Tenosynovial Giant Cell Tumor Observational Platform Project (TOPP) Registry: A 2-Year Analysis of Patient-Reported Outcomes and Treatment Strategies.

BACKGROUND: The Tenosynovial giant cell tumor Observational Platform Project (TOPP) registry is an international prospective study that -previously described the impact of diffuse-type tenosynovial giant cell tumour (D-TGCT) on patient-reported outcomes (PROs) from a baseline snapshot. This analysis describes the impact of D-TGCT at 2-year follow-up based on treatment strategies. MATERIAL AND METHODS: TOPP was conducted at 12 sites (EU: 10; US: 2). Captured PRO measurements assessed at baseline, 1-year, and 2-year follow-ups were Brief Pain Inventory (BPI), Pain Interference, BPI Pain Severity, Worst Pain, EQ-5D-5L, Worst Stiffness, and -Patient-Reported Outcomes Measurement Information System. Treatment interventions were no current/planned treatment (Off-Treatment) and systemic treatment/surgery (On-Treatment). RESULTS: A total of 176 patients (mean age: 43.5 years) were included in the full analysis set. For patients without active treatment strategy -(Off-Treatment) at baseline (n = 79), BPI Pain Interference (1.00 vs. 2.86) and BPI Pain Severity scores (1.50 vs. 3.00) were numerically favorable in patients remaining Off-Treatment compared with those who switched to an active treatment strategy at year 1. From 1-year to 2-year -follow-ups, patients who remained Off-Treatment had better BPI Pain Interference (0.57 vs. 2.57) and Worst Pain (2.0 vs. 4.5) scores compared with patients who switched to an alternative treatment strategy. In addition, EQ-5D VAS scores (80.0 vs. 65.0) were higher in patients who remained -Off-Treatment between 1-year and 2-year follow-ups compared with patients who changed treatment strategy. For patients receiving systemic treatment at baseline, numerically favorable scores were seen in patients remaining on systemic therapy at 1-year follow-up: BPI Pain Interference (2.79 vs. 5.93), BPI Pain Severity (3.63 vs. 6.38), Worst Pain (4.5 vs. 7.5), and Worst Stiffness (4.0 vs. 7.5). From 1-year to 2-year follow-up, EQ-5D VAS scores (77.5 vs. 65.0) were higher in patients who changed from systemic treatment to a different treatment strategy. CONCLUSION: These findings highlight the impact D-TGCT has on patient quality of life, and how treatment strategies may be influenced by these outcome measures. (ClinicalTrials.gov number: NCT02948088).

An adaptive, biomarker-directed platform study of durvalumab in combination with targeted therapies in advanced urothelial cancer.

Durvalumab is a programmed death-ligand 1 (PD-L1) inhibitor with clinical activity in advanced urothelial cancer (AUC)1. AUC is characterized by several recurrent targetable genomic alterations2-5. This study ( NCT02546661 , BISCAY) combined durvalumab with relevant targeted therapies in biomarker-selected chemotherapy-refractory AUC populations including: (1) fibroblast growth factor receptor (FGFR) inhibitors in tumors with FGFR DNA alterations (FGFRm); (2) pharmacological inhibitor of the enzyme poly-ADP ribose polymerase (PARP) in tumors with and without DNA homologous recombination repair deficiency (HRRm); and (3) TORC1/2 inhibitors in tumors with DNA alteration to the mTOR/PI3K pathway3-5.This trial adopted a new, biomarker-driven, multiarm adaptive design. Safety, efficacy and relevant biomarkers were evaluated. Overall, 391 patients were screened of whom 135 were allocated to one of six study arms. Response rates (RRs) ranged 9-36% across the study arms, which did not meet efficacy criteria for further development. Overall survival (OS) and progression-free survival (PFS) were similar in the combination arms and durvalumab monotherapy arm. Biomarker analysis showed a correlation between circulating plasma-based DNA (ctDNA) and tissue for FGFRm. Sequential circulating tumor DNA analysis showed that changes to FGFRm correlated with clinical outcome. Our data support the clinical activity of FGFR inhibition and durvalumab monotherapy but do not show increased activity for any of the combinations. These findings question the targeted/immune therapy approach in AUC.

Pain Progression at Initiation of Cabazitaxel in Metastatic Castration-Resistant Prostate Cancer (mCRPC): A Post Hoc Analysis of the PROSELICA Study.

