Pharmacotherapy and clinical outcomes of hospitalized COVID-19 patients in Chile during the first wave of pandemic

Background: The largest growth in cases of COVID-19 worldwide during 2020 was in the Americas, and Chile was one of the most affected countries. Aim: To describe, characterize, and evaluate the use of drugs as treatment for COVID-19 in hospitalized patients in Chile during the first wave of the pandemic. Methods: We performed a multicenter, observational study that included 442 patients with confirmed SARS-CoV-2 infection admitted in Chilean hospitals between March 21 and September 22, 2020. The analysis included demographics, comorbidities, specific drug therapy, and outcomes over a 28-day follow-up period. Results: The median age of patients was 68 years (IQR 55-73), and 38.9% were women. The most common comorbidities were hypertension (57.7%) and diabetes (36.9%). Fifty-seven (12.9%) patients died. Hypertension (HR 2.99; CI 95% 1.43-6.26) and age ≥ 65 (2.14; CI 95% 1.10- 4.17) were the main predictors of mortality. Primary drugs were azithromycin (58.8%) and corticosteroids (51.1%). In this sample, azithromycin was a protective factor regarding mortality (HR 0.53; CI 95% 0.31-0.90), increasing clinical improvement and avoiding progression. Conclusions: The patterns of use of drugs to treat COVID-19 in Chile during the first wave of the pandemic were very dynamic and followed the international, evidence-based guidelines. The low mortality rate indicates that the clinical management of hospitalized patients was adequate.

Antecedentes: Durante 2020, el mayor incremento de casos de COVID-19 se observó en el continente americano, donde Chile fue uno de los países más afectados. Objetivos: Describir, caracterizar y evaluar el uso de fármacos indicados para tratar el COVID-19 en pacientes hospitalizados en Chile durante la primera ola de pandemia. Pacientes y Métodos: Un estudio multicéntrico observacional incorporó a 442 pacientes con infección confirmada por SARS- CoV-2 admitidos en hospitales chilenos entre el 21 de marzo y el 22 de septiembre de 2020. Se analizaron variables demográficas, comorbilidades, terapia farmacológica específica y desenlaces clínicos para un período de seguimiento de 28 días. Resultados: La mediana de la edad fue de 68 años (RIC 55-73), y un 38,9% fueron mujeres. Las comorbilidades más comunes fueron hipertensión (57,7%) y diabetes (36,9%). Cincuenta y siete (12,9%) de los pacientes murieron. Los principales predictores de mortalidad fueron la hipertensión (HR 2,99; IC 95% 1,43-6,26) y la edad ≥ 65 años (2,14; IC 95% 1,10- 4,17). Los fármacos más utilizados fueron azitromicina (58,8%) y corticosteroides (51,1%). En esta muestra, la azitromicina fue un factor de protección respecto a la mortalidad (HR 0,53; IC 95% 0,31-0,90), incrementando igualmente la mejoría y evitando la progresión. Conclusiones: Los patrones de uso de fármacos para tatar COVID-19 en Chile durante la primera ola de pandemia fueron muy dinámicos y siguieron las directrices internacionales basadas en la evidencia. La baja mortalidad sugiere que el manejo de los pacientes hospitalizados fue adecuado.

Pharmacotherapy and clinical outcomes of hospitalized COVID-19 patients in Chile during the first wave of pandemic.

BACKGROUND: The largest growth in cases of COVID-19 worldwide during 2020 was in the Americas, and Chile was one of the most affected countries. AIM: To describe, characterize, and evaluate the use of drugs as treatment for COVID-19 in hospitalized patients in Chile during the first wave of the pandemic. METHODS: We performed a multicenter, observational study that included 442 patients with confirmed SARS-CoV-2 infection admitted in Chilean hospitals between March 21 and September 22, 2020. The analysis included demographics, comorbidities, specific drug therapy, and outcomes over a 28-day follow-up period. RESULTS: The median age of patients was 68 years (IQR 55-73), and 38.9% were women. The most common comorbidities were hypertension (57.7%) and diabetes (36.9%). Fifty-seven (12.9%) patients died. Hypertension (HR 2.99; CI 95% 1.43-6.26) and age ≥ 65 (2.14; CI 95% 1.10- 4.17) were the main predictors of mortality. Primary drugs were azithromycin (58.8%) and corticosteroids (51.1%). In this sample, azithromycin was a protective factor regarding mortality (HR 0.53; CI 95% 0.31-0.90), increasing clinical improvement and avoiding progression. CONCLUSIONS: The patterns of use of drugs to treat COVID-19 in Chile during the first wave of the pandemic were very dynamic and followed the international, evidence-based guidelines. The low mortality rate indicates that the clinical management of hospitalized patients was adequate.

