Exploring the Complexities of Long COVID.

Since the emergence of the SARS-CoV-2 virus in 2019, nearly 700 million COVID-19 cases and 7 million deaths have been reported globally. Despite most individuals recovering within four weeks, the Center for Disease Control (CDC) estimates that 7.5% to 41% develop post-acute infection syndrome (PAIS), known as 'Long COVID'. This review provides current statistics on Long COVID's prevalence, explores hypotheses concerning epidemiological factors, such as age, gender, comorbidities, initial COVID-19 severity, and vaccine interactions, and delves into potential mechanisms, including immune responses, viral persistence, and gut dysbiosis. Moreover, we conclude that women, advanced age, comorbidities, non-vaccination, and low socioeconomic status all appear to be risk factors. The reasons for these differences are still not fully understood and likely involve a complex relationship between social, genetic, hormonal, and other factors. Furthermore, individuals with Long COVID-19 seem more likely to endure economic hardship due to persistent symptoms. In summary, our findings further illustrate the multifaceted nature of Long COVID and underscore the importance of understanding the epidemiological factors and potential mechanisms needed to develop effective therapeutic strategies and interventions.

Cost-Effectiveness of Community-Based Diet and Exercise for Patients with Knee Osteoarthritis and Obesity or Overweight.

OBJECTIVE: Obesity exacerbates pain and functional limitation in persons with knee osteoarthritis (OA). In the Weight Loss and Exercise for Communities with Arthritis in North Carolina (WE-CAN) study, a community-based diet and exercise (D + E) intervention led to an additional 6 kg weight loss and 20% greater pain relief in persons with knee OA and body mass index (BMI) >27 kg/m2 relative to a group-based health education (HE) intervention. We sought to determine the incremental cost-effectiveness of the usual care (UC), UC + HE, and UC + (D + E) programs, comparing each strategy with the "next-best" strategy ranked by increasing lifetime cost. METHODS: We used the Osteoarthritis Policy Model to project long-term clinical and economic benefits of the WE-CAN interventions. We considered three strategies: UC, UC + HE, and UC + (D + E). We derived cohort characteristics, weight, and pain reduction from the WE-CAN trial. Our outcomes included quality-adjusted life years (QALYs), cost, and incremental cost-effectiveness ratios (ICERs). RESULTS: In a cohort with mean age 65 years, BMI 37 kg/m2, and Western Ontario and McMaster Universities Osteoarthritis Index pain score 38 (scale 0-100, 100 = worst), UC leads to 9.36 QALYs/person, compared with 9.44 QALYs for UC + HE and 9.49 QALYS for UC + (D + E). The corresponding lifetime costs are $147,102, $148,139, and $151,478. From the societal perspective, UC + HE leads to an ICER of $12,700/QALY; adding D + E to UC leads to an ICER of $61,700/QALY. CONCLUSION: The community-based D + E program for persons with knee OA and BMI >27kg/m2 could be cost-effective for willingness-to-pay thresholds greater than $62,000/QALY. These findings suggest that incorporation of community-based D + E programs into OA care may be beneficial for public health.

Frequency-potency analysis of IgG+ memory B cells delineates neutralizing antibody responses at single-cell resolution.

Identifying individual functional B cell receptors (BCRs) is common, but two-dimensional analysis of B cell frequency versus BCR potency would delineate both quantity and quality of antigen-specific memory B cells. We efficiently determine quantitative BCR neutralizing activities using a single-cell-derived antibody supernatant analysis (SCAN) workflow and develop a frequency-potency algorithm to estimate B cell frequencies at various neutralizing activity or binding affinity cutoffs. In an HIV-1 fusion peptide (FP) immunization study, frequency-potency curves elucidate the quantity and quality of FP-specific immunoglobulin G (IgG)+ memory B cells for different animals, time points, and antibody lineages at single-cell resolution. The BCR neutralizing activities are mainly determined by their affinities to soluble envelope trimer. Frequency analysis definitively demonstrates dominant neutralizing antibody lineages. These findings establish SCAN and frequency-potency analyses as promising approaches for general B cell analysis and monoclonal antibody (mAb) discovery. They also provide specific rationales for HIV-1 FP-directed vaccine optimization.

