Association Between Cardiovascular Disease and Death by Anaphylaxis: A 20-Year Retrospective Study in Queensland, Australia.

ABSTRACT: Despite its severity, anaphylaxis carries a low mortality rate of less than 1%, making the cohort seen in the forensic pathology setting a small and unique subset of the majority of cases of anaphylaxis in the community. Clinically, cardiovascular disease has been recognized as a risk factor for fatal anaphylaxis; however, there is scant forensic pathology research investigating this risk factor, whereas autopsy textbooks emphasize physical respiratory changes seen in the broader clinical cohort. This 20-year retrospective study examined all fatal anaphylactic deaths in the state of Queensland, Australia, to document the underlying disease of the cases, tryptase levels, triggers, and postmortem findings. Our study found that cardiovascular disease was prevalent in 83.3% of cases of fatal anaphylaxis. Although asthma was prevalent in food-related fatal anaphylaxis (60%) in our cohort, it was poorly represented overall (28%), in contrast to clinical research. Additionally, only 43% of cases showed respiratory changes that were greater than mild. Our findings emphasize the difference between the clinical and postmortem anaphylaxis cohorts, and provide autopsy evidence of a potential role of cardiovascular disease in fatal anaphylaxis.

Improving prevalence estimates of mental health and well-being indicators among Sexual Minority Men: A Propensity Weighting Approach.

The prevalence and relative disparities of mental health outcomes and well-being indicators are often inconsistent across studies of Sexual Minority Men (SMM) due to selection biases in community-based surveys (non-probability sample), as well as misclassification biases in population-based surveys where some SMM often conceal their sexual orientation identities. The current paper estimated the prevalence of mental health related outcomes (depressive symptoms, mental health service use [MHSU], anxiety) and well-being indicators (loneliness and self-rated mental health) among SMM, broken down by sexual orientation using the Adjusted Logistic Propensity score (ALP) weighting. We applied the ALP to correct for selection biases in the 2019 Sex Now data (a community-based survey of SMMs in Canada) by reweighting it to the 2015-2018 Canadian Community Health Survey (a population survey from Statistics Canada). For all SMMs, the ALP-weighted prevalence of depressive symptoms is 15.96% (95% CI: 11.36%, 23.83%), while for MHSU, it is 32.13% (95% CI: 26.09, 41.20). The ALP estimates lie in between the crude estimates from the two surveys. This method was successful in providing a more accurate estimate than relying on results from one survey alone. We recommend to the use of ALP on other minority populations under certain assumptions.

Potent activity of polymyxin B is associated with long-lived super-stoichiometric accumulation mediated by weak-affinity binding to lipid A.

Polymyxins are gram-negative antibiotics that target lipid A, the conserved membrane anchor of lipopolysaccharide in the outer membrane. Despite their clinical importance, the molecular mechanisms underpinning polymyxin activity remain unresolved. Here, we use surface plasmon resonance to kinetically interrogate interactions between polymyxins and lipid A and derive a phenomenological model. Our analyses suggest a lipid A-catalyzed, three-state mechanism for polymyxins: transient binding, membrane insertion, and super-stoichiometric cluster accumulation with a long residence time. Accumulation also occurs for brevicidine, another lipid A-targeting antibacterial molecule. Lipid A modifications that impart polymyxin resistance and a non-bactericidal polymyxin derivative exhibit binding that does not evolve into long-lived species. We propose that transient binding to lipid A permeabilizes the outer membrane and cluster accumulation enables the bactericidal activity of polymyxins. These findings could establish a blueprint for discovery of lipid A-targeting antibiotics and provide a generalizable approach to study interactions with the gram-negative outer membrane.

Work-related suicide: Evolving understandings of etiology & intervention.

