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Ayer — Mayo 14th 2024PLOS ONE Medicine&Health

Exploring novel immunotherapy biomarker candidates induced by cancer deformation

by Se Min Kim, Namu Park, Hye Bin Park, JuKyung Lee, Changho Chun, Kyung Hoon Kim, Jong Seob Choi, Hyung Jin Kim, Sekyu Choi, Jung Hyun Lee

Triple-negative breast cancer (TNBC) demands urgent attention for the development of effective treatment strategies due to its aggressiveness and limited therapeutic options [1]. This research is primarily focused on identifying new biomarkers vital for immunotherapy, with the aim of developing tailored treatments specifically for TNBC, such as those targeting the PD-1/PD-L1 pathway. To achieve this, the study places a strong emphasis on investigating Ig genes, a characteristic of immune checkpoint inhibitors, particularly genes expressing Ig-like domains with altered expression levels induced by "cancer deformation," a condition associated with cancer malignancy. Human cells can express approximately 800 Ig family genes, yet only a few Ig genes, including PD-1 and PD-L1, have been developed into immunotherapy drugs thus far. Therefore, we investigated the Ig genes that were either upregulated or downregulated by the artificial metastatic environment in TNBC cell line. As a result, we confirmed the upregulation of approximately 13 Ig genes and validated them using qPCR. In summary, our study proposes an approach for identifying new biomarkers applicable to future immunotherapies aimed at addressing challenging cases of TNBC where conventional treatments fall short.

Relationship between personality traits and postpartum depression in Pakistani fathers

by Najam ul Hasan Abbasi, Ahmad Bilal, Khair Muhammad, Saba Riaz, Shakeela Altaf

The previous studies have found an association between Big Five personality traits and postpartum depression in women. The present study aimed to find out an association between Big Five personality traits and postpartum depression in a sample of Pakistani fathers. A total of 400 Pakistani fathers who had birth of a child in the past 1 month to 1 year period and had been living with their married partners were recruited purposively by using Google Form based survey from the major cities of Pakistan. The Urdu translated versions of Big Five Personality Inventory (BFI) and Edinburgh Postnatal Depression Scale (EPDS) were used as the main outcome measures to assess the relationship between personality traits and postpartum depression. The results found a significant negative and moderate association between Big Five personality traits and paternal postpartum depression except openness which had a weak association and neuroticism which had a positive and moderate association with PPPD (r(398) = .45). The multiple linear regression analysis found that Big Five personality traits significantly predicted paternal postpartum depression (F(5, 394) = 53.33, p = .001) except openness (B = .007, p = .98). The analysis of variance (ANOVA) found significant differences in paternal postpartum depression for age of father (F(2, 397) = 6.65, p = .001, ηp2 = .03), spouse age (F(2, 393) = 5.97, p = .003, ηp2 = .02), employment type (F(2, 395) = 9.69, p = .001, ηp2 = .04) and time spent at home (F(2, 397) = 6.23, p = .002, ηp2 = .03) while there were found no significant differences for education (F(2, 397) = 1.29, p = .27, ηp2 = .006), marital duration (F(2, 397) = 2.17, p = .11, ηp2 = .01), and birth number of recent child (F(2, 397) = 1.48, p = .22, ηp2 = .007). The study concluded that Big Five personality traits are significantly correlated with and predict paternal postpartum depression except openness which did not predict paternal postpartum depression. The occurrence of paternal postpartum depression varied significantly for age of father, age of spouse, type of employment and time spent at home.

Distribution and dynamics of <i>Anopheles gambiae</i> s.l. larval habitats in three Senegalese cities with high urban malaria incidence

by Fatou Ndiaye, Abdoulaye Diop, Joseph Chabi, Katherine Sturm-Ramirez, Massila Senghor, El Hadji Diouf, Badara Samb, Seynabou Mocote Diedhiou, Omar Thiaw, Sarah Zohdy, Ellen Dotson, Doudou Sene, Mame Birame Diouf, Valerie Koscelnik, Lilia Gerberg, Abdoulaye Bangoura, Tiffany Clark, Ousmane Faye, Ibrahima Dia, Lassana Konate, El Hadji Amadou Niang

