Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19: Serologic Testing.

BACKGROUND: The role of serologic testing for SARS-CoV-2 has evolved during the pandemic as seroprevalence in global populations has increased. The Infectious Diseases Society of America (IDSA) convened an expert panel to perform a systematic review of the coronavirus disease 2019 (COVID-19) serology literature and construct updated best practice guidance related to SARS-CoV-2 serologic testing. This guideline is an update to the fourth in a series of rapid, frequently updated COVID-19 guidelines developed by IDSA. OBJECTIVE: To develop evidence-based recommendations and identify unmet research needs pertaining to the use of anti-SARS-CoV-2 antibody tests for diagnosis, decisions related to vaccination and administration of monoclonal antibodies or convalescent plasma in immunocompromised patients, and identification of a serologic correlate of immunity. METHODS: A multidisciplinary panel of infectious diseases clinicians, clinical microbiologists and experts in systematic literature reviewed, identified, and prioritized clinical questions related to the use of SARS-CoV-2 serologic tests. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations. RESULTS: The panel recommends against serologic testing to diagnose SARS-CoV-2 infection in the first two weeks after symptom onset (strong recommendations, low certainty of evidence). Serologic testing should not be used to provide evidence of COVID-19 in symptomatic patients with a high clinical suspicion and repeatedly negative nucleic acid amplification test results (strong recommendation, very low certainty of evidence). Serologic testing may assist with the diagnosis of multisystem inflammatory syndrome in children (strong recommendation, very low certainty of evidence). To seek evidence for prior SARS-CoV-2 infection, the panel suggests testing for IgG, IgG/IgM, or total antibodies to nucleocapsid protein three to five weeks after symptom onset (conditional recommendation, low certainty of evidence). In individuals with previous SARS-CoV-2 infection or vaccination, we suggest against routine serologic testing given no demonstrated benefit to improving patient outcomes (conditional recommendation, very low certainty of evidence.) The panel acknowledges further that a negative spike antibody test may be a useful metric to identify immunocompromised patients who are candidates for immune therapy. CONCLUSIONS: The high seroprevalence of antibodies against SARS-CoV-2 worldwide limits the utility of detecting anti-SARS CoV-2 antibody. The certainty of available evidence supporting the use of serology for diagnosis was graded as very low to low. Future studies should use serologic assays calibrated to a common reference standard.

The Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19: Molecular Diagnostic Testing (December 2023).

Accurate molecular diagnostic tests are necessary for confirming a diagnosis of coronavirus disease 2019 (COVID-19) and for identifying asymptomatic carriage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The number of available SARS-CoV-2 nucleic acid detection tests continues to increase as does the COVID-19 diagnostic literature. Thus, the Infectious Diseases Society of America (IDSA) developed an evidence-based diagnostic guideline to assist clinicians, clinical laboratorians, patients, and policymakers in decisions related to the optimal use of SARS-CoV-2 nucleic acid amplification tests. In addition, we provide a conceptual framework for understanding molecular diagnostic test performance, discuss nuances of test result interpretation in a variety of practice settings, and highlight important unmet research needs related to COVID-19 diagnostic testing. IDSA convened a multidisciplinary panel of infectious diseases clinicians, clinical microbiologists, and experts in systematic literature review to identify and prioritize clinical questions and outcomes related to the use of SARS-CoV-2 molecular diagnostics. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations. The panel agreed on 12 diagnostic recommendations. Access to accurate SARS-CoV-2 nucleic acid testing is critical for patient care, hospital infection prevention, and the public health response to COVID-19 infection. Information on the clinical performance of available tests continues to grow, but the quality of evidence of the current literature to support this updated molecular diagnostic guideline remains moderate to very low. Recognizing these limitations, the IDSA panel weighed available diagnostic evidence and recommends nucleic acid testing for all symptomatic individuals suspected of having COVID-19. In addition, testing is suggested for asymptomatic individuals with known or suspected contact with a COVID-19 case when the results will impact isolation/quarantine/personal protective equipment (PPE) usage decisions. Evidence in support of rapid testing and testing of upper respiratory specimens other than nasopharyngeal swabs, which offer logistical advantages, is sufficient to warrant conditional recommendations in favor of these approaches.

The Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19: Antigen Testing.

