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OBJECTIVE: Seizure clusters require prompt medical treatment to minimize possible progression to status epilepticus, increased health care use, and disruptions to daily life. Isolated seizures may exhibit cyclical patterns, including circadian and longer rhythms. However, little is known about the cyclical patterns in seizure clusters. This post hoc analysis of data from a long-term, phase 3, open-label, repeat-dose safety study of diazepam nasal spray modeled the periodicity of treated seizure clusters. METHODS: Mixed-effects cosinor analysis evaluated circadian rhythmicity, and single component cosinors using 12 and 24 h were used to calculate cosinor parameters (e.g., midline statistic of rhythm, wave ampitude, and acrophase [peak]). Analysis was completed for the full cohort and a consistent cohort of participants with two or more seizure clusters in each of four, 3-month periods. The influence of epilepsy type on cosinor parameters was also analyzed. RESULTS: Seizure-cluster events plotted across 24 h showed a bimodal distribution with acrophases (peaks) at ~06:30 and ~18:30. A 12-h plot showed a single peak at ~06:30. Cosinor analyses of the full and consistent cohort aligned, with acrophases for both models predicting peak seizure activity at ~23:30 on a 24-h scale and ~07:30 on a 12-h scale. The consistent cohort was associated with increases in baseline and peak seizure-cluster activity. Analysis by epilepsy type identified distinct trends. Seizure clusters in the focal epilepsy group peaked in the evening (acrophase 19:19), whereas events in the generalized epilepsy group peaked in the morning (acrophase 04:46). Together they compose the bimodal clustering observed over 24 h. SIGNIFICANCE: This analysis of seizure clusters treated with diazepam nasal spray demonstrated that seizure clusters occur cyclically in 12- and 24-h time frames similar to that reported with isolated seizures. Further elucidation of these patterns may provide important information for patient care, ranging from improved patient-centered outcomes to seizure-cluster prediction.
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Epilepsia Generalizada , Epilepsia , Humanos , Anticonvulsivantes/efeitos adversos , Ritmo Circadiano , Diazepam/efeitos adversos , Epilepsia/tratamento farmacológico , Epilepsia Generalizada/tratamento farmacológico , Sprays Nasais , Convulsões/tratamento farmacológicoRESUMO
OBJECTIVES: Most patients with pancreatic cancer who have undergone surgical resection eventually develop disease recurrence. |This study aimed to investigate whether there is evidence to support routine surveillance after pancreatic cancer surgery, with a secondary aim of analyzing the implementation of surveillance strategies in the Nordic countries. MATERIALS AND METHODS: A scoping review was conducted to identify clinical practice guidelines globally and research studies relating to surveillance after pancreatic cancer resection. This was followed by a survey among 20 pancreatic units from four Nordic countries to assess their current practice of follow-up for operated patients. RESULTS: Altogether 16 clinical practice guidelines and 17 research studies were included. The guidelines provided inconsistent recommendations regarding postoperative surveillance of pancreatic cancer. The clinical research data were mainly based on retrospective cohort studies with low level of evidence and lead-time bias was not addressed. Active surveillance was recommended in Sweden and Denmark, but not in Norway beyond the post-operative/adjuvant period. Finland had no national recommendations for surveillance. The Nordic survey revealed a wide variation in reported practice among the different units. About 75% (15 of 20 units) performed routine postoperative surveillance. Routine CA 19-9 testing was used by 80% and routine CT by 67% as part of surveillance. About 73% of centers continued follow-up until 5 years postoperatively. CONCLUSION: Evidence for routine long-term (i.e. 5 years) surveillance after pancreatic cancer surgery remains limited. Most pancreatic units in the Nordic countries conduct regular follow-up, but protocols vary.
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Neoplasias Pancreáticas , Guias de Prática Clínica como Assunto , Humanos , Neoplasias Pancreáticas/cirurgia , Países Escandinavos e Nórdicos , Recidiva Local de Neoplasia , Padrões de Prática Médica/estatística & dados numéricos , Padrões de Prática Médica/normas , Inquéritos e Questionários , Pancreatectomia , Vigilância da PopulaçãoRESUMO
BACKGROUND: Early neurological deterioration (END) occurs in many patients with acute ischemic stroke due to a variety of causes. Although pharmacologically induced hypertension (PIH) and anticoagulants have been investigated in several clinical trials for the treatment of END, the efficacy and safety of these treatments remain unclear. Here, we investigated whether PIH or anticoagulation is better as a rescue therapy for the progression of END in patients with lacunar stroke. METHODS: This study included patients with lacunar stroke who received rescue therapy with END within 3 days of symptom onset between April 2014 and August 2021. In the PIH group, phenylephrine was administered intravenously for 24 h and slowly tapered when symptoms improved or after 5 days of PIH. In the anticoagulation group, argatroban was administered continuously intravenously for 2 days and twice daily for next 5 days. We compared END recovery, defined as improvement in NIHSS from baseline, excellent outcomes (0 or 1 mRS at 3 months), and safety profile. RESULTS: Among the 4818 patients with the lacunar stroke, END occurred in 147 patients. Seventy-nine patients with END received PIH (46.9%) and 68 patients (46.3%) received anticoagulation therapy. There was no significant difference in age (P = 0.82) and sex (P = 0.87) between the two groups. Compared to the anticoagulation group, the PIH group had a higher incidence of END recovery (77.2% vs. 51.5%, P < 0.01) and excellent outcomes (34.2% vs. 16.2%, P = 0.04). PIH was associated with END (HR 2.49; 95% CI 1.06-5.81, P = 0.04). PIH remained associated with END recovery (adjusted HR 3.91; 95% CI 1.19-12.90, P = 0.02). Safety outcomes, like hemorrhagic conversion and mortality, were not significantly different between the two groups. CONCLUSIONS: As a rescue therapy for the progression of END in lacunar stroke patients, PIH with phenylephrine was more effective with similar safety compared to anticoagulation with argatroban.
