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Seizure Jan 2020We performed this analysis to evaluate the efficacy and safety of intravenous levetiracetam (IV LEV) in patients with status epilepticus. (Meta-Analysis)
Meta-Analysis
PURPOSE
We performed this analysis to evaluate the efficacy and safety of intravenous levetiracetam (IV LEV) in patients with status epilepticus.
METHOD
Studies were searched in MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for available randomized controlled trials(RCTs) comparing the efficacy and/or safety of IV LEV with other antiepileptic drugs (AEDs). Meta-analysis was performed using the random-effects model to calculate risk ratio with the RevMan 5.3 software.
RESULTS
Six RCTs with a total of 543 patients were included. There was no significant differences in clinical seizure cessation and hospital mortality, either between IV LEV and IV phenytoin (PHT) or between IV LEV and IV valproate (VPA). Compared with IV PHT, IV LEV had a lower risk of poor neurological outcome. For IV LEV compared with IV lorazepam (LOR), no significant difference in efficacy was found, but IV LEV patients had significantly lower need for ventilatory assistance. Adding IV LEV to clonazepam (CNP), compared with adding placebo showed no significant differences in seizure cessation at 15 min.
CONCLUSIONS
Our results suggested that IV LEV was comparable to IV PHT,VPA, or LOR in efficacy, and IV LEV as add-on therapy of CNP had no superiority in seizure cessation than CNP plus placebo. IV LEV may have a better tolerability than other AEDs do. More RCTs are needed to validate the role of IV LEV in status epilepticus.
Topics: Administration, Intravenous; Anticonvulsants; Humans; Levetiracetam; Randomized Controlled Trials as Topic; Status Epilepticus; Treatment Outcome
PubMed: 31830677
DOI: 10.1016/j.seizure.2019.11.007 -
Clinical and Molecular Hepatology Apr 2020Drug induced liver injury (DILI) may be different in the East compared to the West due to differing disease prevalence, prescribing patterns and pharmacogenetic... (Meta-Analysis)
Meta-Analysis
Drug induced liver injury (DILI) may be different in the East compared to the West due to differing disease prevalence, prescribing patterns and pharmacogenetic profiles. To review existing literature on causative agents of DILI in the East compared to the West, a comprehensive literature search was performed on electronic databases: MEDLINE/PubMed, Embase, Cochrane Library and China National Knowledge Infrastructure without language restrictions. Studies which involve patients having DILI and reported the frequency of causative agents were included. A random effects model was applied to synthesize the current evidence using prevalence of class-specific and agent-specific causative drugs with 95% confidence intervals. Of 6,914 articles found, 12 showed the distribution of drugs implicated in DILI in the East with a total of 33,294 patients and 16 in the West with a total of 26,069 DILI cases. In the East, the most common agents by class were anti-tuberculosis drugs (26.6%), herbal and alternative medications (25.3%), and antibiotics (15.7%), while in the West, antibiotics (34.9%), cardiovascular agents (17.3%), and non-steroidal anti-inflammatory drugs (12.5%) were the commonest. For individual agents, the most common agents in the East were isoniazid-rifampicin-pyrazinamide (25.4%), phenytoin (3.5%), and cephalosporin (2.9%) while in the West, amoxicillin-potassium clavulanate combination acid (11.3%), nimesulide (6.3%), and ibuprofen (6.1%) were the commonest. There was significant heterogeneity due to variability in single-centre compared to multi-centre studies. Differences in DILI in the East versus the West both in drug classes and individual agents are important for clinicians to recognize.
Topics: Anti-Bacterial Agents; Antitubercular Agents; Cardiovascular Agents; Chemical and Drug Induced Liver Injury; Databases, Factual; Humans; Medicine, Traditional; Risk Assessment
PubMed: 31816676
DOI: 10.3350/cmh.2019.1003 -
The Cochrane Database of Systematic... Jul 2019At the end of 2016, 145 countries reported to the World Health Organization (WHO) over 173,000 new cases of leprosy worldwide. In the past 20 years, over 16 million... (Review)
Review
BACKGROUND
At the end of 2016, 145 countries reported to the World Health Organization (WHO) over 173,000 new cases of leprosy worldwide. In the past 20 years, over 16 million people have been treated for leprosy globally. The condition's main complications are injuries and ulceration caused by sensory loss from nerve damage. In this review we explored interventions to prevent or treat secondary damage to the skin in people affected by leprosy (Hansen's disease). This is an update of a Cochrane Review published in 2008.
