Improvement In Dyspnea Research Articles

A Phase II Study of High-Flow Nasal Cannula for Relieving Dyspnea in Advanced Cancer Patients

ContextThe efficacy and tolerability of high-flow nasal cannula (HFNC) for relieving dyspnea in advanced cancer patients with limited prognosis requires elucidation. ObjectivesThe primary aim of this trial was to assess the efficacy and tolerability of HFNC regarding dyspnea including severe as well as moderate for longer durations in patients under palliative care. MethodsIn this prospective study, hospitalized patients with advanced cancer who had dyspnea at rest (numeric rating scale, NRS≥3) and hypoxemia were enrolled. They were treated with HFNC for five days in the respiratory unit. Primary endpoint was mean change of modified Borg scale at 24 hours. Key secondary endpoints consisted of mean changes in modified Borg scale during the study period and feasibility (Trial Identifier, UMIN000035738). ResultsBetween February 2019 and February 2022, 25 patients were enrolled and 21 were analyzed. Twenty patients used inspired oxygen and the mean fraction of inspired oxygen (FiO2) was 0.34 (range, 0.21–1.0). At baseline, mean NRS (dyspnea) was 5.9 (range, 3–10). Median survival time was 19 days (range, 3–657). The mean change of modified Borg scale was 1.4 (80% confidence interval [CI]: 0.8–1.9) at 24 hours, 12 patients (57%) showed 1.0 points improvement of modified Borg scale. Within two hours, 15 patients showed 1.0 points improvement of modified Borg scale and such early responders were likely to maintain dyspnea improvement for 24 hours. Nineteen patients could continue HFNC for 24 hours and 11 patients completed five days of HFNC. ConclusionTo our knowledge, this trial is the first prospective study to assess the five-day efficacy and tolerability of HFNC for dyspnea in patients under palliative care. Although this did not reach the prespecified endpoint, about half of the patients showed 1.0 point improvement, a minimally clinically important difference (MCID) in the chronic lung disease. HFNC can be a palliative treatment option in advanced cancer patients with dyspnea.

Large-bore mechanical thrombectomy for intermediate- and high-risk pulmonary embolism: interim outcomes from the European cohort of the FLASH registry

Abstract Background/Introduction Mechanical thrombectomy is utilized for the treatment of acute pulmonary embolism (PE), but reported outcomes are limited in the European patient population. Purpose To report interim results from the European cohort of a large, prospective all-comer registry of mechanical thrombectomy for PE treatment. Methods The FLASH registry is a multinational, prospective, observational study of safety and effectiveness outcomes for PE treatment using a large-bore mechanical thrombectomy system. FLASH is currently enrolling up to 200 patients in Europe. The primary endpoint is a composite of Major Adverse Events (MAEs) within 48 hours, including device-related deaths, major bleeding, and intraprocedural AEs. Additional assessments include invasive hemodynamics, hospital resource usage, and dyspnea improvement. Results Interim results through 48 hours post-thrombectomy are presented for the first 29 patients enrolled in the European cohort across 4 institutions. Mean patient age was 64.9±14.5 years, 51.7% of patients were male, 10.3% were contraindicated for thrombolysis, 51.7% had concomitant deep vein thrombosis, and 79.3% had centrally located thrombus involving one or both main pulmonary arteries. Per ESC guidelines, 58.6% of patients were classified as high-risk. The remaining 41.4% of patients were classified as intermediate-risk, with 31.0% being intermediate-high-risk. Pre-thrombectomy, the median RV/LV ratio from a composite of computed tomography and echocardiography was 1.31 [IQR: 1.08-1.44], and 38.9% of patients who had cardiac index (CI) measured were in cardiogenic shock (CI ≤2 L/min/m²). Procedural characteristics included a median thrombectomy time of 39 minutes [IQR: 26-49]. Extracorporeal membrane oxygenation was used in 6.9% of patients. Post-thrombectomy, the median length of stay in the intensive care unit (ICU) was 1 overnight [IQR: 0-2], and 48.1% of patients required no overnight ICU stay. In addition, hemodynamic variables, vitals, dyspnea symptoms, and reliance on supplemental oxygen all improved significantly post-thrombectomy (Table 1). Acute safety and mortality outcomes were highly favorable following the procedure (Table 2). All patients survived through 48 hours post-thrombectomy. There were no MAEs (0%), no major access site complications (0%), and no device-related Serious AEs (0%) through 48-hour follow-up. Conclusions Interim results from the first 29 patients in the European cohort of the FLASH registry suggest that large-bore mechanical thrombectomy can be safely performed in both intermediate- and high-risk PE patients, with no MAEs or mortalities observed through 48 hours. Significant improvements observed in multiple hemodynamic and dyspnea-related variables further suggest that thrombectomy can offer effective reperfusion treatment for acute PE.

