Safety of Denervation Following Targeted Lung Denervation Therapy for COPD: AIRFLOW-1 Three-year Outcomes

Abstract Background: Targeted lung denervation (TLD) is a novel bronchoscopic therapy that disrupts parasympathetic pulmonary nerve input to the lung reducing clinical consequences of cholinergic hyperactivity. The AIRFLOW-1 study assessed safety and TLD dose in patients with moderate-to-severe, symptomatic COPD. This analysis evaluated the long-term impact of TLD on COPD exacerbations, pulmonary function, and quality of life over three years of follow up.Methods: TLD was performed in a prospective, energy-level randomized (29 W vs 32 W power), multicenter study (NCT02058459). Additional patients were enrolled in an open label confirmation phase to confirm improved gastrointestinal safety after procedural modifications. Durability of TLD was evaluated at one, two, and three years post-treatment and assessed through analysis of COPD exacerbations, pulmonary lung function, and quality of life. Results: Three-year follow-up data were available for 73.9% of patients (n=34). The annualized rate of moderate to severe COPD exacerbations remained stable over the duration of the study. Lung function (FEV1, FVC, RV, and TLC) and quality of life (SGRQ-C and CAT) remained stable over three years of follow-up. No new gastrointestinal adverse events and no unexpected serious adverse events were observed. Conclusion: TLD in COPD patients demonstrated a positive safety profile out to three years, with no late-onset serious adverse events related to denervation therapy. Clinical stability in lung function, quality of life, and exacerbations were observed in TLD treated patients over three years of follow up.

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Safety of denervation following targeted lung denervation therapy for COPD: AIRFLOW-1 3-year outcomes

Respiratory Research ◽

10.1186/s12931-021-01664-5 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Pison Christophe ◽

L. Shah Pallav ◽

Slebos Dirk-Jan ◽

Ninane Vincent ◽

Janssens Wim ◽

...

Keyword(s):

Quality Of Life ◽

Lung Function ◽

Adverse Events ◽

Late Onset ◽

Open Label ◽

Serious Adverse Events ◽

Copd Exacerbations ◽

Clinical Consequences

Abstract Background Targeted lung denervation (TLD) is a novel bronchoscopic therapy that disrupts parasympathetic pulmonary nerve input to the lung reducing clinical consequences of cholinergic hyperactivity. The AIRFLOW-1 study assessed safety and TLD dose in patients with moderate-to-severe, symptomatic COPD. This analysis evaluated the long-term impact of TLD on COPD exacerbations, pulmonary function, and quality of life over 3 years of follow up. Methods TLD was performed in a prospective, energy-level randomized (29 W vs 32 W power), multicenter study (NCT02058459). Additional patients were enrolled in an open label confirmation phase to confirm improved gastrointestinal safety after procedural modifications. Durability of TLD was evaluated at 1, 2, and 3 years post-treatment and assessed through analysis of COPD exacerbations, pulmonary lung function, and quality of life. Results Three-year follow-up data were available for 73.9% of patients (n = 34). The annualized rate of moderate to severe COPD exacerbations remained stable over the duration of the study. Lung function (FEV1, FVC, RV, and TLC) and quality of life (SGRQ-C and CAT) remained stable over 3 years of follow-up. No new gastrointestinal adverse events and no unexpected serious adverse events were observed. Conclusion TLD in COPD patients demonstrated a positive safety profile out to 3 years, with no late-onset serious adverse events related to denervation therapy. Clinical stability in lung function, quality of life, and exacerbations were observed in TLD treated patients over 3 years of follow up.

