Predicting Dental Caries in Young Children in Primary Health Care Settings.

Young children need increased access to dental prevention and care. Targeting high caries risk children first helps meet this need. The objective of this study was to develop a parent-completed, easy-to-score, short, accurate caries risk tool for screening in primary health care settings to identify children at increased risk for cavities. A longitudinal, prospective, multisite, cohort study enrolled (primarily through primary health care settings) and followed 985 (out of 1,326) 1-y-old children and their primary caregivers (PCGs) until age 4. The PCG completed a 52-item self-administered questionnaire, and children were examined using the International Caries Detection and Assessment Criteria (ICDAS) at 12 ± 3 mo (baseline), 30 ± 3 mo (80% retention), and 48 ± 3 mo of age (74% retention). Cavitated caries lesion (dmfs = decayed, missing, and filled surfaces; d = ICDAS ≥3) experience at 4 y of age was assessed and tested for associations with questionnaire items using generalized estimating equation models applied to logistic regression. Multivariable analysis used backward model selection, with a limit of 10 items. At age 4, 24% of children had cavitated-level caries experience; 49% were female; 14% were Hispanic, 41% were White, 33% were Black, 2% were other, and 10% were multiracial; 58% enrolled in Medicaid; and 95% lived in urban communities. The age 4 multivariable prediction model, using age 1 responses (area under the receiver operating characteristic curve = 0.73), included the following significant (P < 0.001) variables (odds ratios): child participating in public assistance programs such as Medicaid (1.74), being non-White (1.80-1.96), born premature (1.48), not born by caesarean section (1.28), snacking on sugary snacks (3 or more/d, 2.22; 1-2/d or weekly, 1.55), PCG cleaning the pacifier with juice/soda/honey or sweet drink (2.17), PCG daily sharing/tasting food with child using same spoon/fork/glass (1.32), PCG brushing their teeth less than daily (2.72), PCG's gums bleeding daily when brushing or PCG having no teeth (1.83-2.00), and PCG having cavities/fillings/extractions in past 2 y (1.55). A 10-item caries risk tool at age 1 shows good agreement with cavitated-level caries experience by age 4.

Development of gold standard ion-selective electrode-based methods for fluoride analysis.

BACKGROUND/AIMS: Currently available techniques for fluoride analysis are not standardized. Therefore, this study was designed to develop standardized methods for analyzing fluoride in biological and nonbiological samples used for dental research. METHODS: A group of nine laboratories analyzed a set of standardized samples for fluoride concentration using their own methods. The group then reviewed existing analytical techniques for fluoride analysis, identified inconsistencies in the use of these techniques and conducted testing to resolve differences. Based on the results of the testing undertaken to define the best approaches for the analysis, the group developed recommendations for direct and microdiffusion methods using the fluoride ion-selective electrode. RESULTS: Initial results demonstrated that there was no consensus regarding the choice of analytical techniques for different types of samples. Although for several types of samples, the results of the fluoride analyses were similar among some laboratories, greater differences were observed for saliva, food and beverage samples. In spite of these initial differences, precise and true values of fluoride concentration, as well as smaller differences between laboratories, were obtained once the standardized methodologies were used. Intraclass correlation coefficients ranged from 0.90 to 0.93, for the analysis of a certified reference material, using the standardized methodologies. CONCLUSION: The results of this study demonstrate that the development and use of standardized protocols for F analysis significantly decreased differences among laboratories and resulted in more precise and true values.

Predicting Caries in Medical Settings: Risk Factors in Diverse Infant Groups.

