Utility of White Light Scanning as an Alternative to Computed Tomography to Evaluate Severity of Pectus Excavatum Deformity.

BACKGROUND: Pectus excavatum (PE) severity and surgical candidacy are determined by computed tomography (CT)-delineated Haller Index (HI) and Correction Index (CI). White light scanning (WLS) has been proposed as a non-ionizing alternative. The purpose of this retrospective study is to create models to determine PE severity using WLS as a non-ionizing alternative to CT. METHODS: Between November 2015 and February 2023, CT and WLS were performed for children ≤18 years undergoing evaluation at a high-volume, chest-wall deformity clinic. Separate quadratic discriminate analysis models were developed to predict CT HI ≥ 3.25 and CT CI ≥ 28% indicating surgical candidacy. Two bootstrap forest models were trained on WLS measurements and patient demographics to predict CT HI and CT CI values then compared to actual index values by intraclass correlation coefficient (ICC). RESULTS: In total, 242 patients were enrolled (86.4% male, mean [SD] age 15.2 [1.3] years). Quadratic discriminate analysis models predicted CT HI ≥ 3.25 with specificity = 91.7%, PPV = 97.7% (AUC = 0.91), and CT CI ≥ 28% with specificity = 92.3%, PPV = 93.5% (AUC = 0.84). Bootstrap forest model predicted CT HI with training dataset ICC (95% CI) = 0.91 (0.88-0.93, R2 = 0.85) and test dataset ICC (95% CI) = 0.86 (0.71-0.94, R2 = 0.77). For CT CI, training dataset ICC (95% CI) = 0.91 (0.81-0.93, R2 = 0.86) and test dataset ICC (95% CI) = 0.75 (0.50-0.88, R2 = 0.63). CONCLUSIONS: Using noninvasive and nonionizing WLS imaging, we can predict PE severity at surgical threshold with high specificity obviating the need for CT. Furthermore, we can predict actual CT HI and CI with moderate-excellent reliability. We anticipate this point-of-care tool to obviate the need for most cross-sectional imaging during surgical evaluation of PE. LEVEL OF EVIDENCE: Level III. STUDY TYPE: Study of Diagnostic Test.

Chest Wall Dermatitis Patterns Following Thoracoscopic Intercostal Nerve Cryoablation for Surgical Correction of Pectus Excavatum.

BACKGROUND: Intercostal nerve cryoablation (INC) has been shown to reduce postoperative pain and length of stay following surgical correction of pectus excavatum (SCOPE). Some patients have developed chest wall dermatological symptoms after INC that can be mistaken for metal allergy or infection. The purpose of this study is to report the symptoms, severity, incidence, and treatment of post-cryoablation dermatitis. METHODS: A retrospective single institution review was performed for patients who underwent SCOPE with and without INC between June 2016 and March 2023 to assess for incidence of postoperative dermatological findings. Characteristics associated with these findings were evaluated. RESULTS: During study period, 383 patients underwent SCOPE, 165 (43.1%) without INC and 218 (56.9%) with. Twenty-three (10.6%) patients who received INC developed exanthems characteristic of post-cryoablation dermatitis with two distinct phenotypes identified. No patients who underwent SCOPE without INC developed similar manifestations. Early dermatitis, characterized by a painless, erythematous, and blanching rash across the anterior thorax, was observed in 16 patients, presenting on median postoperative day 6.0 [IQR 6.0-8.5], with median time to resolution of 23.0 [IQR 12-71.0] days after symptom onset. Late dermatitis, characterized by hyperpigmentation spanning the anterior thorax, was observed in 7 patients, presenting on median postoperative day 129.0 [IQR 84.5-240.0], with median time to resolution of 114.0 [IQR 48.0-314.3] days. CONCLUSION: This is the first report of dermatological manifestations following SCOPE with INC, a phenomenon of unknown etiology and no known long-term sequela. In our experience, it is self-resolving and lacks systemic symptoms suggesting observation alone is sufficient for resolution. LEVEL OF EVIDENCE: IV.

Frequency of Dengue Virus-Specific T Cells is related to Infection Outcome in Endemic Settings.

