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1.
Acta amaz ; 50(3): 223-231, jul. - set. 2020.
Artigo em Inglês | LILACS | ID: biblio-1118832

RESUMO

We assessed the effect of stocking density on physiological parameters (blood lactate, glucose, cortisol, hematocrit), water quality (temperature, dissolved oxygen, pH, unionized ammonia, carbon dioxide), and survival during the transportation of fingerling (24.5 ± 4.7 g) and juvenile (615.8 ± 122.2 g) pirarucu (Arapaima gigas) for six hours in plastic bags. The tested densities were 65, 80, 95, 110 and 125 g L-1 for fingerlings, and 50, 80, 110, 140 and 170 g L-1 for juveniles (three replicates each). Parameters were measured prior to and immediately after transportation, and at 24 and 96 hours recovery after transportation. No mortality was observed, except for fingerlings (< 3%) at densities of 110 and 125 g L-1 during recovery. All the water quality parameters were significantly altered after the transportation of fingerlings and juveniles. Water temperature, dissolved oxygen, carbon dioxide and unionized ammonia increased, but pH decreased. Only carbon dioxide and unionized ammonia differed among densities. Cortisol levels did not increase over time, except for the juveniles at 170 g L-1, which still had high cortisol after 96 hours. Glucose significantly increased after transportation for all the treatments and returned to the initial values during the recovery period. Conversely, the lactate values were still high after 96 hours. Hematocrit was assessed only for juveniles and was significantly lower after transportation. We conclude that fingerling and juvenile pirarucu can be safely transported at densities up to 95 g L-1 and 140 g L-1, respectively. (AU)


Assuntos
Hidrocortisona , Ácido Láctico , Glucose , Qualidade da Água , Hematócrito
2.
Crit Care Resusc ; 22(3): 191-199, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32900325

RESUMO

OBJECTIVE: To determine whether hydrocortisone is a cost-effective treatment for patients with septic shock. DESIGN: Data linkage-based cost-effectiveness analysis. SETTING: New South Wales and Queensland intensive care units. PARTICIPANTS AND INTERVENTION: Patients with septic shock randomly assigned to treatment with hydrocortisone or placebo in the Adjunctive Glucocorticoid Therapy in Patients with Septic Shock (ADRENAL) trial. MAIN OUTCOME MEASURES: Health-related quality of life at 6 months using the EuroQoL 5-dimension 5-level questionnaire. Data on hospital resource use and costs were obtained by linking the ADRENAL dataset to government administrative health databases. Clinical outcomes included mortality, health-related quality of life, and quality-adjusted life-years gained; economic outcomes included hospital resource use, costs and cost-effectiveness from the health care payer perspective. We also assessed cost-effectiveness by sex. To increase the precision of cost-effectiveness estimates, we conducted unrestricted bootstrapping. RESULTS: Of 3800 patients in the ADRENAL trial, 1772 (46.6%) were eligible and 1513 (85.4% of those eligible) were included. There was no difference between hydrocortisone or placebo groups in regards to mortality (218/742 [29.4%] v 227/759 [29.9%]; HR, 0.93; 95% CI, 0.78-1.12; P = 0.47), mean number of QALYs gained (0.10 ± 0.09 v 0.10 ± 0.09; P = 0.52), or total hospital costs (A$73 515 ± 61 376 v A$69 748 ± 61 793; mean difference, A$3767; 95% CI, -A$2891 to A$10 425; P = 0.27). The incremental cost of hydrocortisone was A$1 254 078 per quality-adjusted life-year gained. In females, hydrocortisone was cost-effective in 46.2% of bootstrapped replications and in males it was cost-effective in 2.7% of bootstrapped replications. CONCLUSIONS: Adjunctive hydrocortisone did not significantly affect longer term mortality, health-related quality of life, health care resource use or costs, and is unlikely to be cost-effective.


Assuntos
Anti-Inflamatórios/economia , Anti-Inflamatórios/uso terapêutico , Hidrocortisona/economia , Hidrocortisona/uso terapêutico , Choque Séptico/tratamento farmacológico , Análise Custo-Benefício , Feminino , Humanos , Masculino , New South Wales , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida , Choque Séptico/mortalidade
3.
J Oral Facial Pain Headache ; 34(3): 281-290, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32870957