BACKGROUND: Immunoassays designed to detect SARS-CoV-2 protein antigens (Ag) are commonly used to diagnose COVID-19. The most widely used tests are lateral flow assays that generate results in approximately 15 minutes for diagnosis at the point-of-care. Higher throughput, laboratory-based SARS-CoV-2 Ag assays have also been developed. The number of commercially available SARS-CoV-2 Ag detection tests has increased rapidly, as has the COVID-19 diagnostic literature. The Infectious Diseases Society of America (IDSA) convened an expert panel to perform a systematic review of the literature and develop best practice guidance related to SARS-CoV-2 Ag testing. This guideline is an update to the third in a series of frequently updated COVID-19 diagnostic guidelines developed by the IDSA. OBJECTIVE: The IDSA's goal was to develop evidence-based recommendations or suggestions that assist clinicians, clinical laboratories, patients, public health authorities, administrators and policymakers in decisions related to the optimal use of SARS-CoV-2 Ag tests in both medical and non-medical settings. METHODS: A multidisciplinary panel of infectious diseases clinicians, clinical microbiologists and experts in systematic literature review identified and prioritized clinical questions related to the use of SARS-CoV-2 Ag tests. A review of relevant, peer-reviewed published literature was conducted through April 1, 2022. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations. RESULTS: The panel made ten diagnostic recommendations. These recommendations address Ag testing in symptomatic and asymptomatic individuals and assess single versus repeat testing strategies. CONCLUSIONS: U.S. Food and Drug Administration (FDA) SARS-CoV-2 Ag tests with Emergency Use Authorization (EUA) have high specificity and low to moderate sensitivity compared to nucleic acid amplification testing (NAAT). Ag test sensitivity is dependent on the presence or absence of symptoms, and in symptomatic patients, on timing of testing after symptom onset. In contrast, Ag tests have high specificity, and, in most cases, positive Ag results can be acted upon without confirmation. Results of point-of-care testing are comparable to those of laboratory-based testing, and observed or unobserved self-collection of specimens for testing yields similar results. Modeling suggests that repeat Ag testing increases sensitivity compared to testing once, but no empirical data were available to inform this question. Based on these observations, rapid RT-PCR or laboratory-based NAAT remains the testing method of choice for diagnosing SARS-CoV-2 infection. However, when timely molecular testing is not readily available or is logistically infeasible, Ag testing helps identify individuals with SARS-CoV-2 infection. Data were insufficient to make a recommendation about the utility of Ag testing to guide release of patients with COVID-19 from isolation. The overall quality of available evidence supporting use of Ag testing was graded as very low to moderate.

Volunteer-led online group exercise for community-dwelling older people: a feasibility and acceptability study.

BACKGROUND: Despite the clear benefits of physical activity in healthy ageing, engagement in regular physical activity among community-dwelling older adults remains low, with common barriers including exertional discomfort, concerns with falling, and access difficulties. The recent rise of the use of technology and the internet among older adults presents an opportunity to engage with older people online to promote increased physical activity. This study aims to determine the feasibility and acceptability of training volunteers to deliver online group exercises for older adults attending community social clubs. METHODS: This was a pre-post mixed-methods study. Older adults aged ≥ 65 years attending community social clubs who provided written consent and were not actively participating in exercise classes took part in the feasibility study. Older adults, volunteers, and staff were interviewed to determine the acceptability of the intervention. The intervention was a once weekly volunteer-led online group seated strength exercises using resistance bands. The duration of the intervention was 6 months. The primary outcome measures were the feasibility of the intervention (determined by the number of volunteers recruited, trained, and retained, participant recruitment and intervention adherence) and its acceptability to key stakeholders. Secondary outcome measures included physical activity levels (Community Health Model Activities Programme for Seniors (CHAMPS) questionnaire), modified Barthel Index, Health-related quality of life (EQ-5D-5L), frailty (PRISMA-7) and sarcopenia (SARC-F), at baseline and 6 months. RESULTS: Nineteen volunteers were recruited, 15 (78.9%) completed training and 9 (47.3%) were retained after 1 year (mean age 68 years). Thirty older adults (mean age 77 years, 27 female) participated, attending 54% (IQR 37-67) of exercise sessions. Participants had no significant changes in secondary outcome measures, with a trend towards improvement in physical activity levels (physical activity in minutes per week at baseline was 1770 min, and 1909 min at six months, p = 0.13). Twenty volunteers, older adults, and staff were interviewed and found the intervention acceptable. The seated exercises were perceived as safe, manageable, and enjoyable. CONCLUSIONS: Trained volunteers can safely deliver online group exercise for community-dwelling older adults which was acceptable to older adults, volunteers, and club staff. TRIALS REGISTRATION: NCT04672200.

A Framework for the Development of Living Practice Guidelines in Health Care.

