Management of infusion-related reactions in cancer therapy: strategies and challenges.

Several anticancer therapies have the potential to cause infusion-related reactions (IRRs) in the form of adverse events that typically occur within minutes to hours after drug infusion. IRRs can range in severity from mild to severe anaphylaxis-like reactions. Careful monitoring at infusion initiation, prompt recognition, and appropriate clinical assessment of the IRR and its severity, followed by immediate management, are required to ensure patient safety and optimal outcomes. Lack of standardization in the prevention, management, and reporting of IRRs across cancer-treating institutions represents not only a quality and safety gap but also a disparity in cancer care. The present article, supported by recently published data, was developed to standardize these procedures across institutions and provide a useful tool for health care providers in clinical practice to recognize early signs and symptoms of an IRR and promptly and appropriately manage the event.

Chronic obstructive pulmonary disease exacerbations' management in Portuguese hospitals - EvaluateCOPDpt, a multicentre, observational, prospective study.

INTRODUCTION AND OBJECTIVES: In order to improve the quality of chronic obstructive pulmonary disease (COPD) patients' care, better knowledge of clinical practice and the factors associated with patient outcomes are needed. This study aimed to evaluate the relation between clinical practice and the outcomes of patients admitted for COPD exacerbations in Portuguese hospitals. MATERIALS AND METHODS: Observational, multicentre, prospective study with a 60-days follow-up period, in 11 hospitals, including patients aged ≥ 30 years, admitted to hospital for at least 24 hours due to an acute exacerbation of COPD. Demographic and clinical data were collected, including sex, age, smoking habits, hospitalisations, pulmonary function, comorbidities, COPD symptoms, and treatment. Sixty days after discharge, COPD exacerbations management, outcome measures, and readmission data were evaluated through a structured phone follow-up interview. RESULTS: 196 patients were included (85.7% male, mean age 71.2 years), the majority admitted through the emergency service. Ex-smokers and current smokers accounted for 51% and 36%, respectively. On admission, 72.4% were on LAMA, 54.6% on LABA, and 45.5% were on LABA/LAMA. Inhaled corticosteroids (ICS) were used in 37.3% and systemic steroids (SCS) in 10.3%. 35.7 % had had at least one exacerbation, with hospitalisation, in the previous year. There was no spirometry data for 23.2%. On hospitalisation, 98.5% of patients were treated with oxygen and 38.3% with non-invasive ventilation. Additionally, 93.4% used SCS and 60.2% ICS. Antibiotics were administered to 85.2%. 95.4% of patients were discharged; 9 died, 5 of whom had a COPD-related death. The median length of stay was 12 days for discharged patients and 33 days for patients who died. At discharge, 79.1% were prescribed with LAMA, 63.6% SCS, 61.5% LABA and 55.6% LAMA+LABA. 26,2% were prescribed with ICS+LABA+LAMA. At follow-up, 44.4% had a scheduled medical appointment within the 60 days after being discharged, and 28.3% were later readmitted due to exacerbation, of whom 52.8% were hospitalised. CONCLUSIONS: The severity of COPD, particularly in exacerbations, is directly related to impaired lung function and quality of life, mortality, and significant health system costs. Knowledge about COPD exacerbations' management in acute hospital admissions in Portugal may help stimulate a national discussion and review of existing data to engage clinicians, policymakers, managers, and patients, raising awareness and promoting action on COPD.

The Vacinómetro® initiative: an eleven-year monitorization of influenza vaccination coverage rates among risk groups in Portugal.

