bluuebunny/crossref_metadata_2025 huggingface dataset:
Young people’s choice and voice concerning sex and relationships: effects of the multicomponent Get Up Speak Out! Programme in Iganga, Uganda
Authors: Kakal Tasneem , Nalwadda Christine , van Reeuwijk Miranda , van Veen Maaike , Kusters Lincie , Chatterjee Ophelia , Owekmeno Charles , Kok Maryse
Published: August 2022

Background

Young people in Uganda face challenges in achieving their sexual and reproductive health and rights (SRHR), such as lack of information, limited access to services, teenage pregnancy and sexually transmitted infections. To address this, their empowerment – including their ability to express themselves and make decisions, is a key strategy. This study assessed how young people’s voice and choice concerning sex and relationships changed over the period of 3 years of implementation of the Get Up Speak Out! programme.

Methods

Data were collected through a household survey with young people (15-24 years) and through focus group discussions, in-depth interviews and key informant interviews with youth and community stakeholders in 2017 for the baseline and 2020 for the end-line. Using the difference-in-difference technique and thematic analysis, changes in key outcomes were assessed over time between intervention and control area.

Results

There were limited changes over time in the intervention area, which did not differ from changes in the control area. Young people were able to express themselves and expand their decision-making space on sex and relationships, in particular if they were older, male and in a relationship. Young women negotiated their agency, often by engaging in transactional sex. However, youth were still restricted in their self-expression and their choices as speaking about sexuality was taboo, particularly with adults. This was influenced by the political and religious climate around SRHR in Uganda, which emphasised abstinence as the best option for young people to prevent SRHR-related problems.

Conclusions

Young people’s SRHR remains a challenge in Uganda in the context of a conservative political and religious environment that reinforces social and gender norms around youth and young women’s sexuality. The limited effect of the programme on increasing young people’s voice and choice concerning relationships in Uganda can be understood in the context of a ban on comprehensive sexuality education (CSE) and the COVID-19 pandemic. These structural and emerging contextual factors enforce the taboo around youth sexuality and hinder their access to SRHR information and services. Multi-component and targeted programmes are needed to influence changes at the structural, community and individual level.
“Everything kind of revolves around technology”: a qualitative exploration of families’ screen use experiences, and intervention suggestions
Authors: Arundell Lauren , Gould Laura , Ridgers Nicola D. , Ayala Ana Maria Contardo , Downing Katherine L. , Salmon Jo , Timperio Anna , Veitch Jenny
Published: August 2022

Background

Managing children’s screen time is challenging for most families. Interventions have had limited success in reducing screen time, potentially due to a lack of understanding of the experiences, needs and recommendations of families. This study aimed to 1) understand the screen time experiences of families, particularly during COVID-19 lockdowns; and 2) explore parent and child suggestions for the design, components, and content of a screen time management program.

Methods

Parents and children from 30 families living in Victoria, Australia completed a semi-structured interview (63 interviews) via Zoom in October–November 2021. Parents were maged 40.8 (± 8.9) years and predominantly female (90%). Children were maged 11.4 (± 2.4) years and 47% female. The interviews were audio recorded, transcribed verbatim and analysed using inductive thematic analysis combined with a summative content analysis approach.

Results

Three themes under Aim 1 emerged. Theme 1) ‘Screen time management experiences and practices’, including rules and strategies, challenges, and the impact of COVID-19 lockdowns. Theme 2) ‘Impact of screens on family interaction and communication’ including conflicts within the family, reduced face-to-face interactions, and negative impact on child’s behaviour and wellbeing. Theme 3) ‘Benefits of increased screen time due to COVID-19 lockdowns’ including continuation of social interactions, extracurricular activities, improved technology skills and using screens as a ‘babysitter’. Findings from Aim 2 suggest that families want a screen time management program delivered online to parents and children, which includes static and interactive content that incorporates health information, alternative activities, cyber-safety information, tips for goal setting and rewards, screen monitoring tools, links to reputable information, and parent social connections. Reminders via text message or through the online platform would help maintain engagement in the program.

Conclusions

Families are experiencing challenges in managing the complex balance between the increased need for screens and the impact it has on the family. These findings provide valuable parent and child insights to assist in developing screen time management programs that are created with an understanding of the needs and challenges of families.
Strengthening causes of death identification through community-based verbal autopsy during the COVID-19 pandemic
Authors: Siregar Kemal Nazarudin , Kurniawan Rico , Nuridzin Dion Zein , BaharuddinNur Ryza Jazid , Retnowati  , Handayani Yolanda , Rohjayanti  , Halim Lindawati
Published: August 2022

Introduction

Indonesia has not optimally provided complete and reliable civil registration and vital statistics (CRVS). Death certification is one of the elements of the CRVS system. Reliable data on death rates and causes serve as the basis for building a strong evidence base for public health policy, planning, monitoring, and evaluation. This study aims to implement an approach to identifying the cause of death through verbal autopsy by empowering community health workers during the pandemic.

Method

This study is implementation research with the empowerment of the community, in this case, health cadres and health facilitators/workers, to identify the cause of death through a mobile-based verbal autopsy. This implementation research consisted of four main activities: community-based verbal autopsy, mobile-based verbal autopsy development, data collection, and analysis of the suspected causes of death using InterVA-5.

