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Objectives: Symptoms of distress and dysfunctional posttraumatic cognitions (PTCs) have been frequently described in parents of children and adolescents with posttraumatic stress symptoms (PTSS), e...

OBJECTIVE. The purpose of this study is to characterize the CT findings of 30 children from mainland China who had laboratory-confirmed coronavirus disease (COVID-19). Although recent American College of Radiology recommendations assert that CT should not be used as a screening or diagnostic tool for patients with suspected COVID-19, radiologists should be familiar with the imaging appearance of this disease to identify its presence in patients undergoing CT for other reasons. MATERIALS AND METHODS. We retrospectively reviewed the CT findings and clinical symptoms of 30 pediatric patients with laboratory-confirmed COVID-19 who were seen at six centers in China from January 23, 2020, to February 8, 2020. Patient age ranged from 10 months to 18 years. Patients older than 18 years of age or those without chest CT examinations were excluded. Two cardiothoracic radiologists and a cardiothoracic imaging fellow characterized and scored the extent of lung involvement. Cohen kappa coefficient was used to calculate interobserver agreement between the readers. RESULTS. Among children, CT findings were often negative (77%). Positive CT findings seen in children included ground-glass opacities with a peripheral lung distribution, a crazy paving pattern, and the halo and reverse halo signs. There was a correlation between increasing age and increasing severity of findings, consistent with reported symptomatology in children. Eleven of 30 patients (37%) underwent follow-up chest CT, with 10 of 11 examinations (91%) showing no change, raising questions about the utility of CT in the diagnosis and management of COVID-19 in children. CONCLUSION. The present study describes the chest CT findings encountered in children with COVID-19 and questions the utility of CT in the diagnosis and management of pediatric patients.

Background Given the inclusion of orthopaedic quality measures in the Centers for Medicare & Medicaid Services national hospital payment programs, the present study sought to assess whether the public reporting of total hip arthroplasty (THA) and total knee arthroplasty (TKA) risk-standardized readmission rates (RSRRs) and complication rates (RSCRs) was temporally associated with a decrease in the rates of these outcomes among Medicare beneficiaries. Methods Annual trends in national observed and hospital-level RSRRs and RSCRs were evaluated for patients who underwent hospital-based inpatient hip and/or knee replacement procedures from fiscal year 2010 to fiscal year 2016. Hospital-level rates were calculated with use of the same measures and methodology that were utilized in public reporting. Annual trends in the distribution of hospital-level outcomes were then examined with use of density plots. Results Complication and readmission rates and variation declined steadily from fiscal year 2010 to fiscal year 2016. Reductions of 33% and 25% were noted in hospital-level RSCRs and RSRRs, respectively. The interquartile range decreased by 18% (relative reduction) for RSCRs and by 34% (relative reduction) for RSRRs. The frequency of risk variables in the complication and readmission models did not systematically change over time, suggesting no evidence of widespread bias or up-coding. Conclusions This study showed that hospital-level complication and readmission rates following THA and TKA and the variation in hospital-level performance declined during a period coinciding with the start of public reporting and financial incentives associated with measurement. The consistently decreasing trend in rates of and variation in outcomes suggests steady improvements and greater consistency among hospitals in clinical outcomes for THA and TKA patients in the 2016 fiscal year compared with the 2010 fiscal year. The interactions between public reporting, payment, and hospital coding practices are complex and require further study. Level of evidence Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Objective To describe demographic, clinical, and lung base CT findings in COVID-19 patients presenting with abdominal complaints. Methods In this retrospective study, 76 COVID-19 patients who underwent abdominal CT for abdominal complaints from March 1 to April 15, 2020, in a large urban multihospital Health System were included. Those with positive abdominal CT findings (n = 14) were then excluded, with 62 patients undergoing final analysis (30M/32F; median age 63 years, interquartile range (IQR) 52–75 years, range 30–90 years). Demographic and clinical data were extracted. CT lung base assessment was performed by a cardiothoracic radiologist. Data were compared between discharged and hospitalised patients using Wilcoxon or Fisher’s exact tests. Results The majority of the population was non-elderly (56.4%, < 65 years) and most (81%) had underlying health conditions. Nineteen percent were discharged and 81% were hospitalised. The most frequent abdominal symptoms were pain (83.9%) and nausea/vomiting/anorexia (46.8%). Lung base CT findings included ground-glass opacities (95.2%) in a multifocal (95.2%) and peripheral (66.1%) distribution. Elevated laboratory values (when available) included C-reactive protein (CRP) (97.3%), D-dimer (79.4%), and ferritin (68.8% of males and 81.8% of females). Older age (p = 0.045), hypertension (p = 0.019), and lower haemoglobin in women (p = 0.042) were more frequent in hospitalised patients. There was no difference in lung base CT findings between discharged and hospitalised patients (p > 0.165). Conclusions COVID-19 patients can present with abdominal symptoms, especially in non-elderly patients with underlying health conditions. Lung base findings on abdominal CT are consistent with published reports. Radiologists should be aware of atypical presentations of COVID-19. Key Points • COVID-19 infected patients can present with acute abdominal symptoms, especially in non-elderly patients with underlying health conditions, and may frequently require hospitalisation (81%). • There was no difference in lung base CT findings between patients who were discharged and those who were hospitalised. • Lung base CT findings included multifocal and peripheral ground-glass opacities, consistent with published reports.

Background Chest radiography has not been validated for its prognostic utility in evaluating patients with coronavirus disease 2019 (COVID-19). Purpose To analyze the prognostic value of a chest radiograph severity scoring system for younger (nonelderly) patients with COVID-19 at initial presentation to the emergency department (ED); outcomes of interest included hospitalization, intubation, prolonged stay, sepsis, and death. Materials and Methods In this retrospective study, patients between the ages of 21 and 50 years who presented to the ED of an urban multicenter health system from March 10 to March 26, 2020, with COVID-19 confirmation on real-time reverse transcriptase polymerase chain reaction were identified. Each patient's ED chest radiograph was divided into six zones and examined for opacities by two cardiothoracic radiologists, and scores were collated into a total concordant lung zone severity score. Clinical and laboratory variables were collected. Multivariable logistic regression was used to evaluate the relationship between clinical parameters, chest radiograph scores, and patient outcomes. Results The study included 338 patients: 210 men (62%), with median age of 39 years (interquartile range, 31-45 years). After adjustment for demographics and comorbidities, independent predictors of hospital admission (n = 145, 43%) were chest radiograph severity score of 2 or more (odds ratio, 6.2; 95% confidence interval [CI]: 3.5, 11; P < .001) and obesity (odds ratio, 2.4 [95% CI: 1.1, 5.4] or morbid obesity). Among patients who were admitted, a chest radiograph score of 3 or more was an independent predictor of intubation (n = 28) (odds ratio, 4.7; 95% CI: 1.8, 13; P = .002) as was hospital site. No significant difference was found in primary outcomes across race and ethnicity or those with a history of tobacco use, asthma, or diabetes mellitus type II. Conclusion For patients aged 21-50 years with coronavirus disease 2019 presenting to the emergency department, a chest radiograph severity score was predictive of risk for hospital admission and intubation. © RSNA, 2020 Online supplemental material is available for this article.

To evaluate whether the implementation of a new population-based primary care payment system, Population-Based Payments for Primary Care (3PC), initiated by Hawaii Medical Service Association (HMSA; the Blue Cross Blue Shield of Hawaii), was associated with changes in spending and utilization for outpatient imaging in its first year.In this observational study, we used claims data from January 1, 2012, to December 31, 2016. We used a propensity-weighted difference-in-differences design to compare 70,284 HMSA patients in Hawaii attributed to 107 primary care physicians (PCPs) and 4 physician organizations participating in 3PC in its first year of implementation (2016) and 195,902 patients attributed to 312 PCPs and 14 physician organizations that used a fee-for-service model during the study period. The primary outcome was total spending on outpatient imaging tests, and secondary outcomes included spending and utilization by modality.The study included 266,186 HMSA patients (mean age of 43.3 years; 51.7% women) and 419 PCPs (mean age of 54.9 years; 34.8% women). The 3PC system was not significantly associated with changes in total spending for outpatient imaging. Of 12 secondary outcomes, only 3 were statistically significant, including changes in nuclear medicine spending (adjusted differential change = -20.1% [95% confidence interval = -27.5% to -12.1%]; P.001) and utilization (adjusted differential change = -18.1% [95% confidence interval = -23.8 to -11.9%]; P.001).The HMSA 3PC system was not associated with significant changes in total spending for outpatient imaging, though spending and utilization on nuclear medicine tests decreased.

Background Chest radiography (CXR) often is performed in the acute setting to help understand the extent of respiratory disease in patients with COVID-19, but a clearly defined role for negative chest radiograph results in assessing patients has not been described. Research Question Is portable CXR an effective exclusionary test for future adverse clinical outcomes in patients suspected of having COVID-19? Study Design and Methods Charts of consecutive patients suspected of having COVID-19 at five EDs in New York City between March 19, 2020, and April 23, 2020, were reviewed. Patients were categorized based on absence of findings on initial CXR. The primary outcomes were hospital admission, mechanical ventilation, ARDS, and mortality. Results Three thousand two hundred forty-five adult patients, 474 (14.6%) with negative initial CXR results, were reviewed. Among all patients, negative initial CXR results were associated with a low probability of future adverse clinical outcomes, with negative likelihood ratios of 0.27 (95% CI, 0.23-0.31) for hospital admission, 0.24 (95% CI, 0.16-0.37) for mechanical ventilation, 0.19 (95% CI, 0.09-0.40) for ARDS, and 0.38 (95% CI, 0.29-0.51) for mortality. Among the subset of 955 patients younger than 65 years and with a duration of symptoms of at least 5 days, no patients with negative CXR results died, and the negative likelihood ratios were 0.17 (95% CI, 0.12-0.25) for hospital admission, 0.09 (95% CI, 0.02-0.36) for mechanical ventilation, and 0.09 (95% CI, 0.01-0.64) for ARDS. Interpretation Initial CXR in adult patients suspected of having COVID-19 is a strong exclusionary test for hospital admission, mechanical ventilation, ARDS, and mortality. The value of CXR as an exclusionary test for adverse clinical outcomes is highest among young adults, patients with few comorbidities, and those with a prolonged duration of symptoms.

