Psychometric Properties of the PANS 31-Item Symptom Rating Scale.

Objectives: Pediatric acute-onset neuropsychiatric syndrome (PANS) is characterized by sudden onset of obsessive-compulsive disorder and/or eating restriction with associated neuropsychiatric symptoms from at least two of seven categories. The PANS 31-Item Symptom Rating Scale (PANS Rating Scale) was developed to identify and measure the severity of PANS symptoms. The objective of this study was to define the psychometric properties of the PANS Rating Scale. Methods: Children with PANS (N = 135) and their parents participated. Parents completed the PANS Rating Scale and other scales on Research Electronic Data Capture. The PANS Rating Scale includes 31 items that are rated on a Likert scale from 0 = none to 4 = extreme. Pearson's correlations were run between the PANS Total score and scores on the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), Yale Global Tic Severity Scale (YGTSS), Modified Overt Aggression Scale (MOAS), Columbia Impairment Scale (CIS), PANS Global Impairment Score (GIS), and Children's Global Assessment Scale (CGAS). Results: Convergent validity was supported by significant correlations between the PANS Total and scores on the CY-BOCS, YGTSS, MOAS, CIS, GIS, and CGAS. The largest correlations were with measures of functional impairment: PANS Total and CIS (r = 0.81) and PANS Total and GIS (r = 0.74). Cronbach's alpha was 0.89 which demonstrates strong internal consistency of the 31 items. PANS Total score was significantly higher in children in a flare of their neuropsychiatric symptoms compared to children who were not in a flare. Conclusions: This study provides preliminary support for the PANS Rating Scale as a valid research instrument with good internal consistency. The PANS Rating Scale appears to be a useful measure for assessing children with PANS.

Altered receptor binding, antibody evasion and retention of T cell recognition by the SARS-CoV-2 XBB.1.5 spike protein.

The XBB.1.5 variant of SARS-CoV-2 has rapidly achieved global dominance and exhibits a high growth advantage over previous variants. Preliminary reports suggest that the success of XBB.1.5 stems from mutations within its spike glycoprotein, causing immune evasion and enhanced receptor binding. We present receptor binding studies that demonstrate retention of binding contacts with the human ACE2 receptor and a striking decrease in binding to mouse ACE2 due to the revertant R493Q mutation. Despite extensive evasion of antibody binding, we highlight a region on the XBB.1.5 spike protein receptor binding domain (RBD) that is recognized by serum antibodies from a donor with hybrid immunity, collected prior to the emergence of the XBB.1.5 variant. T cell assays reveal high frequencies of XBB.1.5 spike-specific CD4+ and CD8+ T cells amongst donors with hybrid immunity, with the CD4+ T cells skewed towards a Th1 cell phenotype and having attenuated effector cytokine secretion as compared to ancestral spike protein-specific cells. Thus, while the XBB.1.5 variant has retained efficient human receptor binding and gained antigenic alterations, it remains susceptible to recognition by T cells induced via vaccination and previous infection.

Using Liver Organoids as Models to Study the Pathobiology of Rare Liver Diseases.

Liver organoids take advantage of several important features of pluripotent stem cells that self-assemble in a three-dimensional culture matrix and reproduce many aspects of the complex organization found within their native tissue or organ counterparts. Compared to other 2D or 3D in vitro models, organoids are widely believed to be genetically stable or docile structures that can be programmed to virtually recapitulate certain biological, physiological, or pathophysiological features of original tissues or organs in vitro. Therefore, organoids can be exploited as effective substitutes or miniaturized models for the study of the developmental mechanisms of rare liver diseases, drug discovery, the accurate evaluation of personalized drug responses, and regenerative medicine applications. However, the bioengineering of organoids currently faces many groundbreaking challenges, including a need for a reasonable tissue size, structured organization, vascularization, functional maturity, and reproducibility. In this review, we outlined basic methodologies and supplements to establish organoids and summarized recent technological advances for experimental liver biology. Finally, we discussed the therapeutic applications and current limitations.

Sentiment analysis of financial Twitter posts on Twitter with the machine learning classifiers.

