The Involvement of Polyunsaturated Fatty Acids in Apoptosis Mechanisms and Their Implications in Cancer.

Cancer is a significant global public health issue and, despite advancements in detection and treatment, the prognosis remains poor. Cancer is a complex disease characterized by various hallmarks, including dysregulation in apoptotic cell death pathways. Apoptosis is a programmed cell death process that efficiently eliminates damaged cells. Several studies have indicated the involvement of polyunsaturated fatty acids (PUFAs) in apoptosis, including omega-3 PUFAs such as alpha-linolenic acid, docosahexaenoic acid, and eicosapentaenoic acid. However, the role of omega-6 PUFAs, such as linoleic acid, gamma-linolenic acid, and arachidonic acid, in apoptosis is controversial, with some studies supporting their activation of apoptosis and others suggesting inhibition. These PUFAs are essential fatty acids, and Western populations today have a high consumption rate of omega-6 to omega-3 PUFAs. This review focuses on presenting the diverse molecular mechanisms evidence in both in vitro and in vivo models, to help clarify the controversial involvement of omega-3 and omega-6 PUFAs in apoptosis mechanisms in cancer.

Influencia de la musicoterapia en la disminución de cifras tensionales moderadamente altas

Fundamento la hipertensión arterial es una enfermedad con alta prevalencia a nivel mundial. Entre las alternativas para su tratamiento, la musicoterapia resulta eficaz junto al tratamiento farmacológico. Objetivo describir la influencia de la musicoterapia en la disminución de cifras tensionales moderadamente altas. Métodos se realizó un estudio observacional, analítico, de casos y controles, con pacientes (n=100) que acudieron al Cuerpo de guardia del Policlínico Rolando Ricardo Estrada, del municipio de Báguanos (Holguín), en el período 2021-2022, seleccionados mediante un muestreo no probabilístico intencional. Fueron creados dos grupos de 50 pacientes cada uno. El grupo de casos fue expuesto a la musicoterapia, no así el de control. Resultados en ambos grupos predominaron los pacientes con edades entre 40 y 59 años (41 %), del sexo femenino (55 %) y con diagnóstico previo de hipertensión arterial (58 %). En el momento de acudir al policlínico, en los dos grupos predominó la presión sistólica entre 140 y 159 mmHg (62 %). Luego de haber transcurrido una hora, en la mayoría de los pacientes del grupo de casos las cifras bajaron hasta 120 y 139 mmHg (32 %). En el grupo control se evidenció una leve disminución, pero se mantuvo mayor porcentaje de pacientes con 140 a 159 mmHg (25 %). Conclusión los pacientes expuestos a la musicoterapia evidenciaron una disminución más marcada de las cifras tensionales moderadamente elevadas, en comparación con los no expuestos.

Background arterial hypertension is a disease with a high prevalence worldwide. Among the alternatives for its treatment, music therapy is effective together with pharmacological treatment. Objective to describe the music therapy influence in the reduction of moderately high blood pressure figures. Methods an observational, analytical, case-control study was carried out with patients (n=100) who attended the Rolando Ricardo Estrada Polyclinic's Emergency Room, in the Báguanos municipality (Holguín), from 2021 to 2022, selected through purposive non- probabilistic sampling. Two groups of 50 patients each were created. The case group was exposed to music therapy, but not the control group. Results in both groups, patients aged between 40 and 59 years (41%), female (55%) and with a previous diagnosis of arterial hypertension (58%) predominated. At the time of going to the polyclinic, systolic pressure between 140 and 159 mmHg (62%) predominated in both groups. After one hour had elapsed, in most of the patients in the case group the figures dropped to 120 and 139 mmHg (32%). In the control group, a slight decrease was observed, but a higher percentage of patients with 140 to 159 mmHg (25%) remained. Conclusion patients exposed to music therapy showed a more marked decrease in moderately elevated blood pressure figures, compared to those not exposed.

Amputación digital en una paciente con úlcera del pie diabético / Digital amputation in a patient with diabetic foot ulcer

Este artículo consta solo de imágenes(AU)

Exhaustive diagnosis of breast implants with capsular contracture: The microbiology laboratory as a major support.

The most frequent complications of post-mastectomy reconstructions are breast implant (BI) infection and capsular contracture (CC). The diagnosis of BI colonization is based on cultures from the sonicated BI and from the capsule tissue. Therefore, we first aimed to assess the yield of conventional culture and molecular techniques in periprosthetic fluid, in addition to BI and capsular tissue. Moreover, we compare colonization and biofilm production between patients with and without CC. During 19 months, we prospectively included patients whose BIs had been removed and divided them into two groups: A (CC, Baker III-IV) and B (no CC). Samples were obtained for conventional culture, 16 s rRNA PCR, and MALDI-TOF. Biofilm production was also evaluated. We included 81 BIs from 69 patients with CC (22) and without CC (53). Forty-three (53.1%) of the 81 BIs had ≥1 positive culture. The culture was positive in 57.1% and 50.9% in groups A and B, respectively (p = 0.645). The highest 16 s rRNA PCR positivity rate was detected in capsular tissue (40.5%). MALDI-TOF was unable to detect colonization in any of the samples. High biofilm production was the following: high biomass: A, 29.8%; B, 39.7% (p = 0.293); high metabolic activity: A, 36.2%; B, 34.5% (p = 0.857). We confirm that cultures from different sites are mandatory to ensure a proper diagnosis of BI colonization. Our study is the first to demonstrate that CC was not associated with BI colonization or high biofilm production. The application of molecular techniques in BI samples was not substantially useful for predicting colonization.

