bluuebunny/crossref_metadata_2025 huggingface dataset:
A polygenic score for acute vaso-occlusive pain in pediatric sickle cell disease
Authors: Rampersaud Evadnie , Kang Guolian , Palmer Lance E. , Rashkin Sara R. , Wang Shuoguo , Bi Wenjian , Alberts Nicole M. , Anghelescu Doralina , Barton Martha , Birch Kirby , Boulos Nidal , Brandow Amanda M. , Brooke Russell John , Chang Ti-Cheng , Chen Wenan , Cheng Yong , Ding Juan , Easton John , Hodges Jason R. , Kanne Celeste K. , Levy Shawn , Mulder Heather , Patel Ashwin P. , Puri Latika , Rosencrance Celeste , Rusch Michael , Sapkota Yadav , Sioson Edgar , Sharma Akshay , Tang Xing , Thrasher Andrew , Wang Winfred , Yao Yu , Yasui Yutaka , Yergeau Donald , Hankins Jane S. , Sheehan Vivien A. , Downing James R. , Estepp Jeremie H. , Zhang Jinghui , DeBaun Michael , Wu Gang , Weiss Mitchell J.
Published: July 2021

Individuals with monogenic disorders can experience variable phenotypes that are influenced by genetic variation. To investigate this in sickle cell disease (SCD), we performed whole-genome sequencing (WGS) of 722 individuals with hemoglobin HbSS or HbSβ0-thalassemia from Baylor College of Medicine and from the St. Jude Children’s Research Hospital Sickle Cell Clinical Research and Intervention Program (SCCRIP) longitudinal cohort study. We developed pipelines to identify genetic variants that modulate sickle hemoglobin polymerization in red blood cells and combined these with pain-associated variants to build a polygenic score (PGS) for acute vaso-occlusive pain (VOP). Overall, we interrogated the α-thalassemia deletion −α3.7 and 133 candidate single-nucleotide polymorphisms (SNPs) across 66 genes for associations with VOP in 327 SCCRIP participants followed longitudinally over 6 years. Twenty-one SNPs in 9 loci were associated with VOP, including 3 (BCL11A, MYB, and the β-like globin gene cluster) that regulate erythrocyte fetal hemoglobin (HbF) levels and 6 (COMT, TBC1D1, KCNJ6, FAAH, NR3C1, and IL1A) that were associated previously with various pain syndromes. An unweighted PGS integrating all 21 SNPs was associated with the VOP event rate (estimate, 0.35; standard error, 0.04; P = 5.9 × 10−14) and VOP event occurrence (estimate, 0.42; standard error, 0.06; P = 4.1 × 10−13). These associations were stronger than those of any single locus. Our findings provide insights into the genetic modulation of VOP in children with SCD. More generally, we demonstrate the utility of WGS for investigating genetic contributions to the variable expression of SCD-associated morbidities.
Minimal clinically important difference in idiopathic pulmonary fibrosis
Authors: Kang Mohleen , Marts Lucian , Kempker Jordan A. , Veeraraghavan Srihari
Published: July 2021

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing lung disease with an estimated median survival of 2–5 years and a significant impact on quality of life (QoL). Current approved medications, pirfenidone and nintedanib, have shown a reduction in annual decline of forced vital capacity but no impact on QoL. The minimal clinically important difference (MCID) is a threshold value for a change in a parameter that is considered meaningful by the patient rather than solely relying on statistically significant change in the parameter. This review provides a brief overview of the MCID methodology along with detailed discussion of reported MCID values for commonly used physiological measures and patient-reported outcome measures in IPF. While there is no gold standard methodology for determining MCID, there are certain limitations in the MCID literature in IPF, mainly the choice of death, hospitalisation and pulmonary function tests as sole anchors, and pervasive use of distribution-based methods which do not take into account the patient's input. There is a critical need to identify accurate thresholds of outcome measures that reflect patient's QoL over time in order to more precisely design and evaluate future clinical trials and to develop algorithms for patient-oriented management of IPF in outpatient clinics.

Educational aims

To understand the concept of MCID and the methods used to determine these values.

To understand the indications and limitations of MCID values in IPF.
Regional disparity of certified teaching hospitals on physicians’ workload and wages, and popularity among medical students in Japan
Authors: Ikki Yutaro , Yamada Masaaki , Sekine Michikazu
Published: July 2021

Background

Regional disparities in the working conditions of medical doctors have not been fully assessed in Japan. We aimed to clarify these differences in hospital characteristics: doctors’ workload, wages, and popularity among medical students by city population sizes.

Methods

We targeted 423 teaching hospitals certified by the Japanese Society of Internal Medicine and assessed the working conditions of physicians specializing in internal medicine. We calculated their workload (the annual number of discharged patients per physician) and retrieved data on junior residents’ monthly wages from the Resinavi Book which is popular among medical students in Japan to know the teaching hospital’s information and each hospital’s website. Furthermore, we explored the interim matching rate of each hospital as its popularity among medical students. Next, we classified cities in which all hospitals were located into eight groups based on their population size and compared the characteristics of these hospitals using a one-way analysis of variance.

