Search

Background Single-centre studies suggest that successive Coronavirus Disease 2019 (COVID-19)-related 'lockdown' restrictions in England may have led to significant changes in the characteristics of major trauma patients. There is also evidence from other countries that diversion of intensive care capacity and other healthcare resources to treating patients with COVID-19 may have impacted on outcomes for major trauma patients. We aimed to assess the impact of the COVID-19 pandemic on the number, characteristics, care pathways, and outcomes of major trauma patients presenting to hospitals in England. Methods and findings We completed an observational cohort study and interrupted time series analysis including all patients eligible for inclusion in England in the national clinical audit for major trauma presenting between 1 January 2017 and 31 of August 2021 (354,202 patients). Demographic characteristics (age, sex, physiology, and injury severity) and clinical pathways of major trauma patients in the first lockdown (17,510 patients) and second lockdown (38,262 patients) were compared to pre-COVID-19 periods in 2018 to 2019 (comparator period 1: 22,243 patients; comparator period 2: 18,099 patients). Discontinuities in trends for weekly estimated excess survival rate were estimated when lockdown measures were introduced using segmented linear regression. The first lockdown had a larger associated reduction in numbers of major trauma patients (-4,733 (21%)) compared to the pre-COVID period than the second lockdown (-2,754 (6.7%)). The largest reductions observed were in numbers of people injured in road traffic collisions excepting cyclists where numbers increased. During the second lockdown, there were increases in the numbers of people injured aged 65 and over (665 (3%)) and 85 and over (828 (9.3%)). In the second week of March 2020, there was a reduction in level of major trauma excess survival rate (-1.71%; 95% CI: -2.76% to -0.66%) associated with the first lockdown. This was followed by a weekly trend of improving survival until the lifting of restrictions in July 2020 (0.25; 95% CI: 0.14 to 0.35). Limitations include eligibility criteria for inclusion to the audit and COVID status of patients not being recorded. Conclusions This national evaluation of the impact of COVID on major trauma presentations to English hospitals has observed important public health findings: The large reduction in overall numbers injured has been primarily driven by reductions in road traffic collisions, while numbers of older people injured at home increased over the second lockdown. Future research is needed to better understand the initial reduction in likelihood of survival after major trauma observed with the implementation of the first lockdown., Author(s): Carl Marincowitz 1,*, Omar Bouamra 2, Tim Coats 3, Dhushy Surendra Kumar 4, David Lockey 5,6, Lyndon Mason 7, Virginia Newcombe 8, Julian Thompson 9, Antoinette Edwards 2, Fiona [...]

Federated learning (FL) is a method used for training artificial intelligence models with data from multiple sources while maintaining data anonymity, thus removing many barriers to data sharing. Here we used data from 20 institutes across the globe to train a FL model, called EXAM (electronic medical record (EMR) chest X-ray AI model), that predicts the future oxygen requirements of symptomatic patients with COVID-19 using inputs of vital signs, laboratory data and chest X-rays. EXAM achieved an average area under the curve (AUC) >0.92 for predicting outcomes at 24 and 72 h from the time of initial presentation to the emergency room, and it provided 16% improvement in average AUC measured across all participating sites and an average increase in generalizability of 38% when compared with models trained at a single site using that site's data. For prediction of mechanical ventilation treatment or death at 24 h at the largest independent test site, EXAM achieved a sensitivity of 0.950 and specificity of 0.882. In this study, FL facilitated rapid data science collaboration without data exchange and generated a model that generalized across heterogeneous, unharmonized datasets for prediction of clinical outcomes in patients with COVID-19, setting the stage for the broader use of FL in healthcare. Federated learning, a method for training artificial intelligence algorithms that protects data privacy, was used to predict future oxygen requirements of symptomatic patients with COVID-19 using data from 20 different institutes across the globe., Author(s): Ittai Dayan [sup.1] , Holger R. Roth [sup.2] , Aoxiao Zhong [sup.3] [sup.4] , Ahmed Harouni [sup.2] , Amilcare Gentili [sup.5] , Anas Z. Abidin [sup.2] , Andrew Liu [...]

Family accommodation occurs frequently among families of children with OCD and anxiety disorders, with higher levels of accommodation repeatedly associated with greater symptom severity, lower functioning, and poorer treatment outcomes for children. This is the first examination of family accommodation of restricted and repetitive behaviors (RRBs) in children with autism spectrum disorder (ASD). Parents of children with ASD (N = 86) completed questionnaires assessing their children's RRBs and parental accommodation of these symptoms. Most participants (80%) reported engaging in accommodation at least once a month and family accommodation was significantly positively correlated with RRB severity. These results suggest accommodation of RRBs follows a pattern similar to that reported in obsessive compulsive and anxiety disorders, and highlight avenues for potential parent-based interventions., Author(s): Inbal Feldman [sup.1] , Judah Koller [sup.1] , Eli R. Lebowitz [sup.2] , Cory Shulman [sup.3] , Esther Ben Itzchak [sup.4] , Ditza A. Zachor [sup.5] [sup.6] Author Affiliations: [...]

