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Clinical Microbiology and Infection :... Apr 2021While the landscape of vaccine and treatment candidates against the novel coronavirus disease 2019 (COVID-19) has been reviewed systematically, prophylactic candidates...
BACKGROUND
While the landscape of vaccine and treatment candidates against the novel coronavirus disease 2019 (COVID-19) has been reviewed systematically, prophylactic candidates remain unexplored.
OBJECTIVES
To map pre- and postexposure prophylactic (PrEP and PEP) candidate for COVID-19.
DATA SOURCES
PubMed/Medline, Embase, International Committee of Medical Journal Editors and International Clinical Trials Registry Platform clinical trial registries and medRxiv.
STUDY ELIGIBILITY CRITERIA AND PARTICIPANTS
All studies in humans or animals and randomized controlled trials (RCTs) in humans reporting primary data on prophylactic candidates against COVID-19, excluding studies focused on key populations.
INTERVENTIONS
PrEP and PEP candidate for COVID-19.
METHODS
Systematic review and qualitative synthesis of COVID-19 PrEP and PEP studies and RCTs complemented by search of medRxiv and PubMed and Embase for studies reporting RCT outcomes since systematic review search completion.
RESULTS
We identified 13 studies (from 2119 database records) and 117 RCTs (from 5565 RCTs listed in the registries) that met the inclusion criteria. Non-RCT studies reported on cross-sectional studies using hydroxychloroquine (HCQ) in humans (n = 2) or reported on animal studies (n = 7), most of which used antibodies. All five completed RCTs focused on the use of HCQ as either PrEP or PEP, and these and the cross-sectional studies reported no prophylactic effect. The majority of ongoing RCTs evaluated HCQ or other existing candidates including non-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, anti(retro)virals or use of vitamins and supplements.
CONCLUSIONS
The key message from completed studies and RCTs seems to be that HCQ does not work. There is little evidence regarding other compounds, with all RCTs using candidates other than HCQ still ongoing. It remains to be seen if the portfolio of existing molecules being evaluated in RCTs will identify successful prophylaxis against COVID-19 or if there is a need for the development of new candidates.
Topics: Animals; Antibodies, Monoclonal; Antibodies, Neutralizing; Antibodies, Viral; Antimalarials; Antiviral Agents; COVID-19; Humans; Hydroxychloroquine; Post-Exposure Prophylaxis; Pre-Exposure Prophylaxis; Randomized Controlled Trials as Topic; SARS-CoV-2; Vaccines
PubMed: 33476807
DOI: 10.1016/j.cmi.2021.01.013 -
BMJ Open Jun 2023We studied the safety and efficacy of hydroxychloroquine (HCQ) as pre-exposure prophylaxis for COVID-19 in healthcare workers (HCWs), using a meta-analysis of randomised... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We studied the safety and efficacy of hydroxychloroquine (HCQ) as pre-exposure prophylaxis for COVID-19 in healthcare workers (HCWs), using a meta-analysis of randomised controlled trials (RCTs).
DATA SOURCES
PubMed and EMBASE databases were searched to identify randomised trials studying HCQ.
STUDY SELECTION
Ten RCTs were identified (n=5079 participants).
DATA EXTRACTION AND SYNTHESIS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used in this systematic review and meta-analysis between HCQ and placebo using a Bayesian random-effects model. A pre-hoc statistical analysis plan was written.
MAIN OUTCOMES
The primary efficacy outcome was PCR-confirmed SARS-CoV-2 infection and the primary safety outcome was incidence of adverse events. The secondary outcome included clinically suspected SARS-CoV-2 infection.
RESULTS
Compared with placebo, HCWs randomised to HCQ had no significant difference in PCR-confirmed SARS-CoV-2 infection (OR 0.92, 95% credible interval (CI): 0.58, 1.37) or clinically suspected SARS-CoV-2 infection (OR 0.78, 95% CI: 0.57, 1.10), but significant difference in adverse events (OR 1.35, 95% CI: 1.03, 1.73).
CONCLUSIONS AND RELEVANCE
Our meta-analysis of 10 RCTs investigating the safety and efficacy of HCQ as pre-exposure prophylaxis in HCWs found that compared with placebo, HCQ does not significantly reduce the risk of confirmed or clinically suspected SARS-CoV-2 infection, while HCQ significantly increases adverse events.
PROSPERO REGISTRATION NUMBER
CRD42021285093.
