Diagnostic and therapeutic approach of central sleep apnea in heart failure - the role of adaptive servo-ventilation. A statement of the Portuguese society of pulmonology and the Portuguese sleep association.

It is known that patients with heart failure (HF) have an increased risk of developing central sleep apnoea (CSA), with Cheyne-Stokes respiration. The development of servo-ventilation aimed to treat CSA and improve the quality of life (QoL) of these patients. A large randomized clinical study, SERVE-HF, was conducted in order to test this theory in patients with HF and reduced ejection fraction (HFrEF). The results from this trial seemed to indicate that, in these patients, there was no beneficial effect of the assisted ventilation in CSA treatment. More surprisingly, an increased rate of all-cause or cardiovascular mortality was observed. This has led to dramatic changes in clinical practice, with decreased frequency of servo-ventilation prescription across Europe, including Portugal, due to changes in the guidelines. However, SERVE-HF was conducted only in severe systolic HF patients with CSA, and caution must be taken when extrapolating these results to HF patients with preserved ejection fraction or CSA patients without HF. The study also showed poor adherence, methodological and statistical gaps, including study design, patient selection, data collection and analysis, treatment adherence, and group crossovers, which have not been discussed in the trial as potential confounding factors and raise several concerns. Moreover, the adaptive servo-ventilation (ASV) device used in SERVE-HF was unable to lower the minimum support pressure below 3 mm H20, and this has been suggested as one of the probable contributing reasons to the excess mortality observed in this study. This limitation has since been solved, and this ASV device is no longer used. This paper describes the results of a Portuguese Task Force on the treatment of central sleep apnoea in patients with chronic HF.

Dance-related musculoskeletal injury leading to forced time-loss in elite pre professional dancers - a retrospective study.

OBJECTIVES: Describe the epidemiology of dance-related musculoskeletal injury leading to forced time-loss in elite pre-professional dancers and provide descriptive data on the prevalence concerning diagnoses, location, and injury type, stratified by gender and skill level. METHODS: Retrospective cohort, over a 3-year period on a full-time pre-professional Portuguese dance school featuring 70 both gender students with a mean age of 14.87 years. A total of 110 injuries were analyzed. Non-parametric statistics were used. RESULTS: The most prevalent diagnosis leading to forced time-loss in female dancers were Medial Tibial Stress Syndrome (MTSS), 14.29%, and Posterior Ankle Impingement Syndrome (PAIS), 7.14%, whereas in male dancers these were Hallux Sprain, 17.50%, and Lumbar Spine Joint Injuries, 7.50%. Differences were found in injuries' anatomical location between genders and in Incidence Proportion and Clinical Incidence between skill levels. 72.20% of the chronic injuries and 50.00% of the acute injuries occurred in Level III students. CONCLUSIONS: With respect to forced time-loss injuries, male dancers were found to sustain more acute traumatic injuries and female dancers overuse, respectively, sprains and MTSS and PAIS. Identifying which injuries are most likely to lead to forced time-loss may be useful for helping health-care professionals in clinical decision-making and in developing more effective injury prevention and management strategies.

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.

Validation of NoSAS (Neck, Obesity, Snoring, Age, Sex) score as a screening tool for obstructive sleep apnea: Analysis in a sleep clinic.

