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Current Allergy and Asthma Reports Dec 2023To analyze and compare the effects of epistaxis treatments for Hereditary Hemorrhagic Telangiectasia (HHT) patients. (Meta-Analysis)
Meta-Analysis Review
PURPOSE OF REVIEW
To analyze and compare the effects of epistaxis treatments for Hereditary Hemorrhagic Telangiectasia (HHT) patients.
RECENT FINDINGS
Of total of 21 randomized controlled trials (RCT), the data from 15 RCTs (697 patients, 7 treatments: timolol, propranolol, bevacizumab, doxycycline, tacrolimus, estriol/estradiol, and tranexamic acid) were pooled for the meta-analyses while the other 6 studies (treatments: electrosurgical plasma coagulation, KTP laser, postoperative packing, tamoxifen, sclerosing agent, and estriol) were reviewed qualitatively. When compared to placebo, propranolol offered the most improved epistaxis severity score, mean difference (MD), -1.68, 95% confidence interval (95%CI) [-2.80, -0.56] followed by timolol, MD -0.40, 95%CI [-0.79, -0.02]. Tranexamic acid significantly reduced the epistaxis frequency, MD -1.93, 95%CI [-3.58, -0.28]. Other treatments had indifferent effects to placebo. Qualitative analysis highlighted the benefits of tamoxifen and estriol. The adverse events of tranexamic acid, tacrolimus, propranolol, and estradiol were significantly reported. Propranolol, timolol, tranexamic acid, tamoxifen, and estriol were effective treatments which offered benefits to HHT patients in epistaxis management. Adverse events of tranexamic acid, tacrolimus, propranolol, and estradiol should be concerned.
Topics: Humans; Epistaxis; Tranexamic Acid; Timolol; Telangiectasia, Hereditary Hemorrhagic; Propranolol; Network Meta-Analysis; Tacrolimus; Estriol; Estradiol; Tamoxifen
PubMed: 37995018
DOI: 10.1007/s11882-023-01116-8 -
Clinical Infectious Diseases : An... Mar 2024Bartonella quintana is a louse-borne bacterium that remains a neglected cause of endocarditis in low-resource settings. Our understanding of risk factors, clinical...
BACKGROUND
Bartonella quintana is a louse-borne bacterium that remains a neglected cause of endocarditis in low-resource settings. Our understanding of risk factors, clinical manifestations, and treatment of B. quintana endocarditis are biased by older studies from high-income countries.
METHODS
We searched Pubmed Central, Medline, Scopus, Embase, EBSCO (CABI) Global Health, Web of Science and international trial registers for articles published before March 2023 with terms related to Bartonella quintana endocarditis. We included articles containing case-level information on B. quintana endocarditis and extracted data related to patient demographics, clinical features, diagnostic testing, treatment, and outcome.
RESULTS
A total of 975 records were identified, of which 569 duplicates were removed prior to screening. In total, 84 articles were eligible for inclusion, describing a total of 167 cases. Infections were acquired in 40 different countries; 62 cases (37.1%) were acquired in low- and middle-income countries (LMICs). Disproportionately more female and pediatric patients were from LMICs. More patients presented with heart failure (n = 70/167 [41.9%]) than fever (n = 65/167 [38.9%]). Mean time from symptom onset to presentation was 5.1 months. Also, 25.7% of cases (n = 43/167) were associated with embolization, most commonly to the spleen and brain; 65.5% of antimicrobial regimens included doxycycline. The vast majority of cases underwent valve replacement surgery (n = 154/167, [98.0%]). Overall case fatality rate was 9.6% (n = 16/167).
CONCLUSIONS
B. quintana endocarditis has a global distribution, and long delays between symptom onset and presentation frequently occur. Improved clinician education and diagnostic capacity are needed to screen at-risk populations and identify infection before endocarditis develops.