Purpose. To assess neurocognitive function (NCF), psychosocial outcome, health-related quality of life (HRQoL), and long-term effects of immune-related adverse events (irAE) on metastatic melanoma survivors treated with ipilimumab (IPI). Methods. Melanoma survivors were identified within two study populations (N=104), at a single-center university hospital, and defined as patients who were disease-free for at least 2 years after initiating IPI. Data were collected using 4 patient-reported outcome measures, computerized NCF testing, and a semistructured interview at the start and 1-year follow-up. Results. Out of 18 eligible survivors, 17 were recruited (5F/12M); median age is 57 years (range 33-86); and median time since initiating IPI was 5.6 years (range 2.1-9.3). The clinical interview revealed that survivors suffered from cancer-related emotional distress such as fear of recurrence (N=8), existential problems (N=2), survivor guilt (N=2), and posttraumatic stress disorder (N=6). The mean EORTC QLQ-C30 Global Score was not significantly different from the European mean of the healthy population. Nine survivors reported anxiety and/or depression (Hospitalization Depression Scale) during the survey. Seven survivors (41%) reported fatigue (Fatigue Severity Scale). Seven patients (41%) had impairment in NCF; only three out of seven survivors had impairment in subjective cognition (Cognitive Failure Questionnaire). Anxiety, depression, fatigue, and neurocognitive symptoms remained stable at the 1-year follow-up. All cases of skin toxicity (N=8), hepatitis (N=1), colitis (N=3), and sarcoidosis (N=1) resolved without impact on HRQoL. Three survivors experienced hypophysitis; all suffered from persistent fatigue and cognitive complaints 5 years after onset. One survivor who experienced a Guillain-Barré-like syndrome suffered from persisting depression, fatigue, and impairment in NCF. Conclusion. A majority of melanoma survivors treated with IPI continue to suffer from emotional distress and impairment in NCF. Timely detection in order to offer tailored care is imperative, with special attention for survivors with a history of neuroendocrine or neurological irAE. The trial is registered with B.U.N. 143201421920., SCOPUS: ar.j, info:eu-repo/semantics/published

Background:The autologous arteriovenous fistula is the primary choice to establish hemodialysis access without high failure rates. Intraoperative ultrasound flow measurements of newly created autologous arteriovenous fistulas represent a possibility of quality control and may therefore be a tool to assess their functionality. The aim of our study was to correlate intraoperative blood flow with access patency.Methods:Between March 2012 and March 2015, intraoperative transit time flow measurements were collected on 89 patients. Measurements were performed 5–10 min after the creation of a standardized anastomosis using 3–6 mm flow probes. To examine the correlation between intraoperative blood flow and access patency, groups of patients with high (> 200 mL/min) versus low flow (Results:In the current short-term follow-up, including 89 patients (age 62 ± 3 years), 61 (68.5%) of the autologous arteriovenous fistulas were currently being used in an observation period ranging from 3 months to 3 years (mean observation period 546 ± 95 days) postoperatively. The intraoperative blood flow in patients with functioning autologous arteriovenous fistula (78) was significantly higher than that of patients without functioning autologous arteriovenous fistulas (407 ± 25 vs 252 ± 42 mL/min, respectively; p Conclusion:The intraoperative measurement of blood flow is a useful tool to predict the outcome of maturation in autologous arteriovenous fistula. With this method, technical problems can be detected and corrected intraoperatively. Routine implementation of intraoperative flow measurements has to be examined by prospective controlled trials.

For diagnosis of coronavirus disease 2019 (COVID-19), a SARS-CoV-2 virus-specific reverse transcriptase polymerase chain reaction (RT–PCR) test is routinely used. However, this test can take up to 2 d to complete, serial testing may be required to rule out the possibility of false negative results and there is currently a shortage of RT–PCR test kits, underscoring the urgent need for alternative methods for rapid and accurate diagnosis of patients with COVID-19. Chest computed tomography (CT) is a valuable component in the evaluation of patients with suspected SARS-CoV-2 infection. Nevertheless, CT alone may have limited negative predictive value for ruling out SARS-CoV-2 infection, as some patients may have normal radiological findings at early stages of the disease. In this study, we used artificial intelligence (AI) algorithms to integrate chest CT findings with clinical symptoms, exposure history and laboratory testing to rapidly diagnose patients who are positive for COVID-19. Among a total of 905 patients tested by real-time RT–PCR assay and next-generation sequencing RT–PCR, 419 (46.3%) tested positive for SARS-CoV-2. In a test set of 279 patients, the AI system achieved an area under the curve of 0.92 and had equal sensitivity as compared to a senior thoracic radiologist. The AI system also improved the detection of patients who were positive for COVID-19 via RT–PCR who presented with normal CT scans, correctly identifying 17 of 25 (68%) patients, whereas radiologists classified all of these patients as COVID-19 negative. When CT scans and associated clinical history are available, the proposed AI system can help to rapidly diagnose COVID-19 patients.

This cross-sectional study evaluates whether hospital-specific adverse event rates are associated with hospital-specific risk-standardized 30-day episode-of-care Medicare expenditures for fee-for-service patients discharged with acute myocardial infarction, heart failure, or pneumonia., Key Points Question What is the association between 30-day episode-of-care expenditures and in-hospital adverse events? Findings This cross-sectional study of 44 807 patients, which linked the 2011 to 2016 hospital-specific risk-standardized 30-day episode-of-care expenditure data from the Centers for Medicare & Medicaid Services and medical record–abstracted in-hospital adverse event data from the Medicare Patient Safety Monitoring System, found that hospitals with high adverse event rates were more likely to have high 30-day episode-of-care Medicare expenditures for patients discharged with acute myocardial infarction, heart failure, or pneumonia. Meaning This study suggests that hospitals with higher adverse event rates are more likely to have higher costs for acute myocardial infarction, heart failure, or pneumonia., Importance Studies have shown that adverse events are associated with increasing inpatient care expenditures, but contemporary data on the association between expenditures and adverse events beyond inpatient care are limited. Objective To evaluate whether hospital-specific adverse event rates are associated with hospital-specific risk-standardized 30-day episode-of-care Medicare expenditures for fee-for-service patients discharged with acute myocardial infarction (AMI), heart failure (HF), or pneumonia. Design, Setting, and Participants This cross-sectional study used the 2011 to 2016 hospital-specific risk-standardized 30-day episode-of-care expenditure data from the Centers for Medicare & Medicaid Services and medical record–abstracted in-hospital adverse event data from the Medicare Patient Safety Monitoring System. The setting was acute care hospitals treating at least 25 Medicare fee-for-service patients for AMI, HF, or pneumonia in the United States. Participants were Medicare fee-for-service patients 65 years or older hospitalized for AMI, HF, or pneumonia included in the Medicare Patient Safety Monitoring System in 2011 to 2016. The dates of analysis were July 16, 2017, to May 21, 2018. Main Outcomes and Measures Hospitals’ risk-standardized 30-day episode-of-care expenditures and the rate of occurrence of adverse events for which patients were at risk. Results The final study sample from 2194 unique hospitals included 44 807 patients (26.1% AMI, 35.6% HF, and 38.3% pneumonia) with a mean (SD) age of 79.4 (8.6) years, and 52.0% were women. The patients represented 84 766 exposures for AMI, 96 917 exposures for HF, and 109 641 exposures for pneumonia. Patient characteristics varied by condition but not by expenditure category. The mean (SD) risk-standardized expenditures were $22 985 ($1579) for AMI, $16 020 ($1416) for HF, and $16 355 ($1995) for pneumonia per hospitalization. The mean risk-standardized rates of occurrence of adverse events for which patients were at risk were 3.5% (95% CI, 3.4%-3.6%) for AMI, 2.5% (95% CI, 2.5%-2.5%) for HF, and 3.0% (95% CI, 2.9%-3.0%) for pneumonia. An increase by 1 percentage point in the rate of occurrence of adverse events was associated with an increase in risk-standardized expenditures of $103 (95% CI, $57-$150) for AMI, $100 (95% CI, $29-$172) for HF, and $152 (95% CI, $73-$232) for pneumonia per discharge. Conclusions and Relevance Hospitals with high adverse event rates were more likely to have high 30-day episode-of-care Medicare expenditures for patients discharged with AMI, HF, or pneumonia.

Objective Internal thoracic lymphadenopathy (ITL) has been associated with malignancies and non-tuberculous empyema. However, the association between ITL and active pulmonary tuberculosis (PTB) and the correlation between ITL and other imaging characteristics of active PTB has not been examined. Materials and methods A retrospective cohort study comprising 137 adults with active PTB who had a concomitant chest CT over a seven-year period was conducted. Two thoracic radiologists evaluated for ITL as well as nine other imaging characteristics of active tuberculosis, including total lung involvement (as measured by a total severity score), number of nodules, presence of tree-in-bud nodularity, highest extent of tree-in-bud nodularity in a lobe, miliary pattern, cavitary lesions, pleural effusion, lymphadenopathy (excluding internal thoracic lymph nodes), and empyema. The Wilcoxon rank-sum test and chi-squared tests were used to assess the correlation between ITL and additional imaging findings. Results Internal thoracic lymphadenopathy was present in 50 of 137 cases (36.5%); most commonly bilateral (19.0%) or isolated on the right side (13.7%), and less commonly isolated on the left side (3.7%). Pleural effusion, lymphadenopathy (apart from internal thoracic compartment), and empyema all showed statistically significant correlations with ITL (p-values of Conclusions While the presence of ITL – particularly when accompanied by other imaging findings such as pleural effusion – may prompt a radiologist to first consider malignancy, active PTB should be an additional consideration in the appropriate clinical context.

