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Frontiers in Surgery 2023There is an ongoing debate on the indications for tonsil surgery in both children and adults with recurrent acute tonsillitis. The aim is to provide practical... (Review)
Review
BACKGROUND
There is an ongoing debate on the indications for tonsil surgery in both children and adults with recurrent acute tonsillitis. The aim is to provide practical recommendations for diagnostics and treatment for recurrent acute tonsillitis including evidence-based decision making for tonsillectomy.
METHODS
A systematic literature search in PubMed, Embase, Web of Science, and ScienceDirect from 2014 until April 2023 resulted in 68 articles. These were the basis for the review and a comprehensive series of consensus statements on the most important diagnostics and indications for both non-surgical and surgical therapy. A consensus paper was circulated among the authors and members of the International Head and Neck Scientific Group until a final agreement was reached for all recommendations.
RESULTS
The differentiation between sore throat and tonsillitis patient episodes is mostly not feasible and hence is not relevant for diagnostic decision making. Diagnostics of a tonsillitis/sore throat episode should always include a classification with a scoring system (Centor, McIssac, FeverPAIN score) to estimate the probability of a bacterial tonsillitis, mainly due to group A (GAS). In ambiguous cases, a point-of-care test GAS swab test is helpful. Consecutive counting of the tonsillitis/sore throat episodes is important. In addition, a specific quality of life score (Tonsillectomy Outcome Inventory 14 or Tonsil and Adenoid Health Status Instrument) should be used for each episode. Conservative treatment includes a combination of paracetamol and/or non-steroidal anti-inflammatory drugs. In case of high probability of bacterial tonsillitis, and only in such cases, especially in patients at risk, standard antibiotic treatment is initiated directly or by delayed prescription. Tonsillectomy is indicated and is highly effective if the patient has had ≥7 adequately treated episodes in the preceding year, ≥5 such episodes in each of the preceding 2 years, or ≥3 such episodes in each of the preceding 3 years. An essential part of surgery is standardized pain management because severe postoperative pain can be expected in most patients.
CONCLUSION
It is necessary to follow a stringent treatment algorithm for an optimal and evidence-based treatment for patients with recurrent acute tonsillitis. This will help decrease worldwide treatment variability, antibiotic overuse, and avoid ineffective tonsillectomy.
PubMed: 37881239
DOI: 10.3389/fsurg.2023.1221932 -
The Cochrane Database of Systematic... Oct 2023Concerns exist regarding antibiotic prescribing for respiratory tract infections (RTIs) owing to adverse reactions, cost and antibacterial resistance. One proposed... (Review)
Review
BACKGROUND
Concerns exist regarding antibiotic prescribing for respiratory tract infections (RTIs) owing to adverse reactions, cost and antibacterial resistance. One proposed strategy to reduce antibiotic prescribing is to provide prescriptions, but to advise delay in antibiotic use with the expectation that symptoms will resolve first. This is an update of a Cochrane Review originally published in 2007, and updated in 2010, 2013 and 2017.
OBJECTIVES
To evaluate the effects on duration and/or severity of clinical outcomes (pain, malaise, fever, cough and rhinorrhoea), antibiotic use, antibiotic resistance and patient satisfaction of advising a delayed prescription of antibiotics in respiratory tract infections.
SEARCH METHODS
From May 2017 until 20 August 2022, this was a living systematic review with monthly searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL and Web of Science. We also searched the WHO International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov on 20 August 2022. Due to the abundance of evidence supporting the review's key findings, it ceased being a living systematic review on 21 August 2022.
SELECTION CRITERIA
Randomised controlled trials involving participants of all ages with an RTI, where delayed antibiotics were compared to immediate or no antibiotics. We defined a delayed antibiotic as advice to delay the filling of an antibiotic prescription by at least 48 hours. We considered all RTIs regardless of whether antibiotics were recommended or not.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodological procedures.
