Kinetics of chloral hydrate and its metabolites in male human volunteers.

Chloral hydrate (CH) is a short-lived intermediate in the metabolism of trichloroethylene (TRI). TRI, CH, and two common metabolites, trichloroacetic acid (TCA) and dichloroacetic acid (DCA) have been shown to be hepatocarcinogenic in mice. To better understand the pharmacokinetics of these metabolites of TRI in humans, eight male volunteers, aged 24-39, were administered single doses of 500 or 1,500 mg or a series of three doses of 500 mg given at 48 h intervals, in three separate experiments. Blood and urine were collected over a 7-day period and CH, DCA, TCA, free trichloroethanol (f-TCE), and total trichloroethanol (T-TCE=trichloroethanol and trichloroethanol-glucuronide [TCE-G]) were measured. DCA was detected in blood and urine only in trace quantities (<2 microM). TCA, on the other hand, had the highest plasma concentration and the largest AUC of any metabolite. The TCA elimination curve displayed an unusual concentration-time profile that contained three distinct compartments within the 7-day follow-up period. Previous work in rats has shown that the complex elimination curve for TCA results largely from the enterohepatic circulation of TCE-G and its subsequent conversion to TCA. As a result TCA had a very long residence time and this, in turn, led to a substantial enhancement of peak concentrations following the third dose in the multiple dose experiment. Approximately 59% of the AUC of plasma TCA following CH administration is produced via the enterohepatic circulation of TCE-G. The AUC for f-TCE was found to be positively correlated with serum bilirubin concentrations. This effect was greatest in one subject that was found to have serum bilirubin concentrations at the upper limit of the normal range in all three experiments. The AUC of f-TCE in the plasma of this individual was consistently about twice that of the other seven subjects. The kinetics of the other metabolites of CH was not significantly modified in this individual. These data indicate that individuals with a more impaired capacity for glucuronidation may be very sensitive to the central nervous system depressant effects of high doses of CH, which are commonly attributed to plasma levels of f-TCE.

The effects of soy milk and isoflavone supplements on cognitive performance in healthy, postmenopausal women.

RATIONALE: The decline in estrogen concentrations in women after menopause can contribute to health related changes including impairments in cognition, especially memory. Because of the health concerns related to hormone replacement therapy (HRT), alternative approaches to treat menopausal symptoms, such as nutritional supplements and/or diet containing isoflavones, are of interest. OBJECTIVES: This study investigated whether soy isoflavones (soy milk and supplement) could improve cognitive functioning in healthy, postmenopausal women. PARTICIPANTS, INTERVENTION AND DESIGN: A total of 79 postmenopausal women, 48-65 years of age, completed a double-blind, placebo-controlled trial in which they were randomly assigned to one of three experimental groups: cow's milk and a placebo supplement (control); soy milk and placebo supplement (soy milk, 72 mg isoflavones/day); or cow's milk and isoflavone supplement (isoflavone supplement, 70 mg isoflavones/day). MEASUREMENTS: Cognitive functioning was assessed using various cognitive tasks before the intervention (baseline) and after the intervention (test). RESULTS: In contrast to predictions, soy isoflavones did not improve selective attention (Stroop task), visual long-term memory (pattern recognition), short-term visuospatial memory (Benton Visual Retention Test), or visuo-spatial working memory (color match task). Also, the soy milk group showed a decline in verbal working memory (Digit Ordering Task) compared to the soy supplement and control groups. CONCLUSION: Soy isoflavones consumed as a food or supplement over a 16-week period did not improve or appreciably affect cognitive functioning in healthy, postmenopausal women.

Adolescent diet and breast cancer in Utah.