Ley chilena de tolerancia cero al alcohol: fortalezas, falencias y carencias que no deben ser obviadas / Alcohol zero tolerance law in Chile: strengths, flaws and shortcomings that should not be overlooked

Background: Chile has recently entered into force Act No. 20.580, which modifies the legal limits of blood alcohol concentration in drivers and increases the penalties for driving under the influence of alcohol, narcotics or psychotropic substances. The aim of this review was to give an account of the strengths of this new law but, at the same time, to alert the scientific and legal community about its flaws. We also present some shortcomings of Chilean regulatory framework that remain uncorrected, those that should be considered in the design of public policies for improving road safety and the criteria that judges should ponder during judgment, to determine either conviction or acquittal.

[Alcohol zero tolerance law in Chile: strengths, flaws and shortcomings that should not be overlooked]. / Ley chilena de tolerancia cero al alcohol: fortalezas, falencias y carencias que no deben ser obviadas.

Chile has recently entered into force Act No. 20.580, which modifies the legal limits of blood alcohol concentration in drivers and increases the penalties for driving under the influence of alcohol, narcotics or psychotropic substances. The aim of this review was to give an account of the strengths of this new law but, at the same time, to alert the scientific and legal community about its flaws. We also present some shortcomings of Chilean regulatory framework that remain uncorrected, those that should be considered in the design of public policies for improving road safety and the criteria that judges should ponder during judgment, to determine either conviction or acquittal.

Costo directo de la farmacoterapia de la leucemia aguda en el Hospital Clínico Regional de Valdivia, Chile: análisis del período 2003 a 2006 / Direct costs of pharmacotherapy for acute leukemia at a Regional Hospital in Chile

Background: In Chile, leukemia is one of the diseases whose treatment is guaranteed by a special law called AUGE (universal access and explicit guaranties). Therefore, the knowledge of its treatment costs is of utmost importance. Aim: To determine and to characterize the direct costs of pharmacotherapy for leukemia at a regional hospital in Chile. Material and methods: Data were retrospectively obtained from electronic and manual records of the hospital for all patients treated for leukemia between 2003 and 2006. Patients were classified into four groups: pediatric and adult patients treated for acute lymphocytic leukemia (ALL children and ALL adults, respectively), and pediatric and adult patients treated for acute myelogenous leukemia (AML children and AML adults, respectively). Results: Total accumulated costs of pharmacotherapy for acute leukemia between 2003 and 2006 were 304,724,845 Chilean pesos (USD 574,952). The higher total or per patient costs, were generated by drugs for chemotherapy compared to other required medications. The exception were AML children, where support drugs, such as antimicrobials, ant emetic drugs and colony stimulating factors, generated the higher costs per patient. Among ALL adults, AML children and AML adults, the costs were concentrated in the first 6 months of treatment. NO children followed this tendency concentrating the costs between the seventh and twenty-fourth months. Conclusions: Annual costs of pharmacotherapy per patient for acute leukemia in this regional hospital were approximately USD 4,717. Chemotherapy was the item with the greatest impact on cost.

Heat hyperalgesia induced by endoneurial nerve growth factor and the expression of substance P in primary sensory neurons.

Endoneurial nerve growth factor (30 ng) produced significant heat hyperalgesia in rats on postinjection days 3 and 5. The percentage of neuron profiles expressing the sensory neuropeptide substance P in the dorsal root ganglion (DRG), and the density and distribution of substance P immunoreactivity at the DRG and the dorsal horn remained essentially unchanged throughout the 10 days of study. NGF increased pain scores in the second phase of the formalin test on postinjection day 3, but not on days 5 and 10. Our results indicate that the observed heat hyperalgesia is not dependent on NGF-induced changes in SP content and release from primary sensory neurons.

[Direct costs of pharmacotherapy for acute leukemia at a Regional Hospital in Chile]. / Costo directo de la farmacoterapia de la leucemia aguda en el Hospital Clínico Regional de Valdivia, Chile: análisis del período 2003 a 2006.