MAIN RESULTS
For this 2022 update, we added one new trial enrolling 448 children (436 analysed) with uncomplicated acute RTIs. Overall, this review includes 12 studies with a total of 3968 participants, of which data from 3750 are available for analysis. These 12 studies involved acute RTIs including acute otitis media (three studies), streptococcal pharyngitis (three studies), cough (two studies), sore throat (one study), common cold (one study) and a variety of RTIs (two studies). Six studies involved only children, two only adults and four included both adults and children. Six studies were conducted in primary care, four in paediatric clinics and two in emergency departments. Studies were well reported and appeared to provide moderate-certainty evidence. Randomisation was not adequately described in two trials. Four trials blinded the outcome assessor, and three included blinding of participants and doctors. We conducted meta-analyses for pain, malaise, fever, adverse effects, antibiotic use and patient satisfaction. Cough (four studies): we found no differences amongst delayed, immediate and no prescribed antibiotics for clinical outcomes in any of the four studies. Sore throat (six studies): for the outcome of fever with sore throat, four of the six studies favoured immediate antibiotics, and two found no difference. For the outcome of pain related to sore throat, two studies favoured immediate antibiotics, and four found no difference. Two studies compared delayed antibiotics with no antibiotic for sore throat, and found no difference in clinical outcomes. Acute otitis media (four studies): two studies compared immediate with delayed antibiotics - one found no difference for fever, and the other favoured immediate antibiotics for pain and malaise severity on Day 3. Two studies compared delayed with no antibiotics: one found no difference for pain and fever severity on Day 3, and the other found no difference for the number of children with fever on Day 3. Common cold (two studies): neither study found differences for clinical outcomes between delayed and immediate antibiotic groups. One study found delayed antibiotics were probably favoured over no antibiotics for pain, fever and cough duration (moderate-certainty evidence).
ADVERSE EFFECTS
there were either no differences for adverse effects or results may have favoured delayed over immediate antibiotics with no significant differences in complication rates (low-certainty evidence). Antibiotic use: delayed antibiotics probably resulted in a reduction in antibiotic use compared to immediate antibiotics (odds ratio (OR) 0.03, 95% confidence interval (CI) 0.01 to 0.07; 8 studies, 2257 participants; moderate-certainty evidence). However, a delayed antibiotic was probably more likely to result in reported antibiotic use than no antibiotics (OR 2.52, 95% CI 1.69 to 3.75; 5 studies, 1529 participants; moderate-certainty evidence). Patient satisfaction: patient satisfaction probably favoured delayed over no antibiotics (OR 1.45, 1.08 to 1.96; 5 studies, 1523 participants; moderate-certainty evidence). There was probably no difference in patient satisfaction between delayed and immediate antibiotics (OR 0.77, 95% CI 0.45 to 1.29; 7 studies, 1927 participants; moderate-certainty evidence). No studies evaluated antibiotic resistance. Reconsultation rates and use of alternative medicines were similar for delayed, immediate and no antibiotic strategies. In one of the four studies reporting use of alternative medicines, less paracetamol was used in the immediate group compared to the delayed group.
AUTHORS' CONCLUSIONS
For many clinical outcomes, there were no differences between prescribing strategies. Symptoms for acute otitis media and sore throat were modestly improved by immediate antibiotics compared with delayed antibiotics. There were no differences in complication rates. Delaying prescribing did not result in significantly different levels of patient satisfaction compared with immediate provision of antibiotics (86% versus 91%; moderate-certainty evidence). However, delay was favoured over no antibiotics (87% versus 82%). Delayed antibiotics achieved lower rates of antibiotic use compared to immediate antibiotics (30% versus 93%). The strategy of no antibiotics further reduced antibiotic use compared to delaying prescription for antibiotics (13% versus 27%). Delayed antibiotics for people with acute respiratory infection reduced antibiotic use compared to immediate antibiotics, but was not shown to be different to no antibiotics in terms of symptom control and disease complications. Where clinicians feel it is safe not to prescribe antibiotics immediately for people with RTIs, no antibiotics with advice to return if symptoms do not resolve is likely to result in the least antibiotic use while maintaining similar patient satisfaction and clinical outcomes to delayed antibiotics. Where clinicians are not confident in not prescribing antibiotics, delayed antibiotics may be an acceptable compromise in place of immediate prescribing to significantly reduce unnecessary antibiotic use for RTIs, while maintaining patient safety and satisfaction levels. Further research into antibiotic prescribing strategies for RTIs may best be focused on identifying patient groups at high risk of disease complications, enhancing doctors' communication with patients to maintain satisfaction, ways of increasing doctors' confidence to not prescribe antibiotics for RTIs, and policy measures to reduce unnecessary antibiotic prescribing for RTIs.
