The aims of this study were to describe patients' experiences after single-tablet regimen (STR) desimplification and its impact on self-reported treatment adherence and quality of life.
We performed ...a survey among all patients from the multicenter cohort of the Spanish HIV/AIDS Network who had desimplified the STRs dolutegravir/abacavir/lamivudine (DGT/ABC/3TC) or rilpivirine/tenofovir disoproxil fumarate/emtricitabine to their separate components (DTG + generic ABC/3TC or RPV + generic TDF/FTC) between December 2016 and November 2018.
Among 216 patients who fulfilled inclusion criteria, 138 (63.9%) completed the questionnaire. Most of the patients (78.3%) knew what generic drugs are, only 8.7% believed that treatment with 2 pills is less effective than treatment with an STR, and 67.4% agreed that it is reasonable to take 2 pills instead of 1 for HIV treatment to decrease costs for the health care system. After desimplification, 13.0% of the patients stated they had more secondary effects, 8.0% had forgotten one or more doses more frequently than before, and 10.9% had sometimes forgotten to take 1 pill, but not the other. A proportion of 30.4% reported not being happy to take more pills a day, and 10.1% experienced a worse quality of life after the treatment desimplification.
After STR desimplification, most of the patients had a fair knowledge about generic antiretrovirals, and they agreed to desimplify their STR to decrease costs. Although almost a third of the respondents were not happy to take 2 pills a day, only a minority reported worse adherence or quality of life.
BackgroundThis systematic review evaluates pneumolysin (PLY) as a target for new treatments against pneumococcal infections. Pneumolysin is one of the main virulence factors produced by all types of ...pneumococci. This toxin (53 kDa) is a highly conserved protein that binds to cholesterol in eukaryotic cells, forming pores that lead to cell destruction.MethodsThe databases consulted were MEDLINE, Web of Science, and Scopus. Articles were independently screened by title, abstract, and full text by two researchers, and using consensus to resolve any disagreements that occurred. Articles in other languages different from English, patents, cases report, notes, chapter books and reviews were excluded. Searches were restricted to the years 2000 to 2021. Methodological quality was evaluated using OHAT framework.ResultsForty-one articles describing the effects of different molecules that inhibit PLY were reviewed. Briefly, the inhibitory molecules found were classified into three main groups: those exerting a direct effect by binding and/or blocking PLY, those acting indirectly by preventing its effects on host cells, and those whose mechanisms are unknown. Although many molecules are proposed as toxin blockers, only some of them, such as antibiotics, peptides, sterols, and statins, have the probability of being implemented as clinical treatment. In contrast, for other molecules, there are limited studies that demonstrate efficacy in animal models with sufficient reliability.DiscussionMost of the studies reviewed has a good level of confidence. However, one of the limitations of this systematic review is the lack of homogeneity of the studies, what prevented to carry out a statistical comparison of the results or meta-analysis.ConclusionA panel of molecules blocking PLY activity are associated with the improvement of the inflammatory process triggered by the pneumococcal infection. Some molecules have already been used in humans for other purposes, so they could be safe for use in patients with pneumococcal infections. These patients might benefit from a second line treatment during the initial stages of the infection preventing acute respiratory distress syndrome and invasive pneumococcal diseases. Additional research using the presented set of compounds might further improve the clinical management of these patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A 6-year-old girl diagnosed with intermediate-risk acute lymphoblastic leukemia (ALL) presented with severe myelotoxicity and multiple infections during phase IB induction treatment with ...6-mercaptopurine (6-MP). In the subsequent treatment phases, which included 6-MP, the patient continued to show bone marrow aplasia and neutropenia, necessitating numerous dose adjustments and interruptions. The recommended dose was eventually reduced to 5 %. A pharmacogenetic analysis, conducted in induction phase IB, detected three single-nucleotide polymorphisms (SNPs) of the thiopurine S-methyltransferase (TPMT) gene, and the phenotype of a normal metabolizer was observed. As a result of a second pharmacogenetic analysis, pathological polymorphisms were revealed in Nudix hydrolase 15 (NUDT15), which may explain the patient’s myelotoxicity. Hence, a pharmacogenetic analysis performed in advance would have been able to prevent her from suffering severe toxicity and/or treatment failure.