This paper presents a sentiment analysis combining the lexicon-based and machine learning (ML)-based approaches in Turkish to investigate the public mood for the prediction of stock market behavior in BIST30, Borsa Istanbul. Our main motivation behind this study is to apply sentiment analysis to financial-related tweets in Turkish. We import 17189 tweets posted as "#Borsaistanbul, #Bist, #Bist30, #Bist100″ on Twitter between November 7, 2022, and November 15, 2022, via a MAXQDA 2020, a qualitative data analysis program. For the lexicon-based side, we use a multilingual sentiment offered by the Orange program to label the polarities of the 17189 samples as positive, negative, and neutral labels. Neutral labels are discarded for the machine learning experiments. For the machine learning side, we select 9076 data as positive and negative to implement the classification problem with six different supervised machine learning classifiers conducted in Python 3.6 with the sklearn library. In experiments, 80 % of the selected data is used for the training phase and the rest is used for the testing and validation phase. Results of the experiments show that the Support Vector Machine and Multilayer Perceptron classifier perform better than other classifiers with 0.89 and 0.88 accuracy and AUC values of 0.8729 and 0.8647 respectively. Other classifiers obtain approximately a 78,5 % accuracy rate. It is possible to increase sentiment analysis accuracy with parameter optimization on a larger, cleaner, and more balanced dataset by changing the pre-processing steps. This work can be expanded in the future to develop better sentiment analysis using deep learning approaches.

AAA ATPase protein-protein interactions as therapeutic targets in cancer.

AAA ATPases are a conserved group of enzymes that couple ATP hydrolysis to diverse activities critical for cellular homeostasis by targeted protein-protein interactions. Some of these interactions are potential therapeutic targets because of their role in cancers which rely on increased AAA ATPase activities for maintenance of genomic stability. Two well-characterized members of this family are p97/VCP and RUVBL ATPases where there is a growing understanding of their structure and function, as well as an emerging landscape of selective inhibitors. Here we highlight recent progress in this field, with particular emphasis on structural advances enabled by cryo-electron microscopy (cryo-EM).

Self-healing polymers for surface scratch regeneration.

Recently, there has been a significant increase in academic and industrial interest in self-healing polymers (SHPs) due to their remarkable ability to regenerate scratched surfaces and materials of astronomical significance. Scientists have been inspired by the magical repairing mechanism of the living world. They transformed the fiction of self-healing into reality by designing engrossing polymeric materials that could self-repair mechanical abrasions repeatedly. As a result, the durability of the materials is remarkably improved. Thus, the idea of studying SHPs passively upholds economic and environmental sustainability. However, the critical areas of self-healing (including healing efficiency, healing mechanism, and thermo-mechanical property changes during healing) are under continuous scientific improvisation. This review highlights recent notable advances of SHPs for application in regenerating scratched surfaces with various distinctive underlying mechanisms. The primary focus of the work is aimed at discussing the impact of SHPs on scratch-healing technology. Beyond that, insights regarding scratch testing, methods of investigating polymer surfaces, wound depths, the addition of healing fillers, and the environmental conditions maintained during the healing process are reviewed thoroughly. Finally, broader future perspectives on the challenges and prospects of SHPs in healing surface scratches are discussed.

Evaluation of Serial Testing After Exposure to COVID-19 in Early Care and Education Facilities, Illinois, March-May 2022.

OBJECTIVE: To understand SARS-CoV-2 transmission in early care and education (ECE) settings, we implemented a Test to Stay (TTS) strategy, which allowed children and staff who were close contacts to COVID-19 to remain in person if they agreed to test twice after exposure. We describe SARS-CoV-2 transmission, testing preferences, and the number of in-person days saved among participating ECE facilities. METHODS: From March 21 through May 27, 2022, 32 ECE facilities in Illinois implemented TTS. Unvaccinated children and staff who were not up to date with COVID-19 vaccination could participate if exposed to COVID-19. Participants received 2 tests within 7 days after exposure and were given the option to test at home or at the ECE facility. RESULTS: During the study period, 331 TTS participants were exposed to index cases (defined as people attending the ECE facility with a positive SARS-CoV-2 test result during the infectious period); 14 participants tested positive, resulting in a secondary attack rate of 4.2%. No tertiary cases (defined as a person with a positive SARS-CoV-2 test result within 10 days after exposure to a secondary case) occurred in the ECE facilities. Most participants (366 of 383; 95.6%) chose to test at home. Remaining in-person after an exposure to COVID-19 saved approximately 1915 in-person days among children and staff and approximately 1870 parent workdays. CONCLUSION: SARS-CoV-2 transmission rates were low in ECE facilities during the study period. Serial testing after COVID-19 exposure among children and staff at ECE facilities is a valuable strategy to allow children to remain in person and parents to avoid missing workdays.

