Beyond tobacco: genomic disparities in lung cancer between smokers and never-smokers.

BACKGROUND: Tobacco use is one of the main risk factors for Lung Cancer (LC) development. However, about 10-20% of those diagnosed with the disease are never-smokers. For Non-Small Cell Lung Cancer (NSCLC) there are clear differences in both the clinical presentation and the tumor genomic profiles between smokers and never-smokers. For example, the Lung Adenocarcinoma (LUAD) histological subtype in never-smokers is predominately found in young women of European, North American, and Asian descent. While the clinical presentation and tumor genomic profiles of smokers have been widely examined, never-smokers are usually underrepresented, especially those of a Latin American (LA) background. In this work, we characterize, for the first time, the difference in the genomic profiles between smokers and never-smokers LC patients from Chile. METHODS: We conduct a comparison by smoking status in the frequencies of genomic alterations (GAs) including somatic mutations and structural variants (fusions) in a total of 10 clinically relevant genes, including the eight most common actionable genes for LC (EGFR, KRAS, ALK, MET, BRAF, RET, ERBB2, and ROS1) and two established driver genes for malignancies other than LC (PIK3CA and MAP2K1). Study participants were grouped as either smokers (current and former, n = 473) or never-smokers (n = 200) according to self-report tobacco use at enrollment. RESULTS: Our findings indicate a higher overall GA frequency for never-smokers compared to smokers (58 vs. 45.7, p-value < 0.01) with the genes EGFR, KRAS, and PIK3CA displaying the highest prevalence while ERBB2, RET, and ROS1 the lowest. Never-smokers present higher frequencies in seven out of the 10 genes; however, smokers harbor a more complex genomic profile. The clearest differences between groups are seen for EGFR (15.6 vs. 21.5, p-value: < 0.01), PIK3CA (6.8 vs 9.5) and ALK (3.2 vs 7.5) in favor of never-smokers, and KRAS (16.3 vs. 11.5) and MAP2K1 (6.6 vs. 3.5) in favor of smokers. Alterations in these genes are comprised almost exclusively by somatic mutations in EGFR and mainly by fusions in ALK, and only by mutations in PIK3CA, KRAS and MAP2K1. CONCLUSIONS: We found clear differences in the genomic landscape by smoking status in LUAD patients from Chile, with potential implications for clinical management in these limited-resource settings.

Downregulation of hsa-miR-132 and hsa-miR-129: non-coding RNA molecular signatures of Alzheimer's disease.

Alzheimer's disease (AD) affects the elderly population by causing memory impairments, cognitive and behavioral abnormalities. Currently, no curative treatments exist, emphasizing the need to explore therapeutic options that modify the progression of the disease. MicroRNAs (miRNAs), as non-coding RNAs, demonstrate multifaceted targeting potential and are known to be dysregulated in AD pathology. This mini review focuses on two promising miRNAs, hsa-miR-132 and hsa-miR-129, which consistently exhibit differential regulation in AD. By employing computational predictions and referencing published RNA sequencing dataset, we elucidate the intricate miRNA-mRNA target relationships associated with hsa-miR-132 and hsa-miR-129. Our review consistently identifies the downregulation of hsa-miR-132 and hsa-miR-129 in AD brains as a non-coding RNA molecular signature across studies conducted over the past 15 years in AD research.

Natural Variation in HIV-1 Entry Kinetics Map to Specific Residues and Reveal an Interdependence Between Attachment and Fusion.

HIV-1 entry kinetics reflect the fluid motion of the HIV envelope glycoprotein through at least three major structural configurations that drive virus-cell membrane fusion. The lifetime of each state is an important component of potency for inhibitors that target them. We used the time-of-addition inhibitor assay and a novel analytical strategy to define the kinetics of pre-hairpin exposure (using T20) and co-receptor engagement (via. maraviroc), through a characteristic delay metric, across a variety of naturally occurring HIV Env isolates. Among 257 distinct HIV-1 envelope isolates we found a remarkable breadth of T20 and maraviroc delays ranging from as early as 30 seconds to as late as 60 minutes. The most extreme delays were observed among transmission-linked clade C isolates. We identified four single-residue determinants of late T20 and maraviroc delays that are associated with either receptor engagement or gp41 function. Comparison of these delays with T20 sensitivity suggest co-receptor engagement and fusogenic activity in gp41 act cooperatively but sequentially to drive entry. Our findings support current models of entry where co-receptor engagement drives gp41 eclipse and have strong implications for the design of entry inhibitors and antibodies that target transient entry states. Author Summary: The first step of HIV-1 infection is entry, where virus-cell membrane fusion is driven by the HIV-1 envelope glycoprotein through a series of conformational changes. Some of the most broadly active entry inhibitors work by binding conformations that exist only transiently during entry. The lifetimes of these states and the kinetics of entry are important elements of inhibitor activity for which little is known. We demonstrate a remarkable range of kinetics among 257 diverse HIV-1 isolates and find that this phenotype is highly flexible, with multiple single-residue determinants. Examination of the kinetics of two conformational landmarks shed light on novel kinetic features that offer new details about the role of co-receptor engagement and provide a framework to explain entry inhibitor synergy.

[Relación entre el estado ponderal y la postura del pie en escolares españoles: estudio transversal]. / Relationship between weight status and foot posture in spanish schools: cross-sectional study.

