Exacerbations Among Patients With Asthma Are Largely Dependent on the Presence of Multimorbidity.

BACKGROUND AND OBJECTIVE: Comorbidities can influence asthma control and promote asthma exacerbations (AEs). However, the impact of multimorbidity in AEs, assessed based on long-term follow-up of patients with asthma of different degrees of severity, has received little attention in real-life conditions. To describe the epidemiological and clinical characteristics and predictors of AEs in patients who had presented at least 1 AE in the previous year in the MEchanism of Genesis and Evolution of Asthma (MEGA) cohort. METHODS: The work-up included a detailed clinical examination, pulmonary function testing, fractional exhaled nitric oxide (FeNO), blood counts, induced sputum, skin prick-tests, asthma questionnaires, and assessment of multimorbidity. The number of moderate-severe AEs in the preceding year was registered for each patient. RESULTS: The study population comprised 486 patients with asthma (23.7% mild, 35% moderate, 41.3% severe). Disease remained uncontrolled in 41.9%, and 47.3% presented ≥1 moderate-severe AE, with a mean (SD) annual exacerbation rate of 0.47 (0.91) vs 2.11 (2.82) in mild and severe asthma, respectively. Comorbidity was detected in 56.4% (66.6% among those with severe asthma). Bronchiectasis, chronic rhinosinusitis with nasal polyps, atopy, psychiatric illnesses, hyperlipidemia, and hypertension were significantly associated with AEs. No associations were found for FeNO, blood eosinophils, or total serum IgE. Sputum eosinophilia and a high-T2 inflammatory pattern were significantly associated with AEs. Multivariable regression analysis showed a significant association with asthma severity, uncontrolled disease, and low prebronchodilator FEV1/FVC. CONCLUSION: Our study revealed a high frequency of AE in the MEGA cohort. This was strongly associated with multimorbidity, asthma severity, poor asthma control, airflow obstruction, higher sputum eosinophils, and a very high-T2 inflammatory pattern.

Improvement in Olfaction in Patients With CRSwNP and Severe Asthma Taking Anti-IgE and Anti-IL-5 Biologics: A Real-Life Study.

BACKGROUND AND OBJECTIVES: Chronic rhinosinusitis with nasal polyps (CRSwNP), which is characterized by partial loss of smell (hyposmia) or total loss of smell (anosmia), is commonly associated with asthma and/or nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD). CRSwNP worsens disease severity and quality of life. The objective of this real-world study was to determine whether biological treatments prescribed for severe asthma can improve olfaction in patients with CRSwNP. A further objective was to compare the improvement in in olfaction in N-ERD and non-N-ERD subgroups. METHODS: We performed a multicenter, noninterventional, retrospective, observational study of 206 patients with severe asthma and CRSwNP undergoing biological treatment (omalizumab, mepolizumab, benralizumab, or reslizumab). RESULTS: Olfaction improved after treatment with all 4 monoclonal antibodies (omalizumab [35.8%], mepolizumab [35.4%], reslizumab [35.7%], and benralizumab [39.1%]), with no differences between the groups. Olfaction was more likely to improve in patients with atopy, more frequent use of short-course systemic corticosteroids, and larger polyp size. The proportion of patients whose olfaction improved was similar between the N-ERD (37%) and non-N-ERD (35.7%) groups. CONCLUSIONS: This is the first real-world study to compare improvement in olfaction among patients undergoing long-term treatment with omalizumab, mepolizumab, reslizumab, or benralizumab for severe asthma and associated CRSwNP. Approximately 4 out of 10 patients reported a subjective improvement in olfaction (with nonsignificant differences between biologic drugs). No differences were found for improved olfaction between the N-ERD and non-N-ERD groups.

Estimated impact of the COVID-19 pandemic on the prevalence and treatment of depressive symptoms in Peru: an interrupted time series analysis in 2014-2021.

