Efficacy and safety of a T-type calcium channel blocker in patients with neuropathic pain: A proof-of-concept, randomized, double-blind and controlled trial.

BACKGROUND: T-type calcium channels have been shown to play an important role in the initiation and maintenance of neuropathic pain and represent a promising therapeutic target for new analgesic treatments. Ethosuximide (ETX), an anticonvulsant and a T-type channel blocker has shown analgesic effect in several chronic pain models but has not yet been evaluated in patients with neuropathic pain. METHODS: This proof-of-concept, multicentre, double-blind, controlled and randomized trial compared the efficacy and safety of ETX (given as add-on therapy) to an inactive control (IC) in 114 patients with non-diabetic peripheral neuropathic pain. After a 7-day run-in period, eligible patients aged over 18 years were randomly assigned (1:1) to ETX or IC for 6 weeks. The primary outcome was the difference between groups in the pain intensity (% of change from the baseline to end of treatment) assessed in the intention-to-treat population. This study is registered with EudraCT (2013-004801-26) and ClinicalTrials.gov (NCT02100046). RESULTS: The study was stopped during the interim analysis due to the high number of adverse events in the active treatment group. ETX failed to reduce total pain and showed a poor tolerance in comparison to IC. In the per-protocol analysis, ETX significantly reduced pain intensity by 15.6% (95% CI -25.8; -5.4) from baseline compared to IC (-7.8%, 95% CI -14.3; -1.3; p = 0.033), but this result must be interpreted with caution because of a small subgroup of patients. CONCLUSION: Ethosuximide did not reduce the severity of neuropathic pain and induces, at the doses used, many adverse events. SIGNIFICANCE: This article shows that ETX is not effective to treat neuropathic pain. Nevertheless, per-protocol analysis suggests a possible analgesic effect of ETX. Thus, our work adds significant knowledge to preclinical and clinical data on the benefits of T-type calcium channel inhibition for the treatment of neuropathic pain.

Efficacy of intralesional sodium thiosulfate injections for disabling tumoral calcinosis: Two cases.

INTRODUCTION: Tumoral calcinosis (TC) is a difficult-to-treat complication that can occur during several diseases such as dermatomyositis or genetic hyperphosphatemia. It is a painful and disabling condition that can lead to local complications including joint mobility reduction, cutaneous ulceration and superinfection. For the largest lesions, the treatment relies essentially on surgery. Intravenous sodium thiosulfate (STS) is efficient to treat calciphylaxis in patients undergoing hemodialysis. Local injections of STS seem efficient in superficial calcifications. OBJECTIVE: To report the efficacy and safety of intra-lesional injections of STS in tumoral calcinosis. RESULTS: We report two cases of successful intra-lesional injections of STS. A 44-year-old woman, with a history of dermatomyositis, presenting large subcutaneous calcifications in the right elbow, and a 42-year-old man, with a history of familial tumoral calcinosis, presenting large intramuscular calcifications in the right buttock, received weekly intra-lesional of 1-3g STS injections for 12 and 21 months, respectively. In both cases, the treatment relieved pain and greatly reduced the tumoral calcinosis with a very significant functional improvement without specific adverse effects. In case 1, TC size decreased from 28.7*56.0mm at baseline to 21.5*30.6mm at M12 treatment (59% reduction). In case 2, TC reduced from 167.5*204.3mm at baseline to 86.2*85.2mm at M21 treatment (79% reduction). CONCLUSION: Local injection of STS could be a promising therapeutic strategy for large and deep TC lesions and could therefore be an alternative to surgery.

[Misuse and dependence on prescription opioids: Prevention, identification and treatment]. / Mésusage et dépendance aux opioïdes de prescription : prévention, repérage et prise en charge.

Since the 1990s, the use of prescription opioids has largely spread, which has brought a real progress in the treatment of pain. The long-term use of prescription opioid is sometimes required, and may lead to pharmacological tolerance and withdrawal symptoms, i.e. pharmacological dependence on prescription opioids. Occasionally, this may also lead to misuse of prescription opioids (MPO). MPO preferentially occurs in vulnerable individuals, i.e., those with a young age, history of other addictive or psychiatric disorders, especially anxious and depressive disorders. MPO is associated with numerous complications, including an increased risk of fatal overdose. Prevention of MPO begins before the opioid prescription, with the identification of potential vulnerability factors. A planned and personalized monitoring should be systematically implemented. In vulnerable patients, contractualizing the prescription is warranted. During follow-up, the relevance of the prescription should be regularly reconsidered, according to the benefit observed on pain and the potential underlying signs of MPO. Patients with suspected MPO should be referred early to pain or addiction centers. The treatment of MPO should be based on multidisciplinary strategies, involving both the addiction and pain aspects: progressive opioid withdrawal, non-pharmacological measures against pain, or switching to medication-assisted treatment of addiction (i.e., buprenorphine or methadone).

