bluuebunny/crossref_metadata_2025 huggingface dataset:
The MOMANT study, a caregiver support programme with activities at home for people with dementia: a study protocol of a randomised controlled trial
Authors: Balvert S. C. E. , Milders M. V. , Bosmans J. E. , Heymans M. W. , van Bommel S. , Dröes R.-M. , Scherder E. J. A.
Published: April 2022

Background

Because of the expected increase in the number of people with dementia, and the associated social and economic costs, there is an urgent need to develop effective and cost-effective care for people with dementia and their caregivers. The intervention proposed here combines two approaches to caregiver support that have shown to be effective in empowering caregivers, i.e., multiple components for caregiver support and actively engaging caregivers to involve the person with dementia in activities at home. The aim is to investigate whether the intervention is effective in improving quality of life in the caregiver and the person with dementia. A further aim will be to investigate whether this intervention can improve caregivers’ feeling of competence, experience of caregiving, and mood.

Methods

The study design is a pragmatic, cluster randomised controlled trial with cost-effectiveness analysis. The study participants are informal caregivers and home-living persons with dementia for whom they care, recruited in various regions in the Netherlands. The trial will compare outcomes in two groups of participants: 85 dyads who receive the intervention, and 85 dyads who receive care as usual. The intervention is a caregiver support training that is manual based and consists of 6 group sessions over 2 months. Training takes place in small groups of caregivers led by a health care professional presented at dementia day care centres. Randomisation occurs at the level of the day care centre. Participants are assessed on the outcome measures at baseline, prior to the intervention, and at 3 and 6 months after baseline.

Discussion

The study will provide insight into effectiveness and cost-effectiveness of an intervention that has not previously been evaluated or implemented in the Netherlands. The intervention potentially adds to the effective support options for informal caregivers of people with dementia without greatly increasing the workload for health- or social care professionals.

Trial registration

The trial is registered at the Dutch Trial Register at NTR6643; August 22nd, 2017.
Effects of a staged integral art-based cognitive intervention (SIACI) program in older adults with cognitive impairments: protocol for a randomized controlled trial
Authors: Yan Yuan-jiao , Ma Ming-ping , Cai Wen-chao , Huang Chen-shan , Lin Rong , Chen Yu-fei , Li Hong
Published: April 2022

Background

Given the aging population worldwide and the COVID-19 pandemic, which has been found to be associated with a deterioration in Alzheimer’s disease (AD) symptoms, investigating methods to prevent or delay cognitive decline in preclinical AD and AD itself is important. The trial described in this protocol aims to evaluate the effects of a staged integral art-based cognitive intervention (SIACI) in older adults with CIs (preclinical AD [SCD or MCI] and mild AD), in order to gather evidence on the effects of SIACI on cognition and psychological/psychosocial health gains and determine the mechanisms.

Methods

The planned study is a single-center, parallel-arm, randomized controlled trial with allocation concealment and outcome assessor blinding. A total of 88 participants will be randomized to two groups: (i) an intervention group that receives the 16-week, 24-session SIACI program and (ii) a waitlist control group (which will receive the SIACI program after completing the follow-up assessment). Global cognitive function, specific domains of cognition (memory, language, executive function, and visuospatial skills), and other health-related outcomes (quality of life, anxiety, depression, sleep quality, and physical activity level) will be measured at baseline, immediately after the intervention, and at the 6-month follow-up. Blood biomarkers, event-related potential (ERP)-P300, and magnetic resonance imaging (MRI) data will be collected at baseline and immediately after the intervention to explore the mechanisms of SIACI.

Discussion

The trial will elucidate the immediate and long-term effects of SIACI based on neuropsychological testing and blood biomarkers, and neuroscience involving ERP-P300 and MRI parameters will make it possible to explore the mechanisms of SIACI in older adults with CIs. The results will provide evidence on the effectiveness of an AT-based cognitive intervention, which may delay or even halt cognitive decline in preclinical AD and AD itself.

Trial registration

ChiCTR,ChiCTR2100044959. Registered 03 April 2021.
Early-life exposure to Chinese famine and stroke risk in mid- to late life: the mediating roles of cognitive function and depression
Authors: Zhou Zi , Zhang Wei , Fang Ya
Published: April 2022

Background

Limited research has examined the role that famine exposure plays in adulthood stroke risk. We aim to explore the causal implications of early exposure to the Great Chinese Famine on stroke risk and determine whether these associations were mediated by cognitive function, and depression.

Methods

We sampled 12,681 individuals aged 45 years and older from the China Health and Retirement Longitudinal Study (CHARLS) and divided them into fetally exposed, childhood-exposed, adolescence/adulthood-exposed and unexposed groups. Stroke was defined by self- or proxy-reported physician diagnosis. Based on a counterfactual framework, marginal structural models were used to estimate the natural direct effect and the natural indirect effects through cognitive function and depression for causal inference.

Results

We found that early-life exposure to Chinese famine was directly related to increased stroke risk in mid- to late life. Cognitive function and depression accounted for a greater part of the effect for childhood famine exposure, mediating 36.35% (95%CI: 14.19, 96.19%) of the overall association between famine exposure and incident stroke, than for the fetal, adolescence/adulthood famine exposure groups. However, the natural indirect effect through depression was not significant in the fetally exposed group. The results were robust in the sensitivity analysis of model specification and unobserved confounding.