PURPOSE: The COVID-19 pandemic increased the burden of mental disorders worldwide. Peru has been one of the countries most affected by COVID-19, however, studies evaluating the medium and long-term consequences of the pandemic on Peruvians' mental health are recent and represent a new field of study in proliferation. We aimed to estimate the impact of the COVID-19 pandemic on the prevalence and treatment of depressive symptoms using nationally representative surveys in Peru. METHODS: Our study is an analysis of secondary data. We carried out a time series cross-sectional analysis based on the National Demographic and Health Survey of Peru, collected using a complex sampling design. The Patient Health Questionnaire-9 was used to measure mild (5-9 points), moderate (10-14 points), and severe (15 points or more) depressive symptoms. The participants were men and women aged 15 years and older, living in urban and rural areas of all regions of Peru. The main statistical analysis used segmented regression with Newey-West standard errors, taking into account that each year of the evaluation was divided into four measures (quarter measure). RESULTS: We included 259,516 participants. An average quarterly increase of 0.17% (95% CI 0.03-0.32%) in the prevalence of moderate depressive symptoms was identified after the onset of the COVID-19 pandemic (approximately an increase of 1583 new cases of moderate depressive symptoms by each quarter). The percentage of cases treated for mild depressive symptoms increased quarterly by an average of 0.46% (95% CI 0.20-0.71%) after the onset of the COVID-19 pandemic (approximately an increase of 1242 new cases treated for mild depressive symptoms by each quarter). CONCLUSION: In Peru, increases in the prevalence of moderate depressive symptoms and the proportion of cases treated with mild depressive symptoms were found after the COVID-19 pandemic. Therefore, this study is a precedent for future research assessing the prevalence of depressive symptoms and the proportion of cases receiving treatment during the pandemic and post-pandemic years.

Usability and perceptions of a one-on-one telementoring program for young physicians in rural settings of Peru: a mixed method study.

BACKGROUND: Telementoring seems to be a promising strategy to deliver training and counselling to physicians in remote areas. In Peru, early graduated physicians must work for the Rural and Urban-Edge Health Service Program where they face important training needs. The aim of this study was to describe the usage of a one-on-one telementoring program for rural physicians and evaluate the aspects related to the perceptions of acceptability and usability. METHODS: Mixed methods study on recently graduated physicians who work in rural areas and participate in the telementoring program. The program used a mobile application to connect these young doctors with specialized mentors to answer queries about real-life problems raised by working in a rural area. We summarize administrative data to assess participant characteristics and their participation in the program. Additionally, we conducted in-depth interviews to explore the perceived usability, ease of use, and reason for non-use of the telementoring program. RESULTS: Of 74 physicians (mean age 25, 51.4% women) enrolled, 12 (16.2%) actively used the program and performed a total of 27 queries, which received response in an average time of 5.4 ± 6.3 h. In the interviews, the main reasons for non-use were connectivity issues, feelings of shame, and self-efficacy. For those who used the telementoring program they referred it was easy to use and solve their inquiries timely. CONCLUSIONS: The implementation of a telementoring program sought to provide guidance to recently graduated physicians working in rural areas. Low use rates show that administrative and process-related deficiencies in the program implementation need to be improved.

Bioengineering potato plants to produce benzylglucosinolate for improved broad-spectrum pest and disease resistance.

In traditional, small-scale agriculture in the Andes, potatoes are frequently co-cultivated with the Andean edible tuber Tropaeolum tuberosum, commonly known as mashua, which is believed to exert a pest and disease protective role due to its content of the phenylalanine-derived benzylglucosinolate (BGLS). We bioengineered the production of BGLS in potato by consecutive generation of stable transgenic events with two polycistronic constructs encoding for expression of six BGLS biosynthetic genes from Arabidopsis thaliana. First, we integrated a polycistronic construct coding for the last three genes of the pathway (SUR1, UGT74B1 and SOT16) into potato driven by the cauliflower mosaic virus 35S promoter. After identifying the single-insertion transgenic event with the highest transgene expression, we stacked a second polycistronic construct coding for the first three genes in the pathway (CYP79A2, CYP83B1 and GGP1) driven by the leaf-specific promoter of the rubisco small subunit from chrysanthemum. We obtained transgenic events producing as high as 5.18 pmol BGLS/mg fresh weight compared to the non-transgenic potato plant producing undetectable levels of BGLS. Preliminary bioassays suggest a possible activity against Phytophthora infestans, causing the late blight disease and Premnotrypes suturicallus, referred to as the Andean potato weevil. However, we observed altered leaf morphology, abnormally thick and curlier leaves, reduced growth and tuber production in five out of ten selected transgenic events, which indicates that the expression of BGLS biosynthetic genes has an undesirable impact on the potato. Optimization of the expression of the BGLS biosynthetic pathway in potato is required to avoid alterations of plant development.

Different methods of cell quantification can lead to different results: a comparison of digital methods using a pilot study of dendritic cells in HIV-positive patients.