OBJECTIVE: Childhood flatfoot and overweight can affect children's quality of life and influence their development, increasing the risk of musculoskeletal problems in adulthood. There is evidence linking overweight to the development of childhood flatfoot. The aim of the study was to assess the relationship between the weight status of school children and their foot posture and to determine whether there are differences between both sexes. METHODS: A cross-sectional study (2021) in a sample of schoolchildren (n=296, 153 boys and 143 girls, mean age 8.5±2.7) from Colegio San Agustín in Zaragoza was carried out. Foot posture was assessed according to the foot postural index, and weight status was obtained using the body mass index according to the criteria of the International Obesity Task Force. The correlation between weight status and foot posture was analyzed using Spearman's coefficient. The Chi-square test was used to determine the differences between the variables according to sex. RESULTS: Weight status showed no correlation with foot posture in boys (right foot p=0.095; left foot p=0.067) and girls (right foot p=-0.04; left foot p=0.008). Boys had a higher prevalence of flat feet than girls (boys foot posture index=8; girls foot posture index=7; right foot p<0.036; left foot p<0.009). Boys had higher prevalence of overweight than girls (28.75; 18.18, p<0.027). CONCLUSIONS: Weight status has no effect on foot posture. The male gender could predispose to the development of flat feet and overweight in childhood.

OBJECTIVE: El pie plano infantil y el sobrepeso pueden afectar a la calidad de vida durante la infancia e influir en su desarrollo, aumentando el riesgo de problemas musculoesqueléticos en la edad adulta. Existe evidencia que relaciona el sobrepeso con el desarrollo de pie plano infantil. El objetivo del estudio fue evaluar la relación entre el estado ponderal de los escolares y su postura del pie y determinar si existían diferencias entre ambos sexos. METHODS: Se realizó un estudio descriptivo de corte transversal en el mes de febrero de 2021, en una población de escolares españoles (n=296, 153 niños y 143 niñas, edad media de 8,5±2,7 años). La postura del pie se evaluó según el índice postural del pie, y el estado ponderal se obtuvo mediante el índice de masa corporal según criterios de la International Obesity Task Force. Se analizó la correlación entre el estado ponderal y la postura del pie con el coeficiente de Spearman. Mediante la prueba Chi-cuadrado se determinaron las diferencias entre las variables según sexo. RESULTS: El estado ponderal no mostró correlación respecto a la postura del pie en niños (pie derecho p=0,095; pie izquierdo p=0,067) y en niñas (pie derecho p=-0,04; pie izquierdo p=0,008). Los niños presentaron una prevalencia mayor de pies planos que las niñas (índice postural del pie en niños=8; índice postural del pie en niñas=7; pie derecho p<0,036; pie izquierdo p<0,009). Los niños tuvieron mayor prevalencia de sobrepeso respecto a las niñas (28,75; 18,18, p<0,027). CONCLUSIONS: El estado ponderal no influye sobre la postura del pie. El sexo masculino podría predisponer al desarrollo de pie plano y sobrepeso en la infancia.

The conundrum of differentiating Cushing's syndrome from non-neoplastic hypercortisolism: a systematic review and meta-analysis.

CONTEXT: Once hypercortisolemia is confirmed, differential diagnosis between Cushing's syndrome (CS) due to neoplastic endogenous hypercortisolism and non-neoplastic hypercortisolism (NNH, pseudo-Cushing's syndrome) is crucial. Due to worldwide corticotropin-releasing hormone (CRH) unavailability, accuracy of alternative tests to dexamethasone (Dex)-CRH, is clearly needed. OBJECTIVE: Assess the diagnostic accuracy of Dex-CRH test, desmopressin stimulation test, midnight serum cortisol (MSC), and late-night salivary cortisol (LNSC) levels to distinguish CS from NNH. METHODS: Articles through March 2022 were identified from Scopus, Web of Science, MEDLINE, EMBASE, and PubMed. All steps through the systematic review were performed independently and in duplicate and strictly adhered to the updated PRISMA-DTA checklist. DATA SYNTHESIS: A total of 24 articles (1900 patients) were included. Dex-CRH had a pooled sensitivity and specificity of 91% (95%CI 87-94%; I2 0%) and 82% (73-88%; I2 50%), desmopressin test 86% (81-90%; I2 28%) and 90% (84-94%; I2 15%), MSC 91% (85-94%; I2 66%) and 81% (70-89%; I2 71%), and LNSC 80% (67-89%; I2 57%) and 90% (84-93%; I2 21%), respectively. Summary receiver operating characteristics areas under the curve were Dex-CRH 0.949, desmopressin test 0.936, MSC 0.942, and LNSC 0.950 without visual or statistical significance. The overall risk of studies bias was moderate. CONCLUSION: Dex-CRH, the desmopressin stimulation test, and MSC have similar diagnostic accuracy, with Dex-CRH and MSC having slightly higher sensitivity, and the desmopressin test being more specific. LNSC was the least accurate, probably due to high heterogeneity, intrinsic variability, different assays, and lack of consistent reported cutoffs. When facing this challenging differential diagnosis, the results presented here should increase clinicians' confidence when deciding which test to perform.

Alteration of gene expression and protein solubility of the PI 5-phosphatase SHIP2 are correlated with Alzheimer's disease pathology progression.

A recent large genome-wide association study has identified EGFR (encoding the epidermal growth factor EGFR) as a new genetic risk factor for late-onset AD. SHIP2, encoded by INPPL1, is taking part in the signalling and interactome of several growth factor receptors, such as the EGFR. While INPPL1 has been identified as one of the most significant genes whose RNA expression correlates with cognitive decline, the potential alteration of SHIP2 expression and localization during the progression of AD remains largely unknown. Here we report that gene expression of both EGFR and INPPL1 was upregulated in AD brains. SHIP2 immunoreactivity was predominantly detected in plaque-associated astrocytes and dystrophic neurites and its increase was correlated with amyloid load in the brain of human AD and of 5xFAD transgenic mouse model of AD. While mRNA of INPPL1 was increased in AD, SHIP2 protein undergoes a significant solubility change being depleted from the soluble fraction of AD brain homogenates and co-enriched with EGFR in the insoluble fraction. Using FRET-based flow cytometry biosensor assay for tau-tau interaction, overexpression of SHIP2 significantly increased the FRET signal while siRNA-mediated downexpression of SHIP2 significantly decreased FRET signal. Genetic association analyses suggest that some variants in INPPL1 locus are associated with the level of CSF pTau. Our data support the hypothesis that SHIP2 is an intermediate key player of EGFR and AD pathology linking amyloid and tau pathologies in human AD.