Omega-6 Polyunsaturated Fatty Acids Enhance Tumor Aggressiveness in Experimental Lung Cancer Model: Important Role of Oxylipins.

Lung cancer is currently the leading cause of cancer death worldwide; it is often diagnosed at an advanced stage and bears poor prognosis. It has been shown that diet is an important environmental factor that contributes to the risk and mortality of several types of cancers. Intake of ω-3 and ω-6 PUFAs plays an important role in cancer risk and progression. Current Western populations have high consumption of ω-6 PUFAs with a ratio of ω-6/ω-3 PUFAs at 15:1 to 16.7:1 This high consumption of ω-6 PUFAs is related to increased cancer risk and progression. However, whether a diet rich in ω-6 PUFAs can contribute to tumor aggressiveness has not been well investigated. We used a murine model of pulmonary squamous cell carcinoma to study the aggressiveness of tumors in mice fed with a diet rich in ω-6 PUFAs and its relationship with oxylipins. Our results shown that the mice fed a diet rich in ω-6 showed a marked increase in proliferation, angiogenesis and pro-inflammatory markers and decreased expression of pro-apoptotic proteins in their tumors. Oxylipin profiling revealed an upregulation of various pro-tumoral oxylipins including PGs, HETEs, DiHETrEs and HODEs. These results demonstrate for the first time that high intake of ω-6 PUFAs in the diet enhances the malignancy of tumor cells by histological changes on tumor dedifferentiation and increases cell proliferation, angiogenesis, pro-inflammatory oxylipins and molecular aggressiveness targets such as NF-κB p65, YY1, COX-2 and TGF-ß.

Pénfigo vulgar / Pemphigus vulgaris

Imágenes

Critical Illness Myopathy: Diagnostic Approach and Resulting Therapeutic Implications.

Purpose of review: Critical illness myopathy (CIM) is a common neuro-muscular complication of intensive care treatment associated with increased morbidity and mortality. The current guidelines for diagnosis include clinical and electrophysiological criteria as well as a muscle biopsy, and allow diagnosis only at an advanced stage of the disease. To date, there is no treatment for CIM available, apart from symptomatic and rehabilitative interventions. In this review, we discuss different diagnostic approaches and describe new treatment possibilities for CIM. Recent findings: Of the diagnostic approaches evaluated, a new electrophysiological technique for measuring muscle excitability has the greatest potential to allow earlier diagnosis of CIM than the current guidelines do and thereby may facilitate the conduction of future pathophysiological and therapeutic studies. Although clinical trials are still lacking, in animal models, BGP-15, vamorolone, and ruxolitinib have been shown to have anti-inflammatory effects, to reduce muscle wasting and to improve muscle function and survival. Summary: In recent years, promising methods for early and confirmatory diagnosis of CIM have been developed, but still need validation. Experimental studies on novel pharmacological interventions show promising results in terms of preventive CIM treatments, but future clinical studies will be needed to study the effectiveness and safety of these drugs.

Development and early diagnosis of critical illness myopathy in COVID-19 associated acute respiratory distress syndrome.

BACKGROUND: The COVID-19 pandemic has greatly increased the incidence and clinical importance of critical illness myopathy (CIM), because it is one of the most common complications of modern intensive care medicine. Current diagnostic criteria only allow diagnosis of CIM at an advanced stage, so that patients are at risk of being overlooked, especially in early stages. To determine the frequency of CIM and to assess a recently proposed tool for early diagnosis, we have followed a cohort of COVID-19 patients with acute respiratory distress syndrome and compared the time course of muscle excitability measurements with the definite diagnosis of CIM. METHODS: Adult COVID-19 patients admitted to the Intensive Care Unit of the University Hospital Bern, Switzerland requiring mechanical ventilation were recruited and examined on Days 1, 2, 5, and 10 post-intubation. Clinical examination, muscle excitability measurements, medication record, and laboratory analyses were performed on all study visits, and additionally nerve conduction studies, electromyography and muscle biopsy on Day 10. Muscle excitability data were compared with a cohort of 31 age-matched healthy subjects. Diagnosis of definite CIM was made according to the current guidelines and was based on patient history, results of clinical and electrophysiological examinations as well as muscle biopsy. RESULTS: Complete data were available in 31 out of 44 recruited patients (mean [SD] age, 62.4 [9.8] years). Of these, 17 (55%) developed CIM. Muscle excitability measurements on Day 10 discriminated between patients who developed CIM and those who did not, with a diagnostic precision of 90% (AUC 0.908; 95% CI 0.799-1.000; sensitivity 1.000; specificity 0.714). On Days 1 and 2, muscle excitability parameters also discriminated between the two groups with 73% (AUC 0.734; 95% CI 0.550-0.919; sensitivity 0.562; specificity 0.857) and 82% (AUC 0.820; CI 0.652-0.903; sensitivity 0.750; specificity 0.923) diagnostic precision, respectively. All critically ill COVID-19 patients showed signs of muscle membrane depolarization compared with healthy subjects, but in patients who developed CIM muscle membrane depolarization on Days 1, 2 and 10 was more pronounced than in patients who did not develop CIM. CONCLUSIONS: This study reports a 55% prevalence of definite CIM in critically ill COVID-19 patients. Furthermore, the results confirm that muscle excitability measurements may serve as an alternative method for CIM diagnosis and support its use as a tool for early diagnosis and monitoring the development of CIM.