Annual vaccination is fundamental for individual and group protection against seasonal influenza infection. International and Portuguese healthcare organizations have established influenza vaccination coverage rate (VCR) targets for risk groups, namely 75% in people ≥ 65 years old. The Vacinómetro® initiative has been monitoring influenza VCR among target risk groups in Portugal since 2009,: Group 1, ≥ 65 years old; Group 2, patients with chronic conditions; Group 3, healthcare workers in direct contact with patients; and Group 4, 60-64 years old. Besides VCR, social-demographic and health-related variables have been evaluated. During the study period (2009/2010 - 2019/2020), the VCR increased in the 4 target risk groups: from 58.6% to 76.0% in Group 1 (reaching the WHO target); 33.3% to 72.0% in Group 2; 25.0% to 58.9% in Group 3; and 36.6% to 42.8% in Group 4. "Physician recommendation" was the main driver for vaccination whereas "lack of habit" was the main barrier to vaccination. Vacinómetro® data demonstrate that free-of-charge vaccination has a positive impact on VCR. The observed positive trends in influenza VCR demonstrate that public health measures implemented in Portugal to facilitate access to influenza vaccine result in increased vaccine uptake. Strategies to promote population literacy and the physician's awareness should be continued and reinforced. Free-of-charge vaccination criteria extended to more risk groups would also contribute to higher influenza VCR in Portugal.

Predictors of immune-related adverse events and outcomes in patients with NSCLC treated with immune-checkpoint inhibitors.

OBJECTIVE: To identify predictors of immune-related adverse events (IRAEs) in patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). Assess associations between outcomes and the development of IRAEs. METHODS: Retrospective analysis of patients with NSCLC treated with ICIs between 2016 and 2020 in the Pulmonology Department of our hospital. Patients with and without IRAEs were compared. A logistic regression analysis was performed to determine predictors of IRAEs. Progression-free survival (PFS) and overall survival (OS) curves were calculated using the Kaplan-Meier method, and the long-rank test was used to assess survival differences between groups. Univariate and multivariate Cox proportional-hazards regression models were used to identify factors associated with PFS and OS. The value considered statistically significant was p≤0.05. RESULTS: A total of 184 patients (77.7% men, mean age 66.9±9.5 years) treated with ICIs were analyzed. During follow-up, 49 (26.6%) patients developed IRAEs and 149 (81.0%) died. According to the multivariate logistic regression analysis, treatment with statins (OR:3.15; p = 0.007), previous systemic corticosteroid therapy (OR:3.99; p = 0.001), disease controlled as response to ICI (OR:5.93; p < 0.001) and higher hemoglobin values (OR:1.28; p = 0.040) were independent predictors for the development of IRAEs. Patients who developed IRAEs had significantly longer medians of PFS (41.0 vs 9.0 weeks, p < 0.001) and OS (89.0 vs 28.0 weeks; p < 0.001). CONCLUSIONS: Patients treated with statins, pre-ICI systemic corticosteroids, higher baseline hemoglobin value and controlled disease as initial response to ICI had a higher risk of developing IRAEs. The development of IRAEs was associated with better outcomes.

Predicting lung nodules malignancy.

BACKGROUND: It is critical to developing an accurate method for differentiating between malignant and benign solitary pulmonary nodules. This study aimed was to establish a predicting model of lung nodules malignancy in a real-world setting. METHODS: The authors retrospectively analysed the clinical and computed tomography (CT) data of 121 patients with lung nodules, submitted to percutaneous CT-guided transthoracic biopsy, between 2014 and 2015. Multiple logistic regression was used to screen independent predictors for malignancy and to establish a clinical prediction model to evaluate the probability of malignancy. RESULTS: From a total of 121 patients, 75 (62%) were men and with a mean age of 64.7 years old. Multivariate logistic regression analysis identified six independent predictors of malignancy: age, gender, smoking status, current extra-pulmonary cancer, air bronchogram and nodule size (p<0.05). The area under the curve (AUC) was 0.8573. CONCLUSIONS: The prediction model established in this study can be used to assess the probability of malignancy in the Portuguese population, thereby providing help for the diagnosis of lung nodules and the selection of follow-up interventions.

Coexistence of DIPNECH and carotid body paraganglioma: is it just a coincidence?

