Relating gastric scintigraphy and symptoms to motility capsule transit and pressure findings in suspected gastroparesis.

BACKGROUND: Wireless motility capsule (WMC) findings are incompletely defined in suspected gastroparesis. We aimed to characterize regional WMC transit and contractility in relation to scintigraphy, etiology, and symptoms in patients undergoing gastric emptying testing. METHODS: A total of 209 patients with gastroparesis symptoms at NIDDK Gastroparesis Consortium centers underwent gastric scintigraphy and WMCs on separate days to measure regional transit and contractility. Validated questionnaires quantified symptoms. KEY RESULTS: Solid scintigraphy and liquid scintigraphy were delayed in 68.8% and 34.8% of patients; WMC gastric emptying times (GET) were delayed in 40.3% and showed 52.8% agreement with scintigraphy; 15.5% and 33.5% had delayed small bowel (SBTT) and colon transit (CTT) times. Transit was delayed in ≥2 regions in 23.3%. Rapid transit was rarely observed. Diabetics had slower GET but more rapid SBTT versus idiopathics (P ≤ .02). GET delays related to greater scintigraphic retention, slower SBTT, and fewer gastric contractions (P ≤ .04). Overall gastroparesis symptoms and nausea/vomiting, early satiety/fullness, bloating/distention, and upper abdominal pain subscores showed no relation to WMC transit. Upper and lower abdominal pain scores (P ≤ .03) were greater with increased colon contractions. Constipation correlated with slower CTT and higher colon contractions (P = .03). Diarrhea scores were higher with delayed SBTT and CTT (P ≤ .04). CONCLUSIONS & INFERENCES: Wireless motility capsules define gastric emptying delays similar but not identical to scintigraphy that are more severe in diabetics and relate to reduced gastric contractility. Extragastric transit delays occur in >40% with suspected gastroparesis. Gastroparesis symptoms show little association with WMC profiles, although lower symptoms relate to small bowel or colon abnormalities.

Diabetic and idiopathic gastroparesis is associated with loss of CD206-positive macrophages in the gastric antrum.

BACKGROUND: Animal studies have increasingly highlighted the role of macrophages in the development of delayed gastric emptying. However, their role in the pathophysiology of human gastroparesis is unclear. Our aim was to determine changes in macrophages and other cell types in the gastric antrum muscularis propria of patients with diabetic and idiopathic gastroparesis. METHODS: Full thickness gastric antrum biopsies were obtained from patients enrolled in the Gastroparesis Clinical Research Consortium (11 diabetic, 6 idiopathic) and 5 controls. Immunolabeling and quantitative assessment was done for interstitial cells of Cajal (ICC) (Kit), enteric nerves protein gene product 9.5, neuronal nitric oxide synthase, vasoactive intestinal peptide, substance P, tyrosine hydroxylase), overall immune cells (CD45) and anti-inflammatory macrophages (CD206). Gastric emptying was assessed using nuclear medicine scintigraphy and symptom severity using the Gastroparesis Cardinal Symptom Index. RESULTS: Both diabetic and idiopathic gastroparesis patients showed loss of ICC as compared to controls (Mean [standard error of mean]/hpf: diabetic, 2.28 [0.16]; idiopathic, 2.53 [0.47]; controls, 6.05 [0.62]; P=.004). Overall immune cell population (CD45) was unchanged but there was a loss of anti-inflammatory macrophages (CD206) in circular muscle (diabetic, 3.87 [0.32]; idiopathic, 4.16 [0.52]; controls, 6.59 [1.09]; P=.04) and myenteric plexus (diabetic, 3.83 [0.27]; idiopathic, 3.59 [0.68]; controls, 7.46 [0.51]; P=.004). There was correlation between the number of ICC and CD206-positive cells (r=.55, P=.008). Enteric nerves (PGP9.5) were unchanged: diabetic, 33.64 (3.45); idiopathic, 41.26 (6.40); controls, 46.80 (6.04). CONCLUSION: Loss of antral CD206-positive anti-inflammatory macrophages is a key feature in human gastroparesis and it is associates with ICC loss.

Early satiety and postprandial fullness in gastroparesis correlate with gastroparesis severity, gastric emptying, and water load testing.