OBJECTIVES
To assess the effects of education, information, self-care programmes, dressings, skin care, footwear and other measures for preventing and healing secondary damage to the skin in persons affected by leprosy.
SEARCH METHODS
We updated our searches of the following databases up to July 2018: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, AMED, LILACS, and CINAHL. We also searched five trial registers, three grey literature databases, and the reference lists of included studies for further references to relevant randomised controlled trials (RCTs).
SELECTION CRITERIA
RCTs or quasi-RCTs or randomised cross-over trials involving anyone with leprosy and potential damage to peripheral nerves who was treated with any intervention designed to prevent damage, heal existing ulcers, and prevent development of new ulcers. Eligible comparisons were usual care, no interventions, or other interventions (e.g. other types of dressings or footwear).
DATA COLLECTION AND ANALYSIS
We adhered to standard methodological procedures expected by Cochrane. Primary outcomes were prevention of ulcer(s), healing of existing ulcer(s) and adverse events. We used GRADE to assess the certainty of evidence for each outcome.
MAIN RESULTS
We included 14 trials (854 participants). Eleven studies reported on gender (men: 472, women: 157). Participant age varied from 18 to 74 years. Most participants had a single, mainly non-infected, wound on one foot, which had been there for less than a year. Only seven studies reported whole study duration (there was no follow-up post-treatment), which was on average six months (range: 1 to 12 months). The studies were conducted in Brazil, Ethiopia, Egypt, Indonesia, Mexico, South Korea, and India. Many 'Risk of bias' assessments were rated as unclear risk due to limited information. Six studies had high risk of bias in at least one domain, including selection and attrition bias.Thirteen studies evaluated different interventions for treating existing ulcers, one of them also evaluated prevention of new ulcers. One study aimed to prevent skin changes, such as cracking and fissures. Investigated interventions included: laser therapy, light-emitting diode (LED), zinc tape, intralesional pentoxifylline, pulsed magnetic fields, wax therapy, ketanserin, human amniotic membrane gel, phenytoin, plaster shoes, and footwear.We are uncertain about the following key results, as the certainty of evidence is very low. All time points were measured from baseline.Three studies compared zinc tape versus other interventions and reported results in favour of zinc tape. One study compared zinc tape versus magnesium sulphate: at one month the number of healed ulcers and reduction in mean ulcer area was higher with zinc tape (risk ratio (RR) 2.00, 95% confidence interval (CI) 0.43 to 9.21, and mean difference (MD) -14.30 mm², 95% CI -26.51 to -2.09, respectively, 28 participants). Another study compared zinc tape and povidone iodine and found that even though there was a greater reduction in ulcer area after six weeks of treatment with zinc tape, there was no clear difference due to the wide 95% CI (MD 128.00 mm², 95% CI -110.01 to 366.01; 38 participants). The third study (90 participants) compared adhesive zinc tape with gauze soaked in Eusol, and found the healing time for deep ulcers was less compared to zinc tape: 17 days (95% CI 12 to 20) versus 30 days (95% CI 21 to 63). Adverse events were only collected in the study comparing zinc tape with gauze soaked in Eusol: there were no signs of skin sensitisation in either group at two months.Two studies compared topical phenytoin versus saline dressing and reported results in favour of phenytoin. One study reported a greater mean percentage reduction of ulcer area after four weeks with phenytoin 2% (MD 39.30%, 95% CI 25.82 to 52.78; 23 participants), and the other study reported a greater mean percentage reduction of ulcer volume (16.60%) after four weeks with phenytoin (95% CI 8.46 to 24.74; 100 participants). No adverse events were observed with either treatment during the four-month treatment period (2 studies, 123 participants). Prevention of ulcers was not evaluated in these nor the zinc studies, as the interventions were not for preventative use.Two studies compared protective footwear (with or without self-care) with either 1) polyvinyl chloride (PVC) boots, or 2) pulsed magnetic fields plus self-care and protective footwear. In the study comparing canvas shoes versus PVC boots, none of the 72 participants with scars at the start of the study developed new ulcers over one-year follow-up. Healing of ulcers was assessed in 38 participants from this study, but we are unclear if there is a difference between groups. In the study comparing pulsed magnetic fields (in addition to self-care and protective footwear) to only self-care and footwear in 33 participants, we are uncertain if the mean volume of ulcers at four to five weeks' follow-up was different between groups; this study did not evaluate the prevention of ulcers. Information for adverse events was only reported in the study comparing canvas shoes with PVC boots; the authors stated that the PVC boots could become hot in strong sunlight and possibly burn the feet.