RESUMO

AIMS: To investigate pain sensitivity in the masseter muscle and index finger in response to acute psychologic stress in healthy participants. METHODS: Fifteen healthy women (23.7 ± 2.3 years) participated in two randomized sessions: in the experimental stress session, the Paced Auditory Serial Addition Task (PASAT) was used to induce acute stress, and in the control session, a control task was performed. Salivary cortisol, perceived stress levels, electrical and pressure pain thresholds (PTs), and pain tolerance levels (PTLs) were measured at baseline and after each task. Mixed-model analysis was used to test for significant interaction effects between time and session. RESULTS: An interaction effect between time and session occurred for perceived stress levels (P < .001); perceived stress was significantly higher after the experimental task than after the control task (P < .01). No interaction effects occurred for salivary cortisol levels, electrical PTs, or pressure PTLs. Although significant interactions did occur for electrical PTL (P < .05) and pressure PT (P < .001), the simple effects test could not identify significant differences between sessions at any time point. CONCLUSION: The PASAT evoked significant levels of perceived stress; however, pain sensitivity to mechanical or electrical stimuli was not significantly altered in response to the stress task, and the salivary cortisol levels were not altered in response to the PASAT. These results must be interpreted with caution, and more studies with larger study samples are needed to increase the clinical relevant understanding of the pain mechanisms and psychologic stress.


Assuntos
Hidrocortisona , Limiar da Dor , Estudos Cross-Over , Feminino , Humanos , Músculo Masseter , Projetos Piloto , Saliva , Estresse Psicológico
5.
Trials ; 21(1): 734, 2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32831155

RESUMO

OBJECTIVES: Primary objective: To estimate the effect of corticosteroids compared with usual care or placebo on mortality up to 28 days after randomization. Secondary objectives: To examine whether the effect of corticosteroids compared with usual care or placebo on mortality up to 28 days after randomization varies between subgroups related to treatment characteristics, disease severity at the time of randomization, patient characteristics, or risk of bias. To examine the effect of corticosteroids compared with usual care or placebo on serious adverse events. STUDY DESIGN: Prospective meta-analysis of randomized controlled trials. Both placebo-controlled and open-label trials are eligible. PARTICIPANTS: Hospitalised, critically ill patients with suspected or confirmed COVID-19. INTERVENTION AND COMPARATOR: Intervention groups will have received therapeutic doses of a steroid (dexamethasone, hydrocortisone or methylprednisolone) with IV or oral administration immediately after randomization. The comparator groups will have received standard of care or usual care or placebo. MAIN OUTCOME: All-cause mortality up to 28 days after randomization. SEARCH METHODS: Systematic searching of clinicaltrials.gov , EudraCT, the WHO ISRCTN registry, and the Chinese clinical trials registry. Additionally, research and WHO networks will be asked for relevant trials. RISK OF BIAS ASSESSMENTS: These will be based on the Cochrane RoB 2 tool, and will use structured information provided by the trial investigators on a form designed for this prospective meta-analysis. We will use GRADE to assess the certainty of the evidence. STATISTICAL ANALYSES: Trial investigators will provide data on the numbers of participants who did and did not experience each outcome according to intervention group, overall and in specified subgroups. We will conduct fixed-effect (primary analysis) and random-effects (Paule-Mandel estimate of heterogeneity and Hartung-Knapp adjustment) meta-analyses. We will quantify inconsistency in effects between trials using I2 statistics. Evidence for subgroup effects will be quantified by ratios of odds ratios comparing effects in the subgroups, and corresponding interaction p-values. Comparisons between subgroups defined by trial characteristics will be made using random-effects meta-regression. Comparisons between subgroups defined by patient characteristics will be made by estimating trial-specific ratios of odds ratios comparing intervention effects between subgroups then combining these using random-effects meta-analysis. Steroid interventions will be classified as high or low dose according to whether the dose is greater or less than or equal to 400 mg hydrocortisone per day or equivalent. We will use network meta-analysis methods to make comparisons between the effects of high and low dose steroid interventions (because one trial randomized participants to both low and high dose steroid arms). PROSPERO REGISTRATION NUMBER: CRD42020197242 FULL PROTOCOL: The full protocol for this prospective meta-analysis is attached as an additional file, accessible from the Trials website (Additional file 1). To expedite dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol for the systematic review.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Glucocorticoides/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Corticosteroides/uso terapêutico , Betacoronavirus , Estado Terminal , Dexametasona/uso terapêutico , Humanos , Hidrocortisona/uso terapêutico , Metilprednisolona/uso terapêutico , Pandemias , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
7.
Int J Biol Sci ; 16(13): 2382-2391, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32760206