BACKGROUND: In the PROSELICA phase III trial (NCT01308580), cabazitaxel 20 mg/m2 (CABA20) was non-inferior to cabazitaxel 25 mg/m2 (CABA25) in mCRPC patients previously treated with docetaxel (DOC). The present post hoc analysis evaluates how the type of progression at randomization affected outcomes. METHODS: Progression type at randomization was defined as follows: PSA progression only (PSA-p; no radiological progression (RADIO-p), no pain), RADIO-p (±PSA-p, no pain), or pain progression (PAIN-p, ±PSA-p, ±RADIO-p). Relationships between progression type and overall survival (OS), radiological progression-free survival (rPFS), and PSA response (confirmed PSA decrease ≥ 50%) were analyzed. RESULTS: All randomized patients (n = 1200) had received prior DOC, and 25.7% had received prior abiraterone or enzalutamide. Progression type at randomization was evaluable in 1075 patients (PSA-p = 24.4%, RADIO-p = 20.8%, PAIN-p = 54.8%). Pain progression was associated with clinical and biological features of aggressive disease. Median OS from CABA initiation or date of mCRPC diagnosis, all arms combined, was shorter in the PAIN-p group than in the RADIO-p or the PSA-p groups (12.0 versus 16.8 and 18.4 months, respectively, p < 0.001). In multivariate analysis, all arms combined, PAIN-p was an independent predictor of poor OS (HR = 1.44, p < 0.001). PSA response, rPFS, and OS were numerically higher with CABA25 versus CABA20 in patients with PAIN-p. CONCLUSIONS: This post hoc analysis of the PROSELICA phase III study shows that pain progression at initiation of CABA in mCRPC patients previously treated with DOC is associated with a poor prognosis. Disease progression should be carefully monitored, even in the absence of PSA rise.

Healthcare resource utilization in patients on lipid-lowering therapies outside Western Europe and North America: findings of the cross-sectional observational International ChoLesterol management Practice Study (ICLPS).

BACKGROUND: Few recent large-scale studies have examined healthcare consumption associated with dyslipidemia in countries outside Western Europe and North America. METHODS: This analysis, from a cross-sectional observational study conducted in 18 countries in Eastern Europe, Asia, Africa, the Middle East and Latin America, evaluated avoidable healthcare consumption (defined as ≥1 hospitalization for cardiovascular reasons or ≥1 visit to the emergency room for any reason in the previous 12 months) in patients receiving stable lipid-lowering therapy (LLT). A total of 9049 patients (aged ≥18 years) receiving LLT for ≥3 months and who had had their low-density lipoprotein cholesterol (LDL-C) value measured on stable LLT in the previous 12 months were enrolled between August 2015 and August 2016. Patients who had received a proprotein convertase subtilisin/kexin type 9 inhibitor in the previous 6 months were excluded. Patients were stratified by cardiovascular risk level using the Systematic Coronary Risk Estimation chart for high-risk countries. RESULTS: The proportion of patients at their LDL-C goal was 32.1% for very-high risk patients compared with 55.7 and 51.9% for patients at moderate and high cardiovascular risk, respectively. Overall, 20.1% of patients had ≥1 reported hospitalization in the previous 12 months (7.9% for cardiovascular reasons), 35.2% had ≥1 intensive care unit stay and 13.8% visited the emergency room. Avoidable healthcare resource consumption was reported for 18.7% patients overall, and in 27.8, 7.7, 7.7 and 13.2% of patients at very-high, high, moderate and low risk, respectively. Across all risk groups 22.4% of patients not at LDL-C goal and 16.6% of patients at LDL-C goal had avoidable healthcare resource consumption. Being at very-high cardiovascular risk, having cardiovascular risk factors (including hypertension and smoking), and having factors indicating that the patient may be difficult to treat (including statin intolerance, comorbidities and chronic medication), were independent risk factors for avoidable healthcare resource consumption (all p <0.05). CONCLUSIONS: Healthcare resource consumption associated with adverse clinical outcomes was observed in patients on stable LLT in countries outside Western Europe and North America, particularly those at very-high cardiovascular risk and those who were difficult to treat.

The challenge of multiple cardiovascular risk factor control outside Western Europe: Findings from the International ChoLesterol management Practice Study.