Experiences of patients with Parkinson's disease belonging to an association. A qualitative approach.

INTRODUCTION: Parkinson's disease (PD) affects the physical, cognitive, emotional, and social domains of people who suffer it. A good strategy for patients is to belong to an Association, using the services they offer. OBJECTIVE: The aim of this study was to explore the experiences and perceptions of patients with PD in a Parkinson's Association. METHODS: A sample of participants with PD who met the inclusion criteria was selected through purpose and theoretical sampling. Semi-structured qualitative interviews were used to collect the data, which was analyzed by thematic phenomenological analysis. Different strategies such as triangulation between researchers were used to ensure methodological rigor. RESULTS: The data analyzed from 10 participants led to two themes: the context of the Association, where the importance of interdisciplinary treatments and the relationship with other patients is collected; and how they see their future, which describes the future perspectives that patients with PD have. DISCUSSION: Patients agree on the importance of belonging to the Association, feeling part of a group, while benefiting from receiving therapies from the interdisciplinary team. The Association plays a relevant role in the evolution of the disease, as it influences how patients imagine their future. Developing strategies based on a good therapeutic alliance with professionals at the service of patients promotes the empowerment, adherence and continuity of treatments at home, which results in improving the quality of life of patients with PD.

An Opportunity for Management of Fatigue, Physical Condition, and Quality of Life Through Asynchronous Telerehabilitation in Patients After Acute Coronavirus Disease 2019: A Randomized Controlled Pilot Study.

OBJECTIVE: To compare the preliminary efficacy of asynchronous telerehabilitation in patients after acute coronavirus disease 2019 (COVID-19) on fatigue, physical condition, quality of life, and feasibility of this pilot study with that of a booklet format. DESIGN: Randomized pilot study with 2 intervention arms: asynchronous telerehabilitation group and booklet-based rehabilitation group, with 2 follow-ups at 3 and 6 months. SETTING: Hospital. PARTICIPANTS: Patients discharged after COVID-19 were recruited and evaluated (N=35). INTERVENTIONS: The intervention consisted of a 12-week multimodal rehabilitation program via telerehabilitation or by a booklet. MAIN OUTCOME MEASURES: Fatigue as the main outcome and functional status, quality of life, and feasibility as secondary outcomes were evaluated. RESULTS: After the intervention, there was no significant difference between groups in fatigue, but there were significant differences in favor of the asynchronous telerehabilitation group for the 6-Minute Walk Test (p=.008), the 30-Second Sit-to-Stand Test (p=.019), and physical quality of life (p=.035). These improvements were maintained throughout the 6-month follow-up. Telerehabilitation was shown to be a viable option, without incidents and with a higher adhesion (p=.028) than the booklet format. CONCLUSIONS: A multimodal rehabilitation program by means of asynchronous telerehabilitation appears as a more effective option than traditional formats in improving post-acute COVID-19 sequelae.

Physical therapy interventions for people experiencing homelessness to improve pain and self-perceived health status.

BACKGROUND: Homeless shelters have emerged as components of the social services network, playing an important role in providing health care to the homeless population. The aim of this study was to evaluate an individualized physical therapy intervention for people experiencing homelessness and to determine the relationship between self-perceived variables. METHODS: Pre and post study, setting at the "Santa y Real Hermandad de Nuestra Señora del Refugio y Piedad" homeless shelter in Zaragoza, Spain. Participants were people experiencing homelessness with musculoskeletal disorders who attended a physical therapy service at shelter facilities. A physical therapy program was implemented including health education, exercise and manual therapy, electrotherapy, thermotherapy and bandaging. Demographic variables (age and gender), nationality, employment situation, educational level, pain location, number of painful areas, feeling of loneliness (3-Item Loneliness Scale; values from 3 to 9), pain intensity (Numerical Pain Rating Scale [NPRS]; from 0 to 10) and self-perceived health (Clinical Global Impression [CGI]; from 1 to 7). RESULTS: Sixty-four homeless people (age of 46.4 ± 10.9 years) participated in the study. Musculoskeletal pain was reported by 98.4% of subjects, with moderate pain intensities (6.1), and 48.4% presenting with pain at multiple sites. Perceptions of loneliness were low (3.7 ± 2.5) and self-perceived health status was moderately ill (3.5 ± 1.7). Positive significant correlations were identified between pain intensity and self-perceived health. The average number of sessions was 1.5 (± 0.8), with manual therapy (35.6%) followed by health education (23.5%) being the most frequently used techniques. Both pain and self-perceived health improved after treatment, even following a brief intervention. CONCLUSIONS: This study demonstrates the potentially negative impact of untreated pain on the self-perceived health of homeless individuals with musculoskeletal disorders that should be targeted for consideration. The findings suggest that a paradigm shift in pain management, including a physical therapy service in shelters, is needed to address the rehabilitation demands of these individuals in a real-life context. This study was approved by the Aragon Ethics Committee (PI19/438) and performed according to the Transparent Reporting of Evaluations with Nonrandomized Designs (TREND) statement.