Dengue is widespread in tropical and subtropical regions globally and leads to a considerable burden of disease. Annually, dengue virus (DENV) causes up to 400 million infections, of which ~25% present with clinical symptoms ranging from mild to fatal. Despite its significance as a growing public health concern, the development of effective DENV vaccines has been highly challenging. One of the reasons is the lack of comprehensive understanding of the influence exerted by prior DENV infections and immune responses with cross-reactive properties. To investigate this, we collected samples from a pediatric cohort study in dengue-endemic Managua, Nicaragua. We characterized T cell responses in a group of 71 healthy children who had previously experienced one or more natural DENV infections and who, within one year after sample collection, had a subsequent DENV infection that was either symptomatic (n=25) or inapparent (n=46, absence of clinical disease). Thus, our study was designed to investigate the impact of pre-existing DENV specific T cell responses on the clinical outcomes of subsequent DENV infection. We assessed the DENV specific T cell responses using an activation-induced marker assay (AIM). Children who had experienced only one prior DENV infection displayed heterogeneous DENV specific CD4+ and CD8+ T cell frequencies. In contrast, children who had experienced two or more DENV infections showed significantly higher frequencies of DENV specific CD4+ and CD8+ T cells that were associated with inapparent as opposed to symptomatic outcomes in the subsequent DENV infection. Taken together, these findings demonstrate the protective role of DENV specific T cells against symptomatic DENV infection and constitute an advancement toward identifying protective immune correlates against dengue fever and clinical disease.

Using Wearable Devices to Profile Demographic-Specific Recovery After Pediatric Appendectomy.

INTRODUCTION: Counseling patients and parents about the postoperative recovery expectations for physical activity after pediatric appendectomy varies significantly and is not specific to patients' demographic characteristics. Consumer wearable devices (CWD) can be used to objectively assess patients' normative postoperative recovery of physical activity. This study aimed to develop demographic-specific normative physical activity recovery trajectories using CWD in pediatric patients undergoing appendectomy. METHODS: Children ages 3-18 y old undergoing laparoscopic appendectomy for acute appendicitis were recruited. Patients wore a Fitbit device for 21 d postoperatively and daily step counts were measured. Patients with postoperative complications were excluded. Segmented regression models were fitted and time-to-plateau was estimated for patients with simple and complicated appendicitis separately for each age group, sex, race/ethnicity, and body mass index category. RESULTS: Among 147 eligible patients; 76 (51.7%) were female, 86 (58.5%) were in the younger group, and 79 (53.7%) had complicated appendicitis. Patients 3-11 y old demonstrated a faster trajectory to a physical activity plateau compared to those 12-18 in both simple (postoperative day [POD] 9 versus POD 17) and complicated appendicitis (POD 17 versus POD 21). Males and females had a similar postoperative recovery trajectory in simple and complicated appendicitis. There was no clear pattern differentiating trajectories based on race/ethnicity. Overweight/obese patients demonstrated a slower recovery trajectory in simple appendicitis. CONCLUSIONS: This study demonstrates that factors other than the disease itself, such as age, may affect recovery, suggesting the need for more tailored discharge instructions. CWDs can improve our understanding of recovery and allow for better data-driven counseling perioperatively.

Ultraviolet light spectroscopic characterization of ibuprofen acid aggregation in deionized water.

This work provides a description of the aggregation equilibria of ibuprofen acid in deionized water at temperatures between 20 and 40 °C in the 0.1-20.1 ppm concentration range. For this goal, we have made use of UV-Visible spectroscopy. A calculation algorithm was developed to obtain the aggregate orders and thermodynamic parameters from the experimental absorbance values. Monomeric ibuprofen acid was found to be absent in water solutions. In addition to the dimer, two aggregates formed by 32 and 128 monomeric units were found to co-exist in solution at the highest concentration tested. A critical micelle concentration of 7.8 ppm was estimated for this system. The appearance of the first aggregate occurs when the pH drops below the pKa value, which was determined to be 4.62. At higher ibuprofen concentrations, a sudden jump in the electrical conductivity coincides with the onset of formation of the second aggregate. A varied menu of alternatives is offered with respect to the calibration curve of ibuprofen in water, though the linear calibration of ibuprofen concentration with absorbance might be reasonably performed at 224 nm. Finally, the dissolution rate of the commercial ibuprofen used in this work was found to obey the Noyes-Whitney first order equation.