Topics: Child; Adult; Humans; Common Cold; Anti-Bacterial Agents; Cough; Respiratory Tract Infections; Pharyngitis; Otitis Media; Fever; Pain
PubMed: 37791590
DOI: 10.1002/14651858.CD004417.pub6 -
Frontiers in Immunology 2023The risk of infection and malignancy may be a concern for patients with psoriasis receiving interleukin (IL)-17 and IL-23 inhibitors, particularly with long-term... (Meta-Analysis)
Meta-Analysis
Short-term risk and long-term incidence rate of infection and malignancy with IL-17 and IL-23 inhibitors in adult patients with psoriasis and psoriatic arthritis: a systematic review and meta-analysis.
UNLABELLED
The risk of infection and malignancy may be a concern for patients with psoriasis receiving interleukin (IL)-17 and IL-23 inhibitors, particularly with long-term treatments. We aimed to estimate the short-term risks and long-term incidence rates of infection and malignancy with IL-17 or IL-23 antagonists in adult patients with psoriasis and psoriatic arthritis through this comprehensive meta-analysis (PROSPERO registration number: CRD42022363127). We searched PubMed, MEDLINE, Web of Science and ClinicalTrials.gov until May 17, 2023 for randomized placebo-controlled trials and long-term (≥ 52 weeks) open-label extension studies. The estimates of short-term risk ratios (RRs) and long-term exposure-adjusted incidence rates (EAIRs) were pooled using R software 4.1.1 and STATA 16.0. This review included 45 randomized placebo-controlled studies and 27 open-label extension studies. Short-term RRs of serious infection, overall infection and malignancy were 1.45 (95% confidence intervals, 95% CI: 0.81-2.59), 1.20 (95% CI: 1.06-1.35), 0.83 (95% CI: 0.41-1.71) with IL-17 inhibitors; and 0.68 (95% CI: 0.38-1.22), 1.13 (95% CI: 1.00-1.28), 0.87 (95% CI: 0.37-2.04) with IL-23 inhibitors. Increased short-term risks of nasopharyngitis and infection with IL-17 inhibitors were found. Long-term EAIRs of serious infection, overall infection, nonmelanoma skin cancer (NMSC), malignancies excluding NMSC, nasopharyngitis and upper respiratory tract infection were 1.11/100 patient-years (PYs), 57.78/100PYs, 0.47/100PYs, 0.24/100PYs, 15.07/100PYs, 8.52/100PYs, 3.41/100PYs with IL-17 inhibitors; and 1.09/100PYs, 48.50/100PYs, 0.40/100PYs, 0.43/100PYs, 10.75/100PYs, 5.84/100PYs with IL-23 inhibitors. Long-term EAIR of infection was 3.41/100PYs with IL-17 inhibitors. No active or reactivated tuberculosis was ever reported in all the trials, and only a few cases of latent tuberculosis, hepatitis, and herpes zoster were reported during the long-term extension periods. No evidence of increased EAIRs of infection and malignancy with longer durations was found. Our study suggested that short-term risk and long-term incidence of infections and malignancies in psoriasis patients receiving IL-17 inhibitors and IL-23 inhibitors are generally low. However, close monitoring is required for nasopharyngitis and infection with IL-17 inhibitors.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022363127.
