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1.
PLoS One ; 16(9): e0256977, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34473766

RESUMO

INTRODUCTION: Coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2. Although most patients with COVID-19 develop asymptomatic or mild disease, some patients develop severe disease. The effectiveness of various therapeutic agents, including antiviral drugs, steroids, and anti-inflammatories for COVID-19, have been being confirmed. The effect of administering steroids in early disease is unclear. This study therefore aimed to evaluate the effectiveness and risk of exacerbation of steroids administered preceding antiviral drugs in patients with COVID-19 pneumonia. METHODS: This retrospective, single-center, observational study included consecutive patients with COVID-19 between March 2020 and March 2021. Patients were divided into a steroids-first group and antiviral-drugs-first group. Mortality, duration of hospitalization, incidence rate and duration of intensive care unit (ICU) admission, intubation, and extracorporeal membrane oxygenation (ECMO) induction of the two groups were compared. RESULTS: A total of 258 patients were admitted during the study period. After excluding patients who received symptomatic treatment only, who were taking immunosuppressive drugs, or who were administered antiviral drugs only, 68 patients were included in the analysis, 16 in the steroids-first group and 52 in the antiviral-drugs-first group. The rate of intubation, ICU admission and ECMO induction were significantly higher in the steroids-first group than in the antiviral-drugs-first group (81.3% vs. 33.3, p<0.001, 75.0% vs. 29.4%, p = 0.001, and 31.3% vs. 7.8%, p = 0.017, respectively). Furthermore, patients who received steroids within ten days after starting antiviral drugs had significantly lower rates of ICU admission, intubation, and ECMO induction. (81.3% vs. 42.9% p = 0.011, 75.0% vs. 37.1% p = 0.012, and 31.3% vs. 8.6% p = 0.039, respectively). CONCLUSIONS: Administering steroids prior to antiviral drugs soon after symptom onset can aggravate disease severity. When administration of steroids is considered soon after symptom onset, it may be safer to initiate antiviral drugs first.


Assuntos
Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Dexametasona/uso terapêutico , Hospitalização/estatística & dados numéricos , Síndrome do Desconforto Respiratório/tratamento farmacológico , SARS-CoV-2/efeitos dos fármacos , Idoso , Antivirais/administração & dosagem , COVID-19/fisiopatologia , COVID-19/virologia , Dexametasona/administração & dosagem , Esquema de Medicação , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Síndrome do Desconforto Respiratório/fisiopatologia , Estudos Retrospectivos , SARS-CoV-2/fisiologia , Índice de Gravidade de Doença , Resultado do Tratamento
2.
S Afr Med J ; 111(6): 550-553, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-34382564

RESUMO

BACKGROUND: The hyperinflammation seen as part of a dysregulated immune response to SARS-CoV-2 in its most severe form leads to acute respiratory distress syndrome (ARDS), multiorgan failure and death. Corticosteroid therapy targets this hyperinflammation, otherwise known as a cytokine storm. It is the only therapeutic agent to date with a mortality benefit, with clear guidelines from national and international health authorities guiding its use. Objectives. To compare severity-of-illness indices, survival, length of intensive care unit (ICU) stay and potential ICU complications in patients treated with different corticosteroid regimens (high-dose hydrocortisone, high-dose methylprednisolone and lower-dose dexamethasone). Methods. In this single-centre descriptive retrospective observational study of a cohort of patients with severe COVID-19 admitted to a COVID-dedicated ICU, we compared patients treated with the three different corticosteroid regimens. Results. In 242 cases we could not demonstrate any statistically or clinically significant difference in the outcome of patients with critical COVID-19 treated with high-dose intravenous hydrocortisone (n=88) or methylprednisolone (n=46) compared with a relatively lower dose of dexamethasone (n=108). The survival rates were 38.6%, 39.1% and 33.3%, respectively (p=0.68). Patients treated with methylprednisolone tended to have a shorter length of ICU stay (median (interquartile range) 6 (4 - 10), 4 (2 - 8) and 5 (2 - 8) days; p=0.015) and fewer episodes of nosocomial sepsis (47.7%, 32.6% and 48.1%; p=0.01). Conclusions. Hydrocortisone or methylprednisolone can be given as an alternative to dexamethasone in the management of critical COVID-19, and this is a feasible alternative, especially in resource-constrained settings.


Assuntos
COVID-19/tratamento farmacológico , Dexametasona/administração & dosagem , Glucocorticoides/administração & dosagem , Hidrocortisona/administração & dosagem , Metilprednisolona/administração & dosagem , Adulto , COVID-19/complicações , COVID-19/mortalidade , Estudos de Coortes , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/virologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Taxa de Sobrevida
3.
Medicine (Baltimore) ; 100(34): e27064, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34449500

