A Common Variant in the Adaptor Mal Regulates Interferon Gamma Signaling.

Humans that are heterozygous for the common S180L polymorphism in the Toll-like receptor (TLR) adaptor Mal (encoded by TIRAP) are protected from a number of infectious diseases, including tuberculosis (TB), whereas those homozygous for the allele are at increased risk. The reason for this difference in susceptibility is not clear. We report that Mal has a TLR-independent role in interferon-gamma (IFN-γ) receptor signaling. Mal-dependent IFN-γ receptor (IFNGR) signaling led to mitogen-activated protein kinase (MAPK) p38 phosphorylation and autophagy. IFN-γ signaling via Mal was required for phagosome maturation and killing of intracellular Mycobacterium tuberculosis (Mtb). The S180L polymorphism, and its murine equivalent S200L, reduced the affinity of Mal for the IFNGR, thereby compromising IFNGR signaling in macrophages and impairing responses to TB. Our findings highlight a role for Mal outside the TLR system and imply that genetic variation in TIRAP may be linked to other IFN-γ-related diseases including autoimmunity and cancer.

Global trends of dalbavancin: A bibliometric analysis.

WHAT IS KNOWN AND OBJECTIVE?: Dalbavancin is used against gram-positive pathogens such as Staphylococcus aureus in acute bacterial skin and skin-structure infections. METHODS: Our main goal was to identify the key articles sustaining the current knowledge of this drug's therapeutic possibilities through a bibliometric analysis of the available literature. RESULTS AND DISCUSSION: On 15 March 2021, we searched the Web of Science electronically for documents that contain within its title the term "dalbavancin." We found a total of 675 documents that average 20.23 citations/publication with a density of 682.60 citations per/year, yielding an h-index of 58. After ranking them by the number of times cited, we extracted the top 100 most-cited records (T100). Number of citations/publication ranged from 13 to 231, publication years were 2002-2019, with the top-cited article published in 2014. All T100 publications were written in English. JMI Laboratories was the institution with the most articles in the T100 (22 documents), and the United States was the top country (75 documents). Five authors participated in at least five of the T100, led by Jones RN with 20 articles. Positions #1, #2, #5, and #9 were clinical trials for acute bacterial skin and skin structure infections (ABSSSI), the on-label indication for dalbavancin. Only one article in the top 10 (T10) was an off-label indication that was published in 2005 with 186 citations, and occupied the third position among the T100. Using the VOSviewer© programme, we observed that the most used keywords were: dalbavancin, lipoglycopeptide, gram-positive, osteomyelitis, vancomycin, and MRSA. WHAT IS NEW AND CONCLUSIONS?: Our study identifies the most significant research on dalbavancin, including the highest impact publications, and highlights the recent trend of dalbavancin in new therapies. The T10 articles include the most important dalbavancin clinical trials, along with other studies and reviews that support the growing role of this antibiotic in clinical use. Emphasis has been on the favourable pharmacokinetic profile that allows administration once-weekly, with minimal risk of severe adverse events.

Surgery and Radiosurgery in Autism: A Retrospective Study in 10 Patients.

INTRODUCTION: A subgroup of patients with autism spectrum disorder (ASD) show self or heteroaggression, dyscontrol episodes, and others are of obsessive-compulsive disorder (OCD) profile; some of them are resistant to medical and behavioural treatment. We describe the long-term outcome in a group of these patients, treated with radiofrequency brain lesions or combined stereotactic surgery and Gamma Knife (GK) radiosurgery. METHODS: We reviewed the medical records of 10 ASD patients with pathological aggressiveness and OCD, who had undergone radiofrequency lesions and/or radiosurgery with GK in our institution. RESULTS: The 10 patients had a significant reduction of their symptoms (PCQ 39.9 and 33, OAS 11.8 and 5, CYBOCS-ASD 30.4 and 20), preoperatively and in the last follow-up, respectively; p < 0.005 (in all cases), although all but 2 needed more than 1 treatment to maintain this improvement. CONCLUSIONS: We observed a marked improvement in behaviour, quality of life, and relationship with the environment in all our 10 patients after the lesioning treatments, without long-lasting side effects.