BACKGROUND: Comprehensive control of multiple cardiovascular risk factors reduces cardiovascular risk but is difficult to achieve. DESIGN: A multinational, cross-sectional, observational study. METHODS: The International ChoLesterol management Practice Study (ICLPS) investigated achievement of European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guideline low-density lipoprotein cholesterol (LDL-C) targets in patients receiving lipid-modifying therapy in countries outside Western Europe. We examined the rate of, and association between, control of multiple risk factors in ICLPS participants with dyslipidaemia, diabetes and hypertension (N = 2377). RESULTS: Mean (standard deviation) age of patients was 61.4 (10.4) years; 51.3% were male. Type 2 diabetes was the most common form of diabetes (prevalence, 96.9%). The prevalence of metabolic syndrome was 67.8%, obesity 40.4%, atherosclerotic disease 39.6% and coronary artery disease 33.5%. All patients were at high (38.2%) or very high (61.8%) cardiovascular risk according to ESC/EAS guidelines. Body mass index (BMI) was <25 kg/m2 in 20.3% of patients, 62.8% had never smoked and 25.2% were former smokers. Overall, 12.2% achieved simultaneous control of LDL-C, diabetes and blood pressure. Risk factor control was similar across all participating countries. The proportion of patients achieving individual guideline-specified treatment targets was 43.9% for LDL-C, 55.5% for blood pressure and 39.3% for diabetes. Multiple correspondence analysis indicated that control of LDL-C, control of blood pressure, control of diabetes, BMI and smoking were associated. CONCLUSION: Comprehensive control of multiple cardiovascular risk factors in high-risk patients is suboptimal worldwide. Failure to control one risk factor is associated with poor control of other risk factors.

Impact of progression at baseline and on-treatment progression events in three large prostate cancer trials.

BACKGROUND: There is a discussion about the optimal timing to initiate or switch treatment in metastatic castration-resistant prostate cancer (mCRPC). This post hoc analysis of 3 large trials for men with mCRPC examined the influence of the type of progression at initiation of first-line chemotherapy, as well as the type of progression during treatment, on treatment outcomes. METHODS: Data from the phase III studies VENICE (n = 1224), TAX327 (n = 1006) and FIRSTANA (n = 1168) were used as independent data sets. Type of progression was defined as follows: prostate-specific antigen (PSA) only (group 1), radiological (±PSA) (group 2) or pain (±PSA, ± radiological) progression (group 3). The impact of baseline type of progression on overall survival (OS) was evaluated in multivariate Cox regression analysis with backward elimination, stratified for the Eastern Cooperative Oncology Group performance score and treatment arm. RESULTS: The median OS (arms combined) from treatment initiation in VENICE was 28.6, 26.3 and 16.9 months for G1, G2 and G3, respectively (hazard ratio: 1.14 [95% confidence interval {CI}: 0.92-1.41%] in G2 and 2.13 [95% CI: 1.75-2.59%] in G3 compared with G1). Multivariate analysis (arms combined) showed that pain progression at baseline was an independent predictor of poor OS. Similar findings were observed in the TAX327 and FIRSTANA data sets. During treatment, pain or radiological progression preceded PSA progression in ~55% of the patients. The retrospective characteristic of this study is a limitation. CONCLUSIONS: The type of progression at baseline strongly predicts OS in men with mCRPC treated with first-line chemotherapy. During treatment, pain and/or radiological progression preceded PSA progression as the first progression event in ~55% of the patients. This finding has the prospect to be incorporated in clinical guidelines and to be practice changing because it implies the need for regular imaging and not to rely on PSA progression alone.

Low-density lipoprotein cholesterol goal achievement in patients with familial hypercholesterolemia in countries outside Western Europe: The International ChoLesterol management Practice Study.

BACKGROUND: The cross-sectional observational International ChoLesterol management Practice Study study assessed achievement of European Society of Cardiology/European Atherosclerosis Society low-density lipoprotein cholesterol (LDL-C) targets in patients outside Western Europe. OBJECTIVE: The aim of the study was to assess LDL-C goal achievement in International ChoLesterol management Practice Study participants with familial hypercholesterolemia (FH). METHODS: A total of 334 patients (aged ≥18 years) with definite or probable FH (Dutch Lipid Clinic Network score ≥6; 43.1% genetically confirmed) who had been receiving stable lipid-modifying therapy (LMT) for ≥3 months were enrolled. RESULTS: The mean ± standard deviation age of the patients was 58.5 ± 13.1 years, 49.1% were male, and 48.2% had coronary artery disease. Most were receiving statin (∼99%). Of these, 57.6% were on high-intensity statin therapy, 49.1% on the highest dose available, and 13.0% used a statin together with a cholesterol absorption inhibitor (CAI). Mean ± standard deviation LDL-C level was 5.6 ± 3.0 mmol/L before LMT and 3.3 ± 2.0 mmol/L at enrollment. Overall, 32.0% of patients achieved their LDL-C target. Target achievement rates were 36.6% for patients with coronary artery disease, and 27.5% for those without, and 27.9%, 28.0%, and 37.5% for patients treated with a statin plus CAI, highest-dose statin (no CAI), and lower-dose statin (no CAI), respectively. CONCLUSIONS: LDL-C target achievement rates were low in patients with FH, even in those receiving intensive LMT. Factors that are likely to have contributed to the low LDL-C target achievement rates include high baseline LDL-C, inadequate statin dosages, and low use of CAI. Many patients would have been eligible for proprotein convertase subtilisin/kexin type 9 inhibitor therapy.