Urban malaria has become a challenge for most African countries due to urbanization, with increasing population sizes, overcrowding, and movement into cities from rural localities. The rapid expansion of cities with inappropriate water drainage systems, abundance of water storage habitats, coupled with recurrent flooding represents a concern for water-associated vector borne diseases, including malaria. This situation could threaten progress made towards malaria elimination in sub-Saharan countries, including Senegal, where urban malaria has presented as a threat to national elimination gains. To assess drivers of urban malaria in Senegal, a 5-month study was carried out from August to December 2019 in three major urban areas and hotspots for malaria incidence (Diourbel, Touba, and Kaolack) including the rainy season (August-October) and partly dry season (November–December). The aim was to characterize malaria vector larval habitats, vector dynamics across both seasons, and to identify the primary eco- environmental entomological factors contributing to observed urban malaria transmission. A total of 145 Anopheles larval habitats were found, mapped, and monitored monthly. This included 32 in Diourbel, 83 in Touba, and 30 in Kaolack. The number of larval habitats fluctuated seasonally, with a decrease during the dry season. In Diourbel, 22 of the 32 monitored larval habitats (68.75%) were dried out by December and considered temporary, while the remaining 10 (31.25%) were classified as permanent. In the city of Touba 28 (33.73%) were temporary habitats, and of those 57%, 71% and 100% dried up respectively by October, November, and December. However, 55 (66.27%) habitats were permanent water storage basins which persisted throughout the study. In Kaolack, 12 (40%) permanent and 18 (60%) temporary Anopheles larval habitats were found and monitored during the study. Three malaria vectors (An. arabiensis, An. pharoensis and An. funestus s.l.) were found across the surveyed larval habitats, and An. arabiensis was found in all three cities and was the only species found in the city of Diourbel, while An. arabiensis, An. pharoensis, and An. funestus s.l. were detected in the cities of Touba and Kaolack. The spatiotemporal observations of immature malaria vectors in Senegal provide evidence of permanent productive malaria vector larval habitats year-round in three major urban centers in Senegal, which may be driving high urban malaria incidence. This study aimed to assess the presence and type of anopheline larvae habitats in urban areas. The preliminary data will better inform subsequent detailed additional studies and seasonally appropriate, cost-effective, and sustainable larval source management (LSM) strategies by the National Malaria Control Programme (NMCP).
AnteayerPLOS ONE Medicine&Health

Multiparameter immunoprofiling for the diagnosis and differentiation of progressive versus nonprogressive nontuberculous mycobacterial lung disease–A pilot study

by Paige K. Marty, Balaji Pathakumari, Thomas M. Cox, Virginia P. Van Keulen, Courtney L. Erskine, Maleeha Shah, Mounika Vadiyala, Pedro Arias-Sanchez, Snigdha Karnakoti, Kelly M. Pennington, Elitza S. Theel, Cecilia S. Lindestam Arlehamn, Tobias Peikert, Patricio Escalante

Clinical prediction of nontuberculous mycobacteria lung disease (NTM-LD) progression remains challenging. We aimed to evaluate antigen-specific immunoprofiling utilizing flow cytometry (FC) of activation-induced markers (AIM) and IFN-γ enzyme-linked immune absorbent spot assay (ELISpot) accurately identifies patients with NTM-LD, and differentiate those with progressive from nonprogressive NTM-LD. A Prospective, single-center, and laboratory technician-blinded pilot study was conducted to evaluate the FC and ELISpot based immunoprofiling in patients with NTM-LD (n = 18) and controls (n = 22). Among 18 NTM-LD patients, 10 NTM-LD patients were classified into nonprogressive, and 8 as progressive NTM-LD based on clinical and radiological features. Peripheral blood mononuclear cells were collected from patients with NTM-LD and control subjects with negative QuantiFERON results. After stimulation with purified protein derivative (PPD), mycobacteria-specific peptide pools (MTB300, RD1-peptides), and control antigens, we performed IFN-γ ELISpot and FC AIM assays to access their diagnostic accuracies by receiver operating curve (ROC) analysis across study groups. Patients with NTM-LD had significantly higher percentage of CD4+/CD8+ T-cells co-expressing CD25+CD134+ in response to PPD stimulation, differentiating between NTM-LD and controls. Among patients with NTM-LD, there was a significant difference in CD25+CD134+ co-expression in MTB300-stimulated CD8+ T-cells (p

Relying on the French territorial offer of thermal spa therapies to build a care pathway for long COVID-19 patients

by Milhan Chaze, Laurent Mériade, Corinne Rochette, Mélina Bailly, Rea Bingula, Christelle Blavignac, Martine Duclos, Bertrand Evrard, Anne Cécile Fournier, Lena Pelissier, David Thivel, on behalf of CAUVIM-19 Group

Background

Work on long COVID-19 has mainly focused on clinical care in hospitals. Thermal spa therapies represent a therapeutic offer outside of health care institutions that are nationally or even internationally attractive. Unlike local care (hospital care, general medicine, para-medical care), their integration in the care pathways of long COVID-19 patients seems little studied. The aim of this article is to determine what place french thermal spa therapies can take in the care pathway of long COVID-19 patients.

Methods

Based on the case of France, we carry out a geographic mapping analysis of the potential care pathways for long COVID-19 patients by cross-referencing, over the period 2020–2022, the available official data on COVID-19 contamination, hospitalisations in intensive care units and the national offer of spa treatments. This first analysis allows us, by using the method for evaluating the attractiveness of an area defined by David Huff, to evaluate the accessibility of each French department to thermal spas.

Results

Using dynamic geographical mapping, this study describes two essential criteria for the integration of the thermal spa therapies offer in the care pathways of long COVID-19 patients (attractiveness of spa areas and accessibility to thermal spas) and three fundamental elements for the success of these pathways (continuity of the care pathways; clinical collaborations; adaptation of the financing modalities to each patient). Using a spatial attractiveness method, we make this type of geographical analysis more dynamic by showing the extent to which a thermal spa is accessible to long COVID-19 patients.

