Final analysis of phase II results with cemiplimab in metastatic basal cell carcinoma after hedgehog pathway inhibitors.

BACKGROUND: Metastatic basal cell carcinoma (mBCC) is a rare condition with no effective second-line treatment options. Cemiplimab is an immune checkpoint inhibitor that blocks the binding of programmed cell death-1 (PD-1) to its ligands, programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2). Here, we present the final analysis of cemiplimab in patients with mBCC after first-line hedgehog pathway inhibitor (HHI) treatment (NCT03132636). PATIENTS AND METHODS: In this open-label, single-arm, phase II study, adults with mBCC and Eastern Cooperative Oncology Group performance status ≤1, post-HHI treatment, received cemiplimab 350 mg intravenously every 3 weeks for ≤93 weeks or until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by independent central review (ICR). Duration of response (DOR) was a key secondary endpoint. Other secondary endpoints were ORR per investigator assessment, progression-free survival (PFS), overall survival (OS), complete response rate, safety, and tolerability. RESULTS: Fifty-four patients were enrolled: 70% were male and the median age of patients was 64 [interquartile range (IQR) 57.0-73.0] years. The median duration of follow-up was 8 months (IQR 4-21 months). The ORR per ICR was 22% [95% confidence interval (CI) 12% to 36%], with 2 complete responses and 10 partial responses. Among responders, the median time to response per ICR was 3 months (IQR 2-7 months). The estimated median DOR per ICR was not reached [95% CI 10 months-not evaluable (NE)]. The disease control rate was 63% (95% CI 49% to 76%) per ICR and 70% (95% CI 56% to 82%) per investigator assessment. The median PFS per ICR was 10 months (95% CI 4-16 months); the median OS was 50 months (95% CI 28 months-NE). The most common treatment-emergent adverse events were fatigue [23 (43%)] and diarrhoea [20 (37%)]. There were no treatment-related deaths. CONCLUSIONS: Cemiplimab demonstrated clinically meaningful antitumour activity, including durable responses, and an acceptable safety profile in patients with mBCC who had disease progression on or intolerance to HHI therapy.

Researching COVID to enhance recovery (RECOVER) pregnancy study: Rationale, objectives and design.

IMPORTANCE: Pregnancy induces unique physiologic changes to the immune response and hormonal changes leading to plausible differences in the risk of developing post-acute sequelae of SARS-CoV-2 (PASC), or Long COVID. Exposure to SARS-CoV-2 during pregnancy may also have long-term ramifications for exposed offspring, and it is critical to evaluate the health outcomes of exposed children. The National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC aims to evaluate the long-term sequelae of SARS-CoV-2 infection in various populations. RECOVER-Pregnancy was designed specifically to address long-term outcomes in maternal-child dyads. METHODS: RECOVER-Pregnancy cohort is a combined prospective and retrospective cohort that proposes to enroll 2,300 individuals with a pregnancy during the COVID-19 pandemic and their offspring exposed and unexposed in utero, including single and multiple gestations. Enrollment will occur both in person at 27 sites through the Eunice Kennedy Shriver National Institutes of Health Maternal-Fetal Medicine Units Network and remotely through national recruitment by the study team at the University of California San Francisco (UCSF). Adults with and without SARS-CoV-2 infection during pregnancy are eligible for enrollment in the pregnancy cohort and will follow the protocol for RECOVER-Adult including validated screening tools, laboratory analyses and symptom questionnaires followed by more in-depth phenotyping of PASC on a subset of the overall cohort. Offspring exposed and unexposed in utero to SARS-CoV-2 maternal infection will undergo screening tests for neurodevelopment and other health outcomes at 12, 18, 24, 36 and 48 months of age. Blood specimens will be collected at 24 months of age for SARS-CoV-2 antibody testing, storage and anticipated later analyses proposed by RECOVER and other investigators. DISCUSSION: RECOVER-Pregnancy will address whether having SARS-CoV-2 during pregnancy modifies the risk factors, prevalence, and phenotype of PASC. The pregnancy cohort will also establish whether there are increased risks of adverse long-term outcomes among children exposed in utero. CLINICAL TRIALS.GOV IDENTIFIER: Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011.

Otitis media at 6-monthly assessments of Australian First Nations children between ages 12-36 months: Findings from two randomised controlled trials of combined pneumococcal conjugate vaccines.

