bluuebunny/crossref_metadata_2025 huggingface dataset:
Perioperative coronary artery spasm after off-pump coronary artery bypass grafting in the non-manipulated coronary artery
Authors: Bai Yunpeng , Bai Yiming , Jiang Nan , Chen Qingliang , Guo Zhigang
Published: April 2022

Background

Perioperative coronary artery spasm (CAS) following coronary artery bypass grafting (CABG) is a severe or lethal condition that is rarely reported. In addition, rare cases with CAS following CABG in the non-manipulated coronary artery are angiographically documented in the perioperative period. We aimed to report our experiences on the diagnosis and treatment of a case with CAS following off-pump CABG in the non-manipulated coronary artery.

Methods

A 57-year old male with coronary heart disease and unstable angina willing to undergo CABG was admitted to our department. CABG was recommended as he showed 90% stenosis in distal left anterior descending artery, 90% stenosis in intermediate branch, 90% stenosis in left circumflex coronary artery, as well as 50% stenosis in proximal right coronary artery (RCA).

Results

After CABG, the patient showed Adams–Stokes syndrome and ST-segment elevation. Then CPR was conducted and coronary angiography indicated perioperative CAS in the non-manipulated posterior descending artery. For the treatment, the patient received nitroglycerin injection into the coronary artery by catheter and pumping of diltiazem. Finally, the patient was discharged on day 7 after surgery. A comprehensive literature search was conducted to summarize the studies focused on the diagnosis and treatment of such condition, which indicated that all of the CAS cases occurred in the manipulated vessels, except one study showing CAS in the untouched native coronary artery which was similar with our case.

Conclusions

Perioperative CAS in the non-manipulated coronary artery following CABG is a severe or lethal condition that is rarely reported, which deserves close attention by the clinicians in clinical practice.
Spinal canal infection caused by Streptococcus suis in human: a case report
Authors: Xu Lejia , Wang Xiaoyun , Lei Ziying , Zhu Jianyun , Pang Yihua , Liu Jing
Published: April 2022

Background

Streptococcus suis is an emerging zoonotic pathogen that mainly causes meningitis, sepsis, arthritis, endocarditis, and endophthalmitis in human. To the best of our knowledge, Spinal canal infection caused by Streptococcus suis has rarely been reported.

Case presentation

Here we report a case of spinal canal infection caused by Streptococcus suis in a 50-year-old male patient. The patient had a history of close contact with sick pigs days before disease onset. Initially he presented with headache and fever. After admission, the patient began to experience lower back pain, which led physicians to perform a lumber puncture. Meta-genomic next generation sequencing helped identify Streptococcus suis in the cerebrospinal fluid. MRI imaging indicated a spinal canal infection caused by Streptococcus suis.

Conclusions

Spinal canal infection is an uncommon disease of Streptococcus suis infection. This case report indicates that people presented with fever, headache and lower back pain should also be suspected as Streptococcus suis infection, especially for those who have had a history of sick pig contact.
Association of urine phthalate metabolites, bisphenol A levels and serum electrolytes with 24-h blood pressure profile in adolescents
Authors: Yalçin Siddika Songül , Erdal İzzet , Oğuz Berna , Duzova Ali
Published: April 2022

Background

Among the possible causes of hypertension in adolescence, electrolyte imbalances and environmental pollutants are drawing increasing attention. We aimed to examine the relationship between bisphenol A (BPA), phthalate metabolites, and serum electrolytes and blood pressure.

Methods

Eighty-six participants aged 12–15 years were included in the study. Body mass index (BMI), office blood pressure and 24-h ambulatory blood pressure measurements (ABPM), and carotid intima-media thickness were determined. Blood samples were taken for hemogram, renal function tests, and serum electrolytes. Free- and total-BPA and phthalate metabolites were analyzed from urine samples.

Results

Of the participants, 34 were evaluated as normal blood pressure profile, 33 as white-coat hypertension (WCHT), and 19 as ABPM-hypertension. Adolescents in ABPM- hypertension groups had higher BMI-standard deviation score (SDS), leucocyte, platelet count; but lower serum chloride, compared to the normal blood pressure profile group. The percentage of adolescents with detectable urinary mono-benzyl phthalate (MBzP) was higher in ABPM-hypertension (42.1%) and WCHT groups (33.3%), compared to the normal blood pressure profile group (5.9%, p = 0.004). Associations between MBzP and ABPM- hypertension and WCHT were remained after confounding factor adjustment. Adolescents with detectable MBzP levels had also higher “albumin-corrected calcium” and lower serum phosphate and “albumin-corrected calcium x phosphate product” compared to others. Adolescents with detectable urinary MBzP levels had higher blood pressure profiles in some 24-h (mean arterial pressure-SDS, systolic blood pressure-SDS), daytime (systolic blood pressure-SDS), and night-time (mean arterial pressure-SDS, systolic blood pressure-SDS, and diastolic blood pressure-SDS) measurements, compared to others. WCHT was found to be associated negatively with monomethyl phthalate and the sum of dibutyl phthalate metabolites and ABPM-HT with MCPP. There was no significant association between blood pressure profiles and free- and total-BPA status.

Conclusion

MBzP was associated with adverse blood pressure profiles in adolescence. Additive follow-up studies are necessary for cause-effect relations.
Factors affecting the mental health of pregnant women using UK maternity services during the COVID-19 pandemic: a qualitative interview study
Authors: McKinlay A. R. , Fancourt D. , Burton A.
Published: April 2022

Background

People using maternity services in the United Kingdom (UK) have faced significant changes brought on by the COVID-19 pandemic and social distancing regulations. We focused on the experiences of pregnant women using UK maternity services during the pandemic and the impact of social distancing rules on their mental health and wellbeing.