A novel, fully digital approach to quantifying volume gain after soft tissue graft surgery. A pilot study.

OBJECTIVE: Measuring soft tissue thickness after mucogingival surgery has traditionally been performed by means of a calibrated transgingival probe. The main aim of this study was to apply a non-invasive technique based on digital images formatted as Standard Tessellation Language (STL) files to quantify soft tissue volume after connective tissue grafting. CLINICAL INNOVATION REPORT: Ten patients who presented Cairo Class I gingival recession were selected for connective tissue grafting using the tunnel technique. In all patients, the initial position of the gingiva and quantity of keratinized tissue were recorded, and gingival recession was scanned with an intra-oral scanner. Six months after surgery, the same intra-oral parameters were recorded and compared with the initial registers using digital volumetric analysis software. RESULTS: Complete root coverage was obtained in most patients (90%), mean coverage being of 2.70 mm with a mean increase in volume of 115.49 mm3 in the treated areas. No pattern was identified that indicated a statistically significant relation between gingival recession and coverage volume in mm3 . CONCLUSIONS: Digital processing of pre- and post-treatment images makes it possible to measure the volume of tissue gained after tissue graft surgery simply and non-invasively. The technique is an objective and reproducible method for measuring soft tissue thickness.

Evaluating UK National Guidance for Screening of Children for Tuberculosis. A Prospective Multicenter Study.

RATIONALE: To identify infected contacts of tuberculosis (TB) cases, the UK National Institute for Health and Care Excellence (NICE) recommended the addition of IFN-γ release assays (IGRA) to the tuberculin skin test (TST) in its 2006 TB guidelines. Treatment for TB infection was no longer recommended for children who screened TST-positive but IGRA-negative. OBJECTIVES: We performed a cohort study to evaluate the risk of TB disease in this group. METHODS: Children exposed to an infectious case of TB in their household were recruited from 11 pediatric TB clinics. TST and IGRA were performed at baseline, with IGRA repeated at 8 weeks and TST repeated if initially negative. Children were treated according to 2006 NICE guidelines and followed for 24 months. MEASUREMENTS AND MAIN RESULTS: Of 431 recruited children, 392 completed the study. We diagnosed 48 (12.2%) cases of prevalent TB disease, 105 (26.8%) with TB infection, and 239 (60.9%) without TB infection or disease. Eighteen children aged 2 years and above had a positive TST but persistently negative IGRA. None received TB infection treatment and none developed TB disease. Ninety (26.1%) children qualified for TB infection treatment according to 2006 NICE guidelines. In contrast, 147 (42.7%) children would have qualified under revised NICE guidance, issued in 2016. CONCLUSIONS: In this low-prevalence setting we saw no incident cases of TB disease in children who were TST-positive but IGRA-negative and did not receive treatment for TB infection. Following the latest NICE guidance, significantly more children will require medication.

Significant Hemorrhage Rate Reduction after Gamma Knife Radiosurgery in Symptomatic Cavernous Malformations: Long-Term Outcome in 95 Case Series and Literature Review.

BACKGROUND: The natural history of cavernous malformations (CMs) has remained unclear. This lack of knowledge has made treatment decisions difficult. Indeed, the use of stereotactic radiosurgery is nowadays controversial. The purpose of this paper is to throw light on the effectiveness of Gamma Knife radiosurgery (GKRS) therapy. METHODS: The authors reviewed data collected from a prospectively maintained database. A total of 95 patients (57 female and 38 male) underwent GKRS for high-surgical-risk CMs. A total of 76 cavernomas were deeply located (64 lesions in the brainstem and 12 lesions in the thalamus). All of them were located in eloquent regions. The median malformation volume was 1,570 mm3. The median tumor margin dose was 11.87 Gy, and the mean tumor maximum dose was 19.56 Gy. RESULTS: Ninety-five cavernous CMs were managed from 1994 to 2014. All patients had experienced at least 1 symptomatic bleeding incident before treatment (only 1 hemorrhage event in 81%). The median length of follow-up review was 78 months. The pretreatment annual hemorrhage rate was 3.06% compared with 1.4% during the first 3-year latency interval, and 0.16% thereafter (p = 0.004). Four patients developed new location-dependent neurological deficits, and 3 patients had edema-related headache after radiosurgery. All of them presented full recovery. CONCLUSIONS: The best dosage range for preventing bleeding was identified as between 11 and 12 Gy in our series. Although the efficacy of radiosurgery in CMs remains impossible to quantify, a very significant reduction in the bleeding rate occurs after a 3-year latency interval. No permanent neurological morbidity is reported in our series. These results defend the safety of GKRS in surgical high-risk CM from the first bleeding event.