Prognostic impact of geriatric frailty profile after transcatheter aortic valve replacement (TAVR): a registry study of a tertiary referral hospital

Abstract Background Assessment of frailty in patients screened for transcatheter aortic valve replacement (TAVR) can improve outcome prediction after TAVR. However, previous studies evaluating frailty indicators in this population provided heterogenic results because of the wide variety of tests and cut-off values used to assess frailty1,2. Recently, the comprehensive geriatric assessment frailty index (CGA-FI) was introduced to ensure a standardized evaluation of patient frailty3. Purpose The aim of our study was to evaluate the potential value of frailty assessment by the CGA-FI for outcome prediction in TAVR patients. The prognostic effect of the geriatric profile including nutrition, cognition, mobility and depression was also examined. Methods A total of 102 patients treated by TAVR between 2015 and 2020 were included retrospectively. Demographic, medical history, hemodynamic, geriatric, procedural, hospital stay, and 2 years follow-up data were collected. The primary study endpoint was defined as 2-year all-cause mortality. The secondary endpoint was defined as lack of dyspnea improvement at 2-year follow-up. Results Mean patient age was 84.2 ± 4.3 years and 14% of patients were classified as frail according to CGA-FI > 0.2. The 2-year mortality rate after TAVR was 29.4% and lack of dyspnea improvement during follow-up was observed in 13.7% of patients. A CGA-FI > 0.2 did not predict all-cause mortality after TAVR (hazard ratio (HR): 1.302, 95% confidence interval (CI): 0.494-3.427, p=0.593 (Figure 1)). However, patients with a geriatric depression scale ≥ 5 had higher all-cause mortality risk after TAVR than patients with a geriatric depression scale < 5 (HR: 3.047, 95% CI: 1.330-6.977, p=0.008 (Figure 1)). Similarly, malnutrition status was associated with higher all-cause mortality and shorter survival time after TAVR (HR: 2.340, 95% CI: 1.008-5.432, p=0.048 (Figure 1)). In contrast, no association of CGA-FI and geriatric profile with 2-year lack of dyspnea improvement was observed. Conclusions A CGA-FI > 0.2 was not associated with 2 years patient mortality after TAVR. However, a geriatric depression scale ≥ 5 and malnutrition may be of prognostic value by predicting all-cause mortality after TAVR.

Patient-Reported Outcomes (PROs) 3 and 6 Months After Pulmonary Rehabilitation Following COVID-19

If COVID-19 disease sequelae also (co-)affect the respiratory organs, national and international guidelines recommend pulmonary rehabilitation (PR). So far, however, no studies are available from Germany on the course after PR, nor on possible course differences between the two Long COVID subgroups "Ongoing symptomatic COVID-19" and "Post-COVID-19 syndrome" (PCS). In a prospective observational study, patient-reported outcomes (PROs) regarding exertional dyspnea, quality of life, pain, fatigue, depression, and anxiety were assessed at the beginning of PR (T1), end of PR (T2), and after 3 (T3) and 6 months (T4). Statistical analyses were performed using latent difference models. There were 224 rehabilitation patients (MAge=54.4; SDAge=10.4; 42.0% female) included in the study. During PR, all PROs improved significantly. After PR, improvements either persisted with large pre-post effect sizes (exertional dyspnea, quality of life), decreased slightly to small pre-post effect sizes (depression, fatigue), or decreased to baseline levels (anxiety, pain). PCS patients had greater burdens in depression, fatigue, and pain at baseline, but did not differ in trajectories. Indicators of the severity of the preceding acute phase (oxygen therapy, ICU treatment, ventilation) were associated with higher burdens at T0 in depression, fatigue, and pain, but not with the courses during and after PR. In contrast, female patients showed higher burdens in both depression and fatigue at T1 and higher pre-post effects than male patients. The fact that improvements in PROs occurred in both subgroups only during PR, but not during the follow-up period suggests that the changes are not due to the natural healing process but at least partly due to PR. Moreover, the results suggest that both patient groups may benefit from PR. Persisting improvements in exertional dyspnea and quality of life and, to a reduced extent, in depression and fatigue until 6 months after PR, but not in pain and anxiety warrant study of additional multimodal interventions that may be needed to maintain these effects.

Rehabilitation Interventions for Physical Capacity and Quality of Life in Adults With Post–COVID-19 Condition

Current rehabilitation guidelines for patients with post-COVID-19 condition (PCC) are primarily based on expert opinions and observational data, and there is an urgent need for evidence-based rehabilitation interventions to support patients with PCC. To synthesize the findings of existing studies that report on physical capacity (including functional exercise capacity, muscle function, dyspnea, and respiratory function) and quality of life outcomes following rehabilitation interventions in patients with PCC. A systematic electronic search was performed from January 2020 until February 2023, in MEDLINE, Scopus, CINAHL, and the Clinical Trials Registry. Key terms that were used to identify potentially relevant studies included long-covid, post-covid, sequelae, exercise therapy, rehabilitation, physical activity, physical therapy, and randomized controlled trial. This study included randomized clinical trials that compared respiratory training and exercise-based rehabilitation interventions with either placebo, usual care, waiting list, or control in patients with PCC. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A pairwise bayesian random-effects meta-analysis was performed using vague prior distributions. Risk of bias was assessed using the Cochrane risk of bias tool version 2, and the certainty of evidence was evaluated using the GRADE system by 2 independent researchers. The primary outcome was functional exercise capacity, measured at the closest postintervention time point by the 6-minute walking test. Secondary outcomes were fatigue, lower limb muscle function, dyspnea, respiratory function, and quality of life. All outcomes were defined a priori. Continuous outcomes were reported as standardized mean differences (SMDs) with 95% credible intervals (CrIs) and binary outcomes were summarized as odds ratios with 95% CrIs. The between-trial heterogeneity was quantified using the between-study variance, τ2, and 95% CrIs. Of 1834 identified records, 1193 were screened, and 14 trials (1244 patients; 45% female participants; median [IQR] age, 50 [47 to 56] years) were included in the analyses. Rehabilitation interventions were associated with improvements in functional exercise capacity (SMD, -0.56; 95% CrI, -0.87 to -0.22) with moderate certainty in 7 trials (389 participants). These improvements had a 99% posterior probability of superiority when compared with current standard care. The value of τ2 (0.04; 95% CrI, 0.00 to 0.60) indicated low statistical heterogeneity. However, there was significant uncertainty and imprecision regarding the probability of experiencing exercise-induced adverse events (odds ratio, 1.68; 95% CrI, 0.32 to 9.94). The findings of this systematic review and meta-analysis suggest that rehabilitation interventions are associated with improvements in functional exercise capacity, dyspnea, and quality of life, with a high probability of improvement compared with the current standard care; the certainty of evidence was moderate for functional exercise capacity and quality of life and low for other outcomes. Given the uncertainty surrounding the safety outcomes, additional trials with enhanced monitoring of adverse events are necessary.

