Bayesian Learning of Personalized Longitudinal Biomarker Trajectory.

This work concerns the effective personalized prediction of longitudinal biomarker trajectory, motivated by a study of cancer targeted therapy for patients with chronic myeloid leukemia (CML). Continuous monitoring with a confirmed biomarker of residual disease is a key component of CML management for early prediction of disease relapse. However, the longitudinal biomarker measurements have highly heterogeneous trajectories between subjects (patients) with various shapes and patterns. It is believed that the trajectory is clinically related to the development of treatment resistance, but there was limited knowledge about the underlying mechanism. To address the challenge, we propose a novel Bayesian approach to modeling the distribution of subject-specific longitudinal trajectories. It exploits flexible Bayesian learning to accommodate complex changing patterns over time and non-linear covariate effects, and allows for real-time prediction of both in-sample and out-of-sample subjects. The generated information can help make clinical decisions, and consequently enhance the personalized treatment management of precision medicine.

Characteristics and variations in young adults with cutaneous melanoma: A national cancer database analysis.

BACKGROUND AND OBJECTIVES: Many cancers in young adulthood differ in terms of biology, histologic variation, and prognosis compared to cancer in other older age groups. Differences in cutaneous melanoma among young adults compared to other older age groups, as well as between sexes in young adults are not well studied. METHODS: The National Cancer Database was queried for patients diagnosed with cutaneous melanoma between 2004 and 2017. Patient characteristics, disease factors, and treatment were stratified by age-based cohorts and compared using standard univariate statistics. The Kaplan-Meier method and log-rank tests were used to evaluate overall survival (OS) between age-based cohorts and young adult sexes. RESULTS: Of the 329 765 patients identified, 10.5% were between 18 and 39 years of age at diagnosis. Compared with other older age groups, young adult patients were more likely to be female and uninsured with higher proportions of superficial spreading melanoma, melanoma of the trunk and extremities, and earlier-stage disease. Young adults had improved OS compared to other older age groups. Young male patients had a greater proportion of no insurance, nodular melanoma, higher-stage disease, and decreased OS compared to young female patients. Additionally, while the 5-year OS difference was statistically significant across all stages of disease between young males and females, the clinical significance is likely limited to later stages. CONCLUSIONS: Age and sex-specific differences in cutaneous melanoma highlight distinct patterns and characteristics, emphasizing the need for tailored approaches to screening, diagnosis, and treatment.

The Affordable Care Act and income-based disparities in health care coverage and spending among nonelderly adults with cancer.

The Patient Protection and Affordable Care Act (ACA) significantly reduced uninsured individuals and improved financial protection; however, escalating costs of cancer treatment has led to substantial out-of-pocket expenses, causing severe financial and mental health distress for individuals with cancer. Mixed evidence on the ACA's ongoing impact highlights the necessity of assessing health-spending changes across income groups for informed policy interventions. In our nationally representative survey evaluating the early- and long-term effects of the ACA on nonelderly adult patients with cancer, we categorized individuals-based income subgroups defined by the ACA for eligibility. We found that ACA implementation increased insurance coverage, which was particularly evident after 2 years of implementation. Early post-ACA (within two years of implementation), there were declines in out-of-pocket spending for the lowest and low-income groups by 26.52% and 38.31%, respectively, persisting long-term only for the lowest-income group. High-income groups experienced continuously increased out-of-pocket and premium spending by 25.39% and 34.28%, respectively, with a notable 122% increase in the risk of high-burden spending. This study provides robust evidence of income-based disparities in financial burden for cancer care, emphasizing the need for health care policies promoting equitable care and addressing spending disparities across income brackets.

Characterising incident opioid use among incident users of prescription sedative hypnotics: A national cohort study.

