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The American Journal of Tropical... Aug 2023Little is known about the adverse health, economic, and social impacts of substandard and falsified medicines (SFMs). This systematic review aimed to identify the...
Little is known about the adverse health, economic, and social impacts of substandard and falsified medicines (SFMs). This systematic review aimed to identify the methods used in studies to measure the impact of SFMs in low- and middle-income countries (LMICs), summarize their findings, and identify gaps in the reviewed literature. A search of eight databases for published papers, and a manual search of references in the relevant literature were conducted using synonyms of SFMs and LMICs. Studies in the English language that estimated the health, social, or economic impacts of SFMs in LMICs published before June 17, 2022 were considered eligible. Search results generated 1,078 articles, and 11 studies were included after screening and quality assessment. All included studies focused on countries in sub-Saharan Africa. Six studies used the Substandard and Falsified Antimalarials Research Impact model to estimate the impact of SFMs. This model is an important contribution. However, it is technically challenging and data demanding, which poses challenges to its adoption by national academics and policymakers alike. The included studies estimate that substandard and falsified antimalarial medicines can account from 10% to ∼40% of total annual malaria costs, and SFMs affect rural and poor populations disproportionately. Evidence on the impact of SFMs is limited in general and nonexistent regarding social outcomes. Further research needs to focus on practical methods that can serve local authorities without major investments in terms of technical capacity and data collection.
Topics: Humans; Counterfeit Drugs; Developing Countries; Social Change; Antimalarials; Malaria
PubMed: 37339762
DOI: 10.4269/ajtmh.22-0525 -
Fundamental & Clinical Pharmacology Jun 2024Benzothiazole derivatives have been reported to possess a wide range of biological activities, including antimalarial activity. This systematic review aims to summarize... (Review)
Review
BACKGROUND
Benzothiazole derivatives have been reported to possess a wide range of biological activities, including antimalarial activity. This systematic review aims to summarize and evaluate the antimalarial activities of benzothiazole analogs.
METHODS
We conducted an electronic search using nine databases in October 2017 and subsequently updated in September 2022. We included all original in vitro and in vivo studies that documented the antimalarial activities of compounds containing benzothiazole analogs with no restriction. The risk of bias of each included study was assessed by ToxRTool.
RESULTS
Twenty-eight articles were included in our study, which are in vitro, in vivo, or both. Of these, 232 substances were identified to have potent antiplasmodial activity against various strains of the malaria parasite. Benzothiazole analogs show different antimalarial mechanisms, including inhibition of Plasmodium falciparum enzymes in in vitro studies and inhibition of blood parasites in in vivo studies.
CONCLUSIONS
Benzothiazole derivatives are promising substances for treating malaria. The structure-activity relationship studies suggest that the substitution pattern of the benzothiazole scaffold plays a crucial role in determining the antimalarial activity of the analog.
Topics: Antimalarials; Benzothiazoles; Plasmodium falciparum; Humans; Structure-Activity Relationship; Animals; Malaria
PubMed: 38146774
DOI: 10.1111/fcp.12974 -
Journal of Global Antimicrobial... Sep 2023Stenotrophomonas maltophilia (S. maltophilia), an opportunistic pathogen, causes infection in patients undergoing immunosuppressive therapy, mechanical ventilation, or... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Stenotrophomonas maltophilia (S. maltophilia), an opportunistic pathogen, causes infection in patients undergoing immunosuppressive therapy, mechanical ventilation, or catheters and in long-term hospitalized patients. Due to its extensive resistance to various antibiotics and chemotherapeutic agents, S. maltophilia is challenging to treat. Using case reports, case series, and prevalence studies, the current study provides a systematic review and meta-analysis of antibiotic resistance profiles across clinical isolates of S. maltophilia.
METHODS
A systematic literature search was performed for original research articles published in Medline, Web of Science, and Embase databases from 2000 to 2022. Statistical analysis was performed using STATA 14 software to report antibiotic resistance of S. maltophilia clinical isolates worldwide.
RESULTS
223 studies (39 case reports/case series and 184 prevalence studies) were collected for analysis. A meta-analysis of prevalence studies demonstrated that the most antibiotic resistance worldwide was to levofloxacin, trimethoprim-sulfamethoxazole (TMP/SMX), and minocycline (14.4%, 9.2%, and 1.4%, respectively). Resistance to TMP/SMX (36.84%), levofloxacin (19.29%), and minocycline (1.75%) were the most prevalent antibiotic resistance types found in evaluated case reports/case series studies. The highest resistance rate to TMP/SMX was reported in Asia (19.29%), Europe (10.52%), and America (7.01%), respectively.