Weight Loss of Over 100 lbs in a Patient of Prader-Willi Syndrome Treated With Glucagon-Like Peptide-1 (GLP-1) Agonists.

Prader-Willi syndrome (PWS) is the most common genetic obesity syndrome. The clinical features of this condition include childhood obesity, hyperphagia, infantile hypotonia, hypogonadism, short stature, and characteristic facial features. The leading cause of morbidity and mortality in PWS is hyperphagia and resultant obesity. Here, we highlight the effectiveness of glucagon-like peptide-1 (GLP-1) agonists by reporting an interesting case of successful rapid weight loss in an adult with PWS using GLP-1 agonists - exenatide and liraglutide. To the best of our knowledge, this report presents the first clinical evidence supporting the use of GLP-1 receptor agonists in the treatment of genetic obesity syndromes; our patient lost a total of 125 lbs on GLP-1 analog and continues to lose weight.

Strategic Electrochemical Determination of Nitrate over Polyaniline/Multi-Walled Carbon Nanotubes-Gum Arabic Architecture.

Significant agricultural and industrial activities necessitate the regular monitoring of nitrate (NO3-) ions levels in feed and groundwater. The current comparative study discloses an innovative user-friendly electrochemical approach for the determination of NO3- over polyaniline (PAni)-based modified electrodes. The electrochemical sensors concocted with PAni, multi-walled carbon nanotubes (CNT), and gum arabic (GA). The unique electrode material GA@PAni-CNT was synthesized by facile one-pot catalytic polymerization of aniline (Ani) with FeCl3/H2O2 in the presence of CNT and GA as integral components. As revealed by cyclic voltammetry (CV), the anchoring/retention of NO3- followed by reduction is proposed to occur when a GA@PAni-CNT electrode is immersed in phosphate buffer electrolyte containing NO3- that eventually results in a significantly higher redox activity of the GA@PAni-CNT electrode upon potential scan. The mechanism of NO3- anchoring may be associated with the non-redox transition of leucomeraldine salt (LS) into emeraldine salt (ES) and the generation of nitrite (NO2-) ions. As a result, the oxidation current produced by CV for redox transition of ES ↔ pernigraniline (PN) was ~9 times of that obtained with GA@PAni-CNT electrode and phosphate buffer electrolyte, thus achieving indirect NO3- voltammetric determination of the GA@PAni-CNT electrode. The prepared GA@PAni-CNT electrode displayed a higher charge transfer ability as compared to that of PAni-CNT and PAni electrodes. The optimum square wave voltammetric (SWV) response resulted in two linear concentration ranges of 1-10 (R2 = 0.9995) and 15-50 µM (R2 = 0.9988) with a detection limit of 0.42 µM, which is significantly lower. The GA@PAni-CNT electrode demonstrated the best detection, sensitivity, and performance among the investigated electrodes for indirect voltammetric determination of NO3- that portrayed the possibility of utilizing GA-stabilized PAni and CNT nanocomposite materials in additional electrochemical sensing applications.

Long-term health after Severe Acute Malnutrition in children and adults- the role of the Pancreas (SAMPA): Protocol.

Background: Prenatal growth retardation may increase the risk of later chronic non-communicable diseases (NCDs), including diabetes; however, long-term effects of wasting malnutrition in childhood or adulthood are less studied. Pancreatic exocrine and endocrine functions, both critical for nutrition and NCD aetiology, may not fully recover following malnutrition. However, the evidence and mechanistic information is piecemeal. We hypothesise that wasting malnutrition at any age has long-term detrimental effects on endocrine and exocrine pancreatic structure and function. Methods: The SAMPA international research programme will assess pancreatic structure and function in 3700 participants from ongoing observational nutrition cohorts, two adolescent and four adult, in Zambia, Tanzania, Philippines, and India. Pancreas size, structure, and calcification will be assessed by ultrasound and computed tomography (CT) scan; exocrine function by faecal elastase and serum lipase; and endocrine function by haemoglobin A1c (HbA1c) and blood glucose, insulin and C-peptide concentrations during an oral glucose tolerance test (OGTT). In-depth hormonal analyses of incretins, glucagon, proinsulin and trypsinogen during OGTT and intravenous glucose tolerance tests will be done in subsets of adult participants. Pancreatic size and function outcomes will be compared between people with and without prior wasting malnutrition. Analyses will investigate effect modification by sex, current age, time since malnutrition, current body mass index and dietary patterns. Mathematical modelling of OGTT data will be used to estimate the relative contribution to glucose dysregulation of decreased insulin production, changes in insulin clearance and increased insulin resistance. Proinsulin/insulin ratio will be analysed in archived samples from the Tanzanian cohort using a nested case-control design to investigate whether abnormal values precede diabetes. Conclusions: SAMPA, a large-scale multi-centre research programme using data from people with or without prior wasting malnutrition to assess several aspects of pancreatic phenotype, will provide coherent evidence for future policies and programmes for malnutrition and diabetes.

