Posts Tagged therapeutics

[Abstract + References] How safe is switching antiepileptic drug manufacturers?

A nationwide German study of prescription data has demonstrated that switching to an antiepileptic drug from a different manufacturer increases the risk of seizure relapse. This finding sparks a debate about the reason for seizure worsening after switching and whether or not it is a pharmacological issue.

References

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    Lang, J. D. et al. Switching the manufacturer of anti-epileptic drugs is associated with higher risk of seizures. Ann. Neurol.https://doi.org/10.1002/ana.25353 (2018).

  2. 2.

    Davit, B. M. et al. Comparing generic and innovator drugs: a review of 12 years of bioequivalence data from the United States Food and Drug Administration. Ann. Pharmacother. 43, 1583–1597 (2009).

  3. 3.

    Krauss, G. L. et al. Assessing bioequivalence of generic antiepilepsy drugs. Ann. Neurol. 70, 221–228 (2011).

  4. 4.

    Labiner, D. M. et al. Generic antiepileptic drugs and associated medical resource utilization in the United States. Neurology 74, 1566–1574 (2010).

  5. 5.

    Andermann, F. et al. Compulsory generic switching of antiepileptic drugs: high switchback rates to branded compounds compared with other drug classes. Epilepsia 48, 464–469 (2007).

  6. 6.

    Ting, T. J. et al. Generic lamotrigine versus brand-name Lamictal bioequivalence in patients with epilepsy: a field test of the FDA bioequivalence standard. Epilepsia 56, 1415–1424 (2015).

  7. 7.

    Privitera, M. D. et al. Generic-to-generic lamotrigine switches in people with epilepsy: the randomised controlled EQUIGEN trial. Lancet Neurol. 15, 365–372 (2016).

  8. 8.

    Gollwitzer, S. et al. Nonadherence to antiepileptic drugs in Germany: a retrospective, population-based study. Neurology 87, 466–472 (2016).

  9. 9.

    Kesselheim, A. S. et al. Variations in pill appearance of antiepileptic drugs and the risk of nonadherence. JAMA Intern. Med. 173, 202–208 (2013).

  10. 10.

    Holtkamp, M. & Theodore, W. H. Generic antiepileptic drugs — safe or harmful in patients with epilepsy? Epilepsia 59, 1273–1281 (2018).

via How safe is switching antiepileptic drug manufacturers? | Nature Reviews Neurology

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[Abstract] Contralaterally Controlled Functional Electrical Stimulation Improves Hand Dexterity in Chronic Hemiparesis

Abstract

Background and Purpose—It is unknown whether one method of neuromuscular electrical stimulation for poststroke upper limb rehabilitation is more effective than another. Our aim was to compare the effects of contralaterally controlled functional electrical stimulation (CCFES) with cyclic neuromuscular electrical stimulation (cNMES).

Methods—Stroke patients with chronic (>6 months) moderate to severe upper extremity hemiparesis (n=80) were randomized to receive 10 sessions/wk of CCFES- or cNMES-assisted hand opening exercise at home plus 20 sessions of functional task practice in the laboratory for 12 weeks. The task practice for the CCFES group was stimulation assisted. The primary outcome was change in Box and Block Test (BBT) score at 6 months post treatment. Upper extremity Fugl–Meyer and Arm Motor Abilities Test were also measured.

Results—At 6 months post treatment, the CCFES group had greater improvement on the BBT, 4.6 (95% confidence interval [CI], 2.2–7.0), than the cNMES group, 1.8 (95% CI, 0.6–3.0), between-group difference of 2.8 (95% CI, 0.1–5.5), P=0.045. No significant between-group difference was found for the upper extremity Fugl–Meyer (P=0.888) or Arm Motor Abilities Test (P=0.096). Participants who had the largest improvements on BBT were <2 years post stroke with moderate (ie, not severe) hand impairment at baseline. Among these, the 6-month post-treatment BBT gains of the CCFES group, 9.6 (95% CI, 5.6–13.6), were greater than those of the cNMES group, 4.1 (95% CI, 1.7–6.5), between-group difference of 5.5 (95% CI, 0.8–10.2), P=0.023.

Conclusions—CCFES improved hand dexterity more than cNMES in chronic stroke survivors.

Source: Contralaterally Controlled Functional Electrical Stimulation Improves Hand Dexterity in Chronic Hemiparesis | Stroke

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[Abstract] Contralaterally Controlled Functional Electrical Stimulation Improves Hand Dexterity in Chronic Hemiparesis – Stroke

Abstract

Background and Purpose—It is unknown whether one method of neuromuscular electrical stimulation for poststroke upper limb rehabilitation is more effective than another. Our aim was to compare the effects of contralaterally controlled functional electrical stimulation (CCFES) with cyclic neuromuscular electrical stimulation (cNMES).

Methods—Stroke patients with chronic (>6 months) moderate to severe upper extremity hemiparesis (n=80) were randomized to receive 10 sessions/wk of CCFES- or cNMES-assisted hand opening exercise at home plus 20 sessions of functional task practice in the laboratory for 12 weeks. The task practice for the CCFES group was stimulation assisted. The primary outcome was change in Box and Block Test (BBT) score at 6 months post treatment. Upper extremity Fugl–Meyer and Arm Motor Abilities Test were also measured.

