The aggregate value of cancer screenings in the United States: full potential value and value considering adherence.

BACKGROUND: Although cancer mortality has been decreasing since 1991, many cancers are still not detected until later stages with poorer outcomes. Screening for early-stage cancer can save lives because treatments are generally more effective at earlier than later stages of disease. Evidence of the aggregate benefits of guideline-recommended single-site cancer screenings has been limited. This article assesses the benefits in terms of life-years gained and associated value from major cancer screening technologies in the United States. METHODS: A mathematical model was built to estimate the aggregate benefits of screenings for breast, colorectal, cervical, and lung cancer over time since the start of US Preventive Services Task Force (USPSTF) recommendations. For each type, the full potential benefits under perfect adherence and the benefits considering reported adherence rates were estimated. The effectiveness of each screening technology was abstracted from published literature on the life-years gained per screened individual. The number of individuals eligible for screening per year was estimated using US Census data matched to the USPSTF recommendations, which changed over time. Adherence rates to screening protocols were based on the National Health Interview Survey results with extrapolation. RESULTS: Since initial USPSTF recommendations, up to 417 million people were eligible for cancer screening. Assuming perfect adherence to screening recommendations, the life-years gained from screenings are estimated to be 15.5-21.3 million (2.2-4.9, 1.4-3.6, 11.4-12.3, and 0.5 million for breast, colorectal, cervical, and lung cancer, respectively). At reported adherence rates, combined screening has saved 12.2-16.2 million life-years since the introduction of USPSTF recommendations, ~ 75% of potential with perfect adherence. These benefits translate into a value of $8.2-$11.3 trillion at full potential and $6.5-$8.6 trillion considering current adherence. Therefore, single-site screening could have saved an additional 3.2-5.1 million life-years, equating to $1.7-$2.7 trillion, with perfect adherence. CONCLUSIONS: Although gaps persist between the full potential benefit and benefits considering adherence, existing cancer screening technologies have offered significant value to the US population. Technologies and policy interventions that can improve adherence and/or expand the number of cancer types tested will provide significantly more value and save significantly more patient lives.

Hemoglobin and End-Organ Damage in Individuals with Sickle Cell Disease.

Background: Sickle cell disease (SCD) is an inherited, chronic, multifaceted blood disorder. Patients with SCD develop anemia, which has been associated with end-organ damage (EOD). Objectives: This retrospective, observational, repeated-measures study systematically characterizes the relationship between hemoglobin (Hb) level and EOD in adolescent and adult patients with SCD. Methods: The study population comprised patients with SCD aged ≥12 years with available Hb data from a US provider-centric health care database. For each patient, each Hb value over time was included as a separate observation. Study outcomes-the onset of any new EOD, including chronic kidney disease, pulmonary hypertension, stroke, and leg ulcer-were ascertained during the 1-year period after each Hb assessment. The association between Hb levels and risk of new EOD was estimated using multivariable generalized estimating equations. Results: A total of 16,043 unique patients with SCD contributed 44,913 observations. Adjusted odds of any EOD during the 1-year follow-up were significantly lower with higher Hb level. Risk reductions with higher Hb levels for chronic kidney disease, pulmonary hypertension, and leg ulcer were comparable. The risk of new EOD was significantly lower among adolescent and adult patients with higher Hb levels. Conclusions: In patients with SCD, higher Hb levels are associated with a reduced risk of developing EOD. Therapeutic strategies that result in higher Hb levels may offer clinical and economic value for patients with SCD. (Curr Ther Res Clin Exp. 2023; 84:XXX-XXX).

What drives transcranial Doppler velocity improvement in paediatric sickle cell anaemia: analysis from the Sickle Cell Clinical Research and Intervention Program (SCCRIP) longitudinal cohort study.

Children with sickle cell anaemia (SCA) and conditional transcranial Doppler (TCD) flow velocities (conditional: 170-199 cm/s; normal: <170 cm/s) have an increased risk of stroke. The Sickle Cell Clinical Research and Intervention Program (SCCRIP), a lifetime observational study, assessed the influence of haematological markers on TCD velocities. In children (≤16 years) with SCA (HbSS/HbSß0 -thalassaemia) and conditional TCD velocities (n = 32), increases in haemoglobin and in fetal haemoglobin after hydroxyurea initiation were significantly associated with decreases in TCD velocities. The benefit of pharmacological intervention to increase haemoglobin and fetal haemoglobin and normalise TCD velocities was demonstrated in this real-world dataset.

Health-related quality of life in adults with relapsed/refractory acute lymphoblastic leukemia treated with blinatumomab.