Achievement of low-density lipoprotein cholesterol goals in 18 countries outside Western Europe: The International ChoLesterol management Practice Study (ICLPS).

Background Little is known about the achievement of low density lipoprotein cholesterol (LDL-C) targets in patients at cardiovascular risk receiving stable lipid-lowering therapy (LLT) in countries outside Western Europe. Methods This cross-sectional observational study was conducted in 452 centres (August 2015-August 2016) in 18 countries in Eastern Europe, Asia, Africa, the Middle East and Latin America. Patients ( n = 9049) treated for ≥3 months with any LLT and in whom an LDL-C measurement on stable LLT was available within the previous 12 months were included. Results The mean±SD age was 60.2 ± 11.7 years, 55.0% of patients were men and the mean ± SD LDL-C value on LLT was 2.6 ± 1.3 mmol/L (101.0 ± 49.2 mg/dL). At enrolment, 97.9% of patients were receiving a statin (25.3% on high intensity treatment). Only 32.1% of the very high risk patients versus 51.9% of the high risk and 55.7% of the moderate risk patients achieved their LDL-C goals. On multivariable analysis, factors independently associated with not achieving LDL-C goals were no (versus lower dose) statin therapy, a higher (versus lower) dose of statin, statin intolerance, overweight and obesity, female sex, neurocognitive disorders, level of cardiovascular risk, LDL-C value unknown at diagnosis, high blood pressure and current smoking. Diabetes was associated with a lower risk of not achieving LDL-C goals. Conclusions These observational data suggest that the achievement of LDL-C goals is suboptimal in selected countries outside Western Europe. Efforts are needed to improve the management of patients using combination therapy and/or more intensive LLTs.

Safety and efficacy of 2-weekly cabazitaxel in metastatic castration-resistant prostate cancer.

OBJECTIVES: To evaluate the safety and efficacy of a 2-weekly cabazitaxel schedule in patients with metastatic castration-resistant prostate cancer (mCRPC). MATERIALS AND METHODS: During the period October 2013 to February 2016, 43 patients with mCRPC were treated with cabazitaxel (16 mg/m2 , on days 1 and 15 of a 4-week cycle) together with prophylactic granulocyte colony-stimulating factor (G-CSF). The safety profile and efficacy (prostate-specific antigen [PSA] response; biological, clinical or radiological progression-free survival [PFS] and overall survival [OS]) of the treatment were analysed. RESULTS: All patients had received prior docetaxel and 79.1% abiraterone acetate. At inclusion, 46.5% were aged >70 years and 27.9% had an Eastern Cooperative Oncology Group performance status ≥2. Six patients stopped treatment because of toxicity. Grade ≥3 toxicities were: asthenia (16.3%); neutropenia (11.6%); thrombocytopenia (9.3%); diarrhoea (7%), anaemia (4.7%), febrile neutropenia (4.7%) and haematuria (2.3%). In all, 52.4% achieved a ≥30% PSA response and 40.5% had a ≥50% PSA response. The median OS was 15.2 months. CONCLUSION: This prospective pilot study suggests that cabazitaxel 16 mg/m² given 2-weekly has a manageable toxicity profile in docetaxel- and abiraterone acetate-pretreated patients with mCRPC. A prospective phase III trial comparing this regimen with the standard cabazitaxel regimen is planned to confirm these results.

Treatment patterns and survival in an exhaustive French cohort of pazopanib-eligible patients with metastatic soft tissue sarcoma (STS).

BACKGROUND: The French EMS study prospectively collected exhaustive data from STS patients diagnosed in the Rhone-Alpes region from 2005 to 07. METHODS: The database included diagnosis/histology, surgery, radiotherapy, systemic treatments and treatment response. Treatment patterns and outcomes of patients with metastatic disease, excluding adipocytic sarcoma and GIST were analyzed. RESULTS: Of 888 total patients, 145 were included based on having metastatic disease and appropriate subtypes. All patients received treatment with systemic therapy being most common (74%, n = 107), followed by radiotherapy (30%, n = 44) and surgery (23%, n = 33). Doxorubicin, alone or in combination, was the most common first line systemic therapy (65%, n = 46). Drugs without license in sarcoma were used in 38-83% of treatments depending on treatment line. 24% of frontline patients demonstrated an objective response, decreasing to 11% objective responses in second line but no responses were documented beyond second line, with median PFS declining with each additional line. Median PFS also declined in patients receiving surgery compared to those receiving no surgery (8-15 m vs 5 m). Median OS from metastatic diagnosis for patients receiving systemic therapy was double that of patients without systemic treatment (24 m vs 12 m, p = 0.007). CONCLUSIONS: Outcomes in this population were poor and declined with successive treatment. However, results suggest that further anticancer therapies in recurrent sarcoma might be beneficial.

