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Arquivos de Neuro-psiquiatria Aug 2022The Creutzfeldt-Jakob disease (CJD) is a spongiform encephalopathy that manifests as a rapidly progressive dementia syndrome. Currently, CJD has no cure, and many... (Review)
Review
BACKGROUND
The Creutzfeldt-Jakob disease (CJD) is a spongiform encephalopathy that manifests as a rapidly progressive dementia syndrome. Currently, CJD has no cure, and many patients die within the first year, but some drugs are being studied as options for managing this condition.
OBJECTIVE
To evaluate the effectiveness of pharmacological treatments offered to patients with CJD as a means to increase survival and reduce cognitive deterioration.
METHODS
A systematic review of the literature was performed using 4 independent reviewers and 1 extra reviewer to resolve possible divergences in the search and analysis of papers indexed in MedLINE (PubMed), SciELO and Lilacs databases. The Medical Subject Heading (MeSH) terms used were: , , , , , , , and , with the Boolean operators and . This search included controlled clinical trials, uncontrolled clinical trials, and case series published from the year 2000 onwards, in the English language.
RESULTS
A total of 85 papers were found using the descriptors used. At the end of the selection analyses, 9 articles remained, which were analyzed fully and individually.
CONCLUSIONS
None of the drugs evaluated proved significantly effective in increasing survival in patients with CJD. Flupirtine appears to have a beneficial effect in reducing cognitive deterioration in patients with CJD. However, additional studies are needed to establish better evidence and therapeutic options for the management of patients with CJD.
Topics: Aminopyridines; Creutzfeldt-Jakob Syndrome; Doxycycline; Humans; Pentosan Sulfuric Polyester; Prion Diseases; Quinacrine
PubMed: 36252593
DOI: 10.1055/s-0042-1755341 -
Clinical Infectious Diseases : An... Oct 2022Anthrax is endemic to many countries, including the United States. The causative agent, Bacillus anthracis, poses a global bioterrorism threat. Without effective... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Anthrax is endemic to many countries, including the United States. The causative agent, Bacillus anthracis, poses a global bioterrorism threat. Without effective antimicrobial postexposure prophylaxis (PEPAbx) and treatment, the mortality of systemic anthrax is high. To inform clinical guidelines for PEPAbx and treatment of B. anthracis infections in humans, we systematically evaluated animal anthrax treatment model studies.
METHODS
We searched for survival outcome data in 9 scientific search engines for articles describing antimicrobial PEPAbx or treatment of anthrax in animals in any language through February 2019. We performed meta-analyses of efficacy of antimicrobial PEPAbx and treatment for each drug or drug combination using random-effects models. Pharmacokinetic/pharmacodynamic relationships were developed for 5 antimicrobials with available pharmacokinetic data. Monte Carlo simulations were used to predict unbound drug exposures in humans.
RESULTS
We synthesized data from 34 peer-reviewed studies with 3262 animals. For PEPAbx and treatment of infection by susceptible B. anthracis, effective monotherapy can be accomplished with fluoroquinolones, tetracyclines, β-lactams (including penicillin, amoxicillin-clavulanate, and imipenem-cilastatin), and lipopeptides or glycopeptides. For naturally occurring strains, unbound drug exposures in humans were predicted to adequately cover the minimal inhibitory concentrations (MICs; those required to inhibit the growth of 50% or 90% of organisms [MIC50 or MIC90]) for ciprofloxacin, levofloxacin, and doxycycline for both the PEPAbx and treatment targets. Dalbavancin covered its MIC50 for PEPAbx.
CONCLUSIONS
These animal studies show many reviewed antimicrobials are good choices for PEPAbx or treatment of susceptible B. anthracis strains, and some are also promising options for combating resistant strains. Monte Carlo simulations suggest that oral ciprofloxacin, levofloxacin, and doxycycline are particularly robust choices for PEPAbx or treatment.