RESUMO

BACKGROUND: Dexmedetomidine (Dexm), a selective alpha-2 adrenoceptor agonist, and dexamethasone (Dexa), a very potent and highly selective glucocorticoid, have both been proven effectively to prolong the duration of local anesthetics (LA) in regional anesthesia. However, data comparing the efficacy of Dexm and Dexa as perineural adjuvants are inconsistent. Therefore, this systematic review and meta-analysis of randomized and quasi-randomized controlled trials (RCTs) was conducted to compare the effects of Dexm and Dexa when used as LA adjuvants on peripheral nerve block (PNB). METHODS: We systematically searched PubMed, Cochrane Library, EMBASE, Web of Science, and ScienceDirect databases up to October, 2020. The primary outcome was the duration of analgesia. Secondary outcomes included incidence of rescue analgesia, cumulative opioid consumption, time required for onset of sensory and motor blockades, duration of sensory and motor blockades, incidence of postoperative nausea and vomiting (PONV), and side effect-associated outcomes (e.g., bradycardia, sedation, hypotension, rates of infection, and neurological complications). The study was registered on PROSPERO, number CRD42020188796. RESULTS: After screening of full-text relevant articles, 13 RCTs that met the inclusion criteria were retrieved for this systematic review. It was revealed that perineural Dexm provided equivalent analgesic duration to perineural Dexa. Besides, the intake of Dexm increased the incidence of rescue analgesia in limbs surgery, as well as the cumulative opioid consumption, and decreased the time required for onset of sensory and motor blockades for long-acting LA (all P < .05). Other analysis revealed insignificant difference between the 2 groups in terms of the incidence of PONV (P > .05). Additionally, 2 studies demonstrated that Dexm possesses more sedative properties than Dexa (P < .05). CONCLUSIONS: This meta-analysis indicated that the analgesic duration of Dexm and Dexa as LA adjuvants in PNB is the same. Meanwhile, the effects of perineural Dexm and Dexa on some secondary outcomes, including the incidence of rescue analgesia, cumulative opioid consumption, and time required for onset of sensory and motor blockades, are associated with the surgical site and type of LA.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Anestesia Local/métodos , Dexametasona/uso terapêutico , Dexmedetomidina/uso terapêutico , Glucocorticoides/uso terapêutico , Bloqueio Nervoso/métodos , Adjuvantes Anestésicos , Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Dexametasona/administração & dosagem , Dexmedetomidina/administração & dosagem , Glucocorticoides/administração & dosagem , Humanos , Nervos Periféricos , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Lancet ; 398(10303): 843-855, 2021 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-34388395

RESUMO

BACKGROUND: A previous efficacy trial found benefit from inhaled budesonide for COVID-19 in patients not admitted to hospital, but effectiveness in high-risk individuals is unknown. We aimed to establish whether inhaled budesonide reduces time to recovery and COVID-19-related hospital admissions or deaths among people at high risk of complications in the community. METHODS: PRINCIPLE is a multicentre, open-label, multi-arm, randomised, controlled, adaptive platform trial done remotely from a central trial site and at primary care centres in the UK. Eligible participants were aged 65 years or older or 50 years or older with comorbidities, and unwell for up to 14 days with suspected COVID-19 but not admitted to hospital. Participants were randomly assigned to usual care, usual care plus inhaled budesonide (800 µg twice daily for 14 days), or usual care plus other interventions, and followed up for 28 days. Participants were aware of group assignment. The coprimary endpoints are time to first self-reported recovery and hospital admission or death related to COVID-19, within 28 days, analysed using Bayesian models. The primary analysis population included all eligible SARS-CoV-2-positive participants randomly assigned to budesonide, usual care, and other interventions, from the start of the platform trial until the budesonide group was closed. This trial is registered at the ISRCTN registry (ISRCTN86534580) and is ongoing. FINDINGS: The trial began enrolment on April 2, 2020, with randomisation to budesonide from Nov 27, 2020, until March 31, 2021, when the prespecified time to recovery superiority criterion was met. 4700 participants were randomly assigned to budesonide (n=1073), usual care alone (n=1988), or other treatments (n=1639). The primary analysis model includes 2530 SARS-CoV-2-positive participants, with 787 in the budesonide group, 1069 in the usual care group, and 974 receiving other treatments. There was a benefit in time to first self-reported recovery of an estimated 2·94 days (95% Bayesian credible interval [BCI] 1·19 to 5·12) in the budesonide group versus the usual care group (11·8 days [95% BCI 10·0 to 14·1] vs 14·7 days [12·3 to 18·0]; hazard ratio 1·21 [95% BCI 1·08 to 1·36]), with a probability of superiority greater than 0·999, meeting the prespecified superiority threshold of 0·99. For the hospital admission or death outcome, the estimated rate was 6·8% (95% BCI 4·1 to 10·2) in the budesonide group versus 8·8% (5·5 to 12·7) in the usual care group (estimated absolute difference 2·0% [95% BCI -0·2 to 4·5]; odds ratio 0·75 [95% BCI 0·55 to 1·03]), with a probability of superiority 0·963, below the prespecified superiority threshold of 0·975. Two participants in the budesonide group and four in the usual care group had serious adverse events (hospital admissions unrelated to COVID-19). INTERPRETATION: Inhaled budesonide improves time to recovery, with a chance of also reducing hospital admissions or deaths (although our results did not meet the superiority threshold), in people with COVID-19 in the community who are at higher risk of complications. FUNDING: National Institute of Health Research and United Kingdom Research Innovation.