Cystinosis is an autosomal recessive metabolic disease that belongs to the family of lysosomal storage disorders (LSDs). Initial symptoms of cystinosis correspond to the renal Fanconi syndrome. Patients then develop chronic kidney disease and multi-organ failure due to accumulation of cystine in all tissue compartments. LSDs are commonly characterized by a defective activity of lysosomal enzymes. Hematopoietic stem and progenitor cell (HSPC) transplantation is a treatment option for several LSDs based on the premise that their progeny will integrate in the affected tissues and secrete the functional enzyme, which will be recaptured by the surrounding deficient cells and restore physiological activity. However, in the case of cystinosis, the defective protein is a transmembrane lysosomal protein, cystinosin. Thus, cystinosin cannot be secreted, and yet, we showed that HSPC transplantation can rescue disease phenotype in the mouse model of cystinosis. In this review, we are describing a different mechanism by which HSPC-derived cells provide cystinosin to diseased cells within tissues, and how HSPC transplantation could be an effective one-time treatment to treat cystinosis but also other LSDs associated with a lysosomal transmembrane protein dysfunction., Author(s): Celine J. Rocca [sup.1] , Stephanie Cherqui [sup.1] Author Affiliations: (Aff1) 0000 0001 2107 4242, grid.266100.3, Department of Pediatrics, Division of Genetics, University of California, , 9500 Gilman Drive, [...]

No prior studies have examined how interventionists' perceptions of participants' weight control challenges or the agreement between participants and interventionists on these perceptions relate to outcomes during group-based behavioral weight loss treatment. This study characterized participants' and interventionists' perceptions of, and agreement about, weight control challenges and assessed how these factors relate to weight loss. Three months into treatment, participants and interventionists independently selected three weight control challenges believed to be most relevant for each participant. Weight was measured at baseline, 3 months, and 12 months. Interventionists and participants had 'no' ([kappa] < 0) or 'slight' (0 < [kappa]< .20) agreement on most challenges. Although endorsement of certain challenges by participants and/or interventionists was related to 3- and 12-month weight losses, agreement between participants and interventionists was unrelated to weight loss at either time point. Additional research is needed to better understand the role of perceived challenges and participant/interventionist agreement about challenges on treatment outcomes., Author(s): Christine C. Call [sup.1] , Leah M. Schumacher [sup.1] , Diane L. Rosenbaum [sup.2] , Alexandra D. Convertino [sup.1] , Fengqing Zhang [sup.1] , Meghan L. Butryn [sup.1] Author [...]

Many adults enter behavioral weight loss (BWL) programs at a weight below their highest lifetime weight. The discrepancy between highest lifetime weight and current weight is known as weight suppression (WS). Research has yet to characterize WS during BWL or investigate its relation to weight loss outcomes or treatment acceptability. Adults (N = 272) in a 12-month BWL program were assessed. WS was calculated by subtracting measured baseline weight from self-reported highest lifetime weight. Participants with higher WS lost significantly less weight than those with lower WS during treatment, although they still had clinically meaningful weight losses (e.g., participants with WS above the median: 7.8 kg; participants with WS below the median: 12.0 kg). WS was unrelated to weight losses at 24-month follow-up. Controlling for weight loss, treatment acceptability was unrelated to WS. BWL appears appropriate for those with high WS, but future research should aim to improve outcomes in this group., Author(s): Christine C. Call [sup.1] , Amani D. Piers [sup.1] , Emily P. Wyckoff [sup.2] , Michael R. Lowe [sup.1] , Evan M. Forman [sup.1] , Meghan L. Butryn [sup.1] [...]

Cystinosis is a rare autosomal-recessive lysosomal storage disease with high morbidity and mortality. It is caused by mutations in the CTNS gene that encodes the cystine transporter, cystinosin, which leads to lysosomal cystine accumulation. Patients with infantile nephropathic cystinosis, the most common and most severe clinical form of cystinosis, commonly present with renal Fanconi syndrome by 6-12 months of age, and without specific treatment, almost all will develop end-stage renal disease (ESRD) by 10-12 years of age. Early corneal cystine crystal deposition is a hallmark of the disease. Cystinosis also presents with gastrointestinal symptoms (e.g., vomiting, decreased appetite, and feeding difficulties) and severe growth retardation and may affect several other organs over time, including the eye, thyroid gland, gonads, pancreas, muscles, bone marrow, liver, nervous system, lungs, and bones. Cystine-depleting therapy with cysteamine orally is the only specific targeted therapy available for managing cystinosis and needs to be combined with cysteamine eye drops for corneal disease involvement. In patients with early treatment initiation and good compliance to therapy, long-term cysteamine treatment delays progression to ESRD, significantly improves growth, decreases the frequency and severity of extrarenal complications, and is associated with extended life expectancy. Therefore, early diagnosis of cystinosis and adequate life-long treatment with cysteamine are essential for preventing end-organ damage and improving the overall prognosis in these patients., Author(s): Gema Ariceta [sup.1] [sup.2] , Vincenzo Giordano [sup.3] , Fernando Santos [sup.4] Author Affiliations: (Aff1) Pediatric Nephrology, Hospital Universitari Vall d'Hebron, Universitat Autónoma de Barcelona, , Barcelona, Spain (Aff2) [...]

Special education policies recognize the need for developing and preserving the heritage languages of individuals with disabilities. Yet there seems to be a disconnect between policy and practice. Should the heritage languages of bilingual individuals with neurodevelopmental disorders be incorporated into interventions? This review evaluated 18 studies that examined the effects of heritage language instruction on treatment outcomes for individuals with neurodevelopmental disorders. Overall, results suggest a small effect favoring interventions delivered in the heritage language versus interventions delivered solely in the majority language. In general, studies were also found to be of high-quality according to What Works Clearinghouse Standards. Findings are discussed in terms of recommendations for future research and practice., Author(s): Nataly Lim [sup.1] , Mark F. O'Reilly [sup.1] , Jeff Sigafoos [sup.2] , Katherine Ledbetter-Cho [sup.1] [sup.3] , Giulio E. Lancioni [sup.4] Author Affiliations: (Aff1) 0000 0004 1936 9924, [...]