BACKGROUND: In Chile, leukemia is one of the diseases whose treatment is guaranteed by a special law called AUGE (universal access and explicit guaranties). Therefore, the knowledge of its treatment costs is of utmost importance. AIM: To determine and to characterize the direct costs of pharmacotherapy for leukemia at a regional hospital in Chile. MATERIAL AND METHODS: Data were retrospectively obtained from electronic and manual records of the hospital for all patients treated for leukemia between 2003 and 2006. Patients were classified into four groups: pediatric and adult patients treated for acute lymphocytic leukemia (ALL children and ALL adults, respectively), and pediatric and adult patients treated for acute myelogenous leukemia (AML children and AML adults, respectively). RESULTS: Total accumulated costs of pharmacotherapy for acute leukemia between 2003 and 2006 were 304,724,845 Chilean pesos (USD 574,952). The higher total or per patient costs, were generated by drugs for chemotherapy compared to other required medications. The exception were AML children, where support drugs, such as antimicrobials, ant emetic drugs and colony stimulating factors, generated the higher costs per patient. Among ALL adults, AML children and AML adults, the costs were concentrated in the first 6 months of treatment. NO children followed this tendency concentrating the costs between the seventh and twenty-fourth months. CONCLUSIONS: Annual costs of pharmacotherapy per patient for acute leukemia in this regional hospital were approximately USD 4,717. Chemotherapy was the item with the greatest impact on cost.

The effect of endoneurial nerve growth factor on calcitonin gene-related peptide expression in primary sensory neurons.

Recent findings indicate that calcitonin gene-related peptide (CGRP) is involved in neuropathic pain, this peptide being up-regulated in a small population of large- and medium-sized primary sensory neurons after peripheral nerve injury. In adult animals, the expression of CGRP is regulated by nerve growth factor (NGF). After nerve injury, NGF is up-regulated at the injury site for several weeks, and this up-regulation contributes to the onset of neuropathic pain. Using immunohistochemistry, we investigated the time course of the effect of an endoneurial injection of NGF on the expression of CGRP in primary sensory neurons. NGF increased the percentage of medium- to large-sized DRG neuron profiles expressing CGRP, did not modify the percentage of small-sized neurons expressing CGRP, and increased CGRP expression in the laminae III and IV of the dorsal horn. The effects of NGF were evident as soon as 1 day after endoneurial injection, and lasted for 5 days. Ten days after the injection of NGF, the patterns of CGRP expression in the DRG were normal, whereas a slight decrease in CGRP content was observed in the dorsal horn. The injection of vehicle did not produce any change on CGRP expression in primary sensory neurons. These results suggest that endoneurial NGF is responsible for the increase in CGRP expression in some large-sized neurons and their central processes observed after nerve injury in animal models of neuropathic pain. Our findings contribute to the understanding of the role of NGF in neuropathic pain.

Behavioral and histological effects of endoneurial administration of nerve growth factor: possible implications in neuropathic pain.

Animal models of neuropathic pain involving incomplete nerve injury result in causalgia-like symptoms, including thermal hyperalgesia and mechanical allodynia. Although current evidence links the overexpression of nerve growth factor (NGF) to peripheral neuropathic pain, the direct effect of NGF inside a nerve has not been evaluated yet. The purpose of this study was to investigate whether a single, low-dose (1-30 ng), endoneurial administration of NGF reproduces behavioral consequences of a partial nerve injury and to analyze the changes on myelinated fibers induced by NGF. Significant thermal hyperalgesia appeared on days 3 and 5 post-injection of NGF. NGF did not evoke mechanical allodynia at any of the assayed doses. On day 1, NGF induced focal degeneration and demyelination of fibers at the site of injection. Starting on day 5 clusters of small axons enclosed within one Schwann cell and associated with fibroblasts were observed, revealing axonal sprouting. Both thermal hyperalgesia and demyelination-sprouting processes induced by NGF were dose-dependent (1-30 ng) and the time course of both effects was similar. The injection of vehicle did not produce any behavioral or histological effect. These results suggest that overexpression of NGF may induce endoneurial sprouting and triggers the development of thermal hyperalgesia, but not mechanical allodynia, in peripheral neuropathic pain states.

Clareamento caseiro em dentes vitais / Night-Guard dental bleaching

Na Odontologia atual, o clareamento dental caseiro tem sido requisitado com maior freqüência por pacientes que desejam uma estética melhorada. O Cirurgião-Dentista, como peça fundamental para o sucesso do tratamento, deve empregar a melhor técnica de acordo com a indicação e contra-indicação, levando-se em conta o diagnóstico da alteração de cor e conservação das estruturas dentais, orientando corretamente o paciente, antes, durante e após o tratameto e saber agir adequadamente em casos de sensibilidade. Possibilitar uma correta indicação, aletar para possíveis efeitos adversos e limitações, discutir riscos e benefícios do clareamento de dentes vitais é o objetivo deste trabalho.