RESUMO

COVID-19 is a public health emergency that has rapidly spread to over 200 countries and regions, and no effective treatment has been established to date. Severe and critical cases have been associated with higher mortality due to acute respiratory distress syndrome (ARDS) and cytokine storm. Based on the novelty and recent emergence of COVID-19, no effective treatment regimen has been identified, thus prompting clinicians to engage in drug repurposing to address the immediate therapeutic need. This study focused on the molecular target angiotensin-converting enzyme 2 (ACE2) of SARS-CoV-2 and screened a group of ACE2 agonists by bioinformatics. Glucocorticoids are a type of ACE2 activator. We verified the efficacy of nine chemicals on regulating ACE2 expression in human GES-1, an upper digestive tract epithelial cell line, and THP-1, a human monocyte cell line, and found that several glucocorticoids imparted activating effects on ACE2 in both cell lines. The drugs triciribine and kinetin riboside activate ACE2 expression or inhibit IL-6 production in macrophages to some extent. In addition, we compared the efficacies of several glucocorticoids. Hydrocortisone showed the strongest effect on ACE2 activation, followed by prednisolone, dexamethasone, and methylprednisolone. We retrospectively analyzed the therapeutic efficacy of nine severe or critical patients from a cohort of 90 COVID-19 cases, who received medium to small doses of glucocorticoids from our integrated medical team in Wuhan. Seven out of nine patients revealed significant improvement in clinical parameters and chest CT images. This study provides experimental and clinical evidence that medium-to-low-dose glucocorticoids may play a protective role in the respiratory and digestive systems by activating ACE2 and suppressing cytokine storm.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Glucocorticoides/uso terapêutico , Interleucina-6/metabolismo , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/tratamento farmacológico , Adenosina/uso terapêutico , Adulto , Idoso , Antivirais/uso terapêutico , Betacoronavirus , Linhagem Celular , Linhagem Celular Tumoral , Infecções por Coronavirus/metabolismo , Citocinas/metabolismo , Células Epiteliais/virologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Hidrocortisona/uso terapêutico , Cinetina/uso terapêutico , Macrófagos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Monócitos/virologia , Pandemias , Pneumonia Viral/metabolismo , Estudos Retrospectivos , Ribonucleosídeos/uso terapêutico , Transcriptoma
9.
Eur J Endocrinol ; 183(4): 357-368, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32621587

RESUMO

Context: Accurate hydrocortisone dosing in children with adrenal insufficiency is important to avoid the risks of over and under treatment including iatrogenic Cushing's syndrome and adrenal crisis. Objective: To establish a population pharmacokinetic model of hydrocortisone in children and use this to refine hydrocortisone replacement regimens. Design and methods: Pharmacokinetic study of hydrocortisone granules, available in 0.5, 1, 2 and 5 mg dose strengths, in 24 children with adrenal insufficiency aged 2 weeks to 6 years. Cortisol concentrations quantified by LC-MS/MS were used to refine an adult pharmacokinetic model to a paediatric population model which was then used to simulate seven different hydrocortisone treatment regimens. Results: Pre-dose cortisol levels were undetectable in 54% of the 24 children. The developed pharmacokinetic model had good predictive performance. Simulations for the seven treatment regimens using either three- or four-times daily dosing showed treatment regimens delivered an AUC0-24h within the 90% reference range for healthy children except in neonates where two regimens had an AUC below the 5th percentile. Cortisol concentrations at individual time points in the 24 h were outside the 90% reference range for healthy individuals in 50%, 55-65% and 70-75% for children, infants and neonates, respectively, with low cortisol levels being most prevalent. Conclusions: Current paediatric hydrocortisone treatment regimens based on either three- or four-times daily administration replicate cortisol exposure based on AUC0-24h, but the majority of cortisol levels are above or below physiological cortisol levels with low levels very common before the next dose.


Assuntos
Insuficiência Adrenal/tratamento farmacológico , Insuficiência Adrenal/metabolismo , Cálculos da Dosagem de Medicamento , Hidrocortisona/administração & dosagem , Hidrocortisona/farmacocinética , Administração Oral , Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Hiperplasia Suprarrenal Congênita/epidemiologia , Hiperplasia Suprarrenal Congênita/metabolismo , Insuficiência Adrenal/epidemiologia , Fatores Etários , Idade de Início , Área Sob a Curva , Pesos e Medidas Corporais , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Terapia de Reposição Hormonal/métodos , Terapia de Reposição Hormonal/normas , Humanos , Lactente , Recém-Nascido , Masculino , Modelos Teóricos
10.
Eur J Endocrinol ; 183(4): 399-409, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32698132

