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Cardiology Journal 2023Colchicine is an effective anti-inflammatory agent used to treat gout, coronary artery disease, viral pericarditis, and familial Mediterranean fever. It has been found... (Review)
Review
Colchicine is an effective anti-inflammatory agent used to treat gout, coronary artery disease, viral pericarditis, and familial Mediterranean fever. It has been found to act by preventing the polymerization of the protein called tubulin, thus inhibiting inflammasome activation, proinflammatory chemokines, and cellular adhesion molecules. Accumulating evidence suggests that some patients with coronavirus disease 2019 (COVID-19) suffer from "cytokine storm" syndrome. The ideal anti-inflammatory in this setting would be one that is readily available, cheap, orally administered, with a good safety profile, well- tolerated, and that prevents or modulates inflammasome activation. The researchers selected colchicine for their study. This paper is a review of the literature describing the effects of colchicine, which is a drug that is being increasingly used, especially when standard therapy fails. Colchicine was shown to reduce inflammatory lung injury and respiratory failure by interfering with leukocyte activation and recruitment. In this publication, we try to systematically review the current data on new therapeutic options for colchicine. The article focuses on new data from clinical trials in COVID-19, rheumatic, cardiovascular, and other treatment such as familial Mediterranean fever, chronic urticaria, and PFAPA syndrome (periodic fever, aphthous, stomatitis, pharyngitis, and cervical adenitis). We also summarize new reports on the side effects, drug interactions, and safety of colchicine.
Topics: Humans; Colchicine; Familial Mediterranean Fever; Rheumatology; Inflammasomes; COVID-19; Pharyngitis; Syndrome
PubMed: 34642922
DOI: 10.5603/CJ.a2021.0123 -
BMJ Open Apr 2022Group A β-haemolytic Streptococcus (GAS), a Gram-positive bacterium, causes skin, mucosal and systemic infections. Repeated GAS infections can lead to autoimmune...
INTRODUCTION
Group A β-haemolytic Streptococcus (GAS), a Gram-positive bacterium, causes skin, mucosal and systemic infections. Repeated GAS infections can lead to autoimmune diseases acute rheumatic fever (ARF) and rheumatic heart disease (RHD). Aboriginal and Torres Strait Islander peoples in Australia have the highest rates of ARF and RHD in the world. Despite this, the contemporaneous prevalence and incidence of GAS pharyngitis and impetigo in remote Australia remains unknown. To address this, we have designed a prospective surveillance study of GAS pharyngitis and impetigo to collect coincident contemporary evidence to inform and enhance primary prevention strategies for ARF.
METHODS AND ANALYSIS
The Missing Piece Study aims to document the epidemiology of GAS pharyngitis and impetigo through collection of clinical, serological, microbiological and bacterial genomic data among remote-living Australian children. The study comprises two components: (1) screening of all children at school for GAS pharyngitis and impetigo up to three times a year and (2) weekly active surveillance visits to detect new cases of pharyngitis and impetigo. Environmental swabbing in remote schools will be included, to inform environmental health interventions. In addition, the application of new diagnostic technologies, microbiome analysis and bacterial genomic evaluations will enhance primary prevention strategies, having direct bearing on clinical care, vaccine development and surveillance for vaccine clinical trials.
ETHICS AND DISSEMINATION
Ethical approval has been obtained from the Western Australian Aboriginal Health Ethics Committee (Ref: 892) and Human Research Ethics Committee of the University of Western Australia (Ref: RA/4/20/5101). Study findings will be shared with community members, teachers and children at participating schools, together with academic and medical services. Sharing findings in an appropriate manner is important and will be done in a suitable way which includes plain language summaries and presentations. Finally, findings and updates will also be disseminated to collaborators, researchers and health planners through peer-reviewed journal publications.
Topics: Child; Humans; Health Services, Indigenous; Impetigo; Pharyngitis; Prospective Studies; Rheumatic Fever; Rheumatic Heart Disease; Streptococcal Infections; Streptococcus pyogenes; Western Australia
PubMed: 35387825
DOI: 10.1136/bmjopen-2021-057296 -
BMC Infectious Diseases Feb 2019Clinical guidelines for the diagnosis of group A streptococcal (GAS) pharyngitis recommend the use of a rapid antigen detection test (RADT) and/or bacterial culture....
BACKGROUND
Clinical guidelines for the diagnosis of group A streptococcal (GAS) pharyngitis recommend the use of a rapid antigen detection test (RADT) and/or bacterial culture. This study evaluated the overall diagnosis and treatment of acute pharyngitis in the United States, including predictors of test type and antibiotic prescription.
