bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tebentafusp in combination with durvalumab and/or tremelimumab in patients with metastatic cutaneous melanoma: a phase 1 study
Authors: Hamid Omid , Hassel Jessica C , Shoushtari Alexander N , Meier Friedegund , Bauer Todd M , Salama April K S , Kirkwood John M , Ascierto Paolo A , Lorigan Paul C , Mauch Cornelia , Orloff Marlana , Evans Thomas R Jeffry , Holland Chris , Edukulla Ramakrishna , Abedin Shaad E , Middleton Mark R 
Published: June 2023

BackgroundImmune checkpoint inhibitors have significantly improved outcomes in first line cutaneous melanoma. However, there is a high unmet need for patients who progress on these therapies and combination therapies are being explored to improve outcomes. Tebentafusp is a first-in-class gp100×CD3 ImmTAC bispecific that demonstrated overall survival (OS) benefit (HR 0.51) in metastatic uveal melanoma despite a modest overall response rate of 9%. This phase 1b trial evaluated the safety and initial efficacy of tebentafusp in combination with durvalumab (anti-programmed death ligand 1 (PDL1)) and/or tremelimumab (anti-cytotoxic T lymphocyte-associated antigen 4) in patients with metastatic cutaneous melanoma (mCM), the majority of whom progressed on prior checkpoint inhibitors.MethodsIn this open-label, multicenter, phase 1b, dose-escalation trial, HLA-A*02:01-positive patients with mCM received weekly intravenous tebentafusp with increasing monthly doses of durvalumab and/or tremelimumab starting day 15 of each cycle. The primary objective was to identify the maximum tolerated dose (MTD) or recommended phase 2 dose for each combination. Efficacy analyses were performed in all tebentafusp with durvalumab±tremelimumab treated patients with a sensitivity analysis in those who progressed on prior anti-PD(L)1 therapy.Results85 patients were assigned to receive tebentafusp in combination with durvalumab (n=43), tremelimumab (n=13), or durvalumab and tremelimumab (n=29). Patients were heavily pretreated with a median of 3 prior lines of therapy, including 76 (89%) who received prior anti-PD(L)1. Maximum target doses of tebentafusp (68 mcg) alone or in combination with durvalumab (20 mg/kg) and tremelimumab (1 mg/kg) were tolerated; MTD was not formally identified for any arm. Adverse event profile was consistent with each individual therapy and there were no new safety signals nor treatment-related deaths. In the efficacy subset (n=72), the response rate was 14%, tumor shrinkage rate was 41% and 1-year OS rate was 76% (95% CI: 70% to 81%). The 1-year OS for triplet combination (79%; 95% CI: 71% to 86%) was similar to tebentafusp plus durvalumab (74%; 95% CI: 67% to 80%).ConclusionAt maximum target doses, the safety of tebentafusp with checkpoint inhibitors was consistent with safety of each individual therapy. Tebentafusp with durvalumab demonstrated promising efficacy in heavily pretreated patients with mCM, including those who progressed on prior anti-PD(L)1.Trial registration numberNCT02535078.
Staging model of PTSD: a strategy for the implementation of precision medicine in military settings
Authors: McFarlane Alexander 
Published: June 2023

Biomarkers have been of considerable interest in military medicine as a strategy to identify objective measures of resilience in the context of the cumulative trauma exposure of combat as well defining the emerging neurobiological dysregulation associated with post-traumatic stress disorder (PTSD). This body of work has been driven by the imperative of developing strategies to optimally manage the long-term health outcomes of personnel and finding novel treatment approaches. However, the challenge of defining the relevant phenotypes of PTSD and in the context of the multiplicity of biological systems of interest has hampered the identification of biomarkers that have clinical utility. One key strategy to improve the utility of precision medicine in military settings is to use a staging approach to define the relevant phenotypes. A staging model of PTSD captures the progression of the disorder and the transitions from being at risk to subsyndromal disorder and the path to chronic disorder.
A staging approach addresses the longitudinal course of PTSD and the fluidity of the disorder across time. Staging describes how symptoms evolve into more stable diagnostic syndromes and the stepwise changes in clinical status which is key to the identification of phenotypes that can be tied to relevant biomarkers. When a population is exposed to a trauma, the individuals will be at different stages in the emergence of risk and the development of PTSD. The staging approach provides a method of capturing the matrix of phenotypes that need to be demarcated to study the role of multiple biomarkers. This paper forms part of the Special issue of
BMJ Military Health
dedicated to personalised digital technology for mental health in the armed forces.
Types of morbidity presenting in frontline-bordering regions of Ukraine: the experience of deploying additional mobile medical units
Authors: Semenov Viktor V , Kumar S , Zak M Y , Kuryata O , Murach A , Syrovatko I , Krupchak N , Cortellino C , Trombatore G 
Published: June 2023

