Feasibility of Collecting Saliva for Biological Verification of Tobacco Use Status in Dental Practices and Patients' Homes: Results from the National Dental PBRN.

OBJECTIVE: To evaluate the feasibility of collecting and analyzing saliva samples from dental practices and patients' homes for biochemical verification of tobacco use status. BASIC RESEARCH DESIGN: Sub-study within single-arm, multi-center, longitudinal clinical study. CLINICAL SETTING: Dental practices in the South Central region of the United States National Dental Practice-Based Research Network and patients' homes. PARTICIPANTS: Fifty-five patients recruited from 30 dental practices. INTERVENTIONS: Participants in the sub-study were instructed on saliva collection for cotinine analysis in dental practices where they enrolled in the primary study. Saliva was collected at the practices and then from patients' homes. MAIN OUTCOME MEASURES: Feasibility for dental practice collection was define as 80% of enrolled participants having analyzable samples. For patients' home collection, feasibility was defined as 70%. RESULTS: Forty-seven samples (i.e., 86% of those enrolled) collected in dental practices were analyzable. Twenty-one samples (i.e. 38% of those enrolled) collected in patients' homes were analyzable. CONCLUSIONS: Collecting saliva samples for cotinine analysis from dental practices, but not from patients' homes, was feasible. Dental practices may provide an advantageous setting for biochemically verifying tobacco use status as part of clinical trials for tobacco cessation.

Nocturnal river water temperatures: Spatial and temporal variations.

Nocturnal water temperature (Tw) affects the behaviour of aquatic biota and metabolism of whole rivers. However, night-time water temperature (nTw) is poorly understood because spot samples are typically taken during daylight hours, or Tw series are aggregated in ways that mask sub-daily properties. This paper examines 15-minute measurements of Tw and air temperature (Ta) collected at 36 sites in the Rivers Dove and Manifold, English Peak District. Data were stratified by day and night then analysed using hysteresis, auto-correlation and logistic regression techniques. Daily hysteresis loops show lagged responses between nTw and previous daylight air temperatures (dTa), plus the influence of groundwater and discharge variations. Logistic regression models were modified using a seasonal factor and explained between 80 and 94% of the variance in daily maximum nTw; minimum nTw were predicted with less skill, particularly for headwater sites in summer. Downstream variations in model parameters also reflect the influence of groundwater and/or riparian shade, and prevailing weather conditions. A case is presented where an intense summer storm resulted in the propagation of a thermal wave that produced maximum Tw at some sites during hours of darkness. Hence, our findings show that Tw management by riparian shade has to be seen in a catchment wide context, with anticipated benefits normalised for weather variability, extreme rainfall events, local influence of groundwater, and channel structures.

Land use and mosquito diversity in the Peruvian Amazon.

Anthropogenic environmental disturbance is a significant factor driving mosquito community composition. However, researchers subjectively define environmental change creating difficulties for cross-study comparison. To examine the relationship between terrestrial change and mosquito composition, we used remote sensing techniques to define spatially explicit land use categories along a gradient with low (rural), medium (peri-urban), and high (urban) anthropogenic influence in the Peruvian Amazon. We found significant differences in mosquito diversity among land use categories. Our results provide baseline data linking mosquito distribution to land use in the Peruvian Amazon and present an easily replicable method of comparison for future research. Creating standardized methods to measure the impact of human influence on the environment is of particular importance in designing targeted public health policies and in predicting disease risk in rapidly changing environments such as the Amazon.

The role of risk factors in the identification of appropriate subjects for caries clinical trials: design considerations.

