Association between hospital volume and mortality of patients with metastatic non-small cell lung cancer.

BACKGROUND: Prior studies have shown superior surgical outcomes of stage I-III non-small cell lung cancer (NSCLC) in centers with higher patient volumes. However, there is a lack of such information in stage IV NSCLC. PATIENTS AND METHODS: This is a retrospective study of stage IV NSCLC patients diagnosed between 2004 and 2014 using the National Cancer Data Base (NCDB). We classified the total number of patients treated at facilities into quartiles: quartile 1 (Q1): ≤23; quartile 2 (Q2): 24-36, quartile 3 (Q3): 37-55, and quartile 4 (Q4): ≥56 cases/year. Cox regression was used to assess whether risk of death differed between quartiles after adjusting for demographics, insurance type, Charlson-Deyo score, and type of therapy received. RESULTS: There were 338, 445 patients with stage IV NSCLC treated at 1326 facilities. We included the patients who received any form of therapy in the survival analysis. The unadjusted median overall survival by facility volume was: Q1: 6 months, Q2: 6 months, Q3: 7 months, and Q4: 8 months (p < .001). Multivariable analysis showed that facility volume was independent predictor of all-cause mortality. Compared with patients treated at Q4 facilities, patients treated at lower-quartile facilities had a small but significantly higher risk of death (Q3 hazard ratio [HR], 1.05 [95%CI, 1.04-1.06]; Q2 HR, 1.12 [95%CI, 1.11-1.14]; Q1 HR, 1.11 [95%CI, 1.10-1.12]). CONCLUSIONS: Patients who were treated for stage IV NSCLC at highest-volume facilities had less risk of all-cause mortality compared with those who were treated at lower-volume facilities. Although the survival advantage of being treated at highest-volume facilities appeared small, the results of this study suggest differences in cancer care delivery models among various facilities, and may become more relevant in the future era of personalized treatment of stage IV NSCLC.

Treatment approaches and outcomes in plasmacytomas: analysis using a national dataset.

Solitary plasmacytomas are uncommon plasma cell disorders, which may present as a single bone lesion (P-bone) or extramedullary plasmacytoma (P-EM). There is a paucity of large studies analyzing prognostic factors and outcomes of plasmacytomas. While the treatment of choice is radiation therapy (RT), there is a lack of data evaluating optimal RT dose. In this study, we sought to answer these questions by utilizing the National Cancer Database plasmacytoma data from 2000 to 2011. A total of 5056 patients were included in the study (median age 62 years; range 52-72). To obtain a pure plasmacytoma cohort, potential multiple myeloma patients were excluded from the study (bone marrow involvement, systemic chemotherapy use). P-bone constituted 70% of the patients. The median overall survival (OS) of P-EM was significantly longer than P-bone (132 vs. 85 months), and for soft/connective tissue it was worse than remainder of P-EM (82 vs. 148 months). On multivariable analysis, factors associated with worse OS included older age (≥65), presence of P-bone, and treatment with a radiation dose <40 Gy.

Younger Adults Initiating Hemodialysis: Antidepressant Use for Depression Associated With Higher Health Care Utilization.

OBJECTIVE: To examine associations between antidepressant use and health care utilization in young adults beginning maintenance hemodialysis (HD) therapy. PATIENTS AND METHODS: Antidepressant use, hospitalizations, and emergency department (ED) visits were examined in young adults (N=130; age, 18-44 years) initiating HD (from January 1, 2001, through December 31, 2013) at a midwestern US institution. Primary outcomes included hospitalizations and ED visits during the first year. RESULTS: Depression diagnosis was common (47; 36.2%) at HD initiation, yet only 28 patients (21.5%) in the cohort were receiving antidepressant therapy. The antidepressant use group was more likely to have diabetes mellitus (18 [64.3%] vs 33 [32.4%]), coronary artery disease (8 [28.6%] vs 12 [11.8%]), and heart failure (9 [32.1%] vs 15 [14.7%]) (P<.05 for all) than the untreated group. Overall, 68 (52.3%) had 1 or more hospitalizations and 33 (25.4%) had 1 or more ED visits in the first year. The risk of hospitalization during the first year was higher in the antidepressant use group (hazard ratio, 2.35; 95% CI, 1.39-3.96; P=.001), which persisted after adjustment for diabetes, coronary artery disease, and heart failure (hazard ratio, 1.94; 95% CI, 1.22-3.10; P=.006). Emergency department visit rates were similar between the groups. CONCLUSION: Depression and antidepressant use for mood indication are common in young adult incident patients initiating HD and and are associated with higher hospitalization rates during the first year. Further research should determine whether antidepressants are a marker for other comorbidities or whether treated depression affects the increased health care use in these individuals.

