2 diabetes of developing countries. This knowledge confirms the health economic importance of early diagnosis of diabetes, education of patients and glycaemic control.

Inverse relationship between vertebral fractures and spine osteoarthritis in postmenopausal women with osteoporosis.

BACKGROUND: Although the coexistence of osteoarthritis and osteoporosis is considered as uncommon, it has been suggested that, in postmenopausal women, disc space narrowing increases the risk of vertebral fracture. The aim of this study was to check this hypothesis in postmenopausal women with osteoporosis. OBJECTIVE: We analysed the relationship between vertebral fractures and spine osteoarthritis in 410 postmenopausal women with osteoporosis: in this population both disc space narrowing and osteophytes are inversely related to vertebral fractures. PATIENTS AND METHODS: This study is based on baseline data collected in a multicentre, prospective and 6-month longitudinal observational study. 410 postmenopausal women (74+/-5 years) were enrolled who had consulted for back pain, and had osteoporosis (according to WHO definition). Spine x-rays were performed according to standardised procedures. Vertebral fractures were evaluated from T4 to L4 using the Genant's semiquantitative method; osteoarthritis was evaluated by scoring osteophytes and disc space narrowing at all levels of the thoracic and lumbar spine, and by a qualitative assessment of facet joint arthritis. RESULTS: The prevalence of vertebral fractures was 52.4%. At least one osteophyte, one disc space narrowing and one facet arthritis were present in 90.2, 64.6 and 77.8% of patients respectively. There was an inverse association between vertebral fractures and osteoarthritis: odds ratios adjusted for age and weight (95% CI) were 0.38 (0.17-0.86), p = 0.02 and 0.27 (0.16-0.46), p<10(-4) for the presence of at least one osteophyte, and of at least three disc space narrowings respectively. In a cluster analysis, it was possible to identify a subgroup of patients without any disc space narrowing, and another subgroup with all patients having at least one disc space narrowing; the proportion of patients having more than three vertebral fractures was 25.2 and 15.9% in these two clusters respectively. CONCLUSIONS: Disc space narrowing and osteophytes are associated with a decreased vertebral fracture prevalence in postmenopausal women with osteoporosis.

HPV vaccination among French girls and women aged 14-23 years and the relationship with their mothers' uptake of Pap smear screening: a study in general practice.

INTRODUCTION: HPV vaccination is recommended in France for girls aged 14 and for those aged 15-23 before sexual debut or who have become sexually active within the previous year. The first aim was to describe vaccination practice among 14-23-year-old girls visiting a general practitioner. A second objective was to investigate factors associated with starting vaccination among girls aged 14-18, in particular the regular practice of Pap-smear screening (PSS) by their mothers. METHODS: A cross-sectional study was conducted from June to August 2009. A total of 87 general practitioners from the large Rhône-Alpes region contributed data on 502 girls/women who came for consultation. RESULTS: 231 (46.0%) of these girls/women had begun the process of HPV vaccination (68.2%, 56.9% and 18.7% of the 14-16, 17-20 and 21-23-year-olds respectively) of whom 139 (60.2%) had received all three doses. 92 girls/women (39.8%) had received only one or two doses at the time of study. However, in 71 (77.2%) cases, the gap between the last dose received and the time of study was within the between-dose interval recommended in the vaccination schedule. GPs reported that 16 (11.5%) had mentioned side effects following injections. Having a mother who practised regular PSS (Odds Ratio 6.2 [1.5-25.8]), having never lived with a partner (4.6 [1.6-13.5]) and vaccination against hepatitis B (3.2 [1.6-6.1]) were found to be independently correlated with the initiation of HPV vaccination among girls/women aged 14-18 years. CONCLUSION: Two years after the start of the programme, only half of girls/women aged 14-23 years had begun the process of HPV vaccination. HPV vaccination status was correlated with PSS in the mother, family status and hepatitis B vaccination. Such information may help to better target girls who are less likely to be vaccinated.

Reporting of vertebral fractures on spine X-rays.

Vertebral fractures are the hallmark of osteoporosis, responsible for increased morbidity and mortality in post-menopausal women. However, two-thirds of vertebral fractures do not come to clinical attention. The aim of this study was to compare the identification of vertebral fractures on spine X-rays among rheumatologists. Study subjects were women aged 60-80 years having potential signs of vertebral fracture and visiting a rheumatologist. X-rays were performed according to standardized procedures. In 629 patients (among 824 included) at least one vertebral fracture was diagnosed, and the X-rays were then sent to a central facility where a semi-quantitative assessment of vertebral fracture was performed by a single rheumatologist trained for this evaluation. According to the vertebral level, kappa scores were between 0.20 to 0.77, i.e., below 0.6 from T4 to T7, and between 0.6 and 0.77 from T8 to L4. The false-negative fractures rate was 25.8% (and 15.7% of them were related to a numbering discrepancy). The rate of false positive fractures was 6.3%. At the patient level 6.8% had actually no fracture. This study shows that 25% of overall vertebral fractures are not diagnosed among patients considered as having at least one fracture. As a consequence, patients who require treatment to reduce fracture risk are not being properly identified.

The severity of vertebral fractures and health-related quality of life in osteoporotic postmenopausal women.

Vertebral fractures are the hallmark of osteoporosis, responsible for increased back pain, impairment of mobility and functional limitations. These factors have an impact on patients' health-related quality of life (QOL). The aim of this study was to assess QOL, using QUALEFFO, in osteoporotic postmenopausal women, according to the number and the severity of the vertebral fractures. A group of 629 osteoporotic postmenopausal women (60-80 years) with symptoms that, according to a rheumatologist, could be related to a vertebral fracture, had spine X-rays with standardized procedures. All the X-rays were assessed in a central facility. The number of fractures was a determinant of a low QOL, as indicated by an increased score in physical function (P=0.001), social function (P=0.002) and total score (P=0.027). Patients with higher grades of vertebral deformities, i.e., more severe fractures, had low QOL in these three domains, too (P<0.0001, P<0.0001 and P=0.005, respectively). There was no difference in QOL according to the thoracic or lumbar location of the fractures. Both anterior and middle deformities of the vertebral bodies had a negative impact on QOL. In none of the analyses were the pain and mental function domains of QUALEFFO discriminant among the patients. QOL, assessed by an osteoporosis-specific instrument, is decreased in osteoporotic women as a function of both the number and the severity of the vertebral fractures. Treating women with prevalent fractures may avoid a further decrease in their quality of life.