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OBJECTIVES: This study assesses exposure to malaria vector mosquitos that is non-preventable through use of nets, the contribution of outdoor and indoor biting towards residual vector exposure, and the risk factors for being bitten and for being infected with malaria parasites on Bioko Island, Equatorial Guinea. METHODS: Human behaviour and malaria infection data were collected from 13,735 randomly selected residents during cross-sectional surveys, concomitantly with entomological human landing catches, indoors and outdoors, in 20 locations on the Island. Self-reported time of going indoors, going to bed and whether using a net were analysed to impute for each respondent the number of bites received outdoors and indoors during the night before the survey. RESULTS: On average, each person received 2.7 (95% CI 2.6 to 2.8) bites per night outdoors, 8.5 (8.3 to 8.7) bites indoors if not using a net, and 4.7 (4.5 to 4.8) bites indoors if using a net. Malaria infection was associated with more bites, regardless of whether received indoors or outdoors. Older age, male gender, not using a net, rural location and going indoors later increased the risk of being bitten. The proportion of bites not averted by using a net was estimated as 66% (61 to 71). CONCLUSIONS: A large proportion of biting, mostly indoors, may not be preventable by LLINs. Tools targeting indoor biting should be prioritised in Bioko. Novel vector control tools are urgently needed to reduce overall exposure to mosquito bites.
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This article aims to measure energy poverty in Colombia in its thirty-two departments and its capital city from 2018 to 2022, using a composite approach. To achieve this, a Multidimensional Energy Poverty Index (MEPI) was designed, according to the methodology proposed by Nussbaumer et al. (2012; 2013) [1,2]. Twenty-eight variables were used, which were distributed across seven dimensions, and recorded by the National Quality of Life Survey (ECV, Spanish acronym), administered by the National Administrative Department of Statistics (DANE) of Colombia. In addition, a nested weighting method was used to assign weights within the index. Subjective weights were given to the dimensions, and an entropy method was used for each of the component variables. The results show that energy poverty has an increasing trend in Colombia throughout the period, especially in the municipal capitals. There are significant differences between urban and rural areas in all territories, and the departments located in the most remote areas of the country have a higher energy poverty. This is consistent with the low population density, as well as with off-grid areas. The results obtained will allow decision makers to conduct a preliminary evaluation of the management and effects of the specific public policy programs and plans that have been implemented in the different territories of the country.
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BACKGROUND: Adherence to anti-malarial treatment regimens is an important aspect of understanding and improving the impact of malaria case management. However, both adherence to artemisinin-based combination therapy (ACT) and the factors driving it vary widely. While many other evaluation activities have been conducted on Bioko Island, until now adherence to anti-malarial treatments, and in particular ACT has not been evaluated. METHODS: The implementation of a malaria indicator survey (MIS) conducted on Bioko in 2023 was leveraged to evaluate adherence to ACT provided to individuals testing positive following the survey. A follow-up team visited the targeted households, physically observed treatment blisters where possible, and provided messaging to household members on the importance of adhering to the treatment guidelines to household members. The team used survey data from the targeted households to make messaging as relevant to the household's particular context as possible. RESULTS: Overall ACT adherence on Bioko Island was low, around 50%, and this varied demographically and geographically. Some of the highest transmission areas had exceptionally low adherence, but no systematic relationship between proper adherence and Plasmodium falciparum prevalence was detected. Estimates of adherence from follow-up visits were much lower than survey-based estimates in the same households (52.5% versus 87.1%), suggesting that lack of proper adherence may be a much larger issue on Bioko Island than previously thought. CONCLUSION: Representative surveys can be easily adapted to provide empirical estimates of adherence to anti-malarial treatments, complementary to survey-based and health facility-based estimates. The large discrepancy between adherence as measured in this study and survey-based estimates on Bioko Island suggests a health facility-based study to quantify adherence among the population receiving treatment for symptomatic malaria may be necessary.
