Stephen R. Evans

Frequency of specific cancer types in dermatomyositis and polymyositis: a population-based study.

BACKGROUND Dermatomyositis and polymyositis are associated with cancer, but previous nationwide studies have not had sufficient cases to test the association between myositis and specific cancer types. Our aim was to investigate the risk of specific cancer types in individuals with dermatomyositis and polymyositis. METHODS We did a pooled analysis of published national data from Sweden, Denmark, and Finland. All patients with dermatomyositis and polymyositis (> or =15 years old) were identified by discharge diagnosis from the Swedish National Board of Health (1964-83), Danish Hospital Discharge Registry (1977-89), and Finnish National Board of Health (1969-85). Personal details were matched to national cancer registries, to identify all cases of cancer up to 1987 in Sweden, 1995 in Denmark, and 1997 in Finland, and to national death registries for the same periods. We calculated standardised incidence ratios (SIR) for individual cancer sites for dermatomyositis and polymyositis separately, using national cancer rates by country, sex, age, and date. FINDINGS We identified 618 cases of dermatomyositis, of whom 198 had cancer. 115 of the 198 developed cancer after diagnosis of dermatomyositis. This disease was strongly associated with malignant disease (SIR 3.0, 95% CI 2.5-3.6), particularly ovarian (10.5, 6.1-18.1), lung (5.9, 3.7-9.2), pancreatic (3.8, 1.6-9.0), stomach (3.5, 1.7-7.3), and colorectal (2.5, 1.4-4.4) cancers, and non-Hodgkin lymphoma (3.6, 1.2-11.1). 137 of the 914 cases of polymyositis had cancer, which developed after diagnosis of polymyositis in 95. Polymyositis was associated with a raised risk of non-Hodgkin lymphoma (3.7, 1.7-8.2), and lung (2.8, 1.8-4.4) and bladder cancers (2.4, 1.3-4.7). In both dermatomyositis and polymyositis, risk of malignant disease was highest at time of myositis diagnosis. INTERPRETATION Our results provide evidence that dermatomyositis is strongly associated with a wide range of cancers. The overall risk of malignant disease is also modestly increased among patients with polymyositis, with an excess for some cancers.

Association of hypogonadism and estradiol levels with bone mineral density in elderly men from the Framingham study

