bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between supportive interventions and healthcare utilization and outcomes in patients on long-term prescribed opioid therapy presenting to acute healthcare settings: a systematic review and meta-analysis
Authors: Deschamps Jean , Gilbertson James , Straube Sebastian , Dong Kathryn , MacMaster Frank P. , Korownyk Christina , Montgomery Lori , Mahaffey Ryan , Downar James , Clarke Hance , Muscedere John , Rittenbach Katherine , Featherstone Robin , Sebastianski Meghan , Vandermeer Ben , Lynam Deborah , Magnussen Ryan , Bagshaw Sean M. , Rewa Oleksa G.
Published: January 2021

Background

Long-term prescription of opioids by healthcare professionals has been linked to poor individual patient outcomes and high resource utilization. Supportive strategies in this population regarding acute healthcare settings may have substantial impact.

Methods

We performed a systematic review and meta-analysis of primary studies. The studies were included according to the following criteria: 1) age 18 and older; 2) long-term prescribed opioid therapy; 3) acute healthcare setting presentation from a complication of opioid therapy; 4) evaluating a supportive strategy; 5) comparing the effectiveness of different interventions; 6) addressing patient or healthcare related outcomes. We performed a qualitative analysis of supportive strategies identified. We pooled patient and system related outcome data for each supportive strategy.

Results

A total of 5664 studies were screened and 19 studies were included. A total of 9 broad categories of supportive strategies were identified. Meta-analysis was performed for the “supports for patients in pain” supportive strategy on two system-related outcomes using a ratio of means. The number of emergency department (ED) visits were significantly reduced for cohort studies (n = 6, 0.36, 95% CI [0.20–0.62], I2 = 87%) and randomized controlled trials (RCTs) (n = 3, 0.71, 95% CI [0.61–0.82], I2 = 0%). The number of opioid prescriptions at ED discharge was significantly reduced for RCTs (n = 3, 0.34, 95% CI [0.14–0.82], I2 = 78%).

Conclusion

For patients presenting to acute healthcare settings with complications related to long-term opioid therapy, the intervention with the most robust data is “supports for patients in pain”.
Thygeson’s superficial punctate keratitis (TSPK): a paediatric case report and review of the literature
Authors: Tang Xiao-Jiao , Liu Qing , Pi Lian-Hong , Chen Xin-Ke , Chen Lin
Published: January 2021

Background

Thygeson’s superficial punctate keratitis (TSPK) is reportedly a rare disease with an insidious onset, numerous remissions and exacerbations, and a long duration. The corneal lesions are elevated, whitish–grey in colour, and granular in the intraepithelium. A few reported cases of TSPK exist, and paediatric experience is limited. Due to the unknown aetiology and controversial treatment strategies for TSPK, we performed a literature review to summarize the criteria for the diagnosis, treatment and prognosis of TSPK to provide a basis for the treatment of TSPK in paediatric patients.

Case presentation

The clinical course of a boy with TSPK who repeatedly presented with episodes of tearing, photophobia and foreign body sensation in both eyes is described. Irritation was uncontrollable with antiviral and antibiotic medications, and it was managed by corticosteroids. No recurrence was reported at the 1-year follow-up after corticosteroid replacement and tapering.

Conclusions

The clinical features, treatment and prognosis between adult and paediatric TSPK patients have many similarities. The diagnosis of TSPK in children is more difficult, leading to missed diagnosis. TSPK needs to be carefully differentiated from other types of keratitis, especially intraepithelial secondary and other infectious ocular surface diseases.
Does obesity persist from childhood to adolescence? A 4-year prospective cohort study of chinese students in Hong Kong
Authors: Tung Joanna Yuet-ling , Ho Frederick Ka-wing , Tung Keith Tsz-suen , Wong Rosa Sze-man , Wong Wilfred Hing-sang , Chow Bik-chu , Ip Patrick
Published: January 2021

Background

Little is known about the progression of obesity from childhood to adolescence. This study aimed to longitudinally examine the obesity status in a cohort of children across their childhood and adolescence, and to identify the factors associated with persistent obesity.

Methods

The study used data from School Physical Fitness Award Scheme (SPFAS), a population-based programme in Hong Kong primary and secondary schools. Students were included if they participated in the SPFAS in both 2014 (Primary 1 and 2) and 2018 (Primary 5 and 6). Their anthropometric and physical fitness parameters were analyzed.

Results

A total of 18,863 students were included. The baseline prevalence of obesity was 5.7 %. After 4 years, the prevalence increased to 6.7 %. Among those with obesity at baseline, 35.3 % remained obese after 4 years. The addition of baseline physical fitness level did not improve the prediction for persistent obesity.

Conclusions

One-third of obese students in junior primary school remained to be obese into adolescence. Their baseline physical fitness level did not improve the predictive value for future obesity. Further studies should investigate the prognostic factors that may influence the natural course of childhood obesity.
Household factors and under-five mortality in Bankass, Mali: results from a cross-sectional survey
Authors: Boettiger David C. , Treleaven Emily , Kayentao Kassoum , Guindo Mahamadou , Coumaré Mama , Johnson Ari D. , Whidden Caroline , Koné Naimatou , Cissé Amadou Beydi , Padian Nancy , Liu Jenny
Published: January 2021

Background

Rural parts of Mali carry a disproportionate burden of the country’s high under-five mortality rate. A range of household factors are associated with poor under-five health in resource-limited settings. However, it is unknown which most influence the under-five mortality rate in rural Mali. We aimed to describe household factors associated with under-five mortality in Bankass, a remote region in central Mali.

