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.

DsrA-deficient mutant of Haemophilus ducreyi is impaired in its ability to infect human volunteers.

Haemophilus ducreyi produces an outer membrane protein called DsrA, which is required for serum resistance. An isogenic dsrA mutant, FX517, was constructed previously in H. ducreyi 35000. Compared to its parent, FX517 cannot survive in normal human serum. When complemented in trans with a plasmid containing dsrA, FX517 is converted to a serum-resistant phenotype (C. Elkins, K. J. Morrow, Jr., and B. Olsen, Infect. Immun. 68:1608-1619, 2000). To test whether dsrA was transcribed in vivo, we successfully amplified transcripts in five biopsies obtained from four experimentally infected human subjects. To test whether DsrA was required for virulence, six volunteers were experimentally infected with 35000 and FX517 and observed for papule and pustule formation. Each subject was inoculated with two doses (70 to 80 CFU) of live 35000 and 1 dose of heat-killed bacteria on one arm and with three doses (ranging from 35 to 800 CFU) of live FX517 on the other arm. Papules developed at similar rates at sites inoculated with the mutant or parent. However, mutant papule surface areas were significantly smaller than parent papules. The pustule formation rate was 58% (95% confidence interval [CI] of 28 to 85%) at 12 parent sites, and 0% (95% CI of 0 to 15%) at 18 mutant sites (P = 0.0004). Although biosafety regulations precluded our testing the complemented mutant in humans, these results suggest that expression of DsrA facilitates the ability of H. ducreyi to progress to the pustular stage of disease.

An isogenic hemoglobin receptor-deficient mutant of Haemophilus ducreyi is attenuated in the human model of experimental infection.

Haemophilus ducreyi expresses a conserved hemoglobin-binding outer-membrane protein (HgbA). To test the role of HgbA in pathogenesis, we infected 9 adults with isolate 35000 and its isogenic hgbA-inactivated mutant (FX504) on their upper arms in a double-blinded, escalating dose-response study. Papules developed at similar rates at sites inoculated with the mutant or parent. The pustule-formation rate was 55% (95% confidence interval [CI], 30. 8%-78.5%) at parent sites and 0 (95% CI, 0-10.5%) at mutant sites (P<.0001). The recovery rate of H. ducreyi from surface cultures was 16% (n=142) from parent sites and 0 (n=213) from mutant sites (P<. 0001). H. ducreyi was recovered at biopsy from 6 of 7 parent sites and from 0 of 3 mutant sites. The results indicate that hemoglobin may be a critical source of heme or iron for the establishment of H. ducreyi infection in humans.

A pilus-deficient mutant of Haemophilus ducreyi is virulent in the human model of experimental infection.

Haemophilus ducreyi expresses fine tangled pili, which are composed predominantly of a major subunit (FtpA). Confocal microscopy showed that an FtpA-specific monoclonal antibody bound to bacteria in biopsy samples obtained from infected human volunteers. To test the role of pili in pathogenesis, an isogenic mutant (35000HP-SMS1) was constructed by insertionally inactivating ftpA. 35000HP-SMS1 did not express FtpA and was nonpiliated but was otherwise identical to its parent, 35000HP. Seven healthy adults were challenged on the upper arm with the isogenic isolates in a double-blinded, escalating dose-response study. Sites inoculated with the mutant produced papules and pustules at rates similar to the rates observed at sites inoculated with the parent. The recovery rate of H. ducreyi from cultures and the histopathology of biopsy samples obtained from pustules inoculated with 35000HP or 35000HP-SMS1 were similar. Although pili are expressed in vivo, FtpA is not required for pustule formation in the human challenge model.

Mucus production by endometrium of reproductively healthy mares and mares with delayed uterine clearance.

