The Non-Invasive Detection of Pulmonary Exacerbations in Disorders of Mucociliary Clearance with Breath Analysis: A Systematic Review.

Background: Disorders of mucociliary clearance, such as cystic fibrosis (CF), primary ciliary dyskinesia (PCD) and bronchiectasis of unknown origin, are characterised by periods with increased respiratory symptoms, referred to as pulmonary exacerbations. These exacerbations are hard to predict and associated with lung function decline and the loss of quality of life. To optimise treatment and preserve lung function, there is a need for non-invasive and reliable methods of detection. Breath analysis might be such a method. Methods: We systematically reviewed the existing literature on breath analysis to detect pulmonary exacerbations in mucociliary clearance disorders. Extracted data included the study design, technique of measurement, definition of an exacerbation, identified compounds and diagnostic accuracy. Results: Out of 244 identified articles, 18 were included in the review. All studies included patients with CF and two also with PCD. Age and the definition of exacerbation differed between the studies. There were five that measured volatile organic compounds (VOCs) in exhaled breath using gas chromatography with mass spectrometry, two using an electronic nose and eleven measured organic compounds in exhaled breath condensate. Most studies showed a significant correlation between pulmonary exacerbations and one or multiple compounds, mainly hydrocarbons and cytokines, but the validation of these results in other studies was lacking. Conclusions: The detection of pulmonary exacerbations by the analysis of compounds in exhaled breath seems possible but is not near clinical application due to major differences in results, study design and the definition of an exacerbation. There is a need for larger studies, with a longitudinal design, international accepted definition of an exacerbation and validation of the results in independent cohorts.

Evaluation of Nonpharmacologic Interventions and Sleep Outcomes in Hospitalized Medical and Surgical Patients: A Nonrandomized Controlled Trial.

Importance: Inadequate sleep negatively affects patients' physical health, mental well-being, and recovery. Nonpharmacologic interventions are recommended as first-choice treatment. However, studies evaluating the interventions are often of poor quality and show equivocal results. Objective: To assess whether the implementation of nonpharmacologic interventions is associated with improved inpatient night sleep. Design, Setting, and Participants: In a nonrandomized controlled trial, patients were recruited on the acute medical unit and medical and surgical wards of a Dutch academic hospital. All adults who spent exactly 1 full night in the hospital were recruited between September 1, 2019, and May 31, 2020 (control group), received usual care. Patients recruited between September 1, 2020, and May 31, 2021, served as the intervention group. The intervention group received earplugs, an eye mask, and aromatherapy. Nurses received sleep-hygiene training, and in the acute medical unit, the morning medication and vital sign measurement rounds were postponed from the night shift to the day shift. All interventions were developed in collaboration with patients, nurses, and physicians. Main Outcomes and Measures: Sleep was measured using actigraphy and the Dutch-Flemish Patient-Reported Outcomes Measurement Information System sleep disturbance item bank. Other outcomes included patient-reported sleep disturbing factors and the use of sleep-enhancing tools. Results: A total of 374 patients were included (222 control, 152 intervention; median age, 65 [IQR, 52-74] years). Of these, 331 were included in the analysis (195 [59%] men). Most patients (138 [77%] control, 127 [84%] intervention) were in the acute medical unit. The total sleep time was 40 minutes longer in the intervention group (control: median, 6 hours and 5 minutes [IQR, 4 hours and 55 minutes to 7 hours and 4 minutes]; intervention: 6 hours and 45 minutes [IQR, 5 hours and 47 minutes to 7 hours and 39 minutes]; P < .001). This was mainly due to a 30-minute delay in final wake time (median clock-time: control, 6:30 am [IQR, 6:00 am to 7:22 am]; intervention, 7:00 am [IQR, 6:30-7:30 am]; P < .001). Sleep quality did not differ significantly between groups. For both groups, the main sleep-disturbing factors were noises, pain, toilet visits, and being awakened by hospital staff. Sleep masks (23 of 147 [16%]) and earplugs (17 of 147 [12%]) were used most. Nightly vital sign checks decreased significantly (control: 54%; intervention: 11%; P < .001). Conclusions and Relevance: The findings of this study suggest that sleep of hospitalized patients may be significantly improved with nonpharmacologic interventions. Postponement of morning vital sign checks and medication administration rounds from the night to the day shift may be a useful way to achieve this. Trial Registration: Netherlands Trial Registry Identifier: NL7995.