Expanded partnership with the medical community is a promising strategy for reducing disparities in dental caries among young children. However, no validated caries risk instrument exists for use in primary health care settings. To help resolve this gap, a 52-item caries risk questionnaire was developed and targeted to primary caregivers (PCGs) to test in a 3-y prospective study. To begin to understand the validity of the questionnaire items, the purpose of this study was to compare responses to the questionnaire based on key demographic characteristics known to be associated with disparities in caries experience (e.g., race/ethnicity and insurance status). A total of 1,323 one-year-old children were recruited primarily through 3 medical research networks. Baseline questionnaire responses were analyzed via logistic regression. The sample was 49% female. Its racial/ethnic makeup was as follows: 13% Hispanic, 37% White, 37% Black, and 13% other or multiracial. Sixty-one percent were enrolled in Medicaid, and 95% resided in urban communities. Mothers represented 94% of PCGs. There were significant differences ( P < 0.05) in baseline responses based on Medicaid status and race/ethnicity. As compared with those not enrolled in Medicaid, children in the Medicaid group were significantly more likely (after adjusting for race/ethnicity) to 1) go to sleep while nursing or drinking something other than water, 2) eat sugary snacks between meals, 3) consume sugary drinks between meals, 4) receive topical fluoride from a health professional, 5) visit the dentist, and 6) not have an employed adult in the household. PCGs of children enrolled in Medicaid were significantly more likely to be the mother, have bleeding gums, eat sugary snacks between meals, consume sugary drinks between meals, eat or drink something other than water before going to bed, and not get regular dental checkups. In conclusion, there are significant differences in caries risk questionnaire responses based on Medicaid status and race/ethnicity that provide construct and criterion validity to the developed caries risk tool (ClinicalTrials.gov NCT01707797).

A case manager intervention to reduce readmissions.

BACKGROUND: Acute hospitalizations represent substantial financial liability to closed health care systems. Among hospitalized patients, those with repeated admissions are high-cost users. Most managed care plans employ case management to control hospital use. This technique attempts to detect and fulfill unmet medical and social needs, intensify postdischarge care, identify and mobilize effective community services, and enhance primary care access. Despite the popularity of case management to control hospital use, few trials have examined its efficacy. METHODS: We conducted a randomized controlled trial of an intervention of case managers at a university-affiliated Veterans Affairs medical center. Six hundred sixty-eight patients aged 45 years or older who were discharged from the general medicine inpatient service, who had access to a telephone, and who received primary care at the hospital's clinics were randomized to the intervention (N = 333) and control (N = 335) groups. Within 24 hours of discharge, case managers mailed educational materials and access information to intervention patients, and within 5 days they called to review and resolve unmet needs, early warning signs, barriers to keeping appointments, and any readmissions. Case managers contacted intervention patients if they made no visits for 30 days. This resulted in a total of 6260 patient-case manager contacts. Control and intervention patients were followed up for 12 months. RESULTS: Intervention patients had more frequent visits per patient per month to the general medicine clinic (0.30 +/- 0.23 vs 0.26 +/- 0.22, P = .008), but we detected no significant differences between groups in nonelective readmissions, readmission days, or total readmissions. CONCLUSIONS: Frequent contacts for education, care, and accessibility by case managers using protocols were ineffective in reducing nonelective readmissions.

Effect of long-term exposure to fluoride in drinking water on risks of bone fractures.

Findings on the risk of bone fractures associated with long-term fluoride exposure from drinking water have been contradictory. The purpose of this study was to determine the prevalence of bone fracture, including hip fracture, in six Chinese populations with water fluoride concentrations ranging from 0.25 to 7.97 parts per million (ppm). A total of 8266 male and female subjects > or =50 years of age were enrolled. Parameters evaluated included fluoride exposure, prevalence of bone fractures, demographics, medical history, physical activity, cigarette smoking, and alcohol consumption. The results confirmed that drinking water was the only major source of fluoride exposure in the study populations. A U-shaped pattern was detected for the relationship between the prevalence of bone fracture and water fluoride level. The prevalence of overall bone fracture was lowest in the population of 1.00-1.06 ppm fluoride in drinking water, which was significantly lower (p < 0.05) than that of the groups exposed to water fluoride levels > or =4.32 and < or =0.34 ppm. The prevalence of hip fractures was highest in the group with the highest water fluoride (4.32-7.97 ppm). The value is significantly higher than the population with 1.00-1.06 ppm water fluoride, which had the lowest prevalence rate. It is concluded that long-term fluoride exposure from drinking water containing > or =4.32 ppm increases the risk of overall fractures as well as hip fractures. Water fluoride levels at 1.00-1.06 ppm decrease the risk of overall fractures relative to negligible fluoride in water; however, there does not appear to be similar protective benefits for the risk of hip fractures.