Assuntos
Budesonida/administração & dosagem , COVID-19/tratamento farmacológico , Glucocorticoides/administração & dosagem , Administração por Inalação , Idoso , Teorema de Bayes , COVID-19/mortalidade , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , SARS-CoV-2 , Resultado do Tratamento
5.
J Proteome Res ; 20(8): 4001-4009, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34291951

RESUMO

Glucocorticoids are the first-line treatment for sensorineural hearing loss, but little is known about the mechanism of their protective effect or the impact of route of administration. The recent development of hollow microneedles enables safe and reliable sampling of perilymph for proteomic analysis. Using these microneedles, we investigate the effect of intratympanic (IT) versus intraperitoneal (IP) dexamethasone administration on guinea pig perilymph proteome. Guinea pigs were treated with IT dexamethasone (n = 6), IP dexamethasone (n = 8), or untreated for control (n = 8) 6 h prior to aspiration. The round window membrane (RWM) was accessed via a postauricular approach, and hollow microneedles were used to perforate the RWM and aspirate 1 µL of perilymph. Perilymph samples were analyzed by liquid chromatography-mass spectrometry-based label-free quantitative proteomics. Mass spectrometry raw data files have been deposited in an international public repository (MassIVE proteomics repository at https://massive.ucsd.edu/) under data set # MSV000086887. In the 22 samples of perilymph analyzed, 632 proteins were detected, including the inner ear protein cochlin, a perilymph marker. Of these, 14 proteins were modulated by IP, and three proteins were modulated by IT dexamethasone. In both IP and IT dexamethasone groups, VGF nerve growth factor inducible was significantly upregulated compared to control. The remaining adjusted proteins modulate neurons, inflammation, or protein synthesis. Proteome analysis facilitated by the use of hollow microneedles shows that route of dexamethasone administration impacts changes seen in perilymph proteome. Compared to IT administration, the IP route was associated with greater changes in protein expression, including proteins involved in neuroprotection, inflammatory pathway, and protein synthesis. Our findings show that microneedles can mediate safe and effective intracochlear sampling and hold promise for inner ear diagnostics.


Assuntos
Dexametasona/administração & dosagem , Glucocorticoides/administração & dosagem , Perilinfa , Proteoma , Animais , Cobaias , Injeção Intratimpânica , Proteômica
6.
FASEB J ; 35(8): e21828, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34325494

RESUMO

Since prenatal glucocorticoids (GC) excess increases the risk of metabolic dysfunctions in the offspring and its effect on ß-cell recovery capacity remains unknown we investigated these aspects in offspring from mice treated with dexamethasone (DEX) in the late pregnancy. Half of the pups were treated with streptozotocin (STZ) on the sixth postnatal day (PN). Functional and molecular analyses were performed in male offspring on PN25 and PN225. Prenatal DEX treatment resulted in low birth weight. At PN25, both the STZ-treated offspring developed hyperglycemia and had lower ß-cell mass, in parallel with higher α-cell mass and glucose intolerance, with no impact of prenatal DEX on such parameters. At PN225, the ß-cell mass was partially recovered in the STZ-treated mice, but they remained glucose-intolerant, irrespective of being insulin sensitive. Prenatal exposition to DEX predisposed adult offspring to sustained hyperglycemia and perturbed islet function (lower insulin and higher glucagon response to glucose) in parallel with exacerbated glucose intolerance. ß-cell-specific knockdown of the Hnf4α in mice from the DS group resulted in exacerbated glucose intolerance. We conclude that high GC exposure during the prenatal period exacerbates the metabolic dysfunctions in adult life of mice exposed to STZ early in life, resulting in a lesser ability to recover the islets' function over time. This study alerts to the importance of proper management of exogenous GCs during pregnancy and a healthy postnatal lifestyle since the combination of adverse factors during the prenatal and postnatal period accentuates the predisposition to metabolic disorders in adult life.


Assuntos
Dexametasona/toxicidade , Glucocorticoides/toxicidade , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/fisiologia , Animais , Animais Geneticamente Modificados , Animais Recém-Nascidos , Dexametasona/administração & dosagem , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Glucocorticoides/administração & dosagem , Teste de Tolerância a Glucose , Insulina/farmacologia , Camundongos , Neoplasias Experimentais , Gravidez , Efeitos Tardios da Exposição Pré-Natal , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
8.
Cochrane Database Syst Rev ; 7: CD013876, 2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34291813

RESUMO

BACKGROUND: Olfactory dysfunction is an early and sensitive marker of COVID-19 infection. Although self-limiting in the majority of cases, when hyposmia or anosmia persists it can have a profound effect on quality of life. Little guidance exists on the treatment of post-COVID-19 olfactory dysfunction, however several strategies have been proposed from the evidence relating to the treatment of post-viral anosmia (such as medication or olfactory training). OBJECTIVES: To assess the effects (benefits and harms) of interventions that have been used, or proposed, to treat persisting olfactory dysfunction due to COVID-19 infection. A secondary objective is to keep the evidence up-to-date, using a living systematic review approach.  SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane COVID-19 Study Register; Cochrane ENT Register; CENTRAL; Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished studies. The date of the search was 16 December 2020. SELECTION CRITERIA: Randomised controlled trials including participants who had symptoms of olfactory disturbance following COVID-19 infection. Only individuals who had symptoms for at least four weeks were included in this review. Studies compared any intervention with no treatment or placebo. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Primary outcomes were the recovery of sense of smell, disease-related quality of life and serious adverse effects. Secondary outcomes were the change in sense of smell, general quality of life, prevalence of parosmia and other adverse effects (including nosebleeds/bloody discharge). We used GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS: We included one study with 18 participants, which compared the use of a 15-day course of oral steroids combined with nasal irrigation (consisting of an intranasal steroid/mucolytic/decongestant solution) with no intervention. Psychophysical testing was used to assess olfactory function at baseline, 20 and 40 days. Systemic corticosteroids plus intranasal steroid/mucolytic/decongestant compared to no intervention Recovery of sense of smell was assessed after 40 days (25 days after cessation of treatment) using the Connecticut Chemosensory Clinical Research Center (CCCRC) score. This tool has a range of 0 to 100, and a score of ≥ 90 represents normal olfactory function. The evidence is very uncertain about the effect of this intervention on recovery of the sense of smell at one to three months (5/9 participants in the intervention group scored ≥ 90 compared to 0/9 in the control group; risk ratio (RR) 11.00, 95% confidence interval (CI) 0.70 to 173.66; 1 study; 18 participants; very low-certainty evidence). Change in sense of smell was assessed using the CCCRC score at 40 days. This study reported an improvement in sense of smell in the intervention group from baseline (median improvement in CCCRC score 60, interquartile range (IQR) 40) compared to the control group (median improvement in CCCRC score 30, IQR 25) (1 study; 18 participants; very low-certainty evidence). Serious adverse events andother adverse events were not identified in any participants of this study; however, it is unclear how these outcomes were assessed and recorded (1 study; 18 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS: There is very limited evidence available on the efficacy and harms of treatments for persistent olfactory dysfunction following COVID-19 infection. However, we have identified other ongoing trials in this area. As this is a living systematic review we will update the data regularly, as new results become available. For this (first) version of the living review we identified only one study with a small sample size, which assessed systemic steroids and nasal irrigation (intranasal steroid/mucolytic/decongestant). However, the evidence regarding the benefits and harms from this intervention to treat persistent post-COVID-19 olfactory dysfunction is very uncertain.


