Validation of the Spanish version of the Pediatric Asthma Severity Score (PASS) in a population of Hispanic children.

BACKGROUND: The Pediatric Asthma Severity Score (PASS) is one of the most-used clinical scoring systems for assessing the severity of asthma exacerbations in children. The aim of the present study was to validate a Spanish version of the PASS in a population of Hispanic children with asthma exacerbations living in urban Bogota, Colombia. METHODS: In a prospective cohort and a validation study, parents/caregivers of children between 2 and 18 years old attended in the emergency department (ED) with asthma exacerbations who were admitted to the inpatient unit were invited to participate in the study. During the hospitalization period, we gathered the necessary data for assessing the criterion validity (comparing its score with the Pediatric Respiratory Assessment Measure [PRAM]), construct validity, interrater reliability, responsiveness, and internal consistency of the Col-PASS, the Colombian version of the PASS. RESULTS: At baseline, the scores of the Col-PASS correlated positively with the scores of the PRAM score (ρ = 0.588, p < .001). The baseline Col-PASS scores in patients who required admission to a more complex service were significantly higher than those in patients who presented clinical improvement (1.0 (0.0-2.0) vs. 0.0 (0.0-0.0), p < .001). The interrater reliability was found to be κ = 0.897, 95% CI 0.699-1.000, p < .001. Cronbach's α was .701 for the questionnaire as a whole. CONCLUSION: The Col-PASS has excellent construct validity, adequate criterion validity, interrater reliability, responsiveness; and acceptable internal consistency when used in children between 2 and 18 years old with asthma exacerbations.

Prevalence of nutritional risk and malnutrition in hospitalized patients: a retrospective, cross-sectional study of single-day screening.

Hospital malnutrition remains a significant public health issue, particularly in developing countries. The Global Leadership Initiative on Malnutrition (GLIM) proposed homogenizing criteria to standardize malnutrition diagnosis. This study aimed to retrospectively determine the prevalence of nutritional risk and malnutrition diagnoses among hospitalized patients using the Nutritional Risk Screening (NRS)-2002 screening instrument and the GLIM criteria, respectively. We conducted a retrospective, cross-sectional study from nutritional records of patients hospitalized in a single centre 2021. Nutrition data from records included medical diagnosis, gender, length of stay, age, weight, height, body mass index, weight loss, calf circumference, and middle upper arm circumference. Nutritional risk and malnutrition were evaluated using NRS-2002 and GLIM criteria. Its concordance was further evaluated by using a Kappa test. The study included 616 records of patients; 52.3% (n = 322) of the population were male. The prevalence of nutritional risk, according to NRS-2002, was 69.5% (n = 428). Nutritional risk as well as malnutrition diagnosis according to GLIM criteria was observed in 87.8% (n = 374) of patienttritional risk and malnutrition were evaluated using NRS-2002 and GLIM criteria. Its concordance was further evaluated by using a Kappa test. Ws. Tools showed a strong concordance (κ= 0.732). All anthropometric data, except for height, were found to be significantly different between patients with moderate and severe malnutrition (p < 0.05). Our findings highlight a high prevalence of malnutrition in this group of hospitalized patients in Mexico. NRS-2002 demonstrated good agreement with the diagnosis of malnutrition according to GLIM criteria and could be considered part of the straightforward two-step approach for malnutrition; however, further studies are needed.

A λ-dynamics investigation of insulin Wakayama and other A3 variant binding affinities to the insulin receptor.

Insulin Wakayama is a clinical insulin variant where a conserved valine at the third residue on insulin's A chain (ValA3) is replaced with a leucine (LeuA3), impairing insulin receptor (IR) binding by 140-500 fold. This severe impact on binding from such a subtle modification has posed an intriguing problem for decades. Although experimental investigations of natural and unnatural A3 mutations have highlighted the sensitivity of insulin-IR binding to minor changes at this site, an atomistic explanation of these binding trends has remained elusive. We investigate this problem computationally using λ-dynamics free energy calculations to model structural changes in response to perturbations of the ValA3 side chain and to calculate associated relative changes in binding free energy (ΔΔGbind). The Wakayama LeuA3 mutation and seven other A3 substitutions were studied in this work. The calculated ΔΔGbind results showed high agreement compared to experimental binding potencies with a Pearson correlation of 0.88 and a mean unsigned error of 0.68 kcal/mol. Extensive structural analyses of λ-dynamics trajectories revealed that critical interactions were disrupted between insulin and the insulin receptor as a result of the A3 mutations. This investigation also quantifies the effect that adding an A3 Cδ atom or losing an A3 Cγ atom has on insulin's binding affinity to the IR. Thus, λ-dynamics was able to successfully model the effects of subtle modifications to insulin's A3 side chain on its protein-protein interactions with the IR and shed new light on a decades-old mystery: the exquisite sensitivity of hormone-receptor binding to a subtle modification of an invariant insulin residue.

