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PLoS Neglected Tropical Diseases Apr 2024Post-kala-azar dermal leishmaniasis (PKDL) is a dermatosis which can occur after successful treatment of visceral leishmaniasis (VL) and is a public health problem in VL...
Post-kala-azar dermal leishmaniasis (PKDL) drug efficacy study landscape: A systematic scoping review of clinical trials and observational studies to assess the feasibility of establishing an individual participant-level data (IPD) platform.
BACKGROUND
Post-kala-azar dermal leishmaniasis (PKDL) is a dermatosis which can occur after successful treatment of visceral leishmaniasis (VL) and is a public health problem in VL endemic areas. We conducted a systematic scoping review to assess the characteristics of published PKDL clinical studies, understand the scope of research and explore the feasibility and value of developing a PKDL individual patient data (IPD) platform.
METHODS
A systematic review of published literature was conducted to identify PKDL clinical studies by searching the following databases: PubMed, Scopus, Ovid Embase, Web of Science Core Collection, WHO Global Index Medicus, PASCAL, Clinicaltrials.gov, Ovid Global Health, Cochrane Database and CENTRAL, and the WHO International Clinical Trials Registry Platform. Only prospective studies in humans with PKDL diagnosis, treatment, and follow-up measurements between January 1973 and March 2023 were included. Extracted data includes variables on patient characteristics, treatment regimens, diagnostic methods, geographical locations, efficacy endpoints, adverse events and statistical methodology.
RESULTS
A total of 3,418 records were screened, of which 56 unique studies (n = 2,486 patients) were included in this review. Out of the 56 studies, 36 (64.3%) were from India (1983-2022), 12 (21.4%) from Sudan (1992-2021), 6 (10.7%) were from Bangladesh (1991-2019), and 2 (3.6%) from Nepal (2001-2007). Five (8.9%) studies were published between 1981-1990 (n = 193 patients), 10 (17.9%) between 1991-2000 (n = 230 patients), 10 (17.9%) between 2001-2010 (n = 198 patients), and 31 (55.4%) from 2011 onwards (n = 1,865 patients). Eight (14.3%) were randomised clinical trials, and 48 (85.7%) were non-randomised studies. The median post-treatment follow-up duration was 365 days (range: 90-540 days) in 8 RCTs and 360 days (range: 28-2,373 days) in 48 non-randomised studies. Disease diagnosis was based on clinical criterion in 3 (5.4%) studies, a mixture of clinical and parasitological methods in 47 (83.9%) and was unclear in 6 (10.7%) studies. Major drugs used for treatment were miltefosine (n = 636 patients), liposomal amphotericin B (L-AmB) (n = 508 patients), and antinomy regimens (n = 454 patients). Ten other drug regimens were tested in 270 patients with less than 60 patients per regimen.
CONCLUSIONS
Our review identified studies with very limited sample size for the three major drugs (miltefosine, L-AmB, and pentavalent antimony), while the number of patients combined across studies suggest that the IPD platform would be valuable. With the support of relevant stakeholders, the global PKDL community and sufficient financing, a PKDL IPD platform can be realised. This will allow for exploration of different aspects of treatment safety and efficacy, which can potentially guide future healthcare decisions and clinical practices.
Topics: Humans; Leishmaniasis, Visceral; Leishmaniasis, Cutaneous; Antiprotozoal Agents; Observational Studies as Topic; Clinical Trials as Topic; Feasibility Studies; Treatment Outcome; India; Bangladesh
PubMed: 38626228
DOI: 10.1371/journal.pntd.0011635 -
PLoS Neglected Tropical Diseases Apr 2024Cutaneous leishmaniasis (CL) is characterized by potentially disfiguring skin ulcers carrying significant social stigma. To mitigate systemic drug exposure and reduce...
BACKGROUND
Cutaneous leishmaniasis (CL) is characterized by potentially disfiguring skin ulcers carrying significant social stigma. To mitigate systemic drug exposure and reduce the toxicity from available treatments, studies addressing new local therapeutic strategies using available medications are coming up. This review systematically compiles preclinical and clinical data on the efficacy of amphotericin B (AmB) administered locally for cutaneous leishmaniasis.