AUTHORS' CONCLUSIONS
Based on the available evidence, we could not draw firm conclusions about the effects of the included interventions. The main evidence limitations were high or unclear risk of bias, including selection, performance, detection, and attrition bias; imprecision due to few participants in the studies; and indirectness from poor outcome measurement and inapplicable interventions. Future research should clearly report important outcomes, such as adverse events, and assess widely available interventions, which should include treatments aimed at prevention. These trials should ensure allocation concealment, blinding, and an adequate sample size.
PubMed: 31425632
DOI: 10.1002/14651858.CD012235.pub2 -
The Cochrane Database of Systematic... Jul 2019This is an update of a Cochrane Review first published in 2001, and last updated in 2013. This review is one in a series of Cochrane Reviews investigating pair-wise... (Review)
Review
BACKGROUND
This is an update of a Cochrane Review first published in 2001, and last updated in 2013. This review is one in a series of Cochrane Reviews investigating pair-wise monotherapy comparisons.Epilepsy is a common neurological condition in which abnormal electrical discharges from the brain cause recurrent unprovoked seizures. It is believed that with effective drug treatment, up to 70% of individuals with active epilepsy have the potential to become seizure-free and go into long-term remission shortly after starting drug therapy with a single antiepileptic drug in monotherapy.Worldwide, particularly in the developing world, phenytoin and phenobarbitone are commonly used antiepileptic drugs, primarily because they are inexpensive. The aim of this review is to summarise data from existing trials comparing phenytoin and phenobarbitone.
OBJECTIVES
To review the time to treatment failure, remission and first seizure with phenobarbitone compared with phenytoin when used as monotherapy in people with focal onset seizures (simple or complex focal and secondarily generalised), or generalised onset tonic-clonic seizures (with or without other generalised seizure types).
SEARCH METHODS
For the latest update, we searched the following databases on 21 August 2018: the Cochrane Register of Studies (CRS Web), which includes Cochrane Epilepsy's Specialized Register and CENTRAL; MEDLINE; the US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov); and the World Health Organization International Clinical Trials Registry Platform (ICTRP). We handsearched relevant journals and contacted pharmaceutical companies, original trial investigators, and experts in the field. SELECTION CRITERIA: Randomised controlled trials comparing monotherapy with either phenobarbitone or phenytoin in children or adults with focal onset seizures or generalised onset tonic-clonic seizures.
DATA COLLECTION AND ANALYSIS
This was an individual participant data (IPD), review. Our primary outcome was time to treatment failure. Our secondary outcomes were time to first seizure post-randomisation, time to six-month remission and time to 12-month remission. We used Cox proportional hazards regression models to obtain trial-specific estimates of hazard ratios (HRs), with 95% confidence intervals (CIs), using the generic inverse variance method to obtain the overall pooled HR and 95% CI.
MAIN RESULTS
Individual participant data were obtained for five studies, which recruited a total of 635 participants, representing 80% of 798 individuals from all seven identified eligible trials. For remission outcomes, an HR of less than 1 indicates an advantage for phenytoin and for first seizure and treatment failure outcomes an HR of less than 1 indicates an advantage for phenobarbitone.Results for the primary outcome of the review were: time to treatment failure for any reason related to treatment (pooled HR adjusted for seizure type for 499 participants: 1.61, 95% CI 1.22 to 2.12, low-certainty evidence), time to treatment failure due to adverse events (pooled HR adjusted for seizure type for 499 participants: 1.99, 95% CI 1.37 to 2.87, low-certainty evidence), time to treatment failure due to lack of efficacy (pooled HR adjusted for seizure type for 499 participants: 1.87, 95% CI 1.32 to 2.66, moderate-certainty evidence), showing a statistically significant advantage for phenytoin compared to phenobarbitone.For our secondary outcomes, we did not find any statistically significant differences between phenytoin and phenobarbitone: time to first seizure post-randomisation (pooled HR adjusted for seizure type for 624 participants: 0.85, 95% CI 0.69 to 1.06, moderate-certainty evidence), time to 12-month remission (pooled HR adjusted for seizure type for 588 participants: 0.90, 95% CI 0.69 to 1.19, moderate-certainty evidence), and time to six-month remission pooled HR adjusted for seizure type for 588 participants: 0.91, 95% CI 0.71 to 1.15, moderate-certainty evidence).For individuals with focal onset seizures (73% of individuals contributing to analysis), numerical results were similar and conclusions the same as for analyses of all individuals and for individuals with generalised onset seizures (27% of individuals contributing to analysis), results were imprecise and no clear differences between the drugs were observed.Several confounding factors, most notably the differences in design of the trials with respect to blinding, were likely to have impacted on the results of the primary outcome 'time to treatment failure', and in turn, the treatment failure rates may have impacted on the secondary efficacy outcomes of time to first seizure and time to 12-month and six-month remission.