Sex and Aggression Characteristics in a Cohort of Patients with Pediatric Acute-Onset Neuropsychiatric Syndrome.

Objective: This study describes for the first time the characteristics by sex of patients with Pediatric Acute-onset Neuropsychiatric Syndrome (PANS), including clinical phenotype, treatment, and psychosocial aspects of disease. Methods: This cross-sectional study included 205 consecutive community patients evaluated between January 1, 2012 and March 30, 2019 and compared 87 females with 118 males. Our primary hypothesis was that males would display more aggression, as measured by the Modified Overt Aggression Scale (MOAS) and would be treated with immunotherapy earlier than females. The MOAS began to be administered 5 years into the study period, and 57 of the 205 families completed the MOAS for this study. Results: Our analysis revealed that males had a higher median MOAS score in the first year of clinic when compared with females (median 11, interquartile range [IQR] [4-24] vs. median 3, IQR [1-9]; p = 0.03) and a higher median subscore for physical aggression (median 4, IQR [0-12] vs. median 0, IQR [0-8]; p = 0.05). The median time from PANS symptom onset to first administration of immunotherapy, which did not include nonsteroidal anti-inflammatory drugs or short bursts of oral steroids, was 6.9 years for females and 3.7 years for males (p = 0.20). The two groups did not differ significantly in age of PANS onset, time from onset to clinic entry, other psychiatric symptom measures, or laboratory markers of inflammation. Conclusion: Among patients with PANS, males exhibit more aggressive behavior when compared with females, which may advance the decision to treat with immunotherapy. Scores that capture a more global level of functioning show that despite there being a higher level of aggression in males, female patients with PANS have similar levels of overall impairment.

Effect of national cultural dimensions and HIV prevalence rates on stigma towards people living with HIV/AIDS.

This paper examines the main and interactive effects of national culture dimensions and HIV prevalence rates on stigma towards people living with HIV/AIDS (PLHIVA). We examined these various relationships using data from a sample of 68,041 individuals from 49 countries, obtained from the World Values Survey. We used Hierarchical Linear Modeling to conduct our cross-level analyses. Our results indicated that collectivistic societies were positively associated while egalitarian and performance-oriented societies were negatively associated with stigma towards PLHIVA. Additionally, HIV prevalence rates interact with several cultural dimensions to worsen stigma towards PLHIVA. Our findings indicate the need to tailor stigma reduction strategies by taking the national culture dimensions of a given society into consideration when designing and implementing programs.

Modulation of Heart and Brain Function by Surah Al-Rehman Recitation Among Distressed Diabetic Patients in Pakistan.

Distress causes psychophysiological alterations that affect autonomic function. The current study explores psychophysiological modulation in diabetic distress in response to Surah Al-Rehman recitation. A single-group experimental study with before and after intervention assessments was conducted during April 2018 to February 2019 in which participants (n = 10) listened to Surah Al-Rehman recitation. Blood pressure, blood glucose, cortisol, ECG and EEG were recorded before and after recitation. Significant reduction in systolic blood pressure, increase in low frequency and absolute alpha power at Fp2 were observed. Heartbeat evoked potentials (HEP) were also significantly modulated at Fp1, Fp2 and F4. These findings suggest that Surah Al-Rehman modulated baroreflex activity thereby reducing sympathetic activity and improved heart brain coherence as reflected by HEP.

Effect of national cultural dimensions and consumption rates on stigma toward alcohol and substance use disorders.

