Possible medication errors in home healthcare patients.

OBJECTIVE: To determine the frequency of possible medication errors in a population of older home healthcare patients according to expert panel objective criteria. DESIGN: A cross-sectional survey. SETTING: Two of the largest urban home healthcare agencies in the United States. PARTICIPANTS: Home healthcare patients age 65 and older admitted to selected offices of these agencies between October 1996 and September 1998. MEASUREMENTS: We used two sets of consensus-based expert panel criteria to define possible medication errors. The Home Health Criteria identify patients with patterns of medication use and signs and symptoms that indicate sufficient likelihood of a medication-related problem to warrant reevaluating the patient. The Beers criteria identify medications that experts have deemed generally inappropriate for older patients. RESULTS: The 6,718 study subjects took a median of five drugs; 19% were taking nine or more medications. A possible medication error was identified for 19% of patients according to Home Health Criteria, 17% according to the Beers criteria, and 30% according to either. Possible errors increased linearly with number of medications taken. When patients taking one to three medications were compared with those taking nine or more drugs, the percentages with possible errors were, respectively, 10% and 32% for the Home Health Criteria, 8% and 32% for the Beers criteria, and 16% and 50% for both. CONCLUSION: Nearly one-third of the home healthcare patients surveyed had evidence of a potential medication problem or were taking a drug considered inappropriate for older people. More-effective methods are needed to improve medication use in this vulnerable population.

Use of nonsteroidal anti-inflammatory drugs and incidence of colorectal cancer: a population-based study.

BACKGROUND: Previous observational studies have provided limited information on the effect of specific nonsteroidal anti-inflammatory drugs (NSAIDs) and different patterns of use (duration and dose) on the incidence of colorectal cancer. OBJECTIVE: To determine how patterns of use (duration, dose, and specific drug) of NSAIDs affect incidence of colorectal cancer. DESIGN: Population-based retrospective cohort study. SETTING: Tennessee Medicaid Program, 1985-1992. SUBJECTS: Enrollees (n = 104217) aged 65 years or older with at least 5 years of enrollment. MAIN OUTCOME MEASURES: Incident histologically confirmed colorectal cancer. RESULTS: Users of nonaspirin NSAIDs for at least 48 months of the previous 5 years had a relative risk (RR) of 0.49 (95% confidence interval [CI], 0.24-1.00) for colon cancer when compared with those with no use of NSAIDs. Among those with more than 12 months of cumulative use, those using NSAIDs in the past year (recent users) had an RR of 0.61 (95% CI, 0.48-0.77), whereas those with no recent use had an RR of 0.76 (95% CI, 0.50-1.15). No specific NSAID offered a unique protective effect and low doses of NSAIDs appeared to be at least as effective as higher doses. Protection was most pronounced for right-sided lesions. The RR among recent users with more than 12 months of cumulative use was 0.81 (95% CI, 0.49-1.32) for rectal cancer, 0.77 (95% CI, 0.55-1.08) for left-sided colon cancer, and 0.48 (95% CI, 0.34-0.68) for right-sided colon cancer. CONCLUSIONS: In this elderly population, long-term use of nonaspirin NSAIDs nearly halved the risk of colon cancer. This study was consistent with previous studies that suggest that duration of use but not daily dose of NSAIDs is an important factor for chemoprevention. Our data also suggest that the protective effect is shared by most NSAIDs, and not confined to a small number of these drugs.

Prenatal exposure to metronidazole and risk of childhood cancer: a retrospective cohort study of children younger than 5 years.

