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Annals of Family Medicine Nov 2016The prevalence of Group C beta-hemolytic and among patients with sore throat in the outpatient setting has not been previously summarized. We set out to derive... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The prevalence of Group C beta-hemolytic and among patients with sore throat in the outpatient setting has not been previously summarized. We set out to derive prevalence information from the existing literature.
METHODS
We performed a systematic review of MEDLINE for studies reporting the prevalence of or Group C or both in prospective, consecutive series of outpatients with sore throat, as well as laboratory-based studies of throat cultures submitted from primary care. We limited searches to studies where the majority of data was collected after January 1, 2000, to reflect contemporary microbiological methods and prevalences. Each author independently reviewed the articles for inclusion and abstraction of data; we resolved discrepancies by consensus discussion. We then performed a meta-analysis to calculate the pooled prevalence estimates using a random effects model of raw proportions.
RESULTS
A total of 16 studies met our inclusion criteria. The overall prevalences of Group C and were 6.1% (95% CI, 3.2%-9.0%) and 18.9% (95% CI, 10.5%-27.2%), respectively. When stratified by study type, the prevalences of Group C and in laboratory-based studies were 6.6% (95% CI, -1.0% to 14.2%) and 18.8% (95% CI, 6.5%-31.1%), respectively. In primary care patients with sore throat, Group C had a prevalence of 6.1% (95% CI, 3.1%-9.2%), while had a prevalence of 19.4% (95% CI, 14.7%-24.1%).
CONCLUSIONS
Group C and are commonly detected in patients with acute pharyngitis. Research is needed, however, to determine whether these bacteria are truly pathogenic in patients with pharyngitis and whether antibiotics reduce the duration of symptoms or the likelihood of complications.
Topics: Anti-Bacterial Agents; Fusobacterium Infections; Fusobacterium necrophorum; Humans; Pharyngitis; Prevalence; Randomized Controlled Trials as Topic; Streptococcal Infections; Streptococcus
PubMed: 28376443
DOI: 10.1370/afm.2005 -
Clinical Infectious Diseases : An... Feb 2023Few studies have assessed participant safety in human challenge trials (HCTs). Key questions regarding HCTs include how risky such trials have been, how often adverse...
BACKGROUND
Few studies have assessed participant safety in human challenge trials (HCTs). Key questions regarding HCTs include how risky such trials have been, how often adverse events (AEs) and serious adverse events (SAEs) occur, and whether risk mitigation measures have been effective.
METHODS
A systematic search of PubMed and PubMed Central for articles reporting on results of HCTs published between 1980 and 2021 was performed and completed by 7 October 2021.
RESULTS
Of 2838 articles screened, 276 were reviewed in full. A total of 15 046 challenged participants were described in 308 studies that met inclusion criteria; 286 (92.9%) of these studies reported mitigation measures used to minimize risk to the challenge population. Among 187 studies that reported on SAEs, 0.2% of participants experienced at least 1 challenge-related SAE. Among 94 studies that graded AEs by severity, challenge-related AEs graded "severe" were reported by between 5.6% and 15.8% of participants. AE data were provided as a range to account for unclear reporting. Eighty percent of studies published after 2010 were registered in a trials database.
CONCLUSIONS
HCTs are increasingly common and used for an expanding list of diseases. Although AEs occur, severe AEs and SAEs are rare. Reporting has improved over time, though not all papers provide a comprehensive report of relevant health impacts. We found very few severe symptoms or SAEs in studies that reported them, but many HCTs did not report relevant safety data. This study was preregistered on PROSPERO as CRD42021247218.
PubMed: 36219704
DOI: 10.1093/cid/ciac820 -
Global Heart Sep 2020National and international political commitments have been made recently on rheumatic heart disease (RHD), a preventable heart condition that is endemic in low-resource... (Meta-Analysis)
Meta-Analysis
BACKGROUND
National and international political commitments have been made recently on rheumatic heart disease (RHD), a preventable heart condition that is endemic in low-resource countries. To inform best practice and identify evidence gaps, we assessed the effectiveness of RHD prevention and control programmes and the extent and nature of their integration into local health systems.
METHODS
We conducted a systematic review and meta-analysis using a previously published protocol that included electronic and manual searches for studies published between January 1990 and July 2019 reporting on prevention and control programmes for populations at risk for streptococcal pharyngitis, rheumatic fever, and/or RHD. We analysed programme integration according to a previously published framework and programme effectiveness using a results-chain framework. We meta-analysed secondary prophylaxis adherence using random-effects models. Study quality was assessed using peer-reviewed checklists (CASP and PRISM). PROSPERO registration: CRD42017076307.
