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Biomedical subjects

Ronald A Thisted

Publications and source records attributed to Ronald A Thisted.

16 recordsLinked to original sources
PubMed2006

Randomized, controlled trial of dextromethorphan/quinidine for pseudobulbar affect in multiple sclerosis.

OBJECTIVE: To evaluate the efficacy and safety of DM/Q (capsules containing dextromethorphan [DM] and quinidine [Q]) compared with placebo, taken twice daily, for the treatment of pseudobulbar affect over a 12-week period in multiple sclerosis patients. METHODS: A total of 150 patients were randomized in a double-blind, placebo-controlled study to assess pseudobulbar affect with the validated Center for Neurologic Study-Lability Scale. Each patient also recorded the number of episodes experienced between visits, estimated quality of life and quality of relationships on visual analog scales, and completed a pain rating scale. RESULTS: Patients receiving DM/Q had greater reductions in Center for Neurologic Study-Lability Scale scores than those receiving placebo (p < 0.0001) at all clinic visits (days 15, 29, 57, and 85). All secondary end points also favored DM/Q, including the number of crying or laughing episodes (p <or= 0.0077), quality of life (p < 0.0001), quality of relationships (p = 0.0001), and pain intensity score (p = 0.0271). DM/Q was well tolerated; only dizziness occurred with greater frequency than with placebo. INTERPRETATION: Results in multiple sclerosis patients were similar to those of a previous study in amyotrophic lateral sclerosis, demonstrating that DM/Q may be beneficial in treating potentially disabling pseudobulbar affect in a variety of neurological disorders.

Affect↗
PubMed2006

Dextromethorphan and quinidine in adult patients with uncontrolled painful diabetic peripheral neuropathy: a 29-day, multicenter, open-label, dose-escalation study.

BACKGROUND: Pain associated with diabetic peripheral neuropathy (DPN) has a substantial negative impact on patients' quality of life. OBJECTIVES: The primary objective of this study was to evaluate the tolerability of capsules containing dextromethorphan (DM) and quinidine (Q) in patients with painful DPN. A secondary objective was to perform a preliminary assessment of the efficacy of DM/Q in this patient population. METHODS: This was a multicenter, open-label, dose-escalation study. Eligible patients were aged between 18 and 80 years, had a confirmed diagnosis of diabetes with acceptable glycemic control, had been receiving established diabetic therapy for at least 3 months, and had a clinical diagnosis of distal symmetric sensory neuropathy with daily DPN-associated pain for the previous 3 months. On study entry, patient-rated diabetic pain had to be moderate or greater. Patients who met the inclusion criteria underwent a 2-week washout period during which all analgesics were discontinued, followed by 29 days of treatment with capsules containing DM 30 mg and Q 30 mg (DM30/Q30), beginning with 1 capsule/d and escalating at approximately 1-week intervals, as tolerated, to a maximum dose of 4 capsules/d (DM120/Q120). Tolerability was assessed based on adverse events and changes in clinical and laboratory parameters and nerve conduction velocity. Preliminary efficacy assessments included changes from baseline in scores on the pain intensity rating scale (PIRS), pain relief rating scale (PRRS), peripheral neuropathy quality-of-life instrument, and patients' diary assessments of sleep, present pain intensity, pain, and activity. RESULTS: The study included 36 men and women (mean age, 58 years; mean body mass index, 32.8 kg/m(2)). Of the 33 subjects who completed the study, 23 (69.7%) did so at the highest permitted dose (DM120/Q120). The most commonly reported adverse events (occurring in > or =5% of subjects) were nausea (27.8%), dizziness (25.0%), and headache (25.0%). Three patients experienced 5 serious adverse events, only 1 of which was considered possibly related to study drug. The most commonly occurring laboratory abnormalities (involving glycosylated hemoglobin, serum glucose, triglycerides, and cholesterol) were considered typical of a population with diabetes. Improvements from baseline in scores on the PIRS, PRRS, and other exploratory efficacy measures were noted (P < 0.001). CONCLUSIONS: The results of this open-label study indicated that the combination of DMIQ (dose range, DM30/Q30-DM120/Q120) was well tolerated in patients with pain associated with DPN. Based on the preliminary efficacy results, a randomized, controlled, double-blind trial is warranted to assess the tolerability and efficacy of this combination in patients with DPN.