BACKGROUND: Early satiety (ES) and postprandial fullness (PPF) are often present in gastroparesis, but the importance of these symptoms in gastroparesis has not been well-described. The aims were: (i) Characterize ES and PPF in patients with gastroparesis. (ii) Assess relationships of ES and PPF with etiology of gastroparesis, quality of life, body weight, gastric emptying, and water load testing. METHODS: Gastroparetic patients filled out questionnaires assessing symptoms (PAGI-SYM) and quality of life (PAGI-QOL, SF-36v2). Patients underwent gastric emptying scintigraphy and water load testing. KEY RESULTS: 198 patients with gastroparesis (134 IG, 64 DG) were evaluated. Early satiety was severe or very severe in 50% of patients. Postprandial fullness was severe or very severe in 60% of patients. Severity scores for ES and PPF were similar between idiopathic and diabetic gastroparesis. Increasing severity of ES and PPF were associated with other gastroparesis symptoms including nausea/vomiting, satiety/early fullness, bloating, and upper abdominal pain and GERD subscores. Increasing severity of ES and PPF were associated with increasing gastroparesis severity, decreased BMI, decreased quality of life from PAGI-QOL and SF-36 physical health. Increasing severity of ES and PPF were associated with increasing gastric retention of a solid meal and decreased volume during water load test. CONCLUSIONS & INFERENCES: Early satiety and PPF are commonly severe symptoms in both diabetic and idiopathic gastroparesis. Early satiety and PPF severity are associated with other gastroparesis symptom severities, body weight, quality of life, gastric emptying, and water load testing. Thus, ES and PPF are important symptoms characterizing gastroparesis. ClinicalTrials.gov number: NCT NCT01696747.

Nausea and vomiting in gastroparesis: similarities and differences in idiopathic and diabetic gastroparesis.

BACKGROUND: Nausea and vomiting are classic symptoms of gastroparesis. It remains unclear if characteristics of nausea and vomiting are similar in different etiologies of gastroparesis. The aims of this article were as follows: to describe characteristics of nausea and vomiting in patients with gastroparesis and to determine if there are differences in nausea and vomiting in diabetic (DG) and idiopathic gastroparesis (IG). METHODS: Gastroparetic patients enrolling in the NIDDK Gastroparesis Registry underwent assessment with history and questionnaires assessing symptoms, quality of life, and a questionnaire characterizing nausea and vomiting. KEY RESULTS: Of 159 gastroparesis patients (107 IG, 52 DG), 96% experienced nausea, whereas 65% experienced vomiting. Nausea was predominant symptom in 28% and vomiting was predominant in 4%. Nausea was severe or very severe in 41%. PAGI-SYM nausea/vomiting subscore was greater with increased vomiting severity, but not nausea severity in DG than IG. Nausea was related to meals in 71%; lasting most of the day in 41%. Increasing nausea severity was related to decreased quality of life. Nausea often preceded vomiting in 82% of patients and vomiting often relieved nausea in 30%. Vomiting was more common in DG (81%) compared to IG (57%; p = 0.004). Diabetic patients more often had vomiting in the morning before eating, during the night, and when not eating. CONCLUSIONS & INFERENCES: Nausea is present in essentially all patients with gastroparesis irrespective of cause and associated with decreased quality of life. In contrast, vomiting was more prevalent, more severe, and occurred more often in DG than IG. Thus, characteristics of vomiting differ in IG vs DG.

Patterns of Growth and Decline in Lung Function in Persistent Childhood Asthma.

BACKGROUND: Tracking longitudinal measurements of growth and decline in lung function in patients with persistent childhood asthma may reveal links between asthma and subsequent chronic airflow obstruction. METHODS: We classified children with asthma according to four characteristic patterns of lung-function growth and decline on the basis of graphs showing forced expiratory volume in 1 second (FEV1), representing spirometric measurements performed from childhood into adulthood. Risk factors associated with abnormal patterns were also examined. To define normal values, we used FEV1 values from participants in the National Health and Nutrition Examination Survey who did not have asthma. RESULTS: Of the 684 study participants, 170 (25%) had a normal pattern of lung-function growth without early decline, and 514 (75%) had abnormal patterns: 176 (26%) had reduced growth and an early decline, 160 (23%) had reduced growth only, and 178 (26%) had normal growth and an early decline. Lower baseline values for FEV1, smaller bronchodilator response, airway hyperresponsiveness at baseline, and male sex were associated with reduced growth (P<0.001 for all comparisons). At the last spirometric measurement (mean [±SD] age, 26.0±1.8 years), 73 participants (11%) met Global Initiative for Chronic Obstructive Lung Disease spirometric criteria for lung-function impairment that was consistent with chronic obstructive pulmonary disease (COPD); these participants were more likely to have a reduced pattern of growth than a normal pattern (18% vs. 3%, P<0.001). CONCLUSIONS: Childhood impairment of lung function and male sex were the most significant predictors of abnormal longitudinal patterns of lung-function growth and decline. Children with persistent asthma and reduced growth of lung function are at increased risk for fixed airflow obstruction and possibly COPD in early adulthood. (Funded by the Parker B. Francis Foundation and others; ClinicalTrials.gov number, NCT00000575.).

