Lixivaptan safely and effectively corrects serum sodium concentrations in hospitalized patients with euvolemic hyponatremia.

Hyponatremia is a common electrolyte disorder associated with increased morbidity and mortality, particularly in the elderly. Lixivaptan, a new selective vasopressin V2-receptor antagonist, safely corrected serum sodium concentrations in phase II studies of patients with euvolemic hyponatremia. Here our multinational, double-blind, placebo-controlled, phase III study assessed the effect of lixivaptan on serum sodium concentrations in 106 initially hospitalized patients with euvolemic hyponatremia (serum sodium less than 130 mmol/l). Of them, 52 were randomized to receive placebo and 54 received 50 mg lixivaptan once daily and were then titrated to receive 25-100 mg once daily depending on serum sodium concentration. Fluid restriction was at the investigator's discretion. Initial titration occurred in a monitored inpatient setting; patients were then treated as outpatients for a total of 30 days. The primary end point was the change in serum sodium concentration from baseline to day 7. Lixivaptan significantly increased the serum sodium concentration from baseline to day 7 (the primary end point) by 6.7 mmol/l compared with placebo (4.5 mmol/l; P=0.034). Importantly, the serum sodium concentration was normalized safely and more rapidly in patients receiving lixivaptan than placebo (P=0.004) and was well tolerated. After drug discontinuation, serum sodium concentrations decreased to near-baseline levels within 7 days. Thus, lixivaptan safely and effectively corrects serum sodium concentrations in patients with euvolemic hyponatremia.

Vaptans are not the mainstay of treatment in hyponatremia: perhaps not yet.

Two vasopressin antagonists ('vaptans') are now in the market for the treatment of euvolemic (Europe) or euvolemic and hypervolemic (United States) hyponatremia: conivaptan for intravenous use and tolvaptan for oral application. Although their specificity and effectiveness are considered established, their indications are not. At present, we do not know which symptoms of hyponatremia and which degree of hyponatremia should serve as indications for vaptans. Other areas of uncertainty relate to the following unanswered questions: do vaptans shorten the duration of hospitalization? Is it justifiable to use them to prevent relapse of hyponatremia in (chronic) SIAD(H)? (In this text we use the abbreviation SIAD(H) instead of the recently proposed abbreviation SIAD to emphasize that vaptans will work only in the presence of ADH ('SIADH') but not in the syndrome of nephrogenic antidiuresis.) Do they decrease the high mortality associated with hyponatremia? How do we justify the cost of chronic vaptan therapy? The optimal vaptan regimen (dose, timing of controls) to treat SIAD(H) is currently not established, as is the procedure to be recommended in a too rapid correction rate of (chronic) hyponatremia. Until these requirements shall be met by additional studies, we are hesitant to consider vaptans a treatment of choice for the appropriate hyponatremias.

Reducing antibiotic overuse: a call for a national performance measure for not treating asymptomatic bacteriuria.

Positive urinary tract culture results often represent asymptomatic bacteriuria, which does not need to be treated with antimicrobial agents. Avoiding treatment of asymptomatic bacteriuria in adults should reduce the risk of development of antibiotic resistance and is consistent with the Infectious Diseases Society of America and US Preventive Services Task Force guidelines on bacteriuria. A similar approach for not treating upper respiratory illnesses with antibiotics was initiated by the Centers for Disease Control and Prevention. We propose that a hospital and ambulatory performance measure should be developed for not treating asymptomatic bacteriuria in adults. In addition, such an effort would aid hospitals in confronting the proposal of the Centers for Medicare and Medicaid Services (to be implemented in 2009) to not pay the expenses associated with catheter-associated urinary tract infection.

A pragmatic approach to implementing best practices for clinical decision support systems in computerized provider order entry systems.

Incorporation of clinical decision support (CDS) capabilities is required to realize the greatest benefits from computerized provider order entry (CPOE) systems. Discussions at a conference on CDS in CPOE held in San Francisco, California, June 21-22, 2005 produced several papers in this issue of JAMIA. The first paper reviews CDS for electronic prescribing within CPOE systems; (1) the second describes current controversies regarding creation, maintenance, and uses of CPOE order sets for CDS; (2) and the third presents issues related to certification as a potential means of validating CPOE systems for widespread use. (3) This manuscript summarizes all of the discussions at the meeting and provides a pragmatically oriented view of how to implement CPOE with CDS.

Viewpoint: controversies surrounding use of order sets for clinical decision support in computerized provider order entry.

Order sets provide straightforward clinical decision support within computerized provider order entry systems. They make "the right thing" easier to do because they are much faster than writing single orders; they deliver real-time, evidence-based prompts; they are easy to update; and they support coverage of multiple patient problems through linkages among order sets. This viewpoint paper discusses controversies surrounding use of order sets--advantages and pitfalls, decision-making criteria, and organizational considerations, including suggestions for vendors. Order sets have the potential to improve clinician efficiency, provide real-time guidance, facilitate compliance with Joint Commission on Accreditation of Healthcare Organizations and Centers for Medicare and Medicaid Services performance measure sets, and encourage overall acceptance of computerized provider order entry, but may not do so unless these controversies are addressed.

The FDA and drug safety: a proposal for sweeping changes.

