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Aims This post hoc analysis assessed the efficacy and safety/tolerability of adjunctive perampanel in patients from China (aged ≥12 years) with focal seizures (FS), with/without focal to bilateral tonic‐clonic seizures (FBTCS), or generalized tonic‐clonic seizures (GTCS). Methods Study centers in China were identified using data from five double‐blind, randomized, phase III studies of adjunctive perampanel (2‐12 mg/day) and their open‐label extensions (OLEx). Efficacy assessments included median percent reduction in seizure frequency per 28 days, and 50% and 75% responder and seizure‐freedom rates. Safety/tolerability assessments included monitoring of treatment‐emergent adverse events (TEAEs). Results Overall, 277 patients (placebo, n = 79; perampanel, n = 198) were included in the double‐blind safety analysis set. The full analysis set comprised 274 patients (FS, n = 238 [placebo, n = 60; perampanel, n = 178]; FBTCS, n = 120 [placebo, n = 31; perampanel, n = 89]; GTCS, n = 36 [placebo, n = 18; perampanel, n = 18]). Median percent reductions in seizure frequency for placebo vs perampanel were as follows: 16.6% vs 32.4% (FS; P, Adjunctive perampanel was associated with greater median percent reductions in seizure frequency per 28 days vs placebo in Chinese patients with focal or generalized seizure types during double‐blind, randomized, phase III studies.During OLEx studies, adjunctive perampanel showed efficacy for up to 4 years for FS and FBTCS, and up to 2 years for GTCS.Perampanel was generally well tolerated during short‐ and long‐term treatment.

Lemborexant (LEM) is a dual orexin receptor antagonist approved for treating adults with insomnia. We analyzed the efficacy (subjective sleep outcomes) and safety of LEM over 12 months in the subgroup of Asian subjects from Study E2006-G000-303 (Study 303).Study 303 was a 12-month, randomized, placebo-controlled (first 6 months), double-blind, parallel-group, phase 3 study of adults with insomnia disorder. During the 6-month Period 1, subjects were randomized (1:1:1) to placebo, LEM 5 mg (LEM5), or LEM 10 mg (LEM10); LEM subjects continued treatment in the following 6-month Period 2. Outcome measures included subject-reported (subjective) sleep onset latency (sSOL), sleep efficiency (sSE), wake after sleep onset (sWASO), total sleep time (sTST), Insomnia Severity Index (ISI), and Patient Global Impression-Insomnia version (PGI-I). Treatment-emergent adverse events (TEAEs) were assessed.Overall, 178 Asian subjects (Japanese,LEM improved subjective sleep parameters and was well-tolerated in Asian subjects with insomnia disorder over 12 months.ClinicalTrials.gov, NCT02952820; ClinicalTrialsRegister.eu, EudraCT Number 2015-001463-39.

This post hoc analysis assessed the long-term safety, tolerability, and efficacy of perampanel in Asian patients with refractory focal seizures; an additional analysis assessed the effect of perampanel on focal impaired awareness seizures (FIAS) with focal to bilateral tonic-clonic (FBTC) seizures. In this subanalysis, data from Asian patients ≥12 years of age who had focal seizures with FBTC seizures despite taking one to 3 concomitant antiepileptic drugs at baseline, and who had entered either the long-term extension phase of 3 phase-3 perampanel trials (study 307) or the 10-week extension phase of study 335, were analyzed for the effect of perampanel on duration of exposure, safety, and seizure outcomes. Of 874 Asian patients included in the analysis, 205 had previously received placebo during the double-blind phase-3 trials and 669 had previously received perampanel 2-12 mg/day; 313 had FIAS with FBTC seizures at core study baseline. The median duration of exposure to perampanel was 385.0 days, and the retention rate at one year was 62.6%. Overall, during the first 52 weeks of perampanel treatment, 777 patients (88.9%) had treatment-emergent adverse events (TEAEs), most of which were mild to moderate in severity. The most frequent TEAEs were dizziness (47.1%), somnolence (22.3%), and nasopharyngitis (17.4%). During the first 52 weeks of perampanel treatment, median percent change in seizure frequency per 28 days from pre-perampanel baseline for all focal seizures was -28.1%, and -51.7% for FIAS with FBTC seizures. The 50% responder rate relative to pre-perampanel baseline for all focal seizures was 33.8%, and 51.1% for FIAS with FBTC seizures. Long-term treatment with perampanel in Asian patients had safety, tolerability, and efficacy similar to that of the global population in the phase-3 trials and extension study 307. The safety profile and response rate suggest benefit for an Asian population of patients with refractory epilepsy.

