PASC (Post Acute Sequelae of COVID-19) is associated with decreased neutralizing antibody titers in both biological sexes and increased ANG-2 and GM-CSF in females.

Post-acute sequelae of COVID-19 (PASC) or the continuation of COVID-19 (Coronavirus disease 2019) symptoms past 12 weeks may affect as many as 30% of people recovering from a SARS-CoV-2 (severe acute respiratory coronavirus 2) infection. The mechanisms regulating the development of PASC are currently not known; however, hypotheses include virus reservoirs, pre-existing conditions, microblood clots, immune dysregulation, as well as poor antibody responses. Importantly, virus neutralizing antibodies are essential for COVID-19 recovery and protection from reinfection but there is currently limited information on these immune regulators and associated cytokines in PASC patients. Understanding the key drivers of general and specific symptoms associated with Long COVID and the presence of virus neutralizing antibodies in PASC will aid in the development of therapeutics, diagnostics, and vaccines which currently do not exist. We designed a cross-sectional study to investigate systemic antibody and cytokine responses during COVID-19 recovery and PASC. In total, 195 participants were recruited in one of four groups: (1) Those who never had COVID-19 (No COVID); (2) Those in acute COVID-19 recovery (Acute Recovery) (4-12 weeks post infection); (3) Those who recovered from COVID-19 (Recovered) (+ 12 weeks from infection); and (4) those who had PASC (PASC) (+ 12 weeks from infection). Participants completed a questionnaire on health history, sex, gender, demographics, experiences with COVID-19 acute and COVID-19 recovery/continuing symptoms. Serum samples collected were evaluated for antibody binding to viral proteins, virus neutralizing antibody titers, and serum cytokine levels using Ella SimplePlex Immunoassay™ panels. We found participants with PASC reported more pre-existing conditions (e.g. such as hypertension, asthma, and obesity), and PASC symptoms (e.g. fatigue, brain fog, headaches, and shortness of breath) following COVID-19 than COVID-19 Recovered individuals. Importantly, we found PASC individuals to have significantly decreased levels of neutralizing antibodies toward both SARS-CoV-2 and the Omicron BA.1 variant. Sex analysis indicated that female PASC study participants had sustained antibody levels as well as levels of the inflammatory cytokines GM-CSF and ANG-2 over time following COVID-19. Our study reports people experiencing PASC had lower levels of virus neutralizing antibodies; however, the results are limited by the collection time post-COVID-19 and post-vaccination. Moreover, we found females experiencing PASC had sustained levels of GM-CSF and ANG-2. With lower levels of virus neutralizing antibodies, this data suggests that PASC individuals not only have had a suboptimal antibody response during acute SARS-CoV-2 infection but may also have increased susceptibility to subsequent infections which may exacerbate or prolong current PASC illnesses. We also provide evidence suggesting GM-CSF and ANG-2 to play a role in the sex-bias of PASC. Taken together, our findings maybe important for understanding immune molecular drivers of PASC and PASC subgroups.

A Mixed Methods Assessment of Home-Based Video Pretransplant Lung Education.

Introduction: Patients awaiting lung transplantation must learn new information to successfully navigate the transplant process. A supplemental video series was piloted to patients at home during the Covid-19 pandemic to improve pre-transplant education. Methods: A mixed methods study was undertaken to assess patient experiences with this method of education, confirm the ideal timing of the education, and identify gaps that require further attention. Semi-structured interviews were conducted with 17 one-on-one or dyadic (patients and caregivers) who viewed the video series at home. A third-party researcher (not involved in creation of the educational materials) conducted the interviews by phone, which were audio recorded and then transcribed verbatim. NVivo 12 Pro for Windows software was used to code the data and identify emerging themes. Results: Participants indicated that home-based videos were applicable, and informative and helpful (4.7 on 5-point Likert scale) and appreciated the advice and experiences of real patients. They were satisfied with their transplant education (4.2/5). While there were few aspects that the participants disliked about the videos, the interviews elicited outstanding questions about the transplant process (eg, logistical aspects of travel) and transplant concerns (eg, medications, expenses, and precautions in daily life). Conclusion: Patients being assessed or listed for lung transplant valued the novel electronic video education, and we will implement the home-based process into standard of care after the patient's initial visit with the transplant respirologist. Pre-transplant education will be tailored to help address the outstanding gaps identified in this program evaluation.

