Digital Communication Technology: Does Offering a Choice of Modality Improve Medication Adherence and Outcomes in a Persistent Asthma Population?

BACKGROUND: Use of digital communication technology has shown potential to improve asthma adherence and outcomes. Few studies have looked at patient preference around mode of medication reminders used to improve and maintain asthma medication adherence. OBJECTIVE: To determine if, in a population already receiving automated medication reminders, offering a choice for preferred mode of reminder (text, email, phone) would improve their adherence and asthma outcomes over a 1-year period. METHODS: This was a pragmatic, randomized controlled trial conducted at Kaiser Permanente Colorado involving 7522 adult patients with persistent asthma. Study patients were randomized to receive usual care or their choice of medication reminder. Differences between the 2 groups in both medication adherence and asthma outcomes were then assessed over the following year. RESULTS: Only 30% of those offered a choice of medication reminder modality responded by making a choice, with 52% preferring text messaging. There was less of a decrease in adherence rate over the 1-year period in those who made a choice regarding the mode of medication refill reminder. There was no difference in asthma outcomes between those who did make a choice compared with those who did not make a choice regarding the mode of medication refill reminder. CONCLUSION: In a patient population already receiving medication reminders, offering a choice about what type of technology-enabled asthma medication reminder patients wanted did not improve outcomes but did enable a subgroup to better maintain their medication adherence.

Predicting the risk of Clostridium difficile infection following an outpatient visit: development and external validation of a pragmatic, prognostic risk score.

Increasing morbidity related to Clostridium difficile infection (CDI) has heightened interest in the identification of patients who would most benefit from recognition of risk and intervention. We sought to develop and validate a prognostic risk score to predict CDI risk for individual patients following an outpatient healthcare visit. We assembled a cohort of Kaiser Permanente Northwest (KPNW) patients with an index outpatient visit between 2005 and 2008, and identified CDI in the year following that visit. Applying Cox regression, we synthesized a priori predictors into a CDI risk score, which we validated among a Kaiser Permanente Colorado (KPCO) cohort. We calculated and plotted the observed 1-year CDI risk for each decile of predicted risk for both cohorts. Among 356 920 KPNW patients, 608 experienced CDI, giving a 1-year incidence of 2.2 CDIs per 1000 patients. The Cox model differentiated between patients who do and do not develop CDI: there was a C-statistic of 0.83 for KPNW. The simpler points-based risk score, derived from the Cox model, was validated successfully among 296 550 KPCO patients, with no decline in the area under the receiver operating characteristic curve: 0.785 (KPNW) vs. 0.790 (KPCO). The predicted risk for CDI agreed closely with the observed risk. Our CDI risk score utilized data collected during usual care to successfully identify patients who developed CDI, discriminating them from patients at the lowest risk for CDI. Our prognostic CDI risk score provides a decision-making tool for clinicians in the outpatient setting.

Improving automated case finding for ectopic pregnancy using a classification algorithm.

BACKGROUND: Research and surveillance work addressing ectopic pregnancy often rely on diagnosis and procedure codes available from automated data sources. However, the use of these codes may result in misclassification of cases. Our aims were to evaluate the accuracy of standard ectopic pregnancy codes; and, through the use of additional automated data, to develop and validate a classification algorithm that could potentially improve the accuracy of ectopic pregnancy case identification. METHODS: Using automated databases from two US managed-care plans, Group Health Cooperative (GH) and Kaiser Permanente Colorado (KPCO), we sampled women aged 15-44 with an ectopic pregnancy diagnosis or procedure code from 2001 to 2007 and verified their true case status through medical record review. We calculated positive predictive values (PPV) for code-selected cases compared with true cases at both sites. Using additional variables from the automated databases and classification and regression tree (CART) analysis, we developed a case-finding algorithm at GH (n = 280), which was validated at KPCO (n = 500). RESULTS: Compared with true cases, the PPV of code-selected cases was 68 and 81% at GH and KPCO, respectively. The case-finding algorithm identified three predictors: ≥ 2 visits with an ectopic pregnancy code within 180 days; International Classification of Diseases, 9th Revision, Clinical Modification codes for tubal pregnancy; and methotrexate treatment. Relative to true cases, performance measures for the development and validation sets, respectively, were: 93 and 95% sensitivity; 81 and 81% specificity; 91 and 96% PPV; 84 and 79% negative predictive value. Misclassification proportions were 32% in the development set and 19% in the validation set when using standard codes; they were 11 and 8%, respectively, when using the algorithm. CONCLUSIONS: The ectopic pregnancy algorithm improved case-finding accuracy over use of standard codes alone and generalized well to a second site. When using administrative data to select potential ectopic pregnancy cases, additional widely available automated health plan data offer the potential to improve case identification.

