Indications and evidence for domiciliary noninvasive ventilation.

INTRODUCTION: Home noninvasive ventilation (HNIV) has expanded globally, with a greater evidence base for its use. HNIV improves multiple patient related outcomes in patients with chronic hypercapnic respiratory failure. Obesity hypoventilation syndrome (OHS) is rapidly taking over as the primary indication for HNIV and COPD patients who overlap with obstructive sleep apnea hypoventilation syndromes (OSAHS) and are increasingly recognized but add to the complexity of HNIV prescribing. Optimal settings vary for differing diseases, with higher inspiratory pressures often required in those with OHS and COPD, yet which settings translate into greatest patient benefit remains unknown. AREAS COVERED: We cover the evidence base underpinning the common indications for HNIV in COPD, OHS, neuromuscular disease (NMD), and chest wall disease (CWD) and highlight common HNIV modes used. EXPERT OPINION: Active screening for nocturnal hypoventilation in OHS and COPD may be important to guide earlier ventilation. Further research on which HNIV modalities best improve patient related outcomes and the right time for initiation in different patient phenotypes is rapidly needed. Worldwide, clinical research trials should aim to bridge the gap by reporting on patient-related outcomes and cost effectiveness in real-world populations to best understand the true benefit of HNIV amongst heterogenous patient populations.

Wearable technology interventions in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death and is associated with multiple medical and psychological comorbidities. Therefore, future strategies to improve COPD management and outcomes are needed for the betterment of patient care. Wearable technology interventions offer considerable promise in improving outcomes, but prior reviews fall short of assessing their role in the COPD population. In this systematic review and meta-analysis we searched ovid-MEDLINE, ovid-EMBASE, CINAHL, CENTRAL, and IEEE databases from inception to April 2023 to identify studies investigating wearable technology interventions in an adult COPD population with prespecified outcomes of interest including physical activity promotion, increasing exercise capacity, exacerbation detection, and quality-of-life. We identified 7396 studies, of which 37 were included in our review. Meta-analysis showed wearable technology interventions significantly increased: the mean daily step count (mean difference (MD) 850 (494-1205) steps/day) and the six-minute walk distance (MD 5.81 m (1.02-10.61 m). However, the impact was short-lived. Furthermore, wearable technology coupled with another facet (such as health coaching or pulmonary rehabilitation) had a greater impact that wearable technology alone. Wearable technology had little impact on quality-of-life measures and had mixed results for exacerbation avoidance and prediction. It is clear that wearable technology interventions may have the potential to form a core part of future COPD management plans, but further work is required to translate this into meaningful clinical benefit.

Clinicians' Perspectives of Wearable Technology to Detect and Monitor Exacerbations of Chronic Obstructive Pulmonary Disease: Mixed-Method Survey.

Objective: To investigate clinicians' perspectives on the current use of wearable technology for detecting COPD exacerbations, and to identify potential facilitators and barriers to its adoption in clinical settings. Methods: A mixed-method survey was conducted through an online survey platform involving clinicians working with COPD patients. The questionnaires were developed by an expert panel specialising in respiratory medicine at UCL. The questionnaire evaluated clinicians' perspectives on several aspects: the current extent of wearable technology utilisation, the perceived feasibility, and utility of these devices, as well as the potential facilitators and barriers that hinder its wider implementation. Results: Data from 118 clinicians were included in the analysis. Approximately 80% of clinicians did not currently use information from wearable devices in routine clinical care. A majority of clinicians did not have confidence in the effectiveness of wearables and their consequent impact on health outcomes. However, clinicians highlighted the potential value of wearables in helping deliver personalised care and more rapid assistance. Ease of use, technical support and accessibility of data were considered facilitating factors for wearable utilisation. Costs and lack of technical knowledge were the most frequently reported barriers to wearable utilisation. Conclusion: Clinicians' perspectives of the use of wearable technology to detect and monitor COPD exacerbations are variable. While accessibility and technical support facilitate wearable implementation, cost, technical issues, and knowledge act as barriers. Our findings highlight the facilitators and barriers to using wearables in patients with COPD and emphasise the need to assess patients' perspectives on wearable acceptability.

Factors Affecting Domiciliary Non-Invasive Ventilation Compliance.

