bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementation of a malaria prevention education intervention in Southern Ethiopia: a qualitative evaluation
Authors: Zerdo Zerihun , Anthierens Sibyl , Van geertruyden Jean-Pierre , Massebo Fekadu , Biresaw Gelila , Shewangizaw Misgun , Endashaw Gesila , Tunje Abayneh , Masne Matewos , Bastiaens Hilde 
Published: September 2022

Abstract
Background
Though school-aged children (SAC) are at high risk of malaria, they are the ones that benefit the least from malaria prevention measures. A cluster randomized controlled trial was conducted to evaluate the effect of malaria prevention education (MPE) on insecticide-treated bed net (ITN) utilization and prompt diagnosis, reported incidence and treatment (PDAT) of malaria. Qualitative evaluation of the implementation of such interventions is vital to explain its effectiveness and will serve as guidance for future interventions. Therefore, this study aimed to evaluate the implementation of the MPE in southern Ethiopia.

Methods
The trial was registered in Pan African Clinical Trials Registry (PACTR202001837195738) on 21/01/2020. A descriptive qualitative study using semi-structured interview with participants of the MPE was conducted in January 2020 and January 2021. The collected data were transcribed verbatim and analyzed thematically. The analysis of the data was supported by NVivo.

Results
The four themes identified after evaluation of MPE training were the setup of the training, challenges for the success of the training, anticipated challenges for practice as per the protocol and experienced immediate influences of the training. Participants appreciated the training: content covered, way of delivery and the mix of the participants. The context specific facilitators to bed net use were the collateral benefits of ITN and perceived at high risk of malaria while its barriers were quality and quantity of the bed nets, bed net associated discomforts, malaria health literacy and housing condition. Severeness of malaria symptoms and malaria health literacy were reported as both barriers and facilitators of the PDAT of malaria. The identified facilitators of PDAT of malaria were health professionals’ attitude and exposure to MPE while its barriers were poverty, use of traditional medicine, health facility problems and Coronavirus Disease 2019 (COVID-19) pandemic.

Conclusion
Low attendance of parents in the training was the major challenge for the success of MPE. National malaria program should ensure the access to malaria prevention measures; and future studies using increased frequency of the intervention embedded with monitoring adherence to the intervention protocol shall be conducted to improve the gains from existing malaria interventions.
Patient characteristics, pain treatment patterns, and incidence of total joint replacement in a US population with osteoarthritis
Authors: Shinde Mayura , Rodriguez-Watson Carla , Zhang Tancy C. , Carrell David S. , Mendelsohn Aaron B. , Nam Young Hee , Carruth Amanda , Petronis Kenneth R. , McMahill-Walraven Cheryl N. , Jamal-Allial Aziza , Nair Vinit , Pawloski Pamala A. , Hickman Anne , Brown Mark T. , Francis Jennie , Hornbuckle Ken , Brown Jeffrey S. , Mo Jingping 
Published: September 2022

Abstract
Background
Currently available medications for chronic osteoarthritis pain are only moderately effective, and their use is limited in many patients because of serious adverse effects and contraindications. The primary surgical option for osteoarthritis is total joint replacement (TJR). The objectives of this study were to describe the treatment history of patients with osteoarthritis receiving prescription pain medications and/or intra-articular corticosteroid injections, and to estimate the incidence of TJR in these patients.

Methods
This retrospective, multicenter, cohort study utilized health plan administrative claims data (January 1, 2013, through December 31, 2019) of adult patients with osteoarthritis in the Innovation in Medical Evidence Development and Surveillance Distributed Database, a subset of the US FDA Sentinel Distributed Database. Patients were analyzed in two cohorts: those with prevalent use of “any pain medication” (prescription non-steroidal anti-inflammatory drugs [NSAIDs], opioids, and/or intra-articular corticosteroid injections) using only the first qualifying dispensing (index date); and those with prevalent use of “each specific pain medication class” with all qualifying treatment episodes identified.