In the phase 3 TOWER study, blinatumomab significantly improved overall survival in adults with relapsed or refractory (R/R) Philadelphia chromosome-negative (Ph-) B-cell precursor acute lymphoblastic leukemia (BCP-ALL) relative to standard-of-care chemotherapy. A secondary objective of this study was to assess the impact of blinatumomab on health-related quality of life (HRQL) as measured by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30). This analysis included the 342 of 405 randomized patients for whom baseline and ≥1 postbaseline result were available in any EORTC multi-item scale or single-item measure. In general, patients receiving blinatumomab (n = 247) reported better posttreatment HRQL across all QLQ-C30 subscales, based on descriptive mean change from baseline, than did those receiving chemotherapy (n = 95). The hazard ratios for time to deterioration (TTD) of ≥10 points from baseline in HRQL or death ranged from 0.42 to 0.81 in favor of blinatumomab, with the upper bounds of the 95% confidence interval <1.0 across all measures, except insomnia, social functioning, and financial difficulties; sensitivity analysis of TTD in HRQL without the event of death were consistent with these findings. When treatment effect over time was tested using a restricted maximum likelihood-based mixed model for repeated measures analysis, P < .05 was reached for blinatumomab vs chemotherapy for all subscale measures except financial difficulties. The clinically meaningful benefits in overall survival and HRQL support the clinical value of blinatumomab in patients with R/R Ph- BCP-ALL when compared with chemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT02013167.

Testing for minimal residual disease in adults with acute lymphoblastic leukemia in Europe: a clinician survey.

BACKGROUND: In acute lymphoblastic leukemia (ALL), the presence of minimal residual disease (MRD) after induction/consolidation chemotherapy is a strong prognostic factor for subsequent relapse and mortality. Accordingly, European clinical guidelines and protocols recommend testing patients who achieve a complete hematological remission (CR) for MRD for the purpose of risk stratification. The aim of this study was to provide quantitative information regarding real-world clinical practice for MRD testing in five European countries. METHODS: A web-based survey was conducted in March/April 2017 in France, Germany, Italy, Spain, and the UK. The survey was developed after consultation with specialist clinicians and a review of published literature. Eligible clinicians (20 per country; 23 in Spain) were board-certified in hemato-oncology or hematology, had at least five years' experience in their current role after training, had treated at least two patients with B-cell precursor ALL in the 12 months before the survey or at least five patients in the last five years, and had experience of testing for MRD in clinical practice. RESULTS: MRD testing is now standard practice in the treatment of adult ALL across the five European countries, with common use of recent treatment protocols which specify testing. Respondents estimated that, among clinicians in their country who conduct MRD testing, 73% of patients in first CR (CR1) and 63% of patients in second or later CR (CR2+) are tested for MRD. The median time point reported as most commonly used for the first MRD test, to establish risk status and to determine a treatment plan was four weeks after the start of induction therapy. The timing and frequency of tests is similar across countries. An average of four or five post-CR1 tests per patient in the 12 months after the first MRD test were reported across countries. CONCLUSIONS: This comprehensive study of MRD testing patterns shows consistent practice across France, Germany, Italy, Spain, and the UK with respect to the timing and frequency of MRD testing, aligning with use of national protocols. MRD testing is used in clinical practice also in patients who reach CR2 + .

Productivity loss and indirect costs associated with cardiovascular events and related clinical procedures.

BACKGROUND: The high acute costs of cardiovascular disease and acute cardiovascular events are well established, particularly in terms of direct medical costs. The costs associated with lost work productivity have been described in a broad sense, but little is known about workplace absenteeism or short term disability costs among high cardiovascular risk patients. The objective of this study was to quantify workplace absenteeism (WA) and short-term disability (STD) hours and costs associated with cardiovascular events and related clinical procedures (CVERP) in United States employees with high cardiovascular risk. METHODS: Medical, WA and/or STD data from the Truven Health MarketScan® Research Databases were used to select full-time employees aged 18-64 with hyperlipidemia during 2002-2011. Two cohorts (with and without CVERP) were created and screened for medical, drug, WA, and STD eligibility. The CVERP cohort was matched with a non-CVERP cohort using propensity score matching. Work loss hours and indirect costs were calculated for patients with and without CVERP and by CVERP type. Wages were based on the 2013 age-, gender-, and geographic region-adjusted wage rate from the United States Bureau of Labor Statistics. RESULTS: A total of 5,808 WA-eligible, 21,006 STD-eligible, and 3,362 combined WA and STD eligible patients with CVERP were well matched to patients without CVERP, creating three cohorts of patients with CVERP and three cohorts of patients without CVERP. Demographics were similar across cohorts (mean age 52.2-53.1 years, male 81.3-86.8%). During the first month of follow-up, patients with CVERP had more WA/STD-related hours lost compared with patients without CVERP (WA-eligible: 23.4 more hours, STD-eligible: 51.7 more hours, WA and STD-eligible: 56.3 more hours) (p < 0.001). Corresponding costs were $683, $895, and $1,119 higher, respectively (p < 0.001). Differences narrowed with longer follow-up. In the first month and year of follow-up, patients with coronary artery bypass graft experienced the highest WA/STD-related hours lost and costs compared with patients with other CVERP. CONCLUSIONS: CVERP were associated with substantial work loss and indirect costs. Prevention or reduction of CVERP could result in WA and STD-related cost savings for employers.