METHODS
A retrospective analysis of pharyngitis events from 2011 through 2015 was conducted using the MarketScan commercial/Medicare databases. A pharyngitis event was defined as occurring within 2 weeks from the index visit. Patient and provider characteristics were examined across 5 testing categories: RADT, RADT plus culture, other tests, nucleic acid amplification testing (NAAT), and no test. Multivariate models were used to identify significant predictors of NAAT use and antibiotic prescription.
RESULTS
A total of 18.8 million acute pharyngitis events were identified in 11.6 million patients. Roughly two-thirds of events (68.2%) occurred once, and roughly a third of patients (29.1%) required additional follow-up, but hospitalization was rare (0.3%). Across all events, 43% were diagnosed by RADT, while 20% were diagnosed by RADT plus culture. The proportion of events diagnosed by NAAT increased 3.5-fold from 2011 to 2015 (0.06% vs 0.27%). Antibiotic use was frequent (49.3%), less often in combination with RADT plus culture (31.2%) or NAAT alone (34.5%) but significantly more often with RADT alone (53.4%) or no test (57.1%). Pediatricians were significantly less likely than other providers to prescribe antibiotics in their patients, regardless of patient age (p < 0.0001).
CONCLUSIONS
Antibiotic use for sore throat remains common, with many clinicians not following current guidelines for diagnosis of GAS pharyngitis. Diagnosis of GAS pharyngitis using RADT plus culture or NAAT alone was associated with lower use of antibiotics. Diagnostic testing can help lower the incidence of inappropriate antibiotic use, and inclusion of NAAT in the clinical guidelines for GAS pharyngitis warrants consideration.
Topics: Adolescent; Adult; Anti-Bacterial Agents; Child; Drug Prescriptions; Female; Humans; Immunologic Tests; Male; Nucleic Acid Amplification Techniques; Pharyngitis; Practice Guidelines as Topic; Retrospective Studies; Streptococcal Infections; Streptococcus pyogenes; United States
PubMed: 30808305
DOI: 10.1186/s12879-019-3835-4 -
BMC Microbiology May 2021Streptococcus pyogenes (S. pyogenes) is a Gram positive bacterium which is a leading cause of pharyngitis, skin and soft tissue infection and post streptococcal...
Prevalence and antibiotics susceptibility profiles of Streptococcus pyogenes among pediatric patients with acute pharyngitis at Felege Hiwot Comprehensive Specialized Hospital, Northwest Ethiopia.
BACKGROUND
Streptococcus pyogenes (S. pyogenes) is a Gram positive bacterium which is a leading cause of pharyngitis, skin and soft tissue infection and post streptococcal syndromes. Due to lack of β-lactamase enzyme production, it was considered universally susceptible to penicillin group and later generation of β-lactam antibiotics. As such, empirical treatment was common which might leads to development of antibiotics resistance. Therefore, the aims of this study were to determine the prevalence, antibiotics susceptibility profile; and associated factors of S. pyogenes among pediatric patients with acute pharyngitis in Felege Hiwot Comprehensive Specialized Hospital (FHCSH), Northwest Ethiopia.
METHODS
Hospital based cross-sectional study was carried out on 154 pediatric patients, whose age ranged from 0 to 18 years old using consecutive convenient sampling technique from 1st February to 19th June 2020 at FHCSH. S. pyogenes were identified by throat swab culture on 5% sheep blood agar with an overnight incubation at 37 °C in candle jar containing 5% CO. Gram stain, catalase test and bacitracin test were used to identify S. pyogenes. Then,the data were entered into EpiData version 3.1 and analyzed by SPSS version 20 software. Finally, stepwise, bivariable and multivariable logistic regressions were carried out for identifyying factors having significant ssociation (p<0.05) with acute pharyngitis. RESULTS: From the total throat swabs, 14 (9.1%) with (95% CI; 4.5-14.3) were culture positive for S. pyogenes. From these, all isolates were sensitive to penicillin and ampicillin. On the otherhand, 4 (35.7%), 4 (35.5%), 3 (21.4%), 2 (14.3%), 1 (7.1%), 7 (50.0%) and 1 (7.1%) isolates were resistant for ceftriaxone, vancomycin, erythromycin, tetracycline, chloramphenicol, clindamycin and levofloxacin, respectively. The presence of any smoker in home showed significant association with S. pyogenes acute pharyngitis. Furthermore, having tender lymphadenopathy and recurrence were clinical predictors for S. pyogenes acute pharyngitis (P < 0.05).