Conclusions

Our findings are consistent with the latency, pathway, and accumulation models, supporting the life-course theory. Early stages of life exposed to the Chinese Famine were associated with higher risk of stroke in mid- to late life. Enhanced cognitive and depression interventions may reduce stroke risk in middle-aged and older Chinese adults who exposure to famine in early life.
Translation of the geriatric emergency department intervention into other emergency departments: a post implementation evaluation of outcomes for older adults
Authors: Marsden Elizabeth , Craswell Alison , Taylor Andrea , Barnett Adrian , Wong Pan-Kar , Wallis Marianne
Published: April 2022

Background

Increasing numbers of older adults with complex health deficits presenting to emergency departments has prompted the development of innovative models of care. One such model designed to reduce poor outcomes associated with acute healthcare, is the Geriatric Emergency Department Intervention. This intervention is a nurse-led, physician-championed, Emergency Department intervention that improves the health outcomes for frail older adults in the emergency department.

Methods

This quantitative cohort study aimed to evaluate the healthcare outcomes and costs associated with the implementation of the Geriatric Emergency Department Intervention (GEDI) for adults aged 70 years and over at two hospital sites that implemented the model using the integrated-Promoting Action on Research Implementation in Health Services (i-PARHIS) framework. Hospital A was large teaching hospital located in the tropical north of Australia. Hospital B was a medium sized teaching hospital near Brisbane, Queensland Australia.

The effect of the intervention was examined in two ways. Outcomes were compared between: 1) all patients in the pre- and post- implementation periods, and 2) patients seen or not seen by the Geriatric Emergency Department Intervention team in the post-implementation period. The outcomes measured were disposition (discharged home, admitted); emergency department length of stay; hospital length of stay; all cause in-hospital mortality within 28 days; time to re-presentation up to 28 days post-discharge; emergency department and in-hospital costs.

Survival analyses were used for the primary and secondary outcome variables and a Cox survival model was used to estimate the associations between variables and outcomes. Multiple regression models were used to examine other secondary outcomes whilst controlling for a range of confounders.

Results

The Geriatric Emergency Department Intervention was successfully translated into two different emergency departments. Both demonstrated an increased likelihood of discharge, decreased emergency department length of stay, decreased hospital costs for those who were admitted, with an associated reduction in risk of mortality, for adults aged 70 years and over.

Conclusions

The Geriatric Emergency Department Intervention was successfully translated into new sites that adapted the model design. Improvement in healthcare outcomes for older adults presenting to the emergency department was demonstrated, although this was more subtle than in the original model setting.
Teleworking from home experiences during the COVID-19 pandemic among public health workers (TelEx COVID-19 study)
Authors: Chow Josephine Sau Fan , Palamidas Dimetrious , Marshall Sonia , Loomes Wendy , Snook Suzie , Leon Rebecca
Published: April 2022

Background

When working from home (WFH) became temporarily necessary for staff as a result of the COVID-19 pandemic in 2020, it had to be implemented without significant organisational experience or understanding of WFH and its complexities. This study aims to determine the impacts experienced by staff who have undertaken WFH during the COVID-19 pandemic.

Methods

This was an observational cross-sectional study using survey with a purposive sampling strategy for staff from corporate and non-clinical departments. These staff undertook WFH during COVID-19 pandemic in 2020. None of these staff had any direct operational roles in a hospital facility and clinical service. Participants’ self-reports of their mood while working in their normal workplace and while WFH were collected via the Scale of Positive and Negative Experience (SPANE), a validated affect balance questionnaire. The responses from the open-ended question were analysed using thematic analysis approach.

Results

A total of 143 participants completed the survey responses. Majority (61%) WFH for four or more months as a result of the COVID-19 pandemic. Participants rated their skills very highly on the technologies with an average rating of 9 (out of 10) for computer skills, smartphones and videoconferencing/teleconferencing applications. Participants felt WFH was an improvement on normal working, in particular in relation to their ability to concentrate and be productive. The “SPANE” relating to affect balance while WFH was completed by 124 participants (85.7%), resulting in a mean score of 5.45 (S.D. 2.98). The SPANE relating to normal working conditions was completed by 127 participant (88.8%) resulting in a mean score of 2.70 (S.D 3.69). This indicated that while participants’ positive emotions typically predominated in both situations, they felt slightly more positive on average with WFH. Over 90% participants reported that they would take the opportunity to WFH again if it were offered. Data obtained from the open-ended questions had complimented the findings of the structure close-ended questions in the benefits of remote working and support for their health and wellbeing. The open-ended questions had provided additional information on challenges which the participants encountered during the WFH experience and their suggested preference to sustain this workplace practice.