Differences among mononuclear cell subpopulations in HIV seropositive or seronegative homosexual and heterosexual men as determined by four-color flow cytometry.

Four-color cell surface immunofluorescence and flow cytometry analysis was used to quantitate mononuclear cell subpopulations from HIV seropositive (HIV+) and seronegative (HIV-) homosexual men and heterosexual men. HIV+ men were divided into two groups based on peripheral blood CD4/mm3 of greater than 500 or less than 500. CD4+ cells that were simultaneously CD45R-, CDw29-, and 13- were significantly less in HIV+ men with less than 500 CD4/mm3 (17%) compared to heterosexual men (34%). This lower percentage of "CD4 only" cells in HIV+ males with less than 500 CD4/mm3 correlated with a significantly higher percentage of CD4+ cells that were CD45R+, CDw29+, and 13+ in these individuals. CD8+ cells that were CD45R+, 13+, but CD38-, were significantly less in HIV+ men with less than 500 CD4 as compared to HIV- homosexual men. In contrast, a second CD8+ subpopulation that was CD45R-, CD38+, and either 13+ or 13- was significantly greater in less than 500 HIV+ men as compared to both HIV- homosexual men and heterosexual men. A significant difference in this subpopulation was observed between the less than 500 and greater than 500 HIV+ groups and correlated with seropositivity for viral p24 antigen. Interestingly, CD8+ cells that were CD45R+, as well as CD38+, and either 13+ or 13- were significantly greater in the less than 500 HIV+ group compared to the greater than 500 HIV+ group, and did not correlate with p24 seropositivity. The percentage of monocyte/macrophages that were CD4- or expressed dim CD4 immunofluorescence, but were 13+, was significantly greater in HIV+ men (43%) compared to HIV- homosexual men (27%). In summary, we have identified previously undescribed mononuclear cell subpopulations that were altered with HIV infection and, in some cases, correlated with the stage of disease.

Locomotion through three-dimensional type I rat tail collagen. A modified mini-assay.

There is an increased application of three-dimensional type I rat tail collagen as an in vitro model for the peritumoral matrix in analysis of lymphocyte migration. The increased demand prompted us to modify the previous methods. We here describe our 'mini'-setup of the collagen model assay, which uses only 1/20 the amount of collagen medium and the number of cells used in the conventional assay. The modified assay was tested for optimal collagen concentration in gel for upward and downward migration, for locomotion from a collagen-gel bead into a collagen overlayer for demonstration of the effect of inhibitors and for differentiation between locomotory properties of lymphocyte subpopulations. The results verify that the mini-assay is an applicable in vitro model, easily read and amenable to limited blood samples such as those obtained from cancer patients, and reflects well known in vivo events.

Effect of successful treatment with amphotericin B on Histoplasma capsulatum variety capsulatum polysaccharide antigen levels in patients with AIDS and histoplasmosis.

PURPOSE: The purpose of this study was to establish the effect of induction and maintenance treatment with amphotericin B on levels of Histoplasma capsulatum var. capsulatum polysaccharide antigen (HPA) in the urine and blood of patients with acquired immunodeficiency syndrome (AIDS) and disseminated histoplasmosis. PATIENTS AND METHODS: This was a retrospective study of the effect of amphotericin B treatment on levels of HPA in the urine or serum from 70 patients with AIDS and disseminated histoplasmosis. All patients received initial intensive induction treatment with amphotericin B, and a subset continued to receive amphotericin B at less frequent intervals for maintenance therapy to prevent relapse. Treatment regimens varied in intensity and duration and specimens were obtained at irregular intervals. Urine and serum specimens were stored and retested for HPA in the same radioimmunoassay. RESULTS: HPA levels in serum decreased by at least 2 units during induction therapy in all 19 (100%) patients with initial levels of greater than or equal to 2.6 units and reverted to negative in 40.9% of those with initial levels of greater than or equal to 1.0 unit. HPA in urine decreased by at least 2 units in 84.8% and reverted to negative in 17.3% of patients. During induction treatment, HPA cleared more rapidly from serum than from urine. During maintenance treatment, HPA levels in serum decreased by at least 2 units in 100% and became negative in 66.7%. HPA in urine decreased by at least 2 units in 54.5% and reverted to negative in 20.0%. Rates of clearance of HPA from the serum and urine were similar, 0.01 unit/week compared with -0.04 unit/week, respectively, but less than rates during induction treatment. CONCLUSIONS: Successful therapy of histoplasmosis with amphotericin B is associated with reduction of HPA in body fluids. Periodic measurement of HPA levels offers a method for monitoring the response to therapy and for comparing new treatments for histoplasmosis.

