Glucagon-Like Peptide-1 Receptor Agonists in Type 2 Diabetes: Their Use and Differential Features The original version of this article unfortunately contained some mistakes. The corrected details are provided below:

Correction to: Safety, Tolerability, and Pharmacokinetics of GDC-0276, a Novel Na V 1.7 Inhibitor, in a First-in-Human, Single- and Multiple-Dose Study in Healthy Volunteers The original version of this article unfortunately contained a mistake. A few entries were incorrect in Table 2.

Safety, Tolerability, and Pharmacokinetics of GDC-0276, a Novel Na V 1.7 Inhibitor, in a First-in-Human, Single- and Multiple-Dose Study in Healthy Volunteers Abstract Background and Objective Current pain therapies often do not provide adequate pain relief and have dose-limiting adverse effects. Genetic evidence indicates that NaV1.7 sodium channels are required for pain transduction and therefore represent an important therapeutic target. GDC-0276 is a novel NaV1.7 inhibitor developed for the treatment of pain. This first-in-human trial evaluated the safety, tolerability, and pharmacokinetics of orally administered GDC-0276 in healthy subjects. Methods This phase I, randomized, double-blind, placebo-controlled study assessed GDC–0276 as powder-in-capsule (PIC) or cyclodextrin solution (CD) single doses (SDs) of 2–270 mg (seven cohorts) and 45–540 mg (five cohorts), respectively. Multiple (MD) PIC doses were administered as total daily doses of 15–540 mg divided into two or three doses/day, up to 10 or 14 days. Safety was assessed by monitoring adverse events (AEs), vital signs, physical examinations, electrocardiograms, and laboratory tests for up to 15 days after the last day of dosing. GDC-0276 plasma pharmacokinetics were also determined. Results Three stages included 183 randomized subjects. GDC-0276 plasma exposure increased with dose level for all stages. Exposure was higher in the SD-CD cohorts compared with the equivalent SD-PIC dose levels. SDs were adequately tolerated up to 270 mg (SD-PIC) and 360 mg (SD-CD). Hypotension limited tolerability in the 540-mg SD-CD cohort. Multiple PIC doses were tolerated up to 270 mg twice daily, however liver transaminase elevations were frequently observed. No deaths or serious AEs occurred. Conclusion GDC-0276 exhibited a safety and pharmacokinetic profile that supports its future investigation as a potential therapeutic for pain.

Hypertension and Health-Related Quality of Life (HRQoL): Evidence from the US Hispanic Population Abstract Background and Objective Little evidence exists regarding the marginal decrease in health-related quality of life (HRQoL) in relation to the presence of hypertension among a Hispanic population based on US population-based research. Method This cross-sectional study used data from the 2014 to 2015 Medical Expenditure Panel Survey (MEPS). The target population was comprised of Hispanic community-dwelling residents with hypertension in the USA. The independent variable was the presence of hypertension. The dependent variable was HRQoL, which was measured using the Short Form-12 (SF-12) physical health composite scale (PCS) and mental health composite scale (MCS). Results A total of 13,933 members of the Hispanic population met the study inclusion criteria, and the estimated population size was 36,440,400 Hispanics. Among them, 82.9% did not have any hypertensive condition (n = 11,466), while 17.7% had some hypertensive condition (n = 2467). SF-12 PCS scores (95% CI) were 46.62 (45.68–47.57) in the Hispanic population with hypertension and 51.62 (51.1–52.14) in the Hispanic population without hypertension. SF-12 MCS scores (95% CI) were 52.67 (52.07–53.27) in patients without hypertension and 50.35 (49.45–51.26) in the Hispanic population with hypertensive conditions. Conclusion The presence of hypertension was associated with lower HRQoL in the Hispanic population. Based on our findings, we suggest that healthcare providers should monitor a hypertensive minority population for anxiety and mood disorders and recommend psychiatric assessment and treatment if appropriate.

