Validity and reliability of the Dutch version of the S3-NIV questionnaire to evaluate long-term noninvasive ventilation.

OBJECTIVES: Noninvasive ventilation (NIV) is an effective treatment for chronic respiratory failure (CRF). Patient-centered outcomes need to be evaluated regularly and the S3-NIV questionnaire seems an applicable tool. We translated this short, self-administered questionnaire into a Dutch version and tested its construct validity and reliability. METHODS: An observational study was conducted, including 127 stable long-term NIV users with CRF or complex sleep related breathing disorders due to different underlying diseases: chronic obstructive pulmonary disease (25%), slowly progressive neuromuscular disorders (35%), rapidly progressive neuromuscular disorders (12%) and 'other disorders' (28%) including complex sleep apnea and obesity hypoventilation syndrome. Construct validity and reliability were tested. RESULTS: The Dutch version of the questionnaire was obtained after a translation and back-translation process. Internal consistency of the total score was good (Cronbach's α coefficient of 0.78) as well as for the 'respiratory symptoms' subdomain and the 'sleep and side effects' subdomain (Cronbach's α coefficient of 0.78 and 0.69, respectively). The reproducibility was excellent with an intraclass correlation of 0.89 (95% CI 0.87-0.93). Construct validity was good for the 'respiratory symptoms' subdomain. CONCLUSION: The Dutch S3-NIV questionnaire is a reliable and valid tool to evaluate symptoms, sleep, and NIV related side effects in long-term NIV users.

Noninvasive Home Mechanical Ventilation in Adult Myotonic Dystrophy Type 1: A Systematic Review.

INTRODUCTION: Chronic hypercapnic respiratory failure induces considerable morbidity and mortality in patients with myotonic dystrophy type 1 (DM1). This study systematically reviews the effects of noninvasive home mechanical ventilation (HMV) on gas exchange, quality of life, survival, and compliance in DM1 patients. METHODS: A systematic Medline and Embase search was performed (January 1995 to January 2020). Records were screened for eligibility criteria, data were extracted from included studies, and risk of bias was assessed. We present findings mainly using a narrative synthesis. RESULTS: Twenty-eight relevant full-text articles were screened for eligibility criteria. Nine studies were included. Randomized controlled trials were not found. Studies had either an observational (n = 8) or interventional (n = 1) design. In the pooled data analysis, HMV showed to improve mean oxygen saturation with 4.8% and decreased mean carbon dioxide values with 3 mm Hg. Compliance varied widely between studies, from no use to more than 12 h per day. Quality of life was not studied extensively, but some studies reported positive effects of HMV on symptoms of chronic respiratory failure. HMV may improve survival in DM1 patients with chronic hypercapnic respiratory failure. CONCLUSION: This review shows that HMV can improve gas exchange and relieve symptoms with a possible survival benefit in DM1 patients with chronic hypercapnic respiratory failure. Future studies should focus on developing strategies to optimize the timing of HMV initiation and to promote compliance.

The Role of Cognition, Affective Symptoms, and Apathy in Treatment Adherence with Noninvasive Home Mechanical Ventilation in Myotonic Dystrophy.

Background: Chronic respiratory failure often occurs in myotonic dystrophy type 1 (DM1) and can be treated with noninvasive home mechanical ventilation (HMV). Treatment adherence with HMV is often suboptimal in patients with DM1, but the reasons for that are not well understood. Objective: The aim of this exploratory study was to gain insight in the prevalence of mild cognitive impairment, affective symptoms, and apathy and to investigate their role in HMV treatment adherence in DM1. Methods: The Montreal Cognitive Assessment (MoCA), the Hospital Anxiety and Depression Scale (HADS), and the Apathy Evaluation Scale (AES) were used to assess cognition, affective symptoms, and apathy in DM1 patients that use HMV. Patients with low treatment adherence (average daily use HMV <5 h or <80% of the days) were compared with patients with high treatment adherence (average daily use of HMV≥5 h and ≥80% of the days). Results: Sixty patients were included. Abnormal scores were found in 40% of the total group for the MoCA, in 72-77% for the AES, and in 18% for HADS depression. There was no difference between the high treatment adherence group (n = 39) and the low treatment adherence group (n = 21) for the MoCA, AES, and HADS depression. The HADS anxiety was abnormal in 30% of the total group, and was significantly higher in the low treatment adherence group (p = 0.012). Logistic regression analysis revealed that a higher age and a higher BMI were associated with a greater chance of high treatment adherence. Conclusions: This exploratory study showed that cognitive impairment and apathy are frequently present in DM1 patients that use HMV, but they are not associated with treatment adherence. Feelings of anxiety were associated with low treatment adherence. Higher age and higher BMI were associated with high treatment adherence with HMV.