BACKGROUND: Although new digital pathology tools have improved the positive cell quantification, there is a heterogeneity of the quantification methods in the literature. The aim of this study was to evaluate and propose a novel dendritic cells quantification method in squamous cell carcinoma comparing it with a conventional quantification method. MATERIAL AND METHODS: Twenty-six squamous cell carcinomas HIV-positive cases affecting the oropharynx, lips and oral cavity were selected. Immunohistochemistry for CD1a, CD83, and CD207 was performed. The immunohistochemical stains were evaluated by automated examination using a positive pixel count algorithm. A conventional quantification method (unspecific area method; UA) and a novel method (specific area method; SA) were performed obtaining the corresponding density of positive dendritic cells for the intratumoral and peritumoral regions. The Mann-Whitney U test was used to verify the influence of the quantification methods on the positive cell counting according to the evaluated regions. Data were subjected to the ANOVA and Student's t-test to verify the influence of the tumour location, stage, histological grade, and amount of inflammation on the dendritic cells density counting. RESULTS: The cell quantification method affected the dendritic cells counting independently of the evaluated region (P-value <0.05). Significant differences between methods were also observed according to the tumour features evaluations. CONCLUSIONS: The positive cell quantification method influences the dendritic cells density results. Unlike the conventional method (UA method), the novel SA method avoids non-target areas included in the hotspots improving the reliability and reproducibility of the density cell quantification.

Oral diseases: a 14-year experience of a Chilean institution with a systematic review from eight countries.

BACKGROUND: Retrospective studies to assess the distribution of oral diseases (ODs) are helpful in estimating the prevalence of oral diagnoses in the population, and thus help in preventive and curative services. Prevalence and frequency data for ODs are available from many countries, but information from Chile is scarce. MATERIAL AND METHODS: This study investigated the frequency of OD in a Chilean population. For this, we included all patients treated at the University of Talca (UTALCA, Chile) between 2001 and 2014. Patient characteristics were retrieved from medical files. To contextualize our results, we conducted a systematic review (SystRev) using Publish or Perish software (PoP), Google Scholar and MEDLINE/PubMed. RESULTS: One hundred sixty-six ODs were diagnosed, and the most prevalent groups were soft tissue tumours, epithelial pathology and salivary gland pathology. Individually, irritation fibroma, oral lichen planus (OLP) and mucocele were the most common diagnoses. ODs frequently affected unspecified parts of the mouth (including cheek, vestibule and retromolar area), gum, lips, tongue and palate. In the SystRev, the more studied diagnoses were leukoplakia, OLP and recurrent aphthous stomatitis; prevalent lesions included Fordyce's spots, recurrent aphthous stomatitis and fissured tongue. Chilean patients and SistRev shared almost all ODs. CONCLUSIONS: The results reflect ODs diagnosed in a specialized service of oral pathology and medicine in Chile and will allow the establishment of preventive/curative policies, adequate health services and dentistry curriculum.

Using the whole cohort in the analysis of countermatched samples.

We present a technique for using calibrated weights to incorporate whole-cohort information in the analysis of a countermatched sample. Following Samuelsen's approach for matched case-control sampling, we derive expressions for the marginal sampling probabilities, so that the data can be treated as an unequally-sampled case-cohort design. Pseudolikelihood estimating equations are used to find the estimates. The sampling weights can be calibrated, allowing all whole-cohort variables to be used in estimation; in contrast, the partial likelihood analysis makes use only of a single discrete surrogate for exposure. Using a survey-sampling approach rather than a martingale approach simplifies the theory; in particular, the sampling weights need not be a predictable process. Our simulation results show that pseudolikelihood estimation gives lower efficiency than partial likelihood estimation, but that the gain from calibration of weights can more than compensate for this loss. If there is a good surrogate for exposure, countermatched sampling still outperforms case-cohort and two-phase case-control sampling even when calibrated weights are used. Findings are illustrated with data from the National Wilms' Tumour Study and the Welsh nickel refinery workers study.

Using the entire history in the analysis of nested case cohort samples.

Countermatching designs can provide more efficient estimates than simple matching or case-cohort designs in certain situations such as when good surrogate variables for an exposure of interest are available. We extend pseudolikelihood estimation for the Cox model under countermatching designs to models where time-varying covariates are considered. We also implement pseudolikelihood with calibrated weights to improve efficiency in nested case-control designs in the presence of time-varying variables. A simulation study is carried out, which considers four different scenarios including a binary time-dependent variable, a continuous time-dependent variable, and the case including interactions in each. Simulation results show that pseudolikelihood with calibrated weights under countermatching offers large gains in efficiency if compared to case-cohort. Pseudolikelihood with calibrated weights yielded more efficient estimators than pseudolikelihood estimators. Additionally, estimators were more efficient under countermatching than under case-cohort for the situations considered. The methods are illustrated using the Colorado Plateau uranium miners cohort. Furthermore, we present a general method to generate survival times with time-varying covariates. Copyright © 2016 John Wiley & Sons, Ltd.

