bluuebunny/crossref_metadata_2025 huggingface dataset:
Long noncoding RNA MALAT1 polymorphism predicts MACCEs in patients with myocardial infarction
Authors: Zhang Tong , Luo Jun-Yi , Liu Fen , Zhang Xue-He , Luo Fan , Yang Yi-Ning , Li Xiao-Mei
Published: April 2022

Background

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) participates in the occurrence and development of cardiovascular and cerebrovascular diseases such as stroke and coronary heart disease by regulating inflammatory reactions, programmed cell death, and other pathological processes. Previous studies revealed that theMALAT1gene polymorphism was associated with cardiac and cerebrovascular diseases. However, the prognostic role of theMALAT1polymorphism in major adverse cardiac and cerebrovascular events (MACCEs) remains unknown. Therefore, this study intends to explore the association between theMALAT1rs3200401 polymorphism and MACCEs.

Method

We enrolled 617 myocardial infarction (MI) patients and 1125 control participants who attended the First Affiliated Hospital of Xinjiang Medical University from January 2010 to 2018. SNPscan™ typing assays were used to detect theMALAT1rs3200401 genotype. During the follow-up, MACCEs were recorded. Kaplan–Meier curves and univariate and multivariate Cox survival analyses were used to explore the correlation betweenMALAT1gene polymorphisms and the occurrence of MACCEs.

Results

Among the total participants and MI patients, the frequencies of the T allele (total Participants 19.5% vs. 15.3%,P = 0.047, MI patients 20.7% vs. 14.1%,P = 0.014) and CT + TT genotypes (total Participants 37.4% vs. 28.1%,P = 0.013, MI patients 39.5% vs. 25.8%,P = 0.003) were significantly higher in subjects with MACCEs than in subjects without MACCEs. However, in control participants, the frequencies of the T allele (16.6% vs. 16.0%,P = 0.860) and CT + TT genotypes (31.4% vs. 29.3%,P = 0.760) were not higher in subjects with MACCEs than in subjects without MACCEs. In addition, among the total participants and MI patients, the Kaplan–Meier curve analysis indicated that the subjects with rs3200401 CT + TT genotypes had a higher incidence of MACCEs than CC genotype carriers (P = 0.015,P = 0.001). Nevertheless, similar results were not observed in the control participants (P = 0.790). Multivariate Cox regression indicated that compared with patients with the CC genotype, patients with CT + TT genotypes had a 1.554-fold increase in MACCE risk (hazard ratio: 1.554, 95% confidence interval: 1.060–2.277,P = 0.024).

Conclusions

TheMALAT1rs3200401 CT + TT genotypes could be a risk factor for MACCEs in MI patients, suggesting that theMALAT1gene may become a biomarker for poor prognosis in MI patients.
De Winter electrocardiogram pattern due to type A aortic dissection: a case report
Authors: Zhang Qing , Yang Dong-dong , Xu Yi-fei , Qiu Yuan-gang , Zhang Zhuo-yi
Published: April 2022

Background

De Winter electrocardiograph (ECG) pattern is an atypical presentation of acute myocardial infarction (AMI) due to severe stenosis of the left anterior descending (LAD). Complications of acute aortic dissection (AD) in the setting of acute myocardial infarction (AMI) with de Winter sign are relatively rare and physicians may easily miss the diagnosis of AD. We report a case of patient with acute chest pain and de Winter ECG pattern due to AD involving the left main coronary artery (LM), LAD and left circumflex artery (LCX).

Case presentation

A 57-year-old male patient was initially diagnosed with AMI and then the diagnosis of acute AD was supported by transthoracic echocardiograph (TTE). After two stents were implanted respectively into the proximal LM-LAD and LM-LCX, he recovered from cardiogenic shock. Two months later, the patient underwent the surgery of ascending aorta replacement. After the surgery, there was no obvious chest discomfort during follow-up.

Conclusions

When an ECG shows a “de Winter pattern”, we should also consider the possibility of AD which result in LAD occlusion. TTE is a useful tool in screening for AD. Further research is needed to prove that percutaneous coronary intervention (PCI) may be a useful treatment strategy in the case of AD leading to severe LAD occlusion and unstable hemodynamics when there’s no condition to perform aortic replacement surgery immediately.
Treatment resistant M-type phospholipase A2 receptor associated membranous nephropathy responds to obinutuzumab: a report of two cases
Authors: Hudson Rebecca , Rawlings Cassandra , Mon Saw Yu , Jefferis Julia , John George T.
Published: April 2022

Background

Membranous Nephropathy (MN) is a common cause of nephrotic syndrome (NS) in adults. Recognition of MN as an antibody mediated autoimmune disease has enabled the introduction of anti-B-cell therapy. Rituximab, a type I anti-CD20 antibody has been used in the management of MN, but has a 35-45% failure rate. Obinutuzumab, a fully humanised type II anti-CD20 monoclonal antibody produces greater CD20 depletion and is superior to rituximab in the treatment of certain B-cell malignancies. In the two reports published to date involving nine patients with M-type phospholipase A2 receptor (PLA2R) associated MN (six of whom were rituximab resistant), treatment with obinutuzumab lead to immunological remission (IR) in 75% of patients, with improvement of proteinuria, normalisation of serum albumin and stable renal function in all patients.