In this retrospective study, chest CTs of 121 symptomatic patients infected with coronavirus disease-19 (COVID-19) from four centers in China from January 18, 2020 to February 2, 2020 were reviewed for common CT findings in relationship to the time between symptom onset and the initial CT scan (i.e. early, 0-2 days (36 patients), intermediate 3-5 days (33 patients), late 6-12 days (25 patients)). The hallmarks of COVID-19 infection on imaging were bilateral and peripheral ground-glass and consolidative pulmonary opacities. Notably, 20/36 (56%) of early patients had a normal CT. With a longer time after the onset of symptoms, CT findings were more frequent, including consolidation, bilateral and peripheral disease, greater total lung involvement, linear opacities, "crazy-paving" pattern and the "reverse halo" sign. Bilateral lung involvement was observed in 10/36 early patients (28%), 25/33 intermediate patients (76%), and 22/25 late patients (88%).

In this retrospective case series, chest CT scans of 21 symptomatic patients from China infected with the 2019 novel coronavirus (2019-nCoV) were reviewed, with emphasis on identifying and characterizing the most common findings. Typical CT findings included bilateral pulmonary parenchymal ground-glass and consolidative pulmonary opacities, sometimes with a rounded morphology and a peripheral lung distribution. Notably, lung cavitation, discrete pulmonary nodules, pleural effusions, and lymphadenopathy were absent. Follow-up imaging in a subset of patients during the study time window often demonstrated mild or moderate progression of disease, as manifested by increasing extent and density of lung opacities. © RSNA, 2020

International audience; Background. Computer vision combined with human annotation could offer a novel method for exploring facial expression (FE) dynamics in children with autism spectrum disorder (ASD).Methods. We recruited 157 children with typical development (TD) and 36 children with ASD in Paris and Nice to perform two experimental tasks to produce FEs with emotional valence. FEs were explored by judging ratings and by random forest (RF) classifiers. To do so, we located a set of 49 facial landmarks in the task videos, we generated a set of geometric and appearance features and we used RF classifiers to explore how children with ASD differed from TD children when producing FEs.Results. Using multivariate models including other factors known to predict FEs (age, gender, intellectual quotient, emotion subtype, cultural background), ratings from expert raters showed that children with ASD had more difficulty producing FEs than TD children. In addition, when we explored how RF classifiers performed, we found that classification tasks, except for those for sadness, were highly accurate and that RF classifiers needed more facial landmarks to achieve the best classification for children with ASD. Confusion matrices showed that when RF classifiers were tested in children with ASD, anger was often confounded with happiness.Limitations. The sample size of the group of children with ASD was lower than that of the group of TD children. By using several control calculations, we tried to compensate for this limitation.Conclusion. Children with ASD have more difficulty producing socially meaningful FEs. The computer vision methods we used to explore FE dynamics also highlight that the production of FEs in children with ASD carries more ambiguity.

Objectives To determine whether patients discharged after hospital admissions for conditions covered by national readmission programs who received care in emergency departments or observation units but were not readmitted within 30 days had an increased risk of death and to evaluate temporal trends in post-discharge acute care utilization in inpatient units, emergency departments, and observation units for these patients. Design Retrospective cohort study. Setting Medicare claims data for 2008-16 in the United States. Participants Patients aged 65 or older admitted to hospital with heart failure, acute myocardial infarction, or pneumonia—conditions included in the US Hospital Readmissions Reduction Program. Main outcome measures Post-discharge 30 day mortality according to patients’ 30 day acute care utilization; acute care utilization in inpatient and observation units and the emergency department during the 30 day and 31-90 day post-discharge period. Results 3 772 924 hospital admissions for heart failure, 1 570 113 for acute myocardial infarction, and 3 131 162 for pneumonia occurred. The overall post-discharge 30 day mortality was 8.7% for heart failure, 7.3% for acute myocardial infarction, and 8.4% for pneumonia. Risk adjusted mortality increased annually by 0.05% (95% confidence interval 0.02% to 0.08%) for heart failure, decreased by 0.06% (−0.09% to −0.04%) for acute myocardial infarction, and did not significantly change for pneumonia. Specifically, mortality increased for patients with heart failure who did not utilize any post-discharge acute care, increasing at a rate of 0.08% (0.05% to 0.12%) per year, exceeding the overall absolute annual increase in post-discharge mortality in heart failure, without an increase in mortality in observation units or the emergency department. Concurrent with a reduction in 30 day readmission rates, stays for observation and visits to the emergency department increased across all three conditions during and beyond the 30 day post-discharge period. Overall 30 day post-acute care utilization did not change significantly. Conclusions The only condition with increasing mortality through the study period was heart failure; the increase preceded the policy and was not present among patients who received emergency department or observation unit care without admission to hospital. During this period, the overall acute care utilization in the 30 days after discharge significantly decreased for heart failure and pneumonia, but not for acute myocardial infarction.

Following treatment with androgen receptor (AR) pathway inhibitors, ∼20% of prostate cancer patients progress by shedding their AR dependence. These tumors undergo epigenetic reprogramming turning castration-resistant prostate cancer adenocarcinoma (CRPC-Adeno) into neuroendocrine prostate cancer (CRPC-NEPC). Currently, no targeted therapies are available for CRPC-NEPCs, and there are minimal organoid models to discover new therapeutic targets against these aggressive tumors. Here, using a combination of patient tumor proteomics, RNA sequencing, spatial omics, immunohistochemistry, and a synthetic hydrogel-based organoid, we define putative extracellular matrix (ECM) cues that regulate the phenotypic, transcriptomic, and epigenetic underpinnings of CRPC-NEPCs. Short-term culture in tumor-expressed ECM differentially regulated DNA methylation and mobilized genes in CRPC-NEPC tumors. The ECM type distinctly regulated the response to small molecule inhibitors of epigenetic repressor EZH2 and Dopamine Receptor D2 (DRD2), the latter being an understudied target in neuroendocrine tumors. In vivo patient-derived xenograft studies in immunocompromised mice showed a robust anti-tumor response when treated with a DRD2 inhibitor. Finally, we demonstrate that therapeutic response in CRPC-NEPCs under drug-resistant ECM conditions can be overcome by first cellular reprogramming with EZH2 inhibitors, followed by DRD2 treatment. The synthetic hydrogel-based organoids suggest the regulatory role ECM may play in therapeutic response to targeted therapies in CRPC-NEPCs and enable the discovery of single drugs and combination therapies to overcome resistance. This article is protected by copyright. All rights reserved.

Background Moxifloxacin is a second-line anti-TB drug that is useful in the treatment of drug-resistant TB. However, little is known about its target site pharmacokinetics. Lower drug concentrations at the infection site (i.e. in severe lung lesions including cavitary lesions) may lead to development and amplification of drug resistance. Improved knowledge regarding tissue penetration of anti-TB drugs will help guide drug development and optimize drug dosing. Methods Patients with culture-confirmed drug-resistant pulmonary TB scheduled to undergo adjunctive surgical lung resection were enrolled in Tbilisi, Georgia. Five serum samples per patient were collected at different timepoints including at the time of surgical resection (approximately at Tmax). Microdialysis was performed in the ex vivo tissue immediately after resection. Non-compartmental analysis was performed and a tissue/serum concentration ratio was calculated. Results Among the seven patients enrolled, the median moxifloxacin dose given was 7.7 mg/kg, the median age was 25.2 years, 57% were male and the median creatinine clearance was 95.4 mL/min. Most patients (71%) had suboptimal steady-state serum Cmax (total drug) concentrations. The median free moxifloxacin serum concentration at time of surgical resection was 1.23 μg/mL (range = 0.12-1.80) and the median free lung tissue concentration was 3.37 μg/mL (range = 0.81-5.76). The median free-tissue/free-serum concentration ratio was 3.20 (range = 0.66-28.08). Conclusions Moxifloxacin showed excellent penetration into diseased lung tissue (including cavitary lesions) among patients with pulmonary TB. Moxifloxacin lung tissue concentrations were higher than those seen in serum. Our findings highlight the importance of moxifloxacin in the treatment of MDR-TB and potentially any patient with pulmonary TB and severe lung lesions.

Background and Purpose— The Centers for Medicare & Medicaid Services publicly reports a hospital-level stroke mortality measure that lacks stroke severity risk adjustment. Our objective was to describe novel measures of stroke mortality suitable for public reporting that incorporate stroke severity into risk adjustment. Methods— We linked data from the American Heart Association/American Stroke Association Get With The Guidelines-Stroke registry with Medicare fee-for-service claims data to develop the measures. We used logistic regression for variable selection in risk model development. We developed 3 risk-standardized mortality models for patients with acute ischemic stroke, all of which include the National Institutes of Health Stroke Scale score: one that includes other risk variables derived only from claims data (claims model); one that includes other risk variables derived from claims and clinical variables that could be obtained from electronic health record data (hybrid model); and one that includes other risk variables that could be derived only from electronic health record data (electronic health record model). Results— The cohort used to develop and validate the risk models consisted of 188 975 hospital admissions at 1511 hospitals. The claims, hybrid, and electronic health record risk models included 20, 21, and 9 risk-adjustment variables, respectively; the C statistics were 0.81, 0.82, and 0.79, respectively (as compared with the current publicly reported model C statistic of 0.75); the risk-standardized mortality rates ranged from 10.7% to 19.0%, 10.7% to 19.1%, and 10.8% to 20.3%, respectively; the median risk-standardized mortality rate was 14.5% for all measures; and the odds of mortality for a high-mortality hospital (+1 SD) were 1.51, 1.52, and 1.52 times those for a low-mortality hospital (−1 SD), respectively. Conclusions— We developed 3 quality measures that demonstrate better discrimination than the Centers for Medicare & Medicaid Services’ existing stroke mortality measure, adjust for stroke severity, and could be implemented in a variety of settings.