Previously published analyses of suicide case investigations suggest that work or working conditions contribute to 10%-13% of suicide deaths. Yet, the way in which work may increase suicide risk is an underdeveloped area of epidemiologic research. In this Commentary, we propose a definition of work-related suicide from an occupational health and safety perspective, and review the case investigation-based and epidemiologic evidence on work-related causes of suicide. We identified six broad categories of potential work-related causes of suicide, which are: (1) workplace chemical, physical, and psychosocial exposures; (2) exposure to trauma on the job; (3) access to means of suicide through work; (4) exposure to high-stigma work environments; (5) exposure to normative environments promoting extreme orientation to work; and (6) adverse experiences arising from work-related injury or illness. We summarise current evidence in a schema of potential work-related causes that can also be applied in workplace risk assessment and suicide case investigations. There are numerous implications of these findings for policy and practice. Various principle- and evidence-based workplace intervention strategies for suicide prevention exist, some of which have been shown to improve suicide-prevention literacy, reduce stigma, enhance helping behaviours, and in some instances maybe even reduce suicide rates. Prevailing practice in workplace suicide prevention, however, overly emphasises individual- and illness-directed interventions, with little attention directed to addressing the working conditions that may increase suicide risk. We conclude that a stronger emphasis on improving working conditions will be required for workplace suicide prevention to reach its full preventive potential.

Cannabis use motives and associations with personal and work characteristics among Canadian workers: a cross-sectional study.

BACKGROUND: Research on cannabis use motives has focused on youth. Little is known about motives among working adults, including how work may play a role. This study aimed to describe cannabis use motives and their connection to work, and identify the personal and work correlates of work-related motives among a sample of workers. METHODS: A national, cross-sectional sample of Canadian workers were queried about their cannabis use. Workers reporting past-year cannabis use (n = 589) were asked their motives for using cannabis and whether each motive was related to work or helped them manage at work (i.e., work-related). Multinomial logistic regression analyses were conducted to estimate the associations of personal and work characteristics with work-related cannabis use motives (no work-related motives, < 50% of motives work-related, ≥ 50% of motives work-related). RESULTS: Use for relaxation (59.3%), enjoyment (47.2%), social reasons (35.3%), coping (35.1%), medical reasons (30.9%), and sleep (29.9%) were the most common motives. Almost 40% of respondents reported one or more of their cannabis use motives were work-related, with coping (19.9%) and relaxation (16.3%) most commonly reported as work-related. Younger age, poorer general health, greater job stress, having a supervisory role, and hazardous work were associated with increased odds of reporting at least some cannabis use motives to be work-related, while work schedule and greater frequency of alcohol use were associated with reduced odds of motives being primarily work-related. CONCLUSIONS: Cannabis use motives among workers are diverse and frequently associated with work. Greater attention to the role of work in motivating cannabis use is warranted.

Modelling and comparing the use of IVF and ICSI in Australia.

PURPOSE: This study estimates the need of IVF/ICSI in Australia as compared to its actual uptake. METHODS: We created a model estimating for the annual demand for IVF/ICSI in a hypothetical infertile population, using demographic data from medical literature and Australian government databases. For each category of infertility (tubal, severe male, endometriosis, anovulation and unexplained), our estimated need for IVF/ICSI was compared to the actual IVF/ICSI uptake (ANZARD 2019). The model consisted of three categories depending on couples' cause of infertility, i.e. couples with absolute indications for IVF/ICSI (couples with severe male factor infertility and tubal obstruction); couples with anovulatory infertility (couples with ovulation disorders) and couples with ovulatory infertility (couples suffering from unexplained infertility and endometriosis). The model was applied to each of these categories to determine the number of couples that would require IVF/ICSI treatment after failing to conceive naturally or after following alternative treatment plans. The main outcomes of this study were the estimate of IVF/ICSI cycles and the difference between the estimate and the reported number of IVF/ICSI cycles (2019 ANZARD report). RESULTS: We estimated that approximately 35,300 couples required IVF/ICSI treatment in Australia in 2019, while in 2019 according to ANZARD, 46,000 couples underwent IVF/ICSI. A higher uptake of IVF/ICSI cycles than expected was specifically reported in couples with unexplained infertility, ovulation disorders and endometriosis, while for tubal and severe male infertility uptake seemed adequate. CONCLUSION: In Australia, there seems to be overservicing of IVF/ICSI, specifically for unexplained, ovulatory and endometriosis-related infertility.

Particulate and gaseous air pollutants exceed WHO guideline values and have the potential to damage human health in Faisalabad, Metropolitan, Pakistan.

