Diabetes mellitus as a cause of premature death in small areas of Spain by socioeconomic level from 2016 to 2020: A multiple-cause approach.

OBJECTIVE: This study aimed to assess premature mortality due to Diabetes in small areas of Spain between 2016 and 2020, and its relationship with socioeconomic level and the immediate cause of death. As a secondary objective, we evaluated the effect of the Covid 19 pandemic. METHODS: This was an ecological study of premature mortality due to Diabetes from 2016 to 2020, with a focus on small areas. All deaths in people under 75 years of age due to Diabetes as the underlying cause were included RESULTS: The final sample comprised 7382 premature deaths in 5967 census tracts. Women living in census tracts with an high level of deprivation(RR=2.40) were at a significantly higher risk. Mortality from Diabetes increased with deprivation, especially people aged 0-54(RR=2.40). People with an immediate cause of death related to a circulatory disease, living in census tracts with an high level of deprivation(RR=3.86) was associated with a significantly greater risk of death with underlying Diabetes. When a disease of the circulatory system was recorded as the immediate cause of death, being 65-74 years (RR=71.01) was associated with a significantly higher risk of premature mortality. CONCLUSIONS: Living in geographic areas with higher levels of socioeconomic deprivation is associated with a higher risk of premature death from Diabetes in Spain. This relationship has a greater impact on women, people under 54 years, and people at risk of death caused directly by diseases of the circulatory system. Premature mortality due to diabetes saw a modest increase in 2020.

Design and validation of a new questionnaire with a gender perspective to measure medication adherence for secondary prevention of ischaemic heart disease: study protocol.

INTRODUCTION AND OBJECTIVES: Only about 50% of chronic patients in high-income countries adhere to their treatment. There are methods to measure medication adherence but none of them can be considered optimal. This study will aim to design and validate a questionnaire to measure medication adherence in patients with ischaemic heart disease using a direct method as a gold-standard adherence measure and taking into account the gender perspective. Moreover, the profile of low adherence in these patients will be determined. METHODS AND ANALYSIS: First study phase consists on the questionnaire design following the next steps: identification of the dimensions, definition of the target population, questionnaire items and order, response coding, questionnaire instructions, content validity by experts and understandability. In the second phase, a cross-sectional study will be performed to end the questionnaire development and validate it. Four hundred and forty patients (50% female) with acute coronary syndrome receiving treatment within the previous 12 months will be included. Patient will answer the initial questionnaire and adherence to aspirin and statin will be measured using a direct method (drug concentration analysis in blood) and other questionnaires. From the set of preselected questionnaire items, those most closely associated with the gold standard measure will be selected using multivariate statistics. ETHICS AND DISSEMINATION: All participants gave their written informed consent before participating in the study. The study protocol follows the recommendations of the Declaration of Helsinki and was approved by the ethics committees of the three participating centres. The results of this study will be displayed at national and international conferences and in peer-reviewed scientific journals.

Multicausal analysis of mortality due to diabetes mellitus in Spain, 2016-2018.

OBJECTIVES: This study aimed to assess multicausal mortality due to diabetes from 2016-2018 in Spain. Specific objectives were to quantify the occurrence of diabetes as an underlying cause or as any registered cause on the death certificate. MATERIALS AND METHODS: A cross-sectional descriptive study taking a multicausal approach. RESULTS: Diabetes appears as an underlying cause of 2.3% of total deaths in Spain, and as any cause in 6.2%. In patients in whom Diabetes appears as an underlying cause on the death certificates, the 15 most frequent immediate causes are cardiovascular diseases in men(prevalence ratio 1,59)and women (PR1,31). In men, the causes associated with diabetes as any cause were skin diseases(prevalence ratio 1.33), followed by endocrine diseases(prevalence ratio 1.26)and genitourinary diseases (prevalence ratio1.14). In women, the causes associated with the presence of diabetes as any cause were endocrine (prevalence ratio 1.13)and genitourinary (prevalence ratio 1.04)diseases. CONCLUSIONS: In patients in whom diabetes appears as an underlying cause on the death certificates, the 15 most frequent immediate causes are cardiovascular diseases. In men, the causes associated with the presence of diabetes as any cause of death are skin, endocrine and genitourinary diseases. In women, the causes associated with diabetes as any cause are endocrine and genitourinary.