Assuntos
COVID-19/complicações , Expectorantes/administração & dosagem , Glucocorticoides/administração & dosagem , Descongestionantes Nasais/administração & dosagem , Transtornos do Olfato/tratamento farmacológico , Administração Oral , Ambroxol/administração & dosagem , Betametasona/administração & dosagem , Viés , Humanos , Lavagem Nasal/métodos , Transtornos do Olfato/etiologia , Prednisona/administração & dosagem , Prevalência , Qualidade de Vida , Recuperação de Função Fisiológica , Olfato/efeitos dos fármacos , Fatores de Tempo
9.
EBioMedicine ; 69: 103434, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34218053

RESUMO

BACKGROUND: The symptom of heavy menstrual bleeding (HMB) diminishes quality-of-life for many mid-age women and imposes substantial societal burden. We investigated our hypothesis that HMB reflects impaired endometrial vasoconstriction due to endometrial glucocorticoid deficiency. Does reversing this deficiency, by short-term luteal-phase treatment with exogenous glucocorticoid (dexamethasone), ameliorate HMB? METHODS: In our Bayesian response-adaptive parallel-group placebo-controlled randomised trial, five pre-planned interim analyses used primary outcome data to adjust randomisation probabilities to favour doses providing most dose-response information. Participants with HMB, recruited from Lothian (Scotland) NHS clinics and via community invitations/advertisements, were aged over 18 years; reported regular 21-42 day menstrual cycles; and had measured menstrual blood loss (MBL) averaging ≥ 50 mL over two screening periods. Identically encapsulated placebo, or one of six Dexamethasone doses (0·2 mg, 0·4 mg, 0·5 mg, 0·6 mg, 0·75 mg, 0·9 mg), were taken orally twice-daily over five days in the mid-luteal phase of three menstrual cycles. Participants, investigators, and those measuring outcomes were masked to group assignment. Primary outcome, change in average MBL from screening to 'treatment', was analysed by allocated treatment, for all with data. TRIAL REGISTRATION: ClinicalTrials.gov NCT01769820; EudractCT 2012-003,405-98 FINDINGS: Recruitment lasted 29/01/2014 to 25/09/2017; 176 were screened, 107 randomised and 97 provided primary outcome data (n = 24,5,9,21,8,14,16 in the seven arms, placebo to 1·8 mg total daily active dose). In Bayesian normal dynamic linear modelling, 1·8 mg dexamethasone daily showed a 25 mL greater reduction in MBL from screening, than placebo (95% credible interval 1 to 49 mL), and probability 0·98 of benefit over placebo. Adverse events were reported by 75% (58/77) receiving dexamethasone, 58% (15/26) taking placebo. Three serious adverse events occurred, two during screening, one in a placebo participant. No woman withdrew due to adverse effects. INTERPRETATION: Our adaptive trial in HMB showed that dexamethasone 1·8 mg daily reduced menstrual blood loss. The role of dexamethasone in HMB management deserves further investigation. FUNDING: UK MRC DCS/DPFS grant MR/J003611/1.


Assuntos
Dexametasona/administração & dosagem , Glucocorticoides/administração & dosagem , Menorragia/tratamento farmacológico , Adulto , Dexametasona/uso terapêutico , Endométrio/irrigação sanguínea , Feminino , Glucocorticoides/uso terapêutico , Humanos , Menorragia/fisiopatologia , Pessoa de Meia-Idade , Vasoconstrição
10.
Pan Afr Med J ; 38: 314, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34285737

RESUMO

This manuscript concerns the case of a patient hospitalized and diagnosed with Evans syndrome. She was hospitalized with signs of thrombocytopenia induced purpura, petechiae, ecchymosis and anemia. She was successfully treated with corticoids and blood transfusions. Our purpose is to explain her clinical presentation and the exams, we used in order to make the diagnosis of Evans syndrome, which requires great suspicion. Moreover, other diseases causing hemolytic anemia and thrombocytopenia must be excluded. We used laboratory tests (blood samples, Coombs examination and virologic test). Bone marrow examination took place twice. Evans syndrome is an autoimmune disease which is characterized by the coexistence of hemolytic anemia and immune-mediated thrombocytopenia. There is no typical clinical presentation. Its etiology is unknown and its therapy is generally poor. Diagnosis of Evans syndrome is very difficult and requires the exclusion of other diseases causing anemia and thrombocytopenia.