Result

From October to November 2020, a total of 143 respondents were willing to do a verbal autopsy interview (response rate of 58%). Of 143 respondents, most of them were women (112 or 78.3%), was the child of the deceased (61 or 42.7%) and lived with the deceased until before he/she died (120 or 83.9%). Based on the characteristics of the deceased, of 143 deceased, 78 (54.5%) were male, 134 (93.7%) were adults, 100 (69.9%) died at home, and 119 (83.2%) did not have a death certificate stating the cause of death. The cause of death of 143 deceased mainly was infectious disease (92 or 64.3%), followed by non-communicable disease (39 or 27.3%), external factors (5 or 3.5%), and unknown factors (4 or 2.8%). In sequence, the top five suspected causes of death are acute respiratory infection, including pneumonia (72 or 50.3%), other and unspecified infectious disease (18 or 12.6%), other and unspecified cardiac disease (17 or 11.9%), acute cardiac disease (4 or 2.8%), and Digestive neoplasms (4 or 2.8%).

Conclusion

The findings showed that the mobile-based verbal autopsy using a community-based mechanism was feasible during the COVID-19 pandemic.
RealTalk evidence-based communication training resources: development of conversation analysis-based materials to support training in end-of-life-related health and social care conversations
Authors: Parry Ruth , Whittaker Becky , Pino Marco , Jenkins Laura , Worthington Esme , Faull Christina
Published: August 2022

Training to enhance healthcare practitioners’ capabilities in engaging people in sensitive and end-of life-related conversations is in demand. However, evaluations have either not measured, or found very limited impact on actual practice and patient experience. Training effectiveness is improved when it is based on in-depth evidence, reflects the complexity of real-life interactions, and instils principles adaptable to everyday practice. A relatively new source of in-depth evidence and practice-relevant insights on healthcare interactions is conversation analytic research, a form of observational analysis of real-life interactions. However, conversation analytic research findings have largely been disseminated by and for scientists, rather than clinicians and trainers. We used conversation analytic evidence to develop resources for use by healthcare trainers. The aim was to increase training’s evidence-base and authenticity. We further aimed to develop resources applicable to working with learners ranging from novices to advanced practitioners.

Methods: Using an intervention development approach, we created online video-clips and supplementary written materials for professionals who deliver training, supervision, and support in healthcare communication for staff and students. The materials were reviewed by an advisory group comprising clinicians, lay consultees, educators, and researchers, and piloted by trainers in UK universities, NHS organisations and independent hospices. We refined materials based on their feedback.

Results: The resulting ‘RealTalk’ resources focus on practices for communicating with patients and their companions about end-of-life and prognosis. Two core training modules were developed, each comprising several patient case studies featuring video-clips from real-life healthcare consultations. The clips featured practices that patients and experienced practitioners use in approaching end-of-life matters. The case studies also included evidence-based descriptions of observable practices and the principles underlying these, alongside transcripts and case synopses.

Conclusions: RealTalk training resources aim to facilitate evidence-based, experiential and reflective learning, focusing on communication challenges, practices and principles for end-of-life-related interactions. The resources are designed for use by trainers for delivering all levels of training, from introductory to advanced, in both formal and informal training settings. Our development process may serve as a blueprint for the production of future evidence-based training resources based on conversation analytic research.
Physical activity knowledge, attitudes and behaviours of pre-clinical medical students attending an Australian university
Authors: Sahlqvist Shannon , Rees Brenton , Hoffmann Samantha , McCoombe Scott , Santoro Giuseppe , Kremer Peter
Published: August 2022

Background

Through the provision of advice and counselling, general practitioners (GPs) play an important part in promoting physical activity (PA). Lack of knowledge is a key barrier to engaging in such practice. Little is known about the knowledge and attitudes of current medical students and their preparedness to engage in PA promoting practice in the future. This study aimed to investigate the PA knowledge, attitudes and behaviours of medical students attending an Australian university.

Methods

A sample of 107 pre-clinical medical students from an Australian university completed an online survey. Questions asked about age, sex and past-week PA behaviour (using the International Physical Activity Questionnaire-Short form) as well as understanding of key PA messages and perceptions of the role of a GP, confidence to engage in PA promoting practices and satisfaction with current medical school training (responses were on 5-point Likert scale). Descriptive statistics (proportions, means) were used to summarise demographic and attitudinal measures.

Results

Almost all students (92%) were categorised as being moderately or highly active in the past-week. Knowledge of key PA messages was moderate (3.6 ± 0.9), however understanding of key messages about the dose of PA varied (ranging from 0% to 80.4% agreement). GPs were regarded as having a role to play in promoting PA; with high agreement that discussing the benefits of PA is a part of the role of a GP (4.7 ± 0.5). There was only moderate agreement that participants had received training in the health benefits of PA (3.1 ± 1.0) and in PA counselling (3.2 ± 1.0). Students indicated lower levels of satisfaction with this training (2.5 ± 0.9).