SUMMARY: We describe the case of a 56 year-old woman with the almost simultaneous appearance of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) and a carotid body paraganglioma. Of interest, 6 years earlier, the patient underwent total thyroidectomy due to papillary thyroid carcinoma and, in the meantime, she was submitted to mastectomy to treat an invasive ductal carcinoma of the breast. In order to explain these lesions, an extensive genetic study was performed. Results showed positivity for the presence of the tumor suppressor gene PALB2, whose presence had already been detected in a niece with breast cancer. The patient underwent different procedures to treat the lesions and currently she is symptom-free over 2 years of follow-up. LEARNING POINTS: The presence of two rare neoplasms in a single person should raise the suspicion of a common etiology. To the best of our knowledge, this is the first case that shows the coexistence of DIPNECH and paraganglioma. The contribution of the PALB2 gene in the etiology of these rare neoplasms is a possibility.

COPD: Analysing factors associated with a successful treatment.

OBJECTIVES: To evaluate if non-adherence to inhaled medications, inhalers mishandling or the prescribers' non-adherence to GOLD strategy are associated with mMRC grade, CAT score, COPD acute exacerbations or FEV1%. METHODS: A cross-sectional study on COPD was conducted in the ambulatory pulmonary clinic of Hospital de Guimarães. Patients ≥40 years diagnosed according to GOLD criteria were recruited consecutively. A survey of demographic and clinical data was used. Adherence was assessed by using the Measure of Treatment Adherence (MTA) questionnaire. Inhalation technique was evaluated by using checklists of correct steps and critical errors, and inhalers' misuse was defined when one or more critical errors were made, whatever the number or types of inhalers in use. To evaluate the prescriber non-adherence to GOLD strategy, the patients' current medication was compared with therapeutic standards proposed by the GOLD 2017 strategy for the same ABCD groups. A statistical analysis was performed with IBM SPSS Statistics for Windows, Version 23.0. Armonk, NY: IBM Corp. RESULTS: We studied 303 participants, 79.5% males, mean age=67.5 years. A total of 285 completed the MTA questionnaire. Non-adherence was referred by 47 (16.5%) patients, and a significant negative association was found between adherence and CAT score and FEV1%. 285 patients performed 499 inhalations manoeuvres with 10 different IDs. Inhaler misuse was observed in 113 (39.6%) patients, and was not associated with CAT score, mMRC grade, ECOPD or FEV1%. We found deviations from the GOLD strategy in 133 (44.3%) patients, which were negatively related to CAT score, mMRC grade and ECOPD. CONCLUSIONS: In the present study we failed to prove a positive association between non-adherence to medication, inhalers mishandling or prescribers' non-adherence to GOLD strategy with symptoms, exacerbations and airflow limitation. Conversely, more symptomatic and more obstructed patients were more adherent to medication, previous ECOPD seems to improve prescribers' adherence to treatment guidelines, and symptoms, ECOPD and FEV1% were not significantly associated with inhaler technique.

Real-world data from the Portuguese Nivolumab Expanded Access Program (EAP) in previously treated Non Small Cell Lung Cancer (NSCLC).