Adult↗
PubMed2006

Loneliness as a specific risk factor for depressive symptoms: cross-sectional and longitudinal analyses.

The extent to which loneliness is a unique risk factor for depressive symptoms was determined in 2 population-based studies of middle-aged to older adults, and the possible causal influences between loneliness and depressive symptoms were examined longitudinally in the 2nd study. In Study 1, a nationally representative sample of persons aged 54 and older completed a telephone interview as part of a study of health and aging. Higher levels of loneliness were associated with more depressive symptoms, net of the effects of age, gender, ethnicity, education, income, marital status, social support, and perceived stress. In Study 2, detailed measures of loneliness, social support, perceived stress, hostility, and demographic characteristics were collected over a 3-year period from a population-based sample of adults ages 50-67 years from Cook County, Illinois. Loneliness was again associated with more depressive symptoms, net of demographic covariates, marital status, social support, hostility, and perceived stress. Latent variable growth models revealed reciprocal influences over time between loneliness and depressive symptomatology. These data suggest that loneliness and depressive symptomatology can act in a synergistic effect to diminish well-being in middle-aged and older adults.

Aged↗
PubMed2005

The prognostic value of a nomogram for exercise capacity in women.

BACKGROUND: Recent studies have demonstrated that exercise capacity is an independent predictor of mortality in women. Normative values of exercise capacity for age in women have not been well established. Our objectives were to construct a nomogram to permit determination of predicted exercise capacity for age in women and to assess the predictive value of the nomogram with respect to survival. METHODS: A total of 5721 asymptomatic women underwent a symptom-limited, maximal stress test. Exercise capacity was measured in metabolic equivalents (MET). Linear regression was used to estimate the mean MET achieved for age. A nomogram was established to allow the percentage of predicted exercise capacity to be estimated on the basis of age and the exercise capacity achieved. The nomogram was then used to determine the percentage of predicted exercise capacity for both the original cohort and a referral population of 4471 women with cardiovascular symptoms who underwent a symptom-limited stress test. Survival data were obtained for both cohorts, and Cox survival analysis was used to estimate the rates of death from any cause and from cardiac causes in each group. RESULTS: The linear regression equation for predicted exercise capacity (in MET) on the basis of age in the cohort of asymptomatic women was as follows: predicted MET = 14.7 - (0.13 x age). The risk of death among asymptomatic women whose exercise capacity was less than 85 percent of the predicted value for age was twice that among women whose exercise capacity was at least 85 percent of the age-predicted value (P<0.001). Results were similar in the cohort of symptomatic women. CONCLUSIONS: We have established a nomogram for predicted exercise capacity on the basis of age that is predictive of survival among both asymptomatic and symptomatic women. These findings could be incorporated into the interpretation of exercise stress tests, providing additional prognostic information for risk stratification.

Adult↗
PubMed2005

Prognostic value of the duke treadmill score in asymptomatic women.

The Duke Treadmill Score (DTS) has been shown to predict mortality in women who have symptomatic heart disease, but its ability to do so in asymptomatic women is unknown, as is its comparative advantage to exercise capacity. We investigated whether a decreased DTS is associated with increased mortality in a prospective cohort of 5,636 asymptomatic women. A symptom-limited exercise treadmill test using Bruce's protocol was performed at baseline. DTS was calculated using exercise time, exercise-induced angina, and ST-segment depression. Exercise capacity was measured in METs. Deaths and cause of death were identified from 1992 to 2000. After adjusting for the Framingham Risk Score, the risk of death decreased by 9% for each unit increase in DTS and by 17% for every 1-MET increase (p <0.001). Those who had a DTS <5 (moderate or high risk) had hazard ratios for death and cardiac death that were 2.2 and 2.5 times greater, respectively, than did those who had a DTS > or =5 (low risk), after adjusting for Framingham Risk Score (p <0.001). Receiver-operating characteristic curves for the DTS model and the exercise capacity model were not significantly different. In conclusion, we have demonstrated that, although the DTS is an independent predictor of mortality and cardiac mortality in asymptomatic women, it does not appear to be a better predictor than exercise capacity alone. The role of ST-segment changes and symptoms with stress testing in asymptomatic women does not provide additional prognostic information.

Adult↗
PubMed2005

The effect of physician disclosure of financial incentives on trust.