Lateral flow immunoassays for detecting biomarkers in body fluids are simple, quick, inexpensive point-of-care tests widely used in disease surveillance, such as during the coronavirus disease 2019 ...(COVID-19) pandemic. Improvements in sensitivity would increase their utility in healthcare, food safety, and environmental control. Recently, biofunctional magnetic nanoclusters have been used to selectively label target proteins, which allows their detection and quantification with a magneto-inductive sensor. This type of detector is easily integrated with the lateral flow immunoassay format. Pneumolysin is a cholesterol-dependent cytolysin and one of the most important protein virulence factors of pneumonia produced by Streptococcus pneumoniae. It is recognized as an important biomarker for diagnosis in urine samples. Pneumonia is the infectious disease that causes the most deaths globally, especially among children under five years and adults over 65 years, most of them in low- and middle-income countries. There especially, a rapid diagnostic urine test for pneumococcal pneumonia with high sensitivity and specificity would be helpful in primary care. In this work, a lateral flow immunoassay with magnetic nanoclusters conjugated to anti-pneumolysin antibodies was combined with two strategies to increase the technique’s performance. First, magnetic concentration of the protein before the immunoassay was followed by quantification by means of a mobile telephone camera, and the inductive sensor resulted in detection limits as low as 0.57 ng (telephone camera) and 0.24 ng (inductive sensor) of pneumolysin per milliliter. Second, magnetic relocation of the particles within the test strip after the immunoassay was completed increased the detected signal by 20%. Such results obtained with portable devices are promising when compared to non-portable conventional pneumolysin detection techniques such as enzyme-linked immunosorbent assays. The combination and optimization of these approaches would have excellent application in point-of-care biodetection to reduce antibiotic misuse, hospitalizations, and deaths from community-acquired pneumonia.
BACKGROUND:Kingella kingae is an emergent pathogen causing septic arthritis (SA) in children.The objective of this study was to analyze the etiology of SA in children before and after the ...implementation of universal 16S rRNA gene polymerase chain reaction and sequencing (16SPCR) in synovial fluid.
METHODS:Children ≤14 years with acute SA from a Madrid cohort (2002–2013) were reviewed. Differences in etiology were analyzed before (period 1) and after (period 2) the implementation of bacterial 16SPCR in 2009. A comparison in epidemiology, clinical syndromes, therapy and outcome between infections caused by K. kingae and other bacteria was performed.
RESULTS:Bacteria were detected from 40/81 (49.4%) children, with a higher proportion of diagnosis after 16SPCR establishment (period 2, 63% vs. period 1, 31.4%; P = 0.005). The main etiologies were Staphylococcus aureus (37.5%) and K. kingae (35%), although K. kingae was the most common microorganism in P2 (48.3%). Children with K. kingae SA were less likely to be younger than 3 months (0 vs. 42.3%; P < 0.001), had less anemia (21.4 vs. 50%; P = 0.010), lower C-reactive protein (3.8 vs. 8.9 mg/dL; P = 0.039), less associated osteomyelitis (0 vs. 26.9%; P = 0.033), shorter intravenous therapy (6 vs. 15 days; P < 0.001), and had a nonsignificant lower rate of sequelae (0 vs. 30%; P = 0.15) than children with SA caused by other bacteria. However, they tended to have higher rate of fever (86 vs. 57%; P = 0.083).
CONCLUSIONS:K. kingae was frequently recovered in children with SA after the implementation of bacterial 16SPCR, producing a milder clinical syndrome and better outcome. Therefore, the use of molecular techniques may be important for the management of these children.
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•A fast, sensitive, and simple on-site method is presented for COVID-19 diagnosis.•Electrochemical detection is combined with RT-LAMP for on-site SARS-CoV-2 detection.•Malachite green ...LAMP probe is monitored electrochemically for quantitative readout.•Electrochemical measurement of malachite green is presented for SARS-CoV-2 monitoring.•Dual visual/electrochemical LAMP detection is made using malachite green indicator.
Loop-mediated isothermal amplification (LAMP) has arisen as an outstanding molecular technique for the amplification of nucleic acids, becoming an important alternative to PCR due to its simplicity and high sensitivity. However, traditional visual readout used in LAMP only provides qualitative results and can thus not provide a precise quantification of the target DNA/RNA in the sample. To overcome this, electroactive reporters incorporated in the reaction mix can provide a subsequent quantitative result of the analysis. In this work, malachite green, a commonly used colorimetric LAMP indicator, is used as an electrochemical probe to obtain quantitative results. For this purpose, its optical and electrochemical behavior has been assessed for further use in LAMP detection. Using SARS-CoV-2 RNA as template, we have developed a quantitative detection method, proving the usefulness of this molecule as a dual optical/electrochemical indicator. Thereby, with the electrochemical detection using screen-printed electrodes on which a drop of the LAMP reaction is deposited, a calibration curve with a linear dynamic range comprised between 22 and 4296 copies/μL was achieved, with a practical limit of detection of 22 copies/µL. In this method, validated with clinical samples, malachite green is used, by the first time, as a dual visual electrochemical/visual probe that can provide both an initial visual qualitative assessment together with an electrochemical quantification.
shows more than 90 capsular serotypes that can be distinguished by their reactivity against antisera. The main objective of this work was the development of a molecular method for serotyping without ...the use of antisera. A computer program containing an algorithm was used to search in a database for potentially useful enzymes for Restriction Fragment Length Polymorphism-RFLP typing, in order to maximize the discrimination between different serotypes. DNA sequences of 90 serotypes for the region between
B and
A genes were compiled, and a computer screening of restriction enzymes was performed. The
region and
9I restriction predicted unique PCR-RFLP patterns for 39 serotypes and eight serogroups. A second restriction enzyme resolved fragment specific patterns for 25 serotypes. The method was tested with 98 serotype-unknown clinical isolates. PCR-RFLP analysis deduced correct serotypes that were confirmed by Quellung reaction for 78.5% of the isolates.