METHODOLOGY
Structured searches were conducted in major databases. Clinical studies reporting cure rates and preclinical studies presenting any efficacy outcome were included. Exclusion criteria comprised nonoriginal studies, in vitro investigations, studies with fewer than 10 treated patients, and those evaluating AmB in combination with other antileishmanial drug components.
PRINCIPAL FINDINGS
A total of 21 studies were identified, encompassing 16 preclinical and five clinical studies. Preclinical assessments generally involved the topical use of commercial AmB formulations, often in conjunction with carriers or controlled release systems. However, the variation in the treatment schedules hindered direct comparisons. In clinical studies, topical AmB achieved a pooled cure rate of 45.6% [CI: 27.5-64.8%; I2 = 79.7; p = 0.002), while intralesional (IL) administration resulted in a 69.8% cure rate [CI: 52.3-82.9%; I2 = 63.9; p = 0.06). In the direct comparison available, no significant difference was noted between AmB-IL and meglumine antimoniate-IL administration (OR:1.7; CI:0.34-9.15, I2 = 79.1; p = 0.00), however a very low certainty of evidence was verified.
CONCLUSIONS
Different AmB formulations and administration routes have been explored in preclinical and clinical studies. Developing therapeutic technologies is evident. Current findings might be interpreted as a favorable proof of concept for the local AmB administration which makes this intervention eligible to be explored in future well-designed studies towards less toxic treatments for leishmaniasis.
Topics: Leishmaniasis, Cutaneous; Amphotericin B; Humans; Antiprotozoal Agents; Administration, Topical; Treatment Outcome
PubMed: 38626196
DOI: 10.1371/journal.pntd.0012127 -
The Lancet Regional Health. Southeast... Mar 2024Occurrences of relapse after 6-months post-treatment has been reported in recent Visceral Leishmaniasis (VL) efficacy studies. A meta-analysis was carried out to...
BACKGROUND
Occurrences of relapse after 6-months post-treatment has been reported in recent Visceral Leishmaniasis (VL) efficacy studies. A meta-analysis was carried out to quantify the proportion of relapses observed at and beyond 6-months using the Infectious Diseases Data Observatory (IDDO) systematic review (SR) database.
METHODS
Studies in the IDDO SR database (1983-2021; 160 studies) were eligible for inclusion if follow-up was at least 6-months, relapse was clearly reported, and patients with HIV coinfections were excluded. Meta-analysis of single proportion was undertaken and the estimates were reported with 95% confidence intervals (CI).
FINDINGS
Overall, 131 studies enrolling 27,687 patients were included; 1193 patients relapsed. In the Indian sub-continent (ISC), relapse estimates at 6-months was 4.5% [95% CI: 2.6%-7.5%; = 66.2%] following single dose liposomal amphotericin B (L-AmB) and 1.5% [95% CI: 0.7%-3.3%; = 0%] for L-AmB in a combination therapy. In East Africa (EA), corresponding estimates were 3.8% [95% CI: 1.3%-10.9%; = 75.8%] following pentavalent antimony (PA), and 13.0% [95% CI: 4.3%-33.6%; = 0%] for PA + paromomycin. From 21 studies with follow-up longer than 6-months, 0.6% [95% CI: 0.2%-1.8%; = 0%] of patients relapsed after 6-months and estimated 27.6% [95% CI: 11.2%-53.4%; = 12%] of relapses would have been missed by a 6-month follow-up.
INTERPRETATION
The estimated relapse proportion ranged from 0.5% to 4.5% in ISC and 3.8%-13.0% in EA with the currently recommended drugs. Over one-quarter of relapses would be missed with 6-months follow-up suggesting a longer follow-up may be warranted.
FUNDING
Wellcome Trust (ref: 208378/Z/17/Z).
PubMed: 38482151
DOI: 10.1016/j.lansea.2023.100317 -
Environmental Research May 2024Metalloestrogens are metals and metalloid elements with estrogenic activity found everywhere. Their impact on human health is becoming more apparent as human activities... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Metalloestrogens are metals and metalloid elements with estrogenic activity found everywhere. Their impact on human health is becoming more apparent as human activities increase.
OBJECTIVE
Our aim is to conduct a comprehensive systematic review and meta-analysis of observational studies exploring the correlation between metalloestrogens (specifically As, Sb, Cr, Cd, Cu, Se, Hg) and Gestational Diabetes Mellitus (GDM).