The durability of operational improvements with rotational patient assignment.

INTRODUCTION: Previous work has suggested that Emergency Department rotational patient assignment (a system in which patients are algorithmically assigned to physicians) is associated with immediate (first-year) improvements in operational metrics. We sought to determine if these improvements persisted over a longer follow-up period. METHODS: Single-site, retrospective analysis focused on years 2-4 post-implementation (follow-up) of a rotational patient assignment system. We compared operational data for these years with previously published data from the last year of physician self-assignment and the first year of rotational patient assignment. We report data for patient characteristics, departmental characteristics and facility characteristics, as well as outcomes of length of stay (LOS), arrival to provider time (APT), and rate of patients who left before being seen (LBBS). RESULTS: There were 140,673 patient visits during the five year period; 138,501 (98.7%) were eligible for analysis. LOS, APT, and LBBS during follow-up remained improved vs. physician self-assignment, with improvements similar to those noted in the first year of implementation. Compared with the last year of physician self-assignment, approximate yearly average improvements during follow-up were a decrease in median LOS of 18min (8% improvement), a decrease in median APT of 21min (54% improvement), and a decrease in LBBS of 0.69% (72% improvement). CONCLUSION: In a single facility study, rotational patient assignment was associated with sustained operational improvements several years after implementation. These findings provide further evidence that rotational patient assignment is a viable strategy in front-end process redesign.

Association between atopic dermatitis and squamous cell carcinoma: a case-control study.

BACKGROUND: Conflicting data have been published on whether an association exists between atopic dermatitis (AD) and nonmelanoma skin cancer. This study aimed to determine whether individuals with AD had an increased risk of squamous cell carcinoma (SCC) development. METHODS: We conducted a retrospective, case-control study of patients residing in Olmsted County, Minnesota. Cases were selected from patients seen at Mayo Clinic (Rochester, Minnesota) who had an initial SCC diagnosis (either invasive SCC or SCC in situ) from January 1, 1996, through December 23, 2010. Age- and sex-matched controls were selected from patients seen at Mayo Clinic with no history of SCC before the case event date. RESULTS: Three hundred ninety-nine individuals with a documented history of SCC were identified and matched with 780 controls who did not have a history of SCC. After adjusting for race, smoking history, ionizing radiation exposure, corticosteroid and cyclosporine use, and non-SCC skin cancers, the odds ratio for SCC development between patients with history of AD versus patients without history of AD was 1.75 (95% CI, 1.05-2.93). CONCLUSIONS: Our findings support an increased risk of SCC development in the setting of AD.

Low-dose CT for the detection and classification of metastatic liver lesions: Results of the 2016 Low Dose CT Grand Challenge.