INTRODUCTION: Screening methods have become increasingly important due to the growing number of patients suspected of having obstructive sleep apnea (OSA) being referred to sleep clinics. The Lausanne NoSAS (Neck circumference, Obesity, Snoring, Age, Sex) score test is a simple, efficient, and easily employed tool enabling identification of individuals at risk for the disease. The score ranges from 0 to 17 and the patient has a high probability of OSA if they have a NoSAS score of 8 or higher. OBJECTIVES: To evaluate the performance of the NoSAS score as a screening tool for the diagnosis of OSA in a sleep clinic. METHODS: Prospectively, for 12 months, we included all the patients referred by primary care physicians to our sleep unit for clinical evaluation who had undergone in-lab polysomnography (PSG) and completed the NoSAS score. This test assigns 4 points for a neck circumference of more than 40cm, 3 points for a body-mass index of 25kg/m2 to less than 30kg/m2 or 5 points for having a body-mass index of 30kg/m2 or more, 2 points for snoring, 4 points for being older than 55 years of age and 2 points for being male. RESULTS: Of the 294 patients, 70.7% were male, aged 53.5±12.1 years, with a neck circumference of 41.0±3.6cm and a BMI of 30.8±5.1kg/m2. OSA was present in 84.0% of the patients, 34.8% with moderate OSA and 36.4% severe OSA. Using the NoSAS model for the prediction of all OSA, moderate/severe OSA and severe OSA, the area under the ROC (Receiver Operating Characteristic) was 0.770 (IC95%: (0.703; 0.837), p<0.001), 0.746 (IC95%: (0.691; 0.802), p<0.001) and 0.686 (IC95%: (0.622; 0.749), p<0.001), respectively, thus confirming the diagnostic ability of the NoSAS model. With a NoSAS score ≥7, the sensitivity and positive predictive value (PPV) were 94.3% and 87.6% for all OSA, 94.9% and 62.8% for moderate/severe OSA and 100% and 33.8% for severe OSA, respectively. With the same cut-off, the negative predictive value (NPV) for moderate/severe and severe OSA were 67.9% and 100%, respectively. Each increase in the NoSAS score was associated with an increase in the probability of OSA, reaching a 97% OSA probability for a score of 17. CONCLUSIONS: The NoSAS score showed high sensitivity and PPV for OSA with specificity and diagnostic accuracy steadily increasing with higher scores. Furthermore, a low score showed high predictive value for the exclusion of moderate/severe OSA. Overall, our results suggest that, in primary care, this score can be a powerful tool for stratifying and prioritizing patients in the diagnosis of OSA. Nevertheless, more studies are needed to evaluate the efficacy of this score in hospital health care, in younger populations, with a predominance of female and non-obese individuals or in cardiovascular disease.

Clinical and molecular markers in COPD.

Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disease, and there is a clinical need for validated markers and biomarkers that can contribute to the assessment of patients, risk prediction, treatment guidance, and assessment of response. Although according to the 2018 GOLD guidelines clinically useful biomarkers for COPD patients in stable condition have yet to be identified, several clinical markers and biomarkers have been proposed for COPD. These include isolated clinical markers, such as symptoms and Health Status assessment, exercise tests, function tests and imaging, and also composite scores and molecular markers. However, and despite strong efforts to identify useful markers in an attempt to improve prognostic and therapeutic approaches, results have not been consistent and expectations of relying on these markers in near future are faint. Current approaches to COPD have shifted from treating the disease to treating the individual patient. There is a clear need to identify treatable traits, focusing more on the patient and not on the disease, in order to implement an increasingly personalized treatment of COPD in the clinic, leading to true precision medicine. There is a need to identify combinations of clinical markers and biomarkers, genetic markers, and phenotypes that can guide the personalized therapy of COPD patients. This critical review will therefore focus not only on currently established markers and biomarkers in COPD but also on possible future approaches toward precision medicine.

Titration with automatic continuous positive airway pressure in obstructive sleep apnea.

BACKGROUND AND OBJECTIVE: Autotitrating positive airway pressure (APAP) is an accepted titration method to determine the optimal positive airway pressure (PAP), for the treatment of obstructive sleep apnea (OSA). The required duration of APAP monitoring to determine a fixed continuous positive airway pressure level still remains to be established. We aimed to evaluate the variation in PAP level, delivered by APAP devices, at different periods of treatment, to determine the APAP treatment duration required to reach an effective and stable PAP level. METHODS: A cross-sectional study of 62 patients newly diagnosed with OSA were evaluated after 3 months of APAP therapy. APAP data corresponding to the first day (D1), first week (W1), seventh week (W7) and twelfth week (W12) under APAP therapy was collected. For the analysis of the pressure behaviour, the difference of P95th pressure level between W12 and W7 (P W12-W7), W12 and W1 (P W12-W1) and W12 and D1 (P W12-D1) was calculated. RESULTS: There was a high correlation in P95th pressure level between D1 and W12 (r=0.771; p>0.0001), W1 and W12 (r=0.817; p>0.0001), and W7 and W12 (r=0.926; p>0.0001). This correlation progressively increased with APAP use. A significance difference was found in concordance between P W12-W7 and P W12-D1 (p=0.046) within the pressure range ±2cmH2O. However there was no significant difference in concordance between P W12-W7 and P W12-W1. CONCLUSIONS: One week of APAP therapy seems sufficient to determine an effective and stable PAP level, within the pressure range ±2cmH2O.

