Predictors of venous thromboembolism recurrence and bleeding among active cancer patients: a population-based cohort study.

Active cancer is the major predictor of venous thromboembolism (VTE) recurrence, but further stratification of recurrence risk is uncertain. In a population-based cohort study of all Olmsted County, Minnesota, residents with active cancer-related incident VTE during the 35-year period from 1966 to 2000 who survived 1 day or longer, we estimated VTE recurrence, bleeding on anticoagulant therapy, and survival and tested cancer and noncancer characteristics and secondary prophylaxis as predictors of VTE recurrence and bleeding, using Cox proportional hazards modeling. Of 477 patients, 139 developed recurrent VTE over the course of 1533 person-years of follow-up. The adjusted 10-year cumulative VTE recurrence rate was 28.6%. The adjusted 90-day cumulative incidence of major bleeding on anticoagulation was 1.9%. Survival was significantly worse for patients with cancer who had recurrent VTE (particularly pulmonary embolism) and with bleeding on anticoagulation. In a multivariable model, brain, lung, and ovarian cancer; myeloproliferative or myelodysplastic disorders; stage IV pancreatic cancer; other stage IV cancer; cancer stage progression; and leg paresis were associated with an increased hazard, and warfarin therapy was associated with a reduced hazard, of recurrent VTE. Recurrence rates were significantly higher for cancer patients with 1 or more vs no predictors of recurrence, suggesting these predictors may be useful for stratifying recurrence risk.

Statin Use, Diabetes Incidence and Overall Mortality in Normoglycemic and Impaired Fasting Glucose Patients.

BACKGROUND: The association between the use of statins and the risk of diabetes and increased mortality within the same population has been a source of controversy, and may underestimate the value of statins for patients at risk. OBJECTIVE: We aimed to assess whether statin use increases the risk of developing diabetes or affects overall mortality among normoglycemic patients and patients with impaired fasting glucose (IFG). DESIGN AND PARTICIPANTS: Observational cohort study of 13,508 normoglycemic patients (n = 4460; 33% taking statins) and 4563 IFG patients (n = 1865; 41% taking statin) among residents of Olmsted County, Minnesota, with clinical data in the Mayo Clinic electronic medical record and at least one outpatient fasting glucose test between 1999 and 2004. Demographics, vital signs, tobacco use, laboratory results, medications and comorbidities were obtained by electronic search for the period 1999-2004. Results were analyzed by Cox proportional hazards models, and the risk of incident diabetes and mortality were analyzed by survival curves using the Kaplan-Meier method. MAIN MEASURES: The main endpoints were new clinical diagnosis of diabetes mellitus and total mortality. KEY RESULTS: After a mean of 6 years of follow-up, statin use was found to be associated with an increased risk of incident diabetes in the normoglycemic (HR 1.19; 95% CI, 1.05 to 1.35; p = 0.007) and IFG groups (HR 1.24; 95%CI, 1.11 to 1.38; p = 0.0001). At the same time, overall mortality decreased in both normoglycemic (HR 0.70; 95% CI, 0.66 to 0.80; p < 0.0001) and IFG patients (HR 0.77, 95% CI, 0.64 to 0.91; p = 0.0029) with statin use. CONCLUSION: In general, recommendations for statin use should not be affected by concerns over an increased risk of developing diabetes, since the benefit of reduced mortality clearly outweighs this small (19-24%) risk.

A population-based study of incidence, risk factors, clinical spectrum, and outcomes of ischemic colitis.

BACKGROUND & AIMS: Little is known about progression of ischemic colitis (IC) among unselected patients. We aimed to estimate the incidence, risk factors, and natural history of IC in a population-based cohort in Olmsted County, Minnesota. METHODS: We performed a retrospective population-based cohort and nested case-control study of IC. Each IC case was matched to 2 controls from the same population on the basis of sex, age, and closest registration number. Conditional logistic regression, the Kaplan-Meier method, and proportional hazards regression were used to assess comorbidities, estimate survival, and identify characteristics associated with survival, respectively. RESULTS: Four hundred forty-five county residents (median age, 71.6 years; 67% female) were diagnosed with IC from 1976 through 2009 and were matched with 890 controls. The age-adjusted and sex-adjusted incidence rates of IC nearly quadrupled from 6.1 cases/100,000 person-years in 1976-1980 to 22.9/100,000 in 2005-2009. The odds for IC were significantly higher among subjects with atherosclerotic diseases; odds ratios ranged from 2.6 for individuals with coronary disease to 7.9 for individuals with peripheral vascular disease. Of IC cases, 59% survived for 5 years (95% confidence interval, 54%-64%), compared with 90% of controls (95% confidence interval, 88%-92%). Age >40 years, male sex, right-sided colon involvement, concomitant small bowel involvement, and chronic obstructive pulmonary disease were all independently associated with mortality (P < .05). CONCLUSIONS: The incidence of IC increased during the past 3 decades in a population-based cohort in Minnesota. IC typically presents in older patients with multiple comorbidities and is associated with high in-hospital mortality (11.5%) and rates of surgery (17%).