Topics: Humans; Female; Child; Bartonella quintana; Trench Fever; Endocarditis; Doxycycline; Endocarditis, Bacterial
PubMed: 37976173
DOI: 10.1093/cid/ciad706 -
Journal of Clinical Pharmacology Feb 2024Macrolides and tetracyclines are antibiotics that have a range of anti-inflammatory properties beyond their microbial capabilities. Although these antibiotics have been... (Meta-Analysis)
Meta-Analysis Review
Macrolides and tetracyclines are antibiotics that have a range of anti-inflammatory properties beyond their microbial capabilities. Although these antibiotics have been in widespread use, the long-term safety profiles are limited. We performed a systematic review and meta-analysis of randomized clinical trials that compared macrolides or tetracyclines with placeboes to provide long-term safety information. We searched Medline and EMBASE from inception to October 2022 and identified studies that reported study drug-related death, serious adverse events (SAEs), or withdrawal rates, and common adverse effects of each drug. Relative risk (RR) and number needed to harm were calculated. Of the 52 randomized clinical trials included, there are 3151 participants on doxycycline, 2519 participants on minocycline, 3049 participants on azithromycin, 763 participants on clarithromycin, 262 participants on erythromycin, and 100 participants on roxithromycin. There was no death related to any study drugs and rates of SAE were not significantly different from placebo in any drug. Overall withdrawal rates were slightly higher than placebo in doxycycline (RR, 1.30; 95% CI, 1.12-1.52) and minocycline (RR, 1.29; 95% CI, 1.15-1.46). Withdrawal rates due to adverse events were higher in doxycycline (RR, 2.82; 95% CI, 1.88-4.22), minocycline (RR, 1.48; 95% CI, 1.09-1.98), and azithromycin (RR, 1.53; 95% CI, 1.13-2.08). Gastrointestinal disturbances are the most common tolerable adverse effects for every drug. Photosensitivity and rash are the second most common adverse effects for doxycycline and minocycline. We found no evidence that long-term use up to 2 years of macrolides or tetracyclines was associated with increased risk of SAEs.
Topics: Humans; Macrolides; Azithromycin; Doxycycline; Minocycline; Anti-Bacterial Agents
PubMed: 37751595
DOI: 10.1002/jcph.2358 -
Sexually Transmitted Diseases Nov 2023Sexually transmitted infections (STIs) such as syphilis, gonorrhea, and chlamydia have significantly increased over the past decade in the United States. Doxycycline as...
BACKGROUND
Sexually transmitted infections (STIs) such as syphilis, gonorrhea, and chlamydia have significantly increased over the past decade in the United States. Doxycycline as chemoprophylaxis (i.e., postexposure prophylaxis) offers promise for addressing bacterial STIs. The goal of the current study was to evaluate the safety of longer-term doxycycline use (defined as 8 or more weeks) in the context of potential use as STI chemoprophylaxis through a systematic literature review and meta-analysis.
METHODS
This review used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to search MEDLINE/PubMed for clinical studies published from August 2003 to January 2023 that reported on adverse events with doxycycline use with a focus on side effects and metabolic effects of long-term use.
RESULTS
A total of 67 studies were included in the systematic review. Overall, studies on longer-term doxycycline use reported 0% to greater than 50% adverse events ranging from mild to severe. Most common adverse events included gastrointestinal symptoms (i.e., nausea, vomiting, and abdominal pain), dermatologic (i.e., rash), and neurological (i.e., headache and dizziness) symptoms. Discontinuation of doxycycline due to adverse events was relatively uncommon in most studies. A meta-analysis of placebo controlled clinical trials (N = 18) revealed that gastrointestinal and dermatological adverse events were more likely to occur in the doxycycline group.
CONCLUSIONS
Longer-term (8+ weeks) doxycycline use is generally safe and may be associated with minor side effects. Further research is needed on the potential metabolic impact of longer-term doxycycline use.