Effects of transcutaneous radiofrequency diathermy versus ultrasound on latent myofascial trigger points in the upper trapezius: A randomized crossover trial.

BACKGROUND: Currently, the use of radiofrequency diathermy for the treatment of neck pain is booming. OBJECTIVE: This study aimed to evaluate the clinical efficacy of Digital Capacitive Diathermy (DCD®) on stiffness, pain, cervical range of motion, and cervical disability and to compare it with ultrasound (US) in patients with latent myofascial trigger point (MTrP) in the upper trapezius. METHODS: Nineteen participants with latent MTrPs in the upper trapezius were included in the assessor-masked, randomized, clinical crossover trial. Subjects were exposed to both interventions: US and DCD® and treatment effectiveness was measured by myotonometric variables, pressure pain threshold (PPT), visual analog scale (VAS), cervical side-bending flexion ranges, and the neck disability index scale (NDI). RESULTS: There were no significant differences between US and DCD® interventions regarding changes in outcome measures. The US group achieved a statistically significant difference of 2.16 to 1.13 points (p= 0.005; r= 0.646) for the VAS. The DCD® intervention showed a statistically significant improvement of 1.11 points for the NDI at 1-week following intervention (95% CI 0.14-2.07; p= 0.27; d= 0.217). CONCLUSION: Our findings suggest that DCD® and US can both be considered effective modalities for the treatment of latent MTrPs, having a longer duration of action with DCD® therapy.

Synthesis of Stable Isotope, Tritiated, and Carbon-14 Labeled Balcinrenone.

As part of a medicinal chemistry program aimed at discovering a mineralocorticoid receptor modulator for treatment of kidney and cardiovascular indications, multiple labeled versions of the lead compound, balcinrenone (AZD9977), were prepared. Four stable isotope labeled versions of the compound were prepared for clinical bioanalysis and biological investigations. Three of these stable isotope labeled compounds were tritiated as well as the parent for biology applications and DMPK investigations. They were prepared using a standard iodination-tritiodehalogentation approach. Finally, AZD9977 was prepared in carbon-14 labeled form for preclinical and clinical applications.

Comparing reactogenicity of COVID-19 vaccine boosters: a systematic review and meta-analysis.

INTRODUCTION: Different COVID-19 vaccines are being utilized as boosters. This systematic review and meta-analysis aims to evaluate the reactogenicity of COVID-19 vaccines given as booster doses, according to vaccine type, dose, timing, participant characteristics and primary immunization regimen received. METHODS: Four databases (MEDLINE, Embase, Web of Science and CENTRAL) were searched for randomized controlled trials between 1 January 2020 and 1 January 2023 according to predetermined criteria. RESULTS: Twenty-eight studies describing 19 vaccines of four different types (viral vector, inactivated, mRNA and protein sub-unit) were identified. BNT162b2 vaccine (Pfizer-BioNTech) was selected as the control as it was most often compared with other vaccines. Fever, fatigue, headache, injection-site pain, redness, and swelling were the most frequently reported solicited events. mRNA vaccines were the most reactogenic, followed by viral vector vaccines and protein sub-unit vaccines, while inactivated vaccines were the least reactogenic. Full-dose vaccines were more reactogenic than half-dose vaccines. Heterologous BNT162b2 boosters were more reactogenic than boosters with the same vaccine used for primary immunization. CONCLUSIONS: COVID-19 vaccine booster schedules have distinct reactogenicity profiles, dependent on dose and vaccine type, which may allow targeted recommendations and provide choice for specific populations. Greater standardization of adverse event reporting will aid future studies.

Assessment of the likelihood of hypothyroidism in dogs diagnosed with and treated for hypothyroidism at primary care practices: 102 cases (2016-2021).

BACKGROUND: There is a possibility that an incorrect diagnosis of hypothyroidism could be made in euthyroid dogs, and the prevalence of hypothyroidism in the dog population remains unknown. OBJECTIVES: To retrospectively assess the percentage of dogs diagnosed with, and treated for, hypothyroidism at first opinion practice which are likely to be hypothyroid and require levothyroxine supplementation. ANIMALS: One hundred two client-owned dogs were included in this study. MATERIALS AND METHODS: The computerized databases of 7 first opinion practices were searched to identify dogs treated with levothyroxine supplementation. Three European College of Veterinary Internal Medicine-Companian Animals (ECVIM-CA) diplomates independently assigned 1 of 4 clinical assessments to each case as follows: confirmed or likely hypothyroid, hypothyroidism suspected but not confirmed, hypothyroidism considered unlikely, and no reason to suspect hypothyroidism. They commented as to whether or not they thought levothyroxine supplementation was appropriate. RESULTS: The clinical assessments of "confirmed or likely hypothyroid"; "Hypothyroidism suspected but not confirmed"; "Hypothyroidism considered unlikely"; and "No reason to suspect hypothyroidism" was assigned respectively by Clinician 1 to 38.2%, 5.9%, 3.9%, and 52% of cases, by Clinician 2 to 48%, 22.6%, 22.6%, 6.9% of cases, and by Clinician 3 to 55.9%, 11.8%, 13.7% and 18.6%. Clinician 1, Clinician 2, and Clinician 3 considered levothyroxine supplementation not indicated in 58.8%, 52.9%, and 45.1% of cases, respectively. CONCLUSION: These results support the concern that hypothyroidism might be overly and incorrectly diagnosed in first opinion practice, and that thyroid function testing should be performed only in those dogs with a high pretest probability of the disease.

