Explore the vast range of titles available.

Abstract Background We aimed to describe the clinical presentation of individuals presenting with prolonged recovery from coronavirus disease 2019 (COVID-19), known as long COVID. Methods This was an analysis within a multicenter, prospective cohort study of individuals with a confirmed diagnosis of COVID-19 and persistent symptoms >4 weeks from onset of acute symptoms. We performed a multiple correspondence analysis (MCA) on the most common self-reported symptoms and hierarchical clustering on the results of the MCA to identify symptom clusters. Results Two hundred thirty-three individuals were included in the analysis; the median age of the cohort was 43 (interquartile range [IQR], 36–54) years, 74% were women, and 77.3% reported a mild initial illness. MCA and hierarchical clustering revealed 3 clusters. Cluster 1 had predominantly pain symptoms with a higher proportion of joint pain, myalgia, and headache; cluster 2 had a preponderance of cardiovascular symptoms with prominent chest pain, shortness of breath, and palpitations; and cluster 3 had significantly fewer symptoms than the other clusters (2 [IQR, 2–3] symptoms per individual in cluster 3 vs 6 [IQR, 5–7] and 4 [IQR, 3–5] in clusters 1 and 2, respectively; P < .001). Clusters 1 and 2 had greater functional impairment, demonstrated by significantly longer work absence, higher dyspnea scores, and lower scores in SF-36 domains of general health, physical functioning, and role limitation due to physical functioning and social functioning. Conclusions Clusters of symptoms are evident in long COVID patients that are associated with functional impairments and may point to distinct underlying pathophysiologic mechanisms of disease.

Research suggests that general practice can play an important role in managing long COVID. However, studies investigating the perspectives of general practitioners (GPs) and patients are lacking and knowledge regarding optimal long COVID care in general practice is therefore limited. To investigate GPs' and patients' perspectives on the topic of long COVID and its management in general practice. Brief questionnaires (GP n = 11, Patient n = 7) and in-depth semi-structured interviews (GP n = 10, Patient n = 7) were conducted with GPs and patients from Irish general practices during July 2022-January 2023. Interviews were conducted via telephone and audio recordings were transcribed. A phenomenological analysis involving reflexive thematic analysis and constant comparison techniques was adopted. Analysis of interviews with GPs (male = 7, female = 3; median age = 50yrs (IQR = 39.5-56)) and patients (males = 2, female = 5; median age = 58yrs (IQR = 45-62yrs) generated four themes. These were (1) Complex presentations (2) the value of standardising care, (3) choosing the right path, and (4) supportive and collaborative doctor-patient relationships. Strong agreement was observed among GPs and patients regarding the need for holistic and integrated multidisciplinary care. Supportive and collaborative doctor-patient relationships were largely well received by GPs and patients also. GPs strongly endorsed standardising long COVID care operations. GPs and patients indicated that structured, integrated, and collaborative care can help optimise long COVID management in general practice. GPs are advised to incorporate these elements into their long COVID care practices going forward. Future research examining stakeholder's perspectives using larger and longitudinal samples is advised to enhance the generalisability of evidence in this area.

Increased levels of chemokine interferon-gamma (IFN-γ)-inducible protein-10 (CXCL10), soluble CD163 (sCD163) and soluble CD14 (sCD14) have been reported in HCV infection. The aim of this study was to compare, sCD163 and sCD14 levels in HCV-infected patients undergoing direct acting antiviral (DAA)-containing regimens with or without interferon (IFN). sCD163, sCD14 and CXCL10 were longitudinally measured by ELISA in 159 plasma samples from 25 HCV-infected patients undergoing IFN-based treatment plus telaprevir or boceprevir and 28 HCV infected subjects treated with DAA IFN-free regimens. Twenty-five healthy donors (HD) were included as controls. At baseline CXCL10, sCD163 and sCD14 levels were higher in HCV-infected patients than in HD. CXCL10 and sCD163 levels were significantly decreased in responder (R) patients who achieved sustained virological response (SVR), with both IFN-based and IFN-free regimens, while they were persistently elevated in non-responders (NR) patients who stopped IFN-based treatments because of failure or adverse events. Conversely, sCD14 levels were apparently unchanged during therapy, but at the end of treatment the levels reached normal ranges. Comparing the two regimens, the extent of CXCL10 reduction was more pronounced in patients undergoing DAA IFN-free therapies, whereas sCD163 and sCD14 reduction was similar in the two groups. Interestingly, only in IFN-based regimens baseline sCD163 levels were significantly higher in NR than in R patients, while in the IFN-free treatment group also patients with high sCD163 plasma levels obtained SVR. At the end of therapy, even if the biomarkers were largely decreased, their levels remained significantly higher compared to HD. Only in the early fibrosis stages, sCD163 values tended to normalize. These results indicate that IFN-free regimens including newer DAA induce an early and marked decrease in circulating inflammatory biomarkers. However, the full normalization of biomarkers was not obtained, especially in patients with advanced fibrosis, thus underlying the need for a treatment in the early stages of HCV infection.