Bordetella spp. block eosinophil recruitment to suppress the generation of early mucosal protection.

Bordetella spp. are respiratory pathogens equipped with immune evasion mechanisms. We previously characterized a Bordetella bronchiseptica mutant (RB50ΔbtrS) that fails to suppress host responses, leading to rapid clearance and long-lasting immunity against reinfection. This work revealed eosinophils as an exclusive requirement for RB50ΔbtrS clearance. We also show that RB50ΔbtrS promotes eosinophil-mediated B/T cell recruitment and inducible bronchus-associated lymphoid tissue (iBALT) formation, with eosinophils being present throughout iBALT for Th17 and immunoglobulin A (IgA) responses. Finally, we provide evidence that XCL1 is critical for iBALT formation but not maintenance, proposing a novel role for eosinophils as facilitators of adaptive immunity against B. bronchiseptica. RB50ΔbtrS being incapable of suppressing eosinophil effector functions illuminates active, bacterial targeting of eosinophils to achieve successful persistence and reinfection. Overall, our discoveries contribute to understanding cellular mechanisms for use in future vaccines and therapies against Bordetella spp. and extension to other mucosal pathogens.

Consumer Wearables Define a Normative Recovery Trajectory Following the Modified Nuss Procedure.

INTRODUCTION: The modified Nuss procedure is an elective procedure associated with a lengthy recovery, uncontrolled pain, and risk of infrequent, yet life-threatening complications. The absence of objective measures of normative postoperative recovery creates uncertainty about the postdischarge period, which remains highly dependent on the patients' and their caregivers' expectations and management of recovery. We aimed to describe an objective-normative, physical activity recovery trajectory after the modified Nuss procedure, using step counts from the Fitbit. METHODS: This observational study enrolled children ≤18 y with pectus excavatum who underwent the modified Nuss procedure from 2021 to 2022. The Fitbit was worn for 21 postoperative days. Postdischarge outcomes and health-care utilization were evaluated. For patients without postoperative complications, piecewise linear regression analysis was conducted to generate a normative recovery trajectory model of daily step counts. RESULTS: Of 80 patients enrolled, 66 (86%) met eligibility criteria (mean age, 15.1 ± 1.3 y; 89.4% male, 62.1% non-Hispanic White). The mean number of telephone and electronic message encounters regarding concerns with the patient's recovery within 30 d postoperatively was 2.1 (standard deviation = 2.7). Ten patients (15.2%) returned to the emergency department (ED) within the 30-d postoperative period. Seven patients (10.6%) presented to the ED one time, and three patients (4.5%) presented to the ED twice. Thirty-day readmission rate was four patients (6.0%). Piecewise regression model showed that patients without complications steadily increased their daily step count on each postoperative day and plateaued on day 18. CONCLUSIONS: We have developed a normative recovery trajectory following the modified Nuss procedure using step count data collected by a consumer wearable device. This offers the potential to inform preoperative patient expectations and reduce avoidable health-care utilization through informed preoperative counseling, thus laying the ground work for the use of consumer wearable devices as a postdischarge remote monitoring tool.

Lessons learnt from the process of designing care coordination interventions through participatory action research in public healthcare networks of six Latin American countries.

