Early Diagnosis and Treatment of COPD and Asthma - A Randomized, Controlled Trial.

BACKGROUND: Many persons with chronic obstructive pulmonary disease (COPD) or asthma have not received a diagnosis, so their respiratory symptoms remain largely untreated. METHODS: We used a case-finding method to identify adults in the community with respiratory symptoms without diagnosed lung disease. Participants who were found to have undiagnosed COPD or asthma on spirometry were enrolled in a multicenter, randomized, controlled trial to determine whether early diagnosis and treatment reduces health care utilization for respiratory illness and improves health outcomes. Participants were assigned to receive the intervention (evaluation by a pulmonologist and an asthma-COPD educator who were instructed to initiate guideline-based care) or usual care by their primary care practitioner. The primary outcome was the annualized rate of participant-initiated health care utilization for respiratory illness. Secondary outcomes included changes from baseline to 1 year in disease-specific quality of life, as assessed with the St. George Respiratory Questionnaire (SGRQ; scores range from 0 to 100, with lower scores indicating better health status); symptom burden, as assessed with the COPD Assessment Test (CAT; scores range from 0 to 40, with lower scores indicating better health status); and forced expiratory volume in 1 second (FEV1). RESULTS: Of 38,353 persons interviewed, 595 were found to have undiagnosed COPD or asthma and 508 underwent randomization: 253 were assigned to the intervention group and 255 to the usual-care group. The annualized rate of a primary-outcome event was lower in the intervention group than in the usual-care group (0.53 vs. 1.12 events per person-year; incidence rate ratio, 0.48; 95% confidence interval [CI], 0.36 to 0.63; P<0.001). At 12 months, the SGRQ score was lower than the baseline score by 10.2 points in the intervention group and by 6.8 points in the usual-care group (difference, -3.5 points; 95% CI, -6.0 to -0.9), and the CAT score was lower than the baseline score by 3.8 points and 2.6 points, respectively (difference, -1.3 points; 95% CI, -2.4 to -0.1). The FEV1 increased by 119 ml in the intervention group and by 22 ml in the usual-care group (difference, 94 ml; 95% CI, 50 to 138). The incidence of adverse events was similar in the trial groups. CONCLUSIONS: In this trial in which a strategy was used to identify adults in the community with undiagnosed asthma or COPD, those who received pulmonologist-directed treatment had less subsequent health care utilization for respiratory illness than those who received usual care. (Funded by Canadian Institutes of Health Research; UCAP ClinicalTrials.gov number, NCT03148210.).

Impact of Undiagnosed Chronic Obstructive Pulmonary Disease and Asthma on Symptoms, Quality of Life, Healthcare Use, and Work Productivity.

Rationale: A significant proportion of individuals with chronic obstructive pulmonary disease (COPD) and asthma remain undiagnosed. Objectives: The objective of this study was to evaluate symptoms, quality of life, healthcare use, and work productivity in subjects with undiagnosed COPD or asthma compared with those previously diagnosed, as well as healthy control subjects. Methods: This multicenter population-based case-finding study randomly recruited adults with respiratory symptoms who had no previous history of diagnosed lung disease from 17 Canadian centers using random digit dialing. Participants who exceeded symptom thresholds on the Asthma Screening Questionnaire or the COPD Diagnostic Questionnaire underwent pre- and post-bronchodilator spirometry to determine if they met diagnostic criteria for COPD or asthma. Two control groups, a healthy group without respiratory symptoms and a symptomatic group with previously diagnosed COPD or asthma, were similarly recruited. Measurements and Main Results: A total of 26,905 symptomatic individuals were interviewed, and 4,272 subjects were eligible. Of these, 2,857 completed pre- and post-bronchodilator spirometry, and 595 (21%) met diagnostic criteria for COPD or asthma. Individuals with undiagnosed COPD or asthma reported greater impact of symptoms on health status and daily activities, worse disease-specific and general quality of life, greater healthcare use, and poorer work productivity than healthy control subjects. Individuals with undiagnosed asthma had symptoms, quality of life, and healthcare use burden similar to those of individuals with previously diagnosed asthma, whereas subjects with undiagnosed COPD were less disabled than those with previously diagnosed COPD. Conclusions: Undiagnosed COPD or asthma imposes important, unmeasured burdens on the healthcare system and is associated with poor health status and negative effects on work productivity.