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Antimaláricos , Cumplimiento de la Medicación , Proyectos Piloto , Guinea Ecuatorial , Antimaláricos/uso terapéutico , Humanos , Femenino , Masculino , Adulto , Cumplimiento de la Medicación/estadística & datos numéricos , Preescolar , Adolescente , Persona de Mediana Edad , Adulto Joven , Niño , Malaria Falciparum/tratamiento farmacológico , Lactante , Artemisininas/uso terapéutico , Encuestas y Cuestionarios , Anciano , IslasRESUMEN
Increasing global food demand will require more food production1 without further exceeding the planetary boundaries2 while simultaneously adapting to climate change3. We used an ensemble of wheat simulation models with improved sink and source traits from the highest-yielding wheat genotypes4 to quantify potential yield gains and associated nitrogen requirements. This was explored for current and climate change scenarios across representative sites of major world wheat producing regions. The improved sink and source traits increased yield by 16% with current nitrogen fertilizer applications under both current climate and mid-century climate change scenarios. To achieve the full yield potential-a 52% increase in global average yield under a mid-century high warming climate scenario (RCP8.5), fertilizer use would need to increase fourfold over current use, which would unavoidably lead to higher environmental impacts from wheat production. Our results show the need to improve soil nitrogen availability and nitrogen use efficiency, along with yield potential.
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Cambio Climático , Fertilizantes , Nitrógeno , Triticum , Triticum/crecimiento & desarrollo , Triticum/metabolismo , Fertilizantes/análisis , Nitrógeno/metabolismo , Suelo/químicaRESUMEN
Background: The association between the administration of sodium-glucose cotransporter 2 inhibitors (SGLT2is) during acute kidney injury (AKI) and the incidence of major adverse kidney events (MAKEs) is not known. Methods: This retrospective cohort study included patients with AKI and compared the outcomes for those who were treated with SGLT2is during hospitalization and those without SGLT2i treatment. The associations of SGLT2i use with MAKEs at 10 and 30-90 days, each individual MAKE component, and the pre-specified patient subgroups were analyzed. Results: From 2021 to 2023, 374 patients were included in the study-316 without SGLT2i use and 58 with SGLT2i use. Patients who were treated with SGLT2is were older; had a greater prevalence of diabetes, hypertension, chronic heart failure, and chronic kidney disease; required hemodialysis less often; and presented stage 3 AKI less frequently than those who were not treated with SGLT2is. Logistic regression analysis with nearest-neighbor matching revealed that SGLT2i use was not associated with the risk of MAKE10 (OR 1.08 [0.45-2.56]) or with MAKE30-90 (OR 0.76 [0.42-1.36]). For death, the stepwise approach demonstrated that SGLT2i use was associated with a reduced risk (OR 0.08; 0.01-0.64), and no effect was found for kidney replacement therapy (KRT). The subgroups of patients who experienced a reduction in the risk of MAKEs in patients with AKI treated with SGLT2is were those older than 61 years, those with an eGFR >81, and those without a history of hypertension or DM (p ≤ 0.05 for all). Conclusion: The use of SGLT2is during AKI had no effect on short- or medium-term MAKEs, but some subgroups of patients may have experienced benefits from SGLT2i treatment.
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[This corrects the article DOI: 10.1371/journal.pgph.0001516.].
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INTRODUCTION: A reduction in platelet count in critically ill patients is a marker of severity of the clinical condition. However, whether this association holds true in acute kidney injury (AKI) is unknown. We analyzed the association between platelet reduction in patients with AKI and major adverse kidney events (MAKE). METHODS: In this retrospective cohort, we included AKI patients at the Hospital Civil of Guadalajara, in Jalisco, Mexico. Patients were divided according to whether their platelet count fell >21% during the first 10 days. Our objectives were to analyze the associations between a platelet reduction >21% and MAKE at 10 days (MAKE10) or at 30-90 days (MAKE30-90) and death. RESULTS: From 2017 to 2023, 400 AKI patients were included, 134 of whom had a > 21% reduction in platelet count. The mean age was 54 years, 60% were male, and 44% had sepsis. The mean baseline platelet count was 194 x 103 cells/µL, and 65% of the KDIGO3 patients met these criteria. Those who underwent hemodialysis (HD) had lower platelet counts. After multiple adjustments, a platelet reduction >21% was associated with MAKE10 (OR 4.2, CI 2.1-8.5) but not with MAKE30-90. The mortality risk increased 3-fold (OR 2.9, CI 1.1-7.7, p = 0.02) with a greater decrease in the platelets (<90 x 103 cells/µL). As the platelets decreased, the incidence of MAKE was more likely to increase. These associations lost significance when accounting for starting HD. CONCLUSION: In our retrospective cohort of patients with AKI, a > 21% reduction in platelet count was associated with MAKE. Our results are useful for generating hypotheses and motivating us to continue studying this association with a more robust design.
