Health care, treatment patterns and cost of services for patients infected with chronic hepatitis C virus in a large insured New England population.

The purpose of this study was to describe the cost of health care and the patterns of treatment of young patients (under 65 years of age) identified in health insurance claims as having received services for chronic hepatitis C virus (HCV) infection. We screened computerized claims from a US indemnity and managed care organization for out-patient and in-patient diagnoses related to HCV. Treatment patterns and costs of services were evaluated in the following sites of care: in-patient care, emergency room, hospital out-patient care, ambulatory office care and pharmaceuticals. There were 191 patients with chronic HCV-related claims in this study population (25 per 100 000), during 1995-97. Medical services and pharmaceutical costs in total (US$ 7.1 million) constituted a considerable cost in patients with chronic HCV-related claims during 1995-97. A subset of 98 patients were prescribed interferon-alpha with substantial variability in treatment regimens. Claims data provides a unique opportunity to estimate dollars paid for treatment patterns and health services in a 'real world' insured population and contributes to the understanding of health services for chronic HCV.

The risk of serious cardiac arrhythmias among cisapride users in the United Kingdom and Canada.

PURPOSE: Serious, although rare, ventricular arrhythmias and deaths have been reported in patients taking cisapride monohydrate. Without quantification of the risk involved, it is impossible to develop rational therapeutic guidelines. SUBJECTS AND METHODS: Arrhythmic events (sudden deaths and other events compatible with serious ventricular arrhythmias) were sought among 36,743 patients prescribed cisapride in the United Kingdom and Saskatchewan, Canada. Prescriptions and cases were identified from computerized medical claims data and physicians' office records. We compared rates of events between periods of recent cisapride use and nonrecent use, using cohort analysis. Potential confounding factors, including concomitant treatment with agents that inhibit CYP3A4 metabolism or that prolong the QT interval, were assessed in a nested case-control study. RESULTS: In the cohort analysis, the incidence of the arrhythmic events was 1.6 times greater (95% confidence interval [CI]: 0.9 to 2.9) in periods of recent use. With adjustment for clinical history, use of CYP3A4 inhibitors, and use of drugs that prolong the QT interval, the odds ratio for cisapride and cardiac outcomes was 1.0 (95% CI: 0.3 to 3.7). There was no identifiable increase in risk when cisapride was dispensed at about the same time as QT-prolonging drugs or CYP3A4 inhibitors. QT-prolonging agents were associated with a 2.5-fold increase in the risk of arrhythmic events (95% CI: 1.1 to 5.8). CONCLUSIONS: Serious rhythm disorders were not associated with cisapride use, although the upper confidence bounds do not rule out an increase in risk.

Risk of emergency care, hospitalization, and ICU stays for acute asthma among recipients of salmeterol.

We used automated health insurance claims records of a New England insurer to assess the relation between salmeterol and severe nonfatal asthma. We identified 61,712 members who received a beta-agonist from January 1, 1993 to August 31, 1995, including 2, 708 recipients of salmeterol. Compared with recipients of other beta-agonists, future salmeterol recipients had higher rates of asthma hospitalization and dispensings of asthma medications during the year before they received salmeterol. We selected as a comparison group 3,825 recipients of sustained-release theophylline. We defined a baseline period as the year before the start of the follow-up period, and we characterized patients according to age, sex, calendar period, presence of baseline hospitalizations for asthma, presence of chronic obstructive pulmonary disease (COPD), and baseline dispensings of asthma medications. After adjusting for baseline factors, incidence rates of severe asthma in the salmeterol group were not elevated for emergency care (rate ratio estimate [RR] = 0.69, 95% confidence intervals [CI] = 0.42, 1.11), hospitalization (RR = 1.09, 95% CI = 0.60, 1.98), or intensive care unit (ICU) stays (RR = 0.81, 95% CI = 0.25, 2.62). We conclude that salmeterol was prescribed preferentially to high-risk patients and, after adjusting for baseline risk, salmeterol recipients did not have a greater risk than theophylline recipients of severe nonfatal asthma.

Mortality in current and former users of clozapine.