CONCLUSION
Considering the high resistance to TMP/SMX, more attention should be paid to patients' drug regimens to prevent the emergence of multidrug-resistant S. maltophilia isolates.
Topics: Humans; Trimethoprim, Sulfamethoxazole Drug Combination; Levofloxacin; Minocycline; Stenotrophomonas maltophilia; Prevalence; Drug Resistance, Bacterial
PubMed: 36906172
DOI: 10.1016/j.jgar.2023.02.018 -
Journal of Oncology Pharmacy Practice :... Jul 2024This systematic review and meta-analysis aimed to determine the safety of liposomal amphotericin B (L-AMB) compared to other antifungal agents for secondary prophylaxis. (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
This systematic review and meta-analysis aimed to determine the safety of liposomal amphotericin B (L-AMB) compared to other antifungal agents for secondary prophylaxis.
METHOD
We conducted a comprehensive search across international databases and reference lists of articles to compile all relevant published evidence evaluating the efficacy and safety of L-AMB versus other antifungals (NLAMB) for secondary prophylaxis against invasive fungal infections. Pooled estimates were calculated after data transformation to evaluate mortality, breakthrough infections, and the frequency of adverse effects, including hypokalemia and nephrotoxicity. Comparisons of breakthrough fungal infection and mortality between the L-AMB and NLAMB groups were performed.
RESULT
We identified 10 studies. The cumulative frequency of patients using L-AMB was 148, compared to 341 patients in the NLAMB group. The mortality rates in the L-AMB and NLAMB groups were 10% and 0%, respectively. However, based on the odds ratio, the mortality in the L-AMB group was lower than that in the NLAMB group. No significant difference was observed in breakthrough invasive fungal infections between the L-AMB and NLAMB groups. The frequencies of nephropathy and hypokalemia in the L-AMB group were 36% and 18%, respectively.
CONCLUSION
Our findings indicate a lower incidence of mortality in the L-AMB group compared to the NLAMB group. No statistically significant difference was observed in the incidence of breakthrough infection between the two groups. L-AMB administration is associated with nephropathy and hypokalemia. However, the refusal to continue treatment due to adverse effects is not significantly high.
Topics: Amphotericin B; Humans; Antifungal Agents; Invasive Fungal Infections; Mycoses; Secondary Prevention; Hypokalemia
PubMed: 38720564
DOI: 10.1177/10781552241241317 -
PLoS Neglected Tropical Diseases Mar 2024Human brucellosis is a neglected, re-emerging, and endemic zoonosis in many countries. The debilitating and disabling potential of the disease is a warning about its... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Human brucellosis is a neglected, re-emerging, and endemic zoonosis in many countries. The debilitating and disabling potential of the disease is a warning about its morbidity, generating socioeconomic impact. This review aims to update the current evidence on the efficacy and safety of therapeutic options for human brucellosis using the network meta-analysis (NMA).
METHODOLOGY
A systematic search was conducted in four different databases by independent reviewers to assess overall therapy failure, adverse events, and time to defervescence associated with different therapies. Randomized clinical trials (RCTs) evaluating any therapeutic drug intervention were selected, excluding non-original studies or studies related to localized forms of the disease or with less than 10 participants. Data were analyzed by frequentist statistics through NMA by random effects model. The risk of bias and certainty of evidence was assessed, this review was registered at PROSPERO.
RESULTS
Thirty-one (31) RCTs involving 4167 patients were included. Three networks of evidence were identified to evaluate the outcomes of interest. Triple therapy with doxycycline + streptomycin + hydroxychloroquine for 42 days (RR: 0.08; CI 95% 0.01-0.76) had a lower failure risk than the doxycycline + streptomycin regimen. Doxycycline + rifampicin had a higher risk of failure than doxycycline + streptomycin (RR: 1.96; CI 95% 1.27-3.01). No significant difference was observed between the regimens when analyzing the incidence of adverse events and time to defervescence. In general, most studies had a high risk of bias, and the results had a very low certainty of evidence.
CONCLUSIONS
This review confirmed the superiority of drugs already indicated for treating human brucellosis, such as the combination of doxycycline and aminoglycosides. The association of hydroxychloroquine to the dual regimen was identified as a potential strategy to prevent overall therapy failure, which is subject to confirmation in future studies.