OBJECTIVE: To evaluate co-prescribing of sedatives hypnotics and opioids. DESIGN: Retrospective study evaluating the association of patient characteristics and comorbidities with coprescribing. SETTING AND PARTICIPANTS: Using the national Merative MarketScan Database between 2005 and 2018, we identified patients who received an incident sedative prescription with or without subsequent, incident opioid prescriptions within a year of the sedative prescription in the USA. OUTCOME MEASURES: Coprescription of sedative-hypnotics and opioids. RESULTS: A total of 2 632 622 patients (mean (SD) age, 43.2 (12.34) years; 1 297 356 (62.5%) female) received incident prescriptions for sedatives over the course of the study period. The largest proportion of sedative prescribing included benzodiazepines (71.1%); however, z-drugs (19.9%) and barbiturates (9%) were also common. About 557 845 (21.2%) patients with incident sedatives also received incident opioid prescriptions. About 59.2% of these coprescribed patients received opioids coprescription on the same day. Multivariate logistic regression findings showed that individuals with a comorbidity index score of 1, 2 or ≥3 (aOR 1.19 (95% CI 1.17 to 1.21), 1.17 (95% C 1.14 to 1.19) and 1.25 (95% C 1.2 to 1.31)) and substance use disorder (1.21 (95% C 1.19 to 1.23)) were more likely to be coprescribed opioids and sedatives. The likelihood of receiving both opioid and sedative prescriptions was lower for female patients (aOR 0.93; 95% CI 0.92 to 0.94), and those receiving a barbiturate (aOR 0.3; 95% CI 0.29 to 0.31) or z-drugs (aOR 0.67; 95% CI 0.66 to 0.68) prescriptions at the index date. CONCLUSIONS: Coprescription of sedatives with opioids was associated with the presence of comorbidities and substance use disorder, gender and types of sedatives prescribed at the index date. Additionally, more than half of the coprescribing occurred on the same day which warrants further evaluation of current prescribing and dispensing best practice guidelines.

Association between Medicaid Expansion and Cutaneous Melanoma Diagnosis and Outcomes: Does Where You Live Make a Difference?

BACKGROUND: Early detection and standardized treatment are crucial for enhancing outcomes for patients with cutaneous melanoma, the commonly diagnosed skin cancer. However, access to quality health care services remains a critical barrier for many patients, particularly the uninsured. Whereas Medicaid expansion (ME) has had a positive impact on some cancers, its specific influence on cutaneous melanoma remains understudied. METHODS: The National Cancer Database identified 87,512 patients 40-64 years of age with a diagnosis of non-metastatic cutaneous melanoma between 2004 and 2017. In this study, patient demographics, disease characteristics, and treatment variables were analyzed, and ME status was determined based on state policies. Standard univariate statistics were used to compare patients with a diagnosis of non-metastatic cutaneous melanoma between ME and non-ME states. The Kaplan-Meier method and log-rank tests were used to evaluate overall survival (OS) between ME and non-ME states. Multivariable Cox regression models were used to examine associations with OS. RESULTS: Overall, 28.6 % (n = 25,031) of the overall cohort was in ME states. The patients in ME states were more likely to be insured, live in neighborhoods with higher median income quartiles, receive treatment at academic/research cancer centers, have lower stages of disease, and receive surgery than the patients in non-ME states. Kaplan-Meier analysis found enhanced 5-year OS for the patients in ME states across all stages. Cox regression showed improved survival in ME states for stage II (hazard ratio [HR], 0.84) and stage III (HR, 0.75) melanoma. CONCLUSIONS: This study underscores the positive association between ME and improved diagnosis, treatment, and outcomes for patients with non-metastatic cutaneous melanoma. These findings advocate for continued efforts to enhance health care accessibility for vulnerable populations.

Opioid Overdose Hospitalizations During COVID-19: The Experience of Pennsylvania.