Perfil clínico de la hipercolesterolemia severa en 156.000 adultos en atención primaria / Clinical profile of severe hypercholesterolemia in 156.000 adults in primary care

Objetivo Estimar la frecuencia y el perfil clínico de la hipercolesterolemia severa (HS) y del fenotipo de hipercolesterolemia familiar (HF) en el ámbito de atención primaria, en un área sanitaria de la comunidad de Madrid (CAM). Material y métodos Estudio transversal, multicéntrico de sujetos con tarjeta sanitaria adscritos a 69 centros de salud (área NorOeste/CAM). Se definió HS como colesterol ≥300mg/dl o colesterol-LDL ≥220mg/dl en alguna analítica realizada (1-1-2018 a 30-12-2021), y fenotipo de HF como cLDL ≥240mg/dl (≥160mg/dl si tratamiento hipolipemiante), con triglicéridos <200mg/dl y TSH <5μIU/ml. Resultados Se analizaron 156.082 adultos ≥18años con perfil lipídico disponible. 6.187 sujetos tenían HS (3,96% de las analíticas estudiadas; IC95%: 3,87-4,06%). El tiempo medio de evolución del diagnóstico de hiperlipemia en la historia clínica informatizada fue 10,8años; el 36,5% tenían hipertensión, el 9,5%, diabetes, y el 62,9%, sobrepeso/obesidad. El 83,7% tomaban hipolipemiantes (65,7% de baja/moderada y 28,6% de alta/muy-alta intensidad). El 6,1% tenían enfermedad cardiovascular (94,2% tratados con hipolipemiantes), con colesterol LDL <55, <70 y <100mg/dl de 1,8%, 5,8% y 20,2%, respectivamente (vs 1%, 2,3% y 11,2% si no había enfermedad cardiovascular). Mil seiscientos sujetos tenían fenotipo de HF (IC95%: 1,03%, 0,98-1,08%). Conclusiones Cuatro de cada 100 pacientes analizados en atención primaria tienen HS. Hay un elevado nivel de tratamiento farmacológico, pero de insuficiente intensidad, y escaso logro de objetivos terapéuticos. Uno de cada 100 tiene fenotipo de HF. La identificación de ambas situaciones por registros informatizados permitiría su detección más precisa y precoz y establecer estrategias preventivas cardiovasculares. (AU)

Objective To examine the frequency of severe hypercholesterolemia (HS) and its clinical profile, and the phenotype of familial hypercholesterolemia (FH), in the primary-care setting in a large health area of the Community of Madrid (CAM). Material and methods Multicenter study of subjects with a health card assigned to 69 health centers (Northwest/CAM area). HS was defined as cholesterol ≥300mg/dL or LDL-cholesterol ≥220mg/dL in any analysis performed (1-1-2018 to 12-30-2021); and FH phenotype as c-LDL ≥240mg/dL (≥160mg/dL if lipid-lowering treatment) with triglycerides <200mg/dL and TSH <5μIU/mL. Results 156,082 adults ≥18years with an available lipid profile were analyzed. 6187 subjects had HS (3.96% of the laboratory tests studied, 95%CI: 3.87-4.06%). The mean evolution time of the diagnosis of hyperlipidemia in the computerized clinical record was 10.8years, 36.5% had hypertension, 9.5% diabetes and 62.9% overweight/obesity. 83.7% were taking lipid-lowering drugs (65.7% low/moderate and 28.6% high/very high intensity). 6.1% had cardiovascular disease (94.2% treated with lipid-lowering agents), with LDL-cholesterol <55, <70 and <100mg/dL of 1.8%, 5.8% and 20.2%, respectively (vs. 1%, 2.3% and 11.2% if no cardiovascular disease). 1600 subjects had FH phenotype (95%CI: 1.03%, 0.98-1.08%). Conclusions Four out of 100 patients analyzed in primary care have HS, with high treatment level, but insufficient intensity, and poor achievement of treatment goals. One in 100 have the FH phenotype. The identification of both dyslipidemias by computerized records would allow their more precise and early detection and establish cardiovascular preventive strategies. (AU)

Clinical profile of severe hypercholesterolemia in 156,000 adults in primary care. / Perfil clínico de la hipercolesterolemia severa en 156.000 adultos en atención primaria.

OBJECTIVE: To examine the frequency of severe hypercholesterolemia (HS) and its clinical profile, and the phenotype of familial hypercholesterolemia (FH), in the primary-care setting in a large health area of the Community of Madrid (CAM). MATERIAL AND METHODS: Multicenter study of subjects with a health card assigned to 69 health centers (Northwest/CAM area). HS was defined as cholesterol ≥300mg/dL or LDL-cholesterol ≥220mg/dL in any analysis performed (1-1-2018 to 12-30-2021); and FH phenotype as c-LDL ≥240mg/dL (≥160mg/dL if lipid-lowering treatment) with triglycerides <200mg/dL and TSH <5µIU/mL. RESULTS: 156,082 adults ≥18years with an available lipid profile were analyzed. 6187 subjects had HS (3.96% of the laboratory tests studied, 95%CI: 3.87-4.06%). The mean evolution time of the diagnosis of hyperlipidemia in the computerized clinical record was 10.8years, 36.5% had hypertension, 9.5% diabetes and 62.9% overweight/obesity. 83.7% were taking lipid-lowering drugs (65.7% low/moderate and 28.6% high/very high intensity). 6.1% had cardiovascular disease (94.2% treated with lipid-lowering agents), with LDL-cholesterol <55, <70 and <100mg/dL of 1.8%, 5.8% and 20.2%, respectively (vs. 1%, 2.3% and 11.2% if no cardiovascular disease). 1600 subjects had FH phenotype (95%CI: 1.03%, 0.98-1.08%). CONCLUSIONS: Four out of 100 patients analyzed in primary care have HS, with high treatment level, but insufficient intensity, and poor achievement of treatment goals. One in 100 have the FH phenotype. The identification of both dyslipidemias by computerized records would allow their more precise and early detection and establish cardiovascular preventive strategies.