Respiratory features of centronuclear myopathy in the Netherlands.

Centronuclear myopathy (CNM) is a heterogeneous group of muscle disorders primarily characterized by muscle weakness and variable degrees of respiratory dysfunction caused by mutations in MTM1, DNM2, RYR1, TTN and BIN1. X-linked myotubular myopathy has been the focus of recent natural history studies and clinical trials. Data on respiratory function for other genotypes is limited. To better understand the respiratory properties of the CNM spectrum, we performed a retrospective study in a non-selective Dutch CNM cohort. Respiratory dysfunction was defined as an FVC below 70% of predicted and/or a daytime pCO2 higher than 6 kPa. We collected results of other pulmonary function values (FEV1/FVC ratio) and treatment data from the home mechanical ventilation centres. Sixty-one CNM patients were included. Symptoms of respiratory weakness were reported by 15/47 (32%) patients. Thirty-three individuals (54%) with different genotypes except autosomal dominant (AD)-BIN1-related CNM showed respiratory dysfunction. Spirometry showed decreased FVC, FEV1 & PEF values in all but two patients. Sixteen patients were using HMV (26%), thirteen of them only during night-time. In conclusion, this study provides insight into the prevalence of respiratory symptoms in four genetic forms of CNM in the Netherlands and offers the basis for future natural history studies.

Role of respiratory characteristics in treatment adherence with noninvasive home mechanical ventilation in myotonic dystrophy type 1, a retrospective study.

Chronic respiratory insufficiency is common in patients with myotonic dystrophy type 1 (DM1) and can be treated with noninvasive home mechanical ventilation (HMV). HMV is not always tolerated well resulting in low treatment adherence. We aimed to analyze if baseline respiratory characteristics such as pulmonary function, level of pCO2 and presence of sleep apnea are associated with HMV treatment adherence in DM1 patients. Pulmonary function testing, polysomnography and blood gas measurement data of DM1 patients were retrospectively collected. Initiation of HMV and treatment adherence after one year was documented. Patients with low treatment adherence (average daily use of HMV <5 h) were grouped with patients that discontinued HMV and compared with patients with high treatment adherence (average daily use of HMV >5 h). HMV was initiated in 101 patients. After one year, 58 patients had low treatment adherence. There were no differences between the low and high treatment adherence group regarding the respiratory characteristics. None of the included predictors (gender, age, body mass index, cytosine-thymine-guanine repeat length, FVC, daytime pCO2, bicarbonate, nighttime pCO2, nighttime base excess, apnea-hypopnea index and mean saturation during sleep) was able to significantly predict high treatment adherence. In conclusion, the respiratory characteristics are not associated with treatment adherence with HMV in DM1 patients and cannot be used to identify patients at risk for low HMV treatment adherence.

A Randomized Trial of Initiation of Chronic Noninvasive Mechanical Ventilation at Home vs In-Hospital in Patients With Neuromuscular Disease and Thoracic Cage Disorder: The Dutch Homerun Trial.