Impaired Recognition of Mycobacterium tuberculosis by Alveolar Macrophages From Diabetic Mice.

BACKGROUND: Diabetes mellitus is associated with increased tuberculosis risk and severity. We previously reported that tuberculosis susceptibility in diabetic mice results from a delay in innate immune response to inhaled Mycobacterium tuberculosis, leading to delayed adaptive immune priming and, consequently, a higher plateau lung bacterial burden and greater immune pathology. METHODS: We tested the capacity of alveolar macrophages from diabetic mice to phagocytose M. tuberculosis ex vivo and promote T-cell activation in vivo. RESULTS: Alveolar macrophages from diabetic mice had reduced expression of CD14 and macrophage receptor with collagenous structure (MARCO), which recognize the bacterial cell wall component trehalose 6,6'-dimycolate (TDM). Diabetic alveolar macrophages exhibited reduced phagocytosis of M. tuberculosis or TDM-coated latex beads. This alveolar macrophage phenotype was absent in peritoneal and bone marrow-derived macrophages. Transfer of infected alveolar macrophages from diabetic mice into nondiabetic recipients confirmed an intrinsic alveolar macrophage defect that hindered T-cell priming. The diabetic alveolar macrophage phenotype depended in part on expression of the receptor for advanced glycation end products. CONCLUSIONS: Reduced MARCO and CD14 expression contributes to defective sentinel function of alveolar macrophages, promoting tuberculosis susceptibility in diabetic hosts at a critical early step in the immune response to aerosol infection.

Fluctuation-driven mechanotransduction regulates mitochondrial-network structure and function.

Cells can be exposed to irregular mechanical fluctuations, such as those arising from changes in blood pressure. Here, we report that ATP production, assessed through changes in mitochondrial membrane potential, is downregulated in vascular smooth muscle cells in culture exposed to monotonous stretch cycles when compared with cells exposed to a variable cyclic stretch that incorporates physiological levels of cycle-by-cycle variability in stretch amplitude. Variable stretch enhances ATP production by increasing the expression of ATP synthase's catalytic domain, cytochrome c oxidase and its tyrosine phosphorylation, mitofusins and PGC-1α. Such a fluctuation-driven mechanotransduction mechanism is mediated by motor proteins and by the enhancement of microtubule-, actin- and mitochondrial-network complexity. We also show that, in aorta rings isolated from rats, monotonous stretch downregulates-whereas variable stretch maintains-physiological vessel-wall contractility through mitochondrial ATP production. Our results have implications for ATP-dependent and mechanosensitive intracellular processes.

Chromatin decondensation and T cell hyperresponsiveness in diabetes-associated hyperglycemia.

Diabetes is linked to increased inflammation and susceptibility to certain infectious diseases including tuberculosis (TB). We previously reported that aerosol TB in mice with chronic (≥ 12 wk) hyperglycemia features increased bacterial load, overproduction of several cytokines, and increased immune pathology compared with normoglycemic controls. A similar phenotype exists in human patients with diabetes with TB. The mechanisms of increased T cell activation in diabetes are unknown. In the current study, we tested the hypothesis that hyperglycemia modifies the intrinsic responsiveness of naive T cells to TCR stimulation. Purified T cells from chronically hyperglycemic (HG) mice produced higher levels of Th1, Th2, and Th17 cytokines and proliferated more than T cells from normoglycemic controls after anti-CD3e or Ag stimulation. In this way, naive T cells from HG mice resembled Ag-experienced cells, although CD44 expression was not increased. Chromatin decondensation, another characteristic of Ag-experienced T cells, was increased in naive T cells from HG mice. That phenotype depended on expression of the receptor for advanced glycation end products and could be reversed by inhibiting p38 MAPK. Chromatin decondensation and hyperresponsiveness to TCR stimulation persisted following transfer of T cells from HG mice into normoglycemic mice. We propose that chronic hyperglycemia causes receptor for advanced glycation end products-mediated epigenetic modification of naive T cells leading to p38 MAPK-dependent chromatin decondensation. This preactivation state facilitates transcription factor access to DNA, increasing cytokine production and proliferation following TCR stimulation. This mechanism may contribute to pathological inflammation associated with diabetes and might offer a novel therapeutic target.