Methods

We conducted 23 qualitative semi-structured interviews from June 2020 to August 2021, with women from across the UK who experienced a pregnancy during the pandemic. Nineteen participants in the study carried their pregnancy to term and four had experienced a miscarriage during the pandemic. Interviews took place remotely over video or telephone call, discussing topics such as mental health during pregnancy and use of UK maternity services. We used reflexive thematic analysis to analyse interview transcripts.

Results

We generated six higher order themes: [1] Some pregnancy discomforts alleviated by social distancing measures, [2] The importance of relationships that support coping and adjustment, [3] Missed pregnancy and parenthood experiences, [4] The mental health consequences of birth partner and visitor restrictions, [5] Maternity services under pressure, and [6] Lack of connection with staff. Many participants felt a sense of loss over a pregnancy experience that differed so remarkably to what they had expected because of the pandemic. Supportive relationships were important to help cope with pregnancy and pandemic-related changes; but feelings of isolation were compounded for some participants because opportunities to build social connections through face-to-face parent groups were unavailable. Participants also described feeling alone due to restrictions on their partners being present when accessing UK maternity services.

Conclusions

Our findings highlight some of the changes that may have affected pregnant women’s mental health during the COVID-19 pandemic. Reduced social support and being unable to have a partner or support person present during maternity service use were the greatest concerns reported by participants in this study. Absence of birth partners removed a protective buffer in times of uncertainty and distress. This suggests that the availability of a birth partner or support person must be prioritised wherever possible in times of pandemics to protect the mental health of people experiencing pregnancy and miscarriage.
The efficacy and acceptability of exposure therapy for the treatment of post-traumatic stress disorder in children and adolescents: a systematic review and meta-analysis
Authors: Huang Tengyue , Li Haomiao , Tan Shiyu , Xie Siyu , Cheng Qisheng , Xiang Yajie , Zhou Xinyu
Published: April 2022

Background

Posttraumatic stress disorder (PTSD) is common among children and adolescents who have experienced traumatic events. Exposure therapy (ET) has been shown to be effective in treating PTSD in adults. However, its efficacy remains uncertain in children and adolescents.

Aims

To evaluate the efficacy and acceptability of ET in children and adolescents with PTSD.

Method

We searched PubMed, EMBASE, Cochrane, Web of Science, PsycINFO, CINAHL, ProQuest, LILACS, and international trial registries for randomized controlled trials (RCTs) assessed ET in children and adolescents (aged ≤18 years) with PTSD up to August 31, 2020. The primary outcomes were efficacy (the endpoint score from PTSD symptom severity rating scales) and acceptability (all-cause discontinuation), secondary outcomes included efficacy at follow-up (score from PTSD scales at the longest point of follow-up), depressive symptoms (end-point score on depressive symptom severity rating scales) and quality of life/social functioning (end-point score on quality of life/social functioning rating scales). This study was registered with PROSPERO (CRD42020150859).

Result

A total of 6 RCTs (278 patients) were included. The results showed that ET was statistically more efficacious than control groups (standardized mean differences [SMD]: − 0.47, 95% confidence interval [CI]: − 0.91 to − 0.03). In subgroup analysis, exposure therapy was more efficacious for patients with single type of trauma (SMD: − 1.04, 95%CI: − 1.43 to − 0.65). Patients with an average age of 14 years and older, ET was more effective than the control groups (SMD: − 1.04, 95%CI: − 1.43 to − 0.65), and the intervention using prolonged exposure therapy (PE) (SMD: − 1.04, 95%CI: − 1.43 to − 0.65) was superior than control groups. Results for secondary outcomes of efficacy at follow-up (SMD: − 0.64, 95%CI: − 1.17 to − 0.10) and depressive symptoms (SMD: − 0.58, 95%CI: − 0.93 to − 0.22) were similar to the previous findings for efficacy outcome. No statistically significant effects for acceptability and quality of life/social functioning were found.

Conclusion

ET showed superiority in efficacy at post-treatment/follow-up and depressive symptoms improvement in children and adolescents with PTSD. Patients with single type of trauma may benefit more from ET. And ET is more effective in patients 14 years or older. Moreover, PE could be a better choice.
Epidemiology of gaming disorder and its effect on anxiety and insomnia in Chinese ethnic minority adolescents
Authors: Wei Qiaoyue , Zhang Shengjie , Pan Yuli , Hu Hong , Chen Fenglan , Yin Wenwen , Lin Qinghong , Pan Shuibo , Tham Chingyuan , Wu Junduan
Published: April 2022

Background

The growing popularity and frequency of online game use have resulted in a large number of studies reporting various mental problems associated with game abuse in adolescents. In this article, we examined the prevalence of gaming disorder (GD) and explored the associations of GD with anxiety and insomnia symptoms in minority youth in China.

Methods

A total of 1494 students completed the Problematic Online Gaming Questionnaire Short-Form (POGQ-SF), the Generalized Anxiety Disorder 7-item questionnaire (GAD-7), and Athens Insomnia Scale (AIS). Chi-square and binary logistic regression analyses were used to explore the associations between gaming disorder and anxiety/insomnia.

Results

A total of 356 (23.83%) respondents reported that they had gaming disorder. Chi-square analysis showed that gender, grade, marital status of parents and exercise situation were significantly associated with GD. Binary logistic regression analysis showed that those who had GD were at significantly higher risk for anxiety and insomnia than those without GD.

