Changes in fibroblast growth factor 23 levels in normophosphatemic patients with chronic kidney disease stage 3 treated with lanthanum carbonate: results of the PREFECT study, a phase 2a, double blind, randomized, placebo-controlled trial.

BACKGROUND: High levels of circulating fibroblast growth factor 23 (FGF23) are associated with chronic kidney disease (CKD) progression and high mortality. In the Phosphate Reduction Evaluation of FGF23 in Early CKD Treatment (PREFECT) study, we assessed the effect of reducing intestinal phosphate absorption using lanthanum carbonate on FGF23 levels in normophosphatemic patients with CKD stage 3. METHODS: Thirty-five individuals were randomized to lanthanum carbonate 3000 mg/day (n=23) or placebo (n=12) for 12 weeks. Levels of intact FGF23 (iFGF23), C-terminal FGF23, serum and urinary phosphate and calcium, intact parathyroid hormone and 1,25-dihydroxyvitamin D were assessed. RESULTS: The median age was 65 years in the lanthanum group and 73 years in the placebo group; 58.8% and 41.7% were men, respectively. No significant difference was seen in mean iFGF23 between groups at week 12. There was, however, a transient reduction from baseline in iFGF23 in the lanthanum group at week 1, from 70.5 pg/ml to 51.9 pg/ml, which was not seen in the placebo group; this between-group difference in percentage change from baseline was significant in post hoc analyses (p=0.0102). Urinary phosphate decreased after 1 week of lanthanum treatment and remained low at week 12. CONCLUSIONS: Reducing intestinal phosphate absorption with lanthanum carbonate did not lead to sustained reductions in iFGF23 in patients with CKD stage 3, although phosphaturia decreased. This suggests that factors other than phosphate burden may be responsible for driving increases in circulating FGF23 in patients with CKD. TRIAL REGISTRATION: ClinicalTrials.gov NCT01128179, 20 May 2010.

Characterization of different regimens for initiating anagrelide in patients with essential thrombocythemia who are intolerant or refractory to their current cytoreductive therapy: results from the multicenter FOX study of 177 patients in France.

OBJECTIVES: To identify switch modalities used when initiating second- or third-line anagrelide for essential thrombocythemia (ET), assess whether anagrelide is initiated consistently with Summary of Product Characteristics (SPC) recommendations, and determine whether different observed switch regimens have any relationship with maintenance, platelet response, or tolerability. METHODS: This observational study was conducted across 43 centers in France. High-risk patients (>60 yr of age and/or history of thrombosis and/or platelet count >1000 × 10(9) /L) with ET starting second- or third-line anagrelide therapy were identified and monitored for 6 months. RESULTS: A total of 177 patients were enrolled. The SPC-recommended starting dose (1 mg/d) was used in 52.6% of patients; 0.5 mg/d was used in 41.1%. 77.1% of patients underwent an anagrelide dose increase during the study. At 6-month follow-up, 84.7% of patients (n = 144/170) were still receiving anagrelide; 70.6% (n = 120/170) achieved a platelet response. A higher proportion of patients who discontinued previous cytoreductive therapy (CRT) after initiating anagrelide achieved a platelet response (n = 34/39, 87.2%) vs. patients who discontinued their previous CRT before anagrelide initiation (n = 77/115, 67.0%). Platelet response rates were higher in patients whose anagrelide initiation was consistent (n = 100/133, 75.2%) vs. inconsistent (n = 20/37, 54.1%) with the SPC. The incidence of adverse drug reactions was lower in patients whose anagrelide treatment was consistent (n = 52/133, 39.1%) vs. inconsistent (n = 25/37, 67.6%) with the SPC. CONCLUSIONS: To our knowledge, the FOX study provides the first comprehensive real-world data on the modalities used when switching from previous CRT to anagrelide. Highest platelet responses were observed when previous CRT was discontinued after anagrelide initiation or when anagrelide was initiated consistently with the SPC. Safety data corresponded with the SPC.

Effects of training on general practitioners' management of pain in osteoarthritis: a randomized multicenter study.