BACKGROUND: The participation of health professionals in designing interventions is considered vital to effective implementation, yet in areas such as clinical coordination is rarely promoted and evaluated. This study, part of Equity-LA II, aims to analyse the design process of interventions to improve clinical coordination, taking a participatory-action-research (PAR) approach, in healthcare networks of Argentina, Brazil, Chile, Colombia, Mexico and Uruguay. This participatory process was planned in four phases, led by a local steering committee (LSC): (1) dissemination of problem analysis results and creation of professionals' platform, (2) selection of problems and intervention (3) intervention design and planning (4) adjustments after evaluation of first implementation stage. METHODS: A descriptive qualitative study based on documentary analysis, using a topic guide, was conducted in each intervention network. Documents produced regarding the intervention design process were selected. Thematic content analysis was conducted, generating mixed categories taken from the topic guide and identified from data. Main categories were LSC characteristics, type of design process (phases, participants' roles, methods) and associated difficulties, coordination problems and interventions selected. RESULTS: LSCs of similar composition (managers, professionals and researchers) were established, with increasing membership in Chile and high turnover in Argentina, Colombia and Mexico. Following results dissemination and selection of problems and interventions (more participatory in Chile and Colombia: 200-479 participants), the interventions were designed and planned, resulting in three different types of processes: (1) short initial design with adjustments after first implementation stage, in Colombia, Brazil and Mexico; (2) longer, more participatory process, with multiple cycles of action/reflection and pilot tests, in Chile; (3) open-ended design for ongoing adaptation, in Argentina and Uruguay. Professionals' time and the political cycle were the main barriers to participation. The clinical coordination problem selected was limited communication between primary and secondary care doctors. To address it, through discussions guided by context and feasibility criteria, interventions based on mutual feedback were selected. CONCLUSIONS: As expected in a flexible PAR process, its rollout differed across countries in participation and PAR cycles. Results show that PAR can help to design interventions adapted to context and offers lessons that can be applied in other contexts.

Immunization with nanovaccines containing mutated K-Ras peptides and imiquimod aggravates heterotopic pancreatic cancer induced in mice.

Purpose: The growing incidence and lethality of pancreatic cancer urges the development of new therapeutic approaches. Anti-tumoral vaccines can potentiate the immune response against the tumor, targeting specific antigens expressed only on tumor cells. In this work, we designed new vaccines for pancreatic cancer, composed by chitosan nanocapsules (CS NCs) containing imiquimod (IMQ) as adjuvant, and targeting the K-Ras mutation G12V. Experimental design: We tested the immunogenicity of our vaccines in mice, carrying different combinations of K-Ras mutated peptides. Then, we analyzed their prophylactic and therapeutic efficacy in mice bearing heterotopic pancreatic cancer. Results: Unexpectedly, although good results were observed at short time points, the different combinations of our CS NCs vaccines seemed to potentiate tumor growth and reduce survival rate. We propose that this effect could be due to an inadequate immune response, partially because of the induction of a regulatory tolerogenic response. Conclusion: Our results call for caution in the use of some NCs containing IMQ in the immunotherapy against pancreatic cancer.

Fecal immunochemical test for hemoglobin versus fecal calprotectin to monitor endoscopic activity in inflammatory bowel disease

Aim: endoscopy identifies inflammatory activity, however, it is an unpleasant test and is not always accessible. The aim of the study was to compare the usefulness of quantitative fecal immunochemical test (FIT) versus fecal calprotectin (FC) to determine endoscopic activity in patients with inflammatory bowel disease (IBD). Methods: cross-sectional prospective observational study. The stool samples were collected within three days before starting the preparation for the colonoscopy. We used the Mayo index for ulcerative colitis (UC) and the simplified endoscopic index for Crohn’s disease (CD). Mucosal healing (MH) was defined as the score 0 points in each of the endoscopic indices. Results: eighty-four patients were included, 40 (47.6 %) with UC. In patients with IBD, FIT and FC showed a significant correlation with the presence of inflammatory activity/MH on endoscopy, with no statistically significant differences between the two receiver-operating characteristic (ROC) curves. Both tests improved their diagnostic performance when assessing patients with UC; the Spearman correlations between FIT and FC and endoscopic inflammatory activity were r = 0.6 (p = 0.0001) and r = 0.7 (p = 0.0001), respectively. In Crohn’s disease, the diagnostic utility of both tests was lower. Conclusions: FIT is an alternative to monitor endoscopic activity among ulcerative colitis patients. In Crohn’s disease, more studies are needed to determine the role of fecal biomarkers. (AU)

Improving equity in access to early diagnosis of cancer in different healthcare systems of Latin America: protocol for the EquityCancer-LA implementation-effectiveness hybrid study.