Methamphetamine (meth) addiction is a prevalent health concern worldwide, yet remains without approved pharmacological treatments. Preclinical evidence suggests that oxytocin may decrease relapse, but the neuronal underpinnings driving this effect remain unknown. Here we investigate whether oxytocin’s effect is dependent on presynaptic glutamatergic regulation in the nucleus accumbens core (NAcore) by blocking metabotropic glutamate receptors 2/3 (mGluR2/3). Male and female Sprague-Dawley rats self-administered meth or sucrose on an escalating fixed ratio, followed by extinction and cue-induced reinstatement sessions. Reinstatement tests consisted of systemic (Experiment 1) or site-specific application of the drugs into the NAcore (Experiments 2 and 3). Before reinstatement sessions, rats received LY341495, an mGluR2/3 antagonist, or its vehicle followed by a second infusion/injection of oxytocin or saline. As expected, both males and females reinstated lever pressing to meth associated cues, and LY341495 alone did not impact this behavior. Oxytocin injected systemically or infused into the NAcore decreased cued meth seeking. Importantly, combined LY341495 and oxytocin administration restored meth cued reinstatement. Interestingly, neither oxytocin nor LY341495 impacted sucrose-cued reinstatement, suggesting distinct mechanisms between meth and sucrose. These findings were consistent between males and females. Overall, we report that oxytocin reduced responding to meth-associated cues and blocking presynaptic mGluR2/3 reversed this effect. Further, oxytocin’s effects were specific to meth cues as NAcore oxytocin was without an effect on sucrose cued reinstatement. Results are discussed in terms of oxytocin receptor localization in the NAcore and modulation of presynaptic regulation of glutamate in response to drug associated cues.

To evaluate the effect of topical application of a matrix regenerating agent (RGTA) in subjects with a persistent epithelial defect after bacterial keratitis treated with topical fortified antibiotics.In this prospective case series of 14 subjects (14 eyes) with a persisting corneal ulcer after the cessation of fortified antibiotics, subjects were treated with an RGTA at a dose of 1 drop every other day. The main outcome measure was the proportion of subjects with complete corneal healing 1 month after initiation of treatment. The secondary outcome measures were the size and depth of corneal ulceration at 1 month, the duration from treatment initiation to complete healing, pain, and tolerability. The ulceration depth was measured with anterior segment optical coherence tomography.Complete corneal healing was observed in 11 (78.6%) of the 14 patients after 1 month and in 14 of the 14 (100%) patients after 3 months. Mean logarithm of the minimum angle of resolution visual acuity improved from 1.22 ± 0.59 at inclusion to 0.57 ± 0.68 at 1 month and to 0.55 ± 0.68 at 3 months (P0.01). Pain according to a visual analog scale decreased from 0.34 ± 0.25 to 0.05 ± 0.09 at 1 month and to 0 at 3 months (P0.001). Amniotic membrane transplantation was not required for any patients. There were no RGTA-related side effects, and none of the patients reported pain or discomfort during instillation of the drops.The RGTA seems to be efficient for the treatment of a persistent epithelial defect after bacterial keratitis treated with topical fortified antibiotics.

Safety-net and teaching hospitals are somewhat more likely to be penalized for excess readmissions, but the association of other hospital characteristics with readmission rates is uncertain and may have relevance for hospital-centered interventions.To examine the independent association of 8 hospital characteristics with hospital-wide 30-day risk-standardized readmission rate (RSRR).This is a retrospective cross-sectional multivariable analysis.US hospitals.Centers for Medicare and Medicaid Services specification of hospital-wide RSRR from July 1, 2013 through June 30, 2014 with race and Medicaid dual-eligibility added.We included 6,789,839 admissions to 4474 hospitals of Medicare fee-for-service beneficiaries aged over 64 years. In multivariable analyses, there was regional variation: hospitals in the mid-Atlantic region had the highest RSRRs [0.98 percentage points higher than hospitals in the Mountain region; 95% confidence interval (CI), 0.84-1.12]. For-profit hospitals had an average RSRR 0.38 percentage points (95% CI, 0.24-0.53) higher than public hospitals. Both urban and rural hospitals had higher RSRRs than those in medium metropolitan areas. Hospitals without advanced cardiac surgery capability had an average RSRR 0.27 percentage points (95% CI, 0.18-0.36) higher than those with. The ratio of registered nurses per hospital bed was not associated with RSRR. Variability in RSRRs among hospitals of similar type was much larger than aggregate differences between types of hospitals.Overall, larger, urban, academic facilities had modestly higher RSRRs than smaller, suburban, community hospitals, although there was a wide range of performance. The strong regional effect suggests that local practice patterns are an important influence. Disproportionately high readmission rates at for-profit hospitals may highlight the role of financial incentives favoring utilization.

BackgroundConcern has been raised about consequences of including patients with left ventricular assist device (LVAD) or heart transplantation in readmission and mortality measures.MethodsWe calculated unadjusted and hospital-specific 30-day risk-standardized mortality (RSMR) and readmission (RSRR) rates for all Medicare fee-for-service beneficiaries with a primary diagnosis of AMI or HF discharged between July 2010 and June 2013. Hospitals were compared before and after excluding LVAD and heart transplantation patients. LVAD indication was measured.ResultsIn the AMI mortality (n = 506,543) and readmission (n = 526,309) cohorts, 1,166 and 1,016 patients received an LVAD while 3 and 2 had a heart transplantation, respectively. In the HF mortality (n = 1,015,335) and readmission (n = 1,254,124) cohorts, 789 and 931 received an LVAD, while 212 and 202 received a heart transplantation, respectively. Less than 2% of hospitals had either ≥6 patients who received an LVAD or, independently, had ≥1 heart transplantation. The AMI mortality and readmission cohorts used 1.8% and 2.8% of LVADs for semi-permanent/permanent indications, versus 73.8% and 78.0% for HF patients, respectively. The rest were for temporary/external indications. In the AMI cohort, RSMR for hospitals without LVAD patients versus hospitals with ≥6 LVADs was 14.8% and 14.3%, and RSRR was 17.8% and 18.3%, respectively; the HF cohort RSMR was 11.9% and 9.7% and RSRR was 22.6% and 23.4%, respectively. In the AMI cohort, RSMR for hospitals without versus with heart transplantation patients was 14.7% and 13.9% and RSRR was 17.8% and 17.7%, respectively; in the HF cohort, RSMR was 11.9% and 11.0%, and RSRR was 22.6% and 22.6%, respectively. Estimations changed ≤0.1% after excluding LVAD or heart transplantation patients.ConclusionHospitals caring for ≥6 patients with LVAD or ≥1 heart transplantation typically had a trend toward lower RSMRs but higher RSRRs. Rates were insignificantly changed when these patients were excluded. LVADs were primarily for acute-care in the AMI cohort and chronic support in the HF cohort. LVAD and heart transplantation patients are a distinct group with differential care requirements and outcomes, thus should be considered separately from the rest of the HF cohort.

This comparative effectiveness research study assesses whether using present on admission codes and single, rather than grouped, diagnostic codes can enhance Centers for Medicare & Medicaid (CMS) models to predict payment for hospitalization for acute myocardial infarction, heart failure, and pneumonia., Key Points Question Does leveraging present on admission codes and using single, rather than grouped, diagnostic codes enhance risk models for acute myocardial infarction, heart failure, and pneumonia payment measures? Findings In this comparative effectiveness research study of risk models on 1 667 983 patients with 1 943 049 Medicare fee-for-service hospitalizations, use of present on admission codes and single diagnosis codes and separation of index admission codes from codes in the previous year improved models predicting payment that were compared with models based on Centers for Medicare & Medicaid Services grouped codes. The patient-level pseudo R2 improved from 0.077 to 0.129 for acute myocardial infarction, from 0.042 to 0.129 for heart failure, and from 0.114 to 0.237 for pneumonia. Meaning Changing candidate variables from the current standard improved models predicting payments, which has implications for research, benchmarking, public reporting, and calculations for population-based programs., Importance Predicting payments for particular conditions or populations is essential for research, benchmarking, public reporting, and calculations for population-based programs. Centers for Medicare & Medicaid Services (CMS) models often group codes into disease categories, but using single, rather than grouped, diagnostic codes and leveraging present on admission (POA) codes may enhance these models. Objective To determine whether changes to the candidate variables in CMS models would improve risk models predicting patient total payment within 30 days of hospitalization for acute myocardial infarction (AMI), heart failure (HF), and pneumonia. Design, Setting, and Participants This comparative effectiveness research study used data from Medicare fee-for-service hospitalizations for AMI, HF, and pneumonia at acute care hospitals from July 1, 2013, through September 30, 2015. Payments across multiple care settings, services, and supplies were included and adjusted for geographic and policy variations, corrected for inflation, and winsorized. The same data source was used but varied for the candidate variables and their selection, and the method used by CMS for public reporting that used grouped codes was compared with variations that used POA codes and single diagnostic codes. Combinations of use of POA codes, separation of index admission diagnoses from those in the previous 12 months, and use of individual International Classification of Diseases, Ninth Revision, Clinical Modification codes instead of grouped diagnostic categories were tested. Data analysis was performed from December 4, 2017, to June 10, 2019. Main Outcomes and Measures The models’ goodness of fit was compared using root mean square error (RMSE) and the McFadden pseudo R2. Results Among the 1 943 049 total hospitalizations of the study participants, 343 116 admissions were for AMI (52.5% male; 37.4% aged ≤74 years), 677 044 for HF (45.5% male; 25.9% aged ≤74 years), and 922 889 for pneumonia (46.4% male; 28.2% aged ≤74 years). The mean (SD) 30-day payment was $23 103 ($18 221) for AMI, $16 365 ($12 527) for HF, and $17 097 ($12 087) for pneumonia. Each incremental model change improved the pseudo R2 and RMSE. Incorporating all 3 changes improved the pseudo R2 of the patient-level models from 0.077 to 0.129 for AMI, from 0.042 to 0.129 for HF, and from 0.114 to 0.237 for pneumonia. Parallel improvements in RMSE were found for all 3 conditions. Conclusions and Relevance Leveraging POA codes, separating index from previous diagnoses, and using single diagnostic codes improved payment models. Better models can potentially improve research, benchmarking, public reporting, and calculations for population-based programs.