Osteoporosis is not a problem confined to women; it has important medical and socioeconomic consequences for men as well (1-3). With advancing age, men lose bone mineral density (4, 5), which leads to increased risk for fracture after minimal trauma (6). It is estimated that 13% of white men older than 50 years of age will experience a fracture during their lifetime (7). Approximately 30% of all hip fractures occur in men (8), and the morbidity and mortality after such fractures are much greater in men than in women (9-11). As the aging population grows worldwide, a better understanding of risk factors that contribute to low bone mineral density in elderly men will be needed. The effect of sex hormones on bone mineral density in elderly men is of particular interest because it could have diagnostic and therapeutic implications, as it does in women (12, 13). Both androgens and estrogens have been shown to be important for bone health in young men, but their role in elderly men is not as clear (14, 15). Testosterone, the predominant circulating androgen in men, is produced mainly by Leydig cells of the testes and is regulated by luteinizing hormone (16, 17). Hypogonadism in men, whether caused by primary or secondary failure of Leydig cell function, results in low testosterone levels. Young adult men who are hypogonadal because of medical conditions or castration have low bone mineral density (18-20); testosterone replacement improves bone mineral density in these men (19, 21). Given the association between hypogonadism and bone mineral density in young men and the decrease in serum testosterone levels with increasing age (22, 23), it has been assumed that hypogonadism related to aging explains low bone mineral density in elderly men. However, evidence to support this association remains weak. Results of studies that include men of a wide age range or hypogonadal men with an identifiable medical cause (such as orchiectomy or pituitary tumors) are not generalizable to elderly men from the general population. Among studies specifically of elderly men from the general population, several failed to show an association between testosterone levels and bone mineral density (24-28). It could be that an association with bone mineral density exists only below the normal reference range for testosterone (29) and that continuous measurement of testosterone levels, as was done in most studies, missed this relation. Previous studies may have also been limited by the fact that single measurements of sex hormones obtained at the same time as bone mineral density measurement may not adequately reflect the influence of these hormones on bone metabolism. Recent evidence suggests that estrogens may also be important for bone health in young and older men (14, 27, 28, 30-36). However, the magnitude of effect of estrogen levels on bone mineral density in elderly men is not known, nor is the relative effect of testosterone and estrogens clearly defined. Only a small fraction of estradiol, the major circulating form of estrogen, is produced directly by the testes; the main source is peripheral conversion of testosterone and adrenal sex steroids by the aromatase enzyme (17, 37). Thus, some or all of the effect of low testosterone on bone mineral density in elderly men could be explained by low estradiol levels. We examined the association of testosterone and estradiol status with bone mineral density among men from the Framingham Study, a population-based cohort with a large number of elderly men who had repeated measurement of sex hormones before bone mineral density assessment. We explored the association of a threshold effect of low testosterone level on bone mineral density in these men by considering different definitions of hypogonadism based on sex hormone measures. Methods The Framingham Study began in 1948 in Framingham, Massachusetts, with the initial goal of evaluating risk factors for heart disease in a population-based cohort (38). As part of this ongoing study, participants have received comprehensive medical examinations every 2 years. The Framingham Osteoporosis Study, designed to study risk factors for osteoporosis, started in 19881989 as a component of the 20th biennial examination and involved surviving members of the cohort, most of whom were white (39). We studied the 448 men of the cohort who had bone mineral density measurements in 19881989 and sex hormones measurements during previous biennial examinations. Assessment of Sex Hormones Total testosterone, total estradiol, and luteinizing hormone were measured in all male participants at four consecutive biennial examinations from 1981 to 1989. Serum samples were measured by using radioimmunoassay for total testosterone (Diagnostic Products Corp., Los Angeles, California; interassay coefficient of variation, 11%; reference range for young adult men, 10 to 35 nmol/L [3 to 10 ng/mL]), total estradiol (Diagnostic Products Corp.; lower limit of assay detection, 2 pg/mL; interassay coefficient of variation, 4%; reference range for young adult men, 7 to 184 pmol/L [2 to 50 pg/mL]), and luteinizing hormone (Serono Laboratories, Randolph, Massachusetts, in 1981 to 1983, then Diagnostic Products Corp. for the three biennial examinations from 1983 to 1989; intraclass correlation, 0.92; interassay coefficient of variation, 6%; reference range for young adult men, 3 to 13 IU/L). Data were originally collected in traditional units, and cutoff values were defined on the basis of these units. Conversions to SI units were performed in accordance with the publication policy of Annals of Internal Medicine. Assessment of Bone Mineral Density In 19881989, bone mineral density was measured at the proximal femur (femoral neck, Ward triangle, and trochanter) and lumbar spine by using dual-photon absorptiometry (LUNAR DP3, Lunar Corp., Madison, Wisconsin) and at the radial shaft (measured at the junction of the proximal two thirds and the distal one third of the radius) by using single-photon absorptiometry (LUNAR SP2, Lunar Corp.) (39). If participants had a history of fracture or hip joint replacement, the contralateral side was scanned. Because the lumbar spine was assessed during a callback examination, the number of participants for whom this measurement was available is smaller than that for the proximal femur or radial shaft. All bone mineral density scans were reviewed to ensure that correct placement and analysis were performed according to the manufacturers recommendations. Scans for which placement was incorrect, those that did not include the complete anatomic region of interest, and those found to include metal or other attenuating material were considered technically inadequate and were deleted. The coefficients of variation in normal persons for bone mineral density at the proximal femur were 2.6% for the femoral neck, 4.1% for Ward triangle, and 2.8% for the trochanter; the coefficients of variation were 2.2% and 2.0% for the lumbar spine and radial shaft, respectively. Assessment of Other Covariates Factors previously shown to be associated with bone mineral density in men were also assessed (15, 39-46). These variables were age, body mass index, serum 25-hydroxyvitamin D level, calcium intake, physical activity, cigarette smoking, alcohol intake, thiazide diuretic use, and glucocorticoid use. Age, body mass index, serum 25-hydroxyvitamin D, calcium intake, and physical activity were determined in 19881989 at the time of the bone mineral density assessment. Serum 25-hydroxyvitamin D was measured by using a competitive binding-protein assay (47) (interassay coefficient of variation, 10%) and was categorized as low (<50 nmol/L), medium (50 to 75 nmol/L), or high (>75 nmol/L). Information on dietary calcium intake, including supplements, was collected by using the Willett 126-item food frequency questionnaire (48, 49) and was categorized as low (<500 mg/d), moderate (500 to 1000 mg/d), or high (>1000 mg/d). Physical activity was assessed by using the Framingham Physical Activity Index, a weighted 24-hour score of typical daily activity based on hours spent performing heavy, moderate, light, or sedentary activity (50, 51). Information on smoking and alcohol intake was available from previous biennial examinations. Participants were characterized as current smokers if they smoked cigarettes during 1981 to 1989, former smokers if they reported smoking before 1981 but not between 1981 and 1989, and never-smokers if they reported no cigarette use since inception of the study in 1948. Alcohol intake was defined according to the average ounces of alcohol consumed per week between 1981 and 1989. Information on thiazide diuretic use among participants was available from three consecutive examinations from 1983 to 1989, and information on glucocorticoid use was available from all four examinations from 1981 to 1989. Statistical Analysis To examine the association between sex hormone status and bone mineral density, we averaged hormone values for each participant if measurements were available from at least three of four examinations from 1981 to 1989. We excluded one participant whose serum estradiol value was considered unreliable. All analyses were performed by using SAS software, version 6.12 (SAS Institute, Inc., Cary, North Carolina). Gonadal Status and Bone Mineral Density Hypogonadism in men is the loss of testicular function, which includes primary and secondary failure of the Leydig cell function in the testes, leading to a deficiency in serum testosterone levels. Studying hypogonadal elderly men from the general population is difficult, however, because there are no standard definitions of hypogonadism, and symptoms and signs are not well correlated with hormonal status (52, 53). Therefore, to examine whether hypogonadism was associated with low bone mineral density in our population-based sample of elderly men, we created a definition based on the mean total testosterone o