Case presentation

We report on two cases of PLA2R-associated MN, two males aged 33 and 36-years, who presented with NS and bilateral sub massive pulmonary emboli requiring anticoagulation. Both were diagnosed serologically as PLA2R-associated MN where a renal biopsy was initially deferred due to bleeding risk on anticoagulation, but later confirmed. Both patients were refractory to multiple lines of therapy including rituximab, but achieved IR, normalistation of serum albumin, improved proteinuria and stable renal function with obinutuzumab.

Conclusions

Our cases add to the current limited literature on the successful use of obinutuzumab in PLA2R associated MN refractory to standard therapy including rituximab.
Pregnancy and obstetric outcomes of dichorionic and trichorionic triamniotic triplet pregnancy with multifetal pregnancy reduction: a retrospective analysis study
Authors: Liu Shuhua , Li Guanjian , Wang Chao , Zhou Ping , Wei Zhaolian , Song Bing
Published: April 2022

Background

It is generally beneficial for triplet gestation or high-order multiple pregnancies to operate multifetal pregnancy reduction (MFPR) after assisted reproductive techniques. However, data on pregnancy outcomes is lacking regarding dichorionic triamniotic (DCTA) and trichorionic triplets (TCTA) pregnancy.

Method

This research analyzes the difference between 128 DCTA and 179 TCTA pregnancies with or without MFPR after in vitro fertilization/intracytoplasmic sperm injection cycles between January 2015 and June 2020. The subdivided subgroups of the two groups are reduction to singleton, reduction to dichorionic twins, and expectant management groups. We also compare the pregnancy and obstetric outcomes between 2104 dichorionic twins and 122 monochorionic twins.

Result

The research subgroups were DCTA to monochorionic singleton pregnancies (n = 76), DCTA to dichorionic twin pregnancies (n = 18), DCTA-expectant management (n = 34), TCTA to monochorionic singleton pregnancies (n = 31), TCTA to dichorionic twin pregnancies (n = 130), and TCTA-expectant management (n = 18). In DCTA-expectant management group, the complete miscarriage rate is dramatically higher, and the survival rate and the rate of take-home babies are lower. However, there was no difference between the rates of complete miscarriages, survival rates, and take-home babies in TCTA-expectant management group. But the complete miscarriage rate of DCTA-expectant management was obviously higher than that of TCTA-expectant management group (29.41 vs. 5.56%, p = 0.044). For obstetric outcomes, MFPR to singleton group had higher gestational week and average birth weight, but lower premature delivery, gestational hypertension rates and low birth weight in both DCTA and TCTA pregnancy groups (all p < 0.05). DCTA to monochorionic singleton had the lowest incidence of gestational diabetes, whereas The subdivided subgroups of TCTA had no significant difference in the incidence of gestational diabetes. Monochorionic twins have higher rates of complete, early, and late miscarriage, premature delivery, and late premature delivery, and lower survival rate (p < 0.05).

Conclusion

MFPR could improve gestational week and average birth weight, reducing premature delivery, LBW, and gestational hypertension rates in DCTA and TCTA pregnancies. Monochorionic twins have worse pregnancy and obstetric outcomes. MFPR to singleton is preferable recommended in the pregnancy and obstetric management of complex triplets with monochorionic pair.
Characteristics of the gut microbiota in pregnant women with fetal growth restriction
Authors: Tu Xinzhi , Duan Chun , Lin Bingying , Li Kangfeng , Gao Jie , Yan Huaying , Wang Kejian , Zhao Zhao
Published: April 2022

Background

Fetal growth restriction (FGR) in utero leads to failure of fetus to reach the genetically normal growth potential. Currently available means of treating FGR are limited. And it remains unknown how pregnant women who give birth to FGR fetus differ in gut microbiota composition from normal pregnant women.

Methods

In this case-control study, fecal samples were obtained from maternal rectum in the operation room by an obstetrician under strict aseptic conditions. We compared gut microbiota of 14 pregnant women with FGR and 18 normal controls by performing 16S rDNA amplicon sequencing.

Results

We identified significant differences in β-diversity between the FGR and control groups (P < 0.05). At genus level,Bacteroides,FaecalibacteriumandLachnospirawere highly abundant in the FGR subjects, which are significantly enriched in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to glycometabolism.

Conclusion

These findings demonstrated that the distinct composition of the gut microbiota between FGR and normal pregnant women could contribute to an improved understanding of the prevention and treatment of FGR.
Is wearing a face mask associated with symptomatic dry eye disease among medical students during the COVID-19 era? An online survey
Authors: Al-dolat Wedad , Abu-Ismail Luai , Khamees Almu’atasim , Alqudah Noor , Abukawan Mohammed M. , Alrawashdeh Hamzeh Mohammad , Al Momani Waleed , Kheirallah Khaled A.
Published: April 2022

Background

Coronavirus disease 2019 has necessitate the routine use of masks worldwide. This study assessed the relationship between wearing a facemask and dry eye disease (DED) among a sample of medical students in Jordan.

Methods

This cross-sectional online survey enrolled medical students from all medical schools in Jordan. The questionnaire, which was shared via social media platforms, assessed sociodemographic information, ocular and medical history, facemask-wearing habits, the use of ocular devices, and the relationship with ocular discomfort. The ocular surface disease index (OSDI) questionnaire was also administered to quantify DED symptoms.