Health care utilization and costs by metabolic syndrome risk factors.

BACKGROUND: This study compared prevalent health utilization and costs for persons with and without metabolic syndrome and investigated the independent associations of the various factors that make up metabolic syndrome. METHODS: Subjects were enrollees of three health plans who had all clinical measurements (blood pressure, fasting plasma glucose, body mass index, triglycerides, and high-density lipoprotein cholesterol) necessary to determine metabolic syndrome risk factors over the 2-year study period (n = 170,648). We used clinical values, International Classification of Diseases, Ninth Revision (ICD-9) diagnoses, and medication dispensings to identify risk factors. We report unadjusted mean annual utilization and modeled mean annual costs adjusting for age, sex, and co-morbidity. RESULTS: Subjects with metabolic syndrome (n = 98,091) had higher utilization and costs compared to subjects with no metabolic syndrome (n = 72,557) overall, and when stratified by diabetes (P < 0.001). Average annual total costs between subjects with metabolic syndrome versus no metabolic syndrome differed by a magnitude of 1.6 overall ($5,732 vs. $3,581), and a magnitude of 1.3 when stratified by diabetes (diabetes, $7,896 vs. $6,038; no diabetes, $4,476 vs. $3,422). Overall, total costs increased by an average of 24% per additional risk factor (P < 0.001). Costs and utilization differed by risk factor clusters, but the more prevalent clusters were not necessarily the most costly. Costs for subjects with diabetes plus weight risk, dyslipidemia, and hypertension were almost double the costs for subjects with prediabetes plus similar risk factors ($8,067 vs. $4,638). CONCLUSIONS: Metabolic syndrome, number of risk factors, and specific combinations of risk factors are markers for high utilization and costs among patients receiving medical care. Diabetes and certain risk clusters are major drivers of utilization and costs.

Sex differences in gout epidemiology: evaluation and treatment.

BACKGROUND: Little is known about the characteristics, evaluation and treatment of women with gout. OBJECTIVE: To examine the epidemiological differences and differences in treatment between men and women in a large patient population. METHODS: The data from approximately 1.4 million people who were members of seven managed care plans in the USA for at least 1 year between 1 January 1999 and 31 December 2003 were examined. Adult members who had pharmacy benefits and at least two ambulatory claims specifying a diagnosis of gout were identified. In addition, men and women who were new users of urate-lowering drugs (ULDs) were identified to assess adherence with recommended surveillance of serum urate levels within 6 months of initiating urate-lowering treatment. RESULTS: A total of 6133 people (4975 men and 1158 women) with two or more International Classification of Disease-9 codes for gout were identified. As compared with men with gout, women were older (mean age 70 (SD 13) v 58 (SD 14), p<0.001) and had comorbidities and received diuretics more often (77% v 40%; p<0.001). Only 37% of new users of urate-lowering treatment had appropriate surveillance of serum urate levels post-initiation of urate-lowering treatment. After controlling for age, comorbidities, gout treatments, number of ULD dispensings and health plan, women were more likely (odds ratio 1.36, 95% confidence interval 1.11 to 1.67) to receive the recommended serum urate level testing. CONCLUSIONS: Women with gout were older, had greater comorbidities and more often used diuretics and received appropriate surveillance of serum urate levels, suggesting that the factors leading to gout as well as monitoring of treatment are very different in women and men.

Multicenter epidemiologic and health services research on therapeutics in the HMO Research Network Center for Education and Research on Therapeutics.

Research and education programs in therapeutics that combine the data, organizational capabilities, and expertise of several managed care organizations working in concert can serve an important role when a single organization is not large enough to address a question of interest, when diversity in populations or delivery systems is required, and when it is necessary to establish consistency of results in different settings. Nine members of the HMO Research Network, a consortium of health maintenance organizations (HMOs) that perform public domain research, have formed a Center for Education and Research on Therapeutics (CERT), sponsored by the Agency for Healthcare Research and Quality, to conduct multicenter research in therapeutics. The CERT uses a distributed organizational model with shared leadership, in which data reside at the originating organization until they are needed to support a specific study. Extraction of data from the host computer systems, and some manipulation of data, is typically accomplished through computer programs that are developed centrally, then modified for use at each site. For complex studies, pooled analysis files are created by a coordinating center, and then analysed by investigators throughout the HMOs. It is also possible to contact HMO members when necessary. This multicenter environment has several benefits, addressing: (1) a wide array of questions about the safety and effectiveness of therapeutics, (2) the impact of efforts to change clinicians' and patients' behavior, and (3) pharmacoeconomic and pharmacogenetic questions.