OBJECTIVE: The main aim of the study was to evaluate the efficacy and safety profile of Nivolumab, an immune-checkpoint-inhibitor antibody, in advanced, previously treated, Non-Small Cell Lung Cancer (NSCLC) patients, in a real world setting. METHODS: We performed a retrospective, multicentre data analysis of patients who were included in the Portuguese Nivolumab Expanded Access Program (EAP). Eligibility criteria included histologically or citologically confirmed NSCLC, stage IIIB and IV, evaluable disease, sufficient organ function and at least one prior line of chemotherapy. The endpoints included Overall Response Rate (ORR), Disease Control Rate (DCR), Progression Free Survival (PFS) and Overall Survival (OS). Safety analysis was performed with the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, and immune-related Adverse Events (irAEs) were treated according to protocol treatment guidelines. Tumour response was assessed using the Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. Data was analysed using SPSS, version 21.0 (IBM Statistics). RESULTS: From June 2015 to December 2016, a total of 229 patients with advanced NSCLC were enrolled at 30 Portuguese centres. Clinical data were collected up to the end of July 2018. The baseline median age was 64 years (range 37-83) and the majority of patients were males (70.3%) and former/current smokers (69.4%). Patients with non-squamous histology predominated (88.1%), and 67.6% of the patients had received 2 or more prior lines of chemotherapy. Out of 229 patients, data was available for 219 patients (3 patients did not start treatment, while data was unavailable in 7 patients); of the 219 patients, 15.5% were not evaluated for radiological tumour assessment, 1.4% had complete response (CR), 21% partial response (PR), 31% stable disease (SD) and 31.1% progressive disease (PD). Thus, the ORR was 22.4% and DCR was 53.4% in this population. At the time of survival analysis the median PFS was 4.91 months (95% CI, 3.89-6.11) and median OS was 13.21 months (95% CI, 9.89-16.53). The safety profile was in line with clinical trial data. CONCLUSIONS: Efficacy and safety results observed in this retrospective analysis were consistent with observations reported in clinical trials and from other centres.

COPD: misuse of inhaler devices in clinical practice.

Background and objectives: Inhalers mishandling remain an important clinical issue worldwide. The aim of this study was to evaluate inhalation technique in stable COPD out-patients. The variables under study were type of inhaler device (ID), patients' preference for an inhaler, number of IDs used by each patient, beliefs about inhaler medication and some demographic, clinical and functional patients' characteristics. We aim to assess how they are related to inhalation technique. Methods: A cross-sectional study was conducted in a hospital outpatient respiratory care. COPD patients over 40 years old, diagnosed according to GOLD criteria, and using IDs were included consecutively. The Beliefs about Medicines Questionnaire (BMQ), a demographic and a clinical survey were applied. The number of IDs used by each patient and the patients' preference for some IDs were recorded. Patients were asked to demonstrate the use of their prescribed inhalation devices, and inhaler technique was assessed by using previously defined checklists, including essential steps and critical errors. A statistics analysis was then performed. Results: We studied 300 subjects performing a total of 521 inhalation manoeuvers with 10 different IDs. At least one step incorrectly performed was found in 48.2% of demonstrations and in 29.9% critical errors were observed. Misuse was related to priming/loading in 6.9%, to inhalation manoeuver in 13.1% and to both in 10%. There was a statistically significant association between critical errors and type of ID (P<0.001). No significant relationship was found between correct performance of key manoeuvers and patients' preference or number of inhalers used per patient. Misuse due to critical errors was observed in 39.3% of patients and was positively related to female gender, age ≥65, lower education level and lower socioeconomic status (higher Graffar classification score), but not to patients' clinical or functional characteristics. In the sub-group of patients presenting critical errors when using IDs, there was a statistically significant inverse association between BMQ Necessity score and number of critical errors. Conclusions: Inhalers mishandling remains disappointingly common. A good inhalation technique depends on the type of ID, and failure of inhalation manoeuver was the main cause of ID misuse. It was not associated to multiple inhalers' use nor to patient's preference, but to the patient's beliefs about the necessity to use them. Elderly patients, women and those with lower education level or lower socioeconomic status demonstrate a worse inhalation technique.

Characterisation of morbidity in a COPD hospital cohort.

