Chronic non-invasive ventilation for chronic obstructive pulmonary disease

BACKGROUND: Chronic non-invasive ventilation (NIV) is increasingly being used to treat people with COPD who have respiratory failure, but the evidence supporting this treatment has been conflicting.OBJECTIVES: To assess the effects of chronic non-invasive ventilation at home via a facial mask in people with COPD, using a pooled analysis of IPD and meta-analysis.SEARCH METHODS: We searched the Cochrane Airways Register of Trials, MEDLINE, Embase, PsycINFO, CINAHL, AMED, proceedings of respiratory conferences, clinical trial registries and bibliographies of relevant studies. We conducted the latest search on 21 December 2020.SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing chronic NIV for at least five hours per night for three consecutive weeks or more (in addition to standard care) versus standard care alone, in people with COPD. Studies investigating people initiated on NIV in a stable phase and studies investigating NIV commenced after a severe COPD exacerbation were eligible, but we reported and analysed them separately. The primary outcomes were arterial blood gases, health-related quality of life (HRQL), exercise capacity (stable COPD) and admission-free survival (post-exacerbation COPD). Secondary outcomes for both populations were: lung function, COPD exacerbations and admissions, and all-cause mortality. For stable COPD, we also reported respiratory muscle strength, dyspnoea and sleep efficiency.DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. After inclusion of a study, we requested the IPD. We analysed continuous and time-to-event data using linear- and cox-regression mixed-effect models with a random effect on study level. We analysed dichotomous IPD using generalised estimating equations. We adjusted all models for age and sex. We assessed changes in outcomes after three and 12 months. We also conducted a meta-analysis on aggregated trial data.MAIN RESULTS: We included 14 new RCTs in this review update, in addition to the seven previously included. Seventeen studies investigated chronic NIV in stable COPD and four studies investigated chronic NIV commenced after a severe COPD exacerbation. Three studies compared NIV to sham continuous positive airway pressure (2 to 4 cmH2O). Seven studies used a nasal mask, one study used an oronasal mask and eight studies used both interfaces. Five studies did not report the interface. The majority of trials (20/21) were at high risk of performance bias due to an unblinded design. We considered 11 studies to have a low risk of selection bias and 13 to have a low risk of attrition bias. We collected and analysed the IPD from 13 stable COPD studies (n = 778, 68% of the participants included) and from three post-exacerbation studies (n = 364, 96% of the participants included). In the stable COPD group, NIV probably results in a minor benefit on the arterial partial pressure of oxygen (PaO2) after three months (adjusted mean difference (AMD) 0.27 kPa, 95% CI 0.04 to 0.49; 9 studies, 271 participants; moderate-certainty evidence), but there was little to no benefit at 12 months (AMD 0.09 kPa, 95% CI -0.23 to 0.42; 3 studies, 171 participants; low-certainty evidence). The arterial partial pressure of carbon dioxide (PaCO2) was reduced in participants allocated to NIV after three months (AMD -0.61 kPa, 95% CI -0.77 to -0.45; 11 studies, 475 participants; high-certainty evidence) and persisted up to 12 months (AMD -0.42 kPa, 95% CI -0.68 to -0.16; 4 studies, 232 participants; high-certainty evidence). Exercise capacity was measured with the 6-minute walking distance (minimal clinical important difference: 26 m). There was no clinically relevant effect of NIV on exercise capacity (3 months: AMD 15.5 m, 95% CI -0.8 to 31.7; 8 studies, 330 participants; low-certainty evidence; 12 months: AMD 26.4 m, 95% CI -7.6 to 60.5; 3 studies, 134 participants; very low-certainty evidence). HRQL was measured with the Severe Respiratory Insufficiency and the St. Georges's Respiratory Questionnaire and may be improved by NIV, but only after three months (3 months: standardised mean difference (SMD) 0.39, 95% CI 0.15 to 0.62; 5 studies, 259 participants; very low-certainty evidence; 12 months: SMD 0.15, 95% CI -0.13 to 0.43; 4 studies, 200 participants; very low-certainty evidence). Lastly, the risk for all-cause mortality is likely reduced by NIV (adjusted hazard ratio (AHR) 0.75, 95% CI 0.58 to 0.97; 3 studies, 405 participants; moderate-certainty evidence). In the post-exacerbation COPD group, there was little to no benefit on the PaO2 after three months, but there may be a slight decrease after 12 months (3 months: AMD -0.10 kPa, 95% CI -0.65 to 0.45; 3 studies, 234 participants; low-certainty evidence; 12 months: -0.27 kPa, 95% CI -0.86 to 0.32, 3 studies; 170 participants; low-certainty evidence). The PaCO2 was reduced by NIV at both three months (AMD -0.40 kPa, 95% CI -0.70 to -0.09; 3 studies, 241 participants; moderate-certainty evidence) and 12 months (AMD -0.52 kPa, 95% CI -0.87 to -0.18; 3 studies, 175 participants; high-certainty evidence). NIV may have little to no benefit on HRQL (3 months: SMD 0.25, 95% CI -0.01 to 0.51; 2 studies, 219 participants; very low-certainty evidence; 12 months: SMD 0.25, 95% -0.06 to 0.55; 2 studies, 164 participants; very low-certainty evidence). Admission-free survival seems improved with NIV (AHR 0.71, 95% CI 0.54 to 0.94; 2 studies, 317 participants; low-certainty evidence), but the risk for all-cause mortality does not seem to improve (AHR 0.97, 95% CI 0.74 to 1.28; 2 studies, 317 participants; low-certainty evidence).AUTHORS' CONCLUSIONS: Regardless of the timing of initiation, chronic NIV improves daytime hypercapnia. In addition, in stable COPD, survival seems to be improved and there might be a short term HRQL benefit. In people with persistent hypercapnia after a COPD exacerbation, chronic NIV might prolong admission-free survival without a beneficial effect on HRQL. In stable COPD, future RCTs comparing NIV to a control group receiving standard care might no longer be warranted, but research should focus on identifying participant characteristics that would define treatment success. Furthermore, the optimal timing for initiation of NIV after a severe COPD exacerbation is still unknown.</p