Immersive Technologies for Depression Care: Scoping Review.

BACKGROUND: Depression significantly impacts quality of life, affecting approximately 280 million people worldwide. However, only 16.5% of those affected receive treatment, indicating a substantial treatment gap. Immersive technologies (IMTs) such as virtual reality (VR) and augmented reality offer new avenues for treating depression by creating immersive environments for therapeutic interventions. Despite their potential, significant gaps exist in the current evidence regarding the design, implementation, and use of IMTs for depression care. OBJECTIVE: We aim to map the available evidence on IMT interventions targeting depression treatment. METHODS: This scoping review followed a methodological framework, and we systematically searched databases for studies on IMTs and depression. The focus was on randomized clinical trials involving adults and using IMTs. The selection and charting process involved multiple reviewers to minimize bias. RESULTS: The search identified 16 peer-reviewed articles, predominantly from Europe (n=10, 63%), with a notable emphasis on Poland (n=9, 56%), which contributed to more than half of the articles. Most of the studies (9/16, 56%) were conducted between 2020 and 2021. Regarding participant demographics, of the 16 articles, 5 (31%) exclusively involved female participants, and 7 (44%) featured participants whose mean or median age was >60 years. Regarding technical aspects, all studies focused on VR, with most using stand-alone VR headsets (14/16, 88%), and interventions typically ranging from 2 to 8 weeks, predominantly in hospital settings (11/16, 69%). Only 2 (13%) of the 16 studies mentioned using a specific VR design framework in planning their interventions. The most frequently used therapeutic approach was Ericksonian psychotherapy, used in 56% (9/16) of the studies. Notably, none of the articles reported using an implementation framework or identified barriers and enablers to implementation. CONCLUSIONS: This scoping review highlights the growing interest in using IMTs, particularly VR, for depression treatment but emphasizes the need for more inclusive and comprehensive research. Future studies should explore varied therapeutic approaches and cost-effectiveness as well as the inclusion of augmented reality to fully realize the potential of IMTs in mental health care.

Anaemia in chronic obstructive pulmonary disease. Does it really matter?

Chronic obstructive pulmonary disease (COPD) is one of the most prevalent chronic diseases, with an increasing rate in morbidity and mortality. In recent years, there has been a greater awareness about the clinical importance of systemic effects and other chronic conditions associated with COPD, as these significantly impact on the course of disease. The most studied extrapulmonary manifestations in COPD include the presence of concomitant cardiovascular disease, skeletal muscle wasting, osteoporosis and lung cancer. Anaemia is a recognised independent marker of mortality in several chronic diseases. Recent studies have shown that anaemia in patients with COPD may be more frequent than expected, with a prevalence ranging from 5% to 33%. Some evidence suggests that systemic inflammation may play an important pathogenic role, but anaemia in COPD is probably multifactorial and may be caused by others factors, such as concealed chronic renal failure, decreased androgenic levels, iron depletion, angiotensin-converting enzyme inhibitor treatment and exacerbations. Low levels of haemoglobin and haematocrit in COPD patients have been associated with poor clinical and functional outcomes as well as with mortality and increased healthcare costs. Despite the potential clinical benefit of successfully treating anaemia in these patients, evidence supporting the importance of its correction on the prognosis of COPD is uncertain.

The impact of COVID-19 pandemic on the quality of life of healthcare workers and the associated factors: A systematic review.

Introduction: The COVID-19 pandemic has exacerbated health issues in healthcare workers which in turn impacts their quality of life. Objective: This review aimed to (i) analyze the impact of the COVID-19 pandemic on the quality of life of healthcare professionals and (ii) identify the associated factors with quality of life. Materials and methods: We conducted a systematic review using the PRISMA guidelines previously registered in PROSPERO (CRD42021253075). The searched in Web of Science, Scopus, MEDLINE and EMBASE databases included original articles published till May 2021. Results: We found 19 articles and 14,352 professionals in total, the median age ranged from 29 to 42.5 years and 37% of the studies used the WHOQOL-BREF instrument to assess the outcome. The report was heterogeneous, 7 studies described global scores and 9 by domains. Depression, anxiety and stress were commonly reported factors affecting professional's quality of life and this was significantly lower among professionals working with COVID-19 patients compared to their counterparts. Conclusion: COVID-19 frontline workers perceived lower quality of life, which was mainly associated with psychological states such as the aforementioned besides to working conditions like not being previously trained in COVID-19 cases. On the other hand, social support, resilience and active coping could improved their quality of life.

