bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of preoperative pain in elderly patients with moderate to severe cognitive deficits and hip fracture: a retrospective, monocentric study in an orthogeriatric unit
Authors: Ruel Mathilde , Boussat Bastien , Boudissa Mehdi , Garnier Virginie , Bioteau Catherine , Tonetti Jérôme , Pailhe Régis , Gavazzi Gaëtan , Drevet Sabine
Published: October 2021

Background

Patients with cognitive deficits are 3 times more likely to suffer a hip fracture than geriatric patients of the same age group without cognitive deficits. The persistence of perioperative pain following hip fracture is a risk factor for the occurrence of delirium, poor functional prognosis, and the development of secondary chronic pain. Patients with cognitive deficits receive 20 to 60% less analgesics than those without cognitive deficits. Our retrospective descriptive monocentric study was performed in an orthogeriatric unit on a cohort of elderly patients hospitalized for hip fracture. The aim of the study was to compare the quantity of strong opioids delivered in a morphine sulfate equivalent daily during the preoperative period after a hip fracture between cognitively intact patients and those with cognitive deficits.

Results

Our total population of 69 patients had a median age of 90 years old, and 46% of these patients had moderate or severe cognitive deficits. During the preoperative period, the same quantity of strong opioids was administered to both groups of patients (13.1 mg/d versus 10.8 mg/d (p = 0.38)). Patients with moderate to severe cognitive deficits more often experienced delirium during their hospitalization (p < 0.01) and received more psychotropic drugs in the first 3 postoperative days (p = 0.025).

Conclusions

We reported that with standardized pain management in an orthogeriatric unit, patients aged 75 years and older received the same daily average quantity of strong opioids during the preoperative period regardless of the presence of cognitive deficits.
Impact of organizational context on patient outcomes in a proactive primary care program:a longitudinal observational study
Authors: Smit Linda C. , De Wit Niek J. , Nieuwenhuizen Meggie L. , Schuurmans Marieke J. , Bleijenberg Nienke
Published: October 2021

Background

The effectiveness of health care interventions is co-determined by contextual factors. Unknown is the extent of this impact on patient outcomes. Therefore, the aim of this study is to explore which characteristics of general practices are associated with patient outcomes in a proactive primary care program, the U-PROFIT 2.0.

Methods

A longitudinal observational study was conducted from January 2016 till October 2017. Two questionnaires were send out, one to collect characteristics of general practices such as practice neighbourhood socio-economic status, general practice versus healthcare centre (involving multiple primary care professionals), and professional- frail older patient ratio per practice of general practitioners and practice nurses. Regarding delivering the program, the practice or district nurse who delivered the program, number of years since the start of the implementation, and choice of age threshold for frailty screening were collected. Patient outcomes collected by the second questionnaire and send to frail patients were daily functioning, hospital admissions, emergency department visits, and general practice out-of-hours consultations. Linear and generalized linear mixed models were used.

Results

A total of 827 frail older people were included at baseline. Delivery of the program by a district nurse compared to a practice nurse was significantly associated with a decrease in daily functioning on patient-level (β = 2.19; P = < 0.001). Duration since implementation of 3 years compared to 9 years was significantly associated with less out-of-hours consultations to a general practice (OR 0.11; P = 0.001). Applying frailty screening from the age of 75 compared to those targeted from the age of 60 showed a significant increase in emergency visits (OR 5.26; P = 0.03).

Conclusion

Three associations regarding the organizational context 1) the nurse who delivered the program, 2) the number of years the program was implemented and 3) the age threshold for defining a frail patient are significant and clinically relevant for frail patients that receive a proactive primary care program. In general, contextual factors need more attention when implementing complex primary care programs which can result in better balanced choices to enhance effective proactive care for older people living in the community.
An exploration of potential output measures to assess efficiency and productivity for labour and birth in Australia
Authors: Eklom Bonnie , Tracy Sally , Callander Emily
Published: October 2021

Background

In maternity services, as in other areas of healthcare, increasing emphasis is placed on improving “efficiency” or “productivity”. The first step in any efficiency and productivity analysis is the selection of relevant input and output measures. Within healthcare quantifying what is produced (outputs) can be difficult.

The aim of this paper is to identify a potential output measure, that can be used in an assessment of the efficiency and productivity of labour and birth in-hospital care in Australia and to assess the extent to which it reflects the principles of woman-centred care.