Results
Among 1 992 670 prevalent users of “any pain medication”, pain medications prescribed on the index date were NSAIDs (596 624 [29.9%] patients), opioids (1 161 806 [58.3%]), and intra-articular corticosteroids (323 459 [16.2%]). Further, 92 026 patients received multiple pain medications on the index date, including 71 632 (3.6%) receiving both NSAIDs and opioids. Altogether, 20.6% of patients used an NSAID at any time following an opioid index dispensing and 17.2% used an opioid following an NSAID index dispensing. The TJR incidence rates per 100 person-years (95% confidence interval [CI]) were 3.21 (95% CI: 3.20–3.23) in the “any pain medication” user cohort, and among those receiving “each specific pain medication class” were NSAIDs, 4.63 (95% CI: 4.58–4.67); opioids, 7.45 (95% CI: 7.40–7.49); and intra-articular corticosteroids, 8.05 (95% CI: 7.97–8.13).

Conclusions
In patients treated with prescription medications for osteoarthritis pain, opioids were more commonly prescribed at index than NSAIDs and intra-articular corticosteroid injections. Of the pain medication classes examined, the incidence of TJR was highest in patients receiving intra-articular corticosteroids and lowest in patients receiving NSAIDs.
Which assisted reproductive technology (ART) treatment strategy is the most clinically and cost-effective for women of advanced maternal age: a Markov model
Authors: Lee Evelyn , Zhang Jinhui 
Published: September 2022

Abstract
Objective
To evaluate the clinical and cost-effectiveness of preimplantation genetic testing for aneuploidy, social freezing, donor and autologous assisted reproductive technology (ART) treatment strategies for women aged 35–45 following 6–12 months of infertility.

Methods
Four Markov decision-analytic models comprising: (i) Preimplantation genetic testing for aneuploidy (PGT-A); (ii) autologous ART from age 40 using oocytes cryopreserved at age 32 (social freezing); (iii) ART using donated oocytes (donor ART); (iv) standard autologous ART treatment (standard care) were developed for a hypothetical cohort of 35 to 45 years old ART naïve women with 6–12 months of infertility. Input probabilities for key parameters including live birth rates were obtained from the available literature. Deterministic and probabilistic sensitivity analyses were conducted to address uncertainty in estimating the parameters and around the model’s assumptions. Cost effectiveness was assessed from both societal and patient perspectives .

Result(s)
For infertile women at age 40 and above, social freezing is the most cost-saving strategy with the highest chance of a cumulative live birth at a lowest cost from a societal perspective. PGT-A and donor ART were associated with higher treatment costs and cumulative live-birth rates compared with the autologous ART. Among the four ART strategies, standard autologous ART has the lowest cumulative live birth rate of 45% at age 35 and decreasing to 1.6% by age 45 years. At a willingness-to-pay threshold of Australian dollars (A$)50,000, our model shows all alternative treatment strategies –PGT-A, social freezing and donor ART have a higher probability of being cost-effective compared to the standard autologous ART treatment. However, higher out-of-pocket expenditure may impede their access to these alternate strategies.

Conclusion
Given current evidence, all alternate strategies have a higher probability of being cost-effective compared to the standard autologous ART treatment. Whether this represents value for money depends on societal and individual’s willingness-to-pay for children conceived with ART treatment.
Patients’ self-triage for unscheduled urgent care: a preliminary study on the accuracy and factors affecting the performance of a Belgian self-triage platform
Authors: Gilbert Allison , Diep Anh Nguyet , Boufraioua Maryame , Pétré Benoit , Donneau Anne-Françoise , Ghuysen Alexandre 
Published: September 2022

Abstract
Background
Management of unscheduled urgent care is a complex concern for many healthcare providers. Facing the challenge of appropriately dispatching unscheduled care, primary and emergency physicians have collaboratively implemented innovative strategies such as telephone triage. Currently, new original solutions tend to emerge with the development of new technologies. We created an interactive patient self-triage platform, ODISSEE, and aimed to explore its accuracy and potential factors affecting its performance using clinical case scenarios.

Methods
The ODISSEE platform was developed based on previously validated triage protocols for out-of-hours primary care. ODISSEE is composed of 18 icons leading to algorithmic questions that finally provide an advised orientation (emergency or primary care services). To investigate ODISSEE performance, we used 100 clinical case scenarios, each associated with a preestablished orientation determined by a group of experts. Fifteen volunteers were asked to self-triage with 50 randomly selected scenarios using ODISSEE on a digital tablet. Their triage results were compared with the experts’ references.