BACKGROUND: Many physicians receive financial incentives to limit their ordering of expensive tests and procedures. While Medicare mandates disclosure of incentives, it is not clear how to inform patients without undermining trust. METHODS: Our objective was to determine public opinion about physician disclosure of financial incentives and how this might be best communicated to patients. The 2002 General Social Survey included 2765 interviews from a probability sample of English-speaking US households. The interview included questions about financial incentives and an audiotaped scenario of a physician discussing the impact of financial incentives on ordering a magnetic resonance image. Respondents heard 1 of 6 randomly selected disclosure strategies. The measurements included ratings of trust, satisfaction, agreement with the physician's decision, and likelihood of remaining with the physician/health plan or seeking a second opinion. RESULTS: Nearly half (48.8%) of respondents had previously heard of financial incentives to limit test ordering. Of the respondents, 94.8% wanted to be told about incentives, at the time of enrollment in a health plan (80.5%), by a health plan representative (44.8%), their physician (17.1%), or both (38.1%). Of the 6 different disclosure strategies, "addressing emotions" and "negotiation" were associated with the best outcomes, while "common enemy" and "denying influences" were most negatively perceived. Black and Hispanic subjects were less likely to express satisfaction or trust and more likely to disenroll or seek a second opinion. CONCLUSIONS: The public wants information about physician financial incentives. Specific communication styles enhance how this information is conveyed to patients, increasing trust and supporting the physician-patient relationship.

Analysis of Variance↗
PubMed2005

Distinct temporal phases in the behavioral pharmacology of LSD: dopamine D2 receptor-mediated effects in the rat and implications for psychosis.

RATIONALE: The effect of LSD in humans has been described as occurring in two temporal phases. The behavioral effects in rats also occur in two temporal phases: an initial suppression of exploration followed by increased locomotor activity. OBJECTIVES: We decided to investigate this phenomenon from the perspective that the pharmacology might have relevance to the neurochemical mechanisms underlying psychosis. METHODS: Twenty-five male Sprague-Dawley rats were trained to discriminate LSD (186 nmol/kg, 0.08 mg/kg, i.p.) with a 30-min preinjection time (LSD-30, N=12) and LSD (372 nmol/kg, 0.16 mg/kg, i.p.) with a 90-min preinjection time (LSD-90, N=13) from saline, using a two-lever, food-reinforced operant conditioning task. RESULTS: LSD (186 or 372 nmol/kg, 0.08 or 0.16 mg/kg) given 30 min prior to training produced a cue that was completely antagonized by 5-HT2A antagonists and lasted no longer than 1 h. LSD (372 nmol/kg, 0.16 mg/kg) injected 90 min before training produced a cue that was not fully blocked by 5-HT2A antagonists, but instead was significantly inhibited by haloperidol. In these rats, substitution no longer occurred with the 5-HT2 agonists DOI or LSD (30 min preinjection), but full substitution was obtained with the D2 agonists apomorphine, N-propyldihydrexidine, and quinelorane. CONCLUSION: The discriminative stimulus effect of LSD in rats occurs in two phases, and these studies provide evidence that the later temporal phase is mediated by D2 dopamine receptor stimulation. A second temporal phase that involves dopaminergic pathways would be consistent with the widespread belief that excessive dopaminergic activity may be an underlying cause of paranoid psychosis.

Amphetamine↗
PubMed2005

Not all patients want to participate in decision making. A national study of public preferences.

BACKGROUND: The Institute of Medicine calls for physicians to engage patients in making clinical decisions, but not every patient may want the same level of participation. OBJECTIVES: 1) To assess public preferences for participation in decision making in a representative sample of the U.S. population. 2) To understand how demographic variables and health status influence people's preferences for participation in decision making. DESIGN AND PARTICIPANTS: A population-based survey of a fully representative sample of English-speaking adults was conducted in concert with the 2002 General Social Survey (N= 2,765). Respondents expressed preferences ranging from patient-directed to physician-directed styles on each of 3 aspects of decision making (seeking information, discussing options, making the final decision). Logistic regression was used to assess the relationships of demographic variables and health status to preferences. MAIN RESULTS: Nearly all respondents (96%) preferred to be offered choices and to be asked their opinions. In contrast, half of the respondents (52%) preferred to leave final decisions to their physicians and 44% preferred to rely on physicians for medical knowledge rather than seeking out information themselves. Women, more educated, and healthier people were more likely to prefer an active role in decision making. African-American and Hispanic respondents were more likely to prefer that physicians make the decisions. Preferences for an active role increased with age up to 45 years, but then declined. CONCLUSION: This population-based study demonstrates that people vary substantially in their preferences for participation in decision making. Physicians and health care organizations should not assume that patients wish to participate in clinical decision making, but must assess individual patient preferences and tailor care accordingly.