Conclusion

We found a high incidence of GD and a positive association among anxiety, insomnia and GD. Thus, special attention should be paid to those who have suffered from GD. It is worth addressing the adverse effects of GD on anxiety and insomnia.
Significant reduction of long non-coding RNAs expression in bipolar disorder
Authors: Maloum Zahra , Taheri Mohammad , Ghafouri-Fard Soudeh , Shirvani-Farsani Zeinab
Published: April 2022

Long non-coding RNAs (lncRNAs) have been recently emerged as critical modulators of oxidative stress pathway. Likewise, rising evidence currently highlights dysfunction of oxidative stress pathways in bipolar disorder (BD) patients.

In the current study, we evaluated the expression levels of H19, SCAL1 (LUCAT1), RMST, MEG3 and MT1DP lncRNAs in the PBMC from 50 patients with BD and 50 control subjects (male/female ratio in each group: 70%/30%). Expression levels of SCAL1, RMST and MEG3 but not H19 and MT1DP were considerably decreased in BD patients compared with healthy individuals. Such significant decrease in the expression of MEG3, RMST and SCAL1 was only reported in male BD patients compared with male controls. Substantial pairwise correlations were observed between expression levels of these lncRNAs in BD subjects. The area under curve values for RMST, MEG3 and SCAL1 were 0.70, 0.63 and 0.61 respectively. On the basis of this finding, RMST had the best efficiency in the discrimination of disease status between BD patients and controls. Taken together, the current results suggest a role for MEG3, RMST and SCAL1 lncRNAs in the pathogenesis of BD. In addition, peripheral expression levels of these lncRNAs might serve as potential peripheral markers for BD.
Prospective association between depressive symptoms and hip fracture and fall among middle-aged and older Chinese individuals
Authors: Zhu Chunsu , Yu Hongyu , Lian Zhiwei , Wang Jianmin
Published: April 2022

Background

The effect of depressive symptoms on hip fracture (HF) and falls among the Chinese population is unclear. This study aims to examine the prospective association between depressive symptoms and HF as well as fall accidents in a nationally representative Chinese population.

Methods

We used data from 10,596 participants in the Chinese Health and Retirement Longitudinal Study (from 2011 to 2018) who were aged ≥45 years and had no HFs at baseline. Depressive symptoms were assessed using the 10-item version of the Center for Epidemiological Studied Depression scale (cutoff for distinguishing high versus low at ≥12). Logistic regression analyses adjusted for demographic characteristics, lifestyle factors and physical comorbidities were performed.

Results

For the analysis of baseline depressive symptoms and HF, 399 (3.8%) participants reported HF accidents in the following 7-year period. Individuals with elevated depressive symptoms at baseline experienced a markedly higher HF risk (odds ratio [OR] = 1.33, 95% confidence interval [CI] = 1.06–1.67) than those without elevated depressive symptoms, after adjusting for a wide range of potential confounders. For the analysis of baseline depressive symptoms and falls, 3974 (37.5%) experienced fall accidents during the follow-up. The presence of elevated depressive symptoms was independently associated with an increased risk of fall events (OR = 1.21, 95% CI = 1.10–1.33). These associations were consistent across multiple characteristics.

Conclusions

In conclusion, elevated depressive symptoms were associated with an increased risk of HF and falls, which may have considerable clinical and preventive implications.
Prioritizing COVID-19 vaccination efforts and dose allocation within Madagascar
Authors: Rasambainarivo Fidisoa , Ramiadantsoa Tanjona , Raherinandrasana Antso , Randrianarisoa Santatra , Rice Benjamin L. , Evans Michelle V. , Roche Benjamin , Randriatsarafara Fidiniaina Mamy , Wesolowski Amy , Metcalf Jessica C.
Published: April 2022

Background

While mass COVID-19 vaccination programs are underway in high-income countries, limited availability of doses has resulted in few vaccines administered in low and middle income countries (LMICs). The COVID-19 Vaccines Global Access (COVAX) is a WHO-led initiative to promote vaccine access equity to LMICs and is providing many of the doses available in these settings. However, initial doses are limited and countries, such as Madagascar, need to develop prioritization schemes to maximize the benefits of vaccination with very limited supplies. There is some consensus that dose deployment should initially target health care workers, and those who are more vulnerable including older individuals. However, questions of geographic deployment remain, in particular associated with limits around vaccine access and delivery capacity in underserved communities, for example in rural areas that may also include substantial proportions of the population.

Methods

To address these questions, we developed a mathematical model of SARS-CoV-2 transmission dynamics and simulated various vaccination allocation strategies for Madagascar. Simulated strategies were based on a number of possible geographical prioritization schemes, testing sensitivity to initial susceptibility in the population, and evaluating the potential of tests for previous infection.

Results

Using cumulative deaths due to COVID-19 as the main outcome of interest, our results indicate that distributing the number of vaccine doses according to the number of elderly living in the region or according to the population size results in a greater reduction of mortality compared to distributing doses based on the reported number of cases and deaths. The benefits of vaccination strategies are diminished if the burden (and thus accumulated immunity) has been greatest in the most populous regions, but the overall strategy ranking remains comparable. If rapid tests for prior immunity may be swiftly and effectively delivered, there is potential for considerable gain in mortality averted, but considering delivery limitations modulates this.

