Real-World Effectiveness of a Third Dose of mRNA-1273 Versus BNT162b2 on Inpatient and Medically Attended COVID-19 Among Immunocompromised US Adults.

INTRODUCTION: Recent data have shown elevated infection rates in several subpopulations at risk of SARS-CoV-2 infection and COVID-19, including immunocompromised (IC) individuals. Previous research suggests that IC persons have reduced risks of hospitalization and medically attended COVID-19 with two doses of mRNA-1273 (SpikeVax; Moderna) compared to two doses of BNT162b2 (Comirnaty; Pfizer/BioNTech). The main objective of this retrospective cohort study was to compare real-world effectiveness of third doses of mRNA-1273 versus BNT162b2 at multiple time points on occurrence of COVID-19 hospitalization and medically attended COVID-19 among IC adults in the United States (US). METHODS: This retrospective, observational comparative effectiveness study identified patients from the US HealthVerity database from December 11, 2020, through August 31, 2022. Medically attended SARS-CoV-2 infections and hospitalizations were assessed following a three-dose mRNA-1273 versus BNT162b2 regimen. Inverse probability weighting was applied to balance baseline confounders between vaccine groups. Relative risk (RR) and risk difference were calculated for subgroup and sensitivity analyses using a non-parametric method. RESULTS: In propensity score-adjusted analyses, receiving mRNA-1273 vs. BNT162b2 as third dose was associated with 32.4% (relative risk 0.676; 95% confidence interval 0.506-0.887), 29.3% (0.707; 0.573-0.858), and 23.4% (0.766; 0.626-0.927) lower risk of COVID-19 hospitalization after 90, 180, and 270 days, respectively. Corresponding reductions in medically attended COVID-19 were 8.4% (0.916; 0.860-0.976), 6.4% (0.936; 0.895-0.978), and 2.4% (0.976; 0.935-1.017), respectively. CONCLUSIONS: Our findings suggest a third dose of mRNA-1273 is more effective than a third dose of BNT162b2 in preventing COVID-19 hospitalization and breakthrough medically attended COVID-19 among IC adults in the US.

Death Following a Skiing Incident: Severe Exsanguination Due to Rupture of the Left Renal Artery.

With the growing popularity of winter sports, it is necessary to pay more attention to the types of traumatic injuries that a person can sustain in various incidents related to their practice. We present a case in which an adult man died as a result of a collision with a tree while skiing. Although the deaths are associated with different types and severity of craniocerebral injuries in the majority of the cases, here we are dealing with an abdominal injury with rupture of the stomach, pancreas, and left renal artery. The exact localization of the resulting traumatic injuries and the mechanism of their occurrence were examined. Both macroscopic autopsy findings (gross pathology) and histologically proven ones are presented and described. Presenting this case, we want to raise awareness of the different types of injuries received while skiing, as well as to emphasize the possibility of death in the absence of visible external injuries over the victim's body.

Accidental Cut-Throat Injury by a Broken Glass: Bloodstain Pattern Analyses and Autopsy Findings.

Injuries in the neck region are rarely observed in forensic practice, especially of accidental origin. Primarily, such cases are associated with homicide or suicide. The neck region comprises different and vital anatomical structures, and even minor trauma could be lethal. In the absence of witnesses to the accident, each finding is of utmost importance, from the death/crime scene investigation - bloodstain patterns and trace evidence - to careful examination of the deceased body. The forensic pathologist has the challenging task of analyzing all the findings to make a statement concerning the cause and manner of death and, if there is something suspicious about the current case, to inform the relevant authorities.

Self-Mutilation: A Way to Protect Yourself From a Committed Crime or to Gain Personal Benefits.

Self-mutilation refers to the state in which a person deliberately hurts himself without the intention to commit suicide but with the motive of some personal gain. Four cases are described in the current study with four different personal motives - drug supply, accusation of intimate partner violence, confrontation of parental prohibition, and a way to hide and escape from a committed crime. Evaluating the injuries due to self-mutilation might be challenging due to atypical lesions and well-structured false stories when the victim has some level of competency. Careful analysis of the victim's story and a thorough evaluation of the sustained injuries are needed. If doubts about artificial injuries exist, immediate consultation with a forensic pathologist is required.

Abdominal Apoplexy: Sudden Death Due to Massive, Nontraumatic Intra-abdominal Hemorrhage.