Erratum: Altered gene expression linked to germline dysfunction following exposure to DEET.

[This corrects the article DOI: 10.1016/j.isci.2023.108699.].

Effects of ultrafiltration membrane processing on the metabolic and sensory profiles of coffee extracts.

In the coffee industry, the use of natural coffee extracts with differentiated attributes is desirable to drive new product development. This study evaluates the impact of ultrafiltration membrane processing on the sensory, metabolic, and physicochemical attributes of four commercially available coffee extracts: cold brew, lightly roasted, freeze concentrated and evaporated standard. The sensory analysis revealed an increase in acidity in the permeate across all extracts, with the most significant profile changes observed in the lightly roasted evaporated and evaporated extracts, accompanied by an enhancement of fruity and floral attributes. Furthermore, the permeate showed reduced total dissolved solids, while the caffeine concentration increased. Metabolomic analysis highlighted key coffee-related metabolites like cinnamic and coumaric acids, explaining observed variations due to their passage through the membrane. Our findings emphasize the potential of permeate as a coffee-based ingredient for ready-to-drink products development, providing a unique coffee experience with organoleptic profiles distinct from traditional beverages.

Urinary metabolomic profiling of a cohort of Colombian patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune and multisystem disease with a high public health impact. Lupus nephritis (LN), commonly known as renal involvement in SLE, is associated with a poorer prognosis and increased rates of morbidity and mortality in patients with SLE. Identifying new urinary biomarkers that can be used for LN prognosis or diagnosis is essential and is part of current active research. In this study, we applied an untargeted metabolomics approach involving liquid and gas chromatography coupled with mass spectrometry to urine samples collected from 17 individuals with SLE and no kidney damage, 23 individuals with LN, and 10 clinically healthy controls (HCs) to identify differential metabolic profiles for SLE and LN. The data analysis revealed a differentially abundant metabolite expression profile for each study group, and those metabolites may act as potential differential biomarkers of SLE and LN. The differential metabolic pathways found between the LN and SLE patients with no kidney involvement included primary bile acid biosynthesis, branched-chain amino acid synthesis and degradation, pantothenate and coenzyme A biosynthesis, lysine degradation, and tryptophan metabolism. Receiver operating characteristic curve analysis revealed that monopalmitin, glycolic acid, and glutamic acid allowed for the differentiation of individuals with SLE and no kidney involvement and individuals with LN considering high confidence levels. While the results offer promise, it is important to recognize the significant influence of medications and other external factors on metabolomics studies. This impact has the potential to obscure differences in metabolic profiles, presenting a considerable challenge in the identification of disease biomarkers. Therefore, experimental validation should be conducted with a larger sample size to explore the diagnostic potential of the metabolites found as well as to examine how treatment and disease activity influence the identified chemical compounds. This will be crucial for refining the accuracy and effectiveness of using urine metabolomics for diagnosing and monitoring lupus and lupus nephritis.

Genetic and physical interactions reveal overlapping and distinct contributions to meiotic double-strand break formation in C. elegans.

Double-strand breaks (DSBs) are the most deleterious lesions experienced by our genome. Yet, DSBs are intentionally induced during gamete formation to promote the exchange of genetic material between homologous chromosomes. While the conserved topoisomerase-like enzyme Spo11 catalyzes DSBs, additional regulatory proteins-referred to as "Spo11 accessory factors"- regulate the number, timing, and placement of DSBs during early meiotic prophase ensuring that SPO11 does not wreak havoc on the genome. Despite the importance of the accessory factors, they are poorly conserved at the sequence level suggesting that these factors may adopt unique functions in different species. In this work, we present a detailed analysis of the genetic and physical interactions between the DSB factors in the nematode Caenorhabditis elegans providing new insights into conserved and novel functions of these proteins. This work shows that HIM-5 is the determinant of X-chromosome-specific crossovers and that its retention in the nucleus is dependent on DSB-1, the sole accessory factor that interacts with SPO-11. We further provide evidence that HIM-5 coordinates the actions of the different accessory factors sub-groups, providing insights into how components on the DNA loops may interact with the chromosome axis.

