Mortality and morbidity ramifications of proposed retractions in healthcare coverage for the United States.

In the absence of universal healthcare in the United States, federal programs of Medicaid and Medicare are vital to providing healthcare coverage for low-income households and elderly individuals, respectively. However, both programs are under threat, with either enacted or proposed retractions. Specifically, raising Medicare age eligibility and the addition of work requirements for Medicaid qualification have been proposed, while termination of continuous enrollment for Medicaid was recently effectuated. Here, we assess the potential impact on mortality and morbidity resulting from these policy changes. Our findings indicate that the policy change to Medicare would lead to over 17,000 additional deaths among individuals aged 65 to 67 and those to Medicaid would lead to more than 8,000 deaths among those under the age of 65. To illustrate the implications for morbidity, we further consider a case study among those people with diabetes who would be likely to lose their health insurance under the policy changes. We project that these insurance retractions would lead to the loss of coverage for over 700,000 individuals with diabetes, including more than 200,000 who rely on insulin.

Disease burden among Ukrainians forcibly displaced by the 2022 Russian invasion.

The Russian invasion of Ukraine on February 24, 2022, has displaced more than a quarter of the population. Assessing disease burdens among displaced people is instrumental in informing global public health and humanitarian aid efforts. We estimated the disease burden in Ukrainians displaced both within Ukraine and to other countries by combining a spatiotemporal model of forcible displacement with age- and gender-specific estimates of cardiovascular disease (CVD), diabetes, cancer, HIV, and tuberculosis (TB) in each of Ukraine's 629 raions (i.e., districts). Among displaced Ukrainians as of May 13, we estimated that more than 2.63 million have CVDs, at least 615,000 have diabetes, and over 98,500 have cancer. In addition, more than 86,000 forcibly displaced individuals are living with HIV, and approximately 13,500 have TB. We estimated that the disease prevalence among refugees was lower than the national disease prevalence before the invasion. Accounting for internal displacement and healthcare facilities impacted by the conflict, we estimated that the number of people per hospital has increased by more than two-fold in some areas. As regional healthcare systems come under increasing strain, these estimates can inform the allocation of critical resources under shifting disease burdens.

Evaluation of Strategies for Transitioning to Annual SARS-CoV-2 Vaccination Campaigns in the United States.

BACKGROUND: The U.S. Food and Drug Administration has proposed administering annual SARS-CoV-2 vaccines. OBJECTIVE: To evaluate the effectiveness of an annual SARS-CoV-2 vaccination campaign, quantify the health and economic benefits of a second dose provided to children younger than 2 years and adults aged 50 years or older, and optimize the timing of a second dose. DESIGN: An age-structured dynamic transmission model. SETTING: United States. PARTICIPANTS: A synthetic population reflecting demographics and contact patterns in the United States. INTERVENTION: Vaccination against SARS-CoV-2 with age-specific uptake similar to that of influenza vaccination. MEASUREMENTS: Incidence, hospitalizations, deaths, and direct health care cost. RESULTS: The optimal timing between the first and second dose delivered to children younger than 2 years and adults aged 50 years or older in an annual vaccination campaign was estimated to be 5 months. In direct comparison with a single-dose campaign, a second booster dose results in 123 869 fewer hospitalizations (95% uncertainty interval [UI], 121 994 to 125 742 fewer hospitalizations) and 5524 fewer deaths (95% UI, 5434 to 5613 fewer deaths), averting $3.63 billion (95% UI, $3.57 billion to $3.69 billion) in costs over a single year. LIMITATIONS: Population immunity is subject to degrees of immune evasion for emerging SARS-CoV-2 variants. The model was implemented in the absence of nonpharmaceutical interventions and preexisting vaccine-acquired immunity. CONCLUSION: The direct health care costs of SARS-CoV-2, particularly among adults aged 50 years or older, would be substantially reduced by administering a second dose 5 months after the initial dose. PRIMARY FUNDING SOURCE: Natural Sciences and Engineering Research Council of Canada, Notsew Orm Sands Foundation, National Institutes of Health, Centers for Disease Control and Prevention, and National Science Foundation.