Results

A total of 1,219 students participated in this study. In total, 58.3% participants were females, and 52% were in the clinical science years. Symptomatic DED was found in 71.7% of participants. Female sex, basic science years, allergy reporting, and spending more than 6 h looking at screens were significantly associated with symptomatic DED.

Conclusion

Wearing a facemask was not significantly associated with symptomatic DED. Further studies are needed to investigate the effect of wearing a facemask on the ocular surface.
Clinical and genetic findings in two siblings with X-Linked agammaglobulinemia and bronchiolitis obliterans: a case report
Authors: Francisco Junior Ronaldo da Silva , de Morais Guilherme Loss , de Carvalho Joseane Biso , dos Santos Ferreira Cristina , Gerber Alexandra Lehmkuhl , de C Guimarães Ana Paula , Amendola Flávia Anisio , Pinto-Mariz Fernanda , de Vasconcelos Zilton Farias Meira , Goudouris Ekaterini Simões , de Vasconcelos Ana Tereza Ribeiro
Published: April 2022

Background

X-linked agammaglobulinemia (XLA) is an Inborn Errors of Immunity (IEI) characterized by pan-hypogammaglobulinemia and low numbers of B lymphocytes due to mutations inBTKgene. Usually, XLA patients are not susceptible to respiratory tract infections by viruses and do not present interstitial lung disease (ILD) such as bronchiolitis obliterans (BO) as a consequence of acute or chronic bacterial infections of the respiratory tract. Although many pathogenic variants have already been described in XLA, the heterogeneous clinical presentations in affected patients suggest a more complex genetic landscape underlying this disorder.

Case presentation

We report two pediatric cases from male siblings with X-Linked Agammaglobulinemia and bronchiolitis obliterans, a phenotype not often observed in XLA phenotype. The whole-exome sequencing (WES) analysis showed a rare hemizygous missense variant NM_000061.2(BTK):c.1751G>A(p.Gly584Glu) in BTKgene of both patients. We also identified a gain-of-function mutation inTGFβ1(rs1800471) previously associated with transforming growth factor-beta1 production, fibrotic lung disease, and graft fibrosis after lung transplantation. TGFβ1 plays a key role in the regulation of immune processes and inflammatory response associated with pulmonary impairment.

Conclusions

Our report illustrates a possible role for WES in patients with known inborn errors of immunity, but uncommon clinical presentations, providing a personalized understanding of genetic basis, with possible implications in the identification of potential treatments, and prognosis for patients and their families.
The power of women’s and men’s Social Networks to catalyse normative and behavioural change: evaluation of an intervention addressing Unmet need for Family Planning in Benin
Authors: Kim Theresa Y. , Igras Susan , Barker Kathryn M. , Diakité Mariam , Lundgren Rebecka I.
Published: April 2022

Background

In Benin, despite good knowledge and availability, modern contraceptive prevalence remains relatively low, and the unmet need for family planning is relatively high. This is partly due to insufficient attention to socio-normative barriers that influence need and method use. Applying social network theory, Tékponon Jikuagou (TJ) aims to reduce socio-normative barriers preventing modern contraceptive use in rural Benin. After community identification, TJ trains influential network actors who encourage critical dialogue about unmet need, family planning, gender, and other social norms within their networks, complemented by radio and services linkages. This paper evaluates TJ's effectiveness and how intervention components affect intermediate and primary FP outcomes.

Methods

We report findings from pre/post-intervention cross-sectional research with a comparison group conducted at baseline with 1,043 women and 1,030 men, and 14 months later at endline with 1,046 women and 1,045 men. Using sex-stratified models, we assessed balance across intervention and comparison groups on background characteristics using Pearson's chi-square tests of independence; performed bivariate tests of independence to assess differences between baseline to endline on intermediate outcomes and primary FP outcomes; used logistic regression to examine the effect of intervention components on intermediate and primary FP outcomes.

Results

Statistically significant improvements in primary outcomes: women's intentions to use modern contraception, achieve met need, and reduce perceived met need. The fourth primary outcome, actual use, showed substantial gains, although not statistically significant. Men's achievement of met FP need and reduced perceived met need were also statistically significant. Assessing intermediate outcomes at individual, couple, normative-network levels, TJ led to statistically significant increases in couple and network communication on fertility desires and family planning use and self-efficacy and confidence to access services. Both women and men showed significant shifts in the acceptability of discussing FP in public. Results for other indicators of norms change were inconsistent.

Conclusions

An easy-to-implement, short-duration, gender-equitable social network intervention with a limited set of network actors, TJ effectively decreases social and normative barriers preventing women and men from seeking and using FP services. Results support the broader use of innovative social and behaviour change strategies that diffuse family planning ideas through social networks, diminish normative and communication barriers, and catalyse modern family planning use.
Dietary branched-chain amino acids and odds of obesity among immigrant Filipino women: the Filipino women’s diet and health study (FiLWHEL)
Authors: Okekunle Akinkunmi Paul , Lee Heejin , Provido Sherlyn Mae P. , Chung Grace H. , Hong Sangmo , Yu Sung Hoon , Lee Chang Beom , Lee Jung Eun
Published: April 2022

Background

The dietary environment promoting adiposity keeps evolving and of interest is the significance of dietary branched-chain amino acids (BCAA). This study assessed the association between dietary BCAA intakes and odds of obesity among immigrant Filipino women in Korea.