Biomimetic Platelet-Cloaked Nanoparticles for the Delivery of Anti-Inflammatory Curcumin in the Treatment of Atherosclerosis.

Atherosclerosis still represents a major driver of cardiovascular diseases worldwide. Together with accumulation of lipids in the plaque, inflammation is recognized as one of the key players in the formation and development of atherosclerotic plaque. Systemic anti-inflammatory treatments are successful in reducing the disease burden, but are correlated with severe side effects, underlining the need for targeted formulations. In this work, curcumin is chosen as the anti-inflammatory payload model and further loaded in lignin-based nanoparticles (NPs). The NPs are then coated with a tannic acid (TA)- Fe (III) complex and further cloaked with fragments derived from platelet cell membrane, yielding NPs with homogenous size. The two coatings increase the interaction between the NPs and cells, both endothelial and macrophages, in steady state or inflamed status. Furthermore, NPs are cytocompatible toward endothelial, smooth muscle and immune cells, while not inducing immune activation. The anti-inflammatory efficacy is demonstrated in endothelial cells by real-time quantitative polymerase chain reaction and ELISA assay where curcumin-loaded NPs decrease the expression of Nf-κb, TGF-ß1, IL-6, and IL-1ß in lipopolysaccharide-inflamed cells. Overall, due to the increase in the cell-NP interactions and the anti-inflammatory efficacy, these NPs represent potential candidates for the targeted anti-inflammatory treatment of atherosclerosis.

Music Therapy Intervention to Reduce Symptom Burden in Hospice Patients: A Descriptive Study.

Background: Music therapy (MT) offers benefits of improved symptom relief and quality of life at the end of life, but its impact on hospice patients and caregivers needs more research. Objective: To assess the impact of MT intervention on symptom burden and well-being of hospice patients and caregivers. Methods: A total of 18 hospice patients, selected based on scores ≥4 on the revised Edmonton Symptom Assessment System (ESAS-r) items on pain, depression, anxiety, or well-being, participated in MT sessions provided by a board-certified music therapist. Over a period of 2-3 weeks, 3-4 MT sessions were conducted for each. Patient Quality of life (QOL) was assessed using the Linear Analogue Self-Assessment (LASA). Depression and anxiety were measured with the Patient Health Questionnaire-4 (PHQ-4). For the 7 caregivers enrolled, stress levels were measured using the Pearlin role overload measure and LASA. Results: Patients reported a reduction in symptom severity and emotional distress and an increase in QOL. All patients endorsed satisfaction with music therapy, describing it as particularly beneficial for stress relief, relaxation, spiritual support, emotional support, and well-being. Scores on overall QOL and stress were worse for caregivers. Conclusion: This study provides evidence that MT reduces symptom burden and enhances the quality of life for hospice patients. Hospice patients and their caregivers endorsed satisfaction with MT. Given the benefits observed, integrating MT into hospice care regimens could potentially improve patient and caregiver outcomes. Larger studies should be conducted to better assess the impact of MT in this population.

Major alteration of Lung Microbiome and the Host Reaction in critically ill COVID-19 Patients with high viral load.

Background: Patients with COVID-19 under invasive mechanical ventilation are at higher risk of developing ventilator-associated pneumonia (VAP), associated with increased healthcare costs, and unfavorable prognosis. The underlying mechanisms of this phenomenon have not been thoroughly dissected. Therefore, this study attempted to bridge this gap by performing a lung microbiota analysis and evaluating the host immune responses that could drive the development of VAP. Materials and methods: In this prospective cohort study, mechanically ventilated patients with confirmed SARS-CoV-2 infection were enrolled. Nasal swabs (NS), endotracheal aspirates (ETA), and blood samples were collected initially within 12 hours of intubation and again at 72 hours post-intubation. Plasma samples underwent cytokine and metabolomic analyses, while NS and ETA samples were sequenced for lung microbiome examination. The cohort was categorized based on the development of VAP. Data analysis was conducted using RStudio version 4.3.1. Results: In a study of 36 COVID-19 patients on mechanical ventilation, significant differences were found in the nasal and pulmonary microbiome, notably in Staphylococcus and Enterobacteriaceae, linked to VAP. Patients with VAP showed a higher SARS-CoV-2 viral load, elevated neutralizing antibodies, and reduced inflammatory cytokines, including IFN-δ, IL-1ß, IL-12p70, IL-18, IL-6, TNF-α, and CCL4. Metabolomic analysis revealed changes in 22 metabolites in non-VAP patients and 27 in VAP patients, highlighting D-Maltose-Lactose, Histidinyl-Glycine, and various phosphatidylcholines, indicating a metabolic predisposition to VAP. Conclusions: This study reveals a critical link between respiratory microbiome alterations and ventilator-associated pneumonia in COVID-19 patients, with elevated SARS-CoV-2 levels and metabolic changes, providing novel insights into the underlying mechanisms of VAP with potential management and prevention implications.

