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Title: Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease. A meta-analysis of patient-level data.
Publication: Annals of Internal Medicine 2001 Jul 17;135(2):73-87.
Authors: Jafar TH et al.
Grant Number: HS10064/HS08532.
Principal Investigator: Christopher Schmid.
Project Officer: Chiang.
Abstract: PURPOSE: To examine the efficacy of ACE inhibitors for treatment of nondiabetic renal disease. DATA SOURCES: 11 randomized, controlled trials comparing the efficacy of antihypertensive regimens including ACE inhibitors to the efficacy of regimens without ACE inhibitors in predominantly nondiabetic renal disease. STUDY SELECTION: Studies were identified by searching the MEDLINE database for English-language studies evaluating the effects of ACE inhibitors on renal disease in humans between May 1977 (when ACE inhibitors were approved for trials in humans) and September 1997. DATA EXTRACTION: Data on 1,860 nondiabetic patients were analyzed. DATA SYNTHESIS: Mean duration of followup was 2.2 years. Patients in the ACE inhibitor group had a greater mean decrease in systolic and diastolic blood pressure (4.5 mm Hg [95 percent CI, 3.0 to 6.1 mm Hg]) and 2.3 mm Hg [CI, 1.4 to 3.2 mm Hg], respectively) and urinary protein excretion (0.46 g/d [CI, 0.33 to 0.59 g/d]). After adjustment for patient and study characteristics at baseline and changes in systolic blood pressure and urinary protein excretion during followup, relative risks in the ACE inhibitor group were 0.69 (CI, 0.51 to 0.94) for end-stage renal disease and 0.70 (CI, 0.55 to 0.88) for the combined outcome of doubling of the baseline serum creatinine concentration or end-stage renal disease. Patients with greater urinary protein excretion at baseline benefited more from ACE inhibitor therapy (P = 0.03 and P = 0.001, respectively), but the data were inconclusive as to whether the benefit extended to patients with baseline urinary protein excretion less than 0.5 g/d. CONCLUSION: Antihypertensive regimens that include ACE inhibitors are more effective than regimens without ACE inhibitors in slowing the progression of nondiabetic renal disease. The beneficial effect of ACE inhibitors is mediated by factors in addition to decreasing blood pressure and urinary protein excretion and is greater in patients with proteinuria. Angiotensin-converting inhibitors are indicated for treatment of nondiabetic patients with chronic renal disease and proteinuria and, possibly, those without proteinuria.
Title: Proteinuria as a modifiable risk factor for the progression of non-diabetic renal disease.
Publication: Kidney International 2001;60:1131-40.
Authors: Jafar TH et al.
Grant Number: HS10064.
Principal Investigator: Christopher Schmid.
Project Officer: Yen-pin Chiang.
Abstract: BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors reduce urine protein excretion and slow the progression of renal disease. The beneficial effect in slowing the progression of renal disease is greater in patients with higher urine protein excretion at the onset of treatment. We hypothesized that the greater beneficial effect of ACE inhibitors on the progression of renal disease in patients with higher baseline levels of proteinuria is due to their greater antiproteinuric effect in these patients. METHODS: Data were analyzed from 1,860 patients enrolled in 11 randomized controlled trials comparing the effect of antihypertensive regimens, including ACE inhibitors to regimens not including ACE inhibitors on the progression of non-diabetic renal disease. Multivariable linear regression analysis was used to assess the relationship between the level of proteinuria at baseline and changes in urine protein excretion during followup. The Cox proportional hazards analysis was used to assess the relationship between changes in urine protein excretion during followup and the effect of ACE inhibitors on the time to doubling of baseline serum creatinine values or onset of end-stage renal disease. RESULTS: Mean (median) baseline urine protein excretion was 1.8 (0.94) g/day. Patients with higher baseline urine protein excretion values had a greater reduction in proteinuria during the followup in association with treatment with ACE inhibitors and in association with lowering systolic and diastolic blood pressures (interaction P < 0.001 for all). A higher level of urine protein excretion during followup (baseline minus change) was associated with a greater risk of progression [relative risk 5.56 (3.87 to 7.98) for each 1.0 g/day higher protein excretion]. After controlling for the current level of urine protein excretion, the beneficial effect of ACE inhibitors remained significant [relative risk for ACE inhibitors vs. control was 0.66 (0.52 to 0.83)], but there was no significant interaction between the beneficial effect of ACE inhibitors and the baseline level of urine protein excretion. CONCLUSIONS: The antiproteinuric effects of ACE inhibitors and lowering blood pressure are greater in patients with a higher baseline urine protein excretion. The greater beneficial effect of ACE inhibitors on renal disease progression in patients with higher baseline proteinuria can be explained by their greater antiproteinuric effects in these patients. The current level of urine protein excretion is a modifiable risk factor for the progression of non-diabetic renal disease. ACE inhibitors provide greater beneficial effect at all levels of current urine protein excretion.