Maternal outcomes associated with planned primary cesarean births compared with planned vaginal births.

OBJECTIVE: To compare the outcomes and costs associated with primary cesarean births with no labor (planned cesareans) to vaginal and cesarean births with labor (planned vaginal). METHODS: Analysis was based on a Massachusetts data system linking 470,857 birth certificates, fetal death records, and birth-related hospital discharge records from 1998 and 2003. We examined a subset of 244,088 mothers with no prior cesarean and no documented prenatal risk. We then divided mothers into two groups: those with no labor and a primary cesarean (planned primary cesarean deliveries—3,334 women) and those with labor and either a vaginal birth or a cesarean delivery (planned vaginal—240,754 women). We compared maternal rehospitalization rates and analyzed costs and length of stay. RESULTS: Rehospitalizations in the first 30 days after giving birth were more likely in planned cesarean (19.2 in 1,000) when compared with planned vaginal births (7.5 in 1,000). After controlling for age, parity, and race or ethnicity, mothers with a planned primary cesarean were 2.3 (95% confidence interval [CI] 1.74–2.9) times more likely to require a rehospitalization in the first 30 days postpartum. The leading causes of rehospitalization after a planned cesarean were wound complications (6.6 in 1,000) (P<.001) and infection (3.3 in 1,000). The average initial hospital cost of a planned primary cesarean of

Disc degeneration/back pain and calcification of the abdominal aorta. A 25-year follow-up study in Framingham.

4,372 (95% C.I.

The Prosorba column for treatment of refractory rheumatoid arthritis: A randomized, double-blind, sham-controlled trial

4,293–4,451) was 76% higher than the average for planned vaginal births of

The Impact of a Novel Computer-Based Decision Aid on Shared Decision Making for Colorectal Cancer Screening: A Randomized Trial

2,487 (95% C.I.

The Association of Estrogen Replacement Therapy and the Raynaud Phenomenon in Postmenopausal Women

2,481–2,493), and length of stay was 77% longer (4.3 days to 2.4 days). CONCLUSION: Clinicians should be aware of the increased risk for maternal rehospitalization after cesarean deliveries to low-risk mothers when counseling women about their choices. LEVEL OF EVIDENCE: II

Different factors influencing the expression of Raynaud's phenomenon in men and women