Prevalence of late-onset pompe disease in Portuguese patients with diaphragmatic paralysis - DIPPER study.

Pompe disease is a rare autosomal recessive neuromuscular disorder caused by acid α-glucosidase enzyme (GAA) deficiency and divided into two distinct variants, infantile- and late-onset. The late-onset variant is characterized by a spectrum of phenotypic variation that may range from asymptomatic, to reduced muscle strength and/or diaphragmatic paralysis. Since muscle strength loss is characteristic of several different conditions, which may also cause diaphragmatic paralysis, a protocol was created to search for the diagnosis of Pompe disease and exclude other possible causes. METHODS: We collected a sample size of 18 patients (10 females, 8 males) with a median age of 60 years and diagnosis of diaphragmatic paralysis of unknown etiology, followed in the Pulmonology outpatient consultation of 9 centers in Portugal, over a 24-month study period. We evaluated data from patient's clinical and demographic characteristics as well as complementary diagnostic tests including blood tests, imaging, neurophysiologic and respiratory function evaluation. All patients were evaluated for GAA activity with DBS (dried blood test) or serum quantification and positive results confirmed by serum quantification and sequencing. RESULTS: Three patients were diagnosed with Pompe's disease and recommended for enzyme replacement therapy. The prevalence of Pompe, a rare disease, in our diaphragmatic paralysis patient sample was 16.8%. CONCLUSION: We conclude that DBS test for GAA activity should be recommended for all patients with diaphragmatic paralysis which, despite looking at all the most common causes, remains of unknown etiology; this would improve both the timing and accuracy of diagnosis for Pompe disease in this patient population. Accurate diagnosis will lead to improved care for this rare, progressively debilitating but treatable neuromuscular disease.

COPD control: Can a consensus be found?

There are currently no reliable instruments for assessing the onset and progression of chronic obstructive pulmonary disease (COPD) or predicting its prognosis. Currently, a comprehensive assessment of COPD including several objective and subjective parameters is recommended. However, the lack of biomarkers precludes a correct assessment of COPD severity, which consequently hampers adequate therapeutic approaches and COPD control. In the absence of a definition of "well-controlled disease", a consensus regarding COPD control will be difficult to reach. However, COPD patient assessment should be multidimensional, and anchored in five points: control of symptoms, decline of pulmonary function, levels of physical activity, exacerbations, and Quality of Life. Several non-pharmacological and pharmacological measures are currently available to achieve disease control. Smoking cessation, vaccination, exercise training programs and pulmonary rehabilitation are recognized as important non-pharmacological measures but bronchodilators are the pivotal therapy in the control of COPD. This paper discusses several objective and subjective parameters that may bridge the gap between disease assessment and disease control. The authors conclude that, at present, it is not possible to reach a consensus regarding COPD control, essentially due to the lack of objective instruments to measure it. Some recommendations are set forth, but true COPD control awaits further objective assessments.

[The importance of dyspnoea in the diagnosis of chronic obstructive pulmonary disease--a descriptive analysis of a stable cohort in Portugal (SAFE trial)]. / A importância da dispneia no diagnóstico da doença pulmonar obstrutiva crónica--uma análise descritiva de uma coorte estável em Portugal (ensaio clínico SAFE).

INTRODUCTION: The aim of this study was to determine patient-perceived characteristics of chronic obstructive pulmonary disease (COPD) in patients participating in a large trial evaluating tiotropium bromide. PATIENTS AND METHODS: Baseline symptoms were assessed by means of a standardized questionnaire. Patients reported symptoms that led to diagnosis as well as their current most troublesome symptom. RESULTS: Data were obtained from 298 patients, mostly male (95%), with mean (standard deviation) baseline forced expiratory volume in 1 second of 1.1 (0.4) L (40.6 [13.3] % of predicted), mean disease duration of 14.4 (10.1) years and smoking history of 55.1 (25.3) pack-years. Dyspnoea was the most frequently reported symptom leading to COPD diagnosis (55.0% of patients), followed by cough (33.2%). Dyspnoea was also the current most troublesome symptom (82.6%), followed by cough (8.4%). The presence of dyspnoea or cough was independent of COPD severity. The most commonly reported co-morbidities were cardiovascular disorders (49% of patients), gastrointestinal disorders (20%) and metabolic disorders (16%), mainly diabetes mellitus. CONCLUSIONS: This analysis confirms the importance of dyspnoea as the most common symptom leading to initial COPD diagnosis and the symptom most troublesome to patients. Co-morbidities are common among COPD patients, and hence spirometric testing is appropriate in a patient who presents with dyspnoea associated with such a condition.