Results
The 15 participants performed a total of 750 self-triages, which matched the experts references regarding the level of care in 85.6% of the cases. The orientation was incorrect in 14.4%, with an undertriage rate of 1.9% and an overtriage rate of 12.5%. The tool’s specificity and sensitivity to advise participants on the appropriate level of care were 69% (95% CI: 64—74) and 97% (95% CI: 95—98) respectively. When combined with advice on the level of urgency, the tool only found the correct orientation in 68.4% with 9.2% of undertriages and 22.4% of overtriages. Some participant characteristics and the types of medical conditions demonstrated a significant association with the tool performance.

Conclusion
Self-triage apps, such as the ODISSEE platform, could represent an innovative method to allow patients to self-triage to the most appropriate level of care. This study based on clinical vignettes highlights some positive arguments regarding ODISSEE safety, but further research is needed to assess the generalizability of such tools to the population without equity issues.
Evaluating the impact of glucokinase activation on risk of cardiovascular disease: a Mendelian randomisation analysis
Authors: Wang Ke , Shi Mai , Huang Chuiguo , Fan Baoqi , Luk Andrea O. Y. , Kong Alice P. S. , Ma Ronald C. W. , Chan Juliana C. N. , Chow Elaine 
Published: September 2022

Abstract
Background
Glucokinase activators (GKAs) are an emerging class of glucose lowering drugs that activate the glucose-sensing enzyme glucokinase (GK). Pending formal cardiovascular outcome trials, we applied two-sample Mendelian randomisation (MR) to investigate the impact of GK activation on risk of cardiovascular diseases.

Methods
We used independent genetic variants in or around the glucokinase gene meanwhile associated with HbA1c at genome-wide significance (P < 5 × 10−8) in the Meta-Analyses of Glucose and Insulin-related traits Consortium study (N = 146,806; European ancestry) as instrumental variables (IVs) to mimic the effects of GK activation. We assessed the association between genetically proxied GK activation and the risk of coronary artery disease (CAD; 122,733 cases and 424,528 controls), peripheral arterial disease (PAD; 7098 cases and 206,541 controls), stroke (40,585 cases and 406,111 controls) and heart failure (HF; 47,309 cases and 930,014 controls), using genome-wide association study summary statistics of these outcomes in Europeans. We compared the effect estimates of genetically proxied GK activation with estimates of genetically proxied lower HbA1c on the same outcomes. We repeated our MR analyses in East Asians as validation.

Results
Genetically proxied GK activation was associated with reduced risk of CAD (OR 0.38 per 1% lower HbA1c, 95% CI 0.29–0.51, P = 8.77 × 10−11) and HF (OR 0.54 per 1% lower HbA1c, 95% CI 0.41–0.73, P = 3.55 × 10−5). The genetically proxied protective effects of GKA on CAD and HF exceeded those due to non-targeted HbA1c lowering. There was no causal relationship between genetically proxied GK activation and risk of PAD or stroke. The estimates in sensitivity analyses and in East Asians were generally consistent.

Conclusions
GKAs may protect against CAD and HF which needs confirmation by long-term clinical trials.
Incremental prognostic value of triglyceride glucose index additional to coronary artery calcium score in asymptomatic low-risk population
Authors: Song Shinjeong , Choi Su‑Yeon , Park Hyo Eun , Han Hae‑Won , Park Sung Hak , Sung Jidong , Jung Hae Ok , Sung Ji Min , Chang Hyuk‑Jae 
Published: September 2022

Abstract
Background
The triglyceride glucose (TyG) index has been suggested as a reliable surrogate marker of insulin resistance which is a substantial risk factor for atherosclerotic cardiovascular disease (ASCVD). Several recent studies have shown the relationship between the TyG index and cardiovascular disease; however, the role of the TyG index in coronary artery calcification (CAC) progression has not been extensively assessed especially in low-risk population.

Methods
We enrolled 5775 Korean adults who had at least two CAC evaluations. We determined the TyG index using ln (fasting triglycerides [mg/dL] x fasting glucose [mg/dL]/2). The CAC progression was defined as either incident CAC in a CAC-free population at baseline or an increase of ≥ 2.5 units between the square roots of the baseline and follow-up coronary artery calcium scores (CACSs) of subjects with detectable CAC at baseline.

Results
CAC progression was seen in 1,382 subjects (23.9%) during mean 3.5 years follow-up. Based on the TyG index, subjects were stratified into four groups. Follow-up CACS and incidence of CAC progression were markedly elevated with rising TyG index quartiles (group I [lowest]:17.6% vs. group II:22.2% vs. group III:24.6% vs. group IV [highest]: 31.3%, p < 0.001). In multivariate logistic regression analysis, the TyG index was independent predictor of CAC progression (odds ratio: 1.57; 95% confidence interval: 1.33 to 1.81; p < 0.001) especially in baseline CACS ≤ 100 group.