Use of digoxin in the emergency department to treat patients with acute heart failure and its impact on short-term outcomes. / Uso de digoxina endovenosa en urgencias para tratar pacientes con insuficiencia cardiaca aguda y su impacto en la evolución a corto plazo.

OBJECTIVES: To analyze factors related to the use of digoxin to treat patients with acute heart failure (AHF) in emergency departments (EDs) and the impact of digoxin treatment on short-term outcomes. MATERIAL AND METHODS: We included patients diagnosed with AHF in 45 Spanish EDs. The patients, who were not undergoing long-term treatment for heart failure, were classified according to whether or not they were given intravenous digoxin in the ED. Fifty-one patient or cardiac decompensation episode variables were recorded to profile ED patients treated with digoxin. Outcome variables studied were the need for hospital admission, prolonged stay in the ED (> 24 hours) for discharged patients, prolonged hospitalization (> 7 days) for admitted patients, and all-cause in-hospital or 30-day mortality. The associations between digoxin treatment and the outcomes were studied with odds ratios (ORs) adjusted for patient and AHF episode characteristics. RESULTS: Data for 15 549 patients (median age, 83 years; 55% women) were analyzed; 1430 (9.2%) were treated with digoxin. Digoxin was used more often in women, young patients, and those with better New York Heart Association (NYHA) classifications but more severe cardiac decompensation, especially if the trigger was atrial fibrillation with rapid ventricular response. Admissions were ordered for 75.4% of the patients overall (81.6% of digoxin-treated patients vs 74.8% of nontreated patients; P .001). The ED stay was prolonged in 38.3% of patients discharged from the ED (52.9% of digoxin-treated patients vs 37.2% of nontreated patients; P .001). The duration of hospital stay was prolonged in 48.1% (digoxin-treated, 49.3% vs 47.9%; P = .385). In-hospital mortality was 7.2% overall (6.9% vs 7.2%, P= .712), and 30-day mortality was 9.7% (9.3% vs 9.7%, P = .625). ED use of digoxin was associated with a prolonged stay in the department (adjusted OR, 1.883; 95% CI, 1.359-2.608) but not with hospitalization or mortality. CONCLUSION: Digoxin continues to be used in one out of ten ED patients who are not already on long-term treatment with the drug. Digoxin use is associated with cardiac decompensation triggered by atrial fibrillation with rapid ventricular response, younger age, women, and patients with better initial NYHA function status but possibly more severe decompensation. Digoxin use leads to a longer ED stay but is safe, as it is not associated with need for admission, prolonged hospitalization, or short-term mortality.

OBJETIVO: Analizar los factores relacionados con el uso de digoxina en urgencias en pacientes con insuficiencia cardiaca aguda (ICA) y el impacto pronóstico a corto plazo. METODO: Se incluyeron pacientes diagnosticados de ICA en 45 servicios de urgencias españoles sin tratamiento crónico con digoxina, los cuales se dividieron según recibiesen digoxina endovenosa en urgencias o no. Se recogieron 51 variables relativas al paciente o al episodio de descompensación y se investigó el perfil del paciente tratado con digoxina en urgencias. Como variables evolutivas se investigaron la necesidad de ingreso, la estancia en urgencias prolongada (> 24 horas) en dados de alta y la hospitalización prolongada (> 7 días) en ingresados, y la mortalidad intrahospitalaria y a 30 días por cualquier causa. Se analizó si el tratamiento con digoxina se asoció a diferencias evolutivas, de forma cruda y ajustada a las características del paciente y el episodio de ICA. RESULTADOS: Se analizaron 15.549 pacientes (mediana = 83 años, mujeres = 55%), de los que 1.430 (9,2%) fueron tratados con digoxina. La digoxina se utilizó más en mujeres, pacientes jóvenes, en mejor clase funcional de la New York Heart Association (NYHA), pero con descompensaciones más graves y, sobre todo, cuando existía una fibrilación auricular (FA) con respuesta ventricular rápida como desencadenante. Se hospitalizó el 75,4% de pacientes (más frecuente en tratados con digoxina; 81,6% vs 74,8%, p 0,001), tuvo estancia prolongada en urgencias el 38,3% (52,9% vs 37,2%, p 0,001), hospitalización prolongada el 48,1% (49,3% vs 47,9%, p = 0,385), mortalidad intrahospitalaria el 7,2% (6,9% vs 7,2%, p = 0,712) y a 30 días el 9,7% (9,3% vs 9,7%, p = 0,625). El modelo ajustado mostró que el uso de digoxina en urgencias sólo se asoció con estancia prolongada en urgencias (OR = 1,883, IC 95% = 1,359-2,608), pero no con la necesidad de ingreso, hospitalización prolongada o mortalidad. CONCLUSIONES: La digoxina continúa utilizándose en uno de cada 10 pacientes con ICA atendidos en urgencias que no utilizaban este fármaco de manera habitual. Su uso se relaciona con un paciente cuya ICA ha sido descompensada por una FA con respuesta ventricular rápida, más joven y más frecuentemente mujer, en mejor clase funcional de la NYHA basal y con una descompensación posiblemente más grave. El uso de digoxina conlleva una estancia en urgencias más prolongada, pero su uso es seguro, pues no se asocia a la necesidad de ingreso, hospitalización prolongada o mortalidad a corto plazo.

Impact of the MEESSI-AHF tool to guide disposition decision-making in patients with acute heart failure in the emergency department: a before-and-after study.