Conclusions

Students in this study were typically physically active, had positive attitudes toward PA and felt that it was the role of the GP to engage in PA promoting practices. Students understood key PA messages, and while they reportedly received some training in providing PA counselling, they were somewhat dissatisfied with this training.
Clinical profile and quality of life in climacteric women
Authors: de Santiago Nogueira Cíntia Mikaelle Cunha , Silva Bárbara Daniely dos Santos , Costa Hosana Mirelle Goes Silva , de Alcantara Jussara Rodrigues , Morais Fátima Raquel Rosado , Ferreira Barros Renata Janice Morais Lima , Feitosa de Melo Rabelo Susy Maria , Vieira Pereira Emanuelly , Lopes de Paiva Cavalcanti José Rodolfo , Teixeira Fernandes Natália , de Melo Fialho Ana Virginia
Published: August 2022

Background

The Quality of Life in climacteric women is intrinsically related to signs and symptoms influenced by the decrease of estrogen and psychosocial factors linked to the natural aging process. Thus, this study aimed to trace the sociodemographic and clinical profiles of climacteric women working at the State University of Rio Grande do Norte (UERN) and evaluate their Quality of Life.

Methods

It is a descriptive, exploratory, and quantitative study. The population consisted of female workers from UERN, aging between 40 and 65 years. The total sample consisted of 63 women who answered the forms. Data collection was completely online, which allowed the women to have free choice to choose the most appropriate time to answer the questions.

Results

The majority of the participants were older than 50 years (53.97%, n = 34), were married or in a stable union (55.56%, n = 35), and lived in Mossoró-RN (82.53%, n = 52). Regarding skin color, white and brown women had the same percentage of 44.44% (n = 28). The pain, general health status, and vitality domains evidence the predominance of poor quality of life in the SF-36 questionnaire. Regarding the level of satisfaction with their current health status, 4.76% (n = 3) stated that they fit the level considered excellent, 44.44% (n = 28) very good, 46, 03% (n = 29) were good, and 4.77% (n = 3) stated unsatisfied with their current health status. The intensity of symptoms related to estrogen deficiency established by the Kupperman menopause index is as Mild 55.56% (n = 35), moderate 41.27% (n = 26), and severe 3.17% (n = 2).

Conclusions

The occurrence of symptoms and perception of these symptoms differs from woman to woman, to a greater or lesser extent. These findings emphasize the need for qualified and individualized care for the needs of these women in health services and the development of applicable solutions for solving problems based on each woman profile.
Inequality in households’ access to primary health care (PHC): a case study in Kerman, southeast Iran
Authors: Rahimi Hamed , Goudarzi Reza , Noorihekmat Somayeh , Haghdoost AliAkbar , Khodabandeh Fatemeh
Published: August 2022

Background

Fair access to health services is a vital issue in low-and middle-income countries. Therefore, the present study was conducted to evaluate the equity in access to primary health care (PHC) services in southeastern Iran.

Methods

This household-based survey was conducted on 1128 households in Kerman, southeastern Iran in 2019-20. A multistage probability method was used to select the samples. The online questionnaire was designed and its link was provided to the questioners. After receiving the training, the questioners went to the door according to the sampling guide. The collected data were analyzed at a significance level of 0.05, using the STATA software. The concentration index (CI) was also used to measure inequality in access to PHC services.

Results

The results showed that there was a significant difference between gender and location in access to PHC services (P < 0.05). However, no significant difference was found between the access rates to PHC services and the variables of age, marital, education, health insurance, and Supplementary insurance (P > 0.05). The mean rate of access to PHC services was 3.51 ± 0.53. Cultural access (3.76 ± 0.54) and timely receipt of PHC services (2.51 ± 0.72) accounted for the highest and the lowest access rates, respectively. The concentration index for the distribution of PHC services among the income-adjusted population was 0.014 (CI 95%: -0.022 to 0.051), indicating pro-rich inequalities in access to PHC services.

Conclusion

The results indicated that pro-rich inequality, but it was close to the equality line. Also, the access level was assessed as moderate to high. Therefore, planning and policy-making seems essential for reduce inequality, and development and promotion of access to PHC services, especially timely provision of services and organizational access.
Improving on-treatment risk stratification of cancer patients with refined response classification and integration of circulating tumor DNA kinetics
Authors: Lv Jiawei , Wu Chenfei , Li Junyan , Chen Foping , He Shiwei , He Qingmei , Zhou Guanqun , Ma Jun , Sun Ying , Wei Denghui , Lin Li
Published: August 2022

Background

Significant intertumoral heterogeneity exists as antitumor treatment is introduced. Heterogeneous therapeutic responses are conventionally evaluated by imaging examinations based on Response Evaluation Criteria in Solid Tumors (RECIST); nevertheless, there are increasing recognitions that they do not fully capture patient clinical benefits. Currently, there is a paucity of data regarding the clinical implication of biological responses assessed by liquid biopsy of on-treatment circulating tumor DNA (ctDNA). Here, we investigated whether biological response evaluated by ctDNA kinetics added critical information to the RECIST, and whether integrating on-treatment biological response information refined risk stratification of cancer patients.

Methods

In this population-based cohort study, we included 821 patients with Epstein-Barr virus (EBV)-associated nasopharynx of head and neck cancer (NPC) receiving sequential neoadjuvant chemotherapy (NAC) and chemoradiotherapy (CRT), who had pretreatment and on-treatment cfEBV DNA and magnetic resonance imaging (MRI) surveillance. Biological responses evaluated by cfEBV DNA were profiled and compared with conventional MRI-based RECIST evaluation. The inverse probability weighting (IPW)-adjusted survival analysis was performed for major survival endpoints. The Cox proportional hazard regression [CpH]-based model was developed to predict the on-treatment ctDNA-based individualized survival.