Utilization of intravenous bisphosphonates in patients with bone metastases secondary to breast, lung, or prostate cancer.

PURPOSE: Cancer patients with bone metastases (BMets) are predisposed to skeletal complications. Bone-targeted therapies such as denosumab or intravenous bisphosphonates (IVBs) reduce the risk of these complications. This study characterized patterns of IVB use in these patients in the USA. METHODS: This was a retrospective, observational study using the Truven Health MarketScan(®) Commercial and Medicare databases (2002-2011). Subjects with ≥1 claims of diagnosis of breast, lung, or prostate cancer (BC, LC, or PC) and ≥1 claims of BMets diagnosis were included. The date of first BMet diagnosis claim was the "index date." Key exclusion criteria were diagnosis of other primary cancer, receipt of IVB, or <6 months continuous enrollment pre-index. Cumulative incidence of treatment initiation, interruption, and discontinuation were estimated. Proportions of IVB claims with chemotherapy administered on the same day and with renal monitoring within 2 weeks prior were summarized. Multivariate regressions assessing factors associated with IVB initiation were conducted. RESULTS: Cumulative incidence of IVB initiation at 12 months post-index was greatest for BC followed by PC and LC, and it declined with age in all tumor types, e.g., in BC from 62 % at age <50 years to 47 % at age ≥75 years. At 12 months, IVB treatment interruption ranged from 16 % (LC) to 31 % (PC), with discontinuation ranging from 46 % (BC) to 83 % (LC). CONCLUSIONS: IVBs are used more frequently in patients with BMets secondary to BC than PC or LC. Many patients interrupt or discontinue IVB therapy within 12 months of initiation potentially impacting effectiveness.

Ziyin Bushen Fang improves Diabetic Osteoporosis by Inhibiting Autophagy and Oxidative Stress In vitro and In vivo.

OBJECTIVE: Diabetic osteoporosis (DOP) belongs to the group of diabetes-induced secondary osteoporosis and is the main cause of bone fragility and fractures in many patients with diabetes. The aim of this study was to determine whether Ziyin Bushen Fang (ZYBSF) can improve DOP by inhibiting autophagy and oxidative stress. METHODS: Type 1 diabetes mellitus (T1DM) was induced in rats using a high-fat high-sugar diet combined with streptozotocin. Micro-CT scanning was used to quantitatively observe changes in the bone microstructure in each group. Changes in the serum metabolites of DOP rats were analyzed using UHPLC-QTOF-MS. The DOP mouse embryonic osteoblast precursor cell model (MC3T3-E1) was induced using high glucose levels. RESULTS: After ZYBSF treatment, bone microstructure significantly improved. The bone mineral density, trabecular number, and trabecular thickness in the ZYBSF-M and ZYBSF-H groups significantly increased. After ZYBSF treatment, the femur structure of the rats was relatively intact, collagen fibers were significantly increased, and osteoporosis was significantly improved. A total of 1239 metabolites were upregulated and 1527 were downregulated in the serum of T1DM and ZYBSF-treated rats. A total of 20 metabolic pathways were identified. In cellular experiments, ZYBSF reduced ROS levels and inhibited the protein expression of LC3II / I, Beclin-1, and p-ERK. CONCLUSION: ZYBSF may improve DOP by inhibiting the ROS/ERK-induced autophagy signaling pathway.

Erythropoiesis-Stimulating Agent (ESA) Practice Patterns in Patients With Chemotherapy-Induced Anemia (CIA) Treated at Hospital Oncology Clinics.