INTRODUCTION: Healthcare fragmentation, a main cause for delay in cancer diagnosis and treatment, contributes to high mortality in Latin America (LA), particularly among disadvantaged populations. This research focuses on integrated care interventions, which have been limitedly implemented in the region. The objective is to evaluate the contextual effectiveness of scaling-up an integrated care intervention to improve early diagnosis of frequent cancers in healthcare networks of Chile, Colombia and Ecuador. METHODS AND ANALYSIS: This research is two pronged: (A) quasi-experimental design (controlled before and after) with an intervention and a control healthcare network in each LA country, using an implementation-effectiveness hybrid approach to assess the intervention process, effectiveness and costs; and (B) case study design to analyse access to diagnosis of most frequent cancers. Focusing on the most vulnerable socioeconomic population, it develops in four phases: (1) analysis of delays and barriers to early diagnosis (baseline); (2) intervention adaptation and implementation (primary care training, fast-track referral pathway and patient information); (3) intracountry evaluation of intervention and (4) cross-country analysis. Baseline and evaluation studies adopt mixed-methods qualitative (semistructured individual interviews) and quantitative (patient questionnaire survey) methods. For the latter, a sample size of 174 patients with cancer diagnosis per healthcare network and year was calculated to detect a proportions difference of 15%, before and after intervention (α=0.05; ß=0.2) in a two-sided test. A participatory approach will be used to tailor the intervention to each context, led by a local steering committee (professionals, managers, policy makers, patients and researchers). ETHICS AND DISSEMINATION: This study complies with international and national legal stipulations on ethics. It was approved by each country's ethical committee and informed consent will be obtained from participants. Besides the coproduction of knowledge with key stakeholders, it will be disseminated through strategies such as policy briefs, workshops, e-tools and scientific papers.

Relational Continuity of Chronic Patients with Primary and Secondary Care Doctors: A Study of Public Healthcare Networks of Six Latin American Countries.

Despite relational continuity (RC) with the doctor being key to care quality for chronic patients, particularly in fragmented healthcare systems, like many in Latin America (LA), little is known about RC and its attributes, particularly regarding specialists. Aim: We aim to analyse chronic patients' perceptions of RC with primary (PC) and secondary (SC) care doctors, and record changes between 2015 and 2017 in the public healthcare networks of six LA countries. An analysis of two cross-sectional studies applying the CCAENA questionnaire to chronic patients (N = 4881) was conducted in Argentina, Brazil, Chile, Colombia, Mexico, and Uruguay. The dependent variables of RC with PC and SC doctors were: consistency, trust, effective communication, and synthetic indexes based on RC attributes. Descriptive and multivariate analyses were performed. Although the RC index was high in 2015, especially in PC in all countries, and at both levels in Argentina and Uruguay, low perceived consistency of PC and SC doctors in Colombia and Chile and of SC doctors in Mexico revealed important areas for improvement. In 2017 the RC index of SC doctors increased in Chile and Mexico, while SC doctors' consistency in Colombia decreased. This study reveals important gaps in achieving RC with doctors, particularly in SC, which requires further structural and organisational reforms.

Combined Inhibition of FOSL-1 and YAP Using siRNA-Lipoplexes Reduces the Growth of Pancreatic Tumor.

Pancreatic cancer evades most of the current therapies and there is an urgent need for new treatments that could efficiently eliminate this aggressive tumor, such as the blocking of routes driving cell proliferation. In this work, we propose the use of small interfering RNA (siRNA) to inhibit the combined expression of FOSL-1 and YAP, two signaling proteins related with tumor cell proliferation and survival. To improve the efficacy of cell transfection, DODAB:MO (1:2) liposomes were used as siRNA nanocarriers, forming a complex denominated siRNA-lipoplexes. Liposomes and lipoplexes (carrying two siRNA for each targeted protein, or the combination of four siRNAs) were physico-chemically and biologically characterized. They showed very good biocompatibility and stability. The efficient targeting of FOSL-1 and YAP expression at both mRNA and protein levels was first proved in vitro using mouse pancreatic tumoral cell lines (KRASG12V and p53 knockout), followed by in vivo studies using subcutaneous allografts on mice. The peri-tumoral injection of lipoplexes lead to a significant decrease in the tumor growth in both Athymic Nude-Foxn1nu and C57BL/6 mice, mainly in those receiving the combination of four siRNAs, targeting both YAP and FOSL-1. These results open a new perspective to overcome the fast tumor progression in pancreatic cancer.

