Systematic Review of the Cost-Effectiveness of Home-Based Palliative Care Interventions in Patients with Cancer: A Critical Analysis.

Background: The increased prevalence of cancer and the negative impact of pain on the quality of life of patients underscore the need to implement efficient palliative care interventions and management of pain. The cost-effectiveness of palliative care interventions for cancer, mostly pharmacological and delivered through home-based palliative care services, is unclear. Most of the studies do not take into account indirect costs nor consider variations across different geographical regions. Objective: To describe existing and cutting-edge knowledge on cost-effectiveness or item costs related to palliative home-based care for patients with cancer. We evaluated various costs, including direct medical, non-medical, and indirect costs in different geographical regions and analysed how different options for care affect the patients' quality of life and associated expenses. Methods: This Prospero-registered systematic review (CRD42023404217) adhered to the PRISMA criteria. Following a multistep selection process, we selected 22 articles published between 2013 and 2023 focused on quality of life outcomes and cost-effectiveness of home-based palliative care for cancer patients. Results: Home-based palliative care decreases the number of hospital visits, while its influence on patients quality of life is currently difficult to demonstrate across geographic regions based on available evidence. Overall, home care decreases the costs associated to the palliative care of patients with cancer. The cost structure analysis revealed that besides healthcare costs, informal care expenses and productivity losses represent a significant proportion of overall expenses). In Europe, the direct medical, non-medical, and indirect costs (in purchasing power parity) were on average $1,941, $842, and $1,241, per month per person, respectively. In the USA and Asia, direct medical and indirect costs are on average $1,095 (USA) vs $1,444 (Asia) and $2,192 (USA) vs $1,162 (Asia). Conclusion: In conclusion, the studies reviewed highlight significant cost variations and potential savings associated with palliative home-based care for cancer patients. Home-based palliative care, particularly involving medications, has shown favorable cost-effectiveness compared to hospital care. Specialized palliative home care, psychological interventions, and outpatient services further contribute to overall cost savings. However, the economic impact varies across different geographical contexts and cost categories, emphasizing the need for tailored approaches in palliative care planning and implementation.

Variability and functional characterization of the Phakopsora pachyrhizi Egh16-like effectors.

Effector proteins in Phakopsora pachyrhizi (Pp), the causative agent of Asian Soybean rust, are involved in the infection process. A previous study identified a rust effector Egh16-like family based expression profile during the interaction with soybean. Herein, we scrutinized available the Pp genomes to validate the predicted Egh16-like family of Pp and identify new family members. We described 22 members of the Egh16-like gene family in the Pp MT2006 genome and 18 in the UFV02 and K8108 genomes, highlighting a family expansion. Family members have a small signal peptide, conserved cysteine-rich R/Y/FxC motifs in the C-terminal region, and a virulence-related Egh16-like domain and were able to suppress PTI related responses in Benthamiana. Phylogenetic analysis placed the family members into eight clusters, with members induced during the early stages of rust infection. Members of clusters VI and VII are present in different copy numbers in Pp genomes and suppressed PAMP-related responses.

Determination of regulated perfluoroalkyl substances (PFAS) in drinking water according to Directive 2020/2184/EU.

Perfluoroalkyl substances (PFAS) are chemical compounds that have been widely used in industry and manufacture. Occurrence, together with persistence and recent toxicological effects data, has promoted the regulation of 20 PFAS (carboxylic and sulfonic) acids in drinking water through the recent Directive 2020/2184/EU. This Regulation included PFAS with different carbon chain lengths (from C4 to C13) and limited the total PFAS concentration (as sum) to a maximum of 0.1 µg/L, for which law-enforcement analytical methods are required. In this work, three different methodologies have been developed and evaluated as regards their performance to determine those 20 PFAS in tap and bottled water, based on on-line and off-line solid-phase extraction (SPE) and direct injection. In all cases, ultra-high pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was used as a determination technique. Off-line SPE with Oasis Weak Anion Exchange (WAX) cartridges provided the best results in terms of limits of quantification (LOQ ≤ 0.3 ng/L) and accuracy (R ≥ 70%) in drinking water samples. On-line SPE and direct injection presented some drawbacks such as background contamination problems and lower accuracies for the least polar compounds. This off-line SPE methodology was then applied to the analysis of 46 drinking water samples (11 commercial bottled samples, 23 Spanish and 12 international tap water samples). Ten PFAS were quantified in such samples at concentrations and detection frequencies ranging from 0.1 to 20.1 ng/L and 2 to 91%, respectively. However, the sum concentration did not surpass the established limit in any sample.