Topics: Amoxicillin-Potassium Clavulanate Combination; Animals; Anthrax; Anti-Bacterial Agents; Anti-Infective Agents; Bacillus anthracis; Cilastatin, Imipenem Drug Combination; Ciprofloxacin; Doxycycline; Glycopeptides; Humans; Levofloxacin; Lipopeptides; Models, Animal; Tetracyclines; United States; beta-Lactams
PubMed: 36251546
DOI: 10.1093/cid/ciac591 -
Frontiers in Medicine 2022We assessed nonconventional interventions that did not traditionally focus on increasing condom use and/or testing among men who have sex with men (MSM) and the evidence...
OBJECTIVES
We assessed nonconventional interventions that did not traditionally focus on increasing condom use and/or testing among men who have sex with men (MSM) and the evidence for these interventions.
METHODS
Guided by the Participants, Concept and Context (PCC) framework, we searched five online databases from inception to 9 August 2021 for original research on interventions that do not focus on increasing condom use and/or testing to prevent gonorrhea and/or syphilis in MSM. Two researchers screened titles and abstracts to assess eligibility, reviewed articles' full text and resolved discrepancies through discussion. We charted relevant study information, and the included studies were critically appraised.
RESULTS
Of 373 articles retrieved, 13 studies were included. These studies were conducted in Australia ( = 3), Belgium ( = 2), China ( = 3), the Netherlands ( = 1) and the US ( = 4). Two randomized controlled trials (RCTs) of doxycycline as pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) reduced any STI incidence (gonorrhea, syphilis, or chlamydia), but only doxycycline PEP significantly reduced syphilis incidence. Six studies of interventions that facilitated self-collection, self-examination, and self-testing, found varied evidence for gonorrhea and/or syphilis prevention. Four RCTs and one single-arm trial examined the efficacy of mouthwash, but the evidence remains inconclusive on whether mouthwash use can prevent transmission between men.
CONCLUSION
We found evidence for doxycycline PEP in reducing syphilis incidence, evidence on the use of mouthwash to prevent gonorrhea transmission between men remains inconclusive. More evidence is needed for interventions that do not focus on increasing condom use and/or testing to prevent gonorrhea and/or syphilis.
PubMed: 36203757
DOI: 10.3389/fmed.2022.952476 -
The Canadian Journal of Infectious... 2022Since the beginning of the novel coronavirus (SARS-CoV-2) disease outbreak, there has been an increasing interest in discovering potential therapeutic agents for this... (Review)
Review
BACKGROUND
Since the beginning of the novel coronavirus (SARS-CoV-2) disease outbreak, there has been an increasing interest in discovering potential therapeutic agents for this disease. In this regard, we conducted a systematic review through an overview of drug development (in silico, in vitro, and in vivo) for treating COVID-19.
METHODS
A systematic search was carried out in major databases including PubMed, Web of Science, Scopus, EMBASE, and Google Scholar from December 2019 to March 2021. A combination of the following terms was used: coronavirus, COVID-19, SARS-CoV-2, drug design, drug development, In silico, In vitro, and In vivo. A narrative synthesis was performed as a qualitative method for the data synthesis of each outcome measure.
RESULTS
A total of 2168 articles were identified through searching databases. Finally, 315 studies (266 in silico, 34 in vitro, and 15 in vivo) were included. In studies with in silico approach, 98 article study repurposed drug and 91 studies evaluated herbal medicine on COVID-19. Among 260 drugs repurposed by the computational method, the best results were observed with saquinavir ( = 9), ritonavir ( = 8), and lopinavir ( = 6). Main protease ( = 154) following spike glycoprotein ( = 62) and other nonstructural protein of virus ( = 45) was among the most studied targets. Doxycycline, chlorpromazine, azithromycin, heparin, bepridil, and glycyrrhizic acid showed both in silico and in vitro inhibitory effects against SARS-CoV-2.
CONCLUSION
The preclinical studies of novel drug design for COVID-19 focused on main protease and spike glycoprotein as targets for antiviral development. From evaluated structures, saquinavir, ritonavir, eucalyptus, Tinospora cordifolia, aloe, green tea, curcumin, pyrazole, and triazole derivatives in in silico studies and doxycycline, chlorpromazine, and heparin from in vitro and human monoclonal antibodies from in vivo studies showed promised results regarding efficacy. It seems that due to the nature of COVID-19 disease, finding some drugs with multitarget antiviral actions and anti-inflammatory potential is valuable and some herbal medicines have this potential.