BACKGROUND: Living practice guidelines are increasingly being used to ensure that recommendations are responsive to rapidly emerging evidence. OBJECTIVE: To develop a framework that characterizes the processes of development of living practice guidelines in health care. DESIGN: First, 3 background reviews were conducted: a scoping review of methods papers, a review of handbooks of guideline-producing organizations, and an analytic review of selected living practice guidelines. Second, the core team drafted the first version of the framework. Finally, the core team refined the framework through an online survey and online discussions with a multidisciplinary international group of stakeholders. SETTING: International. PARTICIPANTS: Multidisciplinary group of 51 persons who have experience with guidelines. MEASUREMENTS: Not applicable. RESULTS: A major principle of the framework is that the unit of update in a living guideline is the individual recommendation. In addition to providing definitions, the framework addresses several processes. The planning process should address the organization's adoption of the living methodology as well as each specific guideline project. The production process consists of initiation, maintenance, and retirement phases. The reporting should cover the evidence surveillance time stamp, the outcome of reassessment of the body of evidence (when applicable), and the outcome of revisiting a recommendation (when applicable). The dissemination process may necessitate the use of different venues, including one for formal publication. LIMITATION: This study does not provide detailed or practical guidance for how the described concepts would be best implemented. CONCLUSION: The framework will help guideline developers in planning, producing, reporting, and disseminating living guideline projects. It will also help research methodologists study the processes of living guidelines. PRIMARY FUNDING SOURCE: None.

Defining Misinformation and Related Terms in Health-Related Literature: Scoping Review.

BACKGROUND: Misinformation poses a serious challenge to clinical and policy decision-making in the health field. The COVID-19 pandemic amplified interest in misinformation and related terms and witnessed a proliferation of definitions. OBJECTIVE: We aim to assess the definitions of misinformation and related terms used in health-related literature. METHODS: We conducted a scoping review of systematic reviews by searching Ovid MEDLINE, Embase, Cochrane, and Epistemonikos databases for articles published within the last 5 years up till March 2023. Eligible studies were systematic reviews that stated misinformation or related terms as part of their objectives, conducted a systematic search of at least one database, and reported at least 1 definition for misinformation or related terms. We extracted definitions for the terms misinformation, disinformation, fake news, infodemic, and malinformation. Within each definition, we identified concepts and mapped them across misinformation-related terms. RESULTS: We included 41 eligible systematic reviews, out of which 32 (78%) reviews addressed the topic of public health emergencies (including the COVID-19 pandemic) and contained 75 definitions for misinformation and related terms. The definitions consisted of 20 for misinformation, 19 for disinformation, 10 for fake news, 24 for infodemic, and 2 for malinformation. "False/inaccurate/incorrect" was mentioned in 15 of 20 definitions of misinformation, 13 of 19 definitions of disinformation, 5 of 10 definitions of fake news, 6 of 24 definitions of infodemic, and 0 of 2 definitions of malinformation. Infodemic had 19 of 24 definitions addressing "information overload" and malinformation had 2 of 2 definitions with "accurate" and 1 definition "used in the wrong context." Out of all the definitions, 56 (75%) were referenced from other sources. CONCLUSIONS: While the definitions of misinformation and related terms in the health field had inconstancies and variability, they were largely consistent. Inconstancies related to the intentionality in misinformation definitions (7 definitions mention "unintentional," while 5 definitions have "intentional"). They also related to the content of infodemic (9 definitions mention "valid and invalid info," while 6 definitions have "false/inaccurate/incorrect"). The inclusion of concepts such as "intentional" may be difficult to operationalize as it is difficult to ascertain one's intentions. This scoping review has the strength of using a systematic method for retrieving articles but does not cover all definitions in the extant literature outside the field of health. This scoping review of the health literature identified several definitions for misinformation and related terms, which showed variability and included concepts that are difficult to operationalize. Health practitioners need to exert caution before labeling a piece of information as misinformation or any other related term and only do so after ascertaining accurateness and sometimes intentionality. Additional efforts are needed to allow future consensus around clear and operational definitions.

Intravenous thrombolysis for multi-ethnic Asians with acute ischaemia stroke in Malaysian public primary stroke centres versus acute stroke ready hospitals: Comparison of real-world clinical outcomes.