Pharmacokinetics of apixaban and tacrolimus or cyclosporine in kidney and lung transplant recipients.

Apixaban is frequently used off-label in transplant recipients. However, a potential drug interaction exists with the calcineurin inhibitors. We conducted an open-label drug-drug interaction study to determine the pharmacokinetics of apixaban in lung and kidney transplant recipients who were taking a calcineurin inhibitor. A single dose of apixaban 10 mg was administered orally to kidney and lung transplant recipients maintained on either tacrolimus or cyclosporine, and pharmacokinetic parameters were compared to a reference cohort of 12 healthy subjects who used the same apixaban dose and pharmacokinetic blood sampling. Fourteen participants were enrolled (n = 6 kidney, n = 8 lung), with 10 maintained on tacrolimus and four on cyclosporine. Data from 13 participants was usable. Participants were taking triple therapy immunosuppression and had a mean (SD) of 12 (3) medications. Participants receiving tacrolimus and cyclosporine had area under the plasma concentration-time curve from time zero to infinity (AUC0-inf ) geometric least square means (90% confidence interval [CI]) of 4312 (95% CI 3682, 5049) and 5388 (95% CI 3277, 8858), respectively. Compared to healthy subjects, the associated geometric mean ratios (GMRs) for apixaban maximum plasma concentration (Cmax ), AUC from time zero to the last quantifiable concentration (AUC0-tlast ) and AUC0-inf were 197% (95% CI 153, 295), 244% (95% CI 184, 323), and 224% (95% CI 170, 295) for transplant recipients on tacrolimus. The GMR (90% CI) Cmax , AUC0-tlast , and AUC0-inf of apixaban for patients on cyclosporine were 256% (95% CI 184, 358), 287% (95% CI 198, 415), and 280% (95% CI 195, 401). Kidney and lung transplant recipients receiving tacrolimus had higher apixaban exposure. A similar trend was noted for patients receiving cyclosporine, but additional patients are needed to confirm this interaction. Future studies are needed before apixaban can be safely recommended in this population, and the impact of dose staggering should be investigated. This study highlights the importance of pharmacokinetic studies in actual patient populations.

Variability in Thyroid Cancer Multidisciplinary Team Meeting Recommendations Is Not Explained by Standard Variables: Outcomes of a Single Centre Review.

Multidisciplinary team (MDT) meetings are the mainstay of the decision-making process for patients presenting with complex clinical problems such as papillary thyroid carcinoma (PTC). Adherence to guidelines by MDTs has been extensively investigated; however, scarce evidence exists on MDT performance and variability where guidelines are less prescriptive. We evaluated the consistency of MDT management recommendations for T1 and T2 PTC patients and explored key variables that may influence therapeutic decision making. A retrospective review of the prospective database of all T1 and T2 PTC patients discussed by the MDT was conducted between January 2016 and May 2021. Univariate analysis (with Bonferroni correction significance calculated at p < 0.006) was performed to establish clinical variables linked to completion thyroidectomy and Radioactive iodine (RAI) recommendations. Of 468 patients presented at thyroid MDT, 144 pT1 PTC and 118 pT2 PTC met the selection criteria. Only 18% (n = 12) of pT1 PTC patients initially managed with hemithyroidectomy were recommended completion thyroidectomy. Mean tumour diameter was the only variable differing between groups (p = 0.003). pT2 patients were recommended completion thyroidectomy in 66% (n = 16) of instances. No measured variable explained the difference in recommendation. pT1 patients initially managed with total thyroidectomy were not recommended RAI in 71% (n = 55) of cases with T1a status (p = 0.001) and diameter (p = 0.001) as statistically different variables. For pT2 patients, 60% (n = 41) were recommended RAI post-total thyroidectomy, with no differences observed among groups. The majority of MDT recommendations were concordant for patients with similar measurable characteristics. Discordant recommendations for a small group of patients were not explained by measured variables and may have been accounted for by individual patient factors. Further research into the MDT decision-making process is warranted.