OBJECTIVES: To characterize erythropoiesis-stimulating agent (ESA) usage initiated in hospital outpatient oncology centers that employ weekly (QW) and every-3-week (Q3W) ESA dosing regimens; describe the frequency of ESA dosing, transfusions, hemoglobin determinations, and anemia-related visits between these 2 regimens; and compare the rates at which inpatient ESA doses are administered on QW versus Q3W schedules. METHODS: This was a retrospective, observational record review evaluating ESA usage in 641 patients from 8 outpatient oncology clinics throughout the United States. Adult patients who initiated myelosuppressive chemotherapy for a documented solid tumor between August 1, 2007 and June 30, 2009 and received their first 3 consecutive outpatient ESA doses on a QW or Q3W schedule were eligible for study inclusion. During a single course of chemotherapy, ESA administrations were recorded as long as ESA therapy was continued on the initial regimen. ESA doses were captured until termination of ESA therapy, until 9 months had elapsed since the first ESA dose, until the patient was switched to another ESA regimen, or until death. ESA administration during inpatient admissions was also recorded. RESULTS: ESA utilization varied between the dosing groups, with fewer ESA doses administered per follow-up month in patients receiving Q3W versus QW ESA therapy (mean, 1 vs 2 doses). Compared to weekly administration, extended-dose ESA therapy also reduced the number of hemoglobin determinations and anemia-related visits without chemotherapy required per follow-up month. Neither the number of transfusions nor the number of packed red blood cell units administered per follow-up month differed between treatment groups. Compared to weekly ESA therapy, Q3W administration reduced costs associated with ESA prescribing and utilization. CONCLUSION: Extended-dose ESA therapy (Q3W dosing) may improve practice efficiency and may be associated with reduced frequencies of hemoglobin determinations and ESA doses required. Q3W dosing may also reduce inpatient ESA utilization by reducing the number of ESA doses required for previously maintained outpatients.

Time duration and health care resource use during cancer diagnoses in the United States: A large claims database analysis.

BACKGROUND: Cancer diagnostic pathways are highly variable and not clearly established in the United States, which can lead to a diagnosis process that takes more time and exposes patients to invasive or unnecessary procedures, delays in treatment, worsening patient outcomes, and elevated health care resource utilization (HRU) and health care system costs. OBJECTIVE: To investigate current trends in time to diagnosis and diagnostic-related HRU preceding the patient's cancer diagnosis across all cancer types in the United States. METHODS: A retrospective claims analysis was conducted on patients newly diagnosed with cancer identified from 2018-2019 using Optum's de-identified Clinformatics Data Mart database, which includes Medicare Advantage and commercially insured members. Patients were identified using International Classification of Diseases, Tenth Revision codes and were required to have at least 2 outpatient visits at least 30 days apart or at least 1 inpatient cancer visit without prior cancer claims. The first diagnostic test was identified based on an algorithm of a 60-day gap between diagnostic tests prior to diagnosis. The index date was defined as the first diagnostic test date or an office visit less than 4 weeks prior to the first diagnostic test date. Patient characteristics, time to diagnosis, and HRU were descriptively analyzed for all patients and by cancer type. RESULTS: Among the 458,818 patients newly diagnosed with cancer included in this analysis, the mean age was 70.6 years, approximately half were female, and most were White people (65.0%) with Medicare Advantage coverage (74.0%). Patients with cancer had an overall mean (SD) time to diagnosis of 156.2 (164.9) days and 15.4% of patients waited longer than 180 days before a cancer diagnosis. High heterogeneity among cancer types was observed, with a mean time to diagnosis ranging from 121.6 days (bladder cancer) to 229.0 days (multiple myeloma). Imaging resource use during the diagnostic pathway was high for radiology (60.7%), computerized tomography (50.8%), magnetic resonance imaging (48.6%), and ultrasound (42.6%). A total of 69.3% of patients had endoscopy without biopsy, 36.5% had endoscopy with biopsy, 62.5% had other biopsies, and most patients did general urine and serum tests (91.3%) and nongenetic cancer-specific laboratory tests (84.3%). Resource use was highly varied by cancer type but tended to increase with a longer time to diagnosis. CONCLUSIONS: The proportion of patients experiencing a diagnostic process of longer than 180 days is clinically and economically meaningful. Diagnostic-related HRU was significant and highly variable, highlighting the inefficiencies in the cancer diagnostic process in the United States and the need for policies, guidelines, or medical interventions to streamline cancer diagnostic pathways to optimize patient outcomes and reduce health care system burden. DISCLOSURES: Dr Cong is an employee of Grail, LLC, which supported this study. Drs Gitlin and McGarvey are employees of BluePath Solutions, and Ms Shivaprakash was an employee of BluePath Solutions, which received financial support from Grail, LLC, for study-related research activities. This study was sponsored by Grail, LLC, a subsidiary of Illumina Inc. currently held separate from Illumina Inc. under the terms of the Interim Measures Order of the European Commission dated October 29, 2021. The sponsor had no role in the collection, management, and analysis of the data. The sponsor contributed to study design and data interpretation.

Transfusion burden in non-dialysis chronic kidney disease patients with persistent anemia treated in routine clinical practice: a retrospective observational study.