Method

We included 423 immigrant Filipino women enrolled in the Filipino Women’s diet and health study in the Republic of Korea. Dietary BCAA intakes were estimated from 24 hour recalls and adjusted for energy intake using the residual method. General obesity was derived from direct anthropometric measurements (height, weight and waist circumference – WC) and defined as body mass index (BMI) ≥25 kg/m2 and abdominal obesity as WC ≥80 cm. Odds ratios (OR) and 95% confidence intervals (CI) by tertile distribution of energy-adjusted BCAA intakes were estimated using multivariable logistic regression with a two-sided P < 0.05.

Results

Median (interquartile range) for BCAA intakes in g/day were; 7.9 (5.8, 10.3) g/day for total BCAA; 2.0 (1.5, 2.6) g/day for isoleucine, 3.5(2.5, 4.6) g/day for leucine and 2.4 (1.8, 3.1) g/day for valine. Mean BMI and WC were 23.6 ± 3.8 kg/m2 and 79.8 ± 9.3 cm, respectively. Also, 30.2% (128) had BMI ≥25 kg/m2 and 42.0% (178) had WC ≥80 cm. ORs (95%CIs) of general obesity across tertile distribution of energy-adjusted total BCAA intakes were 1.00, 0.81 (0.47, 1.37) and 0.62 (0.36, 1.07; P for trend = 0.08). A similar trend was observed across tertile distribution of energy-adjusted isoleucine, leucine and valine intakes. However, there was a statistically significant inverse association between total BCAA intake and odds of general obesity in a subset of non-smokers; 1.00, 0.68 (0.39, 1.20) and 0.55 (0.31, 0.98; P for trend = 0.04).

Conclusion

We found a suggestive inverse association between higher dietary BCAA intake and odds of obesity in this sample of immigrant Filipino women, particularly among non-smokers. Prospective cohort studies among the immigrant population will be necessary to verity these findings.
Excellent PROM results after fast-track hip and knee arthroplasty with no postoperative restrictions: a cohort study validation of fast-track surgery without postoperative restrictions
Authors: Paulsen Aksel , Djuv Ane , Ludvigsen Jarle , Dalen Ingvild
Published: April 2022

Background

Fast-track hip and knee arthroplasty (HA and KA) has been increasingly common over the last decade. In the same time period, there was a strong trend toward less restrictive mobilization. However, few reports have been published on combining these novel programs while measuring the postoperative results by patient-reported outcome measures (PROMs). Descriptions of fast-track surgery programs and their results are warranted.

Methods

The aim of this retrospective cohort study was to examine if it is possible to achieve excellent PROM results for hip and knee arthroplasty patients in a fast-track pathway without postoperative restrictions. During 2014–2017, the stepwise introduction of a PROM program was implemented at Stavanger University Hospital for all scheduled HA and KA patients, with preoperative assessments and postoperative follow-ups at the outpatient clinic. Standardized information with a focus on early mobilization and no postoperative restrictions was also initiated for the same patients. The generic EuroQol questionnaire (EQ-5D) and either the Hip or Knee disability/injury and Osteoarthritis Outcome Score (HOOS or KOOS) were used.

Results

PROM response rates varied from 80 to 99%. The median (interquartile range) change from preoperative to one-year postoperative results were as follows for HA and KA patients, respectively: pain, 55 (43–68) and 47 (31–61); other symptoms, 50 (40–65) and 36 (19–50); function in daily living, 54 (41–65) and 44 (31–55); function in sports and recreation, 56 (38–75) and 40 (15–64); joint-related quality of life, 69 (50–81) and 56 (38–75). The length of stay (LOS) was reduced by 1.9 days (mean), corresponding to a 40% reduction for HA patients and a 37% reduction for KA patients.

Conclusions

We found excellent PROM results after fast-track HA and KA with no postoperative restrictions. We believe that a fast-track program focusing on mobilization without any postoperative restrictions is superior for most patients, but further comparative studies are warranted.
Learning the ropes: strategies program directors use to facilitate organizational socialization of newcomer residents, a qualitative study
Authors: Galema Gerbrich , Duvivier Robbert , Pols Jan , Jaarsma Debbie , Wietasch Götz
Published: April 2022

Background

Many residents experience their transitions, such as from medical student to resident, as demanding and stressful. The challenges they face are twofold: coping with changes in tasks or responsibilities and performing (new) social roles. This process of ‘learning the ropes’ is known as Organizational Socialization (OS). Although there is substantial literature on transitions from the perspective of residents, the voices of program directors (PDs) who facilitate and guide residents through the organizational socialization process have not yet been explored. PDs’ perspectives are important, since PDs are formally responsible for Postgraduate Medical Education (PGME) and contribute, directly or indirectly, to residents’ socialization process. Using the lens of OS, we explored what strategies PDs use to facilitate organizational socialization of newcomer residents.

Methods

We conducted semi-structured interviews with 17 PDs of different specialties. We used a theory-informing inductive data analysis study design, comprising an inductive thematic analysis, a deductive interpretation of the results through the lens of OS and, subsequently, an inductive analysis to identify overarching insights.