FINDINGS
Five observational studies met with the inclusion criteria. Studies were similar in extent and nature of integration into health systems; no programme was completely integrated or non-integrated. A single study reported on programme impact. Secondary prophylaxis adherence improved among partially integrated RHD programmes (RR, 1.18 [95% CI, 1.03 to 1.36], 3 studies, n = 618). Risk of bias was low in two studies, and indeterminable in the remaining three studies.
INTERPRETATION
There is evidence that partially integrated RHD programmes are beneficial for a range of intermediate health outcomes. This review provides a starting point for the design and implementation of future RHD programmes by outlining current best practice for integration and identifying key gaps in knowledge.
FUNDING
National Research Foundation of South Africa.
Topics: Global Health; Humans; Morbidity; Program Evaluation; Rheumatic Heart Disease; Secondary Prevention
PubMed: 33150127
DOI: 10.5334/gh.874 -
EClinicalMedicine Jun 2022Contemporary data for the global burden of sore throat and group A (Strep A) pharyngitis are required to understand the frequency of disease and develop value...
BACKGROUND
Contemporary data for the global burden of sore throat and group A (Strep A) pharyngitis are required to understand the frequency of disease and develop value propositions for Strep A vaccines.
METHODS
We used Clarivate Analytics' Web of Science platform to search WoS core collection, PubMed, Medline, data citation index, KCI-Korean Journal Database, Russian Science Citation Index, and the SciELO Citation Index for articles published between Jan 1, 2000, and Feb 15, 2021, from any country and in any language. The risk of bias was assessed using the JBI critical appraisal checklist. We used random-effects meta-analyses to pool sore throat and Strep A sore throat incidence rates from community-based studies. Our study was registered with PROSPERO (CRD42020181103).
FINDINGS
Of 5,529 articles identified by the search strategy, 26 studies met the inclusion criteria, but only two included data to determine incidence among adults. The pooled incidence rate, calculated for children only, was 82.2 episodes per 100 child-years (95% CI 25.2-286.3, I = 100%) for sore throat (7 studies; 7,964 person years) and 22.1 episodes per 100 child-years (95% CI 14.7-33.1, I = 98%) for Strep A sore throat (9 studies; 15,696 person years). The pooled cumulative incidence rate of sore throat from five studies was 31.9 per 100 children. There was significant methodological and statistical heterogeneity among studies, and five of 26 studies had a risk of bias score less than five (range: nine [maximum score] to one).
INTERPRETATION
Strep A sore throat has a considerable global burden. However, methodologically standardised studies are required to quantify that burden, analyse differences in rates between populations, and evaluate the likely impact of future Strep A vaccines.
FUNDING
This study was funded by Wellcome Trust 215,490/Z/19/Z.
PubMed: 35706486
DOI: 10.1016/j.eclinm.2022.101458 -
The Cochrane Database of Systematic... Nov 2015Infectious mononucleosis, also known as glandular fever or the kissing disease, is a benign lymphoproliferative disorder. It is a viral infection caused by the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Infectious mononucleosis, also known as glandular fever or the kissing disease, is a benign lymphoproliferative disorder. It is a viral infection caused by the Epstein-Barr virus (EBV), a ubiquitous herpes virus that is found in all human societies and cultures. Epidemiological studies show that over 95% of adults worldwide have been infected with EBV. Most cases of symptomatic infectious mononucleosis occur between the ages of 15 and 24 years. It is transmitted through close contact with an EBV shedder, contact with infected saliva or, less commonly, through sexual contact, blood transfusions or by sharing utensils; however, transmission actually occurs less than 10% of the time. Precautions are not needed to prevent transmission because of the high percentage of seropositivity for EBV. Infectious mononucleosis is self-limiting and typically lasts for two to three weeks. Nevertheless, symptoms can last for weeks and occasionally months.Symptoms include fever, lymphadenopathy, pharyngitis, hepatosplenomegaly and fatigue. Symptom relief and rest are commonly recommended treatments. Steroids have been used for their anti-inflammatory effects, but there are no universal criteria for their use.
OBJECTIVES
The objectives of the review were to determine the efficacy and safety of steroid therapy versus placebo, usual care or different drug therapies for symptom control in infectious mononucleosis.
SEARCH METHODS
For this 2015 update we searched the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 7), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register; MEDLINE (January 1966 to August 2015) and EMBASE (January 1974 to August 2015). We also searched trials registries, however we did not identify any new relevant completed or ongoing trials for inclusion. We combined the MEDLINE search with the Cochrane search strategy for identifying randomised controlled trials (RCTs). We adapted the search terms when searching EMBASE.