AUTHORS' CONCLUSIONS
Low-certainty evidence from this review suggests that phenytoin may be a more effective drug than phenobarbitone in terms of treatment retention (treatment failures due to lack of efficacy or adverse events or both). Moderate-certainty evidence from this review also indicates no differences between the drugs in terms of time to seizure recurrence and seizure remission.However, the trials contributing to the analyses had methodological inadequacies and methodological design differences that may have impacted upon the results of this review. Therefore, we do not suggest that results of this review alone should form the basis of a treatment choice for a patient with newly onset seizures. We recommend that future trials should be designed to the highest quality possible with consideration of masking, choice of population, classification of seizure type, duration of follow-up, choice of outcomes and analysis, and presentation of results.
PubMed: 31425629
DOI: 10.1002/14651858.CD002217.pub3 -
The Cochrane Database of Systematic... Aug 2019More than three million persons are disabled by leprosy worldwide. The main complication of sensory nerve damage is neuropathic ulceration, particularly of the feet. In... (Review)
Review
BACKGROUND
More than three million persons are disabled by leprosy worldwide. The main complication of sensory nerve damage is neuropathic ulceration, particularly of the feet. In this review we explored interventions that can prevent and treat secondary damage to skin and limbs.
OBJECTIVES
To assess the effects of self-care, dressings and footwear in preventing and healing secondary damage to the skin in persons affected by leprosy.
SEARCH METHODS
We searched the Cochrane Skin Group Specialised Register (April 2008), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2008), MEDLINE (from 2003 to April 2008), EMBASE (from 2005 to April 2008), CINAHL (1982-2006) and LILACS (1982- April 2008 ) as well as online registers of ongoing trials (April 2008).
SELECTION CRITERIA
Randomised controlled trials involving anyone with leprosy and damage to peripheral nerves treated with any measures designed to prevent damage with the aim of healing existing ulcers and preventing development of new ulcers.
DATA COLLECTION AND ANALYSIS
Two authors assessed trial quality and extracted data.
MAIN RESULTS
Eight trials with a total of 557 participants were included. The quality of the trials was generally poor. The interventions and outcome measures were diverse. Although three studies that compared zinc tape to more traditional dressings found some benefit, none of these showed a statistically significant effect. One trial indicated that topical ketanserin had a better effect on wound healing than clioquinol cream or zinc paste, RR was 6.00 (95% CI 1.45 to 24.75). We did not combine the results of the two studies that compared topical phenytoin to saline dressing, but both studies found statistically significant effects in favour of phenytoin for healing of ulcer (SMD -2.34; 95% CI -3.30 to -1.39; and SMD -0.79; 95% CI -1.20 to 0.39). Canvas shoes were not much better than PVC-boots, and double rocker shoes did not promote healing much more than below-knee plasters.
AUTHORS' CONCLUSIONS
One study suggested that topical ketanserin is more effective than clioquinol cream or zinc paste. Topical phenytoin (two studies) may be more effective than saline dressing regarding ulcer healing. For the other dressings the results were equivocal. Canvas shoes were a little better than PVC-boots, but not significantly, and the effect of double rocker shoes compared to below-knee plasters was no different in promoting the healing of ulcers. No side effects were documented.There is a lack of high quality research in the field of ulcer prevention and treatment in leprosy. New trials should follow the current standards for design and reporting of randomised controlled trials.