Predicting and Preventing Gun Violence: An Experimental Evaluation of READI Chicago.

Gun violence is the most pressing public safety problem in American cities. We report results from a randomized controlled trial (N=2,456) of a community-researcher partnership called the Rapid Employment and Development Initiative (READI) Chicago. The program offered an 18-month job alongside cognitive behavioral therapy and other social support. Both algorithmic and human referral methods identified men with strikingly high scope for gun violence reduction: for every 100 people in the control group, there were 11 shooting and homicide victimizations during the 20-month outcome period. Fifty-five percent of the treatment group started programming, comparable to take-up rates in programs for people facing far lower mortality risk. After 20 months, there is no statistically significant change in an index combining three measures of serious violence, the study's primary outcome. Yet there are signs that this program model has promise. One of the three measures, shooting and homicide arrests, declines 65 percent (p=0.13 after multiple testing adjustment). Because shootings are so costly, READI generates estimated social savings between $182,000 and $916,000 per participant (p=0.03), implying a benefit-cost ratio between 4:1 and 18:1. Moreover, participants referred by outreach workers-a pre-specified subgroup-show enormous declines in both arrests and victimizations for shootings and homicides (79 and 43 percent, respectively) that remain statistically significant even after multiple testing adjustments. These declines are concentrated among outreach referrals with higher predicted risk, suggesting that human and algorithmic targeting may work better together.

The repeatability of periodontal imaging with intraoral ultrasound scanning.

OBJECTIVE: Ultrasound is a non-invasive and low-cost diagnostic tool widely used in medicine. Recent studies have demonstrated that ultrasound imaging might have the potential to be used intraorally to assess the periodontium by comparing it to current imaging methods. This study aims to characterize the repeatability of intraoral periodontal ultrasound imaging. MATERIALS AND METHODS: Two hundred and twenty-three teeth were scanned from fourteen volunteers participating in this study. One operator conducted all the scans in each tooth thrice with a 20 MHz intraoral ultrasound. The repeatability of three measurements, alveolar bone crest to the cementoenamel junction (ABC-CEJ), gingival thickness (GT), and alveolar bone thickness (ABT), was calculated with intercorrelation coefficient (ICC). Measurements were also compared with mean absolute deviation (MAD), repeatability coefficient (RC), and descriptive statistics. RESULTS: ICC scores for intra-rater repeatability were 0.917(0.897,0.933), 0.849(0.816,0.878), and 0.790(0.746,0.898), MAD results were 0.610 mm (± 0.508), 0.224 (± 0.200), and 0.067 (± 0.060), and RC results were 0.648, 0.327, and 0.121 for ABC-CEJ, GT, and ABT measurements, respectively. CONCLUSION: Results of the present study pointed towards good or excellent repeatability of ultrasound as a measurement tool for periodontal structures. CLINICAL RELEVANCE: Clinicians could benefit from the introduction of a novel chairside diagnostic tool. Ultrasound is a non-invasive imaging assessment tool for the periodontium with promising results in the literature. Further validation, establishment of scanning protocols, and commercialization are still needed before ultrasound imaging is available for clinicians.

Altered gene expression linked to germline dysfunction following exposure of Caenorhabditis elegans to DEET.