Conclusion

At a subnational scale, our results support the strategy adopted by the COVAX initiative at a global scale.
Tracking of anthropometric characteristics from childhood to adolescence: an 8-year follow-up findings from the Czech ELSPAC study
Authors: Zvonar Martin , Štefan Lovro , Kasović Mario , Piler Pavel
Published: April 2022

Background

Although evidence suggests that obesity track well from childhood to adolescence, most of the research has been done in Western and high-income countries. Moreover, most of the studies have tracked body-mass index, as a proxy of nutritional status, while tracking characteristics of circumferences and skinfold thicknesses have been less studies. Therefore, the main purpose of the study was to explore tracking characteristics of complete anthropometric data from childhood to adolescence.

Methods

This sub-study was part of the Czech ELSPAC study. In the present 8-year longitudinal study, we collected information from pediatrician’s medical records at the ages of 8 y (n = 888), 11 y (n = 1065), 13 y (n = 811) and 15 y (n = 974), including circumferences (head, chest, waist, hips, and arm), indices (body-mass index, waist-to-hip ratio and waist-to-height ratio) and skinfold thicknesses (biceps, triceps, subscapula, suprailiaca, thigh and the sum of 5 skinfolds). Participants were recruited from the two selected regions of the Czech Republic (Brno and Znojmo). Linear generalized estimating equations were conducted to analyze tracking patterns over an 8-year follow-up period for all anthropometric measurements.

Results

Tracking coefficients were moderate to strong, ranging from 0.40 to 0.62 for circumferences, 0.41 to 0.74 for indices and 0.72 to 0.86 for skinfolds. According to body-mass index and waist circumference standards, overweight/obese children and children with abdominal obesity at the age of 8 y were 11.31 (95% CI = 8.41 to 15.22, p < 0.001) and 10.73 (95% CI = 7.93 to 14.52, p < 0.001) more likely to remain overweight/obese and to have abdominal obesity at the age of 15 y.

Conclusions

Findings show moderate to strong tracking of anthropometric characteristics, i.e. circumferences track moderately well, while strong tracking for indices and skinfold thicknesses is observed. Moreover, strong tracking of general overweight/obesity and abdominal obesity between ages 8 y and 15 y indicates that the detection of these risk factors at the beginning of primary school should be advocated.
Severe asthma as the initial clinical manifestation of IgG4-related disease: a retrospective clinical study
Authors: Liu Xiangning , Shao Chi , Yu Chen , Huang Hui , Pan Ruili , Xu Kai , Zhang Xin , Xu Zuojun
Published: April 2022

Background

Respiratory involvement is common in immunoglobulin G4-related disease (IgG4-RD). However, severe asthma as the initial clinical manifestation of IgG4-RD is rare and might be neglected by respiratory clinicians. We aimed to explore the clinical characteristics and prognoses of patients with immunoglobulin G4-related disease (IgG4-RD) manifesting as severe asthma.

Methods

A retrospective analysis of the clinical characteristics and prognoses of patients with severe asthma who were eventually diagnosed with IgG4-RD was performed in the Peking Union Medical College Hospital from 2013 to 2019.

Results

Twelve patients (5males, 7 females) were included. The mean age at enrollment and age of asthma onset were 59.4 ± 10.1 and 53.8 ± 10.4 years, respectively. The mean duration of asthma symptoms was 5.7 ± 2.0 years. In all patients, the proportion (25.1 ± 10.3%) and count (2.0 ± 1.1) × 109/L of eosinophils in peripheral blood increased. Additionally, all patients exhibited elevated total immunoglobulin E [IgE, (1279.3 ± 1257.9) KU/L] and IgG4 (9155.8 ± 9247.6) mg/dL. Bronchial wall thickening (n = 11) and mediastinal/hilar lymphadenopathy (n = 11) were major chest CT manifestations. All were pathologically diagnosed through surgical biopsy; submandibular gland (n = 8), supraclavicular lymph node (n = 2), stomach (n = 1), rashes (n = 1), lacrimal gland (n = 1) and thoracoscopic lung (n = 1) biopsies were performed. Asthma was well controlled by oral glucocorticoids (GCs), but some patients relapsed during tapering (n = 11). The refractory condition was controlled after increasing the dosage of GCs and add-on immunosuppressants.

Conclusions

For patients with middle age-onset severe asthma with elevated eosinophils, total IgE and IgG4 levels and available salivary gland ultrasound imaging, ruling out IgG4-RD is recommended. GCs used in combination with immunosuppressants is recommended to prevent relapse.
A prospective observational study on the beneficial effects and tolerability of a cetylated fatty acids (CFA) complex in a patch formulation for shoulder tendon disorders
Authors: Lanzisera Rosaria , Baroni Alessandro , Lenti Gaetana , Geri Elisabetta
Published: April 2022

Background

The advancement of physiopathological knowledge of tendon structures has shown that, in conditions of overload, there is the onset of both degenerative phenomena, such as the production of metalloproteases, apoptosis of tendon cells and neoangiogenesis, and regenerative and protective phenomena, such as the production of IGF-1 and nitric oxide. Tendinopathy results from the imbalance between these two groups of factors, leading to degeneration, weakening, and fissuring of the tendons, with the presence of local pain. The aim of the study was to evaluate the efficacy and tolerability of cetylated fatty acids (CFA) patch formulation in the control of acute localized shoulder pain and recovery of function in patients with tendinopathies.

Methods

A prospective, single-center, no-profit observational study conducted in accordance with Good Clinical Practice. Thirty patients with recent onset shoulder pain symptoms (1–3 months) related to bursitis and tenosynovitis, with a diagnosis of shoulder tendon pathology confirmed by ultrasound examination, was evaluated for shoulder pain and function using the Constant Murley Score. Patients used 1 patch containing CFA for 8 h per day for 10 days. At 10 (V1) and 35 (V2) days after the first visit (V0), the Constant Score, treatment compliance and product tolerability were evaluated.