CONCLUSION
The prevalence of S. pyogenes was guaged at 9.1% which is considered as low prevalence. All S. pyogenes isolats remain sensitive to penicillin. However, resistance was reported to clindamycin 7 (50.0%), ceftriaxone 5 (35.7%) and erythromycin 3 (21.4%). The current practice of giving erythromycin, clindamycin instead of penicillin and ampicillin is againest the microbiology result. Therefore, current empirical treatment of acute pharyngitis shall take in to account the current evidences. Continuous surveillance of antibiotics resistance pattern of S. pyogenes for acute pharyngitis must be strengthen to improve the use of antibiotics in hospitals.
Topics: Adolescent; Anti-Bacterial Agents; Child; Child, Preschool; Ethiopia; Humans; Infant; Infant, Newborn; Pharyngitis; Risk Factors; Streptococcal Infections; Streptococcus pyogenes
PubMed: 33941090
DOI: 10.1186/s12866-021-02196-0 -
Mediators of Inflammation 2015PFAPA syndrome is a chronic disease that is characterized by recurrent episodes of high fever, aphthous stomatitis, pharyngitis, and cervical adenitis. Knowledge... (Review)
Review
BACKGROUND
PFAPA syndrome is a chronic disease that is characterized by recurrent episodes of high fever, aphthous stomatitis, pharyngitis, and cervical adenitis. Knowledge regarding the etiology of PFAPA is limited.
OBJECTIVES
To provide up-to-date information considering etiology of PFAPA syndrome, by summarizing what has been explored and established in this area so far.
MATERIALS AND METHODS
PubMed, Web of Science, and Scopus databases were searched for pertinent reports. Eventually 19 articles were selected. The results were classified into categories regarding three areas of interest: familial occurrence, genetic basis, and immunological mechanisms of PFAPA.
RESULTS
Recent findings suggest that there is a familial tendency to PFAPA but the level of evidence does not warrant definite conclusions. The absence of a clear monogenic trait indicates a heterogenous, polygenic, or complex inheritance of PFAPA syndrome. As two mutations with a possible functional effect on the inflammasomes (MEFV E148Q and NLRP3 Q703K) have been found in several PFAPA cohorts, the role of inflammasome-related genes in PFAPA pathogenesis cannot be excluded. Immunological mechanisms of PFAPA involve an abnormal, IL-1β dependent innate immune response to an environmental trigger, which leads to Th1-driven inflammation expressed by recruitment of T-cells to the periphery.
Topics: Animals; Fever; Humans; Inflammation; Lymphadenitis; Pharyngitis; Stomatitis, Aphthous
PubMed: 26457006
DOI: 10.1155/2015/563876 -
The British Journal of General Practice... Apr 2020Centor and McIsaac scores are both used to diagnose group A beta-haemolytic streptococcus (GABHS) infection, but have not been compared through meta-analysis. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Centor and McIsaac scores are both used to diagnose group A beta-haemolytic streptococcus (GABHS) infection, but have not been compared through meta-analysis.
AIM
To compare the performance of Centor and McIsaac scores at diagnosing patients with GABHS presenting to primary care with pharyngitis.
DESIGN AND SETTING
A meta-analysis of diagnostic test accuracy studies conducted in primary care was performed using a novel model that incorporates data at multiple thresholds.
METHOD
MEDLINE, EMBASE, and PsycINFO were searched for studies published between January 1980 and February 2019. Included studies were: cross-sectional; recruited patients with sore throats from primary care; used the Centor or McIsaac score; had GABHS infection as the target diagnosis; used throat swab culture as the reference standard; and reported 2 × 2 tables across multiple thresholds. Selection and data extraction were conducted by two independent reviewers. QUADAS-2 was used to assess study quality. Summary receiver operating characteristic (SROC) curves were synthesised. Calibration curves were used to assess the transferability of results into practice.
RESULTS
Ten studies using the Centor score and eight using the McIsaac score were included. The prevalence of GABHS ranged between 4% and 44%. The areas under the SROC curves for McIsaac and Centor scores were 0.7052 and 0.6888, respectively. The -value for the difference (0.0164) was 0.419, suggesting the SROC curves for the tests are equivalent. Both scores demonstrated poor calibration.