Few international studies have investigated factors affecting domiciliary non-invasive ventilation (D-NIV) compliance, and data from the UK are limited. We assessed compliance (defined as ≥ 4 h/night for at least 70% of the time) in a retrospective UK population study, at three time points (0-1 month, 3-4 months and 11-12 months), for all patients commenced on D-NIV over a 5-year period. A total of 359 patients were included. Non-compliant vs. compliant patients were significantly younger (median age 64 (IQR 52-72) vs. 67 (58-75) years, p = 0.032) and more likely to have schizophrenia, consistent at both 3-4 months (5% vs. 1%, p = 0.033) and 11-12 months (5% vs. 2%, p = 0.049). Repeated measures ANOVA demonstrated that the minutes [median (IQR)] of D-NIV used significantly increased at the three time points (0-1 month, 3-4 months and 11-12 months) for patients with hypertension [310 (147.5-431) vs. 341 (89-450) vs. 378 (224.5-477.5), p = 0.003]; diabetes [296.5 (132.5-417.5) vs. 342.5 (94.5-438.5) vs. 382 (247.5-476.25), p = 0.002] and heart failure [293 (177-403) vs. 326 (123-398) vs. 365 (212-493), p = 0.04]. In conclusion, younger and comorbid schizophrenic patients have lower D-NIV compliance rates, and our data suggest that persistence with D-NIV over a year may improve overall use.

Cardiovascular outcomes in patients with COPD-OSA overlap syndrome: A systematic review and meta-analysis.

Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea (OSA) are prevalent respiratory conditions that are independently associated with increased cardiovascular disease (CVD). It is not clear from current evidence whether COPD-OSA overlap syndrome confers an additive risk. This systematic review and meta-analysis investigated whether CVD was more prevalent in patients with overlap syndrome compared to either condition alone. We searched four electronic databases, screened 1826 records against the inclusion criteria. After screening, 18 retrospective, observational studies involving 4613 overlap patients, 16,046 OSA patients and 1679 COPD patients met the inclusion criteria. A random-effects meta-analysis of five studies (I2 = 61%) showed that overlap was associated with a significantly higher risk of hypertension compared to patients with COPD alone (OR = 1.68, 95%CI 1.21-2.35). Overlap was also associated with an increased risk of peripheral vascular disease compared to OSA alone (OR = 3.30 95%CI 2.66-4.10), with a subset of studies also suggesting an increased risk of ischaemic heart disease, heart failure, and cerebrovascular disease. However, it is worth noting that the findings are limited by the considerable heterogeneity of the studies, all of which were observational and retrospective in nature. This review highlights that patients with overlap syndrome have a high prevalence of CVD with some suggestion of an increased risk compared to patients with either condition alone.

The impact of the COVID-19 pandemic on home mechanical ventilation services: A national survey.

The COVID-19 pandemic has caused major disruption to healthcare services globally. We present the findings of a national survey of home mechanical ventilation (HMV) services in England and Wales. 30 HMV services (60%) responded. There was a significant reduction in outpatient services with 93% of services not offering routine face-to-face appointments, although most centres were able to offer emergency appointments for ventilation review and set-up. HMV inpatient capacity was reassigned, and HMV service staff re-deployed in the majority of centres (97%). The initial wave of the COVID-19 pandemic left a service backlog of a median of 87 outpatient appointments [range 0-1500] and a median of 4 patients (range 0-100) awaiting NIV set-up.

Acute hypercapnic respiratory failure and its management on the acute medical take.

Acute hypercapnic respiratory failure accounts for 50 000 hospital admissions each year in the UK. This article discusses the pathophysiology and common causes of acute hypercapnic respiratory failure, and provides practical considerations for patient management in acute medical settings. Non-invasive ventilation for persistent acute hypercapnic respiratory failure is widely recognised to improve patient outcomes and reduce mortality. National audits highlight a need to improve patients' overall care and outcomes through appropriate patient selection and treatment initiation. Multidisciplinary involvement is essential, as this underpins inpatient care and follow up after hospital discharge. New non-invasive ventilation modalities may offer better patient comfort and compensate better for sleep-related changes in respiratory mechanics. Emerging therapies, such as nasal high flow, may offer an alternative treatment approach in those who cannot tolerate non-invasive ventilation, but more research is required to completely understand its effectiveness in treating acute hypercapnic respiratory failure.

Modulations of human resting brain connectivity by kisspeptin enhance sexual and emotional functions.