The aims of this study were to compare various staining and fixation techniques for endometrial biopsy samples and, thus, to investigate the mucociliary apparatus in endometrium from reproductively healthy mares and mares with delayed uterine clearance. Endometrial samples were collected from the left and right uterine horns of reproductively healthy mares (n=5) and mares with delayed uterine clearance (n=4) during anoestrus, transition, oestrus and dioestrus. Each sample of endometrium was fixed in either Bouin's fixative or formalin, and stained with alcian blue (pH 1.0 or 2.5), periodic acid Schiff (alone and in combination with alcian blue) or mucicarmine. An extracellular mucus blanket was observed more frequently in tissue fixed in Bouin's fixative than in formalin-fixed tissue. Luminal epithelial cells and the extracellular mucus blanket were stained preferentially using alcian blue (pH 2.5). Ciliated cells were observed most readily in biopsy samples fixed with formalin and stained with either alcian blue (pH 2.5) or mucicarmine. Mucus production was increased in fibrotic nests and inflamed endometrial samples. According to image analysis, the amount of intracellular mucus increases during oestrus, but secretions become denser during dioestrus (P < 0.05). In the present study, mucus production in mares with delayed uterine clearance was greater than that of reproductively healthy mares (P < 0.05).

Cervical human papillomavirus deoxyribonucleic acid persists throughout pregnancy and decreases in the postpartum period.

OBJECTIVE: Our goal was to determine the persistence of human papillomavirus infection of the cervix in a prospectively evaluated cohort of pregnant women observed from the first trimester until after delivery. STUDY DESIGN: A group of 232 women were enrolled in the first trimester of pregnancy and had cervico-vaginal lavage specimens collected for detection of the deoxyribonucleic acid of human papillomavirus. They underwent sampling again in the third trimester (146 patients available) and at 4 to 12 weeks after delivery (83 patients available). Human papillomavirus deoxyribonucleic acid was detected by means of the Hybrid Capture assay. RESULTS: In the first trimester of pregnancy, 31% of the patients had positive test results for human papillomavirus deoxyribonucleic acid, whereas 35.6% had positive results in the third trimester (P = 1.0). A comparison of first-trimester test results with postpartum results (paired data available from 83 patients) showed a decline from 39.8% positivity to 26.5% (P =.04). Comparing third-trimester results with postpartum results (paired data available from 74 patients) showed a decline from 35.1% to 25. 7% positivity (P =.12). When specimens positive for human papillomavirus were divided between those containing "high cancer risk" types (9 virus types often associated with dysplasia or malignancy) and "low cancer risk" types (5 types usually found in benign lesions), similar trends were seen, although not all comparisons were statistically significant. CONCLUSION: The increased prevalence, during pregnancy, of detectable human papillomavirus deoxyribonucleic acid, which was previously reported (Fife et al, Am J Obstet Gynecol 1996;174:1487-93), persists at a similar level throughout pregnancy but declines in the postpartum period. This observation is most consistent with activation of the virus by the physiologic changes of pregnancy.

Standardization of the experimental model of Haemophilus ducreyi infection in human subjects.

Human volunteers were challenged with Haemophilus ducreyi. Twenty subjects were inoculated with 2 doses (approximately 30 cfu) of live and 1 dose of heat-killed bacteria at 3 sites on the arm. Eight subjects were assigned to biopsy 1 or 4 days after inoculation, and 12 were biopsied after they developed a painful pustular lesion or were followed until disease resolved. Papules developed at 95% of 40 sites infected with live bacteria (95% confidence interval [CI], 83. 1%-99.4%). In 24 sites followed to end point, 27% of the papules resolved, 69% (95% CI, 47.1%-86.6%) evolved into pustules, and 4% remained at the papular stage. Recovery rates of H. ducreyi from surface cultures ranged from 13% to 41%. H. ducreyi was recovered from biopsies of 12 of 15 pustules and 1 of 7 papules, suggesting that H. ducreyi replicates between the papular and pustular stages of disease.

Chronic fluoride exposure does not cause detrimental, extraskeletal effects in nutritionally deficient rats.