Opinions and perceptions of patients with cardiovascular disease on adherence: a qualitative study of focus groups.

BACKGROUND: Cardiovascular diseases are becoming more frequent throughout the world. Adherence to both pharmacological and non-pharmacological treatment, as well as lifestyles, is important for good management and control of the disease. This study aims to explore the opinions and perceptions of patients with ischemic heart disease on the difficulties associated with therapeutic adherence. METHODS: An interpretive phenomenological study was carried out using focus groups and one semi-structured interview. The MAXQDA qualitative data analysis program was used for inductive interpretation of the group discourses and interview. Data were coded, and these were grouped by categories and then consolidated under the main themes identified. RESULTS: Two in-person focus groups and one remote semi-structured interview were performed. Twelve participants (6 men and 6 women) from the Hospital de San Juan de Alicante participated, two of them being family companions . The main themes identified were aspects related to the individual, heart disease, drug treatment, and the perception of the health care system. CONCLUSIONS: Adhering to recommendations on healthy behaviors and taking prescribed medications for cardiovascular disease was important for most participants. However, they sometimes found polypharmacy difficult to manage, especially when they did not perceive the symptoms of their disease. Participants related the concept of fear to therapeutic adherence, believing that the latter increased with the former. The relationship with health professionals was described as optimal, but, nevertheless, the coordination of the health care system was seen as limited.

Validez en la predicción de riesgo de la escala SCORE en una población mediterránea con hipertensión arterial / Predictive validity of the risk SCORE model in a Mediterranean population with arterial hypertension

Introducción y objetivos: La hipertensión arterial es el factor de riesgo más prevalente a nivel global. Se recomienda el cálculo del riesgo cardiovascular en pacientes hipertensos antes del inicio del tratamiento. Este estudio tuvo como objetivo evaluar el valor predictivo y la utilidad clínica de la escala SCORE para prevenir eventos cardiovasculares y mortalidad por todas las causas en los pacientes con hipertensión arterial. Métodos: Se incluyeron los pacientes con hipertensión arterial de la cohorte ESCARVAL-RISK. El riesgo cardiovascular se calculó mediante la escala SCORE. Todas las muertes y eventos cardiovasculares se registraron durante un periodo de 5 años de seguimiento. Se calculó la sensibilidad, la especificidad y los valores predictivos para diferentes puntos de corte, y se evaluó el efecto de diferentes factores de riesgo sobre la exactitud diagnóstica de las gráficas SCORE. Resultados: En una cohorte final de 9.834 pacientes, hubo 555 eventos cardiovasculares y 69 muertes. El valor de riesgo recomendado para iniciar tratamiento farmacológico (5%) presentó una especificidad del 92% para la muerte y del 91% para los eventos cardiovasculares, y una sensibilidad del 20% para la muerte y del 22% para los eventos cardiovasculares. Además, la escala clasificó al 80,4% de los pacientes que sufrieron un evento cardiovascular, y al 78,3% de los que murieron, como de bajo riesgo. La edad, el índice de masa corporal, la retinopatía y el tratamiento anticoagulante se asociaron con una reducción en la capacidad predictiva de la escala SCORE, mientras que ser mujer se asoció con mejor predicción de riesgo. Conclusiones: La capacidad predictiva de la escala SCORE para la enfermedad cardiovascular y la mortalidad total en los pacientes con hipertensión arterial es limitada.(AU)