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Exercise for patients with major depression: a systematic review with meta-analysis and trial sequential analysis

BMJ Open ◽

10.1136/bmjopen-2016-014820 ◽

2017 ◽

Vol 7 (9) ◽

pp. e014820 ◽

Cited By ~ 34

Author(s):

Jesper Krogh ◽

Carsten Hjorthøj ◽

Helene Speyer ◽

Christian Gluud ◽

Merete Nordentoft

Keyword(s):

Quality Of Life ◽

Systematic Review ◽

Adverse Events ◽

Sequential Analysis ◽

Trial Sequential Analysis ◽

Depression Severity ◽

Serious Adverse Events ◽

Secondary Outcomes

ObjectivesTo assess the benefits and harms of exercise in patients with depression.DesignSystematic reviewData sourcesBibliographical databases were searched until 20 June 2017.Eligibility criteria and outcomesEligible trials were randomised clinical trials assessing the effect of exercise in participants diagnosed with depression. Primary outcomes were depression severity, lack of remission and serious adverse events (eg, suicide) assessed at the end of the intervention. Secondary outcomes were quality of life and adverse events such as injuries, as well as assessment of depression severity and lack of remission during follow-up after the intervention.ResultsThirty-five trials enrolling 2498 participants were included. The effect of exercise versus control on depression severity was −0.66 standardised mean difference (SMD) (95% CI −0.86 to −0.46; p<0.001; grading of recommendations assessment, development and evaluation (GRADE): very low quality). Restricting this analysis to the four trials that seemed less affected of bias, the effect vanished into −0.11 SMD (−0.41 to 0.18; p=0.45; GRADE: low quality). Exercise decreased the relative risk of no remission to 0.78 (0.68 to 0.90; p<0.001; GRADE: very low quality). Restricting this analysis to the two trials that seemed less affected of bias, the effect vanished into 0.95 (0.74 to 1.23; p=0.78). Trial sequential analysis excluded random error when all trials were analysed, but not if focusing on trials less affected of bias. Subgroup analyses found that trial size and intervention duration were inversely associated with effect size for both depression severity and lack of remission. There was no significant effect of exercise on secondary outcomes.ConclusionsTrials with less risk of bias suggested no antidepressant effects of exercise and there were no significant effects of exercise on quality of life, depression severity or lack of remission during follow-up. Data for serious adverse events and adverse events were scarce not allowing conclusions for these outcomes.Systematic review registrationThe protocol was published in the journalSystematic Reviews: 2015; 4:40.

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Bilateral hypoglossal nerve stimulation for treatment of adult obstructive sleep apnoea

European Respiratory Journal ◽

10.1183/13993003.01320-2019 ◽

2019 ◽

Vol 55 (1) ◽

pp. 1901320 ◽

Cited By ~ 21

Author(s):

Peter R. Eastwood ◽

Maree Barnes ◽

Stuart G. MacKay ◽

John R. Wheatley ◽

David R. Hillman ◽

...

Keyword(s):

Quality Of Life ◽

Adverse Events ◽

Nerve Stimulation ◽

Hypoglossal Nerve ◽

Sleep Apnoea ◽

Serious Adverse Events ◽

Obstructive Sleep ◽

Device Use ◽

Post Implantation

Background and aimHypoglossal nerve stimulation (HNS) decreases obstructive sleep apnoea (OSA) severity via genioglossus muscle activation and decreased upper airway collapsibility. This study assessed the safety and effectiveness at 6 months post-implantation of a novel device delivering bilateral HNS via a small implanted electrode activated by a unit worn externally, to treat OSA: the Genio™ system.MethodsThis prospective, open-label, non-randomised, single-arm treatment study was conducted at eight centres in three countries (Australia, France and the UK). Primary outcomes were incidence of device-related serious adverse events and change in the apnoea–hypopnoea index (AHI). The secondary outcome was the change in the 4% oxygen desaturation index (ODI). Additional outcomes included measures of sleepiness, quality of life, snoring and device use. This trial was registered with ClinicalTrials.gov, number NCT03048604.Results22 out of 27 implanted participants (63% male, aged 55.9±12.0 years, body mass index (BMI) 27.4±3.0 kg·m−2) completed the protocol. At 6 months BMI was unchanged (p=0.85); AHI decreased from 23.7±12.2 to 12.9±10.1 events·h−1, a mean change of 10.8 events·h−1 (p<0.001); and ODI decreased from 19.1±11.2 to 9.8±6.9 events·h−1, a mean change of 9.3 events·h−1 (p<0.001). Daytime sleepiness (Epworth Sleepiness Scale; p=0.01) and sleep-related quality of life (Functional Outcomes of Sleep Questionnaire-10; p=0.02) both improved significantly. The number of bed partners reporting loud, very intense snoring, or leaving the bedroom due to participant snoring decreased from 96% to 35%. 91% of participants reported device use >5 days per week, and 77% reported use for >5 h per night. No device-related serious adverse events occurred during the 6-month post-implantation period.ConclusionsBilateral HNS using the Genio™ system reduces OSA severity and improves quality of life without device-related complications. The results are comparable with previously published HNS systems despite minimal implanted components and a simple stimulation algorithm.