Title: Cigarette smoking behavior among US Latino men and women from different countries of origin.
Publication: Am J Public Health 2001 Sep;91(9): 1424-30.
Authors: Perez-Stable EJ et al.
Grant Number: HS07373.
Principal Investigator: A. Eugene Washington.
Project Officer: Heddy Hubbard.
Abstract: OBJECTIVES: This study sought to compare smoking behavior among Latino men and women from different countries of origin. METHODS: A telephone-administered survey was conducted in 8 cities with Latino men and women of different national origin living in census tracts with at least 70 percent Latino individuals. RESULTS: A total of 8,882 participants completed the survey; 53 percent were women. The average age of respondents was 44 years; 63 percent were foreign-born, and 59 percent preferred Spanish for the interview. Current smoking was more prevalent among men (25.0 percent, 95 percent confidence interval [CI] = 23.7, 26.3) than among women (12.1 percent, 95 percent CI = 11.1, 13.0). Smoking rates were not significantly different by national origin among men, but Puerto Rican women had higher rates of smoking than other women. Central American men and women had the lowest smoking rates. Foreign-born respondents were less likely to be smokers (odds ratio [OR] = 0.77, 95 percent CI = 0.66, 0.90) than U.S.-born respondents, and respondents with 12 years or less of education had an increased odds of smoking (OR = 1.17, 95 percent CI = 1.01, 1.35). High ac culturation was associated with more smoking in women (OR = 1.12, 95 percent CI = 1.00-1.25) and less smoking in men (OR = 0.86, 95 percent CI = 0.78-0.95). Puerto Rican and Cuban respondents were more likely to be current smokers and to smoke more than 20 cigarettes per day. CONCLUSIONS: Older, U.S.-born, and more-educated respondents were less likely to be current smokers. Respondents of Puerto Rican and Cuban origin were more likely to smoke. Acculturation has divergent effects on smoking behavior by sex.
Title: Factor variability of the center for epidemiological studies depression scale (CES-D) among urban Latinos.
Publication: Ethnicity Health 2001 May;6(2):137-44.
Authors: Posner SF et al.
Grant Number: HS07373.
Principal Investigator: A. Eugene Washington.
Project Officer: Heddy Hubbard.
Abstract: Establishing comparable measurement properties across different populations or in different population subgroups is a crucial yet often neglected step in instrument development. Failure to have comparable factor structures across groups makes any comparison between groups suspect. Previous analyses of the measurement structure of the Center for Epidemiologic Studies Depression Scale (CES-D) in diverse racial/ethnic populations have resulted in conflicting results. In the present analysis, data from three studies of urban Latinos (N = 1,403) were analyzed using structural equation modeling techniques to (1) fit the original four-factor solution separately in men and women; (2) evaluate configural and metric invariance between men and women; and (3) evaluate the mediating effects of age and acculturation on the fit of this model to the data. Results indicated that the four-factor model proposed by Radloff provided adequate fit to the data for Latina women when age and acculturation were included in the model. The four-factor model did not fit the data for Latino men; thus tests of configural and metric invariance across these two groups failed. We conclude that the CES-D may not measure the same constructs in Latino men and women and that further evaluation of the use of this measure in diverse populations is needed. Additionally, prior to comparison with other groups in which the four-factor solution is observed, the effects of age and acculturation should be controlled in Latinas.
Title: Feasibility of a nurse-run asthma education program for urban African-Americans: a pilot study.
Publication: Journal of Asthma 2001 Feb;38(1):23-32.
Authors: Blixen CE et al.
Grant Number: HS07386.
Principal Investigator: A. Eugene Washington.
Project Officer: Heddy Hubbard.