Topics: Humans; COVID-19; COVID-19 Drug Treatment; Health Personnel; Hydroxychloroquine; SARS-CoV-2; Pre-Exposure Prophylaxis
PubMed: 37328184
DOI: 10.1136/bmjopen-2022-065305 -
Journal of General Internal Medicine Nov 2020There is no effective therapy for COVID-19. Hydroxychloroquine (HCQ) and chloroquine (CQ) have been used for its treatment but their safety and efficacy remain uncertain. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is no effective therapy for COVID-19. Hydroxychloroquine (HCQ) and chloroquine (CQ) have been used for its treatment but their safety and efficacy remain uncertain.
OBJECTIVE
We performed a systematic review to synthesize the available data on the efficacy and safety of CQ and HCQ for the treatment of COVID-19.
METHODS
Two reviewers searched for published and pre-published relevant articles between December 2019 and 8 June 2020. The data from the selected studies were abstracted and analyzed for efficacy and safety outcomes. Critical appraisal of the evidence was done by Cochrane risk of bias tool and Newcastle Ottawa Scale. The quality of evidence was graded as per the GRADE approach.
RESULTS
We reviewed 12 observational and 3 randomized trials which included 10,659 patients of whom 5713 received CQ/HCQ and 4966 received only standard of care. The efficacy of CQ/HCQ for COVID-19 was inconsistent across the studies. Meta-analysis of included studies revealed no significant reduction in mortality with HCQ use [RR 0.98 95% CI 0.66-1.46], time to fever resolution (mean difference - 0.54 days (- 1.19-011)) or clinical deterioration/development of ARDS with HCQ [RR 0.90 95% CI 0.47-1.71]. There was a higher risk of ECG abnormalities/arrhythmia with HCQ/CQ [RR 1.46 95% CI 1.04 to 2.06]. The quality of evidence was graded as very low for these outcomes.
AUTHORS' CONCLUSION
The available evidence suggests that CQ or HCQ does not improve clinical outcomes in COVID-19. Well-designed randomized trials are required for assessing the efficacy and safety of HCQ and CQ for COVID-19.
Topics: Bias; Chloroquine; Humans; Hydroxychloroquine; Research Design; SARS-CoV-2; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 32885373
DOI: 10.1007/s11606-020-06146-w -
Journal of Clinical Pharmacology Mar 2023This systematic review was performed to determine the population that benefited from prophylactic ivermectin. Seven databases of health-related studies were searched for... (Meta-Analysis)
Meta-Analysis Review
This systematic review was performed to determine the population that benefited from prophylactic ivermectin. Seven databases of health-related studies were searched for eligible trials without language restrictions. Randomized controlled trials (RCTs) and cohort studies investigating ivermectin for coronavirus disease 2019 (COVID-19) prevention were included. Data were pooled using a random-effects model, and subgroups were analyzed by study type and the pre- or postexposure population. The certainty of the evidence was determined by the Grading of Recommendations Assessment, Development, and Evaluation approach. Furthermore, 4 RCTs and 4 cohort studies with a moderate to high risk of bias were included in the analysis. The prophylactic use of ivermectin significantly decreased the overall incidence of COVID-19 (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.16-0.44). Nevertheless, the positive result was not supported by the RCT. Ivermectin was associated with a lower risk of COVID-19 (OR, 0.22; 95% CI, 0.12-0.40) in the preexposure population, whereas no protective effect was observed in the postexposure population (OR, 0.39; 95% CI, 0.09-1.67). In summary, prophylactic ivermectin did not prevent COVID-19 in the postexposure population. Although the protective effect of ivermectin was shown in the overall and preexposure populations, the results were unreliable owing to poor-quality evidence.
Topics: Humans; COVID-19; Ivermectin; Bias; Research Design; Odds Ratio
PubMed: 36399336
DOI: 10.1002/jcph.2178 -
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 -
Research in Veterinary Science Dec 2022The objective of this study was to conduct research of the literature available in electronic media on anthelmintic intoxication in sheep and goats. The search for... (Review)
Review
The objective of this study was to conduct research of the literature available in electronic media on anthelmintic intoxication in sheep and goats. The search for primary studies was carried out in five electronic databases: ScienceDirect, PubMed, Scopus, Web of Science, and SciELO. The search terms used were (antihelmintic OR antiparasitic OR vermifuge) AND (poisoning OR toxicity OR overdose OR intoxication) AND (goat OR sheep). A total of 2361 articles were identified from the five databases: Science Direct (n = 1869), PubMed (n = 434), Scopus (n = 37), Web of Science (n = 16), and SciELO (n = 5). As 111 articles were found in duplicates, 2250 were left for review of the title and abstracts, of which 115 were read in full, and 28 were included in the systematic review. Of the 28 articles, 16 involved sheep, 9 involved goats, and 3 involved both species. Twelve drugs were identified in intoxication reports: albendazole (2), closantel (14), disophenol (1), ivermectin (1), levamisole (2), moxidectin (1), netobimin (1), nitroxinil (1), oxfendazole (2), parbendazole (2), tetramizole (1), and thiabendazole (1). The most prevalent symptoms of anthelmintic intoxication reported were showed involvement of the nervous, locomotor, and renal systems, as well as teratogenic influences. Data from this review underscore the need of the care required in the control of parasitic infections through the safe use of antiparasitic drugs to avoid cases of intoxication.