CONCLUSION
Both Centor and McIsaac scores provide only fair discrimination of those with and without GABHS, and appear broadly equivalent in performance. The poor calibration for a positive test result suggests other point-of-care tests are required to rule in GABHS; however, with both Centor and McIsaac scores, a score of ≤0 may be sufficient to rule out infection.
Topics: Humans; Pharyngitis; Primary Health Care; Sensitivity and Specificity; Streptococcal Infections; Streptococcus pyogenes; Symptom Assessment
PubMed: 32152041
DOI: 10.3399/bjgp20X708833 -
International Journal of Medical... Oct 2017Low provider adoption continues to be a significant barrier to realizing the potential of clinical decision support. "Think Aloud" and "Near Live" usability testing were... (Observational Study)
Observational Study
OBJECTIVES
Low provider adoption continues to be a significant barrier to realizing the potential of clinical decision support. "Think Aloud" and "Near Live" usability testing were conducted on two clinical decision support tools. Each was composed of an alert, a clinical prediction rule which estimated risk of either group A Streptococcus pharyngitis or pneumonia and an automatic order set based on risk. The objective of this study was to further understanding of the facilitators of usability and to evaluate the types of additional information gained from proceeding to "Near Live" testing after completing "Think Aloud".
METHODS
This was a qualitative observational study conducted at a large academic health care system with 12 primary care providers. During "Think Aloud" testing, participants were provided with written clinical scenarios and asked to verbalize their thought process while interacting with the tool. During "Near Live" testing participants interacted with a mock patient. Morae usability software was used to record full screen capture and audio during every session. Participant comments were placed into coding categories and analyzed for generalizable themes. Themes were compared across usability methods.
RESULTS
"Think Aloud" and "Near Live" usability testing generated similar themes under the coding categories visibility, workflow, content, understand-ability and navigation. However, they generated significantly different themes under the coding categories usability, practical usefulness and medical usefulness. During both types of testing participants found the tool easier to use when important text was distinct in its appearance, alerts were passive and appropriately timed, content was up to date, language was clear and simple, and each component of the tool included obvious indicators of next steps. Participant comments reflected higher expectations for usability and usefulness during "Near Live" testing. For example, visit aids, such as automatically generated order sets, were felt to be less useful during "Near-Live" testing because they would not be all inclusive for the visit.
CONCLUSIONS
These complementary types of usability testing generated unique and generalizable insights. Feedback during "Think Aloud" testing primarily helped to improve the tools' ease of use. The additional feedback from "Near Live" testing, which mimics a real clinical encounter, was helpful for eliciting key barriers and facilitators to provider workflow and adoption.
Topics: Decision Support Systems, Clinical; Electronic Health Records; Evidence-Based Medicine; Female; Health Personnel; Humans; Male; Middle Aged; Pharyngitis; Pneumonia; Software; User-Computer Interface
PubMed: 28870378
DOI: 10.1016/j.ijmedinf.2017.06.003 -
The American Journal of Managed Care May 2021In the United States, approximately 12 million individuals seek medical care for pharyngitis each year, accounting for about 2% of ambulatory care visits. Although the...
OBJECTIVES
In the United States, approximately 12 million individuals seek medical care for pharyngitis each year, accounting for about 2% of ambulatory care visits. Although the gold standard for diagnosing group A streptococcus (GAS) is culture, it is time intensive. Rapid antigen detection tests (RADT) with or without culture confirmation are commonly used instead. Although RADT provide results quickly, they generally have lower test sensitivity. Recently, point-of-care nucleic acid amplification tests (POC NAAT) have emerged. This study evaluates the cost-effectiveness and budget impact to the US payer of adopting POC NAAT.
STUDY DESIGN
This study was a cost-effectiveness analysis, with costs and outcomes calculated via a decision tree.
METHODS
A decision-tree model quantified costs and outcomes associated with a GAS diagnostic strategy using POC NAAT compared with RADT + culture confirmation. Model inputs were derived from the published literature. Model outputs included costs and clinical effects: quality-adjusted life-days lost, GAS and antibiotic complications, number of patients appropriately treated, and antibiotic utilization. Sensitivity and scenario analyses were performed.
RESULTS
Base-case analysis projected that a POC NAAT strategy would cost $44 per patient compared with $78 for RADT + culture. Compared with RADT + culture, POC NAAT would increase the number of appropriately treated patients and avert unnecessary use of antibiotics. The budget impact of POC NAAT was -0.4% relative to current budget over 5 years. Findings were robust in sensitivity analyses.
