Mucus clears from the trachea in a helix: a new twist to understanding airway diseases.

BACKGROUND: Mucociliary clearance (MCC) is critical to lung health and is impaired in many diseases. The path of MCC may have an important impact on clearance but has never been rigorously studied. The objective of this study is to assess the three-dimensional path of human tracheal MCC in disease and health. METHODS: Tracheal MCC was imaged in 12 ex-smokers, 3 non-smokers (1 opportunistically imaged during acute influenza and repeated after recovery) and 5 individuals with primary ciliary dyskinesia (PCD). Radiolabelled macroaggregated albumin droplets were injected into the trachea via the cricothyroid membrane. Droplet movement was tracked via scintigraphy, the path of movement mapped and helical and axial models of tracheal MCC were compared. MEASUREMENTS AND MAIN RESULTS: In 5/5 participants with PCD and 1 healthy participant with acute influenza, radiolabelled albumin coated the trachea and did not move. In all others (15/15), mucus coalesced into globules. Globule movement was negligible in 3 ex-smokers, but in all others (12/15) ascended the trachea in a helical path. Median cephalad tracheal MCC was 2.7 mm/min ex-smokers vs 8.4 mm/min non-smokers (p=0.02) and correlated strongly to helical angle (r=0.92 (p=0.00002); median 18o ex-smokers, 47o non-smokers (p=0.036)), but not to actual speed on helical path (r=0.26 (p=0.46); median 13.6 mm/min ex-smokers vs 13.9 mm/min non-smokers (p=1.0)). CONCLUSION: For the first time, we show that human tracheal MCC is helical, and impairment in ex-smokers is often caused by flattened helical transit, not slower movement. Our methodology provides a simple method to map tracheal MCC and speed in vivo.

Restless legs syndrome.

BACKGROUND: Restless legs syndrome (RLS) is a common sensorimotor disorder causing significant distress and is commonly seen in the primary care setting. OBJECTIVE: This article outlines the epidemiology, pathophysiology, diagnosis and management of RLS, with a focus on the primary care setting. DISCUSSION: RLS is a clinical diagnosis, although mimics exist. Brain iron deficiency, dopaminergic dysfunction and genetics underpin the poorly understood pathophysiology of this common condition. After repleting iron stores, reviewing any exacerbating medications and attending to non-pharmacological management options, there are pharmacological options that prove to be effective, although with class-specific effects that need to be considered.

Mechanisms of gas transfer impairment utilizing nitric oxide following severe COVID-19 pneumonitis.

Reduced carbon monoxide diffusing capacity (DLCO ) is common after recovery from severe COVID-19 pneumonitis. The extent to which this relates to alveolar membrane dysfunction as opposed to vascular injury is uncertain. Simultaneous measurement of nitric oxide diffusing capacity (DLNO ) and DLCO can partition gas diffusion into its two components: alveolar-capillary membrane conductance (DmCO ) and capillary blood volume (VC ). We sought to evaluate DmCO and VC in the early and later recovery periods after severe COVID-19. Patients attended for post-COVID-19 clinical review and lung function testing including DLNO /DLCO . Repeat testing occurred when indicated and comparisons made using t-tests. Forty-nine (eight female) subjects (mean ± SD age: 58 ± 13, BMI: 34 ± 8) who had severe COVID-19 pneumonitis, WHO severity classification of 6 ± 1, and prolonged (21 ± 22 days) hospital stay, were assessed 2 months (61 ± 35 days) post discharge. DLCO adj (z-score -1.70 ± 1.49, 25/49 < lower limit of normal [LLN]) and total lung capacity (z-score -1.71 ± 1.30) were both reduced. DmCO and VC and were reduced to a similar extent (z-score -1.19 ± 1.05 and -1.41 ± 1.20, p = 0.4). Seventeen (one female) patients returned for repeat testing 4 months (122 ± 61 days) post discharge. In this subgroup with more impaired lung function, DLCO adj improved but remained below LLN (z-score -3.15 ± 0.83 vs. -2.39 ± 0.86, p = 0.01), 5/17 improved to >LNN. DmCO improved (z-score -2.05 ± 0.89 vs. -1.41 ± 0.78, p = 0.01) but VC was unchanged (z-score -2.51 ± 0.55 vs. -2.29 ± 0.59, p = 0.16). Alveolar membrane conductance is abnormal in the earlier recovery phase following severe COVID-19 but significantly improves. In contrast, reduced VC persists. These data raise the possibility that persisting effects of acute vascular injury may contribute to gas diffusion impairment long after severe COVID-19 pneumonitis.

Lung Health in the Solomon Islands: A Mixed Methods Study.