Baseline features and differences in 48 week clinical outcomes in patients with gastroparesis and type 1 vs type 2 diabetes.

BACKGROUND: In studies of diabetic gastroparesis, patients with type 1 and type 2 diabetes mellitus (T1DM, T2DM) are often combined for analyses. We compared gastroparesis severity, healthcare utilization, psychological function, and quality of life in T1DM vs T2DM gastroparesis patients. METHODS: Questionnaire, laboratory, and scintigraphy data from patients with gastroparesis and T1DM and T2DM from seven centers of the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium Registry were compared at enrollment and after 48 weeks. Multiple regression models assessed baseline and follow-up differences between diabetes subtypes. KEY RESULTS: At baseline, T1DM patients (N = 78) had slower gastric emptying, more hospitalizations, more gastric stimulator implantations, higher hemoglobin A1c (HbA1c), and more anxiety vs T2DM patients (N = 59). Independent discriminators of patients with T1DM vs T2DM included worse gastroesophageal reflux disease, less bloating, more peripheral neuropathy, and fewer comorbidities (p ≤ 0.05). On follow-up, gastrointestinal (GI) symptom scores decreased only in T2DM (p < 0.05), but not in T1DM patients who reported greater prokinetic, proton pump inhibitor, anxiolytic, and gastric stimulator usage over 48 weeks (p ≤ 0.03). Gastrointestinal symptoms at baseline and 48 weeks with both subtypes were not associated with HbA1c, peripheral neuropathy, psychological factors, or quality of life. CONCLUSIONS & INFERENCES: Baseline symptoms were similar in T1DM and T2DM patients, even though T1DM patients had worse gastric emptying delays and higher HbA1c suggesting other factors mediate symptom severity. Symptom scores at 48 weeks decreased in T2DM, but not T1DM patients, despite increased medical and surgical treatment utilization by T1DM patients. Defining causes of different outcomes in diabetic gastroparesis warrants further investigation.

Association of low numbers of CD206-positive cells with loss of ICC in the gastric body of patients with diabetic gastroparesis.

BACKGROUND: There is increasing evidence for specific cellular changes in the stomach of patients with diabetic (DG) and idiopathic (IG) gastroparesis. The most significant findings are loss of interstitial cells of Cajal (ICC), neuronal abnormalities, and an immune cellular infiltrate. Studies done in diabetic mice have shown a cytoprotective effect of CD206+ M2 macrophages. To quantify overall immune cellular infiltrate, identify macrophage populations, and quantify CD206+ and iNOS+ cells. To investigate associations between cellular phenotypes and ICC. METHODS: Full thickness gastric body biopsies were obtained from non-diabetic controls (C), diabetic controls (DC), DG, and IG patients. Sections were labeled for CD45, CD206, Kit, iNOS, and putative human macrophage markers (HAM56, CD68, and EMR1). Immunoreactive cells were quantified from the circular muscle layer. KEY RESULTS: Significantly fewer ICC were detected in DG and IG tissues, but there were no differences in the numbers of cells immunoreactive for other markers between patient groups. There was a significant correlation between the number of CD206+ cells and ICC in DG and DC patients, but not in C and IG and a significant correlation between iNOS+ cells and ICC in the DC group, but not the other groups. CD68 and HAM56 reliably labeled the same cell populations, but EMR1 labeled other cell types. CONCLUSIONS & INFERENCES: Depletion of ICC and correlation with changes in CD206+ cell numbers in DC and DG patients suggests that in humans, like mice, CD206+ macrophages may play a cytoprotective role in diabetes. These findings may lead to novel therapeutic options, targeting alternatively activated macrophages.