Abstract: The objective of the study was to assess the feasibility of implementing and evaluating a culturally appropriate in-patient asthma education program specifically targeted for African-Americans. A consecutive sample of 28 African-American patients ages 18-50 who were hospitalized for asthma were randomized to an intervention group, which received three one-on-one sessions on chronic asthma management, or a control group, which received the usual care. Data on symptom frequency, self-management behaviors, quality of life, depression, and health care resource use were collected at baseline and at 3 and 6 months. Although the time required to recruit our sample took longer than anticipated, 28 subjects agreed to be in the study (70 percent acceptance rate) and complete the baseline interview. We observed no statistically significant differences from baseline or changing trends in
frequency of asthma symptoms, self-management behaviors, and health care resource use between the intervention and control groups at 3 and 6 months. However patients in the intervention group demonstrated a greater average increase in asthma-related quality of life and a greater average decrease in depression than the control group. Feasibility issues included shortened length of stay, which necessitated conducting all three self-management sessions together; multiple interruptions during the sessions, and retention issues at 3- and 6-month followups. The lessons learned from this pilot study are invaluable in that they will enable us to make changes in our existing protocol to ensure the success of a larger clinical trial.
Title: Preeclampsia associated with chronic hypertension among African-American and White women.
Publication: Ethnic Disease 2001 Spring-Summer;11(2):192-200.
Authors: Samadi AR et al.
Grant Number: HS07400.
Principal Investigator: Robert Mayberry.
Project Officer: Yen-pin Chiang.
Abstract: OBJECTIVE: To examine the racial differences in preeclampsia/eclampsia (preeclampsia) associated with chronic hypertension among African-American and White women. METHODS: Using hospital discharge summary records from the National Hospital Discharge Survey from 1988 to 1996, we conducted a case-control study to assess the risk of preeclampsia among women with chronic hypertension in two separate identical models: one for African-American and another for White women. Cases were pregnant women who developed preeclampsia. Controls were women without preeclampsia. The main exposure was chronic hypertension. Logistic regression was used to derive odds ratios (OR) and 95 percent confidence intervals (CI) and to assess interaction between hypertension and preeclampsia. Population attributable risk percent associated between chronic hypertension and preeclampsia was calculated for each ethnic group. RESULTS: Preeclampsia was more than eleven times likely among women with chronic hypertension compared to normotensive women for both African-American (OR = 12.4, 95 percent CI = 10.2-15.2) and White women (OR = 11.3, 95 percent CI = 9.7-13.2). Among African-American women, we found an interaction between chronic hypertension and region on preeclampsia. The effect of region magnified the risk of preeclampsia associated with chronic hypertension in general for African-American women, but the effect was lower for the Southern region (OR = 8.9, 95 percent CI = 6.4-12.3). We also found that the point estimate of population attributable risk percent of preeclampsia attributable to chronic hypertension was significantly higher for African-American women (10.3, 95 percent CI = 8.6-12.5) compared to White women (5.3, 95 percent CI = 4.7-6.4). CONCLUSION: The more than eleven-fold higher risk of preeclampsia among both African-American and White women with chronic hypertension compared to normotensive women underscores the potential risk of chronic hypertension for adverse pregnancy outcomes. Furthermore, the two-fold higher population attributable risk percent of preeclampsia among African-American compared to White women quantifies the burden of preeclampsia attributable to chronic hypertension, and indicates a greater opportunity for prevention.
Title: Decision analysis of prenatal testing for chromosomal disorders: what do the preferences of pregnant women tell us?
Publication: Genetic Testing 2001 Spring;5(1):23-32.
Authors: Harris RA et al.
Grant Number: HS07373.
Principal Investigator: A. Eugene Washington.
Project Officer: Heddy Hubbard.
Abstract: Current guidelines recommend offering invasive testing for chromosomal disorders only to women who are aged 35 or older, or who are at similarly elevated risk (as determined by maternal serum and/or ultrasonographic screening). We conducted a decision analysis, using preference scores obtained from pregnant women, to determine whether current guidelines maximize the health-related quality of life of these women. If only miscarriage and chromosomal abnormalities are considered, the expected value of testing exceeds that of not testing for women 30 years of age or older. However, if a comprehensive range of relevant testing outcomes is considered, testing offers a higher expected value than not testing, regardless of age. Furthermore, patient preferences for specific testing outcomes play a much more substantial role in determining the course of action with the highest expected value than does the probability of any of the possible testing outcomes. The current age- and risk-based guideline for prenatal diagnosis does not maximize expected value and fails to appropriately consider individual patient preferences. For counseling purposes, how an individual values the presence and timing of fetal chromosomal information should be carefully understood.
