Serum 25-Hydroxyvitamin D and Subsequent Cancer Incidence and Mortality: A Population-Based Retrospective Cohort Study

ObjectiveTo determine the relationship between 25-hydroxyvitamin D (25[OH]D) values and subsequent cancer incidence and mortality.Patients and MethodsWe identified all adult patients living in Olmsted County, Minnesota, between January 1, 2005, and December 31, 2011, who had at least 1 25(OH)D measurement and no prior diagnosis of cancer. Cancer outcomes were retrieved starting 30 days after 25(OH)D measurement and until patients’ final clinical visit as an Olmsted County resident; December 31, 2014; or death. Cox proportional hazards regression was used to analyze data.ResultsA total of 8700 individuals had a 25(OH)D measurement and no history of cancer, with a mean ± SD 25(OH)D value of 29.7±12.8 ng/mL (to convert to nmol/L, multiply by 2.496). The mean ± SD age was 51.5±16.4 years, and most were women (78.1%; n=6796) and White (85.7%; n=7460). A total of 761 individuals developed cancer (skin cancer, n=360; nonskin cancer, n=401) during a median follow-up of 4.6 (interquartile range, 3.4-6.1) years. Compared with participants with 25(OH)D values of 20 to 50 ng/mL (reference group), those with 25(OH)D values less than 12 ng/mL had a greater nonskin cancer incidence (hazard ratio [HR], 1.56; 95% CI, 1.03 to 2.36; P=.04) after adjustment. There was no association between 25(OH)D values and total cancer or skin cancer incidence. Compared with individuals from the reference group, 25(OH)D levels less than 12 ng/mL (HR, 2.35; 95% CI, 1.01 to 5.48; P=.047) and 12 to 19 ng/mL (HR, 2.10; 95% CI, 1.05 to 4.22; P=.04) were associated with increased cancer mortality.ConclusionLow 25(OH)D levels were associated with increased risk for incident nonskin cancer and cancer-related mortality.     

Associations of Neighborhood Socioeconomic Disadvantage With Chronic Conditions by Age,Sex, Race,and Ethnicity in a Population-Based Cohort

ObjectiveTo determine the association of socioeconomic status at the census block group level with chronic conditions and to determine whether the associations differ by age, sex, race, or ethnicity.MethodsAdults aged 20 years and older on April 1, 2015, from 7 counties in southern Minnesota were identified using the Rochester Epidemiology Project records-linkage system. We estimated the prevalence of 19 chronic conditions (7 cardiometabolic, 7 other somatic, and 5 mental health conditions) at the individual level and a composite measure of neighborhood socioeconomic disadvantage (the area deprivation index [ADI]) at the census block group level (n=249).ResultsAmong the 197,578 persons in our study, 46.7% (92,373) were male, 49.5% (97,801) were aged 50 years and older, 12.3% (24,316) were of non-White race, and 5.3% (10,546) were Hispanic. The risk of most chronic conditions increased with increasing ADI. For each cardiometabolic condition and most other somatic and mental health conditions, the pattern of increasing risk across ADI quintiles was attenuated, or there was no association across quintiles of ADI in the oldest age group (aged ≥70 years). Stronger associations between ADI and several cardiometabolic, other somatic, and mental health conditions were observed in women.ConclusionHigher ADI was associated with increased risk of most chronic conditions, with more pronounced associations in younger persons. For some chronic conditions, the associations were stronger in women. Our findings underscore the importance of recognizing the overall and potentially differential impact of area-level deprivation on chronic disease outcomes for diverse populations.     

Relative Survival With Early-Stage Breast Cancer in Screened and Unscreened Populations

Relative survival and disease-specific survival are two statistics that measure net survival from a cancer diagnosis, excluding other causes of death. In most cases, these two rates are comparable. However, in some cancer types for which cancer screening is performed, relative survival is often greater than disease-specific survival. This divergence has been attributed to mechanisms such as the “healthy user effect” and overdiagnosis of indolent tumors detected by screening. Using relative survival rate as a marker of these mechanisms, we examined the association of breast cancer screening with relative survival rates for women diagnosed with early-stage breast cancer. In population-based data from the National Cancer Institute’s Surveillance, Epidemiology and End Results registry, we examined relative survival rates in women diagnosed with stage I breast cancer or ductal carcinoma in situ who were in highly screened vs less-highly screened groups, based on time period, age group, and insurance status. In this analysis, relative survival rates for early-stage breast cancer were higher than disease-specific survival, even exceeding 100% in populations experiencing higher rates of screening (ie, women diagnosed during the era of widespread uptake of mammography, age older than 40 years, and women with health insurance coverage). The favorable outcomes observed in screen-detected breast cancers are at least in part attributable to the healthy user effect and overdiagnosis of indolent tumors. Therefore, survival rates may not accurately reflect the effectiveness of cancer screening. These findings have implications for counseling of patients and future clinical studies of active monitoring approaches in breast cancer.     