Results

Thirty patients completed the treatment. At V0 the mean Constant Score (CS) was 32.37 ± 11.86, during V1 the mean CS was 50.68 ± 14.30, and at V3 the mean CS was 51.07 ± 15.29. The CS increased significantly between V0 and V1 (p < 0.0001) but did not vary significantly between V1 and V2 (p = 1). The tolerability of the product was excellent.

Conclusions

Application of the CFA-based patch for 10 consecutive days in patients with shoulder tendinopathies was effective in reducing local pain and resulted in a good recovery of function. The results achieved at day 10 were maintained for 25 days, until the follow-up visit at day 35. CFA-based patch, thanks to their efficacy and tolerability, seems to be a promising solution to improve pain and functionality in subject with shoulder tendinopathy.

Trial registration

The study was approved by the Ethics Committee of Azienda USL Toscana Nord Ovest (protocol code 2018RIAB105) and conducted in accordance with Good Clinical Practice and the ethical principles outlined in the Declaration of Helsinki.
A retrospective study on the effect of the COVID-19 pandemic on dental treatments in adults
Authors: Gómez-Costa Diego , Ramírez Juan Manuel , García Guerrero Iván , Giovannini Giovanni , Rojo Rosa , Gómez-de Diego Rafael
Published: April 2022

Background

The aim was to analyze the prevalence of dental treatments that were not performed in a dental care university referral center in the capital of Spain during the first wave of the COVID-19 pandemic.

Methods

This was a retrospective observational study based on the registry of medical records. Sex, age, nationality, and the type of treatment that was not performed in the service of the Integrated Adult Dental Clinic subject of the Dentistry degree at the Rey Juan Carlos University of Madrid were analyzed.

Results

A total of 392 medical records were analyzed. The prevalence of the treatments that were not performed was 58.67% (95% CI 53.74–63.44) of conservative treatments, 47.45% (95% CI 42.55–52.39) of periodontal treatments, 27.30% (95% CI 23.12–31.91) and 13.52% (95% CI 10.49–17.26) of clinical activities. The patients most affected by the absence of dental treatment ranged in age from 35 to 74 years. Age, sex, and nationality were not influential in not performing dental treatments.

Conclusions

The COVID-19 pandemic could have negatively influenced treatments, such as conservative and periodontal treatments, that increasing the risk of tooth loss in adults.
Situational judgment using ethical reasoning in Saudi undergraduate pharmacy students
Authors: Alkhuzaee Fahad Saleh , Ali Majid , Goh Khang Wen , Al-Worafi Yaser Mohammed , Ming Long Chiau
Published: April 2022

Introduction

There is a paramount need for moral development for pharmacists and pharmacy students to practice the patient-centered profession. We aimed to explore the current situational judgment utilizing ethical reasoning among undergraduate pharmacy students.

Methods

A set of ten ethical dilemmas, representing potential real-life situations that the students come across in the university and may face in the future as a pharmacist were developed by a team of students, academic staff, and stakeholders. These ethical dilemmas were validated, checked for accuracy, and piloted. An online questionnaire was created consisting of these ten scenarios as open-ended questions and administered to fourth year and fifth year PharmD students in a public university located at the city of Mecca, Saudi Arabia, asking them how they would react in that situation. Responses of the participants were analyzed using thematic analysis independently by four researchers and inter-rater agreement were achieved through consensus.

Results

Out of 205, 186 students completed the questionnaire with a response rate of 90.7%. Analysis and resulted in the generation of 32 codes, which were then categorized into seven overarching themes: student engagement, social and professional responsibility, academic integrity, legal obligation, moral obligation, signposting, and moral engagement and patient safety.

Conclusions

Undergraduate pharmacy students experience complex state of mind in connection with ethical reasoning. The participants’ situational judgment were driven by cultural norm, authority, and responsibility. Student engagement is also affected by the state of mind and feelings of mutual trust, perceived cultural influence and peer pressure. The students were prone to seek help from university administrators or teachers when faced with situations in which they were helpless.
Development of a complex intervention to support parents of adolescents with chronic illness transferring from pediatrics to adult care (ParTNerSTEPs)
Authors: Thomsen Ena Lindhart , Esbensen Bente Appel , Hanghøj Signe , Hansson Helena , Boisen Kirsten Arntz
Published: April 2022

Background

Transition from pediatric to adult care for adolescents with chronic illness is associated with outpatient non-attendance and low treatment adherence in adolescents, and with anxiety and concerns among parents. Recent studies have shown that parent involvement results in better transitions. The aim of this paper was to describe the development, through participatory design, of a comprehensive transfer program targeted to parents of adolescents with chronic illness.

Methods

The study was based on the UK Medical Research Council’s (MRC) framework on developing and testing complex interventions. To increase the program’s feasibility and relevance, participatory design was chosen as the overall method. A collaboration group of parents, young people and health care professionals (HCP) were actively involved in the development of the program. The program was developed in three development stages, in accordance with the MRC framework: 1) identifying the evidence base, 2) identifying theory, and 3) modelling process and outcomes.

Results

Together with the collaboration group, we developed a comprehensive transfer program targeting parents, by undertaking an iterative process, involving a literature review, individual interviews, workshops and online brainstorms. The program, called ParTNerSTEPs (Parents in Transition – a Nurse-led Support and Transfer Educational Program) comprised three components: 1) an informative website, 2) online educational events for parents, and 3) transfer consultations with providers from both pediatrics and adult care.