New physics searches at kaon and hyperon factories.

Rare meson decays are among the most sensitive probes of both heavy and light new physics. Among them, new physics searches using kaons benefit from their small total decay widths and the availability of very large datasets. On the other hand, useful complementary information is provided by hyperon decay measurements. We summarize the relevant phenomenological models and the status of the searches in a comprehensive list of kaon and hyperon decay channels. We identify new search strategies for under-explored signatures, and demonstrate that the improved sensitivities from current and next-generation experiments could lead to a qualitative leap in the exploration of light dark sectors.

Erratum: Quantifying and Controlling Entanglement in the Quantum Magnet Cs_{2}CoCl_{4} [Phys. Rev. Lett. 127, 037201 (2021)].

This corrects the article DOI: 10.1103/PhysRevLett.127.037201.

First report of epiphytic dinoflagellate Coolia malayensis (Dinophyceae) in the southeastern Pacific Ocean.

Coolia species are epiphytic and benthic dinoflagellates with a cosmopolitan distribution in tropical and subtropical areas. In the austral summer of 2016, during a survey in Bahía Calderilla, a dinoflagellate of the genus Coolia was detected in macroalgae samples, and a clonal culture was established. Subsequently, the cultured cells were observed by scanning electron microscopy (SEM) and identified as C. malayensis based on their morphological characteristics. Phylogenetic analyses based on the LSU rDNA D1/D2 regions confirmed that strain D005-1 corresponded to C. malayensis and clustered with strains isolated from New Zealand, Mexico, and Asia Pacific countries. Although the strain D005-1 culture did not contain yessotoxin (YTX), cooliatoxin, 44-methyl gambierone, or its analogs in detectable amounts by LC-MS/MS, more research is needed to evaluate its toxicity and to determine the possible impact of C. malayensis in northern Chilean waters.

Short Telomere Syndrome presenting with pulmonary fibrosis, liver cirrhosis and hepatopulmonary syndrome: a case report.

BACKGROUND: Idiopathic pulmonary fibrosis is thought to result from aberrant post-injury activation of epithelial cells leading to fibroblast proliferation and activation. A number of genetic aetiologies have been implicated in this disease process, including, among others, the short telomere syndromes. Short telomere syndromes follow an autosomal dominant pattern of inheritance resulting in shortened telomere length, which consequently leads to accelerated cell death. Organs with rapid cell turnover are most affected. CASE PRESENTATION: We describe a case of a 53-year-old man with a chief complaint of cough and dyspnea on exertion. His presentation was otherwise significant for features of accelerated aging, including a history of osteoporosis and early greying, and a family history of pulmonary fibrosis in his father. Pulmonary function testing revealed a restrictive pattern with severely reduced diffusion capacity and high resolution CT of the chest showed diffuse lung disease with mild fibrosis, in pattern suggesting an alternative diagnosis to IPF. Biopsy of the lung was in keeping with chronic fibrosing interstitial pneumonia. Imaging of the abdomen showed splenomegaly, hepatic cirrhosis and portal hypertension. Transthoracic contrast echocardiogram showed intrapulmonary shunting consistent with hepatopulmonary syndrome. Given the constellation of early aging, idiopathic pulmonary fibrosis, cryptogenic cirrhosis and a family history of pulmonary fibrosis in this patient, the Short Telomere Syndrome was suspected. Peripheral blood was sent for Flow-cytometry FISH, which demonstrated granulocyte telomere length below the 10th percentile for the patient's age, consistent with a diagnosis of Short Telomere Syndrome in this clinical context. Targeted genetic testing of mutations known to be associated with short telomere was negative though it was acknowledged that the full spectrum of disease-causing mutations remains unknown. Given the extensive fibrosis on biopsy and his progressive hypoxemia he was treated with mycophenolate and prednisone. Ultimately, he developed progressive respiratory failure and underwent double lung and concurrent liver transplant 18 months after the initial diagnosis was made. CONCLUSIONS: Short Telomere Syndrome is a rare cause of end stage organ disease and testing lacks sensitivity making diagnosis challenging. Organ transplant is still the mainstay of treatment. Nevertheless, disease identification is important because of implications for family member screening and the possibility of future treatment options.