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Anticoagulantes , Acidente Vascular Cerebral Lacunar , Humanos , Masculino , Feminino , Acidente Vascular Cerebral Lacunar/tratamento farmacológico , Idoso , Pessoa de Meia-Idade , Anticoagulantes/uso terapêutico , Anticoagulantes/administração & dosagem , Hipertensão/tratamento farmacológico , Hipertensão/complicações , Idoso de 80 Anos ou mais , Sulfonamidas/uso terapêutico , Sulfonamidas/administração & dosagem , Arginina/análogos & derivados , Arginina/uso terapêutico , Arginina/administração & dosagem , Resultado do Tratamento , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/administração & dosagem , Estudos Retrospectivos , Progressão da Doença , Ácidos PipecólicosRESUMO
PURPOSE OF REVIEW: This review aims to assess the therapeutic strategies available for relapsed/refractory patients with immunoglobulin light chain (AL) amyloidosis who received upfront daratumumab-based regimens. RECENT FINDINGS: The treatment landscape of AL amyloidosis has changed radically thanks to the introduction in the upfront setting of daratumumab in combination with bortezomib, cyclophosphamide and dexamethasone (DaraCyBorD) which improved patients' outcomes increasing the rate of hematologic and organ responses. However, many patients eventually relapse or are refractory to daratumumab and the best salvage therapy is not well defined yet. In this contest, we reviewed the available therapeutic options after daratumumab failure, and we look towards the current advances in Bcl-2 inhibitors, novel immunotherapeutic agents as chimeric antigen receptor (CAR-T) therapy and bispecific antibodies (bsAbs). Relapsed/refractory AL amyloidosis represent an unmet clinical need and novel targeted drugs require urgent prospective assessment.
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BACKGROUND: Benzodiazepines are used in first-line rescue therapy as immediate-use seizure medication for the treatment of seizure clusters and prolonged seizures. Their use varies across clinical practices and conditions, and they can be used promptly when indicated. Clinical studies have demonstrated seizure termination within 2 min when diazepam nasal spray is used to treat seizure clusters within 5 min, but the response when treating longer duration seizures in a cluster remains to be characterized. OBJECTIVE: To describe and assess timing and dosing of diazepam nasal spray in the subset of prolonged seizures within seizure clusters in a larger dataset of all treated seizure clusters collected during a long-term safety study of diazepam nasal spray. METHODS: Using timing data recorded in seizure diaries, this post hoc analysis and associated sensitivity analyses focused on prolonged seizures treated 5 to 15 min after the seizure start. Measures included time to treatment administration and time to seizure termination. Second-dose data were used as a proxy for effectiveness. RESULTS: In this group of seizure clusters treated 5 to 15 min after seizure start, median time drug administration was 6 min after seizure start, median time from drug administration to seizure termination was 7 min, and median overall seizure duration was 15 min. Sensitivity analyses by age, epilepsy type, and high seizure frequency confirmed this pattern. Use of a second dose occurred in 9.3 % of episodes, with the majority of second doses administered ≤ 4 h after the first dose. Safety results from the overall study showed 82.2 % of patients had ≥ 1 treatment-emergent adverse event (TEAE) irrespective of relationship to treatment, during a mean participation of â¼ 1.5 years. In addition, 30.7 % patients had a serious TEAE, and 18.4 % had TEAEs deemed at least possibly related to the study drug, none of which were serious. No events of cardiorespiratory depression were reported. CONCLUSIONS: Although immediate use of diazepam nasal spray (within 5 min) resulted in quicker seizure termination, a treatment delay of 5 to 15 min still produced rapid termination of the seizure cluster with high first-dose effectiveness and an overall acceptable safety profile. These findings suggest that diazepam nasal spray maintains effectiveness in prolonged seizures within a cluster with delayed treatment.