Methods

We analysed baseline household survey data from a trial being conducted in Bankass. The survey was administered to households between December 2016 and January 2017. Under-five deaths in the five years prior to baseline were documented along with detailed information on household factors and women’s birth histories. Factors associated with under-five mortality were analysed using Cox regression.

Results

Our study population comprised of 17,408 under-five children from 8322 households. In the five years prior to baseline, the under-five mortality rate was 152.6 per 1000 live births (158.8 and 146.0 per 1000 live births for males and females, respectively). Living a greater distance from a primary health center was associated with a higher probability of under-five mortality for both males (adjusted hazard ratio [aHR] 1.53 for ≥10 km versus < 2 km, 95% confidence interval [CI] 1.25–1.88) and females (aHR 1.59 for ≥10 km versus < 2 km, 95% CI 1.27–1.99). Under-five male mortality was additionally associated with lower household wealth quintile (aHR 1.47 for poorest versus wealthiest, 95%CI 1.21–1.78), lower reading ability among women of reproductive age in the household (aHR 1.73 for cannot read versus can read, 95%CI 1.04–2.86), and living in a household with access to electricity (aHR 1.16 for access versus no access, 95%CI 1.00–1.34).

Conclusions

U5 mortality is very high in Bankass and is associated with living a greater distance from healthcare and several other household factors that may be amenable to intervention or facilitate program targeting.
Severe COVID-19 with acute respiratory distress syndrome (ARDS) in a sickle cell disease adult patient: case report
Authors: Teulier Marion , Elabbadi Alexandre , Gerotziafas Grigorios , Lionnet François , Voiriot Guillaume , Fartoukh Muriel
Published: January 2021

Background

Sickle-cell anaemia is a widespread genetic disease prevalent worldwide among African and African-American populations. The pathogenesis is most often revealed by pulmonary conditions, including acute thoracic syndrome, which is affecting the life expectancy of these populations. The global spread of CoV2-SARS infection with a respiratory tropism, endothelial damages and procoagulant status endangers the SCD population. However, with only a few case reports, consequences of the Covid-19 pandemic on SCD population remain poorly known.

Case presentation

We report a case of a 33-year-old man with a history of homozygous SS homozygous sickle cell anemia who consulted on March 24, 2020 for febrile dyspnea 11 days after the onset of symptoms. A nasopharyngeal swab was positive for SARS-CoV-2. His respiratory status worsened rapidly in the emergency room and then in ICU leading to severe ARDS requiring intubation, curarization, and venovenous ECMO. Hematologically, severe hemolysis associated with major thrombocytopenia without documented spinal cord injury was noted. Several transfusion exchanges are performed. The evolution was finally slowly favorable and led to discharge from the intensive care unit and then from the hospital.

Conclusions

This case recalls the importance of an increased prevention policy against COVID-19among the SCD population. In addition, from a therapeutic point of view, it advocates (1) a high preventive anticoagulation from the outset according to the level of D-dimers (2) the use of venovenous ECMO in this particular case, whereas this technique has had rather disappointing results in acute chest syndromes. (3) Unexpectedly, our patient did not develop pulmonary arterial hypertension (PAH) and acute cor pulmonale (ACP), whereas this is a common feature of ARDS during SCD. These last two observations suggest a different pathophysiology of pulmonary disorders in SCD patients in the case of SARS COv2. It could be associated with marked hypoxemia secondary to pulmonary vascular vasodilation.
Adaptation of balance reactions following forward perturbations in people with joint hypermobility syndrome
Authors: Bates Alexander Vernon , McGregor Alison , Alexander Caroline M.
Published: January 2021

Background

Joint Hypermobility Syndrome (JHS) is a Heritable Disorder of Connective tissue characterised by joint laxity and chronic widespread arthralgia. People with JHS exhibit a range of other symptoms including balance problems. To explore balance further, the objective of this study is to compare responses to forward perturbations between three groups; people who are hypermobile with (JHS) and without symptoms and people with normal flexibility.

Methods

Twenty-one participants with JHS, 23 participants with Generalised Joint Hypermobility (GJH) and 22 participants who have normal flexibility (NF) stood on a platform that performed 6 sequential, sudden forward perturbations (the platform moved to the anterior to the participant). Electromyographic outcomes (EMG) and kinematics for the lower limbs were recorded using a Vicon motion capture system. Within and between group comparisons were made using Kruskal Wallis tests.

Results

There were no significant differences between groups in muscle onset latency. At the 1st perturbation the group with JHS had significantly longer time-to-peak amplitude than the NF group in tibialis anterior, vastus medialis, rectus femoris, vastus lateralis, and than the GJH group in the gluteus medius. The JHS group showed significantly higher cumulative joint angle (CA) than the NF group in the hip and knee at the 1st and 2nd and 6th perturbation, and in the ankle at the 2nd perturbation. Participants with JHS had significantly higher CA than the GJH group at the in the hip and knee in the 1st and 2nd perturbation. There were no significant differences in TTR.