The relationship between attachment, treatment compliance and treatment outcomes in patients with obstructive sleep apnea.

OBJECTIVE: Obstructive sleep apnea (OSA) is a common condition with numerous health and psychological consequences. While treatment with Continuous Positive Airway Pressure (CPAP) is highly effective, it seems to be impacted by interpersonal aspects of the patient. The current study explores the role of two major interpersonal descriptors (attachment and relationship satisfaction) on treatment initiation and compliance with CPAP. The benefit of CPAP treatment on sleep measures and psychological functioning is also examined. METHODS: Participants in stable relationships, diagnosed with OSA following an inpatient polysomnography test (N = 83), were recruited. Participants were appraised on their decision to initiate treatment and completed interpersonal measures (couples' satisfaction, attachment dimensions) as well as sleep measures and mental health measures. Participants were invited to repeat the measures after 3 months (N = 31 agreed). Associations between interpersonal measures and CPAP initiation and compliance as well as the impact of CPAP on sleep and all psychological measures was assessed. RESULTS: Individuals with high attachment anxiety pursued OSA treatment based on a mutual decision with the partner, while individuals with lower attachment anxiety made the decision themselves. Couples' satisfaction was positively associated with CPAP compliance over 3 months. CPAP compliance significantly improved sleep measures, mood and anxiety symptoms. CONCLUSION: The study brings evidence for a positive role of interpersonal factors in the initiation and compliance with OSA treatment as well as longitudinal benefits on sleep, mood and anxiety levels. The results can inform clinical approaches meant to increase treatment engagement and adherence in OSA patients through psychoeducation.

A Qualitative Study to Explore the Needs of Lung Transplant Caregivers.

INTRODUCTION: Providing support throughout the lung transplant process is an intensive task, which requires a dedicated caregiver. The needs of caregivers who must relocate with their loved one receiving the transplant are currently unknown. The objective of this study is to explore experiences and perceptions of lung transplant caregivers identified from a satellite clinic to inform the development of educational resources. METHODS: A qualitative study with a phenomenology approach was undertaken with individuals who have taken on the role of a caregiver for lung transplant candidates or recipients and must travel to the specialized transplant center. Semistructured interviews were conducted with 12 caregivers. Interviews conducted by phone were audio-recorded and then transcribed verbatim. NVivo software was used to code the data and identify emerging themes. RESULTS: Ideas were classified into the following 4 themes: (1) the stress of being a caregiver, (2) caregivers undertake a variety of roles, (3) caregivers require support, and (4) satisfaction with health care providers. Even though the caregivers lived an average of 7.1 (standard deviation 2) hours from the surgical transplant center, all expressed satisfaction with the level of care that they received. Caregivers identified several stressors during the transplant process and described various strategies for coping. CONCLUSION: Caregivers shared their experiences on the transplant process. It was evident that being a caregiver was a stressful and supports were necessary for those undertaking this role. These insights will help inform the development of a new educational resource for patients and caregivers.

An exploration of adult attachment insecurity and psychiatric symptoms in individuals with obstructive sleep apnea.

OBJECTIVE: Obstructive sleep apnea (OSA) is a common sleep disorder, often associated with multiple medical comorbidities as well as psychological difficulties. Among the latter, relationship difficulties as well as mood and anxiety symptoms have been reported, without a clear understanding of the mechanism. In the current study we wanted to further explore these aspects, while comparing groups of OSA individuals with good vs poor sleep. The primary goal of the study was to examine the relationship between sleep and adult attachment and secondly to explore the relationship between sleep and couple satisfaction as well as symptoms of depression and anxiety. METHODS: Following diagnosis of OSA by overnight polysomnography, 102 participants completed several psychological measures (e.g. adult attachment, couple satisfaction, depression and anxiety symptoms) and sleep measures (sleep quality and daytime sleepiness). Variables of interest were compared between the OSA groups with either good/poor sleep quality or no/excessive daytime sleepiness. RESULTS: Adult attachment avoidance was higher in individuals with low sleep quality (mean difference = 0.33, p = .04, d = 0.46) while adult attachment anxiety was higher in individuals with high daytime sleepiness (mean difference = 0.46, p = .04, d = 0.43). Individuals with either poor sleep quality or excessive daytime sleepiness had greater severity of depression and anxiety (both p < .05). CONCLUSIONS: OSA patients with poor sleep quality and excessive daytime sleepiness have greater attachment insecurity and higher levels of depression and anxiety. A multidisciplinary approach including psychological interventions, should be considered in OSA cases with high levels of sleep disturbance.