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BACKGROUND: Inflammatory bowel disease is a chronic, relapsing, and remitting inflammatory disorder that despite advances in medical therapy often requires hospitalization for treatment of acute flares with intravenous corticosteroids. Many patients will not respond to corticosteroids and require infliximab or cyclosporine as rescue therapy. If medical therapy fails, definitive surgical management is required. Recently, Janus Kinase inhibitors, including upadacitinib, have been proposed as an alternative rescue therapy. AIMS: We hypothesized that upadacitinib may be effective in treating acute severe colitis. METHODS: A retrospective review of 12 inflammatory bowel disease patients admitted for acute severe colitis who received upadacitinib induction therapy was performed. The rates of surgery, repeat or prolonged steroid use, and re-admission within 90 days of index hospitalization were measured. The need for re-induction with upadacitinib, change in medical therapy, rates of clinical remission, change in 6-point partial Mayo score, and laboratory markers of inflammation were measured as secondary outcomes. RESULTS: Five patients met the primary composite endpoint including four patients requiring surgery and one additional patient being unable to withdraw steroids within 90 days of hospital discharge. One patient required re-induction with upadacitinib within 90 days and no patients required change in medical therapy within 90 days. Most patients who did not undergo surgery were in clinical remission within 90 days and showed clinical improvement with decreased 6-point partial Mayo scores. CONCLUSION: Upadacitinib may be effective salvage therapy for acute severe colitis, but larger controlled trials are required to validate these results.
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Colite Ulcerativa , Colite , Compostos Heterocíclicos com 3 Anéis , Doenças Inflamatórias Intestinais , Humanos , Colite Ulcerativa/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Colite/tratamento farmacológico , Corticosteroides/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Resultado do TratamentoRESUMO
BACKGROUND: We compared the efficacy and safety of rifabutin-containing triple therapy with bismuth quadruple therapy for rescue treatment of Helicobacter pylori. METHODS: This was a noninferiority study trial of H. pylori treatment for subjects who had failed at least 2 prior treatments. Subjects were randomly assigned to receive rifabutin triple therapy with 14-day esomeprazole (20 mg), amoxicillin (1.0 g), and rifabutin (150 mg) twice a day; or bismuth quadruple therapy with esomeprazole (20 mg) and bismuth (220 mg) twice a day, plus metronidazole (400 mg) and tetracycline (500 mg) 4 times a day. Antimicrobial susceptibility was assessed by agar dilution and E-test. RESULTS: From May 2021 to October 2022, a total of 364 subjects were randomized. The eradication rates by intention-to-treat, per-protocol, and modified intention-to-treat were 89.0% (162/182; 95% confidence interval [CI], 83.6%-92.8%), 94.0% (157/167; 95% CI, 89.3%-96.7%), and 93.6% (162/173; 95% CI, 89.0%-96.4%) for rifabutin triple group. For bismuth quadruple group, they were 89.6% (163/182; 95% CI, 84.3%-93.2%), 95.3% (143/150; 95% CI, 90.7%-97.7%), and 93.7% (163/174; 95% CI, 89.0%-96.4%). CONCLUSIONS: The rifabutin triple therapy is an alternative to classical bismuth quadruple therapy for the rescue treatment of H. pylori with fewer side effects and higher compliance. CLINICAL TRIALS REGISTRATION: NCT04879992.
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Infecções por Helicobacter , Helicobacter pylori , Humanos , Bismuto/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Esomeprazol/uso terapêutico , Rifabutina/uso terapêutico , Quimioterapia Combinada , Antibacterianos/uso terapêutico , Amoxicilina/uso terapêutico , Metronidazol/uso terapêutico , Resultado do Tratamento , Inibidores da Bomba de Prótons/uso terapêuticoRESUMO
BACKGROUND: Failure of Helicobacter pylori (H. pylori) eradication is principally caused by antimicrobial resistance. Nowadays, multidrug resistance could be a major determinant of eradication failure. To assess minimal inhibitory concentration (MIC), antimicrobial resistance rates and trends in H. pylori isolated from patients with upper gastrointestinal disease with long-term period. MATERIALS AND METHODS: Patients who had H. pylori colonies isolated from culture were consecutively enrolled during the period of 2003-2022. From each patient, one to ten isolates were collected from culture of mucosal biopsy. MIC test was performed for amoxicillin, clarithromycin, metronidazole, tetracycline, levofloxacin, and moxifloxacin using agar dilution method. Trends in MIC distribution, prevalence of resistances with single and multiple were investigated which were suspected to be related to the failure of empirical H. pylori eradication treatment. RESULTS: From 2003 to 2022, a total of 873 patients were enrolled and 2735 H. pylori isolates were successfully collected. Increase in the primary resistance rate was found in clarithromycin (16.1%-31.0%, p = .022), metronidazole (30.6%-38.1%, p < 0.001), and both of levofloxacin and moxifloxacin (7.3%-35.7%, p < 0.001). The prevalence of multidrug resistance to both clarithromycin and metronidazole (9.2%-37.9%, p < 0.001), clarithromycin and fluoroquinolone (2.8%-41.7%, p < 0.001), and clarithromycin, metronidazole, and fluoroquinolone (1.4%-28.2%, p < 0.001) was found to significantly increase. CONCLUSIONS: The prevalence of multiple resistance against H. pylori in Korea is ongoing. Its trend should be considered when establishing an empirical treatment strategy (ClinicalTrials. gov: NCT05247112).