Methods

This paper will survey available perinatal and maternal datasets in Australia to identify potential output measures; map identified output variables against the principles of woman-centred care outlined in Australia’s national maternity strategy; and based on this, create a preliminary composite outcome measure for use in assessing the efficiency and productivity of Australian maternity services.

Results

There are significant gaps in Australia’s maternity data collections with regard to measuring how well a maternity service is performing against the values of respect, choice and access; however safety is well measured. Our proposed composite measure identified that of the 63,215 births in Queensland in 2014, 67% met the criteria of quality outlined in our composite measure.

Conclusions

Adoption in Australia of the collection of woman-reported maternity outcomes would substantially strengthen Australia’s national maternity data collections and provide a more holistic view of pregnancy and childbirth in Australia beyond traditional measure of maternal and neonate morbidity and mortality. Such measures to capture respect, choice and access could complement existing safety measures to inform the assessment of productivity and efficiency in maternity care.
Relationship between the more-affected upper limb function and daily activity performance in children with cerebral palsy: a cross-sectional study
Authors: Park Hyerin , Choi Ja Young , Yi Sook-hee , Park Eun Sook , Shim Dain , Choi Tae Young , Rha Dong-wook
Published: October 2021

Background

There are differences in roles between the more-affected and less-affected upper limb of children with cerebral palsy (CP). However, there is a lack of studies of the relationship between the more-affected limb function and activities of daily living (ADL) in children with CP. Thus, the aim of this prospective cross-sectional study was to investigate the relationship between more-affected upper limb function and ADL in children with CP.

Methods

Children with spastic CP (unilateral CP n = 28, bilateral CP n = 31; 34 males, 25 females; mean age ± SD, 6.8 ± 3.1y [range, 3-14y]) participated in this study. Function of the more-affected upper limb was measured using the Melbourne Assessment of Unilateral Upper limb Function, version 2 (MA2) and the Upper Limb Physician’s Rating Scale (ULPRS). Performance of daily living activities was measured using the Pediatric Evaluation of Disability Inventory-Computer Adaptive Test (PEDI-CAT).

Results

The range, accuracy and fluency dimension of MA2 and ULPRS total scores were moderately correlated with the daily activity domain (r = 0.47, 0.47, 0.56 for MA2 and r = 0.50 for ULPRS, respectively; P < 0.001) rather than the mobility, social/cognitive, and responsibility domains of the PEDI-CAT. ULPRS scores for elbow extension, supination in extension, supination in flexion, and two-handed function were moderately correlated with the PEDI-CAT daily activity domain (r = 0.44, 0.43, 0.41, and 0.49, respectively; P < 0.01). Finger opening and thumb-in-palm deformity of the ULPRS did not correlate with any PEDI-CAT domain.

Conclusions

The MA2 range, accuracy, and fluency domains (rather than dexterity) had the strongest correlations with the PEDI-CAT daily activity domain. Elbow extension, forearm supination, and two-handed function (rather than wrist and finger movements) of the ULPRS had the strongest correlations with the PEDI-CAT daily activity domain.
ADHD overdiagnosis and the role of patient gender among Iranian psychiatrists
Authors: Beheshti Ashkan , Chavanon Mira-Lynn , Schneider Silvia , Christiansen Hanna
Published: October 2021

Background

Regarding the controversy about the overdiagnosis of Attention Deficit/Hyperactivity Disorder (ADHD) in children and adolescents there are two main directions addressed as issue of age bias and issue of gender bias. In this relation, replication of findings demonstrating significant overdiagnosis is of importance which make the systematic evaluation of such occurrence necessary.

Objective

The seminal study by Bruchmüller, Margraf & Schneider, 2012 is replicated here, although in a different cultural context, in this case Iran, as ADHS might be perceived differently there. We assessed both gender bias and the impact of potential overdiagnosis on treatment recommendations.

Methods

A total of 344 licensed Iranian psychiatrists (mean age = 45.17, SD = 9.50) participated in this study. Each psychiatrist received a cover letter that introduced the study as well as a case vignette. Overall, there are eight different cases, one child with ADHD and three non-ADHD children, for both a boy (Ali) and a girl (Sara). Participants also received a questionnaire requesting their particular diagnosis, treatment recommendation and the therapist’s sociodemographic information. Chi square tests and multiple logistic regression were applied for data analyses.