INTRODUCTION: Intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator is beneficial in acute ischaemic stroke (AIS). We aim to compare the realworld clinical outcomes and service efficiency of IVT in Malaysian primary stroke centres (PSCs) versus acute stroke ready hospitals (ASRHs). MATERIALS AND METHODS: We conducted a multi-centre cohort study involving 5 PSCs and 7 ASRHs in Malaysia. Through review of medical records of AIS patients who received IVT from 01 January 2014 to 30 June 2021, real-world data was extracted for analysis. Univariate and multivariate regression models were employed to evaluate the role of PSCs versus ASRHs in post-IVT outcomes and complications. Statistical significance was set at p<0.05. RESULTS: A total of 313 multi-ethnic Asians, namely 231 from PSCs and 82 from ASRHs, were included. Both groups were comparable in baseline demographic, clinical, and stroke characteristics. The efficiency of IVT delivery (door-toneedle time), functional outcomes (mRS at 3 months post- IVT), and rates of adverse events (intracranial haemorrhages and mortality) following IVT were comparable between the 2 groups. Notably, 46.8% and 48.8% of patients in PSCs and ASRHs group respectively (p=0.752) achieved favourable functional outcome (mRS≤1 at 3 months post-IVT). Regression analyses demonstrated that post-IVT functional outcomes and adverse events were independent of the role of PSCs or ASRHs. CONCLUSION: Our study provides real-world evidence which suggests that IVT can be equally safe, effective, and efficiently delivered in ASRHs. This may encourage the establishment of more ASRHs to extend the benefits of IVT to a greater proportion of stroke populations and enhance the regional stroke care.

Pharmacological testing of therapeutics using normothermic machine perfusion: A pilot study of 2,4-dinitrophenol delivery to steatotic human livers.

INTRODUCTION: Normothermic machine perfusion (NMP) provides a platform for drug-delivery. However, pharmacological considerations for therapeutics delivered during NMP are scarcely reported. We aimed to demonstrate the ability of NMP as a platform for pharmacological testing, using a drug which increases metabolism (2,4-dinitrophenol; DNP) as an example therapeutic. METHODS: We performed 25 h of NMP on human livers which had been declined for transplant due to steatosis (n = 7). Three livers received a DNP bolus, three were controls, and one received a DNP infusion. RESULTS: Toxicity studies revealed DNP delivery was safe, without hepatotoxic effects. The liver surface temperature was increased in the DNP group (p = 0.046), but no livers suffered hyperthermia-the mechanism of DNP toxicity in vivo. Pharmacokinetic studies revealed DNP elimination with first-order kinetics and 7.7 h half-life (95% CI = 5.1-15.9 hrs). The clearance of DNP in bile was negligible. As expected, DNP significantly increased oxygen consumption (p = 0.023); this increase was closely correlated with perfusate DNP concentration (r2  = 0.975; p = 0.002) and the effect was lost as DNP was eliminated by the liver. A DNP infusion rate, calculated using our pharmacokinetic data, successfully maintained perfusate DNP concentration. DISCUSSION: Detailed pharmacological testing can be performed during NMP. Our therapeutic (DNP) is rapidly eliminated by the ex vivo liver, meaning the drug effect of increased metabolism is only transient. This demonstrates the importance of assessing pharmacokinetics when delivering therapeutics during NMP, especially for prolonged perfusion of organs with established roles in drug elimination. Rigorous pharmacological testing is needed to unlock the potential of NMP as a clinical drug-delivery platform.

Oral submucous fibrosis and its impact on psychological stress: a case-control study.

Our aim was to evaluate the impact of OSF on psychological stress. Ninety OSF cases and age and sex-matched controls, enrolled from relatives or accompanying person were included in the study. Psychological stress was evaluated by the Psychological General Well Being Index short version (PGWBI-S). Sets of the psychological component were generated by principal component analysis (PCA). Association between components was accommodated for confounder and interaction was evaluated by conditional stepwise logistic regression analysis. Psychological component generated was component 1 (depressed mood, lack of positive well being, low vitality, anxiety, low vitality, and low self-control). The odds ratio (OR) of low score of component 1 for OSF was 3.66. Depressed mood, lack of positive well being, low vitality, anxiety, low vitality, and low self-control were associated with OSF. Psychological intervention should, therefore, be included in the management of OSF.

Distinct Mechanisms of Cytotoxicity in Novel Nitrogenous Heterocycles: Future Directions for a New Anti-Cancer Agent.