Results

The average workload was 110.3, while the average workload in hospitals located in most populated cities (≥ 2,000,000) was 88.4 (p < 0.05). The average monthly wage was 351,199 Japanese yen, while that in most populated cities was 305,635.1 Japanese yen. The average popularity (matching rate) was 101.9%, and the rate in most populated areas was 142.7%, which was significantly higher than in other areas.

Conclusions

Hospitals in most populated areas had significantly lower workloads and wages; however, they were more popular among medical students than those in other areas. This study was the first to quantify the regional disparities in physicians’ working conditions in Japan, and such disparities need to be corrected.
Genetic analysis of egg production traits in turkeys (Meleagris gallopavo) using a single-step genomic random regression model
Authors: Emamgholi Begli Hakimeh , Schaeffer Lawrence R. , Abdalla Emhimad , Lozada-Soto Emmanuel A. , Harlander-Matauschek Alexandra , Wood Benjamin J , Baes Christine F.
Published: July 2021

Background

Egg production traits are economically important in poultry breeding programs. Previous studies have shown that incorporating genomic data can increase the accuracy of genetic prediction of egg production. Our objective was to estimate the genetic and phenotypic parameters of such traits and compare the prediction accuracy of pedigree-based random regression best linear unbiased prediction (RR-PBLUP) and genomic single-step random regression BLUP (RR-ssGBLUP). Egg production was recorded on 7422 birds during 24 consecutive weeks from first egg laid. Hatch-week of birth by week of lay and week of lay by age at first egg were fitted as fixed effects and body weight as a covariate, while additive genetic and permanent environment effects were fitted as random effects, along with heterogeneous residual variances over 24 weeks of egg production. Predictions accuracies were compared based on two statistics: (1) the correlation between estimated breeding values and phenotypes divided by the square root of the trait heritability, and (2) the ratio of the variance of BLUP predictions of individual Mendelian sampling effects divided by one half of the estimate of the additive genetic variance.

Results

Heritability estimates along the production trajectory obtained with RR-PBLUP ranged from 0.09 to 0.22, with higher estimates for intermediate weeks. Estimates of phenotypic correlations between weekly egg production were lower than the corresponding genetic correlation estimates. Our results indicate that genetic correlations decreased over the laying period, with the highest estimate being between traits in later weeks and the lowest between early weeks and later ages. Prediction accuracies based on the correlation-based statistic ranged from 0.11 to 0.44 for RR-PBLUP and from 0.22 to 0.57 for RR-ssGBLUP using the correlation-based statistic. The ratios of the variances of BLUP predictions of Mendelian sampling effects and one half of the additive genetic variance ranged from 0.17 to 0.26 for RR-PBLUP and from 0.17 to 0.34 for RR-ssGBLUP. Although the improvement in accuracies from RR-ssGBLUP over those from RR-PBLUP was not uniform over time for either statistic, accuracies obtained with RR-ssGBLUP were generally equal to or higher than those with RR-PBLUP.

Conclusions

Our findings show the potential advantage of incorporating genomic data in genetic evaluation of egg production traits using random regression models, which can contribute to the genetic improvement of egg production in turkey populations.
Multi-omics approach highlights differences between RLP classes in Arabidopsis thaliana
Authors: Steidele C. E. , Stam R.
Published: July 2021

Background

The Leucine rich-repeat (LRR) receptor-like protein (RLP) family is a complex gene family with 57 members in Arabidopsis thaliana. Some members of the RLP family are known to be involved in basal developmental processes, whereas others are involved in defence responses. However, functional data is currently only available for a small subset of RLPs, leaving the remaining ones classified as RLPs of unknown function.

Results

Using publicly available datasets, we annotated RLPs of unknown function as either likely defence-related or likely fulfilling a more basal function in plants. Then, using these categories, we can identify important characteristics that differ between the RLP subclasses. We found that the two classes differ in abundance on both transcriptome and proteome level, physical clustering in the genome and putative interaction partners. However, the classes do not differ in the genetic di versity of their individual members in accessible pan-genome data.

Conclusions

Our work has several implications for work related to functional studies on RLPs as well as for the understanding of RLP gene family evolution. Using our annotations, we can make suggestions on which RLPs can be identified as potential immune receptors using genetics tools and thereby complement disease studies. The lack of differences in nucleotide diversity between the two RLP subclasses further suggests that non-synonymous diversity of gene sequences alone cannot distinguish defence from developmental genes. By contrast, differences in transcript and protein abundance or clustering at genomic loci might also allow for functional annotations and characterisation in other plant species.
Effect of 12-weeks elastic band resistance training on MyomiRs and osteoporosis markers in elderly women with Osteosarcopenic obesity: a randomized controlled trial
Authors: Banitalebi Ebrahim , Ghahfarrokhi Majid Mardaniyan , Dehghan Mortaza
Published: July 2021

Background

Interorgan communication networks established during exercise in several different tissues can be mediated by several exercise-induced factors. Therefore, the present study aimed to investigate the effects of resistance-type training using elastic band-induced changes of myomiRs (i.e., miR-206 and miR-133), vitamin D, CTX-I, ALP, and FRAX® score in elderly women with osteosarcopenic obesity (OSO).