Conclusion

Based on the example of the French spa offer, this study makes it possible to place the care pathways of long COVID-19 patients in a wider area (at least national), rather than limiting them to clinical and local management in a hospital setting. The identification and operationalization of two geographical criteria for integrating a type of treatment such as a spa cure into a care pathway contributes to a finer conceptualization of the construction of healthcare pathways.

Exploring the impact of OSA on short-term survival in patients with AECOPD admitted to the ICU

by Liangfeng Liu, Yang Chen, Guanwen He, Bingbang Lin, Zhongshou Zhu, Rifu Wei, Yangbin Xu

Background

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is characterized by a sudden worsening of chronic obstructive pulmonary disease (COPD) symptoms, which significantly contributes to hospitalizations related to COPD symptoms. Previous research has mainly focused on the correlation between obstructive sleep apnea (OSA) and COPD. However, there were few studies that investigated the short-term mortality rate of AECOPD patients with or without OSA.

Methods

Data for our research was taken from the Medical Information Mart for Intensive Care Database IV. A total of 1332 patients were included in the study based on well-defined criteria for selection and exclusion. By analyzing the characteristics of AECOPD patients, we compared those with and without OSA.

Results

There were 1122 AECOPD patients without OSA, 210 patients with OSA. In comparison to those without OSA, patients with OSA exhibited lower 30-day and 90-day ICU mortality with unadjusted HR, as well as lower hospital mortality with unadjusted OR. However, after adjustments were made, there were no significant associations observed between OSA and short-term mortality, including 30-day ICU mortality, 90-day ICU mortality, ICU mortality, and hospital mortality in AECOPD patients. Subgroup analysis revealed that OSA may act as a risk factor for AECOPD patients with a BMI lower than 30 kg/m2.

Conclusions

There is no impact on short-term survival in AECOPD patients with OSA under intensive care unit (ICU) management and nursing.

Raman difference spectroscopy and U-Net convolutional neural network for molecular analysis of cutaneous neurofibroma

by Levi Matthies, Hendrik Amir-Kabirian, Medhanie T. Gebrekidan, Andreas S. Braeuer, Ulrike S. Speth, Ralf Smeets, Christian Hagel, Martin Gosau, Christian Knipfer, Reinhard E. Friedrich

In Neurofibromatosis type 1 (NF1), peripheral nerve sheaths tumors are common, with cutaneous neurofibromas resulting in significant aesthetic, painful and functional problems requiring surgical removal. To date, determination of adequate surgical resection margins–complete tumor removal while attempting to preserve viable tissue–remains largely subjective. Thus, residual tumor extension beyond surgical margins or recurrence of the disease may frequently be observed. Here, we introduce Shifted-Excitation Raman Spectroscopy in combination with deep neural networks for the future perspective of objective, real-time diagnosis, and guided surgical ablation. The obtained results are validated through established histological methods. In this study, we evaluated the discrimination between cutaneous neurofibroma (n = 9) and adjacent physiological tissues (n = 25) in 34 surgical pathological specimens ex vivo at a total of 82 distinct measurement loci. Based on a convolutional neural network (U-Net), the mean raw Raman spectra (n = 8,200) were processed and refined, and afterwards the spectral peaks were assigned to their respective molecular origin. Principal component and linear discriminant analysis was used to discriminate cutaneous neurofibromas from physiological tissues with a sensitivity of 100%, specificity of 97.3%, and overall classification accuracy of 97.6%. The results enable the presented optical, non-invasive technique in combination with artificial intelligence as a promising candidate to ameliorate both, diagnosis and treatment of patients affected by cutaneous neurofibroma and NF1.

The efficacy of ferroptosis-inducing compounds IKE and RSL3 correlates with the expression of ferroptotic pathway regulators CD71 and SLC7A11 in biliary tract cancer cells

by Dino Bekric, Tobias Kiesslich, Matthias Ocker, Martina Winklmayr, Markus Ritter, Heidemarie Dobias, Marlena Beyreis, Daniel Neureiter, Christian Mayr

Introduction

Biliary tract cancer (BTC) is a lethal disease with a bad overall survivability, partly arising from inadequate therapeutic alternatives, detection at a belated stage, and a resistance to common therapeutic approaches. Ferroptosis is a form of programmed cell death that depends on reactive oxygen species (ROS) and iron, causing excessive peroxidation of polyunsaturated fatty acids (PUFAs). Therefore, the objective of this investigation is, whether ferroptosis can be induced in BTC in vitro and whether this induction is dependent on specific molecular markers.