Universal healthcare as pandemic preparedness: The lives and costs that could have been saved during the COVID-19 pandemic.

The fragmented and inefficient healthcare system in the United States leads to many preventable deaths and unnecessary costs every year. During a pandemic, the lives saved and economic benefits of a single-payer universal healthcare system relative to the status quo would be even greater. For Americans who are uninsured and underinsured, financial barriers to COVID-19 care delayed diagnosis and exacerbated transmission. Concurrently, deaths beyond COVID-19 accrued from the background rate of uninsurance. Universal healthcare would alleviate the mortality caused by the confluence of these factors. To evaluate the repercussions of incomplete insurance coverage in 2020, we calculated the elevated mortality attributable to the loss of employer-sponsored insurance and to background rates of uninsurance, summing with the increased COVID-19 mortality due to low insurance coverage. Incorporating the demography of the uninsured with age-specific COVID-19 and nonpandemic mortality, we estimated that a single-payer universal healthcare system would have saved about 212,000 lives in 2020 alone. We also calculated that US$105.6 billion of medical expenses associated with COVID-19 hospitalization could have been averted by a single-payer universal healthcare system over the course of the pandemic. These economic benefits are in addition to US$438 billion expected to be saved by single-payer universal healthcare during a nonpandemic year.

Incorporating Synthetic Accessibility in Drug Design: Predicting Reaction Yields of Suzuki Cross-Couplings by Leveraging AbbVie's 15-Year Parallel Library Data Set.

Despite the increased use of computational tools to supplement medicinal chemists' expertise and intuition in drug design, predicting synthetic yields in medicinal chemistry endeavors remains an unsolved challenge. Existing design workflows could profoundly benefit from reaction yield prediction, as precious material waste could be reduced, and a greater number of relevant compounds could be delivered to advance the design, make, test, analyze (DMTA) cycle. In this work, we detail the evaluation of AbbVie's medicinal chemistry library data set to build machine learning models for the prediction of Suzuki coupling reaction yields. The combination of density functional theory (DFT)-derived features and Morgan fingerprints was identified to perform better than one-hot encoded baseline modeling, furnishing encouraging results. Overall, we observe modest generalization to unseen reactant structures within the 15-year retrospective library data set. Additionally, we compare predictions made by the model to those made by expert medicinal chemists, finding that the model can often predict both reaction success and reaction yields with greater accuracy. Finally, we demonstrate the application of this approach to suggest structurally and electronically similar building blocks to replace those predicted or observed to be unsuccessful prior to or after synthesis, respectively. The yield prediction model was used to select similar monomers predicted to have higher yields, resulting in greater synthesis efficiency of relevant drug-like molecules.

Multi-GWAS reveals significant genomic regions for Mungbean yellow mosaic India virus resistance in urdbean (Vigna mungo (L.) across multiple environments.

KEY MESSAGE: Unraveling genetic markers for MYMIV resistance in urdbean, with 8 high-confidence marker-trait associations identified across diverse environments, provides crucial insights for combating MYMIV disease, informing future breeding strategies. Globally, yellow mosaic disease (YMD) causes significant yield losses, reaching up to 100% in favorable environments within major urdbean cultivating regions. The introgression of genomic regions conferring resistance into urdbean cultivars is crucial for combating YMD, including resistance against mungbean yellow mosaic India virus (MYMIV). To uncover the genetic basis of MYMIV resistance, we conducted a genome-wide association study (GWAS) using three multi-locus models in 100 diverse urdbean genotypes cultivated across six individual and two combined environments. Leveraging 4538 high-quality single nucleotide polymorphism (SNP) markers, we identified 28 unique significant marker-trait associations (MTAs) for MYMIV resistance, with 8 MTAs considered of high confidence due to detection across multiple GWAS models and/or environments. Notably, 4 out of 28 MTAs were found in proximity to previously reported genomic regions associated with MYMIV resistance in urdbean and mungbean, strengthening our findings and indicating consistent genomic regions for MYMIV resistance. Among the eight highly significant MTAs, one localized on chromosome 6 adjacent to previously identified quantitative trait loci for MYMIV resistance, while the remaining seven were novel. These MTAs contain several genes implicated in disease resistance, including four common ones consistently found across all eight MTAs: receptor-like serine-threonine kinases, E3 ubiquitin-protein ligase, pentatricopeptide repeat, and ankyrin repeats. Previous studies have linked these genes to defense against viral infections across different crops, suggesting their potential for further basic research involving cloning and utilization in breeding programs. This study represents the first GWAS investigation aimed at identifying resistance against MYMIV in urdbean germplasm.

