Jonathan N. Tobin

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT): clinical center recruitment experience.

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is a randomized clinical outcome trial of antihypertensive and lipid-lowering therapy in a diverse population (including substantial numbers of women and minorities) of 42,419 high-risk hypertensives aged > or = 55 years with a planned mean follow-up of 6 years. In this paper, we describe our experience in the identification, recruitment, and selection of clinical centers for this large simple trial capable of meeting the recruitment goals outlined for ALLHAT, and we highlight factors associated with clinical center performance. Over 135,000 recruitment brochures were mailed to physicians. Requests for information and application packets were received from 9351 (6.8%) interested investigators. A total of 1053 completed applications were received and 909 sites (86%) were eventually approved to join the trial. Of the approved sites, 278 either later declined participation or were never activated, and 8 were closed within a year for lack of enrollment. The final 623 randomizing centers exceeded the trials recruitment goal to enroll at least 40,000 participants into the trial, although the recruitment period was extended 1.5 years longer than planned. Fewer than a quarter of the sites (22.6%) were recruited from academic medical centers or Department of Veterans Affairs Medical Centers. More than half of the sites (54.7%) were private solo or group practices, which contributed 53% of randomized participants. Community health centers comprised about 8% of the ALLHAT sites and 2.9% were part of health maintenance organizations. More than 22% of the principal investigators reported that they had no previous clinical research experience. In summary, ALLHAT was successful in recruiting a diverse group of clinical centers to achieve its patient recruitment goals.

A dynamic posturography study of balance in healthy elderly

Using dynamic posturography, we studied the balance of 234 community-dwelling elderly subjects (mean age, 76 ± 5 years) as well as 34 young controls (mean age, 34 ± 12 years). Almost all measures of balance were worse in elderly subjects compared with young controls. The decrements in older persons indicate a diminished capacity to process conflicting sensory input as well as a possible narrowing of the limit of stability (or, alternatively, an increase in sway). We propose that this occurs most likely as a result of biomechanical or central processing changes as opposed to diminished sensory or vestibular input. Furthermore, with difficult tasks sequentially presented, the performance of the older subjects improved, suggesting that balance, at least in the short term, adapts to stressful conditions. In these elderly subjects screened for age-related diseases affecting balance, only small decrements of balance occurred between the ages of 70 and 85 years. This nominal decrease over a 15-year span suggests that clinically significant balance impairment is the result of age-related disease rather than an inevitable consequence of aging and is therefore potentially treatable.

Telephone Care Management To Improve Cancer Screening among Low-Income Women: A Randomized, Controlled Trial

Context Minority and low-income women have low screening rates for cancer. Contribution In this trial from 11 community and migrant health centers in New York City, 1413 women overdue for cancer screening were randomly assigned to receive a telephone-based intervention (delivered by 8 prevention care managers) or usual care. The intervention included information about breast, cervical, and colorectal cancer and motivational and logistical support for obtaining screening. Within 18 months, the screening rates for all 3 forms of cancer increased more with telephone support than through usual care. Implications Telephone support delivered by trained personnel can improve cancer screening rates among some minority, low-income women. The Editors Higher screening rates for breast, cervical, and colorectal cancer could reduce cancer mortality rates substantially (1-4). Current cancer screening rates are particularly disappointing among ethnic minorities and individuals with low socioeconomic status (5, 6) who often present with late-stage diagnoses (7) and have high mortality rates (8, 9). Interventions to increase cancer screening have shown limited sustainability and effect on health care disparities. A previous study showed that an office systems approach, which used a medical record flowsheet and practice teamwork, increased screening rates by 20% to 33% in small rural community practices (10); however, a similar intervention was less effective in larger urban practices (11). An office intervention in low-income settings in Florida increased mammography use and home fecal occult blood testing at 12 months (12), but rates decreased substantially after research support ended (13). Use of the telephone to support cancer screening is well documented (14-18), but interventions have typically addressed a single form of cancer screening. In some settings, telephone infrastructures to support childhood immunization (19) and patients with chronic illnesses (20-23) already exist. These infrastructures could add screening support for patients who are already enrolled, or they could expand services to others while making minimal additional demands on primary care practices (24). This paper reports the results of a randomized, controlled trial that tested the effect of centralized telephone care management on cancer screening rates among women 50 to 69 years of age who obtained care at community and migrant health centers in New York City. Methods Settings Federally qualified community and migrant health centers provide comprehensive community-oriented primary care to over 12 million patients nationally (25) and are uniquely positioned to deliver cancer screenings to underserved and minority populations. We sought participation from 15 of the 21 community and migrant health centers in New York City because of their anticipated ability to provide sufficient patients for the study and their affiliations with tertiary care facilities that conduct mammography and colorectal screening and provide follow-up services for abnormal test results. Of these 15 sites, 2 were involved in competing research projects, 2 had few patients who were likely to be eligible and therefore served as pilot sites, and the remaining 11 participated. Clinical Directors Network, a practice-based research network in New York City, was responsible for recruiting clinicians, practices, and women and for implementing the intervention and evaluation. The project was approved by the Committee for the Protection of Human Subjects at Dartmouth College, by the institutional review board at Clinical Directors Network, and by all relevant bodies responsible for reviewing research at participating community and migrant health centers. Patients Recruitment Women were approached by research assistants during routine visits to the centers or were referred by a clinician. Research assistants explained the study and obtained written informed consent from women who agreed to participate. Women were compensated