Nasal High-Flow (NHF) Improves Ventilation in Patients with Interstitial Lung Disease (ILD)-A Physiological Study.

Acute hypercapnic respiratory failure has a poor prognosis in patients with interstitial lung disease (ILD). Recent data demonstrated a positive effect of nasal high-flow (NHF) in patients with acute hypoxemic respiratory failure. Preliminary data also show benefits in several hypercapnic chronic lung diseases. The aim of this study was to characterize flow-dependent changes in mean airway pressure, breathing volumes, and breathing frequency and decreases in PCO2. Mean airway pressure was measured in the nasopharyngeal space. To evaluate breathing volumes, a polysomnographic device was used (16 patients). All subjects received 20, 30, 40, and 50 L/min and-to illustrate the effects-nCPAP and nBiPAP. Capillary blood gas analyses were performed in 25 hypercapnic ILD subjects before and 5 h after the use of NHF. Additionally, comfort and dyspnea during the use of NHF were surveyed. NHF resulted in a small flow-dependent increase in mean airway pressure. Tidal volume was unchanged and breathing rate decreased. The calculated minute volume decreased by 20 and 30 L/min NHF breathing. In spite of this fact, hypercapnia decreased at a flow rate of 24 L/min. Additionally, an improvement in dyspnea was observed. NHF leads to a reduction in paCO2. This is most likely achieved by a washout of the respiratory tract and a reduction in functional dead space. NHF enhances the effectiveness of breathing in ILD patients by the reduction in respiratory rate. In summary, NHF works as an effective ventilatory support device in hypercapnic ILD patients.

Clinical Use of Oral Opioid Therapy for Dyspnea in Patients With Advanced Heart Failure - A Single-Center Retrospective Study.

Background: For patients with advanced heart failure, palliative care, including opioids, is needed as a treatment for refractory dyspnea. However, little evidence has been reported on the efficacy and safety of opioids, and their use is not well established. Methods and Results: We have introduced a protocol for the use of opioids for dyspnea in patients with advanced heart failure admitted to Saitama Citizens Medical Center. Following this protocol, differences in clinical variables and outcome were investigated between patients in whom opioids were initiated intravenously or subcutaneously (i.v./s.c. group; n=13) and patients in whom they were initiated orally (oral group; n=18). In a comparison of baseline characteristics, significantly more patients in the oral group had a history of hospitalization for heart failure within the past year, and significantly more patients were treated with dobutamine and tolvaptan. After initiation of opioid treatment, both groups showed improvement in dyspnea; however, serial changes in vital signs were significantly greater in the i.v./s.c. group. The survival rate was significantly higher in the oral group (P<0.0001), with 33% of patients discharged alive. Conclusions: The clinical use of oral opioids using a single-center protocol is reported, suggesting that oral opioids may be practical and effective for dyspnea in patients with advanced heart failure.

Non-Invasive Positive Pressure Ventilation or Standard Oxygen Therapy as Initial Treatment of Acute Cardiogenic Pulmonary Edema in ICU Patients