Conclusion
The TyG index is an independent predictor of CAC progression in low-risk population. It adds incremental risk stratification over established factors including baseline CACS.
Crosstalk between tumor-associated macrophages and tumor cells promotes chemoresistance via CXCL5/PI3K/AKT/mTOR pathway in gastric cancer
Authors: Su Pengfei , Jiang Lin , Zhang Yingjing , Yu Tian , Kang Weiming , Liu Yuqin , Yu Jianchun 
Published: September 2022

Abstract
Background
5-fluorouracil (5-FU)-based chemotherapy regimen has been widely used for the treatment of gastric cancer, but meanwhile the development of chemotherapeutic resistance remains a major clinical challenge. Tumor microenvironment (TME) frequently correlates with the development of chemoresistance in human cancer. As a major component of TME, the role of tumor-associated macrophages (TAMs) in the chemoresistance of gastric cancer has not been fully elucidated.

Methods
Immunohistochemistry (IHC) was applied to detect the density of TAMs in clinical samples of 103 patients with gastric cancer who had undergone 5-FU-based neoadjuvant chemotherapy. 5-FU-resistant gastric cell lines MKN45-R and HGC27-R were established, macrophages were then separately co-cultured with MKN45-R, HGC27-R cells and their parental cells. The effect of gastric cancer cells on the polarization of macrophages, the biological function of M2-polaried macrophages and the mechanism for promoting 5-FU-resistance were investigated. Then the correlation between the expression of CXC motif chemokine ligand 5 (CXCL5) and the infiltration of hemoglobin scavenger receptor (CD163) positive and mannose receptor (CD206) positive macrophages was analyzed, the prognostic value of CXCL5 expression in clinical samples was further explored.

Results
The high infiltration of macrophages marked by CD68 in gastric cancer samples was significantly associated with the resistance of gastric cancer to chemotherapy. Gastric cancer cells could modulate macrophages to M2-like polarization through indirect co-culture, and chemoresistant cells were more efficient in inducing macrophages polarization to M2 phenotype. Co-culturing M2-polarized macrophages in turn enhanced 5-FU-resistance of gastric cancer cells, and it was further verified that CXCL5 derived from M2-polarized macrophages promoted chemoresistance through activing the PI3K/AKT/mTOR pathway. Besides, high level of CXCL5 could recruit monocytes to form more M2-polarized macrophages. Clinically, high expression of CXCL5 in gastric cancer samples was associated with the high infiltration of CD163 positive macrophages and CD206 positive macrophages, and patients with high expression of CXCL5 presented lower overall survival (OS) rates than those with low expression of CXCL5.

Conclusion
Interaction between TAMs and gastric cancer cells promoted chemoresistance in gastric cancer via CXCL5/PI3K/AKT/mTOR pathway. Thus, targeting TAMs and blocking the cell–cell crosstalk between TAMs and gastric cancer cells may represent prospective therapeutic strategies for patients with gastric cancer.
Challenges for drug checking services in Scotland: a qualitative exploration of police perceptions
Authors: Falzon Danilo , Aston Elizabeth V. , Carver Hannah , Masterton Wendy , Wallace Bruce , Sumnall Harry , Measham Fiona , Fletcher Emma , Gittins Rosalind , Priyadarshi Saket , Parkes Tessa 
Published: September 2022

Abstract
Background
The impact of policing practices on the engagement of people who use drugs (PWUD) with harm reduction services is well evidenced. Although the police have traditionally taken an enforcement role in responding to drug use, it is increasingly clear that they can play an important part in multiagency delivery of harm reduction interventions. Despite this, there have been no studies exploring police officer perceptions of drug checking services (DCS), which provide analytical testing of client drug samples alongside harm reduction support and advice.

Methods
Semi-structured interviews were conducted with 10 police officers to explore the policing and legal challenges which could be encountered in the delivery of DCS in Scotland.