Conclusions

This study highlighted factors that impacted workers’ work processes, productivity, physical and mental health well-being while WFH and provided a foundation for considering how to best support a positive WFH experience.
Efficacy of liraglutide in patients with diabetic nephropathy: a meta-analysis of randomized controlled trials
Authors: Mali Niroj , Su Feng , Ge Jie , Fan Wen Xing , Zhang Jing , Ma Jingyuan
Published: April 2022

Background

The efficacy of liraglutide to treat type 2 diabetic nephropathy (T2DN) remains controversial. Thus, we conducted this meta-analysis to systematically evaluate the clinical effect of liraglutide on T2DN patients.

Methods

Eight databases (PubMed, Web of Science, the Cochrane Library, EMBASE, Chinese National Knowledge Infrastructure (CNKI), Wanfang database, China Science and Technology Journal Database, and China Biology Medicine Database (CBM)) were searched for published articles to evaluate the clinical efficacy of liraglutide in subjects with T2DN. The Revman 5.3 and Stata 13 software were used for analyses and plotting.

Results

A total of 18 randomized controlled trials (RCTs) with 1580 diabetic nephropathy patients were screened. We found that the levels of UACR, Scr, Cysc were lower in the experimental group of T2DN patients treated with liraglutide than in the control group intervened without liraglutide. Liraglutide also reduced the levels of blood glucose (including FBG, PBG, and HbA1c), body mass index (BMI), and anti-inflammatory indicators (TNF–α, IL-6). However, there was no significant difference in BUN and eGFR between the experimental group and the control group.

Conclusions

Liraglutide reduced the levels of Blood Glucose, BMI, renal outcome indicators, and serum inflammatory factors of patients with T2DN, suggesting the beneficial effects of liraglutide on renal function.
T-shaped toothbrush for plaque removal and gingival health in children: a randomized controlled trial
Authors: Mamat Noraida , Mani Shani Ann , Danaee Mahmoud
Published: April 2022

Background

To evaluate an experimental T-shaped toothbrush for plaque removal and gingival health when compared to a conventional toothbrush among children.

Methods

This single blind parallel randomized controlled trial was conducted on 8–10-year-old healthy schoolchildren with no history of recent antibiotic intake, proximal caries or more than 3 missing teeth per quadrant. A computer-generated randomization list allocated child to the 2 groups. Each child received detailed instructions for tooth brushing. Gingival health and plaque scores were recorded in school at baseline, 2 weeks, 1 month and 3 months in a portable dental chair by an examiner who was blind to the allocated toothbrush. A general feedback on the use of the T-shaped toothbrush was obtained at 3 months. Data was analyzed using two-way repeated measure ANOVA, Generalized estimating equation and Bonferroni test.

Results

A total of 195 eligible children were invited, 110 parents gave consent and 100 children completed the study; 50 in each group. There were statistically significant reductions in mean gingival and plaque scores at each visit when compared to baseline for both toothbrushes (p < 0.05). There were no statistically significant differences between scores for the two toothbrushes at each visit (p > 0.05). Majority of participants gave positive feedback regarding the T-shaped toothbrush.

Conclusions

Both toothbrushes had similar efficacy in removing plaque and improving gingival health among children. The T-shaped toothbrush is an alternative to the conventional toothbrush for oral hygiene in children.

Trial registration Retrospectively registered at ClinicalTrials.gov Registry—NCT03989479 18/06/2019.
Provider perspectives on emergency department initiation of medication assisted treatment for alcohol use disorder
Authors: Philippine Thibault , Forsgren Ethan , DeWitt Cassandra , Carter Inanna , McCollough Maureen , Taira Breena R.
Published: April 2022

Background

Alcohol use disorder (AUD) is ubiquitous and its sequelae contribute to high levels of healthcare utilization, yet AUD remains undertreated. The ED encounter represents a missed opportunity to initiate medication assisted treatment (MAT) for patients with AUD. The aims of this study are to identify barriers and facilitators to the treatment of AUD in the ED, and to design interventions to address identified barriers.

Methods

Using an implementation science approach based on the Behavior Change Wheel framework, we conducted qualitative interviews with staff to interrogate their perspectives on ED initiation of AUD treatment. Subjects included physicians, nurses, nurse practitioners, clinical social workers, and pharmacists. Interviews were thematically coded using both inductive and deductive approaches and constant comparative analysis. Themes were further categorized as relating to providers’ capabilities, opportunities, or motivations. Barriers were then mapped to corresponding intervention functions.

Results

Facilitators at our institution included time allotted for continuing education, the availability of clinical social workers, and favorable opinions of MAT based on previous experiences implementing buprenorphine for opioid use disorder. Capability barriers included limited familiarity with naltrexone and difficulty determining which patients are candidates for therapy. Opportunity barriers included the limited supply of naltrexone and a lack of clarity as to who should introduce naltrexone and assess readiness for change. Motivation barriers included a sense of futility in treating patients with AUD and stigmas associated with alcohol use. Evidence-based interventions included multi-modal provider education, a standardized treatment algorithm and order set, selection of clinical champions, and clarification of roles among providers on the team.