Assuntos
Anemia Hemolítica Autoimune/diagnóstico , Trombocitopenia/diagnóstico , Idoso de 80 Anos ou mais , Anemia Hemolítica Autoimune/fisiopatologia , Anemia Hemolítica Autoimune/terapia , Transfusão de Sangue/métodos , Diagnóstico Diferencial , Feminino , Glucocorticoides/administração & dosagem , Humanos , Trombocitopenia/fisiopatologia , Trombocitopenia/terapia
11.
Pan Afr Med J ; 38: 333, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34285756

RESUMO

We reported an anaphylactic reaction following ingestion of rivaroxaban in a 48-years-old male, who was recently discharged from the hospital as a case of deep vein thrombosis. At home, the patient developed a diffuse itchy skin rash, shortness of breath, and vomiting 30 minutes after rivaroxaban ingestion. Emergency Medical Service found that the patient had severe dyspnea, low blood pressure, and decreased blood oxygen saturation. The patient was given oxygen, intramuscular epinephrine, intravenous hydrocortisone, diphenhydramine, salbutamol nebulizer, and was immediately transferred to the emergency department of Hamad General Hospital. Subcutaneous enoxaparin was initiated, while hydrocortisone and salbutamol nebulizer continued. On the next day, his vital signs had stabilized, and intravenous hydrocortisone was switched to prednisolone tablets, and salbutamol nebulizer was switched to budesonide/salmeterol inhaler, whereas enoxaparin was overlapped with warfarin. After achieving the target international normalized ratio (INR), enoxaparin was discontinued and the patient was discharged with significant clinical and laboratory improvement.


Assuntos
Anafilaxia/induzido quimicamente , Inibidores do Fator Xa/efeitos adversos , Rivaroxabana/efeitos adversos , Anafilaxia/terapia , Anticoagulantes/administração & dosagem , Broncodilatadores/administração & dosagem , Inibidores do Fator Xa/administração & dosagem , Glucocorticoides/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Rivaroxabana/administração & dosagem , Trombose Venosa/tratamento farmacológico
12.
BMJ ; 374: n1380, 2021 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-34253540

RESUMO

Synthetic glucocorticoids are widely used for their anti-inflammatory and immunosuppressive actions. A possible unwanted effect of glucocorticoid treatment is suppression of the hypothalamic-pituitary-adrenal axis, which can lead to adrenal insufficiency. Factors affecting the risk of glucocorticoid induced adrenal insufficiency (GI-AI) include the duration of glucocorticoid therapy, mode of administration, glucocorticoid dose and potency, concomitant drugs that interfere with glucocorticoid metabolism, and individual susceptibility. Patients with exogenous glucocorticoid use may develop features of Cushing's syndrome and, subsequently, glucocorticoid withdrawal syndrome when the treatment is tapered down. Symptoms of glucocorticoid withdrawal can overlap with those of the underlying disorder, as well as of GI-AI. A careful approach to the glucocorticoid taper and appropriate patient counseling are needed to assure a successful taper. Glucocorticoid therapy should not be completely stopped until recovery of adrenal function is achieved. In this review, we discuss the factors affecting the risk of GI-AI, propose a regimen for the glucocorticoid taper, and make suggestions for assessment of adrenal function recovery. We also describe current gaps in the management of patients with GI-AI and make suggestions for an approach to the glucocorticoid withdrawal syndrome, chronic management of glucocorticoid therapy, and education on GI-AI for patients and providers.


Assuntos
Insuficiência Adrenal/induzido quimicamente , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Síndrome de Abstinência a Substâncias , Doença Aguda , Insuficiência Adrenal/tratamento farmacológico , Doença Crônica , Síndrome de Cushing/induzido quimicamente , Aconselhamento Diretivo , Humanos , Sistema Hipotálamo-Hipofisário , Educação de Pacientes como Assunto , Fatores de Risco , Síndrome de Abstinência a Substâncias/tratamento farmacológico
13.
Nutrients ; 13(6)2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34205537