Optogenetic control of cancer cell survival in ChR2-transfected HeLa cells.

Optogenetics is a molecular biological technique involving transfection of cells with photosensitive proteins and the subsequent study of their biological effects. The aim of this study was to evaluate the effect of blue light on the survival of HeLa cells, transfected with channelrhodopsin-2 (ChR2). HeLa wild-type cells were transfected with a plasmid that contained the gene for ChR2. Transfection and channel function were evaluated by real-time polymerase chain reaction (RT-PCR), fluorescence imaging using green fluorescent protein (GFP) and flow cytometry for intracellular calcium changes using a Fura Red probe. We developed a platform for optogenetic stimulation for use within the cell culture incubator. Different stimulation procedures using blue light (467 nm) were applied for up to 24 h. Cell survival was determined by flow cytometry using propidium iodide and rhodamine probes. Change in cell survival showed a statistically significant (p < 0.05) inverse association with the frequency and time of application of the light stimulus. This change seemed to be associated with the ChR2 cis-trans-isomerization cycle. Cell death was associated with high concentrations of calcium in the cytoplasm and stimulation intervals less than the period of isomerization. It is possible to transfect HeLa cells with ChR2 and control their survival under blue light stimulation. We suggest that this practice should be considered in the future development of optogenetic systems in biological or biomedical research.

The health and economic burden of smoking in 12 Latin American countries and the potential effect of increasing tobacco taxes: an economic modelling study.

BACKGROUND: Worldwide, smoking tobacco causes 7 million deaths annually, and this toll is expected to increase, especially in low-income and middle-income countries. In Latin America, smoking is a leading risk factor for death and disability, contributes to poverty, and imposes an economic burden on health systems. Despite being one of the most effective measures to reduce smoking, tobacco taxation is underused and cigarettes are more affordable in Latin America than in other regions. Our aim was to estimate the tobacco-attributable burden on mortality, disease incidence, quality of life lost, and medical costs in 12 Latin American countries, and the expected health and economic effects of increasing tobacco taxes. METHODS: In this modelling study, we developed a Markov probabilistic microsimulation economic model of the natural history, medical costs, and quality-of-life losses associated with the most common tobacco-related diseases in 12 countries in Latin America. Data inputs were obtained through a literature review, vital statistics, and hospital databases from each country: Argentina, Bolivia, Brazil, Chile, Colombia, Costa Rica, Ecuador, Honduras, Mexico, Paraguay, Peru, and Uruguay. The main outcomes of the model are life-years, quality-adjusted life-years, disease events, hospitalisations, disease incidence, disease cost, and healthy years of life lost. We estimated direct medical costs for each tobacco-related disease included in the model using a common costing methodology for each country. The disease burden was estimated as the difference in disease events, deaths, and associated costs between the results predicted by the model for current smoking prevalence and a hypothetical cohort of people in each country who had never smoked. The model estimates the health and financial effects of a price increase of cigarettes through taxes, in terms of disease and health-care costs averted, and increased tax revenues. FINDINGS: In the 12 Latin American countries analysed, we estimated that smoking is responsible for approximately 345 000 (12%) of the total 2 860 921 adult deaths, 2·21 million disease events, 8·77 million healthy years of life lost, and $26·9 billion in direct medical costs annually. Health-care costs attributable to smoking were estimated to represent 6·9% of the health budgets of these countries, equivalent to 0·6% of their gross domestic product. Tax revenues from cigarette sales cover 36·0% of the estimated health expenditures caused by smoking. We estimated that a 50% increase in cigarette price through taxation would avert more than 300 000 deaths, 1·3 million disease events, gain 9 million healthy life-years, and save $26·7 billion in health-care costs in the next 10 years, with a total economic benefit of $43·7 billion. INTERPRETATION: Smoking represents a substantial health and economic burden in these 12 countries of Latin America. Tobacco tax increases could successfully avert deaths and disability, reduce health-care spending, and increase tax revenues, resulting in large net economic benefits. FUNDING: International Development Research Centre (IDRC), Canada.