Temporal Trends in the Incidence and Natural History of Diverticulitis: A Population-Based Study.

OBJECTIVES: Data on the incidence and natural history of diverticulitis are largely hospital-based and exclude the majority of diverticulitis patients, who are treated in an outpatient setting for uncomplicated diverticulitis. We assessed temporal trends in the epidemiology of diverticulitis in the general population. METHODS: Through the Rochester Epidemiology Project we reviewed the records of all individuals with a diagnosis of diverticulitis from 1980 to 2007 in Olmsted County, Minnesota, USA. RESULTS: In 1980-1989, the incidence of diverticulitis was 115/100,000 person-years, which increased to 188/100,000 in 2000-2007 (P<0.001). Incidence increased with age (P<0.001); however, the temporal increase was greater in younger people (P<0.001). Ten years after the index and second diverticulitis episodes, 22% and 55% had a recurrence, respectively. This recurrence rate was greater in younger people (hazard ratio (HR) per decade 0.63; 95% confidence interval (CI), 0.59-0.66) and women (HR 0.68; 95% CI, 0.58-0.80). Complications were seen in 12%; this rate did not change over time. Recurrent diverticulitis was associated with a decreased risk of complications (P<0.001). Age was associated with increased risk of local (odds ratio (OR) 1.27 per decade; 95% CI, 1.04-1.57) and systemic (OR 1.83; 95% CI, 1.20-2.80) complications. Survival after diverticulitis was lower in older people (P<0.001) and men (P<0.001) and worsened over time (P<0.001). The incidence of surgery for diverticulitis did not change from 1980 to 2007. CONCLUSIONS: The incidence of diverticulitis has increased by 50% in 2000-2007 compared with 1990-1999, and more so in younger people. Complications are relatively uncommon. Recurrent diverticulitis is frequent but typically uncomplicated. Younger people with diverticulitis have less severe disease, more recurrence, and better survival.

The ROKS nomogram for predicting a second symptomatic stone episode.

Most patients with first-time kidney stones undergo limited evaluations, and few receive preventive therapy. A prediction tool for the risk of a second kidney stone episode is needed to optimize treatment strategies. We identified adult first-time symptomatic stone formers residing in Olmsted County, Minnesota, from 1984 to 2003 and manually reviewed their linked comprehensive medical records through the Rochester Epidemiology Project. Clinical characteristics in the medical record before or up to 90 days after the first stone episode were evaluated as predictors for symptomatic recurrence. A nomogram was developed from a multivariable model based on these characteristics. There were 2239 first-time adult kidney stone formers with evidence of a passed, obstructing, or infected stone causing pain or gross hematuria. Symptomatic recurrence occurred in 707 of these stone formers through 2012 (recurrence rates at 2, 5, 10, and 15 years were 11%, 20%, 31%, and 39%, respectively). A parsimonious model had the following risk factors for recurrence: younger age, male sex, white race, family history of stones, prior asymptomatic stone on imaging, prior suspected stone episode, gross hematuria, nonobstructing (asymptomatic) stone on imaging, symptomatic renal pelvic or lower-pole stone on imaging, no ureterovesicular junction stone on imaging, and uric acid stone composition. Ten-year recurrence rates varied from 12% to 56% between the first and fifth quintiles of nomogram score. The Recurrence of Kidney Stone nomogram identifies kidney stone formers at greatest risk for a second symptomatic episode. Such individuals may benefit from medical intervention and be good candidates for prevention trials.

Progression in smoldering Waldenstrom macroglobulinemia: long-term results.