First-ever measurements of particulate matter (PM2.5, PM10, and TSP) along with gaseous pollutants (CO, NO2, and SO2) were performed from June 2019 to April 2020 in Faisalabad, Metropolitan, Pakistan, to assess their seasonal variations; Summer 2019, Autumn 2019, Winter 2019-2020, and Spring 2020. Pollutant measurements were carried out at 30 locations with a 3-km grid distance from the Sitara Chemical Industry in District Faisalabad to Bhianwala, Sargodha Road, Tehsil Lalian, District Chiniot. ArcGIS 10.8 was used to interpolate pollutant concentrations using the inverse distance weightage method. PM2.5, PM10, and TSP concentrations were highest in summer, and lowest in autumn or winter. CO, NO2, and SO2 concentrations were highest in summer or spring and lowest in winter. Seasonal average NO2 and SO2 concentrations exceeded WHO annual air quality guide values. For all 4 seasons, some sites had better air quality than others. Even in these cleaner sites air quality index (AQI) was unhealthy for sensitive groups and the less good sites showed Very critical AQI (> 500). Dust-bound carbon and sulfur contents were higher in spring (64 mg g-1) and summer (1.17 mg g-1) and lower in autumn (55 mg g-1) and winter (1.08 mg g-1). Venous blood analysis of 20 individuals showed cadmium and lead concentrations higher than WHO permissible limits. Those individuals exposed to direct roadside pollution for longer periods because of their occupation tended to show higher Pb and Cd blood concentrations. It is concluded that air quality along the roadside is extremely poor and potentially damaging to the health of exposed workers.

Novel characterization of endogenous transient receptor potential melastatin 3 ion channels from Gulf War Illness participants.

Gulf War Illness (GWI) is a chronic condition characterized by multisystem symptoms that still affect up to one-third of veterans who engaged in combat in the Gulf War three decades ago. The aetiology of GWI is mainly explained by exposure to multiple toxic agents, vaccines, and medications. As there is a significant overlap in symptoms between GWI and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), the objective of this study was to investigate a biomarker widely reported in Natural Killer (NK) cells from ME/CFS patients, the Transient Receptor Potential Melastatin 3 (TRPM3) ion channel. NK cells from 6 healthy controls (HC) and 6 GWI participants were isolated, and TRPM3 function was assessed through whole-cell patch-clamp. As demonstrated by prior studies, NK cells from HC expressed typical TRPM3 function after pharmacomodulation. In contrast, this pilot investigation demonstrates a dysfunctional TRPM3 in NK cells from GWI participants through application of a TRPM3 agonist and confirmed by a TRPM3 antagonist. There was a significant reduction in TRPM3 function from GWI than results measured in HC. This study provides an unprecedented research field to investigate the involvement of TRP ion channels in the pathomechanism and potential medical interventions to improve GWI quality of life.

Unpaid overtime and mental health in the Canadian working population.

BACKGROUND: Unpaid overtime-describing a situation where extra hours are worked but not paid for-is a common feature of the labor market that, together with other forms of wage theft, costs workers billions of dollars annually. In this study, we examine the association between unpaid overtime and mental health in the Canadian working population. We also assess the relative strength of that association by comparing it against those of other broadly recognized work stressors. METHODS: Data were drawn from a survey administered to a heterogeneous sample of workers in Canada (n = 3691). Generalized linear models quantified associations between unpaid overtime, stress, and burnout, distinguishing between moderate (1-5) and excessive (6 or more) hours of unpaid overtime. RESULTS: Unpaid overtime was associated with higher levels of stress and burnout. Relative to those working no unpaid overtime, men working excessive unpaid overtime were 85% more likely to report stress (prevalence ratios [PR]: 1.85, 95% confidence interval [CI]: 1.26-2.72) and 84% more likely to report burnout (PR: 1.84, 95% CI: 1.34-2.54), while women working excessive unpaid overtime were 90% more likely to report stress (PR: 1.90, 95% CI: 1.32-2.75) and 52% more likely to report burnout (PR: 1.52; 95% CI: 1.12-2.06). The association of excessive unpaid overtime with mental health was comparable in magnitude to that of shift work and low job control. CONCLUSIONS: Unpaid overtime may present a significant challenge to the mental health of working people, highlighting the potential role of wage theft as a neglected occupational health hazard.