Malaria epidemiology and economics in a pharmacist-managed international travel clinic.

With high rates of travel and low adherence to malaria prophylaxis, targeting educational efforts to high-risk travelers is vital. We assessed risk factors for acquiring malaria, and resource use and outcomes of these patients in a managed care environment. Patients were identified from January 1, 1994, to December 31, 1997, using microbiology and pharmacy databases, chart reviews, and interviews. Sixteen patients acquired malaria during the study; although only 50% contacted the travel clinic. Only 31% (5) of them had documented adherence. Fifty percent were hospitalized at a cost of $3881/patient. Travelers at greatest risk for nonadherence appear to be expatriates and those visiting Africa. Providers should target these groups with more intensive counseling in an effort to improve therapy adherence and reduce the risk for malaria.

Rotavirus disease and its prevention in infants and children.

Rotavirus disease causes immense morbidity and mortality in developing countries. In the United States, mortality is very rare, but the health care and societal costs of rotavirus-related morbidity exceed one billion dollars annually A new vaccine that prevents the illness recently was marketed in the United States. Economic issues surround national recommendations for its use. Economic, safety, and effectiveness issues will be resolved only with surveillance systems that document the effectiveness of immunization programs and their cost-effectiveness.

Ambulatory management of chemotherapy-induced fever and neutropenia in adult cancer patients.

OBJECTIVE: To review the literature on the management of low-risk adults with chemotherapy-induced fever and neutropenia (CIFN). Included in the review are methods to identify these patients, management options, and economic impact associated with nontraditional treatment options. DATA SOURCES: A MEDLINE and bibliographic search (January 1966-December 1997) for all English-language studies evaluating the identification and treatment of adult, low-risk CIFN patients was completed. Reference lists from identified articles also served as literature sources. STUDY SELECTION AND DATA EXTRACTION: All human studies identified from the data sources were evaluated. Pertinent information, excluding pediatric studies, was selected and critically evaluated for discussion. DATA SYNTHESIS: Alterations in prominent bacterial isolates in CIFN, newer antibiotic choices, enhanced focus on patient comfort, and cost-containment directives have promoted recent research identifying adult cancer patients with low-risk CIFN. Using this information to select low-risk CIFN patients, several investigators have completed trials using antibiotic therapy applicable to the ambulatory setting. Additionally, some investigators have included the use of an oral outpatient antibiotic regimen. Limited data indicate that this approach is a reasonable treatment option for selected patients. CONCLUSIONS: A subset of adult patients with CIFN are at low risk for serious morbidity and mortality when treated with broad-spectrum antibiotics in the ambulatory setting. Managing these patients with this approach requires close patient selection, intense follow-up, data collection, and ongoing evaluation to determine efficacy and patient safety. Currently, ambulatory treatment with oral antibiotics for CIFN is not considered standard of care. Further studies of larger size designed to confirm low-risk patient characteristics and optimal antibiotic selection are required.

Sepsis syndrome and associated sequelae in patients at high risk for gram-negative sepsis.

We conducted a prospective surveillance study of 80 hospitals across the United States to determine the incidence of sepsis syndrome and its associated sequelae in hospitalized patients over age 18 years who were administered antibiotics for suspected or documented gram-negative infection. A sample of 1754 hospitalized patients were followed from onset of antimicrobial therapy to discharge or death. Mortality rates (MR) varied depending on the suspected source of sepsis syndrome. For patients in whom the syndrome was associated with community-acquired urinary tract infections, mortality was 20% (relative risk [RR] = 0.51, p < 0.05), for those with trauma 20.6% (RR = 0.51, p < 0.05), and patients with nosocomial respiratory tract infections 57.1% (RR = 1.66, p < 0.05). More than two complications occurred in 65.2% of patients under age 60 years (MR 31%), 40.8% of those age 60-80 (MR 42%), and 35.6% of patients older than 80 years (MR 33.3%, p > 0.05). Various patient populations had significant differences in both the incidence of the syndrome and its complications, and consequent mortality. Perhaps morbidity as well as mortality should be used as outcomes when testing the efficacy of innovative therapies for sepsis.

Use of antifungal therapy in hospitalized patients. I. Results prior to the marketing of fluconazole.