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Infecções por Helicobacter , Helicobacter pylori , Humanos , Amoxicilina/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Claritromicina/farmacologia , Claritromicina/uso terapêutico , Farmacorresistência Bacteriana , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , Levofloxacino/farmacologia , Levofloxacino/uso terapêutico , Metronidazol/uso terapêutico , Testes de Sensibilidade Microbiana , Moxifloxacina , Prevalência , República da Coreia/epidemiologia , Centros de Atenção TerciáriaRESUMO
BACKGROUND AND AIMS: The early outcomes of ulcerative colitis (UC) after rescue therapy with cyclosporine A (CyA) are well known. Published data on the safety of this treatment in perioperative use and data on the long-term prognosis are scarce and are investigated here. METHODS: All UC patients treated with CyA in Tampere University Hospital between 2009 and 2018 were reviewed from patient records. RESULTS: A total of 182 patients were included with the median follow-up of 3.8 (range 0-13) years. Of all patients, 139 (76%) responded to CyA. A quarter of the responders achieved long-term remission and used thiopurines as maintenance therapy at the end of follow-up. Altogether 83 (46%) needed further enhancement of treatment with corticosteroids (Cs) and 57 (31%) with biologicals or small molecules. Of the nonresponders 27 (55%) were treated surgically within admission to index flare. Infliximab was used as a third-line rescue therapy for 16 patients of whom four benefitted. The overall colectomy rate in this series was 45%. When compared to Cs alone CyA did not increase the risk for severe postoperative complications in patients treated for severe treatment-refractory UC. CONCLUSION: In conclusion, despite the good initial response to CyA, a large proportion of patients relapsed during long-term follow-up and the colectomy rates remain high. Other therapy attempts after failure of CyA merely postpone surgery in many. We therefore recommend informing patients about the possibility of surgery prior to the initiation of rescue therapy.
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Colite Ulcerativa , Humanos , Colite Ulcerativa/induzido quimicamente , Imunossupressores/uso terapêutico , Ciclosporina/uso terapêutico , Ciclosporina/efeitos adversos , Infliximab/uso terapêutico , Corticosteroides , Resultado do Tratamento , Colectomia/efeitos adversos , Estudos RetrospectivosRESUMO
BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) has been proposed as a rescue therapy for patients with refractory cardiac arrest. This study aimed to evaluate the association between ECPR and clinical outcomes among patients with out-of-hospital cardiac arrest (OHCA) using risk-set matching with a time-dependent propensity score. METHODS: This was a secondary analysis of the JAAM-OHCA registry data, a nationwide multicenter prospective study of patients with OHCA, from June 2014 and December 2019, that included adults (≥ 18 years) with OHCA. Initial cardiac rhythm was classified as shockable and non-shockable. Patients who received ECPR were sequentially matched with the control, within the same time (minutes) based on time-dependent propensity scores calculated from potential confounders. The odds ratios with 95% confidence intervals (CI) for 30-day survival and 30-day favorable neurological outcomes were estimated for ECPR cases using a conditional logistic model. RESULTS: Of 57,754 patients in the JAAM-OHCA registry, we selected 1826 patients with an initial shockable rhythm (treated with ECPR, n = 913 and control, n = 913) and a cohort of 740 patients with an initial non-shockable rhythm (treated with ECPR, n = 370 and control, n = 370). In these matched cohorts, the odds ratio for 30-day survival in the ECPR group was 1.76 [95%CI 1.38-2.25] for shockable rhythm and 5.37 [95%CI 2.53-11.43] for non-shockable rhythm, compared to controls. For favorable neurological outcomes, the odds ratio in the ECPR group was 1.11 [95%CI 0.82-1.49] for shockable rhythm and 4.25 [95%CI 1.43-12.63] for non-shockable rhythm, compared to controls. CONCLUSION: ECPR was associated with increased 30-day survival in patients with OHCA with initial shockable and even non-shockable rhythms. Further research is warranted to investigate the reproducibility of the results and who is the best candidate for ECPR.
