Safety of high loading doses of teicoplanin: POSY-TEICO, a prospective, multicentre, observational study.

BACKGROUND: Teicoplanin is used for treating infections caused by Gram-positive bacteria. The POSY-TEICO study assessed the safety of a high loading dose (HLD) of teicoplanin (12 mg/kg twice daily) in a real-world setting. METHODS: This prospective study was conducted across six countries in Europe and enrolled adults prescribed HLD of teicoplanin between 2016 and 2019. The primary objective was to determine the incidence of nephrotoxicity following HLD of teicoplanin over loading dose period. An independent clinical adjudication committee (ICAC) assessed all study outcomes related to nephrotoxicity. RESULTS: The study included 300 patients (males, 68.3%), with a mean age of 63.1 years and median teicoplanin treatment duration of 16 days (interquartile range: 9-38). The number of patients with bone and joint infection, infective endocarditis, and other severe infections was 176, 36, and 80, respectively. During the loading dose period, 41 (13.8%) patients received 3 HLDs and 246 (82.8%) received ≥4 HLDs. Overall, 28 (11.0%) patients (95% CI, 7.4-15.5) experienced nephrotoxicity during loading, and 10 (6.9%) patients (95% CI, 3.4-12.4) during maintenance dose periods. The number of patients who experienced nephrotoxicity certainly or possibly related to teicoplanin according to the ICAC was 20 (7.9%; 95% CI, 4.9-11.9), 8 (5.6%; 95% CI, 2.4-10.7) and 33 (12.4%; 95% CI, 8.7-16.9) across three study periods. CONCLUSIONS: HLD of teicoplanin had an acceptable safety profile in patients treated for bone and joint infection, infective endocarditis, and other severe infections, and no increased risk of nephrotoxicity was observed. However, patients should be closely monitored when HLDs are administered.

Recombinant Thyrotropin vs Levothyroxine Withdrawal in 131I Therapy of N1 Thyroid Cancer: A Large Matched Cohort Study (ThyrNod).

CONTEXT: Recombinant human thyrotropin (rhTSH) has been shown to be an effective stimulation method for radioactive iodine (RAI) therapy in differentiated thyroid cancer, including in those with nodal metastases (N1 DTC). OBJECTIVES: To demonstrate the noninferiority of rhTSH vs thyroid hormone withdrawal (THW) in preparation to RAI regarding disease status at the first evaluation in the real-life setting in patients with N1 DTC. DESIGN: This was a French multicenter retrospective study. Groups were matched according to age (<45/≥45 years), number of N1 nodes (≤5/>5 lymph nodes), and stage (pT1-T2/pT3). RESULTS: The cohort consisted of 404 patients pT1-T3/N1/M0 DTC treated with rhTSH (n = 205) or THW (n = 199). Pathological characteristics and initially administrated RAI activities (3.27 ± 1.00 GBq) were similar between the two groups. At first evaluation (6 to 18 months post-RAI), disease-free status was defined by thyroglobulin levels below threshold and a normal ultrasound. Disease-free rate was not inferior in the rhTSH group (75.1%) compared with the THW group (71.9%). The observed difference between the success rates was 3.3% (-6.6 to 13.0); rhTSH was therefore considered noninferior to THW because the upper limit of this interval was <15%. At the last evaluation (29.7 ± 20.7 months for rhTSH; 36.7 ± 23.8 months for THW), 83.5% (rhTSH) and 81.5% (THW) of patients achieved a complete response. This result was not influenced by any of the known prognostic factors. CONCLUSIONS: A preparation for initial RAI treatment with rhTSH was noninferior to that with THW in our series of pT1-T3/N1/M0-DTC on disease-free status outcomes at the first evaluation and after 3 years.

Superiority of magnesium and vitamin B6 over magnesium alone on severe stress in healthy adults with low magnesemia: A randomized, single-blind clinical trial.