Title: Variations in prevalence of hypotension, hypertension, and vasopressor use in NICUs.
Publication: Journal of Perinatology 2001 Jul-Aug;21(5):272-8.
Authors: Al-Aweel I, Pursley DM, Rubin LP, Shah B, Weisberger S, Richardson DK.
Grant Number: HS07015.
Principal Investigator: Douglas Richardson.
Project Officer: Heddy Hubbard.
Abstract: OBJECTIVE: Very low birth weight infants are vulnerable to hypotension and its associated complications. Vasopressors are used to raise blood pressure (BP), but indications for use are uncertain. Our objectives were (1) to study variations in BP stability among NICUs, (2) to investigate inter-NICU differences in vasopressor use, and (3) to address the association between intraventricular hemorrhage (IVH) and abnormal BPs. STUDY DESIGN: A total of 1288 infants with birth weight <1500 g were admitted to six NICUs in Massachusetts and Rhode Island over 21 months. The lowest and highest mean BPs were collected within the first 12 hours. Also recorded were the use of vasopressors within the first 24 hours and the occurrence of IVH. Logistic
regressions were used to model outcomes, controlling for gestational age and illness severity using the Score for Neonatal Acute Physiology. RESULTS: Two of the six NICUs had significantly higher percentages of infants with at least one hypotensive BP, with prevalences of 24percent to 45percent. Percentages of infants treated with vasopressors ranged from 4percent to 39percent. This range of vasopressor use could not be explained by inter-NICU differences in birth weight, illness severity, or rates of hypotension. We found a borderline association between severe IVH and hypotension (odds ratio 1.6, p=0.055), but not between severe IVH and hypertension. CONCLUSION: Wide differences exist in the prevalence of hypotension, hypertension, and vasopressor use among NICUs. We also found an association between hypotension and IVH, but not between hypertension and IVH.
Title: Urine testing and urinary tract infections in febrile infants seen in office settings: the Pediatric Research in Office Settings' Febrile Infant Study.
Publication: Arch Pediatr Adolesc Med 2002 Jan;156(1):44-54.
Authors: Newman TB et al.
Grant Number: HS06485.
Principal Investigator: RPantell.
Project Officer: Steven Fox.
Abstract: OBJECTIVE: To determine the predictors and results of urine testing of young febrile infants seen in office settings. DESIGN: Prospective cohort study. SETTING: Offices of 573 pediatric practitioners from 219 practices in the American Academy of Pediatrics Pediatric Research in Office Settings' research network. SUBJECTS: A total of 3066 infants 3 months or
younger with temperatures of 38 degrees C or higher were evaluated and treated according to the judgment of their practitioners. MAIN OUTCOME MEASURES: Urine testing results, early and late urinary tract infections (UTIs), and UTIs with bacteremia. RESULTS: Fifty-four percent of the infants initially had urine tested, of whom 10percent had a UTI. The height of the fever was associated
with urine testing and a UTI among those tested (adjusted odds ratio per degree Celsius, 2.2 for both). Younger age, ill appearance, and lack of a fever source were associated with urine testing but not with a UTI, whereas lack of circumcision (adjusted odds ratio, 11.6), female sex (adjusted odds ratio, 5.4), and longer duration of fever (adjusted odds ratio, 1.8 for fever lasting > or = 24 hours) were not associated with urine testing but were associated with a UTI. Bacteremia accompanied the UTI in 10percent of the patients, including 17percent of those younger than 1 month. Among 807 infants not initially tested or treated with antibiotics, only 2 had a subsequent
documented UTI; both did well. CONCLUSIONS: Practitioners order urine tests selectively, focusing on younger and more ill-appearing infants and on those without an apparent fever source. Such selective urine testing, with close followup, was associated with few late UTIs in this large study. Urine testing should focus particularly on uncircumcised boys, girls, the youngest and sickest infants, and those with persistent fever.
Title: SNAP-II and SNAPPE-II: Simplified newborn illness severity and mortality risk scores.
Publication: Journal of Pediatrics 2001 Jan;138(1):92-100.
Authors: Richardson DK et al.
