Moving beyond puberty: Listening to lived experience to expand sexual and reproductive healthcare for adults with muscular dystrophy.

Myotonic dystrophy type 1 (DM1) is the most common form of adult-onset muscular dystrophy with a population-based estimated prevalence of 1 in 2.100, and with a reduced life expectancy of 54–60 years for adult-onset DM1. Respiratory failure is the most frequent cause of death and is due to a complex mechanism of decreased respiratory muscle strength, reduced central respiratory drive, diminished chest wall compliance, and upper airway obstruction. Home mechanical ventilation (HMV), encompassing both invasive and noninvasive ventilation, is presumed to be an effective treatment for chronic respiratory failure in DM1. In clinical practice, HMV in DM1 is most often delivered as noninvasive ventilation. However, studies evaluating the effectiveness of noninvasive HMV in this population are scarce and mainly observational designed without predefined outcome measurements. Randomized controlled trials or prospective studies are lacking. In addition, it is known that HMV is not successful in every DM1 patient, and varies greatly from a very burdensome experience in some, to a highly beneficial treatment in others. Patient selection and treatment adherence remain challenging despite consensus-based recommendations which are completely based on expert opinion rather than backed up by empirical evidence. There is no general agreement on the precise definition of treatment success with regard to HMV. Prolonged survival, reduction of carbon dioxide levels (pCO) and improvement of oxygenation are regarded as important aims to achieve when treating patients with HMV. On the other hand, from a patient's perspective it might be more important to focus on symptom relief, and enhancing or maintaining quality of life and daily functioning. While the pathophysiological pathway from neuromuscular weakness to chronic respiratory failure is largely shared across neuromuscular diseases, important disease-specific differences exist. Evidence from disorders such as amyotrophic lateral sclerosis and Duchenne muscular dystrophy shows that noninvasive HMV improves gas exchange, symptoms, and survival. However, the multisystem nature of DM1, including cognitive impairment and excessive daytime sleepiness, may influence treatment adherence and perceived benefit, underscoring the need for DM1-specific prospective data. Accordingly, in this prospective multicenter study, we aimed to evaluate the effect of noninvasive HMV on gas exchange, quality of life, and daily functioning in DM1 patients following six months of treatment with HMV. A secondary objective was to explore associations between baseline clinical characteristics and treatment response to HMV. A prospective multicenter study was conducted at the four centers of HMV in the Netherlands: Maastricht, Rotterdam, Groningen and Utrecht. These four centers are responsible for all Dutch patients who need HMV. The local Medical Ethics Committee of the Maastricht University Medical Center+ (MUMC+) concluded that the study protocol falls outside the scope of the Medical Research Involving Human Subjects Act (registration number METC2018-0853). The study was conducted according to the applicable research principles. Written informed consent was obtained from all included participants. All adult DM1 patients with an indication to start with noninvasive HMV were asked to participate. HMV indication and inclusion into this study was in accordance with the current consensus-based care recommendations for DM1 patients: at least one or more daytime or nighttime symptoms suggestive of chronic respiratory failure in combination with daytime hypercapnia (PaCO ≥ 6.0 kPa) or evidence of nocturnal hypoventilation (transcutaneous PCO > 6.7 kPa for >50% of total sleep time). Exclusion criteria included: previous treatment with Continuous Positive Airway Pressure (CPAP) or HMV in the past five years; other condition leading to hypercapnia; heart failure New York Heart Association (NYHA) classification 4; unstable angina pectoris. Prior to initiation of HMV, extensive data was collected to characterize the study population. Demographics included CTG (cytosine-thymine-guanine) repeat length, and neurological characterization: the ordinal Medical Research Council (MRC) sum score was used to test muscular strength with a higher score indicating higher muscular strength. The Muscular Impairment Rating Scale (MIRS), a DM1-specific scale for muscle weakness, was used to rate muscular impairment. To assess the pulmonary function, spirometry was performed in every patient (upright sitting and supine). All pulmonary function tests met appropriate standards of the European Respiratory Society/American Thoracic Society. Arterial blood gas analysis was used to assess daytime hypercapnia. When an arterial blood gas was not available, a capillary blood gas was used as an alternative. In order to detect sleep apnea and/or nocturnal hypoventilation, an attended polysomnography (BrainLab RT and Morpheus, Natus Group (OSG) K