Results

Of 821 patients, 71.4% achieved complete biological response (cBR) upon NAC completion. RECIST-based response evaluations had 25.3% discordance with ctDNA-based evaluations. IPW-adjusted survival analysis revealed that cfEBV DNApost-NAC was a preferential prognosticator for all endpoints, especially for distant metastasis. In contrast, radiological response was more preferentially associated with locoregional recurrence. Intriguingly, cfEBV DNApost-NAC further stratified RECIST-responsive and non-responsive patients; RECIST-based non-responsive patients with cBR still derived substantial clinical benefits. Moreover, detectable cfEBV DNApost-NAC had 83.6% prediction sensitivity for detectable post-treatment ctDNA, which conferred early determination of treatment benefits. Finally, we established individualized risk prediction models and demonstrated that introducing on-treatment ctDNA significantly refined risk stratification.

Conclusions

Our study helps advance the implementation of ctDNA-based testing in therapeutic response evaluation for a refined risk stratification. The dynamic and refined risk profiling would tailor future liquid biopsy-based risk-adapted personalized therapy.
αvβ3 integrin-specific exosomes engineered with cyclopeptide for targeted delivery of triptolide against malignant melanoma
Authors: Gu Yongwei , Du Yue , Jiang Liangdi , Tang Xiaomeng , Li Aixue , Zhao Yunan , Lang Yitian , Liu Xiaoyan , Liu Jiyong
Published: August 2022

Background

Melanoma is the most malignant skin tumor and is difficult to cure with the alternative treatments of chemotherapy, biotherapy, and immunotherapy. Our previous study showed that triptolide (TP) exhibited powerful tumoricidal activity against melanoma. However, the clinical potential of TP is plagued by its poor aqueous solubility, short half-life, and biotoxicity. Therefore, developing an ideal vehicle to efficiently load TP and achieving targeted delivery to melanoma is a prospective approach for making full use of its antitumor efficacy.

Results

We applied exosome (Exo) derived from human umbilical cord mesenchymal stromal cells (hUCMSCs) and engineered them exogenously with a cyclic peptide, arginine-glycine-aspartate (cRGD), to encapsulate TP to establish a bionic-targeted drug delivery system (cRGD-Exo/TP), achieving synergism and toxicity reduction. The average size of cRGD-Exo/TP was 157.34 ± 6.21 nm, with a high drug loading of 10.76 ± 1.21%. The in vitro antitumor results showed that the designed Exo delivery platform could be effectively taken up by targeted cells and performed significantly in antiproliferation, anti-invasion, and proapoptotic activities in A375 cells via the caspase cascade and mitochondrial pathways and cell cycle alteration. Furthermore, the biodistribution and pharmacokinetics results demonstrated that cRGD-Exo/TP possessed superior tumor targetability and prolonged the half-life of TP. Notably, cRGD-Exo/TP significantly inhibited tumor growth and extended survival time with negligible systemic toxicity in tumor-bearing mice.

Conclusion

The results indicated that the functionalized Exo platform provides a promising strategy for targeted therapy of malignant melanoma.

Graphical Abstract
Mesoporous silica-coated silver nanoparticles as ciprofloxacin/siRNA carriers for accelerated infected wound healing
Authors: Liu Qiqi , Zhang Ying , Huang Jingkai , Xu Zhourui , Li Xiang , Yang Jingyu , Huang Haoqiang , Tang Shiqi , Chai Yujuan , Lin Jinbo , Yang Chengbin , Liu Jia , Lin Suxia
Published: August 2022

The colonization of bacterial pathogens is a major concern in wound infection and becoming a public health issue. Herein, a core–shell structured Ag@MSN (silver core embedded with mesoporous silica, AM)-based nanoplatform was elaborately fabricated to co-load ciprofloxacin (CFL) and tumor necrosis factor-α (TNF-α) small interfering RNA (siTNF-α) (AMPC@siTNF-α) for treating the bacterial-infected wound. The growth of bacterial pathogens was mostly inhibited by released silver ions (Ag+) and CFL from AMPC@siTNF-α. Meanwhile, the loaded siTNF-α was internalized by macrophage cells, which silenced the expression of TNF-α (a pro-inflammatory cytokine) in macrophage cells and accelerated the wound healing process by reducing inflammation response. In the in vivo wound model, theEscherichia coli (E. coli)-infected wound in mice almost completely disappeared after treatment with AMPC@siTNF-α, and no suppuration symptom was observed during the course of the treatment. Importantly, this nanoplatform had negligible side effects both in vitro and in vivo. Taken together, this study strongly demonstrates the promising potential of AMPC@siTNF-α as a synergistic therapeutic agent for clinical wound infections.