Conclusions

A large evidence-practice gap exists for the treatment of AUD with Naltrexone, and the ED visit is a missed opportunity for intervention. ED providers are optimistic about implementing AUD treatment in the ED but described many barriers, especially related to knowledge, clarification of roles, and stigma associated with AUD. Applying a formal implementation science approach guided by the Behavior Change Wheel allowed us to transform qualitative interview data into evidence-based interventions for the implementation of an ED-based program for the treatment of AUD.
Protein purification strategies must consider downstream applications and individual biological characteristics
Authors: Remans Kim , Lebendiker Mario , Abreu Celeste , Maffei Mariano , Sellathurai Shaila , May Marina M. , Vaněk Ondřej , de Marco Ario
Published: April 2022

Background

Proteins are used as reagents in a broad range of scientific fields. The reliability and reproducibility of experimental data will largely depend on the quality of the (recombinant) proteins and, consequently, these should undergo thorough structural and functional controls. Depending on the downstream application and the biochemical characteristics of the protein, different sets of specific features will need to be checked.

Results

A number of examples, representative of recurrent issues and previously published strategies, has been reported that illustrate real cases of recombinant protein production in which careful strategy design at the start of the project combined with quality controls throughout the production process was imperative to obtain high-quality samples compatible with the planned downstream applications. Some proteins possess intrinsic properties (e.g., prone to aggregation, rich in cysteines, or a high affinity for nucleic acids) that require certain precautions during the expression and purification process. For other proteins, the downstream application might demand specific conditions, such as for proteins intended for animal use that need to be endotoxin-free.

Conclusions

This review has been designed to act as a practical reference list for researchers who wish to produce and evaluate recombinant proteins with certain specific requirements or that need particular care for their preparation and storage.
Medical education interventions influencing physician distribution into underserved communities: a scoping review
Authors: Elma Asiana , Nasser Muhammadhasan , Yang Laurie , Chang Irene , Bakker Dorothy , Grierson Lawrence
Published: April 2022

Background and objective

Physician maldistribution is a global problem that hinders patients’ abilities to access healthcare services. Medical education presents an opportunity to influence physicians towards meeting the healthcare needs of underserved communities when establishing their practice. Understanding the impact of educational interventions designed to offset physician maldistribution is crucial to informing health human resource strategies aimed at ensuring that the disposition of the physician workforce best serves the diverse needs of all patients and communities.

Methods

A scoping review was conducted using a six-stage framework to help map current evidence on educational interventions designed to influence physicians’ decisions or intention to establish practice in underserved areas. A search strategy was developed and used to conduct database searches. Data were synthesized according to the types of interventions and the location in the medical education professional development trajectory, that influence physician intention or decision for rural and underserved practice locations.

Results

There were 130 articles included in the review, categorized according to four categories: preferential admissions criteria, undergraduate training in underserved areas, postgraduate training in underserved areas, and financial incentives. A fifth category was constructed to reflect initiatives comprised of various combinations of these four interventions. Most studies demonstrated a positive impact on practice location, suggesting that selecting students from underserved or rural areas, requiring them to attend rural campuses, and/or participate in rural clerkships or rotations are influential in distributing physicians in underserved or rural locations. However, these studies may be confounded by various factors including rural origin, pre-existing interest in rural practice, and lifestyle. Articles also had various limitations including self-selection bias, and a lack of standard definition for underservedness.

Conclusions

Various educational interventions can influence physician practice location: preferential admissions criteria, rural experiences during undergraduate and postgraduate medical training, and financial incentives. Educators and policymakers should consider the social identity, preferences, and motivations of aspiring physicians as they have considerable impact on the effectiveness of education initiatives designed to influence physician distribution in underserved locations.
Understanding the sustainment of population health programmes from a whole-of-system approach
Authors: Crane Melanie , Nathan Nicole , McKay Heather , Lee Karen , Wiggers John , Bauman Adrian
Published: April 2022

Background

Population health prevention programmes are needed to reduce the prevalence of chronic diseases. Nevertheless, sustaining programmes at a population level is challenging. Population health is highly influenced by social, economic and political environments and is vulnerable to these system-level changes. The aim of this research was to examine the factors and mechanisms contributing to the sustainment of population prevention programmes taking a systems thinking approach.

Methods

We conducted a qualitative study through interviews with population health experts working within Australian government and non-government agencies experienced in sustaining public health programs at the local, state or national level (n = 13). We used a deductive thematic approach, grounded in systems thinking to analyse data.

Results

We identified four key barriers affecting program sustainment: 1) short term political and funding cycles; 2) competing interests; 3) silo thinking within health service delivery; and 4) the fit of a program to population needs. To overcome these barriers various approaches have centred on the importance of long-range planning and resourcing, flexible program design and management, leadership and partnerships, evidence generation, and system support structures.

Conclusion

This study provides key insights for overcoming challenges to the sustainment of population health programmes amidst complex system-wide changes.
Pathogenicity comparison between QX-type and Mass-type infectious bronchitis virus to different segments of the oviducts in laying phase
Authors: Zhang Xiaorong , Yan Kun , Zhang Chengcheng , Guo Mengjiao , Chen Shuqin , Liao Kai , Bo Zongyi , Cao Yongzhong , Wu Yantao
Published: April 2022

Background

The QX-type infectious bronchitis virus (IBV) has become the predominant genotype worldwide in recent years and has caused serious economic losses to the chicken industry. The most significant feature of QX IBV is that its infection in the early growing stage can cause abnormal oviduct development, resulting in a high proportion of ‘false layers’ in poultry flocks of laying hens and breeders. However, few studies have evaluated whether infections of QX-type IBV in laying stages can also cause severe pathological changes in the oviduct.