Conclusions

The JHS group were able to normalise the timing of their muscular response in relation to control groups. They were less able to normalise joint CA, which may be indicative of impaired balance control and strength, resulting in reduced stability.
A novel 3D-printed locking cage for anterior atlantoaxial fixation and fusion: case report and in vitro biomechanical evaluation
Authors: Wang Shenglin , Leng Huijie , Tian Yinglun , Xu Nanfang , Liu Zhongjun
Published: January 2021

Background

Treatment of atlantoaxial dislocation is aimed at reduction and stabilization of the atlantoaxial joint. 3D printing refers to a process where additive manufacturing is achieved under precise computer control. Literature on its utilization in anterior atlantoaxial fixation and fusion is rare. This study is the first report on a 3D-printed locking cage used in the anterior procedure for atlantoaxial dislocation.

Methods

A middle-aged male in his 40s presented with weakness and numbness of his extremities for 3 years and could only walk slowly with assistance. Imaging studies revealed severe anterior migration of C1, irreducible atlantoaxial dislocation, and severe cervical-medullary compression. A preoperative plan consisting of trans-oral soft tissue release and fixation using tailor-designed 3D-printed cages was devised. Following fluoroscopic confirmation of reduction of the atlantoaxial joints, two customized 3D-printed cages made of titanium alloy were inserted into the bilateral facet joints, which were then locked by six screws into the lateral masses of C1 and C2. The microstructure of the inserted cages was optimized for improved biomechanical stability and enhanced osseo-integration, without the need for bone grafting. In addition, a biomechanical test was performed on seven human cadaveric specimens comparing the novel implant with the conventional C1 lateral mass-C2 pedicle screw construct in three modes of motion (flexion-extension, lateral bending, axial rotation).

Results

Improvement of neurologic function in the patient was evident immediately after surgery. He was able to walk independently 1 month post-operatively. At the 12-month follow-up, coronal reconstruction of CT demonstrated properly-positioned 3D-printed cages, evidence of osseo-integration at the bone-implant interface, and no subsidence or displacement of the implant. Eighteen months out of surgery, the mJOA score improved to 15, and lateral X-ray confirmed reduction of atlanto-axial dislocation. Additionally, the new construct provided strong fixation comparable to that conferred by conventional constructs as there was no significant difference observed between the two groups in all three directions of motion.

Conclusions

The novel implant represents a new option in the treatment of irreducible atlantoaxial dislocation. It can provide strong anterior support for solid fixation and fusion with a low profile and a microstructure that obviates the need for bone grafting.
Open reduction and internal fixation of quadrilateral plate fractures in the elderly: association between initial fracture pattern and outcomes
Authors: Wu Haiyang , Shao Qipeng , Shang Ranran , Song Chengjing , Liu Ximing , Cai Xianhua
Published: January 2021

Background

Acetabular fractures with medial displacement of the quadrilateral plate (QLP) are common in the elderly. The presence of QLP fractures greatly increase the surgical difficulty of acetabular fractures. This study aims to evaluate the clinical radiological outcomes of open reduction and internal fixation (ORIF) in QLP fractures in elderly patients and to investigate factors potentially affecting the result.

Methods

We conducted a retrospective study. A series of 37 consecutive patients with acetabular fracture involving the QLP aged 60 years and older who received ORIF between January 2010 and May 2019 were included. QLP fractures were classified according to Walid’s classification system. Radiological outcomes were evaluated using Matta criteria and functional outcomes were assessed using the modified Merle d’Aubigné score. The relationships between Walid’s classification and radiological or functional outcomes were analyzed.

Results

According to Walid’s classification, 18, 13, 6 were classified as QLP1, QLP2 and QLP3, respectively. The average follow-up was 35.5 ± 10.7 months. We obtained anatomic reduction in 48.6 % (18/37) of cases, imperfect reduction in 40.5 % (15/37) of cases, and poor reduction in 10.8 % (4/37) of cases. Excellent-good functional scores were found in 83.7 % (modified Merle d’Aubigné). There were no cases of screw entering the hip, pull-out and loosening or implant failure during the follow-up. Walid’s classification was positively correlated with radiological outcomes of reduction (r = 0.661; P < 0.001), and functional outcomes (r = 0.478; P = 0.003). Unsatisfactory reduction was demonstrated a correlation with the development of post-traumatic arthritis (r =-0.410; P = 0.012).

Conclusions

ORIF may be suggested for quadrilateral plate fractures in the elderly. Walid’s classification system is associated with the reduction quality and functional recovery.
Percutaneous vertebroplasty versus kyphoplasty for the treatment of neurologically intact osteoporotic Kümmell’s disease
Authors: Dai Shou-qian , Qin Rong-qing , Shi Xiu , Yang Hui-lin
Published: January 2021

Background

Percutaneous vertebroplasty (PVP) and kyphoplasty (PKP) have been widely used to treat neurologically intact osteoporotic Kümmell’s disease (KD), but it is still unclear which treatment is more advantageous. Our study aimed to compare and investigate the safety and clinical efficacy of PVP and PKP in the treatment of KD.