Adult↗
PubMed2004

Postoperative maintenance of Crohn's disease remission with 6-mercaptopurine, mesalamine, or placebo: a 2-year trial.

BACKGROUND & AIMS: No therapy has been shown to reliably prevent the evolution of postoperative recurrence of Crohn's disease. The aim of the current trial was to compare 6-mercaptopurine (6-MP) and mesalamine with placebo for the prevention of clinical, endoscopic, and radiographic recurrence of Crohn's disease after resection and ileocolic anastomosis. METHODS: Five centers randomized 131 patients to receive 6-MP (50 mg), mesalamine (3 g), or placebo daily in a double-blind, double-dummy trial. Patients had clinical assessments at 7 weeks and then every 3 months; colonoscopy at 6, 12, and 24 months; and small bowel series at 12 and 24 months. End points were clinical, endoscopic, and radiographic recurrence rates at 24 months. RESULTS: Clinical recurrence rates (intent to treat) by life-table analysis at 24 months were 50% (95% confidence interval [CI], 34%-68%), 58% (95% CI, 41%-75%), and 77% (95% CI, 61%-91%) in patients receiving 6-MP, mesalamine, and placebo, respectively. Endoscopic recurrence rates were 43% (95% CI, 28%-63%), 63% (95% CI, 47%-79%), and 64% (95% CI, 46%-81%), and radiographic recurrence rates were 33% (95% CI, 19%-54%), 46% (95% CI, 29%-66%), and 49% (95% CI, 30%-72%), respectively. 6-MP was more effective than placebo ( P < 0.05) at preventing clinical and endoscopic recurrence over 2 years. Patient withdrawals resulted in 69% of the study population evaluable for the clinical recurrence end point. CONCLUSIONS: 6-MP, 50 mg daily, was more effective than placebo at preventing postoperative recurrence of Crohn's disease and should be considered as a maintenance therapy after ileocolic resection.

Adult↗
PubMed2004

Validation of the CNS emotional lability scale for pseudobulbar affect (pathological laughing and crying) in multiple sclerosis patients.

Pseudobulbar affect (PBA) or pathological laughing and crying (PLC) is a disorder of affect that occurs in about 10% of multiple sclerosis (MS) patients. The objective of this study was to validate the CNS Emotional Lability Scale (CNS-LS) in MS patients and to correlate the results with the frequency and intensity of episodes of PLC. Physicians at seven private practice referral centers in the United States made a diagnosis concerning PLC based on patient interviews. Clinical coordinators separately administered the CNS-LS, a self-report measure of PLC with seven questions, to MS patients, including patients known to exhibit PLC, patients thought to be free of PLC, and newly diagnosed patients where PLC status was unknown, and the physician was blinded as to the results. A receiver operating characteristic (ROC) curve analysis was performed to define a cut-off best correlating with the physician's diagnosis. Of 90 MS patients selected to complete the survey, 50 were physician diagnosed with PLC; 40 were without PLC, and 15 of these 90 patients were newly diagnosed with MS (<6 months). Scores of 17 or higher corresponded to a sensitivity of 0.94 and a specificity of 0.83 (LR+ = 5.5, LR- = 0.07); 89% of patients were correctly diagnosed. The area under the ROC curve was 0.95. Symptoms were greater in patients diagnosed as PLC than in non-PLC patients as evidenced by mean number of episodes/week, number of days/week with episodes, duration of an episode and total time in an episode. Similar results were observed if patients were classified as PLC or non-PLC according to CNS-LS score > or = 17, suggesting that the CNS-LS is a valid measure for the assessment of PLC in MS patients and could be a useful instrument for clinical and research purposes.

Adult↗
PubMed2003

Exercise capacity and the risk of death in women: the St James Women Take Heart Project.