Abstract Background Continuous positive airway pressure ventilation (CPAP) through face mask has been widely used especially in North America, Europe and Australasia to alleviate signs and symptoms of respiratory distress due to cardiogenic pulmonary edema. Continuous positive airway pressure ventilation (CPAP) is ventilatory support that is given without establishing endotracheal intubation. CPAP avoid complication of endotracheal tube and invasive mechanical ventilation, preserving the patient’s ability to speak, eat, and cough reflex, reduces the need for sedation, potential airway trauma, and the risk of ventilator associated pneumonia. Objective: Patients and Methods In our study, 62 patients admitted at critical care unit of the Ain Shams University Hospitals with acute cardiogenic pulmonary edema. Patients divided into two groups. Group I: included 31 patients with acute cardiogenic pulmonary edema receive CPAP with (PS 10 cm h2o, PEEP 5 cm h2o). Group II: included 31 patients with acute cardiogenic pulmonary edema receive Oxygen therapy by face mask. Both groups are compared regarding the following parameter: Pao2, Pco2, respiratory rate and Spo2 on admission, 1-hour and 2-hours, post intervention and after discontinuation of treatment. Both groups were compared regarding the rate of endotracheal intubation, ICU length of stay and hospital mortality. Results Our study showed that the respiratory distress was markedly improved in CPAP group compared to oxygen therapy group by face mask as shown in respiratory rate after institution of CPAP (48.31±4.29, 35.84±5.30). In our study, as regarding to ICU length of stay, there was reduction in the intensive care unit length of stay in patient received CPAP compared to length of stay in standard oxygen treatment received group (2.48 ± 0.51 vs. 4.03± 0.65). Our study show that there is reduction in rate of intubation in group I with CPAP compared with group II with oxygen therapy by face mask. Conclusion Continuous positive air way pressure CPAP is widely used in North America, Europe and Australasia for patients with severe ACPE. There are clear mechanistic reasons why these interventions work in acute pulmonary edema. In conclusion, patients with acute cardiogenic pulmonary edema, CPAP safely provides earlier improvement of dyspnea, respiratory distress and oxygen saturation, and decrease ICU length of stay, improved endotracheal intubation and survival rate than does oxygen therapy.

Predictors of Quality-of-Life Improvement at Different Minimum Clinically Important Difference Values in Patients with Chronic Obstructive Pulmonary Disease after Climatic Rehabilitation Treatment.

The minimum clinically important difference (MCID) for the St George's Respiratory Questionnaire (SGRQ) is debated in chronic obstructive pulmonary disease (COPD) quality-of-life (QoL) assessments. This study aimed to determine whether there is a difference in predictors of clinically significant improvement between the traditional (value of 4) and newly proposed MCID SGRQ (value of 7) after climatic rehabilitation treatment. Climatic rehabilitation treatment consists of two main parts: climatotherapy, which typically involves the controlled exposure of individuals to natural environmental elements, and climatic rehabilitation, which includes other therapeutic factors such as physical activities as well as educating the patient to change their lifestyle. This study included 90 consecutive patients diagnosed with COPD who underwent structured complex pulmonary rehabilitation in High Tatras, part of the Carpathian Mountains. The examination before and after treatment included spirometry, QoL assessment using the SGRQ, 6 min walk test (6-MWT), and the Borg, Beck and Zung scale. Patients showed statistically significant improvement after the intervention in FEV1, FEV1/FVC, 6-MWT, (p < 0.001), anxiety scores, depression, and improvement in dyspnoea both before and after the 6-MWT (p < 0.001). For both MCID for SGRQ levels 4 and 7, we confirmed the same predictors of clinical improvement for bronchial obstruction grade (spirometry) and exercise capacity (6-MWT), for quality of life in activity score and total score. The results suggest that both the proposed MCID for SGRQ values could be sufficient to assess the clinical significance of the achieved change in health status when assessing the need for pulmonary rehabilitation comprising climatotherapy in patients with COPD.

Minimally-Invasive Diaphragmatic Plication in Patients with Unilateral Diaphragmatic Paralysis.

Background: Diaphragm eventration (DE) represents a frequent problem with consecutive major impacts on respiratory function and the quality of life of the patients. The role of diaphragmatic plication (DP) is still underestimated. The aim of the present study is to evaluate the efficacy of minimally-invasive surgical diaphragmatic plication for the management of unilateral diaphragmatic eventration, to the best of our knowledge, this is the largest series reported in the literature using a non-resectional technique. Methods: All patients with unilateral diaphragmatic paralysis admitted for diaphragmatic plication (DP) between January 2008 and December 2022 formed the cohort of this retrospective analysis. DP procedure was done to plicate the diaphragm without resection or replacement with synthetic materials. Patients were divided into two groups: Group I included patients who underwent DP through an open thoracotomy, and Group II included patients who underwent DP through video-assisted thoracoscopic surgery (VATS). Data from all patients were collected prospectively and subsequently analyzed retrospectively. Patients' characteristics, lung function tests, radiological findings, type of surgical procedures, complications, and postoperative follow-up were compared. The primary outcome measure was the postoperative result (deeper position of the paralyzed diaphragm) and improvement of dyspnea. The secondary outcome was lung function values over a long-term follow-up. Results: The study included a total of 134 patients who underwent diaphragmatic plication during the study period. 94 (71.7%) were males, mean age of 64 (SD ± 14.0). Group I (thoracotomy group) consisted of 46 patients (35 male). Group II (VATS-group) consisted of 88 patients (69 male). The majority of patients demonstrated impaired lung functions (n = 126). The mean length of diaphragmatic displacement was 8 cm (SD ± 113.8 cm). The mean duration of the entire procedure, including placement of the epidural catheter (EDC), was longer in group I than in group II (p = 0.016). This was also observed for the mean length of the surgical procedure itself (p = 0.031). Most patients in group I had EDC (n = 38) (p = 0.001). Patients in group I required more medication for pain control (p = 0.022). A lower position of the diaphragm was achieved in all patients (p < 0.001). The length of hospital stay was 7 (SD ± 4.5) days in group I vs. 4.5 (SD ± 3.2) days in group II (p = 0.036). Minor complications occurred in 3% (n = 4) in group I vs. 2% (n = 3) in group II. No mortality was observed in any of the groups. Postoperative follow-up of patients at 6, 12, and 24 months showed a significant increase in forced vital capacity (FVC) up to 25% (SD ± 10%-35%) (p = 0.019), in forced expiratory volume in 1 s (FEV1) up to 20% (SD ± 12%-38%) in both groups (p = 0.026), also in the diffusion capacity of carbon monoxide (DLCO) up to 15% (SD ± 10%-20%) was noticed in both groups. Chronic pain symptoms were noted in 13% (n = 6) in group I vs. 2% (n = 2) in group II (p = 0.014). Except for one patient in group II, no recurrence of DE was observed. Conclusions: Diaphragm plication is an effective procedure to reduce debilitating dyspnea and improve lung function in patients suffering from diaphragm eventration. Minimally invasive diaphragmatic plication using VATS procedures is a safe and feasible procedure for the management of unilateral diaphragmatic paralysis. VATS-DP is superior to open procedure in terms of pain management and length of hospital stay, hence, accelerated recovery is more likely. Careful patient selection is crucial to achieving optimal outcomes. Prospective studies are needed to validate these results.