Introduction and objectives: Hypertension is the most prevalent risk factor globally. Calculation of cardiovascular risk in hypertensive patients before initiation of treatment is recommended. This study aimed to assess the predictive value and clinical utility of the SCORE scale in preventing cardiovascular events and all-cause mortality in patients with hypertension. Methods: Patients with hypertension from the ESCARVAL-RISK cohort were included. Cardiovascular risk was calculated using the SCORE scale. All deaths and cardiovascular events were recorded during a 5-year follow-up period. Sensitivity, specificity and predictive values were calculated for different cut-off points and the effect of different risk factors on the diagnostic accuracy of SCORE charts were assessed. Results: In a final cohort of 9834 patients, there were 555 cardiovascular events and 69 deaths. The recommended risk value for initiating drug treatment (5%) had a specificity of 92% for death and 91% for cardiovascular events, and a sensitivity of 20% for death and 22% for cardiovascular events. In addition, the scale classified 80.4% of patients who experienced a cardiovascular event and 78.3% of those who died as low risk. Age, body mass index, retinopathy and anticoagulant therapy were associated with reduced predictive ability of the SCORE scale, while being female was associated with better risk prediction. Conclusions: The predictive ability of the SCORE scale for cardiovascular disease and total mortality in patients with hypertension is limited.(AU)

Predictive validity of the risk SCORE model in a Mediterranean population with arterial hypertension. / Validez en la predicción de riesgo de la escala SCORE en una población mediterránea con hipertensión arterial.

INTRODUCTION AND OBJECTIVES: Hypertension is the most prevalent risk factor globally. Calculation of cardiovascular risk in hypertensive patients before initiation of treatment is recommended. This study aimed to assess the predictive value and clinical utility of the SCORE scale in preventing cardiovascular events and all-cause mortality in patients with hypertension. METHODS: Patients with hypertension from the ESCARVAL-RISK cohort were included. Cardiovascular risk was calculated using the SCORE scale. All deaths and cardiovascular events were recorded during a 5-year follow-up period. Sensitivity, specificity and predictive values were calculated for different cut-off points and the effect of different risk factors on the diagnostic accuracy of SCORE charts were assessed. RESULTS: In a final cohort of 9834 patients, there were 555 cardiovascular events and 69 deaths. The recommended risk value for initiating drug treatment (5%) had a specificity of 92% for death and 91% for cardiovascular events, and a sensitivity of 20% for death and 22% for cardiovascular events. In addition, the scale classified 80.4% of patients who experienced a cardiovascular event and 78.3% of those who died as low risk. Age, body mass index, retinopathy and anticoagulant therapy were associated with reduced predictive ability of the SCORE scale, while being female was associated with better risk prediction. CONCLUSIONS: The predictive ability of the SCORE scale for cardiovascular disease and total mortality in patients with hypertension is limited.

[Translated article] Cost of Treating Cutaneous T-Cell Lymphoma in Spain: Analysis of MICADOS Study Data by Disease Stage.

BACKGROUND AND OBJECTIVE: The cost of treating cutaneous T-cell lymphoma (CTCL) in Spain is unknown. With the advent of new treatments, it is more important than ever to gain an accurate picture of the true costs involved. The MICADOS study had 2 primary objectives: 1)to evaluate the impact of CTCL on patient quality of life, and 2)to evaluate the costs associated with the disease. This article reports the results of the cost analysis. METHODS: We estimated the cost of treating CTCL over a period of 1year from the perspective of the Spanish National Health System. Twenty-three dermatologists and hematologists from 15 public hospitals analyzed data for adult patients with mycosis fungoides (MF) or Sézary syndrome (SS). RESULTS: A total of 141 patients (57.4% male) with a mean age of 63.6 years (95%CI: 61.4-65.7 years) were included. The mean direct annual cost of treating CTCL was €34,214 per patient. The corresponding costs by stage were €11,952.47 for stageI disease, €23,506.21 for stageII disease, €38,771.81 for stageIII disease, and €72,748.84 for stageIV disease. The total direct annual cost of treating MF/SS in public hospitals in Spain was estimated at €78,301,171; stageI disease accounted for 81% of all costs, stageII for 7%, and stagesIII andIV for 6% each. CONCLUSIONS: The MICADOS study offers an accurate picture of the direct cost of treating CTCL in patients with MF/SS in Spain and shows that costs vary significantly according to disease stage. Patient-borne and indirect costs should be analyzed in future studies.