Electron-rich, nitrogenous heteroaromatic compounds interact more with biological/cellular components than their non-nitrogenous counterparts. The strong intermolecular interactions with proteins, enzymes, and receptors confer significant biological and therapeutic properties to the imidazole derivatives, giving rise to a well-known and extensively used range of therapeutic drugs used for infections, inflammation, and cancer, to name a few. The current study investigates the anti-cancer properties of fourteen previously synthesized nitrogenous heterocycles, derivatives of imidazole and oxazolone, on a panel of cancer cell lines and, in addition, predicts the molecular interactions, pharmacokinetic and safety profiles of these compounds. METHOD: The MTT and CellTiter-Glo® assays were used to screen the imidazole and oxazolone derivatives on six cancer cell lines: HL60, MDA-MB-321, KAIMRC1, KMIRC2, MCF-10A, and HCT8. Subsequently, in vitro tubulin staining and imaging were performed, and the level of apoptosis was measured using the Promega ApoTox-Glo® triplex assay. Furthermore, several computational tools were utilized to investigate the pharmacokinetics and safety profile, including PASS Online, SEA Search, the QikProp tool, SwissADME, ProTox-II, and an in silico molecular docking study on tubulin to identify the critical molecular interactions. RESULTS: In vitro analysis identified compounds 8 and 9 to possess the most significant potent cytotoxic activity on the HL60 and MDA-MB-231 cell lines, supported by PASS Online anti-cancer predictions with pa scores of 0.413 and 0.434, respectively. In addition, compound 9 induced caspase 3/7 dependent-apoptosis and interfered with tubulin polymerization in the MDA-MB-231 cell line, consistent with in silico docking results, identifying binding similarity to the native ligand colchicine. All the derivatives, including compounds 8 and 9, had acceptable pharmacokinetics; however, the safety profile was suboptimal for all the tested derivates except compound 4. CONCLUSION: The imidazole derivative compound 9 is a promising anti-cancer agent that switches on caspase-dependent apoptotic cell death and modulates microtubule function. Therefore, it could be a lead compound for further drug optimization and development.

Prevalence and Predictors of Metabolic Syndrome among Adults in North-Central, Nigeria.

BACKGROUND: Metabolic syndrome contributes to the burden of non-communicable diseases and is a growing public health problem in both developed and developing countries. We determined the prevalence and predictors of metabolic syndrome among adults in Benue State, North-Central, Nigeria to guide targeted interventions. METHODS: We conducted a community-based cross-sectional study in Benue State, North-Central, Nigeria. Multistage sampling technique was used to recruit 823 respondents. We defined metabolic syndrome using the National Cholesterol Education Programme Adult Treatment Panel III guideline and adapted a component of the WHO Stepwise questionnaire for data collection. Prevalence of metabolic syndrome and the associated risk factors were estimated using Chi square test and logistic regression at 5% level of significance. Statistical analysis was done using SPSS version 23.0. RESULTS: The mean age of the respondents was 40.1± 15.7 years. Most of the respondents were literate (86.8%) and married (67.0%). The prevalence of metabolic syndrome was 19.4%. One in every four of the respondents had pre-metabolic syndrome (25.6%) and this was more in females (28.2%) compared to males (22.9%). Thirty-four percent of the respondents had only one whereas 20.7% did not have any of the risk factors for metabolic syndrome. Age [aOR:10.3; 95%CI: 4.8-22.2], sex [aOR:2.4; 95% CI: 1.7-3.5] and education [aOR:2.9; 95%CI: 1.4-6.1] were significantly associated with metabolic syndrome among the respondents. CONCLUSION: The prevalence of metabolic syndrome was high. The associated risk factors were age, gender and educational status. Therefore, interventions should be targeted at young adults to reduce the long-term impact of the disease.

CONTEXTE: Le syndrome métabolique contribue à la fardeau des maladies non transmissibles et est un public croissant problème de santé dans les pays développés comme dans les pays en développement. Nous avons déterminé la prévalence et les prédicteurs du metabolism syndrome chez les adultes dans l'État de Benue, centrenord du Nigéria pour orienter les interventions ciblées. MÉTHODES: Nous avons mené une enquête transversale communautaire étude dans l'État de Benue, centre-nord du Nigéria. Multistage la technique d'échantillonnage a été utilisée pour recruter 823 répondants. Nous avons define syndrome metabolique à l'aide du National Cholesterol Programme d'éducation Groupe de traitement des adultes III lignes directrices eta adapté une composante du questionnaire Par étapes de l'OMS pour collecte de données. Prévalence du syndrome métabolique et des facteurs de risque associés ont été estimés à l'aide du test du chi carré et la régression logistique à un niveau de signification de 5 %. Statistique l'analyse a été effectuée à l'aide de SPSS version 23.0. RÉSULTATS: L'âge moyen des répondants était de 40.1 ± 15,7 ans.La plupart des répondants étaient alphabétisés (86.8 %) et mariés(67.0%). La prévalence du syndrome métabolique était de 19.4%.Un répondant sur quatre avait un prémétabolique (25.6 %) et c'était plus fréquent chez les femmes (28.2 %)comparativement aux hommes (22.9 %). Trente-quatre pour cent des n'en avaient qu'un, alors que 20.7 % n'en avaient aucun les facteurs de risque du syndrome métabolique. Âge [aOR:10.3; IC à 95 %:4.8-22.2], le sexe [aOR:2.4; IC à 95 %: 1.7-3.5] et l'éducation [aOR:2.9;IC à 95 % : 1.4 à 6.1] étaient significativement associés au metabolism chez les répondants. CONCLUSION: La prévalence du syndrome métabolique était haut. Les facteurs de risque associés étaient l'âge, le sexe et le statut scolaire. Par conséquent, les interventions devraient être ciblées chez les jeunes adultes pour réduire l'impact à long terme de la maladie. Mots-clés: Prévalence, facteurs de risque, syndrome métabolique, Nigéria.