Incidence of Clinically Relevant Thyroid Cancers Remains Stable for Almost a Century: A Population-Based Study

ObjectiveTo examine the trends in incidence of clinically relevant thyroid cancers within the overall rising incidence of thyroid cancers.Patients and MethodsThis is a population-based cohort study conducted using the Rochester Epidemiology Project database to identify all new cases of thyroid cancer in Olmsted County, Minnesota, between January 1, 1935, and December 31, 2018. We extracted information about demographics and tumor pathologic type, size, and invasiveness. Clinically relevant cancers included aggressive histology or presence of metastatic disease, size larger than 4 cm, and gross extrathyroidal tumor invasion.ResultsBetween 1935 and 2018, 596 thyroid cancer cases were diagnosed (mean age, 46.4 years; 72% female; 87% papillary cancers; and median tumor size, 1.5 cm). The sex- and age-adjusted incidence of thyroid cancer increased from 1.3 per 100,000 person-years (p-y) from 1935–1949 to 12.0 per 100,000 p-y in 2010–2018, corresponding to an absolute change per decade of 1.4 (95% CI, 0.7 to 2.2). There was a nonsignificant period absolute change for patients with tumor greater than 4 cm (0.03; 95% CI, -0.2 to 0.3), with evidence of tumor invasion (0.1; 95% CI, -0.1 to 0.4), and with aggressive histology or presence of metastatic disease (0.2; 95% CI, -0.1 to 0.6). Thyroid cancer mortality was unchanged over the observation period.ConclusionIncidence rates of clinically relevant thyroid cancers, as defined by histology, size, and invasiveness, have not changed significantly in 80 years. The rising thyroid cancer incidence is driven by indolent thyroid cancers.     

Population-Based Evaluation of Total Protein in Cerebrospinal Fluid

ObjectivesTo present a normal range of cerebrospinal fluid (CSF) protein levels in a community-based population and to evaluate factors that contribute to CSF protein level variability.Patients and MethodsSamples of CSF protein were obtained from participants aged 32 to 95 years who underwent lumbar puncture (LP) between November 1, 2007, and October 1, 2017, as part of the Mayo Clinic Study of Aging, a longitudinal, population-based study of residents of Olmsted County, Minnesota.ResultsA total of 633 participants (58.1% male; 99.1% White; mean ± SD age, 70.9±11.6 years) underwent LP with recorded CSF protein level. Mean ± SD CSF protein level was 52.2±18.4 mg/dL (to convert to mg/L, multiply by 10), with a 95% reference interval of 24.0 to 93.4 mg/dL (range, 14.0-148.0 mg/dL). Spinal stenosis and arterial hypertension were associated with higher CSF protein levels on univariable analysis (P<.001). Increasing age, male sex, and diabetes were all independently associated with higher CSF protein levels on multivariable analysis (P<.001). In the 66 participants with repeated LPs within 2.5 years, the coefficient of repeatability was 26.1 mg/dL. Eleven participants (16.7%) had a CSF protein level difference of 20 mg/dL or more between serial LPs, and 4 (6.1%) had a difference of 25 mg/dL or more. There was a trend toward greater CSF protein level variability in patients with spinal stenosis (P=.054).ConclusionThis large population-based study showed that CSF protein level can vary significantly among individuals. Elevated CSF protein level was independently associated with older age, male sex, and diabetes and is higher than listed in many laboratories. These findings emphasize the necessity of evidence-based reevaluation and standardization of CSF protein metrics.     