Vitamin E and changes in serum alanine aminotransferase levels in patients with non-alcoholic steatohepatitis.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a common cause of serum alanine aminotransferase (ALT) elevations and chronic liver disease, but it is unclear how well ALT elevations reflect the liver injury. AIM: To assess how well changes in ALT elevations reflect improvements in liver histology in response to vitamin E therapy. METHODS: The vitamin E and placebo arms of the Pioglitazone vs. Vitamin E vs. Placebo in Non-alcoholic Steatohepatitis (PIVENS) trial were reassessed for associations among changes in ALT levels, body weight and liver histology. An ALT response was defined as a decrease to ≤40 U/L and by ≥30% of baseline. Liver biopsies taken before and after treatment were scored for non-alcoholic fatty liver disease activity (NAS) and fibrosis. RESULTS: ALT responses were more frequent among vitamin E (48%) than placebo (16%) recipients (P < 0.001). Among vitamin E recipients, ALT responses were associated with decreases in NAS (P < 0.001), but not fibrosis scores (P = 0.34), whereas among placebo recipients, ALT responses were associated with significant decreases in both (P < 0.05). Weight loss (≥2 kg) was also associated with ALT response (P < 0.001), improvements in NAS (P < 0.001) and fibrosis (P < 0.02), but vitamin E had an added effect both with and without weight loss. Weight gain (≥2 kg) was associated with lack of ALT response and worsening NAS and fibrosis scores in patients not on vitamin E. CONCLUSIONS: Decrease of ALT levels to normal in patients with NASH is usually associated with improved histological activity. Management should stress the value of weight loss and strongly discourage weight gain. Vitamin E can improve both ALT levels and histology with and without weight loss. CLINICAL TRIAL NUMBER: NCT00063622.

Factors related to abdominal pain in gastroparesis: contrast to patients with predominant nausea and vomiting.

BACKGROUND: Factors associated with abdominal pain in gastroparesis are incompletely evaluated and comparisons of pain vs other symptoms are limited. This study related pain to clinical factors in gastroparesis and contrasted pain/discomfort- with nausea/vomiting-predominant disease. METHODS: Clinical and scintigraphy data were compared in 393 patients from seven centers of the NIDDK Gastroparesis Clinical Research Consortium with moderate-severe (Patient Assessment of Upper Gastrointestinal Disorders Symptoms [PAGI-SYM] score ≥ 3) vs none-mild (PAGI-SYM < 3) upper abdominal pain and predominant pain/discomfort vs nausea/vomiting. KEY RESULTS: Upper abdominal pain was moderate-severe in 261 (66%). Pain/discomfort was predominant in 81 (21%); nausea/vomiting was predominant in 172 (44%). Moderate-severe pain was more prevalent with idiopathic gastroparesis and with lack of infectious prodrome (P ≤ 0.05) and correlated with scores for nausea/vomiting, bloating, lower abdominal pain/discomfort, bowel disturbances, and opiate and antiemetic use (P < 0.05), but not gastric emptying or diabetic neuropathy or control. Gastroparesis severity, quality of life, and depression and anxiety were worse with moderate-severe pain (P ≤ 0.008). Factors associated with moderate-severe pain were similar in diabetic and idiopathic gastroparesis. Compared to predominant nausea/vomiting, predominant pain/discomfort was associated with impaired quality of life, greater opiate, and less antiemetic use (P < 0.01), but similar severity and gastric retention. CONCLUSIONS & INFERENCES: Moderate-severe abdominal pain is prevalent in gastroparesis, impairs quality of life, and is associated with idiopathic etiology, lack of infectious prodrome, and opiate use. Pain is predominant in one fifth of gastroparetics. Predominant pain has at least as great an impact on disease severity and quality of life as predominant nausea/vomiting.

Clinical-histological associations in gastroparesis: results from the Gastroparesis Clinical Research Consortium.