Methods

The relevant data that 64 patients of neurologically intact osteoporotic KD receiving PVP (30 patients) or PKP (34 patients) were analyzed. Surgical time, operation costs, intraoperative blood loss, volume of bone cement injection, and fluoroscopy times were compared. Occurrence of cement leakage, transient fever and re-fracture were recorded. Universal indicators of visual analogue scale (VAS) and Oswestry disability index (ODI) were evaluated separately before surgery and at 1 day, 6 months, 1 year, 2 years and the final follow-up after operation. The height of anterior edge of the affected vertebra and the Cobb’s angle were assessed by imaging.

Results

All patients were followed up for at least 24 months. The volume of bone cement injection, intraoperative blood loss, occurrence of bone cement leakage, transient fever and re-fracture between two groups showed no significant difference. The surgical time, the operation cost and fluoroscopy times of the PKP group was significantly higher than that of the PVP group. The post-operative VAS, ODI scores, the height of the anterior edge of the injured vertebrae and kyphosis deformity were significantly improved in both groups compared with the pre-operation. The improvement of vertebral height and kyphosis deformity in PKP group was significantly better than that in the PVP group at every same time point during the follow-up periods, but the VAS and ODI scores between the two groups showed no significant difference.

Conclusion

PVP and PKP can both significantly alleviate the pain of patients with KD and obtain good clinical efficacy and safety. By contrast, PKP can achieve better imaging height and kyphosis correction, while PVP has the advantages of shorter operation time, less radiation volume and operation cost.
CRISPR/Cas9-mediated knockout of clinically relevant alloantigenes in human primary T cells
Authors: Kamali Elahe , Rahbarizadeh Fatemeh , Hojati Zohreh , Frödin Morten
Published: January 2021

Background

The ability of CRISPR/Cas9 to mutate any desired genomic locus is being increasingly explored in the emerging area of cancer immunotherapy. In this respect, current efforts are mostly focused on the use of autologous (i.e. patient-derived) T cells. The autologous approach, however, has drawbacks in terms of manufacturing time, cost, feasibility and scalability that can affect therapeutic outcome or wider clinical application. The use of allogeneic T cells from healthy donors may overcome these limitations. For this strategy to work, the endogenous T cell receptor (TCR) needs to be knocked out in order to reduce off-tumor, graft-versus-host-disease (GvHD). Furthermore, CD52 may be knocked out in the donor T cells, since this leaves them resistant to the commonly used anti-CD52 monoclonal antibody lymphodepletion regimen aiming to suppress rejection of the infused T cells by the recipient. Despite the great prospect, genetic manipulation of human T cells remains challenging, in particular how to deliver the engineering reagents: virus-mediated delivery entails the inherent risk of altering cancer gene expression by the genomically integrated CRISPR/Cas9. This is avoided by delivery of CRISPR/Cas9 as ribonucleoproteins, which, however, are fragile and technically demanding to produce. Electroporation of CRISPR/Cas9 expression plasmids would bypass the above issues, as this approach is simple, the reagents are robust and easily produced and delivery is transient.

Results

Here, we tested knockout of either TCR or CD52 in human primary T cells, using electroporation of CRISPR/Cas9 plasmids. After validating the CRISPR/Cas9 constructs in human 293 T cells by Tracking of Indels by Decomposition (TIDE) and Indel Detection by Amplicon Analysis (IDAA) on-target genomic analysis, we evaluated their efficacy in primary T cells. Four days after electroporation with the constructs, genomic analysis revealed a knockout rate of 12–14% for the two genes, which translated into 7–8% of cells showing complete loss of surface expression of TCR and CD52 proteins, as determined by flow cytometry analysis.

Conclusion

Our results demonstrate that genomic knockout by electroporation of plasmids encoding CRISPR/Cas9 is technically feasible in human primary T cells, albeit at low efficiency.
Exploring nursing managers’ perceptions of nursing workforce management during the outbreak of COVID-19: a content analysis study
Authors: Poortaghi Sarieh , Shahmari Mehraban , Ghobadi Akram
Published: January 2021

Background

The COVID-19 pandemic is a serious threat to public health worldwide. Therefore, a coordinated global response is needed to prepare health care systems to face this unprecedented challenge. Proper human resource management can increase nurses’ productivity and quality of care. Therefore, the present study aims to explore the nursing managers’ perception of nursing workforce management during the outbreak of COVID-19.

Methods

This is a qualitative study with conventional content analysis using Granheim and Landman approach. In this study, 15 nursing managers were selected by purposeful sampling method. Data were collected using in-depth semi-structured interviews. Ethical considerations were applied to all stages of the study. In this study, MAXQDA software version 10 was used to help manage the data.

Results

66% of the participants (10/5) were female. The mean age of participants was 44 years, mean work experience of 19 years, and mean management experience of 9 years. Three categories and seven sub-categories emerged from the data analysis: 1) management of workforce recruitment (volunteer workforces, non-volunteer workforces), 2) management of workforce arrangement (flexible work schedule, rearrangement of the workforce), and 3) management of workforce retention (preventive measures, motivational measures, and psychological support).