PURPOSE: Using common datasets, to estimate and compare the diagnostic performance of image-based denoising techniques or iterative reconstruction algorithms for the task of detecting hepatic metastases. METHODS: Datasets from contrast-enhanced CT scans of the liver were provided to participants in an NIH-, AAPM- and Mayo Clinic-sponsored Low Dose CT Grand Challenge. Training data included full-dose and quarter-dose scans of the ACR CT accreditation phantom and 10 patient examinations; both images and projections were provided in the training data. Projection data were supplied in a vendor-neutral standardized format (DICOM-CT-PD). Twenty quarter-dose patient datasets were provided to each participant for testing the performance of their technique. Images were provided to sites intending to perform denoising in the image domain. Fully preprocessed projection data and statistical noise maps were provided to sites intending to perform iterative reconstruction. Upon return of the denoised or iteratively reconstructed quarter-dose images, randomized, blinded evaluation of the cases was performed using a Latin Square study design by 11 senior radiology residents or fellows, who marked the locations of identified hepatic metastases. Markings were scored against reference locations of clinically or pathologically demonstrated metastases to determine a per-lesion normalized score and a per-case normalized score (a faculty abdominal radiologist established the reference location using clinical and pathological information). Scores increased for correct detections; scores decreased for missed or incorrect detections. The winner for the competition was the entry that produced the highest total score (mean of the per-lesion and per-case normalized score). Reader confidence was used to compute a Jackknife alternative free-response receiver operating characteristic (JAFROC) figure of merit, which was used for breaking ties. RESULTS: 103 participants from 90 sites and 26 countries registered to participate. Training data were shared with 77 sites that completed the data sharing agreements. Subsequently, 41 sites downloaded the 20 test cases, which included only the 25% dose data (CTDIvol = 3.0 ± 1.8 mGy, SSDE = 3.5 ± 1.3 mGy). 22 sites submitted results for evaluation. One site provided binary images and one site provided images with severe artifacts; cases from these sites were excluded from review and the participants removed from the challenge. The mean (range) per-lesion and per-case normalized scores were -24.2% (-75.8%, 3%) and 47% (10%, 70%), respectively. Compared to reader results for commercially reconstructed quarter-dose images with no noise reduction, 11 of the 20 sites showed a numeric improvement in the mean JAFROC figure of merit. Notably two sites performed comparably to the reader results for full-dose commercial images. The study was not designed for these comparisons, so wide confidence intervals surrounded these figures of merit and the results should be used only to motivate future testing. CONCLUSION: Infrastructure and methodology were developed to rapidly estimate observer performance for liver metastasis detection in low-dose CT examinations of the liver after either image-based denoising or iterative reconstruction. The results demonstrated large differences in detection and classification performance between noise reduction methods, although the majority of methods provided some improvement in performance relative to the commercial quarter-dose images with no noise reduction applied.

Sex-based disparities in venous thromboembolism outcomes: A National Inpatient Sample (NIS)-based analysis.

Venous thromboembolism (VTE) contributes to significant morbidity, mortality, and socioeconomic burden. There is a paucity of literature regarding sex-based sociodemographic differences in VTE presentation and short-term outcomes. We aimed to compare clinical outcomes between men and women hospitalized for VTE management. We performed a retrospective analysis using data from the National Inpatient Sample (NIS) database from 2012 to 2013. Inclusion criteria were age 18 years and older and a primary discharge diagnosis of VTE. Sociodemographic features and medical comorbidities were analyzed, as were hospital length of stay and in-hospital mortality rates. A total of 107,896 patients met the inclusion criteria; 53% were female. Median age was 65 years (interquartile range 51-77) and women were older than men (65 vs 62 years, p<0.001). There were significant differences between men and women with respect to race, primary insurance payer and medical comorbidities, and small differences with respect to VTE location. Female sex was associated with a small but significantly longer hospital length of stay (mean ratio 1.04, 95% CI 1.03-1.05, p<0.001) but no significant difference in in-hospital mortality (2.2% vs 2.1%, p=0.15). In a multivariate model, there was no significant difference between women and men with respect to hospital length of stay or in-hospital mortality. In conclusion, we used data from the NIS to study over 100,000 patients hospitalized for VTE, and identified several sex-based disparities in sociodemographic factors and location of VTE. However, in a multivariable analysis correcting for these factors, sex was not associated with significant differences in clinical outcomes.

A multi-reader in vitro study using porcine kidneys to determine the impact of integrated circuit detectors and iterative reconstruction on the detection accuracy, size measurement, and radiation dose for small (<4 mm) renal stones.

Background Detection of small renal calculi has benefitted from recent advances in computed tomography (CT) scanner design. Information regarding observer performance when using state-of-the-art CT scanners for this application is needed. Purpose To assess observer performance and the impact of radiation dose for detection and size measurement of <4 mm renal stones using CT with integrated circuit detectors and iterative reconstruction. Material and Methods Twenty-nine <4 mm calcium oxalate stones were randomly placed in 20 porcine kidneys in an anthropomorphic phantom. Four radiologists used a workstation to record each calculus detection and size. JAFROC Figure of Merit (FOM), sensitivity, false positive detections, and calculus size were calculated. Results Mean calculus size was 2.2 ± 0.7 mm. The CTDIvol values corresponding to the automatic exposure control settings of 160, 80, 40, 25, and 10 Quality Reference mAs (QRM) were 15.2, 7.9, 4.2, 2.7, and 1.3 mGy, respectively. JAFROC FOM was ≥ 0.97 at ≥ 80 QRM, ≥ 0.89 at ≥ 25 QRM, and was inferior to routine dose (160 QRM) at 10 QRM (0.72, P < 0.05). Per-calculus sensitivity remained ≥ 85% for every reader at ≥ 25 QRM. Mean total false positive detections per reader were ≤ 3 at ≥ 80 QRM, but increased substantially for two readers ( ≥ 12) at ≤ 40 QRM. Measured calculus size significantly decreased at ≤ 25 QRM ( P ≤ 0.01). Conclusion Using low dose renal CT with iterative reconstruction and ≥ 25 QRM results in high sensitivity, but false positive detections increase for some readers at very low dose levels (≤ 40 QRM). At very low doses with iterative reconstruction, measured calculus size will artifactually decrease.

