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Parasite Immunology Sep 2022Vaccination has potential to eliminate infectious diseases. However, parasitic infections such as helminths may hinder vaccines from providing optimal protection. We... (Meta-Analysis)
Meta-Analysis Review
Vaccination has potential to eliminate infectious diseases. However, parasitic infections such as helminths may hinder vaccines from providing optimal protection. We reviewed existing literature on the effects of helminth infections and their treatment on vaccine responses in humans and animals. We searched literature until 31 January 2022 in Medline, EMBASE, Global health, Scopus, and Web of science; search terms included WHO licensed vaccines and human helminth types. Standardized mean differences (SMD) in vaccine responses between helminth infected and uninfected or anthelminthic treated and untreated individuals were obtained from each study with suitable data for meta-analysis, and combined using a random effects model. Analysis was stratified by whether helminth exposure was direct or prenatal and by vaccine type. This study is registered with PROSPERO (CRD42019123074). Of the 4402 articles identified, 37 were included in the review of human studies and 24 for animal experiments. For human studies, regardless of vaccine type, overall SMD for helminth uninfected/treated, compared to infected/untreated, was 0.56 (95% CI 0.04-1.07 and I = 93.5%) for direct helminth exposure and 0.01 (95% CI -0.04 to 0.07 and I = 85.9%) for prenatal helminth exposure. Effects of anthelminthic treatment were inconsistent, with no overall benefit shown. Results differed by vaccine type, with responses to live vaccines most affected by helminth exposure. For animal studies, the most affected vaccine was BCG. This result indicates that helminth-associated impairment of vaccine responses is more severe for direct, than for prenatal, helminth exposure. Further research is needed to ascertain whether deworming of individuals before vaccination may help improve responses.
Topics: Animals; Anthelmintics; Female; Helminthiasis; Helminths; Humans; Pregnancy; Vaccination; Vaccines
PubMed: 35712983
DOI: 10.1111/pim.12939 -
Journal of the Pediatric Infectious... Aug 2018With the continued high prevalence of chlamydia worldwide and high risk of transfer from mothers to their infant during delivery, a need for safe and effective therapies... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
With the continued high prevalence of chlamydia worldwide and high risk of transfer from mothers to their infant during delivery, a need for safe and effective therapies for infants who acquire a chlamydial infection remains. We conducted a systematic review and meta-analysis of antibiotic treatments, including oral erythromycin, azithromycin, and trimethoprim, for neonatal chlamydial conjunctivitis.
METHODS
We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) from their inception to July 14, 2017. We included randomized and nonrandomized studies that evaluated the effects of erythromycin, azithromycin, or trimethoprim in neonates with chlamydial conjunctivitis. A meta-analysis using a random-effects generic inverse-variance method was performed, and the certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach.
RESULTS
We found 12 studies (n = 292 neonates) and were able to meta-analyze 7 studies that used erythromycin at a dose of 50 mg/kg body weight per day for 14 days. The clinical and microbiological cure were 96% (95% confidence interval [CI], 94%-100%) and 97% (95% CI, 95%-99%), respectively, and adverse gastrointestinal effects occurred in 14% (95% CI, 1%-28%) of the neonates. The microbiological cure in the study that assessed azithromycin at 20 mg/kg per day were 60% (95% CI, 27%-93%) when it was given in a single dose and 86% (95% CI, 61%-100%) when given in a 3-day course. Two studies reported compliance with treatments, and 1 study reported no pyloric stenosis events. Because of the risk of bias and the few neonates included across the studies, the certainty of evidence is low to very low. No studies assessed trimethoprim.
CONCLUSIONS
Although evidence suggests that erythromycin at 50 mg/kg per day for 14 days results in higher numbers of cure than does azithromycin, compliance and risk of pyloric stenosis related to their use for other infections in neonates will factor into treatment recommendations. More data are needed to compare these treatments directly.
Topics: Anti-Bacterial Agents; Azithromycin; Bias; Chlamydia Infections; Chlamydia trachomatis; Conjunctivitis, Bacterial; Drug Administration Schedule; Erythromycin; Female; Gastrointestinal Diseases; Humans; Infant, Newborn; Male; Pyloric Stenosis; Risk Factors; Trimethoprim
PubMed: 30007329
DOI: 10.1093/jpids/piy060 -
BMJ (Clinical Research Ed.) Apr 2021This is the second version (first update) of the living systematic review, replacing the previous version (available as a data supplement). When citing this paper please... (Meta-Analysis)
Meta-Analysis
UPDATES
This is the second version (first update) of the living systematic review, replacing the previous version (available as a data supplement). When citing this paper please consider adding the version number and date of access for clarity.