Conclusion

Management in critical situations requires the use of flexible and situational management principles to recruit, arrange and retain workforce, and also to compensate for the lack of manpower.
Emerging interactions between diet, gastrointestinal helminth infection, and the gut microbiota in livestock
Authors: Williams Andrew R. , Myhill Laura J. , Stolzenbach Sophie , Nejsum Peter , Mejer Helena , Nielsen Dennis S. , Thamsborg Stig M.
Published: January 2021

Increasing evidence suggests that nutritional manipulation of the commensal gut microbiota (GM) may play a key role in maintaining animal health and production in an era of reduced antimicrobial usage. Gastrointestinal helminth infections impose a considerable burden on animal performance, and recent studies suggest that infection may substantially alter the composition and function of the GM. Here, we discuss the potential interactions between different bioactive dietary components (prebiotics, probiotics and phytonutrients) and helminth infection on the GM in livestock. A number of recent studies suggest that host diet can strongly influence the nature of the helminth-GM interaction. Nutritional manipulation of the GM may thus impact helminth infection, and conversely infection may also influence how the GM responds to dietary interventions. Moreover, a dynamic interaction exists between helminths, the GM, intestinal immune responses, and inflammation. Deciphering the mechanisms underlying the diet-GM-helminth axis will likely inform future helminth control strategies, as well as having implications for how health-promoting feed additives, such as probiotics, can play a role in sustainable animal production.
Gene expression profiling for the diagnosis of multiple primary malignant tumors
Authors: Zheng Yu , Sun Yifeng , Kuai Yue , Fu Guoxiang , An Huimin , Chen Jinyun , Chen Jinying , Zhu Jiajun , Wo Yixin , Wu Yiwang , Song Kaibin , Xu Qinghua , Wu Di , Huang Deshuang , Wang Qifeng , Pan Hongming
Published: January 2021

Background

The incidence of multiple primary malignant tumors (MPMTs) is rising due to the development of screening technologies, significant treatment advances and increased aging of the population. For patients with a prior cancer history, identifying the tumor origin of the second malignant lesion has important prognostic and therapeutic implications and still represents a difficult problem in clinical practice.

Methods

In this study, we evaluated the performance of a 90-gene expression assay and explored its potential diagnostic utility for MPMTs across a broad spectrum of tumor types. Thirty-five MPMT patients from Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University and Fudan University Shanghai Cancer Center were enrolled; 73 MPMT specimens met all quality control criteria and were analyzed by the 90-gene expression assay.

Results

For each clinical specimen, the tumor type predicted by the 90-gene expression assay was compared with its pathological diagnosis, with an overall accuracy of 93.2% (68 of 73, 95% confidence interval 0.84–0.97). For histopathological subgroup analysis, the 90-gene expression assay achieved an overall accuracy of 95.0% (38 of 40; 95% CI 0.82–0.99) for well-moderately differentiated tumors and 92.0% (23 of 25; 95% CI 0.82–0.99) for poorly or undifferentiated tumors, with no statistically significant difference (p-value > 0.5). For squamous cell carcinoma specimens, the overall accuracy of gene expression assay also reached 87.5% (7 of 8; 95% CI 0.47–0.99) for identifying the tumor origins.

Conclusions

The 90-gene expression assay provides flexibility and accuracy in identifying the tumor origin of MPMTs. Future incorporation of the 90-gene expression assay in pathological diagnosis will assist oncologists in applying precise treatments, leading to improved care and outcomes for MPMT patients.
Hepatic safety of repeated treatment with pyronaridine‐artesunate versus artemether–lumefantrine in patients with uncomplicated malaria: a secondary analysis of the WANECAM 1 data from Bobo-Dioulasso, Burkina Faso
Authors: Compaoré Yves Daniel , Zongo Issaka , Somé Anyirékun F. , Barry Nouhoun , Nikiéma Frederick , Kaboré Talato N. , Ouattara Aminata , Kabré Zachari , Wermi Kadidiatou , Zongo Moussa , Yerbanga Rakiswende S. , Sagara Issaka , Djimdé Abdoulaye , Ouédraogo Jean Bosco
Published: January 2021

Background

The use of pyronaridine-artesunate (PA) has been associated with scarce transaminitis in patients. This analysis aimed to evaluate the hepatic safety profile of repeated treatment with PA versus artemether–lumefantrine (AL) in patients with consecutive uncomplicated malaria episodes in Bobo-Dioulasso, Burkina Faso.

Methods

This study analysed data from a clinical trial conducted from 2012 to 2015, in which participants with uncomplicated malaria were assigned to either PA or AL arms and followed up to 42 days. Subsequent malaria episodes within a 2-years follow up period were also treated with the same ACT initially allocated. Transaminases (AST/ALT), alkaline phosphatase (ALP), total and direct bilirubin were measured at days 0 (baseline), 3, 7, 28 and on some unscheduled days if required. The proportions of non-clinical hepatic adverse events (AEs) following first and repeated treatments with PA and AL were compared within study arms. The association of these AEs with retreatment in each arm was also determined using a logistic regression model.

Results

A total of 1379 malaria episodes were included in the intention to treat analysis with 60% of all cases occurring in the AL arm. Overall, 179 non-clinical hepatic AEs were recorded in the AL arm versus 145 in the PA arm. Elevated ALT was noted in 3.05% of treated malaria episodes, elevated AST 3.34%, elevated ALP 1.81%, and elevated total and direct bilirubin in 7.90% and 7.40% respectively. Retreated participants were less likely to experience elevated ALT and AST than first episode treated participants in both arms. One case of Hy’s law condition was recorded in a first treated participant of the PA arm. Participants from the retreatment group were 76% and 84% less likely to have elevated ALT and AST, respectively, in the AL arm and 68% less likely to present elevated ALT in the PA arm. In contrast, they were almost 2 times more likely to experience elevated total bilirubin in both arms.