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Tiotropium (SPIRIVA®) in mild COPD: Is it worth it?

Dalhousie Medical Journal ◽

10.15273/dmj.vol46no1.9827 ◽

2019 ◽

Vol 46 (1) ◽

Author(s):

Lina Mahmoud ◽

Hannah Ng ◽

Jade Roberts

Keyword(s):

Quality Of Life ◽

Exercise Duration ◽

Cochrane Library ◽

Chronic Obstructive ◽

Serious Adverse Events ◽

Main Trial ◽

Copd Exacerbations ◽

Increased Risk ◽

Significant Difference

Purpose:Tiotropium (SPIRIVA®) is used in the treatment of moderate to severe chronic obstructive pulmonary disease (COPD) in patients with persistent dyspnea despite using a short acting bronchodilator (SABD).This paper explores the role of tiotropium in the treatment of mild COPD. Methods:The Cochrane Library, EMBASE, Pubmed, and Clinicaltrials.gov were searched on February 2018.We included randomized controlled trials (RCTs) that evaluated tiotropium in patients with mild COPD.Three authors assessed studies for eligibility. Outcomes included symptoms, quality of life, exercise duration, lung function, COPD exacerbations and hospitalizations, and serious adverse events. Results: Three RCTs were selected as the best available evidence. Based on the results of the main trial, quality of life and symptoms were improved with tiotropium as compared to placebo with a difference between groups at 24 months to be 1.2 (95% CI: 0.5 to 1.9; p=0.0011) using the COPD Assessment test (CAT) score. Frequency of acute exacerbations of COPD (AECOPD) requiring hospitalization was reduced by 10.3% (28.9% with tiotropium vs 39.2% with placebo) in patients receiving tiotropium. One RCT reported no statistically significant difference in exercise duration (27 ± 27 secs) in the tiotropium group vs 50 ± 21 secs in the placebo group; (p=0.4153). Oropharyngeal discomfort was more common with tiotropium (number needed to harm of 12) compared to placebo. Conclusions: Evidence suggests that tiotropium may reduce COPD exacerbations and hospitalizations and improve quality of life in patients with mild COPD.There is an increased risk of oropharyngeal discomfort with tiotropium.

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Gender differences at presentation of idiopathic pulmonary fibrosis in Sweden

BMC Pulmonary Medicine ◽

10.1186/s12890-019-0994-4 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 4

Author(s):

Dimitrios Kalafatis ◽

Jing Gao ◽

Ida Pesonen ◽

Lisa Carlson ◽

C. Magnus Sköld ◽

...

Keyword(s):

Quality Of Life ◽

Gender Differences ◽

Lung Function ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Poor Quality ◽

Smoking History ◽

Cross Sectional

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a disease with poor prognosis mainly affecting males. Differences in clinical presentation between genders may be important both for the diagnostic work-up and for follow-up. In the present study, we therefore explored potential gender differences at presentation in a Swedish cohort of IPF-patients. Methods We studied patients included in the Swedish IPF- registry over a three-year period from its launch in 2014. A cross-sectional analysis was performed for data concerning demographics, lung function, 6- min walking test (6MWT) and quality of life (QoL) (King’s Brief Interstitial Lung Disease (K-BILD) score). Results Three hundred forty- eight patients (250 (72%) males, 98 (28%) females, median age 72 years in both genders) were included in the registry during the study period. Smoking history (N = 169 (68%) vs. N = 53 (54%), p < 0.05), baseline lung function (Forced vital capacity, % of predicted (FVC%): 68.9% ± 14.4 vs. 73.0% ± 17.7, p < 0.05; Total lung capacity, % of predicted (TLC%): 62.2% ± 11.8 vs. 68.6% ± 11.3%, p < 0.001) were significantly different at presentation between males and females, respectively. Comorbidities such as coronary artery disease (OR: 3.5–95% CI: 1.6–7.6) and other cardiovascular diseases (including atrial fibrillation and heart failure) (OR: 3.8–95% CI: 1.9–7.8) also showed significant differences between the genders. The K- BILD showed poor quality of life, but no difference was found between genders in total score (54 ± 11 vs. 54 ± 10, p = 0.61 in males vs. females, respectively). Conclusions This study shows that female patients with IPF have a more preserved lung function than males at inclusion, while males have a significant burden of cardiovascular comorbidities. However, QoL and results on the 6MWT did not differ between the groups. These gender differences may be of importance both at diagnosis and follow- up of patients with IPF.