A population-based case-control study was conducted to assess the association between breast cancer risk, body mass index (BMI) and adolescent dietary fat and fiber consumption. Data were collected in Utah from white female cases (N = 172) and controls (N = 190) between the ages of 20 and 54 years. Odds ratios (OR) and 95% test-based confidence intervals (CI) were determined by multiple-logistic regression analysis controlling for age, education, age at menarche, and age at first pregnancy. Menopausal status was identified as an effect modifier, therefore, separate analyses were performed for pre and postmenopausal groups. An elevated risk (OR = 2.9 for highest quartile versus lowest, CI = 1.1-8.1) was associated with a larger BMI at age 12 in premenopausal women; a larger adult BMI lowered the odds ratio (OR = 0.4, CI = 0.2-1.0 for highest quartile versus lowest) in premenopausal women; BMI did not alter risk in postmenopausal women. Although not statistically significant, high fat intake consistently lowered the odds ratios below 1.0 in premenopausal women in the upper three quartiles compared to the lowest fat intake referent quartile (OR = 0.7, CI = 0.2-2.1 for highest versus lowest quartile) but was inconsistent in postmenopausal women (OR = 0.7, CI = 0.2-2.7 for highest versus lowest quartile). When fat intake was assessed by its component parts, fat from milk, cheese and yogurt reduced the odds ratios in both premenopausal (OR = 0.4, CI = 0.1-1.1 for highest versus lowest quartile) and postmenopausal women (OR = 0.2, CI = 0.0-0.8). In postmenopausal women, high fiber intake produced elevated odds ratios in all three upper quartiles (OR = 6.6, CI = 1.5-29.6 for highest versus lowest quartile), while fiber from grains resulted in a decreased risk in both premenopausal (OR = 0.2, 95% CI = 0.2-0.7 for highest versus lowest quartile) and postmenopausal women (OR = 0.7, 95% CI = 0.3-2.0). The possibility of biased estimates from low response rates (cases = 60%, controls = 61%), potential recall bias, and some lack of precision in the dietary instrument should be considered. It appears from these analyses that the relation of breast cancer to dietary intake, especially during adolescent years, is not clear, and that risk associated with fat or fiber intake may be affected by the nutrient source.

Food-consumption trends between adolescent and adult years and subsequent risk of prostate cancer.

A population-based, case-control study of prostate cancer in Utah was used to assess reported food-consumption patterns for the adolescent and adult years. Men reported eating eggs, whole milk, butter, white bread, cereals, and candy less frequently and red meat, fish, low-fat milk, cheese, yogurt, ice cream, margarine, fruits and vegetables, and whole-wheat bread more frequently as adults, indicating that diets changed in the hypothesized direction to correspond to national changes in food-consumption practices. Men who consumed a diet high in saturated fatty acids as adults were at a slightly increased risk of developing aggressive prostate cancer after adjusting for adolescent diet (odds ratio 1.8 comparing high with low intakes), whereas men who consumed a diet high in saturated fatty acids as adolescents were not at increased risk of developing these tumors after controlling for a diet high in saturated fatty acids as adults (odds ratio 1.1).

Dietary intake as a risk factor for cancer of the exocrine pancreas.

Data from 149 cases with pancreatic cancer and 363 control subjects in Utah were obtained from proxy respondents to assess the associations between dietary intake and the development of pancreatic cancer. After adjusting for cigarette smoking status and alcohol and coffee consumption, we observed that foods containing large amounts of fat from all sources increased risk of pancreatic cancer in men [odds ratio (OR), 3.41; 95% CI, 1.59-7.29]. Further division of fat by source of food showed that high intake of bacon and sausages (OR for upper tertile, 2.77; 95% CI, 1.34-5.72) as well as large intakes of fatty foods other than meat or dairy products (OR for upper tertile, 2.80; 95% CI, 1.33-5.89) increased risk of pancreatic cancer in men; high levels of intake of red meat, chicken, fish, and dairy foods did not increase risk of pancreatic cancer in either men or women. In women, fat from nonmeat and nondairy sources also increased risk of pancreatic cancer (OR for upper tertile, 3.44; 95% CI, 1.35-8.78). Although no protective effect was observed among men who consumed large amounts of fruits, vegetables, or high fiber foods, we did observe a protective effect in women for these foods (OR for upper tertile of fruit consumption, 0.37; 95% CI, 0.18-0.81; OR for upper tertile of vegetable consumption, 0.32; 95% CI, 0.13-0.74; and OR for upper tertile of fiber consumption, 0.28; 95% CI, 0.12-0.67). Findings from this study support the hypothesis that diets high in fat contribute to the development of pancreatic cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Economic outcomes with antidepressant pharmacotherapy: a retrospective intent-to-treat analysis.