Prostate-specific antigen flare induced by cabazitaxel-based chemotherapy in patients with metastatic castration-resistant prostate cancer.

BACKGROUND: A prostate-specific antigen (PSA) flare occurs in about 15% of metastatic castration-resistant prostate cancer (mCRPC) patients receiving docetaxel. This flare has no standard definition. Its impact on treatment efficacy is unclear. We sought to evaluate the incidence and characteristics of PSA flare on cabazitaxel, and its impact on survival. METHODS: Multicentre retrospective review of consecutive patients treated with cabazitaxel second-line chemotherapy for mCRPC. Collection of baseline characteristics, disease history and PSA levels before and during cabazitaxel therapy. Overall survival (OS) and radiological/clinical progression-free survival (PFS) for patient groups corresponding to different definitions of PSA flare estimated by the Kaplan-Meier method and compared using the log-rank test. RESULTS: Overall, 125 patients were included. Median PFS and OS were 6.5 and 13.3 months, respectively. Depending upon the definition used, flare incidence ranged from 8.3% to 30.6%. The flare lasted <2.6 months. A PSA flare followed by a ⩾ 50% decrease was associated with a median PFS and OS of 11.2 and 25.2 months, respectively. Median PFS and OS for a ⩾ 30% rather than ⩾ 5 0% decrease were 10.4 and 16.5 months. These outcomes were not significantly different from those in patients with immediate PSA decreases of ⩾ 50% or ⩾ 30% from baseline, but were significantly better than in patients experiencing no PSA decrease (p = 0.006 and 0.015, respectively, for OS). CONCLUSION: The PSA response to cabazitaxel, with or without initial flare, was associated with a strong survival benefit. The taxane-induced flare during the first 12 weeks of therapy can be ignored when evaluating PSA response.

Treatment patterns, clinical outcomes and health care costs associated with HER2-positive breast cancer with central nervous system metastases: a French multicentre observational study.

BACKGROUND: The population of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) who develop central nervous system (CNS) metastases is growing. Treatment strategies in this population are highly diverse. The objective of the study was to assess health care costs for the management of HER2 positive BC with CNS metastases. METHODS: This multicentre, retrospective, observational study was conducted on HER2-positive BC patients diagnosed with CNS metastases between 2006 and 2008. Data were extracted from patient medical records to estimate health care resource use. A partitioned estimator was used to adjust censoring costs by use of the Kaplan-Meier survival estimate. RESULTS: 218 patients were included and costs were estimated for 200 patients. The median time to detection of CNS metastases was 37.6 months. The first metastatic event involved the CNS in 39 patients, and this was the unique first metastatic site in 31 of these patients. Two years following diagnosis of CNS metastases, 70.3% of patients had died. The mean per capita cost of HER2-positive BC with CNS metastases in the first year following diagnosis was €35,735 [95% CI: 31,716-39,898]. The proportion of costs attributed to expensive drugs and those arising from hospitalisation were in the same range. CONCLUSION: A range of individualised disease management strategies are used in HER2-positive BC patients with CNS metastases and the treatments used in the first months following diagnosis are expensive. The understanding of cost drivers may help optimise healthcare expenditure and inform the development of appropriate prevention policies.

One-year effectiveness of a 3-week balneotherapy program for the treatment of overweight or obesity.

Objective. To assess the one-year effectiveness on weight loss of a 3-week balneotherapy program (BT). Method. A Zelen double consent randomised controlled trial to compare one-year BMI loss between a 3-week BT program versus usual care (UC) for overweight or obese patients (BMI: 27-35 kg/m(2)), associated or not with a dietary motivational interview (DMI) during the follow-up, using a 2 × 2 factorial design. Main analysis was a per protocol analysis comparing patients attending BT to patients managed by UC, matched on sex, overweight or obese status, DMI randomisation and a propensity score to attend BT or to be managed by UC. Results. From the 257 patients who completed the follow-up, 70 patients of each group could be matched. Mean BMI loss was 1.91 kg/m(2) [95%CI: 1.46; 2.35] for the BT patients and 0.20 kg/m(2) [-0.24; 0.64] for the UC patients (P < 0.001), corresponding to a significant BT benefit of 1.71 kg/m(2) [1.08; 2.33]. There was no significant effect of DMI and no interaction with BT or UC. No adverse reaction was observed for patients attending BT. Conclusion. A 3-week BT program provided a significant one-year benefit over the usual GP dietary advice for overweight and obese patients.