Graphical Abstract
Pulmonary embolism in a patient with eltrombopag-treated aplastic anaemia and paroxysmal nocturnal haemoglobinuria clone during COVID-19 pneumonia
Authors: Bosi Alessandro , Barcellini Wilma , Fattizzo Bruno
Published: August 2022

Thrombosis in patients with thrombocytopenia has several risk factors, both disease-related and treatment-associated. Recently, COVID-19 infection was recognized as an additional risk factor, further complicating the delicate balance between thrombosis and bleeding in these patients. Here we describe the case of a patient with aplastic anaemia on eltrombopag who developed pulmonary embolism during COVID-19 pneumonia, despite receiving oral anticoagulation with edoxaban. Notably, he was also carrying a large paroxysmal nocturnal haemoglobinuria clone, although without evidence of haemolysis. The presented case recapitulates some of the open questions in thrombotic risk management of cytopenic patients, such as the management of thrombopoietin receptor agonists and the choice of anticoagulation in PNH, while also accounting for the additional thrombotic risk linked to COVID-19.
A retrospective study comparing definitive chemoradiotherapy vs. chemoradiotherapy followed by surgery in T4 esophageal squamous cell carcinoma patients who were downstaged after neochemoradiotherapy
Authors: Zhang Tian , Guo Zhoubo , Chen Xi , Dong Jie , Jiang Hongjing , Tang Peng , Wang Ping , Qian Dong , Zhang Wencheng , Pang Qingsong
Published: August 2022

Background

The outcome of patients with T4 esophageal squamous cell carcinoma (ESCC) is extremely poor. Two distinct therapeutic options are currently available for T4 esophageal cancers: neochemoradiotherapy followed by surgery (CRT-S) and definitive chemoradiotherapy (D-CRT). This study aimed to investigate the clinicopathologic characteristics of T4 ESCC in Chinese patients and compare the survival between the two therapeutic options.

Methods

We retrospectively analyzed 125 patients with clinically unresectable T4 ESCC in Tianjin Medical University Cancer Institute and Hospital from January 2010 to December 2020. Overall survival (OS), progression-free survival (PFS) and associated factors were analyzed.

Results

A total of 106 of 125 T4 ESCC patients were downstaged of the tumor by neoadjuvant CRT. Among 106 patients, 32 patients underwent CRT-S, and 74 patients underwent D-CRT. Patients in the CRT-S group had a higher OS (20.4 months vs. un-reached median OS, p = 0.037) and PFS (8.6 months vs. 21.0 months, p = 0.008) than those in the D-CRT group. In multivariate analysis, treatment was an independent predictor of PFS. After propensity score matching (PSM), 50 patients (CRT-S = 25; D-CRT = 25) were matched. Among these 50 patients, patients in the CRT-S group had a higher OS (15.6 months vs. un-reached median OS, p = 0.025) and PFS (7.2 months vs. 18.8 months, p = 0.026) than those in the D-CRT group. In multivariate analysis, treatment was an independent predictor for PFS.

Conclusion

We demonstrated that CRT-S was superior to D-CRT for T4 ESCC patients who were downstaged by neo-CRT with respect to longer OS and PFS. Randomized controlled trials involving large population samples are needed to define the standard treatment for T4 ESCC.
A rare case of posttraumatic aortic rupture, treated with an endovascular stent graft implantation and complicated with esophageal rupture
Authors: Kyuchukov Dimitar , Simeonov Peyo , Nachev Gencho , Alexieva Magdalena , Yankov Georgi
Published: August 2022

Background

Esophageal necrosis and perforation after thoracic endovascular aortic repair (TEVAR) for ruptured traumatic aortic aneurysm is extremely rare. It is difficult to manage, and patients rarely survive without treatment. Although, there is no certain consensus in relation with the optimal treatment we present a subsequent successful management of both life-threatening conditions.

Case presentation

A 52-year-old man experienced a blunt chest trauma after motor vehicle collision with mild symptoms of pain and fractured ribs. On the 12th day he had severe chest pain and computed tomography (CT) revealed a ruptured traumatic thoracic aortic aneurysm with massive mediastinal hematoma. An emergency thoracic endovascular aortic repair (TEVAR) was performed. Several days later the patient developed a fever. CT suspected a pneumomediastinum, a sign of esophageal rupture, but no confirmation from esophagography and esophagoscopy was achieved. Because of deteriorated septic condition, patient was referred for exploratory thoracotomy. The rupture was found and esophagectomy was performed, with an esophagostomy and gastrostomy to enable enteral nutrition. Almost one year after the esophagectomy, gastric conduit reconstruction through the retrosternal route was performed. The patient was still alive and symptom-free more than 1 year after the reconstruction and no infection of the stent graft was observed.

Conclusion

We successfully managed a rare case of esophageal necrosis after TEVAR for ruptured traumatic thoracic aortic aneurysm. It is essential to diagnose the esophageal necrosis at an early stage and provide appropriate treatment to increase survival.
Accuracy of a community mental health education and detection (CMED) tool for common mental disorders in KwaZulu-Natal, South Africa
Authors: Grant Merridy , Petersen Inge , Mthethwa Londiwe , Luvuno Zamasomi , Bhana Arvin
Published: August 2022

Background

Screening tools for mental health disorders improve detection at a primary health care (PHC) level. However, many people with mental health conditions do not seek care because of a lack of knowledge about mental health, stigma about mental illness and a lack of awareness of mental health services available at a PHC facility level. Interventions at a community level that raise awareness about mental health and improve detection of mental health conditions, are thus important in increasing demand and optimising the supply of available mental health services. This study sought to evaluate the accuracy of a Community Mental Health Education and Detection (CMED) Tool in identifying mental health conditions using pictorial vignettes.