Methods

In this randomized controlled trial, 63 women (aged 65–80 years) with Osteosarcopenic Obesity were recruited and assessed, using a dual-energy X-ray absorptiometry instrument. The resistance-type training via elastic bands was further designed three times per week for 12-weeks. The main outcomes were Fracture Risk Assessment Tool score, bone mineral content, bone mineral density, vitamin D, alkaline phosphatase, C-terminal telopeptides of type I collagen, expression of miR-206 and miR-133.

Results

There was no significant difference between the study groups in terms of the Fracture Risk Assessment Tool score (p = 0.067), vitamin D (p = 0.566), alkaline phosphatase (p = 0.334), C-terminal telopeptides of type I collagen (p = 0.067), microR-133 (p = 0.093) and miR-206 (p = 0.723).

Conclusion

Overall, the results of this study illustrated 12-weeks of elastic band resistance training causes a slight and insignificant improvement in osteoporosis markers in women affected with Osteosarcopenic Obesity.

Trial registration

Randomized controlled trial (RCT) (Iranian Registry of Clinical Trials, trial registration number: IRCT20180627040260N1.

Date of registration: 27/11/2018.
Changes in prevalence of nosocomial infection pre- and post-COVID-19 pandemic from a tertiary Hospital in China
Authors: Su Chunmei , Zhang Zhiqin , Zhao Xu , Peng Hanlin , Hong Yi , Huang Lili , Huang Jie , Yan Xiangming , Wu Shuiyan , Bai Zhenjiang
Published: July 2021

Background

Nosocomial infections (NIs) are an important cause of mortality, and increasing evidence reveals that the prevalence of NIs can be reduced through effective prevention and control measures. The aim of this study was to investigate the impact of the prevention and control measures for the COVID-19 pandemic on NIs.

Methods

A retrospective study was conducted to analyze the prevalence of NIs before and after COVID-19 pandemic for 6 months in the Children’s Hospital of Soochow University.

Results

A total of 39,914 patients in 2019 and 34,645 patients in 2020 were admitted to the hospital during the study. There were 1.39% (481/34645) of patients with NIs in 2020, which was significantly lower than the 2.56% (1021/39914) of patients in 2019. The rate of critical and fatal cases was also decreased. In addition, the rate of appropriate handwashing, the number of protective gloves and aprons used per person and the number of healthcare staff per patients were significantly increased. Except for the ICU, the prevalence of nosocomial infection in most departments decreased from 2019 to 2020. Regarding the source of infections, a significant reduction was mainly observed in respiratory (0.99% vs 0.42%, p = 0.000) and digestive tract (0.63% vs 0.14%, p = 0.000). The microorganism analysis of respiratory infections indicated an obvious decline in acinetobacters and fungi. The most significant decline of pathogens in gastrointestinal infections was observed for rotavirus. The comparison of catheter-related nosocomial infections between 2019 and 2020 did not show significant differences.

Conclusions

The prevention and control measures for the COVID-19 pandemic have reduced the nosocomial infection in almost all departments, except the ICU, mainly regarding respiratory, gastrointestinal, and oral infections, while catheter-related infections did not show any differences.
Analysis of determinants of postpartum emotional disorders
Authors: Iwanowicz-Palus Grażyna , Marcewicz Agnieszka , Bień Agnieszka
Published: July 2021

Background

The birth of a child entails major changes in a woman’s life. In the perinatal period, the woman is particularly susceptible to emotional problems. The objective of the present paper was to investigate the relationship between global orientation to life and its components on the one hand, and socio-demographic factors on the other, with regard to early postpartum emotional disorders.

Methods

The study included 643 patients hospitalized in obstetric departments in Lublin, Poland, who had had a spontaneous vaginal delivery. Research instruments included: the Edinburgh Postnatal Depression Scale (EPDS), the Orientation to Life Questionnaire (SOC-29), and the authors’ own survey questionnaire to record participants’ characteristics.

Results

The study findings indicate an association between lower levels of postpartum blues and higher levels of global sense of coherence, as well as a stronger sense of meaningfulness, manageability, and comprehensibility. More severe emotional disorders were found in patients who were single. Postpartum blues symptoms were more intense in less educated respondents.

Conclusions

Postpartum emotional disorders are associated with a global sense of coherence and its components. Higher levels of SOC reduce the risk of postpartum blues.
Inter-observer variations of the tumor bed delineation for patients after breast conserving surgery in preoperative magnetic resonance and computed tomography scan fusion
Authors: Jiang Jie , Chen Jinhu , Li Wanhu , Li Yongqing , Chen Yiru , Zhang Zicheng , Liu Chengxin , Han Dan , Sun Hongfu , Li Baosheng , Huang Wei
Published: July 2021

Purpose

Tumor bed (TB) delineation based on preoperative magnetic resonance imaging (pre-MRI) fused with postoperative computed tomography (post-CT) were compared to post-CT only to define pre-MRI may aid in improving the accuracy of delineation.