Cyclophosphamide does not benefit patients with focal segmental glomerulosclerosis a report of the international study of kidney disease in children

15 for participating in an interview whether or not they met eligibility criteria. Eligibility Eligible women were 50 to 69 years of age, were overdue for at least 1 cancer screening according to their medical records, were patients of the center for at least 6 months, and had no plans to move or change health centers within 15 months. We excluded women whose primary language was not English, Spanish, or Haitian Creole and those who were acutely ill or currently receiving cancer treatment. After we obtained consent, a research assistant reviewed patient medical records to confirm eligibility. Mammography and Papanicolaou tests that were performed within the past year were seen as evidence of breast and cervical cancer screening, respectively, whereas reports of home fecal occult blood testing within the past year, sigmoidoscopy within the past 5 years, or colonoscopy within the past 10 years were seen as evidence of colorectal cancer screening. Women whose charts indicated that they were up to date on all 3 cancer screenings were excluded. We also excluded women with unresolved abnormal screening results (for example, positive results on home fecal occult blood testing; mammography results that were categorized as American College of Radiology level 0, 4, or 5; and certain Papanicolaou test results) and notified their physicians of these findings. Design Eligible, consenting women were grouped by center, duration of enrollment at their center (12 months or >12 months), and the number of cancer screenings that they had received at recommended intervals (0 or 1 screening or 2 screenings). The New Yorkbased research assistant assigned women in each group to receive the intervention or usual care by using sealed randomization forms that were produced by Dartmouth College staff with a computer-based random-number generator. Patients were informed of their group assignment individually by telephone. At time of consent, all women received the publication titled Put Prevention into Practice Personal Health Guide (26), which contained information regarding recommended preventive services. Women who were assigned to the usual care group received a single telephone call during which trial staff answered questions about preventive care, informed women of their usual care status, advised them to obtain needed preventive care from their primary care clinician, and thanked them for their participation. Women who were assigned to the intervention group received a series of telephone support calls from a trained prevention care manager who was monitored to ensure quality and consistency. In much the same way that patient navigators guide women through the health care system during cancer treatment (27), prevention care managers facilitated the screening process for each woman by addressing barriers that prevent or delay receipt of cancer screenings. Prevention care managers received 7 hours of training, including an overview of the U.S. Preventive Services Task Force guidelines (28-30); a review of barriers to breast, cervical, and colorectal cancer screenings; and detailed explanations of the targeted screenings. Additional training included role-playing telephone calls during which the managers used the intervention scripts. Thereafter, logs were reviewed in monthly meetings to ensure fidelity to the intervention. The 8 prevention care managers were women, and most were college graduates. Their assignments were determined by patient language needs. Each care manager focused most of her work on patients from 1 or 2 sites while supporting smaller numbers of patients from other sites; contact with clinicians was limited. During the first call with a patient in the intervention group, the prevention care manager answered questions about the health guide and confirmed or updated screening dates found in the womans medical record. She next determined how ready the woman was to act on each screening (31) and worked with the woman to prioritize overdue screenings. The prevention care manager then provided motivational support, responding to each participants specific barriers to screening by using a structured script that was developed through an earlier series of interviews with women (32). Some participants had been advised during office visits with their clinicians to undergo screening; those who had not received such recommendations were sent a written recommendation from their clinician. Women who reported that they had difficulty communicating with their physician were sent brightly colored patient activation cards that listed overdue screenings, which they could share with their clinician at their next appointment. Care managers also scheduled appointments, provided accurate information about screenings over the telephone and by mail, prompted women with appointment reminder calls and letters, provided directions to screening facilities, and helped women to find a means of transportation to appointments. During subsequent calls, which continued for 18 months or until the patient was up to date for all screenings, the prevention care manager asked about future appointments and screenings the patient had received since the last call. The manager then responded to new and ongoing barriers for remaining overdue screenings. Only clinicians, not care managers, were responsible for ordering screenings at all but 2 centers, which permitted care managers to mail home fecal occult blood test kits directly to women who were willing to perform this test. Evaluation Descriptive data on the centers were gathered from surveys that were completed by clinicians and clinical directors. Outcome data were based on reviews of patient medical records, which were conducted at least 3 months after the intervention period to allow for the time lag between receipt of a service and the availability of documentation. Data included patient demographic characteristics, screening dates and results, chronic il