On the basis of observations that endemic fluorosis occurs more often in malnourished populations, a series of studies tested the hypothesis that deficient dietary intake of calcium, protein or energy affects fluoride metabolism so that the margin of safe fluoride exposure may be reduced. The objective of the investigation was to determine whether changes in fluoride metabolism in nutritionally deficient rats resulted in manifestation of any extraskeletal toxic fluoride effects not observed in healthy animals. This investigation included two studies, one that monitored the effect of calcium deficiency on the effects of chronic fluoride exposure, and a second study that observed fluoride effects in rats that were deficient either in protein or in energy and total nutrient intake. Control and experimental rats received drinking water containing 0, 0.26 (5), 0.79 (15) or 2.63 (50) mmol fluoride/L (mg/L) for 16 or 48 wk. Control rats were fed optimal diets and experimental rats were fed diets deficient in calcium (Study 1) or protein (Study 2). An additional group of experimental rats (Study 2) was provided with a restricted amount of diet; thus these rats were deficient in energy and total nutrient intake. The intake, excretion and retention of fluoride were monitored; after the rats were killed, tissue fluoride levels and biochemical markers of tissue function were analyzed. Bone marrow cells were harvested from some of the rats, after 48 wk of treatment, for determining the frequency of sister chromatid exchange, a marker of genetic damage. Although there were significant differences among fluoride treatment groups in fluoride excretion and retention that resulted in significantly greater fluoride levels in tissues of the experimental rats, we were unable to detect any harmful, extraskeletal biochemical, physiologic or genetic effects of fluoride in the nutritionally deficient rats.

Revision rates after knee replacement in the United States.

OBJECTIVES: Each year approximately 100,000 Medicare patients undergo knee replacement surgery. Patients, referring physicians, and surgeons must consider a variety of factors when deciding if knee replacement is indicated. One factor in this decision process is the likelihood of revision knee replacement after the initial surgery. This study determined the chance that a revision knee replacement will occur and which factors were associated with revision. METHODS: Data on all primary and revision knee replacements that were performed on Medicare patients during the years 1985 through 1990 were obtained. The probability that a revision knee replacement occurred was modeled from data for all patients for whom 2 full years of follow-up data were available. Two strategies for linking revisions to a particular primary knee replacement for each patient were developed. Predictive models were developed for each linking strategy. ICD-9-CM codes were used to determine hospitalizations for primary knee replacement and revision knee replacement. RESULTS: More than 200,000 hospitalizations for primary knee replacements were performed, with fewer than 3% of them requiring revision within 2 years. The following factors increase the chance of revision within 2 years of primary knee replacement: (1) male gender, (2) younger age, (3) longer length of hospital stay for the primary knee replacement, (4) more diagnoses at the primary knee replacement hospitalization, (5) unspecified arthritis type, (6) surgical complications during the primary knee replacement hospitalization, and (7) primary knee replacement performed at an urban hospital. CONCLUSIONS: Revision knee replacement is uncommon. Demographic, clinical, and process factors were related to the probability of revision knee replacement.

A comparison of ibuprofen versus acetaminophen with codeine in the young tonsillectomy patient.

OBJECTIVE: To compare the use of ibuprofen with the use of acetaminophen with codeine for posttonsillectomy management. BACKGROUND: We were not satisfied with our traditional pain-management practice for tonsillectomy patients. We hoped to find a new approach for improved patient comfort and avoid scheduled, abusable drugs such as codeine. DESIGN: Intervention, prospective, randomized control trial. Follow-up was 1 month. SETTING: University referral center; institutional pediatric practice, ambulatory. PATIENTS: 110 children undergoing tonsillectomy with or without other procedures. Consecutive patients were offered participation. Enrollees were randomly assigned to one of two classes and analyzed with the initial assignment. No patients withdrew for adverse effects, although 12 in group 2 used codeine and 5 of those used acetaminophen, whereas 2 in group 1 received ibuprofen. INTERVENTIONS: Patients received either acetaminophen with codeine (group 1) or ibuprofen (group 2) for postoperative pain control. MAIN OUTCOME MEASURES: The main outcomes, determined before initiation of the study, were assessment of (1) postoperative bleeding, (2) pain, (3) efficacy of relief of pain by drug, (4) nausea, (5) emesis, (6) readmission to hospital, (7) average temperature, and (8) highest temperature after surgery. RESULTS: The only statistically significant difference is less nausea in patients receiving ibuprofen (p = 0.0049). Of note, no difference existed in postoperative bleeding, pain, or temperature control. CONCLUSIONS: Ibuprofen is at least as effective as acetaminophen with codeine for postoperative pain control in children after tonsillectomy.