Results

Overdiagnosis occurred in both girl and boy children, although overdiagnosis was 2.45 more likely in boys than in girls (p < 0.01). With respect to the psychiatrist’s gender, we detected no difference between males or females, as both overdiagnosed ADHD in boys (pfemale < 0.01 and pmale < 0.01). Furthermore, ADHD overdiagnosis had a direct impact on medication prescription (p < 0.01).

Conclusion

This study suggests that diagnosticians should strictly adhere to diagnostic criteria to minimize diagnostic error.
Does substance use by family members and community affect the substance use among adolescent boys? Evidence from UDAYA study, India
Authors: Srivastava Shobhit , Kumar Pradeep , Rashmi  , Paul Ronak , Dhillon Preeti
Published: October 2021

Background

Substance use among adolescents is risky behavior that had emerged as a concern in both developed and developing countries. Evidence revealed that substance use is more frequent among those adolescents whose immediate family members (parents, siblings and grandparents) also indulge in such consumption; however, scarce literature is present in the Indian context. Therefore, the present study examined whether substance use among family members and in the community is associated with the substance use behavior of adolescent boys in Uttar Pradesh and Bihar.

Method

We used the data for 5969 adolescent boys aged 10–19 years from the Understanding the Lives of Adolescents and Young Adults (UDAYA) survey conducted in 2016. A three-level random intercept logit model was utilized to understand the association of adolescent substance use behavior with familial and community context.

Results

We found that 16% of adolescent boys were using any substance (tobacco or alcohol or drug). The substance use was significantly higher among adolescent boys who were school dropouts (40%) than those who were currently in school. The prevalence of substance use is also high among those who were working (35%). Moreover, 19, 24 and 28% of the adolescents come from families where at least one of the family members consumed tobacco, alcohol and drugs, respectively. The odds of substance use were 2.13 times [CI:1.44–3.17] higher among those adolescent boys whose family members also indulged in substance use. Moreover, the likelihood of substance use was 1.24 times [CI:1.01–1.68] higher among the adolescent boys who come from a community with high substance use. Additionally, the risk of substance use is more likely among adolescent boys belonging to the same household of the same community.

Conclusion

It is evident that exposure to substance use in the family and community increases the likelihood of substance use among adolescent boys. There is a need for household- and community-level programmatic interventions to alleviate the risk of substance use among adolescents.
Exploring condom use decision-making among adolescents: the synergistic role of affective and rational processes
Authors: Davids Eugene L. , Zembe Yanga , de Vries Petrus J. , Mathews Catherine , Swartz Alison
Published: October 2021

Background

Condom use remains the most effective behavioural method for the prevention of HIV and unplanned pregnancies. However, condom use remains inconsistent among young people. Exploring the condom use decision-making processes that adolescents engage in might provide information that would assist in the prevention of many challenges related to poor sexual and reproductive health outcomes. This study therefore aimed to explore the factors that influenced decision-making about sexual debut and condom use of adolescents from two schools in the Western Cape, South Africa.

Methods

A sample of 16 adolescents were selected using purposive sampling. Data were collected using semi-structured, individual interviews. Thematic analysis was used to analyse the data generated.

Results

The link between sexual debut and affective processes was frequently discussed in condom use decision-making. Decisions about sexual debut were influenced by the belief that sex was a perceived symbol of ‘true love’ on the one hand, and respect for perceived parental expectations of age-appropriate sex, on the other. Condom use decision-making was shaped by adolescents’ concerns about their future and lack of stability in their lives. Adolescents’ fears of pregnancy, parenthood and disease shaped their condom use decision-making. It became evident that rational and affective decision-making in condom use choice were not mutually exclusive, but that these processes happened simultaneously.

Conclusions

The study highlighted the role of affective states as part of the process of examining alternatives when deciding to use a condom or not. Interventions to strengthen condom use decision-making should therefore incorporate not only rational but also affective processes to improve adolescent sexual and reproductive outcomes.
Effect of public health interventions during the first epidemic wave of COVID-19 in Cyprus: a modelling study
Authors: Gountas Ilias , Quattrocchi Annalisa , Mamais Ioannis , Tsioutis Constantinos , Christaki Eirini , Fokianos Konstantinos , Nikolopoulos Georgios
Published: October 2021

Background

Cyprus addressed the first wave of SARS CoV-2 (COVID-19) by implementing non-pharmaceutical interventions (NPIs). The aims of this study were: a) to estimate epidemiological parameters of this wave including infection attack ratio, infection fatality ratio, and case ascertainment ratio, b) to assess the impact of public health interventions and examine what would have happened if those interventions had not been implemented.