BACKGROUND: Transfusion patterns are not well characterized in non-dialysis (ND) chronic kidney disease (CKD) patients. This study describes the proportion of patients transfused, units of blood transfused and trigger-hemoglobin (Hb) levels for transfusions in severe anemic, ND-CKD patients in routine practice. METHODS: A retrospective cohort study of electronic medical record data from the Henry Ford Health System identified 374 adult, ND-CKD patients with severe anemia (Hb < 10 g/dL and subsequent use of erythropoiesis-stimulating agents [ESA] therapy, blood transfusions, or a second Hb < 10 g/dL) between January 2004 and June 2008. Exclusions included those with prior diagnoses of cancer, renal or liver transplant, end-stage renal disease, acute bleeding, trauma, sickle cell disease, or aplastic anemia. A gap of ≥ 1 days between units of blood transfused was counted as a separate transfusion. RESULTS: At least 1 transfusion (mean of 2 units; range, 1-4) was administered to 20% (75/374) of ND-CKD patients with mean (± SD) follow-up of 459 (± 427) days. The mean (± SD) Hb level closest and prior to a transfusion was 8.8 (± 1.5) g/dL. Patients who were hospitalized in the 6 months prior to their first anemia diagnosis were 6.3 times more likely to receive a blood transfusion than patients who were not hospitalized (p < 0.0001). Patients with peripheral vascular disease (PVD) were twice as likely to have a transfusion as patients without PVD (p = 0.04). CONCLUSIONS: Transfusions were prevalent and the trigger hemoglobin concentration was approximately 9 g/dL among ND-CKD patients with anemia. To reduce the transfusion burden, clinicians should consider other anemia treatments including ESA therapy.

Productivity Loss and Indirect Costs for Patients Newly Diagnosed with Early- versus Late-Stage Cancer in the USA: A Large-Scale Observational Research Study.

BACKGROUND: The total economic burden of cancer reflects direct and indirect costs, including productivity loss due to employment change, absenteeism, and presenteeism of patients and caregivers. OBJECTIVE: This study estimated the magnitude of employment decrease, work absence (WA), short-term disability (STD), long-term disability (LTD), and associated indirect costs among employees newly diagnosed with metastatic versus non-metastatic cancer in the USA. METHODS: IBM® MarketScan® Commercial Claims and Encounters and Health and Productivity Management databases were used to identify employees aged 18-64 years and newly diagnosed with any cancer from 2009 to 2019. Proportions of patients with employment decrease, WA, STD, and LTD claims, and number of days missing from work were summarized by metastatic status during the first 12 months after diagnosis and the entire follow-up period. Subgroup analyses were conducted by age (< 50 years, ≥ 50 years) and cancer type (breast, lung, colon, pancreatic, and liver cancer). RESULTS: During the first year after diagnosis, compared to patients without metastases, significantly higher proportions of patients with metastases had employment decrease and STD or LTD claims (p < 0.001). The mean total number of days missing from work for patients with versus without metastases was 33.39 versus 14.91 (ratio = 2.40), 64.05 versus 27.15 (ratio = 2.36), and 105.93 versus 46.29 (ratio = 2.29) days within 3, 6, and 12 months after diagnosis, respectively. Estimates of indirect cost differences between the two groups ranged from $6,877 to $22,283 in the first year. CONCLUSION: Earlier detection of cancer may reduce productivity loss of patients and indirect costs by initiating treatment before cancer progresses to late stage.

Breast, Colorectal, Lung, Prostate, and Cervical Cancer Screening Prevalence in a Large Commercial and Medicare Advantage Plan, 2008-2020.

This study aimed to comprehensively assess breast, colorectal, cervical, lung, and prostate cancer screening rates and trends in the United States over time among individuals for whom screening is recommended by the United States Preventive Services Task Force (USPSTF). This retrospective study was conducted in two-year intervals from January 1, 2008 to February 29, 2020, using Optum's de-identified Clinformatics® Data Mart Database, which includes Medicare Advantage and commercially insured members. Screening-eligible individuals, who had not previously had the cancer being screened and met USPSTF criteria for screening, were identified at various time points within the study timeframe for relevant screening tests within five cancer types: breast, colorectal, cervical, lung, and prostate. In the 2020 analysis period, patients who were eligible for cancer screening included: breast: 1,620,588; colorectal: 2,763,736; cervical: 1,371,506; lung: 1,491,594; prostate: 1,126,249. Breast and cervical cancer screening prevalence rates were highest (64.4% and 63.8%, respectively), followed by colorectal (29.5%), prostate (11.7%), and lung (3.8%). Black/African American individuals and Hispanics had moderately low screening rates for cervical (58.6%) and breast (61.8%) cancer, respectively; Hispanics had the lowest screening rates for prostate cancer (6.1%). Those residing in the West had lower screening rates for breast (58.9%), cervical (62.1%), and prostate (5.6%) cancer. Screening rates remained stable over time for breast, colorectal, and lung cancer, and changed significantly for cervical (-9.5%, 2012-2020) and prostate (+7.3%, 2008-2020) cancer. Real-world cancer screening rates remain suboptimal and low, and efforts to increase screening uptake and reduce cancer health disparities remain critical.