Diabetes and immunity to tuberculosis.

The dual burden of tuberculosis (TB) and diabetes has attracted much attention in the past decade as diabetes prevalence has increased dramatically in countries already afflicted with a high burden of TB. The confluence of these two major diseases presents a serious threat to global public health; at the same time it also presents an opportunity to learn more about the key elements of human immunity to TB that may be relevant to the general population. Some effects of diabetes on innate and adaptive immunity that are potentially relevant to TB defense have been identified, but have yet to be verified in humans and are unlikely to fully explain the interaction of these two disease states. This review provides an update on the clinical and epidemiological features of TB in the diabetic population and relates them to recent advances in understanding the mechanistic basis of TB susceptibility and other complications of diabetes. Issues that merit further investigation - such as geographic host and pathogen differences in the diabetes/TB interaction, the role of hyperglycemia-induced epigenetic reprogramming in immune dysfunction, and the impact of diabetes on lung injury and fibrosis caused by TB - are highlighted in this review.

Intracellular bacillary burden reflects a burst size for Mycobacterium tuberculosis in vivo.

We previously reported that Mycobacterium tuberculosis triggers macrophage necrosis in vitro at a threshold intracellular load of ~25 bacilli. This suggests a model for tuberculosis where bacilli invading lung macrophages at low multiplicity of infection proliferate to burst size and spread to naïve phagocytes for repeated cycles of replication and cytolysis. The current study evaluated that model in vivo, an environment significantly more complex than in vitro culture. In the lungs of mice infected with M. tuberculosis by aerosol we observed three distinct mononuclear leukocyte populations (CD11b(-) CD11c(+/hi), CD11b(+/lo) CD11c(lo/-), CD11b(+/hi) CD11c(+/hi)) and neutrophils hosting bacilli. Four weeks after aerosol challenge, CD11b(+/hi) CD11c(+/hi) mononuclear cells and neutrophils were the predominant hosts for M. tuberculosis while CD11b(+/lo) CD11c(lo/-) cells assumed that role by ten weeks. Alveolar macrophages (CD11b(-) CD11c(+/hi)) were a minority infected cell type at both time points. The burst size model predicts that individual lung phagocytes would harbor a range of bacillary loads with most containing few bacilli, a smaller proportion containing many bacilli, and few or none exceeding a burst size load. Bacterial load per cell was enumerated in lung monocytic cells and neutrophils at time points after aerosol challenge of wild type and interferon-γ null mice. The resulting data fulfilled those predictions, suggesting a median in vivo burst size in the range of 20 to 40 bacilli for monocytic cells. Most heavily burdened monocytic cells were nonviable, with morphological features similar to those observed after high multiplicity challenge in vitro: nuclear condensation without fragmentation and disintegration of cell membranes without apoptotic vesicle formation. Neutrophils had a narrow range and lower peak bacillary burden than monocytic cells and some exhibited cell death with release of extracellular neutrophil traps. Our studies suggest that burst size cytolysis is a major cause of infection-induced mononuclear cell death in tuberculosis.

Impact of Qigong on quality of life, pain and depressive symptoms in older adults admitted to an intermediate care rehabilitation unit: a randomized controlled trial.