Herein we describe a retrospective intent-to-treat evaluation designed to compare the natural course of antidepressant utilization and direct health service expenditures for the treatment of a single episode of major depression among patients enrolled in a multistate network-model health maintenance organization and initially prescribed either a tricyclic antidepressant (amitriptyline or nortriptyline) or the serotonin selective reuptake inhibitor (SSRI) fluoxetine. Patient-level paid-claims data for the period July 1, 1988, through December 31, 1991, were abstracted. During the above time frame, fluoxetine was the only SSRI available in the United States. Patients prescribed amitriptyline were more than three times as likely to require a change in antidepressant pharmacotherapy (OR = 3.27, 95% CI = 2.31 to 5.49), while patients prescribed nortriptyline were nearly four times more likely to change medication (OR = 3.82, 95% CI = 2.74 to 6.83) relative to patients initially prescribed fluoxetine. Consistent with our intent-to-treat design, all accrued health service expenditures were assigned to the pharmacotherapeutic option initially prescribed. Multivariate analyses revealed that initiation of antidepressant pharmacotherapy with amitriptyline resulted in a 25.7% increase in per capita depression-related health service expenditures per year, while initiation of antidepressant pharmacotherapy with nortriptyline resulted in a 28.1% increase in per capita depression-related health service expenditures per year relative to patients initially prescribed fluoxetine. A financial break-even point was achieved at the conclusion of Month 5, at which time all three intent-to-treat cohorts had comparable health service expenditures in total. From a financial perspective, results stemming from this inquiry suggest that the initiation of antidepressant pharmacotherapy with an SSRI is warranted.

Uncertainty in the diagnosis of histologically confirmed pancreatic cancer cases.

In doing a case-control study of cancer of the exocrine pancreas, a set of criteria was developed to classify cancer of the exocrine pancreas by pathological and diagnostic data as to the probability that the tumor arose in the pancreas. We applied these criteria to the records of 125 consecutive patients between the ages of 40-79 years who were identified as having adenocarcinomas of the exocrine pancreas from a population-based cancer registry. We found that histological confirmation by a cancer registry does not guarantee the site of origin is the pancreas. Of the histologically confirmed cases meeting our study criteria, 28.7% may not have arisen in the pancreas. Forty-seven per cent of non-histologically confirmed cases, which most studies exclude, were almost certainly of pancreatic origin based on computerized tomogram (CT) scan and/or surgical palpation and subsequent clinical course. These figures may underestimate the full extent of diagnostic misclassification, especially in older age groups. We conclude that epidemiological studies of cancer of the exocrine pancreas need more uniform criteria for defining cases, and these criteria should take into account uncertainty as to site of origin. Sufficient detail of our scheme is presented so it can be applied in other studies.

Differences in risk estimations from a hospital and a population-based case-control study.

A hospital-based and population-based case-control study of cervical cancer (in situ and invasive) was conducted in urban Utah to determine if methods of respondent selection affect estimates of risk for variables thought to be associated with the disease. Population cases (N = 409) and cases from two large hospitals (N = 124) were identified through the Utah Cancer Registry. Population-based controls (N = 379) were identified through random-digit dialing; hospital-based controls (N = 150) with gynaecological disorders other than cancers and elective abortions were chosen from the same hospitals as the cases for the hospital study. Both control groups were frequency matched to cases by age. Approximately 79% of the identified cases and 85% of the selected controls completed interviews conducted in their homes. Most risk estimates were lower in the hospital-based study because of the more case-like attributes of this group. Stratified analysis for social class led to adjusted risk estimates which were lower than the unadjusted risk estimates for the population-based study, but not for the hospital-based study. The close social class matching in the hospital-based study seems to have led to concurrent overmatching on other risk factors since many of these are closely related to social class. Findings are discussed in terms of implications for case-control study design.

Ipratropium bromide in the management of chronic obstructive pulmonary disease: effect on health service expenditures.

Chronic obstructive pulmonary disease (COPD), which is estimated to affect 32 million Americans, is the fifth leading cause of death in the United States. This retrospective study was designed to discern the economic utility of initial pharmacotherapy with various individual drugs in the management of COPD, as well as subsequent costs incurred as disease progression necessitated combination therapy. Data for this analysis were derived from the computer archive of a network-model health maintenance organization. During the first 6 months post-diagnosis for COPD, results indicated a significant (P < or = 0.05) increase in expenditures for physicians, hospital care, and total health service utilization for patients prescribed theophylline, a corticosteroid (triamcinolone or beclomethasone) delivered via a metered-dose inhaler, or albuterol delivered via a metered-dose inhaler as initial monotherapy compared with patients prescribed ipratropium bromide (IB) delivered via a metered-dose inhaler. Patients receiving initial pharmacotherapy with ipratropium bromide and subsequently adding albuterol used significantly less health care services (P < or = 0.05) during the first 15 months post-diagnosis for COPD than did patients prescribed all other combination therapies we evaluated.