BACKGROUND: Cardiovascular disease is the leading cause of death among women and accounts for more than half of their deaths. Women have been underrepresented in most studies of cardiovascular disease. Reduced physical fitness has been shown to increase the risk of death in men. Exercise capacity measured by exercise stress test is an objective measure of physical fitness. The hypothesis that reduced exercise capacity is associated with an increased risk of death was investigated in a cohort of 5721 asymptomatic women who underwent baseline examinations in 1992. METHODS AND RESULTS: Information collected at baseline included medical and family history, demographic characteristics, physical examination, and symptom-limited stress ECG, using the Bruce protocol. Exercise capacity was measured in metabolic equivalents (MET). Nonfasting blood was analyzed at baseline. A National Death Index search was performed to identify all-cause death and date of death up to the end of 2000. The mean age of participants at baseline was 52+/-11 years. Framingham Risk Score-adjusted hazards ratios (with 95% CI) of death associated with MET levels of <5, 5 to 8, and >8 were 3.1 (2.0 to 4.7), 1.9 (1.3 to 2.9), and 1.00, respectively. The Framingham Risk Score-adjusted mortality risk decreased by 17% for every 1-MET increase. CONCLUSIONS: This is the largest cohort of asymptomatic women studied in this context over the longest period of follow-up. This study confirms that exercise capacity is an independent predictor of death in asymptomatic women, greater than what has been previously established among men. The implications for clinical practice and health care policy are far reaching.

Cardiovascular Diseases↗
PubMed2003

Causes and consequences of kidney loss in patients with nephrolithiasis.

BACKGROUND: It is unknown whether stone formers may safely donate a kidney. Nephrectomy could accelerate stone formation, or loss of filtration with age. We contrast, here, the course of stone patients with two versus one kidney. METHODS: One hundred fifteen patients with a single functioning kidney were compared with 3151 patients with two kidneys. Cause of kidney loss was determined, along with stone types, rates of stone formation, urine stone risk factors, and creatinine clearance. RESULTS: Women were 49.6% of the patients with kidney loss, compared to 33.6% of ordinary stone formers. Obstruction, stone burden, and infection were the most common reasons for kidney loss. We found an increased number of struvite and calcium phosphate stones among single kidney patients. Before and during treatment, single kidney patients had fewer stones than ordinary stone formers. Creatinine clearance was lower in the single kidney patients; rate of loss of kidney function with age was higher among single kidney males versus two kidney males if all patients are considered. Among males >age 45 years, the difference disappears. Females with one and two kidneys lost function with age at equivalent rates. Compared with nonstone formers, male stone formers lose kidney function with age at an accelerated rate. CONCLUSION: Nephrectomy does not worsen stone disease. It may increase loss of renal function among younger males. The pattern of renal function loss with age differs between stone formers and nonstone formers.

Adult↗
PubMed2003

Are there social determinants of health and disease?

The concept of a determinant is tied to the idea of a mechanism for action. Ideas from epidemiology, particularly the epidemiologic triad of agent, host, and environment, can help to make sense of factors that affect the absence of disease or that interfere with a mechanism that alters health. However, assembling convincing evidence for the existence of social determinants of health is a challenge, in part because of the difficulties of bridging the social and biological realms. While social contexts are measured using aggregates of individuals, disease and dysfunction occur at the individual level, leading to difficult problems of ecological inference. Although social factors have been shown to be associated with differences in mortality from specific causes, these factors account for only a small portion of the mortality from any individual cause. This suggests that the pathways through which social factors influence health are affected by their interactions with other factors.

Female↗
PubMedDate not supplied

The effects of morphine on human articular cartilage of the knee: an in vitro study.

PURPOSE: The purpose of this study was to determine the metabolic, histologic, and ultrastructural effects of morphine and its combination with saline and bupivacaine on human articular cartilage. TYPE OF STUDY: In vitro study. METHODS: Nonfibrillated human articular cartilage was harvested and transferred into an experimental culture consisting of a control medium, saline, or a combination of morphine/saline or morphine/saline/bupivacaine for 12, 24, or 72 hours. Each sample was radiolabeled to assess proteoglycan synthesis. Histologic and ultrastructural effects were also examined. RESULTS: We found a significant, dose-related, transient decrease in 35SO4 incorporation in the morphine/saline samples at 12 hours, and in the saline only samples at 24 hours. We found no evidence of histologic or ultrastructural damage to the cartilage. CONCLUSIONS: Morphine and saline can both produce a transient decrease in 35SO4 incorporation that normalizes by 72 hours. This study does not suggest any contraindication to the use of intra-articular morphine as a postoperative analgesic.

Analgesics, Opioid↗