People of different ethnic or racial backgrounds may experience variations in pharmacokinetic and pharmacodynamic responses to drug therapies. Our post hoc analysis evaluated the efficacy, safety, and tolerability of perampanel in Asian and non-Asian populations with refractory focal seizures with or without focal to bilateral tonic-clonic (FBTC) seizures. This analysis pooled data from 4 randomized, placebo-controlled, phase-3 studies involving patients aged ≥12 years who have focal seizures with or without FBTC seizures. Patients were receiving 2, 4, 8, or 12 mg perampanel (or placebo) by the end of a 6-week titration period and for a further 13 weeks during the maintenance phase. Efficacy endpoints included median percent change in seizure frequency per 28 days, and 50% and seizure-freedom responder rates relative to baseline. The median percent change in seizure frequency per 28 days from baseline was significantly greater than placebo for perampanel 8 and 12 mg (-31.1% and -38.1% change, respectively; each P < 0.0001) in the Asian population, and for perampanel 4, 8, and 12 mg (-21.1% [P = 0.0001], -26.3% [P < 0.0001], and -27.7% [P = 0.0001] change, respectively) in the non-Asian population. The 50% responder rate relative to baseline was significantly greater than placebo for perampanel 8 and 12 mg (40.1% and 43.8%, respectively; each P < 0.0001) in the Asian population, and for perampanel 4, 8, and 12 mg (29.4% [P = 0.0002], 32.8% [P < 0.0001] and 34.5% [P = 0.0001]), respectively, in the non-Asian population. Seizure-freedom rate among all patients was 4.9%-11.7% for perampanel 2, 4, 8, and 12 mg. The most frequently reported treatment-emergent adverse events (TEAEs) across both populations were dizziness, somnolence, irritability, headache, and fatigue. The most common psychiatric TEAEs were aggression and irritability. Perampanel demonstrated a favorable and similar risk-benefit profile in both Asian and non-Asian populations with refractory focal seizures.

BackgroundWe report data from three Phase IV, observational studies (Studies 506 [US;NCT03208660], 508 [India;NCT03836924] and 501 [Italy;NCT04257604]), which assessed real-world safety and efficacy of adjunctive perampanel across different regions.MethodsStudy 506 included patients with any seizure type. Studies 508/501 included patients with focal- onset seizures.Endpoints included: retention rate (Studies 506/501), median percent reduction in seizure frequency/28 days, seizure-freedom rates and safety.ResultsIn Study 506, the 12-month retention rate was 58.5% (n=876/1498). At Months 10–12, the median percent reduction in seizure frequency/28 days was 75.0% (n=123) and the seizure-freedom rate was 30.9% (n=38/123). In Study 508, the 6-month median percent reduction in seizure frequency/28 days was 100.0% (n=174) and seizure-freedom rate was 49.4% (n=86/174). In Study 501, the 6-month median percent reduction in seizure frequency/28 days, retention rate and seizure-freedom rate were 55.4% (n=198), 72.6% (n=170/234) and 18.0% (n=36/200), respectively. Treatment-emergent adverse events occurred in 704/1703 (41.3%; Study 506), 36/199 (18.1%; Study 508) and 132/234 (56.4%; Study 501) patients; the most common was dizziness/vertigo.ConclusionsPerampanel is efficacious and well tolerated during real-world use regardless of geographi- cal region; no unexpected safety signals emerged.FundingEisai Inc., Eisai Pharmaceuticals India Pvt., Ltd., and Eisai s.r.l.