Estimation of Observer Performance for Reduced Radiation Dose Levels in CT: Eliminating Reduced Dose Levels That Are Too Low Is the First Step.

RATIONALE AND OBJECTIVES: This study aims to estimate observer performance for a range of dose levels for common computed tomography (CT) examinations (detection of liver metastases or pulmonary nodules, and cause of neurologic deficit) to prioritize noninferior dose levels for further analysis. MATERIALS AND METHODS: Using CT data from 131 examinations (abdominal CT, 44; chest CT, 44; head CT, 43), CT images corresponding to 4%-100% of the routine clinical dose were reconstructed with filtered back projection or iterative reconstruction. Radiologists evaluated CT images, marking specified targets, providing confidence scores, and grading image quality. Noninferiority was assessed using reference standards, reader agreement rules, and jackknife alternative free-response receiver operating characteristic figures of merit. Reader agreement required that a majority of readers at lower dose identify target lesions seen by the majority of readers at routine dose. RESULTS: Reader agreement identified dose levels lower than 50% and 4% to have inadequate performance for detection of hepatic metastases and pulmonary nodules, respectively, but could not exclude any low dose levels for head CT. Estimated differences in jackknife alternative free-response receiver operating characteristic figures of merit between routine and lower dose configurations found that only the lowest dose configurations tested (ie, 30%, 4%, and 10% of routine dose levels for abdominal, chest, and head CT examinations, respectively) did not meet criteria for noninferiority. At lower doses, subjective image quality declined before observer performance. Iterative reconstruction was only beneficial when filtered back projection did not result in noninferior performance. CONCLUSION: Opportunity exists for substantial radiation dose reduction using existing CT technology for common diagnostic tasks.

Impact of Multiple Chronic Conditions in Patients Hospitalized with Stroke and Transient Ischemic Attack.

BACKGROUND: The prevalence and clinical impact of chronic conditions (CCs) have increasingly been recognized as an important public health concern. We evaluated the prevalence of coexisting CCs and their association with 30-day mortality and readmission in hospitalized patients with stroke and transient ischemic attack (TIA). METHODS: In a retrospective study of patients aged ≥18 years hospitalized for first-ever stroke and TIA, we assessed the prevalence of coexisting CCs and their predictive value for subsequent 30-day mortality and readmission. RESULTS: Study cohort comprised 6771 patients, hospitalized for stroke (n = 4068) and TIA (n = 2703), 51.4% men, with mean age of 68.2 years (standard deviation: ±15.6), mean number of CCs of 2.9 (±1.7), 30-day mortality rate of 8.6% (entire cohort), and 30-day readmission rate of 9.7% (in 2498 patients limited to Olmsted and surrounding counties). In multivariable models, significant predictors of (1) 30-day mortality were coexisting heart failure (HF) (odds ratio [OR]: 1.45, 95% confidence interval [CI]: 1.09-1.92), cardiac arrhythmia (OR: 1.74, 95% CI: 1.40-2.17), coronary artery disease (CAD) (OR: 1.64, 95% CI: 1.29-2.08), cancer (OR: 1.67, 95% CI: 1.31-2.14), and diabetes (HR: 1.28, 95% CI: 1.01-1.62); and (2) 30-day readmission (n = 2498) were CAD (OR: 1.50, 95% CI: 1.09-2.07), cancer (OR: 1.46, 95% CI: 1.01-2.10), and arthritis (OR: 1.62, 95% CI: 1.09-2.40). CONCLUSIONS: In patients hospitalized with stroke and TIA, CCs are highly prevalent and influence 30-day mortality and readmission. Optimal therapeutic and lifestyle interventions for CAD, HF, cardiac arrhythmia, cancer, diabetes, and arthritis may improve early clinical outcome.