Results
Participants expressed general support for DCS and described this support as part of a wider organisational shift towards public health-oriented policing. Participants also discussed different potential approaches to the policing of areas surrounding DCS including: formal limits on police presence around the service and/or stop and search powers in relation to personal possession; the effective decriminalisation of personal possession within a specified boundary around the service; and informal agreements between local divisions and DCS outlining expected policing practices. Any formal limitation on the capacity of police officers to respond to community concerns was viewed as problematic and as having the potential to erode public confidence in policing. Participants also highlighted the potential for frontline officers to utilise discretion in ways which could undermine public health goals. Legislative change, or national strategic guidance from relevant stakeholders, was seen as a means of providing ‘cover’, enabling local divisions to support the operation of drug checking.

Conclusions
Despite a small sample of participants, this study summarises key challenges to be addressed in the implementation and operation of DCS in Scotland, and more widely. The paper concludes with suggested opportunities to develop approaches to policing that can facilitate rather than impede implementation and operation of these services.
The effects of splenectomy in murine models of ischemic stroke: a systematic review and meta-analysis
Authors: Sternak Marko , Glasnović Anton , Josić Paula , Romić Dominik , Gajović Srećko 
Published: September 2022

AbstractBackgroundThe spleen, a substantial reservoir of non-differentiated monocytes, may play a crucial role in the pathophysiology of post-ischemic inflammation and influence outcomes after ischemic stroke.Aim of the studyTo analyze splenectomy as a preclinical intervention in murine models of ischemic stroke.MethodsFollowing systematic searches of PubMed, Scopus and Web of Science, a qualitative synthesis of study characteristics was performed, and the effect of splenectomy estimated by a three-level random-effects meta-analysis of infarct volumes and a conventional two-level random-effects meta-analysis of neurological deficit scores.ResultsDatabase searches identified a total of 14 studies, 13 of which were used for meta-analysis. The ischemic lesion volumes were reduced in splenectomized animals compared to the control groups (difference in standardized mean differences: − 1.42; 95% CI [− 1.98, − 0.85]; 95% PI [− 2.03, − 0.80];I2(2) = 19.04%; 95% CI [0.00%, 65.49%];I2(3) = 47.24%; 95% CI [0.00%, 85.23%]) and neurological deficit scores were improved (− 1.20; 95% CI [− 2.20, − 0.20]; 95% PI [− 4.58, 2.18];I2 = 77.5%; 95% CI [50.0%, 89.9%]). A subgroup analysis for infarct volumes showed that splenectomy performed prior to ischemia achieved a higher reduction of the ischemic lesion than when splenectomy was performed immediately prior or after stroke. Although the overall effect size of splenectomy could be classified as large, there was a significant presence of risks of bias, study heterogeneity, and a potential presence of publication bias.ConclusionDespite limitations related to heterogeneity, risks of bias, and potential publication bias, this meta-analysis points to the spleen and its functional cell populations as promising targets for the therapeutic modulation of post-stroke inflammation.
Prolonged mean response time in older adults with cardiovascular risk compared to healthy older adults
Authors: Kominami Kazuyuki , Akino Masatoshi 
Published: September 2022

Abstract
Background
During incremental exercise (Inc-Ex), the mean response time (MRT) of oxygen uptake (V̇O2) represents the time delay before changes in muscle V̇O2 reflect at the mouth level. MRT calculation by linear regression or monoexponential (τ’) fitting of V̇O2 data are known to be highly variable, and a combination of incremental and constant load exercise (CL-Ex) is more reproducible.

Methods
We evaluated MRT in older adults using linear regression and combination methods. We recruited 20 healthy adults (male: 9, 69.4 ± 6.8 years) and 10 cardiovascular risk subjects (male: 8, 73.0 ± 8.8 years). On day 1, they performed Inc-Ex using a 10W/min ramp protocol, for determination of the ventilatory anaerobic threshold (VAT) using the V-slope method. On day 2, they performed Inc-Ex to VAT exercise intensity and CL-Ex for 25min total. The MRT was calculated from the CL-Ex V̇O2 average and the time at equivalent V̇O2 in the Inc-Ex. We also assessed the amount of physical activity using the International Physical Activity Questionnaire short form (IPAQ-SF).

Results
The MRT of healthy participants and those at cardiovascular risk were 49.2 ± 36.3 vs. 83.6 ± 45.4s (p = 0.033). Total physical activity in the IPAQ-SF was inversely correlated with MRT.

Conclusion
The MRT was significantly prolonged in cardiovascular risk participants compared to healthy participants, possibly related to the amount of daily physical activity. Individual MRT may be useful for adjustment of exercise intensity, but this should also be based on daily physical activity and individual condition during exercise.