Investigation into the restoration of TRPM3 ion channel activity in post-COVID-19 condition: a potential pharmacotherapeutic target.

Introduction: Recently, we reported that post COVID-19 condition patients also have Transient Receptor Potential Melastatin 3 (TRPM3) ion channel dysfunction, a potential biomarker reported in natural killer (NK) cells from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients. As there is no universal treatment for post COVID-19 condition, knowledge of ME/CFS may provide advances to investigate therapeutic targets. Naltrexone hydrochloride (NTX) has been demonstrated to be beneficial as a pharmacological intervention for ME/CFS patients and experimental investigations have shown NTX restored TRPM3 function in NK cells. This research aimed to: i) validate impaired TRPM3 ion channel function in post COVID-19 condition patients compared with ME/CFS; and ii) investigate NTX effects on TRPM3 ion channel activity in post COVID-19 condition patients. Methods: Whole-cell patch-clamp was performed to characterize TRPM3 ion channel activity in freshly isolated NK cells of post COVID-19 condition (N = 9; 40.56 ± 11.26 years), ME/CFS (N = 9; 39.33 ± 9.80 years) and healthy controls (HC) (N = 9; 45.22 ± 9.67 years). NTX effects were assessed on post COVID-19 condition (N = 9; 40.56 ± 11.26 years) and HC (N = 7; 45.43 ± 10.50 years) where NK cells were incubated for 24 hours in two protocols: treated with 200 µM NTX, or non-treated; TRPM3 channel function was assessed with patch-clamp protocol. Results: This investigation confirmed impaired TRPM3 ion channel function in NK cells from post COVID-19 condition and ME/CFS patients. Importantly, PregS-induced TRPM3 currents were significantly restored in NTX-treated NK cells from post COVID-19 condition compared with HC. Furthermore, the sensitivity of NK cells to ononetin was not significantly different between post COVID-19 condition and HC after treatment with NTX. Discussion: Our findings provide further evidence identifying similarities of TRPM3 ion channel dysfunction between ME/CFS and post COVID-19 condition patients. This study also reports, for the first time, TRPM3 ion channel activity was restored in NK cells isolated from post COVID-19 condition patients after in vitro treatment with NTX. The TRPM3 restoration consequently may re-establish TRPM3-dependent calcium (Ca2+) influx. This investigation proposes NTX as a potential therapeutic intervention and TRPM3 as a treatment biomarker for post COVID-19 condition.

Factors Contributing to Increased Workplace Violence Against Nurses During COVID-19 in the Healthcare Settings of a Lower Middle-income Country: A Qualitative Study.

PURPOSE: The aim of this study was to provide the perceptions of nurses, nursing supervisors, and nursing administrators about factors contributing to increased workplace violence (WPV) against nurses within the healthcare settings in Pakistan during the first wave of the COVID-19 pandemic. METHODS: This study used a Descriptive Qualitative design, with a purposive sampling technique. From September to December 2021, In-depth interviews of 45 to 60 minutes, using a semistructured interview guide, we collected data from a private and a public healthcare setting in Pakistan. Given the travel restrictions during the COVID-19 pandemic, these interviews were conducted online, using Zoom audio features. Bedside nurses, nursing supervisors, and nursing administrators with at least six months of work experience participated in this study. RESULTS: The qualitative data analysis steps suggested by Braun and Clarke (2013) were used for thematic analysis. The overarching theme emerging from the data was "Factors perceived by nurses that contributed to increased WPV in their work settings during the first wave of COVID-19, in a lower middle-income country" The subthemes from the participants' narrations were (a) highly stressed patients, attendants, and healthcare workers; (b) the financial burden on patients and their families; (c) lack of resources and shortage of staff; (d) restricted visiting policy and a weak security system; (e) lack of awareness about the seriousness of COVID-19; (f) misconceptions about COVID-19 vaccines and nurses' role in disseminating awareness. CONCLUSIONS: The current pandemic increased the intensity of WPV against nurses in healthcare settings in Pakistan. Despite any supposed reasons for WPV, exposure to violence should never be an acceptable part of nursing. The healthcare system in Pakistan needs to pay equal attention to funding, resource provision, and ensuring a safe working environment for healthcare workers.

