Regional anesthesia in patients with Charcot-Marie-Tooth disease: a historical cohort study of 53 patients.

PURPOSE: Anesthetic management for patients with Charcot-Marie-Tooth disease (CMT) is controversial. Description of the use of regional anesthesia (RA) in patients with CMT is limited. Regional anesthesia has traditionally been avoided because of risk of nerve injury. We retrospectively reviewed patients with CMT who received RA at our institution. METHODS: We performed a historical cohort study of all patients with CMT who received RA from 30 April 2010 to 30 April 2020 within our institution. Charts were reviewed for information on demographics, RA procedures, perioperative variables, evidence of neurologic complications, post-RA neurology consults, and perioperative electromyography (EMG) results. Electromyographs were reviewed by a neurologist who was blinded to the surgical and RA details. RESULTS: Fifty-three patients received a total of 132 regional anesthetics during the study period. Twenty-five patients received RA on more than one occasion. Fifty-five EMGs and 14 postoperative neurology consults were performed. Two patients had neurology consults with peripheral nerve block (PNB) distribution complaints years later. Neither attributed the complaints to the PNB. The other neurology consults were for unrelated complaints. No EMG results suggested injury related to PNB. CONCLUSION: This study found no evidence of documented neurologic complications or an increased risk of nerve injury related to RA in CMT patients.

RéSUMé: OBJECTIF: La prise en charge anesthésique des patients atteints de la maladie de Charcot-Marie-Tooth (CMT) est controversée. Les descriptions de l'utilisation de l'anesthésie régionale (AR) chez les patients atteints de CMT sont limitées. L'anesthésie régionale est traditionnellement évitée en raison du risque de lésion nerveuse. Nous avons rétrospectivement passé en revue les dossiers des patients atteints de CMT ayant reçu une AR dans notre établissement. MéTHODE: Nous avons réalisé une étude de cohorte historique de tous les patients atteints de CMT ayant reçu une AR entre le 30 avril 2010 et le 30 avril 2020 au sein de notre établissement. Les dossiers ont été passés en revue pour en tirer des renseignements sur les données démographiques, les interventions d'AR, les variables périopératoires, les signes de complications neurologiques, les consultations en neurologie post-AR et les résultats de l'électromyographie (EMG) périopératoire. Les électromyographes ont été examinés par un neurologue qui n'avait pas accès aux détails concernant la chirurgie et l'AR. RéSULTATS: Cinquante-trois patients ont reçu un total de 132 anesthésies régionales au cours de la période d'étude. Vingt-cinq patients ont reçu une AR à plus d'une occasion. Cinquante-cinq EMG et 14 consultations postopératoires en neurologie ont été effectuées. Deux patients ont consulté en neurologie après s'être plaints de la distribution du bloc nerveux périphérique (BNP) des années plus tard. Ni l'un ni l'autre n'a attribué ces problèmes au BNP. Les autres consultations en neurologie concernaient des plaintes non liées au BNP. Aucun résultat d'EMG n'a suggéré de lésion liée au BNP. CONCLUSION: Cette étude n'a trouvé aucune preuve de complications neurologiques documentées ou d'un risque accru de lésion nerveuse liée à l'AR chez les patients atteints de CMT.

Antiviral activity of danoprevir (ITMN-191/RG7227) in combination with pegylated interferon α-2a and ribavirin in patients with hepatitis C.

BACKGROUND: Current therapy options for patients with chronic hepatitis C virus (HCV) infection genotype 1 are effective in <50%. Danoprevir (ITMN-191/RG7227) is a potent, selective, and orally active inhibitor of the HCV NS3/4A serine protease. METHODS: The safety and antiviral efficacy of danoprevir was examined over 14 days in combination with pegylated interferon α-2a (180 µg once weekly) and ribavirin (1000-1200 mg/day) in a double-blind, placebo-controlled, phase 1b, multiple ascending dose study consisting of 6 dose cohorts (400 mg, 600 mg, and 900 mg twice daily and 100 mg, 200 mg, and 300 mg 3 times daily). RESULTS: Danoprevir in combination with pegylated interferon α-2a and ribavirin was safe and generally well tolerated. The median change in HCV RNA level from baseline to the end of treatment with danoprevir at 400 mg, 600 mg, and 900 mg twice daily was -4.7 log(10) IU/mL, -5.4 log(10) IU/mL, and -5.3 log(10) IU/mL, respectively, and at 100 mg, 200 mg, and 300 mg 3 times daily was -5.5 log(10) IU/mL, -5.7 log(10) IU/mL, and -5.6 log(10) IU/mL, respectively. Placebo administered in combination with standard of care resulted in median decrease in HCV RNA level of -2.6 log(10) IU/mL (with twice daily regimen) and -2.0 log(10) IU/mL (with 3 times daily regimen). CONCLUSIONS: Our study showed substantial antiviral efficacy of danoprevir in combination with pegylated interferon α-2a and ribavirin. Exploration of the safety and antiviral efficacy of danoprevir in longer clinical studies is warranted.