Conclusions

The MRC framework was successfully applied to develop a comprehensive transfer program targeting parents of adolescents with chronic ilness. By incorporating the principles of participatory design in the development phase, we ensured that both parents’ and adolescents’ needs were represented and addressed in the program.

Trial registration

ClinicalTrials.gov ID NCT04969328.
Hospital utilization in Indonesia in 2018: do urban–rural disparities exist?
Authors: Wulandari Ratna Dwi , Laksono Agung Dwi , Nantabah Zainul Khaqiqi , Rohmah Nikmatur , Zuardin Zuardin
Published: April 2022

Background

The government must ensure equality in health services access, minimizing existing disparities between urban and rural areas. The referral system in Indonesia is conceptually sound. However, there are still problems of uneven service access, and there is an accumulation of patients in certain hospitals. The study aims to analyze the urban–rural disparities in hospital utilization in Indonesia.

Methods

The study used secondary data from the 2018 Indonesian Basic Health Survey. This cross-sectional study gathered 629,370 respondents through stratification and multistage random sampling. In addition to the kind of home and hospital utilization, the study looked at age, gender, marital status, education, occupation, wealth, and health insurance as control factors. The research employed multinomial logistic regression to evaluate the data in the final step.

Results

According to the findings, someone who lives in an urban region has 1.493 times higher odds of using outpatient hospital services than someone in a rural area (AOR 1.493; 95% CI 1.489–1.498). Meanwhile, someone who lives in an urban region has 1.075 times higher odds of using an inpatient facility hospital than someone who lives in a rural one (AOR 1.075; 95% CI 1.073–1.077). Furthermore, someone living in an urban region has 1.208 times higher odds than someone who lives in a rural area using outpatient and inpatient hospital services simultaneously (AOR 1.208; 95% CI 1.204–1.212).

Conclusion

The study concluded there were urban–rural disparities in hospital utilization in Indonesia.
Organ-specific metastatic landscape dissects PD-(L)1 blockade efficacy in advanced non-small cell lung cancer: applicability from clinical trials to real-world practice
Authors: Ma Si-Cong , Bai Xue , Guo Xue-Jun , Liu Li , Xiao Lu-Shan , Lin Yan , Tan Jia-Le , Cai Xiao-Ting , Wen Yu-Xiang , Ma Hu , Fu Q. John , Leng Meng-Xin , Zhang Yan-Pei , Long Li-Li , Guo Ze-Qin , Wu De-Hua , Zhou Jian-Guo , Dong Zhong-Yi
Published: April 2022

Background

Organ-specific metastatic context has not been incorporated into the clinical practice of guiding programmed death-(ligand) 1 [PD-(L)1] blockade, due to a lack of understanding of its predictive versus prognostic value. We aim at delineating and then incorporating both the predictive and prognostic effects of the metastatic-organ landscape to dissect PD-(L)1 blockade efficacy in non-small cell lung cancer (NSCLC).

Methods

A total of 2062 NSCLC patients from a double-arm randomized trial (OAK), two immunotherapy trials (FIR, BIRCH), and a real-world cohort (NFyy) were included. The metastatic organs were stratified into two categories based on their treatment-dependent predictive significance versus treatment-independent prognosis. A metastasis-based scoring system (METscore) was developed and validated for guiding PD-(L)1 blockade in clinical trials and real-world practice.

Results

Patients harboring various organ-specific metastases presented significantly different responses to immunotherapy, and those with brain and adrenal gland metastases survived longer than others [overall survival (OS), p = 0.0105; progression-free survival (PFS), p = 0.0167]. In contrast, survival outcomes were similar in chemotherapy-treated patients regardless of metastatic sites (OS, p = 0.3742; PFS, p = 0.8242). Intriguingly, the immunotherapeutic predictive significance of the metastatic-organ landscape was specifically presented in PD-L1-positive populations (PD-L1 > 1%). Among them, a paradoxical coexistence of a favorable predictive effect coupled with an unfavorable prognostic effect was observed in metastases to adrenal glands, brain, and liver (category I organs), whereas metastases to bone, pleura, pleural effusion, and mediastinum yielded consistent unfavorable predictive and prognostic effects (category II organs). METscore was capable of integrating both predictive and prognostic effects of the entire landscape and dissected OS outcome of NSCLC patients received PD-(L)1 blockade (p < 0.0001) but not chemotherapy (p = 0.0805) in the OAK training cohort. Meanwhile, general performance of METscore was first validated in FIR (p = 0.0350) and BIRCH (p < 0.0001), and then in the real-world NFyy cohort (p = 0.0181). Notably, METscore was also applicable to patients received PD-(L)1 blockade as first-line treatment both in the clinical trials (OS, p = 0.0087; PFS, p = 0.0290) and in the real-world practice (OS, p = 0.0182; PFS, p = 0.0045).

