bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chinese herbal medicine for functional dyspepsia: a network meta-analysis of prokinetic-controlled randomised trials
Authors: Ho Leonard , Zhong Claire C. W. , Wong Charlene H. L. , Wu Justin C. Y. , Chan Karina K. H. , Wu Irene X. Y. , Leung Ting Hung , Chung Vincent C. H. 
Published: December 2021

AbstractBackgroundProkinetic is the first-line conventional treatment for functional dyspepsia (FD) in Asia despite potential adverse events. Chinese herbal medicine (CHM) may be an effective and safe substitution. This network meta-analysis (NMA) aimed to evaluate the comparative effectiveness of different CHM formulae for FD against prokinetics.MethodsSeven international and Chinese databases were searched from their inception to July 2020 for randomised controlled trials (RCTs) on CHM versus prokinetics. Data from each RCT were first pooled using random-effect pairwise meta-analyses and illustrated as risk difference (RD) or standardised mean difference (SMD) with 95% confidence interval (CI). Random-effect NMAs were then performed to evaluate the comparative effectiveness of CHM formulae and displayed as RD with 95% CI or SMD with 95% credible interval (CrI). The GRADE partially contextualised framework was applied for NMA result interpretation.ResultsTwenty-six unique CHM formulae were identified from twenty-eight RCTs of mediocre quality. Pairwise meta-analyses indicated that CHM was superior to prokinetics in alleviating global symptoms at 4-week follow-up (pooled RD: 0.14; 95% CI: 0.10–0.19), even after trim and fill adjustment for publication bias. NMAs demonstrated that Modified Zhi Zhu Decoction may have a moderate beneficial effect on alleviating global symptoms at 4-week follow-up (RD: 0.28; 95% CI: − 0.03 to 0.75). Xiao Pi Kuan Wei Decoction may have a large beneficial effect on alleviating postprandial fullness (SMD: − 2.14; 95% CI: − 2.76 to 0.70), early satiety (SMD: − 3.90; 95% CI: − 0.68 to − 0.42), and epigastric pain (SMD: − 1.23; 95% CI: − 1.66 to − 0.29). No serious adverse events were reported.ConclusionModified Zhi Zhu Decoction and Xiao Pi Kuan Wei Decoction may be considered as an alternative for patients unresponsive to prokinetics. Confirmatory head-to-head trials should be conducted to investigate their comparative effectiveness against prokinetics.
A new approach to identifying patients with elevated risk for Fabry disease using a machine learning algorithm
Authors: Jefferies John L. , Spencer Alison K. , Lau Heather A. , Nelson Matthew W. , Giuliano Joseph D. , Zabinski Joseph W. , Boussios Costas , Curhan Gary , Gliklich Richard E. , Warnock David G. 
Published: December 2021

Abstract
Background
Fabry disease (FD) is a rare genetic disorder characterized by glycosphingolipid accumulation and progressive damage across multiple organ systems. Due to its heterogeneous presentation, the condition is likely significantly underdiagnosed. Several approaches, including provider education efforts and newborn screening, have attempted to address underdiagnosis of FD across the age spectrum, with limited success. Artificial intelligence (AI) methods present another option for improving diagnosis. These methods isolate common health history patterns among patients using longitudinal real-world data, and can be particularly useful when patients experience nonspecific, heterogeneous symptoms over time. In this study, the performance of an AI tool in identifying patients with FD was analyzed. The tool was calibrated using de-identified health record data from a large cohort of nearly 5000 FD patients, and extracted phenotypic patterns from these records. The tool then used this FD pattern information to make individual-level estimates of FD in a testing dataset. Patterns were reviewed and confirmed with medical experts.

Results
The AI tool demonstrated strong analytic performance in identifying FD patients. In out-of-sample testing, it achieved an area under the receiver operating characteristic curve (AUROC) of 0.82. Strong performance was maintained when testing on male-only and female-only cohorts, with AUROCs of 0.83 and 0.82 respectively. The tool identified small segments of the population with greatly increased prevalence of FD: in the 1% of the population identified by the tool as at highest risk, FD was 23.9 times more prevalent than in the population overall. The AI algorithm used hundreds of phenotypic signals to make predictions and included both familiar symptoms associated with FD (e.g. renal manifestations) as well as less well-studied characteristics.