Regulation of Bacteroides acidifaciens by the aryl hydrocarbon receptor in IL-22-producing immune cells has sex-dependent consequential impact on colitis.

Introduction: Colitis is an inflammatory bowel disease (IBD) characterized by immune cell dysregulation and alterations in the gut microbiome. In our previous report, we showed a natural product in cruciferous vegetables and ligand of the aryl hydrocarbon receptor (AhR), indole-3-carbinol (I3C), was able to reduce colitis-induced disease severity and microbial dysbiosis in an interleukin-22 (IL-22) dependent manner. Methods: In the current study, we performed single-cell RNA sequencing (scRNAseq) from colonocytes during colitis induction and supplementation with I3C and show how this treatment alters expression of genes involved in IL-22 signaling. To further define the role of IL-22 signaling in I3C-mediated protection during colitis and disease-associated microbial dysbiosis, we generated mice with AhR deficiency in RAR-related orphan receptor c (Rorc)-expressing cells (AhR ΔRorc ) which depletes this receptor in immune cells involved in production of IL-22. Colitis was induced in wildtype (WT), AhR ΔRorc , and littermate (LM) mice with or without I3C treatment. Results: Results showed AhR ΔRorc mice lost the efficacy effects of I3C treatment which correlated with a loss of ability to increase IL-22 by innate lymphoid type 3 (ILC3s), not T helper 22 (Th22) cells. 16S rRNA microbiome profiling studies showed AhR ΔRorc mice were unable to regulate disease-associated increases in Bacteroides, which differed between males and females. Lastly, inoculation with a specific disease-associated Bacteroides species, Bacteroides acidifaciens (B. acidifaciens), was shown to exacerbate colitis in females, but not males. Discussion: Collectively, this report highlights the cell and sex-specific role of AhR in regulating microbes that can impact colitis disease.

Response inhibition deficits in math-anxious individuals.

We examined whether math anxiety is related to a response inhibition deficit and, if so, whether it is a domain-specific inhibition deficit in numerical tasks or a general inhibition deficit. Behavioral performance and electroencephalogram activity were recorded while 28 highly math-anxious (HMA) and 28 low math-anxious (LMA) individuals performed both a numerical and a non-numerical Go/Nogo task. In the numerical task, single-digit numbers were presented, and participants were asked to press a button if the number was even. In the non-numerical task, letters were presented, and the button had to be pressed if the letter was a vowel. Nogo trials were answered less accurately and elicited larger Nogo-N2 and Nogo-P3 than Go trials in both tasks and both groups. Importantly, behavioral and brain response differences between tasks were only found in the HMA group. First, they were more error-prone in numerical Nogo than in non-numerical Nogo trials; and second, their Nogo-N2 and N2d (Nogo-Go difference) were smaller in the numerical task than in the non-numerical task. No differences were found in the LMA group. These results suggest that HMA individuals' response inhibition is impaired specifically when dealing with numbers, which could contribute to their low achievement in math tasks.

Utility of combining frailty and comorbid disease indices in predicting outcomes following craniotomy for adult primary brain tumors: A mixed-effects model analysis using the nationwide readmissions database.

