Lung cancer screening beliefs in Armenia.

Introduction: In Armenia, an upper-middle income country, 93% of deaths are from non-communicable diseases and over half of the male population smokes. Armenia has more than double the global lung cancer incidence. Over 80% of lung cancer is diagnosed at stages III or IV. However, there is a significant mortality benefit in detecting early-stage lung cancer via screening with low-dose computed tomography. Methods: This study employed a rigorously-translated, previously-validated survey based on the Expanded Health Belief Model to understand how Armenian male smokers' beliefs would affect lung cancer screening participation. Results: Survey responses highlighted key health beliefs that would mediate screening participation. Most respondents felt they were at risk for lung cancer, but over 50% also believed their cancer risk was equivalent to (or less than) non-smokers' risk. Respondents also overwhelmingly agreed a scan could help detect cancer earlier, but fewer agreed early detection could reduce cancer mortality. Important barriers included absence of symptoms and costs of screening and treatment. Discussion: Overall, the potential to reduce lung cancer-related deaths in Armenia is high, but there are a number of central health beliefs and barriers that would limit screening uptake and effectiveness. Improved health education, careful consideration of socioeconomic screening barriers, and appropriate screening recommendations may be useful in overcoming these beliefs.

Evaluating the impact of patient-reported outcome measures on depression and anxiety levels in people with multiple sclerosis: a study protocol for a randomized controlled trial.

BACKGROUND: Multiple sclerosis (MS) is a chronic disease affecting multiple functional aspects of patients' lives. Depression and anxiety are common amongst persons with MS (PwMS). There has been an interest in utilizing patient-reported outcome measures (PROMs) to capture and systematically assess patient's perceptions of their MS experience in addition to other clinical measures, but PROMs are not usually collected in routine clinical practice. Therefore, this study aims to systematically incorporate periodic electronically administered PROMs into the care of PwMS to evaluate its effects on depression and anxiety. METHODS: A randomized controlled trial will be conducted with patients allocated 1:1 to either intervention or conservative treatment groups. Patients in the intervention group will complete PROMs at the start of the study and then every 6 months for 1 year, in addition to having their MS healthcare provider prompted to view their scores. The conservative treatment group will complete PROMs at the start of the study and again after 12 months, and their neurologist will not be able to view their scores. For both groups, pre-determined critical PROM scores will trigger an alert to the patient's MS provider. The difference in change in Hospital Anxiety and Depression Scale score between the intervention and conservative treatment groups at 12 months will be the primary outcome, along with difference in Consultation Satisfaction Questionnaire and CollaboRATE scores at 12 months, and proportion and type of healthcare provider intervention/alerts initiated by different PROMs as secondary outcomes. DISCUSSION: This study will determine the feasibility of utilizing PROMs on an interval basis and its effects on the psychological well-being of PwMS. Findings of this study will provide evidence on use of PROMs in future MS clinical practice. TRIAL REGISTRATION: This trial is registered at the National Institutes of Health United States National Library of Medicine, ClinicalTrials.gov NCT04979546 . Registered on July 28, 2021.

Intraocular Pressure Measurement with Pneumatonometry and a Tonometer Tip Cover During Negative Pressure Application.

Purpose: This is a 2-part study to investigate the agreement between pneumatonometry and direct pressure transducer intraocular pressure (IOP) measurements in a perfusion organ culture (POC) model where (1) the perfusion fluid column is open to atmospheric pressure, holding IOP constant to permit evaluation of the impact of negative pressure (NP) on IOP measurements, and (2) the perfusion fluid column is a closed system, allowing IOP to vary with NP application. Methods: The first part incorporated a fluid column open to atmospheric pressure, maintaining IOP constant to permit evaluation of the effect of applied NP on IOP measurement accuracy. In the second part, the POC column was closed, allowing IOP to vary with NP application and permit evaluation of agreement between pneumatonometry and pressure transducer measurements. In each part, four perfused tissues were used in thirteen paired pre-set IOP (10, 20, 25, 30 mmHg) and NP (0, 5, 10, 15, 20 mmHg) combinations, resulting in a total of 1040 paired measurements (520 per study). The difference in IOP measurements (Δ IOP = Excursion tonometry - pressure transducer) was calculated at each paired configuration. Results: During the first part, the mean Δ IOP was -0.7 ± 1.6 mmHg across all measurements. During the second part, the mean Δ IOP across all measurements was +0.7 ± 1.4 mmHg. At NP settings of -5, -10, -15, and -20 mmHg, across all pre-set IOPs, the mean IOP reduction via Excursion tonometry was 3.1 ± 0.3, 5.6 ± 1.3, 8.5 ± 1.7 and 11.2 ± 1.8 mmHg, respectively. Conclusion: Measurement of IOP via Excursion tonometry yields results within the accuracy range of the pneumatonometry device (per manufacturer) and is minimally impacted by NP application. The IOP-lowering results are consistent with previous studies and further support the effectiveness of the Multi-Pressure Dial in lowering IOP relative to atmospheric pressure.