This article reviews the burden of epilepsy in Asia, the challenges faced by people with epilepsy, and the management of epilepsy. Comparison is made with other parts of the world. For this narrative review, data were collected using specified search criteria. Articles investigating the epidemiology of epilepsy, diagnosis, comorbidities and associated mortality, stigmatization, and treatment were included. Epilepsy is a global health care issue affecting up to 70 million people worldwide. Nearly 80% of people with epilepsy live in low- and middle-income countries with limited resources. People with epilepsy are prone to physical and psychological comorbidities, including anxiety and depression, which can negatively impact their quality of life. Furthermore, people with epilepsy are at higher risk of premature death than people without epilepsy. Discrimination or stigmatization of people with epilepsy is common in Asia and can affect their education, work, and marriage opportunities. Access to epilepsy treatment varies throughout Asia. Although highly advanced treatment is available in some countries, up to 90% of people with epilepsy are not adequately treated or are not treated with conventional antiepileptic therapy in resource-limited countries. People in remote areas often do not receive any epilepsy care. First-generation antiepileptic drugs (AEDs) are available, but usually only in urban areas, and second-generation AEDs are not available in all countries. Newer AEDs tend to have more favorable safety profiles than first-generation AEDs and provide options to tailor therapy for individual patients, especially those with comorbidities. Active epilepsy surgery centers are present in some countries, although epilepsy surgery is often underutilized given the number of patients who could benefit. Further epidemiologic research is needed to provide accurate epilepsy data across the Asian region. Coordinated action is warranted to improve access to treatment and care.

Objectives To assess Asian data from Global Prevalence Study on Infections in Urology (GPIU study) which has been performed more than 10 years. Methods Seventeen Asian countries participated in the GPIU study between 2004 and 2013. Data for these countries were collected from the web-based GPIU database. The point prevalence of urinary tract infections (UTI) and antimicrobial susceptibility of representative pathogens were analysed for Asian geographic regions. Results A total of 6706 patients (5271 male, 1435 female) were assessed during the study period, and 659 patients were diagnosed with a UTI (9.8%). Of these UTI patients, 436 were male and 223 were female. Mean patient age was 54.9 ± 19.3 years. Pyelonephritis and cystitis were the most common clinical diagnoses, representing 30.7% and 29.9% of patients, respectively. Escherichia coli was the most frequently identified uropathogen (38.7%). For the patients with urinary tract infection, cephalosporins were the most frequently used antibiotics (34.4%), followed by fluoroquinolones (24.1%), aminoglycosides (16.8%). Fluoroquinolone resistance was relatively high (ciprofloxacin 54.9%, levofloxacin 39.0%), and cephalosporin resistance 42% (42.5–49.4%). Of the antibiotics evaluated, uropathogens had maintained the highest level of susceptibility to amikacin and imipenem (24.9% and 11.3% resistance rates, respectively). Conclusion Uropathogens in many Asian countries had high resistance to broad-spectrum antibiotics. Knowledge of regional and local resistance data and prudent use of antibiotics are important for proper management of UTI in Asian countries.

Epileptic seizures are refractory to treatment in approximately one-third of patients despite the recent introduction of many newer antiepileptic drugs (AEDs). Development of novel AEDs therefore remains a high priority. Perampanel is a first-in-class non-competitive selective AMPA receptor antagonist with a unique mechanism of action. Clinical efficacy and safety of perampanel as adjunctive treatment for focal seizures with/without secondary generalization (±SG) and primary generalized tonic-clonic (PGTC) seizures have been established in five phase 3 randomized controlled trials (RCTs), and a long-term extension study, and perampanel is approved as monotherapy for focal seizures ±SG in the USA. In patients with focal seizures ±SG, add-on perampanel resulted in median percent reduction in seizure frequency 23.3%-34.5% and ≥50% responder rate 28.5%-37.6%; in PGTC seizures, these results were 76.5% and 64.2%, respectively. Efficacy among adolescents (reduction in seizure frequency 34.8%-35.6%; ≥50% responder rate 40.9%-45.0%) and elderly people (reduction in seizure frequency 12.5%-16.9%; ≥50% responder rate 22.2%-42.9%) is similar to those in adults, and results remain comparable between Asian (reduction in seizure frequency 17.3%-38.0%) and global populations. Perampanel has been extensively studied in real-world clinical practice, with similar efficacy and safety results to the RCTs (≥50% responder rate 12.8%-75.0%; adverse events of somnolence/sedation, dizziness, ataxia, and behavioral changes). Real-world observational studies suggest that perampanel tolerability can be improved by slow titration (2 mg every 2-4 weeks), and bedtime administration can mitigate somnolence and dizziness. Counseling about the potential for behavioral changes and close monitoring are recommended.