Resistance to apoptosis in complicated Crohn's disease: Relevance in ileal fibrosis.

BACKGROUND AND AIMS: The stiffening of the extracellular matrix, and changes in its cellular and molecular composition, have been reported in the pathogenesis of fibrosis. We analyze the mechanisms that perpetuate ileal fibrosis in surgical resections of complicated Crohn's disease patients. METHODS: Ileal resections were obtained from affected and non-affected tissue of stenotic or penetrating Crohn's disease behavior. Ilea from non-IBD patients were used as control tissue. All samples underwent RNA sequencing. Human small intestinal fibroblasts were treated for 48 h with IL-1ß, TFGß1, PDGFB or TNF-α. Resistance to apoptosis was analysed by RT-PCR, western blot and immunohistochemistry in ileal tissue and by RT-PCR and FACS in cultured cells. RESULTS: Growth factor-driven signaling pathways and increased RAS GTPase activity were up-regulated in affected ilea in which we found expression of both the antiapoptotic molecule MCL1 and the transcription factor ETS1 in submucosal fibroblasts, and a senescence-associated secretory phenotype. In cultured intestinal fibroblasts, PDGFB induced an ETS1-mediated resistance to apoptosis that was associated with the induction of both of TGFB1 and IL1B, a cytokine that replicated the expression of SASP detected in ileal tissue. ETS1 drove fibroblast polarization between inflammatory and fibrogenic phenotypes in IL1ß-treated cells. CONCLUSIONS: Our data show resistance to apoptosis in complicated ileal CD, and demonstrate that PDGFB induce an ETS1-mediated resistance to apoptosis associated with an inflammatory and fibrogenic pattern of expression in intestinal fibroblasts. Results point to PDGFRB, IL1R1 or MCL1 as potential targets against ileal fibrosis.

[Predictive validity of Clinical Risk Groups in chronic patients in primary healthcare]. / Validez predictiva del Clinical Risk Groups en pacientes crónicos en el ambito de la atencion primaria.

OBJECTIVE: To analyse a prediction model for admissions and hospital emergencies based on Clinical Risk Groups, in a population of complex chronic patients demanding primary care. DESIGN: A multicentric retrospective observational study, of a cohort of chronic patients with comorbidity, from January until December 2013. PLACE: The study population was assigned to the Santa Pola and Raval health centres from the Health Department of Elche. PARTICIPANTS: Cohort of chronic patients with comorbidity, from January to December 2013. INTERVENTIONS: Data about the number of admissions, reasons and complexity level associated with the admission were collected by the review of medical records. MAIN MEASURES: To determine the level of complexity, the classification included in the chronicity strategy of the Valencian Community based on Clinical Risk Groups was used. RESULTS: Five hundred and four patients were recruited with a high complexity degree (N3) and 272 with moderate/low complexity (N1-N2). A higher comorbidity was observed in N3 patients with high complexity [Charlson 2.9 (DE 1.8) vs. 1.9 (DE 1.3); P<.001], and higher dependence degree for basic diary activities [Barthel 16.1 (n=81) vs. 7.3 (n=20); P<.001]. Association between the number of admissions [0.4 (DE 0.8) vs. 0.1 (DE 0.5); P<.001] and emergency visits [0.8 (DE 1.5) vs. 0.3 (DE 0.8), P<.001] was significatively higher in patients from N3 group than N1-N2 groups. CONCLUSIONS: The predictive capacity of CRG grouper showed high sensibility for the patient classification with a high degree of complexity. Its specificity and positive predictive value were lower for the association of the N3 complexity stratum.

Cost of Treating Cutaneous T-Cell Lymphoma in Spain: Analysis of MICADOS Study Data by Disease Stage. / Evaluación de los costes asociados a la enfermedad de pacientes con linfoma cutáneo de células T en España: análisis en función del estadio clínico (estudio MICADOS).

