Predictors of HBeAg loss after lamivudine treatment for chronic hepatitis B

Elevated alanine transaminase (ALT) levels and low serum hepatitis B virus (HBV) DNA predict a higher likelihood of hepatitis B e antigen (HBeAg) loss in patients with chronic hepatitis B treated with interferon. Predictors of HBeAg loss in patients treated with lamivudine are not known. The objective of this analysis of 4 lamivudine-controlled Phase III trials was to determine patient-dependent or laboratory variables that predict HBeAg loss. Predictors of HBeAg loss in patients treated with interferon, lamivudine plus interferon, or placebo are also described. A total of 805 adults with chronic hepatitis B were treated either with lamivudine (n = 406), matching placebo (n = 196), interferon (n = 68), or the combination of lamivudine plus interferon (n = 135). Demographic and baseline disease characteristics were used in stepwise multivariate analyses to identify features that were predictive of lamivudine-induced HBeAg loss. HBeAg loss correlated with increased pretreatment ALT levels in all groups. The rate of HBeAg loss was highest among patients with pretreatment ALT levels greater than 5 times the upper limit of normal (ULN) and was most pronounced in the lamivudine group (56%). Multivariate modeling indicated that elevated baseline ALT levels (P <.001) and histologic activity index (HAI) score (P <.001) were important predictors of HBeAg loss in response to lamivudine. The effect of pretreatment ALT levels on HBeAg loss was similar for Asians and Caucasians. In conclusion, elevated pretreatment ALT levels and/or active histologic disease were the most important predictors of lamivudine-induced HBeAg loss. Asians and Caucasians had similar rates of response to lamivudine at comparable ALT levels.     

Phone-Based Intervention under Nurse Guidance after Stroke (PINGS II) Study: Protocol for a Phase III Randomized Clinical Trial

ObjectivesThe Sub-Saharan African (SSA) region now has the highest estimated effect size of hypertension for stroke causation worldwide. An urgent priority for countries in SSA is to develop and test self-management interventions to control hypertension among those at highest risk of adverse outcomes. Thus the overall objective of the Phone-based Intervention under Nurse Guidance after Stroke II study (PINGS-2) is to deploy a hybrid study design to assess the efficacy of a theoretical-model-based, mHealth technology-centered, nurse-led, multi-level integrated approach to improve longer term blood pressure (BP) control among stroke survivors.Materials and methodsA phase III randomized controlled trial involving 500 recent stroke survivors to be enrolled across 10 Ghanaian hospitals. Using a computer-generated sequence, patients will be randomly assigned 1:1 into the intervention or usual care arms. The intervention comprises of (i) home BP monitoring at least once weekly with nurse navigation for high domiciliary BP readings; (2) medication reminders using mobile phone alerts and (3) education on hypertension and stroke delivered once weekly via audio messages in preferred local dialects. The intervention will last for 12 months. The control group will receive usual care as determined by local guidelines. The primary outcome is the proportion of patients with systolic BP <140 mm Hg at 12 months. Secondary outcomes will include medication adherence, self-management of hypertension, major adverse cardiovascular events, health related quality of life and implementation outcomes.ConclusionAn effective PINGS intervention can potentially be scaled up and disseminated across healthcare systems in low-and-middle income countries challenged with resource constraints to reduce poor outcomes among stroke survivors.     

The role of weight bias and role-modeling in medical students’ patient-centered communication with higher weight standardized patients

ObjectivePatients with obesity may experience less patient-centered care. We assessed whether medical students’ implicit/explicit weight-related attitudes and perceptions of normative attitudes are associated with patient-centered care for patients with obesity.MethodsThird and fourth year medical students (N = 111) at one medical school completed a survey and participated in a patient care scenario with a standardized patient with obesity. Encounters were coded for patient-centered behavior. Predictors of patient-centered behaviors were assessed.ResultsStudent perceptions that negative attitudes about patients with obesity are normative in medical school were significantly associated with poorer patient-centered behaviors, including lower attentiveness (b=?0.19, p = 0.01), friendliness (b=?0.28, p < 0.001), responsiveness (b=?0.21, p = 0.002), respectfulness (b=?0.17, p = 0.003), interactivity (b=?0.22, p = 0.003), likelihood of being recommended by observers (b=?0.34, p < 0.001), and patient-centeredness index scores (b=?0.16, p = 0.002). Student reported faculty role-modeling of discrimination against patients with obesity predicted lower friendliness (b=?0.16, p = 0.03), recommendation likelihood (b=?0.22, p = 0.04), and patient-centeredness index score (b=?0.12, p = 0.03).ConclusionsNegative normative attitudes and behaviors regarding obesity in the medical school environment may adversely influence the quality of patient-centered behaviors provided to patients with obesity.Practice implicationsEfforts to improve patient-centered communication quality among medical trainees may benefit from intervention to improve group normative attitudes about patients with obesity.     

Dalbavancin exposure in vitro selects for dalbavancin-non-susceptible and vancomycin-intermediate strains of methicillin-resistant Staphylococcus aureus

ObjectivesDalbavancin is a lipoglycopeptide active against methicillin-resistant Staphylococcus aureus (MRSA). Its long half-life (8.5–16 days) allows for once-weekly or single-dose treatments but could prolong the mutant selection window, promoting resistance and cross-resistance to related antimicrobials such as vancomycin. The objective of this study was to evaluate the capacity of post-distributional pharmacokinetic exposures of dalbavancin to select for resistance and cross-resistance in MRSA.MethodsWe simulated average, post-distributional exposures of single-dose (1500 mg) dalbavancin (fCmax 9.9 μg/mL, β-elimination t_1/2 204 h) in an in vitro pharmacokinetic/pharmacodynamic (PK/PD) model for 28 days (672 h) against five MRSA strains and one methicillin-susceptible strain (MSSA). Samples were collected at least daily, and surviving colonies were enumerated and screened for resistance on drug-free and dalbavancin-supplemented medium respectively. Isolates from resistance screening plates were subjected to whole-genome sequencing (WGS) and susceptibly testing against dalbavancin, vancomycin, daptomycin, and six β-lactams with varying penicillin-binding protein (PBP) affinities.ResultsDalbavancin was bactericidal against most strains for days 1–4 before regrowth of less susceptible subpopulations occurred. Isolates with eight-fold increases in dalbavancin MIC were detected as early as day 4 but increased 64–128-fold in all models by day 28. Vancomycin and daptomycin MICs increased 4–16-fold, exceeding the susceptibly breakpoints for both antibiotics; β-lactam MICs generally decreased by two-to eight-fold, suggesting a dalbavancin–β-lactam seesaw effect, but increased by eight-fold or more in certain isolates. Resistant isolates carried mutations in a variety of genes, most commonly walKR, apt, stp1, and atl.ConclusionsIn our in vitro system, post-distributional dalbavancin exposures selected for stable mutants with reduced susceptibility to dalbavancin, vancomycin, and daptomycin, and generally increased susceptibility to β-lactams in all strains of MRSA tested. The clinical significance of these findings remains unclear, but created an opportunity to genotype a unique collection of dalbavancin-resistant strains for the first time. Mutations involved genes previously associated with vancomycin intermediate susceptibility and daptomycin non-susceptibility, most commonly walKR-associated genes.