OBJECTIVE: The escalating healthcare expenditures in the United States, particularly in neurosurgery, necessitate effective tools for predicting patient outcomes and optimizing resource allocation. This study explores the utility of combining frailty and comorbidity indices, specifically the Johns Hopkins Adjusted Clinical Groups (JHACG) frailty index and the Elixhauser Comorbidity Index (ECI), in predicting hospital length of stay (LOS), non-routine discharge, and one-year readmission in patients undergoing craniotomy for benign and malignant primary brain tumors. METHODS: Leveraging the Nationwide Readmissions Database (NRD) for 2016-2019, we analyzed data from 645 patients with benign and 30,991 with malignant tumors. Frailty, ECI, and frailty + ECI were assessed as predictors using generalized linear mixed-effects models. Receiver operating characteristic (ROC) curves evaluated predictive performance. RESULTS: Patients in the benign tumor cohort had a mean LOS of 8.1 ± 15.1 days, and frailty + ECI outperformed frailty alone in predicting non-routine discharge (AUC 0.829 vs. 0.820, p = 0.035). The malignant tumor cohort patients had a mean LOS of 7.9 ± 9.1 days. In this cohort, frailty + ECI (AUC 0.821) outperformed both frailty (AUC 0.744, p < 0.0001) and ECI alone (AUC 0.809, p < 0.0001) in predicting hospital LOS. Frailty + ECI (AUC 0.831) also proved superior to frailty (AUC 0.809, p < 0.0001) and ECI alone (AUC 0.827, p < 0.0001) in predicting non-routine discharge location for patients with malignant tumors. All indices performed comparably to one another as a predictor of readmission in both cohorts. CONCLUSION: This study highlights the synergistic predictive capacity of frailty + ECI, especially in malignant tumor cases, and further suggests that comorbid diseases may greatly influence perioperative outcomes more than frailty. Enhanced risk assessment could aid clinical decision-making, patient counseling, and resource allocation, ultimately optimizing patient outcomes.

Prognostic significance of exercise stress echocardiography using two and three diastolic variable approaches.

BACKGROUND: The prognostic utility of comprehensive, guideline-defined assessment of diastolic measures during routine exercise echocardiography remains unclear. OBJECTIVES: The purpose of the study was to pragmatically assess the prognostic role of obtainable Doppler-derived diastolic variables during treadmill exercise echocardiography. METHODS: In this retrospective study, the authors included 1910 patients undergoing exercise echocardiography. The guideline-defined diastolic measures included resting septal e' velocity, post-exercise E/e' ratio and post-exercise tricuspid regurgitant jet velocity. Since tricuspid regurgitant jet velocity is not routinely obtainable, the authors examined 2 approaches: 2 variable approach using only resting septal e' velocity and post-exercise E/e' ratio and 3 variable approach with all diastolic variables. RESULTS: The mean age of study subjects was 57.6 ± 16 years and 1068 (56 %) were women. The tricuspid jet velocity was not reliably obtained in 501(26 %) of patients. All 3 diastolic variables were associated with the hard outcomes (mortality, acute coronary syndrome, cardiac hospitalization), soft outcomes (subsequent revascularization and cardiac testing), as well as the composite outcome. In the 2-variable approach, the presence of 2 abnormal variables was associated with a worse composite outcome. In the 3 variable approach, the presence of 2 or 3 abnormal variables was associated with a worse composite outcome. The associations persisted after multivariable adjustment and in the propensity matched subgroups. CONCLUSIONS: Guideline-defined diastolic variables during treadmill exercise echocardiography offer prognostic utility when used in combination, especially if all 3 variables are obtainable.

Patient safety reporting and learning system of Catalonia (SNiSP Cat): a health policy initiative to enhance culture, leadership and professional engagement.