RESUMO

Context: Unilateral aldosteronomas should suppress renin and contralateral aldosterone secretion. Complete aldosterone suppression in contralateral adrenal vein sample (AVS) could predict surgical outcomes. Objectives: To retrospectively evaluate the prevalence of basal contralateral suppression using Aldosterone (A)contralateral(CL)/Aperipheral(P) as compared to (A/Cortisol(C)CL)/(A/C)P ratio in primary aldosteronism (PA) patients studied in two Canadian centers. To determine the best cut-off to predict clinical and biochemical surgical cure. To compare the accuracy of ACL/AP to the basal and post-ACTH lateralization index (LI) in predicting surgical cure. Methods: In total, 330 patients with PA and successful AVS were included; 124 lateralizing patients underwent surgery. Clinical and biochemical cure at 3 and 12 months were evaluated using the PASO criteria. Results: Using ACL/AP and (A/C)CL/(A/C)P at the cut-off of 1, the prevalence of contralateral suppression was 6 and 45%, respectively. Using ROC curves, the ACL/AP ratio is associated with clinical cure at 3 and 12 months and biochemical cure at 12 months. (A/C)CL/(A/C)P is associated with biochemical cure only. The cut-offs for ACL/AP offering the best sensitivity (Se) and specificity (Sp) for clinical and biochemical cures at 12 months are 2.15 (Se: 63% and Sp: 71%) and 6.15 (Se: 84% and Sp: 77%), respectively. Basal LI and post-ACTH LI are associated with clinical cure but only the post-ACTH LI is associated with biochemical cure. Conclusions: In lateralized PA, basal contralateral suppression defined by ACL/AP is rare and incomplete compared to the (A/C)CL/(A/C)P ratio and is associated with clinical and biochemical postoperative outcome, but with modest accuracy.


Assuntos
Neoplasias das Glândulas Suprarrenais/sangue , Glândulas Suprarrenais/metabolismo , Adenoma Adrenocortical/sangue , Aldosterona/sangue , Coleta de Amostras Sanguíneas/métodos , Hiperaldosteronismo/sangue , Hiperaldosteronismo/epidemiologia , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/epidemiologia , Neoplasias das Glândulas Suprarrenais/cirurgia , Glândulas Suprarrenais/patologia , Adrenalectomia/estatística & dados numéricos , Adenoma Adrenocortical/diagnóstico , Adenoma Adrenocortical/epidemiologia , Adenoma Adrenocortical/cirurgia , Adulto , Aldosterona/análise , Canadá/epidemiologia , Estudos de Coortes , Técnicas de Diagnóstico Endócrino , Regulação para Baixo , Feminino , Humanos , Hidrocortisona , Hiperaldosteronismo/patologia , Hiperaldosteronismo/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
11.
Lancet Diabetes Endocrinol ; 8(9): 748-761, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32730798

RESUMO

BACKGROUND: Cushing's disease is a rare endocrine disorder characterised by cortisol overproduction with severe complications. Therapies for cortisol reduction are often necessary. Here we report the outcomes from the pivotal phase III study of osilodrostat (a potent oral inhibitor of cytochrome P450 11B1, mitochondrial [11ß-hydroxylase]; Novartis Pharma AG, Basel, Switzerland) in patients with Cushing's disease. METHODS: LINC 3 was a prospective, multicentre, open-label, phase III study with a double-blind randomised withdrawal period, that comprised four periods. Patients aged 18-75 years, with confirmed persistent or recurrent Cushing's disease (defined as mean 24-h urinary free cortisol [UFC] concentration >1·5 times the upper limit of normal [ULN] and morning plasma adrenocorticotropic hormone above the lower limit of normal) who had previously had pituitary surgery or irradiation, or were newly diagnosed and who refused surgery or were not surgical candidates, were recruited from 66 hospital sites and private clinical practices in 19 countries. In period 1, open-label osilodrostat was initiated in all participants and adjusted every 2 weeks (1-30 mg twice daily; film-coated tablets for oral administration) on the basis of mean 24-h UFC concentration and safety until week 12. In period 2, weeks 13-24, osilodrostat was continued at the therapeutic dose determined during period 1. In period 3, beginning at week 26, participants who had a mean 24-h UFC concentration of less than or equal to the ULN at week 24, without up-titration after week 12, were randomly assigned (1:1), via an interactive-response technology, stratified by osilodrostat dose at week 24 and history of pituitary irradiation, to continue osilodrostat or switch to placebo for 8 weeks. Participants and investigators were masked to treatment assignment. Ineligible participants continued open-label osilodrostat. In period 4, weeks 35-48, all participants were given open-label osilodrostat until core-study end. The primary objective was to compare the efficacy of osilodrostat versus placebo at the end of period 3. The primary endpoint was the proportion of participants who had been randomly assigned to treatment or placebo with a complete response (ie, mean 24-h UFC concentration of ≤ULN) at the end of the randomised withdrawal period (week 34), without up-titration during this period. The key secondary endpoint was the proportion of participants with a complete response at the end of the single-arm, open-label period (ie, period 2, week 24) without up-titration during weeks 13-24. Analysis was by intention-to-treat for all patients who received at least one dose of osilodrostat (full analysis set; key secondary endpoint) or randomised treatment (randomised analysis set; primary endpoint) and safety was assessed in all enrolled patients who received at least one dose of osilodrostat and had at least one post-baseline safety assessment. LINC 3 is registered with ClinicalTrials.gov, NCT02180217, and is now complete. FINDINGS: Between Nov 12, 2014, and March 22, 2017, 202 patients were screened and 137 were enrolled. The median age was 40·0 years (31·0-49·0) and 106 (77%) participants were female. 72 (53%) participants were eligible for randomisation during the withdrawal phase, of whom 36 were assigned to continue osilodrostat and 35 were assigned to placebo; one patient was not randomly assigned due to investigator decision and continued open-label osilodrostat. More patients maintained a complete response with osilodrostat versus with placebo at week 34 (31 [86%] vs ten [29%]; odds ratio 13·7 [95% CI 3·7-53·4]; p<0·0001). At week 24, 72 (53%; 95% CI 43·9-61·1) of 137 patients maintained a complete response without up-titration after week 12. Most common adverse events (ie, occurred in >25% of participants) were nausea (57 [42%]), headache (46 [34%]), fatigue (39 [28%]), and adrenal insufficiency (38 [28%]). Hypocortisolism occurred in 70 (51%) patients and adverse events related to adrenal hormone precursors occurred in 58 (42%) patients. One patient died, unrelated to study drug, after the core study phase. INTERPRETATION: Twice-daily osilodrostat rapidly reduced mean 24-h UFC and sustained this reduction alongside improvements in clinical signs of hypercortisolism; it was also generally well tolerated. Osilodrostat is an effective new treatment option that is approved in Europe for the treatment of endogenous Cushing's syndrome and in the USA for Cushing's disease. FUNDING: Novartis Pharma AG.