Methods and materials

The pre-MRI imaging of 10 patients underwent radiotherapy (RT) after breast conserving surgery (BCS) were reviewed. Post-CT scans were acquired in the same prone position as pre-MRI. Pre-MRI and post-CT automatically match and then manual alignment was given to enhance fusion consistency. Three radiation oncologists and 2 radiologists delineated the clinical target volume (CTV) for CT-based. The gross target volume (GTV) of pre-MRI-based was determined by the volume of tumor acquired with 6 sequences: T1, T2, T2W-SPAIR, DWI, dyn-eTHRIVE and sdyn-eTHRIVE, expended 10 mm to form the CTV-pre-MRI. Planning target volume (PTV) for each sequence was determined by CTV extended 15 mm, trimmed to 3 mm from skin and the breast-chest wall interface. The variability of the TB delineation were developed as follows: the mean volume, conformity index (CI) and dice coefficient (DC).

Results

The mean volumes of CTV and PTV delineated with CT were all larger than those with pre-MRI. The lower inter-observer variability was observed from PTV, especially in sdyn-eTHRIVE in all sequences. For each sequence of pre-MRI, all DCs were larger than post-CT, and the largest DC was observed by sdyn-eTHRIVE sequence fusion to post-CT. The overlap for PTV was significantly improved in the pre-MRI-based compared with the CT-based.

Conclusions

TB volumes based on pre-MRI were smaller than post-CT with CVS increased. Pre-MRI provided a more precise definition of the TB with observers performed a smaller inter-observer variability than CT. Pre-MRI, especially in sdyn-eTHRIVE sequence, should help in reducing treatment volumes with the improved accuracy of TB delineation of adjuvant RT of breast cancer.
The combination of 13N-ammonia and 11C-methionine in differentiation of residual/recurrent pituitary adenoma from the pituitary gland remnant after trans-sphenoidal Adenomectomy
Authors: Zhang Fangling , He Qiao , Luo Ganhua , Long Yali , Li Ruocheng , Ding Lei , Zhang Xiangsong
Published: July 2021

Background

This study aimed to assess the clinical usefulness of 13N-ammonia and 11C- Methionine (MET) positron emission tomography (PET)/ computed tomography (CT) in the differentiation of residual/recurrent pituitary adenoma (RPA) from the pituitary gland remnant (PGR) after trans-sphenoidal adenomectomy.

Methods

Between June 2012 and December 2019, a total of 19 patients with a history of trans-sphenoidal adenomectomy before PET/CT scans and histological confirmation of RPA after additional surgery in our hospital were enrolled in this study. Images were interpreted by visual evaluation and semi-quantitative analysis. In semi-quantitative analysis, the maximum standard uptake value (SUVmax) of the target and gray matter was measured and the target uptake/gray matter uptake (T/G) ratio was calculated.

Results

The T/G ratios of 13N-ammonia were significantly higher in PGR than RPA (1.58 ± 0.69 vs 0.63 ± 1.37, P < 0.001), whereas the T/G ratios of 11C-MET were obviously lower in PGR than RPA (0.78 ± 0.35 vs 2.17 ± 0.54, P < 0.001). Using the canonical discriminant analysis, we calculated the predicted accuracy of RPA (100%), PGR (92.9%), and the overall predicted accuracy (96.43%).

Conclusions

The combination of 13N-ammonia and 11C-MET PET/CT is valuable in the differentiation of RPA from PGR after trans-sphenoidal adenomectomy.
Suicide attempt risks among hotline callers with and without the coronavirus disease 2019 related psychological distress: a case-control study
Authors: Tong Yongsheng , Conner Kenneth R. , Yin Yi , Zhao Liting , Wang Yuehua , Wu Mengjie , Wang Cuiling
Published: July 2021

Background

The coronavirus disease 2019 (COVID-19) pandemic profoundly impacts on mental health, yet it is still unclear whether COVID-19 distress makes people more vulnerable to suicidal behavior. The present study aims to examine the association between COVID-19 related psychological distress and risk for suicide attempt, and moderators of this association, among hotline callers.

Methods

This case-control study was conducted at the largest psychological support hotline in China. Hotline callers who sought help for psychological distress and reported whether or not they attempted suicide in the last 2 weeks (recent suicide attempt) were analyzed. The primary predictor of recent suicide attempt was the presence or absence of COVID-19 related psychological distress. Demographic variables and common risk and protective factors for suicidal behavior were also studied. Callers with COVID-19 related distress (COVID-19 callers) and those without such distress (non-COVID-19 callers) were compared on these variables. Recent suicide attempt was regressed on COVID-19 related distress and the other variables, and significant interaction terms of aforementioned predictors by COVID-19 related distress, to identify variables that moderate the association of COVID-19 related distress and recent suicide attempt.

Results

Among 7337 included callers, there were 1252 COVID-19 callers (17.1%) and 6085 non-COVID-19 callers (82.9%). The COVID-19 callers were less likely to report recent suicide attempt (n = 73, 5.8%) than the non-COVID-19 callers (n = 498, 8.2%, P = 0.005). The COVID-19 callers were also less likely to have high scores on depressive symptoms (22.6% vs 26.3%, P < 0.001) and psychological distress (19.5% vs 27.3%, P < 0.001), and were more likely to have high hopefulness scores (46.5% vs 38.0%, P < 0.001). Tests of moderating effects showed that acute life events were associated with one-half lower risk (P = 0.021), and a trend that suicide attempt history was associated with two-thirds greater risk (P = 0.063) for recent suicide attempt, among COVID-19 callers than non-COVID-19 callers.