Alzheimer's disease (AD) is associated with neurodegenerative changes resulting clinically in progressive cognitive and functional deficits. The only therapies are the cholinesterase inhibitors donepezil, galantamine and rivastigmine and the N-methyl-D-aspartate-receptor antagonist memantine. Donepezil acts primarily on the cholinergic system as a symptomatic treatment, but it also has potential for disease modification and may reduce the rate of progression of AD. This review explores the potential for disease modifying effects of donepezil. Several neuroprotective mechanisms that are independent of cholinesterase inhibition, are suggested. Donepezil has demonstrated a range of effects, including protecting against amyloid β, ischaemia and glutamate toxicity; slowing of progression of hippocampal atrophy; and up-regulation of nicotinic acetylcholine receptors. Clinically, early and continuous treatment with donepezil is considered to preserve cognitive function more effectively than delayed treatment. The possible neuroprotective effects of donepezil and the potential for disease pathway modification highlight the importance of early diagnosis and treatment initiation in AD.

Background: The ‘Asia-Pacific Expert Panel (APEX) for donepezil 23 mg' met in November 2015 to review evidence for the recently approved high dose of donepezil and to provide recommendations to help physicians in Asia make informed clinical decisions about using donepezil 23 mg in patients with moderate-to-severe Alzheimer's disease (AD). Summary: In a global phase III study (study 326) in patients with moderate-to-severe AD, donepezil 23 mg/day demonstrated significantly greater cognitive benefits versus donepezil 10 mg/day, with a between-treatment difference in mean change in the Severe Impairment Battery score of 2.2 points (p < 0.001) in the overall population and 3.1 points (p < 0.001) in patients with advanced AD. A subanalysis of study 326 demonstrated that the benefits and risks associated with donepezil 23 mg/day versus donepezil 10 mg/day in Asian patients with moderate-to-severe AD were comparable to those in the global study population. Key Message: Donepezil 23 mg is a valuable treatment for patients with AD, particularly those with advanced disease. The APEX emphasized the importance of patient selection (AD severity, tolerability of lower doses of donepezil, and absence of contraindications), a stepwise titration strategy for dose escalation, and appropriate monitoring and counseling of patients and caregivers in the management of patients with AD.

Background There is growing awareness of the coexistence of Alzheimer's disease and cerebrovascular disease (AD+CVD), however, due to lack of well-defined criteria and treatment guidelines AD+CVD may be underdiagnosed in Asia. Methods Sixteen dementia specialists from nine Asia Pacific countries completed a survey in September 2014 and met in November 2014 to review the epidemiology, diagnosis and treatment of AD+CVD in Asia. A consensus was reached by discussion, with evidence provided by published studies when available. Results AD accounts for up to 60% and AD+CVD accounts for 10-20% of all dementia cases in Asia. The reasons for underdiagnosis of AD+CVD include lack of awareness as a result of a lack of diagnostic criteria, misdiagnosis as vascular dementia or AD, lack of diagnostic facilities, resource constraints and cost of investigations. There is variability in the tools used to diagnose AD+CVD in clinical practice. Diagnosis of AD+CVD should be performed in a stepwise manner of clinical evaluation followed by neuroimaging. Dementia patients should be assessed for cognition, behavioural and psychological symptoms, functional staging and instrumental activities of daily living. Neuroimaging should be performed using computed tomography or magnetic resonance imaging. The treatment goals are to stabilize or slow progression as well as to reduce behavioural and psychological symptoms, improve quality of life and reduce disease burden. First-line therapy is usually an acetylcholinesterase inhibitor such as donepezil. Conclusion AD+CVD is likely to be under-recognised in Asia. Further research is needed to establish the true prevalence of this treatable and potentially preventable disease.