Assuntos
Citocromo P-450 CYP11B2/antagonistas & inibidores , Imidazóis/administração & dosagem , Hipersecreção Hipofisária de ACTH/diagnóstico , Hipersecreção Hipofisária de ACTH/tratamento farmacológico , Piridinas/administração & dosagem , Administração Oral , Adulto , Citocromo P-450 CYP11B2/metabolismo , Método Duplo-Cego , Feminino , Humanos , Hidrocortisona/antagonistas & inibidores , Hidrocortisona/metabolismo , Masculino , Pessoa de Meia-Idade , Hipersecreção Hipofisária de ACTH/metabolismo , Estudos Prospectivos , Resultado do Tratamento
12.
Eur J Endocrinol ; 183(3): 325-333, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32717717

RESUMO

Objective: To identify radiologic features that correlate with mild autonomous cortisol excess using planar and volumetric analysis. Design: Cross-sectional study. Methods: In the study, 64 patients with overt Cushing syndrome (CS), 59 patients with mild autonomous cortisol excess (MACE), and 64 patients with nonfunctioning adrenal tumors (NFAT) with evaluable CT scans were included. Patients with NFAT and MACE were BMI-matched with those with overt CS. Planar and volumetric analyses of CT scans were performed in DICOM images using OsiriX software. Results: The mean age was 56.6 ± 1.01 years, and 123 patients (65.1%) were female. In the order of NFAT, MACE, and overt CS, the diameters and volumes of the adenoma increased, while limb widths and volumes of the contralateral adrenal gland decreased. Patients with MACE or overt CS were more likely to have osteoporosis than those with NFAT (P = 0.006), and patients with overt CS were more likely to experience a fragility fracture than those with NFAT or MACE (P = 0.002). Among radiologic features, the limb width of the contralateral adrenal gland correlated with the cortisol level after overnight dexamethasone suppression test (r = -0.583, P < 0.001). Conclusions: The study showed that the contralateral adrenal limb thinning was a distinctive radiologic feature of autonomous cortisol excess in the planar and volumetric analysis.


Assuntos
Neoplasias das Glândulas Suprarrenais/sangue , Neoplasias das Glândulas Suprarrenais/patologia , Síndrome de Cushing/sangue , Síndrome de Cushing/patologia , Glândulas Suprarrenais/patologia , Hormônio Adrenocorticotrópico/sangue , Idoso , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Hidrocortisona/sangue , Masculino , Pessoa de Meia-Idade
13.
Buenos Aires; s.n; 16 jun. 2020.
Não convencional em Espanhol | LILACS, BRISA/RedTESA | ID: biblio-1116497

