Clinical predictors of asthmatics in identifying subgroup requiring long-term tiotropium add-on therapy: a real-world study.

BACKGROUND: According to several phase III studies, tiotropium [a long-acting muscarinic antagonist (LAMA)] is a well-tolerated add-on therapy to inhaled corticosteroids (ICS) for asthmatics with or without the addition of long-acting beta2-agonists (LABAs). However, real-world studies based on clinical phenotypes to predict the long-term need of tiotropium as an add-on therapy for asthmatics are limited. METHODS: This is a retrospective study conducted at a single medical center in Taiwan from July 2016 to July 2018. An asthma control test (ACT) is applied to uncontrolled asthmatics to evaluate the effectiveness of tiotropium as an add-on therapy. Asthmatic subgroups with different clinical phenotypes and needing long-term tiotropium as a maintenance treatment are identified. The effectiveness of tiotropium add-on therapy is defined as an improvement of ACT score ≥3 points 3 months after the treatment (vs. baseline), while the long-term requirement of tiotropium is defined as tiotropium dependency >1 year. RESULTS: The study analyzed a total of 160 uncontrolled asthmatics regardless of low- or medium-to-high-dose ICS plus LABA. One hundred and twelve patients responded well (ACT score increased ≥3 points) to tiotropium. These patients were further divided into two subgroups: one with tiotropium add-on therapy for ≥1 year due to patients' difficulties in stepping down from tiotropium; the other with tiotropium add-on therapy for <1 year due to successful step-down treatment according to Global Initiative for Asthma (GINA) score. All clinical characteristics of these two groups were collected and analyzed. Univariate and multivariate analyses showed that asthma-and-chronic obstructive pulmonary disease (COPD)-overlap (ACO), initial forced expiratory volume-one second (FEV1) % predicted <80%, or body mass index (BMI) >30 kg/m2 were predictors for asthmatics requiring long-term tiotropium add-on therapy. CONCLUSIONS: Tiotropium add-on therapy is effective for uncontrolled asthmatics. Moreover, patients with ACO, initial FEV1% predicted <80%, or BMI >30 kg/m2 require long-term tiotropium add-on therapy for asthma control.

Association Between Serum Folate Level and Toxicity of Capecitabine During Treatment for Colorectal Cancer.

BACKGROUND: Folate level was proposed to be a predictor for fluoropyrimidine-related toxicity. We conducted a prospective study to determine the association between serum and red-cell folate and capecitabine-related toxicity in patients with colorectal cancers. MATERIALS AND METHODS: Eligibility criteria included diagnosis of colorectal cancers; eligible patients who were scheduled to undergo capecitabine monotherapy or capecitabine-oxaliplatin (CAPOX) for adjuvant or palliative purposes. Exclusion criteria included concomitant radiotherapy or chemotherapy other than capecitabine or CAPOX and creatinine clearance <30 mL/min. Fasting serum and red-cell folate were measured prior to chemotherapy. Capecitabine was administered at 2,500 mg/m2 per day (monotherapy) or 2,000 mg/m2 per day (CAPOX) for 14 days every 3 weeks. The toxicity of the first four cycles was documented by clinical investigators who were blinded to folate levels. RESULTS: A total of 144 patients were recruited, of whom 126 were eligible; 40 patients had capecitabine alone, and 86 patients received CAPOX. The rates of grade 2 and grade 3 toxicity were 63.5% and 14.3%, respectively. Nausea and vomiting were the most common grade ≥2 adverse event (47.7%), followed by hand-foot syndrome (25.4%), diarrhea (23.1%), and neutropenia (22.3%). Combination with oxaliplatin (odds ratio [OR], 2.77; p = .043) and serum folate (OR, 10.33; p = .002) were independent predictors of grade ≥2 toxicity. Red-cell folate was not predictive of toxicity. For every 10 nmol/L increment in serum folate, the risk of grade ≥2 toxicity increased by 9%. CONCLUSION: Serum folate level, but not red-cell folate, was associated with higher rate of grade ≥2 toxicity during capecitabine-based treatment. Excessive folate intake may be avoided before and during capecitabine-based chemotherapy. IMPLICATIONS FOR PRACTICE: This is the first prospective study to evaluate the association between serum folate level and capecitabine-related toxicity in patients with colon cancers. It shows that higher serum folate level is associated with increased risks of moderate to severe toxicity during capecitabine-based treatment. Excessive folate intake should be avoided before and during capecitabine-based chemotherapy.