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Three-year follow-up of prospective trial of focused ultrasound thalamotomy for essential tremor

Neurology ◽

10.1212/wnl.0000000000008561 ◽

2019 ◽

Vol 93 (24) ◽

pp. e2284-e2293 ◽

Cited By ~ 8

Author(s):

Casey H. Halpern ◽

Veronica Santini ◽

Nir Lipsman ◽

Andres M. Lozano ◽

Michael L. Schwartz ◽

...

Keyword(s):

Quality Of Life ◽

Adverse Events ◽

Essential Tremor ◽

Focused Ultrasound ◽

Rating Scale ◽

Prospective Trial ◽

Postural Tremor ◽

Hand Tremor

ObjectiveTo test the hypothesis that transcranial magnetic resonance–guided focused ultrasound (tcMRgFUS) thalamotomy is effective, durable, and safe for patients with medication-refractory essential tremor (ET), we assessed clinical outcomes at 3-year follow-up of a controlled multicenter prospective trial.MethodsOutcomes were based on the Clinical Rating Scale for Tremor, including hand combined tremor–motor (scale of 0–32), functional disability (scale of 0–32), and postural tremor (scale of 0–4) scores, and total scores from the Quality of Life in Essential Tremor Questionnaire (scale of 0–100). Scores at 36 months were compared with baseline and at 6 months after treatment to assess for efficacy and durability. Adverse events were also reported.ResultsMeasured scores remained improved from baseline to 36 months (all p < 0.0001). Range of improvement from baseline was 38%–50% in hand tremor, 43%–56% in disability, 50%–75% in postural tremor, and 27%–42% in quality of life. When compared to scores at 6 months, median scores increased for hand tremor (95% confidence interval [CI] 0–2, p = 0.0098) and disability (95% CI 1–4, p = 0.0001). During the third follow-up year, all previously noted adverse events remained mild or moderate, none worsened, 2 resolved, and no new adverse events occurred.ConclusionsResults at 3 years after unilateral tcMRgFUS thalamotomy for ET show continued benefit, and no progressive or delayed complications. Patients may experience mild degradation in some treatment metrics by 3 years, though improvement from baseline remains significant.Clinicaltrials.gov identifierNCT01827904.Classification of evidenceThis study provides Class IV evidence that for patients with severe ET, unilateral tcMRgFUS thalamotomy provides durable benefit after 3 years.

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Everolimus for the treatment of lymphangioleiomyomatosis: a phase II study

European Respiratory Journal ◽

10.1183/09031936.00210714 ◽

2015 ◽

Vol 46 (3) ◽

pp. 783-794 ◽

Cited By ~ 48

Author(s):

Hilary J. Goldberg ◽

Sergio Harari ◽

Vincent Cottin ◽

Ivan O. Rosas ◽

Elizabeth Peters ◽

...