Pituitary Adenoma Incidence,Management Trends,and Long-term Outcomes: A 30-Year Population-Based Analysis

ObjectiveTo perform a population-based study of pituitary adenoma epidemiology, including longitudinal trends in disease incidence, treatment patterns, and outcomes.Patients and MethodsIn this study of incident pituitary adenomas in Olmsted County, Minnesota, from January 1, 1989, through December 31, 2019, we identified 785 patients who underwent primary screening, 435 of whom were confirmed as harboring incident pituitary adenomas and were included. Primary outcomes of interest included demographic characteristics, presenting features, and disease outcomes (tumor control, biochemical control, and complications).ResultsAmong our 435 study patients, 438 unique pituitary adenomas were diagnosed at a median patient age of 39 years (interquartile range [IQR], 27 to 58 years). Adenomas were incidentally identified in 164 of the 438 tumors (37%). Common symptomatic presentations included hyperprolactinemia (188 of 438 [43%]) and visual field deficit (47 of 438 [11%]). Laboratory tests confirmed pituitary hormone hypersecretion in 238 of the 435 patients (55%), which was symptomatic in 222. The median tumor diameter was 8 mm (IQR, 5 to 17 mm). Primary management strategies were observation (156 of 438 tumors [36%]), medication (162 of 438 tumors [37%]), and transsphenoidal resection (120 of 438 tumors [27%]). Tumor and biochemical control were achieved in 398 (95%) and 216 (91%) secreting tumors, respectively. New posttreatment pituitary or visual deficits were noted in 43 (11%) and 8 (2%); apoplexy occurred in 28 (6%). Median clinical follow-up was 98 months (IQR, 47 to 189 months). Standardized incidence rates were 3.77 to 16.87 per 100,000 population, demonstrating linear expansion over time (R²=0.67). The mean overall standardized incidence rate was 10.1 per 100,000 population; final point prevalence was 175.1 per 100,000 population.ConclusionPituitary adenoma is a highly incident disease, with prolactin-secreting and incidental lesions representing the majority of tumors. Incidence rates and asymptomatic detection appear to be increasing over time. Presenting symptoms and treatment pathways are variable; however, most patients achieve favorable outcomes with observation or a single treatment modality.     

Determinants of Discharge Disposition From Acute Care for Survivors of Hypoxic-Ischemic Brain Injury: Results From a Large Population-Based Cohort Data Set

ObjectiveTo identify determinants of discharge disposition from acute care among survivors of hypoxic-ischemic brain injury (HIBI), stratified by sex.DesignPopulation-based retrospective cohort study using provincial data in Ontario, Canada. The determinants were grouped into predisposing, need, and enabling factors using the Anderson Behavioral Model.SettingAcute care.ParticipantsSurvivors of HIBI aged ≥20 years at the time of hospitalization and discharged alive from acute care between April 1, 2002, and March 31, 2017. There were 7492 patients with HIBI, of whom 28% (N=2077) survived their acute care episode.InterventionsNot applicable.Main Outcome MeasuresDischarge disposition from acute care, categorized as complex continuing care (CCC), long-term care (LTC), inpatient rehabilitation (IR), home with support, home without support, and transferred to another acute care.ResultsThe discharge dispositions for the 2077 survivors were IR 23.4% (n=487), CCC 19.5% (n=404), LTC 6.2% (n=128), home without support 31.2% (n=647), home with support 15.1% (n=314), and other 4.6%. Multinomial multivariable logistic regression analysis using home without support as the reference category revealed that female patients were significantly more likely than male patients to be discharged to LTC/CCC. Those who were older, were frail, and had longer stay in acute care or special care unit (SCU) were more likely to be discharged to LTC/CCC. The only significant determinant for IR was longer stay in acute care. Survivors with cardiac-related injury were less likely to be discharged to LTC/CCC. Income was a significant factor for male patients but not for female patients in the sex-stratified analysis. The following variables were investigated but were not significant determinants in this study: need factors (comorbidity score, prior psychiatric disorders, health care utilization) and enabling factors (income quintile, rural area of residence).ConclusionsPredisposing (age, sex) and need factors (frailty, acute care days, SCU days, type of injury) were significant determinants of discharge disposition from acute care after HIBI. In spite of a system with universal coverage, sex differences were found, with more female patients being discharged to CCC/LTC rather than IR, controlling for age and other confounders. These findings should be considered in appropriate discharge planning from acute care for survivors of HIBI.     