Clozapine (Clozaril), a tricyclic dibenzodiazepine, causes fewer extrapyramidal side effects than do other antipsychotic drugs. Because it can induce agranulocytosis, however, clozapine is indicated only for schizophrenia that is not responsive to other therapies. To describe the drug's effects on mortality, we compared rates of various causes of death in 67,072 current and former clozapine users. We linked data from a national registry of clozapine recipients to the National Death Index and Social Security Administration Death Master Files, obtained death certificates, and calculated mortality rates for underlying causes of death using standardization to adjust for age, sex, and race. During 1991-1993, there were 396 deaths in 85,399 person-years for patients ages 10-54 years. Mortality was lower during current clozapine use than during periods of non-use. Mortality from suicide was decreased in current clozapine users by comparison with past users [rate ratio (RR) = 0.17; 95% confidence interval (CI) = 0.10-0.30]. During clozapine use, there were elevations in mortality rates for less common causes of death, including pulmonary embolism (RR for current exposure compared with past clozapine use = 5.2) and respiratory disorders (RR = 2.9). Clozapine appears to reduce mortality in severe schizophrenics, mostly by decreasing suicide rates.

Resource utilization and cost of care for rheumatoid arthritis and osteoarthritis in a managed care setting: the importance of drug and surgery costs.

OBJECTIVE: To describe the frequency and costs of medical services for patients with osteoarthritis (OA) or rheumatoid arthritis (RA) in a managed care setting. METHODS: Individual utilization records of medical and pharmacy services for OA and RA patients were obtained from a group-model health maintenance organization (HMO). Estimates were made for costs of drugs and medical services for arthritis from July 1, 1993 to June 30, 1994 using Medicare reimbursement schedules and average wholesale drug prices. Calculated rates for each population were expressed as counts of events or as dollars per person-year. RESULTS: The average individual cost rate of arthritis-related care for 365 RA patients was $2,162 per year, and the total cost of RA care to the HMO was $703,053. Prescription medications accounted for 62% ($436,440) of the total cost of RA care, while ambulatory care accounted for 21% ($150,938), and hospital visits accounted for 16% ($115,674). With regard to 10,101 OA patients, the average individual cost rate was $543 per year, and total cost to the HMO was $4,728,425. Hospital care accounted for 46% ($2,170,890) of the total cost of OA care, medications accounted for 32% ($1,509,637), and ambulatory care accounted for 22% ($1,047,898). CONCLUSION: RA care, in the setting of this study, was characterized by intensive treatment, especially frequent use of medications that were delivered to most patients. Although the cost of RA care per patient was high, cost to the managed care provider was relatively low, owing to the rarity of RA. OA care tended to be infrequent, and the largest component of cost was hospital care for a small proportion of patients (5%). Owing to the greater prevalence of OA, care of OA was nearly 7 times more costly to the managed care provider than was care of RA.

Stress-induced subsensitivity to catecholamines depends on the estrous cycle.

In this article we compare how sensitivity to the chronotropic effect of noradrenaline and adrenaline of right atria isolated from female rats is modified after repeated swimming or foot-shock stress, under the influence of the estrous cycle. Right atria from stressed female rats sacrificed at diestrus were subsensitive to both catecholamines, irrespective of the stressor agent. However, although subsensitivity to noradrenaline was of similar intensity, subsensitivity to adrenaline was more pronounced in right atria from foot shock stressed rats as opposed to swimming-stressed rats. Identical stress protocols did not induce any alteration in atrial sensitivity to catecholamines when the stressed female rats were sacrificed at estrus. We conclude that the stress reaction concerning the mediation of cardiac chronotropism by catecholamines is related to the severity of the stressor agent and is strongly influenced by the estrous cycle.

Influence of the estrous cycle on the sensitivity to catecholamines in right atria from rats submitted to foot-shock stress.

We investigated the mechanisms of the alterations in sensitivity to catecholamines in right atria from female rats exhibiting regular 4-day estrous cycles after three foot-shock sessions at estrus, metestrus, and diestrus or at diestrus, proestrus, and estrus. Right atria from stressed rats sacrificed at diestrus showed subsensitivity to noradrenaline and adrenaline. After in vitro sympathetic denervation (38 microM 6-hydroxydopamine) plus inhibition of neuronal reuptake (0.1 microM desipramine) subsensitivity to noradrenaline was abolished, but it was again evident when extraneuronal uptake was also inhibited (10 microM phenoxybenzamine and 30 microM corticosterone). The same pretreatment abolished the subsensitivity to adrenaline. After addition of 1 microM butoxamine, a beta 2-adrenoceptor antagonist, the tissues from stressed rats were subsensitive to adrenaline. Right atria from stressed rats sacrificed at estrus did not show any alteration in sensitivity to catecholamines. We conclude that after foot-shock stress, right atria from female rats sacrificed at diestrus showed subsensitivity of the chronotropic response to catecholamines as a result of a conformational alteration of beta 1-adrenoceptors, simultaneously with an increase in beta 2-adrenoceptor-mediated response. The mechanisms seem to be similar to those which underlie stress-induced alterations in catecholamine sensitivity in right atria from male rats. However, during estrus there are some protective factors that prevent the effects of stress on right atria.

