Melton, L. Joseph

Population-based data on vanicella complications are presented using information both from national sample surveys of hospitalizations and physician office visits and from reviews of medical records for all cases occurring within one community (Olmsted County, Minnesota) during a specified period. Acute cerebellar ataxia is the most common neurologic complication of varicella and occurs about once in 4,000 vanicella cases among children younger than 15 years of age. Among adults, varicella pneumonia is the most common complication and results in hospitalization about once in every 400 varicella cases. Overall, varicella accounts for approximately 4,000 hospitalizations and 364,000 physician office visits annually in the United States and represents an important continuing source of childhood and adult morbidity.

Abstract Confinement to a nursing home (NH) is an independent risk factor for VTE and accounts for 13% of all VTE occurring in the community, but the question of which NH residents are at risk is largely unanswered. Objective: To determine VTE risk factors among NH residents. Methods: Using the Minnesota State Case Mix Review Program Public Research Files, we performed a case-control study of all Olmsted County, MN NH patients with an ICD-9 code-identified diagnosis of VTE from 1988–1994. From the same source, we identified one age-, sex-matched control and used conditional logistic regression to estimate odds ratios for an association of VTE with 46 characteristics assessed in the Minnesota Case Mix data. Results: Univariate associations between characteristics and odds of VTE are described below. Significantly increased odds were observed for residents assessed following hospitalization (a nearly 4-fold increase, p=0.002, Table) and residents considered incapable of self-preservation (i.e., unable to cope with potentially harmful situations) (> 2.0 fold increase, p=0.03). Non-significant 2–3 fold increased odds were observed for limitations in certain specific Activities of Daily Living (ADL) (including walking and dressing) and for limitations in more than 3 ADLs. Similar increased odds were observed for residents using a wheelchair, taking more than 3 oral medications, enrolled in professional activity programs, and needing behavior management. Conclusions: Need for assistance (especially problems with immobility), lack of self preservation, and recent hospitalization may identify a subset of NH residents that are at especially high VTE risk and who may warrant consideration of prophylaxis. Univariate VTE Risk Factors for Nursing Home Residents Characteristic Odds Ratio 95% CI P-value Oral medications > 3 3.00 0.97-9.30 0.06 Activities of Daily Living High/Medium (4-8) vs. low (0-3) 2.20 0.76-6.33 0.14 Help dressing 2.75 0.88-8.64 0.08 Help walking 3.00 0.61-14.86 0.18 Wheelchair use 2.50 0.97-6.44 0.58 Needs behavior management 3.00 0.62-14.86 0.18 Help toileting 2.00 0.68-5.85 0.20 Lack of self-preservation 2.33 1.07-5.10 0.03 Transfer from hospital 3.86 1.68-8.86 0.0015 Anti-depressant drugs 0.50 0.19-1.33 0.16 Professional activity program 2.25 0.69-7.3 0.18

Abstract Active cancer is an independent VTE risk factor (overall 6- to 9-fold increased risk) and accounts for almost 20% of all VTE in the community, but which cancer patients are at risk for VTE is largely unknown. Reportedly, VTE risk varies by tumor site, and cancer of the ovary, pancreas, colon, stomach, lung, prostate, and kidney convey particularly high VTE risk. Objective: To estimate VTE risk by tumor site. Methods: We enumerated observed cancers by tumor site for Olmsted County, MN active cancer patients with incident VTE over the seven-year period, 1991–1997 (n=152). We used 1991–1997 State Surveillance, Epidemiology, and End Results (SEER) data for Iowa to estimate the expected age-specific prevalence of cancer by tumor site in Olmsted County. VTE risk ratios (RR) for each tumor site were estimated by dividing the observed number of cancers by the expected number (calculated as the product of the SEER prevalence and the number of incident VTE cases in the age stratum). Results: For our population of 1991–1997 VTE cases, all tumor sites had RR > 5.0 (range 5.2 to 37.3, all p-values<0.05). Compared to published overall VTE odds ratios of 6–9 for active cancer compared to no cancer, the RR for some tumor sites were particularly increased. A Chi-squared test of heterogeneity of the RR across sites was highly significant (p-value<0.001). Three rare cancer sites - pancreatic cancer, lymphoma, and brain cancer - had unusually high RR (all RR>25). The high number of VTE cases with lymphoma was not due to catheter-related arm vein thrombosis. Liver, leukemia, other gastrointestinal (esophagus, small intestine, gallbladder, other biliary) and other gynecologic (primarily cervical) cancers had over twice the baseline risk (i.e., RR>17.0). On the other hand, the RR for many common cancers (breast, colorectal, ovary, lung, prostate) were essentially the same as the overall baseline risk (all had 9.5<RR<12.0). Conclusions: In contrast to previous reports, pancreas, lymphoma, brain, liver, leukemia, other gastrointestinal, and other gynecologic cancers have the highest VTE risk. Prior estimates of VTE risk by tumor site may have been biased by studies of prevalent cancers among patients hospitalized in tertiary care centers.