Background Defining patterns of symptoms in long COVID is necessary to advance therapies for this heterogeneous condition. Here we aimed to describe clusters of symptoms in individuals with long COVID and explore the impact of the emergence of variants of concern (VOCs) and vaccination on these clusters. Methods In a prospective, multi centre cohort study, individuals with symptoms persisting > 4 weeks from acute COVID-19 were divided into two groups based on timing of acute infection; pre-Alpha VOC, denoted wild type (WT) group and post-Alpha VOC (incorporating alpha and delta dominant periods) denoted VOC group. We used multiple correspondence analysis (MCA) and hierarchical clustering in the WT and VOC groups to identify symptom clusters. We then used logistic regression to explore factors associated with individual symptoms. Results A total of 417 individuals were included in the analysis, 268 in WT and 149 in VOC groups respectively. In both groups MCA identified three similar clusters; a musculoskeletal (MSK) cluster characterised by joint pain and myalgia, a cardiorespiratory cluster and a less symptomatic cluster. Differences in characteristic symptoms were only seen in the cardiorespiratory cluster where a decrease in the frequency of palpitations (10% vs 34% p  = 0.008) and an increase in cough (63% vs 17% p  < 0.001) in the VOC compared to WT groups was observed. Analysis of the frequency of individual symptoms showed significantly lower frequency of both chest pain (25% vs 39% p  = 0.004) and palpitations (12% vs 32% p  < 0.001) in the VOC group compared to the WT group. In adjusted analysis being in the VOC group was significantly associated with a lower odds of both chest pain and palpitations, but vaccination was not associated with these symptoms. Conclusion This study suggests changes in long COVID phenotype in individuals infected later in the pandemic, with less palpitations and chest pain reported. Adjusted analyses suggest that these effects are mediated through introduction of variants rather than an effect from vaccination.

Background It is the investigator’s responsibility to communicate the relevant information about a clinical trial to participants before they provide informed consent to take part. Systematic reviews indicate that participants often have a poor understanding of the concepts which are key to ensuring valid informed consent, such as randomisation and risks/discomforts. Paper-based participant information leaflets and informed consent forms (PIL/ICFs) are becoming longer and are often too complex for many participants. Multimedia interventions and enhanced PIL/ICFs have been trialled in an attempt to improve participants’ understanding of various aspects of research studies. However, there is insufficient empirical evidence to determine how effective such interventions are. This protocol describes a study to evaluate whether an enhanced PIL/ICF and website help research participants to understand important information about a human immunodeficiency virus (HIV) randomised clinical trial. Methods This Study Within A Trial (SWAT) is a prospective, multi-centre, randomised, controlled, parallel-group study embedded in a host clinical trial. The host trial (the SWIFT trial; EudraCT: 2019-002314-39) is a prospective, multi-centre, randomised, open-label, controlled trial investigating if semaglutide along with dietary advice assists individuals with HIV and obesity to lose weight, compared to dietary advice alone. For the SWAT, participants will be randomised in a 1:1 ratio to either the control (standard PIL/ICF) or the intervention (an enhanced PIL/ICF and a website which includes animations). The enhanced PIL/ICF and website were developed in line with the guidance from organisations which promote plain English and accessible public-facing materials in conjunction with HIV Ireland, a HIV advocacy organisation, and our previous work on consent documents. The primary outcome of the SWAT is the quality of informed consent, assessed by a validated comprehension test—the modified Deaconess Informed Consent Comprehension Test (DICCT). The DICCT will be administered within 48 h of consent to the host trial. The secondary is recall, measured by the modified DICCT questionnaire scores 2 weeks post-consent to the host trial. Discussion The results of this SWAT will add to the methodological evidence base on the use of multimedia to improve the quality of informed consent to randomised clinical trials. Trial registration ClinicalTrials.gov NCT04174755 . EudraCT 2019-002314-39. SWAT 160, Northern Ireland Hub for Trials Methodology Research SWAT repository (Clarke M, et al., Trials. 16:P209, 2015).