In seeking new and more effective therapies to delay or prevent caries development, investigators must design clinical trials focused on high-risk populations with a predictable incidence of caries over a limited period of time. In children and adolescents, the strongest predictors of caries incidence appear to be baseline levels of caries activity (present caries, e.g., dmfs, DMFT, caries lesions in first molars). Other predictors of caries risk typically include oral hygiene level, counts of cariogenic micro-organisms in plaque and saliva, fluoride history, sucrose intake, and parent's socio-economic level. This paper will briefly review existing literature to address the most useful and relevant prognostic factors for predicting future caries onset. The relative merits of identifying high-risk subjects based on these factors, either singly or in combination, will be explored in terms of statistical efficiency. Particular attention will focus on the advantages of covariate adjustment in the context of survival-based methods for the analysis of caries data. Further, with the advent of more sophisticated diagnostic procedures (e.g., quantitative light fluorescence) to screen and monitor study subjects for caries activity, there is the potential for earlier states of lesion initiation and progression (or regression) to be detected, with, therefore, improved experimental sensitivity to treatment effects. The validity of risk assessment and outcome measurement on the basis of these new diagnostic tools vs. more conventional methods will be examined.

Safety of controlled-onset extended-release verapamil in middle-aged and older patients with hypertension and coronary artery disease.

BACKGROUND: Our purpose was to study the safety of controlled-onset, extended-release (COER) verapamil in patients with hypertension or coronary artery disease, with a focus on elderly patients. METHODS: Adverse event data were pooled from 7 double-blind, multicenter, randomized trials including 1999 patients with hypertension or chronic stable angina pectoris. There were 1042 patients who received COER verapamil 180 to 540 mg once daily in the evening for up to 10 weeks, 373 patients who received placebo, and 584 who received an active comparator agent. Data were analyzed according to the following groups: all patients, patients with hypertension, patients with angina, older patients (>/=65 years old), and younger patients (<65 years old). Adverse event rates were compared across the treatment groups by the Fisher exact test. RESULTS: In all patients combined, the incidence of constipation (13% vs 2%), dizziness (6% vs 2%), and back pain (3% vs 1%) was higher in patients treated with COER verapamil than with placebo. Patients with hypertension had more back pain (4% vs 1%) and constipation (12% vs 1%) with COER verapamil than with placebo, whereas patients with angina had more bradycardia (2.6% vs 0%), dizziness (8% vs 2%), and constipation (15% vs 3%). Older patients treated with COER verapamil had more bradycardia, constipation, dizziness, and fatigue and had fewer headaches compared with younger patients treated with COER verapamil. Second- or third-degree atrioventricular block was not observed after administration of COER verapamil in any subgroup. CONCLUSION: These data demonstrate that COER verapamil has an acceptable safety profile that is largely unrelated to age in patients with hypertension or coronary artery disease.

1,4-Benzodiazepine peripheral cholecystokinin (CCK-A) receptor agonists.

A series of 1,4-benzodiazepines, N-1-substituted with an N-isopropyl-N-phenylacetamide moiety, was synthesized and screened for CCK-A agonist activity. In vitro agonist activity on isolated guinea pig gallbladder along with in vivo induction of satiety following intraperitoneal administration in a rat feeding assay was demonstrated.

Chronotherapeutic delivery of verapamil in obese versus non-obese patients with essential hypertension.

BACKGROUND: The effect of controlled-onset, extended-release (COER) verapamil on haemodynamic parameters in obese and non-obese patients is evaluated in this analysis. METHODS: Data were pooled from three clinical trials evaluating efficacy and tolerability of COER-verapamil. Hypertensive men and women (stage I to III) were randomised to COER-verapamil (180-540 mg at bedtime) or placebo for 4-8 weeks and stratified according to body mass index (BMI-obese > 28 kg/m2). Efficacy was assessed as change from baseline in blood pressure (BP), heart rate, and rate-pressure product during four time periods throughout the dosing interval. Safety and tolerability were assessed by monitoring all adverse events and changes in metabolic laboratory parameters. RESULTS: Reductions in all haemodynamic parameters were significantly greater following COER-verapamil compared with placebo for all time periods. The haemodynamic effects of COER-verapamil in obese (n = 166, BMI = 32.8 kg/m2) and non-obese patients (n = 115, BMI = 25.0 kg/m2) were similar. COER-verapamil was well tolerated in both subgroups, but the incidence of constipation was significantly less in obese patients (P < 0.001). CONCLUSIONS: COER-verapamil is effective in reducing BP, heart rate, and rate-pressure product independently of BMI.