Anticipating undiagnosed asthma in symptomatic adults with normal pre- and post-bronchodilator spirometry: a decision tool for bronchial challenge testing.

BACKGROUND: Some patients with asthma demonstrate normal spirometry and remain undiagnosed without further testing. OBJECTIVE: To determine clinical predictors of asthma in symptomatic adults with normal spirometry, and to generate a tool to help clinicians decide who should undergo bronchial challenge testing (BCT). METHODS: Using random-digit dialling and population-based case-finding, we recruited adults from the community with respiratory symptoms and no previous history of diagnosed lung disease. Participants with normal pre- and post-bronchodilator spirometry subsequently underwent BCT. Asthma was diagnosed in those with symptoms and a methacholine provocative concentration (PC20) of < 8 mg/ml. Sputum and blood eosinophils, and exhaled nitric oxide were measured. Univariate analyses identified potentially predictive variables, which were then used to construct a multivariable logistic regression model to predict asthma. Model sensitivity, specificity, and area under the receiver operating curve (AUC) were calculated. RESULTS: Of 132 symptomatic individuals with normal spirometry, 34 (26%) had asthma. Of those ultimately diagnosed with asthma, 33 (97%) answered 'yes' to a question asking whether they experienced cough, chest tightness or wheezing provoked by exercise or cold air. Other univariate predictors of asthma included female sex, pre-bronchodilator FEV1 percentage predicted, and percent positive change in FEV1 post bronchodilator. A multivariable model containing these predictive variables yielded an AUC of 0.82 (95% CI: 0.72-0.91), a sensitivity of 82%, and a specificity of 66%. The model was used to construct a nomogram to advise clinicians which patients should be prioritized for BCT. CONCLUSIONS: Four readily available patient characteristics demonstrated a high sensitivity and AUC for predicting undiagnosed asthma in symptomatic adults with normal pre- and post-bronchodilator spirometry. These characteristics can potentially help clinicians to decide which individuals with normal spirometry should be investigated with bronchial challenge testing. However, further prospective validation of our decision tool is required.

Paralytic Shellfish Toxins in the Gastropod Concholepas concholepas: Variability, Toxin Profiles and Mechanisms for Toxicity Reduction.

Harmful algal blooms of toxin-producing microalgae are recurrent in southern Chile. Paralytic shellfish poisoning (PSP) outbreaks pose the main threat to public health and the fishing industry in the Patagonian fjords. This study aims to increase understanding of the individual and spatial variability of PSP toxicity in the foot of Concholepas concholepas, Chile's most valuable commercial benthic invertebrate species, extracted from the Guaitecas Archipelago in Chilean Patagonia. The objective is to determine the effect of pigment removal and freezing during the detoxification process. A total of 150 specimens (≥90 mm length) were collected from this area. The live specimens were transferred to a processing plant, where they were measured and gutted, the foot was divided into two equal parts, and pigment was manually removed from one of these parts. The PSP toxicity of each foot (edible tissue) was determined by mouse bioassay (MBA) and high-performance liquid chromatography with fluorescence detection and postcolumn oxidation (HPLC-FLD PCOX). The individual toxicity per loco, as the species is known locally, varied from <30 to 146 µg STX diHCL eq 100 g−1 (CV = 43.83%) and from 5.96 to 216.3 µg STX diHCL eq 100 g−1 (CV = 34.63%), using MBA and HPLC, respectively. A generalized linear model showed a negative relation between individual weight and toxicity. The toxicological profile showed a dominance of STX (>95%), neoSTX and GTX2. The removal of pigment produced a reduction in PSP toxicity of up to 90% and could represent a good detoxification tool moving forward. The freezing process in the muscle with pigment did not produce a clear pattern. There is a significant reduction (p < 0.05) of PSP toxicity via PCOX but not MBA. Furthermore, the study discusses possible management and commercialization implications of the findings regarding small-scale fisheries.