Methods

The study conducted resazurin assay and IC25/50 calculation to explore the possible cytotoxic outcomes of different classes of ferroptosis-inducing substances (FINs) on a comprehensive in vitro model of 11 BTC cell lines. Combinatory treatments with different cell death inhibitors were performed to evaluate the magnitude of ferroptosis induction. To ascertain whether ferroptotic cell death occurred, liperfluo and iron assay kits were employed to evaluate lipid ROS and intracellular iron abundance. Potential biomarkers of ferroptosis sensitivity were then assessed via western blot analysis, a rtPCR panel and functional assay kits.

Results

The study found that different FINs reduced cell viability in a cell line-dependent manner. In addition, we measured increased lipid ROS and intracellular Fe2+ levels upon exposure to FINs in BTC cells. Combining FINs with inhibitors of ferroptosis, necroptosis or apoptosis suggests the occurrence of ferroptotic events in BTC cell lines CCC-5, HuH-28 and KKU-055. Furthermore, we found that BTC cells display a heterogeneous profile regarding different molecular genes/markers of ferroptosis. Subsequent analysis revealed that sensitivity of BTC cells towards IKE and RSL3 positively correlated with CD71 and SLC7A11 protein expression.

Conclusion

Our results demonstrate that induction of ferroptosis is a promising approach to inhibit BTC cell growth and that the sensitivity of BTC cells towards ferroptosis induction might be dependent on molecular markers such as CD71 and SLC7A11.

Identification of differentially expressed mRNA/lncRNA modules in acutely regorafenib-treated sorafenib-resistant Huh7 hepatocellular carcinoma cells

by Mina Baek, Minjae Kim, Hae In Choi, Bert Binas, Junho Cha, Kyoung Hwa Jung, Sungkyoung Choi, Young Gyu Chai

The multikinase inhibitor sorafenib is the standard first-line treatment for advanced hepatocellular carcinoma (HCC), but many patients become sorafenib-resistant (SR). This study investigated the efficacy of another kinase inhibitor, regorafenib (Rego), as a second-line treatment. We produced SR HCC cells, wherein the PI3K-Akt, TNF, cAMP, and TGF-beta signaling pathways were affected. Acute Rego treatment of these cells reversed the expression of genes involved in TGF-beta signaling but further increased the expression of genes involved in PI3K-Akt signaling. Additionally, Rego reversed the expression of genes involved in nucleosome assembly and epigenetic gene expression. Weighted gene co-expression network analysis (WGCNA) revealed four differentially expressed long non-coding RNA (DElncRNA) modules that were associated with the effectiveness of Rego on SR cells. Eleven putative DElncRNAs with distinct expression patterns were identified. We associated each module with DEmRNAs of the same pattern, thus obtaining DElncRNA/DEmRNA co-expression modules. We discuss the potential significance of each module. These findings provide insights and resources for further investigation into the potential mechanisms underlying the response of SR HCC cells to Rego.

Prevalence and impact of sarcopenia in individuals with heart failure with reduced ejection fraction (the SARC-HF study): A prospective observational study protocol

by Pablo Marino Corrêa Nascimento, Luiz Fernando Rodrigues Junior, Mauro Felippe Felix Mediano, Valéria Gonçalves da Silva, Bernardo Rangel Tura, Fabio César Sousa Nogueira, Gilberto Domont, Adriana Bastos Carvalho, Antônio Carlos Campos de Carvalho, Taís Hanae Kasai-Brunswick, Claudio Tinoco Mesquita, Humberto Villacorta Junior, Helena Cramer Veiga Rey

Sarcopenia, a clinical syndrome primarily associated with reduced muscle mass in the elderly, has a negative impact on quality of life and survival. It can occur secondarily to other diseases such as heart failure (HF), a complex clinical syndrome with high morbidity and mortality. The simultaneous occurrence of these two conditions can worsen the prognosis of their carriers, especially in the most severe cases of HF, as in patients with reduced left ventricular ejection fraction (LVEF). However, due to the heterogeneous diagnostic criteria for sarcopenia, estimates of its prevalence present a wide variation, leading to new criteria having been recently proposed for its diagnosis, emphasizing muscle strength and function rather than skeletal muscle mass. The primary objective of this study is to evaluate the prevalence of sarcopenia and/or dynapenia in individuals with HF with reduced LVEF according to the most recent criteria, and compare the gene and protein expression of those patients with and without sarcopenia. The secondary objectives are to evaluate the association of sarcopenia and/or dynapenia with the risk of clinical events and death, quality of life, cardiorespiratory capacity, ventilatory efficiency, and respiratory muscle strength. The participants will answer questionnaires to evaluate sarcopenia and quality of life, and will undergo the following tests: handgrip strength, gait speed, dual-energy X-ray absorptiometry, respiratory muscle strength, cardiopulmonary exercise, as well as genomic and proteomic analysis, and dosage of N-terminal pro-B-type natriuretic peptide and growth differentiation factor-15. An association between sarcopenia and/or dynapenia with unfavorable clinical evolution is expected to be found, in addition to reduced quality of life, cardiorespiratory capacity, ventilatory efficiency, and respiratory muscle strength.