Objective To propose and evaluate a metric for quantifying hospital-specific disparities in health outcomes that can be used by patients and hospitals. Data sources/study setting Inpatient admissions for Medicare patients with acute myocardial infarction, heart failure, or pneumonia to all non-federal, short-term, acute care hospitals during 2012-2015. Study design Building on the current Centers for Medicare and Medicaid Services methodology for calculating risk-standardized readmission rates, we developed models that include a hospital-specific random coefficient for either patient dual eligibility status or African American race. These coefficients quantify the difference in risk-standardized outcomes by dual eligibility and race at a given hospital after accounting for the hospital's patient case mix and proportion of dual eligible or African American patients. We demonstrate this approach and report variation and performance in hospital-specific disparities. Principal findings Dual eligibility and African American race were associated with higher readmission rates within hospitals for all three conditions. However, this disparity effect varied substantially across hospitals. Conclusion Our models isolate a hospital-specific disparity effect and demonstrate variation in quality of care for different groups of patients across conditions and hospitals. Illuminating within-hospital disparities can incentivize hospitals to reduce inequities in health care quality.

Key Points Question Was the announcement or implementation of the Hospital Readmissions Reduction Program (HRRP) associated with an increase in mortality following hospitalization for acute myocardial infarction, heart failure, or pneumonia among Medicare beneficiaries? Findings In this cohort study, between 2006 and 2014, in-hospital mortality decreased for the 3 conditions while 30-day postdischarge mortality decreased for acute myocardial infarction but increased for heart failure and pneumonia. Before the announcement of the HRRP, postdischarge mortality was stable for acute myocardial infarction and increasing for heart failure and pneumonia, and there were no inflections in slope around the announcement or implementation of the HRRP. Meaning There was no evidence for increase in in-hospital or postdischarge mortality associated with the HRRP announcement or implementation—a period with substantial reductions in readmissions., Importance The US Hospital Readmissions Reduction Program (HRRP) was associated with reduced readmissions among Medicare beneficiaries hospitalized for acute myocardial infarction (AMI), heart failure (HF), and pneumonia. It is important to assess whether there has been a signal for concomitant harm with an increase in mortality. Objective To evaluate whether the announcement or the implementation of HRRP was associated with an increase in either in-hospital or 30-day postdischarge mortality following hospitalization for AMI, HF, or pneumonia. Design, Setting, and Participants In this cohort study, using Medicare data, all hospitalizations for AMI, HF, and pneumonia were identified among fee-for-service Medicare beneficiaries aged 65 years and older from January 1, 2006, to December 31, 2014. These were assessed for changes in trends for risk-adjusted rates of in-hospital and 30-day postdischarge mortality after announcement and implementation of the HRRP using an interrupted time series framework. Analyses were done in November 2017 and December 2017. Exposures Announcement of the HRRP in March 2010, and implementation of its penalties in October 2012. Main Outcomes and Measures Monthly risk-adjusted rates of in-hospital and 30-day postdischarge mortality. Results The sample included 1.7 million AMI, 4 million HF, and 3.5 million pneumonia hospitalizations. Between 2006 and 2014, in-hospital mortality decreased for the 3 conditions (AMI, from 10.4% to 9.7%; HF, from 4.3% to 3.5%; pneumonia, from 5.3% to 4.0%) while 30-day postdischarge mortality decreased from 7.4% to 7.0% for AMI (P for trend .05 for all). In contrast, there were significant negative deflections in slopes for readmission rates at HRRP announcement for all conditions. Conclusions and Relevance Among Medicare beneficiaries, there was no evidence for an increase in in-hospital or postdischarge mortality associated with HRRP announcement or implementation—a period with substantial reductions in readmissions. The improvement in readmission was therefore not associated with any increase in in-hospital or 30-day postdischarge mortality., This cohort study uses Medicare data to evaluate whether the announcement or implementation of the Hospital Readmissions Reduction Program (HRRP) was associated with an increase in either in-hospital or 30-day postdischarge mortality following hospitalization for acute myocardial infarction (AMI), heart failure (HF), or pneumonia.

Background/Aims Optimal bowel preparation is essential for successful screening or for surveillance colonoscopy (SC). Inadequate bowel preparation is associated with older age, the male gender, and the presence of certain comorbidities. However, the association between patients’ functional status and bowel preparation quality has not been studied. We prospectively examined the relationship between functional status, namely, the ability to perform activities of daily living (ADLs) and ambulate, and the quality of bowel preparation in elderly patients undergoing SC. Methods Before undergoing SC, 88 elderly patients were surveyed regarding their functional status, specifically regarding their ability to perform ADLs and ambulate a quarter of a mile. Gastroenterologists then determined the quality of the bowel preparation, which was classified as either adequate or inadequate. Then, the frequency of inadequate bowel preparation in patients who did or did not experience difficulty performing ADLs and ambulating was calculated. Results Difficulty ambulating (unadjusted odds ratio [OR], 4.83; p

Programs from the Centers for Medicare and Medicaid Services simultaneously promote strategies to lower hospital admissions and readmissions. However, there is concern that hospitals in communities that successfully reduce admissions may be penalized, as patients that are ultimately hospitalized may be sicker and at higher risk of readmission. We therefore examined the relationship between changes from 2010 to 2013 in admission rates and thirty-day readmission rates for elderly Medicare beneficiaries. We found that communities with the greatest decline in admission rates also had the greatest decline in thirty-day readmission rates, even though hospitalized patients did grow sicker as admission rates declined. The relationship between changing admission and readmission rates persisted in models that measured observed readmission rates, risk-standardized readmission rates, and the combined rate of readmission and death. Our findings suggest that communities can reduce admission rates and readmission rates in parallel, and that federal policy incentivizing reductions in both outcomes does not create contradictory incentives.

Background Population-based measures of admissions among patients with chronic conditions are important quality indicators of Accountable Care Organizations (ACOs), yet there are challenges in developing measures that enable fair comparisons among providers. Methods On the basis of consensus standards for outcome measure development and with expert and stakeholder input on methods decisions, we developed and tested 2 models of risk-standardized acute admission rates (RSAARs) for patients with diabetes and heart failure using 2010-2012 Medicare claims data. Model performance was assessed with deviance R; score reliability was tested with intraclass correlation coefficient. We estimated RSAARs for 114 Shared Savings Program ACOs in 2012 and we assigned ACOs to 3 performance categories: no different, worse than, and better than the national rate. Results The diabetes and heart failure cohorts included 6.5 and 2.6 million Medicare Fee-For-Service beneficiaries aged 65 years and above, respectively. Risk-adjustment variables were age, comorbidities, and condition-specific severity variables, but not socioeconomic status or other contextual factors. We selected hierarchical negative binomial models with the outcome of acute, unplanned hospital admissions per 100 person-years. For the diabetes and heart failure measures, respectively, the models accounted for 22% and 12% of the deviance in outcomes and score reliability was 0.89 and 0.81. For the diabetes measure, 51 (44.7%) ACOs were no different, 45 (39.5%) were better, and 18 (15.8%) were worse than the national rate. The distribution of performance for the heart failure measure was 61 (53.5%), 37 (32.5%), and 16 (14.0%), respectively. Conclusion Measures of RSAARs for patients with diabetes and heart failure meet criteria for scientific soundness and reveal important variation in quality across ACOs.