Tiotropium improves FEV1 in patients with COPD irrespective of smoking status.

This study evaluated whether the effect of tiotropium on the change in trough forced expiratory volume in 1s (FEV1), vs. placebo, is affected by smoking status. In a 3-month, double-blind study in 31 centres in Portugal, 311 (289 completed) patients were randomised to tiotropium 18 microg once daily or placebo. Baseline mean (standard deviation (SD)) FEV1 was 1.11 (0.39) l in the tiotropium group and 1.13 (0.39) l in the placebo group. Patients had an average smoking history of 55 (25.7) pack-years; 80 (26%) were smokers and 224 (74%) were ex-smokers. The primary end-point was change in morning pre-dose (i.e. trough) FEV1 after 12 weeks. Trough FEV1 at 12 weeks was significantly improved with tiotropium vs. placebo: the difference in means was 102 ml, P=0.0011, 95% confidence interval (CI) (41, 164). The difference in means in smokers was 138 ml, P=0.0105, CI (32, 244); in ex-smokers it was 66 ml, P=0.0375, CI (3, 129). The difference between smokers and ex-smokers was not statistically significant (P=0.6982) and may be due to greater variability and differences in disease severity. The significant improvement in lung function in patients treated with tiotropium vs. placebo in both smokers and ex-smokers suggests that tiotropium is an effective and well-tolerated therapy in chronic obstructive pulmonary disease (COPD), regardless of smoking status.

Oral moxifloxacin vs high-dosage amoxicillin in the treatment of mild-to-moderate, community-acquired, suspected pneumococcal pneumonia in adults.

STUDY OBJECTIVES: Comparison of the efficacy and safety of moxifloxacin vs amoxicillin for treatment of mild-to-moderate, suspected pneumococcal community-acquired pneumonia (CAP) in adult patients. DESIGN: Multinational, multicenter, double-blind, randomized study. SETTING: Eighty-two centers in 20 countries (Argentina, Brazil, Chile, Croatia, Czech Republic, Estonia, France, Hong Kong, Hungary, Lithuania, Mexico, Portugal, Russia, Slovenia, South Africa, Spain, Turkey, Ukraine, United Kingdom, and Uruguay). PATIENTS: Four hundred eleven adults (inpatients or outpatients) with suspected pneumococcal CAP. INTERVENTIONS: Randomization 1:1 to moxifloxacin, 400 mg/d, or amoxicillin, 1,000 g tid, for 10 days. RESULTS: Primary efficacy parameter was clinical response, 3 to 5 days after therapy (end of therapy [EOT]) in the per protocol (PP) population (362 patients). The clinical success rate in the PP population was 91.5% (moxifloxacin) and 89.7% (amoxicillin; two-sided 95% confidence interval, -4.2 to 7.8%). The clinical cure rate in patients with proven pneumococcal pneumonia was similar in both treatment groups (87.8%). The bacteriologic success rate in 136 bacteriologically evaluable patients at the EOT was 89.7% (moxifloxacin) and 82.4% (amoxicillin). The bacteriologic success rate against Streptococcus pneumoniae was 89.6% (moxifloxacin) and 84.8% (amoxicillin). The frequency of adverse events was comparable in both treatment groups. Digestive symptoms were the most common drug-related adverse events in both treatment groups. CONCLUSIONS: Moxifloxacin was statistically at least as effective as high-dose amoxicillin for treatment of mild-to-moderate, suspected pneumococcal CAP. Moxifloxacin may be an alternative for empiric CAP treatment, especially in areas where multidrug resistance in S pneumoniae is sufficiently prevalent to preclude routine penicillin.