Effect of the red uniform on the judgment of position or movement used in Wushu Routine, evaluated by practitioners of the modality

by Jinkun Li, Jingmin Zhang, Shuo Tao, Xiaoying Zeng, Rong Zou, Xiaobin Hong

In the artistic sports program, the referee’ scores directly determine the final results of the athletes. Wushu is a artistic sport that has a Chinese characteristic and has the potential to become an official competition at the Summer Olympic. In this study we tested whether a red uniform color affects Wushu Routine practitioners’ ratings of athletes’ position or movement of Wushu Routine. We also tested whether the effect varied depending on the gender of the athlete and the practitioner, and depending on whether female practitioners were in the ovulation phase of their menstrual cycle. Male (Experiment 1: N = 72) and female (Experiment 1: N = 72; Experiment 2: N = 52) participants who major in Wushu Routine were recruited to take a referee’s perspective and rate the movement quality of male and female athletes wearing red or blue uniforms. The results of Experiment 1 showed that both male and female athletes wearing red uniform (compared to blue uniform) received higher ratings (p = .002, η2 = .066; p = .014, η2 = .043), and the red effect was especially strong when male practitioners rated female athletes (p = .002, η2 = .069). The results of Experiment 2, in an all-female sample, showed that in most cases there was no difference in ratings made by women in the ovulation and non-ovulation phases of their menstrual cycle, with the exception of their ratings of male athletes wearing red; in this condition, women gave higher ratings when they were in the ovulation phase of their cycle (p = .026). The results suggest that there is a red effect in an artistic sport like Wushu Routine, in which gender and the female menstrual cycle play an important role.

Prevalence and risk factors of work-related musculoskeletal disorders among shopkeepers in Ethiopia: Evidence from a workplace cross-sectional study

by Amensisa Hailu Tesfaye, Gebisa Guyasa Kabito, Fantu Mamo Aragaw, Tesfaye Hambisa Mekonnen

Introduction

Work-related musculoskeletal disorders (WRMSDs) are the leading cause of disability worldwide. Shopkeepers are prone to developing work-related musculoskeletal disorders, but they are largely overlooked in research and policy actions, particularly in developing countries. So far, there is a lack of data on the magnitude and factors influencing work-related musculoskeletal disorders among shopkeepers in Ethiopia. Therefore, the current study aimed to explore the prevalence and risk factors of work-related musculoskeletal disorders among shopkeepers in Gondar City, Ethiopia.

Methods

A workplace-based cross-sectional study was conducted from July to August 2022, in Gondar city, Northwest Ethiopia. A multistage sampling technique was used to select 625 shopkeepers. The data were collected using an interviewer-administered standardized Nordic Musculoskeletal Questionnaire. Analysis was made using Stata version 14. Factors associated with the prevalence of work-related musculoskeletal disorders were identified using the multivariable Poisson regression model. The adjusted prevalence ratio with 95% confidence intervals (CIs) and p-value Results

The overall prevalence of work-related musculoskeletal disorders among shopkeepers in the past 12 months was found to be 81.1% (N = 507). The most frequently affected body part was the lower back (46.6%), followed by the upper back (43.8%) and shoulder (35.4%). Being female (p = 0.043), being in the age group of ≥40 years (p = 0.028), being overweight (p = 0.035), experiencing job stress (p = 0.006) and prolonged sitting (p = 0.045) were significant factors for the prevalence of work-related musculoskeletal disorders among shopkeepers.

Conclusion

This study revealed that shopkeepers face an alarmingly high prevalence of work-related musculoskeletal disorders. Female, older, overweight, stressed and shopkeepers who sit in the same position for long periods of time were identified as particularly vulnerable groups. These findings call for the urgent development and implementation of preventive measures, including ergonomic adjustments, education and training programs, stress management techniques and the promotion of physical activity, to protect this vulnerable workforce from the debilitating effects of work-related musculoskeletal disorders and to ensure their long-term health and well-being.

Anxiety disorders among youth with substance use and associated factors in Northwest Ethiopia: A community-based study

by Mamaru Melkam, Demeke Demilew, Tilahun Kassew, Biruk Fanta, Sewbesew Yitayih, Kassahun Alemu, Yassin Muhammed, Berhanie Getnet, Eden Abetu, Gebrekidan Ewnetu Tarekeg, Mohammed Oumer, Goshu Nenko

Introduction

Anxiety disorder is an unpleasant emotional feeling with symptoms related to psychological and autonomic symptoms such as headache, perspiration, palpitations, dizziness, and stomach discomfort. The use of substances become a worldwide problem among youth which brings situation that leads to serious social and health-related problems. Anxiety disorders with substance use have a huge impact on their high prevalence, therapeutic issues, and poor prognosis on clinical effects. Although the prevalence of anxiety disorders is significant among young people who use substances, limited studies were conducted. Therefore, this study revealed the burden of anxiety disorders among youth with substance use and associated factors in Ethiopia.