Results

We identified six strategies PDs used to facilitate organizational socialization of newcomer residents and uncovered two overarching insights. First, PDs varied in the extent to which they planned their guidance. Some PDs planned socialization as an explicit learning objective and assigned residents’ tasks and responsibilities accordingly, making it an intended program outcome. However, socialization was also facilitated by social interactions in the workplace, making it an unintended program outcome. Second, PDs varied in the extent to which they adapted their strategies to the newcomer residents. Some PDs used individualized strategies tailored to individual residents’ needs and skills, particularly in cases of poor performance, by broaching and discussing the issue or adjusting tasks and responsibilities. However, PDs also used workplace strategies requiring residents to adjust to the workplace without much intervention, which was often viewed as an implicit expectation.

Conclusions

PDs’ used both intentional and unintentional strategies to facilitate socialization in residents, which may imply that socialization can occur irrespective of the PD’s strategy. PDs’ strategies varied from an individual-centered to a workplace-centered approach to socialization. Further research is needed to gain a deeper understanding of residents’ perceptions of PD’s efforts to facilitate their socialization process during transitions.
When BERT meets Bilbo: a learning curve analysis of pretrained language model on disease classification
Authors: Li Xuedong , Yuan Walter , Peng Dezhong , Mei Qiaozhu , Wang Yue
Published: April 2022

Background

Natural language processing (NLP) tasks in the health domain often deal with limited amount of labeled data due to high annotation costs and naturally rare observations. To compensate for the lack of training data, health NLP researchers often have to leverage knowledge and resources external to a task at hand. Recently, pretrained large-scale language models such as the Bidirectional Encoder Representations from Transformers (BERT) have been proven to be a powerful way of learning rich linguistic knowledge from massive unlabeled text and transferring that knowledge to downstream tasks. However, previous downstream tasks often used training data at such a large scale that is unlikely to obtain in the health domain. In this work, we aim to study whether BERT can still benefit downstream tasks when training data are relatively small in the context of health NLP.

Method

We conducted a learning curve analysis to study the behavior of BERT and baseline models as training data size increases. We observed the classification performance of these models on two disease diagnosis data sets, where some diseases are naturally rare and have very limited observations (fewer than 2 out of 10,000). The baselines included commonly used text classification models such as sparse and dense bag-of-words models, long short-term memory networks, and their variants that leveraged external knowledge. To obtain learning curves, we incremented the amount of training examples per disease from small to large, and measured the classification performance in macro-averaged$$F_{1}$$F1score.

Results

On the task of classifying all diseases, the learning curves of BERT were consistently above all baselines, significantly outperforming them across the spectrum of training data sizes. But under extreme situations where only one or two training documents per disease were available, BERT was outperformed by linear classifiers with carefully engineered bag-of-words features.

Conclusion

As long as the amount of training documents is not extremely few, fine-tuning a pretrained BERT model is a highly effective approach to health NLP tasks like disease classification. However, in extreme cases where each class has only one or two training documents and no more will be available, simple linear models using bag-of-words features shall be considered.
Patient and family involvement in Choosing Wisely initiatives: a mixed methods study
Authors: de Grood Chloe , Sypes Emma E. , Niven Daniel J. , Clement Fiona , FitzGerald Emily A. , Kupsch Shelly , King-Hunter Shelly , Stelfox Henry T. , Parsons Leigh Jeanna
Published: April 2022

Background

Patients are important stakeholders in reducing low-value care, yet mechanisms for optimizing their involvement in low-value care remain unclear. To explore the role of patients in the development and implementation of Choosing Wisely recommendations to reduce low-value care and to assess the likelihood that existing patient resources will change patient health behaviour.

Methods

Three phased mixed-methods study: 1) content analysis of all publicly available Choosing Wisely clinician lists and patient resources from the United States of America and Canada. Quantitative data was summarized with frequencies and free text comments were analyzed with qualitative thematic content analysis; 2) semi-structured telephone interviews with a purposive sample of representatives of professional societies who created Choosing Wisely clinician lists and members of the public (including patients and family members). Interviews were transcribed verbatim, and two researchers conducted qualitative template analysis; 3) evaluation of Choosing Wisely patient resources. Two public partners were identified through the Calgary Critical Care Research Network and independently answered two free text questions “would this change your health behaviour” and “would you discuss this material with a healthcare provider”. Free text data was analyzed by two researchers using thematic content analysis.

Results

From the content analysis of 136 Choosing Wisely clinician lists, six reported patient involvement in their development. From 148 patient resource documents that were mapped onto a conceptual framework (Inform, Activate, Collaborate) 64% described patient engagement at the level of Inform (educating patients). From 19 interviews stakeholder perceptions of patient involvement in reducing low-value care were captured by four themes: 1) impact of perceived power dynamics on the discussion of low-value care in the clinical interaction, 2) how to communicate about low-value care, 3) perceived barriers to patient involvement in reducing low-value care, and 4) suggested strategies to engage patients and families in Choosing Wisely initiatives. In the final phase of work in response to the question “would this change your health behaviour” two patient partners agreed ‘yes’ on 27% of patient resources.

Conclusions

Opportunities exist to increase patient and family participation in initiatives to reduce low-value care.
SNAP25 is a potential prognostic biomarker for prostate cancer
Authors: Di Longjiang , Gu Maoli , Wu Yan , Liu Guoqiang , Zhang Lishuo , Li Yifei , Zhang Wenjing
Published: April 2022

Background

Prostate cancer (PCa) is one of the most lethal cancers in male individuals. The synaptosome associated protein 25 (SNAP25) gene is a key mediator of multiple biological functions in tumors. However, its significant impact on the prognosis in PCa remains to be elucidated.