Comparison of indium-111 nonspecific polyclonal IgG with indium-111-leukocytes in a canine osteomyelitis model.

Osteomyelitis was surgically produced in the proximal tibia of ten dogs. A sham operation was performed on the other tibia. Early (3 hr) and late (20 hr) imaging was performed 1, 4, 7, 10, and 13 wk later, while the osteomyelitis progressed from acute to chronic. Indium-111-IgG had a significantly greater accumulation at the osteomyelitis site than 111In-leukocytes, both during early (p = 0.001) and late (p = 0.03) imaging, and at each of the weeks studied (p less than 0.001). During early imaging, both agents gave equivalent lesion to background ratios. On the late images, the 111In-leukocytes gave significantly higher lesion-to-background ratios than 111In-IgG (p less than 0.001) and higher ratios than they did during the early images (p less than 0.001). Both agents had greater accumulation in acute osteomyelitis than in chronic osteomyelitis (p less than 0.02). Osteomyelitis in the surgical site can be distinguished from the uptake in the sham surgery site using 111In-leukocytes, but not when using 111In-IgG.

Altered baroreceptor function in children with systolic hypertension after coarctation repair.

To determine whether altered baroreceptor function may contribute to systemic hypertension after coarctation of the aorta (C of A) repair, baroreceptor function was evaluated in 6 children with repaired C of A mild arm systolic hypertension. Data were compared with those from 7 normotensive control children with hemodynamically mild heart disease. Age at C of A repair averaged 9.9 +/- 3.1 years (mean +/- standard deviation [SD]). Arm systolic pressure was 143.8 +/- 2.9 mm Hg in the C of A repair group, compared with 118.3 +/- 9.9 for control subjects (p less than 0.001). At catheterization, steady-state sigmoidal baroreceptor function curves relating mean arterial pressure to R-R interval were derived by increasing and decreasing mean arterial pressure with small injections of phenylephrine and nitroprusside. Compared with control subjects, the baroreceptor function curves of children with repaired C of A (1) are reset about a higher baseline mean arterial pressure (108.8 +/- 6.6 versus 90.3 +/- 8.6 mm Hg, p less than 0.01), (2) have a decreased slope (7.9 +/- 3.7 versus 17.4 +/- 3.6 ms/mm Hg, p less than 0.001), and (3) have a diminished R-R interval range (246.7 +/- 81.5 versus 535.7 +/- 97.2 ms, p less than 0.001). Thus, in children with hypertension after C of A repair, the baroreflex is reset to an elevated mean arterial pressure level and has a diminished sensitivity to changes in arterial pressure.

Rabbit pneumothorax. Feasibility of an animal model to simulate neonatal pneumothorax.

RATIONALE AND OBJECTIVES: The feasibility of developing an animal model to simulate radiographic features of neonatal pneumothorax was investigated, and supine computed radiography (CR) and film-screen radiography (FS) images were compared. METHODS: 5-Fr pigtail catheters were inserted into the right pleural space of three New Zealand white rabbits. Two CR and two FS supine images were obtained using identical technique. After serial 4-mL injections of air, one CR and one FS supine image were obtained. The images were masked and randomized, and four radiologists reviewed the images for typical signs of pneumothorax. Chest computed tomography (CT) was performed before the injection of any air and after completion of the study. RESULTS: At zero-mL air volume, radiologists did not perceive a pneumothorax. As the air volume increased, the number of signs of a pneumothorax increased; there was no significant difference between CR and FS in the number of signs of pneumothorax detected at any volume. Chest CT confirmed that there was no unexplained air leak. The volume of air injected correlated with the calculated volume from the CT. CONCLUSIONS: This induced, volume-controlled, animal model simulated the supine radiographic features of neonatal pneumothorax.