Topics: Adult; Humans; Arthritis, Psoriatic; Candidiasis; Incidence; Interleukin Inhibitors; Interleukin-17; Interleukin-23; Nasopharyngitis; Neoplasms; Psoriasis
PubMed: 38106423
DOI: 10.3389/fimmu.2023.1294416 -
Reviews in Medical Virology Jul 2023Little is known about the ongoing monkeypox (mpox) outbreak, and the clinical features of mpox in patients worldwide have not been rigorously analysed. Thus, we aimed to... (Meta-Analysis)
Meta-Analysis Review
Little is known about the ongoing monkeypox (mpox) outbreak, and the clinical features of mpox in patients worldwide have not been rigorously analysed. Thus, we aimed to investigate the clinical features associated with mpox infection and understand the pathophysiology and characteristics of the disease. For this systematic review and meta-analysis, we searched PubMed/MEDLINE, Embase, CINAHL, Google Scholar, and the Cochrane Database of Systematic Reviews for articles published till 16 September 2022. We used a random effects model to calculate the pooled prevalence and 95% confidence interval (CI). We used the I statistic to assess heterogeneity, Egger's test to assess publication bias, 95% prediction interval to determine the level of uncertainty, and the Newcastle-Ottawa Scale and Joanna Briggs Institute quality assessment tool to assess the risk of bias. Twenty-six relevant articles from 19 countries across 5 continents were included, and data on 5472 mpox patients with 18 unique features were analysed. The pooled prevalence of clinical features of mpox were rash (85.7%, 95% CI: 68.3-94.3; k = 21), chills (77.8%, 95% CI: 70.5-83.7; k = 3), and fever (62.3%, 95% CI: 51.3-71.6; k = 25), lymphadenopathy (58.6%, 95% CI: 47.2-69.2; k = 21), lethargy or exhaustion (46.8%, 95% CI: 30.7-63.5; k = 14), pruritus (40.6%, 95% CI: 28.5-54.0; k = 5), myalgia (36.0%, 95% CI: 24.3-49.7; k = 16), headache (34.6%, 95% CI: 23.4-47.8; k = 17), skin ulcer (31.1%, 95% CI: 18.6-47.1; k = 7), abdomen symptom (24.2%, 95% CI: 17.9-31.9; k = 11), pharyngitis (23.0%, 95% CI: 12.7-37.9; k = 14), respiratory symptom (19.5%, 95% CI: 6.8-44.6; k = 6), nausea or vomiting (13.0%, 95% CI: 4.6-31.9; k = 3), scrotal or penile oedema (10.7%, 95% CI: 6.3-17.7; k = 4), conjunctivitis (7.1%, 95% CI: 2.4-18.9; k = 6), and death (0.9%, 95% CI: 0.4-2.0; k = 26). This is the first international and comprehensive study to examine all clinical presentations of human mpox infection. Our systematic review proposes a comprehensive understanding of the current mpox outbreak and may serve as key data for future studies on the pathological mechanisms and epidemiology of mpox infections.
Topics: Humans; Mpox (monkeypox); Pharyngitis; Prevalence; Exanthema; Fever
PubMed: 37056203
DOI: 10.1002/rmv.2446 -
Frontiers in Immunology 2024Clinicians and healthcare policymakers have been drenched with a deluge of overlapping meta-analyses (MAs), and the necessity for comprehensive and clearly defined...
BACKGROUND
Clinicians and healthcare policymakers have been drenched with a deluge of overlapping meta-analyses (MAs), and the necessity for comprehensive and clearly defined evidence of Janus kinase inhibitors (JKIs) in atopic dermatitis (AD) is urgent.
METHODS
Six databases were searched for MAs published until October 2023. Qualitative description of MAs was mainly used, and Investigator's Global Assessment response (IGA response), the 75% improvement in Eczema Area and Severity Index (the EASI75), peak pruritus Numerical rating score (PP-NRS), and adverse effects were cited to describe the efficacy and safety of JKIs. The methodological quality of the included MAs was assessed by A Measurement Tool to Assess Systematic Reviews II (AMSTAR II), and the quality of evidence was evaluated by the grading of recommendations, assessment, development, and evaluation (GRADE).
RESULTS
Sixteen MAs were pooled in this review, of which five studies appraised JKIs, five appraised systemic JKIs, five papers assessed abrocitinib only, and one assessed baricitinib. Two studies were of "high" methodological quality and 14 MAs were of "moderate" quality. Eleven MAs integrated the results of JKIs and reported that JKIs provide faster onset of IGA response (RR=2.83, 95% CI [2.25, 3.56], high-quality evidence). Similarly, 10 MAs showed that JAK inhibitors were more effective in improving the EASI75 (RR=2.84, 95% CI [2.2, 3.67], high-quality evidence). Results from 12 MAs showed JKIs were active in reducing the PP-NRS (SMD=-0.49, 95% CI [-0.67, -0.32]). All MAs affirmed JKIs added no adverse effects leading to discontinuation and serious adverse events (P<0.05). However, 200mg of abrocitinib had a higher risk of acne (RR=4.34, 95% CI [1.61, 11.71), herpes zoster (RR=1.64, 95% CI [0.42, 6.39]), headache (RR=1.76, 95% CI [1.03, 3]), and nausea (RR=7.81, 95% CI [3.84, 15.87]). Upadacitinib was known to increase acne (RR=6.23, 95% CI [4.08, 9.49]), nasopharyngitis (RR=1.36, 95% CI [1.03, 1.8]) and blood creatine phosphokinase (blood CPK) (RR=2.41, 95% CI [1.47, 3.95]). Baricitinib at 2mg was associated with increased blood CPK (RR=2.25, 95% CI [1.1, 2.97]).