PubMed: 37732844
DOI: 10.1097/OLQ.0000000000001865 -
Le Infezioni in Medicina 2023Leptospirosis is a zoonotic bacterial infection with significant mortality and morbidity, especially in resource-limited settings. This systematic review aimed to study... (Review)
Review
INTRODUCTION
Leptospirosis is a zoonotic bacterial infection with significant mortality and morbidity, especially in resource-limited settings. This systematic review aimed to study the clinical profile and outcome of patients with leptospirosis in India.
METHODOLOGY
All articles up to 02.08.2022 were searched using the two databases, PubMed and Scopus. A total of 542 articles were found using the search terms related to 'leptospirosis' and 'India'. After two rounds of screening, 55 articles were included. The data were collected on epidemiology, clinical features, laboratory features and treatment of patients with leptospirosis.
RESULTS
Most cases of leptospirosis were reported from the coastal belt. A large percentage of patients were identified as farmers, and exposure to rainfall was identified as an important risk factor. Fever was present in 97%, and conjunctival suffusion was present in 35% of cases. Haemoptysis, gastrointestinal bleeding, and haematuria were present in 5%, 5% and 12% of patients, respectively. Liver and kidney were involved in 34% and 35% of the patients, respectively. The average haemoglobin, leucocyte count and platelet count across various studies ranged from 9.6-12.5 grams/dl, 8.8-11.3 thousand/μl and 20-130 thousand/μl, respectively. Treatment details were sparsely available in some studies, with penicillin, ceftriaxone, and doxycycline used commonly. The pooled mortality across various studies was calculated as 11% [95% CI-8-15%, I=93%, P<0.001].
CONCLUSIONS
Leptospirosis is associated with significant mortality in Indian settings. There is a need for studies focussing on treatment modalities.
PubMed: 37701390
DOI: 10.53854/liim-3103-4 -
Annals of Clinical Microbiology and... Sep 2023Urogenital Mycoplasma infections are considered an important public health problem, owing to the presence of antibiotic resistance or decreased susceptibility, the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Urogenital Mycoplasma infections are considered an important public health problem, owing to the presence of antibiotic resistance or decreased susceptibility, the treatment options are limited.
OBJECTIVE
Therefore, this meta-analysis aimed to estimate resistance rates of genital Mycoplasmas to tetracyclines (tetracycline, doxycycline, and minocycline).
METHODS
We searched the relevant published studies in PubMed, Scopus, and Embase until 3, March 2022. All statistical analyses were carried out using the statistical package R.
RESULTS
The 26 studies included in the analysis were performed in 15 countries. In the metadata, the proportions of tetracycline, doxycycline, and minocycline resistance in Mycoplasma and Ureaplasma urogenital isolates were reported 14.2% (95% CI 8.2-23.2%), 5% (95% CI 3-8.1%), and 11.9% (95% CI 6.3-21.5%), respectively. According to the meta-regression, the tetracycline and minocycline resistance rate decreased over time. Although, the doxycycline resistance rate increased over time. There was a statistically significant difference in the tetracyclines resistance rates between different continents/countries (P < 0.05).
CONCLUSION
The prevalence rate and antibiotic susceptibility profiles vary geographically. Therefore, rigorous or improved antimicrobial stewardship, contact tracing, and enhanced intensive surveillance systems are necessitated for preventing the emergence and further spreading of tetracyclines resistance in genital Mycoplasmas.
Topics: Humans; Mycoplasma; Tetracycline; Doxycycline; Minocycline; Anti-Bacterial Agents
PubMed: 37697380
DOI: 10.1186/s12941-023-00628-5 -
Microbial Pathogenesis Oct 2023Brucellosis is a zoonotic disease that can be transmitted from animals to humans. Brucellosis is caused by bacteria of the genus Brucella, which are typically... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Brucellosis is a zoonotic disease that can be transmitted from animals to humans. Brucellosis is caused by bacteria of the genus Brucella, which are typically transmitted through contact with infected animals, unpasteurized dairy products, or airborne pathogens. Tetracyclines (tetracycline and doxycycline) are antibiotics commonly used to treat brucellosis; however, antibiotic resistance has become a major concern. This study assessed the worldwide prevalence of tetracycline-resistant Brucella isolates.