Abdominal apoplexy or idiopathic spontaneous intraperitoneal hemorrhage (ISIH), the modern way to describe this condition, is a rare phenomenon representing intra-abdominal bleeding with no traumatic origin. The condition is severe and potentially life-threatening. A man in his 70s was found dead at his home. The autopsy revealed a massive hemoperitoneum with no visible traumatic injuries externally or internally. The source of the bleeding was unknown despite the careful examination of the internal organs and splanchnic vessels. The cause of death was attributed to massive exsanguination due to the rupture of a small blood vessel as a complication of generalized arteriosclerosis and hypertensive disease. Despite its rare occurrence, the forensic pathologist should always consider this pathological condition when, during the autopsy, a massive intraabdominal hemorrhage with or without a visible source of the bleeding is discovered in the absence of any visible traumas.

A Rare Phenomenon of Natural Precocious Mummification.

Immediately after death, specific changes occur in the human body, leading to the total dissolution of the soft tissues and internal organs. In some cases, when in suitable conditions, the decomposition process could stop and be displaced by mummification. The last one is time-consuming and needs several weeks to months to set in completely. We present a case of a 34-year-old man found dead 16 days after being last seen alive in a stage of complete mummification. Natural mummification occurring in less than one month is termed precocious mummification and is rarely observed in temperate regions. With only a few cases reported globally, this case is essential for the forensic community. It will help better know the mummification processes and estimate the time since death.

Patient and Caregiver Outcomes After Onasemnogene Abeparvovec Treatment: Findings from the Cure SMA 2021 Membership Survey.

INTRODUCTION: Onasemnogene abeparvovec (OA) is the only gene replacement therapy currently approved for spinal muscular atrophy (SMA) treatment. We sought to assess real-world patient and caregiver outcomes after OA treatment for SMA. METHODS: Patients who received OA were identified from the 2021 Cure SMA Membership Survey. Those treated at 6-23 months of age were matched to non-patients treated with OA on the basis of age at the time of survey and survival motor neuron 2 gene copy number. Patient characteristics, motor milestones, and resource and supportive care use, as well as caregiver proxy-reported health-related quality of life (HRQOL), were described. Caregiver unmet needs and HRQOL were also assessed. RESULTS: Of the 614 patients in the survey, 64 received OA, and 17 were matched with 28 non-OA-treated patients. In general, a greater percentage of OA-treated patients achieved various motor milestones, including 100% sitting without support and 58.8% walking with assistance. OA-treated patients also had numerically lower rates of hospitalization and surgery. None required tracheostomy with a ventilator. The rate of using oxygen or a breathing machine for more than 16 h was also lower for OA-treated patients. OA-treated patients had less frequent trouble swallowing. HRQOL was reported to be similar to non-OA-treated patients. Caregivers of OA-treated patients reported better patient mobility scores and less work impairment. CONCLUSIONS: The study suggests that treatment with OA is associated with greater rates of motor milestone achievements and less resource and supportive care use for patients with SMA treated at 6-23 months of age in the real world. For caregivers, it may also potentially reduce unmet needs, improve HRQOL, and reduce work impairment.

Health Care Resource Utilization and Costs for Patients with Spinal Muscular Atrophy: Findings from a Retrospective US Claims Database Analysis.

INTRODUCTION: Spinal muscular atrophy (SMA) is a neurogenic disorder associated with progressive loss of muscle function, respiratory failure, and premature mortality. This study aimed to describe and compare real-world health care resource utilization (HCRU) and costs for US patients with SMA treated with disease-modifying treatments, including onasemnogene abeparvovec, nusinersen, and/or risdiplam. METHODS: This study used claims and structured electronic medical record data from the HealthVerity claims database (January 1, 2017-March 31, 2021). Eligible patients were aged ≤ 2 years at index (treatment initiation or switch), diagnosed with SMA, had ≥ 1 pharmacy/medical claim for onasemnogene abeparvovec, nusinersen, and/or risdiplam, and continuous enrollment ≥ 1 month pre- and ≥ 2 months post-index. SMA-related HCRU and costs during the study period (> 12 months post-index) were compared between treatment groups before and after propensity score weighting. Costs were adjusted to 2021 USD. RESULTS: Of 74 included patients, 62 (83.8%) received nusinersen and 12 (16.2%) received onasemnogene abeparvovec (monotherapy, n = 9; onasemnogene abeparvovec after nusinersen [switching], n = 3). After weighting, nusinersen-treated patients had greater annual numbers of inpatient (mean 5.3 nusinersen vs. 1.8 onasemnogene abeparvovec) and emergency department (mean 3.0 nusinersen vs. 1.5 onasemnogene abeparvovec; p < 0.05) visits, and greater annual SMA-related medical costs (mean $78,446 nusinersen vs. $29,438 onasemnogene abeparvovec; mean difference $49,007, p < 0.05) than onasemnogene abeparvovec-treated patients. Onasemnogene abeparvovec-treated patients incurred greater SMA-treatment pharmacy costs than nusinersen-treated patients (mean $2,241,875 onasemnogene abeparvovec vs. $693,191 nusinersen; mean difference $1,548,684, p < 0.05). CONCLUSIONS: SMA is associated with substantial economic burden. Patients treated with onasemnogene abeparvovec had greater SMA treatment-related pharmacy costs but lower SMA-related HCRU and medical costs compared with patients receiving nusinersen monotherapy.