Conclusions

The COVID-19 calls are from individuals with lower suicide-related risk compared to more typical callers. Acute stressful life events provided a key context for suicide attempt in non-COVID-19 callers, i.e., more typical calls.
Before the 2020 Pandemic: an observational study exploring public knowledge, attitudes, plans, and preferences towards death and end of life care in Wales
Authors: Islam Ishrat , Nelson Annmarie , Longo Mirella , Byrne Anthony
Published: July 2021

Background

Understanding public attitudes towards death and dying is important to inform public policies around End of Life Care (EoLC). We studied the public attitudes towards death and dying in Wales.

Methods

An online survey was conducted in 2018. Social media and the HealthWiseWales platform were used to recruit participants. Data were analysed using descriptive statistics and thematic analysis.

Results

2,210 people participated. Loss of independence (84%), manner of death, and leaving their beloved behind were the biggest fears around death and dying. In terms of EoLC, participants sought timely access to care (84%) and being surrounded by loved ones (62%). Being at home was less of a priority (24%). Only 50% were familiar with Advance Care Planning (ACP). A lack of standard procedures as well as of support for the execution of plans and the ability to revisit those plans hindered uptake. The taboo around death conversations, the lack of opportunities and skills to initiate discussion, and personal fear and discomfort inhibited talking about death and dying. 72% felt that we do not talk enough about death and dying and advocated normalising talking by demystifying death with a positive approach.

Health professionals could initiate and support this conversation, but this depended on communication skills and manageable workload pressure. Participants encouraged a public health approach and endorsed the use of: a) social media and other public platforms, b) formal education, c) formal and legal actions, and d) signposting and access to information.

Conclusions

People are ready to talk about death and dying and COVID-19 has increased awareness. A combination of top-down and bottom-up initiatives across levels and settings can increase awareness, knowledge, and service-utilisation-drivers to support health professionals and people towards shared decisions which align with people’s end of life wishes and preferences.
Why do students skip classroom lectures: A single dental school report
Authors: Alamoudi Waleed A. , Alhelo Azza F. , Almazrooa Soulafa A. , Felemban Osama M. , Binmadi Nada O. , Alhindi Nada A. , Ali Sarah A. , Akeel Sara K. , Alhamed Sana A. , Mansour Ghadah M. , Mawardi Hani H.
Published: July 2021

Background

Conventional classroom lectures continue to represent a major component of the dental education system to ensure optimum delivery of knowledge. Certain number of students are less compliant and likely to skip classes which may impact the overall academic performance. The aim of this study was to investigate dental students’ attitude towards classroom attendance and potential reasons for absenteeism at King Abdulaziz University-Faculty of Dentistry (KAU-FD).

Methods

This was a cross-sectional survey of all dental students actively enrolled at KAU-FD from January to June 2019. The survey included questions on demographics, average travel time to school, current dental year, most recent GPA, student’s perspective toward classroom lectures. The survey was validated and distributed to all students at a pre-selected time frame. Data were analysed and presented as frequencies and percentages; chi-square test was used to explore parameters association.

Results

A total of 678 students consented and completed the survey. Overall, 44.3% of students were more likely to skip two classes or less per month. Second year dental students were more likely to be absent from classroom lectures (31.3%), while 3rd year dental students were less likely to do so (15.4%). Reported students’ justifications for missing classes included early morning classes (47.9%), exams preparation (42%), and lecturer’s weak presentation skills (41.9%).

Conclusion

Compliance of dental students with classroom attendance has been an ongoing challenge for most programs. The current data suggests a multifactorial module for students’ attitude toward classroom attendance. Future studies focusing on reasons behind classroom attendance behavior and addressing students’ concerns are needed.
The stakeholders’ perceptions of the requirements of implementing innovative educational approaches in nursing: a qualitative content analysis study
Authors: Nasrabadi Alireza Nikbakht , Mohammadi Nooredin , Rooddehghan Zahra , Shabani Enayat A. , Bakhshi Fatemeh , Ghorbani Azam
Published: July 2021

Background

Improving the competencies of nurses requires improving educational methods through the use of novel methods in teaching and learning. We aim to explore the perceptions of stakeholders (including nursing education directors, faculty members and nursing students) of the requirements of implementing innovative educational approaches in nursing.

Methods

In this qualitative descriptive study, 19 participants, including educational directors, faculty members, and undergraduate and graduate nursing students, were selected through the purposeful sampling method. Achieving the theoretical saturation in extracted categories was considered as a criterion for determining the sample size and the completion of sampling. The data were collected from December 2019 to May 2020 in nursing schools of Tehran, Iran, through in-depth semi-structured individual face-to-face interviews and were then analyzed based on the Graneheim and Lundman method.

Results

Using qualitative content analysis, eight sub-themes and three themes were extracted. The extracted themes were ‘novel educational policymaking’, ‘Innovative education-oriented platform’, and ‘managing barriers of innovative educational approaches’.