Perampanel is an approved adjunctive treatment for focal seizures with or without focal to bilateral tonic-clonic (FBTC) seizures and generalized tonic-clonic (GTC) seizures. We compared efficacy and safety of perampanel vs placebo in Asian and non-Asian populations in a post hoc analysis of pooled data from 5 randomized phase 3 studies. Patients (≥12 years old) with focal + FBTC seizures received perampanel 2, 4, 8, or 12 mg or placebo; patients with GTC seizures received perampanel 8 mg or placebo (titration: 4-6 weeks; maintenance: 13 weeks). Efficacy endpoints included median percentage change in FBTC or GTC seizure frequency per 28 days and 50% responder rate relative to baseline. Median percentage change in FBTC seizure frequency was significantly greater for perampanel 8 and 12 mg than placebo in the Asian population (median difference from placebo: -30.32%, P = 0.0017; -30.06%, P = 0.0008, respectively) and perampanel 4, 8, and 12 mg in the non-Asian population (-35.07%, P = 0.0001; -37.78%, P < 0.0001; -34.53%, P < 0.0001, respectively). In both populations, median percentage change in GTC seizure frequency was significantly greater for perampanel 8 mg than placebo (median difference from placebo: Asian, -37.37%, P = 0.0139; non-Asian, -27.04%, P = 0.0006). The 50% responder rates were significantly greater than placebo for perampanel 8 and 12 mg for FBTC seizures (Asian: 58.0%, P = 0.0017 and 58.6%, P = 0.0013, respectively; non-Asian: 59.3%, P < 0.0001 and 54.3%, P = 0.0050, respectively) and perampanel 8 mg for GTC seizures (Asian: 57.6%, P = 0.0209; non-Asian: 68.8%, P = 0.0329). Pooled FBTC/GTC seizure data showed generally similar patterns of response to perampanel in both populations. The most frequent treatment-related adverse events were fatigue, irritability, dizziness, somnolence, and headache. Perampanel was effective, well tolerated, and can be considered a therapeutic option for FBTC/GTC seizures in Asian populations.

Aim To assess the clinical trial and real-world data for adjunctive perampanel in adolescents and develop consensus recommendations to guide the use of perampanel in this population in clinical practice. Methods In May 2015, 15 epilepsy experts attended a Consensus Development Meeting to assess the clinical trial data for perampanel, specific to the adolescent age group (12-17 years) and develop consensus treatment recommendations. Results and Discussion Analysis of the adolescent subgroup data of three pivotal placebo-controlled, double-blind, phase 3 trials investigating perampanel in patients with ongoing focal epileptic seizures despite receiving one to three antiepileptic drugs found that perampanel 4–12 mg was superior to placebo. The tolerability profile of perampanel was generally acceptable. Adolescent patients receiving long-term treatment with perampanel in an open-label extension study maintained improvements in seizure control compared with baseline, with a favorable risk-benefit profile. A phase 2 study showed that perampanel had no clinically important effects on cognitive function, growth, and development. Conclusion Perampanel is a welcome addition to the armamentarium of existing antiepileptic drugs as it represents a new approach in the management of epilepsy, with a novel mechanism of action, and the potential to have a considerable impact on the treatment of adolescents with epilepsy.

Amitabh Dash,1 Sangeeta Ravat,2 Avathvadi Venkatesan Srinivasan,3 Ashutosh Shetty,4 Vivek Kumar,5 Renu Achtani,6 Vivek Narain Mathur,7 Boby Varkey Maramattom,8 Veeresh Bajpai,9 Nanjappa C Manjunath,10 Randhi Venkata Narayana,11 Suyog Mehta12 1Eisai Co. Ltd., 2Department of Neurology, Seth GS Medical College & KEM Hospital, Mumbai, 3Department of Neurology, Trinity Acute Care Hospital, Chennai, 4Department of Neurology, Criticare Multispeciality Hospital& Research Centre, Mumbai, 5Department of Neurology, Metro Multispeciality Hospital, Noida, 6Department of Neurology, Mata Chanan Devi Hospital, New Delhi, 7Department of Neurology, Vivekananda Hospital, Hyderabad, 8Department of Neurology, Lourdes Hospital, Kochi, 9Department of Neurology, Sai Neurology Clinic, Lucknow, 10Department of Neurology, Brain and Nerve Care, Bangalore, 11Department of Neurology, Seven Hills Hospital, Visakhapatnam, 12Department of Pharmacology & Therapeutics,Government Medical College, Solapur, India Abstract: A prospective, multicentric, noncomparative open-label observational study was conducted to evaluate the safety and efficacy zonisamide in Indian adult patients for the treatment of partial, generalized, or combined seizures. A total of 655 adult patients with partial, generalized, or combined seizures from 30 centers across India were recruited after initial screening. Patients received 100 mg zonisamide as initiating dose as monotherapy/adjunctive therapy for 24 weeks, with titration of 100 mg every 2 weeks if required. Adverse events, responder rates, and seizure freedom were observed every 4 weeks. Efficacy and safety were also assessed using Clinicians Global Assessment of Response to Therapy and Patients Global Assessment of Tolerability to Therapy, respectively. Follow-up was conducted for a period of 24weeks after treatment initiation. A total of 655 patients were enrolled and received the treatment and 563 completed the evaluation phase. A total of 20.92% of patients received zonisamide as monotherapy or alternative monotherapy and 59.85% patients received zonisamide as first adjunctive therapy. Compared with baseline, 41.22% of patients achieved seizure freedom and 78.6% as responder rate at the end of 24 week study. Most commonly reported adverse events were loss of appetite, weight loss, sedation, and dizziness, but discontinuation due to adverse events of drug was seen in 0.92% of patients. This open label real-world study suggests that zonisamide is an effective and well-tolerated antiepileptic drug in Indian adults for treatment of partial, generalized as well as combined seizures type. No new safety signals were observed. Keywords: zonisamide, partial onset seizures, generalized seizures, responder rate, monotherapy, adjunctive therapy