METHODS
PubMed, Web of Science, and Embase were searched to examine the link between metalloestrogens (As, Sb, Cr, Cd, Cu, Se, and Hg) and GDM until December 2023. Risk estimates were derived using random effects models. Subgroup analyses were conducted based on study countries, exposure sample, exposure assessment method, and detection methods. Sensitivity analyses and adjustments for publication bias were carried out to assess the strength of the findings.
RESULTS
Out of the 389 articles identified initially, 350 met our criteria and 33 were included in the meta-analysis, involving 141,175 subjects (9450 cases, 131,725 controls). Arsenic, antimony, and copper exposure exhibited a potential increase in GDM risk to some extent (As: OR = 1.28, 95 % CI [1.08, 1.52]; Sb: OR = 1.73, 95 % CI [1.13, 2.65]; Cu: OR = 1.29, 95 % CI [1.02, 1.63]), although there is a high degree of heterogeneity (As: Q = 52.93, p < 0.05, I = 64.1 %; Sb: Q = 31.40, p < 0.05, I = 80.9 %; Cu: Q = 21.14, p < 0.05, I = 71.6 %). Conversely, selenium, cadmium, chromium, and mercury exposure did not exhibit any association with the risk of GDM in our study.
DISCUSSION
Our research indicates that the existence of harmful metalloestrogens in the surroundings has a notable effect on the likelihood of GDM. Hence, we stress the significance of environmental elements in the development of GDM and the pressing need for relevant policies and measures.
Topics: Pregnancy; Female; Humans; Diabetes, Gestational; Cadmium; Copper; Arsenic; Mercury; Observational Studies as Topic
PubMed: 38307186
DOI: 10.1016/j.envres.2024.118321 -
PloS One 2023Leishmania aethiopica is a unique species that causes cutaneous leishmaniasis (CL), and studies evaluating treatment outcomes for this condition reported inconsistent... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Leishmania aethiopica is a unique species that causes cutaneous leishmaniasis (CL), and studies evaluating treatment outcomes for this condition reported inconsistent findings. This study aimed to summarize the evidence on treatment outcomes of CL caused by L. aethiopica to support decisions or propose further study.
METHODS
We searched PubMed, Scopus, and ScienceDirect. In addition, we searched grey literature on Google Scholar and performed manual searching on the reference list of articles. Two authors did the screening, selection, critical appraisal, and data extraction. With the narrative synthesis of evidence, we performed a random effects model meta-analysis using the metaprop package in Stata 17. We did sensitivity and subgroup analyses after assessing heterogeneity using the I-squared test and forest plots. The funnel plot and Egger's test were used to assess publication bias.
RESULTS
The review included 22 studies with 808 participants, and the meta-analysis included seven studies with 677 participants. Most studies documented treatment outcomes with antimonial monotherapy, and only one study reported outcomes with combination therapy. The overall pooled proportion of cure was 63% (95% CI: 38-86%). In the subgroup analysis, systemic antimonial monotherapy showed a cure rate of 61%, and the proportion of cure was 87% with topical therapy. Topical therapy showed a better cure for the localized clinical phenotype. A cohort study documented a cure rate of 94.8% with combination therapy for the localized, mucocutaneous, and diffuse clinical phenotypes. The pooled proportion of unfavourable outcomes was partial response (19%), relapse (17%), discontinuation (19%), and unresponsiveness (6%).
CONCLUSIONS
The pooled proportion of cure is low with antimonial monotherapy. Despite limited evidence, combination therapies are a promising treatment option for all clinical phenotypes of CL caused by L. aethiopica. Future high-quality randomized control trials are needed to identify effective monotherapies and evaluate the effectiveness of combination therapies.