Conclusions

Organ-specific metastatic landscape served as a potential predictor of immunotherapy, and METscore might enable noninvasive forecast of PD-(L)1 blockade efficacy using baseline radiologic assessments in advanced NSCLC.
Different methods of eubiotic feed additive provision affect the health, performance, fermentation, and metabolic status of dairy calves during the preweaning period
Authors: Stefańska Barbara , Katzer Frank , Golińska Barbara , Sobolewska Patrycja , Smulski Sebastian , Frankiewicz Andrzej , Nowak Włodzimierz
Published: April 2022

Background

This study aimed to evaluate whether different methods of providing eubiotic feed additives to neonatal calves, during the preweaning period, can improve the calves’ health, performance, ruminal fermentation, and metabolic status. Forty-four (3-day-old) Holstein–Friesian dairy calves (22 female and 22 male) were divided into four treatment groups for the duration of the 8-week trial. The eubiotic feed additive consisted of a combination of probiotic Lactobacillus spp. (multiple-strains at a dose of 250 mg/calf/day) and phytobiotics containing rosmarinic acid, as the main bioactive compound (at a dose of 50 mg/calf/day). The groups were named: CON (control, without eubiotic in either the milk replacer or the starter feed), MR (eubiotic in the milk replacer), SF (eubiotic in the starter feed), MRS (eubiotic in both the milk replacer and the starter feed). The individual intake of starter feed and the fecal scores were measured daily, and body weight and biometric measurements were taken weekly until calves were 56 days of age. Blood samples were collected on day 3 and then every 14 days to determine concentrations of insulin-like-growth-factor-I, β-hydroxybutyrate, non-esterified fatty acids, and blood urea nitrogen. Ruminal fluid was collected on days 28 and 56 for short-chain fatty acids, NH3-N, and pH measurements.

Results

The body weight of the calves of the MR treatment group was higher compared to all other groups on days 28 and 56. Including the eubiotic feed additive in the milk replacer increased average daily gain, starter intake, and total dry matter intake from day 29 to day 56 and the overall experimental period compared to the CON group. The calves with MR treatment had lower fecal scores from days 3 to 28, a number of parasite oocysts/cysts per gram of feces on day 28, and the occurrences of fecal consistency scores of 3 (mild diarrhea) and 4 (severe diarrhea) were 3.2 and 3.0 times lower, respectively, compared with the CON group. The MR group had higher ruminal concentrations of short-chain-fatty-acids, propionate, and butyrate on day 56 than the CON group. Adding eubiotics into milk replacer resulted in the highest concentrations of blood insulin-like-growth-factor-I and β-hydroxybutyrate from days 29 to 56 and the overall experimental period.

Conclusion

The addition of eubiotic feed additives into the milk replacer can improve health, performance, ruminal fermentation, and biochemical blood indices in dairy calves during the preweaning period.
Classification of colorectal carcinoma subtypes based on ferroptosis-associated molecular markers
Authors: Yue Qingfang , Zhang Yuan , Wang Fei , Cao Fei , Duan Xianglong , Bai Jun
Published: April 2022

Background

Ferroptosis is associated with the development of many cancers; the molecular features of colorectal carcinoma (CRC) based on ferroptosis-related genes (FRGs) remain unknown. Herein, we aimed to identify ferroptosis-associated molecular subtypes of CRC based on the expression profiles of FRGs.

Methods

To explore ferroptosis-associated subtypes of CRC, the gene expression data and clinical information of 682 patients were extracted from The Cancer Genome Atlas and Gene Expression Omnibus databases. We performed consensus clustering to identify robust clusters of patients. Then the distribution of the subtypes in terms of prognosis significance, transcriptome features, immune microenvironment, drug sensitivity, gene mutations, and copy number alternations (CNAs) were evaluated respectively. In addition, we analyzed the correlation of these ferroptosis-associated molecular subtypes with the distribution of conventional clinical indicators in CRC.

Results

Four subtypes of CRC (C1, C2, C3, and C4) were identified in which the prognosis, immune cell infiltration, immune score, stromal score, and tumor purity were significantly different between the four subtypes. The C3 subtype had a higher infiltration of B cells, M2 macrophages, resting mast cells, monocytes, natural killer cells, plasma cells, and CD8 T cells. The C3 subtype had the highest immune and stromal scores and the lowest tumor purity. In contrast, the C4 subtype demonstrated the lowest immune and stromal scores and the highest tumor purity. Programmed cell death ligand 1 (PD-L1), an immune checkpoint protein, was differentially expressed in the four subtypes (P < 2e–16) and was significantly correlated with the expression of several FRGs in all subtypes. Significant differences in stem cell indices (P < 0.01) and drug sensitivity (P < 0.01) were observed in the four subtypes. Additionally, gene mutations analysis showed that FRGs such as TP53 had a high frequency of mutation in the four subtypes (49%, 62%, 61%, and 71%, respectively), and the CNAs showed significant difference among all subtypes (P < 0.001).

Conclusion

In summary, the ferroptosis-associated subtypes could serve as an independent biomarker for estimating oncological outcomes in patients with CRC. Our results demonstrated that the high level of heterogeneity in the expression of FRGs might be useful for the stratification of patients with CRC and the implementation of individualized therapeutic strategies.
Environmental factors associated with juvenile idiopathic inflammatory myopathy clinical and serologic phenotypes
Authors: Scalabrini Jonathan C. , Schiffenbauer Adam I. , Farhadi Payam Noroozi , Volochayev Rita , Bayat Nastaran , Jansen Anna , Targoff Ira N. , Miller Frederick W. , Rider Lisa G.
Published: April 2022

Background

Environmental exposures have been associated with the juvenile idiopathic inflammatory myopathies (JIIM). We undertook a questionnaire-based study to evaluate patient-reported exposures as possible risk factors for JIIM.