METHODS
A systematic search was conducted in Scopus, PubMed, Web of Science, and EMBASE using relevant keywords and Medical Subject Headings (MeSH) terms until August 13, 2022, to identify relevant studies for meta-analysis. A random effects model was used to estimate the proportion of resistance. Meta-regression analysis, subgroup analysis, and examination of outliers and influential studies were also performed.
RESULTS
The prevalence rates of resistance to tetracycline and doxycycline were estimated to be 0.017 (95% confidence interval [CI], 0.009-0.035) and 0.017 (95%CI, 0.011-0.026), respectively, based on 51 studies conducted from 1983 to 2020. Both drugs showed increasing resistance over time (tetracycline: r = 0.077, P = 0.012; doxycycline: r = 0.059, P = 0.026).
CONCLUSION
The prevalence of tetracycline and doxycycline resistance in Brucella was low (1.7%) but increased over time. This increase in tetracycline and doxycycline resistance highlights the need for further research to understand resistance mechanisms and develop more effective treatments.
Topics: Animals; Humans; Brucella melitensis; Brucella abortus; Tetracycline; Doxycycline; Prevalence; Brucellosis; Anti-Bacterial Agents; Tetracyclines
PubMed: 37673354
DOI: 10.1016/j.micpath.2023.106321 -
Annales de Dermatologie Et de... Sep 2023Ocular rosacea is an underdiagnosed form of rosacea that may occur without typical cutaneous signs of rosacea. Manifestations include blepharitis, lid margin...
BACKGROUND
Ocular rosacea is an underdiagnosed form of rosacea that may occur without typical cutaneous signs of rosacea. Manifestations include blepharitis, lid margin telangiectasias, and scleritis. A systematic comparison of treatment options for ocular rosacea in children is lacking.
METHODS
A systematic review was conducted according to the PRISMA guidelines on treatment for pediatric ocular rosacea.
RESULTS
Eleven articles were included, representing 135 patients with a mean age of 5 years, of whom 69% (n = 75/108) were female. 55% (n = 55/99) exhibited ocular symptoms prior to cutaneous symptoms. Most patients (83%, n = 34/41) experienced a delay in diagnosis (mean 27 months, range 2-120 months). Doxycycline was the most frequently reported treatment (25%, n = 33/135). A complete response was achieved in 33% of patients treated with doxycycline (n = 10/30), while 53% (n = 16/30) achieved a partial response. Erythromycin was used in 20% of cases (n = 26/135), with a complete response in 58% (n = 15/26) and partial response in 42% (n = 11/26). Metronidazole was used in 14% of patients (n = 19/135), with a complete response being reported in 79% (n = 15/19) and partial response in 21% (n = 4/19).
CONCLUSION
Systemic antibiotics, led by doxycycline, were the most commonly reported treatment modalities for pediatric ocular rosacea. Increased awareness of ocular rosacea in this population is crucial for earlier diagnosis.
Topics: Child; Humans; Female; Child, Preschool; Male; Doxycycline; Rosacea; Anti-Bacterial Agents; Metronidazole; Skin Diseases
PubMed: 37596128
DOI: 10.1016/j.annder.2023.05.004 -
The Cochrane Database of Systematic... Aug 2023Bullous pemphigoid (BP) is the most common autoimmune blistering disease. Oral steroids are the standard treatment. We have updated this review, which was first... (Review)
Review
BACKGROUND
Bullous pemphigoid (BP) is the most common autoimmune blistering disease. Oral steroids are the standard treatment. We have updated this review, which was first published in 2002, because several new treatments have since been tried.
OBJECTIVES
To assess the effects of treatments for bullous pemphigoid.