Methods

We performed a comprehensive analysis of the Cancer Genome Atlas dataset (TCGA) to identify the differentially expressed genes between PCa and normal prostate tissue. We subjected the differentially expressed genes to gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes functional analysis, and constructed a protein–protein interaction network. We then screened for pivotal genes to identify the hub genes of prognostic significance by performing Cox regression analysis. We identified SNAP25 as one such gene and analyzed the relationship between its expression in PCa to poor prognosis using GEPIA interactive web server.

Results

TCGA database demonstrated that SNAP25 was significantly downregulated in PCa. The progressive decrease in SNAP25 expression with the increase in the clinical staging and grading of PCa demonstrates that reduced SNAP25 expression considerably exacerbates the clinical presentation. Our findings confirm that SNAP25 expression strongly correlates with overall survival, which was determined using the Gleason score. We also validated the role of SNAP25 expression in the prognosis of patients with PCa. We used Gene Set Enrichment and Gene Ontology analyses to evaluate the function of SNAP25 and further explored the association between SNAP25 expression and tumor-infiltrating immune cells using the Tumor Immune Assessment Resource database. We found for the first time that SNAP25 is involved in the activation, differentiation, and migration of immune cells in PCa. Its expression was positively correlated with immune cell infiltration, including B cells, CD8+ T cells, CD4+ T cells, neutrophils, dendritic cells, macrophages, and natural killer cells. SNAP25 expression also positively correlated with chemokines/chemokine receptors, suggesting that SNAP25 may regulate the migration of immune cells. In addition, our experimental results verified the low expression of SNAP25 in PCa cells.

Conclusion

Our findings indicate a relationship between SNAP25 expression and PCa, demonstrating that SNAP25 is a potential prognostic biomarker due to its vital role in immune infiltration.
Cement leakage in percutaneous vertebroplasty for spinal metastases: a retrospective study of risk factors and clinical outcomes
Authors: Wang Lin , Zhang Chao , Liang Hao , Huang Tianji , Zhong Weiyang , Zhao Zenghui , Luo Xiaoji
Published: April 2022

Objective

The objective of this research was to investigate the risk factors of cement leakage in patients with metastatic spine tumors following percutaneous vertebroplasty (PVP).

Methods

Sixty-four patients with 113 vertebrae were retrospectively reviewed. Various clinical indexes, including age, sex, body mass index (BMI), smoking history, drinking history, chemotherapy history, radiotherapy history, primary cancer, location, other metastases, collapse, posterior wall defects, the laterality of injection, and the injected cement volume were analyzed as potential risk factors. Multivariate analyses were conducted to identify the independent risk factors.

Results

The cement leakage was found 64 in 113 treated vertebrae (56.63%), in which the incidence of each type was shown as below: spinal canal leakage 18 (15.93%), intravascular leakage around the vertebrae 11 (9.73%), and intradiscal and paravertebral leakage 35 (30.97%). Tomita classification (P = 0.019) and posterior wall destruction (P = 0.001) were considered strong risk factors for predicting cement leakage in general. The multivariate logistic analysis showed that defects of the posterior wall (P = 0.001) and injected volume (P = 0.038) were independently related to the presence of spinal canal leakage. The postoperative visual analog scale (VAS) and activities of daily living (ADL) scores showed significant differences compared with the pre-operative parameters (P < 0.05). No significant differences were found in every follow-up time between the leakage group and the non-leakage group for pain management and improvement of activities in daily life.

Conclusion

In our study, Tomita classification and the destruction of the posterior wall were independent risk factors for leakage in general. The defects of the posterior wall and injected volume were independently related to the presence of spinal canal leakage. The PVP procedure can be an effective way to manage the pain.
Robotic-assisted thoracoscopic resection of anterior mediastinal cystic teratoma: a case report and literature review
Authors: Ramcharran Harry , Wallen Jason
Published: April 2022

Background

Mediastinal teratomas are rare tumors that frequently occur in the anterior mediastinum. The majority of these tumors are benign and slow growing. Due to their low malignant potential, the treatment for these tumors is surgical resection. More recently, the surgical management has shifted from invasive approaches such as a sternotomy to minimally invasive ones such as robotic-assisted thoracoscopic resections utilizing lung isolation ventilation. We present a rare case of a locally advanced mediastinal teratoma requiring resection, which was initially attempted thoracoscopically using double lung ventilation.

Case presentation

A 43 year-old female was found to have an anterior mediastinal mass during work-up for an intermittent cough in 2009. Chest imaging and biopsy at the time showed evidence of a cystic teratoma without concerning features. She underwent imaging surveillance until 2018, when repeat chest imaging showed increasing growth and worrisome radiologic features concerning for malignant degeneration. She underwent an elective robotic-assisted thoracoscopic resection utilizing double lung ventilation, but due to extensive involvement of the right lung, pericardium, superior vena cava, and right phrenic nerve the patient had to be repositioned and started on single lung ventilation mid-procedure to facilitate a safe and complete resection.

