A systematic review of the associations between dose regimens and medication compliance.

BACKGROUND: Previous reviews of the literature on medication compliance have confirmed the inverse relationship between number of daily doses and rate of compliance. However, compliance in most of these studies was based on patient self-report, blood-level monitoring, prescription refills, or pill count data, none of which are as accurate as electronic monitoring (EM). OBJECTIVE: In this paper, we review studies in which compliance was measured with an EM device to determine the associations between dose frequency and medication compliance. METHODS: Articles included in this review were identified through literature searches of MEDLINE, PsychInfo, HealthStar, Health & Psychosocial Instruments, and the Cochrane Library using the search terms patient compliance, patient adherence, electronic monitoring, and MEMS (medication event monitoring systems). The review was limited to studies reporting compliance measured by EM devices, the most accurate compliance assessment method to date. Because EM was introduced only in 1986, the literature search was restricted to the years 1986 to 2000. In the identified studies, data were pooled to calculate mean compliance with once-daily, twice-daily, 3-times-daily, and 4-times-daily dosing regimens. Because of heterogeneity in definitions of compliance, 2 major categories of compliance rates were defined: dose-taking (taking the prescribed number of pills each day) and dose-timing (taking pills within the prescribed time frame). RESULTS: A total of 76 studies were identified. Mean dose-taking compliance was 71% +/- 17% (range, 34%-97%) and declined as the number of daily doses increased: 1 dose = 79% +/- 14%, 2 doses = 69% +/- 15%, 3 doses = 65% +/- 16%, 4 doses = 51% +/- 20% (P < 0.001 among dose schedules). Compliance was significantly higher for once-daily versus 3-times-daily (P = 0.008), once-daily versus 4-times-daily (P < 0.001), and twice-daily versus 4-times-daily regimens (P = 0.001); however, there were no significant differences in compliance between once-daily and twice-daily regimens or between twice-daily and 3-times-daily regimens. In the subset of 14 studies that reported dose-timing results, mean dose-timing compliance was 59% +/- 24%; more frequent dosing was associated with lower compliance rates. CONCLUSIONS: A review of studies that measured compliance using EM confirmed that the prescribed number of doses per day is inversely related to compliance. Simpler, less frequent dosing regimens resulted in better compliance across a variety of therapeutic classes.

Selective serotonin reuptake inhibitor treatment in the UK: risk of relapse or recurrence of depression.

BACKGROUND: Patients with depression are often not prescribed antidepressants for an adequate period of time. AIMS: The impact of antidepressant prescribing patterns on the risk of relapse or recurrence of depression is examined. METHOD: The MediPlus UK Primary Care Database was used to identify patients treated for depression with a selective serotonin reuptake inhibitor (SSRI). Records were used to construct hierarchical prescription patterns (less than 120 days, switching/augmentation, upward titration, or stable use) as indicators for the occurrence of relapse or recurrence of depression. RESULTS: Patients with stable use experienced the lowest risk of relapse or recurrence. Factors significantly associated with increased risk include prior use of anxiolytic medications, more comorbid conditions and younger age. CONCLUSIONS: The SSRI prescription pattern most consistent with recommended depression treatment guidelines was associated with the lowest risk of relapse or recurrence.

Absenteeism among employees treated for depression.

Depression-related costs include a relatively large share of indirect costs. We describe the impact of antidepressant treatment on absenteeism among workers diagnosed and treated for depression. Monthly absenteeism counts from employers were summed in the 6 months before and after the initiation of antidepressant therapy in 630 workers treated for depression with a tricyclic antidepressant or a selective serotonin reuptake inhibitor (fluoxetine, sertraline, paroxetine). Monthly mean absenteeism was compared using pairwise t tests. Absenteeism increased before antidepressant initiation and decreased after the treatment began for all antidepressant cohorts. Absenteeism in the selective serotonin reuptake inhibitor cohorts decreased at similar rates for 4 months but was higher in the paroxetine cohort in months five and six after the treatment initiation. Our data suggest that alternative treatments for depression may have differential impact on indirect costs, but further research is warranted.

Cohort study of serum total cholesterol and in-hospital incidence of infectious diseases.