PubMed: 36199815
DOI: 10.1155/2022/2044282 -
Australian Endodontic Journal : the... Aug 2023The aim of this study was to assess the prevalence and proportions of antimicrobial-resistant species in patients with endodontic infections. A systematic scoping review... (Review)
Review
The aim of this study was to assess the prevalence and proportions of antimicrobial-resistant species in patients with endodontic infections. A systematic scoping review of scientific evidence was accomplished involving different databases. Nine investigations were selected including 651 patients. Enterococcus faecalis was resistant to tetracycline (30%-70%), clindamycin (100%), erythromycin (10%-20%), ampicillin (9%) and azithromycin (60%). On the contrary, Prevotella spp., Fusobacterium spp., Peptostreptococcus spp. and Streptococcus spp. were resistant to penicillin, tetracycline, doxycycline, ciprofloxacin, amoxicillin, erythromycin, metronidazole and clindamycin in different proportions. Fusobacterium nucleatum showed high resistance to amoxicillin, amoxicillin plus clavulanate and erythromycin. Prevotella oralis presented a predisposition to augment its resistance to clindamycin over time. Tanerella forsythia exhibited resistance to ciprofloxacin and rifampicin. Lactococcus lactis presented robust resistance to cephalosporins, metronidazole, penicillin, amoxicillin and amoxicillin-clavulanic acid. It was observed high levels of resistance to antimicrobials that have been utilised in the local and systemic treatment of oral cavity infections.
Topics: Humans; Drug Resistance, Microbial; Periapical Periodontitis; Anti-Bacterial Agents; Observational Studies as Topic; Bacteria
PubMed: 36054305
DOI: 10.1111/aej.12680 -
Frontiers in Cardiovascular Medicine 2022The aim of this study was to determine the association between fluoroquinolones (FQs) use, the risk of aortic aneurysm or dissection (AAD), and the prognosis of...
OBJECTIVE
The aim of this study was to determine the association between fluoroquinolones (FQs) use, the risk of aortic aneurysm or dissection (AAD), and the prognosis of patients with pre-existing AAD.
MATERIALS AND METHODS
We searched PubMed, EMBASE, CENTRAL, Scopus, and Web of Science on 31 March 2022. Observational studies that evaluated the association of FQs with AAD risk in the general population or FQs with the prognosis of patients with preexisting AAD and presented adjusted effect estimates were included. Two reviewers assessed study eligibility, extracted data, and assessed the risk of bias and certainty of evidence using GRADE.
RESULTS
Of the 13 included studies, 11 focused on the association of FQs with AAD incidence, and only one study investigated the association of FQs with the patient with AAD prognosis. FQ use was associated with an increased risk of AAD within 30 days (RR: 1.42; 95% CI: 1.11-1.81; very low certainty) and 60 days (RR: 1.44; 95% CI: 1.26-1.64; low certainty). Specifically, the association was significant when compared with amoxicillin, azithromycin, doxycycline, or no antibiotic use. Furthermore, patients with preexisting AAD exposure to FQ had an increased risk of all-cause mortality (RR: 1.61; 95% CI: 1.50-1.73; moderate certainty) and aortic-specific mortality (RR: 1.80; 95% CI: 1.50-2.15; moderate certainty), compared to the non-exposed FQ group within a 60-day risk period.
CONCLUSION
FQs were associated with an increased incidence of AAD in the general population and a higher risk of adverse outcomes in patients with preexisting AAD. Nevertheless, the results may be affected by unmeasured confounding factors. This should be considered by physicians contemplating using FQs in patients with aortic dilation and those at high risk of AAD.
SYSTEMATIC REVIEW REGISTRATION
[https://www.crd.york.ac.uk/prospero/], identifier [CRD42021230171].