Methods

In this study, 300-day-old specific-pathogen-free chickens were infected either with the QX-type strain QXL or Massachusetts (Mass)-type strain M41 to compare their pathogenicity on different segments of the oviduct.

Results

Both the QXL and M41 strains successfully replicated in all segments of the oviduct; however, the QXL strain was more highly distributed in mucosal layer and caused severe lesions in the lamina propria, including interstitial dilation, inflammatory cell infiltration, and distinct expansion of tubular glands. Moreover, the QXL strain induced high expression of proinflammatory cytokines and cytotoxic molecules in the majority of segments in the oviduct. Further research found that the QXL strain may affected the formation of shell membranes and eggshells by inhibiting the expression of type I collagen and CaBP-D28k.

Conclusions

Our results indicate that the QX-type IBV is more pathogenic than Mass-type IBV to oviduct in laying phase. Collectively, these findings provide detailed information on the pathological changes in different segments of the oviduct in laying phase, which could offer a better understanding about the pathogenicity of IBV.
Safety assessment of graphene oxide and microcystin-LR complex: a toxicological scenario beyond physical mixture
Authors: Ma Ying , Ding Xiaomeng , Liu Qing , Pang Yanting , Cao Yuna , Zhang Ting
Published: April 2022

Background

Nanomaterials have been widely used in electrochemistry, sensors, medicine among others applications, causing its inevitable environmental exposure. A raising question is the “carrier” effect due to unique surface properties of nanomaterials, which may collectively impact the bioavailability, toxicokinetic, distribution and biological effects of classic toxicants. Noteworthy, this aspect of information remains largely unexplored.

Methods

Here, we deliberately selected two entities to mimic this scenario. One is graphene oxide (GO), which is made in ton quantity with huge surface-area that provides hydrophilicity and π–π interaction to certain chemicals of unique structures. The other is Microcystin-LR (MCLR), a representative double-bond rich liver-toxic endotoxin widely distributed in aquatic-system. Firstly, the adsorption of GO and MCLR after meeting under environmental conditions was explored, and then we focused on the toxicological effect and related mechanism of GO-MCLR complex on human skin cutin forming cells (HaCaT cells) and normal liver cells (L02 cells).

Results

Abiotically, our study demonstrated that GO could effectively adsorb MCLR through hydrogen bonding and π–π interaction, the oxidation degree of GO-MCLR decreased significantly and surface defect level raised. Compared to GO or MCLR, GO-MCLR was found to induce more remarkable apoptosis and ferroptosis in both HaCaT and L02 cells. The underlying mechanism was that GO-MCLR induced stronger intracellular reactive oxygen species (ROS) and mtROS generation, followed by Fe2+ accumulation, mitochondrial dysfunction and cytoskeletal damage.

Conclusions

These results suggest that the GO-MCLR complex formed by GO adsorption of MCLR may exhibit more toxic effects than the single material, which demonstrates the necessity for assessing nano-toxicant complexity. Our discovery may serve as a new toxicological paradigm in which nanomaterial mediated surface adsorption effects could impact the degree of cytotoxicity and toxicological mechanisms of classic toxins.

Graphical Abstract
Foot Function Index for Arabic-speaking patients (FFI-Ar): translation, cross-cultural adaptation and validation study
Authors: Khan Shershah , Faulkner Suzanne , Algarni Fahad S. , Almalki Abdulaziz , Almansour Ahmed , Altowaijri Abdulrahman M.
Published: April 2022

Background

Foot Function Index (FFI) is a valid and reliable outcome measure, which is widely used to measure the foot and ankle functional level and disorders. Until now, no validated Arabic version of the FFI is available. This study was conducted at a tertiary care hospital in Riyadh, Saudi Arabia. The purpose of this project was to translate and adapt the FFI into Arabic and to evaluate its psychometric properties of validity and reliability.

Methods

The study consisted of two phases. The first phase was the translation and cultural adaptation of the FFI to Arabic. The next phase involved, testing the psychometric properties of the Arabic version of the FFI on a sample of 50 consecutive participants which included internal consistency, test–retest reliability, floor and ceiling effects and construct validity.

Results

The mean age of the study participants was 38 ± 12.94 years. Both the genders were evenly enrolled with 50% of the participants as male and 50% as female. Majority of them complained of plantar fasciopathy (32%) followed by pes planus (22%) and ankle sprain (18%). The scores of FFI-Ar were normally distributed, confirmed by a significant Shapiro–Wilk test. The mean value of FFI-Ar total score was 47.73 ± 19.85. There were no floor or ceiling effects seen in any of the subscales and total score. The internal consistency was good with the Cronbach’s alpha value of 0.882, 0.936 and 0.850 for the pain, disability and activity limitation subscales, respectively. The reproducibility of the FFI-Ar was analysed by intra-class correlation coefficient which revealed good to excellent test–retest reliability. A significant correlation was found between FFI-Ar and SF-36 and numeric rating scale (NRS) confirming its construct validity.