Spinal muscular atrophy (SMA) is a crippling neurodegenerative disease with symptoms of respiratory failure, muscle weakness and loss of function, and premature death. This study describes and compares real-world health care resource utilization (HCRU) and costs for US patients with SMA receiving current treatments (e.g., onasemnogene abeparvovec, nusinersen, risdiplam) using claims and electronic medical record data from a US claims database. Patients included (n = 74) in the study were ≤ 2 years old at treatment initiation/switching of treatments (index), had been diagnosed with SMA and had one or more pharmacy or medical claim for onasemnogene abeparvovec, nusinersen, or risdiplam, and were continuously enrolled for ≥ 1 month before and ≥ 2 months after index. SMA-related HCRU and costs during the study period (up to 12 months post-index) were compared between treatment groups before and after propensity score weighting, with costs adjusted to 2021 USD. Propensity score weighting allows better comparison between patients in treatment and comparison groups by assigning patients different "weights." This weighting allows investigators to be certain that differences in outcomes between patient groups are a result of a particular treatment. After weighting, nusinersen-treated patients had a greater number of inpatient and emergency department visits and greater SMA-related medical costs annually, whereas patients who received onasemnogene abeparvovec had greater pharmacy costs. Our study indicates the greater medical costs among patients receiving nusinersen were largely driven by invasive procedures, such as tracheostomy and gastrostomy, that required hospitalization, but the exact mechanism of greater HCRU/costs associated with nusinersen needs to be further assessed.

Assessing the impact of open-label designs in patient-reported outcomes: investigation in oncology clinical trials.

BACKGROUND: Knowledge of treatment assignment may affect patient-reported outcomes (PROs), which is of concern in oncology, where open-label trials are common. This study measured the magnitude of open-label bias by comparing PROs for similar patient groups in oncology trials with different degrees of concealment. METHODS: Individual patient data from ipilimumab arms of 2 melanoma and docetaxel arms of 2 non-small cell lung cancer (NSCLC) trials were adjusted for differences using propensity score weighting. Patients were aware of treatment assignment in CA184-022 and CheckMate 057 (open-label) but not in MDX010-20 and VITAL (blinded). Overall survival (OS) and mean changes from baseline to week 12 in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (melanoma) and Lung Cancer Symptom Scale (NSCLC) scores were compared between open-label and blinded groups. RESULTS: After adjustment, baseline characteristics were balanced between blinded (melanoma, n = 125; NSCLC, n = 424) and open-label (melanoma, n = 69; NSCLC, n = 205) groups. Study discontinuation and PRO completion rates at week 12 and OS were similar. There was no clear direction in differences in change scores between groups. In the melanoma trials, role functioning (mean = -5.2, 95% confidence interval [CI] = -15.4 to 5.0), global health status (mean = -1.3, 95% CI = -8.7 to 6.1), and pain (mean = 6.2 , 95% CI = -1.8 to 14.2) favored the blinded, whereas emotional functioning (mean = 2.2, 95% CI = -5.8 to 10.2) and diarrhea (mean = -8.3, 95% CI = -17.3 to 0.7) favored the open-label group. In the NSCLC trials, changes in dyspnea (mean = 5.4, 95% CI = -0.7 to 11.5) favored the blinded and changes in appetite (mean = -1.2, 95% CI = -8.1 to 5.7) favored the open-label group. None were clinically or statistically significant. CONCLUSIONS: This study adds to the growing evidence demonstrating that concerns regarding open-label bias should not prohibit the interpretation of large and meaningful treatment effects on PROs.