A reduction in platelet count in critically ill patients has been associated with a worse prognosis, but it is not yet known whether this relationship also exists in patients with acute kidney injury, who are more susceptible to platelet decrease due to the syndrome or due to the onset of hemodialysis. In our study of acute kidney injury patients, we found that those whose platelet count decreased >21% during the first days were more likely to experience a major kidney event. In addition, the greater the decrease in platelet count was, the more likely these events were to occur. The significance of this association was lost in patients who start hemodialysis. Our conclusions could serve to generate hypotheses about this interesting relationship.
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Lesión Renal Aguda , Humanos , Masculino , Estudios Retrospectivos , Femenino , Lesión Renal Aguda/sangre , Lesión Renal Aguda/mortalidad , Lesión Renal Aguda/etiología , Persona de Mediana Edad , Recuento de Plaquetas , México/epidemiología , Anciano , Adulto , Diálisis Renal , Enfermedad Crítica , Trombocitopenia/sangre , Factores de RiesgoRESUMEN
Fluorogenic RNA aptamer tags with high affinity enable RNA purification and imaging. The G-quadruplex (G4) based Mango (M) series of aptamers were selected to bind a thiazole orange based (TO1-Biotin) ligand. Using a chemical biology and reselection approach, we have produced a MII.2 aptamer-ligand complex with a remarkable set of properties: Its unprecedented KD of 45 pM, formaldehyde resistance (8% v/v), temperature stability and ligand photo-recycling properties are all unusual to find simultaneously within a small RNA tag. Crystal structures demonstrate how MII.2, which differs from MII by a single A23U mutation, and modification of the TO1-Biotin ligand to TO1-6A-Biotin achieves these results. MII binds TO1-Biotin heterogeneously via a G4 surface that is surrounded by a stadium of five adenosines. Breaking this pseudo-rotational symmetry results in a highly cooperative and homogeneous ligand binding pocket: A22 of the G4 stadium stacks on the G4 binding surface while the TO1-6A-Biotin ligand completely fills the remaining three quadrants of the G4 ligand binding face. Similar optimization attempts with MIII.1, which already binds TO1-Biotin in a homogeneous manner, did not produce such marked improvements. We use the novel features of the MII.2 complex to demonstrate a powerful optically-based RNA purification system.
Artificial RNA tags that tightly bind fluorogenic ligands have many RNA imaging and RNA-protein biomolecular purification applications. Here, we report and structurally characterize a very small (20-nt) biologically compatible G-quadruplex based aptamer that can be inserted into commonly found GNRA tetraloops. This aptamer binds its fluorogenic ligand with an unprecedented picomolar binding affinity and is very stable against thermal and chemical insults. As the ligand can be modified to include biotin, this RNA tag can also be bound to streptavidin magnetic beads. After washing, tagged RNA can be cleanly eluted by exposing the beads to intense green light, which photobleaches the bound fluorogenic ligand, triggering the release of the bound RNA complex.