RESUMO

CONTEXTO CLÍNICO: La Enfermedad por el Coronavirus 2019 (COVID­19, por su sigla en inglés Coronavirus Disease 2019) es una enfermedad respiratoria de humanos producida por un nuevo coronavirus identificado con la sigla SARS-CoV-2. El 11 de marzo de 2020 la Organización Mundial de la Salud (OMS) declaro la COVID-19 como una pandemia. Desde ese momento hasta el 15 de junio su circulación se ha reportado en 205 países reportándose más de 7.800.000 casos y la muerte 430.000 personas. El período de incubación de la infección es de 2 a 14 días. La mayor parte de los contagios se producen persona a persona, siendo altamente transmisible.(3) La clínica varía desde casos asintomáticos a cuadros febriles con tos y dificultad respiratoria, neumonía y distrés respiratorio. También puede acompañarse de alteraciones gastrointestinales. En los casos con mal pronóstico, el paciente presenta un importante deterioro respiratorio en 4-8 días. Las imágenes radiológicas muestran generalmente neumonía focal o generalizada semejante al síndrome de distress respiratorio agudo. (3) La mayoría de los casos graves requieren ingreso hospitalario, siendo mayoritariamente casos primarios en pacientes de edad avanzada y con comorbilidades (diabetes, enfermedad crónica renal, hipertensión, enfermedad cardiaca y enfermedad pulmonar crónica). La tasa media de letalidad de los pacientes ingresados a UTI es cercana al 49%, siendo los valores más elevados en pacientes masculinos de más de 50 años con comorbilidades múltiples. Actualmente el tratamiento de la COVID­19 es sintomático y de sostén no existiendo hasta el momento tratamiento farmacológico específico curativo. Debido a la evidencia que sugiere que el daño pulmonar agudo observado en la infección por SARS-CoV-2 estaría asociada a la activación de las células inmunes circulantes, incluyendo células T y las citoquinas que conducen a un síndrome de liberación de citoquinas (similar al síndrome de activación macrofágica y hemofagocítico) por lo que se plantea que el uso de corticoides sistémicos podría disminuir la mortalidad y/o necesidad de soporte ventilatorio invasivo. TECNOLOGÍA: Los glucocorticoides (GCS) son una familia de medicamentos antiinflamatorios e inmunomoduladores que se utilizan en el tratamiento de diversas patologías cuyo principal componente etiopatogénico es la inflamación. Dentro de los mecanismos de acción propuestos se encuentran: inhibición de citoquinas inflamatorias (IL-1 y IL-2), inhibición de la migración de leucocitaria, inhibición de la desgranulación de mastocitos, depleción linfocitaria (principalmente linfocitos T), incremento de citoquinas anti-inflamatorias (IL-10). Dentro de las alternativas para la administración sistémica se pueden mencionar a la hidrocortisona, dexametasona, betametasona, prednisona, prednisolona, metilprednisolona y deflazacort. Todos ellos difieren principalmente en el grado de actividad mineralocorticorticoide y vida media. OBJETIVO: El objetivo del presente informe es evaluar la evidencia disponible acerca de la eficacia, seguridad y aspectos relacionados a las políticas de cobertura del uso de corticoides sistémicos en COVID­19. MÉTODOS: Se realizó una búsqueda en las principales bases de datos bibliográficas, en buscadores genéricos de internet, y financiadores de salud. Se priorizó la inclusión de revisiones sistemáticas (RS), ensayos clínicos controlados aleatorizados (ECAs), evaluaciones de tecnologías sanitarias (ETS), evaluaciones económicas, guías de práctica clínica (GPC) y recomendaciones de diferentes organizaciones de salud. RESULTADOS: Se incluyeron un ECA, una RS, dos estudios observacionales, un documento de evaluación de tecnología sanitaria, 12 guías de práctica clínica, recomendaciones de organismos gubernamentales o sociedades científicas acerca del uso de corticoides sistémicos en pacientes con diagnóstico de COVID­19. CONCLUSIONES: Evidencia de alta calidad proveniente de los resultados de un ensayo clínico aleatorizado aún no publicado sugiere que el uso de corticoides sistémicos se asocia a una disminución en el riesgo de mortalidad principalmente en pacientes con requerimientos de oxigeno suplementario o asistencia mecánica invasiva. Evidencia de muy baja calidad también sugiere que podría tener el mismo beneficio en aquellos pacientes con COVID-19 que presentan síndrome de distrés respiratorio agudo. Múltiples ensayos clínicos aleatorizados en pacientes con cuadros moderados o severos se encuentran en curso. Las guías de práctica clínica de diferentes sociedades internacionales y organismos gubernamentales que lo recomiendan indican su utilización para el tratamiento de pacientes con criterios de síndrome de distrés respiratorio agudo. Si bien no se encontraron estudios de costo-efectividad en Latinoamérica, el costo total del tratamiento al igual que su impacto presupuestario sería muy bajo.


Assuntos
Humanos , Pneumonia Viral/tratamento farmacológico , Betametasona/uso terapêutico , Dexametasona/uso terapêutico , Hidrocortisona/uso terapêutico , Metilprednisolona/uso terapêutico , Prednisolona/uso terapêutico , Prednisona/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Avaliação da Tecnologia Biomédica , Avaliação em Saúde , Análise Custo-Benefício
15.
Bratisl Lek Listy ; 121(6): 428-430, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32484707

RESUMO

OBJECTIVES: Many studies use stimulated saliva for the assessment of cortisol. However, it is not yet clear how stimulation affects the flow of specific markers. The aim was to assess whether stimulation of salivation affects the physiological flow of cortisol during a stressing day as compared to an ordinary day. The second aim was to show how the normalising factor affects the outcome of the study. METHODS: Stimulated saliva was taken from 42 children at 8:00 a.m. and 12:00 a.m. on two separate days one month apart. During the first day, the children were exposed to stress situation, while the second day was considered a control day. The concentration of cortisol was analysed using ELISA. RESULTS: The highest level of cortisol was observed in the morning of the stress day (p 0.99). CONCLUSION: Based on our results, the examination of the cortisol diurnal rhythm is not reliable in stimulated saliva. Moreover, the effect of saliva stimulation has to be taken into account for every marker individually (Fig. 2, Ref. 22).