Synergistic Antitumoral Effect of Epigenetic Inhibitors and Gemcitabine in Pancreatic Cancer Cells.

Epigenetic modifications could drive some of the molecular events implicated in proliferation, drug resistance and metastasis of pancreatic ductal adenocarcinoma (PDAC). Thus, epigenetic enzyme inhibitors could be the key to revert those events and transform PDAC into a drug-sensitive tumor. We performed a systematic study with five different epigenetic enzyme inhibitors (1, UVI5008, MS275, psammaplin A, and BIX01294) targeting either Histone Deacetylase (HDAC) 1 or 1/4, DNA methyltransferase 3a (DNMT3a), Euchromatic histone lysine methyltransferase 2 (EHMT2), or Sirtuin 1 (SIRT1), as well as one drug that restores the p53 function (P53R3), in three different human PDAC cell lines (SKPC-1, MIA PaCa-2, and BxPC-3) using 2D and 3D cell cultures. The synergistic effect of these antitumoral drugs with gemcitabine was tested and the most efficient combinations were characterized by RNA-seq. The inhibition of HDAC1/4 (MS275), HDAC1/4/SIRT1/DNMT3a (UVI5008) or EHMT2 (BIX01294) induced a significant reduction on the cell viability, even in gemcitabine-resistance cells. The combination of UVI5008 or MS275 with gemcitabine induced a synergistic effect at low concentration and the RNA-Seq analysis revealed some synergy candidate genes as potential biomarkers. Reverting aberrant epigenetic modifications in combination with gemcitabine offers an alternative treatment for PDAC patients, with an important reduction of the therapeutic dose.

Implementing joint training sessions of general practitioners and specialists aimed at improving clinical coordination in Colombia: Contributions from participatory action research.

OBJECTIVE: To analyse the contribution of participatory action research (PAR) in designing and implementing joint training sessions as a means to improve clinical coordination in a public health care network in Bogotá, Colombia. METHODS: A qualitative, descriptive-interpretative study using semi-structured individual interviews and focus groups with 40 professionals (GPs, specialists, members of the local steering committee (LSC) and network middle managers) involved in designing and implementing joint training sessions to improve cross-level clinical coordination. The intervention consisted of two forms of joint training sessions for GPs and specialists, implemented through two PAR cycles. RESULTS: The PAR approach in designing and implementing joint training sessions led to greater awareness of clinical coordination problems and helped adapting sessions to the local health care context. Study participants highlighted the role of LSC leadership during the PAR process and the importance of ensuring the necessary resources for adopting the intervention. Limited institutional support and differences between joint training sessions affected doctors' participation and reduced the time available to conduct the sessions. The use of a reflexive method was essential in enhancing doctors' participation, along with session duration, the facilitator's role and session content. CONCLUSIONS: The study provides evidence regarding the contribution of a PAR process to designing and implementing joint training sessions for improving clinical coordination. The findings can inform similar approaches in other health systems.

Contribution and Future of High-Throughput Transcriptomics in Battling Tuberculosis.

While Tuberculosis (TB) infection remains a serious challenge worldwide, big data and "omic" approaches have greatly contributed to the understanding of the disease. Transcriptomics have been used to tackle a wide variety of queries including diagnosis, treatment evolution, latency and reactivation, novel target discovery, vaccine response or biomarkers of protection. Although a powerful tool, the elevated cost and difficulties in data interpretation may hinder transcriptomics complete potential. Technology evolution and collaborative efforts among multidisciplinary groups might be key in its exploitation. Here, we discuss the main fields explored in TB using transcriptomics, and identify the challenges that need to be addressed for a real implementation in TB diagnosis, prevention and therapy.