Conclusions

Anterior mediastinal teratomas can be successfully removed by robotic-assisted thoracoscopic resections utilizing single lung ventilation. Though robotic-assisted thoracoscopic resection utilizing double lung ventilation can be effective in performing certain procedures such as lung wedge resections, thymectomy, pleural biopsies and minimally invasive cardiac procedures, it is limited in removing locally advanced mediastinal tumors.
Assessing the value of orphan drugs using conventional cost-effectiveness analysis: Is it fit for purpose?
Authors: Postma Maarten J. , Noone Declan , Rozenbaum Mark H. , Carter John A. , Botteman Marc F. , Fenwick Elisabeth , Garrison Louis P.
Published: April 2022

Conventional cost-effectiveness analysis—i.e., assessing pharmaceuticals through a cost per quality-adjusted life year (QALY) framework—originated from a societal commitment to maximize population health given limited resources. This "extra-welfarist" approach has produced pricing and reimbursement systems that are not well- aligned with the unique considerations of orphan drugs. This framework has been slow to evolve along with our increased understanding of the impact of rare diseases, which in turn has complicated the assessment of orphan drugs meant to treat rare diseases. Herein, we (i) discuss the limitations of conventional cost-effectiveness analysis as applied to assessing access to, as well as the pricing and reimbursement of, orphan drugs, (ii) critically appraise alternative and supplemental approaches, and (iii) offer insights on plausible steps forward.
Dose-finding studies in drug development for rare genetic diseases
Authors: Wang Lingshan , Wang Jie , Feng Ji , Doi Mary , Pepe Salvatore , Pacanowski Michael , Schuck Robert N.
Published: April 2022

Background

The small patient populations inherent to rare genetic diseases present many challenges to the traditional drug development paradigm. One major challenge is generating sufficient data in early phase studies to inform dose selection for later phase studies and dose optimization for clinical use of the drug. However, optimizing the benefit-risk profile of drugs through appropriate dose selection during drug development is critical for all drugs, including those being developed to treat rare diseases. Recognizing the challenges of conducting dose finding studies in rare disease populations and the importance of dose selection and optimization for successful drug development, we assessed the dose-finding studies and analyses conducted for drugs recently approved for rare genetic diseases.

Results

Of the 40 marketing applications for new molecular entity (NME) drugs and biologics approved by the United States Food and Drug Administration for rare genetic diseases from 2015 to 2020, 21 (53%) of the development programs conducted at least one dedicated dose-finding study. In addition, the majority of drug development programs conducted clinical studies in healthy subjects and included population pharmacokinetic and exposure–response analyses; some programs also conducted clinical studies in patient populations other than the disease for which the drug was initially approved. The majority of primary endpoints utilized in dedicated dose-finding studies were biomarkers, and the primary endpoint of the safety and efficacy study matched the primary endpoint used in the dose finding study in 9 of 13 (69%) drug development programs where primary study endpoints were assessed.

Conclusions

Our study showed that NME drug development programs for rare genetic diseases utilize multiple data sources for dosing information, including studies in healthy subjects, population pharmacokinetic analyses, and exposure–response analyses. In addition, our results indicate that biomarkers play a key role in dose-finding studies for rare genetic disease drug development programs. Our findings highlight the need to develop study designs and methods to allow adequate dose-finding efforts within rare disease drug development programs that help overcome the challenges presented by low patient prevalence and other factors. Furthermore, the frequent reliance on biomarkers as endpoints for dose-finding studies underscores the importance of biomarker development in rare diseases.
Tauopathies: new perspectives and challenges
Authors: Zhang Yi , Wu Kai-Min , Yang Liu , Dong Qiang , Yu Jin-Tai
Published: April 2022

Background

Tauopathies are a class of neurodegenerative disorders characterized by neuronal and/or glial tau-positive inclusions.

Main body

Clinically, tauopathies can present with a range of phenotypes that include cognitive/behavioral-disorders, movement disorders, language disorders and non-specific amnestic symptoms in advanced age. Pathologically, tauopathies can be classified based on the predominant tau isoforms that are present in the inclusion bodies (i.e., 3R, 4R or equal 3R:4R ratio). Imaging, cerebrospinal fluid (CSF) and blood-based tau biomarkers have the potential to be used as a routine diagnostic strategy and in the evaluation of patients with tauopathies. As tauopathies are strongly linked neuropathologically and genetically to tau protein abnormalities, there is a growing interest in pursuing of tau-directed therapeutics for the disorders. Here we synthesize emerging lessons on tauopathies from clinical, pathological, genetic, and experimental studies toward a unified concept of these disorders that may accelerate the therapeutics.

Conclusions

Since tauopathies are still untreatable diseases, efforts have been made to depict clinical and pathological characteristics, identify biomarkers, elucidate underlying pathogenesis to achieve early diagnosis and develop disease-modifying therapies.
DICE: Dual mTorc Inhibition in advanCed/recurrent Epithelial ovarian cancer resistant to standard treatment—a study protocol for a randomised trial investigating a novel therapy called TAK228
Authors: Fiorentino Francesca , Krell Jonathan , de la Rosa Consuelo Nohpal , Webber Lee
Published: April 2022

Background

The standard initial treatment for ovarian cancer is surgery and platinum-based chemotherapy and potentially maintenance therapy with avastin or inhibitors of poly-ADP ribose polymerase (PARP). While a proportion of women are cured by this approach, the vast majority will relapse and become resistant to platinum chemotherapy either initially or on subsequent treatment. There is an unmet need to improve response to treatment and quality of life in these women. TAK228 is a novel therapy that can be added to standard treatment in the participant population and the aim of the DICE trial is to assess its effectiveness. Laboratory and clinical research has shown that these ovarian cancers may respond to the molecular target of a drug such as TAK228, and there have been studies using it in other advanced solid tumours including endometrial cancer.