Conclusions
The AI tool analyzed in this study performed very well in identifying Fabry disease patients using structured medical history data. Performance was maintained in all-male and all-female cohorts, and the phenotypic manifestations of FD highlighted by the tool were reviewed and confirmed by clinical experts in the condition. The platform’s analytic performance, transparency, and ability to generate predictions based on existing real-world health data may allow it to contribute to reducing persistent underdiagnosis of Fabry disease.
Clinical, humanistic, and economic burden of severe haemophilia B in adults receiving factor IX prophylaxis: findings from the CHESS II real-world burden of illness study in Europe
Authors: Burke Tom , Asghar Sohaib , O’Hara Jamie , Chuang Margaret , Sawyer Eileen K. , Li Nanxin 
Published: December 2021

Abstract
Background
Real-world studies of the burden of severe haemophilia B in the context of recent therapeutic advances such as extended half-life (EHL) factor IX (FIX) products are limited. We analysed data from the recent CHESS II study to better understand the clinical, humanistic, and economic burden of severe haemophilia B in Europe. Data from male adults with severe haemophilia B receiving prophylaxis were analysed from the retrospective cross-sectional CHESS II study conducted in Germany, France, Italy, Spain and the United Kingdom. Inhibitors were exclusionary. Patients and physicians completed questionnaires on bleeding, joint status, quality of life, and haemophilia-related direct and indirect costs (2019–2020). All outcomes were summarised using descriptive statistics.

Results
A total of 75 CHESS II patients were eligible and included; 40 patients (53%) provided self-reported outcomes. Mean age was 36.2 years. Approximately half the patients were receiving EHL versus standard half-life (SHL) prophylaxis (44% vs 56%). Most patients reported mild or moderate chronic pain (76%) and had ≥ 2 bleeding events per year (70%), with a mean annualised bleed rate of 2.4. Mean annual total haemophilia-related direct medical cost per patient was €235,723, driven by FIX costs (€232,328 overall, n = 40; €186,528 for SHL, €290,620 for EHL). Mean annual indirect costs (€8,973) were driven by early retirement or work stoppage due to haemophilia. Mean quality of life (EQ-5D) score was 0.67.

Conclusions
These data document a substantial, persistent real-world burden of severe haemophilia B in Europe. Unmet needs persist for these patients, their caregivers, and society.
TDP-43 Pathology in Alzheimer’s Disease
Authors: Meneses Axel , Koga Shunsuke , O’Leary Justin , Dickson Dennis W. , Bu Guojun , Zhao Na 
Published: December 2021

AbstractTransactive response DNA binding protein of 43 kDa (TDP-43) is an intranuclear protein encoded by the TARDBP gene that is involved in RNA splicing, trafficking, stabilization, and thus, the regulation of gene expression. Cytoplasmic inclusion bodies containing phosphorylated and truncated forms of TDP-43 are hallmarks of amyotrophic lateral sclerosis (ALS) and a subset of frontotemporal lobar degeneration (FTLD). Additionally, TDP-43 inclusions have been found in up to 57% of Alzheimer’s disease (AD) cases, most often in a limbic distribution, with or without hippocampal sclerosis. In some cases, TDP-43 deposits are also found in neurons with neurofibrillary tangles. AD patients with TDP-43 pathology have increased severity of cognitive impairment compared to those without TDP-43 pathology. Furthermore, the most common genetic risk factor for AD, apolipoprotein E4 (APOE4), is associated with increased frequency of TDP-43 pathology. These findings provide strong evidence that TDP-43 pathology is an integral part of multiple neurodegenerative conditions, including AD. Here, we review the biology and pathobiology of TDP-43 with a focus on its role in AD. We emphasize the need for studies on the mechanisms that lead to TDP-43 pathology, especially in the setting of age-related disorders such as AD.
Surgical treatment of post-traumatic luxation of rib heads with spinal cord compression in a cat
Authors: Sterna Jacek Cezary , Rogowska Laura , Degórska Beata , Sobczyński Jacek , Łumińska Monika 
Published: December 2021

Abstract
Background
Luxation of the rib head with intrusion into the intervertebral foramen seems to be rare in cats. Only one report has been published describing a cat with non-ambulatory paraparesis, which was managed conservatively. Here we report a case of rib head luxation that was managed surgically.