BACKGROUND: Despite the notion of stigma as a socio-cultural process with the concept rooted in social space rather than in individual space, global studies examining impact of cultural differences on stigma toward substance use disorders are lacking. AIM: In this study, we aim to study the influence of national culture differences on stigma toward alcohol and substance use disorders. METHODS: We analyzed individual-level data from 68,041 respondents from 49 countries on stigma toward alcohol and substance use disorders. We examined the effect of the national culture dimensions and national alcohol and substance consumption rates on stigma toward alcohol and substance use disorders using hierarchical linear modeling. RESULTS: Our hierarchical linear modeling results indicate that cultural dimensions and consumption rates significantly influence stigma. We found significant positive associations between stigma toward AUD and institutional collectivism and assertiveness, but a negative association with future orientation dimension. Like AUD, stigma toward SUD was also positively associated with institutional collectivism and assertiveness, but negatively associated with power distance. CONCLUSIONS: The study findings have immense implications for national interventions to decrease stigma and influence policy making.

Evaluation of Test to Stay Strategy on Secondary and Tertiary Transmission of SARS-CoV-2 in K-12 Schools - Lake County, Illinois, August 9-October 29, 2021.

The COVID-19 pandemic has resulted in school closures and reduction of in-person learning (1). In August 2021, the Lake County Health Department (LCHD) in Illinois introduced a Test to Stay (TTS) strategy, whereby unvaccinated students, teachers, and staff members with certain school-related COVID-19 exposures could remain in school and participate in school-related extracurricular activities. Eligibility to participate in TTS required the following conditions to be met: 1) the exposure occurred while both the person with COVID-19 (index patient) and the close contact were masked; 2) the close contact remained asymptomatic, practiced consistent mask wearing, and maintained physical distancing; and 3) the close contact underwent testing for SARS-CoV-2 (the virus that causes COVID-19) on days 1, 3, 5, and 7 after exposure to the index patient. LCHD permitted kindergarten through grade 12 (K-12) schools in Lake County to implement TTS; 90 schools, representing 31 school districts in Lake County, implemented TTS during August 9-October 29, 2021. During the implementation period, 258 COVID-19 cases were reported. Among 1,035 students and staff members enrolled in TTS, the secondary attack risk (number of close contacts who received a positive SARS-CoV-2 test result within 14 days after exposure to an index patient, divided by total number of close contacts) was 1.5% (16 of 1,035). Among the 16 secondary cases identified, all were in students, and none appeared to transmit SARS-CoV-2 to other school-based contacts. However, nine tertiary cases were identified among household contacts of the 16 secondary cases, and four of the nine were fully vaccinated. Assuming a maximum of 8 missed school days for every 10-day quarantine period, up to 8,152 in-person learning days were saved among TTS participants. Implementation of TTS with other concurrent prevention strategies, including masking and physical distancing, limited further spread of SARS-CoV-2 within K-12 schools and allowed students to safely sustain in-person learning. Although vaccination remains the leading public health recommendation to protect against COVID-19 for those aged ≥5 years, schools might consider TTS as an option for allowing close contacts who are not fully vaccinated to remain in the classroom as an alternative to home quarantine.

The Language of Creativity: Validating Linguistic Analysis to Assess Creative Scientists and Artists.

The purpose of this study was twofold: first, to be among the first attempts to validate linguistic analysis as a method of creativity assessment and second, to differentiate between individuals in varying scientific and artistic creativity levels using personality language patterns. Creativity is most commonly assessed through methods such as questionnaires and specific tasks, the validity of which can be weakened by scorer or experimenter error, subjective and response biases, and self-knowledge constraints. Linguistic analysis may provide researchers with an automatic, objective method of assessing creativity, and free from human error and bias. The current study used 419 creativity text samples from a wide range of creative individuals mostly in science (and some in the arts and humanities) to investigate whether linguistic analysis can, in fact, distinguish between creativity levels and creativity domains using creativity dictionaries and personality dimension language patterns, from the linguistic inquiry and word count (LIWC) text analysis program. Creative individuals tended to use more words on the creativity keyword dictionaries as well as more introversion and openness to experience language pattern words than less creative individuals. Regarding creativity domains, eminent scientists used fewer introversion, and openness to experience language pattern words than eminent artists. Text analysis through LIWC was able to partially distinguish between the three creativity levels, in some cases, and the two creativity domains (science and art). These findings lend support to the use of linguistic analysis as a partially valid assessment of scientific and artistic creative achievement.