Conclusions

Developing and implementing innovative educational approaches entail providing appropriate context, structure, and required facilities by the policymaking system and educational authorities. In addition, developing capacity and related competencies of faculty members and students as the major stakeholders in employing these approaches is crucial.
Health policy experts’ perspectives on implementing mental health specialist video consultations in routine primary care – a qualitative interview study
Authors: Tönnies Justus , Oeljeklaus Lydia , Wensing Michel , Hartmann Mechthild , Friederich Hans-Christoph , Haun Markus W.
Published: July 2021

Background

Many patients with mental disorders are treated by their general practitioner (GP). Innovative technology-based integrated care models (e.g., mental health specialist video consultations) have been proposed to facilitate access to specialist services in primary care settings. While perspectives of patients and providers have been examined, there is little insight into the perspectives of health policy experts on such models. The purpose of this study was to examine the perspectives of health policy experts on (1) current challenges for continuity of care, (2) anticipated benefits and barriers for implementation of mental health specialist video consultations along with (3) practical and regulative preconditions for sustained implementation in primary care.

Methods

In a cross-sectional qualitative study, we conducted 15 semi-structured interviews with health policy experts representing various stakeholders in the German health care system: health insurances, governmental bodies, clinicians’ professional associations, and patient representatives. Following a critical realism approach, we applied a qualitative inductive content analysis to derive key themes from the material.

Results

Health policy experts saw long waiting times for patients and a lack of collaboration between in- and outpatient mental health services as well as mental health specialists and GPs as main barriers for current continuity of care. Health policy experts also felt that video consultations bear great potential to foster coordinated care between GPs and specialists and ensure timely referral for severely burdened patients. Increased workload for the general practice staff to facilitate video consultations and difficulties in establishing reliable therapeutic alliances between patients and specialists via remote treatment were considered as major barriers. Health policy experts varied significantly in their level of knowledge concerning legal frameworks and regulations pertaining to video consultations. However, the implementation of appropriate reimbursement schemes and sufficient data protection were regarded as the major regulative challenges.

Conclusions

Health policy experts mostly consider mental health specialist video consultations as a promising way to overcome current challenges for the management of patients with mental disorders at the interface between primary and specialist care. To ensure sustained implementation, a multi-stakeholder approach accounting for the perspective of health policy experts, patients, and providers should be followed.

Trial registration

German Clinical Trials Register DRKS00012487
Randomized controlled study of the impact of a participatory patient care plan among primary care patients with common chronic diseases: a one-year follow-up study
Authors: Tusa Nina , Kautiainen Hannu , Elfving Pia , Sinikallio Sanna , Mäntyselkä Pekka
Published: July 2021

Backround

Chronic diseases and multimorbidity are common in the ageing population and affect the health related quality of life. Health care resources are limited and the continuity of care has to be assured. Therefore it is essential to find demonstrable tools for best treatment practices for patients with chronic diseases.

Our aim was to study the influence of a participatory patient care plan on the health-related quality of life and disease specific outcomes related to diabetes, ischemic heart disease and hypertension.

Methods

The data of the present study were based on the Participatory Patient Care Planning in Primary Care. A total of 605 patients were recruited in the Siilinjärvi Health Center in the years 2017–2018 from those patients who were followed up due to the treatment of hypertension, ischemic heart disease or diabetes. Patients were randomized into usual care and intervention groups. The intervention consisted of a participatory patient care plan, which was formulated in collaboration with the patient and the nurse and the physician during the first health care visit.

Health-related quality of life with the 15D instrument and the disease-specific outcomes of body mass index (BMI), low density lipoprotein cholesterol (LDL-C), hemoglobin A1c (HbA1C) and blood pressure were assessed at the baseline and after a one-year follow-up.

Results

A total of 587 patients with a mean age of 69 years were followed for 12 months. In the intervention group there were 289 patients (54% women) and in the usual care group there were 298 patients (50% women). During the follow-up there were no significant changes between the groups in health-related quality and disease-specific outcomes.

Conclusions

During the 12-month follow-up, no significant differences between the intervention and the usual care groups were detected, as the intervention and the usual care groups were already in good therapeutic equilibrium at the baseline.

Trial registration

ClinicalTrials.gov Identifier: NCT02992431. Registered 14/12/2016
Impaired cerebrospinal fluid transport due to idiopathic subdural hematoma in pig: an unusual case
Authors: Shanbhag Nagesh C. , Bèchet Nicholas Burdon , Kritsilis Marios , Lundgaard Iben
Published: July 2021

Background

We report the effects of the presentation of an idiopathic subdural hematoma (SDH) in an adult domestic pig on the glymphatic system, a brain-wide solute clearance system. This accidental finding is based on our recently published study that described this system for the first time in large mammals. Our current results define the need to investigate cerebrovascular pathologies that could compromise glymphatic function in gyrencephalic animal models as a tool to bridge rodent and human glymphatic studies.

Case presentation

The pig underwent intracisternal infusion of a fluorescent tracer under general anesthesia to delineate cerebrospinal fluid (CSF) pathways, and was euthanized at the end of 3 h of tracer circulation. During brain isolation, a hematoma measuring approximately 15 × 35 mm in size beneath the dura was evident overlying fronto-parietal brain surface. Interestingly, CSF tracer distribution was markedly reduced on dorsal, lateral and ventral surfaces of the brain when compared with a control pig that was infused with the same tracer. Furthermore, regional distribution of tracer along the interhemispheric fissure, lateral fissure and hippocampus was 4–5-fold reduced in comparison with a control pig. Microscopically, glial-fibrillary acidic protein and aquaporin-4 water channel immunoreactivities were altered in the SDH pig brain.