A multiethnic cohort of adult members of the Kaiser Permanente Medical Care Program (55300 men and 65271 women) was followed for 15 years (1979-93) to assess the association between total cholesterol and risk of infections (other than respiratory and HIV) diagnosed in the in-patient setting. Using multivariate Cox regression, total cholesterol was inversely and significantly related to urinary tract, venereal, musculo-skeletal, and all infections among men; and to urinary tract, all genito-urinary, septicaemia or bacteraemia, miscellaneous viral site unspecified, and all infections among women. The reduction of risk of all infections associated with a 1 S.D. increase in total cholesterol was 8% in both men (95% CI, 4-12 %) and women (95% CI, 5-11%). For urinary tract infections among men, as for septicaemia or bacteraemia and nervous system infections among women, the risk relation was restricted to persons aged 55-89 years. Nervous system infections were positively related to total cholesterol among women aged 25-54. In both genders, the significant inverse association with all infections persisted after excluding the first 5 years of follow-up. Collectively, these data are suggestive of an inverse association, although not entirely consistent, between total cholesterol and incidence of infections either requiring hospitalization or acquired in the hospital. Further research is needed to elucidate whether these associations are biologically plausible or represent uncontrolled confounding by unmeasured risk factors.

Association between serum total cholesterol and HIV infection in a high-risk cohort of young men.

Low serum total cholesterol (TC) is associated with a variety of nonatherosclerotic diseases, but the association of TC with infectious disease has been little studied. In this study, we examined the relationship between serum TC and HIV infection in members of a large health maintenance organization in Northern California. The cohort consisted of 2446 unmarried young men 15 to 49 years of age at high risk of HIV infection, defined as self-reported history of sexually transmitted disease or liver disease. Baseline measurements were taken between 1979 and 1985, and subjects were passively followed for HIV infection until the end of 1993 (average length of follow-up, 7.7 years). From a multivariate-adjusted Cox regression, the rate ratio (RR) of HIV infection was 1.66 (95% CI = 1.07, 2.56) for men with serum TC levels <160 mg/dl compared with those with TC levels between 160 and 199 mg/dl. Similar excess risk of AIDS and AIDS-related death was observed. These findings suggest that low serum TC levels should be considered a marker of increased risk of HIV infection in men already at heightened risk of HIV infection.

Perceived and measured availability of tobacco to youths in 14 Minnesota communities: the TPOP Study. Tobacco Policy Options for Prevention.

INTRODUCTION: Availability of tobacco to young people is believed to be an important factor in the onset of tobacco use. We still do not have a complete picture of how tobacco is obtained by youths or how access can be curtailed. DESIGN: This article describes tobacco availability to youths in 14 communities that are part of a randomized trial, known as TPOP (Tobacco Policy Options for Prevention). The data reported here were obtained from student surveys and tobacco-purchase attempts by underage confederates. RESULTS: Students who have smoked at least once were likely to cite social sources for cigarettes. However, more than half of weekly smokers and almost one third of tenth-grade ever smokers reported purchasing cigarettes in the last 30 days. Tobacco-purchase attempts by confederate buyers at all outlets resulted in an overall success rate of 40.8%, lower than previously reported for urban communities. Fifty-five percent of the over-the-counter outlets had no self-service displays of tobacco at baseline. Store factors that predicted purchase success include tobacco location; purchase success was lower when all tobacco was locked or behind a service counter. The percentage of smokers who reported purchasing their own tobacco soon after starting to smoke was highest in towns where purchase success by teenage study confederates was highest. CONCLUSIONS: These results suggest that sources of cigarettes shift from social to commercial with age and that sources of cigarettes for rural youths may be different than for urban youths.

The role of social influences and tobacco availability on adolescent smokeless tobacco use.

OBJECTIVE: To examine the potential explanatory effect of various demographic, social influence, sanction, and tobacco availability variables on the use of smokeless tobacco (ST) by adolescent males. DESIGN: The data used in our analyses are from a community-based tobacco policy intervention trial that included a 60-item baseline school survey. During Spring 1993, all 8th, 9th, and 10th-grade students enrolled in 14 school districts in small Minnesota cities were surveyed. We used mixed-model logistic regression to determine which variables were significantly correlated with smokeless tobacco use by males in the past week. RESULTS: Of this sample of 2924 adolescent males, 10% (n = 291) reported using smokeless tobacco in the past week. Compared to the overall sample, smokeless tobacco users reported higher family and friend use of smokeless tobacco. In addition, 64% of users reported smoking in the past 30 days, and almost half (49.1%) said they had attempted to purchase tobacco in the past 30 days. Variables found to be significantly associated with smokeless tobacco use in the past week included younger age, having a best friend using tobacco, inflated perceptions of their peers' use of tobacco products, beliefs that school and parental sanctions are not high for tobacco use, recent tobacco purchase, and perceived belief that tobacco is not difficult to obtain from social sources. CONCLUSIONS: This study confirms previous research correlating demographic and social influence factors with ST use and demonstrates the role that sanction and availability variables play in ST use.