Clinical and Mycologic Characteristics of Emerging Mucormycosis Agent Rhizopus homothallicus.

We retrospectively reviewed consecutive cases of mucormycosis reported from a tertiary-care center in India to determine the clinical and mycologic characteristics of emerging Rhizopus homothallicus fungus. The objectives were ascertaining the proportion of R. homothallicus infection and the 30-day mortality rate in rhino-orbital mucormycosis attributable to R. homothallicus compared with R. arrhizus. R. homothallicus accounted for 43 (6.8%) of the 631 cases of mucormycosis. R. homothallicus infection was independently associated with better survival (odds ratio [OR] 0.08 [95% CI 0.02-0.36]; p = 0.001) than for R. arrhizus infection (4/41 [9.8%] vs. 104/266 [39.1%]) after adjusting for age, intracranial involvement, and surgery. We also performed antifungal-susceptibility testing, which indicated a low range of MICs for R. homothallicus against the commonly used antifungals (amphotericin B [0.03-16], itraconazole [0.03-16], posaconazole [0.03-8], and isavuconazole [0.03-16]). 18S gene sequencing and amplified length polymorphism analysis revealed distinct clustering of R. homothallicus.

The implications of silent transmission for the control of COVID-19 outbreaks.

Since the emergence of coronavirus disease 2019 (COVID-19), unprecedented movement restrictions and social distancing measures have been implemented worldwide. The socioeconomic repercussions have fueled calls to lift these measures. In the absence of population-wide restrictions, isolation of infected individuals is key to curtailing transmission. However, the effectiveness of symptom-based isolation in preventing a resurgence depends on the extent of presymptomatic and asymptomatic transmission. We evaluate the contribution of presymptomatic and asymptomatic transmission based on recent individual-level data regarding infectiousness prior to symptom onset and the asymptomatic proportion among all infections. We found that the majority of incidences may be attributable to silent transmission from a combination of the presymptomatic stage and asymptomatic infections. Consequently, even if all symptomatic cases are isolated, a vast outbreak may nonetheless unfold. We further quantified the effect of isolating silent infections in addition to symptomatic cases, finding that over one-third of silent infections must be isolated to suppress a future outbreak below 1% of the population. Our results indicate that symptom-based isolation must be supplemented by rapid contact tracing and testing that identifies asymptomatic and presymptomatic cases, in order to safely lift current restrictions and minimize the risk of resurgence.

Prosocial polio vaccination in Israel.

Regions with insufficient vaccination have hindered worldwide poliomyelitis eradication, as they are vulnerable to sporadic outbreaks through reintroduction of the disease. Despite Israel's having been declared polio-free in 1988, a routine sewage surveillance program detected polio in 2013. To curtail transmission, the Israel Ministry of Health launched a vaccine campaign to vaccinate children-who had only received the inactivated polio vaccine-with the oral polio vaccine (OPV). Determining the degree of prosocial motivation in vaccination behavior is challenging because vaccination typically provides direct benefits to the individual as well as indirect benefits to the community by curtailing transmission. However, the Israel OPV campaign provides a unique and excellent opportunity to quantify and model prosocial vaccination as its primary objective was to avert transmission. Using primary survey data and a game-theoretical model, we examine and quantify prosocial behavior during the OPV campaign. We found that the observed vaccination behavior in the Israeli OPV campaign is attributable to prosocial behavior and heterogeneous perceived risk of paralysis based on the individual's comprehension of the prosocial nature of the campaign. We also found that the benefit of increasing comprehension of the prosocial nature of the campaign would be limited if even 24% of the population acts primarily from self-interest, as greater vaccination coverage provides no personal utility to them. Our results suggest that to improve coverage, communication efforts should also focus on alleviating perceived fears surrounding the vaccine.