The Effect of Periocular Negative Pressure Application on Intraocular and Retrobulbar Pressure in Human Cadaver Eyes.

INTRODUCTION: To investigate the effect of applying negative pressure (vacuum) to the periocular space on intraocular pressure (IOP) and retrobulbar pressure (RBP) by use of the Multi-Pressure Dial (MPD) system (Equinox Ophthalmic, Inc.). METHODS: Two eyes of two full body cadavers were studied. In each subject, the retrobulbar space, posterior segment and intra-goggle space were cannulated to provide direct IOP, RBP and intra-goggle pressure measurements via a pressure transducer data acquisition system. The goggles of the MPD system were placed over the eyes of each subject, and multiple test runs were performed, with negative pressure settings programmed to 5, 10 and 20 mmHg. IOP and RBP measurements were continuously obtained during each run and plotted against time for analysis. RESULTS: For both subjects, the mean reduction (± standard deviation) in IOP was 1.6 ± 0.9 (10%), 3.5 ± 1.8 (23%) and 5.6 ± 2.0 (37%) mmHg at programmed negative pressure levels of - 5, - 10 and - 20 mmHg, respectively. The overall mean change in RBP (mmHg) during negative pressure application was 0.02 ± 0.14 at - 5 mmHg, 0.03 ± 0.19 at - 10 mmHg and - 0.01 ± 0.18 at - 20 mmHg. In both subjects, the magnitude of RBP change during application of negative pressure fell below the uncertainty of the measurement system. CONCLUSIONS: The application of negative pressure to the periocular space with the MPD decreases IOP but does not affect RBP.

A 58-Year-Old Man With Episodic Hypercapnic Respiratory Failure.

CASE PRESENTATION: A 58-year-old man presented to the ED with a 1-week history of progressive weight loss, generalized weakness, unsteadiness, and dizziness. In hospital, he experienced a witnessed episode of loss of consciousness with no observable respirations that lasted for 15 minutes. His arterial blood gas demonstrated hypercapnic respiratory failure, and he required mask ventilation and vasoactive medications. Similar episodes occurred several more times over the course of the night that required the patient to be intubated. The paroxysmal episodes persisted necessitating continued invasive ventilatory support and admission to the ICU. The episodes occurred in both awake and asleep states and required the ventilator settings to dictate a minimum rate, but minimal ventilatory support otherwise. Further history revealed other symptomatic complaints of vertigo, dysphagia, and hypophonia that had progressed over a 2-month period. The patient's medical history was pertinent for a diagnosis of prostatic carcinoma 3 years previously that was found to be castrate resistant. He had metastases to his hip, ribs, and thoracic spine. Previous treatments had included bicalutamide, docetaxel, and abiraterone; he was receiving leuprolide therapy on presentation.

Evaluation of negative pressure transfer through tissue in a benchtop cornea and eyelid model.

PURPOSE: A new glaucoma treatment device, known as the multi-pressure dial (MPD), has been introduced, which offers a novel approach to IOP reduction by delivering negative pressure to the periocular region. Clinical studies have demonstrated the IOP-lowering effect of the MPD via direct measurements using pneumatonometry. It remains unclear whether the eyelids, when closed, affect the transmission of negative pressure and subsequently affect IOP reduction. This study aimed to evaluate whether the transfer of negative pressure and subsequent decrease in IOP are altered by the presence of synthetic eyelid tissue. METHODS: A model with 13 different configurations controlling for eyelid material type, presence of slit/opening, and eyelid-cornea contact was employed. The slit modification was employed to mimic the physiologic separation that exists between the eyelids. Baseline IOP within an eye model was set at various levels ranging from 10 to 30 mmHg with applied negative pressure settings of 10, 15, and 20 mmHg utilized at each baseline IOP. The percentage of vacuum transfer was calculated by comparing baseline IOP to resultant IOP measurements following application of vacuum to the system. RESULTS: In the open configuration (without eyelid tissue), the mean % vacuum transfer was 98.7%. The sealed, full-contact configurations exhibited values of 97.4%, 98.8%, and 97.2%. The slit configurations, which closely mimic the physiologic eyelid, demonstrated a mean % vacuum transfer of 98.7% across all settings. CONCLUSIONS: The impact of eyelid tissue on transfer of negative pressure can be isolated and evaluated. The presence of eyelid tissue has an insignificant impact on the transfer of negative pressure, and the IOP reduction achievable with the MPD would not be altered with the eyelids closed.