Conclusion

The FFI-Arabic version showed good validity and reliability in patients with foot and ankle problems. This tool can be used in usual practice and research for analysing foot and ankle disorders in Arabic-speaking people.
Posterior pilon fracture treated by opening the fibula fracture gap
Authors: Jiang Zhuang , Zhang Chen , Qin Jia-Jun , Wang Guo-Dong , Wang Hua-Song
Published: April 2022

Background

Posterior pilon fracture is a relatively common clinical fracture involving the posterior articular surface of the distal tibia. Currently, this form of fracture is receiving increasing attention. The surgical approach and technique for the treatment of posterior pilon fractures are still controversial. The purpose of this retrospective study was to compare the clinical and imaging outcomes of pilon fractures after treatment with the open fibula fracture line (OFFL) surgical technique versus the traditional posterolateral approach (TPL).

Methods

A retrospective analysis of patients with posterior pilon fractures treated using the open fibula fracture line technique and the traditional posterolateral approach between January 2015 and March 2020. Thirty-one cases were included in the open fibula fracture line technique group and twenty-eight cases were included in the traditional posterolateral approach group. We used the Burwell-Charnley scale to assess the effectiveness of surgical repositioning. The clinical outcomes were evaluated using American Orthopaedic Foot & Ankle Society ankle-hind foot score (AOFAS) and visual analog score (VAS).

Results

The overall anatomic reduction rate was slightly better in the open fibula fracture line group than in the conventional posterolateral group (81% vs. 71%, p = 0.406), but there was no statistically significant difference between the two groups. There were no statistically significant differences between the two groups in terms of fracture healing time and time to full weight bearing (p > 0.05). At the final follow-up, the AOFAS functional score of the open fibula fracture line group was statistically superior to that of the conventional posterolateral group (p < 0.05). However, there was no statistical difference between the two groups in VAS pain scores at rest, during activity, and under weight bearing (p > 0.05).

Conclusion

The trans-fibular fracture approach provides a better surgical option for specific types of posterior pilon fractures with a high rate of anatomic repositioning and a good near-term outcome.

Trial registration: Retrospective registration.
What is the optimal surgical treatment for Neer type IIB (IIC) distal clavicle fractures? A systematic review and meta-analysis
Authors: Panagopoulos Andreas , Solou Konstantina , Tatani Irini , Triantafyllopoulos Ioannis K. , Lakoumentas John , Kouzelis Antonis , Athanasiou Vasileios , Kokkalis Zinon T.
Published: April 2022

Background

The purpose of the present study was to systematically review the current treatment strategies for the treatment of Neer type IIB distal clavicle fractures in terms of functional outcome and complication rates and to examine the most appropriate surgical method by comparing all the available surgical techniques and implants.

Methods

We performed a systematic review of the existing literature (2000–2021) in accordance with the PRISMA statement. We searched PubMed, Scopus, Web of Science, Research Gate and Google Scholar using the general terms ‘distal AND clavicle AND fracture’ to capture as many reports as possible. The MINORS tool was used to assess the risk of bias of the nonrandomized studies. We categorized the reported surgical techniques into four main types: open or arthroscopic coracoclavicular (CC) stabilization, locking plate fixation with or without CC augmentation, hook plate fixation and acromioclavicular joint (ACJ) transfixation. We reported findings for two main outcomes: clinical results and complication rates categorized into major and minor.

Results

Our database search yielded a total of 630 records; 34 studies were appropriate for qualitative analysis. There were 790 patients, with a mean age of 40.1 years, a female percentage of 37% and a mean follow-up period of 29.3 months. In total, 132 patients received a hook plate, 252 received a locking plate, 368 received CC stabilization and 41 received transacromial transfixation. All studies were retrospective and had fair MINORS scores. Locking plate, CC stabilization and ACJ transfixation showed similar clinical results but were much better than hook plate fixation; CC augmentation did not significantly improve the outcome of locking plate fixation. The rate of major complications was similar among groups; hook plate and AC joint transfixation had the worst rates of minor complications. Open CC techniques were slightly better than arthroscopic techniques.

Conclusions

The present systematic review for the optimal fixation method for Neer type IIB fractures of the distal clavicle showed similar major complication rates among techniques; the hook plate technique demonstrated inferior clinical results to other techniques. Open CC stabilization and locking plate fixation without CC augmentation seem to be the best available treatment options.
Challenges in diagnosis and management of acute hepatic porphyrias: from an uncommon pediatric onset to innovative treatments and perspectives
Authors: Marcacci Matteo , Ricci Andrea , Cuoghi Chiara , Marchini Stefano , Pietrangelo Antonello , Ventura Paolo
Published: April 2022