O eletrocardiograma de alta resolução na avaliação da remodelagem elétrica atrial e na predição de recorrência da fibrilação atrial / High resolution electrocardiography in the evaluation of atrial electrical remodeling and to predict of atrial fibrillation

Fundamentos: A fibrilação atrial (FA) apresenta alta taxa de recorrência que pode ser explicada por dois mecanismos: o primeiro diz respeito à capacidade dessa arritmia se perpetuar através da autoindução de alterações eletrofisiológicas, denominadas de remodelagem elétrica. O segundo mecanismo está relacionado a condições cardiovasculares subjacentes que podem estar presentes com alterações estruturais do coração, mesmo que de forma subclínica, por um longo período de tempo até o primeiro episódio de FA. Objetivo: Investigar a importância do eletrocardiograma de alta resolução da onda P (ECGAR-P) na avaliação da remodelagem elétrica atrial e na predição de recorrência da fibrilação atrial. Métodos: Foram realizados dois estudos, o ECGAR-P foi aplicado em ambos. No primeiro avaliaram-se os padrões evolutivos da ativação elétrica atrial durante um mês em 31 pacientes com FA idiopática de longa duração e submetidos à cardioversão. No segundo, investigou-se o ECGAR-P e outros preditores clínicos de não resposta à amiodarona em baixa dose, após a cardioversão do primeiro episódio persistente e altamente sintomático de FA não valvar. O segundo estudo incluiu 87 pacientes e teve seguimento mínimo de 24 meses. Ao final do seguimento, a resposta à terapia antiarrítmica (TA) foi considerada como não responsiva quando ocorreram duas ou mais recorrências de FA ou insucesso em nova cardioversão. Obteve-se de todos os participantes, de ambos os estudos, o Consentimento Livre e Esclarecido, tendo sido o estudo aprovado pelo Comitê de Ética da instituição. Resultados: O primeiro estudo mostrou que entre 31 indivíduos, 9 tiveram recorrência precoce da arritmia, todos nos primeiros sete dias após a cardioversão, e 22 permaneceram em ritmo sinusal por pelo menos um mês. Nesses pacientes a duração da onda P diminuiu progressivamente do primeiro para o terceiro ECGAR. Na análise no domínio da frequência, a turbulência espectral se mostrou inaparente no ECGAR imediato...

Background: Atrial fibrillation is frequently disabling and drug resistant. The high rate of recurrence of AF is represented by two separate mechanisms: the first can be summarized as atrial fibrillation (AF) itself promotes electrophysiological changes, termed "electrical remodeling", facilitationg its recurrence and maintenance. There are evidences that the remodeling process is reversible after restoration of sinus rhythm. However, the timing for recovery of electrophysiological properties is characterized by marked vulnerability to early recurrence of the arrhythmia and still undefined. The second mechanism relates to underlying cardiovascular conditions and cardiac structural changes, which may be hidden for a long time until AF emerges. Objective: In the first article we evaluated the atrial electrical activation by using P-wave signal-averaged electrocardiogram (P-SAECG) post-cardioversion of long-standing lone AF, focusing on the reversal remodeling process to identify the timing of stabilization of the process. The objective of the second article was evaluated the follow-up of patients after cardioversion of the first persistent AF episode, with poorly symptoms and without structural cardiopathy. Methods: In the first study with 31 patients, P-SAECG was performed immediately after cardioversion and repeated on days seven and thirty. The second article included 87 patients with highly symptomatic first-detected persistent AF. After successful electrical cardioversion, echocardiogram and P-SAECG were obtained. During the segment, for all patients were prescribed low-dose of amiodarone and each one were followed-up at least for 24 months. At the end of the follow-up, antiarrythmic therapy (AT) outcome was defined as nonresponse if there were >- 2 recurrences of symptomatic AF or unsuccessful in sequential cardioversion. Results: the results of the first study shows that among 31 subjets, nine underwent early recurrence of AF, all of then...