BACKGROUND AND AIMS: Qigong has been used as a complementary therapy to improve different health-related problems. This study aims to test the effects of Qigong on quality of life, pain and depressive symptoms in older hospitalized patients. METHODS: In this randomized controlled single blind study, we randomized 58 ≥50 years adults admitted to a post-acute intermediate care rehabilitation facility, to receive a 90 min, bi-weekly, 4-week structured Qigong intervention plus usual care and rehabilitation (N = 29) or usual care and rehabilitation alone (N = 29). Outcomes included quality of life (0-100 points visual analogical scale), pain (0-10 points scale), and depressive symptoms (5-item modified Yesavage Geriatric Depression Scale). We also evaluated participants' compliance and safety. RESULTS: Of the enrolled 58 participants (mean age ± SD = 74.3 ± 8.2 years, 88 % women) we dropped-out four in the control group. No statistically significant differences in baseline characteristics were shown between groups, including age, gender, marital status, education, comorbidity and functional status, main diagnostic at admission and number of rehabilitation sessions. In an intention-to-treat analysis (repeated measures ANOVA) the intervention group experienced a significant improvement in quality of life (mean increase of 19 points vs 2.6 points for controls, p = 0.002). Pain and depressive symptoms improved in both groups. Adherence was good (79 % of participants completed the whole program). No adverse events were reported. CONCLUSIONS: According to our results, a structured Qigong intervention, together with usual care, might contribute to improve quality of life of patients admitted to a post-acute intermediate care rehabilitation unit, compared to usual care.

Automated preparation of whole blood-derived platelets suspended in two different platelet additive solutions and stored for 7 days.

BACKGROUND: The Atreus system (Terumo BCT) automates the preparation of blood components from whole blood donations. Intermediate platelet (PLT) products can be pooled manually or with the OrbiSac (Terumo BCT) and suspended in different PLT additive solutions (PASs) to obtain PLT concentrates (PCs). The aim of our study was to compare the in vitro PLT quality of PCs obtained with either the Atreus 2C+ and the OrbiSac or the Atreus 3C and suspended in PAS-II or PAS-IIIM during storage for up to 7 days. STUDY DESIGN AND METHODS: We prepared eight PCs from buffy coats obtained with Atreus 2C+, pooled with the OrbiSac, and suspended in PAS-II and eight PCs from interim PLT units obtained with the Atreus 3C and suspended either in PAS-II or in PAS-IIIM. We measured volume, PLT content, and mean PLT component and performed metabolic assays (pH, glucose, lactate, pO2, and pCO2) and flow cytometry analyses (GPIb, GPIIbIIIa, GPIV, CD62P, CD63, von Willebrand factor [vWF], fibrinogen, Factor V, and annexin V). RESULTS: PCs prepared with the Atreus 3C showed lower volume and higher PLT concentration when compared with PCs prepared with the Atreus 2C+ and the OrbiSac (p < 0.05). Glucose consumption rate and the expression of CD62P, CD63, and vWF were lower in PCs suspended in PAS-IIIM when compared with PCs suspended in PAS-II (p < 0.05). CONCLUSION: PCs prepared with the Atreus 3C and suspended in PAS-IIIM preserve satisfactorily the in vitro PLT quality during 7-day storage. PLT activation during a 7-day storage period was lower when the storage solution was PAS-IIIM in comparison with PAS-II.

Single cell RNA-sequencing reveals molecular signatures that distinguish allergic from irritant contact dermatitis.

Allergic contact dermatitis (ACD) is a pruritic skin disease caused by environmental chemicals that induce cell-mediated skin inflammation within susceptible individuals. Irritant contact dermatitis (ICD) is caused by direct damage to the skin barrier by environmental insults. Diagnosis can be challenging as both types of contact dermatitis can appear similar by visual exam, and histopathological analysis does not reliably distinguish ACD from ICD. To discover specific biomarkers of ACD and ICD, we characterized the transcriptomic and proteomic changes that occur within the skin during each type of contact dermatitis. We induced ACD and ICD in healthy human volunteers and sampled skin using a non-scarring suction blister biopsy method that collects interstitial fluid and cellular infiltrate. Single cell RNA-sequencing analysis revealed that cell-specific transcriptome differences rather than cell type proportions best distinguished ACD from ICD. Allergy-specific genes were associated with upregulation of IFNG, and cell signaling network analysis implicated several other genes such as IL4, despite their low expression levels. We validated transcriptomic differences with proteomic assays on blister fluid and trained a logistic regression model on skin interstitial fluid proteins that could distinguish ACD from ICD and healthy control skin with 93% sensitivity and 93% specificity.