Design and Assessment of Bird-Inspired 3D-Printed Models to Evaluate Grasp Mechanics.

Adapting grasp-specialized biomechanical structures into current research with 3D-printed prostheses may improve robotic dexterity in grasping a wider variety of objects. Claw variations across various bird species lend biomechanical advantages for grasping motions related to perching, climbing, and hunting. Designs inspired by bird claws provide improvements beyond a human-inspired structure for specific grasping applications to offer a solution for mitigating a cause of the high rejection rate for upper-limb prostheses. This research focuses on the design and manufacturing of two robotic test devices with different toe arrangements. The first, anisodactyl (three toes at the front, one at the back), is commonly found in birds of prey such as falcons and hawks. The second, zygodactyl (two toes at the front, two at the back), is commonly found in climbing birds such as woodpeckers and parrots. The evaluation methods for these models included a qualitative variable-object grasp assessment. The results highlighted design features that suggest an improved grasp: a small and central palm, curved distal digit components, and a symmetrical digit arrangement. A quantitative grip force test demonstrated that the single digit, the anisodactyl claw, and the zygodactyl claw designs support loads up to 64.3 N, 86.1 N, and 74.1 N, respectively. These loads exceed the minimum mechanical load capabilities for prosthetic devices. The developed designs offer insights into how biomimicry can be harnessed to optimize the grasping functionality of upper-limb prostheses.

Epidemiological cut-off values for Yersina ruckeri disc diffusion data generated by a standardised method.

In order to establish the meaning of data generated in antimicrobial agent susceptibility tests, it is necessary to develop internationally harmonised interpretive criteria. Currently, such criteria have not been developed for data generated in studies of the susceptibility of the fish pathogen Yersinia ruckeri. This work generated the data that would be required to set epidemiological cut-off values for the susceptibility data of this species that had been generated using a standardised disc diffusion method that specified the use of Mueller Hinton agar and incubation at 22°C for 24-28 h. Using this method, sets of inhibition zones data for 4 antimicrobial agents were generated by 3 independent laboratories. The data from these laboratories were aggregated and analysed using the statistically based normalised resistance interpretation. For ampicillin, florfenicol, oxytetracycline and trimethoprim-sulfamethoxazole the cut-off values calculated by this analysis were ≥16, ≥23, ≥24 and ≥30 mm, respectively. Evidence is presented demonstrating that the data for these 4 agents was of sufficient quantity and quality that they could be used by the relevant authorities to set internationally harmonised, consensus epidemiological cut-off values for Y. ruckeri.

Using unsupervised clustering approaches to identify common mental health profiles and associated mental health-care service-use patterns in Ontario, Canada.

Mental health is a complex, multidimensional concept that goes beyond clinical diagnoses, including psychological distress, life stress, and well-being. In this study, we aimed to use unsupervised clustering approaches to identify multidimensional mental health profiles that exist in the population, and their associated service-use patterns. The data source was the 2012 Canadian Community Health Survey-Mental Health, linked to administrative health-care data; all Ontario, Canada, adult respondents were included. We used a partitioning around medoids clustering algorithm with Gower's proximity to identify groups with distinct combinations of mental health indicators and described them according to their sociodemographic and service-use characteristics. We identified 4 groups with distinct mental health profiles, including 1 group that met the clinical threshold for a depressive diagnosis, with the remaining 3 groups expressing differences in positive mental health, life stress, and self-rated mental health. The 4 groups had different age, employment, and income profiles and exhibited differential access to mental health-care services. This study represents the first step in identifying complex profiles of mental health at the population level in Ontario. Further research is required to better understand the potential causes and consequences of belonging to each of the mental health profiles identified. This article is part of a Special Collection on Mental Health.

Inferring Consciousness in Phylogenetically Distant Organisms.