N,N-diethyl-meta-toluamide (DEET) is a commonly used synthetic insect repellent. Although the neurological effects of DEET have been widely investigated, its effects on the germline are less understood. Here, we show that exposure of the nematode Caenorhabditis elegans, which is highly predictive of mammalian reprotoxicity, resulting in internal DEET levels within the range detected in human biological samples, causes activation of p53/CEP-1-dependent germ cell apoptosis, altered meiotic recombination, chromosome abnormalities, and missegregation. RNA-sequencing analysis links DEET-induced alterations in the expression of genes related to redox processes and chromatin structure to reduced mitochondrial function, impaired DNA double-strand break repair progression, and defects during early embryogenesis. We propose that Caenorhabditis elegans exposure to DEET interferes with gene expression, leading to increased oxidative stress and altered chromatin structure, resulting in germline effects that pose a risk to reproductive health.

Gut microbiome alpha diversity decreases in relation to body weight, antibiotic exposure, and infection with multidrug-resistant organisms.

BACKGROUND: The human gastrointestinal tract is home to a dense and diverse microbiome, predominated by bacteria. Despite the conservation of critical functionality across most individuals, the composition of the gut microbiome is highly individualized, leading to differential responses to perturbations such as oral antibiotics or multidrug-resistant organism (MDRO) infection. Herein, subject responses to these perturbations based on their body weight were evaluated. METHODS: Fecal samples were collected from 45 subjects at the Detroit Medical Center to evaluate the effects of perturbations on subjects' gut microbiome composition. Bacterial profiling was completed using 16S rRNA gene sequencing. RESULTS: Subjects with multiple MDROs, subjects weighing greater than 80 kg infected with MDRO E coli, and subjects weighing less than 80 kg with exposure to vancomycin and carbapenem antibiotics during hospitalization had significantly decreased gut microbiome richness. CONCLUSIONS: Both administration of oral antibiotics and MDRO infections decreased gut microbiome alpha diversity, but the magnitude of these gut microbiome perturbations was body weight dependent.

Mass Drug Administration: Contextual Factor Considerations.

In designing mass drug administration (MDA) campaigns, it is imperative to consider contextual factors that affect uptake of the intervention, including acceptability, cost, feasibility, and health system considerations, to ensure optimal coverage. We reviewed the literature on contextual factors influencing MDA delivery to provide programs with information to design a successful campaign. From 1,044 articles screened, 37 included contextual factors relevant to participants' values and preferences, drivers of MDA acceptability, health equity concerns, financial and economic aspects, and feasibility barriers; 13 included relevant modeling data. Key findings were abstracted by two reviewers and summarized. No studies directly assessed values or direct health equity concerns with respect to MDA, which represents an evidence gap as unequal distributions of effects and factors that impact participant acceptability and program feasibility must be considered to ensure equitable access. Participant acceptability was the most widely surveyed factor, appearing in 28 of 37 studies; perceived adverse events were a frequently noted cause of nonparticipation, mentioned in 15 studies. Feasibility considerations included when, where, and how drugs will be delivered and how to address pregnant women, as these can all have substantial implications for participation. Mass drug administration costs (∼$1.04 to $19.40 per person per round) are driven primarily by drug prices, but the delivery mechanism can have varying costs as well, and integration with other interventions may provide cost savings. Both programmatic goals and sociopolitical and economic contexts must be carefully considered before embarking on an MDA program to ensure programmatic success.

Germline mitotic quiescence and cell death are induced in Caenorhabditis elegans by exposure to pathogenic Pseudomonas aeruginosa.

The impact of exposure to microbial pathogens on animal reproductive capacity and germline physiology is not well understood. The nematode Caenorhabditis elegans is a bacterivore that encounters pathogenic microbes in its natural environment. How pathogenic bacteria affect host reproductive capacity of C. elegans is not well understood. Here, we show that exposure of C. elegans hermaphrodites to the Gram-negative pathogen Pseudomonas aeruginosa causes a marked reduction in brood size with concomitant reduction in the number of nuclei in the germline and gonad size. We define 2 processes that are induced that contribute to the decrease in the number of germ cell nuclei. First, we observe that infection with P. aeruginosa leads to the induction of germ cell apoptosis. Second, we observe that this exposure induces mitotic quiescence in the proliferative zone of the C. elegans gonad. Importantly, these processes appear to be reversible; when animals are removed from the presence of P. aeruginosa, germ cell apoptosis is abated, germ cell nuclei numbers increase, and brood sizes recover. The reversible germline dynamics during exposure to P. aeruginosa may represent an adaptive response to improve survival of progeny and may serve to facilitate resource allocation that promotes survival during pathogen infection.