This study examined the treatment efficacy of PEERS® (Program for the Education and Enrichment of Relational Skills) among Chinese adolescents with autism spectrum disorder (ASD) in Hong Kong. The original PEERS® manual was translated into Chinese, and cultural adjustments were made according to a survey among 209 local adolescents in the general population. 72 high-functioning adolescents with ASD were randomly assigned to a treatment or waitlist control group. The 14-week parent-assisted training significantly improved social skills knowledge and social functioning, and also reduced autistic mannerisms. Treatment outcomes were maintained for 3 months after training and replicated in the control group after delayed treatment. The present study represents one of the few randomized controlled trials on PEERS® conducted outside North America., Author(s): Kathy Kar-Man Shum [sup.1] , Wai Kwan Cho [sup.2] , Lourdes Mei Oi Lam [sup.2] , Elizabeth A. Laugeson [sup.3] , Wai Shan Wong [sup.2] , Louisa S. K. [...]

Background: Standardized care protocols offer the potential to reduce postoperative complication rates. The purpose of this study was to determine whether there was an additive benefit associated with the sequential implementation of the evidence-based surgical site infection bundle (SSIB) and enhanced recovery after surgery (ERAS) protocols for patients undergoing colorectal surgery in a community hospital.Methods: Patients at a single institution who underwent elective colorectal surgery between Apr. 1, 2011, and Dec. 31, 2015, were identified by means of American College of Surgeons National Surgical Quality Improvement Program data. Patients were stratified into 3 groups according to the protocol implementation dates: pre-SSIB/pre-ERAS (control), post-SSIB/pre-ERAS and post-SSIB/post-ERAS. Primary outcomes assessed were length of stay and wound complication rates. We used inverse proportional weighting to control for possible differences between the groups.Results: There were 368 patients included: 94 in the control group, 95 in the post-SSIB/pre-ERAS group and 179 in the post-SSIB/post-ERAS group. In the adjusted analyses, mean length of stay (control group 7.6 d, post-SSIB/post-ERAS group 5.5 d, p = 0.04) and overall wound complication rates (14.7% and 6.5%, respectively, p = 0.049) were reduced after sequential implementation of the protocols.Conclusion: Sequential implementation of quality-improvement initiatives yielded additive benefit for patients undergoing colorectal surgery in a community hospital, with a decrease in length of stay and wound complication rates. The amount of improvement attributable to either initiative is difficult to define as they were implemented sequentially. The improved outcomes were realized after the introduction of the ERAS protocol in adjusted analyses.Contexte: Les protocoles de soins standardises offrent la possibility de reduire les taux de complications postoperatoires. Le but de cette etude etait de determiner s'il y a un avantage additif associe a l'application sequentielle des protocoles fondes sur des donnees probantes SSIB (surgical site infection bundle) et ERAS (enhanced recovery after surgery) chez des patients soumis a une chirurgie colorectale dans un hopital communautaire.Methodes: Les patients d'un seul etablissement ayant subi une chirurgie colorectale non urgente entre le 1 (er) avril 2011 et le 31 decembre 2015 ont ete recenses a partir des donnees du Programme national d'amelioration de la qualite chirurgicale de l'American College of Surgeons. Les patients ont ete stratifies en 3 groupes selon les dates d'application des protocoles: pre-SSIB/pre-ERAS (temoin), post-SSIB/pre-ERAS et post-SSIB/post-ERAS. Les parametres principaux evalues etaient la duree du sejour hospitalier et les taux de complications de plaies. Nous avons utilise une ponderation proportionnelle inverse pour tenir compte des possibles differences entre les groupes.Resultats: Nous avons inclus 368 patients, 94 dans le groupe temoin, 95 dans le groupe post-SSIB/pre-ERAS et 179 dans le groupe post-SSIB/post-ERAS. Dans les analyses ajustees, la duree moyenne des sejours (groupe temoin 7,6 j, groupe post-SSIB/post-ERAS 5,5 j, p = 0,04) et les taux globaux de complications de plaies (14,7% et 6,5% respectivement, p = 0,049) ont diminue apres l'application sequentielle des protocoles.Conclusion: L'application sequentielle des initiatives d'amelioration de la qualite a donne lieu a des bienfaits additifs chez les patients soumis a une chirurgie colorectale dans un hopital communautaire, avec abregement du sejour hospitalier et diminution du taux de complications de plaies. Le degre d'amelioration attribuable a chacune des initiatives est difficile a preciser puisqu'elles ont ete appliquees sequentiellement. L'amelioration des parametres a ete obtenue apres l'introduction du protocole ERAS dans des analyses ajustees., Surgery for resection of the colon or rectum is traditionally associated with a high risk of complications. (1) Historically, patients undergoing colorectal resection could expect a 20%-25% risk of complications [...]