Patient safety reporting and learning systems (PSRLS) are tools to promote patient safety culture in healthcare organisations (HCO). Many PRSLS are locally developed. WHO Global Action Plan on Patient Safety 2021-2030 urges governments to deploy policies for healthcare risk management including PSRLS. The Ministry of Health of Catalonia (MHC) faced challenges in addressing quality and patient safety (Q&PS) issues due to disparate information systems. To address these challenges, the MHC developed a territorial PSRLS and embedded it in the Quality and Patient Safety Strategic Plan of Catalonia 2023-2027 (QPSS Plan Cat). METHODS: Four-step process: (1) creation of a governance model, a web platform and reporting forms for a PSRLS in Catalonia (SNiSP Cat); (2) SNiSP Cat roll out; (3) embed SNiSP Cat information in the accreditation model for HCO and the PS scorecard; (4) Development of SNiSP Cat within the QPSS Plan Cat 2023-2027. RESULTS: The SNiSP Cat is in use by 63/64 acute care hospital (ACH), 376/376 primary healthcare teams (PCT) and 17/98 long-term care facilities (LTCF). 1335/109 273 professionals were trained. Until 2022, 127 051 incidents have been migrated and reported (2013-2022). The system has generated three comprehensive risk maps for HCO: one for ACH, including patients' falls, medication, clinical process and procedures; second for PCT, including clinical process and procedures, clinical administration and medication; and a third for LTCF, included patients' falls, medication, digital/analogical documentation. SNiSP Cat provided information to support 53 standards out of 1312 of the ACH accreditation model and 14 standards out of 379 of PCT one. Regarding the MHC patient safety scorecard, 14 indicators out of 147 of ACH and 4 out of 41 of PCT are supported by SNiSP Cat data. CONCLUSIONS: The availability of a territorial PSRLS (SNiSP Cat) allows MHC leads the Q&PS policy with direct information, risk maps and data support to the standards for the Catalan accreditation models and PS scorecard linked to incentivisation, turning the SNiSP Cat into a driven tool to implement the Quality and Patient Safety Strategic Plan of Catalonia 2023-2027.

Mucor germinans, a novel dimorphic species resembling Paracoccidioides in a clinical sample: questions on ecological strategy.

Dimorphism is known among the etiologic agents of endemic mycoses as well as in filamentous Mucorales. Under appropriate thermal conditions, mononuclear yeast forms alternate with multi-nucleate hyphae. Here, we describe a dimorphic mucoralean fungus obtained from the sputum of a patient with Burkitt lymphoma and ongoing graft-versus-host reactions. The fungus is described as Mucor germinans sp. nov. Laboratory studies were performed to simulate temperature-dependent dimorphism, with two environmental strains Mucor circinelloides and Mucor kunryangriensis as controls. Both strains could be induced to form multinucleate arthrospores and subsequent yeast-like cells in vitro. Multilateral yeast cells emerge in all three Mucor species at elevated temperatures. This morphological transformation appears to occur at body temperature since the yeast-like cells were observed in the lungs of our immunocompromised patient. The microscopic appearance of the yeast-like cells in the clinical samples is easily confused with that of Paracoccidioides. The ecological role of yeast forms in Mucorales is discussed.IMPORTANCEMucormycosis is a devastating disease with high morbidity and mortality in susceptible patients. Accurate diagnosis is required for timely clinical management since antifungal susceptibility differs between species. Irregular hyphal elements are usually taken as the hallmark of mucormycosis, but here, we show that some species may also produce yeast-like cells, potentially being mistaken for Candida or Paracoccidioides. We demonstrate that the dimorphic transition is common in Mucor species and can be driven by many factors. The multi-nucleate yeast-like cells provide an effective parameter to distinguish mucoralean infections from similar yeast-like species in clinical samples.

Epigenetic control of SOX9 gene by the histone acetyltransferase P300 in human Sertoli cells.

Background: The transcription factor SOX9 is a key regulator of male sexual development and Sertoli cell differentiation. Altered SOX9 expression has been implicated in the pathogenesis of disorders of sexual development (DSD) in mammals. However, limited information exists regarding the epigenetic mechanisms governing its transcriptional control during sexual development. Methods: This study employed real-time PCR (qPCR), immunofluorescence (IIF), and chromatin immunoprecipitation (ChIP) assays to investigate the epigenetic mechanisms associated with SOX9 gene transcriptional control in human and mouse Sertoli cell lines. To identify the specific epigenetic enzymes involved in SOX9 epigenetic control, functional assays using siRNAs for P300, GCN5, and WDR5 were performed. Results: The transcriptional activation of SOX9 was associated with selective deposition of active histone modifications, such as H3K4me3 and H3K27ac, at its enhancer and promoter regions. Importantly, the histone acetyltransferase P300 was found to be significantly enriched at the SOX9 enhancers, co-localizing with the H3K27ac and the SOX9 transcription factor. Silencing of P300 led to decreased SOX9 expression and reduced H3K27ac levels at the eSR-A and e-ALDI enhancers, demonstrating the crucial role of P300-mediated histone acetylation in SOX9 transcriptional activation. Interestingly, another histone lysine acetyltransferases like GNC5 and methyltransferases as the Trithorax/COMPASS-like may also have a relevant role in male sexual differentiation. Conclusions: Histone acetylation by P300 at SOX9 enhancers, is a key mechanism governing the transcriptional control of this essential regulator of male sexual development. These findings provide important insights into the epigenetic basis of sexual differentiation and the potential pathogenesis of DSDs.