Improved training of house officers in a rheumatology consult service.

This study examined whether the clinical environment could be used to increase internal medicine house officers' adoption of care recommendations taught in a didactic conference. Subjects were 11 internal medicine house officers who served 6-week rheumatology elective rotations. At the start of each of four rotation periods, house officers attended a 1-hour conference in which periarticular rheumatic disorders associated with knee pain (anserine bursitis, pseudothrombophlebitis) and shoulder pain (bicipital tendinitis) were discussed. All house officers also practiced physical examination techniques on anatomic models simulating the disorders. During alternate rotation periods, reminder sheets were appended to the records of arthritis patients with histories of chronic knee or shoulder pain. The frequency with which house officers followed conference recommendations was documented by direct observation (6 house officers in 17 encounters with reminders, 5 house officers in 30 encounters without reminders). Specific questioning about a recent history of knee or shoulder pain and the performance of four of five recommended physical examination maneuvers were increased significantly by reminder sheets in patients' charts (P < 0.05 for all). Although rheumatology faculty often have limited options available to increase the number of house officer trainees or to intensify clinical activity, qualitative improvements within existing logistic parameters are feasible by assuring that the clinical environment (e.g., patient records) contains salient cues that will prompt desired actions.

Comparison of general internists, family physicians, and rheumatologists managing patients with symptoms of osteoarthritis of the knee.

OBJECTIVE: To evaluate the nature, risks, and benefits of osteoarthritis (OA) management by primary care physicians and rheumatologists. METHODS: Subjects were 419 patients followed for symptoms of knee OA by either a specialist in family medicine (FM) or general internal medicine (GIM) or by a rheumatologist (RH). Management practices were characterized by in-home documentation by a visiting nurse of drugs taken to relieve OA pain or to prevent gastrointestinal side effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and by patient report (self-administered survey) of nonpharmacologic treatments. Changes in outcomes (knee pain and physical function) over 6 months were measured with the Western Ontario and McMaster Universities Osteoarthritis Index. RESULTS: Patients of RHs were 2-3 years older (P = 0.035) and tended to exhibit greater radiographic severity of OA (P = 0.064) and poorer physical function (P = 0.076) at baseline than the other 2 groups. In all 3 groups, knee pain and physical function improved slightly over 6 months; however, between-group differences were not significant. Compared to drug management of knee pain by FMs or RHs, that by the GIMs was distinguished by greater utilization of acetaminophen and nonacetylated salicylates (P = 0.008), lower prescribed doses of NSAIDs (P = 0.007), and, therefore, lower risk of iatrogenic gastroenteropathy (P < 0.001). In contrast, patients of RHs were more likely than those of FMs and GIMs to report that they had been instructed in use of isometric quadriceps and range-of-motion exercises (P < or = 0.001), application of heat (P = 0.051) and cold (P < 0.001) packs, and in the principles of joint protection (P = 0.016). Neither physician specialty nor specific management practices accounted for variations in patient outcomes. CONCLUSION: This observational study identified specialty-related variability in key aspects of the management of knee OA in the community (i.e., frequency and dosing of NSAIDs, use of nonpharmacologic modalities) that bear strong implications for long-term safety and cost. However, changes in knee pain and function over 6 months were unrelated to variations in management practices.

Lack of effect of long-term fluoride ingestion on blood chemistry and frequency of sister chromatid exchange in human lymphocytes.

Two studies were conducted to assess the potential for adverse physiologic and genotoxic effects of long-term fluoride ingestion in adults residing in three communities with varying water fluoride levels (0.2 ppm, 1.0 ppm, and 4.0 ppm). All were long-time (> or = 30 years) residents of their respective communities. Plasma and urine samples were collected for fluoride analyses. Additional plasma was collected to determine blood chemistry, and plasma lymphocytes were examined to determine the frequency of sister chromatid exchange. Significant differences in urine (P = 0.001) and plasma (P = 0.0001) fluoride levels were found in the three communities. Seven of the blood parameters were statistically different among the communities, although all were within the defined normal range of the pathology laboratory. Sister chromatid exchange frequency was statistically higher in the 4.0 ppm fluoride community as compared to the other communities. Because of the higher SCE frequency in the 4.0 ppm fluoride community, a second study was performed to determine if the increased frequency was potentially related to the fluoride level of the communal water supply. Of the 58 adults recruited; 30 had used city water and 28 had used well water (< or = 0.3 ppm fluoride) as their principal water source for 30 years. Data analyses showed that the sister chromatid exchange frequency did not differ between the groups, indicating that the increased sister chromatid exchange frequency was not related to the fluoride level of the communal water. The investigation provided evidence that the long-term ingestion of water containing 4.0 ppm fluoride did not have any clinically important physiologic or genotoxic effects in healthy adults.