Background: A substantial portion of the cost of total knee arthroplasty (TKA) results from the postoperative inpatient length of stay (LOS). Considering the annual increase in TKAs, reducing LOS represents a potential for cost savings. We sought to compare in-hospital costs and patient-reported outcomes for an early discharge protocol compared with the standard LOS following TKA.Methods: We conducted a retrospective matched cohort study, matching patients on age, sex, body mass index and preoperative Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC) score. We compared costs associated with time in the operating room, intraoperative pain control and inpatient stay as well as 1-year postoperative patient-reported outcomes between early discharge and standard LOS groups.Results: We included 50 patients in our study (25 per group). The average LOS in the early discharge group was 26.5 hours, compared with 48.9 hours in the standard care group. The early discharge group had higher intraoperative costs associated with pain control (mean difference 26.98, 95% confidence interval 14.41-37.90, p < 0.01); however, this difference was offset by substantial savings associated with the reduced LOS. The mean total cost for the early discharge group was $649.62 [+ or -] $281.71 versus $1279.71 [+ or -] $515.98 for the standard care group. There were no significant differences in SF12 or WOMAC scores between groups at 1 year postoperative.Conclusion: In-hospital costs were significantly lower with a postoperative day 1 discharge protocol than with standard LOS following TKA, with no difference in patient-reported outcomes.Contexte: Une portion substantielle du cout de l'arthroplastie pour prothese totale du genou (PTG) est liee a la duree du sejour postoperatoire. Compte tenu de l'augmentation annuelle des cas de PTG, abreger les sejours represente une source potentielle d'economies. Nous avons compare les couts hospitaliers et les resultats signales par les patients avec un protocole de conge rapide et avec le sejour de duree standard apres la PTG.Methodes: Nous avons procede a une etude de cohorte retrospective appariee, ou les patients etaient assortis selon le l'age, le sexe, l'indice de masse corporelle et le score WOMAC (Western Ontario & McMaster Universities Osteoarthritis) preoperatoire. Nous avons compare les couts associes au temps passe au bloc operatoire, au controle de la douleur peroperatoire et au sejour hospitalier, de meme que les resultats signales par les patients 1 an apres l'intervention entre les 2 groupes (conge rapide c. duree de sejour standard).Resultats: Nous avons inclus 50 patients dans notre etude (25 par groupe). Le sejour moyen du groupe soumis au conge rapide a ete de 26,5 heures, contre 48,9 heures pour le sejour standard. Le groupe soumis au conge rapide a presente des couts peroperatoires plus eleves associes au controle de la douleur (difference moyenne 26,98, intervalle de confiance de 95% 14,41-37,90, p < 0,01); par contre, cette difference a ete compensee par d'importantes economies associees a des sejours plus courts. Le cout total moyen pour le groupe soumis au conge rapide a ete de 649,62 $ [+ or -] 281,71 $ contre 1279,71 $ [+ or -] 515,98 $ pour le sejour standard. On n'a note aucune difference significative pour ce qui est des scores SF12 ou WOMAC entre les groupes 1 an apres l'intervention.Conclusion: Les couts perhospitaliers ont ete significativement moindres avec le protocole de conge postoperatoire rapide (apres 1 jour), comparativement au sejour standard apres la PTG, sans difference en ce qui concerne les resultats signales par les patients., Total knee arthroplasty (TKA) is an established, effective intervention for advanced osteoarthritis (OA) of the knee. The prevalence of knee OA is rapidly increasing, resulting in a rising demand for [...]

Fibrosis, the progressive accumulation of connective tissue that occurs in response to injury, causes irreparable organ damage and may result in organ failure. The few available antifibrotic treatments modify the rate of fibrosis progression, but there are no available treatments to reverse established fibrosis. Thus, more effective therapies are urgently needed. Molecular imaging is a promising biomedical methodology that enables noninvasive visualization of cellular and subcellular processes. It provides a unique means to monitor and quantify dysregulated molecular fibrotic pathways in a noninvasive manner. Molecular imaging could be used for early detection, disease staging, and prognostication, as well as for assessing disease activity and treatment response. As fibrotic diseases are often molecularly heterogeneous, molecular imaging of a specific pathway could be used for patient stratification and cohort enrichment with the goal of improving clinical trial design and feasibility and increasing the ability to detect a definitive outcome for new therapies. Here we review currently available molecular imaging probes for detecting fibrosis and fibrogenesis, the active formation of new fibrous tissue, and their application to models of fibrosis across organ systems and fibrotic processes. We provide our opinion as to the potential roles of molecular imaging in human fibrotic diseases., IntroductionFibrosis is a progressive scarring process arising from tissue damage or inflammation that can result in both organ damage and failure (1). Fibrotic diseases are responsible for a large proportion [...]

Donor age and recipient age are factors that influence transplantation outcomes. Aside from age-associated differences in intrinsic graft function and alloimmune responses, the ability of young and old cells to exert either rejuvenating or aging effects extrinsically may also apply to the transplantation of hematopoietic stem cells or solid organ transplants. While the potential for rejuvenation mediated by the transfer of youthful cells is currently being explored for therapeutic applications, aspects that relate to accelerating aging are no less clinically significant. Those effects may be particularly relevant in transplantation with an age discrepancy between donor and recipient. Here, we review recent advances in understanding the mechanisms by which young and old cells modify their environments to promote rejuvenation- or aging-associated phenotypes. We discuss their relevance to clinical transplantation and highlight potential opportunities for therapeutic intervention., IntroductionCellular aging is a complex process controlled by a combination of cell-intrinsic and environmental conditions. Young and old cells appear to be capable of regulating aging in a nonautonomous manner, [...]