Topics: Sheep; Animals; Goats; Parasite Egg Count; Sheep Diseases; Anthelmintics; Albendazole; Antiparasitic Agents; Drug Resistance; Goat Diseases; Feces
PubMed: 36219891
DOI: 10.1016/j.rvsc.2022.09.038 -
Infectious Diseases (London, England) Jul 2023Whipple's disease is an uncommon chronic systemic disease caused by . The most characteristic findings of late Whipple's disease include diarrhoea, abdominal pain,... (Review)
Review
Whipple's disease is an uncommon chronic systemic disease caused by . The most characteristic findings of late Whipple's disease include diarrhoea, abdominal pain, weight loss, and arthralgias, however, other clinical findings can occur, including lymphadenopathy, fever, neurologic manifestations, myocarditis and endocarditis. The aim of the present study was to systematically review all cases of Whipple's disease-associated infective endocarditis (IE) in the literature. A systematic review of PubMed, Scopus, and Cochrane Library (all published studies up to 28 May 2022) for studies providing data on epidemiology, clinical characteristics as well as data on treatment and outcomes of Whipple's disease-associated IE was performed. A total of 72 studies, containing data for 127 patients, were included. A prosthetic valve was present in 8% of patients. The aortic valve was the most commonly involved intracardiac site followed by the mitral valve. Heart failure, embolic phenomena, and fever were the most common clinical presentations, however, fever occurred in less than 30% of patients. Sepsis was rarely noted. The diagnosis was most commonly performed through pathology through positive PCR or histology in cardiac valves in 88.2% of patients. Trimethoprim with sulfamethoxazole were the most commonly used antimicrobials followed by cephalosporins and tetracyclines. Surgery was performed in 84.3% of patients. Mortality was 9.4%. A multivariate logistic regression analysis model identified presentation with sepsis or development of a paravalvular abscess to be independently associated with increased mortality, while treatment with the combination of trimethoprim with sulfamethoxazole was independently associated with reduced mortality.
Topics: Humans; Whipple Disease; Endocarditis, Bacterial; Anti-Bacterial Agents; Trimethoprim; Sulfamethoxazole; Sepsis
PubMed: 37198913
DOI: 10.1080/23744235.2023.2214610 -
The Lancet. Global Health Jul 2023Malaria infections during pregnancy can cause adverse birth outcomes, yet many infections are undetected by microscopy. We aimed to describe the epidemiology of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Malaria infections during pregnancy can cause adverse birth outcomes, yet many infections are undetected by microscopy. We aimed to describe the epidemiology of submicroscopic malaria infections in pregnant women in Asia, the Americas, and Africa using aggregated and individual participant data (IPD).
METHODS
For this systematic review and meta-analysis, studies (published Jan 1, 1997 to Nov 10, 2021) with information on both microscopic and submicroscopic infections during pregnancy from Asia, the Americas, or Africa, identified in the Malaria-in-Pregnancy Library, were eligible. Studies (or subgroups or study groups) that selected participants on the basis of the presence of fever or a positive blood smear were excluded to avoid selection bias. We obtained IPD (when available) and aggregated data. Estimates of malaria transmission intensity and sulfadoxine-pyrimethamine resistance, matched by study location and year, were obtained using publicly available data. One-stage multivariable logit and multinomial models with random intercepts for study site were used in meta-analysis to assess prevalence of and risk factors for submicroscopic infections during pregnancy and at delivery. This study is registered with PROSPERO, number CRD42015027342.
FINDINGS
The search identified 87 eligible studies, 68 (78%) of which contributed to the analyses. Of these 68 studies, 45 (66%) studies contributed IPD (48 869 participants) and 23 (34%) studies contributed aggregated data (11 863 participants). During pregnancy, median prevalence estimates were 13·5% (range 0·0-55·9, 66 substudies) for submicroscopic and 8·0% (0·0-50·6, 66 substudies) for microscopic malaria. Among women with positive Plasmodium nucleic acid amplification tests (NAATs), the median proportion of submicroscopic infections was 58·7% (range 0·0-100); this proportion was highest in the Americas (73·3%, 0·0-100), followed by Asia (67·2%, 36·4-100) and Africa (56·5%, 20·5-97·7). In individual patient data analysis, compared with women with no malaria infections, those with submicroscopic infections were more likely to present with fever in Africa (adjusted odds ratio 1·32, 95% CI 1·02-1·72; p=0·038) but not in other regions. Among women with NAAT-positive infections in Asia and the Americas, Plasmodium vivax infections were more likely to be submicroscopic than Plasmodium falciparum infections (3·69, 2·45-5·54; p<0·0001). Risk factors for submicroscopic infections among women with NAAT-positive infections in Africa included older age (age ≥30 years), multigravidity, and no HIV infection.