Conclusions

Pyronaridine-artesunate and artemether–lumefantrine showed similar hepatic safety when used repeatedly in participants with uncomplicated malaria. Pyronaridine-artesunate represents therefore a suitable alternative to the current first line anti-malarial drugs in use in endemic areas.

Trial registrationPan African Clinical Trials Registry. PACTR201105000286876
Dietary intake of branched-chain amino acids in relation to depression, anxiety and psychological distress
Authors: Koochakpoor Glareh , Salari-Moghaddam Asma , Keshteli Ammar Hassanzadeh , Afshar Hamid , Esmaillzadeh Ahmad , Adibi Peyman
Published: January 2021

Background

There is no previous study that examined the association between branched-chain amino acids (BCAAs) intake and odds of psychological disorders. The aim of this study was to investigate the association between dietary BCAAs and odds of psychological disorders including depression, anxiety, and psychological distress in a large sample of Iranian adults.

Methods

In this cross-sectional study on 3175 Iranian adults aged 18–55 years, a validated food frequency questionnaire was used to assess dietary intakes. BCAAs intake was computed by summing up the amount of valine, leucine, and isoleucine intake from all food items in the questionnaire. Psychological health was examined through the use of Iranian validated version of the Hospital Anxiety and Depression Scale (HADS). Psychological distress was assessed using General Health Questionnaire (GHQ). For depression and anxiety, scores of 8 or more on either subscale were considered as psychological disorders and scores of 0–7 were defined as “normal”. In terms of psychological distress, the score of 4 or more was defined as psychological distress.

Results

Mean age of study participants was 36.2 ± 7.8 years. Overall, 26.4% (n = 837) of study subjects had depression, 11.9% (n = 378) had anxiety and 20.9% (n = 665) were affected by psychological distress. After controlling for potential confounders, participants in the highest tertile of total BCAAs intake had lower odds of depression (OR: 0.76; 95% CI: 0.60–0.96) and anxiety (OR: 0.66; 95% CI: 0.47–0.91) compared with those in the lowest tertile. Participants in the top tertile of valine intake had a lower odds of depression (OR: 0.76; 95% CI: 0.60–0.96) and anxiety (OR: 0.65; 95% CI: 0.47–0.90) compared with those in the bottom tertile. A significant inverse association was also seen between leucine intake and depression (OR: 0.77; 95% CI: 0.61–0.98) and anxiety (OR: 0.66; 95% CI: 0.47–0.91). In addition, a significant inverse association was observed between isoleucine intake and odds of depression (OR: 0.75; 95% CI: 0.59–0.95) and anxiety (OR: 0.62; 95% CI: 0.45–0.86). There was no significant association between isoleucine intake and odds of psychological distress.

Conclusion

Evidence indicating an inverse association between dietary intake of BCAAs and odds of depression and anxiety was found. Prospective studies are required to confirm these findings.
The effects of canola and olive oils consumption compared to sunflower oil, on lipid profile and hepatic steatosis in women with polycystic ovarian syndrome: a randomized controlled trial
Authors: Yahay Maryam , Heidari Zahra , Allameh Zahra , Amani Reza
Published: January 2021

Background

Polycystic Ovarian Syndrome (PCOS) is one of the most common endocrinopathies and metabolic disorders in women during their reproductive years. It is often associated with dyslipidemia and other risk factors of cardiovascular diseases (CVD). This study was aimed to evaluate dietary intervention effects with canola and olive oils compared to sunflower oil on lipid profile and fatty liver severity among women with PCOS.

Method

This study was a 10-week intervention including 72 women with PCOS. Patients were randomly assigned to three groups for receiving 25 g/day canola, olive, or sunflower oils for 10 weeks. The primary and secondary outcomes were to assess changes in lipid profile and in fatty liver severity, respectively.

Result

At the end of the study, 72 patients with a mean age of 29.31 were analysed. Canola oil consumption resulted in a significant reduction in serum levels of TG (P = 0.002) and TC/HDL (P = 0.021), LDL/HDL (P = 0.047), and TG/HDL (P = 0.001) ratios, however, there was no significant reduction in lipid profile following olive oil consumption. Canola (P < 0.001) and olive oils (P = 0.005) could significantly reduce the fatty liver grade. Moreover, HOMA-IR in both canola (P < 0.001) and olive (P = 0.004) groups was significantly decreased.

Conclusion

In total, compared to olive and sunflower oils, significant improvements in lipid profile, liver function, and HOMA-IR were observed following canola oil consumption in women with PCOS.

Trial registration

IR.MUI.RESEARCH.REC.1397.315. Registered 30 JUNE 2019 - Retrospectively registered, https://www.irct.ir/trial/38684
Co-production in local government: process, codification and capacity building of new knowledge in collective reflection spaces. Workshops findings from a UK mixed methods study
Authors: van der Graaf Peter , Cheetham Mandy , Redgate Sam , Humble Clare , Adamson Ashley
Published: January 2021

Background

Co-production of research evidence is valued by local government to improve effective decision-making about public services in times of austerity. However, underlying structural issues of power (so-called ‘dark shadows of co-production’) challenge this ambition with limited evidence on how to embed research use sustainably. In this paper we reflect on mechanisms for increasing co-production in local government.