BACKGROUND: Cellular changes associated with diabetic (DG) and idiopathic gastroparesis (IG) have recently been described from patients enrolled in the Gastroparesis Clinical Research Consortium. The association of these cellular changes with gastroparesis symptoms and gastric emptying is unknown. The aim of this study was to relate cellular changes to symptoms and gastric emptying in patients with gastroparesis. METHODS: Earlier, using full thickness gastric body biopsies from 20 DG, 20 IG, and 20 matched controls, we found decreased interstitial cells of Cajal (ICC) and enteric nerves and an increase in immune cells in both DG and IG. Here, demographic, symptoms [gastroparesis cardinal symptom index score (GCSI)], and gastric emptying were related to cellular alterations using Pearson's correlation coefficients. KEY RESULTS: Interstitial cells of Cajal counts inversely correlated with 4 h gastric retention in DG but not in IG (r = -0.6, P = 0.008, DG, r = 0.2, P = 0.4, IG). There was also a significant correlation between loss of ICC and enteric nerves in DG but not in IG (r = 0.5, P = 0.03 for DG, r = 0.3, P = 0.16, IG). Idiopathic gastroparesis with a myenteric immune infiltrate scored higher on the average GCSI (3.6 ± 0.7 vs 2.7 ± 0.9, P = 0.05) and nausea score (3.8 ± 0.9 vs 2.6 ± 1.0, P = 0.02) as compared to those without an infiltrate. CONCLUSIONS & INFERENCES: In DG, loss of ICC is associated with delayed gastric emptying. Interstitial cells of Cajal or enteric nerve loss did not correlate with symptom severity. Overall clinical severity and nausea in IG is associated with a myenteric immune infiltrate. Thus, full thickness gastric biopsies can help define specific cellular abnormalities in gastroparesis, some of which are associated with physiological and clinical characteristics of gastroparesis.

Retinal detachment risk in cytomegalovirus retinitis related to the acquired immunodeficiency syndrome.

OBJECTIVES: To compare the incidence of retinal detachment in patients treated with the ganciclovir implant compared with those treated using systemic therapy only, among 511 patients with the acquired immunodeficiency syndrome (AIDS) and cytomegalovirus (CMV) retinitis and to describe the influence of highly active antiretroviral therapy (HAART) on retinal detachment incidence. PATIENTS AND METHODS: All patients with AIDS and CMV retinitis at 1 center were followed up prospectively from CMV retinitis diagnosis for incidence of retinal detachment. Patient- and eye-specific data regarding demographic and clinical characteristics were collected at the time of CMV retinitis diagnosis. Use of anti-CMV and antiretroviral treatments and the development of an immunologic response to HAART during follow-up were recorded. RESULTS: No significant difference in the rate of retinal detachment was found between eyes treated with systemic therapy only and those treated with ganciclovir implants, whether used as primary therapy or subsequent to using systemic anti-CMV therapy. The use of HAART was associated with a 60% reduction in retinal detachment rate (P<.001), with the greatest benefit observed among patients who developed an immunologic response to HAART. CONCLUSIONS: Our results suggest that there is no substantial excess risk of retinal detachment when patients with AIDS and CMV retinitis are treated with ganciclovir implants as opposed to systemic anti-CMV therapy only. However, the use of HAART in these patients appears to reduce the risk of retinal detachment substantially.

A controlled trial of immunotherapy for asthma in allergic children.

BACKGROUND: Injections of allergens are widely prescribed for patients with asthma, but little is known about the effectiveness of immunotherapy. METHODS: We conducted a double-blind, placebo-controlled trial of multiple-allergen immunotherapy in 121 allergic children with moderate-to-severe, perennial asthma. The children, who required daily medication for their asthma, were randomly assigned to receive subcutaneous injections of either a mixture of up to seven aeroallergen extracts or a placebo. Maintenance injections were continued for 18 months or longer. Medications were adjusted every two to three weeks on the basis of peak flow rates and symptoms. The principal outcome was the daily medication score. Bronchial sensitivity to methacholine (the concentration provoking a 20 percent decrease in the forced expiratory volume in one second [PC20]) was measured twice yearly. RESULTS: The median medication score declined from 5.4 to 4.9 in the immunotherapy group (P<0.001) and from 5.2 to 5.0 in the placebo group (P<0.001), but there was no significant difference between the groups (P>0.6). The number of days on which oral corticosteroids were used was similar in the two groups. Partial or complete remission of asthma occurred in 31 percent of the immunotherapy group and in 28 percent of the placebo group (P>0.5). There was no difference between the groups in the use of medical care, symptoms, or peak flow rates. The median PC20 increased significantly in both groups, but again with no difference between the two groups. CONCLUSIONS: Immunotherapy with injections of allergens for over two years was of no discernible benefit in allergic children with perennial asthma who were receiving appropriate medical treatment.