Evaluating the effectiveness of care coordination interventions designed and implemented through a participatory action research process: Lessons learned from a quasi-experimental study in public healthcare networks in Latin America.

BACKGROUND: Despite increasing recommendations for health professionals to participate in intervention design and implementation to effect changes in clinical practice, little is known about this strategy's effectiveness. This study analyses the effectiveness of interventions designed and implemented through participatory action research (PAR) processes in healthcare networks of Brazil, Chile, Colombia, Mexico and Uruguay to improve clinical coordination across care levels, and offers recommendations for future research. METHODS: The study was quasi-experimental. Two comparable networks, one intervention (IN) and one control (CN), were selected in each country. Baseline (2015) and evaluation (2017) surveys of a sample of primary and secondary care doctors (174 doctors/network/year) were conducted using the COORDENA® questionnaire. Most of the interventions chosen were based on joint meetings, promoting cross-level clinical agreement and communication for patient follow-up. Outcome variables were: a) intermediate: interactional and organizational factors; b) distal: experience of cross-level clinical information coordination, of clinical management coordination and general perception of coordination between levels. Poisson regression models were estimated. RESULTS: A statistically significant increase in some of the interactional factors (intermediate outcomes) -knowing each other personally and mutual trust- was observed in Brazil and Chile INs; and in some organizational factors -institutional support- in Colombia and Mexico. Compared to CNs in 2017, INs of Brazil, Chile, Colombia and Mexico showed significant differences in some factors. In distal outcomes, care consistency items improved in Brazil, Colombia and Uruguay INs; and patient follow-up improved in Chile and Mexico. General perception of clinical coordination increased in Brazil, Colombia and Mexico INs. Compared to CNs in 2017, only Brazil showed significant differences. CONCLUSIONS: Although more research is needed, results show that PAR-based interventions improved some outcomes regarding clinical coordination at network level, with differences between countries. However, a PAR process is, by definition, slow and gradual, and longer implementation periods are needed to achieve greater penetration and quantifiable changes. The participatory and flexible nature of interventions developed through PAR processes poses methodological challenges (such as defining outcomes or allocating individuals to different groups in advance), and requires a comprehensive mixed-methods approach that simultaneously evaluates effectiveness and the implementation process to better understand its outcomes.

Assessing the impact of clinical coordination interventions on the continuity of care for patients with chronic conditions: participatory action research in five Latin American countries.

Although fragmentation in the provision of services is considered an obstacle to effective health care, there is scant evidence on the impact of interventions to improve care coordination between primary care and secondary care in terms of continuity of care-i.e. from the patient perspective-particularly in Latin America (LA). Within the framework of the Equity-LA II project, interventions to improve coordination across care levels were implemented in five Latin American countries (Brazil, Chile, Colombia, Mexico and Uruguay) through a participatory action research (PAR) process. This paper analyses the impact of these PAR interventions on the cross-level continuity of care of chronic patients in public healthcare networks. A quasi-experimental study was performed with measurements based on two surveys of a sample of patients with chronic conditions (392 per network; 800 per country). Both the baseline (2015) and evaluation (2017) surveys were conducted using the CCAENA questionnaire. In each country, two comparable public healthcare networks were selected, one intervention and one control. Outcomes were cross-level continuity of information and clinical management continuity. Descriptive analyses were conducted, and Poisson regression models with robust variance were fitted to estimate changes. With differences between countries, the results showed improvements in cross-level continuity of clinical information (transfer of clinical information) and clinical management continuity (care coherence). These results are consistent with those of previous studies on the effectiveness of the interventions implemented in each country in improving care coordination in Brazil, Chile and Colombia. Differences between countries are probably related to particular contextual factors and events that occurred during the implementation process. This supports the notion that certain context and process factors are needed to improve continuity of care. The results provide evidence that, although the interventions were designed to enhance care coordination and aimed at health professionals, patients report improvements in continuity of care.