IntroductionOn 24 February 2022, the full-scale military invasion of Russia into Ukraine has started, creating one of the largest humanitarian crises in Europe since the World War II. As of 27 July 2022 (by the time when the most of Russian advances have already occurred), more than 900 healthcare facilities in Ukraine were damaged and 127 hospitals were destroyed completely.MethodsMobile medical units (MMU) were deployed in the frontline-bordering areas. An MMU included a family doctor, a nurse, a social worker and a driver, and aimed to provide medical help in remote areas. 18 260 patients who received medical help in MMUs in Dnipro (Dnipro city) and Zaporizhia (Zaporizhia city and Shyroke village) oblasts from July until October 2022 were included in the study. The patients were subdivided by month of visit, area of residence and area of MMU operation. Patients’ sex, age, date of visit and diagnosis were analysed. Comparison between groups was performed using analysis of variance and Pearson’s χ2tests.ResultsMajority of patients were females (57.4%), people aged 60+ years (42.8%) and internally displaced persons (IDPs) (54.8%). The proportion of IDPs increased from 47.4% to 62.8% over the period of study (p<0.01). The most common cause of visit to doctors was cardiovascular diseases (17.9%). The frequency of non-respiratory infections remained stable over the period of study.ConclusionsIn the frontline-bordering areas of Ukraine, females, people older than 60 years and IDPs more frequently sought medical help in MMUs. Causes of morbidity in the studied population were similar to the causes of morbidity before the beginning of full-scale military invasion. Maintaining continuous access to healthcare services may be beneficial for the patient outcomes, especially in terms of cardiovascular disease.
Comparison of remimazolam and dexmedetomidine for intraoperative sedation in patients undergoing lower extremity surgery under spinal anesthesia: a randomized clinical trial
Authors: Kim Hansol , Kim Youngwon , Bae Jinyoung , Yoo Seokha , Lim Young-Jin , Kim Jin-Tae 
Published: June 2023

BackgroundDexmedetomidine sedation has advantages, such as low incidence of respiratory depression and prolonged block duration, but also significant disadvantages, such as slow onset, high rate of sedation failure, and a long context-sensitive half-life. Remimazolam provides rapid sedation and recovery, high sedation efficacy and has minimal hemodynamic effects. We hypothesized that patients who received remimazolam would require less rescue midazolam than dexmedetomidine.MethodsPatients (n=103) scheduled for surgery under spinal anesthesia were randomized to receive dexmedetomidine (DEX group) or remimazolam (RMZ group) targeting a Modified Observer’s Assessment of Alertness/Sedation score of 3 or 4. Rescue midazolam was administered if the patient failed to be sedated after the initial loading dose or despite infusion rate adjustment.ResultsRescue midazolam administration was significantly higher in the DEX group (0% vs 39.2%; p<0.001). Patients in the RMZ group reached the target sedation level more rapidly. The incidences of bradycardia (0% vs 25.5%; p<0.001) and hypertension (0% vs 21.6%; p<0.001) were higher in the DEX group. Respiratory depression occurred at a higher rate in the RMZ group (21.2% vs 2.0%; p=0.002), but no patients required manual ventilation. Patients in the RMZ group recovered faster, had a shorter PACU stay and higher satisfaction scores. Hypotensive episodes in the PACU were more frequent in the DEX group (1.9% vs 29.4%; p<0.001).ConclusionsRemimazolam showed excellent sedation efficacy, minimal hemodynamic effects, and fewer adverse events in the PACU than dexmedetomidine. However, it is important to note that respiratory depression was more frequent with the use of remimazolam.Trial registration numberNCT05447507.
Relationship of Stressors and Psychosocial Support with Occurrence of Post-Traumatic Stress Disorder in Patients with Covid-19
Authors: Ellyamurti Devanti Octavia , Hartanti Monica Dwi 
Published: June 2023