The quality of the epidemiological data on diabetic neuropathies remains poor for a variety of reasons. They include variability in 1) ascertainment of diabetes, 2 the clinical varieties of diabetic patients studied, 3) characterization of neurological dysfunction, 4) abnormal limits for neurological examinations and tests, 5) minimal criteria for neuropathy, 6) correct attribution of nondiabetic neurological disease, 7) correct attribution of type of neuropathy, 8) estimating neuropathy from use of multiple tests, and 9) estimating severity of polyneuropathy. We have tried to remedy these shortcomings in the Rochester Diabetic Neuropathy Study (RDNS). It was not possible to adequately characterize and quantitate diabetic polyneuropathies using only one or two clinical or test abnormalities. To estimate severity of diabetic polyneuropathy, the results of the neurological examination and abnormalities of nerve conduction, quantitative sensory tests, and quantitative autonomie tests were combined into a composite score. One begins by scoring a standard test of neurological deficits (impairments) of the lower limbs (NIS[LL]) and adds to this transformed numbers for percentile abnormality of seven good functional tests. This NIS(LL)+7 tests score appears to provide a much more comprehensive and stable numeric score by which to diagnose and grade severity of diabetic polyneuropathy than does the use of individual clinical or test results. This test score should be useful as a measure of change in diabetic polyneuropathy for purposes of medical practice, epidemiology studies, and controlled clinical trials. The staging approach that we introduced previously continues to provide an important measure of overall severity of diabetic polyneuropathy, taking into account both symptoms and impairments.

Using the records linkage system of the Mayo Clinic and of the Rochester Epidemiology Project, which accesses diagnostic data on the entire population of Olmsted County, Minnesota, we identified 45 new cases of idiopathic dilated cardiomyopathy (DCM) and 19 new cases of hypertrophic cardiomyopathy (HCM) among county residents for the years 1975-1984. Overall age- and sex-adjusted incidence rates were 6.0/100,000 and 2.5/100,000 person-years, respectively. The incidence of DCM doubled from 3.9/100,000 in the first 5 years to 7.9/100,000 person-years in the last 5 years of study. The corresponding change for HCM was from 1.4 to 3.6/100,000 person-years. Age- and sex-adjusted prevalence rates as of January 1, 1985, for DCM and HCM were 36.5/100,000 and 19.7/100,000 population, respectively. The prevalence of DCM in persons less than 55 years old was 17.9/100,000, over a third of whom were New York Heart Association functional Class III or IV at diagnosis. These estimates may be of value in determining the potential use of health care resources, particularly cardiac transplantation.