PubMed: 31425616
DOI: 10.1002/14651858.CD004833.pub4 -
The Cochrane Database of Systematic... Jul 2019This is an update of a Cochrane Review first published in 2002 and last updated in 2017. This review is one in a series of Cochrane Reviews investigating pair-wise...
BACKGROUND
This is an update of a Cochrane Review first published in 2002 and last updated in 2017. This review is one in a series of Cochrane Reviews investigating pair-wise monotherapy comparisons.Epilepsy is a common neurological condition in which abnormal electrical discharges from the brain cause recurrent unprovoked seizures. It is believed that with effective drug treatment, up to 70% of individuals with active epilepsy have the potential to become seizure-free and go into long-term remission shortly after starting drug therapy with a single antiepileptic drug in monotherapy.Worldwide, carbamazepine and phenytoin are commonly-used broad spectrum antiepileptic drugs, suitable for most epileptic seizure types. Carbamazepine is a current first-line treatment for focal onset seizures in the USA and Europe. Phenytoin is no longer considered a first-line treatment, due to concerns over adverse events associated with its use, but the drug is still commonly used in low- to middle-income countries because of its low cost. No consistent differences in efficacy have been found between carbamazepine and phenytoin in individual trials; however, the confidence intervals generated by these trials are wide, and therefore, synthesising the data of the individual trials may show differences in efficacy.
OBJECTIVES
To review the time to treatment failure, remission and first seizure with carbamazepine compared with phenytoin when used as monotherapy in people with focal onset seizures (simple or complex focal and secondarily generalised), or generalised onset tonic-clonic seizures (with or without other generalised seizure types).
SEARCH METHODS
For the latest update, we searched the following databases on 13 August 2018: the Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy's Specialised Register and CENTRAL; MEDLINE; the US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov); and the World Health Organization International Clinical Trials Registry Platform (ICTRP). We handsearched relevant journals and contacted pharmaceutical companies, original trial investigators, and experts in the field.
SELECTION CRITERIA
Randomised controlled trials comparing monotherapy with either carbamazepine or phenytoin in children or adults with focal onset seizures or generalised onset (tonic-clonic) seizures.
DATA COLLECTION AND ANALYSIS
This was an individual participant data (IPD) review. Our primary outcome was time to treatment failure. Our secondary outcomes were time to first seizure post-randomisation, time to six-month remission, time to 12-month remission, and incidence of adverse events. We used Cox proportional hazards regression models to obtain trial-specific estimates of hazard ratios (HRs), with 95% confidence intervals (CIs), using the generic inverse variance method to obtain the overall pooled HR and 95% CI.
MAIN RESULTS
IPD were available for 595 participants out of 1102 eligible individuals, from four out of 11 trials (i.e. 54% of the potential data). For remission outcomes, a HR greater than 1 indicates an advantage for phenytoin; and for first seizure and withdrawal outcomes, a HR greater than 1 indicates an advantage for carbamazepine. Most participants included in analysis (78%) were classified as experiencing focal onset seizures at baseline and only 22% were classified as experiencing generalised onset seizures; the results of this review are therefore mainly applicable to individuals with focal onset seizures.Results for the primary outcome of the review were: time to treatment failure for any reason related to treatment (pooled HR adjusted for seizure type for 546 participants: 0.94, 95% CI 0.70 to 1.26, moderate-certainty evidence); time to treatment failure due to lack of efficacy (pooled HR adjusted for seizure type for 546 participants: 0.99, 95% CI 0.69 to 1.41, moderate-certainty evidence); both showing no clear difference between the drugs and time to treatment failure due to adverse events (pooled HR adjusted for seizure type for 546 participants: 1.27, 95% CI 0.87 to 1.86, moderate-certainty evidence), showing that treatment failure due to adverse events may occur earlier on carbamazepine than phenytoin, but we cannot rule out a slight advantage to carbamazepine or no difference between the drugs.For our secondary outcomes (pooled HRs adjusted for seizure type), we did not find any clear differences between carbamazepine and phenytoin: time to first seizure post-randomisation (582 participants): 1.15, 95% CI 0.94 to 1.40, moderate-certainty evidence); time to 12-month remission (551 participants): 1.00, 95% CI 0.79 to 1.26, moderate-certainty evidence); and time to six-month remission (551 participants): 0.90, 95% CI 0.73 to 1.12, moderate-certainty evidence).For all outcomes, results for individuals with focal onset seizures were similar to overall results (moderate-certainty evidence), and results for the small subgroup of individuals with generalised onset seizures were imprecise, so we cannot rule out an advantage to either drug, or no difference between drugs (low-certainty evidence). There was also evidence that misclassification of seizure type may have confounded the results of this review, particularly for the outcome 'time to treatment failure'. Heterogeneity was present in analysis of 'time to first seizure' for individuals with generalised onset seizures, which could not be explained by subgroup analysis or sensitivity analyses.Limited information was available about adverse events in the trials and we could not compare the rates of adverse events between carbamazepine and phenytoin. Some adverse events reported on both drugs were abdominal pain, nausea, and vomiting, drowsiness, motor and cognitive disturbances, dysmorphic side effects (such as rash).