CONCLUSION
Compared to placebo or dupilumab, the administration of JKIs can ameliorate IGA response more effectively, improve the EASI75, and relieve pruritus without severe adverse effect, while accompanied by more acne, nasopharyngitis, headache, and digestive disturbances. The curative effect of 200 mg of abrocitinib is significant and more caution should be given in patients with gastrointestinal dysfunction, herpes zoster, and those who are acne-prone. Baricitinib and upadacitinib should be avoided in populations at high risk for cardiovascular events.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=369369, PROSPERO (CRD42022369369).
Topics: Humans; Dermatitis, Atopic; Janus Kinase Inhibitors; Nasopharyngitis; Pruritus; Acne Vulgaris; Headache; Herpes Zoster; Immunoglobulin A; Purines; Sulfonamides; Pyrazoles; Pyrimidines; Azetidines
PubMed: 38464512
DOI: 10.3389/fimmu.2024.1342810 -
Clinical Microbiology and Infection :... Apr 2024Centor and McIsaac scores are clinical prediction rules for diagnosing group A streptococcus (GAS) infection in patients with pharyngitis. Their recommended thresholds... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Centor and McIsaac scores are clinical prediction rules for diagnosing group A streptococcus (GAS) infection in patients with pharyngitis. Their recommended thresholds vary between guidelines.
OBJECTIVES
To estimate the sensitivity and specificity of the McIsaac and Centor scores to diagnose GAS pharyngitis and evaluate their impact on antibiotic prescribing at each threshold in patients presenting to secondary care.
DATA SOURCES
MEDLINE, Embase, and Web of Science were searched from inception to September 2022.
STUDY ELIGIBILITY CRITERIA
Studies of patients presenting with acute pharyngitis to emergency or outpatient clinics that estimated the accuracy of McIsaac or Centor scores against throat cultures and/or rapid antigen detection tests (RADT) as reference standards.
TESTS
Centor or McIsaac score.
REFERENCE STANDARD
Throat cultures and/or RADT.
ASSESSMENT OF RISK OF BIAS
Quality Assessment of Diagnostic Accuracy Studies.
METHODS OF DATA SYNTHESIS
The sensitivities and specificities of the McIsaac and Centor scores were pooled at each threshold using bivariate random effects meta-analysis.
RESULTS
Fourteen studies were included (eight McIsaac and six Centor scores). Eight studies had unclear and six had a high risk of bias. The McIsaac score had higher estimated sensitivity and lower specificity relative to Centor scores at equivalent thresholds but with wide and overlapping confidence regions. Using either score as a triage to RADT to decide antibiotic treatment would reduce antibiotic prescription to patients with non-GAS pharyngitis relative to RADT test for everyone, but also reduce antibiotic prescription to patients with GAS.
DISCUSSION
Centor and McIsaac scores are equally ineffective at triaging patients who need antibiotics presenting with pharyngitis at hospitals. At high thresholds, too many true positive cases are missed, whereas at low thresholds, too many false positives are treated, leading to the over prescription of antibiotics. The former may be compensated by adequate safety netting by clinicians, ensuring that patients can seek help if symptoms worsen.
Topics: Humans; Secondary Care; Streptococcal Infections; Pharyngitis; Streptococcus pyogenes; Anti-Bacterial Agents; Sensitivity and Specificity
PubMed: 38182052
DOI: 10.1016/j.cmi.2023.12.025 -
The Journal of Laryngology and Otology Sep 2023Peritonsillar abscess is a localised infection in the peritonsillar space. Pus from the abscess can contain anaerobes. Many clinicians prescribe metronidazole in... (Review)
Review
BACKGROUND
Peritonsillar abscess is a localised infection in the peritonsillar space. Pus from the abscess can contain anaerobes. Many clinicians prescribe metronidazole in addition to penicillin, but evidence to support this is limited. This review assessed the evidence of benefit of metronidazole for the treatment of peritonsillar abscess.