INTERPRETATION
During pregnancy, submicroscopic infections are more common than microscopic infections and are associated with fever in Africa. Malaria control in pregnancy should target both microscopic and submicroscopic infections.
FUNDING
Bill & Melinda Gates Foundation through the Worldwide Antimalarial Resistance Network.
Topics: Female; Humans; Pregnancy; Adult; Prevalence; Malaria; Antimalarials; Malaria, Falciparum; Risk Factors
PubMed: 37276878
DOI: 10.1016/S2214-109X(23)00194-8 -
Expert Opinion on Drug Safety Mar 2021: A century-long history in 8-aminoquinolines, the only anti-malaria drug class preventing malaria relapse, has resulted in the approval of tafenoquine by the U.S. Food... (Meta-Analysis)
Meta-Analysis
: A century-long history in 8-aminoquinolines, the only anti-malaria drug class preventing malaria relapse, has resulted in the approval of tafenoquine by the U.S. Food and Drug Administration (FDA) and the Australian Therapeutic Goods Administration (TGA) and to date registration in Brazil and Thailand. Tafenoquine is an alternative anti-relapse treatment for vivax malaria and malaria prophylaxis. It should not be given in pregnancy, during lactation of infants with glucose-6-phosphate dehydrogenase (G6PD) unknown or deficient status, and in those with G6PD deficiency or psychiatric illness.: This systematic review assesses tafenoquine associated adverse events in English-language, human clinical trials. Meta-analysis of commonly reported adverse events was conducted and grouped by comparison arms.: Tafenoquine, either for radical cure or prophylaxis, is generally well tolerated in adults. There is no convincing evidence for neurologic, ophthalmic, and cardiac toxicities. Psychotic disorder which has been attributed to higher doses is a contraindication for the chemoprophylaxis indication and psychiatric illness is a warning for the radical cure indication. Pregnancy assessment and quantitative G6PD testing are required. The optimal radical curative regimen including the tafenoquine dose along with its safety for parts of Southeast Asia, South America, and Oceania needs further assessment.
Topics: Adult; Aminoquinolines; Animals; Antimalarials; Dose-Response Relationship, Drug; Glucosephosphate Dehydrogenase Deficiency; Humans; Malaria, Vivax; Mental Disorders
PubMed: 33306921
DOI: 10.1080/14740338.2021.1859476 -
The Journal of Dermatological Treatment Feb 2022For severe cases of lichen planopilaris (LPP), unresponsive to first line therapy, systemic or potent agents may be required for disease control. There have been several... (Meta-Analysis)
Meta-Analysis
BACKGROUND
For severe cases of lichen planopilaris (LPP), unresponsive to first line therapy, systemic or potent agents may be required for disease control. There have been several reports of the off-label use of mycophenolate mofetil (MMF) in patients with LPP or have developed adverse effects to initial agents.
METHODS
A systematic review and meta-analysis was performed according to recommended Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies with ≥5 cases reporting the outcomes of MMF in LPP were pooled and a meta-analysis of proportion was performed. Case reports were excluded from analysis.
RESULTS
A total of six studies were identified and included for meta-analysis, comprising 94 LPP patients. The pooled proportion of any good response (partial or complete) was 69.2% (95% confidence interval (CI): 47.8-77). The pooled proportion of complete response was 20% (95% CI: 10.1-36.3). The pooled proportion of partial responses was 49.2% (95% CI: 30.5-63.7). Side effects occurred in 16.9% (95% CI: 17.6-33.2). of cases, which included elevated LFTs, edema, hyperlipidemia, anemia, herpes zoster infection, photosensitivity, and urinary tract infection.
CONCLUSION
The current evidence for MMF remains limited. However, it appears to be a potential treatment option for patients with severe or recalcitrant LPP who have failed hydroxychloroquine and other immunosuppressants.
Topics: Humans; Hydroxychloroquine; Immunosuppressive Agents; Lichen Planus; Mycophenolic Acid; Remission Induction
PubMed: 32281437
DOI: 10.1080/09546634.2020.1755416