OBJECTIVES: In remote communities of northern Australia, First Nations children with hearing loss are disproportionately at risk of poor school readiness and performance compared to their peers with no hearing loss. The aim of this trial is to prevent early childhood persisting otitis media (OM), associated hearing loss and developmental delay. To achieve this, we designed a mixed pneumococcal conjugate vaccine (PCV) schedule that could maximise immunogenicity and thereby prevent bacterial otitis media (OM) and a trajectory of educational and social disadvantage. METHODS: In two sequential parallel, open-label, randomised controlled trials, eligible infants were first allocated 1:1:1 to standard or mixed PCV primary schedules at age 28-38 days, then at age 12 months to a booster dose (1:1) of 13-valent PCV, PCV13 (Prevenar13®, +P), or 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugated vaccine, PHiD-CV10 (Synflorix®, +S). Here we report findings of standardised ear assessments conducted six-monthly from age 12-36 months, by booster dose. RESULTS: From March 2013 to September 2018, 261 children were allocated to booster + P (n = 131) or + S (n = 130). There were no significant differences in prevalence of any OM diagnosis by booster dose or when stratified by primary schedule. We found high, almost identical prevalence of OM in both boost groups at each age (for example 88% of 129 and 91% of 128 children seen, respectively, at primary endpoint age 18 months, difference -3% [95% Confidence Interval -11, 5]). At each age prevalence of bilateral OM was 52%-78%, and tympanic membrane perforation was 10%-18%. CONCLUSION: Despite optimal pneumococcal immunisation, the high prevalence of OM persists throughout early childhood. Novel approaches to OM prevention are needed, along with improved early identification strategies and evaluation of expanded valency PCVs.

Disease burden, comorbidities and antecedents of chronic cough phenotypes in Australian adults.

BACKGROUND AND OBJECTIVES: While adult chronic cough has high burden, its phenotypes, particularly those without aetiologically related underlying conditions, are understudied. We investigated the prevalence, lung function and comorbidities of adult chronic cough phenotypes. METHODS: Data from 3608 participants aged 53 years from the Tasmanian Longitudinal Health Study (TAHS) were included. Chronic cough was defined as cough on most days for >3 months in a year. Chronic cough was classified into "explained cough" if there were any one of four major cough-associated conditions (asthma, COPD, gastroesophageal reflux disease or rhinosinusitis) or "unexplained cough" if none were present. Adjusted regression analyses investigated associations between these chronic cough phenotypes, lung function and non-respiratory comorbidities at 53 years. RESULTS: The prevalence of chronic cough was 10% (95%CI 9.1,11.0%) with 46.4% being "unexplained". Participants with unexplained chronic cough had lower FEV1/FVC (coefficient: -1.2% [95%CI:-2,3, -0.1]) and increased odds of comorbidities including obesity (OR=1.6 [95%CI: 1.2, 2.3]), depression (OR=1.4 [95%CI: 1.0, 2.1]), hypertension (OR=1.7 [95%CI: 1.2, 2.4]) and angina, heart attack or myocardial infarction to a lesser extent, compared to those without chronic cough. Participants with explained chronic cough also had lower lung function than both those with unexplained chronic cough and those without chronic cough. CONCLUSIONS: Chronic cough is prevalent in middle-age and a high proportion is unexplained. Unexplained cough contributes to poor lung function and increased comorbidities. Given unexplained chronic cough is not a symptom of major underlying respiratory conditions it should be targeted for better understanding in both clinical settings and research.

Molecular characterization of porcine circovirus-2 and -3 in pigs in Tanzania.

Like in many other African countries, pig production is increasing in Tanzania. To support farmers and stakeholders, it is important to increase our understanding of porcine pathogens present in the country. Currently, little is known about the circulation of porcine circovirus-2 (PCV-2) and porcine circovirus-3 (PCV-3). For this reason, samples from 124 pigs collected throughout the country between 2018 to 2022 were screened by PCR for the presence of PCV-2 and PCV-3. Sequencing and phylogenetic analysis of positive amplicons identified two PCV-2 genotypes (a and d). Limited genetic heterogenicity was observed among the PCV-3. This study provides important data on pathogens present in pigs in Tanzania and should be of use veterinary authorities involved in porcine disease management.

Researching COVID to enhance recovery (RECOVER) pregnancy study: Rationale, objectives and design.