Methods

Community Health Workers (CHWs) administered the CMED tool to 198 participants on routine visits to households. Consenting family members provided basic biographical information prior to the administration of the tool. To determine the accuracy of the CMED in identifying individuals in households with possible mental health disorders, we compared the number of individuals identified using the CMED vignettes to the validated Brief Mental Health (BMH) screening tool.

Results

The CMED performed at an acceptable level with an area under the curve (AUC) of 0.73 (95% CI 0.67–0.79), identifying 79% (sensitivity) of participants as having a possible mental health problem and 67% (specificity) of participants as not having a mental health problem. Overall, the CMED positively identified 55.2% of household members relative to 49.5% on the BMH.

Conclusion

The CMED is acceptable as a mental health screening tool for use by CHWs at a household level.
Development and pilot testing of a five item traumatic stress screener for use with adolescents in pediatric primary care
Authors: Ng Lauren C. , Oblath Rachel , Brigham Rebecca , Tai Ming Him , Coles Mandy
Published: August 2022

Background

Almost 80% of adolescents in the US have experienced a traumatic event, and approximately 7% have post-traumatic stress disorder. However, there is a lack of validated and feasible assessments for assessing traumatic stress symptoms in pediatric primary care, and traumatic stress symptoms are routinely unidentified. This study aimed to develop, pilot test, and assess the psychometric properties of the Adolescent Primary Care Traumatic Stress Screen (APCTSS), a five-item yes/no screener for post-traumatic stress symptoms in adolescents designed for use in pediatric primary care.

Methods

The APCTSS was developed by pediatricians, psychiatrists, psychologists, and social workers who all provide care to trauma-affected adolescent patients. The providers sought to create a developmentally appropriate tool that accurately reflected DSM-5 posttraumatic stress symptoms and that was feasible and acceptable for use in pediatric primary care. To develop the APCTSS, they combined and adapted the UCLA Post-traumatic Stress Disorder (PTSD) Reaction Index for DSM-5 with the adult Primary Care PTSD Screen for DSM-5. Next, 213 adolescent medicine patients were universally approached during routine clinic visits and 178 agreed to participate and were enrolled. The 178 patients were aged 13-22 (M=18.4, SD=2.3), 64.4% female; 62.1% Black or African-American, and 20.7% Hispanic/Latinx. Patients completed APCTSS, Patient Health Questionnaire for Adolescents (PHQ-A), and the Child PTSD Symptom Scale for DSM-5 Interview (CPSS-5-I), and 61 completed the Traumatic Events Screening Inventory for Children (TESI-C).

Results

56.7% reported a criterion A trauma, 30.1% met criteria for DSM-5 PTSD, 7.4% met criteria for subsyndromal PTSD symptoms, and 19.0% for post-event impairing symptoms. Validity and reliability testing indicated that the APCTSS was internally consistent, had good concurrent and discriminant validity, and demonstrated good sensitivity and specificity in identifying adolescents at high risk for post-trauma symptoms. Over half of patients (56.0%) who screened positive on the APCTSS (score ≥2) would not have been identified as having a mental health concern using the PHQ-A, including 60.8% of patients who had probable PTSD, subsyndromal PTSD, or post-event impairing symptoms.

Conclusions

Many youth with trauma-related mental health symptoms are unidentified in pediatric primary care, which is a missed opportunity for early identification and may contribute to a host of poor outcomes. The development of an effective and feasible traumatic stress screening tool for youth primary care may improve early intervention, and the health and well-being of trauma affected youth.
Towards school-based mental health programs in Nigeria: the immediate impact of a depression-literacy program among school-going adolescents and their teachers
Authors: Atilola Olayinka , Ayinde Olatunde , Obialo Felix-Kingsley , Adeyemo Sunday Oladotun , Adegbaju Dapo , Anthony Robert
Published: August 2022

Background

Depression-literacy, which is the foundational requirement for symptom recognition, positive attitude and help-seeking, is poor among adolescents in Nigeria. This study, therefore, aims to determine the impact of a school-based training program on depression-literacy among a cohort of high-school students and their teachers in South-West Nigeria.

Methods

An adapted version of the Break Free from Depression, a 4-module depression awareness curriculum for staff and students, was implemented among students and their teachers. Paired-sample T-test was used to assess the domain-specific (knowledge, attitude, and confidence) impact of the training by comparing the baseline and immediate (within the week of the training) post-scores.

Results

A total of 3098 students and 294 teachers from 21 schools across three states in South-West Nigeria successfully completed the training. There was a significant positive difference (p < 0.05), at post-test, in the knowledge, attitude, and confidence among the students. The same was observed among teachers except for attitude where positive change did not reach significant level (p = 0.06). When statistically significant, the calculated effect size (eta squared) was highest for knowledge (students: 0.07, p = 0.001; teachers: 0.08, p < 0.000) and least for attitude (students: 0.003, p = 0.002 teachers: 0.085, p = 0.06). Multiple regression analyses result showed that the level of pre-scores predicted the magnitude of change in all domains of depression-literacy (p < 0.05) after controlling for age, gender, and type of school among the students, but not for teachers.