CONCLUSIONS
Our results suggest that POC NAAT would be less costly and more effective than RADT + culture; POC NAAT adoption may yield cost savings to US third-party payers. Access to POC NAAT is important to optimize GAS diagnosis and treatment decisions in the United States.
Topics: Cost-Benefit Analysis; Humans; Nucleic Acid Amplification Techniques; Pharyngitis; Point-of-Care Systems; Streptococcus; United States
PubMed: 34002967
DOI: 10.37765/ajmc.2021.88638 -
Annals of Saudi Medicine 2015Improper prescription of antibiotics for treatment of acute pharyngitis predisposes to emergence of a carrier state and antibiotic-resistant strains of group A...
BACKGROUND
Improper prescription of antibiotics for treatment of acute pharyngitis predisposes to emergence of a carrier state and antibiotic-resistant strains of group A streptococci (GAS). We sought to identify the frequency and antimicrobial susceptibility patterns of group A streptococci among Egyptian children with acute pharyngitis compared with asymptomatic children.
DESIGN AND SETTING
Case-control study conducted from September 2013 to August 2014 at a pediatric outpatient clinic in Egypt.
PATIENTS AND METHODS
Throat swabs were collected from children with acute pharyngitis and from asymptomatic children. We evaluated the accuracy of McIsaac scores and the rapid antigen detection test (RADT) for diagnosis of GAS pharyngitis with throat culture as a reference test. Antimicrobial susceptibility testing of GAS isolates was done by the disc diffusion method.
RESULTS
Of 142 children with acute pharyngitis (cases) and 300 asymptomatic children (controls) (age range, 4-16 years), GAS pharyngitis was diagnosed in 60/142 children (42.2%); 48/300 (16%) were found to be carriers. All GAS isolates in the case group were sensitive to penicillin; however, an MIC90 (0.12 micro g/mL) for penicillin is high and an alarming sign. The resistance rate to macrolides was 70% with the cMLSB phenotype in 65.1%. The sensitivities and specificities were 78.3% and 73.2% for McIsaac score of >=4 and 81.1% and 93.9% for RADT, respectively. GAS isolates in the control group were 100% sensitive to penicillin, while 12.5% and 37.5% were resistant to macrolides and tetracycline, respectively.
CONCLUSION
An increased MIC90 for GAS isolates to penicillin is an alarming sign. A high frequency of resistance to macrolides was also observed.
Topics: Adolescent; Anti-Bacterial Agents; Antigens, Bacterial; Asymptomatic Infections; Carrier State; Case-Control Studies; Child; Child, Preschool; Egypt; Female; Humans; Macrolides; Male; Microbial Sensitivity Tests; Penicillins; Pharyngitis; Sensitivity and Specificity; Streptococcal Infections; Streptococcus pyogenes
PubMed: 26506971
DOI: 10.5144/0256-4947.2015.377 -
JCI Insight Jun 2020Streptococcus pyogenes (group A streptococcus; GAS) causes 600 million cases of pharyngitis annually worldwide. There is no licensed human GAS vaccine despite a century...
Streptococcus pyogenes (group A streptococcus; GAS) causes 600 million cases of pharyngitis annually worldwide. There is no licensed human GAS vaccine despite a century of research. Although the human oropharynx is the primary site of GAS infection, the pathogenic genes and molecular processes used to colonize, cause disease, and persist in the upper respiratory tract are poorly understood. Using dense transposon mutant libraries made with serotype M1 and M28 GAS strains and transposon-directed insertion sequencing, we performed genome-wide screens in the nonhuman primate (NHP) oropharynx. We identified many potentially novel GAS fitness genes, including a common set of 115 genes that contribute to fitness in both genetically distinct GAS strains during experimental NHP pharyngitis. Targeted deletion of 4 identified fitness genes/operons confirmed that our newly identified targets are critical for GAS virulence during experimental pharyngitis. Our screens discovered many surface-exposed or secreted proteins - substrates for vaccine research - that potentially contribute to GAS pharyngitis, including lipoprotein HitA. Pooled human immune globulin reacted with purified HitA, suggesting that humans produce antibodies against this lipoprotein. Our findings provide new information about GAS fitness in the upper respiratory tract that may assist in translational research, including developing novel vaccines.
Topics: Animals; Disease Models, Animal; Genes, Bacterial; Genome-Wide Association Study; Humans; Macaca fascicularis; Pharyngitis; Streptococcal Infections; Streptococcus pyogenes; Virulence Factors
PubMed: 32493846
DOI: 10.1172/jci.insight.137686