Epigenetic targeting of Waldenström macroglobulinemia cells with BET inhibitors synergizes with BCL2 or histone deacetylase inhibition.

Aim: Waldenström macroglobulinemia (WM) is a low-grade B-cell lymphoma characterized by overproduction of monoclonal IgM. To date, there are no therapies that provide a cure for WM patients, and therefore, it is important to explore new therapies. Little is known about the efficiency of epigenetic targeting in WM. Materials & methods: WM cells were treated with BET inhibitors (JQ1 and I-BET-762) and venetoclax, panobinostat or ibrutinib. Results: BET inhibition reduces growth of WM cells, with little effect on survival. This finding was enhanced by combination therapy, with panobinostat (LBH589) showing the highest synergy. Conclusion: Our studies identify BET inhibitors as effective therapy for WM, and these inhibitors can be enhanced in combination with BCL2 or histone deacetylase inhibition.

Firm-based trial to improve central venous catheter insertion practices.

BACKGROUND: Central venous catheters placed in femoral veins increase the risk of complications. At our institution, residents place most catheters in the femoral vein. OBJECTIVE: Determine whether a hands-on educational session reduced femoral venous catheterization and improved residents' confidence and adherence to recommendations for infection control. DESIGN: Firm-based clinical trial between November 2004 and March 2005. SETTING: General medical wards of Cook County (Stroger) Hospital (Chicago, IL), a public teaching hospital. PARTICIPANTS: Internal medicine residents (n = 150). INTERVENTION: Before their 4-week rotation, intervention-firm residents received a lecture and practiced placing catheters in mannequins; control-firm residents received the usual training. MEASUREMENTS: Venous insertion site, adherence to recommendations for infection control, knowledge and confidence about catheter insertion, and catheter-associated complications RESULTS: Residents inserted 54 catheters, or 0.24 insertions per resident per 4-week rotation. There was a nonsignificant decrease in femoral insertions for nondialysis catheters in the intervention group compared to the control group (44% vs. 58%), difference: -14% (95% CI, -52% to 24%). The intervention significantly increased residents' knowledge of complications related to femoral vein catheterization and temporarily increased their confidence about placing internal jugular or subclavian venous catheters. Intervention-group residents were more likely to use masks during catheterization (risk ratio, 2.2; 95% CI, 1.3-2.7), but other practices were similar. CONCLUSIONS: Our intervention improved residents' knowledge of complications and use of masks during catheter insertion; however, it did not significantly change venous insertion sites. Catheter insertions on our general medicine wards are infrequent, and the skills acquired during the skills-building session may have deteriorated given the few clinical opportunities for reinforcement.

Prospective cohort study of central venous catheters among internal medicine ward patients.

BACKGROUND: Central venous catheter (CVC) use is less well described for patients outside the intensive care unit. We evaluated CVCs and the associated bloodstream infection rate among patients admitted to the general medical service. METHODS: We performed a prospective cohort study of patients who had a CVC on admission or inserted during their stay on the general medical service in a public teaching hospital, November 15, 2004, to March 31, 2005. RESULTS: We identified 106 CVCs, 52 were present on admission and 54 were inserted; there were 682 catheter-days. The primary bloodstream infection rate was 4.4 per 1000 catheter-days (95% CI: 0.9-13): highest for catheters inserted in the emergency department compared with those inserted on other units (24 vs 1.7 per 1000 catheter-days), P = .045. By multivariable analysis, inadequate dressings were more likely among patients with a body mass index > or =30 kg/m(2), adjusted odds ratio, 3.4 (95% CI: 1.4-8.0). CONCLUSIONS: Many CVCs had previously been inserted in the emergency department or intensive care unit; therefore, strategies to reduce bloodstream infections that focus on ward insertion practices may not dramatically reduce bloodstream infection rates. Intervention strategies should target improved dressing care and consideration of early removal or replacement of catheters inserted in the emergency department.

Translating clinical research into clinical practice: impact of using prediction rules to make decisions.

Clinical prediction rules, sometimes called clinical decision rules, have proliferated in recent years. However, very few have undergone formal impact analysis, the standard of evidence to assess their impact on patient care. Without impact analysis, clinicians cannot know whether using a prediction rule will be beneficial or harmful. This paper reviews standards of evidence for developing and evaluating prediction rules; important differences between prediction rules and decision rules; how to assess the potential clinical impact of a prediction rule before translating it into a decision rule; methodologic issues critical to successful impact analysis, including defining outcome measures and estimating sample size; the importance of close collaboration between clinical investigators and practicing clinicians before, during, and after impact analysis; and the need to measure both efficacy and effectiveness when analyzing a decision rule's clinical impact. These considerations should inform future development, evaluation, and use of all clinical prediction or decision rules.

Physical examination: bewitched, bothered and bewildered.

Next to nothing is known about physical findings' impact on patient care.