Physicians' preferences for prescribing oral and intravenous anticancer drugs: a Discrete Choice Experiment.

Although efficacy and tolerability are classical criteria for treatment choice, patient adherence and tariff issues related to novel oral anticancer drugs may also influence therapeutic decisions. We estimated the relative influence of efficacy, tolerability, expected adherence and route of administration of a chemotherapy treatment on 203 French physicians' preferences who participated in a Discrete Choice Experiment (DCE), a quantitative method used to elicit preferences. From a questionnaire with six scenarii, respondents had to choose between two treatments which differed with respect to these four attributes. Scenarii were first presented in a curative setting then in a palliative setting. Efficacy, tolerability and expected adherence had two modalities (good versus moderate) and route of administration had three modalities (intravenous (€286-379/session), oral with the current tariff (€28/consultation), oral with a hypothetical tariff (€114)). Efficacy was the reference criterion in choosing a treatment whatever the therapeutic goal (ß: 2.114, p<0.0001 in curative setting versus ß: 1.063, p<0.0001 in palliative setting). The oral route of administration was important but only in a palliative setting (ß: 0.612, p=0.035, and ß: 0.506, p<0.0001 for the current and hypothetical tariff, respectively). Removing the efficacy attribute from logistic regression model, tolerability (ß: 1.228, p=0.0001) and expected adherence (ß: 1.223, p=0.0001) were influent in curative setting while the route of administration was still predominant in palliative setting (ß: 0.431, p<0.0001). Results suggest that economic considerations as well as therapeutic efficacy play a significant role in choosing a treatment. Preference for oral chemotherapy with a hypothetical tariff for a patient support programme should be considered for the development of therapeutic education and healthcare coordination, currently not taken into account in the tariff of oral chemotherapy.

Management of osteoporosis and associated quality of life in post menopausal women.

BACKGROUND: The study aimed to describe the characteristics of women treated for recently-diagnosed osteoporosis, to identify variables associated with different treatment regimens and to assess impact on quality of life. METHODS: This is an observational, cross-sectional pharmacoepidemiological study performed in France. A random sample of 684 general practitioners, gynaecologists and rheumatologists included the first three post-menopausal osteoporotic women consulting in the previous six months on the basis of densitometry or fracture. Data on osteoporosis, fracture risk factors, treatments and comorbidities was collected with a physician questionnaire. Data on quality of life was collected using the SF-12. RESULTS: Data were analysed for 1,306 patients, of whom 1,117 (85.5%) had been evaluated by densitometry within the previous six months and 554 (42.4%) had experienced a fracture, most frequently of the spine or wrist within the previous six months. Osteoporotic fracture risk factors were reported in 1,028 women (78.7%). 746 women (57.1%) were currently receiving treatment, most frequently weekly or monthly bisphosphonates. Five variables were associated with prescription choice: age (p < 0.0001), physician speciality (p < 0.0001), previous fracture history (p = 0.0002), ongoing treatment at the time of consultation (p = 0.0091) and paraclinical investigations performed in the previous six months (p = 0.0060). SF-12 scores were lower in women complaining of pain, with recent fractures and with spine or hip fractures and in women consulting rheumatologists. CONCLUSIONS: A high proportion of women diagnosed with osteoporosis had been evaluated by densitometry, in agreement with national guidelines. Treatment choice varied between physician groups.

Relationship of insulin dose, A1c lowering, and weight in type 2 diabetes: comparing insulin glargine and insulin detemir.