Methods

A dynamic, stochastic, individual-based Susceptible-Exposed-Infected-Recovered (SEIR) model was developed to simulate COVID-19 transmission and progression in the population of the Republic of Cyprus. The model was fitted to the observed trends in COVID-19 deaths and intensive care unit (ICU) bed use.

Results

By May 8th, 2020, the infection attack ratio was 0.31% (95% Credible Interval [CrI]: 0.15, 0.54%), the infection fatality ratio was 0.71% (95% CrI: 0.44, 1.61%), and the case ascertainment ratio was 33.2% (95% CrI: 19.7, 68.7%). If Cyprus had not implemented any public health measure, the healthcare system would have been overwhelmed by April 14th. The interventions averted 715 (95% CrI: 339, 1235) deaths. If Cyprus had only increased ICU beds, without any social distancing measure, the healthcare system would have been overwhelmed by April 19th.

Conclusions

The decision of the Cypriot authorities to launch early NPIs limited the burden of the first wave of COVID-19. The findings of these analyses could help address the next waves of COVID-19 in Cyprus and other similar settings.
Factors impacting test-based management of suspected malaria among caregivers of febrile children and private medicine retailers within rural communities of Fanteakwa North District, Ghana
Authors: Soniran Olajoju Temidayo , Abuaku Benjamin , Anang Abraham , Opoku-Afriyie Patricia , Ahorlu Collins
Published: October 2021

Background

Prompt diagnosis and treatment prevents a mild case of malaria from developing into severe disease and death. Unfortunately, parasitological testing of febrile children is greater in the public and formal private sector than in the informal private sector in sub-Saharan Africa.

Methods

A mixed method study was carried out to determine factors limiting test-based management of suspected malaria cases among caregivers of febrile children and Over-the-Counter medicine sellers (OTCMS) in eight rural communities in Ghana. Structured questionnaires were used to interview 254 adult caregivers. Fourteen in-depth interviews were conducted with OTCMS. The interviews were audio-recorded, transcribed verbatim, and analysed thematically.

Results

The most frequently sought health providers by caregivers of febrile children in descending order were Community Health-Based Planning Services (CHPS) compounds; drug vendors; and OTCMS. Malaria parasitological testing rate of febrile children was highest (94.9%) at the CHPS compound and lowest (10.5%) at the OTCMS shops. Proportion of febrile children not subjected to malaria blood test is 28.3%. Among caregivers who did not ask for malaria blood test, 15.2% reported that healthcare provider did not offer a malaria blood test; 21.7% were financially handicapped to visit the Health Centre; and 63% lacked knowledge of malaria blood test and where to get it. From OTCMS point of view, clients’ inability to pay for malaria blood test, community perception that OTCMS are unqualified to perform malaria blood test, financial loss when unused RDT kits expires, clients’ demand for half dose of ACT, and activities of drug peddlers are factors limiting adherence to WHO recommended policy on testing before treating uncomplicated malaria cases.

Conclusion

The study results suggest the need to implement community friendly interventions aimed at improving test-based management of suspected malaria in febrile children. These may include educating caregivers and community members on the need to test and confirm malaria in febrile children before treating them, and supply of subsidized RDT kits to OTCMS and re-training them to provide testing services to their clients. Further studies pertaining to influence of gender roles on healthcare seeking attitude for febrile children is also suggested.
Goods, causes and intentions: problems with applying the doctrine of double effect to palliative sedation
Authors: Faris Hannah , Dewar Brian , Dyason Claire , Dick David G. , Matthewson Ainsley , Lamb Susan , Shamy Michel C. F.
Published: October 2021

Background

Palliative sedation and analgesia are employed in patients with refractory and intractable symptoms at the end of life to reduce their suffering by lowering their level of consciousness. The doctrine of double effect, a philosophical principle that justifies doing a “good action” with a potentially “bad effect,” is frequently employed to provide an ethical justification for this practice.

Main text

We argue that palliative sedation and analgesia do not fulfill the conditions required to apply the doctrine of double effect, and therefore its use in this domain is inappropriate. Furthermore, we argue that the frequent application of the doctrine of double effect to palliative sedation and analgesia reflects physicians’ discomfort with the complex moral, intentional, and causal aspects of end-of-life care.