SELECTION CRITERIA
RCTs comparing the effectiveness of steroids with placebo, usual care, or other interventions for symptom control for people with documented infectious mononucleosis.
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures expected by Cochrane.
MAIN RESULTS
For this 2015 update, we did not identify any new RCTs for inclusion. The previous version of the review included seven trials with a total of 362 participants. Four trials compared the effectiveness of a steroid to placebo for short-term symptom control in glandular fever, one to aspirin, and two trials explored the effects of steroids in conjunction with an antiviral. Heterogeneity between trials prevented a combined analysis.Trials under-reported methodological design features. Three trials did not adequately describe sequence generation for randomisation. Four trials provided adequate details of allocation concealment. All trials were double-blind but four were not specific as to who was blinded. Loss to follow-up was under-reported in four trials, making it difficult to exclude attrition bias. The risk of selective reporting in the included trials was unclear.Across the trials, no benefit was found in 8/10 assessments of health improvement. Two trials found benefit of steroid therapy over placebo in reducing sore throat at 12 hours (eight-day course odds ratio (OR) 21.00, 95% confidence interval (CI) 1.94 to 227.20; one-dose OR 4.20, 95% CI 1.08 to 16.32), but the benefit was not maintained.In combination with an antiviral drug, participants in the steroid group had less pharyngeal discomfort between days two to four (OR 0.31, 95% CI 0.09 to 1.08) compared to placebo. Across the trials the effects on other common symptoms were less clear. Two trials set out to measure safety; they documented no major adverse effects. In two other trials adverse events were reported, including respiratory distress and acute onset of diabetes. However, the association of the events with the steroid is not definite.
AUTHORS' CONCLUSIONS
There is insufficient evidence to the efficacy of steroids for symptom control in infectious mononucleosis. There is a lack of research on the side effects and long-term complications.
Topics: Adolescent; Adrenal Cortex Hormones; Adult; Humans; Infectious Mononucleosis; Randomized Controlled Trials as Topic; Young Adult
PubMed: 26558642
DOI: 10.1002/14651858.CD004402.pub3 -
JAMA Apr 2016Early, accurate diagnosis of infectious mononucleosis can help clinicians target treatment, avoid antibiotics, and provide an accurate prognosis. (Review)
Review
IMPORTANCE
Early, accurate diagnosis of infectious mononucleosis can help clinicians target treatment, avoid antibiotics, and provide an accurate prognosis.
OBJECTIVE
To systematically review the literature regarding the value of the clinical examination and white blood cell count for the diagnosis of mononucleosis.
DATA SOURCES
The databases of PubMed (from 1966-2016) and EMBASE (from 1947-2015) were searched and a total of 670 articles and abstracts were reviewed for eligibility.
STUDY SELECTION
Eleven studies were included that reported data sufficient to calculate sensitivity, specificity, or both for clinical examination findings and white blood cell count parameters compared with a valid reference standard.
DATA EXTRACTION AND SYNTHESIS
Data were abstracted from each article by at least 2 reviewers, with discrepancies reconciled by consensus. Clinical findings evaluated in only 1 study are reported with sensitivity, specificity, likelihood ratio (LR), and 95% confidence interval, which were calculated from the available data. Findings evaluated in only 2 studies were summarized with their range, findings evaluated in 3 studies were summarized with a univariate random-effects summary, and findings evaluated in 4 or more studies were summarized with a bivariate random-effects meta-analysis.
MAIN OUTCOMES AND MEASURES
Sensitivity, specificity, and LRs for the diagnosis of mononucleosis.
RESULTS
Mononucleosis is most commonly present among patients aged 5 to 25 years (especially those aged 16-20 years, among whom approximately 1 in 13 patients presenting with sore throat has mononucleosis). The likelihood of mononucleosis is reduced with the absence of any lymphadenopathy (summary sensitivity, 0.91; positive LR range, 0.23-0.44), whereas the likelihood increases with the presence of posterior cervical adenopathy (summary specificity, 0.87; positive LR, 3.1 [95% CI, 1.6-5.9]), inguinal or axillary adenopathy (specificity range, 0.82-0.91; positive LR range, 3.0-3.1), palatine petechiae (specificity, 0.95; positive LR, 5.3 [95% CI, 2.1-13]), and splenomegaly (specificity range, 0.71-0.99; positive LR range, 1.9-6.6). Symptoms are of limited value for the diagnosis of mononucleosis; sore throat and fatigue are sensitive (range, 0.81-0.83) but nonspecific. The presence of atypical lymphocytosis significantly increases the likelihood of mononucleosis (summary LR, 11.4 [95% CI, 2.7-35] for atypical lymphocytes ≥10%, 26 [95% CI, 9.6-68] for those with 20%, and 50 [95% CI, 38-64] for those with 40%). The combination of a patient having greater than 50% lymphocytes and greater than 10% atypical lymphocytes also is useful (specificity, 0.99; positive LR, 54 [95% CI, 8.4-189]).