RESUMO

In clinical practice, differences in glucocorticoid sensitivity among healthy subjects may influence the outcome and any adverse effects of glucocorticoid therapy. Thus, a fast and accurate methodology that could enable the classification of individuals based on their tissue glucocorticoid sensitivity would be of value. We investigated the usefulness of untargeted plasma metabolomics in identifying a panel of metabolites to distinguish glucocorticoid-resistant from glucocorticoid-sensitive healthy subjects who do not carry mutations in the human glucocorticoid receptor (NR3C1) gene. Applying a published methodology designed for the study of glucocorticoid sensitivity in healthy adults, 101 healthy subjects were ranked according to their tissue glucocorticoid sensitivity based on 8:00 a.m. serum cortisol concentrations following a very low-dose dexamethasone suppression test. Ten percent of the cohort, i.e., 11 participants, on each side of the ranking, with no NR3C1 mutations or polymorphisms, were selected, respectively, as the most glucocorticoid-sensitive and most glucocorticoid-resistant of the cohort to be analyzed and compared with untargeted blood plasma metabolomics using gas chromatography-mass spectrometry (GC-MS). The acquired metabolic profiles were evaluated using multivariate statistical analysis methods. Nineteen metabolites were identified with significantly lower abundance in the most sensitive compared to the most resistant group of the cohort, including fatty acids, sugar alcohols, and serine/threonine metabolism intermediates. These results, combined with a higher glucose, sorbitol, and lactate abundance, suggest a higher Cori cycle, polyol pathway, and inter-tissue one-carbon metabolism rate and a lower fat mobilization rate at the fasting state in the most sensitive compared to the most resistant group. In fact, this was the first study correlating tissue glucocorticoid sensitivity with serine/threonine metabolism. Overall, the observed metabolic signature in this cohort implies a worse cardiometabolic profile in the most glucocorticoid-sensitive compared to the most glucocorticoid-resistant healthy subjects. These findings offer a metabolic signature that distinguishes most glucocorticoid-sensitive from most glucocorticoid-resistant healthy subjects to be further validated in larger cohorts. Moreover, they support the correlation of tissue glucocorticoid sensitivity with insulin resistance and metabolic syndrome-associated pathways, further emphasizing the need for nutritionists and doctors to consider the tissue glucocorticoid sensitivity in dietary and exercise planning, particularly when these subjects are to be treated with glucocorticoids.


Assuntos
Dexametasona/farmacologia , Dieta , Glucocorticoides/farmacologia , Estilo de Vida Saudável , Metaboloma , Hormônio Adrenocorticotrópico/sangue , Adulto , Dexametasona/administração & dosagem , Feminino , Glucocorticoides/administração & dosagem , Humanos , Hidrocortisona/sangue , Masculino , Receptores de Glucocorticoides/genética , Adulto Jovem
14.
Ann Ital Chir ; 92: 234-241, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34193647

RESUMO

BACKGROUND: Idiopathic granulomatous mastitis that has not had a clear consensus about its treatment since the day it was identified as a rare, benign inflammatory breast disease that mimics malignancy due to its appearance features. AIMS: In our research, we intended to compare the efficiency of intralesional and systemic steroids administration in the treatment of idiopathic granulomatous mastitis. STUDY DESIGN: Prospective randomized controlled study. METHODS: A total of 36 female patients who had been histopathologically diagnosed with idiopathic granulomatous mastitis and whose other factors had been microbiologically excluded were included in the study. The patients were randomized into two sub-groups that would be treated with systemic and intralesional steroids. All patients were evaluated through physical examination one week after the completion of the treatment. Subsequently, the follow-up of the patients was performed thorough physical examination and ultrasonography and/or magnetic resonance imaging at the 1st, 3rd, and 6th months. RESULTS: All patients adapted to treatment. Complete clinical regression occurred in 32 patients, while 30 of 36 patients responded to treatment both radiologically and clinically. A total of 4 patients had minor side effects. It was determined that there was no statistically significant difference between local and systemic steroid groups in terms of complete clinical regression, responded to treatment side effects, and recurrence rates. CONCLUSION: Intralesional steroid administration was also considered just as a successful treatment method as the systemic steroid administration. KEY WORDS: Idiopathic granulomatous mastitis, Intralesional steroid, Systemic steroid.


Assuntos
Glucocorticoides/administração & dosagem , Mastite Granulomatosa , Metilprednisolona/administração & dosagem , Triancinolona/administração & dosagem , Administração Oral , Adulto , Antibacterianos/administração & dosagem , Feminino , Mastite Granulomatosa/diagnóstico , Mastite Granulomatosa/diagnóstico por imagem , Mastite Granulomatosa/tratamento farmacológico , Humanos , Injeções Intralesionais , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Ultrassonografia Mamária
15.
Medicine (Baltimore) ; 100(24): e26315, 2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34128872

RESUMO

RATIONALE: Aseptic meningoencephalitis is a rare central nervous system complication of relapsing polychondritis (RP). PATIENT: We report a 61-year-old Japanese male patient with spiking fever and impaired consciousness. Neurological examination revealed meningealirritation, and cerebrospinal fluid (CSF) examination showed lymphocytic pleocytosis with elevated protein (199 mg/dL) and interleukin-6 (3810 pg/mL). Serological analysis showed high levels of anti-type II collagen antibodies, and the result of auricular biopsy was consistent with the diagnosis of RP showing cartilage degeneration surrounded by inflammatory cell infiltrations. DIAGNOSIS: A clinical diagnosis of RP was made according to the diagnostic criteria established by MacAdams et al. INTERVENTION: Steroid pulse therapy (methylprednisolone 1000 mg, consecutive 3 days) followed by oral prednisolone (60 mg/day) resolved the patient's high fever and disturbance of consciousness. OUTCOMES: The patient rapidly improved after steroid treatments and has a normal quality of life under the maintenance dose of steroid plus methotrexate (4 mg/week). LESSONS: RP-associated meningoencephalitis is a rare complication with significant morbidity and mortality. It should be considered and differentiated in patients with RP with unexplained spiking fever and impaired consciousness. In addition, the assessment of cerebrospinal fluid interleukin-6 levels may be useful to investigate the disease activity of RP-related meningoencephalitis. Further prospective studies are required to confirm this result.