Conclusions

School-based depression-literacy programs can lead to significant positive change in knowledge, attitude, and confidence of students and teachers.
GRK3 is a poor prognosticator and serves as a therapeutic target in advanced gastric adenocarcinoma
Authors: Li Yuan , Fan Yibo , Xu Jinbang , Huo Longfei , Scott Ailing W. , Jin Jiankang , Yang Boxuan , Shao Shan , Ma Lang , Wang Ying , Yao Xiaodan , Pool Pizzi Melissa , Sewastjanow Da Silva Matheus , Zhang Guoliang , Zhuo Lijuan , Cho Eun Jeong , Dalby Kevin N. , Shanbhag Namita D. , Wang Zhenning , Li Wenliang , Song Shumei , Ajani Jaffer A.
Published: August 2022

Background

G protein-coupled receptor (GPCR) is the most targeted protein family by the FDA-approved drugs. GPCR-kinase 3 (GRK3) is critical for GPCR signaling. Our genomic analysis showed that GRK3 expression correlated with poor prognosis of gastric adenocarcinoma (GAC) patients. However, GRK3’s functions and clinical utility in GAC progression and metastases are unknown.

Methods

We studied GRK3 expression in normal, primary, and metastatic GAC tissues. We identified a novel GRK3 inhibitor, LD2, through a chemical-library screen. Through genetic and pharmacologic modulations of GRK3, a series of functional and molecular studies were performedin vitroandin vivo. Impact of GRK3 on YAP1 and its targets was determined.

Results

GRK3 was overexpressed in GAC tissues compared to normal and was even higher in peritoneal metastases. Overexpression (OE) of GRK3 was significantly associated with shorter survival. Upregulation of GRK3 in GAC cells increased cell invasion, colony formation, and proportion of ALDH1+cells, while its downregulation reduced these attributes. Further, LD2 potently and specifically inhibited GRK3, but not GRK2, a very similar kinase to GRK3. LD2 highly suppressed GAC cells’ malignant phenotypesin vitro. Mechanistically, GRK3 upregulated YAP1 in GAC tissues and its transcriptional downstream targets: SOX9, Birc5, Cyr61 and CTGF. Knockdown (KD) YAP1 rescued the phenotypes of GRK3 OE in GAC cells. GRK3 OE significantly increased tumor growth but LD2 inhibited tumor growth in the PDX model and dramatically suppressed peritoneal metastases induced by GRK3 OE.

Conclusions

GRK3, a poor prognosticator for survival, conferred aggressive phenotype. Genetic silencing of GRK3 or its inhibitor LD2 blunted GRK3-conferred malignant attributes, suggesting GRK3 as a novel therapeutic target in advanced GAC.
AZTEC—azithromycin therapy for prevention of chronic lung disease of prematurity: a statistical analysis plan for clinical outcomes
Authors: Lau Tin Man Mandy , Lowe John , Pickles Timothy , Hood Kerenza , Kotecha Sailesh , Gillespie David
Published: August 2022

Background

The AZTEC trial is a multi-centre, randomised, placebo-controlled trial of azithromycin to improve survival without development of chronic lung disease of prematurity (CLD) in preterm infants. The statistical analysis plan for the clinical outcomes of the AZTEC trial is described.

Methods and design

A double-blind, randomised, placebo-controlled trial of a 10-day course of intravenous azithromycin (20 mg/kg for 3 days; 10 mg/kg for 7 days) administered to preterm infants born at < 30 weeks’ gestational age across UK tertiary neonatal units. Following parental consent, infants are randomly allocated to azithromycin or placebo, with allocated treatment starting within 72 h of birth. The primary outcome is survival without moderate/severe CLD at 36 weeks’ postmenstrual age (PMA). Serial respiratory fluid and stool samples are being collected up to 21 days of life. The target sample size is 796 infants, which is based on detecting a 12% absolute difference in survival without moderate/severe CLD at 36 weeks’ PMA (90% power, two-sided alpha of 0.05) and includes 10% loss to follow-up.

Results

Baseline demographic and clinical characteristics will be summarised by treatment arm and in total. Categorical data will be summarised by numbers and percentages. Continuous data will be summarised by mean, standard deviation, if data are normal, or median, interquartile range, if data are skewed. Tests of statistical significance will not be undertaken for baseline characteristics. The primary analysis, on the intention to treat (ITT) population, will be analysed using multilevel logistic regression, within a multiple imputation framework. Adjusted odds ratios, 95% confidence intervals, and p-values will be presented. For all other analyses, the analysis population will be based on the complete case population, which is a modified ITT population. All analyses will be adjusted for gestational age and treatment arm and account for any clustering by centre and/or multiple births as a random effect.

Conclusion

We describe the statistical analysis plan for the AZTEC trial, including the analysis principles, definitions of the key clinical outcomes, methods for primary analysis, pre-specified subgroup analysis, sensitivity analysis, and secondary analysis. The plan has been finalised prior to the completion of recruitment.

Trial registration

ISRCTN registry ISRCTN11650227. Registered on 31 July 2018.
Comparison of various methods for validity evaluation of QSAR models
Authors: Shayanfar Shadi , Shayanfar Ali
Published: August 2022

Background

Quantitative structure–activity relationship (QSAR) modeling is one of the most important computational tools employed in drug discovery and development. The external validation of QSAR models is the main point to check the reliability of developed models for the prediction activity of not yet synthesized compounds. It was performed by different criteria in the literature.

Methods

In this study, 44 reported QSAR models for biologically active compounds reported in scientific papers were collected. Various statistical parameters of external validation of a QSAR model were calculated, and the results were discussed.