Method

A community-based multi-stage with a simple random sampling technique was conducted. A total of 372 substance users study participants were recruited for this study. Alcohol, Smoking, and Substance Involvement Screening Tests, Depression Anxiety Stress Scales, and other tools were used to assess anxiety disorders with substance use and associated factors. Data were entered into Epi-data version 4.6, and exported to SPSS version 20 for further analysis. Bi-variables logistic regression analysis was employed to identify variables with a p-value of Results

From a total of 372 respondents the overall prevalence of anxiety disorders with substance use was 48.1%. Male sex [AOR = 1.99; 95% CI: (1.01–3.93)], low educational status of the father [AOR = 6.38 95%CI: (1.50–7.08)], and the presence of stress [AOR = 2.48; 95% CI: 2.48(2.43–4.40)] were significantly associated factors with anxiety disorders with substances use.

Conclusions and recommendations

The prevalence of anxiety disorders with substance use was 48.1% therefore; it is recommended that the zonal administration give collaborative work with the health bureau and facilitate awareness creation about the impact of substance abuse. Clinicians are recommended to mitigate anxiety disorders with substance use to get a good prognosis for clients with controlling their stress.

Institutional capacity assessment in the lens of implementation research: Capacity of the local institutions in delivering WASH services at Cox’s Bazar district, Bangladesh

by Mahbubur Rahman, Mahbub-Ul Alam, Sharmin Khan Luies, Sharika Ferdous, Zahidul Mamun, Musarrat Jabeen Rahman, Debashish Biswas, Tazrina Ananya, Asadullah, Abul Kamal, Ritthick Chowdhury, Eheteshamul Russel Khan, Dara Johnston, Martin Worth, Umme Farwa Daisy, Tanvir Ahmed

Background

The influx of Forcibly Displaced Myanmar Nationals (FDMNs) has left the Southwest coastal district of Cox’s Bazar with one of the greatest contemporary humanitarian crises, stressing the existing water, sanitation, and hygiene (WASH) resources and services. This study aimed to assess the existing capacity of local institutions involved in delivering WASH services and identify relevant recommendations for intervention strategies.

Methods

We used a qualitative approach, including interviews and capacity assessment workshops with institutions engaged in WASH service delivery. We conducted five key informant interviews (KII) with sub-district level officials of the Department of Public Health Engineering (DPHE), Directorate General of Health Services (DGHS), Directorate of Primary Education (DPE) and Bangladesh Rural Advancement Committee (BRAC) to have a general idea of WASH service mechanisms. Seven capacity assessment workshops were organized with the relevant district and sub-district level stakeholders from August 2019 to September 2019. These workshops followed three key areas: i) knowledge of policy, organizational strategy, guidelines, and framework; ii) institutional arrangements for service delivery such as planning, implementation, coordination, monitoring, and reporting; and iii) availability and management of human, financial and infrastructural resources. Data were categorized using thematic content analysis.

Results

The majority of stakeholders lacked awareness of national WASH policies. Furthermore, the top-down planning approaches resulted in activities that were not context-specific, and lack of coordination between multiple institutions compromised the optimal WASH service delivery at the local level. Shortage of human resources in delivering sustainable WASH services, inadequate supervision, and inadequate evaluation of activities also required further improvement, as identified by WASH stakeholders.

Conclusion

Research evidence suggests that decision-makers, donors, and development partners should consider learning from the WASH implementers and stakeholders about their existing capacity, gaps, and opportunities before planning for any WASH intervention in any particular area.

Inflammatory markers in world trade center workers with asthma: Associations with post traumatic stress disorder

by Juan P. Wisnivesky, Nikita Agrawal, Jyoti Ankam, Adam Gonzalez, Alex Federman, Steven B. Markowitz, Janette M. Birmingham, Paula J. Busse

Background

Post-traumatic stress disorders (PTSD) is associated with worse asthma outcomes in individuals exposed to the World Trade Center (WTC) site.

Research question

Do WTC workers with coexisting PTSD and asthma have a specific inflammatory pattern that underlies the relationship with increased asthma morbidity?

Study design and methods

We collected data on a cohort of WTC workers with asthma recruited from the WTC Health Program. Diagnosis of PTSD was ascertained with a Structured Clinical Interview for DSM-5 (Diagnostic and Statistical Manuel of Mental Disorders) and the severity of PTSD symptoms was assessed with the PTSD Checklist 5. We obtained blood and sputum samples to measure cytokines levels in study participants.

Results

Of the 232 WTC workers with diagnosis of asthma in the study, 75 (32%) had PTSD. PTSD was significantly associated with worse asthma control (p = 0.002) and increased resource utilization (p = 0.0002). There was no significant association (p>0.05) between most blood or sputum cytokines with PTSD diagnosis or PCL-5 scores both in unadjusted and adjusted analyses.

Interpretation

Our results suggest that PTSD is not associated with blood and sputum inflammatory markers in WTC workers with asthma. These findings suggest that other mechanisms likely explain the association between PTSD and asthma control in WTC exposed individuals.