Statistical issues for combining multiple caries diagnostics for demonstrating caries efficacy.

Caries efficacy in clinical trials has been based primarily on visual examinations supplemented by Fiber Optic Transillumination (FOTI) and radiography, with the assessments combined at the surface level to classify each surface as to its caries status. Newer caries diagnostics techniques measure the caries process in a quantitative manner and so thus yield continuous rather than ordinal results. The objective of this study was to examine various methods for the analysis of multiple outcomes in clinical trials and to compare their usefulness for the analysis of caries trials. Four global tests (rank sum, ordinary least squares, general least squares, and generalized estimating equations) and two caries indices (based on average and maximum values of the methods) were evaluated with the use of one-year follow-up data from 1063 children in a recent caries trial. A new hybrid method was also developed and evaluated. All of the methods performed well when the diagnostic measures showed product differences in caries in the same direction. Ease of use, interpretability, and distributional assumptions must be considered before a consensus method for analysis of multiple diagnostic measures in caries trials can be determined.

Sample size considerations in designing studies with intra-oral models.

Especially during recent years, the use of pre-clinical models for predicting the efficacy of fluoride systems has assumed greater importance within the scientific community. Originally utilized primarily to screen experimental fluoride delivery systems, preclinical models are now being considered as predictors of clinical efficacy in lieu of controlled clinical caries trials. Of the various preclinical models presently available, human intra-oral models have the greatest potential for reflecting intended usage conditions and therefore may be the most meaningful models for predicting clinical efficacy. However, only with the proper consideration of numerous critical variables can studies using intra-oral models be appropriately designed to achieve the desired objectives. Clearly, these models must provide relevant information in a manner which reflects clinically established cariostatic activity and be capable of detecting established differences in the amount of cariostatic activity, i.e., dose-response effects. Three sources of variation must be considered before an appropriate study design and sample size can be chosen. Based on fluoride uptake data from an intra-oral model with proximally-located enamel specimens, estimates of variation among subjects, within subjects, and among specimens within subjects were obtained. Multiple specimens per panelist do not affect the first two sources of variation. Thus, the number of panelists, and not the number of specimens, is of primary importance when pre-test data are used to choose the appropriate study design and calculate the required sample size.

Evaluation of biochemical validation measures in determination of smoking status.

This study was designed to evaluate the use of salivary cotinine, salivary thiocyanate, and expired-air carbon monoxide as biochemical validation measures for assessing the smoking status of adults. The participants were 20 known non-smokers plus 216 admitted smokers and 102 proclaimed quitters participating in a clinical trial of approaches to facilitate smoking cessation. Conventional analytical procedures were utilized. By use of data from known non-smokers and admitted smokers, the sensitivity and specificity of the validation measures were as follows: salivary cotinine, 99% and 100%; expired-air carbon monoxide, 96% and 100%; and salivary thiocyanate, 67% and 95%, respectively. The salivary cotinine and expired-air carbon monoxide tests confirmed smoking cessation for 55% and 74%, respectively, of the proclaimed quitters. The length of time since quitting was significantly related to the results observed with the latter measures. Consideration of these observations along with various practical factors suggests that expired-air carbon monoxide assays may be the validation measure of choice for most clinical trials.

Long-term exposure to fluoride in drinking water and sister chromatid exchange frequency in human blood lymphocytes.