Epidermodysplasia verruciformis-associated eccrine neoplasm: a rare entity with distinctive clinical and histopathologic features.

Most tumors are caused by inherited or acquired genetic changes. However, a subset of tumors is driven by viral infection including Kaposi sarcoma, nasopharyngeal carcinoma, and others. Human papillomavirus (HPV) is an especially common cause of epithelial cancers and hyperplasias. Epidermodysplasia verruciformis (EDV) is a rare type of HPV infection with characteristic histopathologic features and a unique spectrum of HPV subtypes. We report here a distinctive form of EDV-associated eccrine neoplasia. Seven tumors from two patients were analyzed and show highly uniform features including multiple clustered clinical lesions, multifocal epidermal origin, eccrine differentiation with close association with the acrosyringium, an anastomosing growth pattern, and a bland monotonous poroid-to-basaloid cytomorphology. Clinical follow-up for one patient has been benign to date. These tumors show strong similarity to two previously reported cases, suggesting that this type of EDV-associated eccrine neoplasia may represent a rare but reproducible form of skin adnexal tumor with distinctive clinicopathologic features.

Pacific patients' reasons for attending the emergency department of Counties Manukau for non-urgent conditions.

AIM: To determine Pacific patients' reasons for Emergency Department (ED) use for non-urgent conditions by Pacific people at Counties Manukau Health. METHODS: Patients who self-presented to Counties Manukau ED with a non-urgent condition in June 2019 were surveyed. Responses to open-ended questions were analysed using a general inductive approach, in discussion with key stakeholders. RESULTS: Of 353 participants with ethnicity reported, 139 (39%) were Pacific, 66 (19%) Maori and 148 (42%) were non-Maori non-Pacific, nMnP. A total of 58 (42%) of Pacific participants had been to their general practitioner prior to presenting to the ED; this proportion was similar for Maori (19 [30%]) and nMnP (59 [40%]) (p=0.215). The most common reasons for ED attendance among Pacific (as well as other) participants were 1) advice by a health professional (41%, 95% CI 33-50%), 2) usual care unavailable (28%, 20-36%), 3) symptoms not improving (21%, 14-28%), and 4) symptoms too severe to be managed elsewhere (19%, 12-26%). CONCLUSIONS: Multiple reasons underlie non-urgent use of EDs by Pacific and other ethnic groups. These reasons need to be considered simultaneously in the design, implementation, and evaluation of multi-dimensional initiatives that discourage non-urgent use of EDs to ensure that such initiatives are effective, equitable, and unintended consequences are avoided.

Strategies Used by Healthcare Systems to Communicate with Hospitalized Patients and Families with Limited English Proficiency During the COVID-19 Pandemic: A Narrative Review.

The COVID-19 pandemic disproportionately affected racial and ethnic minorities in the United States, including many with limited English proficiency (LEP). These patients face various communication barriers, including a shortage of available interpreters and the need for masks that exacerbated communication barriers. It is not known how hospitals responded to these unique challenges to providing language services for the large number of patients with LEP during COVID-19. This narrative review assessed literature and lay media to identify strategies utilized by hospitals to communicate with patients with LEP hospitalized during the COVID-19 pandemic. A search of APA PsychInfo, EBM Reviews, Embase, Ovid MEDLINE, Epub Ahead of Print, and Ebsco Megafile initially yielded 61 articles, 6 of which were ultimately included after reviewing abstracts and full texts. The identified interventions, which sought to increase accessibility of language-concordant care, increase accessibility of professional interpretation, and improve family communication and understanding, were described positively, though only one was tested for effectiveness.

Application of constructivism and cognitive flexibility theory to build a Comprehensive, Integrated, Multimodal Interprofessional Education and Practice (CIM-IPEP) program.