The purpose of this study was to define the risk of progression and survival of patients with smoldering Waldenström macroglobulinemia (SWM). SWM is defined clinically as having a serum monoclonal IgM protein≥3 g/dL and/or≥10% bone marrow lymphoplasmacytic infiltration but no evidence of end-organ damage (anemia, constitutional symptoms, hyperviscosity, lymphadenopathy, or hepatosplenomegaly). We searched a computerized database and reviewed the medical records of all patients at Mayo Clinic who fulfilled the criteria of SWM between 1974 and 1995. During 285 cumulative person-years of follow-up of the 48 patients with SWM (median, 15.4 years), 34 (71%) progressed to symptomatic Waldenström macroglobulinemia (WM) requiring treatment, one to primary amyloidosis, and one to lymphoma (total, 75%). The cumulative probability of progression to symptomatic WM, amyloidosis, or lymphoma was 6% at 1 year, 39% at 3 years, 59% at 5 years, and 68% at 10 years. The major risk factors for progression were percentage of lymphoplasmacytic cells in the bone marrow, size of the serum M-spike, and the hemoglobin value. Patients with SWM should be followed and not treated until symptomatic WM develops. Treatment on a clinical trial for those at greatest risk of progression should be considered.

Multicenter trial of the proficiency of smart quantitative sensation tests.

INTRODUCTION: We assessed proficiency (accuracy and intra- and intertest reproducibility) of smart quantitative sensation tests (smart QSTs) in subjects without and with diabetic sensorimotor polyneuropathy (DSPN). METHODS: Technologists from 3 medical centers using different but identical QSTs independently assessed 6 modalities of sensation of the foot (or leg) twice in patients without (n = 6) and with (n = 6) DSPN using smart computer assisted QSTs. RESULTS: Low rates of test abnormalities were observed in health and high rates in DSPN. Very high intraclass correlations were obtained between continuous measures of QSTs and neuropathy signs, symptoms, or nerve conductions (NCs). No significant intra- or intertest differences were observed. CONCLUSIONS: These results provide proof of concept that smart QSTs provide accurate assessment of sensation loss without intra- or intertest differences useful for multicenter trials. Smart technology makes possible efficient testing of body surface area sensation loss in symmetric length-dependent sensorimotor polyneuropathies.

Lumbar trabecular bone mineral density distribution in patients with and without vertebral fractures: a case-control study.

PURPOSE: The proportion of load transmitted through the lumbar neural arch increases with aging, spinal degeneration, and lordosis, effectively shielding the lumbar vertebral bodies from load. This stress shielding may contribute to bone loss in the vertebral body, leading to increased fracture risk. To test his hypothesis, we performed a study to determine if vertebral body fractures were associated with a higher neural arch/vertebral body volumetric bone mineral density (vBMD) ratio. METHODS: Trabecular vBMD was calculated by quantitative CT in the L3 vertebral body and neural arch (pars interarticularis) of 36 women with vertebral compression fractures and 39 controls. Neural arch/vertebral body vBMD ratio was calculated, and its relationship to fracture status was determined using linear regression models adjusted for age and body mass index. RESULTS: Vertebral body trabecular vBMD was lower in fracture cases as compared to controls (mean ± SD, 49.0 ± 36.0 vs. 87.5 ± 36.8 mg/cm(3), respectively; P < 0.001), whereas trabecular vBMD of the neural arch was similar (96.1 ± 57.6 in cases vs. 118.2 ± 57.4 mg/cm(3) in controls; P = 0.182). The neural arch/vertebral body vBMD ratio was significantly greater in the fracture group than in controls (2.31 ± 1.07 vs. 1.44 ± 0.57, respectively; P < 0.001). CONCLUSION: These results support the hypothesis that stress shielding is a contributor to vertebral body bone loss and may increase fracture risk. Although further studies are needed, there may be a role for interventions that can shift vertebral loading in the spine to help prevent fracture.

Increasing incidence of celiac disease in a North American population.