Readability and Suitability of COPD Consumer Information.

BACKGROUND: Information leaflets have been shown to positively or negatively impact adherence, depending on their content. The objective of this study was to perform an appraisal of the consumer information provided in COPD inhaler monographs. METHODS: COPD inhalers were identified from the Health Canada Drug Product Database. Medication information and instructions for inhaler use were analyzed for readability by seven formulas, with an acceptability threshold of grades 6-8. Three researchers rated suitability using a modified Suitability Assessment of Materials (SAM) tool and assessed leaflets for explicit warnings. RESULTS: Twenty-six inhalers with a COPD indication were evaluated. Medication information sections were rated as "difficult to read" or "hard," and 85% (22/26) had a reading level above grade 8. The instructions for inhaler use were rated as "easy" or "fairly easy" to read and 63% (16/26) met the threshold by all formulas. While all leaflets achieved superior suitability ratings, extreme warnings included risk of premature death (n = 12), risks of serious injury (n = 26), serious interactions (n = 26), and statements that convey a serious consequence to therapy (n = 26). CONCLUSION: While COPD information leaflets in Canada performed well in terms of readability and suitability, overemphasis on side effects, warnings, and precautions may contribute to patient fear and nonadherence.

The utility of the elbow sign in the diagnosis of OSA.

BACKGROUND: Multiple questionnaires have been used to predict the diagnosis of OSA. Such models typically have multiple questions requiring cumulative scoring for interpretation. We wanted to determine whether a simple two-part questionnaire has predictive value in the pretest clinical evaluation for OSA. METHODS: A questionnaire consisting of two questions--(1) Does your bed partner ever poke or elbow you because you are snoring? and (2) Does your bed partner ever poke or elbow you because you have stopped breathing?--was prospectively administered to patients evaluated in a sleep disorders clinic prior to undergoing polysomnography. Age, sex, BMI, and Epworth Sleepiness Scale data were collected. RESULTS: Among the 128 patients who had a polysomnogram, answering "yes" to being awakened for snoring increased the OR of an apnea-hypopnea index≥5/h 3.9 times compared with "no." Answering "yes" to being awakened for apneic spells was associated with an OR of 5.8 for an apnea-hypopnea index≥5/h compared with "no." These associations did not differ by sex, BMI, Epworth Sleepiness Scale or answering "yes" to the other question. Subjects>50 years old with OSA were less likely to report a positive elbow sign and had a significantly lower OR for being awakened for apneic spells than those<50 years old. The sensitivity and specificity of being awakened for apneic spells was 65% and 76%, respectively, with a positive predictive value of 90%. Subgroup analysis revealed that in men with a BMI>31 a positive elbow sign had a specificity of 96.6% for a diagnosis of OSA. CONCLUSIONS: Among patients referred to a sleep disorders clinic, a positive response to being elbowed/poked for apneic spells significantly improves the pretest prediction of OSA.

Normal expiratory flow rate and lung volumes in patients with combined emphysema and interstitial lung disease: a case series and literature review.

Pulmonary function tests in patients with idiopathic pulmonary fibrosis characteristically show a restrictive pattern including small lung volumes and increased expiratory flow rates resulting from a reduction in pulmonary compliance due to diffuse fibrosis. Conversely, an obstructive pattern with hyperinflation results in emphysema by loss of elastic recoil, expiratory collapse of the peripheral airways and air trapping. When the diseases coexist, pulmonary volumes are compensated, and a smaller than expected reduction or even normal lung volumes can be found. The present report describes 10 patients with progressive breathlessness, three of whom experienced severe limitation in their quality of life. All patients showed lung interstitial involvement and emphysema on computed tomography scan of the chest. The 10 patients showed normal spirometry and lung volumes with severe compromise of gas exchange. Normal lung volumes do not exclude diagnosis of idiopathic pulmonary fibrosis in patients with concomitant emphysema. The relatively preserved lung volumes may underestimate the severity of idiopathic pulmonary fibrosis and attenuate its effects on lung function parameters.