METHODS
A systematic review was conducted of the literature and databases including Ovid Medline, Ovid Embase, PubMed and Cochrane library. Search terms included all variations of peritonsillar abscess, penicillin and metronidazole.
RESULTS
Three randomised, control trials were included. All studies assessed the clinical outcomes after treatment for peritonsillar abscess, including recurrence rate, length of hospital stay and symptom improvement. There was no evidence to suggest additional benefit with metronidazole, with studies suggesting increased side effects.
CONCLUSION
Evidence does not support the addition of metronidazole in first-line management of peritonsillar abscess. Further trials to establish optimum dose and duration schedules of oral phenoxymethylpenicillin would benefit clinical practice.
Topics: Humans; Peritonsillar Abscess; Metronidazole; Penicillins; Penicillin V; Drainage; Anti-Bacterial Agents
PubMed: 37194922
DOI: 10.1017/S0022215123000804 -
Reviews in Medical Virology Jan 2024On 23 July 2022, the World Health Organization declared the global mpox outbreak as a public health emergency of international significance. The mpox virus (MPXV) that... (Meta-Analysis)
Meta-Analysis Review
On 23 July 2022, the World Health Organization declared the global mpox outbreak as a public health emergency of international significance. The mpox virus (MPXV) that caused the outbreak was classified as clade IIb, which belongs to the West African clade. However, the relationship between MPXV clades and symptoms, as well as the severity of mpox outcomes, is not fully understood. Thus, we aimed to investigate the global mpox prevalence and the differences in clinical manifestations and outcomes among patients with mpox between pre-outbreak (2003-2021) and the current mpox outbreak. In this systematic review and meta-analysis, PubMed/MEDLINE, Web of Science, Embase, Cumulative Index to Nursing and Allied Health Literature, and Google Scholar were searched using the keyword "monkeypox" and "mpox" up to 13 October 2022. A random effects model was used to obtain the pooled prevalence and 95% confidence intervals. This study included 27 articles, and 5698 patients with mpox with 19 distinctive features from 19 countries across five continents were assessed. Patients with mpox during the 2022 mpox outbreak showed mild clinical manifestations and outcomes compared with those before the 2022 mpox outbreak: mild rash (relative ratio [RR]: 5.09, 95% confidence interval [CI]: 1.52-17.08), fever (0.68, 0.49-0.94), pruritus (0.25, 0.19-0.32), myalgia (0.50, 0.31-0.81), headache (0.56, 0.35-0.88), skin ulcer (0.32, 0.17-0.59), abdominal symptom (0.29, 0.20-0.42), pharyngitis (0.32, 0.18-0.58), nausea or vomiting (0.15, 0.02-0.93), conjunctivitis (0.11, 0.03-0.38), concomitant infection with HIV (1.70, 0.95-3 0.04), and death (0.02, 0.001-0.31). MPXV clade IIb exhibited higher infectivity but may cause mild disease symptoms and low mortality rate. It is important to consider MPXV infection in patients with mpox-related features and/or a history of sexual transmission to prevent the spread of the disease and recognise the current pandemic threat.
Topics: Humans; Mpox (monkeypox); Disease Outbreaks; Public Health; Exanthema; Fever; HIV Seropositivity; HIV-1
PubMed: 38282393
DOI: 10.1002/rmv.2508 -
Frontiers in Endocrinology 2023The safety results of different recommended doses of sodium-glucose cotransporter 2 inhibitors (SGLT-2i) for patients with type 2 diabetes mellitus (T2DM) remain... (Comparative Study)
Comparative Study Meta-Analysis
Comparative safety of different recommended doses of sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes mellitus: a systematic review and network meta-analysis of randomized clinical trials.
OBJECTIVE
The safety results of different recommended doses of sodium-glucose cotransporter 2 inhibitors (SGLT-2i) for patients with type 2 diabetes mellitus (T2DM) remain uncertain. This study aims to comprehensively estimate and rank the relative safety outcomes with different doses of SGLT-2i for T2DM.
METHODS
PubMed, Embase, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Chinese National Knowledge Infrastructure, WanFang database, and SinoMed database were searched from the inception to 31 May 2023. We included double-blind randomized controlled trials (RCTs) comparing SGLT-2i with placebo or another antihyperglycemic as oral monotherapy in the adults with a diagnosis of T2DM.