[Comprehensive evaluation of soil quality of different land use types on the northeastern margin of the Qinghai-Tibet Plateau, China]. / 青藏高原东北缘不同土地利用类型土壤质量综合评价.

Soil quality evaluation is an important prerequisite for the rational soil resource utilization. We collected soil samples from forest (n=9), grassland (n=18) and cropland (n=38) in Tianzhu County, Gansu Province, which is located on the northeastern edge of the Qinghai-Tibet Plateau. Soil quality was evaluated based on thirteen soil physical and chemical indicators, including soil bulk density, field capacity, and organic matter. A minimum data set (MDS) was constructed using principal component analysis and correlation analysis to establish a soil qua-lity evaluation index (SQI) system, which was used in the soil quality evaluation for the three land-use types. The results showed that total porosity, capillary porosity, field capacity, capillary water capacity, saturated water content, organic matter, total nitrogen and available potassium content were significantly higher in forest than those in grassland and cropland. The SQI system of forest was based on field capacity, organic matter, total nitrogen, available nitrogen, and available potassium, and the SQI ranged between 0.329 to 0.678, with a mean value of 0.481. Grassland SQI system was based on field capacity and available nitrogen, with the SQI ranging between 0.302 to 0.703 and a mean value of 0.469. Cropland SQI system was based on capillary water capacity, non-capillary porosity, available nitrogen, available phosphorus, and available potassium, and the SQI ranged from 0.337 to 0.616 with a mean value of 0.462. The most important barriers to soil quality improvement in forest, grassland, and cropland were available potassium, field capacity, and capillary water capacity, respectively. The MDS-based SQI enabled an accurate evaluation of soil quality across different land-use types in the study area, which was best in forest followed by grassland and cropland. The evaluation results would provide important reference for sustainable soil management in the local area.

A systematic review of outcomes after stem cell transplantation in acute lymphoblastic leukemia with or without measurable residual disease.

This systematic literature review compared clinical outcomes post-stem cell transplantation (SCT) among patients with vs. without the measurable residual disease (MRD) pre-transplant. Relevant literature on adults undergoing transplant with known MRD status pre-transplant was extracted from the MEDLINE, Embase, and CENTRAL databases (through 8 May 2018) and oncology conferences (2014-2018) using keywords for acute lymphoblastic leukemia and MRD. Thirty primary studies reporting SCT outcomes were identified. Hazard ratios (HRs) for overall survival indicated that patients with MRD pre-transplant were more likely to die post-SCT vs. patients with no detectable MRD (HR: 1.51-3.856). In post-SCT relapse studies, 16-100% of patients with MRD vs. 0-50% of patients without MRD relapsed. This review found evidence of markedly worse outcomes post-transplant among patients with vs. without MRD pre-transplant, including shorter median survival (overall, relapse-free, and event-free survival), higher risk of death, more relapse events, and decreased likelihood of remaining in hematologic remission.

The Economic Burden of End-Organ Damage Among Medicaid Patients with Sickle Cell Disease in the United States: A Population-Based Longitudinal Claims Study.