OBJECTIVE
To determine and compare the effects of drug prophylaxis on severe acute respiratory syndrome coronavirus virus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (covid-19).
DESIGN
Living systematic review and network meta-analysis (NMA).
DATA SOURCES
World Health Organization covid-19 database, a comprehensive multilingual source of global covid-19 literature to 4 March 2022.
STUDY SELECTION
Randomised trials in which people at risk of covid-19 were allocated to prophylaxis or no prophylaxis (standard care or placebo). Pairs of reviewers independently screened potentially eligible articles.
METHODS
After duplicate data abstraction, we conducted random-effects bayesian network meta-analysis. We assessed risk of bias of the included studies using a modification of the Cochrane risk of bias 2.0 tool and assessed the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach.
RESULTS
The second iteration of this living NMA includes 32 randomised trials which enrolled 25 147 participants and addressed 21 different prophylactic drugs; adding 21 trials (66%), 18 162 participants (75%) and 16 (76%) prophylactic drugs. Of the 16 prophylactic drugs analysed, none provided convincing evidence of a reduction in the risk of laboratory confirmed SARS-CoV-2 infection. For admission to hospital and mortality outcomes, no prophylactic drug proved different than standard care or placebo. Hydroxychloroquine and vitamin C combined with zinc probably increase the risk of adverse effects leading to drug discontinuation—risk difference for hydroxychloroquine (RD) 6 more per 1000 (95% credible interval (CrI) 2 more to 10 more); for vitamin C combined with zinc, RD 69 more per 1000 (47 more to 90 more), moderate certainty evidence.
CONCLUSIONS
Much of the evidence remains very low certainty and we therefore anticipate future studies evaluating drugs for prophylaxis may change the results for SARS-CoV-2 infection, admission to hospital and mortality outcomes. Both hydroxychloroquine and vitamin C combined with zinc probably increase adverse effects.
SYSTEMATIC REVIEW REGISTRATION
This review was not registered. The protocol established a priori is included as a supplement.
FUNDING
This study was supported by the Canadian Institutes of Health Research (grant CIHR-IRSC:0579001321).
Topics: Anti-Infective Agents; COVID-19; Carrageenan; Chemoprevention; Global Health; Humans; Hydroxychloroquine; Ivermectin; SARS-CoV-2; Treatment Outcome; Uncertainty
PubMed: 33903131
DOI: 10.1136/bmj.n949 -
PLoS Neglected Tropical Diseases May 2016Soil-transmitted helminths (STH) have acute and chronic manifestations, and can result in lifetime morbidity. Disease burden is difficult to quantify, yet quantitative... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Soil-transmitted helminths (STH) have acute and chronic manifestations, and can result in lifetime morbidity. Disease burden is difficult to quantify, yet quantitative evidence is required to justify large-scale deworming programmes. A recent Cochrane systematic review, which influences Global Burden of Disease (GBD) estimates for STH, has again called into question the evidence for deworming benefit on morbidity due to STH. In this narrative review, we investigate in detail what the shortfalls in evidence are.
METHODOLOGY/PRINCIPAL FINDINGS
We systematically reviewed recent literature that used direct measures to investigate morbidity from STH and we critically appraised systematic reviews, particularly the most recent Cochrane systematic review investigating deworming impact on morbidity. We included six systematic reviews and meta-analyses, 36 literature reviews, 44 experimental or observational studies, and five case series. We highlight where evidence is insufficient and where research needs to be directed to strengthen morbidity evidence, ideally to prove benefits of deworming.
CONCLUSIONS/SIGNIFICANCE
Overall, the Cochrane systematic review and recent studies indicate major shortfalls in evidence for direct morbidity. However, it is questionable whether the systematic review methodology should be applied to STH due to heterogeneity of the prevalence of different species in each setting. Urgent investment in studies powered to detect direct morbidity effects due to STH is required.