Trends in the rate of depressive illness and use of antidepressant pharmacotherapy by ethnicity/race: an assessment of office-based visits in the United States, 1992-1997.

OBJECTIVE: This study was undertaken to determine ethnicity/race-specific (white, black, and Hispanic) population-adjusted rates of US office-based physician visits in which a diagnosis of a depressive disorder was recorded or in which a diagnosis of a depressive disorder was recorded and antidepressant pharmacotherapy was prescribed. METHODS: Data from the National Ambulatory Medical Care Survey for 1992 through 1997 were partitioned into three 2-year periods: 1992-1993, 1994-1995, and 1996-1997. For each 2-year period, data from office-based physician visits for patients aged 20 to 79 years were extracted to assess, by ethnicity/race, (1) the number of visits in which a diagnosis of a depressive illness was recorded (International Classification of Diseases, Ninth Revision, Clinical Modification codes 296.2-296.36, 300.4, or 311) and (2) the number of visits in which a diagnosis of a depressive illness was recorded and antidepressant pharmacotherapy was prescribed. We calculated ethnicity/race-specific rates (per 100 US population aged 20 to 79 years) of office-based visits in which a diagnosis of a depressive disorder was recorded and in which a diagnosis of a depressive disorder was recorded and antidepressant pharmacotherapy was prescribed. The specialty of the reporting physician and the proportion of patients receiving a selective serotonin reuptake inhibitor (SSRI) were also discerned. RESULTS: From 1992-1993 to 1996-1997, the rate of office-based visits (per 100 US population aged 20 to 79 years) in which a diagnosis of a depressive disorder was recorded increased 3.7% for whites (from 10.9 to 11.3; P = 0.001), 31.0% for blacks (from 4.2 to 5.5; P = 0.001), and 72.9% for Hispanics (from 4.8 to 8.3; P = 0.001). The rate of office-based visits in which a diagnosis of a depressive disorder was recorded and antidepressant pharmacotherapy was prescribed increased 18.5% for whites (from 6.5 to 7.7 per 100; P = 0.001), 38.5% for blacks (from 2.6 to 3.6 per 100; P = 0.001). and 106.7% for Hispanics (from 3.0 to 6.2 per 100; P = 0.001). Between 1992-1993 and 1996-1997, use of an SSRI increased among whites and blacks (from 50.0% to 65.8% and from 40.5% to 58.2%, respectively), but declined among Hispanics (from 51.4% to 48.6%; all comparisons P = 0.001). CONCLUSION: By 1996-1997, the population-adjusted rates for Hispanics were within a quartile of those observed for whites, whereas the rates for blacks remained at less than half those observed in whites. The observed divergence in population-adjusted rates by ethnicity/race may reflect the nature of the patient-physician relationship, sensitivity and specificity of diagnostic techniques and instruments, and the wider social context in which an office-based visit occurs, including access to and type of health insurance and coverage for mental health services.

Effect of pharmaceutical formulation for diltiazem on health care expenditures for hypertension.

A 1-year retrospective analysis was undertaken to discern the economic utility of providing prescription coverage for the sustained-release (SR) formulation of diltiazem, a calcium-channel antagonist, under the state of South Carolina's Medicaid program. Data for this analysis were derived from the state of South Carolina's Medicaid computer archive. The study population consisted of 347 ambulatory beneficiaries diagnosed with hypertension for whom either the SR or immediate-release (IR) formulation of diltiazem was prescribed. Multivariate regression analysis was used to discern the incremental influence of selected demographic characteristics, use of medical services prior to diagnosis for hypertension, and prescribed formulation of diltiazem on health care expenditures 1-year postdiagnosis. Patients for whom the SR formulation of diltiazem was prescribed achieved a significant (P < or = 0.05) increase in the medication possession ratio, an index of compliance (SR, 0.63 +/- 0.17) relative to patients for whom the IR formulation was prescribed (IR, 0.44 +/- 0.13). Results indicate that receipt of diltiazem in an SR formulation was associated with a significant decrease in aggregate health care expenditures over the 1-year study period ($258.80, P < or = 0.05). Receipt of the SR formulation was associated with an increase in expenditures for antihypertensive therapy ($109.26, P < or = 0.05), and a decrease in financial commitments for physician ($128.70, P < or = 0.05), hospital ($211.84, P < or = 0.05), and laboratory ($27.52, NS) services. At the managerial and policy levels, these data argue for an increased use of therapeutic alternatives that facilitate a reduction in the patient's daily dosing schedule for antihypertensive therapy.