Adolescent smokers' provision of tobacco to other adolescents.

OBJECTIVES: This study examined adolescent smokers provision of tobacco to other adolescents. METHODS: Data from a survey of 8th-, 9th-, and 10th-grade students in Minnesota were analyzed by using mixed-model logistic regression. RESULTS: More than two thirds (68.8%) of adolescent smokers had provided tobacco to another adolescent in the previous 30 days. Mother's smoking, number of friends who smoke, owning tobacco merchandise, number of cigarettes smoked in the past week, source of last cigarette (commercial), and recent attempt to buy cigarettes were associated with providing. CONCLUSIONS: The social availability of tobacco to youth needs further examination.

Serum total cholesterol and risk of hospitalization, and death from respiratory disease.

BACKGROUND: In earlier studies, serum total cholesterol was inversely associated with death due to respiratory diseases. METHODS: Relationships of cholesterol with risk of respiratory diseases were examined between 1978 and 1993 in a health maintenance organization in Northern California (48,188 men, 55,276 women, about 60% white, age range 25-89). Incident and fatal endpoints were ascertained using hospital discharge diagnostic codes and underlying cause of death, respectively. RESULTS: An inverse association of cholesterol level with pneumonia/influenza hospitalization was found among men and women except that, contrary to hypothesis, a positive association was seen in women under 55 years of age. Inconsistent inverse associations were found in men, but not women, between cholesterol level and hospitalization for chronic obstructive pulmonary disease (COPD). Hospitalization for asthma was unrelated to cholesterol level. An inverse association existed between cholesterol level and hospitalization for miscellaneous respiratory diseases among men, but not women. Exclusion of early hospitalizations tended to attenuate risk for cholesterol level below 4.14 mmol/l, but not the risk gradient across higher cholesterol levels. For deaths, cholesterol level was statistically significantly inversely associated only with COPD. CONCLUSIONS: Cholesterol had graded inverse associations with some respiratory diseases, but not others, tending to be stronger in men than in women, and in older than in younger participants. Associations varied for hospitalizations compared to deaths. More epidemiological and basic research is needed to elucidate the potential mechanisms underlying the observed associations.

Low total serum cholesterol and intracerebral hemorrhagic stroke: is the association confined to elderly men? The Kaiser Permanente Medical Care Program.

BACKGROUND AND PURPOSE: Epidemiological studies indicate a higher incidence of intracerebral (but not subarachnoid) hemorrhagic stroke among persons with low total serum cholesterol levels. This report further examines the prospective relationship of total serum cholesterol with subsequent intracerebral hemorrhage in a large, well-defined population. METHODS: The cohort included 61756 enrollees in a health plan from the San Francisco-Oakland metropolitan area (46% men, 63% white), aged 40 to 89 years and free of cardiovascular disease at baseline. Sixteen-year incidence of combined nonfatal and fatal intracerebral hemorrhagic stroke (International Classification of Diseases [ICD], 8th revision, code 431, or ICD, 9th revision, codes 431 and 432) was investigated in relation to serum cholesterol measured in multiphasic health checkups made in 1977 through 1985. Intracerebral hemorrhagic events were ascertained using hospital discharge records and as underlying cause of death by the California Mortality Linkage Information System. RESULTS: From 1978 through 1993 (average of 10.7 years), there were 386 events (201 in men, 29% fatal; 185 in women, 42% fatal). By multivariate proportional hazards life-table regression analysis, serum cholesterol level below the sex-specific 10th percentile (< 4.62 mmol/L [178 mg/dL] in men), compared with higher cholesterol level, was associated with a significantly increased risk of intracerebral hemorrhage in men aged 65 years or older (relative risk, 2.7; 95% confidence interval, 1.4 to 5.0). An excess risk was also observed among elderly women at the lowest cholesterol range, but a chance finding could not be ruled out. No relationship was seen among men or women aged 40 to 64, and no statistical interaction of low serum cholesterol with hypertension was found in either sex. CONCLUSIONS: In these data, the association between low serum cholesterol level and intracerebral hemorrhage was confined to elderly men.