Evaluating the safety and potential activity of URO-902 (hMaxi-K) gene transfer by intravesical instillation or direct injection into the bladder wall in female participants with idiopathic (non-neurogenic) overactive bladder syndrome and detrusor overactivity from two double-blind, imbalanced, placebo-controlled randomized phase 1 trials.

AIMS: Two phase 1 trials were performed in healthy women with the overactive bladder (OAB) syndrome and urodynamically demonstrated detrusor overactivity (DO), with the aim to demonstrate the safety and potential efficacy of URO-902, which comprises a gene therapy plasmid vector expressing the human big potassium channel α subunit. METHODS: ION-02 (intravesical instillation) and ION-03 (direct injection) were double-blind, placebo-controlled, multicenter studies without overlap in enrollment between studies. Active doses were administered and evaluated sequentially (lowest dose first) for safety. ION-02 participants received either 5000 µg or 10 000 µg URO-902, or placebo. ION-03 participants received either 16 000 or 24 000 µg URO-902, or placebo, injected directly into the bladder wall using cystoscopy. Primary outcome variables were safety parameters occurring subsequent to URO-902 administration; secondary efficacy variables also were evaluated. RESULTS: Among the safety outcomes, there were no dose-limiting toxicities or significant adverse events (AEs) preventing dose escalation during either trial, and no participants withdrew due to AEs. For efficacy, in ION-02 (N = 21), involuntary detrusor contractions on urodynamics at 24 weeks in patients receiving URO-902 (P < .0508 vs placebo) and mean urgency incontinence episodes in the 5000 µg group (P = .0812 vs placebo) each showed a downward trend. In ION-03 (N = 13), significant reduction versus placebo in urgency episodes (16 000 µg, P = .036; 24 000 µg, P = .046) and number of voids (16 000 µg, -2.16, P = .044; 24 000 µg, -2.73, P = .047) were observed 1 week after injection. CONCLUSION: Promising safety and efficacy results in these preliminary phase 1 studies suggest gene transfer may be a promising therapy for OAB/DO, warranting further investigation.

Linguistic diversity as sociodemographic predictor of nursing program progression and completion.

Attrition from undergraduate nursing programs continues to warrant investigation particularly in the climate of nursing shortages and fiscal reflection on academic institutional programs. This three-year study used a prospective longitudinal survey design to determine entry characteristics of students, attrition, progression and completion in an undergraduate program. Students were surveyed in the first three weeks of commencing their program and gave permission for academic grades to be collected during their six session, three year Bachelor of Nursing program. Of the 740 students enrolled 48% (357 students) were surveyed and 352 students (99%) gave consent for their grades to be collected. One-third of the student cohort graduated in the expected three-year timeframe, one-third had dropped out and one-third was still completing their studies. A higher Grade Point Average and being a native English speaker were most predictive of students completing their course in the minimum expected timeframe.

Clinicians' perceptions of the problem of antimicrobial resistance in health care facilities.

BACKGROUND: Many clinicians do not comply with guidelines regarding antimicrobial resistance (AR). In response, the Centers for Disease Control and Prevention developed a national Campaign to Prevent Antimicrobial Resistance in Healthcare Settings that presents 4 strategies and 12 evidence-based steps. METHODS: To assess clinicians' perceptions of AR, barriers and facilitators to preventing AR, and how best to reach clinicians, a questionnaire and 4 focus groups were conducted after presentation of the Campaign at 4 Pittsburgh Regional Healthcare Initiative hospitals. RESULTS: One hundred seventeen clinicians completed the questionnaire; 28 participated in the focus groups. Clinicians were significantly more likely to perceive that AR was a problem nationally than in their own institution (95% vs 77%; P<.001) or practice (95% vs 65%; P =.002), consistent with focus group results (93% nationally vs 46% institution or practice). The 3 Campaign steps with the most barriers to implementation were "Treat infection, not colonization" (35%), "Stop treatment when infection is cured or unlikely" (35%), and "Practice antimicrobial control" (33%). Clinicians in the focus groups cited the additional barriers of the health care culture, lack of knowledge, and the nursing shortage; facilitators included education, information technology, and consults. Computer programs, posters, and local data were suggested for reaching clinicians about AR. CONCLUSIONS: Clinicians perceive AR to be a complex national problem but less relevant to their own institution or practice. Providing clinicians with information and steps for preventing AR, as in the Campaign, may affect their perceptions of the problem and motivate them to take actions to ensure patient safety.

First dose efficacy of alfuzosin once daily in men with symptomatic benign prostatic hyperplasia.

OBJECTIVES: To evaluate the onset of action of alfuzosin once daily (OD) as determined by uroflowmetry early after initial dosing. Alfuzosin OD is an extended-release formulation of a uroselective, alpha1-adrenoreceptor-blocking agent (alpha-blocker) used in the treatment of lower urinary tract symptoms due to benign prostatic hyperplasia. METHODS: This was a randomized, placebo-controlled, two-way Latin square crossover study. Forty-nine patients were selected for this study on the basis of their symptomatic improvement during previous treatment with alpha-blockers and significant decreases in urinary flow rate when that treatment was withdrawn. RESULTS: Our analysis showed that significant increases in the maximal urinary flow rate (Qmax) in 34 assessable patients occurred as soon as 8 hours after the initial dose of medication and persisted for at least 4 days. The DeltaQmax for alfuzosin 10 mg OD was 3.2 mL/s and for placebo it was 1.1 mL/s. The difference of means for the assessable population was 2.1 (95% confidence interval 0.8 to 3.4, P = 0.002). The overall incidence of adverse events was low. Only dizziness, experienced by 3 patients treated with alfuzosin compared with 1 patient treated with placebo, appeared to be related to the study drug. CONCLUSIONS: Together, our findings suggest that alfuzosin OD exhibits a urodynamically measurable effect on bladder outlet obstruction due to benign prostatic hyperplasia in men with lower urinary tract symptoms within hours of the first administration.