Case presentation
A 4-year-old, female domestic shorthair cat with a two-week history of non-ambulatory paraparesis was presented at our clinic. Based on history and neurological examination, a diagnosis of thoracolumbar spinal cord lesion of traumatic origin was made. Computed tomography scanning revealed mild scoliosis, a luxation of the 3rd and 4th right rib heads and penetration into the spinal canal through intervertbral foramina. Surgical management using right dorsal approach to the spine was performed. The spinal cord was decompressed by cutting and removing of proximal ribs’ fragments by rotation and pulling out from the intervertebral foramina. The cat was ambulatory and paraparetic four weeks after surgery. Two years after surgery the cat regained functional gait, but ataxia remained.

Conclusions
We report the first case of a surgical treatment of rib head luxation and intrusion into the spinal canal in a cat. The applied procedure resulted in an improvement of neurological signs.
Malaria vector control tools in emergency settings: What do experts think? Results from a DELPHI survey
Authors: Boëte Christophe , Burza Sakib , Lasry Estrella , Moriana Silvia , Robertson William 
Published: December 2021

Abstract
Background
The use and implementation of novel tools for malaria control such as long lasting impregnated bednets (LLINs) and Indoor Residual Spraying (IRS) over the last decade has contributed to a substantial reduction in malaria burden globally. However numerous challenges exist particularly in relation to vector control in emergency settings. This study seeks to explore expert opinion on the utility of existing tools within the emergency context setting and to better understand the attitude towards emerging and innovative tools (including Genetically Modified Mosquitoes) to augment current approaches.

Methods
80 experts in the field of malaria and vector control were invited to participate in a two-round Delphi survey. They were selected through a combination of literature (academic and policy publications) review and snowball sampling reflecting a range of relevant backgrounds including vector control experts, malaria programme managers and emergency response specialists. The survey was conducted online through a questionnaire including the possibility for free text entry, and concentrated on the following topics:

Utility and sustainability of current vector control tools, both in and outside emergency settings

Feasibility, utility and challenges of emerging vector control tools, both in and outside emergency settings

Current and unmet research priorities in malaria vector control and in malaria control in general.

Results
37 experts completed the first round and 31 completed the second round of the survey. There was a stronger consensus about the increased utility of LLIN compared to IRS in all settings, while insecticide-treated covers and blankets ranked very high only in emergency settings. When considering the combination of tools, the ones deemed most interesting always involved LLINs and IRS regardless of the setting, and the acceptability and the efficacy at reducing transmission are essential characteristics. Regarding perceptions of tools currently under development, consensus was towards improvement of existing tools rather than investing in novel approaches and the majority of respondents expressed distrust for genetic approaches.

Conclusion
Malaria vector control experts expressed more confidence for tools whose efficacy is backed up by epidemiological evidence, hence a preference for the improvement rather than the combination of existing tools. Moreover, while several novel tools are under development, the majority of innovative approaches did not receive support, particularly in emergency settings. Stakeholders involved in the development of novel tools should involve earlier and raise awareness of the potential effectiveness amongst a wider range of experts within the malaria community to increase acceptability and improve early adoption once the evidence base is established.
Shifting North American drug markets and challenges for the system of care
Authors: Krausz R. Michael , Westenberg Jean N. , Mathew Nickie , Budd George , Wong James S. H. , Tsang Vivian W. L. , Vogel Marc , King Conor , Seethapathy Vijay , Jang Kerry , Choi Fiona 
Published: December 2021