Gender and age effects on the ambulatory blood pressure and heart rate responses to antihypertensive therapy.

BACKGROUND: The aim of this study was to assess potential differences in the 24-h antihypertensive response to treatment with the controlled-onset, extended-release (COER) calcium antagonist, verapamil in men versus women and older versus younger patients with hypertension. METHODS: Meta-analyses were performed of three prospective randomized, double-blind, placebo-controlled trials with COER-verapamil in patients with mid-stage I to stage III essential hypertension. The trials were conducted at medical clinics in the US and Canada in patients with a mean office diastolic blood pressure (BP) of 95 to 115 mm Hg on 2 consecutive weeks and a mean daytime diastolic BP >90 mm Hg. Patients were randomized to treatment with 180 to 540 mg/day of COER-verapamil (N = 273) or placebo (N = 125). Changes from baseline in ambulatory BP and heart rate after COER-verapamil were compared in men versus women and in older versus younger patients. RESULTS: Treatment with COER-verapamil caused significant reductions in 24-h and early-morning systolic and diastolic BP in all of the subpopulations as compared with placebo (P < .001). COER-verapamil induced a greater reduction in both 24-h systolic (-15.1 v -10.0 mm Hg; P < .001) and diastolic (-10.4 v -8.2 mm Hg; P = .003) BP in women compared with men. Older patients showed a greater mean reduction in 24-h diastolic BP (-10.2 v -8.2 mm Hg; P < .05) and heart rate (-5.7 v -4.4 beats/min; P < .05) compared with younger patients. Side effects were similar in all of the COER-verapamil treatment groups. CONCLUSIONS: Both gender and age were significant determinants of the response to COER-verapamil. The antihypertensive effect of verapamil is greater in women than in men and in older patients compared with younger patients.

Outcomes of older persons receiving rehabilitation for medical and surgical conditions compared with hip fracture and stroke.

OBJECTIVE: Older persons with general medical and surgical conditions increasingly receive posthospital rehabilitation care in nursing homes and rehabilitation hospitals. This study describes the characteristics of such patients, contrasted with patients with traditional rehabilitation diagnoses of hip fracture and stroke. DESIGN: Prospective cohort study. SETTING: Seventeen skilled nursing facilities and six rehabilitation hospitals in seven states. PARTICIPANTS: Medicare patients age 65 or older receiving posthospital rehabilitation. METHODS: A total of 290 medical/surgical patients were compared with 336 hip fracture and 429 stroke patients. Data were collected prospectively from charts, nursing assessments, and patient interviews. Patient characteristics associated with functional recovery and mortality were estimated using multivariate regression. RESULTS: Medical/surgical patients had greater premorbid activities of daily living (ADL) (P < .001) and instrumental activities of daily living (IADL) (P < .01) disability, but suffered less decline with the acute event than hip fracture or stroke patients (P < .001). Medical/surgical patients were more likely to recover premorbid ADL function (P < .05) but 1-year mortality was significantly greater (30% vs. 14% hip fracture; 18% stroke; P < .001). Predictors of functional recovery and mortality differed between the three groups. Among medical/surgical patients, premorbid ADL difficulty, cognitive impairment, a pressure ulcer at rehabilitation admission, and depression were associated with failure to recover premorbid function whereas increasing comorbidity and incontinence were associated with mortality. CONCLUSIONS: Medical/surgical patients represent a unique rehabilitation population. They experienced greater premorbid functional disability, less acute decline, but greater mortality than patients with traditional rehabilitation diagnoses. Further study of this distinct rehabilitation population may help identify patients most likely to benefit from rehabilitation.