BACKGROUND: To evaluate the role of in utero exposure to metronidazole (a carcinogen in some animal models) and the risk of subsequent cancer, the authors conducted a retrospective cohort study of childhood cancer. METHODS: The cohort included 328,846 children younger than 5 years born to women enrolled in Tennessee Medicaid at any time between the last menstrual period (LMP) and the date of delivery. The cohort was identified by linking files of Tennessee Medicaid mothers ages 15-44 years and children and the children's birth and death certificates for the period January 1, 1975 through December 31, 1992. Exposure data were obtained from Medicaid pharmacy records and exposure was defined as filling a metronidazole prescription that had at least a day's supply between the 30 days prior to the LMP and the date of delivery. Study cases were cohort children diagnosed with a first primary cancer before age 5 years, identified by linking the cohort with a statewide childhood cancer database for the study period. RESULTS: Cohort members contributed 1,172,696 person-years of follow-up for analysis, with children exposed (8.1%) and not exposed (91.9%) in utero to metronidazole contributing 79,716 and 1,092,980 person-years, respectively. Of 952 children younger than 5 years in the statewide cancer database, 175 met study eligibility criteria. Of these, 42 had leukemia, 30 had central nervous system (CNS) tumors, 28 had neuroblastoma, and 75 had other cancers. Using Poisson regression modeling, children exposed to metronidazole in utero had no significant increase in adjusted relative risk (RR) for all cancers (RR: 0.81; 95% confidence interval [95% CI], 0.41-1.59), leukemia (no exposed case), CNS tumors (RR: 1.23; 95% CI, 0.29-5.21), neuroblastomas (RR: 2.60; 95% CI, 0.89-7.59), and other cancers (RR: 0.57; 95% CI, 0.18-1.82). CONCLUSIONS: The authors conclude that although there was no increase in risk for all cancers associated with in utero exposure to metronidazole, the observed increased risk for neuroblastomas, although not significant, requires further evaluation.

Nonsteroidal anti-inflammatory drug use and increased risk for peptic ulcer disease in elderly persons.

OBJECTIVE: To evaluate the relative risk for peptic ulcer disease that is associated with the use of nonaspirin nonsteroidal anti-inflammatory drugs. DESIGN: Nested case-control study. SETTING: Tennessee Medicaid program. PARTICIPANTS: Medicaid enrollees 65 years of age or older were included in the study. The 1415 case patients had been hospitalized for confirmed peptic ulcer disease at some point from 1984 through 1986. The 7063 control persons represented a stratified random sample of other Medicaid enrollees. MEASUREMENTS AND MAIN RESULTS: The estimated relative risk for the development of peptic ulcer disease among current users of nonaspirin nonsteroidal anti-inflammatory drugs, compared with that among nonusers, was 4.1 (95% CI, 3.5 to 4.7). For current users, the risk increased with increasing dose, from a relative risk of 2.8 (CI, 1.8 to 4.3) for the lowest to a relative risk of 8.0 (CI, 4.4 to 14.8) for the highest dose category. The risk was greatest in the first month of use (relative risk, 7.2; CI, 4.9 to 10.5). If the association is fully causal, 29% of peptic ulcers in the study sample resulted from the use of these drugs, and the excess risk associated with such use was 17.4 hospitalizations for ulcer disease per 1000 person-years of exposure. CONCLUSIONS: These data support other findings indicating that a clinically significant risk for serious ulcer disease is associated with the use of nonaspirin nonsteroidal anti-inflammatory drugs. The data show that this risk increases with dose and recency of use and that use of these drugs may be responsible for a large proportion of peptic ulcer disease among elderly persons.

Genetic predisposition to bladder cancer: ability to hydroxylate debrisoquine and mephenytoin as risk factors.

The hypothesis that the frequency distribution of indices of oxidative drug-metabolizing activity is different between patients with bladder cancer (n = 98) and age, sex-matched control subjects (n = 110) has been investigated. Urinary recovery ratios of debrisoquine and R/S ratios of mephenytoin have been measured in an 8-h urine sample after simultaneous administration of debrisoquine (10 mg) and racemic mephenytoin (100 mg). In addition, alcohol consumption, smoking habit, and acetylation phenotype (using 100 mg dapsone as a substrate) have been measured. Patients with bladder cancer were classified on histological criteria as having aggressive (Stage III) (34%) or nonaggressive (Stages I and II) (66%) disease. The median of the frequency distribution of the debrisoquine urinary recovery ratio in patients with aggressive bladder cancer was greater than in control subjects, and only four patients had recovery ratios lower than the mean of the control group. Using logistic regression analysis, efficient debrisoquine metabolism and a synergistic interaction between smoking and ethanol consumption were significant, independent risk factors, while S-mephenytoin hydroxylation and acetylation phenotype were not significant risk factors. In contrast, patients with non-aggressive bladder cancer had a significant, but weaker, association with rapid hydroxylation of S-mephenytoin, which was independent of a significant synergistic interaction between smoking and alcohol consumption. Acetylation phenotype and debrisoquine urinary recovery ratio were not associated with increased risk of nonaggressive cancer. These results are consistent with the concept that oxidative isozymes might be responsible for conversion of environmental agents to proximate bladder carcinogens in nonindustrial-related bladder cancer. They also suggest that different etiological factors are involved in the pathogenesis of aggressive and nonaggressive bladder cancer.

