real world effectiveness and safety of glecaprevir pibrentasvir for the treatment of patients with chronic hcv infection a meta analysis

Abstract Background and Aims Glecaprevir/pibrentasvir is approved for treating adults infected with hepatitis C virus (HCV) genotypes 1–6. In clinical trials, glecaprevir/pibrentasvir was associated with high rates of sustained virologic response at post-treatment Week 12 (SVR12) and was well tolerated. A systematic review and meta-analysis of the real-world effectiveness and safety of glecaprevir/pibrentasvir were undertaken. Methods Real-world studies reporting SVR12 in adults with HCV infection (N≥20) treated with glecaprevir/pibrentasvir were identified in journal publications from January 1, 2017, to February 25, 2019, and congress presentations through April 14, 2019. Random-effects meta-analysis was used to determine SVR12 rates using data from ≥2 cohorts; intention-to-treat (ITT) analyses included patients treated with glecaprevir/pibrentasvir who had SVR12 data available, discontinued early, or were lost to follow-up; modified ITT (mITT) analyses excluded those with non-virologic failure. Naive pooling was used to calculate adverse event (AE) rates. Results Overall, 12,531 adults were treated with glecaprevir/pibrentasvir (18 cohorts). Of patients with post-treatment Week 12 data, SVR12 rates were 96.7% (95% CI, 95.4–98.1) in the ITT population (n=8,583, 15 cohorts) and 98.1 % (95% CI, 97.1–99.2) in the mITT population (n=7,001, 14 cohorts). SVR12 rates were ≥95% across subgroups (HCV genotype, cirrhosis status, treatment history, treatment duration, on-label treatment, and subgroups of interest). AEs were reported in 17.7% (1,271/7,199) of patients (8 cohorts). Serious AEs were reported in 1.0% (55/5,522) of patients (6 cohorts). The most frequent AEs were pruritus, fatigue, and headache. AE-related treatment discontinuations were reported in 0.6% (33/5,595) of patients (6 cohorts). Conclusions Consistent with clinical trials, real-world evidence indicates that glecaprevir/pibrentasvir is a well-tolerated and highly effective pangenotypic treatment for a broad range of HCV-infected patients

Coexistence of the spin-density-wave and superconductivity in the (Ba,K)Fe2As2

The relation between the spin-density-wave (SDW) and superconducting order is a central topic in current research on the FeAs-based high Tc superconductors. Conflicting results exist in the LaFeAs(O,F)-class of materials, for which whether the SDW and superconductivity are mutually exclusive or they can coexist has not been settled. Here we show that for the (Ba,K)Fe2As2 system, the SDW and superconductivity can coexist in an extended range of compositions. The availability of single crystalline samples and high value of the energy gaps would make the materials a model system to investigate the high Tc ferropnictide superconductivity.Comment: 4 pages, 5 figure

Melatonin the "light of night" in human biology and adolescent idiopathic scoliosis

Melatonin "the light of night" is secreted from the pineal gland principally at night. The hormone is involved in sleep regulation, as well as in a number of other cyclical bodily activities and circadian rhythm in humans. Melatonin is exclusively involved in signalling the 'time of day' and 'time of year' (hence considered to help both clock and calendar functions) to all tissues and is thus considered to be the body's chronological pacemaker or 'Zeitgeber'. The last decades melatonin has been used as a therapeutic chemical in a large spectrum of diseases, mainly in sleep disturbances and tumours and may play a role in the biologic regulation of mood, affective disorders, cardiovascular system, reproduction and aging. There are few papers regarding melatonin and its role in adolescent idiopathic scoliosis (AIS). Melatonin may play a role in the pathogenesis of scoliosis (neuroendocrine hypothesis) but at present, the data available cannot clearly support this hypothesis. Uncertainties and doubts still surround the role of melatonin in human physiology and pathophysiology and future research is needed

Circannual variation in the expression of beta 2-adrenoceptors on human peripheral mononuclear leukocytes (MNLs)