Acute hepatic porphyrias (AHPs) are a family of four rare genetic diseases resulting from a deficiency in one of the enzymes involved in heme biosynthesis. AHP patients can experience potentially life-threatening acute attacks, characterized by severe abdominal pain, along with other signs and symptoms including nausea, mental confusion, hyponatraemia, hypertension, tachycardia and muscle weakness. Some patients also experience chronic manifestations and long-term complications, such as chronic pain syndrome, neuropathy and porphyria-associated kidney disease. Most symptomatic patients have only a few attacks in their lifetime; nevertheless, some experience frequent attacks that result in ongoing symptoms and a significant negative impact on their quality of life (QoL). Initial diagnosis of AHP can be made with a test for urinary porphobilinogen, $$\delta$$
δ
-aminolaevulinic acid and porphyrins using a single random (spot) sample. However, diagnosis is frequently missed or delayed, often for years, because the clinical symptoms of AHP are non-specific and mimic other more common disorders. Delayed diagnosis is of concern as some commonly used medications can trigger or exacerbate acute attacks, and untreated attacks can become severe, potentially leading to permanent neurological damage or fatality. Other attack triggers include hormonal fluctuations in women, stress, alcohol and low-calorie diets, which should be avoided in patients where possible. For the management of attacks, intravenous hemin is approved, whereas new therapeutic approaches are currently being investigated as a baseline therapy for prevention of attacks and improvement of QoL. Among these, a novel siRNA-based agent, givosiran, has shown very promising results in a recently concluded Phase III trial and has been approved for the management of AHPs. Here, we propose a challenging case study-with a very unusual pediatric onset of variegate porphyria-as a starting point to summarize the main clinical aspects (namely, clinical manifestations, diagnostic challenges, and therapeutic management) of AHPs, with a focus on the latest therapeutic innovations.
The role of tumor-infiltrating lymphocytes in cholangiocarcinoma
Authors: Liu Dong , Heij Lara Rosaline , Czigany Zoltan , Dahl Edgar , Lang Sven Arke , Ulmer Tom Florian , Luedde Tom , Neumann Ulf Peter , Bednarsch Jan
Published: April 2022

Cholangiocarcinoma (CCA) is the second most common primary liver cancer and associated with a dismal prognosis due to the lack of an efficient systemic therapy. In contrast to other cancers, new immunotherapies have demonstrated unsatisfactory results in clinical trials, underlining the importance of a deeper understanding of the special tumor microenvironment of CCA and the role of immune cells interacting with the tumor. Tumor-infiltrating lymphocytes (TILs) are an important component of the adaptive immune system and the foundation of current immunotherapy. Therefore, the aim of this systemic review is to summarize the current literature focusing on the proportions and distribution, molecular pathogenesis, prognostic significance of TILs and their role in immunotherapy for CCA patients.

In CCA, CD8+ and CD4+ T lymphocytes represent the majority of TILs and are mostly sequestered around the cancer cells. CD20+ B lymphocytes and Natural Killer (NK) cells are less frequent. In contrast, Foxp3+ cells (regulatory T cells, Tregs) are observed to infiltrate into the tumor. In the immune microenvironment of CCA, cancer cells and stromal cells such as TAMs, TANs, MSDCs and CAFs inhibit the immune protection function of TILs by secreting factors like IL-10 and TGF-β. With respect to molecular pathogenesis, the Wnt/-catenin, TGF-signaling routes, aPKC-i/P-Sp1/Snail Signaling, B7-H1/PD-1Pathway and Fas/FasL signaling pathways are connected to the malignant potential and contributed to tumor immune evasion by increasing TIL apoptosis. Distinct subtypes of TILs show different prognostic implications for the long-term outcome in CCA. Although there are occasionally conflicting results, CD8+ and CD4+ T cells, and CD20+ B cells are positively correlated with the oncological prognosis of CCA, while a high number of Tregs is very likely associated with worse overall survival. TILs also play a major role in immunotherapy for CCA.

In summary, the presence of TILs may represent an important marker for the prognosis and a potential target for novel therapy, but more clinical and translational

data is needed to fully unravel the importance of TILs in the treatment of CCA.
Amniotic fluid embolism rescued by venoarterial extracorporeal membrane oxygenation
Authors: Aissi James Sarah , Klein Thomas , Lebreton Guillaume , Nizard Jacky , Chommeloux Juliette , Bréchot Nicolas , Pineton de Chambrun Marc , Hékimian Guillaume , Luyt Charles-Edouard , Levy Bruno , Kimmoun Antoine , Combes Alain , Schmidt Matthieu
Published: April 2022

Background

Amniotic fluid embolism (AFE) is a rare but often catastrophic complication of pregnancy that leads to cardiopulmonary dysfunction and severe disseminated intravascular coagulopathy (DIC). Although few case reports have reported successful use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) with AFE, concerns can be raised about the increased bleeding risks with that device.

Methods

This study included patients with AFE rescued by VA-ECMO hospitalized in two high ECMO volume centers between August 2008 and February 2021. Clinical characteristics, critical care management, in-intensive care unit (ICU) complications, and hospital outcomes were collected. ICU survivors were assessed for health-related quality of life (HRQL) in May 2021.