Effect of pharmaceutical formulation for antihypertensive therapy on health service utilization.

A significant factor in the management of hypertension is the extent to which patients comply with the treatment regimen. A retrospective analysis was undertaken to determine the relationship between antihypertensive formulation, regimen compliance, and the utilization of health care services. Data for this analysis were derived from the state of South Carolina's Medicaid computer archive. The study population consisted of 1000 randomly selected patients initially prescribed one of the following antihypertensive regimens as monotherapy: atenolol once daily, captopril BID, oral clonidine BID, transdermal clonidine once weekly, diltiazem BID, enalapril BID, metoprolol BID, prazosin BID, terazosin once daily, and sustained-release verapamil once daily. Multivariate regression analysis was used to determine the incremental influence of selected demographic characteristics, use of medical services before diagnosis of hypertension, initial antihypertensive medication, medication possession ratio for antihypertensive therapy, and number of maintenance medications for diseases other than hypertension on post-period health care expenditures. The results indicated that patients initially prescribed antihypertensive medication requiring once-daily or once-weekly administration experienced an increased utilization of antihypertensive medication, needed fewer changes in their therapeutic regimen, and far less need for concomitant therapy for blood pressure control compared with those prescribed a BID regimen. Patients in the once-daily or once-weekly groups also used significantly fewer physician, hospital, and laboratory services (P < or = 0.05).

Antidepressant pharmacotherapy: economic outcomes in a health maintenance organization.

Recent pharmacotherapeutic advances in the treatment of depression have included the development of selective serotonin re-uptake inhibitors (SSRIs). The present study was designed to contrast direct health service expenditures for the treatment of depression among patients enrolled in a health maintenance organization (HMO) and prescribed either the SSRI fluoxetine or one of three tricyclic antidepressants (TCAs) (amitriptyline, nortriptyline, or desipramine). Information regarding health service utilization was derived from the computer archive of a network-model HMO system serving 400,000 beneficiaries. A total of 701 HMO beneficiaries were found to satisfy the study selection criteria. Multivariate regression analysis was used to discern the incremental influence of selected demographic, clinical, financial, and provider characteristics on 1 year post-period expenditures (PPE) for health care. Analysis-of-variance procedures with Duncan's multiple-range test, or chi-square analyses, revealed no significant difference across antidepressant pharmacotherapy for age, sex, 6-month prior-period expenditures for physician visits, psychiatric visits, laboratory tests, hospitalizations, or psychiatric hospital services related to the treatment of depression, or number of prescribed therapeutic agents for disease state processes other than depression. Receipt of fluoxetine was associated with a significantly (P < or = 0.05) higher rate of initial prescribing by psychiatrists, an increase in the number of prescriptions for antidepressant pharmacotherapy obtained (30-day supplies), and a reduction in the number of monthly intervals during which time antidepressant pharmacotherapy was not procured. Receipt of fluoxetine as antidepressant pharmacotherapy was associated with a significantly (P < or = 0.05) higher mean medication possession ratio (MPR) relative to amitriptyline, nortriptyline, or desipramine. Multivariate findings for patient-level data reflecting a definitive diagnosis of depression (n = 555) indicate that receipt of a TCA resulted in a significant (P < or = 0.05) increase in the use of physician visits ($36.07), psychiatric visits ($41.38), laboratory tests ($1.71), hospitalizations ($208.77), and psychiatric hospital services ($187.27), and a significant (P < or = 0.05) reduction in expenditures for antidepressant pharmacotherapy (-$162.21), for a total increase in health service utilization of $312.99 (P < or = 0.05) 1 year post-initiation of antidepressant pharmacotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

The need for an iterative process for assessing economic outcomes associated with SSRIs.