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Reanimação Cardiopulmonar , Parada Cardíaca Extra-Hospitalar , Adulto , Humanos , Parada Cardíaca Extra-Hospitalar/terapia , Pontuação de Propensão , Estudos Prospectivos , Japão/epidemiologia , Reprodutibilidade dos Testes , Reanimação Cardiopulmonar/métodos , Hospitais , Sistema de Registros , Estudos RetrospectivosRESUMO
Seizure emergencies and potential emergencies, ranging from seizure clusters to prolonged seizure and status epilepticus, may affect adults with epilepsy despite stable antiseizure therapy. Seizure action plans (SAPs) are designed for patients and their caregivers/care partners to provide guidance on the individualized treatment plan, including response to potential seizure emergencies and appropriate use of rescue therapy. The use of pediatric SAPs is common (typically required by schools), however, most adults with epilepsy do not have a plan. Patient-centered action plans are integral to care for other chronic conditions and may offer insights applicable to the care of adults with epilepsy. This review analyzes the potential benefits of action plans for medical conditions by exploring their utility in conditions such as asthma, diabetes, chronic obstructive pulmonary disease, heart disease, and opioid overdose. Evidence across these conditions substantiates the value of action plans for patients, and the benefits of adult SAPs in epilepsy are emerging. Because wide implementation of SAPs has faced barriers, other conditions may provide insights that are relevant to implementing SAPs in epilepsy. Based on these analyses, we propose concrete steps to improve the use of SAPs among adults. A recent consensus statement promoting the use of formal SAPs in epilepsy and advances in rescue therapy delivery methods provides support to engage patients around the value of SAPs. The precedent for use of SAPs for pediatric epilepsy patients serves as the foundation to support increased usage in adults. Seizure action plans in the context of improved clinical outcomes are expected to reduce healthcare utilization, improve patient quality of life, and optimize epilepsy management.
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Epilepsia , Doença Pulmonar Obstrutiva Crônica , Estado Epiléptico , Humanos , Adulto , Criança , Emergências , Qualidade de Vida , Epilepsia/tratamento farmacológico , Convulsões/terapiaRESUMO
INTRODUCTION: Myasthenia gravis is a long-lasting autoimmune neuromuscular disease caused by antibodies attacking the neuromuscular junction, which can result in muscle weakness, fatigue, and respiratory failure in severe cases. Myasthenic crisis is a life-threatening event that requires hospitalization and treatments with intravenous immunoglobulin or plasma exchange. We reported the case of an AChR-Ab-positive myasthenia gravis patient with refractory myasthenic crisis, in which starting eculizumab as rescue therapy led to a complete resolution of the acute neuromuscular condition. CASE PRESENTATION: A 74-year-old man diagnosed with myasthenia gravis. ACh-receptor antibodies positivity comes to our observation for a recrudescence of symptoms, unresponsive to conventional rescue therapies. Due to the clinical worsening over the following weeks, the patient was admitted to intensive care unit, where he underwent therapy with eculizumab. About 5 days after the treatment, there was a significant and complete recovery of clinical condition with weaning-off from invasive ventilation and discharge to outpatient regimen, with reduction of steroid intake and biweekly maintenance with eculizumab. DISCUSSION: Eculizumab, a humanized monoclonal antibody that inhibits complement activation, is now approved as treatment for refractory generalized myasthenia gravis with anti-AChR antibodies. The use of eculizumab in myasthenic crisis is still investigational, but this case report suggests that it may be a promising treatment option for patients with severe clinical condition. Ongoing clinical trials will be needed to further evaluate the safety and efficacy of eculizumab in myasthenic crisis.
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Anticorpos Monoclonais Humanizados , Inativadores do Complemento , Miastenia Gravis , Receptores Colinérgicos , Humanos , Masculino , Idoso , Miastenia Gravis/imunologia , Miastenia Gravis/terapia , Anticorpos Monoclonais Humanizados/uso terapêutico , Inativadores do Complemento/uso terapêutico , Receptores Colinérgicos/imunologia , Autoanticorpos/sangueRESUMO
BACKGROUND: Treatment of chronic hepatitis C virus (HCV) infection with direct-acting antivirals achieves a sustained virologic response rate higher than 95%. However, virologic failure remains a clinical challenge, and data on retreatment are limited, especially in special populations such as liver transplant (LT) recipients. OBJECTIVES: This study evaluated the sofosbuvir plus glecaprevir-pibrentasvir (GLE/PIB) regimen in LT recipients who had failed to a nonstructural protein 5A (NS5A) inhibitor-based regimen. MATERIAL AND METHODS: Retrospective study of 111 liver transplant recipients between January 2018 and December 2020; 18 patients presented with HCV recurrent infection after LT, out of whom three had a history of at least one NS5A inhibitor-based regimen. Salvage therapy with sofosbuvir plus GLE/PIB was started for 12 weeks; baseline characteristics and outcomes were recorded. RESULTS: All three patients (100%) achieved an undetectable HCV viral load 12 weeks after treatment completion. No serious adverse events were observed. CONCLUSION: In our series, sofosbuvir plus GLE/PIB for 12 weeks is an effective and safe salvage therapy after LT in patients previously treated with NS5A inhibitors.