Objective: The COVID-19 pandemic placed extreme burden on hospitals, while opioid overdose is another challenging public health issue. This study aimed to examine the trends and outcomes of opioid overdose hospitalizations in Pennsylvania during 2018 to 2021. Design: We identified opioid overdose hospitalizations in the state of Pennsylvania using the state-wide hospital discharge database (PHC4) 2018 to 2021. We examined the number of opioid overdose hospitalizations, the corresponding mortality and discharges against medical advice comparing the pre-COVID period (2018-2019) and the COVID period (2020-2021). We also assessed what patient and hospital characteristics were associated with in-hospital death or leaving against medical advice. Results: A total of 13 446 opioid-related hospitalizations were identified in 2018 to 2021. Compared to pre-pandemic, a higher percentage of cases involving synthetics (17.0%vs 10.3%, P < .0001) were observed during COVID. After controlling for covariates, there was no significant difference in opioid overdose in-hospital deaths in the years 2020 to 2021 compared to 2018 to 2019 (OR = 0.846, 95% CI: 0.71-1.01, P = .065). The COVID period was significantly associated with more leaving against medical advice compared to years 2018 to 2019 (OR = 1.265, 95% CI: 1.11-1.44, P = .0003). Compared to commercial insurance, Medicaid insurance was associated with higher odds of both in-hospital death (OR = 1.383, 95% CI: 1.06-1.81, P = .0176) and leaving against medical advice (OR = 1.903, 95% CI: 1.56-2.33, P < .0001). Conclusion: There were no substantial changes in the number of overall opioid overdose cases and deaths at hospitals following the outbreak of COVID-19 in Pennsylvania. This observation suggests that an increased number of patients may have succumbed to overdoses outside of hospital settings, possibly due to a higher severity of overdoses. Further, we found that patients were more likely to leave against medical advice during the COVID-19 pandemic.

Relationship Between Availability of Urologists and Primary Care Providers and Stage of Diagnosis for Invasive Urinary Bladder Cancer.

INTRODUCTION: With no recommended screening approach, urinary bladder cancer patients rely on referral to urologists to ensure timely diagnosis of bladder cancer. This requires coordination between primary and specialty care. We provide estimates of the relative association between primary care physician and urologist density on stage of urinary bladder cancer diagnosis. METHODS: We used 2010 to 2016 Pennsylvania Cancer Registry data to identify all adult patients diagnosed with bladder cancer. Our primary outcome was locoregional stage of diagnosis, since treatment modality changes and prognosis worsens beyond this stage. Based on patient's residential location at the time of diagnosis we defined both density of urologists and number of primary care providers (defined as providers per population) within the patient's county. We used univariate and multivariate logistic regression to estimate the association between provider density and likelihood of locoregional stage of diagnosis. We also controlled for age, sex, race/ethnicity, insurance type, and year. RESULTS: Our sample included 11,771 urinary bladder cancer patients with 10,607 diagnosed at locoregional stage and 1164 at distant stage. Multivariate regression results show primary care density was associated with significantly higher odds of locoregional stage of diagnosis (odds ratio of 1.05 [95% CI: 1.02-1.08]) while urologist density was associated with significantly lower odds of locoregional stage (odds ratio of 0.65 [95% CI: 0.48-0.89]). CONCLUSIONS: We found primary care density but not urologist density was associated with earlier stage of diagnosis, highlighting the importance of access to primary care and need for timely referral to urologic care.

Stress Due to Inflation: Changes over Time, Correlates, and Coping Strategies among Working-Age Adults in the United States.

BACKGROUND: During the COVID-19 pandemic, the annual US inflation rate increased from 1.2% in July 2020 to 8% in July 2022. It has since declined to 3.4% (December 2023). This study examined the prevalence of stress due to inflation during a period when it declined from 8.2% in September 2022 to 3% in June 2023 and its association with demographic and social determinants of health (SDOH). METHODS: We conducted a cross-sectional analysis of the online Household Pulse Survey (HPS), which surveils the experiences of US households. Beginning September 2022, HPS initiated data collection on "stress due to inflation" through a question on how stressful the increase in prices in the last 2 months has been. Participants could respond: very, moderately, a little, or not stressful. We analyzed data on working-age adults (18-64 years) who responded to the above question of stress due to inflation during 14-26 September 2022 (N = 32,579) and 7-19 June 2023 (N = 36,229). We used replicate weights in chi-squared tests and ordinal logistic regression analyses controlling for gender, age, race and ethnicity, COVID-19, COVID-19 vaccination, health insurance, and SDOH, including education, lost employment income, poverty status, marital status, food affordability, and region. RESULTS: The prevalence of stress due to inflation (price increases being very or moderately stressful) significantly increased from 76.9% in September 2022 to 78.9% in June 2023. The odds of stress due to inflation were higher for individuals with the following characteristics: female, transgender, having income below 400% of the federal poverty line, having lost employment income, not being able to afford food, had long or acute COVID-19, and did not have a COVID-19 vaccine. CONCLUSIONS: More than three quarters of working-age adults in the US experienced stress due to inflation. Despite a declining national inflation rate in recent months, stress due to inflation has significantly increased among working-age adults. Inflation-related stress warrants further research and policy attention.