OBJECTIVES: The prevalence of celiac disease (CD) varies greatly, potentially because of incomplete ascertainment of cases and small study samples with limited statistical power. Previous reports indicate that the incidence of CD is increasing. We examined the prevalence of CD in a well-defined US county. METHODS: Population-based study in Olmsted County, Minnesota, USA. Using the infrastructure of the Rochester Epidemiology Project, medical, histopathology, and CD serology records were used to identify all new cases of CD in Olmsted County since 2000. Age- and sex-specific and adjusted (to the US white 2000 population) incidence rates for CD were estimated. Clinical presentation at diagnosis was also assessed. RESULTS: Between 2000 and 2010, 249 individuals (157 female or 63%, median age 37.9 years) were diagnosed with CD in Olmsted County. The overall age- and sex-adjusted incidence of CD in the study period was 17.4 (95% confidence interval (CI)=15.2-19.6) per 100,000 person-years, increasing from 11.1 (95% CI=6.8-15.5) in 2000-2001 to 17.3 (95% CI=13.3-21.3) in 2008-2010. The temporal trend in incidence rates was modeled as a two-slope pattern, with the incidence leveling off after 2004. Based on the two classic CD symptoms of diarrhea and weight loss, the relative frequency of classical CD among incident cases decreased over time between 2000 and 2010 (P=0.044). CONCLUSIONS: The incidence of CD has continued to increase in the past decade in a North-American population.

Effect of age on the clinical presentation of incident symptomatic urolithiasis in the general population.

PURPOSE: We characterized variation in the clinical presentation between older and younger first time symptomatic stone formers in the general population. MATERIALS AND METHODS: We studied a random sample of Olmsted County, Minnesota residents with their first diagnostic code for urolithiasis between 1984 and 2003. Chart validated symptomatic stone formers had a confirmed stone by imaging or stone passage. Clinical presentation characteristics were compared between age groups. RESULTS: Among the 3,473 charts reviewed there were 1,590 validated incident symptomatic stone formers (mean age 43 years, range 18 to 96). Older individuals were more likely to present with atypical or no pain, fever, diarrhea, pyuria, urinary tract infections and bacteremia (p <0.001). Stone size and location did not differ by patient age. Calcium phosphate stone disease was associated with younger age, while uric acid stone and atypical stone composition was associated with older age (p <0.001). Older individuals were less likely to pass the stone spontaneously and were more likely to require surgical intervention (p <0.001). Surgical intervention was required in 516 (32.5%) individuals. Younger individuals were more likely to undergo ureteroscopy while older individuals were more likely to undergo shock wave lithotripsy, temporizing stent placement and percutaneous nephrolithotomy. CONCLUSIONS: The detection of stone disease in older individuals can be challenging due to atypical pain or absence of pain, as well as the presence of other comorbid conditions such as urinary tract infections and diarrhea. A higher index of suspicion for urolithiasis may be needed in the elderly for a more timely diagnosis and intervention to prevent morbidity.

Heparin and warfarin anticoagulation intensity as predictors of recurrence after deep vein thrombosis or pulmonary embolism: a population-based cohort study.

To test recommended anticoagulation measures as predictors of 180-day venous thromboembolism (VTE) recurrence, we identified all Olmsted County, MN residents with incident VTE over the 14-year period of 1984-1997, and followed each case (N = 1166) forward in time for VTE recurrence. We tested the activated partial thromboplastin time (APTT), international normalized ratio (INR), and other measures of heparin and warfarin anticoagulation as predictors of VTE recurrence while controlling for baseline and time-dependent characteristics using Cox proportional hazards modeling. Overall, 1026 (88%) and 989 (85%) patients received heparin and warfarin, respectively, and 85 (8%) developed VTE recurrence. In multivariable analyses, increasing proportions of time on heparin with an APTT ≥ 0.2 anti-X(a) U/mL and on warfarin with an INR ≥ 2.0 were associated with significant reductions in VTE recurrence, while the hazard with active cancer was significantly increased. Time from VTE onset to heparin start, duration of overlapping heparin and warfarin, and inferior vena cava (IVC) filter placement were not independent predictors of recurrence. At a heparin dose ≥ 30 000 U/d, the median proportion of time with an APTT ≥ 0.2 anti-X(a) U/mL was 92%, suggesting that routine APTT monitoring and heparin dose adjustment may be unnecessary. In summary, lower-intensity heparin and standard-intensity warfarin anticoagulation are effective in preventing VTE recurrence.

Bone microstructural changes revealed by high-resolution peripheral quantitative computed tomography imaging and elevated DKK1 and MIP-1α levels in patients with MGUS.