Disease Progression and Longitudinal Clinical Outcomes of Lewy Body Dementia in the NACC Database.

INTRODUCTION: As the identification of Lewy body dementia (LBD) is often confirmed postmortem, there is a paucity of evidence on the progression of disease antemortem. This study aimed to comprehensively assess the course of LBD over time across cognitive, functional, and neuropsychiatric outcomes using real-world data. METHODS: Adults with at least one visit to an Alzheimer's Disease Center with a diagnosis of mild cognitive impairment/dementia (index date), indication of LBD, and at least one follow-up visit were identified in the National Alzheimer's Coordinating Center database (September 2005-June 2020). Participant characteristics, medication use, comorbidities, and changes in outcomes were assessed over a 5-year follow-up period and stratified by disease severity based on the Clinical Dementia Rating (CDR®) Dementia Staging Instrument-Sum of Boxes (CDR-SB) score at index. RESULTS: A total of 2052 participants with LBD (mean age at index 73.4 years) were included (mild, 219; moderate, 988; severe, 845). Mean annualized increase over 5 years was 0.9 points for CDR-Global Score, 5.6 points for CDR-SB, 10.4 points for the Functional Activities Questionnaire, and 2.0 points for the Neuropsychiatric Inventory-Questionnaire. Disease progression was greater among participants with moderate and severe LBD at index compared with those with mild LBD. CONCLUSION: Participants with LBD experienced decline across all outcomes over time, and impairment increased with disease severity. Findings highlight the substantial clinical burden associated with LBD and the importance of earlier diagnosis and effective treatment. Further research is needed to understand the predictors of cognitive and functional decline in LBD which may help inform clinical trials.

Child Sexual Abuse: Forensic Medical Assessment of the Traumatic Injuries Over the Victim's Body.

Child sexual abuse is a public health problem that affects children worldwide in all ethnic, educational, and socioeconomic groups. These assaults are extremely dangerous not only due to their direct physical traumas received at the time of the abuse, but they also have long-term consequences that can worsen the future quality of the victim's life. A retrospective study of all cases related to child sexual abuse for five years was performed by materials of the Clinic of Forensic Medicine and Deontology, Sofia, Bulgaria. Ninety-five cases involve children from both genders. The traumatic injuries were carefully examined and classified according to their localization over the victim's bodies and based on the time that had passed after the reported assaults. In cases of sexual violence, the most informative and pointing at the exact type of violence are the injuries situated in the anogenital area. Too often, there is a lack of physical findings, depending on the type of sexual violence or associated with the prolonged time that passes after the crime. Children are unaware of what they have to do after suffering such traumas, or they are scared to share their experience with different family members, which can lead to late forensic examination and lack of physical and biological findings, which are the most critical traces in the criminal prosecution of the crimes and this can be a possibility for the perpetrator not to be charged for his unlawful actions.

Epidemiology and economic burden of Lewy body dementia in the United States.

OBJECTIVE: To describe the trends in epidemiology, healthcare resource use (HCRU), and costs associated with Lewy body dementia (LBD), dementia with Lewy bodies (DLB), and Parkinson's disease dementia (PDD) in the United States. METHODS: This retrospective study used administrative claims data for Medicare fee-for-service (2010-2018) and commercially-insured beneficiaries (2010-2017). The annual prevalence and incidence were calculated among the Medicare beneficiaries by dividing the number of prevalent or incident LBD, DLB, and PDD patients by the total eligible population of that calendar year. Baseline patient characteristics, HCRU, and costs over time were described for Medicare and commercially insured patients with continuous health plan enrollment for ≥12 months before and ≥24 months after first cognitive impairment (CI) diagnosis. RESULTS: From 2010 to 2016, the incidence and prevalence rates of LBD among Medicare beneficiaries ranged from 0.21%-0.18% and 0.90%-0.83%, respectively. Of 9019 Medicare patients with LBD who met other inclusion criteria, 4796 (53.2%) had DLB and 4223 (46.8%) had PDD. The mean age was 78 years and the mean Charlson Comorbidity Index score was 1.6. On average, patients with LBD incurred $18,309 in medical costs during the 1-year pre-diagnosis and $29,174 and $22,814 at years 1 and 5 after diagnosis, respectively. The main cost drivers were inpatient and outpatient visits. Similar trends were observed for DLB and PDD as well as for commercially-insured patients. CONCLUSIONS: Our findings highlight the substantial epidemiological and economic burden across the LBD spectrum and underscore a high unmet need for effective treatments to improve patient outcomes.