Bayesian Network Meta-Analysis for Assessing Adverse Effects of Anti-hepatitis B Drugs Abstract Background and Objective Oral nucleoside/nucleotide analogues (NAs) have been advocated for chronic hepatitis B (CHB) treatment with good efficacy. However, less attention has been put on their adverse events. Therefore, a Bayesian network meta-analysis (NMA) was performed to evaluate the relative safety of five NAs (lamivudine, adefovir dipivoxil, entecavir, telbivudine, and tenofovir disoproxil fumarate) in CHB treatment among adults. Methods Eligible randomized clinical trials (RCTs) and prospective cohort studies were systematically and thoroughly searched until May 1, 2019. Poisson-prior-based Bayesian NMA was performed to synthesize both direct and indirect evidence with reporting hazard ratios (HRs) and 95% credible intervals (CrIs) for serious adverse events (SAEs) and hepatic/renal impairments. Results Thirty-three RCTs and 11 prospective cohort studies were identified. As to SAEs, no statistically significant difference was found of any comparison among five NAs. In terms of hepatotoxicity, lamivudine was safer than telbivudine (HR 0.45; 95% CrI 0.21, 0.85), and entecavir increased the risk by 102% (entecavir vs lamivudine: HR 2.02; 95% CrI 1.19, 3.27). Conclusions The findings from this large NMA could influence clinical practice, and the methodological framework of this study could provide evidence-based support to analyze sparse safety data in the field.

Drug–Drug Interactions in Children and Adolescents Receiving Ledipasvir/Sofosbuvir for the Treatment of Hepatitis C Virus Infection Abstract Background and Objective Drug–drug interactions need to be considered to optimize the pharmacotherapeutic outcome of direct-acting antivirals. The aim of this study was to report on possible drug–drug interactions between ledipasvir/sofosbuvir and other medications received by children and adolescents with hepatitis C virus, in addition to suggested management for these drug–drug interactions. Methods Hepatitis C virus-infected children and adolescents, 12–17 years of age and/or weighing ≥ 35 kg, who presented to the Pediatric Hepatology Unit at Cairo University Pediatric Hospitals for ledipasvir/sofosbuvir treatment were included. Medication history was taken including long-term medications for chronic conditions and on-demand medications for inter-current illnesses. Medications were reviewed by the Kasr Alainy Drug Information Center to identify possible drug–drug interactions with prescribed ledipasvir/sofosbuvir and their management. HEP Drug Interactions provided by the University of Liverpool, Lexicomp®, and Medscape were the utilized references. Each drug–drug interaction was assigned a risk rating of A, B, C, D, or X. Results Sixty hepatitis C virus-infected children and adolescents assigned to receive ledipasvir/sofosbuvir were enrolled. Thirty percent of patients had associated chronic co-morbid conditions. The overall number of medications received was 48; 39 were prescribed as long-term medications with a median of 3 (interquartile range 4.24) medications per patient. Proton pump inhibitors, antacids, histamine H2 receptor antagonists, sodium bicarbonate, and colchicine were reported to be associated with a drug–drug interaction risk D necessitating therapy modification, which occurred prior to administration. Conclusions Early identification and prompt response to drug–drug interactions with the aid of pharmacists optimize the pharmacotherapeutic outcome and eliminate possible morbidities when using direct-acting antivirals in children and adolescents with hepatitis C virus.

Proton Pump Inhibitor Therapy and Hepatic Encephalopathy Risk in Cirrhotic Patients: A Systematic Review with Meta-analysis Abstract Background and Objectives Use of proton pump inhibitor (PPI) in patients with cirrhosis has been linked to the development of hepatic encephalopathy (HE). Little is known about the incidence rate of HE due to PPI therapy. We conducted a meta-analysis to explore the association between PPI use and the incidence of HE. Methods We searched PubMed, EMBASE databases and The Cochrane Library from inception to March 2019 for studies describing the association between PPI exposure and incidence of HE; we identified studies that provided the adjusted estimates of odds ratio (OR)/relative ratio (RR)/hazard ratio (HR), and the pooled RRs on the incidence of HE were calculated. Summary estimates were calculated using random effects models. Results We analyzed data from 10 eligible studies; PPI users had an increased risk of HE compared with non-PPI user, with a pooled RR of 1.81 (95% CI 1.58–2.06), with notable heterogeneity (I2 = 85.2%, p <0.0001). In subgroup of considering the incidence of HE after yrans-jugular intrahepatic portosystemic shunt (TIPS), the pooled RR was 3.09 (95% CI 2.23–4.27), with no statistical heterogeneity (I2 = 0.0%, p = 0.484); another subgroup analysis was conducted for the complication of the enrolled patients with the status of ascites, the pooled RR was 1.39 (95% CI 1.10–1.77). The result of statistical heterogeneity was low (I2 = 46.2%, p = 0.156). Conclusions We found PPI therapy increased the risk of HE in cirrhotic patients, and higher risk was found in post-operative TIPS. Additional studies are warranted to inform clinical decision making.