Assuntos
Meningoencefalite/etiologia , Policondrite Recidivante/complicações , Glucocorticoides/administração & dosagem , Humanos , Interleucina-6/líquido cefalorraquidiano , Leucocitose/líquido cefalorraquidiano , Leucocitose/complicações , Masculino , Meningoencefalite/líquido cefalorraquidiano , Meningoencefalite/terapia , Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Policondrite Recidivante/líquido cefalorraquidiano , Policondrite Recidivante/terapia
16.
Medicine (Baltimore) ; 100(25): e26416, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160429

RESUMO

BACKGROUND: Cough variant asthma (CVA) is classified as a distinct form of asthma. As the primary or only symptom, cough is the leading cause for the most prevalent chronic cough among kids. The American College of Clinical Pharmacy, British Thoracic Society, and Chinese guidelines established for diagnosing and treating chronic cough in kids recommend inhaled corticosteroids, combined with leukotriene receptor antagonists when necessary. METHODS: We will conduct a comprehensive search in major databases using keywords to find studies related to the analysis of montelukast sodium and budesonide for treating CVA in kids. Two reviewers will independently assess the quality of the selected research articles and perform data extraction. Next, we will use the RevMan software (version: 5.3) to conduct the statistical analysis of the present study. RESULTS: This study will assess the efficacy and safeness of using montelukast sodium and budesonide to treat kids with CVA by pooling the results of individual studies. CONCLUSION: Our findings will provide vigorous evidence to judge whether montelukast sodium and budesonide therapy is an efficient form of therapy for CVA patients. ETHICS AND DISSEMINATION: Ethics approval is not needed for the present meta-analysis. OSF REGISTRATION NUMBER: May 17, 2021.osf.io/cuvjz (https://osf.io/cuvjz/).


Assuntos
Asma/tratamento farmacológico , Tosse/tratamento farmacológico , Glucocorticoides/administração & dosagem , Antagonistas de Leucotrienos/administração & dosagem , Acetatos/administração & dosagem , Acetatos/efeitos adversos , Administração por Inalação , Asma/diagnóstico , Asma/imunologia , Budesonida/administração & dosagem , Budesonida/efeitos adversos , Criança , Doença Crônica/tratamento farmacológico , Tosse/diagnóstico , Tosse/imunologia , Ciclopropanos/administração & dosagem , Ciclopropanos/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Glucocorticoides/efeitos adversos , Humanos , Antagonistas de Leucotrienos/efeitos adversos , Metanálise como Assunto , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Sulfetos/administração & dosagem , Sulfetos/efeitos adversos , Revisões Sistemáticas como Assunto , Resultado do Tratamento
17.
Medicine (Baltimore) ; 100(25): e26469, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160454

RESUMO

RATIONALE: With the absence of ophthalmopathy, thyroid dermopathy especially lesions at atypical locations is a very rare presentation. We herein report an original case of bilateral breast myxedema caused by Grave's disease. PATIENT CONCERNS: A 21-year-old unmarried woman presented with a 4-month history of Grave's disease and a 1-month history of progressive bilateral breast enlargement. She had symmetrical bilateral breast enlargement with redness and nonpitting thickening of the skin, diffusely enlarged thyroid glands, and no exophthalmos. DIAGNOSIS: Ultrasonography, magnetic resonance imaging scan, and skin biopsy confirmed the diagnosis of bilateral breast myxedema. INTERVENTIONS: The patient was treated with multipoint subcutaneous injections of triamcinolone acetonide in each breast every month. OUTCOMES: The bilateral breast returned approximately to its normal size after therapy for 6 months. CONCLUSIONS: Our case illustrates that multipoint subcutaneous injection of glucocorticoids is beneficial for bilateral breast myxedema.


Assuntos
Doenças Mamárias/tratamento farmacológico , Glucocorticoides/administração & dosagem , Doença de Graves/complicações , Mixedema/tratamento farmacológico , Biópsia , Mama/diagnóstico por imagem , Mama/patologia , Doenças Mamárias/diagnóstico , Doenças Mamárias/etiologia , Doenças Mamárias/patologia , Feminino , Humanos , Injeções Subcutâneas , Imageamento por Ressonância Magnética , Mixedema/diagnóstico , Mixedema/etiologia , Mixedema/patologia , Pele/diagnóstico por imagem , Pele/patologia , Resultado do Tratamento , Triancinolona Acetonida/administração & dosagem , Ultrassonografia Mamária , Adulto Jovem
18.
Medicine (Baltimore) ; 100(25): e26508, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160471

RESUMO

ABSTRACT: This study was conducted to examine whether Korean veterans from the US-Vietnam War who had a diagnosis of type II diabetes mellitus (T2DM) as well as past history of exposure to agent orange (AO) are vulnerable to hyperglycemia when receiving intra-articular corticosteroid injection (IACI) for pain relief.The current study included a total of 49 patients (n = 49) who received an injection of triamcinolone 20 or 40 mg to the shoulder under sonographic guidance or did that of dexamethasone 10 mg or triamcinolone 40 mg combined with dexamethasone 20 mg to the spine under fluoroscopic guidance. Their 7-day fasting blood glucose (FBG) levels were measured and then averaged, serving as baseline levels. This is followed by measurement of FBG levels for 14 days of IACI. Respective measurements were compared with baseline levels. The patients were also evaluated for whether there are increases in FBG levels depending on insulin therapy as well as HbA1c ≥ 7% or HbA1c < 7%.Overall, there were significant increases in FBG levels by 64.7 ±â€Š42.5 mg/dL at 1 day of IACI from baseline (P < .05). HbA1c ≥ 7% and HbA1c < 7% showed increases in FBG levels by 106.1 ±â€Š49.0 mg/dL and 46.5 ±â€Š3.8 mg/dL, respectively, at 1 day of IACI from baseline (P < .05). In the presence and absence of insulin therapy, there were significant increases in them by 122.6 ±â€Š48.7 mg/dL and 48.0 ±â€Š20.4 mg/dL, respectively, at 1 day of IACI from baseline (P < .05). But there were decreases in them to baseline levels at 2 days of IACI.Clinicians should consider the possibility of hyperglycemia when using corticosteroids for relief of musculoskeletal pain in Korean veterans from the US-Vietnam War who had a history of exposure to AO.