Grant Number: HS07015.
Principal Investigator: Douglas Richardson.
Project Officer: Heddy Hubbard.
Abstract: OBJECTIVES: Illness severity scores for newborns are complex and restricted by birth weight and have dated validations and calibrations. We developed and validated simplified neonatal illness severity and mortality risk scores. The primary outcome was in-hospital mortality.STUDY DESIGN: Thirty neonatal intensive care units in Canada, California, and New England collected data on all admissions during the mid 1990s; patients moribund at birth or discharged to normal newborn care in <24 hours were excluded. Starting with the 34 data elements of the Score for Neonatal Acute Physiology (SNAP), we derived the most parsimonious logistic model for in-hospital mortality using 10,819 randomly selected Canadian cases. SNAP-II includes 6 physiologic items; to this are added points for birth weight, low Apgar score, and small for gestational age to create a 9-item SNAP-Perinatal Extension-II (SNAPPE-II).
We validated SNAPPE-II on the remaining 14,610 cases and optimized the calibration. RESULTS: In all birth weights, SNAPPE-II had excellent discrimination and goodness of fit. Area under the receiver operator characteristic curve was .91 +/- 0.01. Goodness of fit (Hosmer-Lemeshow) was 0.90.CONCLUSIONS: SNAP-II and SNAPPE-II are empirically validated illness severity and mortality risk scores for newborn intensive care. They are simple, accurate, and robust across populations.
Title: Relationship of race and severity of neonatal illness.
Publication: American Journal of Obstetrics Gynecology 2001 Mar;184(4):668-72.
Authors: Berman S et al.
Grant Number: HS07015.
Principal Investigator: Douglas Richardson.
Project Officer: Heedy Hubbard.
Abstract: OBJECTIVE: Our goal was to determine whether there are racial differences in the severity of illness on admission for premature newborn infants independent of gestational age. STUDY DESIGN: The study population consisted of all African American and Caucasian singleton infants with gestational ages <34 weeks who were admitted to the neonatal intensive care unit at Brigham and Women's Hospital between December 1994 and November 1995. Illness severity was measured with a neonatal severity of illness score, the SNAP score (Score for Neonatal Acute Physiology). The SNAP score is a physiologic scoring system that ranks the worst physiologic derangements in each organ system in the first 12 hours of life. It is an objective measure of neonatal illness severity with scores ranging from 0 (healthy) to 42 (most severely ill). Student t tests, chi(2) analysis, and Fisher exact tests were used to assess statistical significance. Linear and logistic regression analyses were used to examine associations while confounding factors were controlled for. RESULTS: There were 129 (79 percent) Caucasian and 36 (22 percent) African American newborns included in the analysis. Caucasian newborns had significantly higher mean SNAP scores than African American newborns (8.8 vs. 6.3; P <.05). Compared with African American newborns, Caucasian newborns were more than twice as likely to have a SNAP score >10 (33 percent vs. 14 percent; P <.05). In a linear regression analysis in which we controlled for gestational age, birth weight, preterm premature rupture of membranes, preterm labor, preeclampsia, intrapartum fever > or =100.4 degrees F, route of delivery, and other maternal and fetal factors, African American newborns were predicted to have a SNAP score that was on average 3.0 points lower than that of Caucasian newborns (P =.005). In a logistic regression in which we controlled for the above-mentioned confounders, African American newborns were only 14 percent as likely to have a SNAP score >10 when compared with Caucasian newborns (odds ratio, 0.14; 95 percent confidence interval, 0.04-0.51). CONCLUSIONS: Over a broad range of prematurity, Caucasian newborns were more ill than African American newborns on admission to the neonatal intensive care unit.
Title: Does the concordance concept serve patient medication management?
Publication: International Journal of Pharmacy Practice June 2001;9:71-9.
Authors: Chewning B et al. (PCOPR Investigative Research Team).
Grant Number: HS07773.
Principal Investigator: Betty Chewning.
Project Officer: Charlotte Mullican.