Classification, Prediction, and Concordance of Cognitive and Functional Progression in Patients with Mild Cognitive Impairment in the United States: A Latent Class Analysis.

BACKGROUND: Progression trajectories of patients with mild cognitive impairment (MCI) are currently not well understood. OBJECTIVE: To classify patients with incident MCI into different latent classes of progression and identify predictors of progression class. METHODS: Participants with incident MCI were identified from the US National Alzheimer's Coordinating Center Uniform Data Set (09/2005-02/2019). Clinical Dementia Rating (CDR®) Dementia Staging Instrument-Sum of Boxes (CDR-SB), Functional Activities Questionnaire (FAQ), and Mini-Mental State Examination (MMSE) score longitudinal trajectories from MCI diagnosis were fitted using growth mixture models. Predictors of progression class were identified using multivariate multinomial logistic regression models; odds ratios (ORs) and 95% confidence intervals (CIs) were reported. RESULTS: In total, 21%, 22%, and 57% of participants (N = 830) experienced fast, slow, and no progression on CDR-SB, respectively; for FAQ, these figures were 14%, 23%, and 64%, respectively. CDR-SB and FAQ class membership was concordant for most participants (77%). Older age (≥86 versus≤70 years, OR [95% CI] = 5.26 [1.78-15.54]), one copy of APOE ɛ4 (1.94 [1.08-3.47]), higher baseline CDR-SB (2.46 [1.56-3.88]), lower baseline MMSE (0.85 [0.75-0.97]), and higher baseline FAQ (1.13 [1.02-1.26]) scores were significant predictors of fast progression versus no progression based on CDR-SB (all p < 0.05). Predictors of FAQ class membership were largely similar. CONCLUSION: Approximately a third of participants experienced progression based on CDR-SB or FAQ during the  4-year follow-up period. CDR-SB and FAQ class assignment were concordant for the vast majority of participants. Identified predictors may help the selection of patients at higher risk of progression in future trials.

The Impact of Progression on Healthcare Resource Utilization and Costs Among Patients with High-Grade Non-Muscle Invasive Bladder Cancer After Bacillus Calmette-Guérin Therapy: A Retrospective SEER-Medicare Analysis.

INTRODUCTION: We evaluated the real-world healthcare resource utilization (HRU) and costs among patients with high-grade non-muscle invasive bladder cancer (HG-NMIBC) following Bacillus Calmette-Guérin (BCG) therapy. METHODS: Patients aged ≥ 65 years diagnosed with HG-NMIBC between 2008 and 2015 who received adequate BCG induction and were identified in the SEER-Medicare database. Those who received intravesical chemotherapy or radical cystectomy within 12 months of the last BCG induction dose, and had ≥ 6 months of data availability after treatment (index date), were included. Annualized HRU and mean medical costs (2020 United States dollars) were estimated and compared between patients with versus without progression. Inverse probability of treatment weighting was used to adjust for differences in baseline characteristics. RESULTS: Of 986 patients diagnosed with HG-NMIBC who met the inclusion criteria, 257 (26.1%) progressed; the mean ages were similar between patients who did and did not progress (77.6 vs. 77.0 years). The overall population had a mean of 0.96 [standard deviation (SD): 1.18] inpatient admissions, 6.47 (11.40) hospitalization days, 1.38 (2.19) emergency department (ED) visits, and 48.03 (44.97) outpatient visits per patient-year during the study period; total annualized costs per patient post-BCG were $39,102 ($44,244). Patients experiencing progression had significantly higher mean numbers of inpatient admissions [1.61 (SD 1.40) vs. 0.72 (0.99)], hospitalization days [11.77 (14.96) vs. 4.59 (9.29)], ED visits [2.34 (2.92) vs. 1.03 (1.76)], and outpatient visits [65.97 (44.72) vs. 41.63 (43.09)] per patient-year compared with patients without progression (all p < 0.05). Total mean annualized costs per patient after BCG among those who progressed [$65,668 (SD $53,943)] were more than double compared with patients who did not [$29,780 ($36,425)]. CONCLUSIONS: Existing treatments for HG-NMIBC after BCG therapy are associated with substantial HRU and medical costs, particularly after progression. Novel treatments and earlier detection are needed to reduce progression rates and associated costs in this difficult-to-treat population.