BACKGROUND: A pooled analysis of randomized controlled trials of individuals with type 2 diabetes mellitus (T2DM) was conducted to compare dosing and impact of two basal insulin analogs, insulin glargine (glargine) and insulin detemir (detemir), on weight and hemoglobin A1c (A1c). METHODS: Twenty-two studies of at least 20 weeks in duration in individuals with T2DM initiating glargine/detemir were included. Results were combined using a weighted-average method and a bivariate random effect model. Outcomes included changes in weight, A1c, and insulin dose from study start to end. RESULTS: One study was head-to-head comparison of glargine and detemir. Detemir (four studies) was administered once or twice daily, with 50% starting on detemir once daily but needing therapy intensification. Glargine was used once daily in all 22 studies. The Egger test was borderline significant for change in weight over the course of the treatment for glargine (0.29; 90% confidence interval [CI] -0.01, 0.58), and heterogeneity was not observed for detemir (-0.18; 90% CI -0.59, 0.23). Heterogeneity was observed for change in A1c over the course of the treatment (glargine, -1.19, 90% CI -1.74, -0.63; detemir, -2.65, 90% CI -4.86, -0.45). Nonheterogeneity for change in A1c over the course of the treatment was achieved by excluding five studies for glargine and one study for detemir; however, all studies were included in subsequent analyses. In the unadjusted model, glargine and detemir showed similar results for mean A1c change (-1.4% vs. -1.4%), weight gain (2.5 vs. 1.7 kg), and weight/A1c (1.8 vs. 1.2 kg/%). A significantly higher detemir dose was needed to achieve the same A1c change (51.5 vs. 38.8 U/day). CONCLUSIONS: Although absolute weight gain was higher with glargine versus detemir, weight gain per A1c change was similar. A higher detemir dose was required to achieve a similar A1c reduction.

Compliance and treatment satisfaction of post menopausal women treated for osteoporosis. Compliance with osteoporosis treatment.

BACKGROUND: Adherence to anti-osteoporosis treatments is poor, exposing treated women to increased fracture risk. Determinants of poor adherence are poorly understood. The study aims to determine physician- and patient- rated treatment compliance with osteoporosis treatments and to evaluate factors influencing compliance. METHODS: This was an observational, cross-sectional pharmacoepidemiological study with a randomly-selected sample of 420 GPs, 154 rheumatologists and 110 gynaecologists practicing in France. Investigators included post-menopausal women with a diagnosis of osteoporosis and a treatment initiated in the previous six months. Investigators completed a questionnaire on clinical features, treatments and medical history, and on patient compliance. Patients completed a questionnaire on sociodemographic features, lifestyle, attitudes and knowledge about osteoporosis, treatment compliance, treatment satisfaction and quality of life. Treatment compliance was evaluated with the Morisky Medication-taking Adherence Scale. Variables collected in the questionnaires were evaluated for association with compliance using multivariate logistic regression analysis. RESULTS: 785 women were evaluated. Physicians considered 95.4% of the sample to be compliant, but only 65.5% of women considered themselves compliant. The correlation between patient and physician perceptions of compliance was low (κ: 0.11 [95% CI: 0.06 to 0.16]). Patient-rated compliance was highest for monthly bisphosphonates (79.7%) and lowest for hormone substitution therapy (50.0%). Six variables were associated with compliance: treatment administration frequency, perceptions of long-term treatment acceptability, perceptions of health consequences of osteoporosis, perceptions of knowledge about osteoporosis, exercise and mental quality of life. CONCLUSION: Compliance to anti-osteoporosis treatments is poor. Reduction of dosing regimen frequency and patient education may be useful ways of improving compliance.

Calcium intake and the risk of osteoporosis and fractures in French women.

OBJECTIVES: To evaluate dietary calcium intake in postmenopausal women over 45 years of age and compare intake according to osteoporosis diagnosis and fracture history. METHODS: A cross-sectional epidemiological survey of osteoporosis in postmenopausal women over 45 years in the general population was conducted using a stratified random sampling method and face-to-face interviews. Information was collected on osteoporosis diagnosis, fracture history and risk factors. Information on dietary calcium intake was collected using a validated questionnaire. RESULTS: Two thousand six hundred and thirty-one women (mean age: 67.9+/-10.0 years) were included. Two hundred and fifty-four (9.7%) had received a diagnosis of osteoporosis by bone densitometry, of whom 154 (45.3%) reported at least one previous fracture. Total mean daily dietary calcium intake was 754 mg/day, of which dairy products (milk, cheese and others) were the principal source. Overall, 37.2% of the sample consumed<600 mg/day and 20.1% >1000 mg/d. The proportion of women consuming <600 mg/day increased with age (p=0.0028). No difference in mean daily calcium intake was observed between women with or without a diagnosis of osteoporosis or with or without fractures. CONCLUSIONS: Mean dietary calcium intake in this population is well below that recommended in current national guidelines (> or =1500 mg/day), notably in those most at risk for fractures, such as women with a diagnosis of osteoporosis or those in older age groups. Intake does not appear to be influenced by osteoporosis diagnosis or fracture experience.