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Aptámeros de Nucleótidos , Colorantes Fluorescentes , G-Cuádruplex , Aptámeros de Nucleótidos/química , Aptámeros de Nucleótidos/metabolismo , Colorantes Fluorescentes/química , Ligandos , Benzotiazoles/química , Quinolinas/química , Biotina/química , ARN/química , ARN/metabolismo , Sitios de Unión , Modelos Moleculares , Cristalografía por Rayos X , Conformación de Ácido NucleicoRESUMEN
Background: Since 2015, malaria vector control on Bioko Island has relied heavily upon long-lasting insecticidal nets (LLIN) to complement other interventions. Despite significant resources utilised, however, achieving and maintaining high coverage has been elusive. Here, core LLIN indicators were used to assess and redefine distribution strategies. Methods: LLIN indicators were estimated for Bioko Island between 2015 and 2022 using a 1×1 km grid of areas. The way these indicators interacted was used to critically assess coverage targets. Particular attention was paid to spatial heterogeneity and to differences between urban Malabo, the capital, and the rural periphery. Results: LLIN coverage according to all indicators varied substantially across areas, decreased significantly soon after mass distribution campaigns (MDC) and, with few exceptions, remained consistently below the recommended target. Use was strongly correlated with population access, particularly in Malabo. After a change in strategy in Malabo from MDC to fixed distribution points, use-to-access showed significant improvement, indicating those who obtained their nets from these sources were more likely to keep them and use them. Moreover, their use rates were significantly higher than those of whom sourced their nets elsewhere. Conclusions: Striking a better balance between LLIN distribution efficiency and coverage represents a major challenge as LLIN retention and use rates remain low despite high access resulting from MDC. The cost benefit of fixed distribution points in Malabo was deemed significant, providing a viable alternative for guaranteeing access to LLINs to those who use them.
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The Equatorial Guinea Malaria Vaccine Initiative (EGMVI) highlights how long-term African government and international energy industry investment, plus novel partnerships, can enable clinical development of vaccines in Africa, for Africa. We review achievements and challenges of this pioneering, award-winning, public-private partnership which offers a model for future Africa-centric clinical research and development (R&D).
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Vacunas contra la Malaria , Desarrollo de Vacunas , Guinea Ecuatorial , Vacunas contra la Malaria/inmunología , Humanos , Malaria/prevención & control , Asociación entre el Sector Público-Privado , ÁfricaRESUMEN
Background: Diffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma worldwide. DLBCL is an aggressive disease that can be cured with upfront standard chemoimmunotherapy schedules. However, in approximately 35-40% of the patients DLBCL relapses, and therefore, especially in this setting, the search for new prognostic and predictive biomarkers is an urgent need. Natural killer (NK) are effector cells characterized by playing an important role in antitumor immunity due to their cytotoxic capacity and a subset of circulating NK that express CD8 have a higher cytotoxic function. In this substudy of the R2-GDP-GOTEL trial, we have evaluated blood CD8+ NK cells as a predictor of treatment response and survival in relapsed/refractory (R/R) DLBCL patients. Methods: 78 patients received the R2-GDP schedule in the phase II trial. Blood samples were analyzed by flow cytometry. Statistical analyses were carried out in order to identify the prognostic potential of CD8+ NKs at baseline in R/R DLBCL patients. Results: Our results showed that the number of circulating CD8+ NKs in R/R DLBCL patients were lower than in healthy donors, and it did not change during and after treatment. Nevertheless, the level of blood CD8+ NKs at baseline was associated with complete responses in patients with R/R DLBCL. In addition, we also demonstrated that CD8+ NKs levels have potential prognostic value in terms of overall survival in R/R DLBCL patients. Conclusion: CD8+ NKs represent a new biomarker with prediction and prognosis potential to be considered in the clinical management of patients with R/R DLBCL. Clinical trial registration: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-001620-29 EudraCT, ID:2014-001620-29.