Assessment of performance and comparison of three commercial HDV RNA detection assays: implications for diagnosis and treatment monitoring.

Objectives: Precise HDV-RNA detection and quantification are pivotal for diagnosis and monitoring of response to newly approved treatment. We evaluate the performance of three HDV RNA detection and quantification assays. Methods: Hepatitis Delta RT-PCR system kit, EurobioPlex HDV assay, and RoboGene HDV RNA Quantification kit 2.0 were used for testing 151 HBsAg-positive samples, 90 HDV-RNA negative and 61 HDV-RNA positive. We also evaluated serial dilutions of the WHO international standard for HDV, PEI 7657/12. All HDV-RNA positive samples were genotyped using a next-generation sequencing strategy. Results: Qualitative results indicated a 100% concordance between tests. Quantitative results correlated well, r2 = 0.703 (Vircell-vs-Eurobio), r2 = 0.833 (Vircell-vs-RoboGene), r2 = 0.835 (Robogene-vs-Eurobio). Bias index was 2.083 (Vircell-vs-Eurobio), -1.283 (Vircell-vs-RoboGene), and -3.36 (Robogene-vs-Eurobio). Using the WHO IS, Vircell overestimated the viral load by 0.98 log IU/mL, Eurobio by 1.46 log IU/mL, and RoboGene underestimated it by 0.98 log IU/mL. Fifty-nine samples were successfully genotyped (Genotype 1, n=52; Genotype 5, n=7; Genotype 6, n=1), with similar results for correlation and bias. Conclusion: This study underscores the necessity of using reliable HDV-RNA detection and quantification assays, as evidenced by the high concordance rates in qualitative detection and the observed variability in quantitative results. These findings highlight the importance of consistent assay use in clinical practice to ensure accurate diagnosis and effective treatment monitoring of HDV infection.

Production of a bacterial secretome highly efficient for the deconstruction of xylans.

Bacteria within the Paenibacillus genus are known to secrete a diverse array of enzymes capable of breaking down plant cell wall polysaccharides. We studied the extracellular xylanolytic activity of Paenibacillus xylanivorans and examined the complete range of secreted proteins when grown on carbohydrate-based carbon sources of increasing complexity, including wheat bran, sugar cane straw, beechwood xylan and sucrose, as control. Our data showed that the relative abundances of secreted proteins varied depending on the carbon source used. Extracellular enzymatic extracts from wheat bran (WB) or sugar cane straw (SCR) cultures had the highest xylanolytic activity, coincidently with the largest representation of carbohydrate active enzymes (CAZymes). Scaling-up to a benchtop bioreactor using WB resulted in a significant enhancement in productivity and in the overall volumetric extracellular xylanase activity, that was further concentrated by freeze-drying. The enzymatic extract was efficient in the deconstruction of xylans from different sources as well as sugar cane straw pretreated by alkali extrusion (SCRe), resulting in xylobiose and xylose, as primary products. The overall yield of xylose released from SCRe was improved by supplementing the enzymatic extract with a recombinant GH43 ß-xylosidase (EcXyl43) and a GH62 α-L-arabinofuranosidase (CsAbf62A), two activities that were under-represented. Overall, we showed that the extracellular enzymatic extract from P. xylanivorans, supplemented with specific enzymatic activities, is an effective approach for targeting xylan within lignocellulosic biomass.