Importance: Pregnancy induces unique physiologic changes to the immune response and hormonal changes leading to plausible differences in the risk of developing post-acute sequelae of SARS-CoV-2 (PASC), or Long COVID. Exposure to SARS-CoV-2 during pregnancy may also have long-term ramifications for exposed offspring, and it is critical to evaluate the health outcomes of exposed children. The National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC aims to evaluate the long-term sequelae of SARS-CoV-2 infection in various populations. RECOVER- Pregnancy was designed specifically to address long-term outcomes in maternal-child dyads. Methods: RECOVER-Pregnancy cohort is a combined prospective and retrospective cohort that proposes to enroll 2,300 individuals with a pregnancy during the COVID-19 pandemic and their offspring exposed and unexposed in utero, including single and multiple gestations. Enrollment will occur both in person at 27 sites through the Eunice Kennedy Shriver National Institutes of Health Maternal-Fetal Medicine Units Network and remotely through national recruitment by the study team at the University of California San Francisco (UCSF). Adults with and without SARS-CoV-2 infection during pregnancy are eligible for enrollment in the pregnancy cohort and will follow the protocol for RECOVER-Adult including validated screening tools, laboratory analyses and symptom questionnaires followed by more in-depth phenotyping of PASC on a subset of the overall cohort. Offspring exposed and unexposed in utero to SARS-CoV-2 maternal infection will undergo screening tests for neurodevelopment and other health outcomes at 12, 18, 24, 36 and 48 months of age. Blood specimens will be collected at 24 months of age for SARS-CoV-2 antibody testing, storage and anticipated later analyses proposed by RECOVER and other investigators. Discussion: RECOVER-Pregnancy will address whether having SARS-CoV-2 during pregnancy modifies the risk factors, prevalence, and phenotype of PASC. The pregnancy cohort will also establish whether there are increased risks of adverse long-term outcomes among children exposed in utero. Registration: NCT05172024.

Application of machine learning algorithms to predict osteoporosis in postmenopausal women with type 2 diabetes mellitus.

PURPOSE: The screening and diagnosis of osteoporosis in patients with type 2 diabetes mellitus (T2DM) based on bone mineral density remains challenging because of the limited availability and accessibility of dual-energy X-ray absorptiometry. We aimed to develop and validate models to predict the risk of osteoporosis in postmenopausal women with T2DM based on machine learning (ML) algorithms. METHODS: This retrospective study included 303 postmenopausal women with T2DM. To develop prediction models for osteoporosis, we applied nine ML algorithms combined with demographic, clinical, and laboratory data. The least absolute shrinkage and selection operator were used to perform feature selection. We used the bootstrap resampling technique for model training and validation. To test the performance of the models, we calculated indices including the area under the receiver operating characteristic curve (AUROC), accuracy, sensitivity, specificity, positive predictive value, negative predictive value, F1 score, calibration curve, and decision curve analysis. Furthermore, we conducted fivefold cross-validation for parameter optimization and model validation. Feature importance was assessed using the SHapley additive explanation (SHAP). RESULTS: We identified 10 independent predictors as the most valuable features. An AUROC of 0.616-1.000 was observed for nine ML algorithms. The extreme gradient boosting (XGBoost) model exhibited the best performance, outperforming conventional risk assessment tools and registering 0.993 in the training set, 0.798 in the validation set, and 0.786 in the test set for fivefold cross-validation. Using SHAP, we found that the explanatory variables contributed to the model and their relationship with osteoporosis occurrence. Furthermore, we developed a user-friendly tool for calculating the risk of osteoporosis. CONCLUSIONS: With the integration of demographic and clinical risk factors, ML algorithms can accurately predict osteoporosis. The XGBoost model showed ideal performance. With the incorporation of these models in the clinic, patients may benefit from early osteoporosis diagnosis and treatment.

Age-Dependent Electroencephalogram Features in Infants Under Spinal Anesthesia Appear to Mirror Physiologic Sleep in the Developing Brain: A Prospective Observational Study.