Background & Aims Colonoscopy is a common procedure, yet little is known about variations in colonoscopy quality among outpatient facilities. We developed an outcome measure to profile outpatient facilities by estimating risk-standardized rates of unplanned hospital visits within 7 days of colonoscopy. Methods We used a 20% sample of 2010 Medicare outpatient colonoscopy claims (331,880 colonoscopies performed at 8140 facilities) from patients ≥65 years or older, and developed a patient-level logistic regression model to estimate the risk of unplanned hospital visits (ie, emergency department visits, observation stays, and inpatient admissions) within 7 days of colonoscopy. We then used the patient-level risk model variables and hierarchical logistic regression to estimate facility rates of risk-standardized unplanned hospital visits using data from the Healthcare Cost and Utilization Project (325,811 colonoscopies at 992 facilities), from 4 states containing 100% of colonoscopies per facility. Results Outpatient colonoscopies were followed by 5412 unplanned hospital visits within 7 days (16.3/1000 colonoscopies). Hemorrhage, abdominal pain, and perforation were the most common causes of unplanned hospital visits. Fifteen variables were independently associated with unplanned hospital visits (c = 0.67). A history of fluid and electrolyte imbalance (odds ratio [OR] = 1.43; 95% confidence interval [CI]: 1.29−1.58), psychiatric disorders (OR = 1.34; 95% CI: 1.22−1.46), and, in the absence of prior arrhythmia, increasing age past 65 years (aged >85 years vs 65−69 years: OR = 1.87; 95% CI: 1.54−2.28) were most strongly associated. The facility risk-standardized unplanned hospital visits calculated using Healthcare Cost and Utilization Project data showed significant variation (median 12.3/1000; 5th−95th percentile, 10.5−14.6/1000). Median risk-standardized unplanned hospital visits were comparable between ambulatory surgery centers and hospital outpatient departments (each was 10.2/1000), and ranged from 16.1/1000 in the Northeast to 17.2/1000 in the Midwest. Conclusions We calculated a risk-adjusted measure of outpatient colonoscopy quality, which shows important variation in quality among outpatient facilities. This measure can make transparent the extent to which patients require follow-up hospital care, help inform patient choices, and assist in quality-improvement efforts.

Background: Women with ST-segment elevation myocardial infarction (STEMI) experience greater delays for percutaneous coronary intervention-facilitated reperfusion than men. Whether women and men benefit equally from current strategies to reduce ischaemic time and whether there are gender differences in factors determining delays is unclear. Methods: Patient delay (symptom onset to first medical contact) and system delay (first medical contact to percutaneous coronary intervention-facilitated reperfusion) were compared between women ( n=967) and men ( n=3393) in a Swiss STEMI treatment network. Trends from 2000 to 2016 were analysed, with additional comparisons between three time periods (2000–2005, 2006–2011 and 2012–2016). Factors predicting delays and hospital mortality were determined by multivariate regression modelling. Results: Female gender was independently associated with greater patient delay ( P=0.02 vs. men), accounting for a 12% greater total ischaemic time among women in 2012–2016 (median 215 vs. 192 minutes, PConclusions: STEMI-related ischaemic time in women remains greater than in men due to persistently greater patient delays. In contrast to men, clinical signs of ongoing chest discomfort do not predict delays in women, suggesting that female STEMI patients are less likely to attribute symptoms to a condition requiring urgent treatment.

BACKGROUND: Temporal changes in the readmission rates for patient groups and conditions that were not directly under the purview of Hospital Readmissions Reduction Program (HRRP) can help assess whether efforts to lower readmissions extended beyond targeted patients and conditions. METHODS: Using Nationwide Readmissions Database (2010–2015), we assessed trends in all-cause readmission rates for one of the 3 HRRP conditions (acute myocardial infarction, heart failure, pneumonia) or conditions not targeted by HRRP in 6 age-insurance groups defined by age-groups (≥65 or

The goal of this study was to define patterns for tumor recurrence on PET following RFA, compare time to imaging recurrence by PET versus CT, evaluate whether pre-treatment tumor uptake predicts recurrence and propose an optimal post-RFA surveillance strategy.A retrospective cohort study was performed of biopsy confirmed primary stage I lung cancers treated with RFA. FDG PET and near contemporaneous diagnostic CT imaging pre-ablation, within 30 days post-ablation, and beyond 6 months were independently and retrospectively evaluated for features supportive of recurrence. Time to imaging recurrence by PET (TTR_PET) and by CT (TTR_CT) were determined and compared. FDG avidity of untreated tumors was compared between recurrent and non-recurrent groups.Thirteen recurrences after 72 RFA treatments were confirmed by diagnostic CT. All recurrences were associated with focally intense and increasing FDG uptake beyond 6 months (sensitivity 100%; specificity 98.5%). Mean TTR_PET was 14 months compared to mean TTR_CT of 17 months (not statistically significant). Normalized SUVmax and total lesions glycolysis of lung cancers that recurred after RFA was 4.0 and 6.0, respectively compared to 2.8 and 5.0, respectively for cancers that did not recur (p = .068).A pattern of focally intense and increasing FDG PET uptake has high sensitivity and specificity for detecting recurrent lung cancer following RFA. Surveillance after RFA should include a contrast enhanced diagnostic CT at 1 month to diagnose procedural complications, PET at 6 months as a post-treatment metabolic baseline (with diagnostic CT if PET is abnormal) and alternating diagnostic CTs or PET every 6 months for 2 years.

Background Hospital readmission rates are publicly reported by the Centers for Medicare & Medicaid Services (CMS); however, the implications of emergency department (ED) visits following hospital discharge on readmissions are uncertain. We describe the frequency, diagnoses, and hospital-level variation in ED visitation following hospital discharge, including the relationship between risk-standardized ED visitation and readmission rates. Methods This is a cross-sectional analysis of Medicare beneficiaries hospitalized for acute myocardial infarction (AMI), heart failure, and pneumonia between July 2011 and June 2012. We used Medicare Standard Analytic Files to identify admissions, readmissions, and ED visits consistent with CMS measures. Postdischarge ED visits were defined as treat-and-discharge ED services within 30 days of hospitalization without readmission. We utilized hierarchical generalized linear models to calculate hospital risk-standardized postdischarge ED visit rates and readmission rates. Results We included 157,035 patients hospitalized at 1656 hospitals for AMI, 391,209 at 3044 hospitals for heart failure, and 342,376 at 3484 hospitals for pneumonia. After hospitalization for AMI, heart failure, and pneumonia, there were 14,714 (9%), 31,621 (8%), and 26,681 (8%) ED visits, respectively. Hospital-level variation in postdischarge ED visit rates was substantial: AMI (median: 8.3%; 5th and 95th percentile: 2.8%-14.3%), heart failure (median: 7.3%; 5th and 95th percentile: 3.0%-13.3%), and pneumonia (median: 7.1%; 5th and 95th percentile: 2.4%-13.2%). There was statistically significant inverse correlation between postdischarge ED visit rates and readmission rates: AMI (-0.23), heart failure (-0.29), and pneumonia (-0.18). Conclusions Following hospital discharge, ED treatand- discharge visits are half as common as readmissions for Medicare beneficiaries. There is wide hospital-level variation in postdischarge ED visitation, and hospitals with higher ED visitation rates demonstrated lower readmission rates.

Background/objective Patients with multiple chronic conditions (MCCs) are a critical but undefined group for quality measurement. We present a generally applicable systematic approach to defining an MCC cohort of Medicare fee-for-service beneficiaries that we developed for a national quality measure, risk-standardized rates of unplanned admissions for Accountable Care Organizations. Research design To define the MCC cohort we: (1) identified potential chronic conditions; (2) set criteria for cohort conditions based on MCC framework and measure concept; (3) applied the criteria informed by empirical analysis, experts, and the public; (4) described "broader" and "narrower" cohorts; and (5) selected final cohort with stakeholder input. Subjects Subjects were patients with chronic conditions. Participants included 21.8 million Medicare fee-for-service beneficiaries in 2012 aged 65 years and above with ≥1 of 27 Medicare Chronic Condition Warehouse condition(s). Results In total, 10 chronic conditions were identified based on our criteria; 8 of these 10 were associated with notably increased admission risk when co-occurring. A broader cohort (2+ of the 8 conditions) included 4.9 million beneficiaries (23% of total cohort) with an admission rate of 70 per 100 person-years. It captured 53% of total admissions. The narrower cohort (3+ conditions) had 2.2 million beneficiaries (10%) with 100 admissions per 100 person-years and captured 32% of admissions. Most stakeholders viewed the broader cohort as best aligned with the measure concept. Conclusions By systematically narrowing chronic conditions to those most relevant to the outcome and incorporating stakeholder input, we defined an MCC admission measure cohort supported by stakeholders. This approach can be used as a model for other MCC outcome measures.

On the basis of the National Lung Screening Trial data released in 2011, the U.S. Preventive Services Task Force made lung cancer screening (LCS) with low-dose computed tomography (CT) a public health recommendation in 2013. The Centers for Medicare and Medicaid Services (CMS) currently reimburse LCS for asymptomatic individuals aged 55-77 years who have a tobacco smoking history of at least 30 pack-years and who are either currently smoking or had quit less than 15 years earlier. Commercial insurers reimburse the cost of LCS for individuals aged 55-80 years with the same smoking history. Effective care for the millions of Americans who qualify for LCS requires an organized step-wise approach. The 10-pillar model reflects the elements required to support a successful LCS program: eligibility, education, examination ordering, image acquisition, image review, communication, referral network, quality improvement, reimbursement, and research frontiers. Examination ordering can be coupled with decision support to ensure that only eligible individuals undergo LCS. Communication of results revolves around the Lung Imaging Reporting and Data System (Lung-RADS) from the American College of Radiology. Lung-RADS is a structured decision-oriented reporting system designed to minimize the rate of false-positive screening examination results. With nodule size and morphology as discriminators, Lung-RADS links nodule management pathways to the variety of nodules present on LCS CT studies. Tracking of patient outcomes is facilitated by a CMS-approved national registry maintained by the American College of Radiology. Online supplemental material is available for this article.