Quantitative analysis of mRNA-1273 COVID-19 vaccination response in immunocompromised adult hematology patients.

Vaccination guidelines for patients treated for hematological diseases are typically conservative. Given their high risk for severe COVID-19, it is important to identify those patients that benefit from vaccination. We prospectively quantified serum immunoglobulin G (IgG) antibodies to spike subunit 1 (S1) antigens during and after 2-dose mRNA-1273 (Spikevax/Moderna) vaccination in hematology patients. Obtaining S1 IgG ≥ 300 binding antibody units (BAUs)/mL was considered adequate as it represents the lower level of S1 IgG concentration obtained in healthy individuals, and it correlates with potent virus neutralization. Selected patients (n = 723) were severely immunocompromised owing to their disease or treatment thereof. Nevertheless, >50% of patients obtained S1 IgG ≥ 300 BAUs/mL after 2-dose mRNA-1273. All patients with sickle cell disease or chronic myeloid leukemia obtained adequate antibody concentrations. Around 70% of patients with chronic graft-versus-host disease (cGVHD), multiple myeloma, or untreated chronic lymphocytic leukemia (CLL) obtained S1 IgG ≥ 300 BAUs/mL. Ruxolitinib or hypomethylating therapy but not high-dose chemotherapy blunted responses in myeloid malignancies. Responses in patients with lymphoma, patients with CLL on ibrutinib, and chimeric antigen receptor T-cell recipients were low. The minimal time interval after autologous hematopoietic cell transplantation (HCT) to reach adequate concentrations was <2 months for multiple myeloma, 8 months for lymphoma, and 4 to 6 months after allogeneic HCT. Serum IgG4, absolute B- and natural killer-cell number, and number of immunosuppressants predicted S1 IgG ≥ 300 BAUs/mL. Hematology patients on chemotherapy, shortly after HCT, or with cGVHD should not be precluded from vaccination. This trial was registered at Netherlands Trial Register as #NL9553.

Hospitalized COVID-19 Patients Were Five Times More Likely to Suffer From Total Sleep Deprivation Compared to Non-COVID-19 Patients; an Observational Comparative Study.

Objectives: Sleeping disorders are a common complaint in patients who suffer from an acute COVID-19 infection. Nonetheless, little is known about the severity of sleep disturbances in hospitalized COVID-19 patients, and whether these are caused by disease related symptoms, hospitalization, or the SARS-CoV-2 virus itself. Therefore, the aim of this study was to compare the quality and quantity of sleep in hospitalized patients with and without COVID-19, and to determine the main reasons for sleep disruption. Methods: This was an observational comparative study conducted between October 1, 2020 and February 1, 2021 at the pulmonary ward of an academic hospital in the Netherlands. This ward contained both COVID-19-positive and -negative tested patients. The sleep quality was assessed using the PROMIS-Sleep Disturbance Short Form and sleep quantity using the Consensus Sleep Diary. Patient-reported sleep disturbing factors were summarized. Results: A total of 79 COVID-19 patients (mean age 63.0, male 59.5%) and 50 non-COVID-19 patients (mean age 59.5, male 54.0%) participated in this study. A significantly larger proportion of patients with COVID-19 reported not to have slept at all (19% vs. 4% of non-COVID-19 patients, p = 0.011). The Sleep quality (PROMIS total score) and quantity (Total Sleep Time) did not significantly differ between both groups ((median PROMIS total score COVID-19; 26 [IQR 17-35], non-COVID-19; 23 [IQR 18-29], p = 0.104), (Mean Total Sleep Time COVID-19; 5 h 5 min, non-COVID-19 mean; 5 h 32 min, p = 0.405)). The most frequently reported disturbing factors by COVID-19 patients were; 'dyspnea', 'concerns about the disease', 'anxiety' and 'noises of other patients, medical staff and medical devices'. Conclusion: This study showed that both patients with and without an acute COVID-19 infection experienced poor quality and quantity of sleep at the hospital. Although the mean scores did not significantly differ between groups, total sleep deprivation was reported five times more often by COVID-19 patients. With one in five COVID-19 patients reporting a complete absence of night sleep, poor sleep seems to be a serious problem. Sleep improving interventions should focus on physical and psychological comfort and noise reduction in the hospital environment.