BACKGROUND: Infants under spinal anesthesia appear to be sedated despite the absence of systemic sedative medications. In this prospective observational study, we investigated the electroencephalogram (EEG) of infants under spinal anesthesia and hypothesized that we would observe EEG features similar to those seen during sleep. METHODS: We computed the EEG power spectra and spectrograms of 34 infants undergoing infraumbilical surgeries under spinal anesthesia (median age 11.5 weeks postmenstrual age, range 38-65 weeks postmenstrual age). Spectrograms were visually scored for episodes of EEG discontinuity or spindle activity. We characterized the relationship between EEG discontinuity or spindles and gestational age, postmenstrual age, or chronological age using logistic regression analyses. RESULTS: The predominant EEG patterns observed in infants under spinal anesthesia were slow oscillations, spindles, and EEG discontinuities. The presence of spindles, observed starting at about 49 weeks postmenstrual age, was best described by postmenstrual age ( P =.002) and was more likely with increasing postmenstrual age. The presence of EEG discontinuities, best described by gestational age ( P = .015), was more likely with decreasing gestational age. These age-related changes in the presence of spindles and EEG discontinuities in infants under spinal anesthesia generally corresponded to developmental changes in the sleep EEG. CONCLUSIONS: This work illustrates 2 separate key age-dependent transitions in EEG dynamics during infant spinal anesthesia that may reflect the maturation of underlying brain circuits: (1) diminishing discontinuities with increasing gestational age and (2) the appearance of spindles with increasing postmenstrual age. The similarity of these age-dependent transitions under spinal anesthesia with transitions in the developing brain during physiological sleep supports a sleep-related mechanism for the apparent sedation observed during infant spinal anesthesia.

A Phylogeographic Analysis of Porcine Parvovirus 1 in Africa.

Porcine parvovirus 1 (PPV1) is recognized as a major cause of reproductive failure in pigs, leading to several clinical outcomes globally known as SMEDI. Despite being known since the late 1960s its circulation is still of relevance to swine producers. Additionally, the emergence of variants such as the virulent 27a strain, for which lower protection induced by vaccines has been demonstrated, is of increasing concern. Even though constant monitoring of PPV1 using molecular epidemiological approaches is of pivotal importance, viral sequence data are scarce especially in low-income countries. To fill this gap, a collection of 71 partial VP2 sequences originating from eight African countries (Burkina Faso, Côte d'Ivoire, Kenya, Mozambique, Namibia, Nigeria, Senegal, and Tanzania) during the period 2011-2021 were analyzed within the context of global PPV1 variability. The observed pattern largely reflected what has been observed in high-income regions, i.e., 27a-like strains were more frequently detected than less virulent NADL-8-like strains. A phylogeographic analysis supported this observation, highlighting that the African scenario has been largely shaped by multiple PPV1 importation events from other continents, especially Europe and Asia. The existence of such an international movement coupled with the circulation of potential vaccine-escape variants requires the careful evaluation of the control strategies to prevent new strain introduction and persistence.

Prior differences in previous trauma exposure primarily drive the observed racial/ethnic differences in posttrauma depression and anxiety following a recent trauma.

BACKGROUND: Racial and ethnic groups in the USA differ in the prevalence of posttraumatic stress disorder (PTSD). Recent research however has not observed consistent racial/ethnic differences in posttraumatic stress in the early aftermath of trauma, suggesting that such differences in chronic PTSD rates may be related to differences in recovery over time. METHODS: As part of the multisite, longitudinal AURORA study, we investigated racial/ethnic differences in PTSD and related outcomes within 3 months after trauma. Participants (n = 930) were recruited from emergency departments across the USA and provided periodic (2 weeks, 8 weeks, and 3 months after trauma) self-report assessments of PTSD, depression, dissociation, anxiety, and resilience. Linear models were completed to investigate racial/ethnic differences in posttraumatic dysfunction with subsequent follow-up models assessing potential effects of prior life stressors. RESULTS: Racial/ethnic groups did not differ in symptoms over time; however, Black participants showed reduced posttraumatic depression and anxiety symptoms overall compared to Hispanic participants and White participants. Racial/ethnic differences were not attenuated after accounting for differences in sociodemographic factors. However, racial/ethnic differences in depression and anxiety were no longer significant after accounting for greater prior trauma exposure and childhood emotional abuse in White participants. CONCLUSIONS: The present findings suggest prior differences in previous trauma exposure partially mediate the observed racial/ethnic differences in posttraumatic depression and anxiety symptoms following a recent trauma. Our findings further demonstrate that racial/ethnic groups show similar rates of symptom recovery over time. Future work utilizing longer time-scale data is needed to elucidate potential racial/ethnic differences in long-term symptom trajectories.

Recent Advances In Silicon Carbide Chemical Mechanical Polishing Technologies.