Efficacy of threshold inspiratory muscle trainer versus diaphragmatic plus pursed lip breathing in occupational COPD

BackgroundSmoking mainly induces COPD, but occupational threats play a significant role in the development of COPD. Previous studies concerning pulmonary rehabilitation mainly focus on COPD caused by smoking, but COPD induced by occupational hazards has not been studied yet. We aimed to identify the efficacy of IMT (Inspiratory Muscle training) using classic POWERbreathe versus DB (Diaphragmatic breathing) plus PLB (Pursed-lip Breathing) exercise in dyspnea, exercise capacity and pulmonary function parameters in occupational COPD farmers with moderate-to-severe COPD (GOLD II–III) FEV1% 30–79%.MethodsA prospective supervised RCT (Randomized Controlled Trial) included 60 farmers with COPD assigned randomly into two groups; Group A performed IMT using a classic POWERbreathe, and Group B performed DB plus PLB. Both groups completed two daily sessions for three months, seven days/week.ResultsBetween-group differences outcome scores were compared, and there was a more remarkable significant improvement in exercise capacity, lung parameters, and dyspnea using the mMRC scale in the IMT group compared to DB plus PLB group. The 6MWT distance (effect size Cohen’s d: 1.69), FEV1 (effect size Cohen’s d: 0.78), FEV1/FVC (effect size Cohen’s d: 0.86), FVC (effect size Cohen’s d: 1.01), and mMRC score (effect size Cohen's d: 1.12) were significantly improved in group A (p < 0.05).ConclusionThis study demonstrated that the IMT group showed better exercise capacity, dyspnea, and pulmonary function outcomes in occupational COPD farmers. Further studies require COPD patients from different occupations.

Pulmonary rehabilitation improves sleep efficiency measured by actigraphy in poorly sleeping COPD patients

Chronic insomnia is reported by up to 50% of chronic obstructive pulmonary disease (COPD) patients. This may be attributable to several factors including nocturnal dyspnea, reduced physical activity, and less time outside. Pulmonary rehabilitation (PR) is recommended in COPD to improve both physical and psychological conditioning. The aim of this study was to assess the effect of PR on sleep efficiency (SE, measured by actigraphy) in COPD patients. COPD eligible for PR were prospectively included. Baseline and post PR (30 sessions) assessments included incremental and maximal exercise testing, 6-min walking distance test (6MWT), actigraphy, and questionnaires [Pittsburgh Sleep Quality Index (PSQI), Hospital Anxiety Depression scale, St George Respiratory, and modified Medical Research Council dyspnea scale]. Sixty-one patients were included, and 31 patients completed the study protocol (68% of males, age 63 ± 9 y, FEV1 44.2 ± 12.3%). After PR, SE remained unchanged, p = 0.07, as well as PSQI score (p = 0.22), despite improvements in exercise capacity (incremental exercise test, 6MWT) and dyspnea. However, SE improved significantly in the poor sleeper subgroup (SE < 85%, n = 24, p = 0.02), whereas the PSQI remained unchanged. The present study shows, in COPD patients included in a PR program, that improvement in exercise capacity was disappointingly not associated with a better SE assessed by actigraphy. Subjective sleep quality was also unchanged at the end of PR program. However, SE improved significantly in the poor sleeper subgroup (SE < 85%). Further studies are required to better characterize the origin of sleep disturbances in COPD and the potential benefit of some (non-)pharmacologic interventions.

Prevalence of Long COVID Symptoms Related to SARS-CoV-2 Strains.