Pharmacotherapeutic advances in the treatment of depression have included the development of the selective serotonin reuptake inhibitors (SSRIs), thereby providing alternatives to tricyclic antidepressants. Concurrent with these events have been significant structural (e.g. pharmaceutical formularies) and regulatory (e.g. required pharmacoeconomic evaluations) changes in the delivery, financing, and oversight of healthcare programmes throughout the world. International cost-containment initiatives are increasingly mandating a demonstration of value for money, defined in terms of a measurable health and/or financial outcome, and, in the case of medicines, attributable to a given expenditure, for a given pharmacotherapeutic option. We examine the inherent strengths and weaknesses of 5 study designs used to discern and contrast financial outcomes stemming from the use of antidepressant pharmacotherapy for the treatment of depressive illness [randomised controlled trials (RCTs); meta-analyses; decision-analytical models (DAMs); retrospective database investigations; randomised naturalistic inquiry]. We argue that the economic appraisal of pharmacotherapy requires an iterative process extending from the developmental (RCTs; meta-analyses; DAMs) through to the postmarketing phase (database reviews; naturalistic inquiry), thereby resulting in a portfolio of evidence as to the safety, efficacy and effectiveness of a given pharmacotherapeutic category (e.g. SSRIs) and/or a specific medication. Database reviews, while nonrandomised, and prospective naturalistic inquiry afford greater insight into the patterns of use and financial merits of prescribing specific pharmacotherapeutic options for the treatment of depression within the context of clinical practice as compared with RCTs, meta-analyses and DAMs. The portfolio of evidence to date indicates that the first-line use of SSRIs in the treatment of depression is clinically warranted, and represents value for money.

Ethnicity and the prescribing of antidepressant pharmacotherapy: 1992-1995.

Little is known about the prescribing pattern for antidepressant pharmacotherapy by ethnicity. The present study was designed to determine the rates of office-based visits documenting the utilization of antidepressant pharmacotherapy, a diagnosis of a depressive disorder, or both, among whites, blacks, and Hispanics age 20-79 years. Data from the National Ambulatory Medical Care Survey for 1992-93 and 1994-95 were utilized for this analysis. Comparing these time periods, we observed several trends: (1) The annualized mean rate per 100 US population of office-based visits documenting the use of antidepressant pharmacotherapy for any reason increased from 13.4 to 15.9 among whites (p < or = 0.0001) and from 6.5 to 7.7 among blacks (p < or = 0.0001), but remained unchanged at 7.3 for Hispanics (p > 0.05). (2) Documentation of a diagnosis of a depressive disorder increased for whites (10.9 to 12.0; p < or = 0.0001), for blacks (4.2 to 5.6; p < or = 0.0001), and for Hispanics (4.8 to 5.6; p < or = 0.0001). (3) The recording of a diagnosis of a depressive disorder in concert with the initial prescription or continuation of antidepressant pharmacotherapy also increased for whites (6.5 to 7.7; p < or = 0.0001), for blacks (2.6 to 3.4; p < or = 0.0001), and for Hispanics (3.0 to 3.2; p < or = 0.0001). We conclude that the rate of office-based visits documenting the utilization of antidepressant pharmacotherapy, a diagnosis of a depressive disorder, or both, was comparable among blacks and Hispanics by 1994-95, but was less than half the rate for whites in either time period examined. Further prospective research is required to discern the reasons for observed differences by ethnicity.

Comparison of the effects of iodine and iodide on thyroid function in humans.

Concerns have been raised over the use of iodine for disinfecting drinking water on extended space flights. Most fears revolve around effects of iodide on thyroid function. iodine (I2) is the form used in drinking-water disinfection. Risk assessments have treated the various forms of iodine as if they were toxicologically equivalent. Recent experiments conducted in rats found that administration of iodine as I- (iodide) versus I2 had opposite effects on plasma thyroid hormone levels. I2-treated animals displayed elevated thyroxine (T4) and thyroxine/triiodothyronine (T/T3) ratios, whereas those treated with I- displayed no change or reduced plasma concentrations of T4 at concentrations in drinking water of 30 or 100 mg/L. The study herein was designed to assess whether similar effects would be seen in humans as were observed in rats. A 14-d repeated-dose study utilizing total doses of iodine in the two forms at either 0.3 or 1 mg/kg body weight was conducted with 33 male volunteers. Thyroid hormones evaluated included T4, T3, and thyroid-stimulating hormone (TSH). TSH was significantly increased by the high dose of both I2 and I-, as compared to the control. Decreases in T4 were observed with dose schedules with I- and I2, but none were statistically significant compared to each other, or compared to the control. This human experiment failed to confirm the differential effect of I2 on maintenance of serum T4 concentrations relative to the effect of I- that was observed in prior experiments in rats. However, based on the elevations in TSH, there should be some concern over the potential impacts of chronic consumption of iodine in drinking water.