Real-world systemic therapy utilization in Medicare patients with locally advanced or metastatic urothelial carcinoma diagnosed between 2008 and 2012.

PURPOSE: Treatment of advanced urothelial carcinoma (UC) remains a challenging clinical entity occurring predominantly in older patients with limited treatment options. However, real-world treatment patterns, differential cancer center access, and association with outcomes is lacking in nationally representative clinical practice and will provide context for emerging therapies. MATERIALS AND METHODS: We used SEER-Medicare data to identify patients with locally advanced or metastatic UC of the bladder or upper urinary tract diagnosed between 2008 and 2012. We characterized utilization systemic therapy, including first- and second-line chemotherapy. Patients receiving neoadjuvant chemotherapy were excluded; results were stratified by academic versus non-academic setting. RESULTS: 3569 patients met study criteria; 48% received some form of chemotherapy within 2 years of diagnosis. Of these, one-third subsequently received second-line chemotherapy. The majority received a regimen including ≥2 agents. Gemcitabine alone or in combination with platinum was the most common first- and second-line treatment. Similar patterns of first- and second-line chemotherapy were observed between patients treated in academic and non-academic centers. Sensitivity analyses of trial-similar patients demonstrated increased utilization (69%). Receipt of platinum doublet as 1st line therapy was less likely in older patients and those with renal disease, and more likely for grade IV disease. CONCLUSIONS: Roughly half of all Medicare patients with locally advanced/metastatic UC receive systemic therapy regardless of access to academic cancer centers and despite poor oncologic outcomes. Cytotoxic, gemcitabine-based doublet chemotherapy remains the most common treatment. A substantial population of older patients exists for whom alternative, non-cytotoxic, treatment options may be of benefit.

Evidence-based Assessment of Current and Emerging Bladder-sparing Therapies for Non-muscle-invasive Bladder Cancer After Bacillus Calmette-Guerin Therapy: A Systematic Review and Meta-analysis.

CONTEXT: Currently, there is no standard of care for patients with non-muscle-invasive bladder cancer (NMIBC) who recur despite bacillus Calmette-Guerin (BCG) therapy. Although radical cystectomy is recommended, many patients decline to undergo or are ineligible to receive it. Multiple agents are being investigated for use in this patient population. OBJECTIVE: To systematically synthesize and describe the efficacy and safety of current and emerging treatments for NMIBC patients after treatment with BCG. EVIDENCE ACQUISITION: A systematic literature search of MEDLINE, Embase, and the Cochrane Controlled Register of Trials (period limited to January 2007-June 2019) was performed. Abstracts and presentations from major conference proceedings were also reviewed. Randomized controlled trials were assessed using the Cochrane risk of bias tool. Data for single-arm trials were pooled using a random-effect meta-analysis with the proportions approach. Trials were grouped based on the minimum number of prior BCG courses required before enrollment and further stratified based on the proportion of patients with carcinoma in situ (CIS). EVIDENCE SYNTHESIS: Thirty publications were identified with data from 23 trials for meta-analysis, of which 17 were single arm. Efficacy and safety outcomes varied widely across studies. Heterogeneity across trials was reduced in subgroup analyses. The pooled 12-mo response rates were 24% (95% confidence interval [CI]: 16-32%) for trials with two or more prior BCG courses and 36% (95% CI: 25-47%) for those with one or more prior BCG courses. In a subgroup analysis, inclusion of ≥50% of patients with CIS was associated with a lower response. CONCLUSIONS: The variability in efficacy and safety outcomes highlights the need for consistent endpoint reporting and patient population definitions. With promising emerging treatments currently in development, efficacious and safe therapeutic options are urgently needed for this difficult-to-treat patient population. PATIENT SUMMARY: We examined the efficacy and safety outcomes of treatments for non-muscle-invasive bladder cancer after bacillus Calmette-Guerin therapy. Outcomes varied across studies and patient populations, but emerging treatments currently in development show promising efficacy.

Simulated Costs of the ASCO Patient-Centered Oncology Payment Model in Medicare Beneficiaries With Newly Diagnosed Advanced Ovarian Cancer.