Topics: Anemia; Animals; Anthelmintics; Ascariasis; Ascaris lumbricoides; Chronic Disease; Cost of Illness; Helminthiasis; Humans; Prevalence; Soil
PubMed: 27196100
DOI: 10.1371/journal.pntd.0004566 -
Annals of Palliative Medicine Feb 2022First-line medications for acne vulgaris include retinoids and antibiotics. Dapsone is a topical drug approved by the U.S. Food and Drug Administration for the treatment... (Meta-Analysis)
Meta-Analysis
BACKGROUND
First-line medications for acne vulgaris include retinoids and antibiotics. Dapsone is a topical drug approved by the U.S. Food and Drug Administration for the treatment of acne. However, due to its side effects, the clinical application of dapsone has not been promoted, and the value of the medication is still unclear. The aim of this study is to determine the efficacy and safety of dapsone gel in patients with acne.
METHODS
Systematic searches were performed using the following databases on January 4, 2020: PubMed, EMBASE, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI), China Biomedical Literature Service System (SinoMed), China Science and Technology Journal Database (CQVIP), and Wanfang Data Knowledge Service Platform. A meta-analysis of randomized controlled trials was then conducted to analyze the efficacy and adverse events of dapsone gel treatment compared with excipient and other drug therapies. RevMan 5.3 software was used to calculate the odds ratio (OR), and the confidence interval (CI) was 95%.
RESULTS
Data of 11,424 participants across 7 trials which met the inclusion criteria were analyzed. Meta-analysis showed that dapsone gel alone or dapsone gel combined with isotretinoin was superior to excipient alone or oral isotretinoin alone in the treatment of acne (OR =1.51, 95% CI: 1.38-1.66, P<0.0001 random effects model, I2=0%). This indicates that dapsone gel is effective for the treatment of acne. We also found that dapsone gel is a more effective treatment for females (OR =1.80, 95% CI: 1.46-2.23). There was no significant difference in the incidence of adverse events between the dapsone group and the control group (OR =0.94, 95% CI: 0.82-1.14, P=0.24 random effects model; I2=29%). The common local adverse reactions in the dapsone group, such as dryness, heat, and eczema, were not statistically significant compared with those in the control group, and the side effects were transient.
DISCUSSION
Dapsone gel is effective in treating acne, and there is no significant difference in adverse events compared with other drugs.
Topics: Acne Vulgaris; Anti-Bacterial Agents; Dapsone; Eczema; Female; Humans; Treatment Outcome; United States
PubMed: 35249339
DOI: 10.21037/apm-21-3935 -
Seminars in Nuclear Medicine Sep 2023Fibroblast activation protein inhibitor (FAPI) is a promising tracer in oncologic positron emission tomography/computed tomography (PET/CT). Numerous studies have... (Review)
Review
Fibroblast activation protein inhibitor (FAPI) is a promising tracer in oncologic positron emission tomography/computed tomography (PET/CT). Numerous studies have demonstrated the superior sensitivity of FAPI PET/CT over fluorodeoxyglucose (FDG) PET/CT in several types of cancer. However, the cancer specificity of FAPI uptake remains understudied, and several cases of false-positive FAPI PET/CT findings have been reported. A systematic search of PubMed, Embase, and Web of Science was conducted for studies published prior to April 2022 reporting nonmalignant FAPI PET/CT findings. We included original peer-reviewed articles of studies in humans using FAPI tracers radiolabeled with Ga or F that were published in English. Papers without original data and studies with insufficient information were excluded. Nonmalignant findings were presented on a per-lesion basis and grouped according to the type of organ or tissue involved. The search identified a total of 1.178 papers, of which 108 studies were eligible. Eighty studies were case reports (74%), and the remaining 28 were cohort studies (26%). A total of 2.372 FAPI-avid nonmalignant findings were reported, with the most frequent being uptake in the arteries, e.g., related to plaques (n = 1178, 49%). FAPI uptake was also frequently related to degenerative and traumatic bone and joint lesions (n = 147, 6%) or arthritis (n = 92, 4%). For organs, diffuse or focal uptake was often seen in cases of inflammation, infection, fibrosis, and IgG4-related disease (n = 157, 7%). FAPI-avid inflammatory/reactive lymph nodes (n = 121, 5%) and tuberculosis lesions (n = 51, 2%) have been reported and could prove to be potential pitfalls in cancer staging. Periodontitis (n = 76, 3%), hemorrhoids (n = 47, 2%), and scarring/wound healing (n = 35, 2%) also presented as focal uptake on FAPI PET/CT. The present review provides an overview of the reported FAPI-avid nonmalignant PET/CT findings to date. A large number of benign clinical entities may show FAPI uptake and should be kept in mind when interpreting FAPI PET/CT findings in patients with cancer.