BACKGROUND AND OBJECTIVES: Despite a population of 600,000 people from 900 islands, there is little published data on the prevalence of lung disease in the Solomon Islands. We sought to 1) estimate the prevalence of obstructive lung disease (OLD) in Gizo, Solomon Islands, 2) identify risk factors for respiratory disease in this population and 3) review current management practices for respiratory disease through an audit of local emergency department (ED) presentations. METHODS: A two-part mixed methods study was performed between March and May 2019; the first was a population-based, cross-sectional study conducted in Gizo, Solomon Islands, with a random sample undergoing questionnaires and spirometry. The second was an audit of Gizo Hospital ED records to assess presentation numbers, diagnoses and outcomes. RESULTS: A total of 104 patients were randomly selected for spirometry. The mean age was 46.9 years. Current smoking rates were high (24.0% overall, 43.3% age < 40, 16.2% age ≥ 40) as was regular (>10h/week) exposure to indoor/enclosed wood fire ovens (51.5%). The prevalence of COPD was 3.2% overall. A further 9.7% of participants demonstrated significant bronchodilator responsiveness suggestive of possible asthma. Most patients seen in ED presented with a respiratory condition or fever/viral illness, but spirometry was not available. Only four outpatients were prescribed salbutamol and two patients inhaled corticosteroid. CONCLUSION: There appears to be a high burden of obstructive lung disease in the Solomon Islands with high smoking rates, indoor smoke exposure and bronchodilator responsiveness. Respiratory symptoms are common amongst hospital ED presentations; however, inhaled asthma treatments are infrequently prescribed to outpatients.

The SaniPath Exposure Assessment Tool: A quantitative approach for assessing exposure to fecal contamination through multiple pathways in low resource urban settlements.

Inadequate sanitation can lead to exposure to fecal contamination through multiple environmental pathways and can result in adverse health outcomes. By understanding the relative importance of multiple exposure pathways, sanitation interventions can be tailored to those pathways with greatest potential public health impact. The SaniPath Exposure Assessment Tool allows users to identify and quantify human exposure to fecal contamination in low-resource urban settings through a systematic yet customizable process. The Tool includes: a project management platform; mobile data collection and a data repository; protocols for primary data collection; and automated exposure assessment analysis. The data collection protocols detail the process of conducting behavioral surveys with households, school children, and community groups to quantify contact with fecal exposure pathways and of collecting and analyzing environmental samples for E. coli as an indicator of fecal contamination. Bayesian analyses are used to estimate the percentage of the population exposed and the mean dose of fecal exposure from microbiological and behavioral data. Fecal exposure from nine pathways (drinking water, bathing water, surface water, ocean water, open drains, floodwater, raw produce, street food, and public or shared toilets) can be compared through a common metric-estimated ingestion of E. coli units (MPN or CFU) per month. The Tool generates data visualizations and recommendations for interventions designed for both scientific and lay audiences. When piloted in Accra, Ghana, the results of the Tool were comparable with that of an in-depth study conducted in the same neighborhoods and highlighted consumption of raw produce as a dominant exposure pathway. The Tool has been deployed in nine cities to date, and the results are being used by local authorities to design and prioritize programming and policy. The SaniPath Tool is a novel approach to support public-health evidence-based decision-making for urban sanitation policies and investments.

Variation in E. coli concentrations in open drains across neighborhoods in Accra, Ghana: The influence of onsite sanitation coverage and interconnectedness of urban environments.

Alongside efforts to improve safe management of feces along the entire sanitation chain, including after the toilet, global sanitation efforts are focusing on universal access 'basic' services: onsite facilities that safely contain excreta away from human contact. Although fecal sludge management is improving in urban areas, open drains remain a common fate for feces in these often densely-populated neighborhoods in low-income countries. To-date, it is unclear to what extent complete coverage of onsite sanitation reduces fecal contamination in the urban environment and how fecal contamination varies within urban drains across neighborhoods by sanitation status within a city. We assessed how neighborhood levels of environmental fecal contamination (via spatially-representative sampling of open drains for E. coli) varied across four neighborhoods with varying income, type and coverage of household sanitation facilities, and population density in Accra, Ghana. Neighborhoods with very high sanitation coverage (≥89%) still had high (>4 log10 CFU/100 mL) E. coli concentrations in drains. Between-neighborhood variation in E. coli levels among the high coverage neighborhoods was significant: drain concentrations in neighborhoods with 93% and 89% coverage (4.7 (95% CI: 4.5, 4.9) & 4.9 (95% CI: 4.5, 5.3) log10 CFU/100 mL, respectively) were higher than in the neighborhood with 97% coverage (4.1 log10 CFU/100 mL, 95% CI: 3.8, 4.4 log10 CFU/100 mL). Compared with the highest coverage neighborhood, the neighborhood with lowest coverage (48%) also had higher E. coli concentrations (5.6 log10 CFU/100 mL, 95% CI: 5.3, 5.9 log10 CFU/100 mL). Although fecal contamination in open drains appeared lower in neighborhoods with higher onsite sanitation coverage (and vice versa), other factors (e.g. fecal sludge management, animals, population density) may affect drain concentrations. These results underscore that neighborhood-level onsite sanitation improvements alone may not sufficiently reduce fecal hazards to public health from open drains. These findings supporting the need for integrated, city-level fecal sludge management alongside multifaceted interventions to reduce fecal contamination levels and human exposure.