Dinophysis acuminata or Dinophysis acuta: What Makes the Difference in Highly Stratified Fjords?

Dinophysis acuminata and D. acuta, which follows it seasonally, are the main producers of lipophilic toxins in temperate coastal waters, including Southern Chile. Strains of the two species differ in their toxin profiles and impacts on shellfish resources. D. acuta is considered the major cause of diarrhetic shellfish poisoning (DSP) outbreaks in Southern Chile, but there is uncertainty about the toxicity of D. acuminata, and little information on microscale oceanographic conditions promoting their blooms. During the austral summer of 2020, intensive sampling was carried out in two northern Patagonian fjords, Puyuhuapi (PUY) and Pitipalena (PIT), sharing D. acuminata dominance and D. acuta near detection levels. Dinophysistoxin 1 (DTX 1) and pectenotoxin 2 (PTX 2) were present in all net tow samples but OA was not detected. Although differing in hydrodynamics and sampling dates, D. acuminata shared behavioural traits in the two fjords: cell maxima (>103 cells L-1) in the interface (S ~ 21) between the estuarine freshwater (EFW)) and saline water (ESW) layers; and phased-cell division (µ = 0.3-0.4 d-1) peaking after dawn, and abundance of ciliate prey. Niche analysis (Outlying Mean Index, OMI) of D. acuta with a high marginality and much lower tolerance than D. acuminata indicated an unfavourable physical environment for D. acuta (bloom failure). Comparison of toxin profiles and Dinophysis niches in three contrasting years in PUY-2020 (D. acuminata bloom), 2018 (exceptional bloom of D. acuta), and 2019 (bloom co-occurrence of the two species)-shed light on the vertical gradients which promote each species. The presence of FW (S < 11) and thermal inversion may be used to provide short-term forecasts of no risk of D. acuta blooms and OA occurrence, but D. acuminata associated with DTX 1 pose a risk of DSP events in North Patagonian fjords.

Surveying the Epigenetic Landscape of Tuberculosis in Alveolar Macrophages.

Tuberculosis (TB) remains the leading cause of bacterial disease-related death and is among the top 10 overall causes of death worldwide. The complex nature of this infectious lung disease has proven difficult to treat, and significant research efforts are now evaluating the feasibility of host-directed, adjunctive therapies. An attractive approach in host-directed therapy targets host epigenetics, or gene regulation, to redirect the immune response in a host-beneficial manner. Substantial evidence exists demonstrating that host epigenetics are dysregulated during TB and that epigenetic-based therapies may be highly effective to treat TB. However, the caveat is that much of the knowledge that exists on the modulation of the host epigenome during TB has been gained using in vitro, small-animal, or blood-derived cell models, which do not accurately reflect the pulmonary nature of the disease. In humans, the first and major target cells of Mycobacterium tuberculosis are alveolar macrophages (AM). As such, their response to infection and treatment is clinically relevant and ultimately drives the outcome of disease. In this review, we compare the fundamental differences between AM and circulating monocyte-derived macrophages in the context of TB and summarize the recent advances in elucidating the epigenomes of these cells, including changes to the transcriptome, DNA methylome, and chromatin architecture. We will also discuss trained immunity in AM as a new and emerging field in TB research and provide some perspectives for the translational potential of targeting host epigenetics as an alternative TB therapy.