Racism and ambulatory blood pressure in a community sample.

Sixty children, with biopsy diagnosed focal segmental glomerulosclerosis (FSGS) and with unremitting nephrotic syndrome despite intensive therapy with adrenocortical steroids, were randomly allocated into a clinical trial comparing prednisone, 40 mg/m2 on alternate days for a period of 12 months (control group), with the same prednisone regimen plus a 90-day course of daily cyclophosphamide, 2.5 mg/kg in a single morning dose (experimental group). One-quarter of the children in each group had complete resolution of proteinuria. The proportions of children with increased, unchanged, and decreased proteinuria by the end of the study were the same in the two groups. Treatment fialure was defined as an increase in serum creatinine of 30% or more or greater than 0.4 mg/dl, or onset of renal failure. Treatment failure occurred in 36% of the control group and 57% of the experimental group (P>0.1). Five patients died during the trial, 3 in the experimental group and 2 in the control group. A Kaplan-Meier survival analysis revealed no significant differences between the two groups. Cyclophosphamide therapy for children with steroid-resistant FSGS is not recommended.

Cognitive-behavioral interventions improve quality of life in women with AIDS.

Objective: Racism has been identified as a psychosocial stressor that may contribute to disparities in the prevalence of cardiovascular disease. The goal of the present article was to investigate the relationship of perceived racism to ambulatory blood pressure (ABP) in a sample of American-born Blacks and Latinos. Methods: Participants included English-speaking Black or Latino(a) adults between the ages of 24 and 65. They completed daily mood diaries and measures of perceived racism, socioeconomic status, and hostility. Participants were outfitted with ABP monitors; 357 provided data on waking hours only, and 245 provided data on both waking and nocturnal ABP. Results: Perceived racism was positively associated with nocturnal ABP even when controlling for personality factors and socioeconomic status. Conclusions: The results suggest that racism may influence cardiovascular disease risk through its effects on nocturnal BP recovery. ABP = ambulatory blood pressure; SBP = systolic blood pressure; DBP = diastolic blood pressure; CVD = cardiovascular disease; SES = socioeconomic status; HTN = hypertension; AHA = American Heart Association; GHI = gross household income; BMI = body mass index; PEDQ-CV = Perceived Ethnic Discrimination Questionnaire-Community Version.

Treatment of mesangiocapillary glomerulonephritis with alternate-day prednisone : a report of the International Study of Kidney Disease in Children

OBJECTIVE We tested the effects of a 10-week group-based cognitive-behavioral stress management/expressive-supportive therapy intervention (CBSM+) and a time-matched individual psychoeducational condition for 330 women with AIDS reporting moderate to poor baseline quality of life (QOL). The goal of this study was to examine treatment effects on total QOL and 11 QOL domains from baseline to post-intervention follow-up. METHODS Participants were assessed at baseline, randomized to a treatment condition (individual psychoeducation condition n=180, group-based CBSM+ condition n=150), participated in the intervention for 10 weeks and assessed again within 4 weeks following the intervention. QOL was measured using the Medical Outcomes Study-HIV-30. RESULTS QOL scores increased over the course of both interventions for the total QOL score and three QOL domains: cognitive functioning, health distress and overall health perceptions. While women in the CBSM+ group condition showed a significant improvement in mental health QOL from pre- to post-intervention, women in the individual condition did not change. No changes were observed for energy/fatigue, health transition, single-item overall QOL, pain, physical well-being, role functioning or social functioning in either condition. CONCLUSION Results suggest that group-based CBSM+ and individual psychoeducational interventions are effective at improving certain aspects of QOL and that group-based CBSM+ may be particularly effective at increasing QOL related to mental health in this population of women with AIDS.