Topics: Humans; Doxycycline; Network Meta-Analysis; Hydroxychloroquine; Brucellosis; Streptomycin
PubMed: 38466771
DOI: 10.1371/journal.pntd.0012010 -
JAMA Dermatology May 2024Sulfamethoxazole (SMX) and cotrimoxazole (CTX), a fixed-dose combination of SMX and trimethoprim in a 5:1 ratio, are antibacterial sulfonamides commonly used for... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Sulfamethoxazole (SMX) and cotrimoxazole (CTX), a fixed-dose combination of SMX and trimethoprim in a 5:1 ratio, are antibacterial sulfonamides commonly used for treating various diseases. A substantial prevalence of severe cutaneous adverse reactions (SCARs) following the administration of these drugs has been reported. However, the association between human leukocyte antigen (HLA) genotypes and SMX/CTX-induced SCARs has remained unclear.
OBJECTIVE
To investigate the association between HLA genotypes and SMX/CTX-induced SCARs.
DATA SOURCES
A comprehensive search was conducted in CENTRAL (Cochrane Library), MEDLINE, and Embase from inception to January 17, 2023.
STUDY SELECTION
Case-control studies that recruited patients who had experienced SCARs following SMX or CTX were included, and HLA alleles were analyzed.
DATA EXTRACTION AND SYNTHESIS
Two independent authors extracted data on study characteristics and outcome data. The Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline and the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed. The Newcastle-Ottawa Scale for case-control studies was used to assess study quality. Odds ratios (ORs) were calculated using a random-effects model for meta-analysis.
MAIN OUTCOMES AND MEASURES
The prespecified outcome was the OR comparing SMX/CTX-induced SCARs with healthy or SMX/CTX-tolerant controls based on different HLA alleles.
RESULTS
Six studies involving 322 patients with SCAR were included, including 236 patients with Stevens-Johnson syndrome/toxic epidermal necrolysis, 86 with drug reaction with eosinophilia and systemic symptoms, 8448 healthy controls, and 229 tolerant controls. Significant associations were found in HLA-A*11:01 (OR, 2.10; 95% CI, 1.11-4.00), HLA-B*13:01 (OR, 5.96; 95% CI, 1.58-22.56), HLA-B*15:02 (OR, 2.23; 95% CI, 1.20-4.14), HLA-B*38:02 (OR, 3.47; 95% CI, 1.42-8.48), and HLA-C*08:01 (OR, 2.63; 95% CI, 1.07-6.44) compared with tolerant controls. In the Stevens-Johnson syndrome/toxic epidermal necrolysis subgroup, significant associations were found in HLA-B*15:02 (OR, 3.01; 95% CI, 1.56-5.80) and HLA-B*38:02 (OR, 5.13; 95% CI, 1.96-13.47). In the drug reaction with eosinophilia and systemic symptoms subgroup, significant associations were found in HLA-A*68:01 (OR, 12.86; 95% CI, 1.09-151.34), HLA-B*13:01 (OR, 23.09; 95% CI, 3.31-161.00), HLA-B*39:01 (OR, 4.56; 95% CI, 1.31-15.82).
CONCLUSIONS AND RELEVANCE
The results of this systematic review and meta-analysis suggest that multiple HLA alleles (HLA-A*11:01, HLA-B*13:01, HLA-B*15:02, HLA-B*38:02, and HLA-C*0801) are associated with SMX/CTX-induced SCARs.
Topics: Humans; Trimethoprim, Sulfamethoxazole Drug Combination; HLA Antigens; Drug Eruptions; Sulfamethoxazole; Genotype; Severity of Illness Index; Anti-Bacterial Agents; Case-Control Studies
PubMed: 38568509
DOI: 10.1001/jamadermatol.2024.0210 -
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 Pollution (Barking, Essex... Jan 2024As aluminum nanoparticles (Al-NPs) are widely used in our daily life and various industries, Al-NPs has been becoming an emerging pollution in the environment. The... (Review)
Review
As aluminum nanoparticles (Al-NPs) are widely used in our daily life and various industries, Al-NPs has been becoming an emerging pollution in the environment. The impact of this NP has been attracting more and more attention from the scientific communities. In this review, we systematically summarized the interactions, uptake, and transport of Al-NPs in the plant system. Al-NPs can enter plants through different pathways and accumulate in various tissues, leading to alter plant growth and development. Al-NPs also affected root, shoot, and leaf characteristics as well as changing nutrient uptake and distribution and inducing oxidative stress via excess reactive radical generation, thereby impairing plant defense systems. Additionally, Al-NPs altered gene expression, which involved in various signaling pathways and metabolic processes in plants, that further altered plants susceptible or tolerant to stressors. The review also emphasized the effects of Al-NP size, surface charge, concentration, and exposure duration on plant growth and development. In the future, more research should be focused on mechanisms underlying Al-NPs phytotoxicity and potential risk to humans and off-target species.