SEARCH METHODS
We updated searches of the following databases to November 2021: Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase. We searched five trial databases to January 2022, and checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs).
SELECTION CRITERIA
RCTs of treatments for immunofluorescence-confirmed bullous pemphigoid.
DATA COLLECTION AND ANALYSIS
At least two review authors, working independently, evaluated the studies against the review's inclusion criteria and extracted data from included studies. Using GRADE methodology, we assessed the certainty of the evidence for each outcome in each comparison. Our primary outcomes were healing of skin lesions and mortality.
MAIN RESULTS
We identified 14 RCTs (1442 participants). The main treatment modalities assessed were oral steroids, topical steroids, and the oral anti-inflammatory antibiotic doxycycline. Most studies reported mortality but adverse events and quality of life were not well reported. We decided to look at the primary outcomes 'disease control' and 'mortality'. Almost all studies investigated different comparisons; two studies were placebo-controlled. The results are therefore based on a single study for each comparison except azathioprine. Most studies involved only small numbers of participants. We assessed the risk of bias for all key outcomes as having 'some concerns' or high risk, due to missing data, inappropriate analysis, or insufficient information. Clobetasol propionate cream versus oral prednisone Compared to oral prednisone, clobetasol propionate cream applied over the whole body probably increases skin healing at day 21 (risk ratio (RR 1.08, 95% confidence interval (CI) 1.03 to 1.13; 1 study, 341 participants; moderate-certainty evidence). Skin healing at 21 days was seen in 99.8% of participants assigned to clobetasol and 92.4% of participants assigned to prednisone. Clobetasol propionate cream applied over the whole body compared to oral prednisone may reduce mortality at one year (RR 0.73, 95% CI 0.53 to 1.01; 1 study, 341 participants; low-certainty evidence). Death occurred in 26.5% (45/170) of participants assigned to clobetasol and 36.3% (62/171) of participants assigned to oral prednisone. This study did not measure quality of life. Clobetasol propionate cream may reduce risk of severe complications by day 21 compared with oral prednisone (RR 0.65, 95% CI 0.50 to 0.86; 1 study, 341 participants; low-certainty evidence). Mild clobetasol propionate cream regimen (10 to 30 g/day) versus standard clobetasol propionate cream regimen (40 g/day) A mild regimen of topical clobetasol propionate applied over the whole body compared to the standard regimen probably does not change skin healing at day 21 (RR 1.00, 95% CI 0.97 to 1.03; 1 study, 312 participants; moderate-certainty evidence). Both groups showed complete healing of lesions at day 21 in 98% participants. A mild regimen of topical clobetasol propionate applied over the whole body compared to the standard regimen may not change mortality at one year (RR 1.00, 95% CI 0.75 to 1.32; 1 study, 312 participants; low-certainty evidence), which occurred in 118/312 (37.9%) participants. This study did not measure quality of life. A mild regimen of topical clobetasol propionate applied over the whole body compared to the standard regimen may not change adverse events at one year (RR 0.94, 95% CI 0.78 to 1.14; 1 study, 309 participants; low-certainty evidence). Doxycycline versus prednisolone Compared to prednisolone (0.5 mg/kg/day), doxycycline (200 mg/day) induces less skin healing at six weeks (RR 0.81, 95% CI 0.72 to 0.92; 1 study, 213 participants; high-certainty evidence). Complete skin healing was reported in 73.8% of participants assigned to doxycycline and 91.1% assigned to prednisolone. Doxycycline compared to prednisolone probably decreases mortality at one year (RR 0.25, 95% CI 0.07 to 0.89; number needed to treat for an additional beneficial outcome (NNTB) = 14; 1 study, 234 participants; moderate-certainty evidence). Mortality occurred in 2.4% (3/132) of participants with doxycycline and 9.7% (11/121) with prednisolone. Compared to prednisolone, doxycycline improved quality of life at one year (mean difference 1.8 points lower, which is more favourable on the Dermatology Life Quality Index, 95% CI 