Survival of Xanthomonas vasicola pv. vasculorum in Soil and in Corn Crop Residues under the Humid Subtropical Climate of Southern Brazil.

Bacterial leaf streak caused by Xanthomonas vasicola pv. vasculorum (Xvv) is an emerging disease in several corn-producing regions around the world. In Brazil, there is a lack of information on the survival of this bacterium in soil and crop residues. Thus, the objective of this study was to determine the survival of Xvv in soil and also in infected corn crop residues under the humid subtropical climate of southern Brazil. The survival of Xvv in soil was initially investigated in sandy and clayey soils maintained at 20, 25 and 30 °C under controlled conditions. The survival of the bacterium under field conditions was studied in artificially infested clayey soil. The survival of Xvv in corn crop residues was investigated in infected residues maintained on the soil surface or buried in the soil at 20 cm deep. Under controlled conditions, regardless of the type of soil, the bacterium survived longer at 20 °C than at higher temperatures. The bacterium survived for 40 days in clayey soil kept at 20 °C and four days in sandy soil maintained at 30 °C. Under field conditions, the survival of Xvv in the soil was only for 48 h and in infected corn crop residues for up to 15 days in the samples maintained on the soil surface. In samples of infected corn residues buried in the soil, the bacterium was only detected at the time the experiment was set up. In general, the results obtained in this study revealed that Xvv survives for a short period of time in soil and in infected corn crop residues under humid subtropical conditions. Therefore, soil and corn residues may not be highly important sources of primary inoculum for the development of bacterial leaf streak on corn crops under these conditions.

The Use of COVID-19 Mobile Apps in Connecting Patients with Primary Healthcare in 30 Countries: Eurodata Study.

BACKGROUND: The COVID-19 pandemic has necessitated changes in European healthcare systems, with a significant proportion of COVID-19 cases being managed on an outpatient basis in primary healthcare (PHC). To alleviate the burden on healthcare facilities, many European countries developed contact-tracing apps and symptom checkers to identify potential cases. As the pandemic evolved, the European Union introduced the Digital COVID-19 Certificate for travel, which relies on vaccination, recent recovery, or negative test results. However, the integration between these apps and PHC has not been thoroughly explored in Europe. OBJECTIVE: To describe if governmental COVID-19 apps allowed COVID-19 patients to connect with PHC through their apps in Europe and to examine how the Digital COVID-19 Certificate was obtained. METHODOLOGY: Design and setting: Retrospective descriptive study in PHC in 30 European countries. An ad hoc, semi-structured questionnaire was developed to collect country-specific data on primary healthcare activity during the COVID-19 pandemic and the use of information technology tools to support medical care from 15 March 2020 to 31 August 2021. Key informants belong to the WONCA Europe network (World Organization of Family Doctors). The data were collected from relevant and reliable official sources, such as governmental websites and guidelines. MAIN OUTCOME MEASURES: Patient's first contact with health system, governmental COVID-19 app (name and function), Digital COVID-19 Certification, COVID-19 app connection with PHC. RESULTS: Primary care was the first point of care for suspected COVID-19 patients in 28 countries, and 24 countries developed apps to complement classical medical care. The most frequently developed app was for tracing COVID-19 cases (24 countries), followed by the Digital COVID-19 Certificate app (17 countries). Bulgaria, Italy, Serbia, North Macedonia, and Romania had interoperability between PHC and COVID-19 apps, and Poland and Romania's apps considered social needs. CONCLUSIONS: COVID-19 apps were widely created during the first pandemic year. Contact tracing was the most frequent function found in the registered apps. Connection with PHC was scarcely developed. In future pandemics, connections between health system levels should be guaranteed to develop and implement effective strategies for managing diseases.

Gender Disparities in Adverse Events Resulting From Low-Value Practices in Family Practice in Spain: A Retrospective Cohort Study.