Conclusions

We are concerned that this misapplication of the doctrine of double effect can consequently impair physicians’ ethical reasoning and relationships with patients at the end of life.
The protective role of professional self-concept and job embeddedness on nurses’ burnout: structural equation modeling
Authors: Goliroshan Soghra , Nobahar Monir , Raeisdana Nayyereh , Ebadinejad Zahra , Aziznejadroshan Parvin
Published: October 2021

Background

Job embeddedness and professional self-concept are among the important nursing components, the existence of which help decrease occupational burnout among nurses. This study aimed to determine the protective role of Professional Self-concept and Job embeddedness on nurses’burnout.

Methods

This descriptive, correlational study had a predictive design and was conducted on nurses working in training and healthcare centers of Babol University of Medical Sciences in 2019. In total, 308 nurses participated in this study and were selected by stratified random sampling. In addition, data were collected using demographic characteristics questionnaire, Professional Self-concept questionnaire, Job embeddedness scale and nurses’ burnout questionnaire. Moreover, data analysis was performed in SPSS version 25 and Smart PLS version 3.3 using correlational statistics and structural equation modeling.

Results

Both the variables of professional self-concept and job embeddedness, had a significant effect on nurses’ burnout at 99% confidence level (P < 0.001) and the negative beta value for these two variables shows the inverse relationship between both professional self-concept and job embeddedness with nurses’ burnout. The value of the coefficient of determination for burnout indicates that both the variables of professional self-concept and job embeddedness, together explain 78% of the changes in the variable of burnout. The beta coefficient for professional self-concept (− 0.50) is higher than the same coefficient for job embeddedness (− 0.42). As a result, the role of professional self-concept in predicting burnout of clinical nurses has been more than the role of job embeddedness. The indirect effect of professional self-concept on burnout of clinical nurses mediated by job embeddedness has been equal to − 0.347. As a result, it can be said that nurses’ professional self-concept has a significant effect on nurses’ burnout through mediation of job embeddedness.

Conclusion

According to the results of the study, Professional Self-concept had an effective role in nurses’ burnout. In other words, the higher the Professional Self-concept of nurses, the lower their burnout. Therefore, it is suggested that effective interventional strategies be designed by nursing managers through better planning and a supportive workplace be established to improve Professional Self-concept among nurses and decrease their burnout.
Australian hospital staff perceptions of barriers and enablers of domestic and family violence screening and response
Authors: Creedy Debra K. , Baird Kathleen , Gillespie Kerri , Branjerdporn Grace
Published: October 2021

Background

Hospital presentations provide unique opportunities to detect DFV. However, up to 70% of women experiencing Domestic and Family Violence (DFV) go undetected by hospital staff. While routine DFV screening is internationally encouraged, there is still much debate surrounding its implementation. The aim of the study was to determine staff perceptions of barriers and enablers of DFV screening and response.

Methods

A cross-sectional survey was conducted at a tertiary level public hospital and health service. Health care staff in allied health, maternity and mental health divisions (n = 615) were invited to participate by email and through team meetings. 172 responses were analysed.

Results

Less than a third of respondents reported routinely asking patients about DFV, with 34.9% reporting they did not have sufficient training to assist with DFV. Increased levels of training were positively correlated with screening practices, preparedness and knowledge. Major barriers were presence of partner and language barriers, while written protocols and supportive work environment were the principal enablers of screening.

Conclusion

Staff generally believed that routine screening was important and should encompass all forms of abuse. Many felt ill-equipped to ask about or manage disclosure of DFV. More training improves staff capacity for DFV detection and response, and written guidelines should be made available to all staff.
Effects of the cefazolin shortage on the sales, cost, and appropriate use of other antimicrobials
Authors: Koizumi Ryuji , Kusama Yoshiki , Asai Yusuke , Yoshiaki Gu , Muraki Yuichi , Ohmagari Norio
Published: October 2021

Background

Shortages of antimicrobials lead to treatment failures, increase medical costs, and accelerate the development of antimicrobial resistance. We evaluated the effects of the serious cefazolin shortage in 2019 in Japan on the sales, costs, and appropriate use of other antimicrobials.