The neural dynamics of subjectivity (NDS) approach to the biological explanation of consciousness is outlined and applied to the problem of inferring consciousness in animals phylogenetically distant from ourselves. The NDS approach holds that consciousness or felt experience is characteristic of systems whose nervous systems have been shaped to realize subjectivity through a combination of network interactions and large-scale dynamic patterns. Features of the vertebrate brain architecture that figure in other accounts of the biology of consciousness are viewed as inessential. Deep phylogenetic branchings in the animal kingdom occurred before the evolution of complex behavior, cognition, and sensing. These capacities arose independently in brain architectures that differ widely across arthropods, vertebrates, and cephalopods, but with conservation of large-scale dynamic patterns of a kind that have an apparent link to felt experience in humans. An evolutionary perspective also motivates a strongly gradualist view of consciousness; a simple distinction between conscious and nonconscious animals will probably be replaced with a view that admits differences of degree, perhaps on many dimensions.

Bullying in the Arab World: Definition, Perception, and Implications for Public Health and Interventions.

The present research aimed to examine bullying among diverse Arab nationalities residing in Qatar across two separate studies. Study 1 examined how Arabic-speaking adolescents and adults describe and perceive bullying, participants (N = 36) from different Arab nationalities (i.e., Egyptians, Qataris, Syrians, and other Arabs) were presented with three tasks in a focus group where they were asked questions about how they describe and perceive three scenarios without reference to the term "bullying". Findings indicated that (1) the majority of participants referred to the intention to cause harm and the imbalance of power in their descriptions, and (2) differences in describing the behaviours in the scenarios were notable when comparing Egyptians with the three other nationalities. Overall, participants frequently chose different Arabic terms (e.g., Ta'adi (تعدي)) in their descriptions of the scenarios. Interestingly, the term Tanammor (تنمُّر), which has been used in previous studies as the Arabic term for bullying, was chosen the least by the current sample. Study 2 examined how Arab-speaking students (N = 117) describe bullying behaviour in seven scenarios using Arabic and English terms. The procedure was administered in English in the international schools, and Arabic in the independent schools. English-speaking students often used the term "bullying", whereas Arabic-speaking students often used behavioural descriptions (e.g., the term "solok sayea" (سلوك سيء) which translates to "bad behaviour"). These findings are discussed in relation to the definition and perspective of bullying among Arabic speakers. There is a need for further investigations to introduce a novel term for bullying within the Arabic language while considering cultural values, norms, and beliefs. This has the potential to promote heightened awareness and comprehension, enabling the formulation of customised intervention approaches, policies, and educational initiatives intended to prevent and alleviate bullying behaviours.

The adequacy of workplace accommodation and the incidence of permanent employment separations after a disabling work injury or illness.

OBJECTIVE: This study aimed to estimate the influence of the adequacy of employer accommodations of health impairments in predicting permanent separation from the employment relationship in a cohort of workers disabled by a work-related injury or illness. METHODS: The study used data from a retrospective, observational cohort of 1793 Ontario workers who participated in an interviewer-administered survey 18 months following a disabling injury or illness. The relative risks (RR) of a permanent employment separation associated with inadequate employer accommodations were estimated using inverse probability of treatment weights to reduce confounding. RESULTS: Over the 18-month follow-up, the incidence of permanent separation was 30.1/100, with 49.2% of separations related to health status. Approximately 51% of participants experiencing a separation were exposed to inadequate workplace accommodations, compared to 27% of participants in continuing employment. The propensity score adjusted RR of a health-related separation associated with inadequate accommodation was substantial [RR 2.72; 95% confidence interval (CI) 2.20-3.73], greater than the RR of separations not related to health (RR 1.68; 95% CI 1.38-2.21). CONCLUSIONS: Incidence of permanent separation in this cohort of Ontario labor force participants was approximately two times more frequent than would be expected. The adequacy of employer accommodation was a strong determinant of the risk of permanent separation. These findings emphasize the potential for strengthened workplace accommodation practices in this setting.

Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting in Patients With Left Main Disease With and Without Diabetes: Findings From a Pooled Analysis of 4 Randomized Clinical Trials.