AUTHORS' CONCLUSIONS
Moderate-certainty evidence provided by this systematic review does not show any differences between carbamazepine and phenytoin in terms of effectiveness (retention) or efficacy (seizure recurrence and seizure remission) for individuals with focal onset or generalised onset seizures.However, some of the trials contributing to the analyses had methodological inadequacies and inconsistencies, which may have had an impact on the results of this review. We therefore do not suggest that results of this review alone should form the basis of a treatment choice for a person with newly-onset seizures. We did not find any evidence to support or refute current treatment policies. We implore that future trials be designed to the highest quality possible, with consideration of masking, choice of population, classification of seizure type, duration of follow-up, choice of outcomes and analysis, and presentation of results.
Topics: Anticonvulsants; Carbamazepine; Child; Epilepsy; Humans; Phenytoin; Randomized Controlled Trials as Topic; Remission Induction; Seizures; Treatment Failure; Treatment Outcome
PubMed: 31318037
DOI: 10.1002/14651858.CD001911.pub4 -
British Journal of Anaesthesia Aug 2019Trigeminal neuralgia (TN) can have a significant impact on wellbeing and quality of life. Limited data exist for treatments that improve TN pain acutely, within 24 h of...
BACKGROUND
Trigeminal neuralgia (TN) can have a significant impact on wellbeing and quality of life. Limited data exist for treatments that improve TN pain acutely, within 24 h of administration. This systematic review aims to identify effective treatments that acutely relieve TN exacerbations.
METHODS
We searched Medline and Cochrane Central Register of Controlled Trials (CENTRAL) for relevant English language publications. The reference list for all articles was searched for other relevant publications. All studies that satisfied the following PICO criteria were included: (i) Population-adults with acute exacerbation of primary TN symptoms; (ii) Intervention-any medication or intervention with the primary goal of pain relief within 24 h; (iii) Comparator-usual medical care, placebo, sham or active treatment; (iv) Outcome-more than 50% reduction in pain intensity within 24 h of administration.
RESULTS
Of 431 studies, 17 studies were identified that reported immediate results of acute treatment in TN. The evidence suggests that the following interventions may be beneficial: local anaesthetic, mainly lidocaine (ophthalmic, nasal or oral mucosa, trigger point injection, i.v. infusion, nerve block); anticonvulsant, phenytoin or fosphenytoin (i.v. infusion); serotonin agonist, sumatriptan (s.c. injection, nasal). Other referenced interventions with very limited evidence include N-methyl-d-aspartate receptor antagonist (magnesium sulphate infusion) and botulinum toxin (trigger point injection).
CONCLUSIONS
Several treatment options exist that may provide fast and safe relief of TN. Future studies should report on outcomes within 24 h to improve knowledge of the acute analgesic TN treatments.
Topics: Acute Disease; Analgesia; Analgesics; Anticonvulsants; Botulinum Toxins; Humans; Magnesium Sulfate; Neurotoxins; Trigeminal Neuralgia
PubMed: 31208761
DOI: 10.1016/j.bja.2019.05.026 -
Medicine Mar 2019To determine the influence of phenytoin (PHT) monotherapy on the serum levels of homocysteine (Hcy), folate and vitamin B12 in patients with epilepsy. (Meta-Analysis)
Meta-Analysis
BACKGROUND
To determine the influence of phenytoin (PHT) monotherapy on the serum levels of homocysteine (Hcy), folate and vitamin B12 in patients with epilepsy.
METHODS
Literature retrieval was performed through PubMed, Web of Science, Embase, Cochrane Library, Chinese Wanfang Data, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Database databases as of the end of March 2018. Pooled weighted mean difference (WMD) and 95% CIs were calculated using a random effect model.