Abstract: Objectives: To assess how people with arthritis evaluate and calibrate their complex medication regimens. Building on these findings, to explore how the concept of concordance helps to describe a patient-provider partnership model which can aid optimum medication regimen selection, calibration and management of chronic conditions. Method: A longitudinal study of 689 patients diagnosed with osteoarthritis (OA) or rheumatoid arthritis (RA) was conducted to identify patient perceptions, decision-making and behaviour related to their medication management. Face to face interviews with the Brief Medication Questionnaire, health quality of life questionnaires (AIMS2 and SF-36) and telephone interviews were conducted in waves centered around patient visits every six months for two years. Data about medication regimens were abstracted from the clinic medication profile record for each visit. Setting: Three rheumatology clinics in the United States: a university clinic, a private clinic and a Veterans Administration clinic. Key findings: About half of the patients in the sample had complex regimens with eight or more medications at any one time. The majority of physicians altered patients'' medication orders every six months. The majority of patients reported that they evaluated the effectiveness and side effects of individual medicines based largely on symptoms. There were 248 reported deviations in the scheduled medications at baseline and the majority (61 per cent) were intentional, largely based on symptoms. Conclusion: Providers and patients each had unique expertise and were engaged in a dynamic process of calibrating patients'' ever-changing regimens. In the absence of a perfect static regimen for patients, the concept of concordance productively reflects the partnership and mutual respect needed for ongoing medication regimen selection, calibration and management for a long-term condition.
Title: Suboptimal prescribing in older inpatients and outpatients.
Publication: Journal of the Americal Geriatric Society 2001 Feb;49(2):200-9.
Authors: Hanlon JT et al.
Grant Number: HS09083.
Principal Investigator: Morris Weinberger.
Project Officer: Bosco.
Abstract: Investigators searched Medline and HealthSTAR databases from January 1, 1985, through June 30, 1999, to identify articles on suboptimal prescribing in those age 65 years and older. A manual search of the reference lists from identified articles and the authors' article files, book chapters, and recent reviews was conducted to identify additional articles. The definitions for various types of suboptimal prescribing (polypharmacy, inappropriate, and underutilization) are numerous, and measurement varies from study to study. The literature suggests that suboptimal prescribing is common in older outpatients and inpatients. Moreover, there is significant morbidity and mortality associated with suboptimal prescribing for these older patients. Evidence from well-controlled studies suggests that multidisciplinary teams and clinical pharmacy interventions can modify suboptimal drug use in older people. Future research is necessary to measure and test other methods for tackling this major public health problem facing older people.
Title: Pharmaceutical care program for patients with reactive airways disease.
Publication: American Journal of Health Syst Pharm 2001 May;58(9):791-6.
Authors: Weinberger M et al.
Grant Number: HS09083.
Principal Investigator: Morris Weinberger.
Project Officer: Lynn Bosco.
Abstract: A pharmaceutical care program for patients with reactive airways disease (RAD) is described. A pharmaceutical care program for patients with RAD was developed and implemented at 36 CVS pharmacies. The impact on patient outcomes, pharmacist job satisfaction, and other variables is currently being evaluated in a controlled trial with more than 1,100 patient enrollees. Guiding the program are the beliefs that pharmacists must have clinically relevant, patient-specific data to provide appropriate care; that pharmacists must have adequate training to provide pharmaceutical care; that the program must be sensitive to organizational barriers, particularly time demands; and that there must be ongoing support for the program. The program has five components: (1) computer display of patient-specific data for patients enrolled in the study, (2) distribution of tailored patient education materials, (3) use of a resource guide to facilitate the implementation of pharmaceutical care, (4) strategies to reinforce and facilitate the program, and (5) pharmacist training. While developed for community pharmacies, the program is applicable to most ambulatory care pharmacy practices. A pharmaceutical care program for patients with RAD was developed for use in community pharmacies.
Title: Derivation of adherence metrics from electronic dosing records.
Publication: Journal of Clinical Epidemiology 2001;54:619-26.
Authors: Choo PW et al.
Grant Number: HS07821.
Principal Investigator: Richard Platt.
Project Officer: Lynn Bosco.