Influencing medication adherence among women with AIDS

It has been claimed that long-term prednisone treatment ameliorates the course of children with mesangiocapillary glomerulonephritis (MCGN). The International Study of Kidney Disease in Children conducted a randomized, double-blinded, placebo-controlled clinical trial in 80 children with idiopathic MCGN, including 42 patients with type I disease, 14 with type II disease, 17 with type III disease, and 7 with nontypable disease. Criteria for admission included heavy proteinuria and a glomerular filtration rate of greater than or equal to 70 ml/min per 1.73 m2. Prednisone or lactose, 40 mg/m2, was given every other day as a single morning dose. The mean duration of treatment was 41 months, renal failure being the most common reason for termination of therapy. Treatment failure was defined as an increase from baseline of 30% or more in serum creatinine, or more than 35 μmol/l. Overall, treatment failure occurred in 55% of patients treated with lactose, compared with 40% in the prednisone group. Life-table analysis showed a renal survival rate (i.e., stable renal function) at 130 months of 61% among patients receiving prednisone and 12% among patients receiving lactose (P=0.07). Of patients with type I or III MCGN, 33% treated with prednisone were treatment failures, compared with 58% in the lactose group. Long-term treatment with prednisone appears to improve the outcome of children with MCGN.

Lower standing systolic blood pressure as a predictor of falls in the elderly: a community-based prospective study

This study examined the effects of a ten-session cognitive-behavioural stress management/expressive supportive therapy (CBSM+) intervention on adherence to antiretroviral medication. Although the intervention was not designed to influence adherence, it was theorized that improved coping and social support could enhance adherence. Women with AIDS (N=174) in Miami, New York and New Jersey, USA, were randomized to a group CBSM+ intervention or individual control condition. Participants were African American (55%), Latina (18%) and Caribbean (18%) with drug (55%) and/or alcohol (32%) histories. Participants were assessed on self-reported medication adherence over seven days, HIV-related coping strategies and beliefs regarding HIV medication. Baseline overall self-reported adherence rates were moderate and related to coping strategies and HIV medication beliefs. Low adherent (80%) participants in the intervention condition increased their mean self-reported medication adherence (30.4% increase, t44=3.1, p<0.01), whereas low adherent women in the control condition showed a non-significant trend (19.6% increase, t44=2.0, p>0.05). The intervention did not improve adherence in this population; conditions did not differ significantly on self-reported adherence. Low adhering intervention participants significantly decreased levels of denial-based coping (F1,88=5.97, p<0.05). Results suggest that future interventions should utilize group formats and address adherence using coping and medication-knowledge focused strategies.

Diagnostic heterogeneity in clinical trials for congestive heart failure

OBJECTIVES We investigated prospectively the relationships among falls, physical balance, and standing and supine blood pressure (BP) in elderly persons. BACKGROUND Falls occur often and adversely affect the activities of daily living in the elderly; however, their relationship to BP has not been clarified thoroughly. METHODS A total of 266 community-dwelling elderly persons age 65 years or over (123 men and 143 women, mean age of 76 years) were selected from among residents of Coop City, Bronx, New York. Balance was evaluated at baseline using computerized dynamic posturography (DPG). During a one-year follow-up, we collected information on subsequent falls on a monthly basis by postcard and telephone follow-up. RESULTS One or more falls occurred in 60 subjects (22%) during the one-year follow-up. Women fell more frequently than men (28% vs. 16%, p < 0.03), and fallers were younger than nonfallers. Fallers (n = 60) had lower systolic BP (SBP) levels when compared with nonfallers (n = 206) (128 +/- 17 vs. 137 +/- 22 mm Hg for standing, p < 0.006; 137 +/- 16 vs. 144 +/- 22 mm Hg for lying, p < 0.02), whereas diastolic BP was not related to falls. Falls occurred 2.8 times more often in the lower BP subgroup (<140 mm Hg for standing SBP) than in the higher BP subgroup (> or =140 mm Hg, p < 0.0003), and gender-related differences were observed (p = 0.006): 3.4 times for women (p < 0.0001) versus 1.9 times for men (p = 0.30). Loss of balance, as detected by DPG, did not predict future falls and was also not associated with baseline BP levels. Multiple logistic regression analysis demonstrated that female gender (relative risk [RR] = 2.1, p = 0.02), history of falls (RR = 2.5, p = 0.008) and lower standing SBP level (RR = 0.78 for 10 mm Hg increase, p = 0.005) were independent predictors of falls during one year of follow-up. CONCLUSIONS Lower standing SBP, even within normotensive ranges, was an independent predictor of falls in the community-dwelling elderly. Elderly women with a history of falls and with lower SBP levels should have more attention paid to the prevention of falls and related accidents.