Study Design. A 25‐year follow‐up study of 606 members of the population‐based Framingham cohort, who had received lateral lumbar radiographs in 1967‐1968 and 1992‐1993, and completed an interview on back symptoms at the second examination. Objectives. To evaluate whether calcific lesions in the posterior wall of the abdominal aorta, the source of the feeding arteries of the lumbar spine, are associated with disc degeneration or back pain, which would suggest that ischemia of the lumbar spine leads to disc degeneration. Methods. The presence of radiographic aortic calcification was ascertained in front of each lumbar segment from L1 through L4, and disc degeneration at intervertebral spaces from L1‐L2 through L4‐L5. The associations between aortic calcification, disc degeneration, and back pain were tested using logistic regression with adjustment for age and sex. Results. At the baseline examination, aortic calcification was significantly associated with general disc degeneration, that is, disc space narrowing or endplate sclerosis at any lumbar level (odds ratio 1.6; 95% confidence interval 1.0‐2.5; P = 0.034). In longitudinal, level‐specific analyses, comparing local aortic calcifications with disc degeneration at the matching level, aortic calcifications predicted disc deterioration, that is, a decrease in disc space or appearance of endplate sclerosis, between the examinations (odds ratio 1.5; 95% confidence interval 1.3‐1.8; P < 0.001). Furthermore, subjects in whom aortic calcifications developed between the examinations had disc deterioration twice as frequently as those in whom aortic calcifications did not develop (odds ratio 2.0; 95% confidence interval 1.2‐3.5; P = 0.013). Also, individuals with severe (Grade 3) posterior aortic calcification in front of any lumbar segment were more likely than others to report back pain during adult life (odds ratio 1.6; 95% confidence interval 1.1‐2.2; P = 0.014). Conclusions. Advanced aortic atherosclerosis, presenting as calcific deposits in the posterior wall of the aorta, increases a persons risk for development of disc degeneration and is associated with the occurrence of back pain.

Problems in the development and validation of questionnaire-based screening instruments for ascertaining cases with symptomatic knee osteoarthritis: The Framingham Study

OBJECTIVE To evaluate the efficacy and safety of the Prosorba column as a treatment for rheumatoid arthritis (RA) in patients with active and treatment-resistant (refractory) disease. METHODS A sham-controlled, randomized, double-blind, multicenter trial of Prosorba versus sham apheresis was performed in patients with RA who had failed to respond to treatment with methotrexate or at least 2 other second-line drugs. Patients received 12 weekly treatments with Prosorba or sham apheresis, with efficacy evaluated 7-8 weeks after treatment ended. Patients were characterized as responders if they experienced improvement according to the American College of Rheumatology (ACR) response criteria at the efficacy time point. A data safety monitoring board (DSMB) evaluated interim analyses for the possibility of early completion of the trial. RESULTS Patients in the trial had RA for an average of 15.5 years (range 1.7-50.6) and had failed an average of 4.2 second-line drug treatments prior to entry. After the completion of treatment of 91 randomized patients, the DSMB stopped the trial early due to successful outcomes. Of the 47 patients in the Prosorba arm, 31.9% experienced ACR-defined improvement versus 11.4% of the 44 patients in the sham-treated arm (P = 0.019 after adjustment for interim analysis). When results from 8 additional patients, who had completed blinded treatments at the time of DSMB action, were added to the analysis (n = 99), results were unchanged. The most common adverse events were a short-term flare in joint pain and swelling following treatment, a side effect that occurred in most subjects at least once in both treatment arms. Other side effects, although common, occurred equally as frequently in both treatment groups. CONCLUSION Apheresis with the Prosorba column is an efficacious treatment for RA in patients with active disease who have failed other treatments.

Use of the Americans With Disabilities Act by Persons With Rheumatic Diseases and Factors Associated With Use

Background. Eliciting patients’ preferences within a framework of shared decision making (SDM) has been advocated as a strategy for increasing colorectal cancer (CRC) screening adherence. Our objective was to assess the effectiveness of a novel decision aid on SDM in the primary care setting. Methods. An interactive, computer-based decision aid for CRC screening was developed and evaluated within the context of a randomized controlled trial. A total of 665 average-risk patients (mean age, 57 years; 60% female; 63% black, 6% Hispanic) were allocated to 1 of 2 intervention arms (decision aid alone, decision aid plus personalized risk assessment) or a control arm. The interventions were delivered just prior to a scheduled primary care visit. Outcome measures (patient preferences, knowledge, satisfaction with the decision-making process [SDMP], concordance between patient preference and test ordered, and intentions) were evaluated using prestudy/poststudy visit questionnaires and electronic scheduling. Results. Overall, 95% of patients in the intervention arms identified a preferred screening option based on values placed on individual test features. Mean cumulative knowledge, SDMP, and intention scores were significantly higher for both intervention groups compared with the control group. Concordance between patient preference and test ordered was 59%. Patients who preferred colonoscopy were more likely to have a test ordered than those who preferred an alternative option (83% v. 70%; P < 0.01). Intention scores were significantly higher when the test ordered reflected patient preferences. Conclusions. Our interactive computer-based decision aid facilitates SDM, but overall effectiveness is determined by the extent to which providers comply with patient preferences.