Results at age 8 years of early intervention for low-birth-weight premature infants. The Infant Health and Development Program.

OBJECTIVE: To reevaluate at age 8 years children who had participated during the first 3 years of life in a randomized clinical trial of special services for low-birthweight (LBW) premature infants. DESIGN: Follow-up of a randomized controlled trial of premature infants (< or = 37 weeks' gestation), stratified by 2 LBW groups (lighter [< or = 2000 g] and heavier [2001-2500 g]) and divided into intervention (n=377) and follow-up only (n=608) groups. SETTING: Eight sites serving diverse populations. PARTICIPANTS: At age 8 years, 874 children were assessed: 336 in the intervention group and 538 in the follow-up only group. INTERVENTION: The 3-year intervention consisted of home visits (birth to 3 years), child development center services (ages 1 to 3 years), and parent group meetings (ages 1 to 3 years). PRIMARY OUTCOME MEASURES: Cognitive functioning (Weschler Intelligence Scale for Children-III; Peabody Picture Vocabulary Test-Revised); academic achievement (Woodcock-Johnson Tests of Achievement-Revised); and parental reports of school performance, behavior (Child Behavior Checklist), and health (Child General Health Survey). RESULTS: At age 8 years, in the entire cohort and in the lighter LBW stratum, the intervention and follow-up only groups were similar on all primary outcome measures. Differences favoring the intervention group were found within the heavier LBW group: full-scale IQ score (4.4 points higher, P=.007), verbal IQ score (4.2 points higher, P=.01), performance IQ score (3.9 points higher, P=.02), mathematics achievement score (4.8 points higher, P=.04), and receptive vocabulary score (6.7 points higher, P=.001). On a physical functioning subscale, the whole intervention group received less favorable ratings, while the lighter LBW intervention group had lower maternal ratings assessing social limitations caused by behavior. CONCLUSION: Although at age 8 years there were modest intervention-related differences in the cognitive and academic skills of heavier LBW premature children, attenuation of the large favorable effects seen at 3 years was observed in both the heavier and lighter LBW groups. This indicates a need to develop additional intervention strategies for LBW premature children that can provide sustained benefits.

Early educational intervention for very low birth weight infants: results from the Infant Health and Development Program.

OBJECTIVE: To examine the effect of early educational intervention after discharge from the hospital on the health and developmental status of very low birth weight (< or = 1500 gm) infants. DESIGN: Randomized, controlled trial, with post hoc analysis. SETTING: Eight sites, heterogeneous for sociodemographic and health care use. PARTICIPANTS: Infants (N = 280) born weighing < or = 1500 gm and selected for the Infant Health and Development Program. Eligibility was limited primarily by geographic distance from the day care center. One third were randomly assigned to the intervention (INT) group and two thirds to follow-up only. INTERVENTIONS: All children received intensive pediatric and developmental surveillance. The INT group received home visits and center-based educational interventions until 36 months of age (corrected for gestational age when final assessments were completed). OUTCOMES: Cognitive development (Stanford-Binet Intelligence Scale), behavioral competence (Achebach Child Behavior Checklist), and health status (indexes summarizing reported morbidity, the Functional Status II (R) Scale, and General Health Ratings Index). RESULTS: Cognitive development scores were 7.2 points higher (p = 0.002) in the INT group, after adjustment for baseline differences in site, sociodemographic characteristics, and neonatal morbidity, and were 9.4 points higher (p < 0.0003) when the 29 children with significant cerebral palsy were removed. No differences in behavior, serious morbidity, functional status, or health rating were found overall. The infants in the INT group who weighted < or = 1000 gm at birth had significantly lower behavior problem scores but no differences on other outcomes. All children in the INT group had slightly higher rates of less serious morbidity. CONCLUSION: The advantage conferred by being in the INT group, as previously reported for heavier infants, extends to very low birth weight children, supporting the use of early intervention in this group.

Recruitment in the Hypertension Prevention trial. Hypertension Prevention Trial Research Group.