Results—At 6 months post treatment, the CCFES group had greater improvement on the BBT, 4.6 (95% confidence interval [CI], 2.2–7.0), than the cNMES group, 1.8 (95% CI, 0.6–3.0), between-group difference of 2.8 (95% CI, 0.1–5.5), P=0.045. No significant between-group difference was found for the upper extremity Fugl–Meyer (P=0.888) or Arm Motor Abilities Test (P=0.096). Participants who had the largest improvements on BBT were <2 years post stroke with moderate (ie, not severe) hand impairment at baseline. Among these, the 6-month post-treatment BBT gains of the CCFES group, 9.6 (95% CI, 5.6–13.6), were greater than those of the cNMES group, 4.1 (95% CI, 1.7–6.5), between-group difference of 5.5 (95% CI, 0.8–10.2), P=0.023.

Conclusions—CCFES improved hand dexterity more than cNMES in chronic stroke survivors.

Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00891319.

Source: Contralaterally Controlled Functional Electrical Stimulation Improves Hand Dexterity in Chronic Hemiparesis | Stroke

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[ARTICLE] Contralaterally Controlled Functional Electrical Stimulation Improves Hand Dexterity in Chronic Hemiparesis – Full Text PDF

Abstract

Background and Purpose—It is unknown whether one method of neuromuscular electrical stimulation for poststroke upper limb rehabilitation is more effective than another. Our aim was to compare the effects of contralaterally controlled functional electrical stimulation (CCFES) with cyclic neuromuscular electrical stimulation (cNMES).

Methods—Stroke patients with chronic (>6 months) moderate to severe upper extremity hemiparesis (n=80) were randomized to receive 10 sessions/wk of CCFES- or cNMES-assisted hand opening exercise at home plus 20 sessions of functional task practice in the laboratory for 12 weeks. The task practice for the CCFES group was stimulation assisted. The primary outcome was change in Box and Block Test (BBT) score at 6 months post treatment. Upper extremity Fugl–Meyer and Arm Motor Abilities Test were also measured.

Results—At 6 months post treatment, the CCFES group had greater improvement on the BBT, 4.6 (95% confidence interval [CI], 2.2–7.0), than the cNMES group, 1.8 (95% CI, 0.6–3.0), between-group difference of 2.8 (95% CI, 0.1–5.5), P=0.045. No significant between-group difference was found for the upper extremity Fugl–Meyer (P=0.888) or Arm Motor Abilities Test (P=0.096). Participants who had the largest improvements on BBT were <2 years post stroke with moderate (ie, not severe) hand impairment at baseline. Among these, the 6-month post-treatment BBT gains of the CCFES group, 9.6 (95% CI, 5.6–13.6), were greater than those of the cNMES group, 4.1 (95% CI, 1.7–6.5), between-group difference of 5.5 (95% CI, 0.8–10.2), P=0.023.

Conclusions—CCFES improved hand dexterity more than cNMES in chronic stroke survivors.

Download Full Text PDF

 

Source: Contralaterally Controlled Functional Electrical Stimulation Improves Hand Dexterity in Chronic Hemiparesis

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[ARTICLE] Cathepsin B is a New Drug Target for Traumatic Brain Injury Therapeutics: Evidence for E64d as a Promising Lead Drug Candidate

There is currently no therapeutic drug treatment for traumatic brain injury (TBI) despite decades of experimental clinical trials. This may be because the mechanistic pathways for improving TBI outcomes have yet to be identified and exploited. As such, there remains a need to seek out new molecular targets and their drug candidates to find new treatments for TBI. This review presents supporting evidence for cathepsin B, a cysteine protease, as a potentially important drug target for TBI. Cathepsin B expression is greatly up-regulated in TBI animal models, as well as in trauma patients. Importantly, knockout of the cathepsin B gene in TBI mice results in substantial improvements of TBI-caused deficits in behavior, pathology, and biomarkers, as well as improvements in related injury models. During the process of TBI-induced injury, cathepsin B likely escapes the lysosome, its normal subcellular location, into the cytoplasm or extracellular matrix (ECM) where the unleashed proteolytic power causes destruction via necrotic, apoptotic, autophagic, and activated glia-induced cell death, together with ECM breakdown and inflammation. Significantly, chemical inhibitors of cathepsin B are effective for improving deficits in TBI and related injuries including ischemia, cerebral bleeding, cerebral aneurysm, edema, pain, infection, rheumatoid arthritis, epilepsy, Huntington’s disease, multiple sclerosis, and Alzheimer’s disease. The inhibitor E64d is unique among cathepsin B inhibitors in being the only compound to have demonstrated oral efficacy in a TBI model and prior safe use in man and as such it is an excellent tool compound for preclinical testing and clinical compound development. These data support the conclusion that drug development of cathepsin B inhibitors for TBI treatment should be accelerated.

Source: Frontiers | Cathepsin B is a New Drug Target for Traumatic Brain Injury Therapeutics: Evidence for E64d as a Promising Lead Drug Candidate | Neurotrauma

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