TRPV1-Estradiol Stereospecific Relationship Underlies Cell Survival in Oxidative Cell Death.

17ß-estradiol is a neuronal survival factor against oxidative stress that triggers its protective effect even in the absence of classical estrogen receptors. The polymodal transient receptor potential vanilloid subtype 1 (TRPV1) channel has been proposed as a steroid receptor implied in tissue protection against oxidative damage. We show here that TRPV1 is sufficient condition for 17ß-estradiol to enhance metabolic performance in injured cells. Specifically, in TRPV1 expressing cells, the application of 17ß-estradiol within the first 3 h avoided H2O2-dependent mitochondrial depolarization and the activation of caspase 3/7 protecting against the irreversible damage triggered by H2O2. Furthermore, 17ß-estradiol potentiates TRPV1 single channel activity associated with an increased open probability. This effect was not observed after the application of 17α-estradiol. We explored the TRPV1-Estrogen relationship also in primary culture of hippocampal-derived neurons and observed that 17ß-estradiol cell protection against H2O2-induced damage was independent of estrogen receptors pathway activation, membrane started and stereospecific. These results support the role of TRPV1 as a 17ß-estradiol-activated ionotropic membrane receptor coupling with mitochondrial function and cell survival.

Health and Economic Impact of Health Warnings and Plain Tobacco Packaging in Seven Latin American Countries: Results of a Simulation Model.

INTRODUCTION: The burden of disease attributable to tobacco use in Latin America is very high. Our objective was to evaluate the 10-year potential impact of current legislation related to cigarette packaging and warnings and expected effects of moving to a higher level of strategies implementing cigarette plain packaging on health and cost outcomes in Argentina, Bolivia, Brazil, Chile, Colombia, Mexico, and Peru, using a microsimulation model. AIMS AND METHODS: We used a probabilistic state-transition microsimulation model, considering natural history, costs, and quality of life losses associated with main tobacco-related diseases. We followed up individuals in hypothetical cohorts and calculated health outcomes annually to obtain aggregated long-term population health outcomes and costs. We performed a literature review to estimate effects and analyzed studies and information from ministries, relevant organizations, and national surveys. We calibrated the model comparing the predicted disease-specific mortality rates with local statistics. RESULTS: Current graphic warnings already in place in each country could avert, during 10 years, 69 369 deaths and 638 295 disease events, adding 1.2 million years of healthy life and saving USD 5.3 billion in the seven countries. If these countries implemented plain packaging strategies, additional 155 857 premature deaths and 4 133 858 events could be averted, adding 4.1 million healthy years of life and saving USD 13.6 billion in direct health care expenses of diseases attributable to smoking. CONCLUSIONS: Latin American countries should not delay the implementation of this strategy that will alleviate part of the enormous health and financial burden that tobacco poses on their economies and health care systems. IMPLICATIONS: Tobacco smoking is the single most preventable and premature mortality cause in the world. The Framework Convention on Tobacco Control, supported by the World Health Organization, introduced a package of evidence-based measures for tobacco control. This study adds evidence on the potential health effects and savings of implementing cigarette plain packaging in countries representing almost 80% of the Latin American population; findings are valuable resources for policy makers in the region.

Importance of the Role of ω-3 and ω-6 Polyunsaturated Fatty Acids in the Progression of Brain Cancer.

Brain cancer is one of the most malignant types of cancer in both children and adults. Brain cancer patients tend to have a poor prognosis and a high rate of mortality. Additionally, 20-40% of all other types of cancer can develop brain metastasis. Numerous pieces of evidence suggest that omega-3-polyunsaturated fatty acids (ω-PUFAs) could potentially be used in the prevention and therapy of several types of cancer. PUFAs and oxylipins are fundamental in preserving physiological events in the nervous system; it is, therefore, necessary to maintain a certain ratio of ω-3 to ω-6 for normal nervous system function. Alterations in PUFAs signaling are involved in the development of various pathologies of the nervous system, including cancer. It is well established that an omega-6-polyunsaturated fatty acid (ω-6 PUFA)-rich diet has a pro-tumoral effect, whereas the consumption of an ω-3 rich diet has an anti-tumoral effect. This review aims to offer a better understanding of brain cancer and PUFAs and to discuss the role and impact of PUFAs on the development of different types of brain cancer. Considering the difficulty of antitumor drugs in crossing the blood-brain barrier, the therapeutic role of ω-3/ω-6 PUFAs against brain cancer would be a good alternative to consider. We highlight our current understanding of the role of PUFAs and its metabolites (oxylipins) in different brain tumors, proliferation, apoptosis, invasion, angiogenesis, and immunosuppression by focusing on recent research in vitro and in vivo.

Factors associated with hindering the acceptance of HPV vaccination among caregivers - A cross-sectional study in Argentina.