Interprofessional Education (IPE) is challenging to implement and assess due to barriers preventing interprofessional communication, inadequately defined accreditation criteria, ambiguous professional roles and responsibilities, and the inherently "ill-structured" educational construct of IPE. To address these gaps, a novel comprehensive, integrated, and multimodal interprofessional education and practice (CIM-IPEP) curriculum involving students from pharmacy, medicine, psychology, and nursing professional degree programmes was created. CIM-IPEP was carefully designed based on cognitive flexibility theory (CFT) to reinforce the complexities associated with teaching and learning for multi-faceted and dynamic domains such as IPE. CFT emphasises pluralistic representation, repetition, and cognitive layering in experiential learning for ill-structured domains. Thus, CIM-IPEP was vertically and horizontally aligned within individual colleges and included diverse IPE experiences in required courses such as Foundations of IPE, and high-fidelity simulation events, culminating in an IPE-Hotspotting elective, which exposed learners to real-world patient cases. Cases were presented in a format of increasing complexity emphasising the integration of foundational and skills-based learning using constructivist methods such as Team-Based and Case-Based Learning. CIM-IPEP offers a novel IPE model. Here we present a stepwise development and implementation blueprint for similar IPE programmes that is readily transferable to other health profession education (HPE) programmes.

Attitude theory and measurement in implementation science: a secondary review of empirical studies and opportunities for advancement.

BACKGROUND: Implementation science studies often express interest in "attitudes," a term borrowed from psychology. In psychology, attitude research has an established methodological and theoretical base, which we briefly summarize here. We then review implementation studies designed to measure attitudes and compare their definitions and methods with those from psychology. METHODS: A recent review identified 46 studies empirically examining factors associated with implementation. For each of these studies, we evaluated whether authors included attitudes as a construct of interest, and if so, whether and how the construct was defined, measured, and analyzed. RESULTS: Most of the articles (29/46 [63%]) mention attitudes as an implementation factor. Six articles include a definition of the construct. Nineteen studies were designed to measure attitudes but lacked clarity in describing how attitudes were measured. Those that explained their measurement approach used methods that differed from one another and from validated methods in social psychology. Few articles described associated analyses or provided results specific to attitudes. Despite the lack of specificity regarding relevant measurement, analysis, and results, the articles often included causal conclusions about the role of attitudes. CONCLUSIONS: Attitudes may be an important construct to implementation scientists, but studies to date are ambiguous in their definitions of attitudes and inconsistent in the methods used to measure and analyze attitudes. We discuss how implementation studies can apply psychology's standardized definitions, validated measurement approaches, and causal models that include attitudes. This application of attitude theory and methods could offer implementation research valuable scientific opportunities.

Clinical trial transparency and data sharing among biopharmaceutical companies and the role of company size, location and product type: a cross-sectional descriptive analysis.

OBJECTIVES: To examine company characteristics associated with better transparency and to apply a tool used to measure and improve clinical trial transparency among large companies and drugs, to smaller companies and biologics. DESIGN: Cross-sectional descriptive analysis. SETTING AND PARTICIPANTS: Novel drugs and biologics Food and Drug Administration (FDA) approved in 2016 and 2017 and their company sponsors. MAIN OUTCOME MEASURES: Using established Good Pharma Scorecard (GPS) measures, companies and products were evaluated on their clinical trial registration, results dissemination and FDA Amendments Act (FDAAA) implementation; companies were ranked using these measures and a multicomponent data sharing measure. Associations between company transparency scores with company size (large vs non-large), location (US vs non-US) and sponsored product type (drug vs biologic) were also examined. RESULTS: 26% of products (16/62) had publicly available results for all clinical trials supporting their FDA approval and 67% (39/58) had public results for trials in patients by 6 months after their FDA approval; 58% (32/55) were FDAAA compliant. Large companies were significantly more transparent than non-large companies (overall median transparency score of 95% (IQR 91-100) vs 59% (IQR 41-70), p<0.001), attributable to higher FDAAA compliance (median of 100% (IQR 88-100) vs 57% (0-100), p=0.01) and better data sharing (median of 100% (IQR 80-100) vs 20% (IQR 20-40), p<0.01). No significant differences were observed by company location or product type. CONCLUSIONS: It was feasible to apply the GPS transparency measures and ranking tool to non-large companies and biologics. Large companies are significantly more transparent than non-large companies, driven by better data sharing procedures and implementation of FDAAA trial reporting requirements. Greater research transparency is needed, particularly among non-large companies, to maximise the benefits of research for patient care and scientific innovation.