CONCLUSIONS AND RELEVANCE
In adolescent and adult patients presenting with sore throat, the presence of posterior cervical, inguinal or axillary adenopathy, palatine petechiae, splenomegaly, or atypical lymphocytosis is associated with an increased likelihood of mononucleosis.
Topics: Adolescent; Adult; Axilla; Fatigue; Humans; Infectious Mononucleosis; Leukocyte Count; Lymphatic Diseases; Lymphocyte Count; Neck; Pharyngitis; Physical Examination; Purpura; Sensitivity and Specificity; Splenomegaly; Symptom Assessment; Young Adult
PubMed: 27115266
DOI: 10.1001/jama.2016.2111 -
Antibiotics (Basel, Switzerland) Oct 2020To evaluate the effectiveness of short courses of antibiotic therapy for patients with acute streptococcal pharyngitis. (Review)
Review
BACKGROUND
To evaluate the effectiveness of short courses of antibiotic therapy for patients with acute streptococcal pharyngitis.
METHODS
Randomized controlled trials comparing short-course antibiotic therapy (≤5 days) with long-course antibiotic therapy (≥7 days) for patients with streptococcal pharyngitis were included. Two primary outcomes: early clinical cure and early bacterial eradication.
RESULTS
Fifty randomized clinical trials were included. Overall, short-course antibiotic treatment was as effective as long-course antibiotic treatment for early clinical cure (odds ratio (OR) 0.85; 95% confidence interval (CI) 0.79 to 1.15). Subgroup analysis showed that short-course penicillin was less effective for early clinical cure (OR 0.43; 95% CI, 0.23 to 0.82) and bacteriological eradication (OR 0.34; 95% CI, 0.19 to 0.61) in comparison to long-course penicillin. Short-course macrolides were equally effective, compared to long-course penicillin. Finally, short-course cephalosporin was more effective for early clinical cure (OR 1.48; 95% CI, 1.11 to 1.96) and early microbiological cure (OR 1.60; 95% CI, 1.13 to 2.27) in comparison to long-course penicillin. In total, 1211 (17.7%) participants assigned to short-course antibiotic therapy, and 893 (12.3%) cases assigned to long-course, developed adverse events (OR 1.35; 95% CI, 1.08 to 1.68).
CONCLUSIONS
Macrolides and cephalosporins belong to the list of "Highest Priority Critically Important Antimicrobials"; hence, long-course penicillin V should remain as the first line antibiotic for the management of patients with streptococcal pharyngitis as far as the benefits of using these two types of antibiotics do not outweigh the harms of their unnecessary use.
PubMed: 33114471
DOI: 10.3390/antibiotics9110733 -
CMAJ : Canadian Medical Association... Jan 2015Several clinical prediction rules for diagnosing group A streptococcal infection in children with pharyngitis are available. We aimed to compare the diagnostic accuracy... (Review)
Review
Selective testing strategies for diagnosing group A streptococcal infection in children with pharyngitis: a systematic review and prospective multicentre external validation study.
BACKGROUND
Several clinical prediction rules for diagnosing group A streptococcal infection in children with pharyngitis are available. We aimed to compare the diagnostic accuracy of rules-based selective testing strategies in a prospective cohort of children with pharyngitis.
METHODS
We identified clinical prediction rules through a systematic search of MEDLINE and Embase (1975-2014), which we then validated in a prospective cohort involving French children who presented with pharyngitis during a 1-year period (2010-2011). We diagnosed infection with group A streptococcus using two throat swabs: one obtained for a rapid antigen detection test (StreptAtest, Dectrapharm) and one obtained for culture (reference standard). We validated rules-based selective testing strategies as follows: low risk of group A streptococcal infection, no further testing or antibiotic therapy needed; intermediate risk of infection, rapid antigen detection for all patients and antibiotic therapy for those with a positive test result; and high risk of infection, empiric antibiotic treatment.