1.02 to 2.58 lower; 1 study, 234 participants; high-certainty evidence). Doxycycline compared to prednisolone probably reduces severe or life-threatening treatment-related adverse events at one year (RR 0.59, 95% CI 0.35 to 0.99; 1 study, 234 participants; moderate-certainty evidence). Prednisone plus azathioprine versus prednisone It is unclear whether azathioprine plus prednisone compared to prednisone alone affects skin healing or mortality because there was only very low-certainty evidence from two trials (98 participants). These studies did not measure quality of life. Adverse events were reported in a total of 20/48 (42%) participants assigned to azathioprine plus prednisone and 15/44 (34%) participants assigned to prednisone. Nicotinamide plus tetracycline versus prednisone It is unclear whether nicotinamide plus tetracycline compared to prednisone affects skin healing or mortality because there was only very low-certainty evidence from one trial (18 participants). This study did not measure quality of life. Fewer adverse events were reported in the nicotinamide group. Methylprednisolone plus azathioprine versus methylprednisolone plus dapsone It is unclear whether azathioprine plus methylprednisolone compared to dapsone plus methylprednisolone affects skin healing or mortality because there was only very low-certainty evidence from one trial (54 participants). This study did not measure quality of life. A total of 18 adverse events were reported in the azathioprine group and 13 in the dapsone group.
AUTHORS' CONCLUSIONS
Clobetasol propionate cream applied over the whole body is probably similarly effective as, and may cause less mortality than, oral prednisone for treating bullous pemphigoid. Lower-dose clobetasol propionate cream applied over the whole body is probably similarly effective as standard-dose clobetasol propionate cream and has similar mortality. Doxycycline is less effective but causes less mortality than prednisolone for treating bullous pemphigoid. Other treatments need further investigation.
Topics: Humans; Azathioprine; Prednisone; Clobetasol; Pemphigoid, Bullous; Doxycycline; Methylprednisolone; Dapsone; Niacinamide
PubMed: 37572360
DOI: 10.1002/14651858.CD002292.pub4 -
European Journal of Neurology Dec 2023Evidence-based recommendations for treatment of Lyme neuroborreliosis (LNB) should rely on the available literature. As new data emerges, close review and evaluation of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Evidence-based recommendations for treatment of Lyme neuroborreliosis (LNB) should rely on the available literature. As new data emerges, close review and evaluation of the recent literature is needed to build evidence-based recommendations to inform clinical practice and management of LNB. We performed an update of a previous systematic review on treatment of LNB.
METHODS
A systematic literature search of Medline and CENTRAL was performed for published studies from 2015 to 2023 to update a previous systematic review. Randomized controlled trials (RCTs) and non-randomized studies (NRS) were evaluated. Risk of bias was assessed using the Cochrane risk of bias tools for RCTs; NRS were assessed using the ROBINS-I-tool. Quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Data were integrated into an existing meta-analysis of the available literature.
RESULTS
After screening 1530 records, two RCTs and five NRS with new and relevant data were additionally identified. Meta-analysis showed no statistically significant difference between doxycycline and beta-lactam antibiotics regarding residual neurological symptoms after 12 months. Meta-analysis showed no benefit of extended antibiotic treatment of LNB. Three NRS show no benefit for additional steroid use in LNB with facial palsy.
DISCUSSION
Additional incorporated recent research corroborates existing guideline recommendations for treatment of LNB. New RCTs add to the certainty of previous analysis showing similar efficacy for doxycycline and beta-lactam antibiotics in LNB. Available evidence shows no benefit for extended antibiotic treatment in LNB. NRS do not suggest a role for steroids in facial palsy due to LNB.
Topics: Humans; Lyme Neuroborreliosis; Doxycycline; Facial Paralysis; Anti-Bacterial Agents; Monobactams
PubMed: 37565386
DOI: 10.1111/ene.16034