Population-Based Trends in Amputations and Revascularizations for Peripheral Artery Disease From 1990 to 2009

ObjectiveTo determine trends in amputations and revascularizations for peripheral artery disease (PAD) in a well-defined population.MethodsA population-based cohort study of Olmsted County, Minnesota, residents with PAD undergoing amputation or revascularization was conducted between January 1, 1990, and December 31, 2009. Population-level 5-year incidence trends for endovascular, open surgical, and hybrid revascularizations and major and minor amputations were determined. Limb-specific outcomes after revascularization, including major adverse limb events and amputation-free survival, were compared between initial surgical and endovascular or hybrid revascularization groups using Kaplan-Meier analysis.ResultsWe identified 773 residents who underwent 1906 limb-procedures, including 689 open revascularizations, 685 endovascular or hybrid revascularizations, and 220 major amputations. During the 20-year study period, the incidence of endovascular and hybrid revascularizations increased, whereas the incidence of open surgical revascularizations and major amputations decreased. Incidence of revascularizations for chronic limb-threatening ischemia (CLTI) did not change. Among residents with CLTI undergoing their first revascularization on a limb, endovascular revascularization was associated with more major adverse limb events and major amputations compared with surgical revascularization during the ensuing 15 years.ConclusionThe rising incidence of endovascular and hybrid revascularizations and the decreasing incidence of open surgical revascularizations for PAD were associated with a decreasing incidence of major amputations in this population between 1990 and 2009, despite a stable incidence of revascularizations for CLTI. With more major adverse limb events and major amputations after endovascular revascularization, these trends suggest that additional emphasis should be placed on improving limb salvage efforts beyond just mode of revascularization.     

Early Detection of Pancreatic Cancer in Patients With Chronic Liver Disease Under Hepatocellular Carcinoma Surveillance

ObjectiveTo evaluate whether patients with hepatitis B virus (HBV)– and hepatitis C virus (HCV)–related chronic liver disease were diagnosed as having pancreatic cancer (PC) at an early stage during abdominal imaging surveillance for hepatocellular carcinoma (HCC).Patients and MethodsWe retrospectively examined 447 patients with PC diagnosed at Ehime University Hospital and affiliated centers (2011-2013). Data were collected regarding HBV and HCV status, likelihood of PC diagnosis, and Union for International Cancer Control (UICC) stage. Intergroup comparisons were performed using the χ² test.ResultsThe UICC stage distribution in the HCC surveillance group (n=16) was stage 0 (n=2, 12.5%), stage IA (n=3, 18.8%), stage IB (n=2, 12.5%), stage IIA (n=2, 12.5%), stage IIB (n=2, 12.5%), stage III (n=1, 6.3%), and stage IV (n=4, 25%). The UICC stage distribution in the nonsurveillance group (n=431) was stage 0 (n=4, 0.9%), stage IA (n=28, 6.5%), stage IB (n=27, 6.3%), stage IIA (n=86, 20.0%), stage IIB (n=48, 11.1%), stage III (n=56, 13.0%), and stage IV (n=182, 42.2%). The HCC surveillance group had significantly more patients with stage 0 disease than with stages IA through IV (P=.02). Similar results were observed when including stages IA (P=.007) and IB (P=.004) as early stages but not stage IIA (P=.10). A dilated pancreatic duct led to a PC diagnosis in all 6 patients with stage 0 disease.ConclusionPatients with HBV- and HCV-related chronic liver disease had an early PC diagnosis during HCC surveillance. Careful evaluation of the pancreas is warranted during HCC surveillance.     

Preventing Breast Cancer Through Identification and Pharmacologic Management of High-Risk Patients

Breast cancer remains the most common cancer in women in the United States. For certain women at high risk for breast cancer, endocrine therapy (ET) can greatly decrease the risk. Tools such as the Breast Cancer Risk Assessment Tool (or Gail Model) and the International Breast Cancer Intervention Study risk calculator are available to help identify women at increased risk for breast cancer. Physician awareness of family history, reproductive and lifestyle factors, dense breast tissue, and history of benign proliferative breast disease are important when identifying high-risk women. The updated US Preventive Services Task Force and American Society of Clinical Oncology guidelines encourage primary care providers to identify at-risk women and offer risk-reducing medications. Among the various ETs, which include tamoxifen, raloxifene, anastrozole, and exemestane, tamoxifen is the only one available for premenopausal women aged 35 years and older. A shared decision-making process should be used to increase the usage of ET and must be individualized. This individualized approach must account for each woman’s medical history and weigh the benefits and risks of ET in combination with the personal values of the patient.     