Potential efficacy of caffeine ingestion on balance and mobility in patients with multiple sclerosis: Preliminary evidence from a single-arm pilot clinical trial

by Afsoon Dadvar, Melika Jameie, Mehdi Azizmohammad Looha, Mohammadamin Parsaei, Meysam Zeynali Bujani, Mobina Amanollahi, Mahsa Babaei, Alireza Khosravi, Hamed Amirifard

Objectives

Caffeine’s potential benefits on multiple sclerosis (MS), as well as on the ambulatory performance of non-MS populations, prompted us to evaluate its potential effects on balance, mobility, and health-related quality of life (HR-QoL) of persons with MS (PwMS).

Methods

This single-arm pilot clinical trial consisted of a 2-week placebo run-in and a 12-week caffeine treatment (200 mg/day) stage. The changes in outcome measures during the study period (weeks 0, 2, 4, 8, and 12) were evaluated using the Generalized Estimation Equation (GEE). The outcome measures were the 12-item Multiple Sclerosis Walking Scale (MSWS-12) for self-reported ambulatory disability, Berg Balance Scale (BBS) for static and dynamic balance, Timed Up and Go (TUG) for dynamic balance and functional mobility, Multiple Sclerosis Impact Scale (MSIS-29) for patient’s perspective on MS-related QoL (MS-QoL), and Patients’ Global Impression of Change (PGIC) for subjective assessment of treatment efficacy. GEE was also used to evaluate age and sex effect on the outcome measures over time. (Iranian Registry of Clinical Trials, IRCT2017012332142N1).

Results

Thirty PwMS were included (age: 38.89 ± 9.85, female: 76.7%). Daily caffeine consumption significantly improved the objective measures of balance and functional mobility (BBS; P-value Conclusions

Caffeine may enhance balance, functional mobility, and QoL in PwMS. Being male was associated with a sharper increase in self-reported ambulatory disability over time. The effects of aging on balance get more pronounced over time.

Trial registration

This study was registered with the Iranian Registry of Clinical Trials (Registration number: IRCT2017012332142N1), a Primary Registry in the WHO Registry Network.

Developing a PRogram to Educate and Sensitize Caregivers to Reduce the Inappropriate Prescription Burden in the Elderly with Alzheimer’s Disease (D-PRESCRIBE-AD): Trial protocol and rationale of an open-label pragmatic, prospective randomized controlled

by Sonal Singh, Noelle M. Cocoros, Xiaojuan Li, Kathleen M. Mazor, Mary T. Antonelli, Lauren Parlett, Mark Paullin, Thomas P. Harkins, Yunping Zhou, Paula A. Rochon, Richard Platt, Inna Dashevsky, Carly Massino, Cassandra Saphirak, Sybil L. Crawford, Jerry H. Gurwitz

Context

Potentially inappropriate prescribing of medications in older adults, particular those with dementia, can lead to adverse drug events including falls and fractures, worsening cognitive impairment, emergency department visits, and hospitalizations. Educational mailings from health plans to patients and their providers to encourage deprescribing conversations may represent an effective, low-cost, “light touch”, approach to reducing the burden of potentially inappropriate prescription use in older adults with dementia.

Objectives

The objective of the Developing a PRogram to Educate and Sensitize Caregivers to Reduce the Inappropriate Prescription Burden in Elderly with Alzheimer’s Disease (D-PRESCRIBE-AD) trial is to evaluate the effect of a health plan based multi-faceted educational outreach intervention to community dwelling patients with dementia who are currently prescribed sedative/hypnotics, antipsychotics, or strong anticholinergics.

Methods

The D-PRESCRIBE-AD is an open-label pragmatic, prospective randomized controlled trial (RCT) comparing three arms: 1) educational mailing to both the health plan patient and their prescribing physician (patient plus physician arm, n = 4814); 2) educational mailing to prescribing physician only (physician only arm, n = 4814); and 3) usual care (n = 4814) among patients with dementia enrolled in two large United States based health plans. The primary outcome is the absence of any dispensing of the targeted potentially inappropriate prescription during the 6-month study observation period after a 3-month black out period following the mailing. Secondary outcomes include dose-reduction, polypharmacy, healthcare utilization, mortality and therapeutic switching within targeted drug classes.

Conclusion

This large pragmatic RCT will contribute to the evidence base on promoting deprescribing of potentially inappropriate medications among older adults with dementia. If successful, such light touch, inexpensive and highly scalable interventions have the potential to reduce the burden of potentially inappropriate prescribing for patients with dementia.ClinicalTrials.gov Identifier: NCT05147428.