Results

During that 13-year study period, VA-ECMO was initiated in 54 parturient women in two high ECMO volume centers. Among that population, 10 patients with AFE [median (range) age 33 (24–40), SAPS II at 69 (56–81)] who fulfilled our diagnosis criteria were treated with VA-ECMO. Pregnancy evolved for 36 (30–41) weeks. Seven patients had a cardiac arrest before ECMO and two were cannulated under cardiopulmonary resuscitation. Pre-ECMO hemodynamic was severely impaired with an inotrope score at 370 (55–1530) μg/kg/min, a severe left ventricular ejection fraction measured at 14 (0–40)%, and lactate at 12 (2–30) mmol/L. 70% of these patients were alive at hospital discharge despite an extreme pre-ECMO severity and massive blood product transfusion. However, HRQL was lower than age-matched controls and still profoundly impaired in the role-physical, bodily pain, and general health components after a median of 44 months follow-up.

Conclusion

In this rare per-delivery complication, our results support the use of VA-ECMO despite intense DIC and ongoing bleeding. Future studies should focus on customized, patient-centered, rehabilitation programs that could lead to improved HRQL in this population.
Evaluation of the effect of targeted Mass Drug Administration and Reactive Case Detection on malaria transmission and elimination in Eastern Hararghe zone, Oromia, Ethiopia: a cluster randomized control trial
Authors: Abdelmenan Semira , Teka Hiwot , Hwang Jimee , Girma Samuel , Chibsa Sheleme , Tongren Eric , Murphy Matthew , Haile Mebrahatom , Dillu Dereje , Kassim Jawar , Behaksra Sinknesh , Tadesse Fitsum G. , Yukich Joshua , Berhane Yemane , Worku Alemayehu , Keating Joseph , Zewde Ayele , Gadisa Endalamaw
Published: April 2022

Background

Reactive and proactive case detection measures are widely implemented by national malaria elimination programs globally. Ethiopia decided to include Reactive Case Detection (RCD) and targeted Mass Drug Administration (tMDA) approaches as part of their elimination strategy along with rigorous evaluation. The purpose of this study is to compare the impact of RCD and tMDA on malaria elimination over the 2-year study period, by looking at the annual parasite incidence before and after the intervention.

Methods

The study will be conducted in the East Hararghe zone of Ethiopia. Malaria transmission in the area is low to moderate. This study will deploy a community-based, three-arm, cluster-randomized control trial implemented over 2 years. Forty-eight clusters (16 clusters per arm) will be selected based on the annual number of confirmed malaria cases seen in the cluster. All clusters will receive the current standard of care in terms of malaria elimination interventions provided by the national malaria control program. In addition, following the identification of malaria parasite infection, individuals who reside within a 100-m radius of the index case will receive a diagnosis for malaria and treatment if positive in the RCD arm or presumptive treatment in the tMDA arm. The primary effectiveness endpoint will be measured at baseline and endline for each intervention arm and compared to the control arm using a difference in difference approach.

Discussion

This randomized controlled trial will provide evidence of the impact of the proposed intervention approaches for malaria elimination.

Trial registration

ClinicalTrials.gov NCT04241705. Registration date: January 27, 2020.
Repurposing Probenecid for the Treatment of Heart Failure (Re-Prosper-HF): a study protocol for a randomized placebo-controlled clinical trial
Authors: Rubinstein Jack , Robbins Nathan , Evans Karen , Foster Gabrielle , Mcconeghy Kevin , Onadeko Toluwalope , Bunke Julie , Parent Melanie , Luo Xi , Joseph Jacob , Wu Wen-Chih
Published: April 2022

Background

Improving contractility in heart failure with reduced ejection fraction (HFrEF) has resurfaced as a potential treatment goal. Inotropic therapy is now better understood through its underlying mechanism as opposed to the observed effect of increasing contractility. Calcitropes are a subgroup of inotropes that largely depend on the stimulation of adenylyl cyclase to transform ATP into cyclic adenosine monophosphate (cAMP). At least two clinically relevant calcitropes—istaroxime and probenecid—improve contractility through an increase in systolic intracellular calcium without activating cAMP production.

Probenecid, which has been safely used clinically for decades in non-cardiac conditions, has recently been identified as an agonist of the transient receptor potential vanilloid 2 channel. Translational studies have shown that it improves calcium cycling and contractility without activating noxious pathways associated with cAMP-dependent calcitropes and can improve cardiac function in patients with HFrEF.

Methods

The Re-Prosper-HF study (Repurposing Probenecid for the Treatment of Heart Failure with Reduced Ejection Fraction) is a three-site double-blinded randomized-controlled trial that will test the hypothesis that probenecid can improve cardiac function in patients with HFrEF. Up to 120 patients will be randomized in this double-blind, placebo-controlled study that will assess whether oral probenecid administered at 1 g orally twice per day for 180 days in patients with NYHA II-III HFrEF improves systolic function (aim 1), functional status (aim 2), and self-reported health status (aim 3).

Discussion

Findings from this study will provide data informing its use for improving symptomatology in patients with HFrEF as well as exploratory data for outcomes such as hospital admission rates.

Trial tegistration

The Re-Prosper HF Study (Re-Prosper HF) is registered on ClinicalTrials.gov with the identifier as NCT04551222. Registered on 9 September 2020.