Use of ultrasound imaging for assessment of the periodontium: A systematic review.

The objective of this study was to systematically review the literature regarding diagnostic applications of ultrasound imaging for evaluation of the periodontium in humans. The search was conducted on Medline, EMBASE, Web of Science, Scopus, Cochrane, and PubMed up to April 3, 2023. The studies included were exclusively human studies that assessed the periodontium with ultrasound (US) imaging (b-mode). Outcomes measured included alveolar bone level, alveolar bone thickness, gingival thickness, and blood flow quantification. References were imported to Covidence. Two reviewers conducted phases 1 and 2. The JBI risk assessment tool for cross-sectional studies was used. Extracted data included the transducer and measurements used and the study's outcomes. The search yielded 4892 studies after removing duplicates. From these, 25 studies were included and selected for extraction. Included studies retrieved outcomes from US examinations of the periodontal tissues. From the selected studies, 15 used US on natural teeth, 4 used US on implants, 2 used US on edentulous ridges, and 4 used color flow/power in US to evaluate the blood flow. The results of the present systematic review suggest that US might be a feasible and valuable diagnostic tool for the periodontium, with the potential to complement shortfalls of current radiographic technologies.

Family 3 CBM improves the biochemical properties, substrate hydrolysis and coconut oil extraction by hemicellulolytic and holocellulolytic chimeras.

To understand the influence of family 3 Carbohydrate Binding Module (hereafter CBM3), single (GH5 cellulase; CelB, CelBΔCBM), bi-chimeric [GH26 endo-mannanase (ManB-1601) and GH11 endo-xylanase (XynB); ManB-XynB [1], ManB-XynB-CBM] and tri-chimeric [ManB-XynB-CelB [1], ManB-XynB-CelBΔCBM] enzyme variants (fused or deleted of CBM) were produced and purified to homogeneity. CBM3 did not alter the pH and temperature optima of bi- and tri-chimeric enzymes but improved the pH and temperature stability of ManB in CBM variants of bi-/tri-chimeric enzymes. Truncation of CBM in CelB shifted the pH optimum and increased the melting temperature (Tm 65 â„ƒ). CBM3 improved both substrate affinity (Km) and catalytic efficiency (kcat/Km) of fused enzymes in tri-chimera and CelB but only Km for bi-chimera. Far-UV CD of CelB and bi- and tri-chimeric enzymes suggested that CBM3 improved the α-helical content and compactness in the native state but did not prevent disintegration of secondary structural contents at acidic pH. Steady-state fluorescence studies suggested that under acidic conditions CBM3 prevented the exposure of hydrophobic patches in bi-chimeric protein but could not avert the opening up of chimeric enzyme structure. Aqueous enzyme assisted treatment of mature coconut kernel using single, bi- and tri-chimeric enzymes led to cracks, peeling and fracturing of the matrix and improved the oil yield by up to 22%.

Mass Relapse Prevention to Reduce Transmission of Plasmodium vivax- A Systematic Review.

Several temperate countries have used mass chemoprevention interventions with medicines of the 8-aminoquinoline class that prevent relapses from Plasmodium vivax before peak transmission to reduce transmission of malaria. The WHO commissioned a systematic review of the literature and evidence synthesis to inform development of recommendations regarding this intervention referred to as "mass relapse prevention" (MRP). Electronic databases were searched, 866 articles screened, and 25 assessed for eligibility after a full-text review. Two nonrandomized studies were included, one from the Democratic People's Republic of Korea (391,357 participants) and the second from the Azerbaijan Soviet Socialist Republic (∼30,000 participants). The two studies administered a single round of primaquine over 14 days (0.25 mg/kg per day). From 1 to 3 months after the treatment round, the incidence of P. vivax infections was significantly lower in areas that received MRP than those that did not (pooled rate ratio [RR] 0.08, 95% CI 0.07-0.08). At 4 to 12 months after the treatment round, the prevalence of P. vivax infection was significantly lower in MRP villages than non-MRP villages (odds ratio 0.12, 95% CI 0.03-0.52). No severe adverse events were found. The certainty of evidence for all outcomes was very low and no conclusions as to the effectiveness or safety of MRP could be drawn. However, it is not likely that this intervention will be needed in the future as most temperate countries where P. vivax is transmitted are nearing or have already eliminated malaria.