Mental health and risk of death and hospitalization in COVID–19 patients. Results from a large-scale population-based study in Spain

by Aida Moreno-Juste, Beatriz Poblador-Plou, Cristina Ortega-Larrodé, Clara Laguna-Berna, Francisca González-Rubio, Mercedes Aza-Pascual-Salcedo, Kevin Bliek-Bueno, María Padilla, Concepción de-la-Cámara, Alexandra Prados-Torres, Luis A. Gimeno-Feliú, Antonio Gimeno-Miguel

The COVID–19 pandemic has created unprecedented challenges for health care systems globally. This study aimed to explore the presence of mental illness in a Spanish cohort of COVID-19-infected population and to evaluate the association between the presence of specific mental health conditions and the risk of death and hospitalization. This is a retrospective cohort study including all individuals with confirmed infection by SARS-CoV-2 from the PRECOVID (Prediction in COVID–19) Study (Aragon, Spain). Mental health illness was defined as the presence of schizophrenia and other psychotic disorders, anxiety, cognitive disorders, depression and mood disorders, substance abuse, and personality and eating disorders. Multivariable logistic regression models were used to examine the likelihood of 30-day all-cause mortality and COVID–19 related hospitalization based on baseline demographic and clinical variables, including the presence of specific mental conditions, by gender. We included 144,957 individuals with confirmed COVID–19 from the PRECOVID Study (Aragon, Spain). The most frequent diagnosis in this cohort was anxiety. However, some differences were observed by sex: substance abuse, personality disorders and schizophrenia were more frequently diagnosed in men, while eating disorders, depression and mood, anxiety and cognitive disorders were more common among women. The presence of mental illness, specifically schizophrenia spectrum and cognitive disorders in men, and depression and mood disorders, substance abuse, anxiety and cognitive and personality disorders in women, increased the risk of mortality or hospitalization after COVID–19, in addition to other well-known risk factors such as age, morbidity and treatment burden. Identifying vulnerable patient profiles at risk of serious outcomes after COVID–19 based on their mental health status will be crucial to improve their access to the healthcare system and the establishment of public health prevention measures for future outbreaks.

Creating a psychosocial intervention combining growth mindset and implementation intentions (GMII) to reduce alcohol consumption: A mixed method approach

by Sacha Parada, Bérengère Rubio, Elsa Taschini, Xavier Laqueille, Malika El Youbi, Pierre Paris, Bernard Angerville, Alain Dervaux, Jean-François Verlhiac, Eve Legrand

This work aimed at creating a psychosocial intervention based on growth mindset theory and implementation intention strategies, in order to reduce alcohol consumption among users in the general population, and the clinical population of individuals with alcohol use disorder. A mixed method approach was used, combining qualitative and quantitative research methods among both populations. Four focus groups were first conducted to extract arguments in favor of a malleable view of alcohol consumption (study 1A), situations that trigger the desire to drink alcohol, as well as strategies used by people to counteract this need (study 1B). Data were analyzed using reflective thematic analysis in line with the scientific literature on alcohol consumption. The results were used to create a questionnaire scoring the relevance of each argument, situation and strategy (study 2). The 20 best scored arguments, situations and strategies were selected to create the intervention. The created intervention consisted in a popularized scientific article describing alcohol consumption as malleable, including the selected arguments and followed by two internalization exercises. Then, a volitional help sheet included the selected situations and solutions was presented, allowing forming up to three plans. The discussion focused on the added value of the created material compared to pre-existing tools in the literature, and presents plans to test the intervention in a future study.

Supporting regional pandemic management by enabling self-service reporting—A case report

by Richard Gebler, Martin Lehmann, Maik Löwe, Mirko Gruhl, Markus Wolfien, Miriam Goldammer, Franziska Bathelt, Jens Karschau, Andreas Hasselberg, Veronika Bierbaum, Toni Lange, Katja Polotzek, Hanns-Christoph Held, Michael Albrecht, Jochen Schmitt, Martin Sedlmayr

Background

The COVID-19 pandemic revealed a need for better collaboration among research, care, and management in Germany as well as globally. Initially, there was a high demand for broad data collection across Germany, but as the pandemic evolved, localized data became increasingly necessary. Customized dashboards and tools were rapidly developed to provide timely and accurate information. In Saxony, the DISPENSE project was created to predict short-term hospital bed capacity demands, and while it was successful, continuous adjustments and the initial monolithic system architecture of the application made it difficult to customize and scale.

Methods

To analyze the current state of the DISPENSE tool, we conducted an in-depth analysis of the data processing steps and identified data flows underlying users’ metrics and dashboards. We also conducted a workshop to understand the different views and constraints of specific user groups, and brought together and clustered the information according to content-related service areas to determine functionality-related service groups. Based on this analysis, we developed a concept for the system architecture, modularized the main services by assigning specialized applications and integrated them into the existing system, allowing for self-service reporting and evaluation of the expert groups’ needs.

Results

We analyzed the applications’ dataflow and identified specific user groups. The functionalities of the monolithic application were divided into specific service groups for data processing, data storage, predictions, content visualization, and user management. After composition and implementation, we evaluated the new system architecture against the initial requirements by enabling self-service reporting to the users.

Discussion

By modularizing the monolithic application and creating a more flexible system, the challenges of rapidly changing requirements, growing need for information, and high administrative efforts were addressed.

Conclusion

We demonstrated an improved adaptation towards the needs of various user groups, increased efficiency, and reduced burden on administrators, while also enabling self-service functionalities and specialization of single applications on individual service groups.

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