Knowledge, attitudes, and patterns of cancer screening: a self-report among foreign born Hispanic women utilizing rural migrant health clinics.

Hispanics are the fastest growing minority in the United States and are currently Washington state's largest minority, with the highest growth rates found in the rural agricultural areas of eastern Washington state. Because breast and cervical cancer mortality rates are higher in Hispanics than other U.S. women, subgroups of Hispanic women with the lowest cancer screening utilization rates need to be identified and targeted for cancer control intervention to most effectively reduce late-stage cancer diagnoses and mortality. A study was conducted at six migrant health clinics located throughout eastern Washington state to discern age-specific proportions for utilization of mammography, breast self-examination, and Pap smears among Hispanic migrants to the United States. Knowledge and attitudes regarding these procedures also were assessed and face-to-face interviews were completed with 512 women. Among women 20 years or older, 15 percent had never heard of a Pap smear, only 78 percent had ever received a Pap smear, and only 44 percent had received a Pap smear within the prior year. In all, 73 percent of the women had been taught breast self-examination, 62 percent performed breast self-examination, and 41 percent had performed a breast self-examination in the prior month. Among women 40 years or older, only 38 percent had never heard of a mammogram, 38 percent had ever received a mammogram, and only 30 percent had received a mammogram in the prior two years. Cost was reported as a major barrier for screening in this population. Additionally, a substantial proportion of the women perceived Pap smears and mammography as unnecessary or diagnostic procedures, rather than preventive health measures.

Cancer-screening determinants among Hispanic women using migrant health clinics.

This study was designed to identify determinants of breast and cervical cancer screening among rural, low-income Hispanic women using migrant health clinics in eastern Washington state. Five hundred and twelve foreign-born Hispanic women were interviewed. Odds ratios and 95 percent confidence intervals generated via logistic regression analysis were used to discern the influence of independent factors on use or nonuse of Papanicolaou (Pap) smear, breast self-examination (BSE), and mammography. Being married, having a higher income, more years of education, and longer U.S. residency predicted receipt of Pap smear. Women who performed BSE had higher incomes and were more likely to have been taught how to perform the procedure. Low concern for direct expenditure and increasing years of U.S. residency predicted receipt of mammogram. On the basis of these findings, implications for developing cancer-screening interventions using inreach and outreach strategies to target this high-risk subgroup are discussed.

Prescribing rationale and budgetary outcomes associated with the introduction of a combined formulation of diclofenac sodium and misoprostol in Canada.

The budgetary impact of prescribing a combined formulation of diclofenac sodium and misoprostol to patients previously using nonsteroidal anti-inflammatory agents (NSAIDs), cytoprotective agents, or a combination of agents from both therapeutic categories is assessed, as is the clinical rationale for prescribing the combined formulation. Analysis of data for Canada on claims paid by third parties showed that the use of the combined formulation in Canada had resulted in significant initial overall savings and that the greatest cost savings were made for those who had previously used both an NSAID and a cytoprotective concomitantly. The inclusion of shadow costs (secondary costs) indicates that the use of the combined formulation over a 6-month period involves very low shadow costs (medical expenses related to ulcer treatment) compared with other NSAIDs: the shadow cost multiplication factor was 1.03 for the combined formulation compared with 1.22 to 3.47 for other NSAIDs. Pharmaceutical costs alone are insufficient for evaluating total budgetary impacts.

Metered-dose inhaler technique and quality of life with airways disease: assessing the value of the Vitalograph in educational intervention.

The efficacy of delivering medicines by metered-dose inhaler (MDI) is well established, and the patient's technique with MDIs is related directly to achieving the desired clinical outcome. The present study was designed to assess and improve MDI technique by using a Vitalograph Aerosol Inhalation Monitor (VAIM) in an airways disease education programme. Baseline measurements were made immediately prior to educational intervention incorporating feedback from a VAIM unit. At 6 weeks' follow-up, MDI technique was found to have regressed to the sub-optimal measures recorded at baseline prior to educational intervention. However, patients reported a significant improvement in physical function between baseline and follow-up as measured by the Rand 36-Item Health Survey (SF-36), Version 1.0. The results reinforce the need for a longitudinal educational programme for patients prescribed medications delivered by MDI. The VAIM unit provided health educators and patients with both a visual and a quantitative assessment of patients' MDI technique, and was thus of positive value as part of the intervention process.