Epidemiology, Genetics and Epigenetics of Congenital Heart Diseases in Twins.

Congenital heart defects (CHDs) refer to abnormalities in the heart function that arise at the fetal stages. It is the most common birth defect that affects 0.8% of all liveborn infants. There is an increase in the incidence of congenital heart disease in monochorionic twin gestation. A six-fold increase in CHDs exists among monochorionic twins especially in association with twin-twin transfusion syndrome (TTTS) compared to dichorionic twin pregnancy. In this review article, we discussed the epidemiology, the role of genetics like protein-coding genes, epigenetics, placenta, hemodynamics and environmental factors in the etiology of CHD in twins. We conducted a literature search in PubMed indexed journals using the medical terms "twin pregnancy" and "congenital heart defect" to provide an overview of the uptrend in CHD in twin pregnancies, primarily due to assisted reproductive technologies (ARTs) and multiple other factors. Both the heart and placenta are vascular and share a common development window; therefore, CHD can develop secondary to placental pathologies. Among environmental factors, the strongest association of maternal smoking with CHD has been seen. We studied the causative factors to suggest improvement in echocardiographic skills in case of abnormal findings in twin gestations to decrease the CHD-associated morbidity and mortality, as early diagnosis allows doctors to precisely determine the risk of CHD. Systemic ultrasound scanning with five transverse views is very effective in diagnosing fetal CHD in twin pregnancy. In the case of genetics, prenatal counseling allows the expectant to understand the full ramifications of possible events after the pregnancy. The pathological basis of malformations specific to conjoined twinning and twin reversed arterial perfusion sequence is addressed. Also, there is evidence that folate supplementation may be protective against CHD but more research is needed to clarify the mechanisms. We concluded from the literature that monochorionic twins are at high risk of CHD. Chorionicity seems to play a more vital role than zygosity. Even the type of heart defect in monochorial twin pregnancies was unique from single, dizygotic, or dichorionic twin pregnancies. We also emphasize improving echocardiographic skills of technicians in referring ART dichorionic twin fetuses with suspicious findings to fetal cardiologists and performing postnatal scans in the case of TTTS. To understand the role of the placenta, making use of newer technologies and examining the placenta both during pregnancy and beyond delivery will play a vital role in understanding the etiology. Even identifying early signals impacting the heart and placental vasculature and correcting them using advanced technology could downtrend the incidence in coming years. Increased maternal age as well as multiple pregnancies increasing the risk of CHD has also been implicated. For more clarity on the role of genetics, the cost of DNA sequencing needs to decrease. This will enable whole-genome sequencing in the future thus helping to discover the gene responsible for CHD ultimately proving beneficial for future generations. For environmental factors, we have to rely on observational studies to assess the risk to the unborn child. There is difficulty in studying natural factors due to the unreliability of exposure to contaminants like pesticides and air pollution.

High Prevalence of Vaccine-Type Infections Among Children with Pneumococcal Pneumonia and Effusion After 13-Valent Pneumococcal Conjugate Vaccine Introduction in the Dominican Republic.

BACKGROUND: In 2013, the Dominican Republic introduced 13-valent pneumococcal conjugate vaccine (PCV13) using a 3-dose schedule (at 2, 4 and 12 months of age). We evaluated the impact of PCV13 on serotypes causing pneumococcal pneumonia with pleural effusion. METHODS: Surveillance data after PCV13 introduction (July 2014 to June 2016) were compared with data before PCV13 introduction (July 2009 to June 2011). Cases were defined as radiologic evidence of pneumonia with pleural effusion in a child aged <15 years. Pneumococcus was detected in pleural fluid by either culture or polymerase chain reaction, and serotyping was performed. The Ministry of Health's PCV13 uptake data for 2014-2016 were obtained. RESULTS: The prevalence of pneumococcus among cases was similar before and after PCV13 introduction (56.4% and 52.8%, respectively). The proportion of pneumococcal cases caused by vaccine serotypes was 86% for children <2 years old both before and PCV13 introduction. Compared with before PCV13, serotype 14 accounted for a smaller (28% vs 13%, respectively; P = .02) and serotype 1 for a larger (23% vs 37%; P = .09) proportion of pneumococcal cases after PCV13 introduction. National uptake for the first, second, and third PCV13 doses was 94%, 81%, and 28%, respectively, in 2014 and 75%, 61%, and 26% in 2015. DISCUSSION: While the decrease in pneumococcal pneumonia with pleural effusion caused by serotype 14 may reflect an early effect of PCV13 implementation, other vaccine serotypes, including serotype 1, are not well controlled. Better PCV13 coverage for all 3 doses is needed.