Few studies have assessed the differences of patterns of Long COVID (L-COVID) with regards to the pathogenetic SARS-CoV-2 strains. To investigate the relationship between demographic and clinical characteristics of acute phase of infection and the persistence of L-COVID symptoms and clinical presentation across different SARS-CoV-2 strains. In this observational-multicenter study we recorded all demographic and clinical characteristics, severity of infection, presence/persistence of symptoms of fatigue, dyspnoea and altered quality of life (QoL) at baseline and after 6 months, in a sample of Italian patients from Liguria between March 2020 and March 2022. 308 patients (mean age 63.2 years; 55.5% men) with previous COVID were enrolled. Obese patients were 21.2% with a significant difference in obesity prevalence across the second and third wave (p = 0.012). Treatment strategies differed between waves (p < 0.001): more patients required invasive mechanical ventilation in the first wave, more patients were treated with high-flow nasal cannula/non-invasive ventilation in the in the second and more patients were treated with oxygen-therapy in the fourth wave. At baseline, a high proportion of patients were symptomatic (dyspnoea and fatigue), with impairment in some QoL indicators. A higher prevalence of patients with pain, were seen in the first wave compared to later infections (p = 0.01). At follow-up, we observed improvement of dyspnoea, fatigue and some dimensions of QoL scale evaluation such as mobility, usual activities, pain evaluations; instead there was no improvement in remaining QoL scale indicators (usual care and anxiety-depression). There were no significant differences in the prevalence of the most frequent L-COVID symptoms, except for QoL pain domain that was especially associated with classical variant. Our results show substantial impact on social and professional life and usual care activities. These findings highlight the importance of multidisciplinary post COVID follow-up care including mental health support and rehabilitation program.

Short-course Palliative Hypofractionated Radiotherapy in Patients with Poor-prognosis High-grade Glioma: Survival and Quality of Life Outcomes from a Prospective Phase II Study

AimsTo report longitudinal quality of life (QoL) outcomes and survival in patients with poor-prognosis high-grade glioma (HGG) treated with palliative hypofractionated radiotherapy. Materials and methodsPatients with poor-prognosis HGG were accrued on a prospective study of short-course palliative hypofractionated radiotherapy (35 Gy/10 fractions/2 weeks). The European Organization for Research and Treatment of Cancer QoL core questionnaire (QLQ-C30) and brain cancer module (BN20) were used in English or validated Indian vernacular languages (Hindi and Marathi) for QoL assessment at baseline (before radiotherapy), the conclusion of radiotherapy, 1 month post-radiotherapy and subsequently at 3-monthly intervals until disease progression/death. Baseline QoL scores were compared with corresponding scores from a historical HGG cohort. Summary QoL scores were compared longitudinally over time by related samples Friedman's two-way test. Progression-free survival and overall survival were calculated using the Kaplan–Meier method and reported as 1-year estimates with 95% confidence intervals. ResultsForty-nine (89%) of 55 patients completed the planned course of hypofractionated radiotherapy. Longitudinal QoL data were available in 42 (86%) of 49 patients completing radiotherapy, comprising the present cohort. The median age of included patients, comprised mainly of glioblastoma patients (81%), was 57 years, with an interquartile range (IQR) of 50–66 years and a median baseline Karnofsky score of 60 (IQR = 50–60). Baseline QoL scores were significantly worse for several domains compared with a historical institutional cohort of HGG patients treated previously with conventionally fractionated radiotherapy, indicating negative selection bias. QoL scores remained stable for most domains after palliative hypofractionated radiotherapy, with statistically significant improvements in fatigue (P = 0.032), dyspnoea (P = 0.042) and motor dysfunction (P = 0.036) over time. At a median follow-up of 8 months, Kaplan–Meier estimates of 1-year progression-free survival and overall survival were 33.3% (95% confidence interval 21.7–51.1%) and 38.1% (95% confidence interval 25.9–56%), respectively. ConclusionShort-course palliative hypofractionated radiotherapy in patients with poor-prognosis HGG is associated with stable and/or improved QoL scores in several domains, making it a viable resource-sparing regimen.

Comparison of Diaphragmatic Stretch and Manual Diaphragmatic Release Technique Along with Chest Proprioceptive Neuromuscular Facilitation in Mild-to-moderate Chronic Obstructive Pulmonary Disease: A Randomized Clinical Trial

Background: Diaphragmatic stretch technique, manual diaphragmatic release technique, and chest proprioceptive neuromuscular facilitation (PNF) have been suggested as an alternative method for the treatment of chronic obstructive pulmonary disease (COPD). Aims: The aim of this study was to compare the effects of diaphragmatic stretch and manual diaphragmatic release technique along with chest PNF on peak expiratory flow rate (PEFR), exercise capacity, dyspnea, chest expansion, and inspiratory pressure in mild-to-moderate COPD participants. Settings and Design: A randomized clinical trial took place on 30 subjects with COPD. Materials and Methods: Subjects were divided into two groups, of which Group A received a diaphragmatic stretch technique with chest PNF and Group B received a manual diaphragmatic release technique with chest PNF. Six-day intervention protocol was given to the participants of both the groups and PEFR, maximum inspiratory pressure, chest expansion, exercise capacity, and dyspnea were assessed before the intervention and after 6 days of intervention. Statistical Analysis: Normality of all continuous data was checked using the Kolmogorov–Smirnov test. Independent t-test was used to analyze the parameters between Group A and Group B. Comparison of difference in pre and post within group was done using independent t-test. Results: Data analyzed in Group A as well as in B, when compared within the group, showed highly significant improvements. When compared between the groups, both the groups showed no difference. Conclusion: The study concluded that there was statistical significance in improvement of PEFR, exercise capacity, dyspnea, chest expansion, and inspiratory pressure within both the groups, but significant changes were not seen between groups. Hence, diaphragmatic stretch and manual release technique along with chest PNF can be used as an alternative/adjunct for the treatment of COPD.