OBJECTIVES: To characterise the morbidity of COPD out-patients based on symptoms, acute exacerbations, FEV1 and comorbidities, and to explore the association between different patients' characteristics such as social, demographic, clinical history or exposure. METHODS: Stable COPD outpatients over 40 years old diagnosed according to GOLD criteria were included consecutively; the exclusion criteria were only refusal to participate and inability to understand clinical questionnaires. A survey of demographic and clinical data was conducted. Symptoms were evaluated using the CAT and mMRC questionnaires. The number of COPD acute exacerbations reported in the previous year was assessed, and spirometry performed on all participants according to ATS/ERS recommendations. Different variables were collected and then related to each other. RESULTS: We studied 303 COPD outpatients, all Caucasians, 79.5% males and mostly elderly. 65.7% of participants reported having low monthly income and 87.8% a low education level. Tobacco smoking was the most common exposure identified but a substantial proportion of COPD patients were non-smokers (26%). Frequent acute exacerbations were reported by 38.0% of patients. The mean post-bronchodilator FEV1 was 53.2%. The distribution of patients according to GOLD 2017 stage and classification was respectively 9.9%, 41.9%, 35.0% and 13.2% from 1 to 4 and 23.1%, 39.6%, 2.3% and 35.0% from GOLD A to D. Only 29 patients (9.5%) presented no comorbid conditions, and the most common were hypertension, heart diseases and dyslipidaemia. CONCLUSIONS: Our data confirms COPD as a complex and heterogeneous disorder, with a significant morbidity due to the nature of symptoms, frequent comorbidities and exacerbations. A substantial proportion of COPD patients were never-smokers, mainly women, calling attention to the need for COPD recognition in these cases. COPD in women, in never-smokers and in patients with a previous diagnosis of asthma presented some specific characteristics. Some patient characteristics are associated with frequent acute exacerbations. FEV1 was strongly related both to symptoms and exacerbations.

Bronchiectasis: a retrospective study of clinical and aetiological investigation in a general respiratory department.

BACKGROUND: Bronchiectasis can result from many diseases, which makes the aetiological investigation a complex process demanding special resources and experience. The aetiological diagnosis has been proven to be useful for the therapeutic approach. OBJECTIVE: Evaluate how accurately and extensive the clinical and aetiological research was for adult bronchiectasis patients in pulmonology outpatient service which were not following a pre-existing protocol. METHODS: We retrospectively reviewed the records of 202 adult patients with bronchiectasis, including the examinations performed to explain the aetiology. RESULTS: The mean age of the patients was 54 ± 15 years, there was a predominance of female (63.9%) and non-smoker (70%) patients. Functional evaluation showed a mild airway obstruction. The sputum microbiological examination was available for 168 patients (43.1% had 3 or more sputum examinations during one year). Immunoglobulins and α1-antitrypsin were measured in around 50% of the patients. The sweat test and the CF genotyping test were performed in 18% and 17% of the patients, respectively. The most commonly identified cause was post-infectious (30.3%), mostly tuberculosis (27.2%). No definitive aetiological diagnosis was established in 57.4% of the patients. We achieved a lower aetiological diagnosis if we compare our series with studies in which a diagnostic algorithm was applied prospectively. CONCLUSIONS: The general characteristics of our patients were similar with other series. Detailed investigation of bronchiectasis is not a standard practice in our outpatient service. These results suggest that the use of a predefined protocol, based on current guidelines, could improve the assessment of these patients and facilitate the achievement of a definitive aetiology.

Lung cancer during pregnancy: an unusual case.

The incidence of pregnancy-associated cancer is relatively low, complicating only 0.02-0.1% of all pregnancies. The authors describe a case of a 36-year-old woman, a light smoker, who was admitted to the hospital at 27 weeks of pregnancy, with respiratory symptoms since second trimester. Chest-X ray showed total left lung opacity with contralateral mediastinal deviation, suggestive of pleural effusion, and the pleural biopsy revealed invasion by lung adenocarcinoma. EGFR mutation test was negative. After a multidisciplinary meeting, it was decided to start fetal lung maturation and cesarean section at 29 weeks gestation. The patient received two lines of chemotherapy and bone metastasis radiotherapy, but there was progression of the disease. An EML4-ALK translocation was identified in an additional genetic test. Crizotinib 250mg BID was started. The patient showed a progression-free survival of 9 months and died 19 months after lung adenocarcinoma was diagnosed.