BACKGROUND AND OBJECTIVE: The cost of treating cutaneous T-cell lymphoma (CTCL) in Spain is unknown. With the advent of new treatments, it is more important than ever to gain an accurate picture of the true costs involved. The MICADOS study had 2 primary objectives: 1)to evaluate the impact of CTCL on patient quality of life, and 2)to evaluate the costs associated with the disease. This article reports the results of the cost analysis. METHODS: We estimated the cost of treating CTCL over a period of 1year from the perspective of the Spanish National Health System. Twenty-three dermatologists and hematologists from 15 public hospitals analyzed data for adult patients with mycosis fungoides (MF) or Sézary syndrome (SS). RESULTS: A total of 141 patients (57.4% male) with a mean age of 63.6 years (95%CI: 61.4-65.7 years) were included. The mean direct annual cost of treating CTCL was €34,214 per patient. The corresponding costs by stage were €11,952.47 for stageI disease, €23,506.21 for stageII disease, €38,771.81 for stageIII disease, and €72,748.84 for stageIV disease. The total direct annual cost of treating MF/SS in public hospitals in Spain was estimated at €78,301,171; stageI disease accounted for 81% of all costs, stageII for 7%, and stagesIII andIV for 6% each. CONCLUSIONS: The MICADOS study offers an accurate picture of the direct cost of treating CTCL in patients with MF/SS in Spain and shows that costs vary significantly according to disease stage. Patient-borne and indirect costs should be analyzed in future studies.

Association of Visiting the Physiotherapist with Mortality in the Spanish General Population: A Population-Based Cohort Study.

Background and Objectives: The purpose of this retrospective population-based cohort study was to analyse the association between attendance of physiotherapy with mortality in the Spanish general population and describe the profile of people who do not visit a physiotherapist in Spain. Material and Methods: The data sources were the 2011/2012 National Health Survey (ENSE11) and the national database of death in Spain, and the participants were all adult respondents in the ENSE11. Results: Of 20,397 people, 1101 (5.4%) visited the physiotherapist the previous year, and the cumulative incidence of total mortality was 5.4% (n = 1107) at a mean follow-up of 6.2 years. Visiting the physiotherapist was associated with lower all-cause mortality in the population residing in Spain, quantified at 30.1% [RR = 0.699; 95% CI (0.528-0.927); p = 0.013]. The factors associated with not visiting a physiotherapist were the following: rating one's health as good (9.8%; n = 1017; p < 0.001), not having any hospital admission in the previous year (9.6%; n = 1788; p < 0.001), not having visited the general practitioner in the previous month (9.6%; n = 1408; p < 0.001), and not having attended a day hospital in the previous year (9.7%; n = 1836; p < 0.001). Conclusions: Visiting a physiotherapist was associated with a lower mortality from all causes in the population living in Spain.

Investigation of Thermal, Mechanical and Shape Memory Properties of 3D-Printed Functionally Graded Nanocomposite Materials.

In this study, a 3D-printed photocurable resin was developed by incorporating graphene nanoplatelets functionalised with melamine to investigate the thermal, mechanical, fracture and shape memory behaviours. The objective of this work was to produce a printed functionally graded nanocomposite material that has a smart temperature-responsive structure; presents good thermal stability, strength and fracture toughness; and can demonstrate shape-changing motions, such as sequential transformations, over time. The functionalised graphene nanoplatelets were examined via thermogravimetric analysis, Fourier transform infrared spectroscopy, Raman spectroscopy and ultraviolet-visible spectroscopy. Thermogravimetric analysis showed that the degradation temperature of the nanocomposite containing 0.1 wt% of functionalised graphene nanoplatelets at the weight loss of 5% was 304 °C, greater than that of the neat one by 29%. Dynamic mechanical analysis results showed property enhancements of the storage modulus and glass transition temperature. Fracture toughness, tensile strength and impact resistance were improved by 18%, 35% and 78%, respectively. The shape memory tests were performed to obtain the temperature-time recovery behaviour of the 3D-printed structures. The addition of functionalised graphene nanoplatelets demonstrated an enhancement in the shape recovery ratios. Generally, the five subsequent cycles were notably stable with a high recovery ratio of 97-100% for the flat shape and circular shape of the M-GNP specimens. On the other hand, these values were between 91% and 94% for the corresponding neat specimens.