Impact of international travel and border control measures on the global spread of the novel 2019 coronavirus outbreak.

The novel coronavirus outbreak (COVID-19) in mainland China has rapidly spread across the globe. Within 2 mo since the outbreak was first reported on December 31, 2019, a total of 566 Severe Acute Respiratory Syndrome (SARS CoV-2) cases have been confirmed in 26 other countries. Travel restrictions and border control measures have been enforced in China and other countries to limit the spread of the outbreak. We estimate the impact of these control measures and investigate the role of the airport travel network on the global spread of the COVID-19 outbreak. Our results show that the daily risk of exporting at least a single SARS CoV-2 case from mainland China via international travel exceeded 95% on January 13, 2020. We found that 779 cases (95% CI: 632 to 967) would have been exported by February 15, 2020 without any border or travel restrictions and that the travel lockdowns enforced by the Chinese government averted 70.5% (95% CI: 68.8 to 72.0%) of these cases. In addition, during the first three and a half weeks of implementation, the travel restrictions decreased the daily rate of exportation by 81.3% (95% CI: 80.5 to 82.1%), on average. At this early stage of the epidemic, reduction in the rate of exportation could delay the importation of cases into cities unaffected by the COVID-19 outbreak, buying time to coordinate an appropriate public health response.

Projecting hospital utilization during the COVID-19 outbreaks in the United States.

In the wake of community coronavirus disease 2019 (COVID-19) transmission in the United States, there is a growing public health concern regarding the adequacy of resources to treat infected cases. Hospital beds, intensive care units (ICUs), and ventilators are vital for the treatment of patients with severe illness. To project the timing of the outbreak peak and the number of ICU beds required at peak, we simulated a COVID-19 outbreak parameterized with the US population demographics. In scenario analyses, we varied the delay from symptom onset to self-isolation, the proportion of symptomatic individuals practicing self-isolation, and the basic reproduction number R0 Without self-isolation, when R0 = 2.5, treatment of critically ill individuals at the outbreak peak would require 3.8 times more ICU beds than exist in the United States. Self-isolation by 20% of cases 24 h after symptom onset would delay and flatten the outbreak trajectory, reducing the number of ICU beds needed at the peak by 48.4% (interquartile range 46.4-50.3%), although still exceeding existing capacity. When R0 = 2, twice as many ICU beds would be required at the peak of outbreak in the absence of self-isolation. In this scenario, the proportional impact of self-isolation within 24 h on reducing the peak number of ICU beds is substantially higher at 73.5% (interquartile range 71.4-75.3%). Our estimates underscore the inadequacy of critical care capacity to handle the burgeoning outbreak. Policies that encourage self-isolation, such as paid sick leave, may delay the epidemic peak, giving a window of time that could facilitate emergency mobilization to expand hospital capacity.

Pelvic lymph node dissection before or after laparoscopic radical cystectomy: An ambispective study comparing ease of surgery and operative outcomes.

Introduction: It is unclear when pelvic lymph node dissection (PLND) should be performed during laparoscopic radical cystectomy. Proponents of PLND performed before cystectomy claim that early PLND skeletonizes the urinary bladder's vascular pedicles, making cystectomy easy. Others contend that an early cystectomy provides space and flexibility during subsequent PLND. This first-of-its-kind study compared PLND before and after cystectomy for the ease of performing surgery (total operative time, cystectomy time, and PLND time) and the operative outcomes (number of lymph nodes removed, blood loss, and complication rates). Methods: This ambispective cohort study included a predetermined sample size of 44 patients. The first 22 patients underwent PLND after cystectomy (Group 1), and the following 22 underwent PLND before cystectomy (Group 2). The primary outcome was total operative time. Secondary outcomes included cystectomy time, PLND time, number of lymph nodes removed, blood loss, and complication rates. Results: The baseline characteristics were similar in both groups. The total operative time (344.23 ± 41.58 min vs. 326.95 ± 43.63 min, P = 0.19), cystectomy time (119.36 ± 34.44 min vs. 120.91 ± 35.16 min, P = 0.53), PLND time (126.82 ± 18.75 min vs. 119.36 ± 23.34 min, 0.25), number of dissected lymph nodes (13.27 ± 4.86 vs. 14.5 ± 4.76, P = 0.40), and blood loss (620.45 ± 96.23 ml vs. 642.27 ± 131.8 ml, P = 0.20) were similar in the two groups. The complication rates categorized by Clavien-Dindo grading were identical in the two groups. Conclusions: PLND done after cystectomy was comparable to PLND done before cystectomy regarding the ease of surgery and the operative outcomes.