Background: In chronic heart failure, left ventricular ejection fraction (LVEF) is considered to be stable. Intensified therapy may improve survival, but little is known whether this is associated with reverse remodeling and dependent on age and NT-proBNP guidance. We aimed to define the evolution of LVEF under intensified therapy in relation to age and NT-proBNP guidance.Methods and results: Echocardiography was performed at baseline, 12 and 18 months in TIME-CHF, a trial comparing NT-proBNP versus symptom-guided therapy in patients aged 60 to 74 and >= 75 years. LVEF, LV end diastolic volume index (LVEDVI) and end systolic volume index (LVESVI) were assessed. LVEF increased from 31.3 +/- 10.7% to 39.1 +/- 11.8% at 18 months (p Conclusions: In elderly heart failure patients, intensified medical therapy leads to an improvement in LVEF and to reverse remodeling. NT-proBNP guided therapy was associated with a larger improvement in LVEF than symptom guided therapy both in patients aged 60 to 74 and = 75 years. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

Documentation of Helicobacter pylori infection and eradication is important, prompting some clinicians and pathologists to request ancillary stains on all gastric samples that do not demonstrate H. pylori on initial histologic review. Studies evaluating the utility of ancillary stains in patients with minimal inflammation are lacking. We used Giemsa, Warthin-Starry, acridine orange, and immunohistochemical stains to search for organisms in 56 patients with biochemical evidence of H. pylori infection (positive Campylobacter-like organism test) and gastric mucosal samples interpreted to be H pylori negative by hematoxylin and eosin (H&E). We correlated the findings with severity of inflammation and patients' histories of medication use. Nineteen (34%) patients had histologically normal mucosae, 22 (39%) had chronic inflammation with or without focal activity, and 15 (27%) had chemical gastropathy. Fifty (89%) cases were negative for H. pylori with additional stains, and 6 contained bacteria that were detected with all 4 ancillary stains and on retrospective review of H&E-stained sections that also showed chronic inflammation. Eleven (20%) patients were taking proton pump inhibitors, and 4 (7%) had previously received H. pylori eradication therapy. We conclude that H&E stains demonstrate H. pylori in most infected patients, so preemptive stain requests are largely unnecessary. Failure to identify bacteria by H&E evaluation generally reflects their absence in biopsy material, even among Campylobacter-like organism test--positive patients. However, organisms may be overlooked in patients with mild inflammation and in those receiving proton pump inhibitor or antibiotic therapy, so one should consider ordering ancillary stains to enhance detection of bacteria in these settings.

A 66-year-old male with 2-vessel coronary artery disease presented for a staged percutaneous coronary intervention (PCI) to a long lesion of the left anterior descending (LAD) coronary artery. Four...

Objective To compare trends in readmission rates among safety net and non-safety net hospitals under the US Hospital Readmission Reduction Program (HRRP). Design A retrospective time series analysis using Medicare administrative claims data from January 2008 to June 2015. Setting We examined 3254 US hospitals eligible for penalties under the HRRP, categorised as safety net or non-safety net hospitals based on the hospital’s proportion of patients with low socioeconomic status. Participants Admissions for Medicare fee-for-service patients, age ≥65 years, discharged alive, who had a valid five-digit zip code and did not have a principal discharge diagnosis of cancer or psychiatric illness were included, for a total of 52 516 213 index admissions. Primary and secondary outcome measures Mean hospital-level, all-condition, 30-day risk-adjusted standardised unplanned readmission rate, measured quarterly, along with quarterly rate of change, and an interrupted time series examining: April–June 2010, after HRRP was passed, and October–December 2012, after HRRP penalties were implemented. Results 58.0% (SD 15.3) of safety net hospitals and 17.1% (SD 10.4) of non-safety net hospitals’ patients were in the lowest quartile of socioeconomic status. The mean safety net hospital standardised readmission rate declined from 17.0% (SD 3.7) to 13.6% (SD 3.6), whereas the mean non-safety net hospital declined from 15.4% (SD 3.0) to 12.7% (SD 2.5). The absolute difference in rates between safety net and non-safety net hospitals declined from 1.6% (95% CI 1.3 to 1.9) to 0.9% (0.7 to 1.2). The quarterly decline in standardised readmission rates was 0.03 percentage points (95% CI 0.03 to 0.02, p

Homologous recombination (HR) DNA repair-deficient (HRD) breast cancers have been shown to be sensitive to DNA repair targeted therapies. Burgeoning evidence suggests that sporadic breast cancers, lacking germline BRCA1/BRCA2 mutations, may also be HRD. We developed a functional ex vivo RAD51-based test to identify HRD primary breast cancers. An integrated approach examining methylation, gene expression, and whole-exome sequencing was employed to ascertain the aetiology of HRD. Functional HRD breast cancers displayed genomic features of lack of competent HR, including large-scale state transitions and specific mutational signatures. Somatic and/or germline genetic alterations resulting in bi-allelic loss-of-function of HR genes underpinned functional HRD in 89% of cases, and were observed in only one of the 15 HR-proficient samples tested. These findings indicate the importance of a comprehensive genetic assessment of bi-allelic alterations in the HR pathway to deliver a precision medicine-based approach to select patients for therapies targeting tumour-specific DNA repair defects. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John WileySons, Ltd.

International audience; BACKGROUND:Propionic acidemia (PA) is a rare but severe recessive autosomal disease, presenting with non specific signs in the first years of life. Prenatal diagnosis is invasive (amniocentesis) and limited to suspect cases. No screening test has been described, in particular no correlations between prenatal sonography and PA have been documented so far.CASE PRESENTATION:We report the case of a boy with fetal bilateral nephromegaly and hyperechogenic kidneys, along with neonatal acute kidney injury; no etiology could be found in the first months of life. At 3 months of life, he presented with tachypnea and altered mental status, which lead to the diagnosis of PA. The renal ultrasound at 8 months of life, after a symptomatic treatment of PA had been initiated, showed a regression of the renal abnormalities.CONCLUSION:This case describes PA as a novel cause of large and hyperechogenic kidneys in the antenatal period. It suggests that, when confronted to fetal nephromegaly, hyperechogenic kidneys and risk factors of metabolic disease such as consanguineous parents, PA should be considered, and a prenatal test should be proposed.

BACKGROUND: Chronic whiplash-associated disorders (chronic WAD) cover a large variety of clinical manifestations that can occur after a whiplash injury. Women have an increased risk of developing chronic WAD, and it is suggested that psychosocial factors are related to long-term pain and functioning following whiplash injury and persistence of chronic pain. This leads to the question whether there are sex differences in psychosocial factors in chronic WAD. METHODS: This study included 117 subjects who had experienced a whiplash injury at least 3 months before the start of the study (mean duration of pain: 67.29 ± 63.86 months, range: 297 months). They were selected as chronically symptomatic, by excluding those who had recovered from their whiplash injury. Psychosocial aspects (including depression, fear, somatization, social support, and personality traits) were assessed by validated questionnaires, and sex differences were tested using a univariate analysis of variance (ANCOVA), with age and time from whiplash injury as covariates. RESULTS: No differences in depression, fear, somatization, discrepancy in social support personality trait, Neck Disability Index scores, physical functioning, bodily pain, or general health were present between women and men with chronic WAD. Women with chronic WAD reported higher levels of emotional support in problem situations and social companionship. CONCLUSION: Except for emotional support in problem situations and social companionship, psychosocial factors do not differ between men and women with chronic WAD. These findings imply little to no risk for sex bias in studies investigating psychosocial issues in patients with chronic WAD.

Background— Recent studies show an association between neighborhood-level measures of socioeconomic status (SES) and outcomes for patients with heart failure. We do not know whether neighborhood SES has a primary effect or is a marker for individual SES. Methods and Results— We used the data from participants of the Telemonitoring to Improve Heart Failure Outcomes (Tele-HF) trial, recruited from 33 US internal medicine and cardiology practices and examined the association between neighborhood SES and outcomes of patients with heart failure. We used census tracts as proxies for neighborhoods and constructed summary SES scores that included information about wealth and income, education, and occupation. The primary end points were readmission and all-cause mortality at 6 months. We conducted patient interviews and medical chart reviews to obtain demographic information, clinical factors, therapies, and individual SES. We included 1557 patients: 524, 516, and 517 from low, medium, and high SES neighborhoods, respectively (mean age, 61.1±15.2 years; 42.2% women).Overall, 745 patients (47.8%) had ≥1 readmission and 179 patients (11.5%) died. When compared with patients in high SES neighborhoods, those living in low-SES neighborhoods were more likely to be readmitted (odds ratio, 1.35; 95% confidence interval, 1.01–1.82), but the mortality rates were not significantly different (odds ratio, 0.78; 95% confidence interval, 0.50–1.18). The results were consistent after multivariable adjustments for individual demographics, clinical factors, and individual SES. Conclusions— Among patients with heart failure, neighborhood SES was significantly associated with 6-month all-cause readmission even after adjusting for other patient-level factors, including individual SES. Greater number of events and longer follow-up is required to ascertain the potential effect of neighborhood SES on mortality. Clinical Trial Registration— URL: http://clinicaltrials.gov/ . Unique identifier: NCT00303212.