Methods

This paper presents findings from a Health Foundation funded research project that explored how a culture of evidence use to improve population health could be embedded in UK local government. Five linked work packages were undertaken using mixed methods. In this paper, we report the views of UK local authority staff who participated in four workshops (n = 54), informed by a rapid literature review and an online scoping survey.

Results

We identified five themes that facilitate public health evidence use in local government: (1) new governance arrangements to integrate national and local policies, (2) codifying research evidence through local system-wide approaches and (3) ongoing evaluation of programmes, and (4) overcoming political and cultural barriers by increasing absorptive capacity of Local Authorities to embed co-produced knowledge in their cognitive structures. This requires adaptive governance through relationship building between academic researchers and Local Authority staff and shared understanding of fragmented local policy making, which are supported by (5) collective spaces for reflection within local government.

Conclusions

Creating collective spaces for reflection in between government departments allows for iterative, interactive processes of co-production with external partners that support emergence of new governance structures to socially action the co-produced knowledge in context and build capacity for sustained evidence use.
Acute systemic LPS-exposure impairs perivascular CSF distribution in mice
Authors: Manouchehrian Oscar , Ramos Marta , Bachiller Sara , Lundgaard Iben , Deierborg Tomas
Published: January 2021

Background

The exchange of cerebrospinal (CSF) and interstitial fluid is believed to be vital for waste clearance in the brain. The sleep-dependent glymphatic system, which is comprised of perivascular flow of CSF and is largely dependent on arterial pulsatility and astrocytic aquaporin-4 (AQP4) expression, facilitates much of this brain clearance. During the last decade, several observations have indicated that impaired glymphatic function goes hand in hand with neurodegenerative diseases. Since pathologies of the brain carry inflammatory components, we wanted to know how acute inflammation, e.g., with lipopolysaccharide (LPS) injections, would affect the glymphatic system. In this study, we aim to measure the effect of LPS on perivascular CSF distribution as a measure of glymphatic function.

Methods

Three hours after injection of LPS (1 mg/kg i.p.), C57bl/6 mice were (1) imaged for two CSF tracers, injected into cisterna magna, (2) transcardially perfused with buffer, or (3) used for physiological readouts. Tracer flow was imaged using a low magnification microscope on fixed brains, as well as using vibratome-cut slices for measuring tracer penetration in the brain. Cytokines, glial, and BBB-permeability markers were measured with ELISAs, Western blots, and immunohistochemistry. Cerebral blood flow was approximated using laser Doppler flowmetry, respiration and heart rate with a surgical monitor, and AQP4-polarization was quantified using confocal microscopy of immunolabeled brain sections.

Results

LPS-injections significantly lowered perivascular CSF tracer flow and penetration into the parenchyma. No differences in AQP4 polarization, cytokines, astroglial and BBB markers, cerebral blood flow, or respiration were detected in LPS-injected mice, although LPS did elevate cortical Iba1+ area and heart rate.

Conclusions

This study reports another physiological response after acute exposure to the bacterial endotoxin LPS, namely the statistically significant decrease in perivascular distribution of CSF. These observations may benefit our understanding of the role of systemic inflammation in brain clearance.
A comparison of methods for interpreting random forest models of genetic association in the presence of non-additive interactions
Authors: Orlenko Alena , Moore Jason H.
Published: January 2021

Background

Non-additive interactions among genes are frequently associated with a number of phenotypes, including known complex diseases such as Alzheimer’s, diabetes, and cardiovascular disease. Detecting interactions requires careful selection of analytical methods, and some machine learning algorithms are unable or underpowered to detect or model feature interactions that exhibit non-additivity. The Random Forest method is often employed in these efforts due to its ability to detect and model non-additive interactions. In addition, Random Forest has the built-in ability to estimate feature importance scores, a characteristic that allows the model to be interpreted with the order and effect size of the feature association with the outcome. This characteristic is very important for epidemiological and clinical studies where results of predictive modeling could be used to define the future direction of the research efforts. An alternative way to interpret the model is with a permutation feature importance metric which employs a permutation approach to calculate a feature contribution coefficient in units of the decrease in the model’s performance and with the Shapely additive explanations which employ cooperative game theory approach. Currently, it is unclear which Random Forest feature importance metric provides a superior estimation of the true informative contribution of features in genetic association analysis.

Results

To address this issue, and to improve interpretability of Random Forest predictions, we compared different methods for feature importance estimation in real and simulated datasets with non-additive interactions. As a result, we detected a discrepancy between the metrics for the real-world datasets and further established that the permutation feature importance metric provides more precise feature importance rank estimation for the simulated datasets with non-additive interactions.

Conclusions

By analyzing both real and simulated data, we established that the permutation feature importance metric provides more precise feature importance rank estimation in the presence of non-additive interactions.
Infection control strategy and primary care assistance in Campania region during the national lockdown due to COVID-19 outbreak: the experience of two tertiary emergency centers
Authors: Mauro Angela , Improda Nicola , Zenzeri Letizia , Valitutti Francesco , Vecchione Erica , Esposito Sara , Tipo Vincenzo
Published: January 2021

Background

COVID-19 pandemic has markedly affected emergency care, due to sudden limitation of health care capacity by general practitioners (GP) and urgent need for infection control strategies. We evaluated the activity of the Emergency Department (ED) during the national lockdown (March 8–April 30), as well as the outcomes of our infection control strategy.