Introducción: La pandemia de COVID-19 ha agravado los problemas de salud del personal sanitario, lo que a su vez repercute en su calidad de vida. Objetivo: Esta revisión tiene como objetivo: (a) Analizar el impacto de la pandemia COVID-19 en la calidad de vida de los profesionales sanitarios y (2) Identificar los factores asociados a su calidad de vida. Materiales y métodos: Se realizó una revisión sistemática utilizando las pautas PRISMA previamente registradas en PROSPERO (CRD42021253075). La búsqueda en las bases de datos Web of Science, Scopus, MEDLINE y EMBASE incluyó artículos originales publicados hasta mayo de 2021. Resultados: Se encontraron 19 artículos y 14.352 profesionales en total, la mediana de edad osciló entre 29 y 42,5 años y el 37% de los estudios utilizaron el instrumento WHOQOL-BREF para evaluar el resultado. El informe fue heterogéneo, 7 estudios describieron puntuaciones globales y 9 por dominios. La depresión, la ansiedad y el estrés fueron los factores comúnmente reportados que afectan a la calidad de vida del profesional, y esta fue significativamente menor entre los profesionales que trabajan con pacientes de COVID-19 en comparación con sus homólogos. Conclusión: Los trabajadores de primera línea de COVID-19 percibieron una menor calidad de vida, que se asoció principalmente a estados psicológicos como los mencionados, además de a condiciones de trabajo como no haber recibido formación previa en casos de COVID-19. Por otro lado, el apoyo social, la resiliencia y el afrontamiento activo mejoraron su calidad de vida.

Profiles of depressive symptoms in Peru: An 8-year analysis in population-based surveys.

Background Profiles of depressive symptoms have been described due to heterogeneity in symptomatology and presentation. In our study, we estimate depressive symptom profiles and relate these symptom profiles to risk factors in the Peruvian population. Methods We carried out an observational study based on the Peruvian Demographic and Health Survey (2014-2022). Men and women aged 15 years and older living in urban and rural areas in all regions of Peru were included. The Patient Health Questionnaire-9 was used to define depressive symptom profiles. We estimated latent class models to define the profiles and performed a Poisson regression analysis to determine the associated factors. Results A total of 259,655 participants were included. The three-class model was found to be the most appropriate, and the classes were defined according to the severity of depressive symptoms (moderate-severe symptoms, mild symptoms, and without depressive symptoms). Also, it was found that the three classes identified have not changed during the years of evaluations, presenting very similar prevalence over the years. In addition, women are more likely than men to belong to a class with more severe depressive symptoms; and the older the age, the higher the probability of belonging to a class with greater severity of depressive symptoms. Conclusions Our study found that at the population level in Peru, depressive symptoms are grouped into three classes according to the intensity of the symptomatology present (no symptoms, mild symptoms and moderate-severe symptoms).

Sustainable volume sweep imaging lung teleultrasound in Peru: Public health perspectives from a new frontier in expanding access to imaging.

Background: Pulmonary disease is a common cause of morbidity and mortality, but the majority of the people in the world lack access to diagnostic imaging for its assessment. We conducted an implementation assessment of a potentially sustainable and cost-effective model for delivery of volume sweep imaging (VSI) lung teleultrasound in Peru. This model allows image acquisition by individuals without prior ultrasound experience after only a few hours of training. Methods: Lung teleultrasound was implemented at 5 sites in rural Peru after a few hours of installation and staff training. Patients were offered free lung VSI teleultrasound examination for concerns of respiratory illness or research purposes. After ultrasound examination, patients were surveyed regarding their experience. Health staff and members of the implementation team also participated in separate interviews detailing their views of the teleultrasound system which were systematically analyzed for key themes. Results: Patients and staff rated their experience with lung teleultrasound as overwhelmingly positive. The lung teleultrasound system was viewed as a potential way to improve access to imaging and the health of rural communities. Detailed interviews with the implementation team revealed obstacles to implementation important for consideration such as gaps in lung ultrasound understanding. Conclusions: Lung VSI teleultrasound was successfully deployed to 5 health centers in rural Peru. Implementation assessment revealed enthusiasm for the system among members of the community along with important areas of consideration for future teleultrasound deployment. This system offers a potential means to increase access to imaging for pulmonary illness and improve the health of the global community.