The accrual of myeloid-derived suppressor cells (MDSCs) represents a major obstacle to effective immunotherapy in cancer patients, but the mechanisms underlying this process in the human setting remain elusive. Here, we describe a set of microRNAs (miR-146a, miR-155, miR-125b, miR-100, let-7e, miR-125a, miR-146b, miR-99b) that are associated with MDSCs and resistance to treatment with immune checkpoint inhibitors in melanoma patients. The miRs were identified by transcriptional analyses as being responsible for the conversion of monocytes into MDSCs ([CD14.sup.+][HLA-DR.sup.neg] cells) mediated by melanoma extracellular vesicles (EVs) and were shown to recreate MDSC features upon transfection. In melanoma patients, these miRs were increased in circulating [CD14.sup.+] monocytes, plasma, and tumor samples, where they correlated with the myeloid cell infiltrate. In plasma, their baseline levels clustered with the clinical efficacy of CTLA-4 or programmed cell death protein 1 (PD-1) blockade. Hence, MDSC-related miRs represent an indicator of MDSC activity in cancer patients and a potential blood marker of a poor immunotherapy outcome., IntroductionImmunotherapy with immune checkpoint inhibitors (ICIs) has achieved a remarkable improvement in overall survival (OS) in different tumor histologies, albeit the majority of patients display intrinsic resistance (1). The response [...]

Cancer cells evade the immune system through a variety of different mechanisms, including the inhibition of antitumor effector T cells via checkpoint ligand-receptor interaction. Moreover, studies have shown that blocking these checkpoint pathways can reinvigorate the antitumor immunity, thereby prompting the development of numerous checkpoint immunotherapies, several of which are now being approved to treat multiple types of cancer. However, only a fraction of patients achieves promising long-term outcomes in response to checkpoint inhibition, suggesting the existence of additional unknown tumor-induced immunosuppressive pathways. In this issue of theJCI, Klement and colleagues describe an additional pathway of T cell inhibition in cancer. Specifically, the authors demonstrate that downregulation of IRF8, a molecular determinant of apoptotic resistance, in tumor cells aborts repression of osteopontin, which in turn binds to its physiological receptor CD44 on activated T cells and suppresses their activation. These results suggest that osteopontin may act as another immune checkpoint and may serve as a target to expand the number of patients who respond to immune checkpoint inhibitor therapy., How do tumors escape immunological surveillance?The immune system plays a crucial role in destroying cancerous cells. However, cancer cells also evolve and gain the ability to escape immunological elimination. Mechanisms [...]

Doctors have long known that patients' expectations have a significant impact on the effectiveness of treatments prescribed for them. But much less is known about the effect of providers' expectations [...]

Intolerance of uncertainty (IU) is indicated as an important transdiagnostic process variable in a range of anxiety disorders. Anxiety is very common in autistic adults. This study evaluates a manualised treatment programme for autistic adults, which focused on IU. An eight session programme (CUES-A©) was developed and delivered to four autistic adults on an individual basis. A single case experimental design was used to provide a preliminary evaluation of the feasibility, acceptability and preliminary effectiveness of the programme. Data regarding retention, acceptability and feasibility indicate that the participants valued the programme. Analyses of outcome measures indicate that the programme has promise as a treatment option for autistic adults experiencing IU., Author(s): J. Rodgers [sup.1] , R. Herrema [sup.2] , E. Honey [sup.3] , M. Freeston [sup.2] [sup.3] Author Affiliations: (Aff1) 0000 0001 0462 7212, grid.1006.7, Clinical Psychology, Faculty of Medical [...]

Nicotinic acetylcholine receptors (nAChRs), particularly the [alpha]7 nAChR, are implicated in the pathophysiology of both autism spectrum disorder (ASD) and aggressive behavior. We explored the feasibility, tolerability, and preliminary efficacy of targeting nAChRs using transdermal nicotine to reduce aggressive symptoms in adults with ASD. Eight subjects were randomized in a double-blind crossover trial of 7 mg transdermal nicotine or placebo, each for 1 week. All participants tolerated nicotine treatment well. Five subjects contributed data to the primary outcome, Aberrant Behavior Checklist-Irritability (ABC-I) subscale change from baseline, which was improved by nicotine compared to placebo. Sleep ratings were also improved by nicotine and correlated with ABC-I improvement. These findings support further investigation of nAChR agonists for aggression and sleep in ASD., Author(s): Alan S. Lewis [sup.1] [sup.4] , Gerrit Ian van Schalkwyk [sup.2] [sup.3] , Mayra Ortiz Lopez [sup.2] , Fred R. Volkmar [sup.2] , Marina R. Picciotto [sup.1] , Denis [...]

Background Atypical hemolytic uremic syndrome (aHUS) is a chronic disease characterized by thrombotic microangiopathy and a high risk of end-stage kidney disease. Dysregulation and/or excessive activation of the complement system results in thrombotic microangiopathy. Interest in extrarenal manifestations of aHUS is increasing. This study aimed to determine the clinical characteristics of patients with extrarenal manifestations of aHUS in childhood. Methods This study included 70 children with extrarenal manifestations of HUS from the national Turkish aHUS Registry. The demographics, clinical characteristics, genetic test results, all treatments, and renal/hematologic status of aHUS patients with extrarenal involvement were recorded. Results The most common extrarenal manifestation was neurological system involvement (n = 46 [27.2%]), followed by gastrointestinal (n = 20 [11.8%]), cardiovascular (n = 12 [7%]), and respiratory (n = 12 [7%]) involvement. The patients with neurological involvement had a higher mortality rate and a lower estimated glomerular filtration rate (eGFR) than the other patients at last follow-up. Eculizumab (with or without plasma exchange/plasma infusion) treatment increased the renal and hematologic recovery rates. Conclusions The most common and serious extrarenal manifestation of aHUS is neurological involvement and treatment outcome findings presented herein are important to all relevant clinicians., Author(s): Kibriya Fidan [sup.1] , Nilüfer Göknar [sup.2] , Bora Gülhan [sup.3] , Engin Melek [sup.4] , Zeynep Y. Yildirim [sup.5] , Esra Baskin [sup.6] , Mutlu Hayran [sup.3] , [...]