Methods

One hundred twenty-four eligible women will be recruited from participating research sites in the United Kingdom (UK) and Germany. Randomised participants will receive either weekly paclitaxel alone (standard treatment, n = 62) or TAK228 plus weekly paclitaxel (n = 62) until the cancer significantly worsens; there are significant adverse events or any other protocol-defined stopping criteria. Participants will be monitored for response to treatment (using radiological imaging), adverse events and quality of life during both randomised treatment and subsequent follow-up.

Discussion

The primary objective/endpoint of the study is to compare the two treatments in terms of progression-free survival, or the length of time that each participant is alive without the cancer significantly worsening according to defined assessment criteria. If the addition of TAK228 to weekly paclitaxel chemotherapy is shown to significantly improve this statistically, and adverse events and quality of life are not significantly worse than standard treatment, then TAK228 plus weekly paclitaxel could potentially be taken forward within the context of a larger phase III trial.

Trial registration

ClinicalTrials.govNCT03648489. Registered on 27 August 2018.
Turning walking pneumonia into recurrent abscesses: a curious case of CVID and review of the literature
Authors: Gao David X. , Hussain Habiba , Bobber Brianna , Phan Peter
Published: April 2022

Background

Common variable immunodeficiency (CVID) is a primary immunodeficiency disorder associated with a broad symptom presentation that is still being characterized. We report a rare case of recurrent mycoplasma skin abscesses in a patient with a history of autoimmune disorders and prolonged mycoplasma pneumonia who was diagnosed with CVID.

Case presentation

A 34-year-old woman presented with a history of recurrent abscesses previously confirmed positive for Mycoplasma pneumoniae. Her past medical history of recurrent mycoplasma abscesses, prolonged mycoplasma pneumonia, and autoimmune disorders (mixed connective tissue disease and immune thrombocytopenia) raised suspicion of CVID. Workup included negative anti-mycoplasma antibody titers, hypogammaglobulinemia, and negative anti-pneumococcal antibody titers despite prior vaccination, solidifying the diagnosis of CVID. The patient was discharged on antibiotic and intravenous immunoglobulin therapy and now follows allergy and immunology long-term for treatment.

Conclusions

Her diagnostic history underscores the importance of considering the various criteria of CVID for diagnosis, and her unique presentation of M. pneumoniae skin abscesses highlights the broad sequelae patients with CVID can manifest.
More than three times as many Indigenous Australian clients at risk from drinking could be supported if clinicians used AUDIT-C instead of unstructured assessments
Authors: Conigrave James H. , Lee K. S. Kylie , Haber Paul S. , Vnuk Julia , Doyle Michael F. , Conigrave Katherine M.
Published: April 2022

Background

Aboriginal and Torres Strait Islander (‘Indigenous’) Australians experience a greater burden of disease from alcohol consumption than non-Indigenous peoples. Brief interventions can help people reduce their consumption, but people drinking at risky levels must first be detected. Valid screening tools (e.g., AUDIT-C) can help clinicians identify at-risk individuals, but clinicians also make unstructured assessments. We aimed to determine how frequently clinicians make unstructured risk assessments and use AUDIT-C with Indigenous Australian clients. We also aimed to determine the accuracy of unstructured drinking risk assessments relative to AUDIT-C screening. Finally, we aimed to explore whether client demographics influence unstructured drinking risk assessments.

Methods

We performed cross-sectional analysis of a large clinical dataset provided by 22 Aboriginal Community Controlled Health Services in Australia. We examined instances where clients were screened with unstructured assessments and with AUDIT-C within the same two-monthly period. This aggregated data included 9884 observations. We compared the accuracy of unstructured risk assessments against AUDIT-C using multi-level sensitivity and specificity analysis. We used multi-level logistic regression to identify demographic factors that predict risk status in unstructured assessments while controlling for AUDIT-C score.

Results

The primary variables were AUDIT-C score and unstructured drinking risk assessment; demographic covariates were client age and gender, and service remoteness. Clinicians made unstructured drinking risk assessments more frequently than they used AUDIT-C (17.11% and 10.85% of clinical sessions respectively). Where both measures were recorded within the same two-month period, AUDIT-C classified more clients as at risk from alcohol consumption than unstructured assessments. When using unstructured assessments, clinicians only identified approximately one third of clients drinking at risky levels based on their AUDIT-C score (sensitivity = 33.59% [95% CI 22.03, 47.52], specificity = 99.35% [95% CI 98.74, 99.67]). Controlling for AUDIT-C results and demographics (gender and service remoteness), clinicians using unstructured drinking risk assessments were more likely to classify older clients as being at risk from alcohol consumption than younger clients.

Conclusions

Evidence-based screening tools like AUDIT-C can help clinicians ensure that Indigenous Australian clients (and their families and communities) who are at risk from alcohol consumption are better detected and supported.