Treatment of chronic hepatitis C patients with the NS3/4A protease inhibitor danoprevir (ITMN-191/RG7227) leads to robust reductions in viral RNA: a phase 1b multiple ascending dose study.

BACKGROUND & AIMS: Danoprevir is a potent and selective inhibitor of the hepatitis C virus (HCV) NS3/4A serine protease. The present study assessed the safety, pharmacokinetics, and antiviral activity of danoprevir in a randomized, placebo-controlled, 14-day multiple ascending dose study in patients with chronic HCV genotype 1 infection. METHODS: Four cohorts of treatment-naïve (TN) patients (100 mg q12 h, 100 mg q8 h, 200 mg q12 h, 200 mg q8 h) and one cohort of non-responders (NR) to prior pegylated interferon alfa-ribavirin treatment (300 mg q12 h) were investigated. RESULTS: Danoprevir was safe and well tolerated; adverse events were generally mild, transient and were not associated with treatment group or dose level. Danoprevir displayed a slightly more than proportional increase in exposure with increasing daily dose and was rapidly eliminated from the plasma compartment. Maximal decreases in HCV RNA were: -3.9 log(10)IU/ml and -3.2 log(10)IU/ml in TN receiving 200 mg q8 h and 200 mg q12 h, respectively. End of treatment viral decline in these two cohorts was within 0.1 log(10)IU/ml of the viral load nadir. HCV RNA reduction in NR was more modest than that observed in upper dose TN cohorts. The overall incidence of viral rebound was low (10/37) and was associated with the R155K substitution in NS3 regardless of the HCV subtype. CONCLUSIONS: Danoprevir was safe and well tolerated when administered for 14 days in patients with chronic HCV genotype 1 infection. Treatment resulted in sustained, multi-log(10) IU/ml reductions in HCV RNA in upper dose cohorts. These results support further clinical evaluation of danoprevir in patients with chronic HCV.

A double blind, randomized, placebo-controlled study of SP-303 (Provir) in the symptomatic treatment of acute diarrhea among travelers to Jamaica and Mexico.

OBJECTIVE: The study was designed to evaluate the effectiveness of SP-303 (Provir), a plant-derived product with novel antisecretory properties, in the treatment of travelers' diarrhea. METHODS: A total of 184 persons from the United States who acquired diarrhea in Jamaica or Mexico were enrolled in a double-blind, placebo-controlled study examining the effectiveness of three doses of SP-303 in reducing illness. Subjects were treated with 125 mg, 250 mg, or 500 mg SP-303 or a matching placebo four times a day for 2 days. Subjects kept daily diaries of symptoms and were seen each day for 3 days. Of the subjects, 169 (92%) were included in the efficacy analysis. RESULTS: The most common etiological agent identified was enterotoxigenic Escherichia coli, found in 19% of subjects. The mean time interval from taking the first dose of medication until passage of the last unformed stool during 48 h therapy (TLUS48) was 38.7 h for the placebo group. TLUS48 was shortened by SP-303: 30.6 h for the 125-mg dose group (p = 0.005); 30.3 h for the 250-mg group; and 32.6 h for the 500-mg group (p = 0.01). Treatment failures were seen in 29.3% in the placebo group compared with 7.3% (p = 0.01), 4.3 (p = 0.002), and 9.8 (p = 0.026) in the three treatment groups. SP-303 was well tolerated at all doses. CONCLUSIONS: SP-303 was effective in shortening the duration of travelers' diarrhea by 21%. This antisecretory approach works directly against the pathophysiology of travelers' diarrhea and is not likely to potentiate invasive forms of diarrhea or to produce posttreatment constipation.