Amphotericin-B nephrotoxicity in humans decreased by sodium supplements with coadministration of ticarcillin or intravenous saline.

Previous observations suggest that salt loading can help reverse amphotericin-B induced nephrotoxicity. Evidence is presented indicating that sodium supplements provide prophylaxis against the development of amphotericin-B nephrotoxicity. In a retrospective study at Vanderbilt University, 14/21 patients receiving amphotericin B (target dose, 25 mg/day) without salt supplements developed impaired renal function; in 10 instances amphotericin B was temporarily withdrawn. In contrast, only 2/17 patients who received amphotericin B with ticarcillin (with its obligatory sodium supplement) developed nephrotoxicity (P less than 0.01). All four patients, who were receiving the combination of amphotericin B and ticarcillin and who had their ticarcillin therapy stopped, developed nephrotoxicity in the subsequent week. In a prospective observational study at Essen, 20 patients had 24 courses of amphotericin B (target dose, 40 mg/day) with routine supplementation of 1 liter of 0.9% sodium chloride daily. Only two patients showed evidence of nephrotoxicity and no dosage modification of amphotericin B was required in any patient. Four patients with initial evidence of mildly impaired renal function received full supplements without adverse effects or the development of nephrotoxicity. These observations suggest that routine parenteral administration of sodium supplements can help minimize the nephrotoxic potential of amphotericin B.

High-dose cytosine arabinoside and daunorubicin as consolidation therapy for acute nonlymphocytic leukemia in first remission: an update.

High-dose (HD) cytosine arabinoside (ara-C) is more effective treatment than conventional-dose ara-C regimens for patients with relapsed acute nonlymphocytic leukemia (ANLL). Previously, we have reported that HD-ara-C administered during the first remission of ANLL has resulted in long remission durations and a high proportion of patients with long-term disease-free survival. In this update, those patients have been observed further and additional patients have been treated, affirming the initial conclusions. Since August 1979, 55 adult patients with ANLL in first remission received one to three courses of HD-ara-C (3 g/m2 by one-hour infusion every 12 hours for 12 doses on days 1 to 6) alone or with daunorubicin (30 mg/m2 for two or three doses on days 7 to 9). Three patients died of sepsis or hemorrhage during consolidation and 19 patients have relapsed from 5 to 48 months after diagnosis. The remaining 33 patients remain in continued complete remission (CCR) from 5 to 75 months. Denoting all deaths in remission as relapse, the actuarial probability of CCR is 51% at 75 months with an apparent plateau in the survival curve. Of the first 22 patients is 27 months. Using univariate and multivariate analysis, age is the only statistically significant prognostic parameter with the actuarial CCR of ages less than 25, 25 to 44, and greater than 44 being 100%, 48%, and 23%, respectively. Due to its heightened antileukemic activity, HD-ara-C allows brief but effective consolidation of ANLL in first remission with long-term disease-free survival comparable with other approaches including bone-marrow transplantation.

Statistical analysis of multi-eye data in ophthalmic research.

An apparently common error in statistical analysis of ophthalmic data is to perform statistical tests that do not account for the correlation generally present between observations made for the right and left eyes of a subject. This error has as a consequence an overstatement of the precision of the study, resulting in incorrect P values which indicate a greater measure of statistical significance than the data warrant. As measures to reduce the occurrence of this serious error in statistical analyses, the authors recommend increased emphasis on educational programs for investigators, stimulation of nontechnical articles reviewing statistical methods, and a sharper focus upon statistical analysis in the peer review process.

Statistical analysis for experimental models of ocular disease: continuous response measures.

Experimental designs in ophthalmologic research frequently treat both eyes of a subject in the same fashion: e.g., therapy with a specific drug or control. In these two-eye designs, observations from the same subject are often positively correlated. Failure to account for this correlation is a serious error which overstates the precision of studies, resulting in falsely significant results. This paper reviews the statistical methods appropriate for studies where endpoints are quantitative. We present: (1) the use of analysis of variance (t-test when there are 2 treatment conditions) to estimate differences between all experimental treatments, (2) the use of contrasts to estimate differences between specific treatments, and (3) methods for analysis of data from multiple experiments. Because of the ubiquity of incorrect analysis of data from two-eye designs in the ophthalmologic research literature and the serious consequences of this error, we propose a limited statistical review of manuscripts to ascertain if the statistical analysis matched the experimental design.