Chemical mechanical polishing (CMP) is a well-known technology that can produce surfaces with outstanding global planarization without subsurface damage. A good CMP process for Silicon Carbide (SiC) requires a balanced interaction between SiC surface oxidation and the oxide layer removal. The oxidants in the CMP slurry control the surface oxidation efficiency, while the polishing mechanical force comes from the abrasive particles in the CMP slurry and the pad asperity, which is attributed to the unique pad structure and diamond conditioning. To date, to obtain a high-quality as-CMP SiC wafer, the material removal rate (MRR) of SiC is only a few micrometers per hour, which leads to significantly high operation costs. In comparison, conventional Si CMP has the MRR of a few micrometers per minute. To increase the MRR, improving the oxidation efficiency of SiC is essential. The higher oxidation efficiency enables the higher mechanical forces, leading to a higher MRR with better surface quality. However, the disparity on the Si-face and C-face surfaces of 4H- or 6H-SiC wafers greatly increases the CMP design complexity. On the other hand, integrating hybrid energies into the CMP system has proven to be an effective approach to enhance oxidation efficiency. In this review paper, the SiC wafering steps and their purposes are discussed. A comparison among the three configurations of SiC CMP currently used in the industry is made. Moreover, recent advances in CMP and hybrid CMP technologies, such as Tribo-CMP, electro-CMP (ECMP), Fenton-ECMP, ultrasonic-ECMP, photocatalytic CMP (PCMP), sulfate-PCMP, gas-PCMP and Fenton-PCMP are reviewed, with emphasis on their oxidation behaviors and polishing performance. Finally, we raise the importance of post-CMP cleaning and make a summary of the various SiC CMP technologies discussed in this work.

A pre-admission triaging tool to predict severe COVID-19 cases: ABCD score.

INTRODUCTION: Isolation of SARS-CoV-2-infected individuals is an important COVID-19 pandemic control measure. While most cases have uncomplicated infection, a small proportion of them has developed life-threatening disease. We set up a retrospective study to determine preadmission triaging tool to predict the development of severe COVID-19. MATERIALS AND METHODS: A retrospective study was conducted from 1 October 2020 to 31 January 2021 with enrolment of all SARS-CoV-2 PCR-confirmed persons aged ≥13 years. The disease severity was assessed on admission and daily throughout the hospitalisation. Test-positive individuals were considered as having "severe COVID-19" if they had ≥1 of the following: room air oxygen saturation 30 breaths/minute, signs of severe respiratory distress, or received mechanical ventilation and/or vasopressor therapy. Uni- and multi-variate analyses using SPSS Statistics Ver. 26 were performed. RESULTS: We showed that age ≥ 60 years, BMI ≥ 30.0, presentation on days 7-12 of illness, and ≥1 comorbidity were associated with development of severe COVID-19. A scoring system based on the four variables is a useful COVID-19 risk assessment tool. A total score ≥2 had a sensitivity of 60.9%, specificity of 88.2%, positive predictive value of 37.8% and negative predictive value of 95.0%. CONCLUSION: Development of preadmission triaging tool can help health care providers (HCPs) decide on the placement of test-positive individuals to appropriate isolation facilities according to the risk of developing severe COVID-19.

Characterization of dermatological diagnoses among hospitalized patients experiencing homelessness.

While previous studies have characterized the types of dermatological disease among people experiencing homelessness (PEH) in the outpatient setting, dermatological disease among hospitalized PEH has never been evaluated. Therefore, we performed a cross-sectional analysis of hospitalized patients who received dermatology consultations at two San Francisco hospitals between March 2018 and March 2020 and compared the odds of diagnostic categories between PEH and patients with stable housing. In both unadjusted and adjusted analyses, PEH had significantly higher odds of bacterial skin infections [adjusted odds ratio (aOR) = 2.29, 95% CI 1.46-3.61], ectoparasitic disease (aOR = 9.43, 95% CI 3.79-23.47), psoriasis or seborrhoeic dermatitis (aOR = 2.50, 95% CI 1.43-4.36) and venous stasis or lymphoedema (aOR = 2.54, 95% CI 1.23-5.27) and significantly lower odds of drug reactions (aOR = 0.34, 95% CI 0.18-0.67). Overall, these findings highlight the unique dermatological challenges among hospitalized PEH and suggest potential strategies to facilitate equitable dermatology care delivery.

Novel role of estrogen receptor-α on regulating chondrocyte phenotype and response to mechanical loading.

