The novel TLR-9 agonist QbG10 shows clinical efficacy in persistent allergic asthma.

BACKGROUND: Allergen-specific TH2 responses contribute to the development of allergic asthma. Their increase may be due to a reduced early exposure to environmental pathogens, which induces a TH1 response, and thereby suppresses the allergic TH2 response. QbG10 (bacteriophage Qbeta-derived virus-like particle with CpG-motif G10 inside), a novel Toll-like receptor 9 agonist packaged into virus-like particles, was designed to stimulate the immune system toward a TH1-mediated protective response. OBJECTIVE: We examined clinical efficacy, safety, and tolerability of QbG10 with patient-reported and objective clinical outcome parameters in patients with mild-to-moderate persistent allergic asthma. METHODS: In this proof-of-concept parallel-group, double-blind, randomized trial, 63 asthmatic patients followed conversion to a standardized inhaled steroid and were treated with 7 injections of either QbG10 or placebo. Incorporating a controlled steroid withdrawal, the effects on patient-reported (day- and nighttime asthma symptoms, salbutamol usage, and 7-item-Asthma Control Questionnaire scores) and objective clinical outcome measures (FEV1, fraction of exhaled nitric oxide, and blood eosinophils) were assessed over 12 weeks (ClinicalTrials.gov number, NCT00890734). RESULTS: All patient-reported parameters improved overall between week 0 and 12 in QbG10-treated patients (n = 33) despite steroid withdrawal, compared with deteriorations observed under placebo (n = 30, P < .05). At week 12, two thirds of the QbG10-treated patients had their asthma "well controlled" (Asthma Control Questionnaire score ≤0.75) compared with one third under placebo. FEV1 had worsened to a clinically significant extent in patients on placebo, while it remained stable in QbG10 patients. Adverse events were mostly injection site reactions occurring after QbG10 administration. CONCLUSION: Treatment with QbG10 may contribute to continued asthma control during steroid reduction in patients on moderate or high-dose inhaled steroids.

Effect of immunisation against angiotensin II with CYT006-AngQb on ambulatory blood pressure: a double-blind, randomised, placebo-controlled phase IIa study.

BACKGROUND: Hypertension can be controlled adequately with existing drugs such as angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. Nevertheless, treatment success is often restricted by patients not adhering to treatment. Immunisation against angiotensin II could solve this problem. We investigated the safety and efficacy of CYT006-AngQb-a vaccine based on a virus-like particle-that targets angiotensin II to reduce ambulatory blood pressure. METHODS: In this multicentre, double-blind, randomised, placebo-controlled phase IIa trial, 72 patients with mild-to-moderate hypertension were randomly assigned with a computer-generated randomisation list to receive subcutaneous injections of either 100 mug CYT006-AngQb (n=24), 300 mug CYT006-AngQb (24), or placebo (24), at weeks 0, 4, and 12. 24-h ambulatory blood pressure was measured before treatment and at week 14. The primary outcomes were safety and tolerability. Analyses were done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00500786. FINDINGS: Two patients in the 100 mug group, three in the 300 mug group, and none in the placebo group discontinued study treatment. All patients were included in safety analyses; efficacy analyses did not include the five dropouts, for whom no data were available at week 14. Five serious adverse events were reported (two in the 100 mug group, two in the 300 mug group, and one in the placebo group); none were deemed to be treatment related. Most side-effects were mild, transient reactions at the injection site. Mild, transient influenza-like symptoms were seen in three patients in the 100 mug group, seven in the 300 mug group, and none in the placebo group. In the 300 mug group, there was a reduction from baseline in mean ambulatory daytime blood pressure at week 14 by -9.0/-4.0 mm Hg compared with placebo (p=0.015 for systolic and 0.064 for diastolic). The 300 mug dose reduced the early morning blood-pressure surge compared with placebo (change at 0800 h -25/-13 mm Hg; p<0.0001 for systolic, p=0.0035 for diastolic). INTERPRETATION: Immunisation with CYT006-AngQb was associated with no serious adverse events; most observed adverse events were consistent with local or systemic responses similar to those seen with other vaccines. The 300 mug dose reduced blood pressure in patients with mild-to-moderate hypertension during the daytime, especially in the early morning. FUNDING: Cytos Biotechnology AG.

Shared Decision-Making Training in Internal Medicine: A Multisite Intervention Study.

BACKGROUND: Research shows that when patients and health care providers share responsibility for clinical decisions, both patient satisfaction and quality of care increase, and resource use decreases. Yet few studies have assessed how to train residents to use shared decision-making (SDM) in their practice. OBJECTIVE: We developed and evaluated a SDM training program in internal medicine. METHODS: Senior internal medicine residents from 3 hospitals in Switzerland were assessed shortly before and 2 months after completing a program that included a 2-hour workshop and pocket card use in clinical practice. Encounters with standardized patients (SPs) were recorded and SDM performance was assessed using a SDM completeness rating scale (scores ranging from 0 to 100), a self-reported questionnaire, and SPs rating the residents. RESULTS: Of 39 eligible residents, 27 (69%) participated. The mean (SD) score improved from 65 (SD 13) to 71 (SD 12; effect size [ES] 0.53; P = .011). After training, participants were more comfortable with their SDM-related knowledge (ES 1.42, P < .001) and skills (ES 0.91, P < .001), and with practicing SDM (ES 0.96, P < .001). Physicians applied SDM concepts more often in practice (ES 0.71, P = .001), and SPs felt more comfortable with how participants discussed their care (ES 0.44, P = .031). CONCLUSIONS: The SDM training program improved the competencies of internal medicine residents and promoted the use of SDM in clinical practice. The approach may be of interest for teaching SDM to residents in other disciplines and to medical students.

Floppy kid syndrome caused by D-lactic acidosis in goat kids.

BACKGROUND: Goat kids with floppy kid syndrome have metabolic acidosis, muscle weakness, and depression but no dehydration. HYPOTHESIS: D-Lactate is the major component of acidemia in goat kids with floppy kid syndrome. ANIMALS: Fifty-five goat kids with floppy kid syndrome (group F) and 35 clinically healthy goat kids (group C). METHODS: Clinical, biochemical, microbiologic, virologic, parasitologic, and pathologic examinations. RESULTS: The animals in group F had a blood pH of 7.13 +/- 0.11 and a base excess of -17.8 +/- 3.8 mM, which were both lower than the values in the control animals (pH, 7.32 +/- 0.31; base excess, -0.1 +/- 2.7 mM; P < .001). Floppy kids had a significantly larger anion gap than healthy kids (31.2 +/- 3.7 versus 21.5 +/- 8.5 mM; P < .001). The concentration of L-lactate was lower in floppy kids than in healthy kids (0.67 +/- 0.49 versus 1.60 +/- 1.02 mM), but the concentration of D-lactate was higher in floppy kids (7.43 +/- 2.71 versus 0.26 +/- 0.24 mM; P < .001). Intravenous and oral administration of sodium bicarbonate in floppy kids resulted in a significant increase in blood pH and base excess and a decrease in the anion gap (P < .001). In addition, the concentration of L-lactate increased (P = .039). CONCLUSIONS AND CLINICAL IMPORTANCE: Metabolic acidosis in goat kids with floppy kid syndrome is caused by an increase in the plasma concentration of D-lactate.