OBJECTIVE: To evaluate the effects of a short interactive training program for general practitioners (GP) on pain management in patients with osteoarthritis (OA). METHODS: A multicenter, parallel-group study. GP were randomized to receive training on relationships and communication, pain evaluation, prescription, and negotiation of a patient contract or to a control group receiving a presentation about obtaining consent in trials. Outcomes were patient assessments of pain and functional ability. We invited 1500 GP to take part in the study. Those who volunteered to receive the training recruited outpatients from May 2001 to April 2002. Patients participating in the evaluation of the effects of the general practitioners' training had lower limb OA and pain on motion [> or = 40 mm on a visual analog scale (VAS)] and had indications for treatment with acetaminophen. The primary endpoint: sum of patient pain relief based on the daily VAS self-evaluation during the 2 weeks of the trial. RESULTS: In total, 180 GP (84 trained, 96 nontrained) enrolled 842 patients (414 and 428, respectively). Mean baseline VAS pain was 63 +/- 14 mm. Patients in the trained-GP group had better overall pain relief (316 +/- 290 mm/day vs 265 +/- 243 mm; p < 0.0001), greater improvement in Lequesne and WOMAC scores (p < 0.0001), and better overall perception of treatment (p = 0.002). Acetaminophen use was slightly higher in the trained group; however, the difference in pain relief remained statistically significant (p = 0.0003) after adjustment for this difference. CONCLUSION: This is the first study to demonstrate a positive effect of physician training on patients with a painful condition.

[Data recording using a personal digital assistant. Experience of prospective survey on pain in 3196 patients]. / Recueil de données par assistant personnel digital. Expérience d'un Observatoire prospectif de la douleur portant sur 3196 patients.

OBJECTIVE: To assess the interest of a personal digital assistant (PDA) when used as data collector in a prospective survey on pain in general practice. METHODS: Prospective, multicentre and national survey concerning the identification of 4g/24h paracetamol prescription conditions as well as the characterization of the pain justifying it. Data were collected with a dedicated PDA including an electronic visual analogue scale (VAS). It also included a data controlling program of probability, consistency, date recording and time of data entry. RESULTS: 3.196 patients were enrolled by 830 general practitioners (GPs). For 1.066 of them enrolled by 277 GPs, the consistency analysis showed an a posteriori data entry. However, for assessment of pain intensity using the VAS, the physical presence of the patient is mandatory because self-evaluation is the rule. CONCLUSION: The use of an electronic questionnaire permits the collection of good quality data and the possibility of a posteriori control and hence the identification of breaches in clinical trial protocols.

Acetaminophen as symptomatic treatment of pain from osteoarthritis.

Osteoarthritis is a major public health burden. The incidence of osteoarthritis increases with advancing age. Symptomatic treatments aimed at alleviating the pain and thereby restoring joint function form the basis of the treatment. The chronic course requires long-term treatment with special attention to minimizing the side effects of drugs. Acetaminophen has a good risk/benefit ratio that has prompted international consensus panels to recommend its use as first-line therapy in dosages of up to 4 g/day. This review discusses safety and efficacy data from randomized double-blind trials of acetaminophen used to alleviate pain caused by osteoarthritis.

[Mucoregulators in acute bronchitis syndromes: focus on use by general practitioners and data from the literature]. / Les mucorégulateurs dans les syndromes bronchiques aigus: point sur les pratiques en médecine générale et les données de la littérature.

Antibiotics have long been used in the initial treatment of acute bronchitis (AB) and acute exacerbations of chronic bronchitis (AECB). However, their lack of value in AB has been clearly demonstrated and antibiotic therapy is justified in only a few cases of AECB. In parallel, although the value of mucoregulators in these diseases is still debated, their prescription remains important in general practice. In this context, our aim was to determine the prescribing behaviour of general practitioners (GPs) with regard to these drugs, as well as the beliefs of GPs concerning the place of mucoregulators in the treatment of AB in children and adult smokers, as well as in patients with non-obstructive AECB. A survey was carried out in 370 GPs, who were presented with three standardised and computerised medical cases: (i) rhinopharyngitis + AB in a child; (ii) AB in an adult smoker without a previous medical history; and (iii) a patient with non-obstructive AECB. The results showed that mucoregulators are frequently prescribed by GPs for children and adults with AB, or in AECB. This high prescribing rate is due to the belief of the GPs that these drugs are effective and well tolerated, which is confirmed by the literature. Their use avoids the frequent and unjustified prescription of antibiotics in situations where they are not recommended but where the patients request drug therapy.