Efficacy of Platelet-rich Plasma for Treating Androgenic Alopecia of Varying Grades Abstract Background and Objectives Platelet-rich plasma (PRP) has received growing attention as a valuable therapeutic tool in androgenetic alopecia (AGA). However, knowledge regarding specific effectiveness and satisfaction of PRP for different grades of AGA in male pattern hair loss (MPHL) and female pattern hair loss (FPHL) is missing. This study aims to ascertain and compare the efficacy and safety of PRP treatment for different grades of AGA in males and females over 6 months. Methods In this study, 51 MPHL patients with Norwood-Hamilton stage II-V and 42 FPHL patients with Ludwig stage I to III were enrolled for 6 monthly sessions of PRP injections. A longitudinal analysis was used to compare the hair density, thickness, and hair pull test over 6 months for MPHL and FPHL through generalized estimating equation (GEE) models. Phototrichograms of scalp inflammation and oil secretion, global photographs and overall patient satisfaction were also assessed. Results Consequently, improvement of hair density, hair thickness, hair pull test, the level of scalp inflammation and oil secretion were observed with statistical significance in all stages for both MPHL and FPHL at 6 months. Noteworthy, lower level of alopecia (Grade II, III in MPHL and Grade I in FPHL) had better response to PRP, and also had a better tendency of increment of hair growth than that of high-grade patients with prolonged treatment. Conclusions PRP injections, as an efficacious and reliable therapy, can be recommended for Grade II and Grade III in MPHL and Grade I in FPHL.

Determinants of Antithrombotic Treatment for Atrial Fibrillation in Octogenarians: Results of the OCTOFA Study Abstract Background and Objective Atrial fibrillation, the most frequent form of arrhythmia, affects 5–15% individuals aged > 80 years. Stroke is a major risk for atrial fibrillation patients. The benefits of anticoagulant therapy clearly outweigh the risk of hemorrhage, even in the elderly. Despite the efficacy of warfarin, many eligible patients receive no prophylactic antithrombotic therapy. New generation oral anticoagulants compare favorably with vitamin K antagonists in the prevention of thromboembolic events and hemorrhage. These new agents are likely to influence the prescribing habits of anticoagulants in atrial fibrillation. The aim of this study to investigate both the frequency and the determining factors of anticoagulant prescriptions in AF patients aged ≥ 80 years and followed up by private-practice cardiologists in France. Methods The OCTOFA (Atrial Fibrillation in Octogenarians) Study assessed the anticoagulant prescribing habits of cardiologists in France. The volunteer cardiologists recruited all consecutive patients fulilling the inclusion criteria. Results Between June 2013 and September 2016, 89 cardiologists recruited 738 eligible patients: age ≥ 80 years, non-valvular atrial fibrillation, no other compelling indication for anticoagulation therapy, no recent acute coronary syndrome or stroke. Most (90.7%) patients were on oral anticoagulant therapy: vitamin K antagonist or non-vitamin K antagonist oral anticoagulants, low molecular weight heparin (1.4%), aspirin (5.7%), and no antithrombotic treatment (2.2%). Patients on vitamin K antagonists were older (p < 0.001), had lower renal function (p = 0.033), and had a more frequent history of myocardial infarction (p < 0.001), heart failure (p = 0.001), peripheral artery disease (p = 0.033), major hemorrhage (p = 0.025), and falls (p = 0.045). Four determining factors of anticoagulant prescriptions were statistically significant: high CHA2DS2-VASc score (p < 0.001), high HAS-BLED score (p < 0.001), age > 90 years (p = 0.001), and moderate/severe cognitive impairment (p = 0.002). Conclusions Most private-practice cardiologists prescribe anticoagulant treatment according to current guidelines in elderly atrial fibrillation patients. Non-vitamin K antagonist oral anticoagulants represent a significant proportion of prescriptions.

Severe Exacerbation of Multiple Sclerosis Following Withdrawal of Fingolimod Abstract Background Fingolimod is an effective therapy for multiple sclerosis (MS). Isolated reports of very aggressive MS rebound after discontinuation of fingolimod are drawing neurologists’ attention to this potentially severe complication of the drug. Objective Our objective was to collect literature data on cases of MS rebound following fingolimod withdrawal. In addition, we report six new cases of this adverse event in Brazil. Methods We carried out a systematic review of published data on cases of MS rebound after fingolimod was discontinued. In addition, the study reports a retrospective data series of Brazilian patients presenting this rebound reaction. Results Twenty papers have been published reporting on 52 patients with severe MS rebound after fingolimod withdrawal. Six new patients are included in the present paper, all of them with aggressive rebound and accumulated disability sequelae. Conclusion We recommend gradual discontinuation of fingolimod with replacement by other treatment. The washout period should not exceed 4 weeks.