Keyword(s):

Lung Function ◽

Adverse Events ◽

Mammalian Target Of Rapamycin ◽

Mtor Inhibitors ◽

Collagen Iv ◽

Blood Levels ◽

Forced Expiration ◽

Open Label ◽

Serious Adverse Events ◽

Cystic Lung

Lymphangioleiomyomatosis is a rare, progressive cystic lung disorder characterised by dysregulated activation of mammalian target of rapamycin (mTOR) signalling.This was a phase IIa, multicentre, open-label study of the mTOR inhibitor everolimus (2.5 mg·day−1 escalated to 10 mg·day−1) in 24 women with lymphangioleiomyomatosis. Primary endpoints were safety, pharmacokinetics and serum vascular endothelial growth factor-D (VEGF-D) levels; secondary endpoints were measures of lung function.Following 26 weeks of everolimus treatment, forced vital capacity exhibited stability, while forced expiration volume in 1 s improved from baseline, with mean changes (95% confidence interval) of 10 mL (−111–132) and 114 mL (11–217), respectively; 6-min walk distance improved by 47 m. Median VEGF-D and collagen IV levels decreased from baseline, from 1730 pg·mL−1 to 934.5 pg·mL−1, and 103 ng·mL−1 to 80.5 ng·mL−1, respectively. Adverse events were mostly grade 1−2; mouth ulceration, headache, nausea, stomatitis and fatigue were common. Serious adverse events suspected to be treatment related included peripheral oedema, pneumonia, cardiac failure and Pneumocystis jirovecii infection. Everolimus blood levels increased dose proportionally.In this study, everolimus improved some measures of lung function and exercise capacity and reduced serum VEGF-D and collagen IV. Side effects were generally consistent with known toxicities of mTOR inhibitors, although some were severe.

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Isolated Pubic Ramus Fractures Are Serious Adverse Events for Elderly Persons: An Observational Study on 138 Patients with Fragility Fractures of the Pelvis Type I (FFP Type I)

Journal of Clinical Medicine ◽

10.3390/jcm9082498 ◽

2020 ◽

Vol 9 (8) ◽

pp. 2498 ◽

Cited By ~ 1

Author(s):

Pol Maria Rommens ◽

Johannes Christof Hopf ◽

Michiel Herteleer ◽

Benjamin Devlieger ◽

Alexander Hofmann ◽

...

Keyword(s):

Quality Of Life ◽

Normal Population ◽

Fragility Fractures ◽

Type I ◽

Elderly Persons ◽

Serious Adverse Events ◽

Pubic Ramus ◽

One Year

Background: Fractures of the pubic ramus without involvement of the posterior pelvic ring represent a minority of fragility fractures of the pelvis (FFP). The natural history of patients suffering this FFP Type I has not been described so far. Material and methods: All patients, who were admitted with isolated pubic ramus fractures between 2007 and mid-2018, have been reviewed. Epidemiologic data, comorbidities, in-hospital complications, and one-year mortality were recorded. Of all surviving patients, living condition before the fracture and at follow-up was noted. Mobility was scored with the Parker Mobility Score, quality of life with the European Quality of Life 5 Dimensions 3 Level (EQ-5D-3L), subjective sensation of pain with the Numeric Rating Scale (NRS). Results: A consecutive series of 138 patients was included in the study. There were 117 women (84.8%) and 21 men (15.2%). Mean age was 80.6 years (SD 8.6 years). 89.1% of patients presented with comorbidities, 81.2% of them had cardiovascular diseases. Five patients (4%) died during hospital-stay. Median in-hospital stay was eight days (2–45 days). There were in-hospital complications in 16.5%, urinary tract infections, and pneumonia being the most frequent. One-year mortality was 16.7%. Reference values for the normal population of the same age are 5.9% for men and 4.0% for women. One-year mortality rate was 22.2% in the patient group of 80 years or above and 8.8% in the patient group below the age of 80. The rate of surviving patients living at home with or without assistance dropped from 80.5% to 65.3%. The median EQ-5D-Index Value was 0.62 (0.04–1; IQR 0.5–0.78). Reference value for the normal population is 0.78. Average PMS was 4 and NRS 3. Within a two-year period, additional fragility fractures occurred in 21.2% and antiresorptive medication was taken by only 45.2% of patients. Conclusion. Pubic ramus fractures without involvement of the posterior pelvis (FFP Type I) are serious adverse events for elderly persons. During follow-up, there is an excess mortality, a loss of independence, a restricted mobility, and a decreased quality of life. Pubic ramus fractures are indicators for the need to optimize the patient’s general condition.

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