Improvement in hypercapnia does not predict survival in COPD patients on chronic noninvasive ventilation

Purpose: It has recently been shown that chronic noninvasive ventilation (NIV) improves a number of outcomes including survival, in patients with stable hypercapnic COPD. However, the mechanisms responsible for these improved outcomes are still unknown. The aim of the present study was to identify parameters associated with: 1) an improved arterial partial pressure of carbon dioxide (PaCO2) and 2) survival, in a cohort of hypercapnic COPD patients treated with chronic NIV. Patients and methods: Data from 240 COPD patients treated with chronic NIV were analyzed. Predictors for the change in PaCO2 and survival were investigated using multivariate linear and Cox regression models, respectively. Results: A higher level of bicarbonate before NIV initiation, the use of higher inspiratory ventilator pressures, the presence of anxiety symptoms, and NIV initiated following an exacerbation compared to NIV initiated in stable disease were associated with a larger reduction in PaCO2. A higher body mass index, a higher FEV1, a lower bicarbonate before NIV initiation, and younger age and NIV initiation in stable condition were independently associated with better survival. The change in PaCO2 was not associated with survival, neither in a subgroup of patients with a PaCO2 >7.0 kPa before the initiation of NIV. Conclusion: Patients with anxiety symptoms and a high bicarbonate level at NIV initiation are potentially good responders in terms of an improvement in hypercapnia. Also, higher inspiratory ventilator pressures are associated with a larger reduction in PaCO2. However, the improvement in hypercapnia does not seem to be associated with an improved survival and emphasizes the need to look beyond PaCO2 when considering NIV initiation

Original Article

By using a new method for estimation of histamine, evolved in Pharmacological Department of our Univesity, a study was made on the relation between histamine and hemothorax, in order to determine the part which a vascular factor may play in the development of hemothorax following resection of the lung. In animal experiments using grown-up dogs, it was observed that performing thoracotomy and lung operation, as well as anoxia, caused histamine in the pulmonary veins to increase. In rabbits in which pleurisy and hemothorax had been experimentally induced, it was observed that the amount of histamine in the blood and thoracic exudation showed an increase immediately after induction of inflammation. Histopathologic investigation showed a multiplication of mast cells in the pleural cavity of rabbits in which hemothorax had experimentally been induced. There was an increase in the amount of histamine in the blood and thoracic exudation in 23 patients who had undergone resection of the lung ; some showed a sudden decrease, while some a gradual increase. A study made on the relation between the amount of histamine and the amount of blood lost during operation and aspirated after operation showed that the greater the amount of histamine, the greater was the amount of blood wasted during and after operation and the higher was a tendency to postoperative development of hemothorax. Histamine, having actions of dilating the capillaries and promoting their permeability and of lowering resistance of the blood vessels, may cause hemothorax to occur when it is abnormally increased in amount