BACKGROUND: The northeastern region of Argentina has the highest age-adjusted cervical cancer mortality rates. Given the strong link between HPV infections and cervical cancer, one of the main interventions is the population-based use of HPV vaccines. However, the acceptability is not very clear in low- and middle-income countries. The purpose of this study was to estimate the level of HPV vaccine acceptance and associated determinants among caregivers of girls in a northeastern city of Argentina. METHODS: A school-based survey was conducted in 2015 using a multistage sampling method. The primary sample unit were schools stratified by socioeconomic status selected at random, and caregivers of school girls were interviewed. The acceptability was determined using the adapted Theory of Planned Behavior. We performed logistic regression models to assess associated determinants. RESULTS: The study included 347 caregivers. The intention to vaccinate was 59.88%. A positive attitude of caregivers (aOR 4.67; 3.11-7.03) and positive influence of social norms (aOR 1.95; 1.03-3.70) were the main predictors independently associated to the intention to vaccinate against HPV. In contrast, practicing a Christian non-Catholic religion decreased the intention to vaccinate against HPV (OR 0.59; 0.36-0.95). All other factors evaluated were not significantly associated with intention to vaccinate against HPV. CONCLUSIONS: This study shows that evaluating attitudes, normative social beliefs, and perceived self-efficacy regarding HPV vaccination can be of utmost importance for mapping and planning of health-related strategies in developing countries.

Experience with ambulatory high-dose methotrexate administration as CNS prophylaxis in patients with non-Hodgkin lymphoma.

BACKGROUND: We describe the feasibility and safety of an oral administration schedule of hydration, alkalinization and leucovorin rescue with an ambulatory high-dose methotrexate regimen. METHODS: Single-centre prospective observational study conducted within a tertiary hospital where all patients have received systemic high-dose methotrexate (3.5 g/m2). Patients were instructed to keep an adequate ambulatory oral hydration and alkalinization to monitor urine pH and to adjust bicarbonate according to our institution's treatment protocol. High-dose methotrexate was infused over 4 h. Urine pH was checked before high-dose methotrexate administration, and for any value less than 7 a sodium bicarbonate bolus was given. Leucovorin at a standard dose was begun 24 h after high-dose methotrexate. methotrexate serum concentrations were monitored daily from 24 h after administration until clearance (level ≤ 0.1 µmol/L). RESULTS: From January 2016 to June 2018, 49 ambulatory high-dose methotrexate courses were given to 18 patients. No dose reduction was required afterwards. All patients completed succesfully the planned three doses in an outpatient basis, except four patients, one of them due to pneumonitis. Previous to methotrexate infusion, urinary pH > 7 was achieved in 35 (79.5%) cycles. Methotrexate clearance was achieved by 72 h in 35 courses (71.4%), and by 96 h in 100%. Neutropenia/trombocytopenia grades III/IV were observed in four cycles (8.16%) and two (4.08%) cycles, respectively. Around 20.40% were associated with stomatitis, 14.20% vomiting, 10.20% asthenia, 8.16% diarrhea and 6.12% with renal toxicity. CONCLUSIONS: Ambulatory administration of high-dose methotrexate as CNS prophylaxis is safe and feasible following the described approach, allowing us to optimize healthcare resources.

Burden of smoking in Brazil and potential benefit of increasing taxes on cigarettes for the economy and for reducing morbidity and mortality. / Carga do tabagismo no Brasil e benefício potencial do aumento de impostos sobre os cigarros para a economia e para a redução de mortes e adoecimento.

The prevalence of smoking in Brazil has decreased considerably in recent decades, but the country still has a high burden of disease associated with this risk factor. The study aimed to estimate the burden of mortality, morbidity, and costs for society associated with smoking in 2015 and the potential impact on health outcomes and the economy based on price increases for cigarettes through taxes. Two models were developed: the first is a mathematical model based on a probabilistic microsimulation of thousands of individuals using hypothetical cohorts that considered the natural history, costs, and quality of life of these individuals. The second is a tax model applied to estimate the economic benefit and health outcomes in different price increase scenarios in 10 years. Smoking was responsible for 156,337 deaths, 4.2 million years of potential life lost, 229,071 acute myocardial infarctions, 59,509 strokes, and 77,500 cancer diagnoses. The total cost was BRL 56.9 billion (USD 14.7 billion), with 70% corresponding to the direct cost associated with healthcare and the rest to indirect cost due to lost productivity from premature death and disability. A 50% increase in cigarette prices would avoid 136,482 deaths, 507,451 cases of cardiovascular diseases, 64,382 cases of cancer, and 100,365 cases of stroke. The estimated economic benefit would be BRL 97.9 billion (USD 25.5 billion). In conclusion, the burden of disease and economic losses associated with smoking is high in Brazil, and tax increases are capable of averting deaths, illness, and costs to society.