Background Hemolytic uremic syndrome related to Shiga-toxin-secreting Escherichia coli infection (STEC-HUS) remains a common cause of acute kidney injury in young children. No specific treatment has been validated for this severe disease. Recently, experimental studies highlight the potential role of complement in STEC-HUS pathophysiology. Eculizumab (EC), a monoclonal antibody against terminal complement complex, has been used in severe STEC-HUS patients, mostly during the 2011 German outbreak, with conflicting results. Methods On behalf of the French Society of Pediatric Nephrology, we retrospectively studied 33 children from 15 centers treated with EC for severe STEC-HUS. Indication for EC was neurologic involvement in 20 patients, cardiac and neurologic involvement in 8, cardiac involvement in 2, and digestive involvement in 3. Based on medical status at last follow-up, patients were divided into two groups: favorable (n = 15) and unfavorable outcomes (n = 18). Results Among patients with favorable outcome, 11/14 patients (79%) displayed persistent blockade of complement activity before each EC reinjection. Conversely, in patients with unfavorable outcome, only 9/15 (53%) had persistent blockade (p = n.s.). Among 28 patients presenting neurological symptoms, 19 had favorable neurological outcome including 17 with prompt recovery following first EC injection. Only two adverse effects potentially related to EC treatment were reported. Conclusions Taken together, these results may support EC use in severe STEC-HUS patients, especially those presenting severe neurological symptoms. The study, however, is limited by absence of a control group and use of multiple therapeutic interventions in treatment groups. Thus, prospective, controlled trials should be undertaken., Author(s): Lucas Percheron [sup.1] , Raluca Gramada [sup.2] , Stéphanie Tellier [sup.1] , Remi Salomon [sup.3] , Jérôme Harambat [sup.4] , Brigitte Llanas [sup.4] , Marc Fila [sup.5] , Emma [...]

Purpose The maintaining of asthma control is difficult due to high variability in response to therapy among patients. Since matrix metalloproteinase 9 (MMP9) is implicated in inflammation and remodeling of asthmatic airways, it could be associated with adequate response to asthma therapy. The aim of this study was to investigate whether variants in 3' end of the MMP9 gene are associated with clinical phenotype and responsiveness to treatment in children with asthma. Methods The study included 127 asthmatic children from Slovenia. Variants in the 3' end of the MMP9 gene were analyzed by direct DNA sequencing and the obtained results were correlated with clinical parameters. Results Two variants were detected, rs13925 and rs20544. For the variant rs20544, statistically significant difference in airway hyperresponsiveness (p = 0.011) and asthma control (p = 0.049) between genotypes was found. Patients with TT genotype had lower airway sensitivity, and after 12 months of treatment showed significant improvement in Asthma Control Test (ACT) scores compared to CC and CT genotype. For the variant rs13925, the association with lung function was observed. The carriers of A allele showed noticeable improvement of lung function after the first 6 months of treatment in comparison to the carriers of G allele (p = 0.046). Conclusion The main finding of our study is the association of MMP9 genotypes rs20544 TT and rs13925 AA and AG with better asthma control, and indirectly better response to treatment. Based on these results, MMP9 deserves further research as a potential predictive biomarker for asthma., Author(s): Sandra Dragicevic [sup.1] , Mitja Kosnik [sup.2] , Aleksandra Divac Rankov [sup.1] , Matija Rijavec [sup.2] , Katarina Milosevic [sup.3] , Peter Korosec [sup.2] , Maja Skerbinjek Kavalar [sup.4] [...]

Introduction: The World Health Organization's (WHO) recommendation of 'Treat All' has accelerated the call for differentiated antiretroviral therapy (ART) delivery, a method of care that efficiently uses limited resources to increase access to HIV treatment. WHO has further recommended that stable individuals on ART receive refills every 3 to 6 months and attend clinical visits every 3 to 6 months. However, there is not yet consensus on how to ensure that the quality of services is maintained as countries strive to meet these standards. This commentary responds to this gap by defining a pragmatic approach to the monitoring and evaluation (M&E) of the scale up of differentiated ART delivery for global and national stakeholders. Discussion: Programme managers need to demonstrate that the scale up of differentiated ART delivery is achieving the desired effectiveness and efficiency outcomes to justify continued support by national and global stakeholders. To achieve this goal, the two existing global WHO HIV treatment indicators of ART retention and viral suppression should be augmented with two broad aggregate measures. The addition of indicators measuring the frequency of (1) clinical and (2) refill visits by PLHIV per year will allow evaluation of the pace of scale up while monitoring its overall effect on the quality and efficiency of services. The combination of these four routinely collected aggregate indicators will also facilitate the comparison of outcomes among facilities, regions or countries implementing different models of ART delivery. Enhanced monitoring or additional assessments will be required to answer other critical questions on the process of implementation, acceptability, effectiveness and efficiency. Conclusions: These proposed outcomes are useful markers for the effectiveness and efficiency of the health system's attempts to deliver quality treatment to those who need it--and still reserve as much of the available resource pool as possible for other key elements of the HIV response. Keywords: HIV; differentiated care; differentiated service delivery; monitoring and evaluation; efficiency; productivity; health care worker experience; patient experience, 1 | INTRODUCTION: THE POTENTIAL OF DIFFERENTIATED SERVICE DELIVERY AND THE NEED TO MEASURE ITS IMPACT The World Health Organization's (WHO) recommendation that all people living with HIV (PLHIV) should [...]