Nitrofurantoin-associated bronchiolitis obliterans organizing pneumonia: report of a case.

Bronchiolitis obliterans organizing pneumonia due to nitrofurantoin has rarely been reported and is associated with poor outcomes. A case of nitrofurantoin-associated bronchiolitis obliterans organizing pneumonia responsive to drug withdrawal and corticosteroids is presented.

Hypersensitivity pneumonitis as a cause of airway-centered interstitial fibrosis.

BACKGROUND: Airway-centered interstitial fibrosis (ACIF) has been postulated to be related to environmental exposures. OBJECTIVE: To describe a patient with ACIF associated with hypersensitivity pneumonitis. METHODS: We evaluated a patient with a 2-year history of progressive dyspnea and exercise intolerance. We performed computed tomography, pulmonary function tests, and skin prick tests. RESULTS: The patient's computed tomogram suggested hypersensitivity pneumonitis. Pulmonary function testing demonstrated a restrictive pattern. Results of skin prick tests to chicken, goose, canary, and budgie were negative. However, serum precipitins were positive to serum from pigeon, goose, duck, and chicken feathers. The patient was diagnosed as having ACIF. CONCLUSION: We believe that ACIF may represent a final common pathway for lung injury due to environmental exposure.

Human brain dopamine metabolism in levodopa-induced dyskinesia and wearing-off.

The objective of this study was to identify dopamine (DA) metabolism pattern in Lewy body Parkinson's disease (PD) patients with dyskinesia (Dysk) only, with wearing-off (WO) only, or no motor complications (NMC) induced by levodopa (LD). DA, homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC), and 3-methoxytyramine (3-MT) were measured individual basal ganglia nuclei of nine PD patients who received LD for 6-18 years. Three patients had only Dysk, three only WO, and three had neither Dysk nor WO. Biochemical measurements in PD brains were compared with four non-neurological control brains from individuals matched for age and post-mortem retrieval time. DA levels in the PD were reduced in the caudate by 87% and putamen by 99%. In the caudates, the HVA/DA molar ratio as an index of DA metabolism was similar in the WO and the Dysk patients. However, in the putamen, the ratio of HVA/DA was significantly higher in the WO compared with the Dysk (p = 0.03)and the NMC (p = 0.04) groups of patients. In the putamen, the DOPAC levels were higher in the WO cases while in the Dysk cases, 3-MT levels were higher. The results suggest that in the WO only cases, the putaminal DA was in large measure metabolized intraneuronally while the DA metabolism in our Dysk only patients was mainly extraneuronal. We conclude that the magnitude and the site (intra vs. extraneuronal) of the synaptic DA metabolism in the putamen plays a significant role in LD-induced Dysk and WO.

Clinical-pathological study of levodopa complications.

We sought to determine the continued benefit and the pattern of motor complications of long-term levodopa treatment in Parkinson's disease. Patients were evaluated between 1968 and 1996. Only those who had an adequate levodopa trial and in whom autopsy revealed Lewy body Parkinson's disease were included. Total levodopa and mean daily dose were calculated in each case. Dyskinesia, wearing-off and on-off were collectively classified as motor adverse effects and reported as cumulative incidence. Forty-two patients (male, 30; female, 12) with mean 15.9 years of illness and 9.1 years follow-up received on average 500-mg levodopa daily over 9.8 years. Seventeen of 21 patients assessed during the last 18 months of life reported some motor benefit. Adverse effects were seen in 71.4% of patients. The most common was dyskinesia, in 61.9%; wearing-off in 35.7%; and on-off in 16.7% of patients. The earliest adverse effect was dyskinesia and the last to emerge was on-off. Isolated dyskinesia was seen in 35.7% and wearing-off in 7.1% of patients; 15.5% of patients developed dyskinesia after 2.6 years and 31% after 6.4 years on levodopa. We concluded that levodopa benefit declined and adverse effects increased with time. Dyskinesia was the earliest and the most common isolated adverse effect.