Review: Unveiling the effect of beta-nerve growth factor on the reproductive function in llamas and cows.

The actions of the beta-nerve growth factor (ß-NGF) on the neuroendocrine and reproductive system have challenged classical views on the control of reproductive function. After endometrial absorption, ß-NGF triggers ovulation and promotes the development of functional corpora lutea in camelids. In this article, we review evidence showing that, in camelids, ß-NGF exerts its actions by acting in both the hypothalamus and the ovary. In the hypothalamus, ß-NGF may induce gonadotropin-releasing hormone (GnRH) release by interacting with neurons or glial cells expressing receptors for ß-NGF. The LH surge occurs under the influence of ovarian estradiol and requires the release of GnRH into the portal vessels to reach the pituitary gland. In the ovary, ß-NGF may be promoting the differentiation of follicular to luteal cells by modifying the steroidogenic profile of ovarian follicular cells in both camelids and ruminants. Although the mechanisms for these actions are largely undetermined, we aim to offer an update on the current understanding of the effects of ß-NGF controlling reproductive function in camelids and ruminants.

The benefits of measuring the size and number of lipoprotein particles for cardiovascular risk prediction: A systematic review and meta-analysis / Los beneficios de medir el tamaño y el número de partículas de lipoproteínas para la predicción del riesgo cardiovascular: una revisión sistemática y un metaanálisis

Objective: Cardiovascular risk (CVR) is conventionally calculated by measuring the total cholesterol content of high-density lipoproteins (HDL) and low-density lipoproteins (LDL). The purpose of this systematic review was to assess the CVR associated with LDL and HDL particle size and number as determined by nuclear magnetic resonance (NMR) spectroscopy. Material and methods: A literature search was performed using the electronic databases MEDLINE and Scopus. All cohort and case–control studies published before January 1, 2019 that met the following inclusion criteria were included: HDL-P, LDL-P, HDL-Z and/or LDL-Z measured by NMR spectroscopy; cardiovascular event as an outcome variable; risk of cardiovascular events expressed as odds ratios or hazard ratios; only adult patients. A meta-analysis was performed for each exposure variable (4 for LDL and 5 for HDL) and for each exposure measure (highest versus lowest quartile and 1-standard deviation increment). Results: This review included 24 studies. Number of LDL particles was directly associated with CVR: risk increased by 28% with each standard deviation increment. LDL particle size was inversely and significantly associated with CVR: each standard deviation increment corresponded to an 8% risk reduction. CVR increased by 12% with each standard deviation increase in number of small LDL particles. HD, particle number and size were inversely associated with CVR. Conclusion: Larger particle size provided greater protection, although this relationship was inconsistent between studies. Larger number of LDL particles and smaller LDL particle size are associated with increased CVR. Risk decreases with increasing number and size of HDL particles.(AU)

Objetivo: El riesgo cardiovascular (RCV) se calcula convencionalmente midiendo el contenido de colesterol total de las lipoproteínas de alta densidad (HDL) y las lipoproteínas de baja densidad (LDL). El propósito de esta revisión sistemática fue evaluar el RCV asociado con el tamaño y el número de partículas de LDL y HDL, según lo determinado por espectroscopia de resonancia magnética nuclear (RMN). Material y métodos: Se realizó una búsqueda bibliográfica utilizando las bases de datos electrónicas Medline y Scopus. Se incluyeron todos los estudios de cohortes y de casos y controles publicados antes del 1 de enero de 2019, que cumplieron con los siguientes criterios de inclusión: HDL-P, LDL-P, HDL-Z y/o LDL-Z medidos por espectroscopia de RMN; evento cardiovascular como variable de resultado; riesgo de eventos cardiovasculares expresado como cociente de posibilidades o cociente de riesgos instantáneos; solo pacientes adultos. Se realizó un metaanálisis para cada variable de exposición (cuatro para LDL y cinco para HDL) y para cada medida de exposición (cuartil más alto vs. más bajo e incremento de 1 desviación estándar [DE]). Resultados: Esta revisión incluyó 24 estudios. El número de partículas LDL se asoció directamente con el RCV: el riesgo aumentó 28% con cada incremento de la DE. El tamaño de las partículas de LDL se asoció inversa y significativamente con el RCV: cada incremento de la DE correspondió a una reducción del riesgo de 8%. El RCV aumentó 12% con cada aumento de la DE en el número de partículas pequeñas de LDL. HDL, número y tamaño de partículas se asociaron inversamente con CVR. Conclusión: El tamaño de partícula más grande proporcionó una mayor protección, aunque esta relación fue inconsistente entre los estudios. Un mayor número de partículas de LDL y un tamaño de partícula de LDL más pequeño se asocian con un aumento de la RCV. El riesgo disminuye con el aumento del número y tamaño de las partículas de HDL.(AU)