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Linfoma de Células B Grandes Difuso , Linfoma no Hodgkin , Humanos , Biomarcadores , Linfocitos T CD8-positivos/patología , Células Asesinas Naturales/patología , Lenalidomida/uso terapéutico , Linfoma de Células B Grandes Difuso/patología , Recurrencia Local de Neoplasia/patología , Respuesta Patológica CompletaRESUMEN
BACKGROUND: Blood transfusion reactions may have a negative impact on organ function. It is unknown whether this association holds true for acute kidney injury (AKI). Therefore, we conducted a cohort study to assess the association between transfusion reactions and the incidence of AKI and major adverse kidney events. METHODS: In this retrospective cohort study, we included patients who received transfusion of blood products during hospitalization at the Hospital Civil of Guadalajara. We analyzed them according to the development of transfusion reactions, and the aim was to assess the association between transfusion reactions and AKI during long-term follow-up. RESULTS: From 2017 to 2021, 81,635 patients received a blood product transfusion, and 516 were included in our study. The most common transfusion was red blood cell packaging (50.4%), fresh frozen plasma (28.7%) and platelets (20.9%); of the 516 patients, 129 (25%) had transfusion reactions. Patients who had transfusion reactions were older and had more comorbidities. The most common type of transfusion reaction was allergic reaction (70.5%), followed by febrile nonhemolytic reaction (11.6%) and anaphylactoid reaction (8.5%). Most cases were considered mild. Acute kidney injury was more prevalent among those who had transfusion reactions (14.7%) than among those who did not (7.8%), p = < 0.01; those with AKI had a higher frequency of diabetes, vasopressors, and insulin use. Transfusion reactions were independently associated with the development of AKI (RR 2.1, p = < 0.02). Major adverse kidney events were more common in those with transfusion reactions. The mortality rate was similar between subgroups. CONCLUSION: In our retrospective cohort of patients who received blood product transfusions, 25% experienced transfusion reactions, and this event was associated with a twofold increase in the probability of developing AKI and some of the major adverse kidney events during long follow-up.
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Lesión Renal Aguda , Reacción a la Transfusión , Humanos , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/terapia , Lesión Renal Aguda/etiología , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Reacción a la Transfusión/epidemiología , Anciano , Incidencia , Factores de Riesgo , Adulto , Medición de RiesgoRESUMEN
Plastics and other materials commonly used in horticulture for plant support (e.g. raffia) and soil protection (e.g. mulching film) pose a challenge to achieving a circular economy. These materials contaminate plant residues, hampering their direct reuse due to the need for separation and cleaning. As a result, contaminated plant residues is often landfilled or incinerated. This study investigates the replacement of conventional plastic raffia and mulching film with biodegradable and compostable alternatives. Polypropylene raffia is compared with a biodegradable viscose polymer and compostable jute fibre, while polyethylene mulching film is compared with a biodegradable polylactic acid film. Conventional and novel alternatives are compared economically using Life-Cycle Costing and environmentally using Life-Cycle Assessment. The economic assessment is based on case studies with two horticultural companies in Almeria (south-eastern Spain), while the environmental analysis uses data from the Ecoinvent database. The use of biodegradable and compostable alternatives for raffia and mulching film proved to be 49% more expensive than conventional options. However, when conventional plastic waste is incinerated rather than landfilled, biodegradable and compostable alternatives have a lower carbon footprint. Although biodegradable and compostable options can be more expensive and have higher impacts in certain situations, proper waste management can lead to environmental benefits. With optimisation and incentives, these alternative options support the transition of horticulture to a sustainable circular economy.
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Suelo , Administración de Residuos , Análisis Costo-Beneficio , España , Plásticos/químicaRESUMEN
The establishment of aging clocks highlighted the strong link between changes in DNA methylation and aging. Yet, it is not known if other epigenetic features could be used to predict age accurately. Furthermore, previous studies have observed a lack of effect of age-related changes in DNA methylation on gene expression, putting the interpretability of DNA methylation-based aging clocks into question. In this study, we explore the use of chromatin accessibility to construct aging clocks. We collected blood from 159 human donors and generated chromatin accessibility, transcriptomic, and cell composition data. We investigated how chromatin accessibility changes during aging and constructed a novel aging clock with a median absolute error of 5.27 years. The changes in chromatin accessibility used by the clock were strongly related to transcriptomic alterations, aiding clock interpretation. We additionally show that our chromatin accessibility clock performs significantly better than a transcriptomic clock trained on matched samples. In conclusion, we demonstrate that the clock relies on cell-intrinsic chromatin accessibility alterations rather than changes in cell composition. Further, we present a new approach to construct epigenetic aging clocks based on chromatin accessibility, which bear a direct link to age-related transcriptional alterations, but which allow for more accurate age predictions than transcriptomic clocks.