Topics: Humans; Leishmania; Cohort Studies; Leishmaniasis, Cutaneous; Treatment Outcome; Combined Modality Therapy
PubMed: 37917604
DOI: 10.1371/journal.pone.0293529 -
International Journal of Sports Medicine Mar 2024The objective of this systematic review with meta-analysis was to compare the endurance performance chronic adaptations induced by running-based high-intensity interval... (Meta-Analysis)
Meta-Analysis
The objective of this systematic review with meta-analysis was to compare the endurance performance chronic adaptations induced by running-based high-intensity interval training (HIIT), small-sided games (SSGs), and combined HIIT+SSGs in male and female youth and adult soccer players. The studies included in this review followed the PICOS criteria: (i) healthy soccer players; (ii) interventions based on SSGs; (iii) comparators exposed to only HIIT or combined SSGs+HIIT; (iv) endurance performance variables. Studies were searched for in the following databases: (i) PubMed; (ii) Scopus; (iii) SPORTDiscus; (iv) Web of Science. After conducting an initial database search that retrieved a total of 5,389 records, a thorough screening process resulted in the inclusion of 20 articles that met the eligibility criteria. Sixteen studies reported outcomes related to endurance performance measured through field-based tests, while five studies provided results from direct measurements of maximal oxygen uptake (VO2max). Results showed a non-significant small-magnitude favoring effect for the HIIT groups compared to the SSG groups (ES=0.37, 0.074) for endurance, while a non-significant small-magnitude favoring SSGs was observed (ES=-0.20, 0.303) for VO2max. Despite the very low certainty of evidence, the findings suggest similar effects induced by both SSG and HIIT on improving endurance performance and VO2max.
Topics: Adult; Adolescent; Humans; Female; Male; High-Intensity Interval Training; Soccer; Nutritional Status; Antimony Sodium Gluconate; Running
PubMed: 37678559
DOI: 10.1055/a-2171-3255 -
Environmental Monitoring and Assessment May 2023Antimony (Sb) has been classified as a high-priority contaminant in the environment. Sb contamination resulting from the use of antimony-containing compounds in industry... (Review)
Review
Antimony (Sb) has been classified as a high-priority contaminant in the environment. Sb contamination resulting from the use of antimony-containing compounds in industry necessitates the development of efficient methods to remove it from water and wastewater. Adsorption is a highly efficient and reliable method for pollutants removal owing to its availability, recyclability, and low cost. Recently, carbonaceous materials and their applications for the removal of Sb from the aqueous matrices have received special attention worldwide. Herein, this review systematically summarizes the occurrence and exposure of Sb in the environment and on human health, respectively. Different carbon-based adsorbents have been classified for the adsorptive removal of Sb and their adsorption characteristics have been delineated. Recent development in the adsorption performance of the adsorbent materials for improving the Sb removal from the aqueous medium has been outlined. Further, to develop an understanding of the effect of different parameters like pH, competitive ions, and dissolved ions for Sb adsorption and subsequent removal have been discussed. A retrospective analysis of literature was conducted to present the adsorption behavior and underlying mechanisms involved in the removal of Sb using various adsorbents. Moreover, this study has identified emerging research gaps and emphasized the need for developing modified/engineered carbonaceous adsorbents to enhance Sb adsorption from various aqueous matrices.
Topics: Humans; Water; Wastewater; Antimony; Carbon; Retrospective Studies; Water Pollutants, Chemical; Environmental Monitoring; Adsorption
PubMed: 37248306
DOI: 10.1007/s10661-023-11322-6 -
ACS Infectious Diseases Mar 2023Leishmaniasis is an infectious disease responsible for a huge rate of morbidity and mortality in humans. Chemotherapy consists of the use of pentavalent antimonial,... (Review)
Review
Leishmaniasis is an infectious disease responsible for a huge rate of morbidity and mortality in humans. Chemotherapy consists of the use of pentavalent antimonial, amphotericin B, pentamidine, miltefosine, and paromomycin. However, these drugs are associated with some drawbacks such as high toxicity, administration by parenteral route, and most seriously the resistance of some strains of the parasite to them. Several strategies have been used to increase the therapeutic index and reduce the toxic effects of these drugs. Among them, the use of nanosystems that have great potential as a site-specific drug delivery system stands out. This review aims to compile results from studies that were carried out using first- and second-line antileishmanial drug-carrying nanosystems. The articles referred to here were published between 2011 and 2021. This study shows the promise of effective applicability of drug-carrying nanosystems in the field of antileishmanial therapeutics, with the perspective of providing better patient adherence to treatment, increased therapeutic efficacy, reduced toxicity of conventional drugs, as well as the potential to efficiently improve the treatment of leishmaniasis.