RESULTS
A total of ten eligible studies were identified. The result revealed that the serum level of homocysteine in PHT-treated patients with epilepsy was significantly higher than that in control group (WMD = 8.47, 95% CI: 6.74 to 10.20, P < .001). In addition, the serum levels of folate (WMD = -3.51, 95% CI: -4.20 to -2.83, P < .001) and vitamin B12 (WMD = -62.23, 95% CI: -83.27 to -41.19, P < .001) were decreased significantly compared with the control group.
CONCLUSIONS
Our meta-analysis indicates that PHT monotherapy is associated with the increase in the serum homocysteine levels and decreased levels of folate and vitamin B12, and hyperhomocysteinaemia may contribute to the acceleration of the atherosclerotic process. Therefore, the patients under these medications should be monitored plasma homocysteine.
Topics: Anticonvulsants; Epilepsy; Folic Acid; Homocysteine; Humans; Phenytoin; Research Design; Vitamin B 12
PubMed: 30896627
DOI: 10.1097/MD.0000000000014844 -
Medicine Dec 2018In this study, we aimed to review the literature on phenytoin intoxication induced by compound phenytoin sodium, ephedrine hydrochloride and theophylline tablets...
OBJECTIVE
In this study, we aimed to review the literature on phenytoin intoxication induced by compound phenytoin sodium, ephedrine hydrochloride and theophylline tablets (CPEHTT).
METHOD
A literature search was performed in the following databases: WANFANG DATA, HowNet, National Library Reference and Consultation Alliance, Full-text Database of Foreign Medical Journals, PubMed and Ovid. The search terms were "Compound Phenytoin Sodium, ephedrine Hydrochloride and Theophylline Tablets," and "poisoning," or "toxicity," in Chinese and in English.
RESULT
Ten articles including 104 patients with CPEHTT intoxication were identified. The ages of the patients ranged from 52 to 82 years. Sixty-seven patients were male and thirty-seven patients were female (the male/female ratio, approximately 2:1). The most common clinical manifestations were dizziness (85%) and ataxia (85%), followed by limb weakness (65%), diplopia (25%), binocular horizontal nystagmus (24%), limb numbness (13%), nausea and vomiting (12%), somnolence (10%), tremor and high muscle tension (7%), lag in response (5%), dysarthria (6%), choking cough (2%), auditory hallucination and visual fantasy (1%), and involuntary movement (1%). All patients had chronic lung disease, and the most common disease was chronic bronchitis. The dosage ranged 4 to 15 tablets per day with medication duration of more than 1 year for most patients.
CONCLUSION
The CPEHTT intoxication caused by phenytoin toxicity represents a drug safety problem in China. The common clinical manifestations, serum phenytoin concentrations, and associated factors of CPEHTT intoxication are important for diagnosis and prevention. These findings may help guide clinicians to correctly attend to the use of CPEHTT and avoid its toxicity.
Topics: Bronchodilator Agents; China; Drug Combinations; Ephedrine; Humans; Phenytoin; Tablets; Theophylline
PubMed: 30572493
DOI: 10.1097/MD.0000000000013689 -
The Cochrane Database of Systematic... Oct 2018This is an updated version of the Cochrane Review previously published in 2013. This review is one in a series of Cochrane Reviews investigating pair-wise monotherapy... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This is an updated version of the Cochrane Review previously published in 2013. This review is one in a series of Cochrane Reviews investigating pair-wise monotherapy comparisons.Epilepsy is a common neurological condition in which abnormal electrical discharges from the brain cause recurrent unprovoked seizures. It is believed that with effective drug treatment, up to 70% of individuals with active epilepsy have the potential to become seizure-free and go into long-term remission shortly after starting drug therapy with a single antiepileptic drug in monotherapy.Worldwide, phenytoin is a commonly used antiepileptic drug. It is important to know how newer drugs, such as oxcarbazepine, compare with commonly used standard treatments.
OBJECTIVES
To review the time to treatment failure, remission and first seizure with oxcarbazepine compared to phenytoin, when used as monotherapy in people with focal onset seizures or generalised tonic-clonic seizures (with or without other generalised seizure types).
SEARCH METHODS
We searched the following databases on 20 August 2018: the Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid, 1946 to 20 August 2018), ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We handsearched relevant journals and contacted pharmaceutical companies, original trial investigators and experts in the field.