OBJECTIVE: In knee cartilage from patients with osteoarthritis (OA), both preserved cartilage and damaged cartilage are observed. In this study, we aim to compare preserved with damaged cartilage to identify the molecule(s) that may be responsible for the mechanical loading-induced differences within cartilage degradation. METHODS: Preserved and damaged cartilage were harvested from the same OA knee joint. RNA Sequencing was performed to examine the transcriptomic differences between preserved and damaged cartilage cells. Estrogen receptor-α (ERα) was identified, and its function of was tested through gene knockin and knockout. The role of ERα in mediating chondrocyte response to mechanical loading was examined via compression of chondrocyte-laded hydrogel in a strain-controlled manner. Findings from the studies on human samples were verified in animal models. RESULTS: Level of estrogen receptor α (ERα) was significantly reduced in damaged cartilage compared to preserved cartilage, which were observed in both human and mice samples. Knockdown of ESR1, the gene encoding ERα, resulted in an upregulation of senescence- and OA-relevant markers in chondrocytes. Conversely, knockin of ESR1 partially reversed the osteoarthritic and senescent phenotype of OA chondrocytes. Using a three-dimensional (3D) culture model, we demonstrated that mechanical overload significantly suppressed ERα level in chondrocytes with concomitant upregulation of osteoarthritic phenotype. When ESR1 expression was suppressed, mechanical loading enhanced hypertrophic and osteogenic transition. CONCLUSION: Our study demonstrates a new estrogen-independent role of ERα in mediating chondrocyte phenotype and its response to mechanical loading, and suggests that enhancing ERα level may represent a new method to treat osteoarthritis.

Porcine circovirus-2 in Africa: Identification of continent-specific clusters and evidence of independent viral introductions from Europe, North America and Asia.

Porcine circovirus-2 (PCV-2) is associated with several disease syndromes in domestic pigs that have a significant impact on global pig production and health. Currently, little is known about the status of PCV-2 in Africa. In this study, a total of 408 archived DNA samples collected from pigs in Burkina Faso, Cameroon, Cape Verde, Ethiopia, the Democratic Republic of the Congo, Mozambique, Nigeria, Senegal, Tanzania and Zambia between 2000 and 2018 were screened by PCR for the presence of PCV-2. Positive amplicons of the gene encoding the viral capsid protein (ORF2) were sequenced to determine the genotypes circulating in each country. Four of the nine currently known genotypes of PCV-2 were identified (i.e. PCV-2a, PCV-2b, PCV-2d and PCV-2 g) with more than one genotype being identified in Burkina Faso, Ethiopia, Nigeria, Mozambique, Senegal and Zambia. Additionally, a phylogeographic analysis which included 38 additional ORF2 gene sequences of PCV-2s previously identified in Mozambique, Namibia and South Africa from 2014 to 2016 and 2019 to 2020 and available in public databases, demonstrated the existence of several African-specific clusters and estimated the approximate time of introduction of PCV-2s into Africa from other continents. This is the first in-depth study of PCV-2 in Africa and it has important implications for pig production at both the small-holder and commercial farm level on the continent.

Discontinuation Patterns and Cost Avoidance of a Pharmacist-Driven Methicillin-Resistant Staphylococcus aureus Nasal Polymerase Chain Reaction Testing Protocol for De-escalation of Empiric Vancomycin for Suspected Pneumonia.

A pharmacist-driven methicillin-resistant Staphylococcus aureus (MRSA) nasal polymerase chain reaction (PCR)-based testing protocol with a 70% acceptance rate for vancomycin discontinuation within 24 hours of negative results significantly reduced unnecessary vancomycin use with an estimated cost avoidance of $40 per vancomycin course. We found high concordance (141 of 147, 96%) of culture-based versus PCR-based MRSA nasal screening.

External quality assessment of Rift Valley fever diagnosis in countries at risk of the disease: African, Indian Ocean and Middle-East regions.