Background Ethnic diversity between different populations may affect treatment safety and efficacy. Aims and methods A subanalysis to a global trial (study 326) was carried out to ascertain the safety and efficacy of donepezil 23 mg/day compared with donepezil 10 mg/day in Asian patients with moderate-to-severe Alzheimer's disease. Changes in cognition and global functioning were measured by the Severe Impairment Battery (SIB) and Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus), respectively, at week 24. Results Cognitive improvement measured by SIB score was greater with donepezil 23 mg than with donepezil 10 mg (+1.36 vs −1.56]; difference, 2.92). There was no difference between the groups in global function measured by the CIBIC-Plus (3.94 and 3.95, respectively). Overall, 119 patients (82.1%) receiving donepezil 23 mg and 56 (71.8%) receiving donepezil 10 mg experienced ≥1 treatment emergent adverse events (TEAEs). In the donepezil 23 mg group, the incidence of TEAEs was higher among patients of lower weight (

Alzheimer's disease (AD) is a progressive condition that affects cognition, function, and behavior. Approximately 60-90% of patients with AD develop neuropsychiatric symptoms (NPS) such as hallucinations, delusions, agitation/aggression, dysphoria/depression, anxiety, irritability, disinhibition, euphoria, apathy, aberrant motor behavior, sleep disturbances, appetite and eating changes, or altered sexual behavior. These noncognitive behavior changes are thought to result from anatomical and biochemical changes within the brain, and have been linked, in part, to cholinergic deficiency. Cholinesterase inhibitors may reduce the emergence of NPS and have a role in their treatment. These agents may delay initiation of, or reduce the need for, other drugs such as antipsychotics. This article summarizes the effects of donepezil, a cholinesterase inhibitor, on the NPS of dementia with emphasis on AD and dementia with Lewy bodies.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. In addition to the renin pathway, certain bioactive molecules are involved in its pathogenesis. Strategies to interrupt pathophysiological pathways are on the horizon. Aliskiren, a renin inhibitor, blocks the first step in the renin pathway. Protein kinase C overexpression is blocked by ruboxistaurin. Pentoxifylline and m-TOR inhibitors are anti-inflammatory agents in the pathogenesis of diabetic nephropathy. Inhibitors of advanced glycation, oxidative stress, and plasminogen activator inhibitor-1 have proved useful in animal models of diabetic nephropathy. Avosentan, an endothelin antagonist, decreases urinary albumin. Such targeted therapies have opened up avenues for researchers to develop agents that can halt and may even reverse the progression of diabetic nephropathy.