ANTECEDENTES: El tratamiento del virus de la hepatitis C (VHC) crónica con antivirales de acción directa logra tasas de respuesta virológica sostenida superiores a 95 %. Sin embargo, el manejo del fracaso virológico sigue siendo un desafío clínico y la evidencia sobre el retratamiento es limitada, especialmente en poblaciones como los receptores de trasplante hepático (TH). OBJETIVO: Este estudio evaluó el régimen de sofosbuvir más glecaprevir/pibrentasvir (GLE/PIB) en receptores de TH en quienes falló el régimen basado en inhibidores de la proteína no estructural 5A (NS5A). MATERIAL Y MÉTODOS: Estudio retrospectivo de 111 pacientes trasplantados entre enero de 2018 y diciembre de 2020; 18 pacientes presentaron infección recurrente por VHC posterior al TH, tres de ellos tuvieron antecedentes de al menos un régimen basado en inhibidores de NS5A. Se inició terapia de rescate con sofosbuvir más GLE/PIB durante 12 semanas posterior al TH; se registraron las características basales de los pacientes y sus desenlaces. RESULTADOS: En los tres pacientes se logró obtener una carga viral indetectable de VHC a las 12 semanas de finalizar el tratamiento. No se observaron eventos adversos graves. CONCLUSIÓN: En nuestra serie, sofosbuvir más GLE/PIB durante 12 semanas demostró ser una terapia de rescate efectiva y segura posterior al TH en pacientes previamente tratados con inhibidores de NS5A.
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Hepatite C Crônica , Hepatite C , Transplante de Fígado , Humanos , Sofosbuvir/uso terapêutico , Terapia de Salvação , Hepatite C Crônica/tratamento farmacológico , Antivirais/uso terapêutico , Estudos RetrospectivosRESUMO
Hypothyroidism is a frequently occurring side effect in patients under treatment with immune checkpoint inhibitors (ICIs). Actually, the origin of hypothyroidism with ICI use is classified as a primary (thyroid) or as secondary/tertiary hypothyroidism (hypothalamus-pituitary). Treatment consists of levothyroxine (L-T4) substitution. Recently, we were rarely confronted with a clinically overt hypothyroidism in three patients under treatment with ICIs who were non-responsive to T4 therapy. As a therapeutical escape, liothyronine (L-T3) was started with a significant clinical and/or biochemical improvement suggesting an underlying functional defect in the peripheral free T4 (fT4) to free T3 (fT3) conversion (as supported by calculation of SPINA-GD). Against this background, we discussed our three patients along an extended review of this clinical topic.
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Hipotireoidismo , Tri-Iodotironina , Humanos , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/metabolismo , Inibidores de Checkpoint Imunológico/uso terapêutico , Hormônios Tireóideos/metabolismo , Hormônios Tireóideos/uso terapêutico , Tireotropina , Tiroxina/uso terapêuticoRESUMO
It is important for patients with epilepsy and their caregivers, including care partners, to understand the patient's seizure clusters and what to do when they occur. In many instances, seizure clusters are unique to each patient. The knowledge gained from understanding a patient's seizure cluster or seizure pattern provides a foundation for taking prompt action to prevent worsening to prolonged seizures, status epilepticus, and potentially death. Seizure action plans (SAPs), which are similar to the disease-related treatment action plans for other conditions, can be developed by a health care provider (HCP) in conjunction with the patient with epilepsy and/or caregivers, and SAPs are specifically customized for the individual patient and his or her seizure management. However, the current literature lacks unified guidance on how to design SAPs that will help prepare patients and caregivers for rapidly determining and initiating appropriate treatment of acute seizure emergencies in the community and at home. Here, we examine the current usage and value of SAPs for pediatric and adult patients with epilepsy, and we introduce the concept of the acute SAP (ASAP) for use specifically during seizure emergencies, such as seizure clusters. This type of standardized, simplified, and customized plan can rapidly and concisely provide patients and caregivers with a practical protocol to treat a seizure cluster consistently, appropriately, and in a timely manner. Details on potential content and formats of ASAPs are provided. Following this is a discussion of barriers to ASAP use that may affect HCPs or patients and caregivers, including lack of standardization, relevance, and personalization and pitfalls associated with technology. This leads into a discussion of guidance for developing, implementing, and updating ASAPs that suggests ways to address the barriers and ensure that the ASAP is best suited to the patient's needs.