Objectives: This study aimed to evaluate gender-based disparities in preventable adverse events due to low-value practices (LVPs) in primary care. Methods: A retrospective cohort study in Alicante, Spain. Results: A total of 1,516 patient records were examined, finding that older individuals and women experienced more LVP-related events. Female patients faced a higher volume of such events than males with the same health issue. Interaction analysis revealed patients treated by male physicians had more severe events, while those attended by females experienced milder ones. Adverse events were more frequent in LVPs associated with gender-based reasons. Conclusion: These results highlight the need for tailored healthcare professional awareness programs on overuse's impact on safety. Addressing outcome differences between male and female patients should inform awareness campaigns.

Temporal summation of second pain is affected by cognitive load.

This work attempted to clarify the interaction of cognition and pain sensitization during a paradigm of Temporal Summation of Second Pain (TSSP). We analyzed pain ratings and electroencephalographic (EEG) activity obtained from 21 healthy participants during the presentation of four experimental conditions that differed in the manipulation of attention to painful stimuli or working memory load (Attention to hand & TSSP; 0-back & TSSP (low cognitive load); 2-back & TSSP (high cognitive load); 2-back (without pain)). We found that the TSSP was reduced when the attention was diverted and the cognitive load increased, and this reduction was accompanied by higher midfrontal theta activity and lower posterior alpha and central beta activity. Although it is well established that TSSP is a phenomenon that occurs at the spinal level, here we show that it is also affected by supraspinal attentional mechanisms. Delivery of painful repeated stimuli did not affect the performance of the 2-back task but was associated with smaller amplitudes of attentional event-related potentials (ERPs) after standard stimuli (not the target). The study of brain activity during TSSP allowed to clarify the role of top-down attentional modulation in pain sensitization processes. Results contribute to a better understanding of cognitive dysfunction in pain conditions and reinforce the use of therapeutic strategies based on distracting attention away from pain.

Patient Safety Incidents in Primary Care: Comparing APEAS-2007 (Spanish Patient Safety Adverse Events Study in Primary Care) with Data from a Health Area in Catalonia (Spain) in 2019.

The initial APEAS study, conducted in June 2007, examined adverse events (AEs) in Spanish Primary Healthcare (PHC). Since then, significant changes have occurred in healthcare systems. To evaluate these changes, a study was conducted in the Camp de Tarragona PHC region (CTPHC) in June 2019. This cross-sectional study aimed to identify AEs in 20 PHC centres in Camp de Tarragona. Data collection used an online questionnaire adapted from APEAS-2007, and a comparative statistical analysis between APEAS-2007 and CTPHC-2019 was performed. The results revealed an increase in nursing notifications and a decrease in notifications from family doctors. Furthermore, fewer AEs were reported overall, particularly in medication-related incidents and healthcare-associated infections, with an increase noted in no-harm incidents. However, AEs related to worsened clinical outcomes, communication issues, care management, and administrative errors increased. Concerning severity, there was a decrease in severe AEs, coupled with an increase in moderate AEs. Despite family doctors perceiving a reduction in medication-related incidents, the overall preventability of AEs remained unchanged. In conclusion, the reporting patterns, nature, and causal factors of AEs in Spanish PHC have evolved over time. While there has been a decrease in medication-related incidents and severe AEs, challenges persist in communication, care management, and clinical outcomes. Although professionals reported reduced severity, the perception of preventability remains an area that requires attention.

The polymorphism Val158Met in the COMT gene: disrupted dopamine system in fibromyalgia patients?

ABSTRACT: The single-nucleotide polymorphism (SNP) rs4680 in the catechol-O-methyltransferase gene ( COMT ) is a missense variant (Val158Met) associated with altered activity of the COMT enzyme and suggested as a predictive feature for developing some chronic pain conditions. However, there are controversial results on its role in fibromyalgia (FM). Here, the SNP Val158Met was analyzed in 294 FM patients (without comorbidities) and 209 healthy controls (without chronic pain). The concurrent impact of Val158Met genotypes and FM comorbid disorders (depression and sleep impairment) on FM risk were tested. In addition, the genotypic distribution of FM patients in relation to pain intensity was evaluated. The G allele (Val) resulted in being more represented in the FM group (57.8%) compared with the control group (48.8%; P = 0.037). Logistic regression highlighted that having the G/G (Val/Val) homozygous genotype was associated with 2 times higher risk of having FM compared with the A/A (Met/Met) carriers ( P = 0.038), whereas depression and sleep impairment increased FM risk by 12 and 8 times, respectively ( P < 0.001). However, considering only the FM patient group, the A/A homozygous genotype was significantly associated with severe pain intensity ( P = 0.007). This study highlighted associations between the SNP Val158Met and both FM and pain intensity, suggesting a link between dopaminergic dysfunction and vulnerability to chronic pain. Further studies should explore this SNP in FM patients in conjunction with COMT enzymatic activity and other symptoms connected with the dopaminergic system such as depression or sleep impairment.