Topics: Humans; Aluminum; Plant Development; Artesunate; Biological Transport; Nanoparticles
PubMed: 37931678
DOI: 10.1016/j.envpol.2023.122875 -
The Cochrane Database of Systematic... Feb 2024Meibomian gland dysfunction (MGD) is the most common underlying cause of dry eye disease (DED). MGD leads to pathological alteration of the composition or quantity of... (Review)
Review
BACKGROUND
Meibomian gland dysfunction (MGD) is the most common underlying cause of dry eye disease (DED). MGD leads to pathological alteration of the composition or quantity of meibum, or both, which subsequently results in tear evaporation and the typical signs and symptoms associated with DED. The LipiFlow Thermal Pulsation System (LipiFlow) is a medical device used to treat MGD in office; however, it is unclear if LipiFlow can outperform other DED treatments.
OBJECTIVES
To evaluate the effectiveness of LipiFlow for treating DED signs and symptoms and the safety of LipiFlow compared with sham or other available treatments for MGD in adults.
SEARCH METHODS
The Cochrane Eyes and Vision Information Specialist searched the electronic databases for randomized controlled trials. There were no restrictions on language or date of publication. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, including the Cochrane Eyes and Vision Trials Register; 2022, Issue 6), MEDLINE Ovid, Embase.com, PubMed, LILACS (Latin American and Caribbean Health Science Information database), ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) electronic databases. We also examined the reference lists of identified trials, review articles, and guidelines for information about relevant trials that may not have been identified by our search strategy. We contacted investigators regarding ongoing trials. The last database search was performed on 24 October 2022.
SELECTION CRITERIA
We included studies conducted in adults (over 18 years of age) with DED or MGD as defined by the primary trial investigators. We imposed no restrictions on race, ethnicity, or sex. We considered trials involving contact lens wearers if they were equally represented between groups.
DATA COLLECTION AND ANALYSIS
We applied standard Cochrane methodology.
MAIN RESULTS
We included 13 trials that randomized a total of 1155 participants (28 to 236 participants randomized per study). Six trials were conducted in the USA, three in China, two in Thailand, one in France, and one in Italy. Eight trials were of single-center design, while four trials were of multicenter design; one trial did not report the number of participating centers. Study characteristics The study population of the included trials was 66% female (range 48% to 80%), with an age range of 19 to 86 years. LipiFlow, used as a stand-alone intervention, was compared with basic warm compresses in five studies, thermostatic device in five studies, oral intervention in one trial, and topical dry eye medications in one trial. LipiFlow was also evaluated together with eyelid hygiene product versus eyelid hygiene products alone in one trial. Findings Five trials compared LipiFlow with a basic warm compress applied for varying durations and frequencies during the trial period; only one of these trials combined a warm compress with eyelid massage. Analyzing symptom scores by different questionnaires (Ocular Surface Disease Index [OSDI] and Standard Patient Evaluation of Eye Dryness [SPEED]) yielded conflicting evidence of a difference in symptoms between LipiFlow and basic warm compresses after four weeks. There was no evidence of a difference in meibomian gland expression, meibum quality, or tear breakup time when comparing LipiFlow with basic warm compresses. Another five trials compared LipiFlow with thermostatic devices. Analysis of symptom scores at four weeks showed that thermostatic devices had reduced OSDI scores by a mean difference (MD) of 4.59 (95% confidence interval [CI] 1.23 to 7.95; I = 0, P = 0.007; 553 participants; very low certainty evidence) as compared with LipiFlow. When we compared LipiFlow plus eyelid hygiene with eyelid hygiene alone, there was no evidence of difference in signs or symptoms at any time point evaluated. Only one trial compared LipiFlow with a topical DED medication (lifitegrast 5%). The single-trial estimate suggested that 5% lifitegrast may increase meibomian gland expression scores compared with LipiFlow at day 42 (MD -1.21, 95% CI -2.37 to -0.05; 50 participants; low certainty evidence) by using a meibomian gland expression scale of 0 to 8. One trial compared LipiFlow with an oral intervention (doxycycline), finding that LipiFlow may result in significantly better SPEED scores than doxycycline at three months (MD -4.00, 95% CI -7.33 to -0.67; 24 participants; very low certainty evidence). No other significant differences in signs or symptoms were found between LipiFlow and doxycycline at three months. We did not find any other statistically significant differences in symptoms or signs for any other analysis performed in this review at the one- to four-week time point. Adverse events No trial reported any intervention-related, vision-threatening adverse events.