The current Food and Drug Administration (FDA) system of regulating drug safety has serious limitations and is in need of changes. The major problems include the following: the design of initial preapproval studies lets uncommon, serious adverse events go undetected; massive underreporting of adverse events to the FDA postmarketing surveillance system reduces the ability to quantify risk accurately; manufacturers do not fulfill the majority of their postmarketing safety study commitments; the FDA lacks authority to pursue sponsors who violate regulations and ignore postmarketing safety study commitments; the public increasingly perceives the FDA as having become too close to the regulated pharmaceutical industry; the FDA's safety oversight structure is suboptimal; and the FDA's expertise and resources in drug safety and public health are limited. To address these problems, we urge Congress, which is ultimately responsible for the FDA's performance, to implement the following 5 recommendations: (1) give the FDA more direct legal authority to pursue violations, (2) authorize the adoption of a conditional drug approval policy, at least for selected drugs, (3) provide additional financial resources to support the safety operations, (4) mandate a reorganization of the agency with emphasis on strengthening the evaluation and proactive monitoring of drug safety, and (5) require broader representation of safety experts on the FDA's advisory committees.

Barriers to hyperglycemia control in hospitalized patients: a descriptive epidemiologic study.

OBJECTIVE: To identify barriers that prevent appropriate control of hyperglycemia in a university teaching hospital and to document their frequency in patients hospitalized for cardiothoracic surgery. METHODS: In this observational study, our inpatient diabetes team identified barriers to adequate glycemic control for diabetic patients in the cardiothoracic surgical intensive care unit between September 1, 2006, and January 3, 2007. Data were collected through chart review and patient and staff interviews. Blood glucose concentrations greater than 160 mg/dL prompted intervention, which involved speaking to the prescribing practitioner and making a treatment recommendation. Each intervention was reviewed by the diabetes nurses using the critical incident technique. The nurses determined which underlying barriers were responsible for the lack of glycemic control and had necessitated the intervention. RESULTS: Of 105 patients, 6 (5.7%) demonstrated good glucose control (75% of their blood glucose measurements were 80-160 mg/dL) and did not require intervention, and 99 (94.3%) required intervention. Diabetes nurses intervened 202 times; each patient averaged 2.04 interventions during their hospital stay. Nurses coded 398 barriers to the 202 interventions; each intervention had between 1 and 5 barriers coded as the underlying reason(s) for the intervention. Thirty barriers to adequate glycemic control were identified. Eight barriers represented 74% of the barriers encountered. Therapeutic reluctance was the most common followed by inappropriate titration of medication, lack of basal insulin, lack of weekend staff trained in diabetes management, use of a sliding scale, inappropriate medications being prescribed, knowledge deficit of the weekend staff, and outpatient diabetes medications not being restarted. CONCLUSIONS: We identified the most frequent barriers to adequate glycemic control in this group of patients and suggest how limited resources should be focused to improve glycemic control. Barrier incidence should be determined in other populations of diabetic patients.

A nurse practitioner intervention model to maximize efficient use of telemetry resources.

BACKGROUND: Telemetry monitoring is widely used in hospitals; the importance of being able to monitor and examine dysrhythmias has been universally accepted. Yet it is often used for patients who do not actually require this technology. A model to improve the efficiency of telemetry use entailed the use of an advanced practice nurse (APN; identical to a nurse practitioner) to provide concurrent review and intervention of floating telemetry, which is available for patients independently of the floor location and who do not need an intensive care unit bed. ADDRESSING OVERUSE: The demand for floating telemetry at Hackensack University Medical Center had equaled or exceeded the telemetry availability virtually 100% of the time, even after local guidelines had been disseminated in 1998. The APN carried out concurrent monitoring and intervened with the attending physician when patients were on telemetry for longer than 48 hours and did not meet the local telemetry guidelines. RESULTS: The mean number (standard error [SE]) of hours per patient declined from 65.2 +/- 0.7 hours (95% confidence interval, 63.8 to 66.6 hours) for the 11 months before the intervention to a mean of 49.6 +/- 0.4 hours (95% confidence interval, 48.7 to 50.2 hours) for the 29 months after intervention--representing a decrease of 34% (p < 0.0001). This decrease led to an increase in the number of patients per month put on telemetry. DISCUSSION: The APN model, an aggressive approach that induced change almost immediately, was then applied to other quality improvement projects.

Extending the nurse practitioner concurrent intervention model to community-acquired pneumonia and chronic obstructive pulmonary disease.

BACKGROUND: A Nurse Practitioner (NP) Concurrent Intervention Model shown effective for controlling telemetry usage was extended to patients with community-acquired pneumonia (CAP) and patients with chronic obstructive pulmonary disease (COPD). METHODS: In spring 2000, investigators at Hackensack University Medical Center and the University of Medicine and Dentistry of New Jersey-New Jersey Medical School began an intervention to increase compliance with the Centers for Medicare & Medicaid Services (CMS) performance measures for CAP. Cost-reduction efforts were introduced by using previously described criteria for switching from intravenous to oral medication and for hospital discharge. RESULTS: Use of the NP intervention model for patients admitted with CAP and for COPD patients resulted in significant reductions in length of stay and cost savings. DISCUSSION: Concurrent intervention by a nurse practitioner can help achieve excellent compliance with performance measures for CAP and be applied to other chronic respiratory diseases such as COPD.