Management of recurrent haemoptysis in malignancy with combined TISSEEL and intrabronchial valves.

Management of recurrent haemoptysis poses a difficult clinical scenario. TISSEEL (Baxter Healthcare Corporation Deerfield, IL, USA) is a fibrin sealant often used in surgery to aid control of bleeding. However, when endoscopic TISSEEL is used independently, migration, dislodgement, or even expectoration of the fibrin clot is a common complication that may lead to recurrence of haemoptysis. Here we describe two patients with recurrent haemoptysis in the context of malignancy who underwent bronchoscopy, during which they were managed with application of topical TISSEEL to the bleeding area, followed by deployment of an intrabronchial valve, followed by a further application of TISSEEL over the valve. The combination of TISSEEL and intrabronchial valve appeared to control haemoptysis and was resistant to expectoration or migration in these two cases. Thus, this combination may provide a safe and effective therapeutic option for the control of bronchial bleeding secondary to malignancy.

Intake of Sugar-sweetened Beverages and Fecundability in a North American Preconception Cohort.

BACKGROUND: Dietary factors, including sugar-sweetened beverages, may have adverse effects on fertility. Sugar-sweetened beverages were associated with poor semen quality in cross-sectional studies, and female soda intake has been associated with lower fecundability in some studies. METHODS: We evaluated the association of female and male sugar-sweetened beverage intake with fecundability among 3,828 women planning pregnancy and 1,045 of their male partners in a North American prospective cohort study. We followed participants until pregnancy or for up to 12 menstrual cycles. Eligible women were aged 21-45 (male partners ≥21), attempting conception for ≤6 cycles, and not using fertility treatments. Participants completed a comprehensive baseline questionnaire, including questions on sugar-sweetened beverage consumption during the previous 4 weeks. We estimated time-to-pregnancy from follow-up questionnaires completed every 2 months by the female partner. We calculated adjusted fecundability ratios (FR) and 95% confidence intervals (CIs) according to intake of sugar- sweetened beverages using proportional probabilities regression. RESULTS: Both female and male intakes of sugar-sweetened beverages were associated with reduced fecundability (FR = 0.81; 95% CI = 0.70, 0.94 and 0.78; 95% CI = 0.63, 0.95 for ≥7 sugar-sweetened beverages per week compared with none, for females and males, respectively). Fecundability was further reduced among those who drank ≥7 servings per week of sugar-sweetened sodas (FR = 0.75, 95% CI = 0.59, 0.95 for females and 0.67, 95% CI = 0.51, 0.89 for males). CONCLUSIONS: Sugar-sweetened beverages, particularly sodas and energy drinks, were associated with lower fecundability, but diet soda and fruit juice had little association.

The mCME Project: A Randomized Controlled Trial of an SMS-Based Continuing Medical Education Intervention for Improving Medical Knowledge among Vietnamese Community Based Physicians' Assistants.

BACKGROUND: Community health workers (CHWs) provide critical services to underserved populations in low and middle-income countries, but maintaining CHW's clinical knowledge through formal continuing medical education (CME) activities is challenging and rarely occurs. We tested whether a Short Message Service (SMS)-based mobile CME (mCME) intervention could improve medical knowledge among a cadre of Vietnamese CHWs (Community Based Physician's Assistants-CBPAs) who are the leading providers of primary medical care for rural underserved populations. METHODS: The mCME Project was a three arm randomized controlled trial. Group 1 served as controls while Groups 2 and 3 experienced two models of the mCME intervention. Group 2 (passive model) participants received a daily SMS bullet point, and were required to reply to the text to acknowledge receipt; Group 3 (interactive model) participants received an SMS in multiple choice question format addressing the same thematic area as Group 2, entering an answer (A, B, C or D) in their response. The server provided feedback immediately informing the participant whether the answer was correct. Effectiveness was based on standardized examination scores measured at baseline and endline (six months later). Secondary outcomes included job satisfaction and self-efficacy. RESULTS: 638 CBPAs were enrolled, randomized, and tested at baseline, with 592 returning at endline (93.7%). Baseline scores were similar across all three groups. Over the next six months, participation of Groups 2 and 3 remained high; they responded to >75% of messages. Group 3 participants answered 43% of the daily SMS questions correctly, but their performance did not improve over time. At endline, the CBPAs reported high satisfaction with the mCME intervention, and deemed the SMS messages highly relevant. However, endline exam scores did not increase over baseline, and did not differ between the three groups. Job satisfaction and self-efficacy scores also did not improve. Average times spent on self-study per week did not increase, and the kinds of knowledge resources used by the CBPAs did not differ between the three groups; textbooks, while widely available, were seldom used. CONCLUSIONS: The SMS-based mCME intervention, while feasible and acceptable, did not result in increased medical knowledge. We hypothesize that this was because the intervention failed to stimulate lateral learning. For an intervention of this kind to be effective, it will be essential to find more effective ways to couple SMS as a stimulus to promote increased self-study behaviors. TRIAL REGISTRATION: ClinicalTrials.gov NCT02381743.