Derivation and validation of the UCAP-Q case-finding questionnaire to detect undiagnosed asthma and COPD.

BACKGROUND: Many people with asthma and COPD remain undiagnosed. We developed and validated a new case-finding questionnaire to identify symptomatic adults with undiagnosed obstructive lung disease. METHODS: Adults in the community with no prior history of physician-diagnosed lung disease who self-reported respiratory symptoms were contacted via random-digit dialling. Pre- and post-bronchodilator spirometry was used to confirm asthma or COPD. Predictive questions were selected using multinomial logistic regression with backward elimination. Questionnaire performance was assessed using sensitivity, predictive values and area under the receiver operating characteristic curve (AUC). The questionnaire was assessed for test-retest reliability, acceptability and readability. External validation was prospectively conducted in an independent sample and predictive performance re-evaluated. RESULTS: A 13-item Undiagnosed COPD and Asthma Population Questionnaire (UCAP-Q) case-finding questionnaire to predict undiagnosed asthma or COPD was developed. The most appropriate risk cut-off was determined to be 6% for either disease. Applied to the derivation sample (n=1615), the questionnaire yielded a sensitivity of 92% for asthma and 97% for COPD; specificity of 17%; and an AUC of 0.69 (95% CI 0.64-0.74) for asthma and 0.82 (95% CI 0.78-0.86) for COPD. Prospective validation using an independent sample (n=471) showed sensitivities of 93% and 92% for asthma and COPD, respectively; specificity of 19%; with AUCs of 0.70 (95% CI 0.62-0.79) for asthma and 0.81 (95% CI 0.74-0.87) for COPD. AUCs for UCAP-Q were higher compared to AUCs for currently recommended case-finding questionnaires for asthma or COPD. CONCLUSIONS: The UCAP-Q demonstrated high sensitivities and AUCs for identifying undiagnosed asthma or COPD. A web-based calculator allows for easy calculation of risk probabilities for each disease.

Lung disease burden assessment by oscillometry in a systematically disadvantaged urban population experiencing homelessness or at-risk for homelessness in Ottawa, Canada from a prospective observational study.

RATIONALE: Oscillometry is an emerging technique that offers some advantages over spirometry as it does not require forced exhalation and may detect early changes in respiratory pathology. Obstructive lung disease disproportionately impacts people experiencing homelessness with a high symptoms burden, yet oscillometry is not studied in this population. OBJECTIVES: To assess lung disease and symptom burden using oscillometry in people experiencing homelessness or at-risk of homelessness using a community-based participatory action research approach (The Bridge Model™). METHODS: Of 80 recruited, 55 completed baseline oscillometry, 64 completed spirometry, and all completed patient-reported outcomes with demographics, health, and respiratory symptom related questionnaires in the Participatory Research in Ottawa: Management and Point-of-Care for Tobacco Dependence project. Using a two-tail t-test, we compared mean oscillometry values for airway resistance (R5-20), reactance area under the curve (Ax) and reactance at 5 Hz (X5) amongst individuals with fixed-ratio method (FEV1/FVC ratio < 0.70) and LLN (FEV1/FVC ratio ≤ LLN) spirometry diagnosed chronic obstructive pulmonary disease (COPD). We compared mean oscillometry parameters based on participants' COPD assessment test (CAT) scores using ANOVA test. RESULTS: There was no significant difference between the pre- and post- bronchodilator values of R5-20 and Ax for the fixed ratio method (p = 0.63 and 0.43) and the LLN method (p = 0.45 and 0.36). There was a significant difference in all three of the oscillometry parameters, R5-20, Ax and X5, based on CAT score (p = 0.009, 0.007 and 0.05, respectively). There was a significant difference in R5-20 and Ax based on the presence of phlegm (p = 0.03 and 0.02, respectively) and the presence of wheeze (p = 0.05 and 0.01, respectively). Oscillometry data did not correlate with spirometry data, but it was associated with CAT scores and correlated with the presence of self-reported symptoms of phlegm and wheeze in this population. CONCLUSIONS: Oscillometry is associated with respiratory symptom burden and highlights the need for future studies to generate more robust data regarding the use of oscillometry in systematically disadvantaged populations where disease burden is disproportionately higher than the general population. TRIAL REGISTRATION: ClinicalTrails.gov-NCT03626064, Retrospective registered: August 2018, https://clinicaltrials.gov/ct2/show/NCT03626064.