[Physicians and the danger of nuclear war]. / Les médecins et le danger de guerre nucléaire.

International Physicians for the Prevention of Nuclear War (IPPNW), the 1985 Nobel Peace Prize winners, are active in some sixty different countries. Their action is based on the outlook that any nuclear war would cause not only millions of deaths, but also millions of severely injured or burnt victims for whom the medical profession, decimated as well, would be most helpless. They strive to obtain that governments, in agreement with treaties that almost all countries have signed, ascertain that nuclear weapons, which are internationally illegal, be globally abolished. The impact on political authorities would undoubtedly be reinforced if the number of physicians supporting the action of IPPNW was increased.

[Torsades de pointe. Apropos of 60 cases]. / Les torsades de pointe. A propos de 60 observations.

The authors report a personal series of 60 cases of "torsade de pointe" (the largest series published to date) seen in the Cardiology department of Amiens Hospital over a period of 11 years. They review the essential features of this arrhythmia, which was well described by F. Dessertenne in 1966, but which is still sometimes confused with certain forms of ventricular tachycardia. "Torsade de pointe" is still a topical issue, as 25% of the cases in this series were seen over the last two years. These cases were classified into three groups according to their aetiology: severe bradycardia (21 cases), potassium depletion (16 cases), drug causes (23 cases). This arrhythmia was essentially associated with iatrogenic factors, in particular potassium depletion (41.6% of cases). The classical notion of predisposed patients was confirmed: elderly patients (mean age of 68 years), with cardiovascular disease in 70% of cases (i.e. heart failure or coronary insufficiency, hypertension) and with a marked female predominance (70% women). The ECG between episodes of "torsade de pointe" always revealed a prolonged QT interval which, in relation to the heart rate, was more marked in the patients with potassium depletion. During an attack, the average ventricular rate was 210/min (range: 170 to 290/min). 20% of cases subsequently developed ventricular fibrillation. The overall mortality was 16.6% (10 out of 60 cases), but there have been no deaths since 1977 due to the better understanding of this arrhythmia.(ABSTRACT TRUNCATED AT 250 WORDS)

[Diagnostic and prognostic value of ST segment depression greater than or equal to 3 mm during exercise testing]. / Valeur diagnostique et pronostique du sous-décalage du segment ST supérieur ou égal à 3 mm au cours de l'épreuve d'effort.

This study was undertaken to assess the diagnostic and prognostic value of ST depression equal to or more than 3 mm during exercise stress testing (EST). Out of 4050 EST performed over an 8 year period, 128 patients (3,2%) had this degree of ST depression. These changes were observed in leads V4 V6 in 92% of cases. Coronary angiography was performed in 56 patients: all had significant coronary artery disease (greater than 50% stenoses) with 50% three vessel, 30% two vessel and only 20% single vessel disease; all patients had at least one severe stenosis (greater than 75%) of a main coronary artery. The predictive value of EST was therefore 100% in the 56 patients undergoing coronary angiography. Angina or ventricular extrasystoles during EST or greater than 5 mm ST depression were predictive of multiple vessel disease. The following correlations were observed between EST and the extent of coronary artery disease: maximal heart rate and systolic pressure were lower, ischemic changes appeared sooner (less than 2 min) and lasted longer during the recovery phase (greater than 7 min) in patients with multiple vessel disease. The 5 year prognosis was studied in 58 patients; it was poor (death or infarction) in 31 cases (53%). The following factors were associated with a poor prognosis: low maximal heart rate and systolic blood pressure, early ischemic changes and frequent ventricular extrasystoles on EST; on the other hand, the development of anginal pain during EST was not of significant prognostic value in this series. ST depression greater than 3 mm on EST is rare.(ABSTRACT TRUNCATED AT 250 WORDS)

[Rhythm disorders occurring after surgical closure of the interatrial communication]. / Troubles du rythme survenant apres fermeture chirurgicale di la communication interauriculaire

A detailed evaluation is presented about the frequency and the type of arrhythmias following the surgical correction of 147 cases of atrial septal defects not associated with other congenital heart malformations. A total of 131 arrhythmias occurred in 84 patients. The nodal and the coronary sinus rhythms are the most frequently encountered after surgery, attaining 53,8% of all arrhythmias, while atrial fibrillation or flutter represented about 22%. The follow-up of these arrhythmias concerned the 3 month period immediately after surgery. After that time 20% of the arrhythmias occurring in the early postoperative period persisted. The frequency of arrhythmias increased with age, was relatively independent of the importance of the left to right shunt, the level of the mean pulmonary artery pressure and the sex of the patients; but statistically increased in patients in whom the correction was made with a patch. The authors concluded that there must exist at least two mechanisms to explain the occurrence of arrhythmias. A first one must be in relation to the surgical manipulation; the second, which is only an hypothesis, stipulates an alteration of the conduction pathways due to the auricular distention or the existence of a congenital anomaly of the conduction pathways.