Peptic ulcer and gastrointestinal hemorrhage associated with nonsteroidal anti-inflammatory drug use in patients younger than 65 years. A large health maintenance organization cohort study.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with an elevated risk of peptic ulcer and upper gastrointestinal hemorrhage, but published reports have lacked information on rates of outpatient disease, have concentrated on the elderly, and have not provided comparisons of rates for specific types of NSAIDs. METHODS: We compared incidence rates of peptic ulcer and upper gastrointestinal hemorrhage in 68 028 people younger than 65 years who used diclofenac sodium, naproxen, piroxicam, or sulindac, and who were members of a network of health maintenance organizations. We reviewed automated insurance claims data and medical records to ascertain cases and included conditions treated on an outpatient basis. RESULTS: Medical claims data were adequate for crude identification of potential cases, but review of medical records led to rejection of 63% of these, representing either no abnormality or diseases other than peptic ulcer or upper gastrointestinal hemorrhage. Of the total 112 cases, 64 (57%) were treated as outpatients. The crude incidence rate per 1000 person-years in users of any current, recent, or past NSAID was 2.2 and in distant-past users of NSAIDs was 0.75. For diclofenac, naproxen, piroxicam, and sulindac, we found a consistent pattern of decreasing NSAID effects from current to recent to past exposure. The risk of peptic ulcer or upper gastrointestinal hemorrhage was 1.6 cases per 1000 people using NSAIDs. CONCLUSIONS: Combining use of automated claims records with review of medical records promotes efficiency while maintaining specificity of case ascertainment. This study, with 57% of cases treated as outpatients, had results consistent with other published reports that were based on hospitalized patients. Within the limits of statistical error, the incidence rates of peptic ulcer and upper gastrointestinal hemorrhage appeared to be similar for the various NSAIDs studied.

Toxic shock syndrome, contraceptive methods, and vaginitis.

To elucidate further the etiology of toxic shock syndrome, we assessed the effects of certain contraceptive methods and recent history of vaginal infection on the incidence of toxic shock syndrome, with confounding effects of other risk factors controlled. We found a strong but imprecise positive association between toxic shock syndrome and tubal ligation (rate ratio = 7.9, 90% confidence interval 1.4 to 42.7). We also observed a negative association with oral contraceptives (rate ratio = 0.49, 90% confidence interval 0.22 to 1.1) and a positive association with a recent history of vaginitis (rate ratio = 2.1, 90% confidence interval 1.2 to 3.9).

Breast cancer in mothers given diethylstilbestrol in pregnancy.

We compared the incidence of breast cancer in 3033 women who had taken diethylstilbestrol (DES) in pregnancy during the period from 1940 to 1960 with the incidence in a comparable group of unexposed parous women. We ascertained vital status in 95 per cent of the exposed women and in 93 per cent of the unexposed women and received completed questionnaires for 88 and 85 per cent, respectively. With over 85,000 woman-years of follow-up in each group, the incidence of breast cancer per 100,000 woman-years was 134 in the exposed group and 93 in the unexposed group, yielding a crude relative risk of 1.4 (95 per cent confidence interval, 1.1 to 1.9). The elevated incidence did not appear to be due to bias or to confounding by other risk factors measured in the study. Breast-cancer mortality was slightly higher in the exposed women (relative risk, 1.1) but not significantly so (95 per cent confidence interval, 0.7 to 2.0). We conclude that the incidence of breast cancer is moderately increased in women given DES, but we cannot exclude the possibility that some unrecognized concomitant of DES exposure accounts for this increase.

PIP: The authors compared the incidence of breast cancer in 3033 women who had taken diethylstilbestrol (DES) in pregnancy during the period 1940-60 with the incidence in a comparable group of unexposed parous women. The vital status was ascertained in 95% of the exposed women and in 93% of the unexposed women and completed questionnaires were received for 88 and 85% respectively. With over 85,000 women-years of follow-up in each group, the incidence of breast cancer/100,000 woman-years was 134 in the exposed group and 93 in the unexposed group, yielding a crude relative risk of 1.4 (95% confidence interval, 1.1-1.9). The elevated incidence did not appear to be due to bias or to confounding by other risk factors measured in the study. Breast cancer mortality was slightly higher in the exposed women (relative risk, 1.1) but not significantly so (95% confidence interval, 0.7-2.0). The incidence of breast cancer is moderately increased in women given DES, but the possibility cannot be excluded that some unrecognized concomitant of DES exposure accounts for this increase.