Background: Little is known about the variation in complication rates among U.S. hospitals that perform elective total hip arthroplasty (THA) and total knee arthroplasty (TKA) procedures. The purpose of this study was to use National Quality Forum (NQF)-endorsed hospital-level risk-standardized complication rates to describe variations in, and disparities related to, hospital quality for elective primary THA and TKA procedures performed in U.S. hospitals. Methods: We conducted a cross-sectional analysis of national Medicare Fee-for-Service data. The study cohort included 878,098 Medicare fee-for-service beneficiaries, sixty-five years or older, who underwent elective THA or TKA from 2008 to 2010 at 3479 hospitals. Both medical and surgical complications were included in the composite measure. Hospital-specific complication rates were calculated from Medicare claims with use of hierarchical logistic regression to account for patient clustering and were risk-adjusted for age, sex, and patient comorbidities. We determined whether hospitals with higher proportions of Medicaid patients and black patients had higher risk-standardized complication rates. Results: The crude rate of measured complications was 3.6%. The most common complications were pneumonia (0.86%), pulmonary embolism (0.75%), and periprosthetic joint infection or wound infection (0.67%). The median risk-standardized complication rate was 3.6% (range, 1.8% to 9.0%). Among hospitals with at least twenty-five THA and TKA patients in the study cohort, 103 (3.6%) were better and seventy-five (2.6%) were worse than expected. Hospitals with the highest proportion of Medicaid patients had slightly higher but similar risk-standardized complication rates (median, 3.6%; range, 2.0% to 7.1%) compared with hospitals in the lowest decile (3.4%; 1.7% to 6.2%). Findings were similar for the analysis involving the proportion of black patients. Conclusions: There was more than a fourfold difference in risk-standardized complication rates across U.S. hospitals in which elective THA and TKA are performed. Although hospitals with higher proportions of Medicaid and black patients had rates similar to those of hospitals with lower proportions, there is a continued need to monitor for disparities in outcomes. These findings suggest there are opportunities for quality improvement among hospitals in which elective THA and TKA procedures are performed. Level of Evidence: Therapeutic Level III. See Instruction to Authors for a complete description of levels of evidence.

Background Pulmonary hypertension due to left heart disease is very common. Our aim was to investigate the relationship of the severity of left ventricular diastolic dysfunction with precapillary and postcapillary pulmonary hypertension (PH) in an elderly heart failure (HF) population. Methods and Results A post hoc analysis of the Trial of Intensified Medical Therapy in Elderly Patients With Congestive Heart Failure data was done. Baseline transthoracic echocardiography was used to categorize diastolic function, estimate pulmonary artery pressure and pulmonary capillary wedge pressure, and calculate the transpulmonary pressure gradient (TPG). Among 392 HF patients, PH was present in 31% of patients with grade 1, in 37% of patients with grade 2, and in 65% of patients with grade 3 diastolic dysfunction; 54% of all HF patients with PH had a TPG >12 mm Hg, suggesting not only a postcapillary but also an additional precapillary component of PH. Survival was not related to the severity of diastolic dysfunction, but was worse in patients with PH (hazard ratio 1.63, 95% confidence interval 1.07–2.51; P = .024). Conclusions Our data indicate that HF patients with even mild diastolic dysfunction often have PH. Echocardiographic assessment suggest that the presence of PH might not simply be due to increased PCWP, but in part due to a precapillary component.

This cohort study analyzes Centers for Medicare & Medicaid Services data for heart failure and pneumonia discharges to ascertain hospital payment profiles associated with hospitalization costs for Medicare beneficiaries., Key Points Question Is the amount that the Centers for Medicare & Medicaid Services pays hospitals associated with characteristics of the hospital independent of non–time-varying characteristics of patients? Findings In this cohort study of 1615 Medicare beneficiaries hospitalized with heart failure and 708 beneficiaries hospitalized with pneumonia, the same patients admitted with the same diagnosis to hospitals in the highest Medicare payment quartile had higher costs than when they were admitted to hospitals in the lowest quartile. Meaning Findings from this study suggest that hospitals operate at different cost levels independent of their patients., Importance Some uncertainty exists about whether hospital variations in cost are largely associated with differences in case mix. Objective To establish whether the same patients admitted with the same diagnosis (heart failure or pneumonia) at 2 different hospitals incur different costs associated with the hospital’s Medicare payment profile. Design, Setting, and Participants This observational cohort study used Centers for Medicare & Medicaid Services (CMS) discharge data of patients with a principal diagnosis of heart failure (n = 1615) or pneumonia (n = 708) occurring between July 1, 2013, and June 30, 2016. Patients were individuals aged 65 years or older who were enrolled in Medicare fee-for-service Part A and Part B and were discharged from nonfederal, short-term, acute care or critical access hospitals in the United States. Data were analyzed from March 16, 2018, to September 25, 2019. Main Outcomes and Measures The CMS heart failure and pneumonia payment measure cohorts were divided into 2 random samples. In the first sample, hospitals were classified into payment quartiles for heart failure and pneumonia. In the second sample, patients with 2 admissions for heart failure or pneumonia, one in a lowest-quartile hospital and one in a highest-quartile hospital more than 1 month apart, were identified. Standardized Medicare payments for these patients were compared for the lowest- and the highest-quartile payment hospitals. Results The study sample included 1615 patients with heart failure (mean [SD] age, 78.7 [8.0] years; 819 [50.7%] male) and 708 with pneumonia (mean [SD] age, 78.3 [8.0] years; 401 [56.6%] male). The observed 30-day mortality rates for patients among lowest- compared with highest-payment hospitals were not significantly different. The median (interquartile range) hospital 30-day risk-standardized mortality rates were 8.1% (7.7%-8.5%) for heart failure and 11.3% (10.7%-12.1%) for pneumonia. The 30-day episode payment for hospitalization for the same patients at the lowest-payment hospitals was $2118 (95% CI, $1168-$3068; P

This comparative effectiveness study examines current US Centers for Medicare & Medicaid Services 30-day mortality risk models vs novel risk models for acute myocardial infarction, heart failure, and pneumonia hospitalizations., Key Points Question Could present on admission indicators and ungrouped diagnostic codes enhance risk models for acute myocardial infarction, heart failure, and pneumonia mortality measures and improve discrimination of hospital-level performance? Findings In this comparative effectiveness study including all Medicare fee-for-service beneficiaries hospitalized for acute myocardial infarction, heart failure, or pneumonia at acute care hospitals, incorporating present on admission coding and ungrouped historical and index admission International Classification of Diseases, Ninth Revision, Clinical Modification codes was associated with greater discrimination in patient-level and hospital-level 30-day mortality risk models. Meaning Changes incurring no additional cost could enhance the risk adjustment for mortality and increase discrimination of hospital-level performance., Importance Risk adjustment models using claims-based data are central in evaluating health care performance. Although US Centers for Medicare & Medicaid Services (CMS) models apply well-vetted statistical approaches, recent changes in the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) coding system and advances in computational capabilities may provide an opportunity for enhancement. Objective To examine whether changes using already available data would enhance risk models and yield greater discrimination in hospital-level performance measures. Design, Setting, and Participants This comparative effectiveness study used ICD-9-CM codes from all Medicare fee-for-service beneficiary claims for hospitalizations for acute myocardial infarction (AMI), heart failure (HF), or pneumonia among patients 65 years and older from July 1, 2013, through September 30, 2015. Changes to current CMS mortality risk models were applied incrementally to patient-level models, and the best model was tested on hospital performance measures to model 30-day mortality. Analyses were conducted from April 19, 2018, to September 19, 2018. Main Outcomes and Measures The main outcome was all-cause death within 30 days of hospitalization for AMI, HF, or pneumonia, examined using 3 changes to current CMS mortality risk models: (1) incorporating present on admission coding to better exclude potential complications of care, (2) separating index admission diagnoses from those of the 12-month history, and (3) using ungrouped ICD-9-CM codes. Results There were 361 175 hospital admissions (mean [SD] age, 78.6 [8.4] years; 189 225 [52.4%] men) for AMI, 716 790 hospital admissions (mean [SD] age, 81.1 [8.4] years; 326 825 [45.6%] men) for HF, and 988 225 hospital admissions (mean [SD] age, 80.7 [8.6] years; 460 761 [46.6%] men) for pneumonia during the study; mean 30-day mortality rates were 13.8% for AMI, 12.1% for HF, and 16.1% for pneumonia. Each change to the models was associated with incremental gains in C statistics. The best model, incorporating all changes, was associated with significantly improved patient-level C statistics, from 0.720 to 0.826 for AMI, 0.685 to 0.776 for HF, and 0.715 to 0.804 for pneumonia. Compared with current CMS models, the best model produced wider predicted probabilities with better calibration and Brier scores. Hospital risk-standardized mortality rates had wider distributions, with more hospitals identified as good or bad performance outliers. Conclusions and Relevance Incorporating present on admission coding and using ungrouped index and historical ICD-9-CM codes were associated with improved patient-level and hospital-level risk models for mortality compared with the current CMS models for all 3 conditions.

In France gamete donation and notably sperm donation are anonymous. It has been claimed that anonymous artificial insemination by donor (AID) could highly contribute to an increase in the level of consanguinity and the incidence of autosomal recessive diseases, due to the unions between offspring of anonymous donors, unaware of their biological kinship, with the special case of unions between half-siblings. The actual incidence of consanguinity due to AID was compared with that resulting from the two other main sources of consanguinity and recessive diseases, i.e. voluntary unions between related individuals or inadvertent unions between the offspring of a common unknown male ancestor (false paternity). From these data, we estimated that expected unions in France between half sibs per year are 0.12 between offspring of sperm donors (1.2 every 10 years) and 0.5 between offspring of common male ancestors through false paternity (5 every 10 years). More generally, the inadvertent unions between false paternity offspring are roughly four times more frequent than those resulting from anonymous AID. We estimated that in the future, when AID has been in practice for several generations, out the 820 000 annual births in France, respectively, 6 and 25 births will be consanguineous through an unknown common ancestor related to anonymous AID and to a false paternity, both of which are negligible when compared with the 1256 children born from first-degree cousins. About 672 children per year are born with a recessive genetic disease due to the panmictic risk and additional affected cases due to consanguinity would be 34.54 for first-cousin offspring, 0.33 for offspring of individuals related due to false paternity and 0.079 for offspring of individuals related due to anonymous AID. Anonymous AID would therefore be responsible for 0.46% of consanguineous births and for 0.01% of recessive diseases. Therefore, the effect of anonymous AID on half-sibling unions, consanguinity and recessive disease incidence can be regarded as marginal.