BACKGROUND: The management of sickle cell disease (SCD), an inherited, chronic, and multifaceted condition, is associated with considerable health care resource utilization (HRU) and costs, especially for Medicaid. Anemia affects most patients with SCD and correlates with end-organ damage (EOD), such as stroke, chronic kidney disease (CKD), end-stage renal disease (ESRD), and pulmonary hypertension (PH). Limited research has been conducted to quantify the economic burden of EOD among patients with SCD. OBJECTIVE: To estimate the effect of EOD on HRU and direct costs and productivity loss incurred by patients with SCD on Medicaid. METHODS: Patients with ≥ 3 nondiagnostic SCD ICD-9-CM/ICD-10-CM codes in ≤ 5 years (January 1, 2013-December 31, 2017) were identified in the MarketScan Medicaid claims database. The earliest SCD diagnosis date was the index date. Continuous enrollment at least 3 months before and 1 month after the index date were required. Patients' post-index periods were divided into 3-month intervals (referred to as "intervals"). History of stroke, CKD, ESRD, and PH were identified in patients' claims histories from January 1, 2008. Intervals within 1 year and more than 1 year after an acute stroke event were also defined. All-cause HRU, direct costs, and productivity losses were summed across intervals and stratified by EOD type. Multivariate regression models were used to estimate the effect of stroke, CKD, ESRD, and PH on annual total cost, inpatient days, and number of emergency department visits by controlling for patients' demographic characteristics and other SCD complications. RESULTS: In total, 10,784 Medicaid patients with SCD (average age: 18.5 years; female: 54.5%) contributed to 152,455 intervals. Approximately 12% of the intervals had EOD. Patients with EOD had higher all-cause health care costs and more inpatient days, emergency department visits, outpatient visits, laboratory tests, and outpatient pharmacy claims than patients without EOD. After controlling for patient characteristics, among Medicaid patients with SCD annual costs within 1 year after stroke were 4.68-fold versus patients with no EOD (more than 1 year after stroke: 2.08-fold; CKD: 2.19-fold; ESRD: 3.40-fold; PH: 2.32-fold). Adjusted mean annual costs for adult patients with SCD on Medicaid were $285,816 and $127,393 within 1 year and more than 1 year after stroke and $135,493, $209,172, and $148,174 for CKD, ESRD, and PH, respectively. Patients with multiple SCD complications had even higher costs. The mean annual time patients with SCD spent receiving health care services ranged from 56 to 62 days for those with EOD versus 21 to 25 days among those without EOD, which created additional economic burden. CONCLUSIONS: When Medicaid patients with SCD experience EOD, the economic burden is significantly increased through direct costs to the health care system and indirect costs from productivity loss to society. SCD management strategies that potentially reduce the risk of EOD offer clinical and economic value to patients and society. DISCLOSURES: Funding for this study was provided by Global Blood Therapeutics (GBT). Campbell is a consultant for GBT, Bluebird Bio, and Cyclerion and receives research funding from Novartis, GBT, and Cyclerion. Cong and Agodoa are employees of and have equity ownership in GBT. Song, Martinez, Black, Lew, Varker, and Chan are employees of IBM Watson Health, which received research funding from GBT for this study. Lanzkron receives research funding from GBT, Pfizer, Ironwood, HRSA, and NIH. A poster based on this study was presented at the 61st ASH Annual Meeting and Exposition; December 7-10, 2019; Orlando, FL.

[Health care status of female workers exposed to occupational hazards in Haidian district of Beijing].

OBJECTIVE: To investigate the health care status of female workers exposed to occupational hazards in Haidian district of Beijing and improve the labor protection of female workers. METHODS: A questionnaire provided by National Center for Women and Children's Health of Chinese CDC was used in the survey conducted to collect information about health care status of female workers in 141 factories with occupational hazards including chemical poisons and physical factors (noise, libration, microwave, high frequency and low temperature). RESULTS: 141 factories were investigated, including 53 state-owned enterprises, 21 collective enterprises, 46 joint-stock enterprises, and 21 non-public enterprises. 12 251 female workers were surveyed, 10.19% (1249/12 251) of whom were exposed to occupational hazards. Of 141 factories studied, 16.31% (23/141) had no labor protection management organization.27.66% (39/141) did not provide pre-employment physical examination service to female workers.48.94% (69/141) didn't establish labor protection system for female workers in menstrual period. While, 21.28% (30/141) of the studied institutes deducted some salaries in the pregnancy, and 32.62% (46/141) deducted their wages during the puerperal period. 2.13% (3/141) arranged female workers in the posts which are forbidden by law (continuous heavy work load operation).9.93% (14/141) arranged pregnant female workers on the post forbidden by law.31.91% (45/141) and 33.33% (47/141) would deduct the time of prenatal medical examination and lactation from their working hours, respectively.39.01% (55/141) didn't afford the cost of fertility. 68.09% (96/141) had annual gynecological examination.45 factories were collected occupational examination reports, accounted for 31.91% (45/141). No female workers were found suffering from occupational disease. Of the 1865 occupational hazard factor monitoring points in 34 factories, there were 155 monitoring points, which were all noise monitoring points, did not meet the standard. CONCLUSION: The current health-care status of female workers is not optimistic. It is necessary to consistently improve health care legislations, establish coordinated management mechanism and strengthen the publicity of policy to protect female workers.

Clinicians' Perspectives on Cure in Adult Patients with Acute Lymphoblastic Leukemia with Minimal Residual Disease: A Delphi Study.