Assuntos
Hidrocortisona , Saliva , Estresse Fisiológico , Biomarcadores , Criança , Ritmo Circadiano , Humanos , Hidrocortisona/análise , Saliva/química
16.
Eur J Endocrinol ; 183(2): 119-127, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32580144

RESUMO

Objective: Patients with adrenal insufficiency (AI) suffer from impaired quality of life and are at risk of adrenal crisis (AC) despite established replacement therapy. Patient education is regarded an important measure for prevention of AC and improvement of AI management. A standardized education programme was elaborated for patients with chronic AI in Germany. Design: Longitudinal, prospective, questionnaire-based, multi-centre study. Methods: During 2-h sessions, patients (n = 526) were provided with basic knowledge on AI, equipped with emergency cards and sets and trained in self-injection of hydrocortisone. To evaluate the education programme, patients from eight certified centres completed questionnaires before, immediately after and 6-9 months after training. Results: 399 completed data sets were available for analysis. Questionnaire score-values were significantly higher after patient education, indicating successful knowledge transfer (baseline: 17 ± 7.1 of a maximum score of 29; after training: 23 ± 4.2; P < 0.001), and remained stable over 6-9 months. Female sex, younger age and primary cause of AI were associated with higher baseline scores; after education, age, cause of AI and previous adrenal crisis had a significant main effect on scores. 91% of patients would dare performing self-injection after training, compared to 68% at baseline. An improvement of subjective well-being through participation in the education programme was indicated by 95% of the patients 6-9 months after participation. Conclusion: Patient group education in chronic AI represents a helpful tool for the guidance of patients, their self-assurance and their knowledge on prevention of adrenal crises. Repeated training and adaptation to specific needs, for example, of older patients is needed.


Assuntos
Insuficiência Adrenal/tratamento farmacológico , Educação de Pacientes como Assunto/métodos , Educação de Pacientes como Assunto/normas , Doença Aguda/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Etiquetas de Emergência Médica , Tratamento de Emergência , Feminino , Alemanha , Terapia de Reposição Hormonal , Humanos , Hidrocortisona/administração & dosagem , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Autoadministração , Inquéritos e Questionários , Adulto Jovem
17.
Crim Behav Ment Health ; 30(2-3): 117-131, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32535969

RESUMO

BACKGROUND: Early puberty is associated with higher than average risk of antisocial behaviour, both in girls and boys. Most studies of such association, however, have focused on psychosocial mediating and moderating factors. Few refer to coterminous hormonal measures. AIM: The aim of this review is to consider the role of hormonal markers as potential mediating or moderating factors between puberty timing and antisocial behaviour. METHOD: A systematic literature search was conducted searching Medline, Embase, Web of Science, Scopus, Psycinfo, Cochrane and Google Scholar. RESULTS: Just eight studies were found to fit criteria, all cross-sectional. Measurements were too heterogeneous to allow meta-analysis. The most consistent associations found were between adrenal hormones-both androgens and cortisol-which were associated with early adrenarche and antisocial behaviours in girls and later adrenarche and antisocial behaviour in boys. CONCLUSIONS: The findings from our review suggest that longitudinal studies to test bidirectional hormone-behaviour associations with early or late puberty would be worthwhile. In view of the interactive processes between hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes, integrated consideration of the hormonal end products is recommended.


Assuntos
Comportamento do Adolescente/psicologia , Adrenarca/psicologia , Transtorno da Personalidade Antissocial/etiologia , Hormônios/sangue , Menarca/fisiologia , Puberdade/fisiologia , Maturidade Sexual/fisiologia , Adolescente , Comportamento do Adolescente/fisiologia , Adrenarca/fisiologia , Androgênios , Transtorno da Personalidade Antissocial/diagnóstico , Transtorno da Personalidade Antissocial/metabolismo , Criança , Feminino , Hormônios Esteroides Gonadais/sangue , Gonadotropinas Hipofisárias/sangue , Humanos , Hidrocortisona/metabolismo , Masculino , Fatores de Tempo
18.
Shanghai Kou Qiang Yi Xue ; 29(1): 93-96, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32524130