Introduction: The 'greying' of the HIV epidemic necessitates a better understanding of the healthcare needs of older HIV-positive adults. As these individuals age, it is unclear whether comorbidities and their associated therapies or the ageing process itself alter the response to antiretroviral therapy (ART). In this study HIV treatment outcomes and corresponding risk factors were compared between older ART initiators and those who were younger using data from the Caribbean, Central and South America Network for HIV Epidemiology (CCASAnet). Methods: HIV-positive adults ([greater than or equal to]18 years) initiating ART at nine sites in Argentina, Brazil, Chile, Haiti, Honduras, Mexico and Peru were included. Patients were classified as older ([greater than or equal to]50 years) or younger ( Results: Among 26,311 patients initiating ART between 1996 and 2016, 3389 (13%) were [greater than or equal to]50 years. The majority of patients in both [greater than or equal to]50 and Conclusions: Older age at ART initiation was associated with increased mortality and decreased risk of virologic failure in our cohort of more than 26,000 ART initiators in Latin America and the Caribbean. To the best of our knowledge this is the first study from the region to evaluate ART outcomes in this growing and important population. Given the complexity of issues related to ageing with HIV, a greater understanding is needed in order to properly respond to this shifting epidemic. Keywords: HIV; Ageing; Over 50; Latin America; Caribbean; ART outcomes; Virologic failure, 1 | INTRODUCTION Worldwide, HIV-positive populations are ageing. In 2013, an estimated 13% of the global adult population living with HIV was 50 years and older (defined as 'older adults' [...]

Introduction: Adolescents and youth receiving antiretroviral treatment (ART) in sub-Saharan Africa have high attrition and inadequate ART outcomes, and evaluations of interventions improving ART outcomes amongst adolescents are very limited. Sustainable Development Goal (SDG) target 3c is to substantially increase the health workforce in developing countries. We measured the effectiveness and cost-effectiveness of community-based support (CBS) provided by lay health workers for adoescents and youth receiving ART in South Africa. Methods: A retrospective cohort study including adolescents and youth who initiated ART at 47 facilities. Previously unemployed CBS-workers provided home-based ART-related education, psychosocial support, symptom screening for opportunistic infections and support to access government grants. Outcomes were compared between participants who received CBS plus standard clinic-based care versus participants who received standard care only. Cumulative incidences of all-cause mortality and loss to follow-up (LTFU), adherence measured using medication possession ratios (MPRs), CD4 count slope, and virologica suppression were analysed using multivariable Cox, competing-risks regression, generalized estimating equations and mixed-effects models over five years of ART. An expenditure approach was used to determine the incremental cost of CBS to usual care from a provider perspective. Incremental cost-effectiveness ratios were calculated as annual cost per patient-loss (through death or LTFU) averted. Results: Amongst 6706 participants included, 2100 (31.3%) received CBS. Participants who received CBS had reduced mortality, adjusted hazard ratio (aHR) = 0.52 (95% CI: 0.37 to 0.73; p < 0.0001). Cumulative LTFU was 40% lower amongst participants receiving CBS (29.9%) compared to participants without CBS (38.9%), aHR = 0.60 (95% CI: 0.51 to 0.71); p < 0.0001). The effectiveness of CBS in reducing attrition ranged from 42.2% after one year to 35.9% after five years. Virological suppression was similar after three years, but after five years 18.8% CBS participants versus 37.2% non-CBS participants failed to achieve viral suppression, adjusted odds ratio = 0.24 (95% CI: 0.06 to 1.03). There were no significant differences in MPR or CD4 slope. The cost of CBS was US$49.5/patient/year. The incremental cost per patient-loss averted was US$600 and US$776 after one and two years, respectively. Conclusions: CBS for adolescents and youth receiving ART was associated with substantially reduced patient attrition, and is a low-cost intervention with reasonable cost-effectiveness that can aid progress towards several health, economic and equality-related SDG targets. Keywords: HIV; antiretroviral treatment; adolescents; United Nations Sustainable Development Goals; community-based support; cost-effectiveness, 1 | INTRODUCTION The UN Sustainable Development Goals (SDGs) are 17 universal, ambitious and interrelated goals established to guide the development policy and agenda of member states till 2030 [1]. [...]