A prevalência do tabagismo no Brasil reduziu sobremaneira nas últimas décadas, mas o país ainda tem uma elevada carga de doença associada a este fator de risco. O objetivo deste trabalho foi estimar a carga de mortalidade, morbidade e custos para a sociedade associada ao tabagismo em 2015 e o potencial impacto gerado em desfechos de saúde e para a economia a partir do aumento de preços dos cigarros por meio de impostos. Foram desenvolvidos dois modelos: o primeiro é um modelo matemático baseado em uma microssimulação probabilística de milhares de indivíduos usando-se coortes hipotéticas que considerou a história natural, custos e a qualidade de vida destes indivíduos. O segundo é um modelo de impostos aplicado para estimar o benefício econômico e em desfechos de saúde de diferentes cenários de aumento de preços em 10 anos. O tabagismo foi responsável por 156.337 mortes, 4,2 milhões de anos de vida perdidos, 229.071 infartos agudos do miocárdio, 59.509 acidentes vasculares cerebrais e 77.500 diagnósticos de câncer. O custo total foi de R$ 56,9 bilhões, dos quais 70% corresponderam ao custo direto associado à assistência à saúde e o restante ao custo indireto devido à perda de produtividade por morte prematura e incapacidade. Um aumento de 50% do preço do cigarro evitaria 136.482 mortes, 507.451 casos de doenças cardiovasculares, 64.382 de casos de câncer e 100.365 acidentes vasculares cerebrais. O benefício econômico estimado seria de R$ 97,9 bilhões. Concluiu-se que a carga da doença e econômica associada ao tabagismo é elevada no Brasil e o aumento de impostos é capaz de evitar mortes, adoecimento e custos para a sociedade.

La prevalencia del tabaquismo en Brasil se redujo sobremanera en las últimas décadas, pero el país todavía cuenta con una elevada carga de enfermedad asociada a este factor de riesgo. El objetivo de este trabajo fue estimar la carga de mortalidad, morbilidad y costes para la sociedad, asociada al tabaquismo en 2015, y el impacto potencial generado en los desenlaces de salud y para la economía a partir del aumento de precios del tabaco a través de impuestos. Se desarrollaron dos modelos: el primero es un modelo matemático, basado en una microsimulación probabilística de millares de individuos, a través de cohortes hipotéticas, que consideró la historia natural, costes y calidad de vida de esos individuos. El segundo se trata de un modelo de impuestos aplicado para estimar el beneficio económico y en desenlaces de salud de diferentes escenarios con el aumento de precios durante 10 años. El tabaquismo fue responsable de 156.337 muertes, 4,2 millones de años de vida perdidos, 229.071 infartos agudos de miocardio, 59.509 accidentes vasculares cerebrales y 77.500 diagnósticos de cáncer. El coste total fue de BRL 56,9 billones (USD 14,7 billones), de los cuales un 70% correspondieron al coste directo asociado a la asistencia a la salud y lo restante al coste indirecto, debido a la pérdida de productividad por muerte prematura e incapacidad. Un aumento de un 50% del precio del tabaco evitaría 136.482 muertes, 507.451 casos de enfermedades cardiovasculares, 64.382 de casos de cáncer y 100.365 accidentes vasculares cerebrales. El beneficio económico estimado sería de BRL 97,9 billones (USD 25,5 billones). Se concluyó que la carga de la enfermedad y económica asociada al tabaquismo es elevada en Brasil y el aumento de impuestos es capaz de evitar muertes, enfermedad y costes para la sociedad.

Evaluation of the Alfred™ turbidity monitoring system (Alifax®) following sonication in the diagnosis of central venous catheter colonization.

The conventional diagnostic techniques for catheter colonization (CC) take at least 48 h to yield results. Therefore, new diagnostic procedures that speed up the time necessary for results are needed. Our main objective was to assess the efficacy of the combination of sonication, turbidity monitoring, and MALDI-TOF to detect CC and catheter-related bloodstream infection (C-RBSI). For 1 year, we assessed central venous catheter (CVC) tips that arrived at the microbiology laboratory from adult patients admitted to our institution. CVC tips were cut, inoculated into 2.5 ml of BHI, and sonicated for 1 min. The suspension was then processed using Gram stain, quantitative culture (gold standard), and preincubation on the Alfred™ system. We analyzed the validity values of our new diagnostic approach for prediction of CC and C-RBSI and compared them with those of the gold standard. We collected a total of 167 catheters, 33 (19.8%) of which were colonized. We confirmed 21 episodes of C-RBSI. The distribution of microorganisms in colonized CVCs was as follows: Gram-positive, 68.4%; Gram-negative, 5.3%; and yeasts, 26.3%. The validity values for CC and C-RBSI using the new procedure were as follows: S, 39.4%/61.9%; Sp, 100%/100%; PPV, 100%/100%; and NPV, 87.0%/94.8%. The combination of sonication with a pre-incubation period based on turbidity monitoring using the Alfred™ system followed by MALDI-TOF proved to be a useful tool that was faster than conventional culture for ruling out C-RBSI. Future studies are needed to assess the clinical and economic impact of this diagnostic approach.

Choroideremia Gene Therapy Phase 2 Clinical Trial: 24-Month Results.