Conclusions

This is the first case of impaired glymphatic pathway due to an idiopathic SDH in a pig. Potential etiology could involve an acceleration-deceleration injury inflicted prior to arrival at our housing facility (e.g., during animal transportation) leading to disruption of bridging veins along the superior sagittal sinus and impairing CSF pathways in the whole brain. This accidental finding of globally impaired glymphatic function sheds light on a novel consequence of SDH, which may play a role in the enhanced cognitive decline seen in elderly presenting with chronic SDH.
Molecular profiling of basal cell carcinomas in young patients
Authors: Abi Karam Marc , Kourie Hampig Raphael , Jalkh Nadine , Mehawej Cybel , Kesrouani Carole , Haddad Fady Gh , Feghaly Iman , Chouery Eliane , Tomb Roland
Published: July 2021

Background

Basal cell carcinoma (BCC) represents by far the most common non-melanoma skin cancer (NMSC) in the world with an increasing incidence of 3% to 10% per year, especially in patients under the age of 40. While variants in the sonic Hedgehog and cell cycle regulation pathways account for the majority of BCC cases in adults, the molecular etiology of BCC in young patients is unelucidated yet. This study aims to investigate the molecular profile of BCC in the young population.

Methods

28 tumors belonging to 25 Lebanese patients under the age of 40, presenting different stages of BCC and diagnosed at Hôtel Dieu de France—Saint Joseph University Medical Center were included in this study. A selected panel of 150 genes involved in cancer was analyzed by Next Generation Sequencing (NGS) in the 28 included tumors.

Results

Genetic variants detected in more than 5% of the reads, with a sequencing depth ≥ 50x, were selected. Two hundred and two genetic variants in 48 different genes were detected, with an overall average sequencing depth of 1069x. Among the 28 studied tumors, 18 (64.3%) show variations in the PTCH1 gene, 6 (21.4%) in TP53 and 3 (10.7%) in SMO.

Conclusions

This is the first study reporting NGS-based analysis of BCC in a cohort of young patients. Our results highlight the involvement of the hedgehog and cell cycle regulation pathways in the genesis of BCC in the general population. The inclusion of a larger cohort of young patients is needed to confirm our findings.
Fibrinogen/albumin ratio index is an independent predictor of recurrence-free survival in patients with intrahepatic cholangiocarcinoma following surgical resection
Authors: Liu Hu , Qiu Guoteng , Hu Fengjuan , Wu Hong
Published: July 2021

Background

Systemic inflammation and nutritional status are associated with tumor development and progression. This study investigated the prognostic value of fibrinogen/albumin ratio index (FARI) in predicting recurrence-free survival (RFS) in patients with intrahepatic cholangiocarcinoma (ICC) undergoing hepatectomy.

Methods

A retrospective cohort was conducted including patients who received curative hepatectomy for ICC at our hospital between May 2010 and December 2016. We collected the preoperative hematologic parameters and clinical data of all patients. Time-dependent receiver operating characteristic curve was used to identify the optimal cutoff value of FARI. The association between FARI-high and FARI-low group was investigated by using the Kaplan–Meier method. A nomogram based on the results of univariate and multivariate analysis was established.

Results

A total of 394 patients with ICC who underwent hepatectomy at our hospital were enrolled. K-M analysis revealed that increased FARI was related to reduced RFS (P < 0.001). The multivariate analysis indicated that tumor number, tumor–node–metastasis stage, lymph node metastasis, cirrhosis, serum carbohydrate antigen 19-9, and FARI were independent predictors of RFS, and the ROC curve analysis showed that the optimal cutoff value for FARI was 0.084 based on the Youden index. The nomogram for FARI showed satisfactory accuracy in predicting RFS for ICC patients undergoing hepatectomy (C index = 0.663; AIC = 3081.07).

Conclusion

Preoperative FARI is an independent predictor of RFS in patients undergoing hepatectomy for ICC, and the nomogram can be useful for clinical decision-making in the postoperative management of these patients.
Comparing options for females seeking permanent contraception in high resource countries: a systematic review
Authors: Gormley Rebecca , Vickers Brian , Cheng Brooke , Norman Wendy V.
Published: July 2021

Background

Multiple options for permanent or long-acting contraception are available, each with adverse effects and benefits. People seeking to end their fertility, and their healthcare providers, need a comprehensive comparison of methods to support their decision-making. Permanent contraceptive methods should be compared with long-acting methods that have similar effectiveness and lower anticipated adverse effects, such as the levonorgestrel-releasing intrauterine contraception (LNG-IUC). We aimed to understand the comparability of options for people seeking to end their fertility, using high-quality studies. We sought studies comparing laparoscopic tubal ligation, hysteroscopic tubal occlusion, bilateral salpingectomy, and insertion of the LNG-IUC, for effectiveness, adverse events, tolerability, patient recovery, non-contraceptive benefits, and healthcare system costs among females in high resource countries seeking to permanently avoid conception.