The exacerbation of Ebola outbreaks by conflict in the Democratic Republic of the Congo.

The interplay between civil unrest and disease transmission is not well understood. Violence targeting healthcare workers and Ebola treatment centers in the Democratic Republic of the Congo (DRC) has been thwarting the case isolation, treatment, and vaccination efforts. The extent to which conflict impedes public health response and contributes to incidence has not previously been evaluated. We construct a timeline of conflict events throughout the course of the epidemic and provide an ethnographic appraisal of the local conditions that preceded and followed conflict events. Informed by temporal incidence and conflict data as well as the ethnographic evidence, we developed a model of Ebola transmission and control to assess the impact of conflict on the epidemic in the eastern DRC from April 30, 2018, to June 23, 2019. We found that both the rapidity of case isolation and the population-level effectiveness of vaccination varied notably as a result of preceding unrest and subsequent impact of conflict events. Furthermore, conflict events were found to reverse an otherwise declining phase of the epidemic trajectory. Our model framework can be extended to other infectious diseases in the same and other regions of the world experiencing conflict and violence.

Ebola vaccination in the Democratic Republic of the Congo.

Following the April 2018 reemergence of Ebola in a rural region of the Democratic Republic of the Congo (DRC), the virus spread to an urban center by early May. Within 2 wk of the first case confirmation, a vaccination campaign was initiated in which 3,017 doses were administered to contacts of cases and frontline healthcare workers. To evaluate the spatial dynamics of Ebola transmission and quantify the impact of vaccination, we developed a geographically explicit model that incorporates high-resolution data on poverty and population density. We found that while Ebola risk was concentrated around sites initially reporting infections, longer-range dissemination also posed a risk to areas with high population density and poverty. We estimate that the vaccination program contracted the geographical area at risk for Ebola by up to 70.4% and reduced the level of risk within that region by up to 70.1%. The early implementation of vaccination was critical. A delay of even 1 wk would have reduced these effects to 33.3 and 44.8%, respectively. These results underscore the importance of the rapid deployment of Ebola vaccines during emerging outbreaks to containing transmission and preventing global spread. The spatiotemporal framework developed here provides a tool for identifying high-risk regions, in which surveillance can be intensified and preemptive control can be implemented during future outbreaks.

Conductive thermal mattress versus routine care to reduce neonatal hypothermia during transport among low-birthweight neonates: An experimental study with historical controls.

Background: Neonatal hypothermia at delivery, during transport and in the postnatal wards is common, under-recognized and infrequently monitored with prevalence ranging from 32% to 85%. This study compared conductive thermal mattress to routine care for prevention of hypothermia among low-birthweight (LBW) neonates during transport. Methods: From July 2015 to November 2016 (historical controls), all eligible LBW neonates (1500-2499 g) were transported from the labour room/operation theatre to the neonatal intensive care unit (NICU)/postnatal wards using routine care (towels, blankets, cap, mittens and socks) and from December 2016 to December 2018 using conductive thermal mattress (EMBRACETM) Axillary temperature was measured before transport and at arrival in the NICU/postnatal wards using a digital thermometer. Results: A total of 154 and 102 neonates were transported using conductive thermal mattress and routine care, respectively. The mean standard deviation (SD) axillary temperature at arrival in the postnatal wards in conductive thermal mattress and routine care group was 36.6 (0.6) °C and 36.4 (0.5) °C, respectively (p-value 0.005). Relative Risk (RR) of mild and moderate neonatal hypothermia among neonates transported using conductive thermal mattress compared to routine care group was 0.59 (0.33,1.07), number needed to treat (NNT) of 13 and 0.22 (0.04,1.07), NNT 22 respectively. Conclusions: Use of conductive thermal mattress for transport among LBW neonates led to a significant, although clinically small improvement in admission temperatures at the NICU/postnatal ward and non-significant decrease in the incidence of hypothermia.