SELECTION CRITERIA
We included randomised controlled trials comparing monotherapy with either oxcarbazepine or phenytoin in children or adults with focal onset seizures or generalised onset tonic-clonic seizures.
DATA COLLECTION AND ANALYSIS
This was an individual participant data (IPD) review. Our primary outcome was time to treatment failure and our secondary outcomes were time to first seizure post-randomisation, time to six-month and 12-month remission, and incidence of adverse events. We used Cox proportional hazards regression models to obtain trial-specific estimates of hazard ratios (HRs) with 95% confidence intervals (CIs), using the generic inverse variance method to obtain the overall pooled HR and 95% CI.
MAIN RESULTS
Individual participant data were available for 480 out of a total of 517 participants (93%), from two out of three included trials. For remission outcomes, a HR of less than one indicated an advantage for phenytoin; and for first seizure and treatment failure outcomes, a HR of less than one indicated an advantage for oxcarbazepine.The results for time to treatment failure for any reason related to treatment showed a potential advantage of oxcarbazepine over phenytoin, but this was not statistically significant (pooled HR adjusted for epilepsy type: 0.78 95% CI 0.53 to 1.14, 476 participants, two trials, moderate-quality evidence). Our analysis showed that treatment failure due to adverse events occurred later on with oxcarbazepine than phenytoin (pooled HR for all participants: 0.22 (95% CI 0.10 to 0.51, 480 participants, two trials, high-quality evidence). Our analysis of time to treatment failure due to lack of efficacy showed no clear difference between the drugs (pooled HR for all participants: 1.17 (95% CI 0.31 to 4.35), 480 participants, two trials, moderate-quality evidence).We found no clear or statistically significant differences between drugs for any of the secondary outcomes of the review: time to first seizure post-randomisation (pooled HR adjusted for epilepsy type: 0.97 95% CI 0.75 to 1.26, 468 participants, two trials, moderate-quality evidence); time to 12-month remission (pooled HR adjusted for epilepsy type 1.04 95% CI 0.77 to 1.41, 468 participants, two trials, moderate-quality evidence) and time to six-month remission (pooled HR adjusted for epilepsy type: 1.06 95% CI 0.82 to 1.36, 468 participants, two trials, moderate-quality evidence).The most common adverse events reported in more than 10% of participants on either drug were somnolence (28% of total participants, with similar rates for both drugs), headache (15% of total participants, with similar rates for both drugs), dizziness (14.5% of total participants, reported by slightly more participants on phenytoin (18%) than oxcarbazepine (11%)) and gum hyperplasia (reported by substantially more participants on phenytoin (18%) than oxcarbazepine (2%)).The results of this review are applicable mainly to individuals with focal onset seizures; 70% of included individuals experienced seizures of this type at baseline. The two studies included in IPD meta-analysis were generally of good methodological quality but the design of the studies may have biased the results for the secondary outcomes (time to first seizure post-randomisation, time to six-month and 12-month remission) as seizure recurrence data were not collected following treatment failure or withdrawal from the study. In addition, misclassification of epilepsy type may have impacted on results, particularly for individuals with generalised onset seizures.
AUTHORS' CONCLUSIONS
High-quality evidence provided by this review indicates that treatment failure due to adverse events occurs significantly later with oxcarbazepine than phenytoin. For individuals with focal onset seizures, moderate-quality evidence suggests that oxcarbazepine may be superior to phenytoin in terms of treatment failure for any reason, seizure recurrence and seizure remission. Therefore, oxcarbazepine may be a preferable alternative treatment than phenytoin, particularly for individuals with focal onset seizures. The evidence in this review which relates to individuals with generalised onset seizures is of low quality and does not inform current treatment policy.We recommend that future trials should be designed to the highest quality possible with regards to choice of population, classification of seizure type, duration of follow-up (including continued follow-up after failure or withdrawal of randomised treatment), choice of outcomes and analysis, and presentation of results.
Topics: Anticonvulsants; Epilepsies, Partial; Epilepsy, Tonic-Clonic; Humans; Induction Chemotherapy; Oxcarbazepine; Phenytoin; Proportional Hazards Models; Randomized Controlled Trials as Topic; Treatment Failure
PubMed: 30350354
DOI: 10.1002/14651858.CD003615.pub4