Dexmedetomidine alleviated sepsis­induced myocardial ferroptosis and septic heart injury.

Cardiac dysfunction resulting from sepsis may cause significant morbidity and mortality, and ferroptosis plays a role in this pathology. Dexmedetomidine (Dex), a α2­adrenergic receptor (α2­AR) agonist exerts cardioprotective effects against septic heart dysfunction, but the exact mechanism is unknown. In the present study, sepsis was induced by cecal ligation and puncture (CLP) in male C57BL/6 mice. Dex and yohimbine hydrochloride (YOH), an α2­AR inhibitor, were administered before inducing CLP. Then, 24 h after CLP, serum and heart tissue were collected to detect changes of troponin­I (TN­I), interleukin 6 (IL­6), superoxide dismutase (SOD), malonaldehyde (MDA) and glutathione (GSH) levels, and iron release. Ferroptosis­targeting proteins, apoptosis and inflammatory factors were assessed by western blotting or ELISA. It was found that, 24 h after CLP, TN­I, a biomarker of myocardial injury, was significantly increased compared with the control group. Furthermore, the levels of MDA, 8­hydroxy­2'­deoxyguanosine and the inflammatory factors IL­6 and monocyte chemoattractant protein­1 were also significantly increased. It was demonstrated that treatment with Dex reverted or attenuated these changes (CLP + Dex vs. CLP; P<0.05), but these protective effects of Dex were reversed by YOH. Moreover, CLP significantly decreased the protein expression levels of glutathione peroxidase 4 (GPX4), SOD and GSH. However, CLP increased expression levels of heme oxygenase­1 (HO­1), transferrin receptor, cleaved caspase 3, inducible nitric oxide synthase and gasdermin D, and iron concentrations. It was found that Dex reversed these changes, but YOH abrogated the protective effects of Dex (CLP + Dex + YOH vs. CLP + Dex; P<0.05). Therefore, the present results suggested that the attenuation of sepsis­induced HO­1 overexpression and iron concentration, and the reduction of ferroptosis via enhancing GPX4, may be the major mechanisms via which Dex alleviates sepsis­induced myocardial cellular injury.

Complement activation in obesity, insulin resistance, and type 2 diabetes mellitus.

Amplified inflammatory reaction has been observed to be involved in cardiometabolic diseases such as obesity, insulin resistance, diabetes, dyslipidemia, and atherosclerosis. The complement system was originally viewed as a supportive first line of defense against microbial invaders, and research over the past decade has come to appreciate that the functions of the complement system extend beyond the defense and elimination of microbes, involving in such diverse processes as clearance of the immune complexes, complementing T and B cell immune functions, tissue regeneration, and metabolism. The focus of this review is to summarize the role of the activation of complement system and the initiation and progression of metabolic disorders including obesity, insulin resistance and diabetes mellitus. In addition, we briefly describe the interaction of the activation of the complement system with diabetic complications such as diabetic retinopathy, nephropathy and neuropathy, highlighting that targeting complement system therapeutics could be one of possible routes to slow down those aforementioned diabetic complications.

Prevalence of tuberculosis infection and disease in children referred for tuberculosis medical surveillance in Ontario: a single-cohort study.