The efficacy of first-line Paclitaxel-Carboplatin with advanced non-small cell lung cancer

ABSTRACT Objective: The aim of this study was to evaluate the outcomes of initial Paclitaxel - Carboplatin (TC) treatment in patients with advanced non - small cell lung cancer. Methods: A total of 38 patients diagnosed with de novo NSCLC stage from IIIB to IV were underwent TC regimen from 2 to 6 cycles between February 2021 and July 2022 at Hue university of medicine and pharmacy hospital and Hue central hospital. They were assessed the response, progression - free survival, overall survival, and toxicity. Results: The mean age was 58.4 ± 6.7. All patients had ECOG scores of 0 and 1. There was 18.4% cases with underweight. The figure for stage IV and non - squamous cell carcinoma (non - SCC) were 86.8% and 84.2%, respectively. 44.7% of patients received Pegfilgrastim. The improvement of cough, chest pain and dyspnea occurred after the first 6 weeks and maintained stable these symptoms until the 12th week. The object response rate (ORR) was 31.6%. The median progress - free survival and overall survival were 7.0 months and 14.0 months, in turn. Adverse events (AEs) at grades 3 or 4 presented 10.6% and 5.2% of patients with neutropenia and anemia. Hepatitis and renal impairment were less common. Conclusion: In patients with previously untreated advanced non - small cell lung cancer, Paclitaxel - Carboplatin not only had efficacy and safety with an acceptable toxicity profile but also reduced the specific symptoms

Sublingual fentanyl for refractory episodic acute dyspnea in patients with advanced chronic obstructive pulmonary disease (COPD): A real-world study

BACKGROUND Dyspnea is an extremely prevalent and debilitating symptom in chronic obstructive pulmonary disease (COPD), affecting up to 74% of patients despite optimal medical therapy. Sublingual fentanyl citrate (SLF) has a fast onset of action and a short half-life, both interesting characteristics to treat acute breakthrough dyspnea without inducing metabolite accumulation. The Montreal Chest Institute (MCI) COPD specialty clinic has been using low-dose SLF for patients with advanced COPD experiencing significant episodic dyspnea despite high intensity inhaled therapy. We present here a retrospective chart review, the largest to date, to report on a “real life” experience. METHODS All included patients had a formal diagnosis of COPD and were seen in the MCI COPD specialty clinic between January 1, 2015 and January 1, 2021. All patients prescribed SLF, irrespective of the duration of use, were enrolled in this chart review. Extent of symptom relief, categorized into either major, intermediate or no improvements, and adverse effects were inferred from in-person or telephone follow-up appointment clinical notes. An exacerbation was defined as a self-reported acute increase in symptoms leading to oral corticosteroid use or hospitalization. Rates of exacerbation and hospitalization in the 12 months before SLF initiation and during SLF use were compared. RESULTS In total, 17 COPD patients were given SLF during the study period. The mean FEV1 was 0.51 L (21% predicted). All participants reported MRC5/5 dyspnea and were prescribed regular low-dose oral morphine for daily breathlessness prior to SLF initiation. Most patients used SLF for more than 6 months, and 76.5% of the study group found intermediate or major improvement in breathlessness episodes. There was no significant change in the rates of exacerbation and admission for acute respiratory failure while on SLF. CONCLUSION In this review, we report real-life, long-term data on severe COPD patients using self-controlled as-needed SLF, showing patient acceptability, an improvement in dyspnea, and limited side effects. Hence, this represents an important step toward the first effective alternative rescue medication for the relief of breakthrough dyspnea since short-acting inhalers. Further study using a randomized trial design is required to confirm the efficacy of this therapy.

Patient-reported outcomes in patients with metastatic non-squamous non-small cell lung cancer from the PERLA trial comparing first-line chemotherapy plus dostarlimab or pembrolizumab.