Lipophilic Toxins in Chile: History, Producers and Impacts.

A variety of microalgal species produce lipophilic toxins (LT) that are accumulated by filter-feeding bivalves. Their negative impacts on human health and shellfish exploitation are determined by toxic potential of the local strains and toxin biotransformations by exploited bivalve species. Chile has become, in a decade, the world's major exporter of mussels (Mytilus chilensis) and scallops (Argopecten purpuratus) and has implemented toxin testing according to importing countries' demands. Species of the Dinophysis acuminata complex and Protoceratium reticulatum are the most widespread and abundant LT producers in Chile. Dominant D. acuminata strains, notwithstanding, unlike most strains in Europe rich in okadaic acid (OA), produce only pectenotoxins, with no impact on human health. Dinophysis acuta, suspected to be the main cause of diarrhetic shellfish poisoning outbreaks, is found in the two southernmost regions of Chile, and has apparently shifted poleward. Mouse bioassay (MBA) is the official method to control shellfish safety for the national market. Positive results from mouse tests to mixtures of toxins and other compounds only toxic by intraperitoneal injection, including already deregulated toxins (PTXs), force unnecessary harvesting bans, and hinder progress in the identification of emerging toxins. Here, 50 years of LST events in Chile, and current knowledge of their sources, accumulation and effects, are reviewed. Improvements of monitoring practices are suggested, and strategies to face new challenges and answer the main questions are proposed.

Molecular Epidemiology of Mycobacterium tuberculosis To Describe the Transmission Dynamics Among Inuit Residing in Iqaluit Nunavut Using Whole-Genome Sequencing.

BACKGROUND: In the last decade, tuberculosis (TB) incidence among Inuit in the Canadian Arctic has been rising. Our aim was to better understand the transmission dynamics of TB in this remote region of Canada using whole-genome sequencing. METHODS: Isolates from patients who had culture-positive pulmonary TB in Iqaluit, Nunavut, between 2009 and 2015 underwent whole-genome sequencing (WGS). The number of transmission events between cases within clusters was calculated using a threshold of a ≤3 single nucleotide polymorphism (SNP) difference between isolates and then combined with detailed epidemiological data using a reproducible novel algorithm. Social network analysis of epidemiological data was used to support the WGS data analysis. RESULTS: During the study period, 140 Mycobacterium tuberculosis isolates from 135 cases were sequenced. Four clusters were identified, all from Euro-American lineage. One cluster represented 62% of all cases that were sequenced over the entire study period. In this cluster, 2 large chains of transmission were associated with 3 superspreading events in a homeless shelter. One of the superspreading events was linked to a nonsanctioned gambling house that resulted in further transmission. Shelter to nonshelter transmission was also confirmed. An algorithm developed for the determination of transmission events demonstrated very good reproducibility (κ score .98, 95% confidence interval, .97-1.0). CONCLUSIONS: Our study suggests that socioeconomic factors, namely residing in a homeless shelter and spending time in a gambling house, combined with the superspreading event effect may have been significant factors explaining the rise in cases in this predominantly Inuit Arctic community.

Origin of Insulating Ferromagnetism in Iron Oxychalcogenide Ce_{2}O_{2}FeSe_{2}.