Ethnic Disparities in Patient-Centered Communication with Healthcare Providers: A Comparison of Non-Hispanic Asians and Non-Hispanic Whites.

BACKGROUND: Patient-centered communication (PCC) is an important metric related to patient health outcomes. Non-Hispanic Asian (NHA) individuals reported lower PCC scores with healthcare providers than individuals of other races and ethnicities. We aim to determine the ethnic disparities in PCC and further investigate the association between PCC, individual's confidence in obtaining health-related information (health literacy), and confidence in taking care of themselves (health self-efficacy) among NHA in comparison to the Non-Hispanic White (NHW) population. METHODS: This is a cross-sectional study. We used data from the Health Information National Trends Survey 5 (HINTS) cycles 1 and 3. PCC was measured using seven validated survey questions with scores ranging from 7 to 28. Individuals' health literacy and self-efficacy were accessed using two-item survey questions. Multivariable logistic regression analyses were performed to determine the association of independent factors (e.g., self-efficacy, health literacy, and race and ethnicity) with PCC. RESULTS: We included 3,831 participants. Fewer NHAs (35.43%) reported high PCC scores compared to NHWs (48.99%, p = 0.0184). In fully adjusted logistic regression model, although NHAs were less likely to have high PCC scores (aOR = 0.78, 95% CI 0.46-1.32) compared to NHWs, the association was not statistically significant (p = 0.350). However, the aOR of confidence in self-efficacy associated with high PCC scores was 2.27 (95% CI 1.68-3.07, p < 0.001) and the aOR of confidence in health literacy with high PCC scores was 2.13 (95% CI 1.64-2.76, p < 0.001). CONCLUSIONS: High PCC scores reported by NHA were not significantly different from those of NHW individuals in adjusted comparisons. Individual's confidence in self-efficacy and health literacy was positively associated with high PCC regardless of race and ethnicity.

Predicting operative time for metabolic and bariatric surgery using machine learning models: a retrospective observational study.

BACKGROUND: Predicting operative time is essential for scheduling surgery and managing the operating room. This study aimed to develop machine learning (ML) models to predict the operative time for metabolic and bariatric surgery (MBS) and to compare each model. METHODS: The authors used the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database between 2016 and 2020 to develop ML models, including linear regression, random forest, support vector machine, gradient-boosted tree, and XGBoost model. Patient characteristics and surgical features were included as variables in the model. The authors used the mean absolute error, root mean square error, and R 2 score to evaluate model performance. The authors identified the 10 most important variables in the best-performing model using the Shapley Additive exPlanations algorithm. RESULTS: In total, 668 723 patients were included in the study. The XGBoost model outperformed the other ML models, with the lowest root mean square error and highest R 2 score. Random forest performed better than linear regression. The relative performance of the ML algorithms remained consistent across the models, regardless of the surgery type. The surgery type and surgical approach were the most important features to predict the operative time; specifically, sleeve gastrectomy (vs. Roux-en-Y gastric bypass) and the laparoscopic approach (vs. robotic-assisted approach) were associated with a shorter operative time. CONCLUSIONS: The XGBoost model best predicted the operative time for MBS among the ML models examined. Our findings can be useful in managing the operating room scheduling and in developing software tools to predict the operative times of MBS in clinical settings.

Cost Effectiveness of Zanubrutinib Versus Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia.