9099 Background: PERLA (NCT04581824) is a global, randomized, Phase II, double-blind study assessing the efficacy and safety of chemotherapy (CT) combined with programmed death 1 (PD-1) inhibitors dostarlimab (dostCT) and pembrolizumab (pembCT) as first-line (1L) treatment (tx) for patients (pts) with metastatic non-oncogene-driven, non-squamous, NSCLC. DostCT had similar efficacy and safety to pembCT [1]. Exploratory analyses of patient-reported outcomes (PROs) from PERLA have been conducted. Methods: In PERLA, pts with ECOG status 0–1 were randomized 1:1 to receive ≤35 cycles (C) of dostCT or pembCT Q3W (CT was ≤35 cycles [C] of 500 mg/m2 pemetrexed every 3 weeks [Q3W] and ≤4C of cisplatin or carboplatin). PROs were collected at baseline (BL), Q3W until C4, Q9W until C16, Q12W until end of tx and at 30-day safety follow-up. Change from BL in EORTC QLQ-C30 &amp; QLQ-LC13 were analyzed using a longitudinal mixed model, with a ≥10-point change from BL considered clinically meaningful; scores were categorized as improved, stable, or worsened. Time to deterioration (TTD) in QLQ-C30 and selected QLQ-LC13 symptoms were estimated using Kaplan–Meier methods. Results: Analysis populations for dostCT/pembCT included 102/99 pts for QLQ-C30 and 96/90 pts for QLQ-LC13. Completion rates for QLQ-C30 and QLQ-LC13 were &gt;80% up to C4 in both tx arms, decreasing after C7. At C13, 55.0% [n=33/60] and 54.2% [n=32/59] of dostCT pts, and 37.1% [n=23/62] and 35.7% [n=20/56] of pembCT pts completed QLQ-C30 and QLQ-LC13, respectively. Overall, least squares (LS) mean QLQ-C30 and QLQ-LC13 scores remained stable up to C13. Relative to BL, average pt functioning (e.g., physical, role) and cancer symptoms (e.g., pain, cough, dyspnea) were stable through C13 (~1 yr on tx); no clinically meaningful difference in LS mean QLQ-C30 or QLQ-LC13 scores were observed between tx arms. Across most QLQ-C30 and QLQ-LC13 subscales, &gt;60% pts in both tx arms had stable or improved responses up to C13. At C13, meaningful improvements in chest pain and dyspnea were reported in a higher % of dostCT pts (34.4% [n=11/32] and 40.6% [n=13/32], respectively) than pembCT pts (10.0% [n=2/20] and 25.0% [n=5/20], respectively). TTD for QLQ-C30 and QLQ-LC13 subscales were comparable between tx arms, except for longer median TTD in dyspnea in dostCT pts (N=96) than pembCT pts (N=90) (4.24 vs 1.54 months; HR 0.64 [95% CI: 0.44–0.93]). Conclusions: HRQoL was similar and stable through C13 in both tx arms. These results supplement efficacy and safety data reported in PERLA and support further investigation of dostarlimab as an appropriate PD-1 inhibitor for use in combination with standard of care and novel therapies in metastatic NSCLC.

High-dose-rate brachytherapy for airway malignancy a single institution experience

To evaluate clinical outcomes of endobronchial malignancy treated using high-dose-rate endobronchial brachytherapy (HDREB). A retrospective chart review was conducted for all patients treated with HDREB for malignant airway disease between 2010 and 2019 at a single institution. Most patients had a prescription of 14 Gy in two fractions given a week apart. The Wilcoxon signed rank test and paired samples t test were used to compare changes in mMRC dyspnea scale prior to and after brachytherapy at first followup appointment. Toxicity data were collected for dyspnea, hemoptysis, dysphagia, and cough. A total of 58 patients were identified. Most (84.5%) had primary lung cancer with advanced cancers, stage III or IV (86%). Eight were treated while admitted in the ICU. Previous external beam radiotherapy (EBRT) was received by 52%. An improvement in dyspnea was seen in 72%, with an mMRC dyspnoea scale score improvement of 1.13 points (p < 0.001). Most (22, 88%) had an improvement in hemoptysis and 18 out of 37 (48.6%) had an improvement in cough. Grade four to five events occurred in 8 (13%) at the median time of 2.5 months from brachytherapy. Twenty-two patients (38%) had complete obstruction of the airway treated. Median progression free survival was 6.5 months and median survival was 10 months. We report a significant symptomatic benefit among patients receiving brachytherapy with endobronchial malignancy, with rates of treatment related toxicities similar to prior studies. Our study identified new subgroups of patients, ICU patients & those with complete obstruction, who benefited from HDREB.

P485 CONSERVATIVE MANAGEMENT OF A BIOLOGICAL MITRAL VALVE THROMBOSIS IN A PATIENT WITH RECENT COVID19 INFECTION

Abstract Prosthetic valve thrombosis is defined as the presence of non–infectious material, within the valve apparatus, that interferes with the normal function of the prosthesis itself. The rate of thrombosis is normally higher in patients with mechanical valves respect to those with a biological valve. It is a potentially fatal complication of valve replacement surgery. Treatment options include: surgery, fibrinolysis, and anticoagulant therapy; those depending on multiple factors: position of the valve, thrombotic burden, surgical risk, clinical presentation and patient‘s wishes. Complications of SARS–CoV2 infections can also extend beyond the respiratory system, triggering sometimes a systemic pro–inflammatory and pro–thrombotic state with potential cardiovascular complications. We present the case of a 74–year–old man with a mitral bioprosthetic valve (Carpentier–Edwards n29) and an aortic bioprosthesis valve (Carpentier–Edwards pericardial n27) taking anticoagulant therapy (Apixaban) for previous episodes of atrial fibrillation. One year after the surgery, the patient was affected by COVID19 infection characterized by fever and asthenia lasting for about 14 days. Subsequently, he experienced exertional dyspnea with a mitral valve thrombosis (25 mm) as echocardiographic finding and with pulmonary hypertension (PAPs 50 mmHg). After a multidisciplinary team discussion, once signs of peripheral embolization had been ruled out and considering NOAC therapy, it was decided to modify the therapy with low–molecular heparin and subsequently with Warfarin (INR 2.5–3.5). Four days later during a follow–up examination, was observed the improvement of dyspnoea and flow parameters and the reduction of thrombus size (21 mm) without any sign of embolic complications. Considering clinical stability in the following period, it was decided to continue with the same therapy. Subsequent checks showed an unchanged echocardiographic examination with same thrombus dimensions. In order to verify echocardiographic findings, a cardiac CT was performed which confirmed the presence of hypodense material compatible with thrombus formation (11 mm by 15 mm) on the mitral prosthesis.