Tomographic Findings in the Retina of Unvaccinated Patients with COVID Pneumonia: Prospective Longitudinal Study.

There is no definitive evidence on the extent of SARS-CoV-2's effect on the retina. This study aims to determine if the natural history of SARS-CoV-2 infection affects tomographic findings in the retina of patients with COVID-19 pneumonia. This is a prospective cohort study of patients hospitalized with COVID-19 pneumonia. The patients underwent ophthalmological explorations and optical coherence tomography during the acute phase of the infection and at a follow-up 12 weeks later. The primary outcomes were the central retinal thickness and central choroidal thickness, which were compared longitudinally and with non-COVID-19 historical controls. No statistically relevant differences were observed in the longitudinal analysis of the thickness of the central retina (p = 0.056), central choroid (p = 0.99), retinal nerve fiber layer (p = 0.21), or ganglion cell layer (p = 0.32). Patients with acute COVID-19 pneumonia showed significantly greater central retinal thickness than non-COVID controls (p = 0.006). In conclusion, tomographic measures of the retina and choroid are not influenced by the phase of COVID-19 infection and remain stable during 12 weeks. The central retinal thickness may increase in the acute phase of COVID-19 pneumonia, but more epidemiological studies using optical coherence tomography in the early stages of the disease are needed.

Epidemiological study on gender bias and low-value practices in primary care: a study protocol.

INTRODUCTION: Evidence shows that gender has a substantial impact on health behaviours, access to and use of health systems and health system responses. This study aims to assess gender bias in patients subjected to low-value practices in the primary care setting and to develop recommendations for reducing adverse events that women experience for this reason. METHODS AND ANALYSIS: A Delphi study will be performed to reach a consensus on the 'Do Not Do' recommendations with a possible gender bias. A retrospective cohort study in a random selection of medical records will then be carried out to identify the frequency of adverse events that occur when the selected 'Do Not Do' recommendations are ignored. Qualitative research techniques (consensus conference and nominal group) will be carried out to develop recommendations to address any gender bias detected, considering barriers and facilitators in clinical practice. ETHICS AND DISSEMINATION: The study was approved by the ethics committee of San Juan de Alicante Hospital (San Juan de Alicante, Spain) Reference N. 21/061. We will disseminate the research findings via peer-reviewed articles, presentations at national and international scientific forums and webinars. TRIAL REGISTRATION NUMBER: The study was registered at ClinicalTrials.gov (NCT05233852) on 10 February 2022.

Consensus-based recommendations on physical activity and exercise in patients with diabetes at risk of foot ulcerations: a Delphi study.