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Reposicionamento de Medicamentos , Epilepsia Generalizada , Epilepsia , Convulsões , Estado Epiléptico , Adulto , Dano Encefálico Crônico , Criança , Emergências , Feminino , Humanos , Masculino , Convulsões/terapia , Estado Epiléptico/terapiaRESUMO
BACKGROUND: The currently recommended quadruple regimens as rescue therapy on Helicobacter pylori infection were not as effective as being supposed, especially in those who had failed two or more times. Dual regimen composed of vonoprazan (a potassium-competitive acid blocker) and amoxicillin might be an option since it's effective in eradication therapy as first-line treatment. OBJECTIVE: As a real-world retrospective study, data were collected to evaluate the efficacy and safety of vonoprazan and amoxicillin dual regimen as rescue therapy in Helicobacter pylori positive patients who had failed one or more times in their previous treatment. METHODS: From May 2020 to June 2021, the clinical data of patients who had failed in Helicobacter pylori infection treatment were collected in GI department of Peking University First Hospital, Beijing, China. Patients were given vonoprazan 20 mg or 40 mg per day and amoxicillin 3000 mg per day (VA dual therapy) for 14 days as rescue treatment. Helicobacter pylori status was evaluated by 13 C-urease breath test 6 weeks after treatment. All adverse effects during treatment were recorded. RESULTS: A total of 186 patients were enrolled, including 67 males and 119 females. All of them had failed for 1 ~ 7 times in their previous treatment. Successful eradication was achieved in 172 patients (92.5%, 172/186). The adverse effects (referring to skin rash, abdominal pain, diarrhea, and headache), mainly mild and did not cause quit of treatment, occurred in 14 patients (7.5%, 14/186) and all symptoms relieved spontaneously. CONCLUSIONS: Dual regimen composed of vonoprazan and amoxicillin for 14 days was effective and safe as rescue therapy in Helicobacter pylori infection treatment. It could be chosen as a "simplified rescue therapy" with relatively high eradication rate no matter how many times the patients had failed and what regimens they had used previously.
Assuntos
Infecções por Helicobacter , Helicobacter pylori , Amoxicilina/efeitos adversos , Antibacterianos/efeitos adversos , Claritromicina/uso terapêutico , Quimioterapia Combinada , Feminino , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/tratamento farmacológico , Humanos , Masculino , Potássio/uso terapêutico , Inibidores da Bomba de Prótons/efeitos adversos , Pirróis/efeitos adversos , Estudos Retrospectivos , Sulfonamidas/efeitos adversos , Resultado do Tratamento , UreaseRESUMO
BACKGROUND: Rifabutin-based regimens are used as rescue therapy for refractory Helicobacter pylori infection; however, the duration for which treatment is required and side effects are concerning. This study assessed the efficacy and safety of 7-day rifabutin, amoxicillin, and vonoprazan triple therapy as third- or later-line treatment for H. pylori infection. MATERIALS AND METHODS: Patients who did not respond to second-line therapy were enrolled. After H. pylori infection was confirmed with the culture method, the patients received rifabutin-containing triple therapy (20 mg vonoprazan b.i.d., 500 mg amoxicillin q.i.d., and 150 mg rifabutin q.d.) for 7 days. Twelve weeks after the eradication therapy, successful eradication was confirmed using a 13 C urea breath test or the H. pylori stool antigen test. The results obtained from our previous study that reported a 10-day or 14-day esomeprazole based rifabutin-containing triple therapy as a third- or fourth-line rescue therapy treated patients were used as historical control. We determined the minimum inhibitory concentrations of amoxicillin and rifabutin. We also evaluated whether the patients were positive for the mutation of the rpoB gene. RESULTS: Intention-to-treat and per-protocol analyses showed that our regimen resulted in a high eradication rate (91.2%, 95% CI: 84%-99% and 92.7%, 95% CI: 86%-100%, respectively). Adverse events occurred in 31.6% of the patients, and two patients discontinued the therapy. CONCLUSIONS: This is the first study to evaluate the efficacy and safety of a 7-day low-dose rifabutin-based triple therapy with vonoprazan and amoxicillin. Our results suggest that our regimen was effective and safe as a third- or later-line H. pylori eradication regimen. To clarify what component in this regimen are critical, subsequent studies using a factorial design (comparing vonoprazan-amoxicillin dual therapy vs. vonoprazan-rifabutin triple therapy) will be needed.