Methods

We evaluated monthly defined daily doses/1000 inhabitants/day (DID) values of antimicrobial sales from January 2016 to December 2019 using wholesaler’s sales databases. Using 2016–2018 sales data, we generated a prediction model of DID in 2019 under the assumption that the cefazolin shortage did not occur. We then compared the predicted DID and actual DID. Cefazolin, government-recommended alternatives, and government-not-recommended broad-spectrum alternatives were assessed. Antimicrobial groups according to the AWaRe classification were also assessed to evaluate the effect on appropriate antimicrobial use. In addition, we evaluated changes in costs between 9 months before and after the cefazolin shortage.

Results

DID values of total antimicrobials increased sharply 1 month before the decrease in cefazolin. Actual DIDs were higher than predicted DIDs for ceftriaxone, flomoxef, clindamycin, cefotiam, piperacillin/tazobactam, and meropenem. Actual DID values were higher than the predicted DID values in the Watch group. The costs of antimicrobials between pre- and post- cefazolin shortage were unchanged.

Conclusion

The cefazolin shortage brought confusion to the antimicrobial market and led to a setback in the appropriate use of antimicrobials. Early recognition and structures for prompt reactions to antimicrobial shortages are needed. Moreover, development of a system to secure the supply of essential antimicrobials is required.
High vitamin K status is prospectively associated with decreased left ventricular mass in women: the Hoorn Study
Authors: Beulens Joline W. J. , Dal Canto Elisa , Stehouwer Coen D. A. , Rennenberg Roger J. M. W. , Elders Petra J. M. , van Ballegooijen Adriana Johanne
Published: October 2021

Background

Vitamin K is associated with reduced cardiovascular disease risk such as heart failure, possibly by carboxylation of matrix-gla protein (MGP), a potent inhibitor of vascular calcification. The relationship of vitamin K intake or status with cardiac structure and function is largely unknown. Therefore this study aims to investigate the prospective association of vitamin K status and intake with echocardiographic measures.

Methods

This study included 427 participants from the Hoorn Study, a population-based cohort. Vitamin K status was assessed at baseline by plasma desphospho-uncarboxylated MGP (dp-ucMGP) with higher concentrations reflecting lower vitamin K status. Vitamin K intake was assessed at baseline with a validated food-frequency questionnaire. Echocardiography was performed at baseline and after a mean follow-up time of 7.6, SD=±0.7 years. We used linear regression for the association of vitamin K status and intake with left ventricular ejection fraction (LVEF), left atrial volume index (LAVI) and left ventricular mass index (LVMI), adjusted for potential confounders.

Results

The mean age was 66.8, SD=±6.1 years (51% were male). A high vitamin K status was prospectively associated with decreased LVMI (change from baseline to follow-up: -5.0, 95% CI: -10.5;0.4 g/m2.7) for the highest quartile compared to the lowest in women (P-interaction sex=0.07). No association was found in men. Vitamin K status was not associated with LVEF or LAVI. Vitamin K intake was not associated with any of the echocardiographic measures.

Conclusions

This study showed a high vitamin K status being associated with decreased LVMI only in women, while intakes of vitamin K were not associated with any cardiac structure or function measures. These results extend previous findings for a role of vitamin K status to decrease heart failure risk.
An optimal window of platelet reactivity by LTA assay for patients undergoing percutaneous coronary intervention
Authors: Wang Jing , Wang Jing , Dong Zhou , Ma Jiazheng , Teng Jianzhen , Wang Tong , Zhang Xiaofeng , Gu Qian , Ye Zekang , Ullah Inam , Tan Chuchu , Abdus Samee , Shi Lu , Gong Xiaoxuan , Li Chunjian
Published: October 2021

Objective

This study was aimed to determine how platelet reactivity (PR) on dual antiplatelet therapy predicts ischemic and bleeding events in patients underwent percutaneous coronary intervention (PCI).

Design

A total of 2768 patients who had received coronary stent implantation and had taken aspirin 100 mg in combination with clopidogrel 75 mg daily for > 5 days were consecutively screened and 1885 were enrolled. The recruited patients were followed-up for 12 months. The primary end-point was the net adverse clinical events (NACE) of cardiovascular death, nonfatal myocardial infarction (MI), target vessel revascularization (TVR), stent thrombosis (ST) and any bleeding.