Post Traumatic Stress Disorder (PTSD) is common in COVID-19 survivors and can be caused by a variety of stressors, including the duration of infection, severity, and location of isolation when infected with COVID-19. Furthermore, public anxiety caused by the rapid increase in the number of cases and deaths caused by COVID-19 plays a role in the occurrence of PTSD. To reduce the risk of mental disorders, psychosocial support is required. The purpose of this study was to describe the incidence of PTSD in COVID-19 survivors, to describe aspects of psychosocial support for COVID-19 survivors, and to assess the relationship between stressor factors and psychosocial support and the occurrence of PTSD in COVID-19 survivors. This research used an analytical observational research design with a cross sectional approach, involving 149 respondents aged 17-65 years, 52 men and 97 women from the COVID-19 survivor community known as COVID Survivor Indonesia (CSI) in DKI Jakarta. The Medical Outcomes Study–Social Support Survey (MOS-SSS) and The Impact Of Event Scale-Revised (IES-R) questionnaires were distributed via Google Form to collect data. Data was processed and analyzed using the Statistical Package for Social Sciences (SPSS) for Windows version 26.0, and results were analyzed using descriptive univariate and bivariate using Chi Square. There is a significant relationship between stressor factors and the occurrence of PTSD, specifically the duration of infection with COVID-19 (P = 0,026), severity when infected with COVID-19 (P = 0,027), and place of isolation when infected with COVID-19 (P = 0,023). Furthermore, there was a significant relationship between psychosocial support and the occurrence of PTSD (p = 0,001). Management of COVID-19 patients is required to detect stressor factors and provide psychosocial support so that COVID-19 survivors can return physical and psychological health.
Development and Validation of Learning Activity Sheets in Rational Expressions and Linear Equations and Inequalities
Authors: Lacea Justine P , Buscano Jay D. 
Published: June 2023

The purpose of this research study is to develop Learning Activity Sheets (LAS) in Rational Expressions and Linear Equations and Inequalities for the students. Data were collected via survey questionnaire from three sets of evaluators. The LAS was also administered from 100 students of New Society National High School to further scrutinize its validity. The results were interpreted and analysed using the rating scale and statistical tools including on-way ANOVA and mean.
Based from the results of the study, the researcher concluded that: there were fourteen competencies included in the developed LAS which are the not mastered and least mastered competencies of the students. The competency that received the highest mean percentage on the competency test was LAS 17 (graphs and illustrates a linear function and its (a) domain; (b) range; (c) table of values; (d) intercepts; and (e) slope). On the other hand, the competency that received the lowest mean percentage on the competency test was LAS 12 (solves problems involving systems of linear inequalities in two variables). The evaluators found the developed LAS to be effective and useful in terms of objectives, concepts, skills, usability, appropriateness, and adequacy with an interpreted mean rating of very high extent. The researcher also concluded that there is no significant difference in the standard response of the evaluators which is composed of Grade 8 math teachers, master teachers, and LRMDS-trained teachers. Based on the mean percentage results of the administered LAS, there was also a considerable improvement in the students' learning.
Falls Among Older Adults During the COVID-19 Pandemic Compared to a Pre-pandemic Period: A Case-Control Study
Authors: Zayat Marisa-Nicole , Griend Micah Vander , Flesher Nathan , Lightwine Kelly , Ablah Elizabeth , Okut Hayrettin , Haan James M. 
Published: June 2023

Background Little is known about how the COVID-19 pandemic impacted older adults admitted to the hospital with fall-related injuries. This research sought to determine if there was a difference in patient characteristics and hospital outcomes among older adults with fall-related injuries during the COVID-19 pandemic compared to a non-pandemic period. Methods A retrospective chart review of patients 65 years or older admitted for traumatic falls before and during COVID-19 was undertaken. Data abstracted included demographics, fall details, injury data, and hospital course. Results Of 1598 patients, 50.5% presented during COVID-19 (cases), and 49.5% presented pre-pandemic (controls). Fewer cases fell in rural areas (28.6% vs 34.1%, P = .018) and were transferred from outside hospitals (32.1% vs 38.2%, P = .011). More cases experienced alcohol (4.6% vs 2.4%, P = .017) and substance use disorders (1.4% vs .4%, P = .029). Fewer cases had subdural hemorrhages (11.8% vs 16.4%, P = .007), and more had pneumothoraxes (3.5% vs 1.8%, P = .032). More patients admitted during COVID-19 experienced acute respiratory failure (2.0% vs .0%, P < .001), hypoxia (1.5% vs .3%, P = .005), and delirium (6.3% vs 1.0%, P < .001). Fewer cases were discharged to skilled nursing facilities (50.8% vs 57.3%, P = .009) and more to home with services (13.1% vs 8.3%, P = .002). Discussion This study suggested there was a similar frequency of presentation for falls among older adults during the two study periods. Older adults with fall-related injuries experienced differences in presenting comorbidities, injury patterns, complications, and discharge locations during the study periods.
Effect of multiple loading FIT sample collection devices on faecal haemoglobin concentration
Authors: John Cerin , Piggott Carolyn , Benton Sally C 
Published: June 2023