Effect of glecaprevir/pibrentasvir on weight-adjusted tacrolimus trough/dose ratios in heart and kidney transplant recipients.

OBJECTIVE: The pharmacokinetic implications of direct-acting antiviral (DAA) use on tacrolimus posttransplant are unknown. This study sought to investigate the effects of glecaprevir/pibrentasvir (G/P), a CYP3A4 substrate and inhibitor, on weight-adjusted tacrolimus (FK) trough/dose ratio (T/D) following heart or kidney transplantation. MATERIAL AND METHODS: This was a single-center, retrospective analysis of hepatitis C virus (HCV) viremic donors to HCV negative heart or kidney transplant recipients who received 12 weeks of G/P therapy. Weight-adjusted T/D was assessed while patients were at steady-state before, during, and after G/P treatment. Forty-one HCV negative recipients (three heart, 38 kidney) were evaluated. RESULTS: The weight-adjusted T/D significantly increased during G/P treatment (119.31, IQR 88-173.8) compared to before G/P treatment (67.4, IQR 53.4-115.9) (p < 0.01), but decreased after completion of treatment (90.1, IQR 52.9-122.7) (p < 0.01). There was no difference in weight-adjusted T/D before and after G/P treatment (p = 0.42). Four patients experienced acute rejection. CONCLUSION: Initiation of G/P in heart or kidney transplant recipients induces a reversible change in tacrolimus metabolism. A 33%-50% tacrolimus dose reduction may be considered at the time of G/P initiation. Regardless of tacrolimus dose adjustment, tacrolimus trough levels should be monitored 3 days after initiation of G/P. No clear relationship between HCV viremic organ transplantation and rejection risk was found. Larger studies are warranted to validate these findings.

High occurrence of postintensive care syndrome identified in surgical ICU survivors after implementation of a multidisciplinary clinic.

BACKGROUND: Postintensive care syndrome (PICS) has been identified in a large proportion of medical intensive care unit survivors; however, the occurrence surgical intensive care unit (SICU) survivors is unknown. We implemented a multidisciplinary critical care outpatient clinic (CCOC) to identify the occurrence of PICS in SICU survivors. METHODS: Seventy acute care surgery and trauma patients, 18 years or older, who remained in the SICU for 72 hours or longer at a Level I trauma center were seen in CCOC at 2 weeks, 12 weeks, and 24 weeks after hospital discharge. The CCOC staffing included a nurse coordinator, social worker, critical care pharmacist, physical therapist, and acute care surgeon who identified PICS sequelae in their respective specialties by clinical criteria and screening questionnaires. RESULTS: Of 82 eligible patients, 70 (85.4%) were seen at least once for 116 total visits. Forty-three (61.4%) patients suffered traumatic injuries and 27 (38.6%) underwent emergent general surgery. Sixty-seven (95.7%) demonstrated at least one PICS criterion. Over all visits, 26 (37.1%) patients presented with one PICS criterion, 24 (34.3%) patients with two, and 17 (24.3%) with three. Cognitive impairment was observed in 29 (41.4%) patients, psychiatric in 30 (42.9%), and physical symptoms in 65 (92.9%). Activity Measure for Post-Acute Care scores improved from severe impairment at admission to full function by 12 weeks postdischarge, yet 6 Minute Walk Test scores remained below age-matched references through all visits. Patients expressed mild to moderate depression based on Patient Health Questionnaire-9 scores. A medication reconciliation was completed at 96.5% (112/116) of the visits with 116 total medication recommendations. By 24 weeks following discharge, only 26.4% (14/53) of previously employed patients had resumed work. CONCLUSION: Through the successful implementation of a multidisciplinary CCOC, this study identifies an exorbitant rate of PICS among SICU survivors. LEVEL OF EVIDENCE: Therapeutic/epidemiological, level III.