Visual field loss in patients with refractory partial epilepsy treated with vigabatrin: final results from an open-label, observational, multicentre study.

BACKGROUND: Use of the antiepileptic drug vigabatrin is associated with an elevated risk of visual field loss. OBJECTIVE: To determine the frequency of, and risk factors for, vigabatrin-attributed visual field loss (VAVFL) in the setting of a large-scale, multinational, prospective, observational study. STUDY DESIGN: A comparative, open-label, parallel-group, multicentre study. SETTING: Hospital outpatient clinics at 46 centres in five countries. PATIENTS: 734 patients with refractory partial epilepsy, divided into three groups and stratified by age (8-12 years; >12 years) and exposure to vigabatrin. Group I comprised patients treated with vigabatrin for > or =6 months. Group II comprised patients previously treated with vigabatrin for > or =6 months who had withdrawn from the drug for > or =6 months. Group III comprised patients never treated with vigabatrin. Patients underwent perimetry at either 4- or 6-month intervals, for up to 36 months. Visual field outcome was evaluated masked to drug exposure. INTERVENTION: Perimetry. MAIN OUTCOME MEASURE: The visual field outcome at each of four analysis points: (i) at enrolment (i.e. baseline, all patients); (ii) for patients exhibiting a conclusive outcome at the initial visual field examination; (iii) for patients exhibiting at least one conclusive outcome to the visual field examinations; and (iv) at the last conclusive outcome to the visual field examinations. RESULTS: Of the 734 patients, 524 yielded one or more conclusive visual field examinations. For Group I, the frequency of VAVFL at the last conclusive examination was 10/38 (26.3%) for those aged 8-12 years and 65/150 (43.3%) for those aged >12 years. For Group II, the respective frequencies were 7/47 (14.9%) and 37/151 (24.5%). One case resembling VAVFL was present amongst the 186 patients in Group III at the last conclusive examination. The frequency of VAVFL in Groups I and II combined was 20.0% for those aged 8-12 years and 33.9% for those aged >12 years. VAVFL was associated with duration of vigabatrin therapy (odds ratio [OR] up to 15.2; 95% CI 4.4, 51.7), mean daily dose of vigabatrin (OR up to 26.4; 95% CI 2.4, 291.7) and male gender (OR 2.51; 95% CI 1.5, 4.1). VAVFL was more frequently detected with static than with kinetic perimetry (OR up to 0.43; 95% CI 0.24, 0.75). CONCLUSIONS: Since the probability of VAVFL is positively associated with treatment duration, careful assessment of the risk-benefit ratio of continuing treatment with vigabatrin is recommended in patients currently receiving this drug. All patients continuing to receive vigabatrin should undergo visual field examination at least every 6 months for the duration of treatment. We recommend two-level (three-zone), gradient-adapted, suprathreshold static perimetry of the peripheral field together with threshold perimetry of the central field out to 30 degrees from fixation. The frequency of ophthalmological and perimetric examinations should be increased in the presence of VAVFL.

Uranyl-Se(IV) interaction in aqueous acid solutions studied by time-resolved laser-induced fluorescence spectroscopy (TRLFS) and UV-Vis spectrophotometry.

The uranyl-selenium(IV) interaction was studied by time-resolved laser-induced fluorescence spectroscopy in aqueous perchloric acid solutions containing 1 x 10(-4) M U(VI) and Se(IV) at different concentrations (from 0 up to 0.3 M) at pH 1 and 2. The quenching of uranyl fluorescence is observed. HSeO(3)(-) is demonstrated to be responsible for the fluorescence quenching. Stern-Volmer analysis gives the dynamic quenching rate constant value (k(q)) (5.0 +/- 0.4) x 10(9) L M(-1) s(-1) at ionic strength (mu) 0.05 M. The bimolecular excited-state process is shown to be diffusion-controlled as k(q) is practically identical to the diffusion rate constant as calculated for uranyl and hydroselenite charged species. With an increase of HSeO(3)(-) concentration, static quenching occurs in addition to the dynamic quenching. The hypothesis of the formation of a weak fluorescent ground state complex between uranyl and HSeO(3)(-) is supported. The logarithm of the stability constant value (beta) is found to be 3.35 +/- 0.12 (mu= 0.05 M) and 3.32 +/- 0.15 (mu = 0.2 M). These constants are confirmed by UV-Vis spectrophotometry. The modelling factor analysis of absorption spectra gives logbeta = 3.35 +/- 0.17 (mu = 0.035 M). Extrapolation to mu = 0 by the specific ion interaction theory (SIT) gives logbeta degrees = 3.62 +/- 0.15 at 20 degrees C.