Introduction Cognitive changes are very frequently reported by people with post‐COVID‐19 syndrome (PCS), but there is limited understanding of the underpinning mechanisms leading to these difficulties. It is possible that cognitive difficulties are related to immune status and/or low mood. The aim of the present study was to examine the relationship between immune status and cognitive functioning in PCS, while considering whether depression symptoms also influence this association. Methods Participants were recruited in an online study of cognitive and psychological consequences of PCS, involving individuals attending a post‐COVID clinic in an acute general hospital in Ireland, and a comparison sample of age‐ and sex‐matched community controls who had also been infected with COVID‐19 but had not experienced PCS. Participants with PCS (n = 71) and community controls (n = 50) completed the immune status questionnaire, Cognitive Failures Questionnaire (CFQ), Hospital Anxiety and Depression Scale (HADS), and the Functional Assessment of Chronic Illness Therapy‐Fatigue Scale (FACIT‐F). Results Significant differences were observed between groups in terms of perceived immune status, perceived cognitive function, depression scores, and fatigue, with the “PCS” group reporting lower immune status, more cognitive difficulties, and higher levels of depression and fatigue. Regression analysis in the PCS group indicated that immune status and depression significantly contributed to variance in subjective cognitive functioning, with immune status remaining a significant predictor of cognitive functioning scores even when accounting for depression, fatigue, and other covariates related to PCS, such as Body Mass Index (BMI). Conclusion Our findings suggest that subjective cognitive functioning is influenced by self‐reported immune status in PCS, emphasising the importance of immune status, cognitive, and mood screening as part of routine clinical care in PCS.  

Measles is an infectious disease that represents a serious public health problem worldwide, being associated with increased susceptibility to secondary infections, especially in the respiratory and gastrointestinal tracts. The aim of this study was to evaluate sCD163 and sCD14 levels in measles virus (MV) infected patients, as markers of immune activation, in order to better understand their role in the pathogenesis of the disease. TNF-α plasma levels were also evaluated. sCD163, sCD14 and TNF-α were measured by ELISA in plasma samples of 27 MV infected patients and 27 healthy donors (HD) included as controls. At the time of hospital admission, sCD163 and sCD14 levels were significantly higher in MV infected patients than in HD, while a decrease in TNF-α levels were found even if without statistical significance. sCD163 and sCD14 levels were significantly decreased after two months from acute infection compared to hospital admission although they remained significantly higher compared to HD. TNF-α levels increased significantly during the follow-up period. Considering clinical parameters, sCD163 levels positively correlated with aspartate aminotransferase, white blood cell count and neutrophils rate, while negatively correlated with the lymphocyte percentage. sCD14 levels positively correlated with the neutrophil and lymphocyte percentages. These results indicate that, despite the resolution of symptoms, an important macrophage/monocyte activation persists in measles patients, even after two months from infection.

Introduction: Skeletal tuberculosis (TB) accounts for about 10 to 35% of extrapulmonary cases and the knee is the most frequent site after the spine and hip. The diagnosis is difficult and largely clinical. Case presentation: This is a case of a young Pakistani man with a history of joint pain for about 4 years, who was diagnosed with chronic arthritis of the right knee. Microscopy of synovial fluid and conventional diagnostic tests to identify Mycobacterium tuberculosis were negative, while a non-classical method based on intracellular cytokine flow cytometry response of CD4 T-cells in synovial fluid helped us to address the diagnosis, which was subsequently confirmed by Polymerase Chain Reaction (PCR). Conclusions: Thanks to an innovative immunological approach, supported by PCR for detection of M. tuberculosis DNA, we were able to diagnose tuberculous arthritis of the knee, which allowed prompt initiation of treatment to reduce morbidity and mortality.

Chronic hepatitis C virus infection leads to the activation of innate immunity, a key component in HCV fibrosis. In the past, the use of IFN-based treatment regimens did not permit an adequate evaluation of the impact of HCV clearance on immune cells, because of their antiviral and immunomodulatory properties. The recent development of direct-acting antiviral (DAA) therapy, which is associated with high rates of sustained virological response, enables a more accurate analysis of the immunological modifications following HCV eradication. We studied the dynamics of blood myeloid dendritic cells, monocytes, slan-DCs, and T lymphocytes during IFN-free and IFN-based regimens in hepatitis C virus infection.

Purpose of Review This review aims to summarize recently published peer reviewed papers on the influence of treatment with Integrase Strand Transfer Inhibitors (InSTI) in people with HIV (HIV) on metabolic health, including weight gain, lipid parameters, glucose homeostasis, and bone health. Recent Findings InSTI have a mild/moderate effect on weight gain in both antiretroviral (ART) naïve and ART experienced PWH, which is more pronounced in certain groups (i.e. women, people of Black African ethnicity, those with lower socioeconomic status, and older people). The effect on weight is also driven by other components of the ART regimen as well as previous exposure to certain ART. InSTI have a relatively safe profile in terms of lipid parameters and bone health, compared to other ART classes, although some studies suggest a greater risk of insulin resistance and diabetes in PWH using InSTI, especially 2nd generation InSTI. Summary While there is some evidence suggesting a negative impact of InSTI on some aspects of metabolic health (weight gain and glucose homeostasis), they remain the preferred treatment option for most PWH, due to their high efficacy and tolerability. However, an individualised approach to ART choice in PWH should be used in order to avoid negative outcomes in populations at higher risks of metabolic complications.