BACKGROUND: Diabetes may be associated with differential outcomes in patients undergoing left main coronary revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). The aim of this study was to investigate outcomes in patients with left main disease with and without diabetes randomized to PCI versus CABG. METHODS: Individual patient data were pooled from 4 trials (SYNTAX [Synergy Between PCI With Taxus and Cardiac Surgery], PRECOMBAT [Premier of Randomized Comparison of Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease], NOBLE [Nordic-Baltic-British Left Main Revascularisation Study], and EXCEL [Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization]) that randomized patients with left main disease to PCI or CABG. Patients were considered suitable for either approach. Patients were categorized by diabetes status. Kaplan-Meier event rates, Cox model hazard ratios, and interactions were assessed. RESULTS: Among 4393 patients, 1104 (25.1%) had diabetes. Patients with diabetes experienced higher rates of 5-year death (158/1104 [Kaplan-Meier rate, 14.7%] versus 297/3289 [9.3%]; P<0.001), spontaneous myocardial infarction (MI; 67/1104 [6.7%] versus 114/3289 [3.7%]; P<0.001), and repeat revascularization (189/1104 [18.5%] versus 410/3289 [13.2%]; P<0.001). Rates of all-cause mortality did not differ after PCI versus CABG in those with (84/563 [15.3%] versus 74/541 [14.1%]; hazard ratio, 1.11 [95% CI, 0.82-1.52]) or without (155/1634 [9.7%] versus 142/1655 [8.9%]; hazard ratio, 1.08 [95% CI, 0.86-1.36; PintHR=0.87) diabetes. Rates of stroke within 1 year were lower with PCI versus CABG in the entire population, with no heterogeneity based on diabetes status (PintHR=0.51). The 5-year rates of spontaneous MI and repeat coronary revascularization were higher after PCI regardless of diabetes status (spontaneous MI: 45/563 [8.9%] versus 22/541 [4.4%] in diabetes and 82/1634 [5.3%] versus 32/1655 [2.1%] in no diabetes, PintHR=0.47; repeat revascularization: 127/563 [24.5%] versus 62/541 [12.4%] in diabetes and 254/1634 [16.3%] versus 156/1655 [10.1%] in no diabetes, PintHR=0.18). For spontaneous MI and repeat revascularization, there were greater absolute risk differences beyond 1 year in patients with diabetes (4.9% and 9.9%) compared with those without (2.1% and 4.3%; PintARD=0.047 and 0.016). CONCLUSIONS: In patients with left main disease considered equally suitable for PCI or CABG and with largely low to intermediate SYNTAX scores, diabetes was associated with higher rates of death and cardiovascular events through 5 years. Compared with CABG, PCI resulted in no difference in the risk of death and a lower risk of early stroke regardless of diabetes status, and a higher risk of spontaneous MI and repeat coronary revascularization, with larger late absolute excess risks in patients with diabetes. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01205776, NCT0146651, NCT00422968, and NCT00114972.

Nonallergic Rhinopathy: A Comprehensive Review of Classification, Diagnosis, and Treatment.

Chronic nonallergic rhinitis syndromes encompass various conditions, of which vasomotor rhinitis is the most common form, representing approximately 80% of patients, also referred to as nonallergic rhinopathy (NAR), nasal hyperreactivity, neurogenic rhinitis, or idiopathic rhinitis. Expert panels have recommended replacing vasomotor rhinitis terminology because it is more descriptive of this condition that is characterized by symptoms triggered by chemical irritants and weather changes through chemosensors, mechanosensors, thermosensors, and/or osmosensors activated through different transient receptor potential calcium ion channels. Elucidating the specific role of transient receptor potential vanilloid 1, triggered by capsaicin, has been an important advancement in better understanding the pathophysiology of NAR because it has now been shown that downregulation of transient receptor potential vanilloid 1 receptors by several therapeutic compounds provides symptomatic relief for this condition. The classification of NAR is further complicated by its association with allergic rhinitis referred to as mixed rhinitis, which involves both immunoglobulin E-mediated and neurogenic mechanistic pathways. Comorbidities associated with NAR, including rhinosinusitis, headaches, asthma, chronic cough, and sleep disturbances, underscore the need for comprehensive management. Treatment options for NAR include environmental interventions, pharmacotherapy, and in refractory cases, surgical options, emphasizing the need for a tailored approach for each patient. Thus, it is extremely important to accurately diagnose NAR because inappropriate therapies lead to poor clinical outcomes and unnecessary health care and economic burdens for these patients. This review provides a comprehensive overview of NAR subtypes, focusing on classification, diagnosis, and treatment approaches for NAR.