Peripheral mononuclear leukocytes (MNLs) are widely used as a tissue model in studies of beta-adrenoceptor disturbances in hypertension and asthmatic diseases. The beta 2-adrenoceptor density (Bmax), however, depends not only on the gender of the person under study and on the time of day the blood specimens are obtained. Evidence is now reported for a circannual variation in the expression of beta 2-adrenoceptor sites on peripheral MNLs. In male volunteers the 24-h mean was found to be highest in the men studied in April/May (1135 +/- 10 sites/cell) and decreased to 891 +/- 16 sites/cell in August and to 712 +r90 sites/cell in December (means +/- SE, P less than 0.01 April/May compared to December). Concomitantly the circadian amplitude increased from 17.3% +/- 6.4% of 24-h mean in April/May to 28.2% +/- 1.4% of 24-h mean in August and to 34.2% +/- 4.2% of 24-h mean in December (means +/- SE, P less than 0.05, April/May compared to December). The circadian acrophase remained constant (190 degrees +/- 30 degrees equivalent to 12 h 40 min +/- 2 h 00 min, means +/- SE)

Long-term safety and tolerability of entecavir in patients with chronic hepatitis B in the rollover study ETV-901

PubMed ID: 22233350Objective: To review long-term safety data from the rollover study ETV-901, focusing on adverse events (AEs) with a potential nucleos(t)ide association. Methods: The open-label study ETV-901 (AI463901) assessed the safety of entecavir in chronic hepatitis B patients who received entecavir, lamivudine or adefovir monotherapy in previous entecavir Phase II/III studies. Long-term cumulative safety results are based on reported AEs, regardless of causal relationship. Results: Median exposure to entecavir in study ETV-901 was 184 weeks. Commonly reported AEs (? 10%) were upper respiratory tract infection, headache and nasopharyngitis. Most AEs were mild to moderate; 203 (19%) patients reported grade 3 4 AEs, with 45 (4%) considered related to entecavir. There were 14 (1%) discontinuations due to AEs. On-treatment alanine aminotransferase (ALT) flares were reported in 32 (3%) patients and were associated with a reduction in hepatitis B virus DNA of more than 2 log10 copies/ml in 25/32 patients. AEs potentially associated with nucleos(t)ide analogs were infrequent, the most common being myalgia (n = 54; 5%) and neuropathy-related AEs (hypoparesthesia and hyperparesthesia, polyneuropathy; n = 42; 4%). Conclusions: Long-term administration of entecavir was associated with low rates of serious AEs, discontinuations due to AEs and ALT flares. AEs potentially associated with nucleos(t)ide use occurred at low rates. © 2012 Informa UK, Ltd.Gilead Sciences Novartis Pharma Novartis Bristol-Myers Squibb Merck GlaxoSmithKline, GSK Roche Bristol-Myers SquibbThe study was sponsored by Bristol-Myers Squibb. The sponsor designed the study in collaboration with expert hepatologists. The sponsor also collected the data, monitored study conduct, performed the statistical analyses and coordinated writing of the article with all authors. Medical writing assistance was provided by Esther Race of ArticulateScience and was funded by Bristol-Myers Squibb. A Pangerl, S Beebe, M Yu and S Wongcharatrawee are employees of Bristol-Myers Squibb. MP Manns has received grant support, consulting fees or honorarium from Merck, Roche, Bristol-Myers Squibb, Gilead, Novartis, GlaxoSmithKline; he has received grants from Merck, Roche, Gilead, Novartis and -- Bristol-Myers Squibb and has received payment for development of educational presentations from Merck, Roche, Bristol-Myers Squibb, GlaxoSmithKline, Novartis and Gilead. TT Chang received consulting fees or honorarium from Bristol-Myers Squibb. N Tsai received research grant support, consulting fees or honorarium from Bristol-Myers Squibb, USA. W Sievert, SK Yoon and A Min have no conflicts of interest to declare. -