Results

The findings revealed that employing the coefficient of determination (r2) alone could not indicate the validity of a QSAR model. The established criteria for external validation have some advantages and disadvantages which should be considered in QSAR studies.

Conclusion

This study showed that these methods alone are not only enough to indicate the validity/invalidity of a QSAR model.
ESBL plasmids in Klebsiella pneumoniae: diversity, transmission and contribution to infection burden in the hospital setting
Authors: Hawkey Jane , Wyres Kelly L. , Judd Louise M. , Harshegyi Taylor , Blakeway Luke , Wick Ryan R. , Jenney Adam W. J. , Holt Kathryn E.
Published: August 2022

Background

Resistance to third-generation cephalosporins, often mediated by extended-spectrum beta-lactamases (ESBLs), is a considerable issue in hospital-associated infections as few drugs remain for treatment. ESBL genes are often located on large plasmids that transfer horizontally between strains and species of Enterobacteriaceae and frequently confer resistance to additional drug classes. Whilst plasmid transmission is recognised to occur in the hospital setting, the frequency and impact of plasmid transmission on infection burden, compared to ESBL + strain transmission, is not well understood.

Methods

We sequenced the genomes of clinical and carriage isolates of Klebsiella pneumoniae species complex from a year-long hospital surveillance study to investigate ESBL burden and plasmid transmission in an Australian hospital. Long-term persistence of a key transmitted ESBL + plasmid was investigated via sequencing of ceftriaxone-resistant isolates during 4 years of follow-up, beginning 3 years after the initial study.

Results

We found 25 distinct ESBL plasmids. We identified one plasmid, which we called Plasmid A, that carried blaCTX-M-15 in an IncF backbone similar to pKPN-307. Plasmid A was transmitted at least four times into different Klebsiella species/lineages and was responsible for half of all ESBL episodes during the initial 1-year study period. Three of the Plasmid A-positive strains persisted locally 3–6 years later, and Plasmid A was detected in two additional strain backgrounds. Overall Plasmid A accounted for 21% of ESBL + infections in the follow-up period.

Conclusions

Here, we systematically surveyed ESBL strain and plasmid transmission over 1 year in a single hospital network. Whilst ESBL plasmid transmission events were rare in this setting, they had a significant and sustained impact on the burden of ceftriaxone-resistant and multidrug-resistant infections. If onward transmission of Plasmid A-carrying strains could have been prevented, this may have reduced the number of opportunities for Plasmid A to transmit and create novel ESBL + strains, as well as reducing overall ESBL infection burden.
A pseudo-spectral method based on reproducing kernel for solving the time-fractional diffusion-wave equation
Authors: Fardi Mojtaba , Al-Omari Shrideh K. Qasem , Araci Serkan
Published: August 2022

In this paper, we focus on the development and study of the finite difference/pseudo-spectral method to obtain an approximate solution for the time-fractional diffusion-wave equation in a reproducing kernel Hilbert space. Moreover, we make use of the theory of reproducing kernels to establish certain reproducing kernel functions in the aforementioned reproducing kernel Hilbert space. Furthermore, we give an approximation to the time-fractional derivative term by applying the finite difference scheme by our proposed method. Over and above, we present an appropriate technique to derive the numerical solution of the given equation by utilizing a pseudo-spectral method based on the reproducing kernel. Then, we provide two numerical examples to support the accuracy and efficiency of our proposed method. Finally, we apply numerical experiments to calculate the quality of our approximation by employing discrete error norms.
Association between sex and outcomes in patients with non-small-cell lung cancer receiving combination chemoimmunotherapy as a first-line therapy: a systematic review and meta-analysis of randomized clinical trials
Authors: Takada Kazuki , Shimokawa Mototsugu , Mizuki Fumitaka , Takamori Shinkichi , Takenaka Tomoyoshi , Miura Naoko , Shikada Yasunori , Yoshizumi Tomoharu
Published: August 2022

Introduction

Recently, several meta-analyses have investigated the association between sex and the efficacy of immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC). However, this issue remains controversial, because the results have been inconsistent. Moreover, the effect of sex on outcomes in patients with NSCLC receiving combination chemoimmunotherapy as a first-line therapy is poorly understood. The aim of this study was to examine the association between sex and outcomes in patients with NSCLC receiving combination chemoimmunotherapy as a first-line therapy.

Methods

We searched PubMed and Scopus from database inception to Feb 18, 2022 and performed a systematic review and meta-analysis of randomized and controlled clinical trials investigating ICI+non-ICI vs non-ICI as a first-line therapy in NSCLC. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS) in male and female patients were calculated using common and random-effects models.

Results

We analyzed 5,830 patients, comprising 4,137 (71.0%) males and 1,693 (29.0%) females, from nine randomized clinical trials. The pooled HR (95%CI) for OS comparing ICI+non-ICI vs non-ICI was 0.80 (0.72–0.87) for males and 0.69 (0.54–0.89) for females. The pooled HR (95%CI) for PFS comparing ICI+non-ICI vs non-ICI was 0.60 (0.55–0.66) for males and 0.56 (0.44–0.70) for females.

Conclusions

In patients with NSCLC receiving combination chemoimmunotherapy as a first-line therapy, a greater improvement in OS and PFS was observed in female patients than in male patients.