Polyvalent Bacterial Lysate with Potential Use to Treatment and Control of Recurrent Urinary Tract Infections.

Overuse of antimicrobials has greatly contributed to the increase in the emergence of multidrug-resistant bacteria, a situation that hinders the control and treatment of infectious diseases. This is the case with urinary tract infections (UTIs), which represent a substantial percentage of worldwide public health problems, thus the need to look for alternatives for their control and treatment. Previous studies have shown the usefulness of autologous bacterial lysates as an alternative for the treatment and control of UTIs. However, a limitation is the high cost of producing individual immunogens. At the same time, an important aspect of vaccines is their immunogenic amplitude, which is the reason why they must be constituted of diverse antigenic components. In the case of UTIs, the etiology of the disease is associated with different bacteria, and even Escherichia coli, the main causal agent of the disease, is made up of several antigenic variants. In this work, we present results on the study of a bacterial lysate composed of 10 serotypes of Escherichia coli and by Klebsiella pneumoniae, Klebsiella aerogenes, Enterococcus faecalis, Proteus mirabilis, Citrobacter freundii, and Staphylococcus haemolyticus. The safety of the compound was tested on cells in culture and in an animal model, and its immunogenic capacity by analysing in vitro human and murine macrophages (cell line J774 A1). The results show that the polyvalent lysate did not cause damage to the cells in culture or alterations in the animal model used. The immunostimulatory activity assay showed that it activates the secretion of TNF-α and IL-6 in human macrophages and TNF-α in murine cells. The obtained results suggest that the polyvalent lysate evaluated can be an alternative for the treatment and control of chronic urinary tract infections, which will reduce the use of antimicrobials.

NOD2 activation enhances macrophage Fcγ receptor function and may increase the efficacy of antibody therapy.

Introduction: Therapeutic antibodies have become a major strategy to treat oncologic diseases. For chronic lymphocytic leukemia, antibodies against CD20 are used to target and elicit cytotoxic responses against malignant B cells. However, efficacy is often compromised due to a suppressive microenvironment that interferes with cellular immune responses. To overcome this suppression, agonists of pattern recognition receptors have been studied which promote direct cytotoxicity or elicit anti-tumoral immune responses. NOD2 is an intracellular pattern recognition receptor that participates in the detection of peptidoglycan, a key component of bacterial cell walls. This detection then mediates the activation of multiple signaling pathways in myeloid cells. Although several NOD2 agonists are being used worldwide, the potential benefit of these agents in the context of antibody therapy has not been explored. Methods: Primary cells from healthy-donor volunteers (PBMCs, monocytes) or CLL patients (monocytes) were treated with versus without the NOD2 agonist L18-MDP, then antibody-mediated responses were assessed. In vivo, the Eµ-TCL1 mouse model of CLL was used to test the effects of L18-MDP treatment alone and in combination with anti-CD20 antibody. Results: Treatment of peripheral blood mononuclear cells with L18-MDP led to activation of monocytes from both healthy donors and CLL patients. In addition, there was an upregulation of activating FcγR in monocytes and a subsequent increase in antibody-mediated phagocytosis. This effect required the NF-κB and p38 signaling pathways. Treatment with L18-MDP plus anti-CD20 antibody in the Eµ-TCL model of CLL led to a significant reduction of CLL load, as well as to phenotypic changes in splenic monocytes and macrophages. Conclusions: Taken together, these results suggest that NOD2 agonists help overturn the suppression of myeloid cells, and may improve the efficacy of antibody therapy for CLL.