OBJECTIVES: To determine the impact of risk stratification using the MEESSI-AHF (Multiple Estimation of risk based on the Emergency department Spanish Score In patients with acute heart failure) scale to guide disposition decision-making on the outcomes of ED patients with acute heart failure (AHF), and assess the adherence of emergency physicians to risk stratification recommendations. METHODS: This was a prospective quasi-experimental study (before/after design) conducted in eight Spanish EDs which consecutively enrolled adult patients with AHF. In the pre-implementation stage, the admit/discharge decision was performed entirely based on emergency physician judgement. During the post-implementation phase, emergency physicians were advised to 'discharge' patients classified by the MEESSI-AHF scale as low risk and 'admit' patients classified as increased risk. Nonetheless, the final decision was left to treating emergency physicians. The primary outcome was 30-day all-cause mortality. Secondary outcomes were days alive and out of hospital, in-hospital mortality and 30-day post-discharge combined adverse event (ED revisit, hospitalisation or death). RESULTS: The pre-implementation and post-implementation cohorts included 1589 and 1575 patients, respectively (median age 85 years, 56% females) with similar characteristics, and 30-day all-cause mortality was 9.4% and 9.7%, respectively (post-implementation HR=1.03, 95% CI=0.82 to 1.29). There were no differences in secondary outcomes or in the percentage of patients entirely managed in the ED without hospitalisation (direct discharge from the ED, 23.5% vs 24.4%, OR=1.05, 95% CI=0.89 to 1.24). Adjusted models did not change these results. Emergency physicians followed the MEESSI-AHF-based recommendation on patient disposition in 70.9% of cases (recommendation over-ruling: 29.1%). Physicians were more likely to over-rule the recommendation when 'discharge' was recommended (56.4%; main reason: need for hospitalisation for a second diagnosis) than when 'admit' was recommended (12.8%; main reason: no appreciation of severity of AHF decompensation by emergency physician), with an OR for over-ruling the 'discharge' compared with the 'admit' recommendation of 8.78 (95% CI=6.84 to 11.3). CONCLUSIONS: Implementing the MEESSI-AHF risk stratification tool in the ED to guide disposition decision-making did not improve patient outcomes.

[Evaluation of a change in the serological diagnostic algorithm for Chagas disease in ColombiaAvaliação da mudança do algoritmo de diagnóstico sorológico da doença de Chagas na Colômbia]. / Evaluación del cambio del algoritmo de diagnóstico serológico para la enfermedad de Chagas en Colombia.

Objective: To evaluate the effects of changing the algorithm for serological diagnosis of T. cruzi infection in departmental-level public health laboratories and in the National Reference Laboratory of Colombia, from the perspective of access to diagnosis. Methods: A descriptive, cross-sectional study was carried out, based on secondary sources between 2015 and 2021, consolidating the number of serological tests carried out by the laboratories. A survey was developed to identify benefits and limitations in the implementation of the new algorithm for serological diagnosis. Totals, proportions, and averages of the number of tests were estimated by comparing two different periods. Results: Information from 33 public health laboratories was analyzed, 87.9% of which processed serological assays during the period under study. The use of serological tests increased after the publication of the new guideline in 2017, and the capacity to perform the second test increased from four to 33 public health laboratories. In absolute terms, ELISAs for antigens and recombinant antigens became the most performed tests in Colombia after 2017. Conclusions: The change in the algorithm for serological diagnosis of Chagas disease in Colombia in 2017 had positive effects on access to diagnosis since it facilitated the use of the second test. This change resulted in increased diagnostic coverage. The country's laboratories have access to a simple, timely, quality algorithm that could be implemented in almost any clinical laboratory in the country.

Objetivo: Avaliar os efeitos da mudança do algoritmo de diagnóstico sorológico da infecção por T. cruzi nos Laboratórios Departamentais de Saúde Pública e no Laboratório Nacional de Referência da Colômbia desde a perspectiva do acesso ao diagnóstico. Métodos: Foi realizado um estudo descritivo transversal a partir de fontes secundárias do período entre 2015 e 2021, consolidando-se o número de testes sorológicos realizados pelos laboratórios. Foi desenvolvido um questionário para identificar benefícios e limitações na implementação do novo algoritmo de diagnóstico sorológico. Os totais, as proporções e as médias do número de testes foram estimados pela comparação de dois períodos diferentes. Resultados: Dados de 33 laboratórios de saúde pública foram analisados, e constatou-se que 87,9% processaram testes sorológicos durante o período analisado. O uso de testes sorológicos aumentou após a publicação das novas diretrizes em 2017, e a capacidade de realizar um segundo teste aumentou de 4 para 33 laboratórios de saúde pública. O ELISA com antígeno total e o ELISA com antígeno recombinante se consolidaram como os testes mais realizados na Colômbia após 2017. Conclusões: A mudança no algoritmo de diagnóstico sorológico da doença de Chagas na Colômbia em 2017 teve efeitos positivos no acesso ao diagnóstico, facilitando o uso do segundo teste, o que resultou em maior cobertura diagnóstica. Os laboratórios do país têm à sua disposição um algoritmo simples, oportuno e de alta qualidade que poderia ser implementado em quase todos os laboratórios clínicos do país.