Association Between Treatment Facility Volume and Mortality of Patients With Multiple Myeloma.

Purpose To determine the association between the number of patients with multiple myeloma (MM) treated annually at a treatment facility (volume) and all-cause mortality (outcome). Methods Using the National Cancer Database, we identified patients diagnosed with MM between 2003 and 2011. We classified the facilities by quartiles (Q; mean patients with MM treated per year): Q1: < 3.6; Q2: 3.6 to 6.1, Q3: 6.1 to 10.3, and Q4: > 10.3. We used random intercepts to account for clustering of patients within facilities and Cox regression to determine the volume-outcome relationship, adjusting for demographic (sex, age, race, ethnicity), socioeconomic (income, education, insurance type), geographic (area of residence, treatment facility location, travel distance), and comorbid (Charlson-Deyo score) factors and year of diagnosis. Results There were 94,722 patients with MM treated at 1,333 facilities. The median age at diagnosis was 67 years, and 54.7% were men. The median annual facility volume was 6.1 patients per year (range, 0.2 to 109.9). The distribution of patients according to facility volume was: Q1: 5.2%, Q2: 12.6%, Q3: 21.9%, and Q4: 60.3%. The unadjusted median overall survival by facility volume was: Q1: 26.9 months, Q2: 29.1 months, Q3: 31.9 months, and Q4: 49.1 months ( P < .001). Multivariable analysis showed that facility volume was independently associated with all-cause mortality. Compared with patients treated at Q4 facilities, patients treated at lower-quartile facilities had a higher risk of death (Q3 hazard ratio [HR], 1.12 [95% CI, 1.08 to 1.16]; Q2 HR, 1.17 [95% CI, 1.12 to 1.21]; Q1 HR, 1.22 [95% CI, 1.17 to 1.28]). Conclusion Patients who were treated for MM at higher-volume facilities had a lower risk of mortality compared with those who were treated at lower-volume facilities.

Physician in Triage Versus Rotational Patient Assignment.

BACKGROUND: Physician in triage and rotational patient assignment are different front-end processes that are designed to improve patient flow, but there are little or no data comparing them. OBJECTIVE: To compare physician in triage with rotational patient assignment with respect to multiple emergency department (ED) operational metrics. METHODS: Design-Retrospective cohort review. Patients-Patients seen on 23 days on which we utilized a physician in triage with those patients seen on 23 matched days when we utilized rotational patient assignment. RESULTS: There were 1,869 visits during physician in triage and 1,906 visits during rotational patient assignment. In a simple comparison, rotational patient assignment was associated with a lower median length of stay (LOS) than physician in triage (219 min vs. 233 min; difference of 14 min; 95% confidence interval [CI] 5-27 min). In a multivariate linear regression incorporating multiple confounders, there was a nonsignificant reduction in the geometric mean LOS in rotational patient assignment vs. physician in triage (204 min vs. 217 min; reduction of 6.25%; 95% CI -3.6% to 15.2%). There were no significant differences between groups for left before being seen, left subsequent to being seen, early (within 72 h) returns, early returns with admission, or complaint ratio. CONCLUSIONS: In a single-site study, there were no statistically significant differences in important ED operational metrics between a physician in triage model and a rotational patient assignment model after adjusting for confounders.

Emergency Department Rotational Patient Assignment.

STUDY OBJECTIVE: We compare emergency department (ED) operational metrics obtained in the first year of a rotational patient assignment system (in which patients are assigned to physicians automatically according to an algorithm) with those obtained in the last year of a traditional physician self-assignment system (in which physicians assigned themselves to patients at physician discretion). METHODS: This was a pre-post retrospective study of patients at a single ED with no financial incentives for physician productivity. Metrics of interest were length of stay; arrival-to-provider time; rates of left before being seen, left subsequent to being seen, early returns (within 72 hours), and early returns with admission; and complaint ratio. RESULTS: We analyzed 23,514 visits in the last year of physician self-assignment and 24,112 visits in the first year of rotational patient assignment. Rotational patient assignment was associated with the following improvements (percentage change): median length of stay 232 to 207 minutes (11%), median arrival to provider time 39 to 22 minutes (44%), left before being seen 0.73% to 0.36% (51%), and complaint ratio 9.0/1,000 to 5.4/1,000 (40%). There were no changes in left subsequent to being seen, early returns, or early returns with admission. CONCLUSION: In a single facility, the transition from physician self-assignment to rotational patient assignment was associated with improvement in a broad array of ED operational metrics. Rotational patient assignment may be a useful strategy in ED front-end process redesign.