Mourning and orienting to the future in a liminal occasion: (Re)defining British national identity after Queen Elizabeth II's death.

In this paper, we conceptualize the days of mourning that followed the passing of Queen Elizabeth II. as constituting a liminal occasion, a moment of in-betweenness through which we can explore sense-making in times of transition. How do people navigate through liminal occasions, and are they always transformative? Through a rapid response ethnography (Ninterviews = 64, Nparticipants = 122), we were able to capture the raw moments within which a collective comes together, as part of a national ritual, to transition from 'here' to 'there'. In our data, liminality prompted participants to strategically define British national identity and its future by positioning the Queen as representative of Britishness, her loss as a national identity loss. No longer taken for granted, participants reasserted the value of the monarchy as an apolitical and unifying feature in an otherwise divided society, characterizing the continuity of the institution as an essential part of British identity and society. The analysis illustrates how liminality offers a useful conceptual tool for addressing how temporality and change are negotiated in relation to a shared identity, and how navigating transitional moments brings with it political implications for the future.

Quality and stability studies of red blood cell concentrates from umbilical cord blood compared to their adult counterparts.

BACKGROUND: Prematurity is a significant health issue due to its incidence and associated complications. Anemia is common in extremely preterm infants (EPI) and often requires transfusions. Red blood cells (RBC) from adult blood (AB) donors have been linked to oxygen-related complications in EPI, leading to the exploration of cord blood (CB) as an alternative source. However, standardization of CB-RBC manufacturing and comparison with AB-RBC characteristics are necessary before clinical studies can be conducted. MATERIALS AND METHODS: This study investigated the quality and characteristics of leukoreduced, gamma-irradiated CB-RBC obtained using a commercial closed system from CB donations not meeting hematopoietic transplantation criteria. CB-RBC units were compared with AB-RBC units, both stored in saline-adenine-glucose-mannitol (SAGM). Various parameters, including hematological and biochemical characteristics, pH, 2,3-DPG levels, blood gases and potential toxicants, were evaluated during storage. RESULTS: CB-RBC units had acceptable initial quality parameters and a hematocrit (55±2%) comparable to AB-RBC. The main finding during storage was a faster rise in hemolysis compared to AB-RBC. Potassium (K+) significantly increased during storage in both sources. As expected, glucose levels decreased, and conversely, lactate levels increased, indicating similar patterns of anaerobic glycolysis during storage. pH decreased, affecting the oxygen dissociation curve due to reduced 2,3-DPG levels. After irradiation at 14 days of storage, CB-RBC were less stable as hemolysis and K+ significantly increased compared to AB-RBC at 24 hours. Phthalate concentrations, indicative of plasticizers, increased during storage, but significantly less in CB compared to AB-RBC. Most metals measured were within acceptable ranges. DISCUSSION: The quality of CB-RBC during storage is primarily influenced by levels of hemolysis and extracellular K+ content. Based on the analyzed parameters, we suggest that the expiration date for CB-RBC stored with SAGM should be set at 14 days, with transfusion occurring within <24 hours after irradiation.

Beyond the patella: Treatment of cam femoroacetabular impingement syndrome improves anterior knee pain.