Quality Improvement of Pancreatic Surgery by Centralization in the Western Part of the Netherlands

BACKGROUND: Centralization of pancreatic surgery in high-volume hospitals is under debate in many countries. In the western part of the Netherlands, the professional network of surgical oncologists agreed to centralize all pancreatic surgery from 2006 in two high-volume hospitals. Our aim is to evaluate whether centralization of pancreatic surgery has improved clinical outcomes and has changed referral patterns. MATERIALS AND METHODS: Data of the Comprehensive Cancer Centre West (CCCW) of all 249 patients who had a resection for suspected pancreatic cancer between 1996 and 2008 in the western part of the Netherlands were analyzed. Multivariable modeling was used to evaluate survival for 3 time periods; 1996–2000, 2001–2005 (introduction of quality standards), and 2006–2008 (after centralization). In addition, the differences in referral pattern were analyzed. RESULTS: From 2006, all pancreatic surgery was centralized in 2 hospitals. The 2-year survival rate increased after centralization from 39% to 55% (P = .09) for all patients who had a pancreatic resection for pancreatic cancer. After adjustment for age, tumor location, stage, histology, and adjuvant treatment, the latter period was significantly associated with improved survival (hazard ratio [HR] 0.50; 95% confidence interval [95% CI] 0.34–0.73). CONCLUSIONS: Centralization of pancreatic surgery was successful and has resulted in improved clinical outcomes in the western part of the Netherlands, demonstrating the effectiveness of centralization

Home initiation of chronic non-invasive ventilation in COPD patients with chronic hypercapnic respiratory failure:a randomised controlled trial

Introduction Chronic non-invasive ventilation (NIV) has become evidence-based care for stable hypercapnic COPD patients. While the number of patients increases, home initiation of NIV would greatly alleviate the healthcare burden. We hypothesise that home initiation of NIV with the use of telemedicine in stable hypercapnic COPD is non-inferior to in-hospital NIV initiation. Methods Sixty-seven stable hypercapnic COPD patients were randomised to initiation of NIV in the hospital or at home using telemedicine. Primary outcome was daytime arterial carbon dioxide pressure (PaCO 2) reduction after 6 months NIV, with a non-inferiority margin of 0.4 kPa. Secondary outcomes were health-related quality of life (HRQoL) and costs. Results Home NIV initiation was non-inferior to in-hospital initiation (adjusted mean difference in PaCO 2 change home vs in-hospital: 0.04 kPa (95% CI-0.31 to 0.38 kPa), with both groups showing a PaCO 2 reduction at 6 months compared with baseline (home: from 7.3±0.9 to 6.4±0.8 kPa (p<0.001) and in-hospital: from 7.4±1.0 to 6.4±0.6 kPa (p<0.001)). In both groups, HRQoL improved without a difference in change between groups (Clinical COPD Questionnaire total score-adjusted mean difference 0.0 (95% CI-0.4 to 0.5)). Furthermore, home NIV initiation was significantly cheaper (home: median €3768 (IQR €3546-€4163) vs in-hospital: median €8537 (IQR €7540-€9175); p<0.001). Discussion This is the first study showing that home initiation of chronic NIV in stable hypercapnic COPD patients, with the use of telemedicine, is non-inferior to in-hospital initiation, safe and reduces costs by over 50%. Trial registration number NCT02652559

Schema therapy for emotional dysregulation: Theoretical implication and clinical applications