BACKGROUND: There is an increasing demand for home mechanical ventilation (HMV) in patients with chronic respiratory insufficiency. At present, noninvasive ventilation is exclusively initiated in a clinical setting at all four centers for HMV in the Netherlands. In addition to its high societal costs and patient discomfort, commencing HMV is often delayed because of a lack of hospital bed capacity. RESEARCH QUESTION: Is HMV initiation at home, using a telemonitoring approach, noninferior to in-hospital initiation in a nationwide study? STUDY DESIGN AND METHODS: We conducted a nationwide, randomized controlled noninferiority trial, in which every HMV center recruited 24 patients (home [n = 12] vs hospital [n = 12]) with a neuromuscular disease or thoracic cage disorder, all with an indication to start HMV. Change in arterial CO2 (Paco2) over a 6-month period was considered the primary outcome, and quality of life and costs were assessed as secondary outcomes. RESULTS: A total of 96 patients were randomized, most of them diagnosed with neuromuscular disease. We found a significant improvement in Paco2 within both groups (home: from 6.1 to 5.6 kPa [P < .01]; hospital: from 6.3 to 5.6 kPa [P < .01]), with no significant differences between groups. Health-related quality of life showed significant improvement on various subscales; however, no significant differences were observed between the home and hospital groups. From a societal perspective, a cost reduction of more than €3,200 ($3,793) per patient was evident in the home group. INTERPRETATION: This nationwide, multicenter study shows that HMV initiation at home is noninferior to hospital initiation, as it shows the same improvement in gas exchange and health-related quality of life. In fact, from a patient's perspective, it might even be a more attractive approach. In addition, starting at home saves over €3,200 ($3,793) per patient over a 6-month period. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03203577; URL: www.clinicaltrials.gov.

Predictors for long-term mortality in COPD patients requiring non-invasive positive pressure ventilation for the treatment of acute respiratory failure.

INTRODUCTION: The effectiveness of non-invasive mechanical ventilation (NIV) in the management of COPD patients suffering from acute respiratory failure (ARF) as a consequence of exacerbation of the disease, is well established. However, data on long-term outcomes and their predictors, including the individual response to NIV, are scarce. OBJECTIVES: To investigate predictors for short- and long-term mortality in this study population. METHODS: A retrospective cohort study was performed including all patients admitted to the Medium Respiratory Care Unit of Maastricht University Medical Center in Maastricht, the Netherlands, with hospitalized exacerbation of COPD (H-ECOPD) with ARF requiring NIV for the first time between January 2009 and December 2011. An extensive number of potential predictors of outcomes, including the response to NIV, were determined on admission and during hospitalization. Univariate and multivariate logistic regression was used for statistical analysis. RESULTS: Seventy-eight consecutive patients with moderate to severe COPD (mean age 71.0 ± 10.7 years; 48.7% males) were included; In-hospital, 1-year and 2-year mortality rates were 14.1%, 43.6% and 56.4%, respectively. Independent risk factors for 2-year mortality were: advanced age (odds ratio(OR) 1.025; confidence interval (CI) 1.002-1.049; P = 0.037), prolonged NIV use more than 8 days (OR:1.054;CI:1.006-1.104; P = 0.027) and no successful response to NIV (OR:2.392;CI:1.297-4.413; P = 0.005). CONCLUSION: Patients with an H-ECOPD requiring NIV for the first time, constitute a severely ill patient group with high in-hospital and 2-year mortality. This study identified advanced age, NIV use more than 8 days and unsuccessful response to NIV as clinical important independent predictors for long-term mortality.

The frontotemporal syndrome of ALS is associated with poor survival.

Thirty percent of ALS patients have a frontotemporal syndrome (FS), defined as behavioral changes or cognitive impairment. Despite previous studies, there are no firm conclusions on the effect of the FS on survival and the use of non-invasive ventilation (NIV) in ALS. We examined the effect of the FS on survival and the start and duration of NIV in ALS. Behavioral changes were defined as >22 points on the ALS-Frontotemporal-Dementia-Questionnaire or ≥3 points on ≥2 items of the Neuropsychiatric Inventory. Cognitive impairment was defined as below the fifth percentile on ≥2 tests of executive function, memory or language. Classic ALS was defined as ALS without the frontotemporal syndrome. We performed survival analyses from symptom onset and time from NIV initiation, respectively, to death. The impact of the explanatory variables on survival and NIV initiation were examined using Cox proportional hazards models. We included 110 ALS patients (76 men) with a mean age of 62 years. Median survival time was 4.3 years (95 % CI 3.53-5.13). Forty-seven patients (43 %) had an FS. Factors associated with shorter survival were FS, bulbar onset, older age at onset, short time to diagnosis and a C9orf72 repeat expansion. The adjusted hazard ratio (HR) for the FS was 2.29 (95 % CI 1.44-3.65, p < 0.001) in a multivariate model. Patients with an FS had a shorter survival after NIV initiation (adjusted HR 2.70, 95 % CI 1.04-4.67, p = 0.04). In conclusion, there is an association between the frontotemporal syndrome and poor survival in ALS, which remains present after initiation of NIV.