The genetic toxicity of fluoride has been investigated extensively by various test systems. However, results obtained have been inconsistent. Fluoride has been reported to be non-genotoxic, genotoxic, and synergistic or antagonistic with certain mutagens. To date, there are no published human studies on the genotoxicity of fluoride. The purpose of this investigation was to determine genotoxic risks of long-term exposure to various concentrations of fluoride in drinking water in humans with normal or inadequate nutrition. Six groups of subjects with either normal or inadequate nutritional intakes were selected from areas of approximately 0.2, 1.0, or 4.8 ppm (10.5, 52.6, or 252.6 mumol/L) fluoride in water. The subjects had been continuous residents in the area for at least 35 years. Samples of drinking water, plasma, and urine were analyzed for fluoride content. Blood lymphocytes were examined to determine the frequency of sister chromatid exchange (SCE). Blood chemistry and electrolytes were also analyzed. The results showed that average daily fluoride intake as well as urine and plasma fluoride levels increased with increase in the fluoride content of the drinking water. The blood chemistry and electrolyte values were within the normal range for all populations, but several parameters were significantly different. While the numerical differences were small, the subjects with low fluoride in the water (0.11 and 0.23 ppm or 5.8 and 12.1 mumol/L) had significantly higher SCE frequencies than those with higher fluoride exposures.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of aging on animal response to chronic fluoride exposure.

This study was conducted to test the hypothesis that physiological changes which occur during aging increase the biological impact of fluoride and reduce the threshold of safe fluoride exposure. Four groups of rats were fed a low-fluoride diet (< 1.2 ppm) ad libitum and received 0, 5, 15, or 50 ppm fluoride in their drinking water. Animals were killed after three, six, 12, or 18 months of treatment. Blood and urine were monitored for biochemical markers of tissue function, and plasma, urine, feces, and representative tissues were analyzed for fluoride. In addition, bone marrow cells from animals killed after 18 months of treatment were examined for frequency of sister chromatid exchange (SCE), a marker of genetic damage. Study results indicated that, within treatment groups, fluoride intake, excretion, and retention did not change significantly between three and 18 months. Fluoride concentration in soft tissues did not change with treatment duration in the fluoride-treated animals. Mineralized tissue fluoride concentration and the total fluoride in the carcasses increased continually as the animals aged. In spite of significant, dose-related differences in tissue fluoride levels which occurred in all age groups in this study, there were no indications that increased fluoride in the tissues caused any adverse physiological or genotoxic effects. None of the monitored clinical "wellness" markers of tissue integrity and function was altered by fluoride in a clinically significant manner. Therefore, there was no evidence from this study that aging reduces the threshold of safe chronic fluoride exposure.

Demographic variation in the rate of knee replacement: a multi-year analysis.

OBJECTIVE: The aim of this study is to describe the practice variation of knee replacements (KRs) in the elderly ( > or = 65) over time from 1985-1990 in terms of the number of primary, bilateral, and revision KRs; the extent of large area variation in performance rates; and the degree to which demographic variables are the determinants of area rates. DATA SOURCES/STUDY SETTING: Data analyzed are from every hospital in the United States that performed a KR on a Medicare patient during the study period. Data were obtained from the MEDPAR, HISKEW, and denominator files of the Medicare Statistical System. STUDY DESIGN: This is a cohort study of all Medicare beneficiaries who received a KR between 1985 and 1990. The dependent variable in the analyses was the count of the KRs performed in each area. DATA COLLECTION/EXTRACTION METHODS: This is a population-based sample of Medicare enrollees in the United States. All hospitalizations for Medicare-reimbursed KRs were included in the initial data set. Exclusion criteria were used to identify the Medicare covered population with a definite KR. These criteria resulted in 7.3 percent exclusions and a final set of 414,079 KR hospitalizations. PRINCIPAL FINDINGS: The number of Medicare-funded KRs increased in each of the study years corresponding to an annual rate of increase of 18.45 percent. The likelihood of receiving a KR was a function of age, gender, and race. For each year, KRs were almost-twice as likely to be performed on women than on men. The odds of whites getting the surgery were over 1.5 times greater than for blacks. Even after adjusting for demographic factors, significant regional variation remained. CONCLUSIONS: Much about area variation and the rate of growth in KR rates remains unexplained. For answers to emerge, better data and different types of studies are required.