The term emotional dysregulation refers to an impaired ability to regulate unwanted emotional states. Scientific evidence supports the idea that emotional dysregulation underlies several psychological disorders as, for example: personality disorders, bipolar disorder type II, interpersonal trauma, anxiety disorders, mood disorders and posttraumatic stress disorder. Emotional dysregulation may derive from early interpersonal traumas in childhood. These early traumatic events create a persistent sensitization of the central nervous system in relation to early life stressing events. For this reason, some authors suggest a common endophenotypical origin across psychopathologies. In the last 20 years, cognitive behavioral therapy has increasingly adopted an interactiveontogenetic view to explain the development of disorders associated to emotional dysregulation. Unfortunately, standard Cognitive Behavior Therapy (CBT) methods are not useful in treating emotional dysregulation. A CBT-derived new approach called Schema Therapy (ST), that integrates theory and techniques from psychodynamic and emotion focused therapy, holds the promise to fill this gap in cognitive literature. In this model, psychopathology is viewed as the interaction between the innate temperament of the child and the early experiences of deprivation or frustration of the subject\u2019s basic needs. This deprivation may lead to develop early maladaptive schemas (EMS), and maladaptive Modes. In the present paper we point out that EMSs and Modes are associated with either dysregulated emotions or with dysregulatory strategies that produce and maintain problematic emotional responses. Thanks to a special focus on the therapeutic relationship and emotion focused-experiential techniques, this approach successfully treats severe emotional dysregulation. In this paper, we make several comparisons between the main ideas of ST and the science of emotion regulation, and we present how to conceptualize pathological phenomena in terms of failed regulation and some of the ST strategies and techniques to foster successful regulation in patients

High torque tenovirus (TTV) load before first vaccine dose is associated with poor serological response to COVID-19 vaccination in lung transplant recipients

BACKGROUND: : Serological responses to COVID-19 vaccination are diminished in recipients of solid organ transplants, especially in lung transplant recipients (LTR), probably as result of immunosuppressive treatment. There is currently no marker of immunosuppression that can be used to predict the COVID-19 vaccination response. Here, we study whether torque tenovirus (TTV), a highly prevalent virus can be used as an indicator of immunosuppression. METHODS: : The humoral response to the mRNA 1273 vaccine was assessed in 103 LTR, who received a transplant between 4 and 237 months prior to vaccination, by measuring Spike (S)-specific IgG levels at baseline, 28 days after first, and 28 days after the second vaccination. TTV loads were determined by RT-PCR and Pearson's correlation coefficient was calculated to correlate serological responses to TTV load. RESULTS: : Humoral responses to COVID-19 vaccination were observed in 41/103 (40%) LTR at 28 days after the second vaccination. 62/103 (60%) were non-responders. Lower TTV loads at baseline (significantly) correlated with higher S-specific antibodies and a higher percentage of responders. Lower TTV loads also strongly correlated with longer time since transplantation, indicating that participants with lower TTV loads were longer after transplantation. CONCLUSIONS: : This study shows a better humoral response to the SARS-CoV-2 vaccine in subjects with a lower TTV load pre-vaccination. In addition, TTV load correlates with the time after transplantation. Further studies on the use of TTV load in vaccination efficacy studies in immunocompromised cohorts should provide leads for the potential use of this marker for optimizing vaccination response

A rare polymorphism in Toll Like Receptor 2 is associated with systemic sclerosis phenotype and increases production of inflammatory mediators

T.R. was sponsored by the Dutch association of Research (NWO). J.M. was sponsored by grants SAF2009-1110, cts-4977 T.R. and J.M. were sponsored by the Orphan Disease program grant from the European League Againts Rheumatism (EULAR)Peer Reviewe

A Restricted Role for FcγR in the Regulation of Adaptive Immunity.

By their interaction with IgG immune complexes, FcγR and complement link innate and adaptive immunity, showing functional redundancy. In complement-deficient mice, IgG downstream effector functions are often impaired, as well as adaptive immunity. Based on a variety of model systems using FcγR-knockout mice, it has been concluded that FcγRs are also key regulators of innate and adaptive immunity; however, several of the model systems underpinning these conclusions suffer from flawed experimental design. To address this issue, we generated a novel mouse model deficient for all FcγRs (FcγRI/II/III/IV-/- mice). These mice displayed normal development and lymphoid and myeloid ontogeny. Although IgG effector pathways were impaired, adaptive immune responses to a variety of challenges, including bacterial infection and IgG immune complexes, were not. Like FcγRIIb-deficient mice, FcγRI/II/III/IV-/- mice developed higher Ab titers but no autoantibodies. These observations indicate a redundant role for activating FcγRs in the modulation of the adaptive immune response in vivo. We conclude that FcγRs are downstream IgG effector molecules with a restricted role in the ontogeny and maintenance of the immune system, as well as the regulation of adaptive immunity