An insulating ferromagnetic (FM) phase exists in the quasi-one-dimensional iron oxychalcogenide Ce_{2}O_{2}FeSe_{2}, but its origin is unknown. To understand the FM mechanism, here a systematic investigation of this material is provided, analyzing the competition between ferromagnetic and antiferromagnetic tendencies and the interplay of hoppings, Coulomb interactions, Hund's coupling, and crystal-field splittings. Our intuitive analysis based on second-order perturbation theory shows that large entanglements between doubly occupied and half filled orbitals play a key role in stabilizing the FM order in Ce_{2}O_{2}FeSe_{2}. In addition, via many-body computational techniques applied to a multiorbital Hubbard model, the phase diagram confirms the proposed FM mechanism.

Quantifying and Controlling Entanglement in the Quantum Magnet Cs_{2}CoCl_{4}.

The lack of methods to experimentally detect and quantify entanglement in quantum matter impedes our ability to identify materials hosting highly entangled phases, such as quantum spin liquids. We thus investigate the feasibility of using inelastic neutron scattering (INS) to implement a model-independent measurement protocol for entanglement based on three entanglement witnesses: one-tangle, two-tangle, and quantum Fisher information (QFI). We perform high-resolution INS measurements on Cs_{2}CoCl_{4}, a close realization of the S=1/2 transverse-field XXZ spin chain, where we can control entanglement using the magnetic field, and compare with density-matrix renormalization group calculations for validation. The three witnesses allow us to infer entanglement properties and make deductions about the quantum state in the material. We find QFI to be a particularly robust experimental probe of entanglement, whereas the one and two-tangles require more careful analysis. Our results lay the foundation for a general entanglement detection protocol for quantum spin systems.

Social and behavioral risk reduction strategies for tuberculosis prevention in Canadian Inuit communities: a cost-effectiveness analysis.

BACKGROUND: Tuberculosis (TB) is an important public health problem in Inuit communities across Canada, with an annual incidence rate in 2017 that was nearly 300 times higher than in Canadian-born non-Indigenous individuals. Social and behavioral factors that are prevalent in the North, such as commercial tobacco use, excessive alcohol use, food insecurity and overcrowded housing put individuals at higher risk for TB morbidity and mortality. We examined the potential impact of mitigation strategies for these risk factors, in reducing TB burden in this setting. METHODS: We created a transmission model to simulate the epidemiology of TB in Nunavut, Canada. We then used a decision analysis model to assess the potential impact of several evidence-based strategies targeting tobacco use, excessive alcohol use, food insecurity and overcrowded housing. We predicted TB incidence, TB-related deaths, quality adjusted life years (QALYs), and associated costs and cost-effectiveness over 20 years. All costs were expressed in 2018 Canadian dollars. RESULTS: Compared to a status quo scenario with no new interventions for these risk factors, the reduction strategy for tobacco use was most effective and cost-effective, reducing TB incidence by 5.5% (95% uncertainty range: 2.7-11%) over 20 years, with an estimated cost of $95,835 per TB case prevented and $49,671 per QALY gained. The addition of the food insecurity reduction strategy reduced incidence by a further 2% (0.5-3%) compared to the tobacco cessation strategy alone, but at significant cost. CONCLUSIONS: Strategies that aim to reduce commercial tobacco use and improve food security will likely lead to modest reductions in TB morbidity and mortality. Although important for the communities, strategies that address excess alcohol use and overcrowding will likely have a more limited impact on TB-related outcomes at current scale, and are associated with much higher cost. Their benefits will be more substantial with scale up, which will also likely have important downstream impacts such as improved mental health, educational attainment and food security.

Prevalence and burden of obstructive lung disease in the urban poor population of Ottawa, Canada: a community-based mixed-method, observational study.