The Hypertension Prevention Trial (HPT) was a randomized, controlled, multicenter (four clinics, four resource centers) trial designed to test the feasibility of achieving and sustaining dietary changes in the intake of calories, sodium, and potassium and to assess the effect of those changes on blood pressure in a normotensive population. The trial involved 841 men and women (plus a test cohort of 78) who, at the first baseline (BL) examination were in the age range of 25-49 years and had diastolic blood pressure (DBP) greater than or equal to 76 but less than 100 mm Hg (average of two readings), and at the examination prior to randomization (BL 2), had DBP greater than or equal to 78 but less than 90 mm Hg (also averaged). Participants were randomly assigned to a control treatment group (no dietary counseling) or to one of four dietary treatment groups involving counseling designed to reduce calorie intake, reduce sodium intake, reduce sodium and calorie intake, and reduce sodium and increase potassium intake. This chapter describes the process of recruiting participants for the trial. Methods used to identify and contact study participants are presented. Details of the steps involved in the recruitment process and strategies for reducing costs are discussed.

The validity of questionnaire-reported work history in live respondents.

The ability of subjects to recall their year of hire, year of termination, and job title was studied by comparing reported information to that recorded in personnel records. Former shipyard workers were interviewed in 1982. A majority was first employed in one of two shipyards during the early 1940s and 1950s. kappa statistics and crude and adjusted measures of percent agreement were derived to determine whether reported work history agreed with what was recorded in the subjects' personnel record and to determine whether recall was associated with race, age of the respondent at the time of interview, years since leaving the yard, length of employment, and year of hire. After adjusting for other covariates, only the number of years since leaving the yard was associated with recall of year of hire and termination, but not job title. In addition, however, there were several other noteworthy findings. Individuals who were 65-69 years of age at the time of interview had the poorest recall. Recall of both the year of hire and the job title appears to improve with increasing length of employment.

Bladder cancer in young women.

The authors describe a population-based case-control study of cancer of the urinary bladder in New York State women aged 20-49 years (173 matched pairs) in 1975-1980. Both known and suspected risk factors for bladder cancer were examined for these rare, early-onset female cases. The odds ratio (OR) for cigarette smoking was 2.4 (95% confidence interval (CI) = 1.5-4.0). Cases consumed more coffee per day than did controls (p less than 0.05). More cases than controls reported heavy use of drugs that contained phenacetin (OR = 6.5, 95% CI = 1.5-59.2). In addition, more cases than controls reported that they had had a thyroid uptake procedure with radioactive iodine (iodine-131) (OR = 3.7, 95% CI = 1.4-11.0). The odds ratios for these factors remained elevated after simultaneous adjustment with conditional logistic regression models. Consumption of artificial sweeteners, occupational history, bladder or kidney cancer in a first-degree relative, and a history of bladder infections were examined and found not to be risk factors for bladder cancer in this study.

Heavy phenacetin use and bladder cancer in women aged 20 to 49 years.

We investigated the use of analgesics containing phenacetin or acetaminophen in 173 young women with urinary bladder cancer and 173 matched controls. The cases, who were 20 to 49 years old at the time of diagnosis of cancer, were 6.5 times more likely to report regular use of analgesics containing phenacetin at least one year before diagnosis than were their matched controls (odds ratio, 6.5; 95 per cent confidence interval, 1.5 to 59.2). Among the 15 women (13 cases and 2 controls) reporting regular use of phenacetin-containing drugs, 8 of the cases and 1 of the controls reported daily use for over one year (P = 0.04). Excessive use of analgesics containing acetaminophen was not reported. The increased risk of bladder cancer in young women who regularly used phenacetin-containing products remained present after adjustments for all other identified risk factors.

Estrogen use and myocardial infarction risk: a case-control study.

A case-control study was conducted to examine the relationship of estrogen use to myocardial infarction in postmenopausal white women. After exclusion of proxy responses and of controls with discharge diagnoses of gynecologic or gallbladder diseases, there remained 39 matched sets (33 pairs and 6 triplets). The unadjusted relative odds ratio (RO) for past estrogen use was found to be 0.83. However, after simultaneous adjustment for cardiovascular diseases, smoking, education, and type of menopause, the net RO was 0.61. Type of menopause was found to interact with estrogen use, in that the protective effect was seen mainly in surgical menopause women, in whom the net RO for estrogen use was 0.37. Although none of the results reached statistical significance, they are consistent with recent results indicating a protective effect for estrogen therapy in regard to coronary heart disease, mainly among women undergoing surgical menopause.