Topics: Humans; Biological Transport; Fluorodeoxyglucose F18; Gallium Radioisotopes; Inflammation; Positron Emission Tomography Computed Tomography
PubMed: 36813670
DOI: 10.1053/j.semnuclmed.2023.02.001 -
Parasitology Nov 2022From a systematic review framework, we analysed the clinical evidence on the effectiveness and safety of monotherapy and combination chemotherapy for Chagas disease... (Review)
Review
From a systematic review framework, we analysed the clinical evidence on the effectiveness and safety of monotherapy and combination chemotherapy for Chagas disease (ChD) treatment. The research protocol was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and patient, intervention, comparison and outcome strategy. Only randomized controlled trials (RCT) were retrieved from Embase, Medline, Scopus and Web of Science databases. Diagnostic tools, treatment protocols, seroconversion rates and adverse events were investigated. Fifteen RCT mainly concentrated in endemic countries were identified. ChD diagnosis was mainly based on haemagglutination, immunofluorescence, enzyme-linked immunosorbent assay and polymerase chain reaction. Benznidazole (BNZ), nifurtimox, fosravuconazole, posaconazole, allopurinol and thioctic acid were the identified drugs. The best negative seroconversion results (100, 96, 94 and 91.3%) were, respectively, based on BNZ (5 mg kg day, 200 mg day, 150 mg day and 2.5 mg kg) administration for 60 days. Negative seroconversion was not achieved with allopurinol (300 mg day for 60 days). Adverse reactions ranged from 5 to 73% in patients receiving antiparasitic chemotherapy. Treatment discontinuation (1.5–57%) was mainly associated with gastrointestinal, cutaneous and neurological manifestations. Current RCT-based evidence indicates that BNZ is the most viable option for ChD treatment. However, new protocols need to be developed to mitigate side effects and increase patient adherence to antiparasitic chemotherapy. Therefore, shorter regimens, lower concentrations and treatments combining BNZ with posaconazole, fosravuconazole or ravuconazole may be viable to ensure comparable efficacy to BZN-based monotherapy, contributing to reduce dose- and time-dependent toxicity reactions.
Topics: Humans; Trypanosoma cruzi; Trypanocidal Agents; Allopurinol; Randomized Controlled Trials as Topic; Chagas Disease; Nitroimidazoles; Drug Therapy, Combination; Treatment Outcome
PubMed: 35957576
DOI: 10.1017/S0031182022001081 -
Italian Journal of Dermatology and... Jun 2023The human skin barrier is structurally and functionally immature at birth, with elevated skin surface pH, lower lipid content, and lower resistance to chemicals and...
The human skin barrier is structurally and functionally immature at birth, with elevated skin surface pH, lower lipid content, and lower resistance to chemicals and pathogens. Infants at risk for atopic dermatitis (AD) may present with xerosis almost immediately after birth. The current algorithm on skincare for newborns and infants aims to promote a healthy skin barrier and potential mitigation of AD. The project used a modified Delphi hybrid process comprising face-to-face discussions followed by an online follow-up replacing a questionnaire. During the meeting, a panel of eight clinicians who treat newborns and infants discussed the systematic literature review results and a draft algorithm addressing non-prescription skincare for neonates and infants. Online the panel reviewed and adopted the algorithm using evidence coupled with the panel's expert opinion and clinical experience. The algorithm provides clinical information for pediatric dermatologists, dermatologists, and pediatric healthcare providers treating neonates and infants. The advisors adopted a scale based on clinical signs for the algorithm: 1) scaling/xerosis; 2) erythema; and 3) erosion/oozing. Skincare for newborns and infants includes: aim for a cool environment and soft cotton clothing, give lukewarm baths (~5 min, 2-3 x week) with consideration of a gentle cleanser (pH 4-6) and the application of a full-body moisturizing after bath, while avoiding products with toxic and irritating ingredients. A growing body of evidence recognizes the benefits of ongoing daily use of non-alkaline cleansers and moisturizers. Gentle cleansers and moisturizers containing barrier lipids help maintain the protective skin barrier when applied from birth onwards.