Postnatal development of persistent inward currents in rat XII motoneurons and their modulation by serotonin, muscarine and noradrenaline.

KEY POINTS: Persistent inward currents (PICs) in spinal motoneurons are long-lasting, voltage-dependent currents that increase excitability; they are dramatically potentiated by serotonin, muscarine, and noradrenaline (norepinephrine). Loss of these modulators (and the PIC) during sleep is hypothesized as a major contributor to REM sleep atonia. Reduced excitability of XII motoneurons that drive airway muscles and maintain airway patency is causally implicated in obstructive sleep apnoea (OSA), but whether XII motoneurons possess a modulator-sensitive PIC that could be a factor in the reduced airway tone of sleep is unknown. Whole-cell recordings from rat XII motoneurons in brain slices indicate that PIC amplitude increases ∼50% between 1 and 23 days of age, when potentiation of the PIC by 5HT2 , muscarinic, or α1 noradrenergic agonists peaks at <50%, manyfold lower than the potentiation observed in spinal motoneurons. α1 noradrenergic receptor activation produced changes in XII motoneuron firing behaviour consistent with PIC involvement, but indicators of strong PIC activation were never observed; in vivo experiments are needed to determine the role of the modulator-sensitive PIC in sleep-dependent reductions in airway tone. ABSTRACT: Hypoglossal (XII) motoneurons play a key role in maintaining airway patency; reductions in their excitability during sleep through inhibition and disfacilitation, i.e. loss of excitatory modulation, is implicated in obstructive sleep apnoea. In spinal motoneurons, 5HT2 , muscarinic and α1 noradrenergic modulatory systems potentiate persistent inward currents (PICs) severalfold, dramatically increasing excitability. If the PICs in XII and spinal motoneurons are equally sensitive to modulation, loss of the PIC secondary to reduced modulatory tone during sleep could contribute to airway atonia. Modulatory systems also change developmentally. We therefore characterized developmental changes in magnitude of the XII motoneuron PIC and its sensitivity to modulation by comparing, in neonatal (P1-4) and juvenile (P14-23) rat brainstem slices, the PIC elicited by slow voltage ramps in the absence and presence of agonists for 5HT2 , muscarinic, and α1 noradrenergic receptors. XII motoneuron PIC amplitude increased developmentally (from -195 ± 12 to -304 ± 19 pA). In neonatal XII motoneurons, the PIC was only potentiated by α1 receptor activation (5 ± 4%). In contrast, all modulators potentiated the juvenile XII motoneurons PIC (5HT2 , 5 ± 5%; muscarine, 22 ± 11%; α1 , 18 ± 5%). These data suggest that the influence of the PIC and its modulation on XII motoneuron excitability will increase with postnatal development. Notably, the modulator-induced potentiation of the PIC in XII motoneurons was dramatically smaller than the 2- to 6-fold potentiation reported for spinal motoneurons. In vivo measurements are required to determine if the modulator-sensitive, XII motoneuron PIC is an important factor in sleep-state dependent reductions in airway tone.

Neuroglia and their roles in central respiratory control; an overview.

While once viewed as mere housekeepers, providing structural and metabolic support for neurons, it is now clear that neuroglia do much more. Phylogenetically, they have undergone enormous proliferation and diversification as central nervous systems grew in their complexity. In addition, they: i) are morphologically and functionally diverse; ii) play numerous, vital roles in maintaining CNS homeostasis; iii) are key players in brain development and responses to injury; and, iv) via gliotransmission, are likely participants in information processing. In this review, we discuss the diverse roles of neuroglia in maintaining homeostasis in the CNS, their evolutionary origins, the different types of neuroglia and their functional significance for respiratory control, and finally consider evidence that they contribute to the processing of chemosensory information in the respiratory network and the homeostatic control of blood gases.