PubMed: 36017083
DOI: 10.3389/fcvm.2022.949538 -
Management of juvenile and aneurysmal bone cysts: a systematic literature review with meta-analysis.European Journal of Trauma and... Feb 2023Numerous approaches to the management of juvenile and aneurysmal bone cysts (ABC) are described in the specialist literature together with discussion of the associated... (Meta-Analysis)
Meta-Analysis
PURPOSE
Numerous approaches to the management of juvenile and aneurysmal bone cysts (ABC) are described in the specialist literature together with discussion of the associated healing and recurrence rates. Since there is currently no evidence-based treatment standard for these conditions, the aim of this systematic literature review with meta-analysis was to examine the different management approaches, evaluate the corresponding clinical outcomes and, as appropriate, to formulate a valid treatment recommendation.
METHODS
A systematic search on OVID Medline based on a pre-existing search strategy returned 1333 publications. Having defined inclusion and exclusion criteria and analysis of the relevant full texts, 167 publications were included in the descriptive analysis and 163 in the meta-analysis. For this purpose, different subgroups were created, based on the type of cyst and the therapeutic procedure. Those subgroups were then analysed in relation to their healing rates, the number of recurrences and complication rates.
RESULTS
For aneurysmal bone cysts, both surgical removal and Doxycycline injection lead to excellent outcomes (98% healing) and low recurrence rates (6% and 11% resp.). Curettage (91% healing), including its combination with autologous cancellous bone graft (96% healing), showed very good healing rates but higher recurrence rates (22% and 15%, resp.), which were however improved by preoperative selective arterial embolization. A critical view must be taken of radiotherapy (90% healing) and the injection of alcohol (92% healing) because of their high complication rates (0.43/cyst and 0.42/cyst, resp.). In the management of juvenile bone cysts, surgical interventions like curettage and cancellous bone graft (87% healing) are far superior to non-surgical approaches (51% healing), furthermore, the application of autologous cancellous bone graft reduced the recurrence rate (3% recurrence) compared to curettage alone (20% recurrence). In subgroup analysis, treatment by ESIN was found to produce excellent outcomes (100% healing), though the patient collectives were small.
CONCLUSION
Surgical procedures to treat aneurysmal bone cysts appear to be the method of choice whereby Doxycycline injection may be an alternative. A surgical approach should be preferred in the treatment of juvenile bone cysts.
Topics: Humans; Bone Cysts, Aneurysmal; Doxycycline; Bone Cysts; Curettage; Bone Transplantation; Treatment Outcome
PubMed: 35989377
DOI: 10.1007/s00068-022-02077-9 -
The Journal of Laryngology and Otology May 2023The objective of this systematic review and meta-analysis was to evaluate the role of doxycycline in the management of chronic rhinosinusitis. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The objective of this systematic review and meta-analysis was to evaluate the role of doxycycline in the management of chronic rhinosinusitis.
METHOD
This was a systematic review using Ovid Medline, Cinahl, Scopus and Cochrane and was limited to meta-analyses, systematic reviews and randomised, clinical trials. A combination of the following search terms was used: 'sinusitis', 'nasal polyps', 'doxycycline' and 'tetracycline'. Raw means and standard deviations were extracted from the included studies. The meta-analysis was performed using mean differences of pre- versus post-doxycycline treatment.
RESULTS
A total of 279 studies were screened, of which 5 studies met the criteria (all randomised, controlled trials published between 2010 and 2021). The interventions, endpoints and measured outcomes varied across all studies. Meta-analysis performed on pre- versus post-doxycycline treatment for Sino-Nasal Outcome Test-22, nasal polyp scores and symptom scores did not yield statistically significant results.
CONCLUSION
This review identified a small number of high-quality studies on the use of doxycycline in chronic rhinosinusitis. There does not seem to be convincing evidence for the routine use of doxycycline in patients with chronic rhinosinusitis. Further research may try to identify certain phenotypes of chronic rhinosinusitis that may better respond to doxycycline.