Novel delivery of cellular therapy to reduce ischemia reperfusion injury in kidney transplantation.

Ex vivo normothermic machine perfusion (NMP) of donor kidneys prior to transplantation provides a platform for direct delivery of cellular therapeutics to optimize organ quality prior to transplantation. Multipotent Adult Progenitor Cells (MAPC® ) possess potent immunomodulatory properties that could minimize ischemia reperfusion injury. We investigated the potential capability of MAPC cells in kidney NMP. Pairs (5) of human kidneys, from the same donor, were simultaneously perfused for 7 hours. Kidneys were randomly allocated to receive MAPC treatment or control. Serial samples of perfusate, urine, and tissue biopsies were taken for comparison. MAPC-treated kidneys demonstrated improved urine output (P = .009), decreased expression of injury biomarker NGAL (P = .012), improved microvascular perfusion on contrast-enhanced ultrasound (cortex P = .019, medulla P = .001), downregulation of interleukin (IL)-1ß (P = .050), and upregulation of IL-10 (P < .047) and Indolamine-2, 3-dioxygenase (P = .050). A chemotaxis model demonstrated decreased neutrophil recruitment when stimulated with perfusate from MAPC-treated kidneys (P < .001). Immunofluorescence revealed prelabeled MAPC cells in the perivascular space of kidneys during NMP. We report the first successful delivery of cellular therapy to a human kidney during NMP. Kidneys treated with MAPC cells demonstrate improvement in clinically relevant parameters and injury biomarkers. This novel method of cell therapy delivery provides an exciting opportunity to recondition organs prior to transplantation.

Volunteer-led physical activity interventions to improve health outcomes for community-dwelling older people: a systematic review.

BACKGROUND: Physical activity (PA) is important for older people to maintain functional independence and healthy ageing. There is strong evidence to support the benefits of physical activity interventions on the health outcomes of older adults. Nonetheless, innovative approaches are needed to ensure that these interventions are practical and sustainable. AIM: This systematic review explores the effectiveness of volunteer-led PA interventions in improving health outcomes for community-dwelling older people. METHODS: Five databases (MEDLINE, Embase, CINAHL, PEDro, Cochrane library) were systematically searched for studies using trained volunteers to deliver PA interventions for community-dwelling older people aged ≥ 65 years. Meta-analysis was not conducted due to included study heterogeneity. RESULTS: Twelve papers describing eight studies (five papers reported different outcomes from the same study) were included in the review. All eight studies included strength and balance exercises and frequency of PA ranged from weekly to three times a week. Volunteer-led exercises led to improvements in functional status measured using the short physical performance battery, timed up and go test, Barthel Index, single leg stand, step touch test, chair stand test, and functional reach. Frailty status identified by grip strength measurement or the use of long-term care insurance improved with volunteer-led exercises. Interventions led to improvement in fear of falls and maintained or improved the quality of life. The impact on PA levels were mixed. CONCLUSION: Limited evidence suggests that volunteer-led PA interventions that include resistance exercise training, can improve outcomes of community-dwelling older adults including functional status, frailty status, and reduction in fear of falls. More high-quality RCTs are needed to investigate the effects of volunteer-led PA interventions among older people.

Hypothermic machine perfusion is superior to static cold storage in deceased donor kidney transplantation: A meta-analysis.