Results

Despite a reduction in access by one fifth, a proportion of febrile patients comparable to 2019 was seen (829/2492, 33.3% vs 4580/13.342, 34.3%, p = 0.3). Diagnostic swab for COVID-19 was performed in 25% of patients, especially in subjects with co-morbidities or multiple access. Six infected cases were identified, all presenting with febrile disease. Only two positive patients fulfilled the criteria for diagnostic swab provided by the Italian Health Authorities, because of close contact with suspected or confirmed cases.

The rate of admission for febrile or respiratory conditions was higher than the same period of 2019 (33.4% vs 25.9%, p < 0.0001). None of the 105 health-care professionals working during the study time lapse exhibited anti-SARS-CoV-2 seroconversion. Among the 589 patients with information available, 54.9% declared no medical consultation at all prior to coming to ED, while only 40 (of which 27 with fever) had been examined by their GP before coming to ED. Nevertheless, 35.6% of the cases were already taking medications. None of the 9 patients requiring intensive care reported recent pediatric consultation, despite symptoms duration up to 30 days.

Conclusion

Our results provide evidence that the reduced capacity of primary care facilities during the national lockdown may have caused a high rate of self-medication as well as a delayed provision of care in some patients. Identification of pediatric patients affected with SARS-CoV-2 infection remains a challenge because of the absence of reliable predictive factors. Finally, the use of specific triage centers, with dedicated pathways to diagnose SARS-CoV-2 infection, trace contacts and allow adequate care after swabs, is effective in preventing spreading of the infection.
Augmentation of EMDR with multifocal transcranial current stimulation (MtCS) in the treatment of fibromyalgia: study protocol of a double-blind randomized controlled exploratory and pragmatic trial
Authors: Gardoki-Souto I. , Martín de la Torre O. , Hogg B. , Redolar-Ripoll D. , Valiente-Gómez A. , Martínez Sadurní L. , Blanch J. M. , Lupo W. , Pérez V. , Radua J. , Amann B. L. , Moreno-Alcázar A.
Published: January 2021

Background

Fibromyalgia (FM) is a generalized, widespread chronic pain disorder affecting 2.7% of the general population. In recent years, different studies have observed a strong association between FM and psychological trauma. Therefore, a trauma-focused psychotherapy, such as eye movement desensitization and reprocessing (EMDR), combined with a non-invasive brain stimulation technique, such as multifocal transcranial current stimulation (MtCS), could be an innovative adjunctive treatment option. This double-blind randomized controlled trial (RCT) analyzes if EMDR therapy is effective in the reduction of pain symptoms in FM patients and if its potential is boosted with the addition of MtCS.

Methods

Forty-five patients with FM and a history of traumatic events will be randomly allocated to Waiting List, EMDR + active-MtCS, or EMDR + sham-MtCS. Therapists and patients will be kept blind to MtCS conditions, and raters will be kept blind to both EMDR and MtCS. All patients will be evaluated at baseline, post-treatment, and follow-up at 6 months after post-treatment. Evaluations will assess the following variables: sociodemographic data, pain, psychological trauma, sleep disturbance, anxiety and affective symptoms, and wellbeing.

Discussion

This study will provide evidence of whether EMDR therapy is effective in reducing pain symptoms in FM patients, and whether the effect of EMDR can be enhanced by MtCS.

Trial registration

ClinicalTrials.gov NCT04084795. Registered on 2 August 2019.
The role of CT imaging for management of COVID-19 in epidemic area: early experience from a University Hospital
Authors: Bollineni Vikram rao , Nieboer Koenraad Hans , Döring Seema , Buls Nico , de Mey Johan
Published: January 2021

Background

To evaluate the clinical value of the chest CT scan compared to the reference standard real-time polymerase chain reaction (RT-PCR) in COVID-19 patients.

Methods

From March 29th to April 15th of 2020, a total of 240 patients with respiratory distress underwent both a low-dose chest CT scan and RT-PCR tests. The performance of chest CT in diagnosing COVID-19 was assessed with reference to the RT-PCR result. Two board-certified radiologists (mean 24 years of experience chest CT), blinded for the RT-PCR result, reviewed all scans and decided positive or negative chest CT findings by consensus.

Results

Out of 240 patients, 60% (144/240) had positive RT-PCR results and 89% (213/240) had a positive chest CT scans. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of chest CT in suggesting COVID-19 were 100% (95% CI: 97–100%, 144/240), 28% (95% CI: 19–38%, 27/240), 68% (95% CI: 65–70%) and 100%, respectively. The diagnostic accuracy of the chest CT suggesting COVID-19 was 71% (95% CI: 65–77%). Thirty-three patients with positive chest CT scan and negative RT-PCR test at baseline underwent repeat RT-PCR assay. In this subgroup, 21.2% (7/33) cases became RT-PCR positive.

Conclusion

Chest CT imaging has high sensitivity and high NPV for diagnosing COVID-19 and can be considered as an alternative primary screening tool for COVID-19 in epidemic areas. In addition, a negative RT-PCR test, but positive CT findings can still be suggestive of COVID-19 infection.