Troponin T as a Predictor of End-Stage Renal Disease and All-Cause Death in African Americans and Whites From Hypertensive Families.

OBJECTIVE: To evaluate cardiac troponin T (cTnT) as a predictor of end-stage renal disease (ESRD) and death in a cohort of African American and white community-dwelling adults with hypertensive families. PATIENTS AND METHODS: A total of 3050 participants (whites from Rochester, Minnesota; African Americans from Jackson, Mississippi) of the Genetic Epidemiology Network of Arteriopathy study were followed from baseline examination (June 1, 1996, through August 31, 2000) through January 22, 2010. Cox proportional hazards regression models were used to examine the association of cTnT with ESRD and death after adjusting for traditional risk factors. RESULTS: Cohort demographic characteristics and measurements included 1395 whites (45.7%), 2174 hypertensive (71.3%), 992 estimated glomerular filtration rate of less than 60 mL/min per 1.73 m(2) (32.5%), 1574 high-sensitivity C-reactive protein level of greater than 3 mg/L (51.6%), and 66 abnormal cTnT level of 0.01 ng/mL or higher (2.2%). The estimated cumulative incidence of ESRD at 10 years was 27.4% among those with abnormal cTnT levels compared with 1.3% for those with normal levels. Similarly, the estimated cumulative incidence of death at 10 years was 47% among those with abnormal cTnT compared with 7.3% among those with normal cTnT. Abnormal cTnT levels were strongly associated with ESRD and death. This effect was attenuated but was still highly significant after adjustment for demographic characteristics, estimated glomerular filtration rate, and traditional risk factors for ESRD (unadjusted hazard ratio [HR], 23.91; 95% CI, 12.9-44.2; adjusted HR, 2.81; 95% CI, 1.3-5.9) and death (unadjusted HR, 8.43; 95% CI, 6.0-11.9; adjusted HR, 3.46; 95% CI, 2.3-5.1). CONCLUSION: Cardiac troponin T makes an independent contribution to the prediction of ESRD and all-cause death in community-dwelling individuals beyond traditional risk markers. Further studies may be needed to determine whether cTnT screening in individuals with hypertension or in a subset of hypertensive individuals would help identify those at risk of ESRD and all-cause death.

Effect of menstrual cycle phase on background parenchymal uptake at molecular breast imaging.

RATIONALE AND OBJECTIVES: The level of Tc-99m sestamibi uptake within normal fibroglandular tissue on molecular breast imaging (MBI), termed background parenchymal uptake (BPU), has been anecdotally observed to fluctuate with menstrual cycle. Our objective was to assess the impact of menstrual cycle phase on BPU appearance. MATERIALS AND METHODS: Premenopausal volunteers who reported regular menstrual cycles and no exogenous hormone use were recruited to undergo serial MBI examinations during the follicular and luteal phase. A study radiologist, blinded to cycle phase, categorized BPU as photopenic, minimal mild, moderate, or marked. Change in BPU with cycle phase was determined, as well as correlations of BPU with mammographic density and hormone levels. RESULTS: In 42 analyzable participants, high BPU (moderate or marked) was observed more often in luteal phase compared to follicular (P = .016). BPU did not change with phase in 30 of 42 participants (71%) and increased in the luteal phase compared to follicular in 12 (29%). High BPU was more frequent in dense breasts compared to nondense breasts at both the luteal (58% [15 of 26] vs. 13% [2 of 16], P = .004) and follicular phases (35% [9 of 26] vs. 6% [1 of 16], P = .061). Spearman correlation coefficients did not show any correlation of BPU with hormone levels measured at either cycle phase and suggested a weak correlation between change in BPU and changes in estrone and estradiol between phases. CONCLUSIONS: We observed variable effects of menstrual cycle on BPU among our cohort of premenopausal women; however, when high BPU was observed, it was most frequently seen during the luteal phase compared to follicular phase and in women with dense breasts compared to nondense breasts.