RESUMO

PURPOSE: To investigate the correlation between salivary stress markers chromogranin A (CgA), cortisol, α-amylase, ß-endorphin and clinical parameters of periodontitis, including sulcus bleeding index (SBI), periodontal probing depth (PD) and attachment loss (AL). METHODS: A total of 105 patients with chronic periodontitis (periodontitis group) and 105 healthy individuals (control group) visiting our hospital from December 2017 to December 2018 were selected. Indicators including CgA, cortisol, α-amylase, ß-endorphin levels, SBI, PD, and AL were detected in both groups, and the correlation among them was determined by Pearson's analysis, multivariate logistic regression was used to analyze the risk factors associated with periodontitis using SPSS 22.0 software package. RESULTS: The levels of CgA, cortisol, α-amylase and ß-endorphin in the periodontitis group were significantly higher than those in the control group (P<0.05). SBI, PD and AL in the periodontitis group were significantly higher than those in the control group (P<0.05). The levels of CgA, cortisol, α-amylase and ß-endorphin in saliva were positively correlated with SBI, PD, and AL (P<0.05). CgA, cortisol, α-amylase, and ß-endorphin were independent risk factors for periodontitis (P<0.05). CONCLUSIONS: Salivary stress markers CgA, cortisol, α-amylase, and ß-endorphin are significantly associated with clinical parameters of periodontitis, suggesting that they can reflect the progression of periodontitis, thus providing an effective reference for diagnosis and efficacy monitoring of periodontitis.


Assuntos
Periodontite Crônica , Biomarcadores , Cromogranina A , Humanos , Hidrocortisona , Saliva
19.
Clinics (Sao Paulo) ; 75: e2022, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32555949

RESUMO

The coronavirus disease 2019 (COVID-19) is an emerging pandemic challenge. Acute respiratory distress syndrome (ARDS) in COVID-19 is characterized by a severe cytokine storm. Patients undergoing glucocorticoid (GC) replacement therapy for adrenal insufficiency (AI) represent a highly vulnerable group that could develop severe complications due to the SARS-CoV-2 infection. In this review, we highlight the strategies to avoid an adrenal crisis in patients with AI and COVID-19. Adrenal crisis is a medical emergency and an important cause of death. Once patients with AI present symptoms of COVID-19, the dose of GC replacement therapy should be immediately doubled. In the presence of any emergency warning signs or inability to administer oral GC doses, we recommend that patients should immediately seek Emergency services to evaluate COVID-19 symptoms and receive 100 mg hydrocortisone by intravenous injection, followed by 50 mg hydrocortisone intravenously every 6 h or 200 mg/day by continuous intravenous infusion.


Assuntos
Insuficiência Adrenal/complicações , Insuficiência Adrenal/tratamento farmacológico , Betacoronavirus , Infecções por Coronavirus/prevenção & controle , Glucocorticoides/administração & dosagem , Hidrocortisona/administração & dosagem , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Humanos , Injeções Intravenosas , Fatores de Risco , Índice de Gravidade de Doença
20.
J Environ Sci Health B ; 55(8): 749-755, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32558613

RESUMO

This study assessed the hematological, enzymatic and osmoregulatory responses of silver catfish (Rhamdia quelen) exposed to sublethal concentrations (1.125 and 3.750 µg/L) of a commercial thiamethoxam-containing insecticide used on rice crops. Groups of 6 fish per tank (in triplicate, n = 3, total 54 fish) were exposed for up to 96 h to different concentrations of the compound. After this period, fish were placed in clean water for 48 h. Two fish from each tank (6 per treatment) that had been exposed to the insecticide for 24 h were anesthetized with eugenol and blood was collected to evaluate hematological and biochemical parameters. Blood, liver and muscle were collected for determination of metabolic parameters, plasma cortisol, Cl-, Na+ and K+ levels and H+-ATPase and Na+/K+-ATPase activity in the gill. H+-ATPase activity was higher in fish exposed to 1.125 µg/L insecticide at 24 h compared to control (0.0 µg/L). Differences in cortisol levels were evidenced throughout the experimental period. These results indicated that exposure to the insecticide changed the hematological, biochemical and metabolic profile of the animals, suggesting concern about environmental safety. Therefore, we discourage the use of this pesticide in areas that come into contact with water bodies inhabited by fish.


Assuntos
Peixes-Gato/fisiologia , Inseticidas/toxicidade , Tiametoxam/toxicidade , Adenosina Trifosfatases/metabolismo , Animais , Peixes-Gato/sangue , Ecotoxicologia/métodos , Brânquias/efeitos dos fármacos , Brânquias/metabolismo , Hidrocortisona/sangue , Fígado/efeitos dos fármacos , Músculos/efeitos dos fármacos , Músculos/metabolismo , Potássio/metabolismo , Sódio/metabolismo , Testes de Toxicidade Aguda , Poluentes Químicos da Água/toxicidade
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