OBJECTIVE: To evaluate the use of antifungal agents in hospitalized patients prior to marketing of fluconazole and to assess characteristics associated with their use. DESIGN: A cohort of hospitalized patients receiving topical or systemic antifungal therapy was monitored concurrently. SETTING: Sixty-nine hospitals ranging in size from 100 to more than 500 beds, 70.1 percent affiliated with medical schools. PATIENTS: Participating clinical pharmacists each identified 15 consecutive patients receiving systemic antifungal therapy and 5 consecutive patients receiving topical antifungal therapy at their institutions. Data collection began October 1989 and ended March 1990. INTERVENTION: All data collected were observational in nature, and no patient intervention was required. MEASURES: Characteristics of patients receiving antifungal therapy were compared using t-tests and chi-square tests. Utilization and patterns of use of antifungal therapy were reported. RESULTS: The most common risk factors necessitating antifungal therapy, in descending order, were: administration of broad-spectrum antibiotics and/or presence of invasive catheters, carcinoma, AIDS, leukemia or lymphoma, diabetes mellitus, solid organ or bone marrow transplantation, and chronic obstructive pulmonary disease. Five hundred seventeen patients received systemic therapy and 464 (89.7 percent) received a single systemic agent. Of these, 242 (52.2 percent) received amphotericin B, 215 (46.3 percent) received ketoconazole, 6 (1.3 percent) received flucytosine, and 1 (0.2 percent) received intravenous miconazole. Fifty-three patients received two systemic agents either concurrently or consecutively. Ketoconazole was most often used for presumed or documented oral, urogenital, or esophageal infections and amphotericin B was the preferred agent for disseminated infections and fungemia (p < 0.001). Almost half of the patients receiving amphotericin B or ketoconazole (48.3 percent) received these drugs as empiric therapy. Documented infections were more likely to be treated with amphotericin B (54.8 percent) than with ketoconazole (27.4 percent) (p < 0.001). The predominant fungal isolates were Candida albicans, Candida spp., and unspecified yeasts. Amphotericin B toxicity led to discontinuation of drug therapy in only 5.1 percent of cases. Two hundred sixty-nine patients (34.2 percent) received topical antifungal therapy only. Nystatin oral suspension was prescribed to 65.3 percent of the patients, clotrimazole troches to 23.0 percent, amphotericin B irrigation to 10.9 percent, and nystatin tablets to 0.8 percent. CONCLUSIONS: The utilization patterns of antifungal agents in this survey follow established therapeutic guidelines. Prior to the introduction of fluconazole, amphotericin B was the agent of choice for documented systemic fungal infections. Ketoconazole was more often used for prophylaxis of fungal infections and treatment of oral and esophageal infections.

Insect repellent (N,N-diethyl-m-toluamide) cardiovascular toxicity in an adult.

OBJECTIVE: To describe a case of N,N-diethyl-m-toluamide (DEET)-induced cardiovascular toxicity in an adult and reviews other cases that have been reported in the published literature. Human and animal data available on DEET pharmacokinetics are reviewed and factors that predispose an individual to DEET toxicity are identified. DATA SOURCES: Case report information was obtained through personal contact with the patient during hospitalization and by telephone, and also from the patient's medical records. Computerized literature searches were conducted with the following systems to obtain medical literature on DEET toxicity: TOXLINE, International Pharmaceutical Abstracts, and MEDLINE. Index Medicus was searched manually. STUDY SELECTION: All reported cases of DEET toxicity in children and adults were reviewed. DATA EXTRACTION: Case reports were evaluated for the quantity of the DEET exposure (topical or oral), the clinical manifestations of the exposure, and the outcome of the exposure. DATA SYNTHESIS: This case is similar in some aspects to those already in the literature; however, very few cases of DEET toxicity in adults have been reported. Cardiovascular toxicity in humans related to DEET application has not been previously reported in the published medical literature. DEET exposure (topical or oral) results in a highly variable clinical course. Whether the outcome is death or recovery without sequelae is difficult to predict. CONCLUSIONS: Adults, as well as children, are at risk for toxicity from insect repellents. The use of highly concentrated DEET-containing insect repellents should be avoided to reduce the risk of toxicity in both children and adults. The consequences of DEET toxicity are variable and unpredictable.

Clindamycin, erythromycin, and the newer macrolides.

Clindamycin continues to be an important agent for the management of infections due to gram-positive cocci and anaerobes. Such pathogens are frequently important in skin, soft tissue, and deep infections of the foot. Erythromycin has an impressive safety record and has retained its activity against many organisms, including several that play a role in infections of the foot. Clindamycin and erythromycin are frequently used as alternatives to the penicillins and cephalosporins. Newer macrolides, in comparison to erythromycin, have similar antimicrobial spectra of activity, improved pharmacokinetic parameters, and better tissue penetration. As new microorganisms emerge as clinical problems, newer macrolides may play a therapeutic role.

Magnesium sulfate versus phenytoin for seizure prophylaxis in pregnancy-induced hypertension.