The clinical value of ferric ammonium citrate: a positive oral contrast agent for T1-weighted MR imaging of the upper abdomen.

This study was undertaken to determine whether ferric ammonium citrate (FAC), a positive magnetic resonance (MR) contrast agent, is of clinical value in demonstrating or excluding pathology of the upper gastrointestinal tract. A retrospective review was performed of pre- and post-FAC studies of MR examinations in 203 patients from phase II and III clinical trials in whom final diagnoses had been established based on the results of biopsy, surgery, or independent imaging procedures. Two independent reviewers made randomized and blinded assessments of the stomach, duodenum, and pancreas. FAC significantly increased the certainty of diagnosis for normal studies of the stomach and duodenum for both readers (P < 0.001) and for abnormal studies of the stomach for one reader (P = 0.004). FAC also significantly increased the certainty of diagnosis for normal pancreas for one reader (P < 0.001). FAC significantly (P < 0.001) increased accuracy and specificity for diagnoses involving the stomach and duodenum for both readers and for one reader for the pancreas. There was significant improvement in sensitivity for gastric diagnoses (P = 0.013) for one reader but not for the duodenum or pancreas. We conclude that FAC is helpful in demonstrating and excluding upper gastrointestinal pathology on MR.

Circadian heart rate response to chronotherapy versus conventional therapy in patients with hypertension and myocardial ischemia.

BACKGROUND: Changes in heart rate (HR) may contribute to the higher incidence of cardiovascular events in the morning. HYPOTHESIS: The objectives of this analysis were to assess HR patterns in two populations (patients with chronic stable angina or stage I to III hypertension) and to compare the effects of various antianginal and antihypertensive treatments on HR. METHODS: This was a retrospective analysis of HR data from two clinical trials evaluating the efficacy of controlled-onset, extended-release (COER)-verapamil. The effects of COER-verapamil were compared with placebo, nifedipine gastrointestinal therapeutic system (GITS), amlodipine, and the combination of amlodipine and atenolol. RESULTS: In patients with angina (n = 498), the change from baseline in HR following 4 weeks of treatment was -6.7 +/- 10.5 beats/min in the COER-verapamil group, -10.8 +/- 10.8 beats/min in the amlodipine/atenolol group, + 2.5 +/- 9.1 beats/ min in the amlodipine monotherapy group, and -1.3 +/- 10.5 beats/min in the placebo group (p<0.001). Data were stratified based on whether patients experienced asymptomatic ischemia during baseline ambulatory electrocardiographic monitoring. The circadian HR pattern was morphologically similar in all groups; however, differences in the magnitude of HR response were evident. In the subset of patients with asymptomatic ischemia (n = 101), treatment with amlodipine monotherapy increased HR compared with placebo. In this same subset of patients, HR reductions were achieved with COER-verapamil and amlodipine/atenolol. In patients with hypertension (n = 557), the change in HR following 10 weeks of treatment was -3.3 beats/min for patients treated with COER-verapamil compared with + 2.0 beats/min for patients treated with nifedipine GITS (p < 0.0001, between-group differences). CONCLUSION: This analysis demonstrates that morphologically similar circadian patterns of HR occur in both hypertensive patients and those with angina. In addition, significant variation exists among antianginal and antihypertensive agents regarding HR effects.

Project GRAD: two-year outcomes of a randomized controlled physical activity intervention among young adults. Graduate Ready for Activity Daily.

