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Summary: Background: Serum hepatitis B virus (HBV) RNA is a novel biomarker for evaluating treatment response. Detailed information regarding serum HBV RNA kinetics during treatment with nucleos(t)ide analogues (NAs) is limited. Aims: To ascertain serum HBV RNA kinetics during long‐term NA treatment and identify associated factors. Methods: We enrolled 76 HBeAg‐positive chronic hepatitis B patients receiving NA from randomised controlled trials. Laboratory assays were undertaken every 3 months. Factors associated with serum HBV RNA kinetics were identified by generalised estimating equations. Results: Baseline serum HBV RNA was 8.5 ± 1.0 log10 copies/mL. Decline in serum HBV RNA during NA therapy was biphasic: the first phase (HBV DNA detectable) had a fast decrease (median slope, −0.207 log10 copies/mL/month) and was followed by a second phase (HBV DNA undetectable) with slow decrease (median slope, −0.071 log10 copies/mL/month). In the first phase, factors independently associated with lower initial serum HBV RNA were male sex (OR, 0.685, P = 0.044), low baseline HBsAg (OR, 0.525, P = 0.001) and rapid virological response (RVR) (OR, 0.624, P = 0.031). In the second phase, only RVR was independently associated with serum HBV RNA kinetics, including its lower initial level (OR, 0.694, P = 0.043) and greater decline (OR, 0.966, P = 0.002). Based on viral dynamics, time needed to achieve undetectable serum HBV RNA from baseline was 43.56 (IQR: 29.49‐66.40) months. Conclusion: RVR was a significant determinant for biphasic decline in serum HBV RNA during NA treatment, which significantly influenced the treatment duration required to achieve undetectable serum HBV RNA. [ABSTRACT FROM AUTHOR]

Objectives: Transversus abdominis plane (TAP) block is an analgesic technique. Adding dexmedetomidine can enhance regional anesthesia. This study's aim was to evaluate whether dexmedetomidine prolonged analgesic time of TAP block after gastrectomy.Methods: Patients scheduled for gastrectomy were randomly assigned to receive a TAP block with saline (group S), ropivacaine (group R), or ropivacaine and dexmedetomidine (group RD). Visual analogue scale (VAS) scores, postoperative nausea and vomiting (PONV) scores, sedation scores, tramadol consumption, ropivacaine concentration, and Quality of Recovery Questionnaire 40 (QoR-40) were recorded.Results: Patients in group R and group RD had lower VAS scores 2, 4, 12, and 24 h after surgery compared with group S (P < 0.05). PONV scores were lower in group R and group RD compared with group S after 2, 12, 24, and 36 h (P < 0.05). Patients in group R and group RD required less tramadol and had better QoR-40 scores than those in group S (P < 0.05). The aforementioned variables and ropivacaine concentrations did not differ between group R and group RD (P > 0.05). Sedation scores were similar between three groups (P > 0.05).Conclusions: TAP block can provide analgesia and improve the quality of recovery. Adding dexmedetomidine does not significantly improve the quality or duration of TAP block. [ABSTRACT FROM AUTHOR]