OBJECTIVES: This study aimed to investigate if there is a relationship between cam femoroacetabular impingement syndrome (cam-FAIS) and chronic anterior knee pain (AKP). METHODS: This is a pilot retrospective review of 12 AKP patients with no structural anomalies in the patellofemoral joint and no skeletal malalignment in the lower limbs. All the patients were resistant to proper conservative treatment for AKP (AKP-R). Subsequently, these patients developed pain in the ipsilateral hip several months later, and upon evaluation, were diagnosed with cam-FAIS. Arthroscopic femoral osteoplasty and labral repair were performed and clinical follow-up of hip and knee pain and function (Kujala Score and Non-arthritic Hip Score -NAHS-) was carried out. RESULTS: All the patients showed improvement in the knee and hip pain scores with a statistically significant clinical difference in all of them at 69 months follow up (range: 18 to 115) except one patient without improvement in the groin VAS score post-operatively. Visual analogical scale (VAS) of knee pain improved from 6.3 (range: 5 to 8) to a postoperative 0.5 (range: 0 to 3.5), (p â€‹< â€‹0.001). The VAS of groin pain improved from 4.4 (range: 2 to 8) to a postoperative 0.9 (range: 0 to 3), (p â€‹< â€‹0.001). NAHS improved from a preoperative 67.9 (range: 28.7 to 100) to a postoperative 88 (range: 70 to 100), (p â€‹< â€‹0.015) and knee Kujala's score improved from a preoperative 48.7 (range: 22 to 71) to a postoperative 96 (range: 91 to 100), (p â€‹< â€‹0.001). CONCLUSION: This study's principal finding suggests an association between cam-FAIS and AKP-R in young patients who exhibit normal knee imaging and lower limbs skeletal alignment. Addressing cam-FAIS in these cases leads to resolution of both groin and knee pain, resulting in improved functional outcomes for both joints. STUDY DESIGN: Retrospective cohort series with a single contemporaneous long-term follow-up. LEVEL OF EVIDENCE: IV.

Changes in entire acute bronchiolitis seasons before, during, and after the COVID-19 pandemic in Spain.

Background: Paediatric acute bronchiolitis normally occurs from October to April in the temperate northern hemisphere, peaking in January. Nonpharmacological measures to control the spread of COVID-19 resulted in a decrease in the number of cases of bronchiolitis during the 2020-21 season. The discontinuation of these measures created an uncertain scenario. Aim: To describe the epidemiological evolution of acute bronchiolitis seasons and the changes in the demographics of the affected population before, during, and after the implementation of nonpharmacological interventions for COVID-19 in Spain. Methods: This was a multicentre and descriptive study. A total of 6,334 infants aged up to 12 months who were diagnosed with acute bronchiolitis were recruited from sixteen Spanish hospitals. We collected data from participants from September 1st, 2021, through August 31st, 2023, as part of the ECEALHBA research project. The study periods were before (P1), during (P2), and after (P3) the COVID-19 pandemic. Findings: In P2 and after the discontinuation of nonpharmacological interventions, an unexpected increase in the number of acute bronchiolitis cases was observed from June-August 2021, resulting in an out-of-season peak. A subsequent peak was observed in November 2021, earlier than expected for the 2021-22 season. In the 2022-23 season, admissions followed a historical trend, with a greater number of cases than in the two previous seasons. Statistically significant differences in the length of stay (p<0.001), number of RSV infections (p=0.021), and number of paediatric intensive care unit admissions (p<0.001) were observed among the periods. Conclusions: Two out-of-season peaks in the number of acute bronchiolitis cases were observed in 2020-2021 and 2021-2022. However, following the relaxation of nonpharmacological intervention measures, the peak observed in 2022-2023, although occurring 2-6 weeks earlier, was more similar to the peaks observed in the prepandemic seasons. Additionally, increased case severity was observed during these periods.

School bullying in children and adolescents with neurodevelopmental and psychiatric conditions: a systematic review and meta-analysis.