INTRODUCTION: Project Graduate Ready for Activity Daily evaluated a program to promote physical activity through the transition of university graduation in a randomized controlled trial. METHODS: Three hundred thirty-eight university seniors participated in either a cognitive-behavioral intervention course or a knowledge-oriented general health course during the semester before graduation. Behaviorally oriented phone and mail follow-up was delivered to the intervention group for 18 months. Physical activity outcomes and mediating variables were assessed at baseline, 1 and 2 years (93% retention rate). RESULTS: There were no significant intervention effects on physical activity outcomes at 2 years for either men or women. Experiential and behavioral processes of change were significantly improved for intervention women over 2 years. CONCLUSIONS: Despite excellent participation in a theoretically based, well-attended intervention, few long-term effects on physical activity or its mediators were found. Additional research is needed to determine optimal interventions for physical activity and to validate or alter current behavior change theory.

Patients' perceptions of physicians' recommendations for comfort care differ by patient age and gender.

OBJECTIVE: To determine patient characteristics associated with patient and proxy perceptions of physicians' recommendations for life-prolonging care versus comfort care, and with acceptance of such recommendations. DESIGN: Cross-sectional. SETTING: Five teaching hospitals in Denver, Colo. PATIENTS: We studied 239 hospitalized adults believed by physicians to have a high likelihood of dying within 6 months. MEASUREMENTS AND MAIN RESULTS: Interviews with patients or proxies were conducted to determine perceptions of physicians' recommended goal of care and roles in decision making. RESULTS: Patients' mean age was 66.6 years; 44% were women. In adjusted analysis, age greater than 70 years and female gender were associated with a higher likelihood of believing that comfort care had been recommended by the physician (odds ratio [OR], 3.70; 95% confidence interval [CI], 1.89 to 7.24; OR, 1.99; 95% CI, 1.04 to 3. 84, respectively). Patients and proxies gave substantial decision-making authority to physicians: 29% responded that physicians dominate decision making, 55% that decision making is equally shared by physicians and patients, and only 16% that patients make decisions. Increasing age was associated with an increased likelihood of believing that physicians should dominate decision making (P <.005). CONCLUSIONS: Among patients with advanced illness, perceived comfort care recommendations were related to patient age and gender, raising concern about possible gender and age bias in physicians' recommendations. Although all patients and proxies gave significant decision-making authority to physicians, older individuals were more likely to give physicians decision-making authority, making them more vulnerable to possible physician bias.

Effects of the chronotherapeutic delivery of verapamil on circadian blood pressure in African-American patients with hypertension.

OBJECTIVE: To evaluate the effects of COER-verapamil on circadian blood pressure (BP) and heart rate in African-American patients with hypertension. DESIGN: Retrospective pooled analyses of efficacy and tolerability data from three prospective, randomized, double-blind, placebo-controlled trials with COER-verapamil in hypertension. PATIENTS/PARTICIPANTS: Sixty-eight African-American patients with stages I-III hypertension (seated diastolic BP, 95-114 mm Hg) were randomized to receive placebo or treatment with 180-540 mg of COER-verapamil once daily at bedtime for 4 to 8 weeks. METHODS: Using ambulatory monitoring, efficacy was assessed by measuring change from baseline in systolic and diastolic BP, heart rate, and the heart rate-systolic pressure product during three time intervals: early morning (0600 to 1000), daytime (0800 to 2200), and nighttime (2200 to 0800). Changes also were compared to data from the non-African-American population. Adverse effects were tabulated at each visit. RESULTS: Mean changes from baseline in early-morning BP, heart rate, and rate-pressure product for patients treated with COER-verapamil were -13.8/-11.2 mm Hg, -6.2 beats/minute, and -1960 mm Hg-beats/min, respectively (P<0.01 for all parameters compared to placebo). Significant and similar reductions also were observed for daytime and nighttime BP, heart rate, and the rate-pressure product. The incidence of side effects in the COER-verapamil-treated patients was similar to placebo and the African-American patients had similar incidences to the non-African-American patients. CONCLUSIONS: The chronotherapeutic delivery of verapamil significantly reduced circadian BP, heart rate, and the rate-pressure product. The side effect profile of COER-verapamil was similar to that of placebo. Thus, this therapy for delivery of a heart-rate lowering calcium channel blocker is a useful antihypertensive strategy for African-American patients with hypertension.