Topics: Humans; Rhinitis; Quality of Life; Doxycycline; Nasal Polyps; Anti-Bacterial Agents; Sinusitis; Chronic Disease
PubMed: 35919933
DOI: 10.1017/S0022215122001803 -
Clinical Infectious Diseases : An... Feb 2023Doxycycline has been recommended as a treatment option for non-severe community-acquired pneumonia (CAP) in adults. We sought to review the evidence for the efficacy of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Doxycycline has been recommended as a treatment option for non-severe community-acquired pneumonia (CAP) in adults. We sought to review the evidence for the efficacy of doxycycline in adult patients with mild-to-moderate CAP.
METHODS
We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) of doxycycline versus comparator to assess the clinical efficacy. The primary outcome was the clinical cure rate. Random effects model meta-analyses were used to generate pooled odds ratio (OR) and evaluate heterogeneity (I2). Risk of bias (RoB) and quality of evidence (QoE) were evaluated using the Cochrane Risk of Bias 2.0 tool and GRADE methods, respectively.
RESULTS
We included 6 RCTs with 834 clinically evaluable patients. The trials were performed between 1984 and 2004. Comparators were 3 macrolides (roxithromycin, spiramycin, and erythromycin) and 3 fluoroquinolones (ofloxacin, fleroxacin, and levofloxacin). Four trials had an overall high RoB. The clinical cure rate was similar between the doxycycline and comparator groups (87.2% [381/437] vs 82.6% [328/397]; OR 1.29 [95% confidence interval {CI}: .73-2.28]; I2 = 30%; low QoE). Subgroup analysis of two studies with a low RoB showed significantly higher clinical cure rates in the doxycyline group (87.1% [196/225] vs 77.8% [165/212]; OR 1.92 [95% CI: 1.15-3.21]; P = .01; I2 = 0%). Adverse event rates were comparable between the doxycycline and comparator groups.
CONCLUSIONS
The efficacy of doxycycline was comparable to macrolides or fluoroquinolones in mild-to-moderate CAP and thus represents a viable treatment option. Considering the lack of recent trials, it warrants large-scale clinical trials.
Topics: Adult; Humans; Doxycycline; Randomized Controlled Trials as Topic; Anti-Bacterial Agents; Macrolides; Fluoroquinolones; Pneumonia
PubMed: 35903011
DOI: 10.1093/cid/ciac615 -
Microorganisms Jul 2022is an emerging, Gram-negative, obligate intracellular pathogen that is transmitted by a tick vector. Human infection ranges from asymptomatic to severe disease that can... (Review)
Review
is an emerging, Gram-negative, obligate intracellular pathogen that is transmitted by a tick vector. Human infection ranges from asymptomatic to severe disease that can present with pancytopenia, multiorgan failure, and death. The aim of this systematic review is to analyze case reports and case series reported over the last two decades in peer-reviewed journals indexed in the Medline/PubMed database according to the PRISMA guidelines. We found 110 unique patients from 88 case reports and series. The most common mode of transmission was tick bite (60.9%), followed by blood transfusion (8.2%). Infection was acquired by blood transfusion in nearly half (42%) of the immunocompromised patients. Most patients reported fever (90%), followed by constitutional (59%) and gastrointestinal symptoms (56%). Rash was present in 17% of patients, much higher than in previous studies. Thrombocytopenia was the most common laboratory abnormality (76%) followed by elevated aspartate aminotransferase (AST) (46%). The diagnosis was most commonly established using whole-blood polymerase chain reaction (PCR) in 76% of patients. Coinfection rate was 9.1% and was most commonly isolated in seven patients (6.4%). Doxycycline was used to treat 70% of patients but was only used as an empiric treatment in one-third of patients (33.6%). The overall mortality rate was 5.7%, and one patient died from trauma unrelated to HGA. The mortality rates among immunocompetent and immunocompromised patients were 4.2% ( = 4/95) and 18.2% ( = 2/11), respectively. Four of the six patients who died (66.6%) received appropriate antibiotic therapy. Among these, doxycycline was delayed by more than 48 h in two patients.
PubMed: 35889152
DOI: 10.3390/microorganisms10071433