BACKGROUND: Bullying is a common form of violence among children and adolescents. Young people with neurodevelopmental or psychiatric conditions might have an increased risk of bullying victimisation and perpetration. We aimed to assess the odds of bullying involvement and its association with mental health measures in these populations. METHODS: In this systematic review and meta-analysis, we searched PubMed, ERIC, Psychology and Behavioural Sciences Collection, Web of Science Core Collection, PsycArticles, and PsycInfo databases from inception up to Aug 8, 2023, and included articles reporting data on bullying outcomes of current bullying (within the past year) among children and adolescents (aged 4-17 years) with a diagnosis of a neurodevelopmental or psychiatric condtion provided by a health professional. Bullying type was classified as traditional (physical, verbal, or relational) or as cyberbullying (intentional and repeated harm inflicted through electronic devices and social media), and bullying involvement was classified as victimisation, perpetration, and perpetration-victimisation. Mental health measures were collected and the associations with bullying involvement assessed. We used random-effects meta-analyses to estimate prevalence and odds ratios (ORs) for bullying involvement. Heterogeneity was assessed using the I2 statistic, and publication bias was tested with Egger's regression. This study is registered with PROSPERO, CRD42021235043. FINDINGS: We included 212 studies in the meta-analysis. The total sample comprised 126 717 cases (mean age 12·34 years [SD 1·82], 37·6% girls) and 504 806 controls (12·5 years [SD 1·86], 47·6% girls). For traditional bullying, the pooled prevalence was 42·2% (95% CI 39·6-44·9) for victimisation, 24·4% (22·6-26·3) for perpetration, and 14·0% (11·4-17·1) for perpetration-victimisation. For cyberbullying, the prevalence was 21·8% (16·0-28·9) for victimisation, 19·6% (13·4-27·7) for perpetration, and 20·7% (8·4-42·6) for perpetration-victimisation. Compared with controls, young people with neurodevelopmental or psychiatric conditions were more likely to be involved in traditional and cyberbullying as a victim (OR 2·85 [95% CI 2·62-3·09] and 2·07 [1·63-2·61]), perpetrator (2·42 [2·20-2·66] and 1·91 [1·60-2·28]), and perpetrator-victim (3·66 [2·83-4·74] and 1·85 [1·05-3·28]). Bullying involvement was associated with higher scores in mental health measures in young people with neurodevelopmental or psychiatric conditions, particularly internalising symptoms and externalising symptoms. INTERPRETATION: Our study underscores bullying involvement as a prevalent risk factor in young people with neurodevelopmental or psychiatric conditions that might add to their disease burden through its negative effects on mental health. Interventions targeting these vulnerable populations are warranted to improve their mental health and their future social integration. FUNDING: Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Consorcio Centro de Investigación Biomédica en Red.

Dispensation of outpatient hospital medicines by hospital only versus hospital-community pharmacies collaboration: a cross-sectional study and survey of patient's satisfaction.

Goal: To describe the experience of a dispensing model of outpatient hospital medicines (OHM) via collaboration of hospital and community pharmacies, and to explore patient satisfaction with the strategy as compared with the hospital pharmacy only service. Background: Patient satisfaction is an important component of the quality of health care. Study: A new model of dispensing OHM was conducted in the Outpatients Unit of the Service of Hospital Pharmacy of Hospital del Mar, in Barcelona, Spain. Participants were patients on stable chronic treatment with clinical or social fragility, immunocompromised patients, and those whose residence was located at a distance from the hospital that justified drug delivery through the community pharmacy. A cross sectional study was done using an ad hoc 14-item questionnaire collecting demographic data, duration of treatment, usual mode of collecting medication, and the degree of satisfaction regarding waiting time for the collection of medication, attention received by professionals, information received on treatment, and confidentiality. Results: The study population included a total of 4,057 patients (66.8% men) with a mean age of 53 (15.5) years, of whom 1,286 responded, with a response rate of 31.7%. Variables significantly associated with response to the survey were age over 44 years, particularly the age segment of 55-64 years (odds ratio [OR] 2.51) and receiving OHM via the community pharmacy (OR 12.76). Patients in the community pharmacy group (n = 927) as compared with those in the hospital pharmacy group (n = 359) showed significantly higher percentages of 'satisfied' and 'very satisfied' (p < 0.001) in the waiting time for the collection of OHM (88.1% vs. 66%), attention received by professionals (92.5% vs. 86.1%), and information received on treatment (79.4% vs. 77.4%). In relation to confidentiality, results obtained were similar in both pharmacy settings. Conclusion: Dispensing OHM through the community pharmacy was a strategy associated with greater patient satisfaction as compared with OHM collection at the hospital pharmacy service, with greater accessibility, mainly due to close distance to the patient's home. The participation of community pharmacists could further optimize the care received by patients undergoing OHM treatment.