Abstract
Objectives
Drug-related problems (DRPs) are a well-known cause of emergency department (ED) visits. The objective of the FARM-URG project was to assess the prevalence of DRPs using an annual ...cross-sectional registry. Herein we report results of the first 3 years, indicating the prevalence of DRPs, drugs involved, and patient characteristics.
Methods
A point-prevalence multicenter study was conducted across EDs of hospitals in Spain. A specified day and hour was assigned to collect data from all adult patients attending the ED due to DRPs during three consecutive years. Medical records were retrospectively reviewed, with data recorded in REDCap.
Key findings
Overall, 4752 patients were evaluated at 32 centres, of which 366 (7.7%) visited the ED due to DRPs, with a prevalence ranging from 0 to 16.7%. Antithrombotic drugs accounted for the highest number of DRPs, responsible for 96 (26.8%) episodes. Falls (n = 29; 8.0%) were the most frequent DRPs, followed by haemorrhage (n = 26; 7.12%). Furthermore, 198 (54.2%) reported DRPs were unrelated to medication errors, 80 (21.2%) were overdose errors, and 40 (11.0%) were attributed to poor treatment adherence. Of 366 DRPs-related visits, 54 (14.8%) were due to inappropriately prescribed drugs according to the STOPP-START criteria. Overall, 86 (23.5%) patients revisited the ED within 30 days of discharge, with 34 (9.4%) returning to the ED for new DRPs.
Conclusions
DRPs are frequently responsible for ED visits and are associated with a considerable percentage of post-discharge visits. The goal of the FARM-URG project is to periodically gather data to design and implement preventive measures.
Heart failure with preserved ejection fraction (HFpEF) is a disorder related to patient comorbidities and aging. Whether mitochondrial dysfunction is present during HFpEF decompensation versus the ...stable phase is largely unknown. The aim of the present study was to identify mitochondrial and cell metabolism blood biomarkers in older patients with acute and stable HFpEF.
Peripheral blood biomarkers were investigated in a group of eight to 12 patients aged 80–96 years and diagnosed with HFpEF first when they were in decompensated phase and then at least three months later in stable phase. Their data were compared to two control groups with an equal number of participants and sex proportions. One group was age matched and the other included individuals aged between 22 and 44 years.
Decompensated patients experienced an increased mitochondrial superoxide production and mitochondrial mass, lower mitochondrial DNA copy number and LDHB expression, and higher lactate level compared to the stable stage. The stable phase was characterized by a sharp reduction in formate level. Multivariate analysis indicated that formate, lactate, and histidine can distinguish both of the HFpEF phases. Many of these parameters, including LDHB, lactate, formate, and mitochondrial mass, followed an age-related pattern, with acute HFpEF at its apex or nadir, suggesting that it represents an exacerbation of an aging-related process.
We identified distinct blood biomarkers of chronic and decompensated HFpEF phases. The data underlined the relationship between HFpEF and aging. These findings could be used to monitor patients and might be therapeutically targeted.
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•Acute HFpEF patients have higher mitochondrial mass and normal for the age mtDNA.•These “congestive-like mitochondria” have elevated ROS production.•Increased mtDNA and low formate are marks of HFpEF stable phase.•Acute phase LDHB drop and lactate increase worsen the glycolytic pattern of aging.•Formate, lactate and histidine distinguish acute and stable HFpEF.
Pneumonia is an acute pulmonary infection whose high hospitalization and mortality rates can, on occasion, bring healthcare systems to the brink of collapse. Both viral and bacterial pneumonia are ...uncovering many gaps in our understanding of host–pathogen interactions, and are testing the effectiveness of the currently available antimicrobial strategies. In the case of bacterial pneumonia, the main challenge is antibiotic resistance, which is only expected to increase during the current pandemic due to the widespread use of antibiotics to prevent secondary infections in COVID-19 patients. As a result, alternative therapeutics will be necessary to keep this disease under control. This review evaluates the advantages of phage therapy to treat lung bacterial infections, in particular those caused by the Gram-positive bacteria Streptococcus pneumoniae and Staphylococcus aureus, while also highlighting the regulatory impediments that hamper its clinical use and the difficulties associated with phage research.
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