AUTHORS' CONCLUSIONS
LipiFlow performs similarly to other commonly used DED treatments with regard to DED signs and symptoms. The best available evidence was deemed to have a high level of bias, leading to low or very low certainty evidence. Additional research with adequate masking, a standardized testing methodology, and a sample representative of the MGD population is therefore needed before any firm conclusions can be drawn regarding comparative benefits and harms.
Topics: Adult; Humans; Female; Adolescent; Young Adult; Middle Aged; Aged; Aged, 80 and over; Male; Doxycycline; Dry Eye Syndromes; Meibomian Gland Dysfunction; China; Multicenter Studies as Topic; Phenylalanine; Sulfones
PubMed: 38314898
DOI: 10.1002/14651858.CD015448.pub2 -
Contact Lens & Anterior Eye : the... Jun 2024Demodex blepharitis, often overlooked in ocular surface disease, involves Demodex mites, prevalent ectoparasites on human skin. Current treatments may not effectively... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Demodex blepharitis, often overlooked in ocular surface disease, involves Demodex mites, prevalent ectoparasites on human skin. Current treatments may not effectively eliminate these mites, prompting a need for targeted therapies. Lotilaner, an antiparasitic agent, shows promise. This systematic review and meta-analysis assesses 0.25% lotilaner ophthalmic solution's efficacy in reducing Demodex mite populations and its impact on ocular surface inflammation in Demodex blepharitis patients.
METHODS
A comprehensive literature search was performed in the PubMed and Cochrane Library databases from inception until February 2024 to identify relevant trials investigating the use of lotilaner in patients with Demodex blepharitis. The included studies were assessed for quality, and a meta-analysis was conducted to determine the overall treatment effects of lotilaner. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated for binary variables. All statistical analyses were performed using the R Statistical Software.
RESULTS
Five studies met the inclusion criteria and were included in this systematic review and meta-analysis. Lotilaner demonstrated significant efficacy in Collarette Cure [OR = 6.64; 95 % CI 3.78 to 11.04; p < 0.00001, I = 62 %] %], clinically meaningful collarette reduction [OR = 6.21; 95 % CI 3.67 to 10.49; p < 0.00001, I = 90 %], and achieving at least 1-grade collarette improvement [OR = 5.12; 95 % CI (2.96 to 8.88); p < 0.00001, I = 90 %] compared to the placebo group. The treatment also resulted in mite eradication [OR = 6.18; 95 % CI 4.67 to 6.18; p < 0.00001, I = 34 %], reduction in mite density [OR = 9.37; 95 % CI 5.36 to 16.36; p < 0.00001, I = 84 %], and erythema cure [OR = 2.29; 95 % CI 2.24 to 3.39; p < 0.00001, I = 5 %] and composite cure [OR = 7.05; 95 % CI 3.66 13. 61; p < 0.00001, I = 11 %]. The study suggests that lotilaner is a promising therapeutic option for collarette and associated symptoms, but the high heterogeneity in some outcomes and limited long-term data warrant further research to confirm its effectiveness and safety.
CONCLUSION
This systematic review and meta-analysis provides robust evidence supporting the efficacy of 0.25% lotilaner ophthalmic solution in treating Demodex blepharitis. Approval of this targeted therapy represents a significant milestone in ophthalmology and offers a promising treatment option for patients with Demodex blepharitis. Eye care professionals should consider the potential benefits of lotilaner in managing and alleviating the symptoms associated with Demodex infestations on the eyelids. Further research and long-term follow-up studies are warranted to assess the safety and effectiveness of lotilaner in treating Demodex blepharitis.
Topics: Blepharitis; Mite Infestations; Randomized Controlled Trials as Topic; Humans; Animals; Eye Infections, Parasitic; Ophthalmic Solutions; Mites; Treatment Outcome; Antiparasitic Agents
PubMed: 38514290
DOI: 10.1016/j.clae.2024.102148