Assuntos
Agente Laranja/efeitos adversos , Artralgia/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Glucocorticoides/efeitos adversos , Hiperglicemia/epidemiologia , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Idoso , Glicemia/análise , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Seguimentos , Glucocorticoides/administração & dosagem , Humanos , Hiperglicemia/sangue , Hiperglicemia/diagnóstico , Hiperglicemia/etiologia , Injeções Intra-Articulares , Insulina/administração & dosagem , Masculino , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Transtornos de Estresse Pós-Traumáticos/psicologia , Triancinolona/administração & dosagem , Triancinolona/efeitos adversos , Veteranos/psicologia , Veteranos/estatística & dados numéricos , Guerra do Vietnã , Exposição à Guerra/efeitos adversos
19.
Ann Neurol ; 90(2): 315-318, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34114269

RESUMO

Although SARS-CoV-2 vaccines are very safe, we report 4 cases of the bifacial weakness with paresthesias variant of Guillain-Barré syndrome (GBS) occurring within 3 weeks of vaccination with the Oxford-AstraZeneca SARS-CoV-2 vaccine. This rare neurological syndrome has previously been reported in association with SARS-CoV-2 infection itself. Our cases were given either intravenous immunoglobulin, oral steroids, or no treatment. We suggest vigilance for cases of bifacial weakness with paresthesias variant GBS following vaccination for SARS-CoV-2 and that postvaccination surveillance programs ensure robust data capture of this outcome, to assess for causality. ANN NEUROL 2021;90:315-318.


Assuntos
Vacinas contra COVID-19/efeitos adversos , Síndrome de Guillain-Barré/induzido quimicamente , Síndrome de Guillain-Barré/diagnóstico , Vacinas contra COVID-19/administração & dosagem , Glucocorticoides/administração & dosagem , Síndrome de Guillain-Barré/tratamento farmacológico , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Masculino , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Vacinação/efeitos adversos , Adulto Jovem
20.
Ann Rheum Dis ; 80(9): 1175-1182, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34162597

RESUMO

BACKGROUND: Quality of care is receiving increased attention in systemic lupus erythematosus (SLE). We developed quality indicators (QIs) for SLE based on the 2019 update of European League Against Rheumatism recommendations. METHODS: A total of 44 candidate QIs corresponding to diagnosis, monitoring and treatment, were independently rated for validity and feasibility by 12 experts and analysed by a modified Research and Development Corporation/University of California Los Angeles model. Adherence to the final set of QIs and correlation with disease outcomes (flares, hospitalisations and organ damage) was tested in a cohort of 220 SLE patients with a median monitoring of 2 years (IQR 2-4). RESULTS: The panel selected a total of 18 QIs as valid and feasible. On average, SLE patients received 54% (95% CI 52.3% to 56.2%) of recommended care, with adherence ranging from 44.7% (95% CI 40.8% to 48.6%) for diagnosis-related QIs to 84.3% (95% CI 80.6% to 87.5%) for treatment-related QIs. Sustained remission or low disease activity were achieved in 26.8% (95% CI 21.1% to 33.2%). Tapering of prednisone dose to less than 7.5 mg/day was achieved in 93.6% (95% CI 88.2% to 97.0%) while 73.5% (95% CI 66.6% to 79.6%) received the recommended hydroxychloroquine dose. Higher adherence to monitoring-related QIs was associated with reduced risk for a composite adverse outcome (flare, hospitalisation or damage accrual) during the last year of observation (OR 0.97 per 1% adherence rate, 95% CI 0.96 to 0.99). CONCLUSION: We developed QIs for assessing and improving the care of SLE patients. Initial real-life data suggest face validity, but a variable degree of adherence and a need for further improvement.


Assuntos
Lúpus Eritematoso Sistêmico/terapia , Indicadores de Qualidade em Assistência à Saúde , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Antirreumáticos/administração & dosagem , Aspirina/uso terapêutico , Redução da Medicação , Europa (Continente) , Feminino , Glucocorticoides/administração & dosagem , Fidelidade a Diretrizes/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Humanos , Hidroxicloroquina/administração & dosagem , Imunossupressores/uso terapêutico , Rim/patologia , Lúpus Eritematoso Sistêmico/diagnóstico , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/terapia , Masculino , Programas de Rastreamento , Osteoporose/diagnóstico , Inibidores da Agregação Plaquetária/uso terapêutico , Guias de Prática Clínica como Assunto , Pré-Eclâmpsia/prevenção & controle , Prednisona/administração & dosagem , Gravidez , Indução de Remissão , Reprodutibilidade dos Testes , Medição de Risco , Sociedades Médicas , Exacerbação dos Sintomas
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