BACKGROUND: While the efficacy and safety of zanubrutinib have been established in relapsed or refractory chronic lymphocytic leukemia, the evidence on cost effectiveness is still lacking. OBJECTIVE: We aimed to evaluate the cost effectiveness of zanubrutinib versus ibrutinib in relapsed or refractory chronic lymphocytic leukemia from the commercial payer perspective in the USA. METHODS: A partitioned survival model was developed based on survival curves from the phase III ALPINE trial. We reconstructed patient-level data for each curve and conducted a parametric estimation to incorporate long-term clinical outcomes and treatment costs into the model. Medical costs and utilities were obtained from public data and previous cost-effectiveness studies. A discount rate of 3.0% per annum was applied and costs were adjusted to 2023 US dollars. The incremental cost-effectiveness ratio was calculated by dividing the incremental costs of zanubrutinib over ibrutinib by the incremental life-years or quality-adjusted life-years. Deterministic and probabilistic sensitivity analyses were performed to examine the robustness of the results. RESULTS: Over a 10-year analysis period, the incremental cost-effectiveness ratio of zanubrutinib versus ibrutinib was $91,260 per life-year gained and $120,634 per quality-adjusted life-year gained, making it cost effective within a threshold of $150,000 per quality-adjusted life-year gained. The incremental cost-effectiveness ratio was most sensitive to drug acquisition costs and progression-free survival distributions, and the probability of zanubrutinib being cost effective was approximately 52.8%, with a 30.0% likelihood of dominance. CONCLUSIONS: Zanubrutinib is likely to be cost effective versus ibrutinib in relapsed or refractory chronic lymphocytic leukemia in the USA, but the high threshold should be noted. Our findings may provide a basis for pricing strategy and reimbursement decisions for zanubrutinib.

Racial and Socioeconomic Differences and Surgical Outcomes in Pancreaticoduodenectomy Patients: A Systematic Review of High- Versus Low-Volume Hospitals in the United States.

BACKGROUND: Pancreaticoduodenectomy (PD) is associated with better outcomes in high-volume hospitals. However, it is unknown whether and to what extent the improved performance of high-volume hospitals may be associated with racial and socioeconomic factors, which have been shown to impact operative and postoperative outcomes in major surgeries. This review aims to identify the differences in racial and socioeconomic characteristics of patients who underwent PD surgery in high- and low-volume hospitals. METHODS: PubMed, Cochrane, and Web of Science were systematically searched between May 1, 2023 and May 7, 2023 without any time restriction on publication date. Studies that were conducted in the United States and had a direct comparison between high- and low-volume hospitals were included. RESULTS: A total of 30 observational studies were included. When racial proportions were compared by hospital volume, thirteen studies reported that compared to high-volume hospitals, a higher percentage of racial minorities underwent PD in low-volume hospitals. Disparities in traveling distance, education levels, and median income at baseline between high- and low-volume hospitals were reported by four, three, and two studies, respectively. CONCLUSION: A racial difference at baseline between high- and low-volume hospitals was observed. Socioeconomic factors were less frequently included in existing literature. Future studies are needed to understand the socioeconomic differences between patients receiving PD surgery in high- and low-volume hospitals.

Opioid and Non-Opioid Pharmacotherapy Use for Pain Management Among Privately Insured Pediatric Patients With Cancer in the United States.

BACKGROUND: This study examined the trends and patterns of opioid and non-opioid pharmacotherapy use among a large national sample of privately insured pediatric patients with cancer in the United States. MATERIALS AND METHODS: We identified pediatric (aged < 21) patients diagnosed with central nervous system (CNS), lymphoma, gonadal, leukemia, or bone cancer from MarketScan data 2005-2019. We examined the proportion of patients who filled a prescription for the following 5 types of pharmacotherapy: opioid, anticonvulsant, non-steroidal anti-inflammatory drug (NSAID), antidepressant, and muscle relaxant during active cancer treatment. We assessed the trends and patterns in pharmacotherapy using multivariable logistic regressions. RESULTS: Among 4174 patients included, 2979 (71%) had an opioid prescription; 746 (18%), 384 (9%), 202 (5%), and 169 (4%) had anticonvulsant, NSAID, antidepressant and muscle relaxant prescriptions, respectively. Multivariable logistic regression showed a nonlinear trend in the use of opioids among pediatric patients with cancer over time such that use slightly increased until 2012 (OR of 1.40 [95% CI, 1.12-1.73] for 2012 vs. 2006) but then decreased thereafter (OR of 0.51 [0.37-0.68] for 2018 vs. 2012). The use of anticonvulsants, NSAIDs, and muscle relaxants increased significantly linearly over time (all P < .005). CONCLUSION: There has been a downward trend in the use of opioids in recent years among pediatric patients with cancer and an upward trend in the use of non-opioid pharmacotherapy for pain management potentially as an alternative to opioids.