Cytomorphologic correlates of human papillomavirus infection in the "normal" cervicovaginal smear.

OBJECTIVE: To determine if cytologic abnormalities less striking than those usually considered diagnostic could predict the presence of human papillomavirus (HPV). STUDY DESIGN: Cervical scrapings were obtained from 403 women and examined by conventional Papanicolaou staining and for the presence of low- and high-risk human HPV DNA. The cytologic smears from 63 HPV DNA-positive and 63 matched HPV DNA-negative patients whose smears were initially read as normal or inflammatory were reviewed by a single cytotechnologist and a cytopathologist, who were blind to the HPV result. RESULTS: The cytologic diagnosis was upgraded to atypical squamous cells of undetermined significance (ASCUS) in nine cases and to low grade squamous intraepithelial lesion in one. All 10 upgraded cases were from the HPV DNA-positive group. A review diagnosis of ASCUS was significantly associated with both HPV in general and the presence of high-risk HPV DNA. Partial koilocytosis and multinucleation were associated with the detection of high-risk HPV DNA, while only partial koilocytosis was associated with the presence of low-risk HPV DNA. CONCLUSION: Because infection with high-risk HPV types is associated with cervical neoplasia, partial koilocytosis and multinucleation should be viewed with greater concern and possibly added to the ASCUS definition.

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.

Cancer-associated human papillomavirus types are selectively increased in the cervix of women in the first trimester of pregnancy.

OBJECTIVE: Because of incomplete data in the current literature, we sought to determine whether pregnancy is an independent risk for the detection of human papillomavirus infection. STUDY DESIGN: Pregnant patients in their first trimester who are seen for routine care at an obstetrics clinic and nonpregnant patients receiving routine care at a sexually transmitted diseases clinic and a gynecology clinic were recruited. Cervical cells were collected by saline solution lavage, and deoxyribonucleic acid was extracted and tested for the presence of human papillomavirus deoxyribonucleic acid with the hybrid capture assay. This assay detects the deoxyribonucleic acid of five "low cancer risk" and nine "high cancer risk" human papillomavirus types with two separate pools of deoxyribonucleic acid probes. RESULTS: Results from 245 pregnant women, 248 patients from the sexually transmitted diseases clinics, and 246 gynecology clinic patients were analyzed. Human papillomavirus deoxyribonucleic acid was detected in samples from 31% of the pregnant patients compared with 17.7% and 18.6% of the sexually transmitted diseases clinic and gynecology clinic patients, respectively. There was no significant difference in positivity for the "low-risk" human papillomavirus types among the three groups (positivity rates from 8.9% to 12.7%), but the pregnant patients had a significantly higher positivity rate for the "high-risk" human papillomavirus types (24.9% compared with 13.3% and 11.4% for the sexually transmitted diseases and gynecology clinic patients, respectively; p < 0.001). A multiple logistic regression analysis showed that pregnancy was an independent predictor of a positive test result for a "high-risk" human papillomavirus type (odds ratio 1.79, 95% confidence interval 1.11 to 2.89) but not a positive test result for a "low-risk" type. CONCLUSIONS: Because sexual activity was not greater among the pregnant patients, we propose that the increased detection of "high-risk" human papillomavirus types among the pregnant patients represents a selective activation of these viruses by hormonal or immunologic factors associated with pregnancy.