Recent population-based studies demonstrate an increased fracture risk with monoclonal gammopathy of undetermined significance (MGUS). The etiology of this increased risk remains unclear, however, because areal bone mineral density (aBMD) measurements by dual-energy x-ray absorptiometry cannot assess bone microstructural properties critical to determining bone quality and strength. To better define the skeletal effects of MGUS, we performed aBMD and high-resolution peripheral quantitative computed tomography volumetric bone mineral density (vBMD) measurements in 50 MGUS patients (20 females, 30 males; mean ± SEM age, 70.5 ± 1.4 years) and 100 matched control subjects. Relative to controls, MGUS patients had decreased aBMD at the femoral neck (P = .05) and total femur (P < .05) but no differences at other sites. In contrast, high-resolution peripheral quantitative computed tomography showed markedly diminished cortical thickness (P < .05) and increased endocortical area (P < .01). Average vBMD (P < .01), cortical vBMD (P < .001), and trabecular thickness (P < .01) were all significantly decreased in MGUS patients, suggestive of impaired bone formation. Serum levels of the Wnt pathway inhibitor Dickkopf-related protein 1 (P < .001) and osteoclast-activating factor MIP-1α (P < .05) also were significantly elevated in MGUS patients. Our data provide the first evidence of altered bone microstructure in MGUS and suggest that cytokines elevated in osteolytic myeloma also may be associated with bone loss in MGUS.

A trial of proficiency of nerve conduction: greater standardization still needed.

INTRODUCTION: The aim of this study was to test the proficiency (accuracy among evaluators) of measured attributes of nerve conduction (NC). METHODS: Expert clinical neurophysiologists, without instruction or consensus development, from 4 different medical centers, independently assessed 8 attributes of NC in 24 patients with diabetes mellitus (DM) on consecutive days. RESULTS: No significant intraobserver differences between days 1 and 2 were found, but significant interobserver differences were seen. Use of standard reference values did not correct for these observed differences. CONCLUSIONS: Interobserver variability was attributed to differences in performance of NC. It was of sufficient magnitude that it is of concern for the conduct of therapeutic trials. To deal with interrater variability in therapeutic trials, the same electromyographers should perform all NC assessments of individual patients or, preferably, NC procedures should be more standardized. A further trial is needed to test whether such standardization would eliminate interobserver variability.

Association between myocardial infarction and fractures: an emerging phenomenon.

BACKGROUND: Data on the association between myocardial infarction (MI) and fractures are scarce. Recent changes in the epidemiology of MI justify exploring this relationship. We evaluated whether MI constitutes a risk factor for osteoporotic fracture and examined secular trends in this association. METHODS AND RESULTS: Consecutive Olmsted County, Minnesota, residents with incident MI diagnosed in 1979 to 2006 and community control subjects individually matched (1:1) to cases on age, sex, and year of onset (n=6642) were followed up through 2009. Outcome measures were time to osteoporotic fracture, overall and by anatomic site, and death. Fracture incidence rates were stable in controls but increased markedly over time among MI cases. Accordingly, although an overall excess of fracture risk after MI was observed (adjusted hazard ratio, 1.32; 95% confidence interval, 1.12 to 1.56), substantial temporal variations were noted (1979 to 1989: hazard ratio, 0.81; 95% confidence interval, 0.58 to 1.12; 1990 to 1999: hazard ratio, 1.47; 95% confidence interval, 1.10 to 1.96; 2000 to 2006: hazard ratio, 1.73; 95% confidence interval, 1.32 to 2.27; P for trend <0.001). Trends were similar regardless of age, sex or fracture site. Conversely, the overall hazard ratio for death in MI cases versus controls did not change materially despite a continuous decline in 30-day case fatality rate (12.5% in 1979 to 1989; 6.7% in 2000 to 2006). Observed changes in the baseline prevalence of cardiovascular risk factors, MI characteristics, and comorbidities did not fully account for the trends in fracture risk. CONCLUSIONS: Over the past decades, the association between MI and osteoporotic fractures increased steadily. The trend is consistent with the displacement of post-MI outcomes toward noncardiovascular events, highlighting the need for comprehensive prevention strategies to accommodate the changing epidemiology of MI.

Obstetric trauma, pelvic floor injury and fecal incontinence: a population-based case-control study.