Background Faecal immunochemical tests (FIT) are routinely used in colorectal cancer (CRC) screening programmes around the world. More recently, quantitative FIT has been recommended to help triage patients presenting to primary care with symptoms suggestive of CRC. Participants collect faecal samples using sampling probes which are inserted into sample collection devices (SCDs) containing preservative buffer. The SCDs have an internal collar designed to remove excess sample. The aim of this study was to investigate the impact of multiple loading on faecal haemoglobin concentration (f-Hb) using SCDs of four FIT systems. Methods Pools of f-Hb negative samples were spiked with blood, homogenised and loaded into SCDs 1, 3 and 5 times, with insertion of the sampling probes into the SCDs with and without mixing between loads. The f-Hb was measured using the relevant FIT system. The percentage change in f-Hb for multiple loads was compared with a single load for each system for the mixed and unmixed groups. Results The p values show a significant difference ( p < 0.05) in the mass and f-Hb for the mixed and unmixed group, for 1–3 and 1–5 loads for all systems. The median percentage change in f-Hb for the mixed is higher than the unmixed group. Conclusion This study showed that multiple loading does significantly increase the f-Hb in the SCDs.
Transgenerational trauma and collective resilience: A qualitative analysis of the experiences of settler-colonial violence among three generations of Palestinian refugees
Authors: Veronese Guido , Mahamid Fayez , Bdier Dana 
Published: June 2023

Background: Palestinian people have endured collective dispossession and social suffering for 74 years from the so-called Al-Nakba (Palestinian catastrophe). Aims: The present exploratory work sought to analyze experiences of settler-colonial violence over three generations of Palestinian refugees. Methods: Forty-five participants (Mage = 44.45; range 13–85) were recruited via snowball sampling and interviewed to explore their understanding of transgenerational and collective trauma. Interviews were analyzed through thematic content analysis, resulting in four emerging themes distributed among the three generations. Results: The four themes encompassed (1) The impact of Al-Nakba, (2) Hardships, challenges, and quality of life, (3) Coping strategies, and (4) Dreams and hopes for the future. The results have been discussed using local idioms of distress and resilience. Conclusions: The Palestinian experience of transgenerational trauma and resilience depicts a portrait of extreme trauma and endurance that cannot be reduced to the mere nosographic collection of Western-informed psychiatric symptoms. Instead, a human rights approach to Palestinian social suffering is most recommended.
The Effect of the Meditation Based Mandala Programme on Distress, Anxiety and Depression in the Caregivers of Cancer Patients in Palliative Care Unit
Authors: Karabuga Yakar Hatice , Yılmaz Banu , Çelik Emine , Özkol Ozan , Gevher Fadime , Oruc Özlem , Şen Hülya 
Published: June 2023

Mental health problems were found to be more common than physical health problems in cancer caregivers in palliative care units. This is a quasi-experimental study planned to determine the effect of the meditation based mandala programme on distress, anxiety and depression in caregivers of cancer patients in a palliative care unit. Planned as a single-group pre-test/post-test design, with a total of 11 caregivers. Data were collected with the Caregiver Diagnosis Form, Distress Thermometer, Beck Depression Inventory, and Beck Anxiety Inventory. Caregivers participated in the Meditation Based Mandala Programme once a week, which lasted 2 hours for 5 weeks. The distress, depression and anxiety levels of the patients were measured before the programme started and at the end of the programme. Meditation based mandala programme is effective in reducing the distress, depression and anxiety levels of caregivers of cancer patients in the palliative care unit.
A placebo-controlled, randomized, single and multiple dose study to evaluate the safety, tolerability, and pharmacokinetics of rimegepant in healthy participants
Authors: Bertz Richard , Bhardwaj Rajinder , Morris Beth A. , Ashbrenner Eric , Coric Vladimir , Croop Robert 
Published: June 2023