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)

Detection of multiple human papillomavirus types in condylomata acuminata from immunosuppressed patients.

Using the hybrid capture method, condylomata acuminata from healthy patients (controls) and patients with altered cell-mediated immunity were analyzed for multiple human papillomavirus (HPV) DNA: 82.9% and 38.0% of lesions from 41 controls and 21 patients, respectively, were HPV DNA-positive only with probes for low-risk HPV types (P = .00035). Using probes for both low- and high-risk HPV types, 16.3% and 52.3% of lesions from 43 controls and 21 patients, respectively, were positive for both probes (P = .0038). Evidence of multiple HPV types was also found by Southern blot and in situ hybridization studies. The mean HPV copy number detected by either probe did not differ significantly among patient groups. Using sensitive techniques, such as hybrid capture, multiple HPV types, including those associated with genital malignancy, can be detected in condylomata acuminata. Serial biopsies demonstrate the dynamic nature of genital HPV infection and that changes in the predominant HPV types may be reflected in tissue pathology.

Tricompartmental knee replacement. A comparison of orthopaedic surgeons' self reported performance rates with surgical indications, contraindications, and expected outcomes. Knee Replacement Patient Outcomes Research Team.

The chance of a person with osteoarthritis of the knee receiving a knee replacement is highly variable. To understand better the reasons for this variation, all practicing orthopaedists in Indiana were surveyed about their management of severe knee osteoarthritis and their perception of tricompartmental knee replacement as a therapeutic option. Their perceptions of indications and outcomes of knee replacement were compared with the self reported annual number of patients for whom they performed (or referred to other surgeons for) tricompartmental knee replacements. A completed survey was returned by 220 (79%) of the 280 orthopaedists surveyed; analyses were limited to the 188 respondents who had cared for at least one patient with osteoarthritis of the knee in the prior 2 weeks (mean = 13). These surgeons reported performing (or referring patients for) a mean of 31 knee replacements in the prior year (SD 45, median 21, range 0-480 knee replacements). There was strong agreement (> 95%) among respondents for seven (21%) of 33 surgical indications and contraindications, and more general agreement (> 60%) for 21 (64%). In the five factors (15%) for which there was disagreement, there was no consistent relationship between opinions and self reported knee replacement performance rate. Surgeons reporting more knee replacements had significantly higher estimates of pain relief and functional improvement following surgery, and lower estimates of prosthesis infection and failure rates. When all responses were considered together, four decision factors correlated independently with the performance of more knee replacements, but these four factors explained only 24% of the variation in self reported knee replacement performance.(ABSTRACT TRUNCATED AT 250 WORDS)

A randomized, double blind, placebo controlled trial of intravenous loading with S-adenosylmethionine (SAM) followed by oral SAM therapy in patients with knee osteoarthritis.

OBJECTIVE: We evaluated the effectiveness and rapidity of onset of S-adenosylmethionine (SAM), administered as daily intravenous boluses of 400 mg for 5 days, followed by oral tablets, 200 mg thrice daily for 23 days, versus a matching placebo regimen, in the treatment of 81 patients with symptomatic knee osteoarthritis (OA). METHODS: The study was bicentric, randomized, double blinded, and placebo controlled. Patients underwent a 7-day washout of arthritis medications prior to initiation of this study treatment. Major outcome measures were the Stanford Health Assessment Questionnaire disability and pain scales, and supplemental visual analog scales for rest and walking pain. RESULTS: At one site, patients had milder OA, the baseline characteristics of the treatment groups were well matched, and the SAM treated group showed significantly greater reduction in overall pain and rest pain (p < 0.05) than the placebo treated group. At the other site, the patients had more severe OA, randomization yielded markedly different treatment groups, and the response to treatment did not differ between groups. Onset of SAM effect was seen as early as 14 days after the start of treatment. CONCLUSION: SAM may be an effective treatment for some patients with symptomatic knee OA, and merits further study. Intravenous loading before oral maintenance therapy may be advantageous.