PURPOSE: To report the final results of a phase 2 high-dose gene therapy clinical trial in choroideremia. METHODS: Design: Phase 2 clinical trial. PARTICIPANTS: Six men (aged 32-72 years) with genetically-confirmed advanced choroideremia. Patients received subfoveal injection of AAV2-REP1 (1011 genome particles in 0.1 mL) in the worse-sighted eye. OUTCOME MEASURES: Primary measure was best-corrected visual acuity (BCVA) change from baseline in the treated eye compared to the untreated eye. Secondary endpoints included change from baseline in microperimetry, fundus autofluorescence, and spectral-domain optical coherence tomography (OCT). Safety evaluations included adverse events, viral shedding in body fluids, and vector antibody responses. RESULTS: Baseline mean ETDRS BCVA was 65.3 ± 8.8 (SD, range 56-77, 20/32-20/80) letters in the treated eyes and 77.0 ± 4.2 (69-81, 20/25-20/40) letters in the untreated eyes. At 2 years, 1 treated eye improved by 10 letters and another by 5 letters, while 1 untreated eye improved by 4 letters. All other eyes were within 2 letters of baseline. Baseline microperimetry sensitivities in the treated eyes were poor (1.2 ± 2.1 (0, 5.1) dB) and showed no significant change. No serious adverse event occurred. Two patients developed an atrophic retinal hole in a nonfunctioning macular area where baseline OCT showed preexisting thinning. Intraoperative microscope-integrated OCT allowed proper subretinal injection with avoidance of excessive foveal stretching and macular hole formation. CONCLUSIONS: Sustained improvement or maintenance of BCVA is achievable in choroideremia with high-dose AAV2-REP1, indicating BCVA is a viable primary outcome in advanced choroideremia. Choroideremia gene therapy delivered with intraoperative OCT has a good safety profile.

Carga do tabagismo no Brasil e benefício potencial do aumento de impostos sobre os cigarros para a economia e para a redução de mortes e adoecimento / Carga del tabaquismo en Brasil y beneficio potencial del aumento de impuestos sobre el tabaco para la economía y para la reducción de muertes por enfermedad / Burden of smoking in Brazil and potential benefit of increasing taxes on cigarettes for the economy and for reducing morbidity and mortality

A prevalência do tabagismo no Brasil reduziu sobremaneira nas últimas décadas, mas o país ainda tem uma elevada carga de doença associada a este fator de risco. O objetivo deste trabalho foi estimar a carga de mortalidade, morbidade e custos para a sociedade associada ao tabagismo em 2015 e o potencial impacto gerado em desfechos de saúde e para a economia a partir do aumento de preços dos cigarros por meio de impostos. Foram desenvolvidos dois modelos: o primeiro é um modelo matemático baseado em uma microssimulação probabilística de milhares de indivíduos usando-se coortes hipotéticas que considerou a história natural, custos e a qualidade de vida destes indivíduos. O segundo é um modelo de impostos aplicado para estimar o benefício econômico e em desfechos de saúde de diferentes cenários de aumento de preços em 10 anos. O tabagismo foi responsável por 156.337 mortes, 4,2 milhões de anos de vida perdidos, 229.071 infartos agudos do miocárdio, 59.509 acidentes vasculares cerebrais e 77.500 diagnósticos de câncer. O custo total foi de R$ 56,9 bilhões, dos quais 70% corresponderam ao custo direto associado à assistência à saúde e o restante ao custo indireto devido à perda de produtividade por morte prematura e incapacidade. Um aumento de 50% do preço do cigarro evitaria 136.482 mortes, 507.451 casos de doenças cardiovasculares, 64.382 de casos de câncer e 100.365 acidentes vasculares cerebrais. O benefício econômico estimado seria de R$ 97,9 bilhões. Concluiu-se que a carga da doença e econômica associada ao tabagismo é elevada no Brasil e o aumento de impostos é capaz de evitar mortes, adoecimento e custos para a sociedade.

La prevalencia del tabaquismo en Brasil se redujo sobremanera en las últimas décadas, pero el país todavía cuenta con una elevada carga de enfermedad asociada a este factor de riesgo. El objetivo de este trabajo fue estimar la carga de mortalidad, morbilidad y costes para la sociedad, asociada al tabaquismo en 2015, y el impacto potencial generado en los desenlaces de salud y para la economía a partir del aumento de precios del tabaco a través de impuestos. Se desarrollaron dos modelos: el primero es un modelo matemático, basado en una microsimulación probabilística de millares de individuos, a través de cohortes hipotéticas, que consideró la historia natural, costes y calidad de vida de esos individuos. El segundo se trata de un modelo de impuestos aplicado para estimar el beneficio económico y en desenlaces de salud de diferentes escenarios con el aumento de precios durante 10 años. El tabaquismo fue responsable de 156.337 muertes, 4,2 millones de años de vida perdidos, 229.071 infartos agudos de miocardio, 59.509 accidentes vasculares cerebrales y 77.500 diagnósticos de cáncer. El coste total fue de BRL 56,9 billones (USD 14,7 billones), de los cuales un 70% correspondieron al coste directo asociado a la asistencia a la salud y lo restante al coste indirecto, debido a la pérdida de productividad por muerte prematura e incapacidad. Un aumento de un 50% del precio del tabaco evitaría 136.482 muertes, 507.451 casos de enfermedades cardiovasculares, 64.382 de casos de cáncer y 100.365 accidentes vasculares cerebrales. El beneficio económico estimado sería de BRL 97,9 billones (USD 25,5 billones). Se concluyó que la carga de la enfermedad y económica asociada al tabaquismo es elevada en Brasil y el aumento de impuestos es capaz de evitar muertes, enfermedad y costes para la sociedad.