Methods

We followed PRISMA guidelines, searched EMBASE, Pubmed (Medline), Web of Science, and screened retrieved articles to identify additional studies. We extracted data on population, interventions, outcomes, follow-up, health system costs, and study funding source. We used the Newcastle–Ottawa Scale to assess risk of bias and excluded studies with medium–high risk of bias (NOS < 7). Due to considerable heterogeneity, we performed a narrative synthesis.

Results

Our search identified 6,612 articles. RG, BV, BC independently reviewed titles and abstracts for relevance. We reviewed the full text of 154 studies, yielding 34 studies which met inclusion criteria. We excluded 10 studies with medium–high risk of bias, retaining 24 in our synthesis. Most studies compared hysteroscopic tubal occlusion and/or laparoscopic tubal ligation. Most comparisons reported on effectiveness and adverse events; fewer reported tolerability, patient recovery, non-contraceptive benefits, and/or healthcare system costs. No comparisons reported accessibility, eligibility, or follow-up required. We found inconclusive evidence comparing the effectiveness of hysteroscopic tubal occlusion to laparoscopic tubal ligation. All studies reported adverse events. All forms of tubal interruption reported a protective effect against cancers. Tolerability appeared greater among tubal ligation patients compared to hysteroscopic tubal occlusion patients. No high-quality studies included the LNG-IUC.

Conclusions

Studies are needed to directly compare surgical forms of permanent contraception, such as tubal ligation or removal, with alternative options, such as intrauterine contraception to support decision-making.

Systematic review registration

PROSPERO [CRD42016038254].
Clinical significance and mechanisms associated with segmental UPD
Authors: Papenhausen Peter R. , Kelly Carla A. , Harris Samuel , Caldwell Samantha , Schwartz Stuart , Penton Andrea
Published: July 2021

Whole chromosome uniparental disomy (UPD) has been well documented with mechanisms largely understood. However, the etiology of segmental limited UPD (segUPD) is not as clear. In a 10-year period of confirming (> 300) cases of whole chromosome UPD, we identified 86 segmental cases in both prenatal and postnatal samples. Thirty-two of these cases showed mosaic segmental UPD at 11p due to somatic selection associated with Beckwith–Wiedemann syndrome. This study focuses on apparent mechanisms associated with the remaining cases, many of which appear to represent corrections of genomic imbalance such as deletions and derivative chromosomes. In some cases, segmental UPD was associated with the generation of additional genomic imbalance while in others it apparently resulted in restoration of euploidy. Multiple tests utilizing noninvasive prenatal testing (NIPT), chorionic villus sampling (CVS) and amniotic fluid samples from the same pregnancy revealed temporal evidence of correction and a “hotspot” at 1p. Although in many cases the genomic imbalance was dosage “repaired” in the analyzed tissue, clinical effects could be sustained due to early developmental effects of the original imbalance or due to its continued existence in other tissues. In addition, if correction did not occur in the gametes there would be recurrence risks for the offspring of those individuals. Familial microarray allele patterns are presented that differentiate lack of gamete correction from somatic derived gonadal mosaicism. These results suggest that the incidence of segUPD mediated correction is underestimated and may explain the etiology of some clinical phenotypes which are undetected by routine microarray analysis and many exome sequencing studies.
Statistical analysis plan for a pragmatic phase III randomised controlled trial examining behaviour change physiotherapy intervention to increase physical activity following hip and knee replacements: the PEP-TALK trial
Authors: Ooms Alexander , Dutton Susan J. , Parsons Scott , Fordham Beth , Hing Caroline , Lamb Sarah , Smith Toby
Published: July 2021

Background

Total hip (THR) and total knee replacements (TKR) are two highly successful orthopaedic procedures that reduce pain for people with osteoarthritis. Previous evidence suggests that physical activity, at best, remains the same pre- to post-operatively, and in some instances declines. The PEP-TALK trial evaluates the effects of a group-based, behaviour change intervention on physical activity following a THR or TKR.

Methods

PEP-TALK is an open, phase III, pragmatic, multi-centre, parallel, two-arm, two-way superiority randomised controlled trial investigating the effectiveness of usual care plus a behaviour change therapy compared with usual care alone following primary THR or TKR. The primary outcome is the UCLA Activity Score at 12 months post-randomisation which will be analysed using a linear mixed effects model. Secondary outcomes measured at 6 months and 12 months after randomisation include the UCLA Activity Score, Lower Extremity Functional Scale, Oxford Hip/Knee Score, Numerical Rating Scale for Pain, Generalised Self-Efficacy Scale, Tampa Scale for Kinesiophobia, Hospital Anxiety and Depression Scale, EuroQoL EQ-5D-5L index and EQ-VAS and complications or adverse events. Full details of the planned analysis approaches for the primary and secondary outcomes, as well as the planned sensitivity analyses to be undertaken due to the COVID-19 pandemic, are described here. The PEP-TALK study protocol has been published previously.

Discussion

This paper provides details of the planned statistical analyses for the PEP-TALK trial. This is aimed to reduce the risk of outcome reporting bias and enhance transparency in reporting.

Trial registration

International Standard Randomised Controlled Trials database, ISRCTN Number: 29770908. Registered on October 2018.