RESULTS
Twenty-five RCTs with 12,990 patients randomly assigned to 10 pharmacological interventions and placebo were included. Regarding genital infections (GI), all SGLT-2i, except for ertugliflozin and ipragliflozin, were associated with a higher risk of GI compared to placebo. Empagliflozin 10mg/d (88.2%, odds ratio [OR] 7.90, 95% credible interval [CrI] 3.39 to 22.08) may be the riskiest, followed by empagliflozin 25mg/d (83.4%, OR 7.22, 95%CrI 3.11 to 20.04)) and canagliflozin 300mg/d (70.8%, OR 5.33, 95%CrI 2.25 to 13.83) based on probability rankings. Additionally, dapagliflozin 10mg/d ranked highest for urinary tract infections (UTI, OR 2.11, 95%CrI 1.20 to 3.79, 87.2%), renal impairment (80.7%), and nasopharyngitis (81.6%) when compared to placebo and other treatments. No increased risk of harm was observed with different doses of SGLT-2i regarding hypoglycemia, acute kidney injury, diabetic ketoacidosis, or fracture. Further subgroup analysis by gender revealed no significantly increased risk of UTI. Dapagliflozin 10mg/d (91.9%) and canagliflozin 300mg/d (88.8%) ranked first in the female and male subgroups, respectively, according to the probability rankings for GI.
CONCLUSION
Current evidence indicated that SGLT-2i did not significantly increase the risk of harm when comparing different doses, except for dapagliflozin 10mg/d, which showed an increased risk of UTI and may be associated with a higher risk of renal impairment and nasopharyngitis. Additionally, compared with placebo and metformin, the risk of GI was notably elevated for empagliflozin 10mg/d, canagliflozin 300mg/d, and dapagliflozin 10mg/d. However, it is important to note that further well-designed RCTs with larger sample sizes are necessary to verify and optimize the current body of evidence.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023396023.
Topics: Female; Humans; Male; Canagliflozin; Diabetes Mellitus, Type 2; Glucose; Nasopharyngitis; Network Meta-Analysis; Randomized Controlled Trials as Topic; Sodium; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 38027214
DOI: 10.3389/fendo.2023.1256548 -
The Cochrane Database of Systematic... Nov 2023Antibiotics provide only modest benefit in treating sore throat, although their effectiveness increases in people with positive throat swabs for group A beta-haemolytic... (Review)
Review
BACKGROUND
Antibiotics provide only modest benefit in treating sore throat, although their effectiveness increases in people with positive throat swabs for group A beta-haemolytic streptococci (GABHS). It is unclear which antibiotic is the best choice if antibiotics are indicated. This is an update of a review first published in 2010, and updated in 2013, 2016, and 2021.
OBJECTIVES
To assess the comparative efficacy of different antibiotics in: (a) alleviating symptoms (pain, fever); (b) shortening the duration of the illness; (c) preventing clinical relapse (i.e. recurrence of symptoms after initial resolution); and (d) preventing complications (suppurative complications, acute rheumatic fever, post-streptococcal glomerulonephritis). To assess the evidence on the comparative incidence of adverse effects and the risk-benefit of antibiotic treatment for streptococcal pharyngitis.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2023, Issue 2), MEDLINE Ovid, Embase Elsevier, and Web of Science (Clarivate) up to 19 March 2023.
SELECTION CRITERIA
Randomised, double-blind trials comparing different antibiotics, and reporting at least one of the following: clinical cure, clinical relapse, or complications and/or adverse events.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened trials for inclusion and extracted data using standard methodological procedures recommended by Cochrane. We assessed the risk of bias in the included studies according to the methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions, and used the GRADE approach to assess the overall certainty of the evidence for the outcomes. We reported the intention-to-treat analysis, and also performed an analysis of evaluable participants to explore the robustness of the intention-to-treat results.