Care continuity across levels of care perceived by patients with chronic conditions in six Latin-American countries / La continuidad de la atención entre niveles percibida por pacientes con enfermedades crónicas en seis países latinoamericanos

Objective: To analyse the care continuity across levels of care perceived by patients with chronic conditions in public healthcare networks in six Latin American countries (Argentina, Brazil, Chile, Colombia, Mexico and Uruguay), and to explore associated factors. Method: Cross-sectional study by means of a survey conducted to a random sample of chronic patients in primary care centres of the study networks (784 per country) using the questionnaire Cuestionario de Continuidad Asistencial Entre Niveles de Atención (CCAENA)©. Patients had at least one chronic condition and had used two levels of care in the 6 months prior to the survey for the same medical condition. Descriptive analysis and multivariable logistic regression were carried out. Results: Although there are notable differences between the networks analysed, the results show that chronic patients perceive significant discontinuities in the exchange of clinical information between primary care and secondary care doctors and in access to secondary care following a referral; as well as, to a lesser degree, regarding clinical coherence across levels. Relational continuity with primary care and secondary care doctors and information transfer are positively associated with care continuity across levels; no individual factor is systematically associated with care continuity. Conclusions: Main perceived discontinuities relate to information transfer and access to secondary care after a referral. The study indicates the importance of organisational factors to improve chronic patients' quality of care. (AU)

Objetivo: Analizar la continuidad asistencial entre niveles de atención percibida por pacientes con enfermedades crónicas en redes sanitarias públicas de seis países latinoamericanos (Argentina, Brasil, Chile, Colombia, México y Uruguay) y explorar los factores asociados. Método: Estudio transversal mediante una encuesta realizada a una muestra aleatoria de pacientes crónicos en los centros de atención primaria de las redes de estudio (784 por país) utilizando el Cuestionario de Continuidad Asistencial Entre Niveles de Atención (CCAENA©). Los pacientes presentaban al menos una afección crónica y habían utilizado dos niveles de atención en los 6 meses anteriores a la encuesta por el mismo motivo. Se realizaron un análisis descriptivo y una regresión logística multivariante. Resultados: Aunque existen diferencias notables entre las redes analizadas, los resultados muestran que los pacientes crónicos perciben discontinuidades significativas en el intercambio de información clínica entre médicos de atención primaria y secundaria, y en el acceso a la atención secundaria tras una derivación, así como, en menor medida, en la coherencia clínica entre niveles. La continuidad de relación con los médicos de atención primaria y secundaria, y la transferencia de información, se asocian de manera positiva con la continuidad asistencial en ambos niveles; ningún factor individual se asocia sistemáticamente con la continuidad asistencial. Conclusiones: Las principales discontinuidades percibidas se relacionan con la transferencia de información y el acceso a la atención secundaria después de una derivación. El estudio indica la importancia de los factores organizativos para mejorar la calidad de la atención de los pacientes crónicos. (AU)

The PI3Kδ Inhibitor Idelalisib Diminishes Platelet Function and Shows Antithrombotic Potential.

BACKGROUND: Clinical management of ischemic events and prevention of vascular disease is based on antiplatelet drugs. Given the relevance of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) as a candidate target in thrombosis, the main goal of the present study was to identify novel antiplatelet agents within the existing inhibitors blocking PI3K isoforms. METHODS: We performed a biological evaluation of the pharmacological activity of PI3K inhibitors in platelets. The effect of the inhibitors was evaluated in intracellular calcium release and platelet functional assays, the latter including aggregation, adhesion, and viability assays. The in vivo drug antithrombotic potential was assessed in mice undergoing chemically induced arterial occlusion, and the associated hemorrhagic risk evaluated by measuring the tail bleeding time. RESULTS: We show that PI3K Class IA inhibitors potently block calcium mobilization in human platelets. The PI3K p110δ inhibitor Idelalisib inhibits platelet aggregation mediated by ITAM receptors GPVI and CLEC-2, preferentially by the former. Moreover, Idelalisib also inhibits platelet adhesion and aggregation under shear and adhesion to collagen. Interestingly, an antithrombotic effect was observed in mice treated with Idelalisib, with mild bleeding effects at high doses of the drug. CONCLUSION: Idelalisib may have antiplatelet effects with minor bleeding effects, which provides a rationale to evaluate its antithrombotic efficacy in humans.