Background Rimegepant is an oral, small molecule calcitonin gene-related peptide receptor antagonist for acute treatment of migraine and migraine prevention. Methods This was a single-site, placebo-controlled, sequential, single and multiple ascending dose study in healthy males and females, aged 18–55 years, with no clinically significant medical history. The objectives were to assess the safety, tolerability, and pharmacokinetics of the oral capsule free-base formulation. Single oral doses of rimegepant from 25–1500 mg were evaluated in the single ascending dose phase, and 75–600 mg/day doses administered for 14 days were evaluated in the multiple ascending dose phase. Results No dose-related trends were observed in orthostatic systolic and diastolic blood pressure or heart rate after rimegepant administration. Rimegepant was rapidly absorbed with the median time of maximum observed plasma concentration from 1–3.5 hours. Rimegepant showed a more than dose-proportional increase in exposure from 25–1500 mg following a single dose and from 75–600 mg/day following multiple doses. Conclusions Rimegepant was safe and generally well tolerated at single oral doses up to 1500 mg and multiple doses up to 600 mg/day for 14 days in healthy participants in this study. Median terminal half-life ranged from 8–12 hours across the wide range of single doses studied.
Domestic Violence, Mental Health, and Resilience Among Older Adults in the U.S. During COVID-19
Authors: Yoon Sukyung , Mahapatra Neely 
Published: June 2023

Objectives The current study based on the Stress Process Model investigated the impact of experiences of domestic violence on mental health as well as resilience against negative mental health outcomes among older adults in U.S. during COVID-19. Method Participants included 522 older adults (ages 51–80 and older) living in US at the time of the survey. Path analysis using Mplus was employed. Results:The experience of domestic violence among older adults during the pandemic was positively associated with loneliness and anxiety directly and indirectly. However, resilience acted as a protective factor between the experiences of domestic violence and anxiety. Conclusion: The experience of domestic violence may increase loneliness and anxiety among older adults during challenging times; however, resilience may weaken these negative psychological outcomes both directly and indirectly. Findings and implications are discussed.
Prevalence of migraine in systemic lupus erythematosus: A meta-analysis
Authors: Sarangi Surjyapratap , Nahak Suraj K , Rupashree Anisha , Panigrahi Jogeswar , Panda Aditya K 
Published: June 2023

Background Systemic lupus erythematosus (SLE) is an autoimmune disorder with a wide range of clinical manifestations, including neurological issues in about 25%–75% of cases. Among the neurological involvement cases, most cases show migraine. However, the prevalence of migraine varied worldwide, and in some studies, a higher incidence of migraine in SLE cases was reported compared to healthy controls. In the present study, we adopted a meta-analysis approach to find out the prevalence of migraine in SLE patients worldwide and investigate whether migraine frequency is more prevalent in SLE patients than controls. Material and methods Various literature databases such as Scopus, PubMed, Science Direct, and Google Scholar were screened for eligible studies. The last search was performed on January 21, 2023. Publication biases were accessed by Egger’s regression analysis and funnel plots. Cochrane Q statistics and I2 values explored the presence or absence of heterogeneity. All statistical analysis of meta-analysis was performed in comprehensive meta-analysis software v3. Results Based on predefined inclusion and exclusion criteria, 17 reports comprising 2901 SLE patients and 575 healthy controls were considered in the present study. The meta-analysis revealed the prevalence of migraine to be 34.8%. Furthermore, migraine was more prevalent in SLE patients than healthy controls (OR: 1.964, p = 0.000, 95% CI = 1.512–2.550). Similar trends were also observed while considering another 10 independent reports those were not disclosed about the migraine diagnosis criteria (number of reports: 27, SLE: 3473, HC: 741, prevalence: 33.5%, SLE vs HC: OR = 2.107, p = 0.000, 95% CI = 1.672–2.655). Subgroup analysis demonstrated that SLE patients from South America had a higher prevalence of migraine (56.2%). Conclusions About one-third of SLE patients experience migraine worldwide. The prevalence of migraine is more frequent in SLE patients than the healthy controls.