BACKGROUND: Patients with diabetes mellitus are exposed to important complications. Currently little evidence exist on the guidelines that these patients, at some risk of foot ulceration, should follow for physical exercise. OBJECTIVES: To reach a consensus among multidisciplinary and international experts on physical activity/exercise recommendations for patients with diabetes, according to foot ulcer risk. METHODS: Using a three-round Delphi method, a panel composed of 28 multidisciplinary experts in the management of diabetic foot assessed 109 recommendations on physical activity/exercise for patients with diabetes mellitus, according to their risk of foot ulcer. Consensus was assumed when 80% of responses matched the same category (agreement/disagreement). RESULTS: Twenty-nine experts participated in the first and second rounds of consultation, and twenty-eight did so in the third, reaching final agreement on 86 of the 109 recommendations considered (78.9%). The study, thus, generated a consensus set of recommendations concerning different aspects of diabetic footcare before, during, and after exercise (e.g. when to examine the foot, how to assess it, what type of sock and insole to use, what types of exercise to perform, and when it is advisable to return to activity after an ulceration). CONCLUSION: This Delphi study generated recommendations based on the consensus of international experts on physical activity and exercise by patient with diabetes at risk of ulceration. Recommendations considered the state of the foot and the patient's history and status before physical activity and included information on intensity, duration, frequency, and progressions of physical activity/exercise, and the use of custom-made plantar orthoses, shoe prescription, and the convenience of returning to physical activity after an ulceration.

Pneumonia-Induced Inflammation, Resolution and Cardiovascular Disease: Causes, Consequences and Clinical Opportunities.

Pneumonia is inflammation in the lungs, which is usually caused by an infection. The symptoms of pneumonia can vary from mild to life-threatening, where severe illness is often observed in vulnerable populations like children, older adults, and those with preexisting health conditions. Vaccines have greatly reduced the burden of some of the most common causes of pneumonia, and the use of antimicrobials has greatly improved the survival to this infection. However, pneumonia survivors do not return to their preinfection health trajectories but instead experience an accelerated health decline with an increased risk of cardiovascular disease. The mechanisms of this association are not well understood, but a persistent dysregulated inflammatory response post-pneumonia appears to play a central role. It is proposed that the inflammatory response during pneumonia is left unregulated and exacerbates atherosclerotic vascular disease, which ultimately leads to adverse cardiac events such as myocardial infarction. For this reason, there is a need to better understand the inflammatory cross talk between the lungs and the heart during and after pneumonia to develop therapeutics that focus on preventing pneumonia-associated cardiovascular events. This review will provide an overview of the known mechanisms of inflammation triggered during pneumonia and their relevance to the increased cardiovascular risk that follows this infection. We will also discuss opportunities for new clinical approaches leveraging strategies to promote inflammatory resolution pathways as a novel therapeutic target to reduce the risk of cardiac events post-pneumonia.

A multiple comorbidities mouse lung infection model in ApoE­deficient mice.

Acute pneumonia is characterised by a period of intense inflammation. Inflammation is now considered to be a key step in atherosclerosis progression. In addition, pre-existing atherosclerotic inflammation is considered to play a role in pneumonia progression and risk. In the present study, a multiple comorbidities murine model was used to study respiratory and systemic inflammation that results from pneumonia in the setting of atherosclerosis. Firstly, a minimal infectious dose of Streptococcus pneumoniae (TIGR4 strain) to produce clinical pneumonia with a low mortality rate (20%) was established. C57Bl/6 ApoE -/- mice were fed a high-fat diet prior to administering intranasally 105 colony forming units of TIGR4 or phosphate-buffered saline (PBS). At days 2, 7 and 28 post inoculation (PI), the lungs of mice were imaged by magnetic resonance imaging (MRI) and positron emission tomography (PET). Mice were euthanised and investigated for changes in lung morphology and changes in systemic inflammation using ELISA, Luminex assay and real-time PCR. TIGR4-inoculated mice presented with varying degrees of lung infiltrate, pleural effusion and consolidation on MRI at all time points up to 28 days PI. Moreover, PET scans identified significantly higher FDG uptake in the lungs of TIGR4-inoculated mice up to 28 days PI. The majority (90%) TIGR4-inoculated mice developed pneumococcal-specific IgG antibody response at 28 days PI. Consistent with these observations, TIGR4-inoculated mice displayed significantly increased inflammatory gene expression [interleukin (IL)-1ß and IL-6] in the lungs and significantly increased levels of circulating inflammatory protein (CCL3) at 7 and 28 days PI respectively. The mouse model developed by the authors presents a discovery tool to understand the link between inflammation related to acute infection such as pneumonia and increased risk of cardiovascular disease observed in humans.