Rift Valley fever virus (RVFV), an arbovirus belonging to the Phlebovirus genus of the Phenuiviridae family, causes the zoonotic and mosquito-borne RVF. The virus, which primarily affects livestock (ruminants and camels) and humans, is at the origin of recent major outbreaks across the African continent (Mauritania, Libya, Sudan), and in the South-Western Indian Ocean (SWIO) islands (Mayotte). In order to be better prepared for upcoming outbreaks, to predict its introduction in RVFV unscathed countries, and to run efficient surveillance programmes, the priority is harmonising and improving the diagnostic capacity of endemic countries and/or countries considered to be at risk of RVF. A serological inter-laboratory proficiency test (PT) was implemented to assess the capacity of veterinary laboratories to detect antibodies against RVFV. A total of 18 laboratories in 13 countries in the Middle East, North Africa, South Africa, and the Indian Ocean participated in the initiative. Two commercial kits and two in-house serological assays for the detection of RVFV specific IgG antibodies were tested. Sixteen of the 18 participating laboratories (88.9%) used commercial kits, the analytical performance of test sensitivity and specificity based on the seroneutralisation test considered as the reference was 100%. The results obtained by the laboratories which used the in-house assay were correct in only one of the two criteria (either sensitivity or specificity). In conclusion, most of the laboratories performed well in detecting RVFV specific IgG antibodies and can therefore be considered to be prepared. Three laboratories in three countries need to improve their detection capacities. Our study demonstrates the importance of conducting regular proficiency tests to evaluate the level of preparedness of countries and of building a network of competent laboratories in terms of laboratory diagnosis to better face future emerging diseases in emergency conditions.

Current assessment of parental and health professional perception of the colour of neonatal vomiting: Results of a scoping survey.

PURPOSE: To determine current perceptions of doctors, nurses and parents for the colour of a neonatal vomit which should prompt an urgent surgical review. METHODS: A voluntary scoping survey of parents/guardians of patients and non-surgical healthcare professionals was conducted with respondents asked to choose from 8 different selections in a colour swatch from pale yellow to dark green. A control group consisted of 13 paediatric surgeons. Data were analysed using the paired t test, Fishers exact test. A p value of < 0.05 was considered to be significant. RESULTS: 365 participants responded: 36% (131/365) parents, 18% (64/365) nurses and 46% (166/365) doctors. 4/365 (1%) did not state their role. 343 participants completed all questions and responses were analysed using total responses for each question. 82% (121/148) of doctors and 78% (50/64) of nurses had more than 3 years of post-graduate experience. Overall, 63% (227/361) of participants (100% paediatric surgeons, 78% other doctors, 75% nurses/midwives & 30% parents) considered dark and light green vomits to be a sign of intestinal obstruction. 67% (242/361) of participants (100% paediatric surgeons, 72% other doctors, 56% nurses/midwives and 62% parents) believed dark and light green vomiting needed an urgent surgical referral. There were significant differences between the control group and other groups in terms of whether the neonate could wait until the next day for a review; nursing staff (p = 0.0002), postnatal/midwifery (p = < 0.0001), emergency medicine (p = 0.04), general practice (p = 0.002), neonatal (p = 0.0001) and paediatricians (p = 0.005). Only the neonatologists (p = 0.04), nursing staff (p = 0.001) and postnatal/midwifery (p = 0.004) believed that the neonate could have safe observation. CONCLUSION: Although the perception that green vomiting is potentially serious is acknowledged by the majority of healthcare professionals surveyed, there is still a requirement for more targeted educational practices in nursing, midwifery and medical staff.

CRS-related coagulopathy in BCMA targeted CAR-T therapy: a retrospective analysis in a phase I/II clinical trial.

Chimeric antigen receptor (CAR) T-cell therapy that targets B-cell maturation antigen (BCMA) has shown promising effects in the treatment of patients with refractory/relapsed multiple myeloma (R/R MM) patients. In this retrospective analysis of phase I/II clinical trial (ChiCTR1800017404), 37 patients with R/R MM received their first BCMA-targeted CAR T-cells following lymphodepletion chemotherapy. The response rate was high (97%), while accompanied by a high incidence of adverse events including coagulation dysfunction. Of 37 patients, all (100%) had cytokine release syndrome (CRS) and 34 (91%) developed at least one abnormal coagulation parameter. The values of coagulation parameters were positively correlated with the severity of CRS as well as with the levels of some cytokines, such as interleukin (IL)-6, IL-10, and interferon (IFN)-γ, etc. Furthermore, levels of the plasma tissue factor (TF), Factor X (FX), Factor XII (FXII), and P-selectin also showed a positive correlation with severity of CRS as well as some specific cytokines, which indicates that these factors are likely to play important roles in CRS-related coagulopathy. Our study suggests that there exists relationship in some extent between coagulation disorder and CRS. Moreover, coagulation dysfunction can be managed with daily monitoring and early intervention despite high incidence.