BACKGROUND: Globally the burden of Obstructive Lung Diseases (OLD) is growing, however its effect on urban poor populations with the high prevalence of tobacco dependence is virtually unknown. The purpose of this project is to estimate the prevalence and burden of OLD in the urban, low-income populations of Ottawa, Canada. METHODS: The study presented in this paper was part of the PROMPT (Management and Point-of-Care for Tobacco Dependence) project; a prospective cohort study in a community-based setting (n = 80) with meaningful Patient Engagement from design to dissemination. Spirometry data, standardized questionnaires and semi-structured interviews from PROMPT were interpreted to understand the lung function, disease burden and social determinants (respectively) in this population. RESULTS: The prevalence of OLD among those who completed spirometry (N = 64) was 45-59%. Generic and disease-specific quality of life was generally poor in all PROMPT participants, even those without OLD, highlighting the higher disease burden this vulnerable population faces. Quality of life was impacted by two major themes, including i) socioeconomic status and stress and ii) social networks and related experiences of trauma. CONCLUSION: The prevalence and disease burden of OLD is significantly higher in Ottawa's urban poor population than what is observed in the general Canadian population who smoke, suggesting an etiological role of the social determinants of health. This urges the need for comprehensive care programs addressing up-stream factors leading to OLDs, including poor access and utilization of preventive healthcare addressing the social determinants of health. TRIAL REGISTRATION: ClinicalTrails.gov - NCT03626064 , Retrospective registered: August 2018.

A multi-objective formulation of improving flexibility in the operation of electric power systems: Application to mitigation measures during the coronavirus pandemic.

The coronavirus pandemic has infected more than 23 million people worldwide by August 2020 along with more than 800,000 deaths. To face this pandemic, a joint effort among different areas has been required. In this context, the correct supply of basic services is the key to enhance the complex circumstance. The operation of the electric power systems is needed to ensure the answer to the situation. Basic services in areas of health, security, food, and communications depend on the electricity supply. Consequently, this paper introduces a multi-objective procedure that enhances the operations of power systems under these circumstances. It considers geographical areas that are affected by coronavirus cases and their effects on the personnel of power plants. To obtain the best combinations of total cost and protection of the workers, lexicographic optimization is implemented. The effectiveness of this approach is studied by solving two test cases: a 6-bus system and the Argentine Electric System with real data about the infection cases. The effects on the electricity generation and transportation stages are studied. The results allow identifying critical areas and proposing corrective actions. The method can reach feasible solutions with a low computational requirement.

The potential impact and cost-effectiveness of tobacco reduction strategies for tuberculosis prevention in Canadian Inuit communities.

BACKGROUND: Tuberculosis (TB) remains a significant public health problem in Canadian Inuit communities. In 2016, Canadian Inuit had an incidence rate 35 times the Canadian average. Tobacco use is an important risk factor for TB, and over 60% of Inuit adults smoke. We aimed to estimate changes in TB-related outcomes and costs from reducing tobacco use in Inuit communities. METHODS: Using a transmission model to estimate the initial prevalence of latent TB infection (LTBI), followed by decision analysis modelling, we conducted a cost-effectiveness analysis that compared the current standard of care for management of TB and LTBI without additional tobacco reduction intervention (Status Quo) with (1) increased tobacco taxation, (2) pharmacotherapy and counselling for smoking cessation, (3) pharmacotherapy, counselling plus mass media campaign, and (4) the combination of all these. Projected outcomes included the following: TB cases, TB-related deaths, quality-adjusted life years (QALYs), and health system costs, all over 20 years. RESULTS: The combined strategy was projected to reduce active TB cases by 6.1% (95% uncertainty range 4.9-7.0%) and TB deaths by 10.4% (9.5-11.4%) over 20 years, relative to the status quo. Increased taxation was the only cost-saving strategy. CONCLUSIONS: Currently available strategies to reduce commercial tobacco use will likely have a modest impact on TB-related outcomes in the medium term, but some may be cost saving.