PURPOSE: Efforts to curb the rising costs of cancer care while improving quality include alternative payment models (APMs), which offer incentives to reduce avoidable spending and provide high-quality and cost-efficient care. The impact of proposed APMs has not been quantified in real-world practice. In this study, we evaluated ASCO's Patient-Centered Oncology Payment (PCOP) model in existing fee-for-service (FFS) Medicare beneficiaries to understand the magnitude of potential cost savings. MATERIALS AND METHODS: SEER-Medicare data were used to identify women with advanced ovarian cancer diagnosed between 2000 and 2012 who either (1) underwent primary debulking surgery followed by chemotherapy or (2) received neoadjuvant chemotherapy followed by surgery. Medicare payments in each cohort were used to compare FFS and PCOP and to estimate the potential for cost savings across health care services received, including outpatient emergency department visits, hospitalizations, and imaging. RESULTS: Three thousand seven hundred seventy-seven primary debulking surgery and 866 neoadjuvant chemotherapy patients were included in the study, with mean total costs of $75,433 and $95,138 in 2016 US$, respectively Most costs were related to chemotherapy or hospitalization. Additional PCOP-related payments would be offset if hospitalizations could be reduced by 11.6% or imaging claims by 88%. CONCLUSION: APMs have the potential to reduce costs of current FFS reimbursement via either a large reduction in imaging or a modest reduction in hospitalizations during treatment of ovarian cancer. PCOP is a reasonable payment structure for oncologists if the additional payments can provide the necessary resources to invest in improved coordination of care.

Comparison of the Harms, Advantages, and Costs Associated With Alternative Guidelines for the Evaluation of Hematuria.

IMPORTANCE: Existing recommendations for the diagnostic testing of hematuria range from uniform evaluation of varying intensity to patient-level risk stratification. Concerns have been raised about not only the costs and advantages of computed tomography (CT) scans but also the potential harms of CT radiation exposure. OBJECTIVE: To compare the advantages, harms, and costs associated with 5 guidelines for hematuria evaluation. DESIGN, SETTING, AND PARTICIPANTS: A microsimulation model was developed to assess each of the following guidelines (listed in order of increasing intensity) for initial evaluation of hematuria: Dutch, Canadian Urological Association (CUA), Kaiser Permanente (KP), Hematuria Risk Index (HRI), and American Urological Association (AUA). Participants comprised a hypothetical cohort of patients (n = 100 000) with hematuria aged 35 years or older. This study was conducted from August 2017 through November 2018. EXPOSURES: Under the Dutch and CUA guidelines, patients received cystoscopy and ultrasonography if they were 50 years or older (Dutch) or 40 years or older (CUA). Under the KP and HRI guidelines, patients received different combinations of cystoscopy, ultrasonography, and CT urography or no evaluation on the basis of risk factors. Under the AUA guidelines, all patients 35 years or older received cystoscopy and CT urography. MAIN OUTCOMES AND MEASURES: Urinary tract cancer detection rates, radiation-induced secondary cancers (from CT radiation exposure), procedural complications, false-positive rates per 100 000 patients, and incremental cost per additional urinary tract cancer detected. RESULTS: The simulated cohort included 100 000 patients with hematuria, aged 35 years or older. A total of 3514 patients had urinary tract cancers (estimated prevalence, 3.5%; 95% CI, 3.0%-4.0%). The AUA guidelines missed detection for the fewest number of cancers (82 [2.3%]) compared with the detection rate of the HRI (116 [3.3%]) and KP (130 [3.7%]) guidelines. However, the simulation model projected 108 (95% CI, 34-201) radiation-induced cancers under the KP guidelines, 136 (95% CI, 62-229) under the HRI guidelines, and 575 (95% CI, 184-1069) under the AUA guidelines per 100 000 patients. The CUA and Dutch guidelines missed detection for a larger number of cancers (172 [4.9%] and 251 [7.1%]) but had 0 radiation-induced secondary cancers. The AUA guidelines cost approximately double the other 4 guidelines ($939/person vs $443/person for Dutch guidelines), with an incremental cost of $1 034 374 per urinary tract cancer detected compared with that of the HRI guidelines. CONCLUSIONS AND RELEVANCE: In this simulation study, uniform CT imaging for patients with hematuria was associated with increased costs and harms of secondary cancers, procedural complications, and false positives, with only a marginal increase in cancer detection. Risk stratification may optimize the balance of advantages, harms, and costs of CT.