Introduction: By 2020, 90% of all people diagnosed with HIV should receive long-term combination antiretroviral therapy (ART). In sub-Saharan Africa, this target is threatened by loss to follow-up in ART programmes. The proportion of people retained on ART long-term cannot be easily determined, because individuals classified as lost to follow-up, may have self-transferred to another HIV treatment programme, or may have died. We describe retention on ART in sub-Saharan Africa, first based on observed data as recorded in the clinic databases, and second adjusted for undocumented deaths and self-transfers. Methods: We analysed data from HIV-infected adults and children initiating ART between 2009 and 2014 at a sub-Saharan African HIV treatment programme participating in the International epidemiology Databases to Evaluate AIDS (IeDEA). We used the Kaplan--Meier method to calculate the cumulative incidence of retention on ART and the Aalen-Johansen method to calculate the cumulative incidences of death, loss to follow-up, and stopping ART. We used inverse probability weighting to adjust clinic data for undocumented mortality and self-transfer, based on estimates from a recent systematic review and meta-analysis. Results: We included 505,634 patients: 12,848 (2.5%) from Central Africa, 109,233 (21.6%) from East Africa, 347,343 (68.7%) from Southern Africa and 36,210 (7.2%) from West Africa. In crude analyses of observed clinic data, 52.1% of patients were retained on ART, 41.8% were lost to follow-up and 6.0% had died 5 years after ART initiation. After accounting for undocumented deaths and self-transfers, we estimated that 66.6% of patients were retained on ART, 18.8% had stopped ART and 14.7% had died at 5 years. Conclusions: Improving long-term retention on ART will be crucial to attaining the 90% on ART target. Naive analyses of HIV cohort studies, which do not account for undocumented mortality and self-transfer of patients, may severely underestimate both mortality and retention on ART. Keywords: retention; mortality; loss to follow-up; antiretroviral therapy; sub-Saharan Africa, 1 | INTRODUCTION Over the past 15 years antiretroviral therapy (ART) has been scaled up massively in low- and middle-income countries: by mid-2017 globally almost 21 million people were receiving [...]

Previous studies on social skills training on ASD were done almost exclusively in the West with children as the main subjects. Demonstrations of the applicability of social interventions in different cultures and age groups are warranted. The current study outlined the development and preliminary evaluation of a CBT-context-based social competence training for ASD (CBT-CSCA) developed in Hong Kong for Chinese adolescents with ASD. Twenty-five adolescents (aged 12-17 years, with a FSIQ above 80) were recruited. Significant improvements in social competence, autistic symptoms and general psychopathology at post-training and 3-month follow-up were reported by the parents. The study provided initial evidence support to the applicability of social competence training for adolescents with ASD in a different culture., Author(s): Raymond Won Shing Chan [sup.1] , Cecilia Nga Wing Leung [sup.1] , Denise Ching Yiu Ng [sup.1] , Sania Sau Wai Yau [sup.1] Author Affiliations: (1) The Jockey Club [...]

Introduction Liver-kidney transplantation is a rare procedure in children, with just ten to 30 cases performed annually worldwide. The main indications are autosomal recessive polycystic liver-kidney disease and primary hyperoxaluria. This study aimed to report outcomes of liver-kidney transplantation in a cohort of pediatric patients. Methods We retrospectively analyzed all pediatric liver-kidney transplantations performed in our center between September 2000 and August 2015. Patient data were obtained by reviewing inpatient and outpatient medical records and our transplant database. Results A total of 14 liver-kidney transplants were performed during the study period, with a median patient age and weight at transplant of 144.4 months (131.0-147.7) and 27.3 kg (12.0-45.1), respectively. The indications for liver-kidney transplants were autosomal recessive polycystic liver-kidney disease (8/14), primary hyperoxaluria -1 (5/14), and idiopathic portal hypertension with end-stage renal disease (1/14). Median time on waiting list was 8.5 months (5.7-17.3). All but two liver-kidney transplants were performed simultaneously. Patients with primary hyperoxaluria-1 tended to present a delayed recovery of renal function compared with patients transplanted for other indications (62.5 vs 6.5 days, respectively, P 0.076). Patients with liver-kidney transplants tended to present a lower risk of acute kidney rejection than patients transplanted with an isolated kidney transplant (7.2% vs 32.7%, respectively; P < 0.07). Patient and graft survival at 1, 3, and 5 years were 100%, 91.7%, 91.7%, and 91.7%, 83.3%, 83.3%, respectively. No other grafts were lost. Conclusion Long-term results of liver-kidney transplants in children are encouraging, being comparable with those obtained in isolated liver transplantation., Author(s): Jesús Quintero Bernabeu [sup.1] , Javier Juamperez [sup.1] , Marina Muñoz [sup.2] , Olalla Rodriguez [sup.3] , Ramon Vilalta [sup.2] , José A. Molino [sup.4] , Marino Asensio [sup.4] [...]

Transplantation of neural progenitor cells (NPCs) is a potential therapy for treating neurodegenerative disorders, but this approach has faced many challenges and limited success, primarily because of inhospitable host brain environments that interfere with enriched neuron engraftment and function. Astrocytes play neurotrophic roles in the developing and adult brain, making them potential candidates for helping with modification of hostile brain environments. In this study, we examined whether astrocytic function could be utilized to overcome the current limitations of cell-based therapies in a murine model of Parkinson's disease (PD) that is characterized by dopamine (DA) neuron degeneration in the midbrain. We show here that cografting astrocytes, especially those derived from the midbrain, remarkably enhanced NPC-based cell therapeutic outcomes along with robust DA neuron engraftment in PD rats for at least 6 months after transplantation. We further show that engineering of donor astrocytes with Nurr1 and Foxa2, transcription factors that were recently reported to polarize harmful immunogenic glia into the neuroprotective form, further promoted the neurotrophic actions of grafted astrocytes in the cell therapeutic approach. Collectively, these findings suggest that cografting astrocytes could be a potential strategy for successful cell therapeutic outcomes in neurodegenerative disorders., Introduction Given the clinical experience of fetal mesencephalic transplantation in Parkinson's disease (PD), a neurodegenerative disorder characterized by dopamine (DA) neuron loss in the midbrain substantial nigra (SN), stem cell [...]