Abstract Fractures are increased among men with prostate cancer, especially those on androgen-deprivation therapy (ADT), but few data are available on men with localized prostate cancer. The purpose of this investigation was to estimate fracture risk among unselected community men with prostate cancer and systematically assess associations with ADT and other risk factors for fracture. In a population-based retrospective cohort study, 742 Olmsted County, MN, men with prostate cancer first diagnosed in 1990–1999 (mean age 68.2 ± 8.9 years) were followed for 6821 person-years. We estimated cumulative fracture incidence, assessed relative risk by standardized incidence ratios, and evaluated risk factors in time-to-fracture regression models. All together, 482 fractures were observed in 258 men (71 per 1000 person-years). Overall fracture risk was elevated 1.9-fold, with an absolute increase in risk of 9%. Relative to rates among community men generally, fracture risk was increased even among men not on ADT but was elevated a further 1.7-fold among ADT-treated compared with untreated men with prostate cancer. The increased risk following various forms of ADT was accounted for mainly by associations with pathologic fractures (14% of all fractures). Among men not on ADT (62% of the cohort), more traditional osteoporosis risk factors were implicated. In both groups, underlying clinical characteristics prompting different treatments (indication bias) may have been partially responsible for the associations seen with specific therapies. To the extent that advanced-stage disease and pathologic fractures account for the excess risk, the effectiveness of fracture prevention among men with prostate cancer may be limited. © 2011 American Society for Bone and Mineral Research

Abstract Finite-element analysis (FEA) of quantitative computed tomography (QCT) scans can estimate site-specific whole-bone strength. However, it is uncertain whether the site-specific detail included in FEA-estimated proximal femur (hip) strength can determine fracture risk at sites with different biomechanical characteristics. To address this question, we used FEA of proximal femur QCT scans to estimate hip strength and load-to-strength ratio during a simulated sideways fall and measured total hip areal and volumetric bone mineral density (aBMD and vBMD) from QCT images in an age-stratified random sample of community-dwelling adults age 35 years or older. Among 314 women (mean age ± SD: 61 ± 15 years; 235 postmenopausal) and 266 men (62 ± 16 years), 139 women and 104 men had any prevalent fracture, whereas 55 Women and 28 men had a prevalent osteoporotic fracture that had occurred at age 35 years or older. Odds ratios by age-adjusted logistic regression analysis for prevalent overall and osteoporotic fractures each were similar for FEA hip strength and load-to-strength ratio, as well as for total hip aBMD and vBMD. C-statistics (estimated areas under ROC curves) also were similar [eg, 0.84 to 0.85 (women) and 0.75 to 0.78 (men) for osteoporotic fractures]. In women and men, the association with prevalent osteoporotic fractures increased below an estimated hip strength of approximately 3000 N. Despite its site-specific nature, FEA-estimated hip strength worked equally well at predicting prevalent overall and osteoporotic fractures. Furthermore, an estimated hip strength below 3000 N may represent a critical level of systemic skeletal fragility in both sexes that warrants further investigation. © 2011 American Society for Bone and Mineral Research.

Abstract Because they are not reliably discriminated by areal bone mineral density (aBMD) measurements, it is unclear whether minimal vertebral deformities represent early osteoporotic fractures. To address this, we compared 90 postmenopausal women with no deformity (controls) with 142 women with one or more semiquantitative grade 1 (mild) deformities and 51 women with any grade 2–3 (moderate/severe) deformities. aBMD was measured by dual-energy X-ray absorptiometry (DXA), lumbar spine volumetric bone mineral density (vBMD) and geometry by quantitative computed tomography (QCT), bone microstructure by high-resolution peripheral QCT at the radius (HRpQCT), and vertebral compressive strength and load-to-strength ratio by finite-element analysis (FEA) of lumbar spine QCT images. Compared with controls, women with grade 1 deformities had significantly worse values for many bone density, structure, and strength parameters, although deficits all were much worse for the women with grade 2–3 deformities. Likewise, these skeletal parameters were more strongly associated with moderate to severe than with mild deformities by age-adjusted logistic regression. Nonetheless, grade 1 vertebral deformities were significantly associated with four of the five main variable categories assessed: bone density (lumbar spine vBMD), bone geometry (vertebral apparent cortical thickness), bone strength (overall vertebral compressive strength by FEA), and load-to-strength ratio (45-degree forward bending ÷ vertebral compressive strength). Thus significantly impaired bone density, structure, and strength compared with controls indicate that many grade 1 deformities do represent early osteoporotic fractures, with corresponding implications for clinical decision making. © 2010 American Society for Bone and Mineral Research