Hematologic complete remission (CR) is achievable for most adults with B cell precursor acute lymphoblastic leukemia (BCP-ALL). However, minimal residual disease (MRD) in patients with hematologic CR is associated with increased risk of relapse, shorter survival, and poorer transplantation outcomes. This study explored the concept of cure in adults with Philadelphia chromosome-negative (Ph-) BCP-ALL by MRD status at first hematologic CR (CR1) to inform evaluation of the clinical and economic benefits of new agents, where the concept of cure is important but long-term data are not available. The study used modified Delphi methodology involving clinicians experienced in the treatment of adult ALL. Participants completed a questionnaire, which was followed by country-specific panel discussions to discuss results and identify consensus on concepts and definitions. Clinicians from France (n = 4), Germany (n = 4), and the UK (n = 5) took part. Participants described cure in terms of the probability of future relapse. Relapse-free survival (RFS) was the preferred outcome measure to describe cure for the three patient groups considered (patients with MRD at CR1; patients who become negative for MRD after further treatment; patients who continue to have MRD). Consensus was reached on definitions of cure: that cure would begin to be considered at 3 years' RFS and/or would be highly likely at 5 years' RFS. Participants agreed that patients with MRD should usually undergo hematopoietic stem cell transplantation to have the best chance of survival; consensus was reached that alternatives are required when transplantation is not an option. Panels agreed that patients who achieve cure have a higher mortality rate and lower health-related quality of life than the general population. This study provides quantitative and qualitative information on the concept of cure in Ph- BCP-ALL in CR by MRD status applicable to interpreting the value of new therapies.Funding: Amgen.Plain Language Summary: Plain language summary available for this article.

Clinician Concepts of Cure in Adult Relapsed and Refractory Philadelphia-Negative B Cell Precursor Acute Lymphoblastic Leukemia: A Delphi Study.

INTRODUCTION: Despite the poor prognosis for adults with relapsed or refractory (RR) Philadelphia chromosome (Ph)-negative B cell precursor acute lymphoblastic leukemia (ALL), long-term survival is possible and may even be considered as "cure". METHODS: This study used a Delphi panel approach to explore concepts of cure in RR Ph-negative B cell precursor ALL. Ten European experts in this disease area participated in a survey and face-to-face panel meeting. RESULTS: Findings showed that clinicians conceptualize "cure" as a combination of three broad treatment outcomes that vary depending on the treatment stage: complete remission early in treatment (1-3 months) indicates initial success; eradicating cancer cells (minimal residual disease negative status) consolidates the early clinical response; leukemia-free survival is required in the long term. CONCLUSIONS: Although such terminology remains contested, clinicians would begin considering "cure" as early as 2 years provided the patient is off therapy, with most considering the term applicable by the third year. FUNDING: Amgen Inc.

Matching-Adjusted Indirect Comparison of Blinatumomab vs. Inotuzumab Ozogamicin for Adults with Relapsed/Refractory Acute Lymphoblastic Leukemia.

INTRODUCTION: In the absence of head-to-head trials, this analysis aimed to provide a fair indirect comparison of the efficacy between blinatumomab and inotuzumab ozogamicin (InO), two treatments for adult patients with relapsed or refractory acute lymphoblastic leukemia (R/R ALL) who received no more than one prior salvage therapy, by adjusting for cross-trial differences. METHODS: Patient-level data from the Phase 3 blinatumomab trial TOWER and published aggregated data from the Phase 3 InO trial INO-VATE-ALL were used to conduct matching-adjusted indirect comparisons. Patients with 2+ prior salvage therapies from TOWER were excluded because such patients were not included in INO-VATE-ALL. To ensure balance in the remaining patients, baseline characteristics for the TOWER patients were weighted to match the average baseline characteristics in INO-VATE-ALL, including sex, age, race, performance status, bone marrow blast, previous salvage therapy, previous allogeneic transplantation, complete remission with complete hematologic recovery (CR) to most recent induction therapy, and duration of first remission. Overall survival (OS), including median and restricted mean survival time (RMST) at 12 and 20.7 months, and CR were estimated and compared. RESULTS: A total of 310 patients in TOWER were included (blinatumomab, n = 203; standard of care chemotherapy, n = 107). After matching the listed baseline characteristics, the median OS was 9.3 months for blinatumomab and 7.7 months for InO (weighted log-rank test p = 0.4). The relative RMST at 12 months was 1.6 months longer for blinatumomab than for InO [95% CI (0.1, 3.2); p = 0.04]; at 20.7 months the RMST was not significantly different. The CR rates were similar [anchor-based difference = - 2.8%, 95% CI (- 17.5%, 11.9%); p = 0.71]. CONCLUSIONS: After adjusting for cross-trial differences, blinatumomab demonstrated a similar CR rate and potential OS benefit versus InO among adult patients with R/R ALL who received no more than one prior salvage therapy. Further studies are suggested to confirm this finding. FUNDING: Amgen.