Background: Retigabine is an antiepileptic drug developed for the adjunctive treatment of adults with epilepsy and partial-onset seizures (POS). Following its approval in 2011, reports of ophthalmological/dermatological pigmentation/discoloration led to a restriction of the indication in 2013, and in 2017, retigabine was voluntarily withdrawn from the market because of its limited usage. Here, data are reported from four open-label extension studies focusing on long-term safety with particular emphasis on ophthalmological and dermatological events. Methods: Studies 113413 (NCT01336621), 114873 (NCT01777139), 115097 (NCT00310388), and 115098 (NCT00310375) were multicenter, open-label extension studies of retigabine (300-1200 mg/day) for the adjunctive treatment of adults with POS. Safety assessments included monitoring treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). When new safety issues were identified, protocols were amended to include additional on-treatment safety evaluations, including ophthalmological and dermatological examinations. Patients who had abnormal retinal pigmentation, unexplained vision change, pigmentation of nonretinal ocular tissue, or abnormal discoloration of skin, lips, nails, and/or mucosa at the end of the treatment phase were asked to enter a safety follow-up continuation phase comprising 6-monthly ophthalmological/dermatological assessments. Results: The safety population (patients receiving ≥1 dose of retigabine in the open-label phase) comprised 98, 30, 376, and 181 patients for studies 113413, 114873, 115097, and 115098, respectively. Mean (standard deviation) treatment exposure ranged from 529 (424) to 1129 (999) days. In total, 68%-96% and 4%-27% of patients across the studies experienced TEAEs and TE SAEs, respectively. There were seven on-treatment deaths and two after discontinuation. Overall, 14%-73% of patients had an on-treatment eye examination, of whom 8/53, 4/22, 17/54, and 14/36 had abnormal retinal pigmentation and 15/53, 7/22, 15/54, and 11/36 had nonretinal ocular pigmentation in studies 113413, 114873, 115097, and 115098, respectively. Four patients had confirmed acquired vitelliform maculopathy. In patients with unresolved events at discontinuation and ≥1 posttreatment follow-up, retinal pigmentation resolved completely in 1/3, 0/3, 0/10, and 1/7 patients and nonretinal ocular pigmentation in 1/4, 0/3, 8/10, and 4/6 patients, respectively. Overall, 12%-83% of patients had an on-treatment dermatological examination, of whom 11/58, 0/25, 23/46, and 23/37 had any-tissue discoloration, respectively. In patients with unresolved events at discontinuation and ≥1 posttreatment follow-up, discoloration of skin, lips, nails, and/or mucosa resolved completely in 2/3, 0/0, 7/13, and 1/11 patients, respectively.
Background The impact of nocturnal disturbance (ND) in Parkinson’s disease on quality of life of patients in Western Countries is increasingly understood. Our study aimed to investigate ND prevalence and its quality of life impact in patients with advanced Parkinson’s disease in China. Methods In a multicenter, tertiary-care hospital, outpatient-based, cross-sectional study, patients with advanced Parkinson’s disease (Modified Hoehn & Yahr [H&Y] Stage II–IV with ≥3 h awake “off” time/day) from 10 tertiary hospitals throughout China completed the Parkinson’s Disease Sleep Scale-2 (PDSS-2) and Parkinson’s Disease Questionnaire-39 (PDQ-39). The primary endpoint was the percentage of patients with significant ND (PDSS-2 total score ≥ 15). Additional endpoints were demographic and clinical characteristics, PDSS-2 and PDQ-39 total and subscale scores, correlation between PDSS-2 and PDQ-39, and risk factors for ND and higher PDSS-2 or PDQ-39 scores. Results Of 448 patients analyzed (mean age 63.5 years, 47.3% female), 70.92% (95% confidence interval: 66.71, 75.13) had significant ND. Presence of ND and higher PDSS-2 scores were associated with longer disease duration and higher H&Y stage. Presence of ND was also associated with more awake “off” time/day and female sex. PDQ-39 scores were significantly worse for patients with ND versus those without ND; worse scores were associated with more awake “off” time/day, female sex, and higher H&Y stage. PDSS-2 and PDQ-39 total scores were associated: Pearson correlation coefficient 0.62 (p < 0.001). Conclusions In China, ND was highly prevalent in patients with advanced Parkinson’s disease and adversely impacted quality of life. This study highlights the importance of early diagnosis and optimized management of ND in patients with Parkinson’s disease in China.
<p class="abstract"><strong>Background:</strong> Hearing loss has been reported with lamivudine therapy. The World Health Organization (WHO) international database of suspected adverse drug reactions (Vigibase) prioritised clinical review of lamivudine and hearing loss in 2015. This manuscript provides the details of research protocol for a systematic review of association of lamivudine with hearing loss.</p><p class="abstract"><strong>Methods: </strong>English-language publications that assess hearing loss within patients who are receiving lamivudine therapy will be included. All study types like clinical trial designs, case-control study, cohort study, retrospective study, case-series or a case report will be included. Preclinical studies, studies enrolling patients with known differential diagnosis such as presbycusis etc will be excluded. Electronic databases (PubMed, Cochrane reviews, Embase and Google scholar), international clinical trials registry, clinicaltrials.gov and pharmaceutical company clinical study registries will be searched for key words related to lamivudine and hearing loss. After a thorough electronic/manual search of manuscript they will undergo a screening process and selected articles will be assessed for risk of bias using online ROBINS-I tool. We will explore outcomes as an observational systematic review.</p><p class="abstract"><strong>Conclusions:</strong> This review will provide detailed benefit-risk analysis of lamivudine with respect to hearing loss in patients with chronic conditions such as Human immunodeficiency virus (HIV) and Hepatitis B virus (HBV) infection.</p><p class="abstract"><strong>Trial Registration:</strong> PROSPERO registration number is CRD42018112205.0.001.</p>
<b><i>Introduction:</i></b> The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing and is fueled by a twin-epidemic of obesity and diabetes mellitus in India. The objective of the study was to estimate various noninvasive NAFLD scores (NINS) for the baseline risk-assessment of NAFLD in patients with type 2 diabetes mellitus (T2DM). <b><i>Methods:</i></b> An observational, cross-sectional, open label, study of investigator-rated NINS was conducted ensuring adherence to relevant ethical standards. <b><i>Results:</i></b> In a 3-month period, 29 patients with T2DM were enrolled (age [mean ± SD]: 55.8 ± 9.72 years; men [<i>n</i>, %]: 18, 62%). One patient (3.45%) by fibrosis-4 index (cutoff for advanced fibrosis ≥2.67) and by AST to platelet ratio index (cutoff ≥0.98); 2 (6.90%) by NAFLD fibrosis score (cutoff ≥0.676); 20 (69%) by body mass index (BMI), AST to ALT ratio, and DM score (BARD; cuff-off ≥2); and 27 (93.10%) by BMI, age, ALT, triglyceride score (cutoff ≥1) indicated high risk for advanced hepatic fibrosis. Only the BARD score (median [min-max]: 3 [1–4]) was elevated above the cutoff values while other scores were below cutoff values. The study failed to demonstrate any correlation between age, gender, anthropometric and metabolic parameters, and NINS. <b><i>Conclusion:</i></b> While this study did not demonstrate significant elevation of NINS, scores were found be elevated in some T2DM patients and they may be at high risk of advanced liver fibrosis. Further well-designed studies in this domain are required for early detection, management, and reducing the burden of liver disease in Indian patients with diabetes.
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