Detection of human papillomavirus L1 protein in condylomata acuminata from various anatomical sites.

BACKGROUND AND OBJECTIVES: Though human papillomavirus (HPV) DNA can be detected in the majority of condylomata acuminata, the major capsid protein of HPV (L1 protein) can be detected in only 10% to 50% of lesions in immunohistochemical assays. GOAL OF STUDY: To evaluate the association between anatomic location of genital HPV infections and the ability to detect HPV L1 protein. METHODS: Condylomata acuminata from 49 male and 51 female patients were evaluated for L1 protein by immunohistochemistry. Thirty of these lesions were vulvar; 20 were cervical; 1 was vaginal; 45 were penile; and 4 were perianal. A quantitative analysis of L1-positive nuclei in the lesions was performed. RESULTS: L1 protein was detected in 20 (20%) of all lesions. L1 protein was detected in seven (35%) of the cervical lesions compared to nine (12%) of exophytic condylomata acuminata of males and females (P = 0.038). A statistically significant difference was noted between cervical and exophytic condylomata acuminata lesions (46.6 vs. 7.8) (P = 0.0006). No association between oral contraceptive use and L1 protein detection was found. CONCLUSIONS: The major capsid protein of HPV can be detected in condylomata acuminata of the uterine cervix more often, and in higher quantities, than in lesions of the vulva or penis. Further studies are needed to assess the effects of sex hormones and the anatomic location of the infection as they relate to transmission of HPV.

Current practices for monitoring ocular toxicity related to hydroxychloroquine (Plaquenil) therapy.

OBJECTIVE: Growing interest in aggressive early management of rheumatoid arthritis (RA) with hydroxychloroquine (alone or in combination with other immunomodulating drugs) is reason to review current practices for monitoring ocular toxicity in patients who take antimalarial therapy. METHODS: We surveyed by mail all ophthalmologists and rheumatologists in the State of Indiana about their practices in this regard. RESULTS: Twenty-nine of 31 rheumatologists (94%) responded. All but one recommended ophthalmologic examinations every 6 months and 41% would leave the choice of testing procedures to the ophthalmologist. Fifty percent had discontinued hydroxychloroquine because of a patient's failure to make and/or keep an appointment with the ophthalmologist. Of 213 ophthalmologists surveyed, 150 (70%) responded. Seventy-nine percent recommended semiannual examinations. Funduscopy, visual acuity, and color vision tests were reported to be performed routinely. Eleven of 13 retina specialists (85%), but only 25% of 127 general ophthalmologists, would obtain macular photographs (p < 0.001). Forty-two percent of general ophthalmologists, compared with 8% of retina specialists, would perform computerized perimetry (p < 0.001). Recognition of retinal hyperpigmentation as a classic sign was surprisingly low in both groups. Concurrent review of the medical records of 24 patients with RA or systemic lupus erythematosus showed extremely variable followup intervals for ophthalmologic examination; 7 of the 24 patients had no record of an ophthalmologic evaluation. CONCLUSION: As interest in the early, aggressive management of RA continues to grow, significant education needs to be devoted to the monitoring and diagnosis of ocular toxicity of hydroxychloroquine by both rheumatologists and ophthalmologists.

Cost-effectiveness of increased telephone contact for patients with osteoarthritis. A randomized, controlled trial.

OBJECTIVE: To evaluate the cost-effectiveness of telephone intervention for patients with osteoarthritis. METHODS: Randomized, controlled trial. RESULTS: The intervention did not significantly increase health care costs. The annual costs for a 1-unit improvement in physical functioning and in pain, as measured by the Arthritis Impact Measurement Scales, were $70.86 and $31.00, respectively. CONCLUSION: Telephone contact is a potentially cost-effective intervention in osteoarthritis.