Topics: Humans; Pharmaceutical Preparations; Antiprotozoal Agents; Leishmaniasis; Pentamidine; Paromomycin
PubMed: 36795604
DOI: 10.1021/acsinfecdis.2c00632 -
Current Environmental Health Reports Dec 2022In epidemiologic studies, biomarkers are the best possible choice to assess individual exposure to toxic metals since they integrate all exposure sources. However,... (Review)
Review
Validity of Geolocation and Distance to Exposure Sources from Geographical Information Systems for Environmental Monitoring of Toxic Metal Exposures Based on Correlation with Biological Samples: a Systematic Review.
PURPOSE OF REVIEW
In epidemiologic studies, biomarkers are the best possible choice to assess individual exposure to toxic metals since they integrate all exposure sources. However, measuring biomarkers is not always feasible, given potential budgetary and time constraints or limited availability of samples. Alternatively, approximations to individual metal exposure obtained from geographic information systems (GIS) have become popular to evaluate diverse metal-related health outcomes. Our objective was to conduct a systematic review of epidemiological studies that evaluated the validity of GIS-based geolocation and distance to pollutant sources as an approximation of individual metal exposure based on correlation with biological samples.
RECENT FINDINGS
We considered 11 toxic metals: lead (Pb), cadmium (Cd), antimony (Sb), aluminum (Al), arsenic (As), chromium (Cr), nickel (Ni), mercury (Hg), tungsten (W), uranium (U), and vanadium (V). The final review included 12 manuscripts which included seven metals (Pb, Cd, Al, As, Cr, Hg, and Ni). Many studies used geolocation of the individuals to compare exposed (industrial, urban, agricultural, or landfill sources) and unexposed areas and not so many studies used distance to a source. For all metals, except lead, there was more animal than human biosampling to conduct biological validation. We observed a trend towards higher levels of Cd, Cr, Hg, and Pb in biosamples collected closer to exposure sources, supporting that GIS-based proxies for these metals might approximate individual exposure. However, given the low number and heterogeneity of the retrieved studies, the accumulated evidence is, overall, not sufficient. Given the practical benefits and potential of modern GIS technologies, which allow environmental monitoring at a reasonable cost, additional validation studies that include human biosampling are needed to support the use of GIS-based individual exposure measures in epidemiologic studies.
Topics: Humans; Geographic Information Systems; Cadmium; Environmental Monitoring
PubMed: 36447111
DOI: 10.1007/s40572-022-00383-3 -
Chemosphere Feb 2023The various ingredients and impurities that can be detected within tattoo inks have been associated with a myriad of dermatologic complications. Legislation regarding... (Meta-Analysis)
Meta-Analysis Review
The various ingredients and impurities that can be detected within tattoo inks have been associated with a myriad of dermatologic complications. Legislation regarding these antigenic substances varies widely around the world, with Europe serving as both the research and regulatory center on these intradermal formulations. Although industry is said to be moving away from metallic and metalloid pigments in exchange for organic or organometallic dyes, surveys of commercially available inks continue to detect these elements at concentrations considered unsafe for application into the dermis. In order to better assess the formulation and safety of tattoo ink, we present a systematic review and meta-analysis of studies quantifying restricted metals and metalloids in commercially available tattoo ink products. Among the papers selected, inconsistencies were noted in the degree of specificity by which ink products were identified and the elements sampled for. In addition, the analytical targets' valency and/or solubility were not always considered in accordance with regulation criteria. Of note, chromium, by total content and that of its regulated +6 valency, exceeded its maximum allowed concentration in nearly every sample tested. Total copper content exceeded the limit for soluble copper in half of inks sampled. In descending order, concentrations of cadmium, barium, mercury, soluble copper, arsenic, zinc, antimony, and lead violated regulations in one-sixth or fewer of samples tested. Cobalt and tin levels never violated regulation. Overall, our findings indicate that unsafe levels of restricted elements continue to be detected across studies, warranting further investigation under a regulatory lens.
Topics: Tattooing; Ink; Copper; Metalloids; Metals; Coloring Agents
PubMed: 36436582
DOI: 10.1016/j.chemosphere.2022.137291