Seizure prophylaxis is standard intrapartum therapy for patients with pregnancy-induced hypertension. Magnesium sulfate is used in the United States in spite of limited literature comparing its efficacy with other anticonvulsants. Fifty patients with pregnancy-induced hypertension were prospectively randomized to receive magnesium sulfate or phenytoin for seizure prophylaxis. Patients were observed for toxicity, side effects, and labor outcomes, and the neonates were evaluated for side effects of the therapy. Three patients were excluded with adverse reactions to medications (one in magnesium sulfate group, two in phenytoin group). No differences were found in patient tolerance, adverse reactions, or neonatal outcomes between groups. Maternal free phenytoin levels were 13.0% +/- 0.4% of total phenytoin (serum albumin, 2.5 to 3.5 gm/dl), significantly higher than in nonpregnant patients. Neither free phenytoin levels nor percentage of total phenytoin that was free correlated significantly with maternal albumin levels. The pharmacokinetics of phenytoin loading in the massively obese pregnant patient may differ and require further evaluation. Phenytoin is a well-tolerated alternative to magnesium sulfate for seizure prophylaxis in the patient with mild pregnancy-induced hypertension.

A clinical pharmacy-oriented drug surveillance network: II. Results of a pilot project.

A nationwide network of clinical pharmacists has been organized for the purpose of collecting drug experience data generated during the routine clinical care of patients. In order to assess the utility of this network a pilot project was performed to obtain a cross-sectional view of antibiotic utilization in the U.S. and to identify potential problems with a more widespread implementation of this program. One hundred eleven pharmacists enrolled in the drug surveillance network participated in this survey and collected information on more than 2000 patients treated with antimicrobial agents over approximately a three-month period (February-April 1987). The most common sites of infection were the lung, genitourinary tract, skin and soft tissue, and the abdomen, and accounted for approximately 75 percent of infections. Overall, the aminoglycosides, the first-generation cephalosporins, and the aminopenicillins remain the most commonly used antibiotics and represent approximately 50 percent of antimicrobials used in the surveyed population. The results of this pilot project suggest that the use of a nationwide network of clinical pharmacists is a promising source of clinically relevant drug experience data. The ability to concurrently evaluate patients and link information regarding patient demographics, drug therapy regimens, diagnosis, and clinical outcomes fills an important gap in our knowledge of clinical drug utilization.

Twenty-four-hour single-container system for parenteral nutrient admixtures.

Development and implementation of a procedure for preparing parenteral nutrient (PN) solutions in 3-L containers at a 385-bed teaching hospital is described. After identifying problems in procedures for PN therapy, pharmacists collected time and cost data for preparing PN solutions using gravity flow and 1-L containers versus an automated compounding device and 3-L containers. They prepared a proposal for mixing a single daily solution in a 3-L container. A change in hospital policy to permit each PN solution to hang for 24 instead of 12 hours, a change in the pharmacy's schedule for preparing PN solutions, and a policy of hanging all fresh PN solutions between 1800 and 2400 were also proposed. After a one-month trial, the new procedures were adopted. To prepare an average of six PN solutions per day, time decreased from 5.32 to 2.33 hours. Inventory of PN supplies was reduced by 56%. Patients were charged approximately $25 less for three liters of PN solution. Standardized procedures improved efficiency of order filling. A standard procedure for preparing parenteral nutrient solutions in 3-L containers resulted in cost savings for the hospital and the patients and more efficient patient care.

Continuous infusion of naloxone in the treatment of narcotic overdose.

Based on the pharmacokinetic parameters of naloxone and the clinical studies discussed in this paper, it is evident that naloxone infusion may be useful in cases of opiate overdose. The infusion protocol presented in Appendix I was formulated based on the pharmacokinetic data available from the literature including Nelson's animal data. An infusion of naloxone was used with apparent success in the two cases presented. Both patients presented with narcotic overdose; although immediate patient history could not be obtained, the presentations were classic for narcotic overdose. It is of note that it may be possible to keep a patient from relapsing into narcosis after overdose by the use of naloxone infusion. Additionally, the extreme safety of naloxone is certainly an advantage with any administration technique. We feel that the administration of continuous infusion of naloxone is an especially important advance in the overdose treatment of longer-acting agents such as methadone, as well as of other narcotics. Therefore, it is recommended that further clinical trials of naloxone by infusion be undertaken, as suggested by J. Nelson, et al. (A protocol for treatment with continuous infusion of naloxone [Narcan] in selected cases of opiate [narcotic] overdose. Austin: University of Texas; May, 1976, unpublished), to further document the effectiveness of an infusion of naloxone in narcotic overdose.