The prevalence of smoking in Brazil has decreased considerably in recent decades, but the country still has a high burden of disease associated with this risk factor. The study aimed to estimate the burden of mortality, morbidity, and costs for society associated with smoking in 2015 and the potential impact on health outcomes and the economy based on price increases for cigarettes through taxes. Two models were developed: the first is a mathematical model based on a probabilistic microsimulation of thousands of individuals using hypothetical cohorts that considered the natural history, costs, and quality of life of these individuals. The second is a tax model applied to estimate the economic benefit and health outcomes in different price increase scenarios in 10 years. Smoking was responsible for 156,337 deaths, 4.2 million years of potential life lost, 229,071 acute myocardial infarctions, 59,509 strokes, and 77,500 cancer diagnoses. The total cost was BRL 56.9 billion (USD 14.7 billion), with 70% corresponding to the direct cost associated with healthcare and the rest to indirect cost due to lost productivity from premature death and disability. A 50% increase in cigarette prices would avoid 136,482 deaths, 507,451 cases of cardiovascular diseases, 64,382 cases of cancer, and 100,365 cases of stroke. The estimated economic benefit would be BRL 97.9 billion (USD 25.5 billion). In conclusion, the burden of disease and economic losses associated with smoking is high in Brazil, and tax increases are capable of averting deaths, illness, and costs to society.

Carga de enfermedad atribuible al uso del tabaco en Paraguay y potencial impacto sanitario y económico del aumento del precio a través de impuestos / Burden of disease attributable to tobacco use in Paraguay, and potential health and financial impact of increasing prices through taxing

RESUMEN Objetivos. Estimar la carga de enfermedad asociada al consumo de tabaco en Paraguay y evaluar el potencial efecto económico y sanitario del aumento de precio mediante impuestos. Materiales y métodos. Se diseñó un modelo de microsimulación de Monte Carlo que incorporó la historia natural, costos y calidad de vida de enfermedades asociadas al tabaquismo para el 2015. Asimismo, se estimó el impacto en varios escenarios de aumento de impuestos sobre la prevalencia de tabaquismo y la recaudación fiscal. Resultados. 3354 personas mueren al año en Paraguay por consecuencia del tabaquismo. El 19 % de las muertes son por enfermedad isquémica cardíaca, el 15 % por accidentes cerebrovasculares. El 77 % de las muertes por enfermedad pulmonar obstructiva crónica y el 83 % de cáncer de pulmón son atribuibles al tabaquismo. Estas enfermedades en Paraguay representan un costo médico directo anual de más de 1,5 x 106 millones de guaraníes, mientras la recaudación impositiva por la venta de cigarrillos apenas llega a cubrir un 20 % de este gasto. Un aumento en el precio de los cigarrillos del 50 % vía impuestos, podría llevar a evitar 2507 muertes en diez años y generar recursos por 2,4 x 106 millones por ahorro en gastos sanitarios y aumento de recaudación. Conclusiones. El costo y la carga de enfermedad asociado al consumo de tabaco en el sistema de salud es elevado en Paraguay. Un aumento del precio de los cigarrillos a través de los impuestos tendría importantes beneficios sanitarios y podría compensar parcialmente los costos sanitarios.

ABSTRACT Objectives . To consider the burden of disease associated to tobacco consumption in Paraguay and to evaluate the potential economic and health effect of price increase through taxes. Materials and Methods . A Monte Carlo simulation model was designed incorporating natural history, costs, and quality of life of diseases associated to smoking for 2015. Also, several scenarios were considered for the impact of tax raises on the prevalence of smoking and fiscal collection. Results . In Paraguay, 3,354 people die every year as a consequence of smoking. Nineteen percent of deaths are due to cardiac ischemia, 15% due to stroke. 77% of deaths due to chronic obstructive pulmonary disease (COPD), and 83% of lung cancer can be attributed to smoking. These diseases in Paraguay represent an annual direct medical cost of more than 1.5 trillion PYG, while the tax collection from cigarette sales barely covers 20% of this expense. A 50% increase in the price of cigarettes via taxes could avoid 2507 deaths in ten years and generate resources by 2.4 trillion in savings in health expenses and tax of collection. Conclusions . The cost and the burden of disease associated to tobacco consumption is high in the health system in Paraguay. An increase in cigarette price through taxes could have significant health benefits and could offset health costs in part.