OBJECTIVES: Current concepts based on referral center data suggest that pelvic floor injury from obstetric trauma is a major risk factor for fecal incontinence (FI) in women. In contrast, a majority of community women only develop FI decades after vaginal delivery, and obstetric events are not independent risk factors for FI. However, obstetric events are imperfect surrogates for anal and pelvic floor injury, which is often clinically occult. Hence, the objectives of this study were to evaluate the relationship between prior obstetric events, pelvic floor injury, and FI among community women. METHODS: In this nested case-control study of 68 women with FI (cases; mean age 57 years) and 68 age-matched controls from a population-based cohort in Olmsted County, MN, pelvic floor anatomy and motion during voluntary contraction and defecation were assessed by magnetic resonance imaging. Obstetric events and bowel habits were recorded. RESULTS: By multivariable analysis, internal sphincter injury (cases-28%, controls-6%; odds ratio (OR): 8.8; 95% confidence interval (CI): 2.3-34) and reduced perineal descent during defecation (cases-2.6 ± 0.2 cm, controls-3.1 ± 0.2 cm; OR: 1.7; 95% CI: 1.2-2.4) increased FI risk, but external sphincter injury (cases-25%, controls-4%; P<0.005) was not independently predictive. Puborectalis injury was associated (P<0.05) with impaired anorectal motion during squeeze, but was not independently associated with FI. Grades 3-4 episiotomy (OR: 3.9; 95% CI: 1.4-11) but not other obstetric events increased the risk for pelvic floor injury. Heavy smoking (≥ 20 pack-years) was associated (P=0.052) with external sphincter atrophy. CONCLUSIONS: State-of-the-art imaging techniques reveal pelvic floor injury or abnormal anorectal motion in a minority of community women with FI. Internal sphincter injury and reduced perineal descent during defecation are independent risk factors for FI. In addition to grades 3-4 episiotomy, smoking may be a potentially preventable, risk factor for pelvic floor injury.

Risk of gastroparesis in subjects with type 1 and 2 diabetes in the general population.

OBJECTIVES: In patients with diabetes mellitus (DM) and upper gastrointestinal symptoms, a diagnosis of diabetic gastroparesis is often considered, but population-based data on the epidemiology of diabetic gastroparesis are lacking. We aimed to estimate the frequency of and risk factors for gastroparesis among community subjects with DM. METHODS: In this population-based, historical cohort study, the medical records linkage system of the Rochester Epidemiology Project was used to identify 227 Olmsted County, MN residents with type 1 DM in 1995, a random sample of 360 residents with type 2 DM, and an age- and sex-stratified random sample of 639 nondiabetic residents. Using defined diagnostic criteria, we estimated the subsequent risk of developing gastroparesis in each group through 2006. The risk in DM, compared with frequency-matched community controls, was assessed by Cox proportional hazards modeling. RESULTS: The cumulative proportions developing gastroparesis over a 10-year time period were 5.2% in type 1 DM, 1.0% in type 2 DM, and 0.2% in controls. The age- and gender-adjusted hazard ratios (HRs) for gastroparesis (relative to controls) was 33 (95% confidence interval (CI): 4.0, 274) in type 1 DM and 7.5 (95% CI: 0.8, 68) in type 2 DM. The risk of gastroparesis in type 1 DM was significantly greater than in type 2 DM (HR: 4.4 (1.1, 17)). Heartburn (HR: 6.6 (1.7, 25)) at baseline was associated with diabetic gastroparesis in type 1 DM. CONCLUSIONS: Gastroparesis is relatively uncommon in patients with DM, although an increased risk for gastroparesis was observed in type 1 DM.

Impact of optimal follow-up of monoclonal gammopathy of undetermined significance on early diagnosis and prevention of myeloma-related complications.

Monoclonal gammopathy of undetermined significance (MGUS) is associated with a long-term risk of progression to multiple myeloma (MM) or related malignancy. To prevent serious myeloma-related complications, lifelong annual follow-up has been recommended, but its value is unknown. We reviewed all patients from southeastern Minnesota seen at Mayo Clinic between 1973 and 2004 with MGUS who subsequently progressed to MM. Of 116 patients, 69% had optimal follow-up of MGUS. Among these, abnormalities on serial follow-up laboratory testing led to the diagnosis of MM in 16%, whereas MM was diagnosed only after serious MM-related complications in 45%. In the remaining, workup of less serious symptoms (25%), incidental finding during workup of unrelated medical conditions (11%), and unknown (3%) were the mechanisms leading to MM diagnosis. High-risk MGUS patients (≥ 1.5 g/dL and/or non-IgG MGUS) were more likely to be optimally followed (81% vs 64%), and be diagnosed with MM secondary to serial follow-up testing (21% vs 7%). This retrospective study suggests that routine annual follow-up of MGUS may not be required in low-risk MGUS. Future studies are needed to replicate and expand our findings and to determine the optimal frequency of monitoring in higher-risk MGUS patients.