Sleep disturbances associated with periodic leg movements in chronic sarcoidosis.

BACKGROUND AND AIM OF THE WORK: Many sarcoidosis patients suffer from fatigue and sleep disturbances. Recently, it was demonstrated that obstructive sleep apnea (OSA) is rather common in sarcoidosis. Moreover, sheet intolerance and painful legs are frequently reported in sarcoidosis patients. These symptoms might interfere with sleep quality. METHODS: In order to determine the relationship between objective and subjective sleep disturbance full polysomnography, including leg EMG analysis, was performed in 46 chronic sarcoidosis patients indicating awakening unrefreshed in the morning. RESULTS: In 20 (44%) patients OSA activity [60% with PLM (n=12), 40% without (n = 8)] was demonstrated, while in 7 patients (15%) significant PLM without OSA were found. In 19 patients (42%) no OSA or PLM activity was present. Moreover restless legs (RLS) were reported by 52% of the patients (45% in OSA; 71% in PLM; 47% in others). Distribution of sleep stages and sleep fragmentation was comparable in all groups. In a healthy snoring control group (n = 102) a prevalence of PLM was found in 13.7% (17.8% in men; 3.4% in women), while RLS were only reported by 1.4% (men) and 6.9% (women). CONCLUSIONS: Sleep disturbance (OSA and/or PLM) and RLS were demonstrated in more than half of the studied sarcoidosis patients. A high prevalence of RLS or PLM (primary and secondary) has not been reported before in sarcoidosis. Further studies are needed to establish whether RLS, OSA and/or PLM might contribute to fatigue and whether fatigue complaints improve after treatment of RLS/PLM/OSA.

[Home mechanical ventilation in the Netherlands]. / Chronische beademing in Nederland.

Over the last 20 years the number of Dutch patients on home mechanical ventilation has increased from 200 to 2000. Home mechanical ventilation is a cost-effective treatment which significantly improves the quality of life of patients. In 2011 83% of patients on home mechanical ventilation in the Netherlands is living at home. In the future further growth can be expected in the number of patients with obesity hypoventilation syndrome and a potential new group of patients with COPD. Strict conditions are necessary to ensure safety in the complex care that home mechanical ventilation entails.

Upper limb function in adults with Duchenne muscular dystrophy.

OBJECTIVE: To determine upper limb function and associated factors in adults with Duchenne muscular dystrophy. DESIGN: Cross-sectional study. SUBJECTS: A sample of 70 men with Duchenne muscular dystrophy (age range 20-43 years). METHODS: General motor function and, in particular, upper limb distal motor function, were assessed with the Motor Function Measure. Muscle strength and range of motion of the upper limb were evaluated using hand-held dynamo-metry, manual muscle-testing and goniometry. Associations were studied using Spearman's correlation coefficients and multiple linear regression analysis. RESULTS: General motor function was severely impaired. Wide variability was found in distal motor function, muscle strength and range of motion of the upper limb, especially in early adulthood. Muscle strength and range of motion explained 76% of the variance in upper limb distal motor function. CONCLUSION: This study illustrates a large variability in upper limb function in adult patients with Duchenne muscular dystrophy, and identifies muscle strength and range of motion as factors strongly associated with upper limb function. These results suggest that preserving muscle strength and range of motion in Duchenne patients might be relevant for a better outcome of distal motor function of the upper limb when adult.