BACKGROUND: Resting brain connectivity is a crucial component of human behavior demonstrated by disruptions in psychosexual and emotional disorders. Kisspeptin, a recently identified critical reproductive hormone, can alter activity in certain brain structures but its effects on resting brain connectivity and networks in humans remain elusive. METHODS: We determined the effects of kisspeptin on resting brain connectivity (using functional neuroimaging) and behavior (using psychometric analyses) in healthy men, in a randomized double-blinded 2-way placebo-controlled study. RESULTS: Kisspeptin's modulation of the default mode network (DMN) correlated with increased limbic activity in response to sexual stimuli (globus pallidus r = 0.500, P = 0.005; cingulate r = 0.475, P = 0.009). Furthermore, kisspeptin's DMN modulation was greater in men with less reward drive (r = -0.489, P = 0.008) and predicted reduced sexual aversion (r = -0.499, P = 0.006), providing key functional significance. Kisspeptin also enhanced key mood connections including between the amygdala-cingulate, hippocampus-cingulate, and hippocampus-globus pallidus (all P < 0.05). Consistent with this, kisspeptin's enhancement of hippocampus-globus pallidus connectivity predicted increased responses to negative stimuli in limbic structures (including the thalamus and cingulate [all P < 0.01]). CONCLUSION: Taken together, our data demonstrate a previously unknown role for kisspeptin in the modulation of functional brain connectivity and networks, integrating these with reproductive hormones and behaviors. Our findings that kisspeptin modulates resting brain connectivity to enhance sexual and emotional processing and decrease sexual aversion, provide foundation for kisspeptin-based therapies for associated disorders of body and mind. FUNDING: NIHR, MRC, and Wellcome Trust.

Kisspeptin modulates sexual and emotional brain processing in humans.

BACKGROUND: Sex, emotion, and reproduction are fundamental and tightly entwined aspects of human behavior. At a population level in humans, both the desire for sexual stimulation and the desire to bond with a partner are important precursors to reproduction. However, the relationships between these processes are incompletely understood. The limbic brain system has key roles in sexual and emotional behaviors, and is a likely candidate system for the integration of behavior with the hormonal reproductive axis. We investigated the effects of kisspeptin, a recently identified key reproductive hormone, on limbic brain activity and behavior. METHODS: Using a combination of functional neuroimaging and hormonal and psychometric analyses, we compared the effects of kisspeptin versus vehicle administration in 29 healthy heterosexual young men. RESULTS: We demonstrated that kisspeptin administration enhanced limbic brain activity specifically in response to sexual and couple-bonding stimuli. Furthermore, kisspeptin's enhancement of limbic brain structures correlated with psychometric measures of reward, drive, mood, and sexual aversion, providing functional significance. In addition, kisspeptin administration attenuated negative mood. CONCLUSIONS: Collectively, our data provide evidence of an undescribed role for kisspeptin in integrating sexual and emotional brain processing with reproduction in humans. These results have important implications for our understanding of reproductive biology and are highly relevant to the current pharmacological development of kisspeptin as a potential therapeutic agent for patients with common disorders of reproductive function. FUNDING: National Institute for Health Research (NIHR), Wellcome Trust (Ref 080268), and the Medical Research Council (MRC).

Investigating the KNDy Hypothesis in Humans by Coadministration of Kisspeptin, Neurokinin B, and Naltrexone in Men.

CONTEXT: A subpopulation of hypothalamic neurons colocalize three neuropeptides, namely kisspeptin, neurokinin B (NKB), and dynorphin, collectively termed KNDy neurons. Animal studies suggest they interact to affect pulsatile GnRH release (KNDy hypothesis); kisspeptin stimulates, NKB modulates, and dynorphin (an opioid) inhibits. OBJECTIVE: To investigate the KNDy hypothesis in humans, we assessed for the first time the effects of the coadministration of kisspeptin-54, NKB, and an opioid receptor antagonist, naltrexone, on LH pulsatility (surrogate marker for GnRH pulsatility) and gonadotropin release. DESIGN, SETTING, AND PARTICIPANTS: This was an ethically approved prospective, single-blinded, placebo-controlled study. Healthy male volunteers (n = 5/group) attended our research facility for eight study visits. INTERVENTION AND MAIN OUTCOME MEASURE: After 1 hour of baseline blood sampling, participants received a different intervention at each visit: oral 50 mg naltrexone, 8-hour iv infusions of vehicle, 2.56 nmol/kg · h NKB, 0.1 nmol/kg · h kissspeptin-54 (KP) alone and in combination. Frequent blood sampling to measure plasma gonadotropins and sex steroids was conducted and LH pulsatility was determined using blinded deconvolution analysis. RESULTS: All kisspeptin and naltrexone containing groups potently increased LH and LH pulsatility (P < .001 vs vehicle). NKB alone did not affect gonadotropins. NKB+KP had significantly lower increases in gonadotropins compared with kisspeptin alone (P < .01). Naltrexone+KP was the only group to significantly increase LH pulse amplitude (P < .001 vs vehicle). CONCLUSIONS: Our results suggest significant interactions between the KNDy neuropeptides on LH pulsatility and gonadotropin release in humans. This has important implications for improving our understanding of GnRH pulse generation in humans.