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Cromatina , Epigénesis Genética , Humanos , Cromatina/genética , Envejecimiento/genética , Metilación de ADN , Perfilación de la Expresión GénicaRESUMEN
Background: Paliperidone palmitate 6-monthly (PP6M) is the first long-acting antipsychotic injectable (LAI) to allow for only two medication administrations per year, though there is presently limited insight into its effectiveness and potential added value in real clinical practice conditions. Objectives: To present our ongoing study and draw its preliminary data on patient characteristics initiating PP6M and adherence during the first year of treatment. Methods: The paliperidone 2 per year (P2Y) study is a 4-year, multicentre, prospective mirror-image pragmatic study taking place at over 20 different sites in Europe. The mirror period covers 2 years either side of the PP6M LAI initiation. Retrospective data for the previous 2 years are collected for each patient from the electronic health records. Prospective data are recorded at baseline, 6, 12, 18 and 24 months of drug administration and also cover information on concomitant psychiatric medication, relapses, hospital admissions, side effects, discontinuation and its reasons. Meanwhile, here we present preliminary data from the P2Y study at basal and 6-month period (first and second PP6M administration). Results: At the point of PP6M initiation, the most frequent diagnosis was schizophrenia (69%), the clinical global impression scale mean score was 3.5 (moderately markedly ill) and the rate of previous hospital admissions per patient and year was 0.21. PP6M was initiated after a median of 3-4 years on previous treatment: 146 (73%) from paliperidone palmitate 3-monthly, 37 (19%) from paliperidone palmitate 1-monthly and 17 (9%) from other antipsychotics. The mean dose of the first PP6M was 1098.9 mg. The retention rate at 6 months and 1 year of treatment on PP6M in our cohort was 94%. Conclusion: Patient and clinician preference for LAIs with longer dosing intervals was the main reason for PP6M initiation/switching resulting in high treatment persistence. Future data are needed to evaluate the full impact of PP6M in clinical practice.
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BACKGROUND: Indoor residual spraying (IRS) is a common vector control strategy in countries with high malaria burden. Historically, social norms have prevented women from working in IRS programmes. The Bioko Island Malaria Elimination Project has actively sought to reduce gender inequality in malaria control operations for many years by promoting women's participation in IRS. METHODS: This study investigated the progress of female engagement and compared spray productivity by gender from 2010 to 2021, using inferential tests and multivariable regression. Spray productivity was measured by rooms sprayed by spray operator per day (RSOD), houses sprayed by spray operator per day (HSOD), and the daily productivity ratio (DPR), defined as the ratio of RSOD to HSOD, which standardized productivity by house size. RESULTS: The percentage of women participating in IRS has increased over time. The difference in DPR comparing male and female spray operators was only statistically significant (p < 0.05) for two rounds, where the value was higher for women compared to men. Regression analyses showed marginal, significant differences in DPR between men and women, but beta coefficients were extremely small and thus not indicative of a measurable effect of gender on operational performance. CONCLUSIONS: The quantitative analyses of spray productivity are counter to stigmatizing beliefs that women are less capable than male counterparts during IRS spray rounds. The findings from this research support the participation of women in IRS campaigns, and a renewed effort to implement equitable policies and practices that intentionally engage women in vector control activities.