Potential mediators of change in a physical activity promotion course for university students: Project GRAD.

The purpose of the study is to evaluate the performance of theoretically-derived mediators of health behavior change. Participants were university seniors (184 females; 154 males) randomly assigned to an intervention course designed to promote physical activity or to a control course. Five physical activity outcomes and nine psychosocial mediating variables were assessed at baseline and the end of the 16-week course. For women, the intervention had significant effects on five of the mediators, including self-efficacy for making time, self-efficacy for resisting relapse, social support from friends, and experiential and behavioral processes of change. Among men, the intervention improved use of behavioral processes of change but also had the unintended effect of increasing perceived barriers to activity. For women, significant contributors to regressions explaining physical activity change were social support from friends (for total activity) and change in self-efficacy for resisting relapse (for vigorous exercise). For men, significant explanatory variables included change in enjoyment (for total activity), change in self-efficacy for resisting relapse (for strength exercise), and change in benefits (for moderate intensity activity). For both sexes, there were significant findings in the unexpected direction. Across the five physical activity outcomes, hypothesized mediators were inconsistent and weak contributors to the models. Investigating mediators of behavior change has the potential to stimulate improvements in theories and interventions.

Evaluation of a university course to promote physical activity: project GRAD.

Project GRAD (Graduate Ready for Activity Daily) evaluates a university course to promote physical activity. In a randomized study, 338 university seniors participated in either an intervention or control course for academic credit, and posttest data were collected on 321. The control course was knowledge-oriented. The intervention course taught behavior change skills in weekly lectures and peer-led labs. Physical activity was assessed with 7-Day Physical Activity Recall interviews. The intervention had no significant effects on men. Among women, the intervention increased total physical activity during leisure, strengthening exercises, and flexibility exercise. This university course had the intended effects of promoting healthful patterns of physical activity among women, but no effects were observed on men, who were more active than women at baseline.

Sulfated cholecystokinin (26-33) induces mild taste aversion conditioning in rats when administered by three different routes.

We investigated the ability of sulfated cholecystokinin (26-33) (CCK-8) and cholecystokinin (30-33) (CCK-4) to induce taste aversion or avoidance conditioning (TAC) in a one-bottle testing paradigm after either intravenous (i.v.), intracerebroventricular (i.c.v.), or intraperitoneal (i.p.) administration. Significant TAC was induced by i.p. administration of CCK-8 at 0.1 but not at 0.025, 0.5, or 1.0 micromol/kg; the TAC was not robust and, in this case, not even dose related. I.p. administration of CCK-4 at 0.05, 0.1, 0.5, or 1.0 micromol/kg did not induce TAC, replicating other studies from our lab. Mild but significant TAC was also induced by i.v. administration of CCK-8 (at 0.025 and 1.0 but not 0.1 or 0.5 micromol/kg) but not by i.v. administration of CCK-4 (at 0.05, 0.1, 0.5, or 1.0 micromol/kg). Finally, mild but significant TAC was induced by i.c.v. (i.e., lateral ventricular) administration of CCK-8 (at 0.0015 but not at 0.015 micromol/brain) but not by i.c.v. administration of CCK-4 (at 0.005 or 0.010 micromol/brain). Because CCK-4 failed to induce TAC, CCK-8 apparently induced TAC via all three routes by an action at a CCK(a), not CCK(B), receptor mechanism. Because i.c.v. or i.v. administrations of CCK-8 were not more efficacious than i.p. administration, the taste avoidance induced by i.p. administration of CCK-8 was not so mild simply because it failed to reach a critical central locus adequately or because it failed to be delivered at a critical speed (i.e., via i.v. injections). We demonstrate that CCK-8 can induce mild TAC at either peripheral or central sites and suggest that these effects of CCK-8 may be independent and may be a sign of salience but not necessarily of toxicosis.