Findings

One-hundred-seven patients with JIIM were enrolled in a myositis natural history protocol and completed environmental questionnaires. Frequencies of exposures in clinical and myositis-specific autoantibody (MSA) groups were examined. Patients with juvenile dermatomyositis (JDM) and juvenile connective tissue myositis (JCTM) more frequently received an immunization within 1 year of diagnosis compared to juvenile polymyositis (57.5 and 71.4% vs 0.0%, p ≤ 0.017). JCTM patients were more often underweight at diagnosis relative to JDM patients (42.9% vs 7.0%, p = 0.002). MSA-negative patients more frequently had gastroenteritis within a year of diagnosis compared to patients with anti-MDA5 autoantibodies (28.6% vs 0.0%, p = 0.032). Heavy exercise was more frequent in MSA-negative and anti-MDA5 groups compared to the anti-TIF-1 autoantibody group (42.9 and 35.3% vs. 9.0%, p ≤ 0.047). Medications received within 1 year of diagnosis were more frequent in MSA-negative patients relative to those with anti-MDA5 autoantibodies (92.9% vs. 52.8% p = 0.045). Being breastfed > 6 months was more frequent in MSA-negative patients (88.9%) compared to anti-TIF-1 and anti-MDA5 autoantibody groups (41.2 and 28.6%, p ≤ 0.036).

Conclusions

Certain environmental exposures prior to diagnosis differed among clinical and serologic subgroups of JIIM, suggesting additional exposures to be explored as possible risk factors for JIIM phenotypes.
Soluble TREM2 is associated with death and cardiovascular events after acute ischemic stroke: an observational study from CATIS
Authors: Lu Yaling , Zhao Yu , Zhang Qi , Fang Chongquan , Bao Anran , Dong Wenjing , Peng Yanbo , Peng Hao , Ju Zhong , He Jiang , Zhang Yonghong , Xu Tan , Zhong Chongke
Published: April 2022

Background

Soluble triggering receptor expressed on myeloid cells 2 (sTREM2), which reflects microglia activation, has been reported closely associated with neuronal injury and neuroinflammation. We aimed to prospectively investigate the associations between plasma sTREM2 and clinical outcomes in acute ischemic stroke (AIS) patients.

Methods

Study participants were from the China Antihypertensive Trial in Acute Ischemic Stroke, plasma sTREM2 levels in the acute phase of AIS were measured in 3285 participants. The study outcomes were death, cardiovascular events and severe disability at 1 year after AIS. Cox proportional hazards models or logistic regression models were performed to examine the associations of plasma sTREM2 and clinical outcomes.

Results

After 1-year follow-up, 288 participants (8.8%) experienced cardiovascular events or died. Multivariable-adjusted hazard ratios or odds ratios (95% confidence intervals) for the highest quartile of sTREM2 were 1.57 (1.11–2.21) for the composite outcome of death and cardiovascular events, 1.68 (1.09–2.60) for death, and 1.53 (1.08–2.18) for death or severe disability compared to the lowest quartile. Moreover, incorporation sTREM2 into traditional risk factors model significantly improved risk prediction of the composite outcome of death and cardiovascular events as evidenced by net reclassification index and integrated discrimination improvement (all p values < 0.05). There were joint effects of sTREM2 and galectin-3 on death and cardiovascular events. Participants with simultaneous elevation of sTREM2 and galectin-3 levels had the highest risk of the composite outcome of death and cardiovascular events.

Conclusions

Elevated sTREM2 levels were independently associated with increased risks of death and cardiovascular events after AIS.
Microglial cell response in α7 nicotinic acetylcholine receptor-deficient mice after systemic infection with Escherichia coli
Authors: Hoogland Inge C. M. , Yik Jutka , Westhoff Dunja , Engelen-Lee Joo-Yeon , Valls Seron Merche , Man Wing Kit , Houben-Weerts Judith H. P. M. , Tanck Michael W. T. , van Westerloo David J. , van der Poll Tom , van Gool Willem A. , van de Beek Diederik
Published: April 2022

Background

Development of neurodegeneration in older people has been associated with microglial cell activation triggered by systemic infection. We hypothesize that α7 nicotinic acetylcholine receptor (α7nAChR) plays an important role in regulation of this process.

Methods

8- to 10-week-old male wild-type (WT) and α7nAChR knock-out (α7nAChR−/−) mice were intraperitoneally inoculated with live Escherichia (E.) coli or saline. After inoculation, all mice were treated with ceftriaxone (an antimicrobial drug) at 12 and 24 h and killed at 2 or 3 days. The microglial response was characterized by immunohistochemical staining with an ionized calcium-binding adaptor molecule 1 (Iba-1) antibody and flow cytometry. To quantify inflammatory response, mRNA expression of pro- and anti-inflammatory mediators was measured in brain and spleen.

Results

We observed no differences in Iba-1 positive cell number or morphology and flow cytometry (CD11b, CD45 and CD14) of microglial cells between WT and α7nAChR−/− mice after systemic infection. Infected α7nAChR−/− mice showed significantly higher mRNA expression in brain for tumor necrosis factor alpha (TNF-α) at day 2 and 3, interleukin 6 (IL-6) at day 2 and monocyte chemotactic protein 1 (MCP-1) and suppressor of cytokine signaling 1 (SOCS1) at day 3, there was significantly lower mRNA expression in brain for mitogen-activated protein kinase 1 (MAPK1) at day 2 and 3, high-mobility group 1 (HMGB-1) and CD11b at day 2, and deubiquitinase protein A20 (A20) at day 3 compared to infected WT mice.

Interpretation

Loss of function of α7nAChR during systemic infection led to an increased expression of TNF-α and IL-6 in brain after systemic infection with E. coli, but not to distinct differences in microglial cell number or morphological activation of microglia.