AbstractDrug markets are dynamic systems which change based on demand, competition, legislation and revenue. Shifts that are not met with immediate and appropriate responses from the healthcare system can lead to public health crises with tragic levels of morbidity and mortality, as experienced Europe in the early 1990s and as is the case in North America currently. The major feature of the current drug market shift in North America is towards highly potent synthetic opioids such as fentanyl and fentanyl analogues. An additional spike in stimulant use further complicates this issue. Without understanding the ever-changing dynamics of drug markets and consequent patterns of drug use, the healthcare system will continue to be ineffective in its response, and morbidity and mortality will continue to increase. Economic perspectives are largely neglected in research and clinical contexts, but better treatment alternatives need to consider the large-scale macroeconomic conditions of drug markets as well as the behavioural economics of individual substance use. It is important for policy makers, health authorities, first responders and medical providers to be aware of the clinical implications of drug market changes in order to best serve people who use drugs. Only with significant clinical research, a comprehensive reorganization of the system of care across all sectors, and an evidence-driven governance, will we be successful in addressing the challenges brought on by the recent shifts in drug markets.
MEIS2 (15q14) gene deletions in siblings with mild developmental phenotypes and bifid uvula: documentation of mosaicism in an unaffected parent
Authors: Zhang Bin , Liu Michel , Fong Chin-To , Iqbal M. Anwar 
Published: December 2021

AbstractMEIS2 (Meis homeobox 2) encodes a homeobox protein in the three amino acid loop extension (TALE) family of highly conserved homeodomain-containing transcription regulators important for development. MEIS2 deletions/mutations have been associated with cleft lip/palate, dysmorphic facial features, cardiac defects, as well as intellectual disability at a variable severity. Here we report on one familial case that two affected siblings carry the same non-mosaic ~ 423 kb genomic deletion at 15q14 encompassing the entirety of CDIN1 and the last three exons (ex. 10, 11, 12) of the MEIS2 gene, while their unaffected father is mosaic for the same deletion in about 10% lymphocytes. Both siblings presented with mild developmental delay and bifid uvula, while no congenital cardiac abnormalities were identified. The elder sister also showed syncopal episodes and mild speech delay and the father had atrial septal defects. This is the first report showing multiple family members inherit a genomic deletion resulting in a MEIS2 partial truncation from a mosaic parent. Taken all together, this study has important implications for genetic counseling regarding recurrence risk and also points to the importance of offering MEIS2 gene tests covering both point mutations and microdeletions to individuals with milder bifid uvula and developmental delay.
A pilot study of trained ICU doulas providing early psychological support to critically ill patients
Authors: Karnatovskaia Lioudmila V. , Varga Katalin , Niven Alexander S. , Schulte Phillip J. , Mujic Midhat , Gajic Ognjen , Bauer Brent A. , Clark Matthew M. , Benzo Roberto P. , Philbrick Kemuel L. 
Published: December 2021

Abstract
Background
Over a third of critical illness survivors suffer from mental health problems following hospitalization. Memories of delusional experiences are a major risk factor. In this project, ICU doulas delivered a unique positive suggestion intervention targeting the vulnerable time period during critical illness when these memories are formed.

Methods
Adult critically ill patients were recruited for this single-arm, prospective pilot study. These ICU patients received a positive suggestion intervention daily during their ICU stay in parallel with their medical treatment. The intervention was designed to be delivered over a minimum of two sessions. Feasibility was defined as intervention delivery on ≥ 70% of ICU days after patient enrollment. As a secondary analysis, psychometric questionnaires were compared to those of a historic control cohort of patients receiving standard care in the ICU using adjusted linear regression models.

Results
Of the 97 patients who received the intervention and were alive at the end of their ICU course, 54 were excluded from analyses mostly for having received only one session because of a short ICU length of stay of < 2 days, transitioning to comfort care or not wanting to answer the study questionnaires. Forty-three patients who completed 2 or more sessions of the positive therapeutic suggestion intervention provided by two trained ICU doulas received it for a median of 4 days (IQR 3, 5), with each session lasting for a median of 20 min (IQR 14, 25). The intervention was delivered on 71% of days, meeting our pre-determined feasibility goal. Compared to historical controls (N = 299), patients receiving the intervention had higher severity of illness and longer length of stay. When adjusted for baseline differences, patients both with and without mechanical ventilation who received the intervention scored lower on the Hospital Anxiety and Depression Scale (HADS)—Depression subscale. The intervention was also associated with reduced HADS-Anxiety subscale among ventilated patients.