Topics: Humans; Infant; Infant, Newborn; Child; Dermatitis, Atopic; Skin; Skin Care; Erythema; Health Status; Autonomic Nervous System Diseases
PubMed: 37278500
DOI: 10.23736/S2784-8671.23.07336-X -
Travel Medicine and Infectious Disease 2017Mefloquine is recommended in international health guidelines for preventing malaria in travellers. Reports of psychosis and suicide are often alluded to but are not... (Review)
Review
BACKGROUND
Mefloquine is recommended in international health guidelines for preventing malaria in travellers. Reports of psychosis and suicide are often alluded to but are not clearly established.
METHODS
We carried out a systematic review of the literature to identify and critically appraise any reported death or parasuicide associated with mefloquine prophylaxis. We developed a comprehensive search that included publications up to 11 July 2017. We included case studies but excluded newspaper reports. Two authors independently appraised each death or parasuicide against a standardised causality assessment tool. The protocol was registered on PROSPERO (CRD42016041988).
RESULTS
We identified 527 articles that required full-text retrieval; of these 17 were unique publications that reported deaths or parasuicide. Eight unique publications had sufficient detail to be included in causality assessment. We identified 2 deaths with a probable association that appeared to be idiosyncratic drug reactions; we categorised the remaining 8 deaths as "unlikely" to be related to mefloquine, or "unclassifiable". There was one parasuicide with a possible causal association. There were 9 additional publications that searched spontaneous drug reporting databases; none provided sufficient detail to perform a causality assessment.
CONCLUSIONS
Overall, the number of deaths that we could reliably attribute to the prophylactic use of mefloquine is very low.
Topics: Antimalarials; Cause of Death; Chemoprevention; Humans; Malaria; Mefloquine; Self-Injurious Behavior; Travel Medicine
PubMed: 29107173
DOI: 10.1016/j.tmaid.2017.10.011 -
PLoS Neglected Tropical Diseases Jan 2018By means of meta-analysis of information from all relevant epidemiologic studies, we examined the hypothesis that Schistosoma infection in school-aged children (SAC) is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
By means of meta-analysis of information from all relevant epidemiologic studies, we examined the hypothesis that Schistosoma infection in school-aged children (SAC) is associated with educational loss and cognitive deficits.
METHODOLOGY/PRINCIPAL FINDINGS
This review was prospectively registered in the PROSPERO database (CRD42016040052). Medline, Biosis, and Web of Science were searched for studies published before August 2016 that evaluated associations between Schistosoma infection and cognitive or educational outcomes. Cognitive function was defined in four domains-learning, memory, reaction time, and innate intelligence. Educational outcome measures were defined as attendance and scholastic achievement. Risk of bias (ROB) was evaluated using the Newcastle-Ottawa quality assessment scale. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated to compare cognitive and educational measures for Schistosoma infected /not dewormed vs. uninfected/dewormed children. Sensitivity analyses by study design, ROB, and sequential exclusion of individual studies were implemented. Thirty studies from 14 countries, including 38,992 SAC between 5-19 years old, were identified. Compared to uninfected children and children dewormed with praziquantel, the presence of Schistosoma infection and/or non-dewormed status was associated with deficits in school attendance (SMD = -0.36, 95%CI: -0.60, -0.12), scholastic achievement (SMD = -0.58, 95%CI: -0.96, -0.20), learning (SMD = -0.39, 95%CI: -0.70, -0.09) and memory (SMD = -0.28, 95%CI: -0.52, -0.04) tests. By contrast, Schistosoma-infected/non-dewormed and uninfected/dewormed children were similar with respect to performance in tests of reaction time (SMD = -0.06, 95%CI: -0.42, 0.30) and intelligence (SMD = -0.25, 95%CI: -0.57, 0.06). Schistosoma infection-associated deficits in educational measures were robust among observational studies, but not among interventional studies. The significance of infection-associated deficits in scholastic achievement was sensitive to ROB. Schistosoma infection-related deficits in learning and memory tests were invariant by ROB and study design.
CONCLUSION/SIGNIFICANCE
Schistosoma infection/non-treatment was significantly associated with educational, learning, and memory deficits in SAC. Early treatment of children in Schistosoma-endemic regions could potentially mitigate these deficits.
TRIAL REGISTRATION
ClinicalTrials.gov CRD42016040052.
Topics: Adolescent; Animals; Anthelmintics; Child; Child, Preschool; Cognition; Cognitive Dysfunction; Humans; Intelligence; Learning Disabilities; Memory; Memory Disorders; Memory and Learning Tests; Praziquantel; Reaction Time; Schistosoma; Schistosomiasis
PubMed: 29329293
DOI: 10.1371/journal.pntd.0005524