INTRODUCTION: Animal and clinical studies suggest complementary effects of magnesium and high-dose pyridoxine (vitamin B6) on stress reduction. This is the first randomized trial evaluating the effects of combined magnesium and vitamin B6 supplementation on stress in a stressed population with low magnesemia using a validated measure of perceived stress. METHODS: In this Phase IV, investigator-blinded trial (EudraCT: 2015-003749-24), healthy adults with Depression Anxiety Stress Scales (DASS-42) stress subscale score >18 and serum magnesium concentration 0.45 mmol/L-0.85 mmol/L, were randomized 1:1 to magnesium-vitamin B6 combination (Magne B6 [Mg-vitamin B6]; daily dose 300 mg and 30 mg, respectively) or magnesium alone (Magnespasmyl [Mg]; daily dose 300 mg). Outcomes included change in DASS-42 stress subscale score from baseline to Week 8 (primary endpoint) and Week 4, and incidence of adverse events (AEs). RESULTS: In the modified intention-to-treat analysis (N = 264 subjects), both treatment arms substantially reduced DASS-42 stress subscale score from baseline to Week 8 (Mg-vitamin B6, 44.9%; Mg 42.4%); no statistical difference between arms was observed (p>0.05). An interaction (p = 0.0097) between baseline stress level and treatment warranted subgroup analysis (as per statistical plan); adults with severe/extremely severe stress (DASS-42 stress subscale score ≥25; N = 162) had a 24% greater improvement with Mg-vitamin B6 versus Mg at Week 8 (3.16 points, 95% CI 0.50 to 5.82, p = 0.0203). Consistent results were observed in the per protocol analysis and at Week 4. Overall, 12.1% of Mg-vitamin B6 treated and 17.4% of Mg-treated subjects experienced AEs potentially treatment related. CONCLUSIONS: These findings suggest oral Mg supplementation alleviated stress in healthy adults with low magnesemia and the addition of vitamin B6 to Mg was not superior to Mg supplementation alone. With regard to subjects with severe/extremely severe stress, this study provides clinical support for greater benefit of Mg combined with vitamin B6.

Correlates of pain intensity in men and women with hip and knee osteoarthritis. Results of a national survey: The French ARTHRIX study.

AIMS OF THE STUDY: To examine the clinical and demographic correlates of pain intensity in patients with hip and knee osteoarthritis (OA). PATIENTS AND METHODS: In a national cross-sectional survey, 1811 general practitioners recruited and assessed 5324 patients with hip and knee OA. The patients rated the intensity of pain at rest, on movement over the last 24 hours, and during the last 8 days on 11-point numeric rating scales. The patients also completed the Western Ontario and McMaster Universities Osteoarthritis Index. Clinical and demographic correlates of pain intensity and function were investigated by univariate, stepwise multiple logistic regression and odds ratio analyses. RESULTS: Data for 4598 patients were analyzed (86.4% of surveyed patients). The mean pain intensity was 4.1+/-2.2 at rest, 5.9+/-1.8 on movement during the last 24 hours, and 5.1+/-1.7 during the last 8 days. Pain on movement during the last 24 hours and during the last 8 days showed a strong positive correlation (r=0.78; P<0.0001), which suggests that the most of the latter pain was related to movement. Patients with knee or hip OA did not differ in pain intensity, but patients with both joints affected rated pain intensity significantly higher than did those with only 1 affected joint [4.6+/-2.1, 6.3+/-1.8, and 5.5+/-1.6, for the 3 pain assessments, respectively (P>0.01)]. Patients with high pain ratings were more likely to be women, be older than 75 years, and have a body mass index of greater than 40 kg/m. In addition, patients who were retired, unemployed, farmers, or widowed, or had a long duration of OA gave high pain ratings. Patients with regular physical activities reported less intense pain. CONCLUSIONS: Pain intensity ratings for patients with lower limb OA differed significantly with respect to sex, age, body mass index, physical activity, professional activity, marital status, and conditions of assessment.

Tramadol in post-herpetic neuralgia: a randomized, double-blind, placebo-controlled trial.

The efficacy and safety of sustained-release tramadol compared to placebo in the treatment of post-herpetic neuralgia were evaluated in a multicenter, randomized, double-blind, parallel-group study in 127 outpatients. Treatment was administrated for 6 weeks. The dose of tramadol could be increased from 100 mg/day to 400 mg/day (300 mg/day in patients more than 75 years old). Groups were compared on changes in pain intensity on a Visual Analogue Scale (VAS) between inclusion and the 6th week of treatment (covariance analysis as main analysis and repeated measures analysis as complementary analysis) in the per protocol (PP) population. The randomized population comprised 127 patients aged 35-85 years, mostly females (72.4%). Groups were comparable at inclusion both in the intent to treat (ITT) population (63 patients in the tramadol group and 62 patients in the placebo group) and in the PP population (53 patients in the tramadol group and 55 patients in the placebo group). Mean pain intensity on day 43 adjusted on day 1 (covariance analysis) was significantly lower in the tramadol group than in the placebo group in both the PP (P=0.0499), and the ITT (P=0.031) populations. The two groups significantly differed on change in pain intensity over time (repeated measures analysis) in the ITT population (P=0.012). The percentage of pain relief over the 6th week was significantly higher in the tramadol group than in the placebo group (P=0.017). During the 6th week, patients in the tramadol group required less rescue medication than patients in the placebo group (P=0.022). No significant difference was found between groups either in pain intensity on a 5-point Verbal Scale (VRS) or in quality of life measurements. Tramadol was administered at an average dosage of 275.5 (89.7) mg/day after a 1-week dose-adaptation period. Tramadol was well tolerated. No notable difference appeared between groups either in the percentage of patients with treatment-associated adverse events (TAAE) (29.7% in the tramadol group and 31.8% in the placebo group) or in the total number of TAAE (31 in the tramadol group and 28 in the placebo group).