MAIN RESULTS
We included 19 trials reported in 18 publications (5839 randomised participants): six trials compared penicillin with cephalosporins; six compared penicillin with macrolides; three compared penicillin with carbacephem; one compared penicillin with sulphonamides; one compared clindamycin with ampicillin; and one compared azithromycin with amoxicillin in children. All participants had confirmed acute GABHS tonsillopharyngitis, and ages ranged from one month to 80 years. Nine trials included only, or predominantly, children. Most trials were conducted in an outpatient setting. Reporting of randomisation, allocation concealment, and blinding was poor in all trials. We downgraded the certainty of the evidence mainly due to lack of (or poor reporting of) randomisation or blinding, or both, heterogeneity, and wide confidence intervals. Cephalosporins versus penicillin We are uncertain if there is a difference in symptom resolution (at 2 to 15 days) for cephalosporins versus penicillin (odds ratio (OR) for absence of symptom resolution 0.79, 95% confidence interval (CI) 0.55 to 1.12; 5 trials, 2018 participants; low-certainty evidence). Results of the sensitivity analysis of evaluable participants differed (OR 0.51, 95% CI 0.27 to 0.97; 5 trials, 1660 participants; very low-certainty evidence). Based on an analysis of evaluable participants, we are uncertain if clinical relapse may be lower for cephalosporins compared with penicillin (OR 0.55, 95% CI 0.30 to 0.99; number needed to treat for an additional beneficial outcome (NNTB) 50; 4 trials, 1386 participants; low-certainty evidence). Very low-certainty evidence showed no difference in reported adverse events. Macrolides versus penicillin We are uncertain if there is a difference between macrolides and penicillin for resolution of symptoms (OR 1.11, 95% CI 0.92 to 1.35; 6 trials, 1728 participants; low-certainty evidence). Sensitivity analysis of evaluable participants resulted in an OR of 0.79 (95% CI 0.57 to 1.09; 6 trials, 1159 participants). We are uncertain if clinical relapse may be different (OR 1.21, 95% CI 0.48 to 3.03; 6 trials, 802 participants; low-certainty evidence). Children treated with macrolides seemed to experience more adverse events than those treated with penicillin (OR 2.33, 95% CI 1.06 to 5.15; 1 trial, 489 participants; low-certainty evidence). However, the test for subgroup differences between children and adults was not significant. Azithromycin versus amoxicillin Based on one unpublished trial in children, we are uncertain if resolution of symptoms is better with azithromycin in a single dose versus amoxicillin for 10 days (OR 0.76, 95% CI 0.55 to 1.05; 1 trial, 673 participants; very low-certainty evidence). Sensitivity analysis for per-protocol analysis resulted in an OR of 0.29 (95% CI 0.11 to 0.73; 1 trial, 482 participants; very low-certainty evidence). We are also uncertain if there was a difference in relapse between groups (OR 0.88, 95% CI 0.43 to 1.82; 1 trial, 422 participants; very low-certainty evidence). Adverse events were more common with azithromycin compared to amoxicillin (OR 2.67, 95% CI 1.78 to 3.99; 1 trial, 673 participants; very low-certainty evidence). Carbacephem versus penicillin There is low-certainty evidence that compared with penicillin, carbacephem may provide better symptom resolution post-treatment in adults and children (OR 0.70, 95% CI 0.49 to 0.99; NNTB 14.3; 3 trials, 795 participants). Studies did not report on long-term complications, so it was unclear if any class of antibiotics was better at preventing serious but rare complications.
AUTHORS' CONCLUSIONS
We are uncertain if there are clinically relevant differences in symptom resolution when comparing cephalosporins and macrolides with penicillin in the treatment of GABHS tonsillopharyngitis. Low-certainty evidence in children suggests that carbacephem may be more effective than penicillin for symptom resolution. There is insufficient evidence to draw conclusions regarding the other comparisons in this review. Data on complications were too scarce to draw conclusions. Antibiotics have a limited effect in the treatment of GABHS pharyngitis and the results do not demonstrate that other antibiotics are more effective than penicillin. In the context of antimicrobial stewardship, penicillin can be used if treatment with an antibiotic is indicated. All studies were conducted in high-income countries with a low risk of streptococcal complications, so there is a need for trials in low-income countries and disadvantaged populations, where the risk of complications remains high.
Topics: Adult; Child; Humans; Infant; Amoxicillin; Anti-Bacterial Agents; Azithromycin; Cephalosporins; Chronic Disease; Macrolides; Penicillins; Pharyngitis; Randomized Controlled Trials as Topic; Recurrence; Streptococcus pyogenes; Systematic Reviews as Topic
PubMed: 37965935
DOI: 10.1002/14651858.CD004406.pub6