Background : Contact lens induced trauma to the corneal epithelium results in increased release of inflammatory mediators. The keratocyte apoptosis is directly related to epithelial injury and has been correlated with increased production of nitric oxide. Potent antioxidant enzymes protect cells from oxidative damage by inactivating reactive oxygen species and thus inhibiting apoptosis. This study aims at determination of total nitric oxide and antioxidant enzymes in tears which will be an indirect criteria for assessing apoptosis. Materials and Methods : Nitric oxide and antioxidant enzymes were estimated in tears of 25 soft contact lens wearers and compared with 25 age and sex matched controls. Results : Statistically significant increase of nitric oxide (P< 0.001), superoxide dismutase (P< 0.001) and glutathione peroxidase (P< 0.001) levels was seen in tears of contact lens wearers as compared to controls. There was also statistically significant increase in the levels of antioxidant enzymes, superoxide dismutase (P< 0.05) and glutathione peroxidase (P< 0.01), with increase in the total duration of contact lens wear in years. Conclusions : Increase in the level of nitric oxide and antioxidant enzymes in tears of contact lens wearers suggested that contact lens wear suppresses the process of apoptosis. However, it was also postulated that the increased levels of nitric oxide balances the anti-apoptotic activities of increased levels of antioxidant enzymes by its pro-apoptotic activity leading to protective outcomes in contact lens wearers.

Alzheimer's disease (AD) is an irreversible and progressive neurodegenerative disorder. AD is the most common cause of dementia worldwide, and its incidence is increasing in line with population aging. The primary feature of AD is progressive cognitive decline, and severe AD is characterized by reduced communication skills and mobility. However, successful treatment can substantially improve quality of life. Donepezil is an acetylcholinesterase inhibitor approved for use across the full spectrum of mild, moderate, and severe AD. Donepezil has been available at doses of 5 or 10 mg once daily for more than a decade and, more recently, a single high once-daily sustained-release 23-mg dose has been approved for treatment of patients with moderate to severe AD. The rationale for the higher dose formulation was the expected increase in acetylcholinesterase inhibition given the dose-response relationship of donepezil, with the benefits of the higher dose being most apparent in patients with more advanced AD. Donepezil 5 and 10 mg/day have been well studied in mild-to-moderate AD, and a clinical trial has confirmed the benefits of donepezil 23 mg/day in patients with moderate to severe AD, particularly for language and visuospatial ability. This review presents an overview of the evidence for donepezil across the spectrum of AD, with a focus on dose optimization for disease progression.

Zonisamide is an orally administered antiepileptic drug that was first approved for clinical use in Japan in 1989. Since then, it has been licensed in Korea for a broad spectrum of epilepsies in adults and children, and in the USA for adjunctive therapy of adults with partial seizures, and in Europe for monotherapy of adults with newly diagnosed partial seizures and adjunctive therapy of adults and adolescents and children aged ≥6 years with partial seizures with or without secondary generalization. Zonisamide is a benzisoxazole derivative with a unique chemical structure, predictable dose-dependent pharmacokinetics, and multiple complementary mechanisms of action. Treatment with zonisamide is well tolerated and is not known to be associated with clinically significant drug-drug interactions, including with oral contraceptives or other antiepileptic drugs. There have been >2 million patient-years of experience with zonisamide for treatment of epilepsy, and this drug has International League Against Epilepsy level A evidence for efficacy/effectiveness as initial monotherapy for adults with partial-onset seizures. This review presents the evidence for zonisamide across the spectrum of epilepsy, with emphasis on real-world clinical practice and special populations of patients (children, elderly patients, and women of childbearing age) who are likely to be treated in daily clinical practice.

Objective. To evaluate the analgesic efficacy and safety of intramuscular drotaverine hydrochloride vs diclofenac sodium in treatment of acute renal colic. Methods. We conducted a randomized, single-blind study comparing single intramuscular doses of drotaverine hydrochloride (80 mg) vs diclofenac sodium (75 mg) on 100 patients (50 in each arm) presenting to the emergency department (ED) with renal colic. Subjects with inadequate pain relief at 30 minutes received rescue intramuscular tramadol (100 mg). Pain intensity was recorded using a visual analog scale (VAS), which is the primary outcome measure of this study, before drug administration and 30 and 60 minutes afterwards. The drug effectiveness was defined as ≥50% decrease in pain intensity 60 minutes after intramuscular administration, without exacerbation during the following 2 hours. The need for rescue medication and the presence of adverse effects were considered as secondary outcome of the study. Result. VAS decreased significantly (P