Evaluación del cambio del algoritmo de diagnóstico serológico para la enfermedad de Chagas en Colombia / Evaluation of a change in the serological diagnostic algorithm for Chagas disease in Colombia / Avaliação da mudança do algoritmo de diagnóstico sorológico da doença de Chagas na Colômbia

[RESUMEN]. Objetivo. Evaluar los efectos del cambio del algoritmo de diagnóstico serológico para la infección por T. cruzi en los Laboratorios de Salud Pública Departamentales y en el Laboratorio Nacional de Referencia de Colombia, desde una perspectiva del acceso al diagnóstico. Métodos. Se realizó un estudio descriptivo, transversal, a partir de fuentes secundarias entre el 2015 y 2021, se consolidó el número de ensayos serológicos realizados por los laboratorios. Se elaboró una encuesta para identificar beneficios y limitaciones en la implementación del nuevo algoritmo de diagnóstico serológico. Se estimaron totales, proporciones y promedios del número de pruebas comparando dos periodos diferentes. Resultados. Se analizó la información de 33 Laboratorios de Salud Pública, encontrando que el 87,9% de ellos procesaron ensayos serológicos durante el periodo analizado. El uso de las pruebas serológicas aumentó después de la publicación del nuevo lineamiento en 2017 y la capacidad de realización de la segunda prueba paso de 4 a 33 Laboratorios de Salud Pública. La ELISA de antígenos totales y de antígenos recombinantes se consolidaron como las pruebas más realizadas en Colombia después del 2017. Conclusiones. El cambio del algoritmo de diagnóstico serológico para la enfermedad de Chagas en Colombia en 2017 tuvo efectos positivos en el acceso al diagnóstico ya que facilitó el uso de la segunda prueba, esta modificación se tradujo en aumento de la cobertura diagnóstica. Los laboratorios del país tienen disponible un algoritmo sencillo, oportuno, de calidad y que podría ser implementado en casi cualquier laboratorio clínico del país.

[ABSTRACT]. Objective. To evaluate the effects of changing the algorithm for serological diagnosis of T. cruzi infection in departmental-level public health laboratories and in the National Reference Laboratory of Colombia, from the perspective of access to diagnosis. Methods. A descriptive, cross-sectional study was carried out, based on secondary sources between 2015 and 2021, consolidating the number of serological tests carried out by the laboratories. A survey was developed to identify benefits and limitations in the implementation of the new algorithm for serological diagnosis. Totals, proportions, and averages of the number of tests were estimated by comparing two different periods. Results. Information from 33 public health laboratories was analyzed, 87.9% of which processed serological assays during the period under study. The use of serological tests increased after the publication of the new guideline in 2017, and the capacity to perform the second test increased from four to 33 public health laboratories. In absolute terms, ELISAs for antigens and recombinant antigens became the most performed tests in Colombia after 2017. Conclusions. The change in the algorithm for serological diagnosis of Chagas disease in Colombia in 2017 had positive effects on access to diagnosis since it facilitated the use of the second test. This change resulted in increased diagnostic coverage. The country's laboratories have access to a simple, timely, quality algorithm that could be implemented in almost any clinical laboratory in the country.

[RESUMO]. Objetivo. Avaliar os efeitos da mudança do algoritmo de diagnóstico sorológico da infecção por T. cruzi nos Laboratórios Departamentais de Saúde Pública e no Laboratório Nacional de Referência da Colômbia desde a perspectiva do acesso ao diagnóstico. Métodos. Foi realizado um estudo descritivo transversal a partir de fontes secundárias do período entre 2015 e 2021, consolidando-se o número de testes sorológicos realizados pelos laboratórios. Foi desenvolvido um questionário para identificar benefícios e limitações na implementação do novo algoritmo de diagnóstico sorológico. Os totais, as proporções e as médias do número de testes foram estimados pela comparação de dois períodos diferentes. Resultados. Dados de 33 laboratórios de saúde pública foram analisados, e constatou-se que 87,9% processaram testes sorológicos durante o período analisado. O uso de testes sorológicos aumentou após a publicação das novas diretrizes em 2017, e a capacidade de realizar um segundo teste aumentou de 4 para 33 laboratórios de saúde pública. O ELISA com antígeno total e o ELISA com antígeno recombinante se consolidaram como os testes mais realizados na Colômbia após 2017. Conclusões. A mudança no algoritmo de diagnóstico sorológico da doença de Chagas na Colômbia em 2017 teve efeitos positivos no acesso ao diagnóstico, facilitando o uso do segundo teste, o que resultou em maior cobertura diagnóstica. Os laboratórios do país têm à sua disposição um algoritmo simples, oportuno e de alta qualidade que poderia ser implementado em quase todos os laboratórios clínicos do país.

CHLOROQUINE INDUCED MACULAR TOXICITY IN A PATIENT LATER DEVELOPING SECTOR RETINITIS PIGMENTOSA: A CASE REPORT.

PURPOSE: To describe how underlying retinal diseases, such as retinitis pigmentosa, increase the risk of chloroquine-induced macular toxicity. METHODS: Observational case report. RESULTS: We present the case of a 57-year-old woman being annually followed-up in the Ophthalmology service due to a systemic treatment with chloroquine (CQ). The explorations were successive normal, until a 10:2 visual field (VF) shows central defects in both eyes. Despite CQ treatment is discontinued, 10:2 VF reveal slowly progressive macular defects. During follow-up, fundus examination disclosed bone spicules in the inferonasal middle periphery: the electroretinogram (ERG) shows slow amplitude responses under scotopic conditions and the electrooculogram (EOG) also shows pathological responses. Therefore, the diagnosis of sector retinitis pigmentosa plus chloroquine maculopathy is made. Currently, the slow but constant progression of both peripheral and central defects is evident, despite having discontinued CQ treatment more than 15 years ago. CONCLUSION: Underlying retinal diseases seem to increase the risk of photoreceptor damage when undergoing a toxic insult. Thus, we hypothesize a potential interplay between retinal dystrophies and toxic maculopathy induced by CQ, and the influence of each of them in the evolution and prognosis of the other.