Disparities in Surgical Treatment of Resectable Pancreatic Adenocarcinoma at Minority Serving Hospitals.

INTRODUCTION: Minority serving hospitals (MSH) are those serving a disproportionally high number of minority patients. Previous research has demonstrated that treatment at MSH is associated with worse outcomes. We hypothesize that patients treated at MSH are less likely to undergo surgical resection of pancreatic adenocarcinoma compared to patients treated at non-MSH. METHODS: Patients with resectable pancreatic cancer were identified using the National Cancer Database. Institutions treating Black and Hispanic patients in the top decile were categorized as an MSH. Factors associated with the primary outcome of definitive surgical resection were evaluated using multivariable logistic regression. Univariate and multivariable survival analysis was performed. RESULTS: Of the 75,513 patients included in this study, 7.2% were treated at MSH. Patients treated at MSH were younger, more likely to be uninsured, and higher stage compared to those treated at non-MSH (P < 0.001). Patients treated at MSH underwent surgical resection at lower rates (MSH 40% versus non-MSH 44.5%, P < 0.001). On multivariable logistic regression, treatment at MSH was associated with decreased likelihood of undergoing definitive surgery (odds ratio 0.91, P = 0.006). Of those who underwent surgical resection, multivariable survival analysis revealed that treatment at an MSH was associated with increased morality (hazard ratio 1.12, P < 0.001). CONCLUSIONS: Patients with resectable pancreatic adenocarcinoma treated at MSH are less likely to undergo surgical resection compared to those treated at non-MSH. Targeted interventions are needed to address the unique barriers facing MSH facilities in providing care to patients with pancreatic adenocarcinoma.

Productivity Loss Among Opioid and Benzodiazepine Users in the United States: A Medical Expenditure Panel Survey From 2010 to 2019.

OBJECTIVE: The aim of the study is to estimate the association between productivity losses and the use of prescription opioids and benzodiazepines among employed US adults with painful conditions. METHODS: Using Medical Expenditures Panel Survey (2010-2019), we used two-part (logistic regression and generalized linear model with zero-truncated negative binomial link) model to compare missed workdays due to illness or injury among employed adults with a painful condition. RESULTS: Of the eligible sample of 57,413 working US individuals, 14.65% were prescription opioid users, 2.95% were benzodiazepine users, and 1.59% were both opioid and benzodiazepine users. The predicted missed workdays were 5.75 (95% Confidence Limit [CL]: 5.58-5.92) days for benzodiazepine users, 13.06 (95% CL: 12.88-13.23) days among opioid users, and 15.18 (95% CL: 14.46-15.90) days for opioid and benzodiazepine concomitant users. CONCLUSIONS: Concomitant use of prescription opioids and benzodiazepines was significantly associated with having more missed workdays among employed adults with documented painful conditions.

Management of Male Patients With Occult Breast Cancer: Analysis of the National Cancer Database.