Assuntos
Infecções por Helicobacter , Helicobacter pylori , Amoxicilina/efeitos adversos , Antibacterianos/efeitos adversos , Claritromicina/uso terapêutico , Quimioterapia Combinada , Infecções por Helicobacter/tratamento farmacológico , Humanos , Inibidores da Bomba de Prótons/uso terapêutico , Rifabutina/efeitos adversos , Resultado do TratamentoRESUMO
Background: The long-term benefits of conversion from calcineurin inhibitors (CNIs) to belatacept in kidney transplant recipients (KTr) are poorly documented.Methods: A single-center retrospective work to study first-time CNI to belatacept conversion as a rescue therapy [eGFR <30 ml/min/1.73 m2, chronic histological lesions, or CNI-induced thrombotic microangiopathy (TMA)]. Patient and kidney allograft survivals, eGFR, severe adverse events, donor-specific antibodies (DSA), and histological data were recorded over 36 months after conversion. Results: We included N = 115 KTr. The leading cause for switching was chronic histological lesions with non-optimal eGFR (56.5%). Three years after conversion, patient, and death-censored kidney allograft survivals were 88% and 92%, respectively, eGFR increased significantly from 31.5 ± 17.5 to 36.7 ± 15.7 ml/min/1.73 m2 (p < 0.01), the rejection rate was 10.4%, OI incidence was 5.2 (2.9-7.6) per 100 person-years. Older age was associated with death, eGFR was not associated with death nor allograft loss. No patient developed dnDSA at M36 after conversion. CNI-induced TMA disappeared in all cases without eculizumab use. Microvascular inflammation and chronic lesions remained stable. Conclusion: Post-KT conversion from CNIs to belatacept, as rescue therapy, is safe and beneficial irrespective of the switch timing and could represent a good compromise facing organ shortage. Age and eGFR at conversion should be considered in the decision whether to switch.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Rim , Microangiopatias Trombóticas , Abatacepte/uso terapêutico , Inibidores de Calcineurina/uso terapêutico , Humanos , Estudos Retrospectivos , TransplantadosRESUMO
AIMS: Quinolone-containing triple therapy has been considered as the second-line therapy for eradication of Helicobacter pylori (H. pylori). At present, there are no data to show the efficacy and safety of antofloxacin-based rescue therapy for the eradication of H. pylori, and this pilot clinical trial was designed. METHODS: A total of 196 patients who failed H. pylori eradication using the clarithromycin-based or metronidazole-based triple or bismuth quadruple therapy were randomly allocated to one of the following rescue eradication therapy groups: AEA group (antofloxacin 200 mg once daily, esomeprazole 20 mg + amoxicillin 1000 mg twice daily) for 14 days, or LEA group (levofloxacin 500 mg once daily, esomeprazole 20 mg + amoxicillin 1000 mg twice daily) for 14 days. The minimal inhibitory concentrations were tested by the E-test method. The gyrA mutation was analyzed by sequencing. Follow-up 13/14C-urea breath test was examined at 1 month after discontinuation. RESULTS: A total of 178 eligible patients were included in this study. The eradication rate was significantly higher in AEA group than in LEA group according to both ITT (87.6% vs. 68.5%; P = 0.002) and PP analyses (90.7% vs. 70.1%; P = 0.001). ITT analyses indicated that the eradication rate was significantly higher in AEA group than in LEA group with Asn87 mutation (78.9% vs. 31.3%; P = 0.005) and levofloxacin-resistant strains (76.9% vs. 44.2%; P = 0.003). Two groups exhibited similar adverse event rates (AEA 14.6% vs. LEA 20.2%, P = 0.323). CONCLUSIONS: The findings showed that antofloxacin may be a promising candidate in rescue therapy for H. pylori eradication failure in China.
Assuntos
Amoxicilina/administração & dosagem , Esomeprazol/administração & dosagem , Gastrite , Infecções por Helicobacter , Levofloxacino/administração & dosagem , Ofloxacino/análogos & derivados , Adulto , Antibacterianos/administração & dosagem , Testes Respiratórios/métodos , China , Quimioterapia Combinada , Feminino , Gastrite/tratamento farmacológico , Gastrite/microbiologia , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Testes de Sensibilidade Microbiana/métodos , Ofloxacino/administração & dosagem , Inibidores da Bomba de Prótons/administração & dosagem , Resultado do TratamentoRESUMO
BACKGROUND: Steroid exposure has been associated with poorer outcomes following colectomy in acute severe ulcerative colitis (ASUC). AIM: To examine the effect of prolonged oral corticosteroid therapy immediately prior to admission on the likelihood of requiring rescue therapy along with predictors of intravenous corticosteroid failure on Day 1 of admission. METHODS: A retrospective case note and electronic record review was conducted at a tertiary inflammatory bowel disease referral centre of admissions for ASUC meeting Truelove and Witts criteria from 2013 to 2019.The data was analysed for the effect of pre-admission steroid exposure on need for rescue therapy and for predictors of intravenous corticosteroid failure. RESULTS: Ninety-two admissions were identified for ASUC meeting Truelove and Witts criteria. Over 1 week of steroid therapy prior to admission was associated with need for rescue therapy and trended to significance for colectomy at admission and at 12 months. A generalised linear model was constructed with multivariate regression significant for over 1 week of steroid therapy prior to admission, endoscopic Mayo score and albumin. The area under the receiver operator curve for this model was 0.86. CONCLUSION: Prolonged steroid use prior to ASUC admission is a significant predictor of need for rescue therapy. A generalised linear model incorporating steroid prior to admission, endoscopic Mayo score and albumin was highly accurate at predicting failure of corticosteroid. Consideration should be given for commencement of rescue therapy prior to Day 3, especially in those with prolonged steroid prior to admission.