Sclerostin levels during growth in children.

UNLABELLED: Serum sclerostin levels are associated with cortical porosity, suggesting that changes in sclerostin production during growth may play a role in defining cortical structure. INTRODUCTION: Sclerostin, produced by osteocytes, is a potent inhibitor of Wnt signaling and bone formation. While sclerostin levels increase with age in adults and are higher in men compared to women, there is currently no information on changes in circulating sclerostin levels during growth in humans. METHODS: We measured serum sclerostin levels in 6- to 21-year-old girls (n = 62) and boys (n = 56) and related these to trabecular and cortical bone microarchitectural parameters using high-resolution peripheral quantitative computed tomography and to markers of bone turnover. RESULTS: Serum sclerostin levels were higher in boys as compared to girls and declined in both sexes following the onset of puberty. There was no consistent relationship between sclerostin levels and trabecular bone parameters in either sex. However, serum sclerostin levels were inversely associated with cortical volumetric bone mineral density and cortical thickness in girls and positively associated with the cortical porosity index in both girls and boys. Bone turnover markers were positively correlated with serum sclerostin levels in both sexes. CONCLUSION: The gender difference in serum sclerostin levels appears to be established during puberty, and sclerostin levels tend to decline in late puberty in both girls and boys. Serum sclerostin levels are associated with cortical porosity, suggesting that changes in sclerostin production during growth may play a role in defining cortical structure.

Use of a medical records linkage system to enumerate a dynamic population over time: the Rochester epidemiology project.

The Rochester Epidemiology Project (REP) is a unique research infrastructure in which the medical records of virtually all persons residing in Olmsted County, Minnesota, for over 40 years have been linked and archived. In the present article, the authors describe how the REP links medical records from multiple health care institutions to specific individuals and how residency is confirmed over time. Additionally, the authors provide evidence for the validity of the REP Census enumeration. Between 1966 and 2008, 1,145,856 medical records were linked to 486,564 individuals in the REP. The REP Census was found to be valid when compared with a list of residents obtained from random digit dialing, a list of residents of nursing homes and senior citizen complexes, a commercial list of residents, and a manual review of records. In addition, the REP Census counts were comparable to those of 4 decennial US censuses (e.g., it included 104.1% of 1970 and 102.7% of 2000 census counts). The duration for which each person was captured in the system varied greatly by age and calendar year; however, the duration was typically substantial. Comprehensive medical records linkage systems like the REP can be used to maintain a continuously updated census and to provide an optimal sampling framework for epidemiologic studies.

Prevalence and risk of progression of light-chain monoclonal gammopathy of undetermined significance: a retrospective population-based cohort study.

BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) is defined by expression of heavy-chain immunoglobulin (IgH) and is the precursor lesion for 80% of cases of multiple myeloma. The remaining 20% are characterised by absence of IgH expression; we aimed to assess prevalence of a corresponding precursor entity, light-chain MGUS. METHODS: We used a population-based cohort, previously assembled to estimate MGUS prevalence, of 21,463 residents of Olmsted County, MN, USA, aged 50 years and older. We did a serum free light-chain assay on all samples with sufficient serum remaining, and immunofixation electrophoresis was done for all samples with an abnormal free light-chain ratio or abnormal protein electrophoresis results from the original study. Light-chain MGUS was defined as an abnormal free light-chain ratio with no IgH expression, plus increased concentration of the involved light chain. We calculated age-specific and sex-specific prevalence and rates of progression to lymphoproliferative disorders for light-chain and conventional MGUS and assessed incidence of renal disorders in patients with light-chain MGUS. FINDINGS: 610 (3.3%) of 18,357 people tested had an abnormal free light-chain ratio, of whom 213 had IgH expression that was diagnostic of conventional MGUS. 146 of the remaining 397 individuals had an increase of at least one free light chain and met criteria for light-chain MGUS. Prevalence of light-chain MGUS was 0.8% (95% CI 0.7-0.9), contributing to an overall MGUS prevalence of 4.2% (3.9-4.5). Risk of progression to multiple myeloma in patients with light-chain MGUS was 0.3% (0.1-0.8) per 100 person-years. 30 (23%) of 129 patients with light-chain MGUS were diagnosed with renal disease. INTERPRETATION: We define a clinical entity representing the light-chain equivalent of conventional MGUS and posing a risk of progression to light-chain multiple myeloma and related disorders. FUNDING: US National Cancer Institute.