Background: Septal reduction therapy (SRT), surgical myectomy or alcohol ablation, is recommended for obstructive hypertrophic cardiomyopathy (oHCM) patients with intractable symptoms despite maximal medical therapy, but is associated with morbidity and mortality.Objectives: This study sought to determine whether the oral myosin inhibitor mavacamten enables patients to improve sufficiently to no longer meet guideline criteria or choose to not undergo SRT.Methods: Patients with left ventricular (LV) outflow tract (LVOT) gradient ≥50 mm Hg at rest/provocation who met guideline criteria for SRT were randomized, double blind, to mavacamten, 5 mg daily, or placebo, titrated up to 15 mg based on LVOT gradient and LV ejection fraction. The primary endpoint was the composite of the proportion of patients proceeding with SRT or who remained guideline-eligible after 16 weeks' treatment.Results: One hundred and twelve oHCM patients were enrolled, mean age 60 ± 12 years, 51% men, 93% New York Heart Association (NYHA) functional class III/IV, with a mean post-exercise LVOT gradient of 84 ± 35.8 mm Hg. After 16 weeks, 43 of 56 placebo patients (76.8%) and 10 of 56 mavacamten patients (17.9%) met guideline criteria or underwent SRT, difference (58.9%; 95% CI: 44.0%-73.9%; P < 0.001). Hierarchical testing of secondary outcomes showed significant differences (P < 0.001) favoring mavacamten, mean differences in post-exercise peak LVOT gradient -37.2 mm Hg; ≥1 NYHA functional class improvement 41.1%; improvement in patient-reported outcome 9.4 points; and NT-proBNP and cardiac troponin I between-groups geometric mean ratio 0.33 and 0.53.Conclusions: In oHCM patients with intractable symptoms, mavacamten significantly reduced the fraction of patients meeting guideline criteria for SRT after 16 weeks. Long-term freedom from SRT remains to be determined. (A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive HCM Who Are Eligible for Septal Reduction Therapy [VALOR-HCM]; NCT04349072). [ABSTRACT FROM AUTHOR]

Background: Improving symptoms is a primary treatment goal in patients with obstructive hypertrophic cardiomyopathy. Currently available pharmacological options for hypertrophic cardiomyopathy are not disease-specific and are often inadequate or poorly tolerated. We aimed to assess the effect of mavacamten, a first-in-class cardiac myosin inhibitor, on patients' health status-ie, symptoms, physical and social function, and quality of life.Methods: We did a health status analysis of EXPLORER-HCM, a phase 3, double-blind, randomised, placebo-controlled trial. The study took place at 68 clinical cardiovascular centres in 13 countries. Adult patients (≥18 years) with symptomatic obstructive hypertrophic cardiomyopathy (gradient ≥50 mm Hg and New York Heart Association class II-III) were randomly assigned (1:1) to mavacamten or placebo for 30 weeks, followed by an 8-week washout period. Both patients and staff were masked to study treatment. The primary outcome for this secondary analysis was the Kansas City Cardiomyopathy Questionnaire (KCCQ), a well validated disease-specific measure of patients' health status. It was administered at baseline and weeks 6, 12, 18, 30 (end of treatment), and 38 (end of study). Changes from baseline to week 30 in KCCQ overall summary (OS) score and all subscales were analysed using mixed model repeated measures. This study is registered with ClinicalTrials.gov, NCT03470545.Findings: Between May 30, 2018, and July 12, 2019, 429 adults were assessed for eligibility, of whom 251 (59%) were enrolled and randomly assigned. Of 123 patients randomly assigned to mavacamten, 92 (75%) completed the KCCQ at baseline and week 30 and of the 128 patients randomly assigned to placebo 88 (69%) completed the KCCQ at baseline and week 30. At 30 weeks, the change in KCCQ-OS score was greater with mavacamten than placebo (mean score 14·9 [SD 15·8] vs 5·4 [13·7]; difference +9·1 [95% CI 5·5-12·8]; p<0·0001), with similar benefits across all KCCQ subscales. The proportion of patients with a very large change (KCCQ-OS ≥20 points) was 36% (33 of 92) in the mavacamten group versus 15% (13 of 88) in the placebo group, with an estimated absolute difference of 21% (95% CI 8·8-33·4) and number needed to treat of five (95% CI 3-11). These gains returned to baseline after treatment was stopped.Interpretation: Mavacamten markedly improved the health status of patients with symptomatic obstructive hypertrophic cardiomyopathy compared with placebo, with a low number needed to treat for marked improvement. Given that the primary goals of treatment are to improve symptoms, physical and social function, and quality of life, mavacamten represents a new potential strategy for achieving these goals.Funding: MyoKardia, a Bristol Myers Squibb company. [ABSTRACT FROM AUTHOR]