INTRODUCTION: Occult breast cancer (OBC) consists of <0.1% of breast cancer cases in the United States. Male occult breast cancer (mOBC) has not been well-studied outside of case reports, and management is largely based on female OBC (fOBC) studies. We aim to examine the prevalence of mOBC among those in the National Cancer Database with breast cancer and describe treatment modalities received by mOBC compared to fOBC. METHODS: The National Cancer Database was queried for patients with OBC from 2004 to 2018. Chi-Square test and Fisher's exact tests compared patient, clinical, and facility characteristics by sex. Treatment modalities [systemic therapy, radiation therapy, axillary lymph node dissection, modified radical mastectomy (MRM)] were compared. A subgroup analysis examined pathologic upstaging in patients who underwent MRM. RESULTS: Of 23,374 male patients with breast cancer, 0.13% were identified to have mOBC [versus 0.09% in fOBC]. cN2/N3 disease was significantly more prevalent in the mOBC cohort (61.3%) than in the fOBC cohort (30.7%, P < 0.001). Receipt of axillary lymph node dissection or MRM was not significantly different by sex. Male OBC (mOBC) patients were less likely to receive trimodality treatment than fOBC patients. In patients who underwent MRM, more mOBC patients [75%] were pathologically upstaged as T+ after mastectomy than fOBC patients [30%, P < 0.001], questioning the adequacy of diagnostic workup for mOBC compared to fOBC. CONCLUSIONS: This review confirms mOBC as an extremely rare disease. Multimodal treatments have been highly utilized to optimize care in this patient population. Further investigation is warranted to examine the survival benefit of treatment regimens for mOBC.

[Preliminary Study on the Relationship between the Developmental Stage of Multiple Myeloma Disease and the Results of Bone Marrow Whole Exome Sequencing].

OBJECTIVE: To investigate the genetic results of whole exome sequencing of bone marrow from new onset multiple myeloma (MM) patients to analyze the process of genetic clonal evolution in MM patients. METHODS: Genomic DNA was extracted from bone marrow samples of 15 MM patients and the whole exomes sequencing was performed using next generation sequencing technology. Using own buccal cells as germline controls, combinated with clinical information, the mutation profile of genes from high-risk asymptomatic myeloma to symptomatic myeloma were analyzed, and genes that may be associated with the efficacy and side effects of bortezomib were screened. RESULTS: Except for two patients in whom no peripheral neuropathy was observed after a short treatment period, other patients peripheral neuropathy developed of various degrees during treatment with bortezomib containing chemotherapy, and the vast majority of patients achieved remission after receiving this bortezomib-related chemotherapy regimen. All patients had comparable levels of the inherited mutations number, but the somatic mutations was correlated with disease evolution. CONCLUSION: different gene "mutational spectra" exist in myeloma patients at different stages and are associated with progression through all stages of the disease.

Hospital- and county-level characteristics explain geographic variability in prices of cancer-related procedures: Implications for policy and interventions.

BACKGROUND: Healthcare costs in the U.S. are high and variable, which can hinder access and impact health outcomes across communities. This study examined hospital- and county-level characteristics to identify factors that explain geographic variation in prices for four cancer-related procedures. METHODS: Data sources included Turquoise Health, which compiles publicly-available price data from U.S. hospitals. We examined list prices for four procedures: abdominal ultrasound, diagnostic colonoscopy, brain MRI, and pelvis CT scan, which we linked to characteristics of hospitals (e.g., number of beds) and counties (e.g., metropolitan status). We used multilevel linear regression models to assess multivariable relationships between prices and hospital- and county-level characteristics. Supplementary analyses repeated these models using procedures prices for commercial insurance plans. RESULTS: For each procedure, list prices varied across counties (intraclass correlation: abdominal ultrasound = 23.2%; colonoscopy = 17.1%; brain MRI = 37.2%; pelvis CT = 50.9%). List prices for each procedure were associated with hospital ownership (all p < 0.001) and percent of population without health insurance (all p < 0.05). For example, list prices for abdominal ultrasound were higher for proprietary versus Government-owned hospitals (ß = 539.10, 95% confidence interval [CI]: 256.12, 822.08, p < 0.001) and for hospitals in counties with more uninsured residents (ß = 23.44, 95% CI: 2.55, 44.33, p = 0.03). Commercial insurance prices were negatively associated with metropolitan status. CONCLUSIONS: Prices for cancer-related healthcare procedures varied substantially, with considerable heterogeneity associated with county location as well as county-level social determinants of health (e.g., health insurance coverage). Interventions and policy changes are needed to alleviate the financial burden of cancer care among patients, including geographic variation in prices for cancer-related procedures.