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Insecticidas , Malaria , Humanos , Masculino , Femenino , Guinea Ecuatorial , Control de Mosquitos , Malaria/prevención & controlRESUMEN
Malaria surveillance is hampered by the widespread use of diagnostic tests with low sensitivity. Adequate molecular malaria diagnostics are often only available in centralized laboratories. PlasmoPod is a novel cartridge-based nucleic acid amplification test for rapid, sensitive, and quantitative detection of malaria parasites. PlasmoPod is based on reverse-transcription quantitative polymerase chain reaction (RT-qPCR) of the highly abundant Plasmodium spp. 18S ribosomal RNA/DNA biomarker and is run on a portable qPCR instrument which allows diagnosis in less than 30 minutes. Our analytical performance evaluation indicates that a limit-of-detection as low as 0.02 parasites/µL can be achieved and no cross-reactivity with other pathogens common in malaria endemic regions was observed. In a cohort of 102 asymptomatic individuals from Bioko Island with low malaria parasite densities, PlasmoPod accurately detected 83 cases, resulting in an overall detection rate of 81.4%. Notably, there was a strong correlation between the Cq values obtained from the reference RT-qPCR assay and those obtained from PlasmoPod. In an independent cohort, using dried blood spots from malaria symptomatic children living in the Central African Republic, we demonstrated that PlasmoPod outperforms malaria rapid diagnostic tests based on the PfHRP2 and panLDH antigens as well as thick blood smear microscopy. Our data suggest that this 30-minute sample-to-result RT-qPCR procedure is likely to achieve a diagnostic performance comparable to a standard laboratory-based RT-qPCR setup. We believe that the PlasmoPod rapid NAAT could enable widespread accessibility of high-quality and cost-effective molecular malaria surveillance data through decentralization of testing and surveillance activities, especially in elimination settings.
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BACKGROUND: The risk of peritonitis has limited wider adoption of peritoneal dialysis (PD) in the United States. We developed a prototype bedside dialysate turbidity monitoring system, aiming to improve diagnostic accuracy relative to conventional approaches which depend on visual inspection and reporting of insensitive and non-specific symptoms. METHODS: The prototype system was tested in a single-centre, proof-of-principle clinical study in patients receiving intermittent PD. We obtained multiple effluent dialysate samples from each consenting participant. We compared turbidity measurements with diagnostic criteria endorsed by the International Society of Peritoneal Dialysis (ISPD). RESULTS: Overall, we analysed 983 specimens from 65 patients, including 105 samples from patients with peritonitis and 878 samples from patients without peritonitis. An operating point derived from a previous in vitro study yielded an unadjusted sensitivity and specificity of 95.2% and 91.5%, respectively. The majority of samples that did not meet ISPD diagnostic criteria were either cases detected before criteria were met or were related to active peritonitis treatment and resolution. CONCLUSION: This proof-of-principle study demonstrates the feasibility and diagnostic accuracy of a prototype dialysate turbidity monitoring system for peritonitis surveillance.
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INTRODUCTION: During acute kidney injury (AKI) due to sepsis, the intestinal microbiota changes to dysbiosis, which affects the kidney function recovery (KFR) and amplifies the injury. Therefore, the administration of probiotics could improve dysbiosis and thereby increase the probability of KFR. METHODS: In this double-blind clinical trial, patients with AKI associated with sepsis were randomized (1:1) to receive probiotics or placebo for 7 consecutive days, with the objectives of evaluate the effect on KFR, mortality, kidney replacement therapy (KRT), urea, urine volume, serum electrolytes and adverse events at day 7. RESULTS: From February 2019 to March 2022, a total of 92 patients were randomized, 48 to the Probiotic and 44 to Placebo group. When comparing with placebo, those in the Probiotics did not observe a higher KFR (HR 0.93, 0.52-1.68, p = 0.81), nor was there a benefit in mortality at 6 months (95% CI 0.32-1.04, p = 0.06). With probiotics, urea values decreased significantly, an event not observed with placebo (from 154 to 80 mg/dl, p = 0.04 and from 130 to 109 mg/dl, p = 0.09, respectively). Urinary volume, need for KRT, electrolyte abnormalities, and adverse events were similar between groups. (ClinicalTrial.gov NCT03877081) (registered 03/15/2019). CONCLUSION: In AKI related to sepsis, probiotics for 7 consecutive days did not increase the probability of KFR, nor did other variables related to clinical improvement, although they were safe.