COVID-19 outcomes in hospitalized patients with active cancer: Experiences from a major New York City health care system.

BACKGROUND: The authors sought to study the risk factors associated with severe outcomes in hospitalized coronavirus disease 2019 (COVID-19) patients with cancer. METHODS: The authors queried the New York University Langone Medical Center's records for hospitalized patients who were polymerase chain reaction-positive for severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) and performed chart reviews on patients with cancer diagnoses to identify patients with active cancer and patients with a history of cancer. Descriptive statistics were calculated and multivariable logistic regression was used to determine associations between clinical, demographic, and laboratory characteristics with outcomes, including death and admission to the intensive care unit. RESULTS: A total of 4184 hospitalized SARS CoV-2+ patients, including 233 with active cancer, were identified. Patients with active cancer were more likely to die than those with a history of cancer and those without any cancer history (34.3% vs 27.6% vs 20%, respectively; P < .01). In multivariable regression among all patients, active cancer (odds ratio [OR], 1.89; CI, 1.34-2.67; P < .01), older age (OR, 1.06; CI, 1.05-1.06; P < .01), male sex (OR for female vs male, 0.70; CI, 0.58-0.84; P < .01), diabetes (OR, 1.26; CI, 1.04-1.53; P = .02), morbidly obese body mass index (OR, 1.87; CI, 1.24-2.81; P < .01), and elevated D-dimer (OR, 6.41 for value >2300; CI, 4.75-8.66; P < .01) were associated with increased mortality. Recent cancer-directed medical therapy was not associated with death in multivariable analysis. Among patients with active cancer, those with a hematologic malignancy had the highest mortality rate in comparison with other cancer types (47.83% vs 28.66%; P < .01). CONCLUSIONS: The authors found that patients with an active cancer diagnosis were more likely to die from COVID-19. Those with hematologic malignancies were at the highest risk of death. Patients receiving cancer-directed therapy within 3 months before hospitalization had no overall increased risk of death. LAY SUMMARY: Our investigators found that hospitalized patients with active cancer were more likely to die from coronavirus disease 2019 (COVID-19) than those with a history of cancer and those without any cancer history. Patients with hematologic cancers were the most likely among patients with cancer to die from COVID-19. Patients who received cancer therapy within 3 months before hospitalization did not have an increased risk of death.

Global Risk and Elimination of Yellow Fever Epidemics.

BACKGROUND: Yellow fever (YF) is a vector-borne viral hemorrhagic disease endemic in Africa and Latin America. In 2016, the World Health Organization (WHO) developed the Eliminate YF Epidemics strategy aiming at eliminating YF epidemics by 2026. METHODS: We developed a spatiotemporal model of YF, accounting for the impact of temperature, vector distribution, and socioeconomic factors on disease transmission. We validated our model against previous estimates of YF basic reproductive number (R0). We used the model to estimate global risk of YF outbreaks and vaccination efforts needed to achieve elimination of YF epidemics. RESULTS: We showed that the global risk of YF outbreaks is highly heterogeneous. High-risk transmission areas (R0 > 6) are mainly found in West Africa and the Equatorial region of Latin America. We showed that vaccination coverage needed to eliminate YF epidemics in an endemic country varies substantially between districts. In many endemic countries, a 90% vaccination coverage is needed to achieve elimination. However, in some high-risk districts in Africa, a 95% coverage may be required. CONCLUSIONS: Global elimination of YF epidemics requires higher population-level immunity than the 80% coverage recommended by the WHO. Optimal YF vaccination strategy should be tailored to the risk profile of each endemic country.

Pulse oximetry screening to detect critical congenital heart diseases in asymptomatic neonates.