Abstract: Numerous adherence variables have been created from electronic dosing records hindering synthesis of the vast body of adherence research. To elucidate the mathematical foundation for electronic adherence monitoring and to understand how diverse electronic adherence metrics are related to each other and the underlying construct of adherence behavior. Several representative adherence metrics are derived mathematically and their relationship to the underlying consumption (or dosing event) rate analyzed. Data from a 3-month study of 286 individuals on single-drug antihypertensive therapy are then used to empirically study the statistical properties of several of these electronic adherence metrics. As suggested by their common link to the consumption (or dosing event) rate, the analyzed electronic adherence metrics were generally strongly correlated r <- .6 and > .4). The lowest correlation (r = .15) involved the ratio of the observed number of doses to the recommended number (called average adherence), which tended to emphasize quantity consumed, and the ratio of the observed to maximum mean squared rate deviation (MSRD ratio), which focused more on dose timing. Despite their different formulations, electronic adherence variables are generally closely correlated. Adherence metrics that average the consumption rate over multiple doses (by summing up the number of doses and dividing by the monitored time) may be less sensitive to short-term fluctuations in medication intake. Metrics that are more sensitive to timing variability may thus be preferable when timing as well as quantity of dosing are of interest.
Title: Differences in HIV disease progression by injection drug use and by sex in the era of highly active antiretroviral therapy.
Publication: AIDS 2001;15:1115-23.
Authors: Poundstone KE et al.
Grant number: HS07809.
Principal Investigator: Richard Moore.
Project Officer: Lynn Bosco.
Abstract: BACKGROUND: The advent of highly active antiretroviral therapy (HAART) has reduced the incidence of most AIDS-related opportunistic illnesses (OI) and death in HIV-infected individuals. We investigated whether there are demographic disparities in HIV disease progression in the HAART era compared with before. METHODS: HIV-infected patients in an urban HIV clinical practice in the USA were compared using survival methods for time to a new AIDS-defining OI or death in therapeutic era 1 (monotherapy and combination therapy;1990-1995; n = 2016) versus era 2 (HAART; 1996-1999; n = 2165). RESULTS: A total of 1037 (51.4 percent) events occurred in era 1; 666 (30.8 percent) events occurred in era 2. In women, the median disease-free survival time increased by 14 percent (CD4 cell counts > 200 cells/mm3 at baseline) and 34 percent (CD4 cell counts </= 200) in era 2 compared with era 1, whereas for men it increased by 43 and 100 percent. The relative hazard (RH) of progression for women compared with men in era 2 compared with era 1 was 1.34. For injecting drug use (IDU), disease-free survival time increased by 16 percent and 34 percent in era 2 compared with era 1, whereas non-IDU improved by 65 and 135 percent. The RH of progression for IDU compared with non-IDU in era 2 compared with era 1 was 1.39. No significant differences were detected by race or other HIV transmission risk group. CONCLUSION: Disease-free survival time was extended with the use of HAART, but these gains were not equally distributed by sex and IDU in our cohort.
Title: Methods for testing equality of means of health care costs in a paired design study.
Publication: Stat Med 2001 Jun 15;20(11):1703-20.
Authors: Zhou XH et al.
Grant Number: HS09083.
Principal Investigator: Morris Weinberger.
Project Officer: Lynn Bosco.
Abstract: In this paper we propose five new tests for the equality of paired means of health care costs. The first two tests are the parametric tests, a Z-score test and a likelihood ratio test, both derived under the bivariate normality assumption for the log-transformed costs. The third test (Z-score with jack-knife)is a semi-parametric Z-score method, which only requires marginal log-normal assumptions. The last two tests are the non-parametric bootstrap tests: one is based on a t-test statistic, and the other is based on Johnson's modified t-test statistic. We conduct a simulation study to compare the performance of these tests, along with some commonly used tests when the sample size is small to moderate. The simulation results demonstrate that the commonly used paired t-test on the log-scale and the Wilcoxon signed rank for differences of the two original scales can yield type I error rates larger than the preset nominal levels. The commonly used paired t-test on the original data performs well with slightly skewed data, but can yield inaccurate results when two populations have different skewness. The likelihood ratio test, the parametric and semi-parametric Z-score tests all have very good type I error control with the likelihood ratio test being the best. However, the semi-parametric Z-score test requires less distributional assumptions than the two parametric tests. The percentile-t bootstrap test and bootstrapped Johnson's modified t-test have better type I error control than the paired t-test on the original-scale and Johnson's modified t-test, respectively. Combining with the propensity-score method, we can also apply the proposed methods to test the mean equality of two cost outcomes in the presence of confounders. Our two applications are from health services research. In the first one, we want to know the effect of Medicaid reimbursement policy change on outpatient health care costs. The second one is to evaluate the effect of a hospitalist programme on health care costs in an observational study, and the imbalanced covariates between intervention and control patients are taken into account using a propensity score approach.