BACKGROUND: There remains a lack of consensus on the optimal storage method for deceased donor kidneys. This meta-analysis compares storage with hypothermic machine perfusion (HMP) vs traditional static cold storage (SCS). METHODS: The Cochrane Kidney and Transplant Specialised Register was searched to identify (quasi-) randomized controlled trials (RCTs) to include in our meta-analysis. PRISMA guidelines were used to perform and write this review. RESULTS: There is high-certainty evidence that HMP reduces the risk of delayed graft function (DGF) when compared to SCS (2138 participants from 14 studies, RR = 0.77; 0.67-0.90, P = .0006). This benefit is significant in both donation following circulatory death (DCD; 772 patients from seven studies, RR = 0.75; 0.64-0.87, P = .0002) and donation following brainstem death (DBD) grafts (971 patients from four studies, RR = 0.78; 0.65-0.93, P = .006). The number of perfusions required to prevent one episode of DGF was 7.26 and 13.60 in DCD and DBD grafts, respectively. There is strong evidence that HMP also improves graft survival in both DBD and DCD grafts, at both 1 and 3 years. Economic analyses suggest HMP is cost-saving at 1 year compared with SCS. CONCLUSION: Hypothermic machine perfusion is superior to SCS in deceased donor renal transplantation. Direct comparisons with normothermic machine perfusion in RCTs are essential to identify optimal preservation methods in kidney transplantation.

Treatment of colorectal cancer in Sub-Saharan Africa: Results from a prospective Nigerian hospital registry.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide. Mortality for CRC is improving in high income countries, but in low and middle income countries, rates of disease and death from disease are rising. In Sub-Saharan Africa, the ratio of CRC mortality to incidence is the highest in the world. This study investigated the nature of CRC treatment currently being offered and received in Nigeria. METHODS: Between April 2013 and October 2017, a prospective study of consecutively diagnosed cases of CRC was conducted. Patient demographics, clinical features, and treatment recommended and received was recorded for each case. Patients were followed during the study period every 3 months or until death. RESULTS: Three hundred patients were included in our analysis. Seventy-one percent of patients received a recommended surgical operation. Of those that didn't undergo surgery as recommended, 37% cited cost as the main reason, 30% declined due to personal reasons, and less than 5% absconded or were lost to follow up. Approximately half of patients (50.5%) received a chemotherapy regimen when it was recommended, and 4.1% received radiotherapy when this was advised as optimal treatment. With therapy, the median overall survival for patients diagnosed with stage III and stage IV CRC was 24 and 10.5 months respectively. Overall, we found significantly better median survival for patients that received the recommended treatment (25 vs 7 months; P < .01). CONCLUSIONS: A number of patients were unable to receive the recommended treatment, reflecting some of the burden of untreated CRC in the region. Receiving the recommended treatment was associated with a significant difference in outcome. Improved healthcare financing, literacy, training, access, and a better understanding of tumor biology will be necessary to address this discrepancy.

CO2 activation through C-N, C-O and C-C bond formation.

A comparative model for the chemisorption of CO2 was explored via three representative reaction pathways: carboxylation of cyclohexanone, carbonation of cyclohexanol, and carbamation of cyclohexylamine. The model substrates were activated using 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, an amidine superbase). For each of these reactions, the formation of the corresponding CO2 adducts was confirmed by 13C nuclear magnetic resonance and Fourier-transform infrared spectroscopy measurements. It was demonstrated that CO2 fixation occurred through either an enol-CO2 adduct (i.e. carboxylation), proton shuttling process (i.e. carbonation), or self-activation mechanism (i.e. carbamation). Volumetric adsorption measurements indicated that cyclohexanol was superior in its uptake capacity (11.7 mmol CO2 g-1 sorbent) in comparison to cyclohexylamine (9.3 mmol CO2 g-1 sorbent) or cyclohexanone (8.5 mmol CO2 g-1 sorbent). As supported by density functional theory calculations, this trend was expected given the fact that the carbonation reaction proceeded through a more thermodynamically favorable reaction process.

Population-based prevalence and associated risk factors of hypertension among adults in Benue State, Nigeria.

BACKGROUND: The increasing prevalence of hypertension in low- and middle-income countries is associated with increased morbidity and mortality. AIM: To determine the prevalence of hypertension and associated risk factors in Benin state, Nigeria. MATERIALS AND METHODS: A population-based cross-sectional study was conducted among 1265 adults selected by multistage sampling technique. The World Health Organization (WHO) STEPwise approach was used to collect data. Data were analyzed using Statistical Package for the Social Sciences (SPSS) software program, version 23.0 (IBM). We estimated prevalence and odds of hypertension at 5% level of significance. RESULTS: The prevalence of hypertension was 35.6%. The odds of hypertension was higher among age 30-39 (aOR: 2.0; 95% CI: 1.3-3.1) compared to age 18-29 years, males (aOR: 1.4; 95% CI: 1.1-2.0) compared to females, overweight (aOR: 2.3; 95%CI: 1.6-3.2), and obesity (aOR: 4.9; 95%CI: 3.2-7.7) compared to normal weight, and high cholesterol (aOR: 1.6; 95% CI: 1.1-2.3) compared to normal cholesterol. CONCLUSION: The prevalence of hypertension was high among young adults in Benue State. The associated risk factors for hypertension were age, sex, overweight, obesity, and high total cholesterol.