BACKGROUND: There are few data about the utility of the Canadian tuberculosis medical surveillance system for detecting tuberculosis in children and adolescents. We sought to assess the prevalence of tuberculosis infection and disease in children and adolescents referred by the tuberculosis medical surveillance program who were evaluated at The Hospital for Sick Children (SickKids) tuberculosis program. METHODS: We retrospectively studied clinical records, radiographic findings and results of interferon-γ release assays (IGRAs) of all children less than 18 years of age referred by the tuberculosis medical surveillance program and evaluated at SickKids between November 2012 and June 2016. RESULTS: The median age of the 216 children was 10.0 years. Most were born in the Philippines (157 [72.7%]) or India (39 [18.0%]). Of the 216, 166 (76.8%) had a history of prior treatment for tuberculosis, and 34 (15.7%) were federal-sponsored refugees from settings with a high tuberculosis burden. Negative IGRA results were found in 110/130 (84.6%) of those with prior tuberculosis treatment. Thirty-one children (14.4%) had any chest radiographic abnormality, of whom 4 had changes thought to be due to tuberculosis. No child received a diagnosis of active tuberculosis at assessment or during follow-up; 3 (1.4%) were treated for latent tuberculosis infection following IGRA testing at SickKids. A positive IGRA result was associated with contact with infectious tuberculosis (odds ratio [OR] 5.97, 95% confidence interval [CI] 2.06-17.52) and older age at first clinic visit (OR 2.98, 95% CI 1.24-8.30) but not with radiographic abnormalities or history of prior tuberculosis treatment. INTERPRETATION: Most children were referred because of a history of prior treatment for tuberculosis; few had clinical or laboratory evidence of infection or prior disease. The tuberculosis medical surveillance process did not identify any children who required treatment for active disease and requires improvement.

Components in aqueous Hibiscus rosa-sinensis flower extract inhibit in vitro melanoma cell growth.

Skin cancer is extremely common, and melanoma causes about 80% of skin cancer deaths. In fact, melanoma kills over 50 thousand people around the world each year, and these numbers are rising. Clearly, standard treatments are not effectively treating melanoma, and alternative therapies are needed to address this problem. Hibiscus tea has been noted to have medicinal properties, including anticancer effects. Extracts from Hibiscus have been shown to inhibit the growth of a variety of cancer cells. In particular, recent studies found that polyphenols extracted from Hibiscus sabdariffa by organic solvents can inhibit melanoma cell growth. However, effects of aqueous extracts from Hibiscus rosa-sinesis flowers, which are commonly used to make traditional medicinal beverages, have not been examined on melanoma cells. Here, we report that aqueous H. rosa-sinesis flower extract contains compounds that inhibit melanoma cell growth in a dose dependent manner at concentrations that did not affect the growth of nontransformed cells. In addition, these extracts contain low molecular weight growth inhibitory compounds below 3 kD in size that combine with larger compounds to more effectively inhibit melanoma cell growth. Future work should identify these compounds, and evaluate their potential to prevent and treat melanoma and other cancers.

The positive duration of varicella zoster immunoglobulin M antibody test in herpes zoster.

Laboratory tests for herpes zoster (HZ) are required to confirm varicella zoster virus (VZV) infection, especially when a skin lesion is not typical or apparent. The serological test for VZV IgM antibody is simple and cost-effective; however, the change in the VZV IgM-positive rate over the time course of the disease has not been investigated. Therefore, we conducted an observational study to evaluate the positive rate of VZV IgM results during the time course of HZ and estimate the VZV IgM-positive period.After obtaining serum from patients with typical HZ, the VZV IgM titer was examined using enzyme-linked immunosorbent assay methods. After logarithmic transformation of the VZV IgM titer and the period after the onset of HZ, regression analysis was performed with the 2 transformed variables.A total of 62 patients were included in this study, and VZV IgM antibody was positive only in 23 patients (37%). The estimated antibody-positive period after HZ onset was 3.5 weeks (95% confidence interval 2.8-4.6 weeks).These findings suggest that the serological diagnosis of VZV IgM to confirm HZ is only useful within 3.5 weeks after the onset of symptoms.