BACKGROUND: Critical congenital heart diseases (CCHDs), 10% to 25% of all CHD, are duct-dependent defects that are life threatening without intervention in the neonatal period or infancy. One third of neonates with CCHDs are discharged home undetected and have a poorer outcome. Pulse oximetry screening before discharge is increasingly being used to diagnose CCHDs in developed countries. METHODS: This prospective observational study conducted at a tertiary care hospital from September 2016 to March 2019 screened all asymptomatic intramural neonates after 24 hours of life using a Masimo pulse oximeter with signal extraction technology using the standard American Academy of Pediatrics algorithm. A positive screen was followed by a confirmatory echocardiography (gold standard) and a negative screen by clinical examination at 6, 10 and 14 weeks and identification of readmissions during the study period. RESULTS: A total of 1855 neonates (82.99% of the eligible 2235 neonates) underwent screening at a mean (SD) age at screening of 32.4 (6.8) hours and took a mean (SD) time of 3.5 (1.2) minutes. The sensitivity, specificity, positive and negative predictive value of pulse oximetry screening for detection of CCHDs in asymptomatic neonates was 75% (95% CI: 28.91% to 96.59%), 99.29% (95% CI: 98.79% to 99.60%), 18.75% (95% CI: 5.80% to 43.80%) and 99.94% (95% CI: 99.66 to 99.99%), respectively. CONCLUSION: Pulse oximetry screening of asymptomatic neonates between 24 and 48 hours of life improved the detection of CCHDs with high specificity and negative predictive value, moderate sensitivity and a reasonably low false positivity rate.

Human platelets express functional ectonucleotidases that restrict platelet activation signaling.

Platelets play central role in thrombosis and haemostasis. Platelets store adenine nucleotides in their dense granules, which are released upon agonist-stimulation. Level of these nucleotides in extracellular fluid is regulated by activities of ectonucleotidases such as ectonucleoside triphosphate diphosphohydrolase-1 (CD39) and ecto-5'-nucleotidase (CD73) expressed on platelet surface. Here we demonstrate that, expression of surface-bound ectonucleotidases rose significantly in platelets, concomitant with upregulation of their enzymatic activities, when cells were stimulated with thrombin. Interestingly, inhibition of CD73 in thrombin-treated platelets led to enhanced tyrosine phosphorylation of proteins and rise in intracellular free calcium, [Ca2+]i, thus signifying the inhibitory role of the ectonucleotidase on agonist-mediated platelet signaling.

External validation of novel magnetic resonance imaging-based models for prostate cancer prediction.

OBJECTIVES: To validate, in an external cohort, three novel risk models, including the recently updated European Randomized Study of Screening for Prostate Cancer (ERSPC) risk calculator, that combine multiparametric magnetic resonance imaging (mpMRI) and clinical variables to predict clinically significant prostate cancer (PCa). PATIENTS AND METHODS: We retrospectively analysed 307 men who underwent mpMRI prior to transperineal ultrasound fusion biopsy between October 2015 and July 2018 at two German centres. mpMRI was rated by Prostate Imaging Reporting and Data System (PI-RADS) v2.0 and clinically significant PCa was defined as International Society of Urological Pathology Gleason grade group ≥2. The prediction performance of the three models (MRI-ERSPC-3/4, and two risk models published by Radtke et al. and Distler et al., ModRad and ModDis) were compared using receiver-operating characteristic (ROC) curve analyses, with area under the ROC curve (AUC), calibration curve analyses and decision curves used to assess net benefit. RESULTS: The AUCs of the three novel models (MRI-ERSPC-3/4, ModRad and ModDis) were 0.82, 0.85 and 0.83, respectively. Calibration curve analyses showed the best intercept for MRI-ERSPC-3 and -4 of 0.35 and 0.76. Net benefit analyses indicated clear benefit of the MRI-ERSPC-3/4 risk models compared with the other two validated models. The MRI-ERSPC-3/4 risk models demonstrated a discrimination benefit for a risk threshold of up to 15% for clinically significant PCa as compared to the other risk models. CONCLUSION: In our external validation of three novel prostate cancer risk models, which incorporate mpMRI findings, a head-to-head comparison indicated that the MRI-ERSPC-3/4 risk model in particular could help to reduce unnecessary biopsies.