Prevalence and Risk Factors of Adhesive Capsulitis in Asian Breast Cancer Patients Undergoing an Outpatient Community Cancer Rehabilitation Program

ObjectivesTo investigate the prevalence and risk factors for adhesive capsulitis in postoperative breast cancer patients up to 5 years after surgery who were attending an outpatient community cancer rehabilitation program, and to determine whether any significant relationship exists between arm lymphedema and adhesive capsulitis.DesignCross-sectional observational study.SettingNational cancer rehabilitation center.ParticipantsAsian women (N=135) who underwent breast surgery and were referred for an outpatient community cancer rehabilitation program.InterventionsNot applicable.Main Outcome MeasuresPresence of adhesive capsulitis, lymphedema.ResultsThe prevalence of adhesive capsulitis and lymphedema in this population was 22.2% and 33.3%, respectively. A history of mastectomy (odds ratio [OR], 3.93; 95% confidence interval [CI], 1.23-12.63; P=.021), mastectomy with reconstruction (OR, 2.72; 95% CI, 1.27-30.54; P=.024), and lymphedema (OR, 7.92; 95% CI, 2.73-22.95; P<.001) were found to be significantly associated with adhesive capsulitis on multivariate analysis.ConclusionsAdhesive capsulitis and lymphedema are common in breast cancer survivors. The design of cancer rehabilitation programs for breast cancer survivors should include surveillance and management of adhesive capsulitis, especially in the presence of lymphedema.     

Association of Self-reported Walking Pace With Type 2 Diabetes Incidence in the UK Biobank Prospective Cohort Study

ObjectiveTo investigate the association between self-reported walking pace and type 2 diabetes (T2D) incidence and whether it differed by physical activity levels and walking time.MethodsThere were 162,155 participants (mean age, 57.1 years; 54.9% women) from the UK Biobank prospective study, recruited between 2006 and 2010, included in the study. Walking pace was self-reported and classified as brisk, average, or slow. Total physical activity and walking time were self-reported using the International Physical Activity Questionnaire. Association between walking pace and T2D incidence and the potential moderating role of physical activity and walking time were investigated using Cox proportional hazards models.ResultsThe median follow-up was 7.4 (interquartile range, 6.7 to 8.2) years. There were 4442 participants in whom T2D developed during the follow-up period. In the fully adjusted model (sociodemographic factors, diet, body mass index, and physical activity), average walking pace (hazard ratio [HR], 1.28; 95% CI, 1.14 to 1.44) and slow walking pace (HR, 1.91; 95% CI, 1.62 to 2.24) were associated with a higher T2D risk compared with brisk walking among women. Among men, average walking pace (HR, 1.28; 95% CI, 1.17 to 1.40) and slow walking pace (HR, 1.73; 95% CI, 1.50 to 1.99) were also associated with higher T2D risk. Compared with slow walkers, brisk walkers have the same diabetes incidence rate 18.6 and 16.0 years later, for women and men, respectively.ConclusionAverage and slow walking pace was associated with a higher risk of incident T2D in both men and women, independent of major confounding factors. The associations were consistent across different physical activity levels and walking time.     

Association of Lifestyle Behaviors With Hearing Loss: The UK Biobank Cohort Study

ObjectiveTo examine the combined association of five healthy lifestyle behaviors with hearing loss (HL) in the UK Biobank cohort, established between 2006 and 2010 in the United Kingdom.MethodsThis longitudinal analysis included 61,958 participants aged 40 to 70 years from April 2007 to December 2016. The healthy behaviors examined were: never smoking, high level of physical activity, high diet quality, moderate alcohol intake, and optimal sleep. Hearing loss was self-reported at baseline and in any physical exam during the follow-up.ResultsOver a median follow-up of 3.9±2.5 years, 3072 (5.0%) participants reported incident HL. After adjustment for potential confounders, including age, social factors, exposure to high-intensity noise, ototoxic medication, and comorbidity, the HRs of HL associated with having 1, 2, 3, and 4 to 5 vs 0 behaviors were: 0.85 (95% CI, 0.75 to 0.96), 0.85 (95% CI, 0.75 to 0.96), 0.82 (95% CI, 0.71 to 0.94), and 0.80 (95% CI, 0.67 to 0.97), respectively (P for trend, 0.02). We estimated that the population attributable risk percent for not adhering to any five low-risk lifestyle behaviors was 15.6%.ConclusionIn this large study, an increasing number of healthy behaviors was associated with decreased risk of HL.