RESULTS
We identified 8 clinical prediction rules, 6 of which could be prospectively validated. Sensitivity and specificity of rules-based selective testing strategies ranged from 66% (95% confidence interval [CI] 61-72) to 94% (95% CI 92-97) and from 40% (95% CI 35-45) to 88% (95% CI 85-91), respectively. Use of rapid antigen detection testing following the clinical prediction rule ranged from 24% (95% CI 21-27) to 86% (95% CI 84-89). None of the rules-based selective testing strategies achieved our diagnostic accuracy target (sensitivity and specificity>85%).
INTERPRETATION
Rules-based selective testing strategies did not show sufficient diagnostic accuracy in this study population. The relevance of clinical prediction rules for determining which children with pharyngitis should undergo a rapid antigen detection test remains questionable.
Topics: Bacteriological Techniques; Child; Diagnosis, Differential; Humans; Multicenter Studies as Topic; Pharyngitis; Practice Guidelines as Topic; Predictive Value of Tests; Prospective Studies; Streptococcal Infections; Streptococcus pyogenes; Validation Studies as Topic
PubMed: 25487666
DOI: 10.1503/cmaj.140772 -
Otolaryngology--head and Neck Surgery :... Nov 2020The role of vitamin D deficiency has been linked with recurrent upper respiratory tract infections, but its impact on the frequency of tonsillitis is not yet fully... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The role of vitamin D deficiency has been linked with recurrent upper respiratory tract infections, but its impact on the frequency of tonsillitis is not yet fully understood. The objective of this study is to determine the association between vitamin D deficiency and recurrent tonsillitis based on current literature.
DATA SOURCE
A systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Data were collected from online medical databases (PubMed, MEDLINE, EMBASE, and Cochrane Collaboration Registry of Controlled Trials).
REVIEW METHODS
All studies addressing the association of vitamin D deficiency and recurrent tonsillitis prior to March 2019. The data were collected in different phases: screening review using search words and controlled vocabularies followed by detailed review of screened articles based on inclusion and exclusion criteria, then a full review that included screening the references of selected articles.
RESULTS
Fifty-three studies were potentially eligible; of these, 4 publications met the inclusion criteria and were included in the quantitative synthesis. There was a statistically significant reduction of vitamin D levels in patients with recurrent tonsillitis as compared to healthy controls (mean difference, -10.71; 95% CI, -19.12 to -2.31; = .01). The odds of vitamin D insufficiency were significantly higher in patients with recurrent tonsillitis as compared to the control group (odds ratio, 4.37; 95% CI, 2.78-6.88; < .001).
CONCLUSION
Vitamin D deficiency was present in patients with recurrent tonsillitis and might be associated with an increase in the risk of recurrent tonsillitis. There is a need to explore these findings via clinical trials based on large populations.
Topics: Adult; Bacterial Infections; Child; Humans; Tonsillitis; Vitamin D Deficiency
PubMed: 32689892
DOI: 10.1177/0194599820935442 -
The Laryngoscope Jan 2018This study systematically reviews the existing literature on the efficacy of adjuvant corticosteroids in improving clinical outcomes after peritonsillar abscess (PTA)... (Review)
Review
OBJECTIVES
This study systematically reviews the existing literature on the efficacy of adjuvant corticosteroids in improving clinical outcomes after peritonsillar abscess (PTA) drainage.
STUDY DESIGN
Systematic review.
METHODS
We performed a literature search of MEDLINE, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Scopus, Embase, and ClinicalTrials.gov from inception to June 2016. Inclusion criteria included randomized controlled trials (RCTs) evaluating adjuvant corticosteroids after PTA drainage. Data were systematically collected on study design, patient demographics, and clinical characteristics. Two independent investigators reviewed all manuscripts and summarized the data.
RESULTS
Three RCTs comprising 153 patients were included. The results were not pooled due to heterogeneity in the method in which outcomes were measured and reported. The trials also varied on the type of steroid (dexamethasone, methylprednisolone) administered and method of drainage (incision, aspiration). All three RCTs reported statistically significant improvement in body temperature from adjuvant steroid administration compared to placebo. Pain scores, mouth opening, time to painless oral intake, and duration of hospitalization were significantly improved in only one or two of the three RCTs between the steroid and control group. No adverse side effects from steroid administration were reported.
CONCLUSIONS
Steroids as an adjunct therapy to the treatment of PTA may result in faster recovery. However, further investigation with larger RCTs and standardized outcomes are warranted.
LEVEL OF EVIDENCE
1a. Laryngoscope, 128:72-77, 2018.
Topics: Chemotherapy, Adjuvant; Drainage; Glucocorticoids; Humans; Peritonsillar Abscess
PubMed: 28561258
DOI: 10.1002/lary.26672