Practitioner Education and Feedback to Decrease Ciprofloxacin Prescriptions in Patients with Acute Uncomplicated Cystitis.

CONTEXT: Current guidelines recommend a nonfluoroquinolone agent as first-line treatment of acute uncomplicated cystitis (AUC) because of concerns of antimicrobial resistance and adverse effects. OBJECTIVE: To test whether a multifaceted intervention involving education and feedback reduced primary care practitioners' ciprofloxacin prescriptions for AUC therapy. DESIGN: Primary care practitioners at 3 medical offices participated: 65 in the intervention group and 51 in the control group. Intervention group participants received an educational lecture and emailed summary of antimicrobial guidelines, their AUC prescriptions were audited, and feedback was provided on inappropriate antibiotic choices. Prescriptions at AUC encounters were tracked during baseline, intervention, and postintervention periods. MAIN OUTCOME MEASURES: Proportion of AUC encounters at which ciprofloxacin was prescribed vs recommended first-line antibiotics. RESULTS: Intervention group participants had 5262 eligible AUC encounters, and control group participants had 5473. At baseline, ciprofloxacin was prescribed at 29.7% and 33.7% of eligible AUC encounters in the intervention and control groups, respectively (p = 0.003). After intervention, ciprofloxacin was prescribed at 10.8% of eligible AUC encounters in the intervention group and 34.3% in the control (p < 0.001). Adjusted odds ratios of ciprofloxacin prescription for AUC therapy were significantly lower in the intervention group during postintervention and intervention periods vs baseline (0.29, 95% confidence interval = 0.20-0.44, p < 0.001 and 0.80, 95% confidence interval = 0.66-0.97, p = 0.03). Adjusted odds ratios did not change over time in the controls. CONCLUSION: Educating primary care practitioners and conducting audit and feedback reduced their prescriptions of ciprofloxacin for AUC therapy.

Human centromeric CENP-A chromatin is a homotypic, octameric nucleosome at all cell cycle points.

Chromatin assembled with centromere protein A (CENP-A) is the epigenetic mark of centromere identity. Using new reference models, we now identify sites of CENP-A and histone H3.1 binding within the megabase, α-satellite repeat-containing centromeres of 23 human chromosomes. The overwhelming majority (97%) of α-satellite DNA is found to be assembled with histone H3.1-containing nucleosomes with wrapped DNA termini. In both G1 and G2 cell cycle phases, the 2-4% of α-satellite assembled with CENP-A protects DNA lengths centered on 133 bp, consistent with octameric nucleosomes with DNA unwrapping at entry and exit. CENP-A chromatin is shown to contain equimolar amounts of CENP-A and histones H2A, H2B, and H4, with no H3. Solid-state nanopore analyses show it to be nucleosomal in size. Thus, in contrast to models for hemisomes that briefly transition to octameric nucleosomes at specific cell cycle points or heterotypic nucleosomes containing both CENP-A and histone H3, human CENP-A chromatin complexes are octameric nucleosomes with two molecules of CENP-A at all cell cycle phases.

A two-step mechanism for epigenetic specification of centromere identity and function.

The basic determinant of chromosome inheritance, the centromere, is specified in many eukaryotes by an epigenetic mark. Using gene targeting in human cells and fission yeast, chromatin containing the centromere-specific histone H3 variant CENP-A is demonstrated to be the epigenetic mark that acts through a two-step mechanism to identify, maintain and propagate centromere function indefinitely. Initially, centromere position is replicated and maintained by chromatin assembled with the centromere-targeting domain (CATD) of CENP-A substituted into H3. Subsequently, nucleation of kinetochore assembly onto CATD-containing chromatin is shown to require either the amino- or carboxy-terminal tail of CENP-A for recruitment of inner kinetochore proteins, including stabilizing CENP-B binding to human centromeres or direct recruitment of CENP-C, respectively.