UK registry analysis of donor substance misuse and outcomes following pancreas transplantation.

Substance abuse is unfortunately common in organ donors. Often, these organs are declined for transplant, not only because of concerns around blood-borne virus transmission but also because of perceived poor outcomes. In kidney transplantation, previous studies have demonstrated donor smoking status significantly impacts transplant outcome, but intravenous drug use or alcohol dependence does not. This study aims to clarify these issues in pancreas transplantation. Retrospective data on all UK solid organ pancreas transplants from 1994 to 2015 were obtained from the NHSBT UK Transplant Registry. The impact of illicit drug misuse, alcohol abuse, and smoking on graft and patient survival were analyzed using Kaplan-Meier plots and a Cox regression model. A total of 1175 of the 2317 (49.5%) donors were categorized as substance misusers. Univariate survival analysis revealed no significant impact of substance misuse on 10-year graft or patient survival. Multivariate analysis confirmed substance misuse was not associated with impaired graft or patient survival. A history of donor substance misuse does not negatively impact 10-year graft or patient survival following pancreas transplantation. This is a large national registry analysis with long-term follow-up data and should therefore provide clinicians with reassurance when considering pancreas grafts from substance misuse donors.

Salivary Bacterial Count and its Implications on the Prevalence of Oral Conditions.

AIM: To determine the relationship between salivary bacterial count and some oral lesions. MATERIALS AND METHODS: This research was designed as a cross- sectional study assessing the mean bacterial count in the saliva of Nigerians in Ile-Ife who has no history of medical illness. Subjects were randomly selected from consenting staffs and students of Obafemi Awolowo University, Ile-Ife, Nigeria. Oral examinations were done and their saliva collected using spitting method. The bacterial count was determined in the laboratory by culture the bacteria after which the counting was done using colony counter. Data analysis was done using STATA 13 software. RESULTS: A total of sixty participants were recruited for the study, 41 males and 19 females, their mean age was 23.12+3.8 years. The mean salivary bacteria count among the participants was 8.41 × 108 + 1.06 × 109 per mL. The salivary bacterial count is highest among those with poor oral hygiene (1.89 × 109) and also increases with age. Males have a higher bacterial load compared to female. Subjects with periodontitis have the highest bacterial load and are significantly higher in patients with periodontitis in comparison with those who do not have periodontitis p = 0.03 Conclusion: Periodontitis is associated with the significantly higher salivary bacterial load. Male sex and increasing age were also associated with increased bacterial load in saliva. CLINICAL SIGNIFICANCE: This study showed another potential role of saliva as a reliable diagnostic tool to monitor the severity of oral infections. It also showed the association between salivary bacterial count and some oral lesions further substantiating the possibility of using saliva to monitor disease progression and treatment responses.

Administration of tranexamic acid for victims of severe trauma within pre-hospital care ambulance services (PHCAS) in Malaysia.

INTRODUCTION: Trauma is a Global threat and the 5th highest cause of all-cause mortality in Malaysia caused predominantly due to road traffic accidents. Majority of trauma victims are young adults aged between 21-40 years old. In Malaysia, 24 out of 100,000 population die annually due to trauma, rating us amongst the highest in South East Asia. These alarming figures justify aggressive preventive and mitigation strategies. The aim of this paper is to promote the implementation of evidence-based interventions that will reduce the rate of preventable death because of trauma. Tranexamic acid is one of the few interventions in the early management of severe trauma with level-one evidence. Tranexamic acid has been proven to reduce all causes of mortality and mortality due to bleeding. Evidence proves that it is most effective when administered early, particularly within the 1st hour of trauma. This proposed guideline is formulated based upon quality evidence from multicentre studies, clinical practices in other countries and consideration of the local demographic factors with the intent of enabling an easy and simple pathway to administer tranexamic acid early in the care of the severely injured. CONCLUSION: The guideline highlights select pre-hospital criteria's and the methods for drug administration. The authors recognise that some variants may be present amongst certain institutions necessitating minor adaptations, nevertheless the core principles of advocating tranexamic acid early in the course of pre-hospital trauma should be adhered to.