Conclusions
Positive therapeutic suggestion delivered by ICU doulas is feasible in the ICU setting. A randomized trial is warranted to better delineate the role that positive suggestion and ICU doulas may play in ongoing interprofessional efforts to humanize critical care medicine.
The study was registered on clinicaltrials.gov (NCT03736954) on 03/14/2018 prior to the first patient enrollment https://clinicaltrials.gov/ct2/show/NCT03736954?cond=ICU+Doulas+Providing+Psychological+Support&draw=2&rank=1.
Promoting Independence Through quality dementia Care at Home (PITCH): a research protocol for a stepped-wedge cluster-randomised controlled trial
Authors: Savvas Steven , Goh Anita M. Y. , Batchelor Frances , Doyle Colleen , Wise Erica , Tan Esther , Panayiotou Anita , Malta Sue , Winbolt Margaret , Clarke Phillip , Burton Jason , Low Lee-Fay , Loi Samantha M. , Fairhall Anne , Polacsek Meg , Stiles Jay , Muliadi Fenny , Chau Nadia , Scherer Samuel , Ames David , Sousa Tanara Vieira , Dow Briony 
Published: December 2021

Abstract
Background
Home care service providers are increasingly supporting clients living with dementia. Targeted and comprehensive dementia-specific training for home care staff is necessary to meet this need. This study evaluates a training programme delivered to care staff (paid personal carers) of clients living with dementia at home.

Methods
This study is a pragmatic stepped-wedge cluster-randomised controlled trial (SW-CRT). Home care workers (HCWs) from seven home care service providers are grouped into 18 geographical clusters. Clusters are randomly assigned to intervention or control groups. The intervention group receives 7 h of a dementia education and upskilling programme (Promoting Independence Through quality dementia Care at Home [PITCH]) after baseline measures. The control group receives PITCH training 6 months after baseline measures. This approach will ensure that all participants are offered the program. Home care clients living with dementia are also invited to participate, as well as their family carers. The primary outcome measure is HCWs’ sense of competence in dementia care provision.

Discussion
Upskilling home care staff is needed to support the increasing numbers of people living with dementia who choose to remain at home. This study uses a stepped-wedge cluster-randomised trial to evaluate a training programme (PITCH) for dementia care that is delivered to front-line HCWs.

Trial registration
anzctr.org.au; ACTRN12619000251123. Registered on 20 February 2019.
Comparison of extended reality and conventional methods of basic life support training: protocol for a multinational, pragmatic, noninferiority, randomised clinical trial (XR BLS trial)
Authors: Lee Dong Keon , Im Chang Woo , Jo You Hwan , Chang Todd , Song Joo Lee , Luu Cindy , Mackinnon Ralph , Pillai Suresh , Lee Chuen Neng , Jheon Sanghoon , Ahn Soyeon , Won Seung Hyun 
Published: December 2021

Abstract
Background
Conventional cardiopulmonary resuscitation (CPR) training for the general public involves the use of a manikin and a training video, which has limitations related to a lack of realism and immersion. To overcome these limitations, virtual reality and extended reality technologies are being used in the field of medical education. The aim of this study is to explore the efficacy and safety of extended reality (XR)-based basic life support (BLS) training.

Methods
This study is a prospective, multinational, multicentre, randomised controlled study. Four institutions in 4 countries will participate in the study. A total of 154 participants will be randomly assigned to either the XR group or the conventional group stratified by institution and sex (1:1 ratio). Each participant who is allocated to either group will be sent to a separate room to receive training with an XR BLS module or conventional CPR training video. All participants will perform a test on a CPR manikin after the training. The primary outcome will be mean compression depth. The secondary outcome will be overall BLS performance, including compression rate, correct hand position, compression, and full release and hands-off time.

Discussion
Using virtual reality (VR) to establish a virtual educational environment can give trainees a sense of realism. In the XR environment, which combines the virtual world with the real world, trainees can more effectively learn various skills. This trial will provide evidence of the usefulness of XR in CPR education.

Trial registration
ClinicalTrials.gov NCT04736888. Registered on 29 January 2021