Result

1709 patients completed the clinical follow-up. By using the receiver operating characteristic (ROC) curve analysis, the optimal cut-off values were found to be 37.5 and 25.5% respectively in predicting ischemic and bleeding events. Patients were classified into 2 groups according to PR: inside the window group (IW) [adenosine diphosphate (ADP) induced platelet aggregation (PLADP) 25.5–37.4%)] and outside the window group (OW) (PLADP < 25.5% or ≥ 37.5%). The incidence of NACE was 16.8 and 23.1% respectively in the IW and OW group. The hazard ratio of NACE in IW group was significantly lower [0.69 (95% CI, 0.54–0.89, P = 0.004)] than that in the OW group during 12-month follow-up.

Conclusion

An optimal therapeutic window of 25.5–37.4% for PLADP predicts the lowest risk of NACE, which could be referred for tailored antiplatelet treatment while using LTA assay.

Trial registration

Trial registration number: ClinicalTrials.govNCT01968499. Registered 18 October 2013 - Retrospectively registered.
HMGB1 mediates cognitive impairment caused by the NLRP3 inflammasome in the late stage of traumatic brain injury
Authors: Tan Si-Wei , Zhao Yan , Li Ping , Ning Ya-Lei , Huang Zhi-Zhong , Yang Nan , Liu Dong , Zhou Yuan-Guo
Published: October 2021

Background

Cognitive impairment in the late stage of traumatic brain injury (TBI) is associated with the NOD-, LRR and pyrin domain-containing protein 3 (NLRP3) inflammasome, which plays an important role in neuroinflammation. Although classical inflammatory pathways have been well-documented in the late stage of TBI (4–8 weeks post-injury), the mechanism by which the NLRP3 inflammasome impairs cognition is still unclear.

Methods

Mice lacking the gene encoding for NLRP3 (NLRP3-knockout mice) and their wild-type littermates were used in a controlled cortical impact model of TBI. Levels of NLRP3 inflammasome and inflammatory factors such as IL-1β and HMGB1 were detected in post-injury hippocampal tissue, as well as long-term potentiation. Behaviors were assessed by T-maze test, novel object recognition, and nesting tests. Glycyrrhizin was used to antagonize HMGB1. Calcium imaging were performed on primary neuronal cultures.

Results

By using the NLRP3-knockout TBI model, we found that the continuous activation of the NLRP3 inflammasome and high mobility group box 1 (HMGB1) release were closely related to cognitive impairment. We also found that inhibition of HMGB1 improved LTP reduction and cognitive function by increasing the phosphorylation level of the NMDAR1 subunit at serine 896 while reducing NLRP3 inflammasome activation.

Conclusion

NLRP3 inflammasome damages memory in the late stage of TBI primarily through HMGB1 upregulation and provides an explanation for the long-term progression of cognitive dysfunction.
Blockade of the NLRP3/caspase-1 axis attenuates ketamine-induced hippocampus pyroptosis and cognitive impairment in neonatal rats
Authors: Zhang Zhiheng , Bai Hui , Ma Xiangying , Shen Meilun , Li Rouqian , Qiu Di , Li Siyao , Gao Li
Published: October 2021

Background

Multiple studies have revealed that repeated or long-term exposure to ketamine causes neurodegeneration and cognitive dysfunction. Pyroptosis is an inflammatory form of programmed cell death that has been linked to various neurological diseases. However, the role of NLRP3/caspase-1 axis-related pyroptosis in ketamine-induced neurotoxicity and cognitive dysfunction remains uncertain.

Methods

To evaluate whether ketamine caused NLRP3/caspase1-dependent pyroptosis, flow cytometry analysis, western blotting, ELISA test, histopathological analysis, Morris water maze (MWM) test, cell viability assay, and lactate dehydrogenase release (LDH) assay were carried out on PC12 cells, HAPI cells, and 7-day-old rats. In addition, the NLRP3 inhibitor MCC950 or the caspase-1 inhibitor VX-765 was used to investigate the role of the NLRP3/caspase-1 axis in ketamine-induced neurotoxicity and cognitive dysfunction.

Results

Our findings demonstrated that ketamine exposure caused cell damage and increased the levels of pyroptosis in PC12 cells, HAPI cells, and the hippocampus of neonatal rats. After continuous exposure to ketamine, targeting NLRP3 and caspase-1 with MCC950 or VX765 improved pyroptosis, reduced neuropathological damages, and alleviated cognitive dysfunction.

Conclusion

NLRP3/Caspase-1 axis-dependent pyroptosis is involved in ketamine-induced neuroinflammation and cognitive dysfunction, and it provides a promising strategy to treat ketamine-related neurotoxicity.
Serum uric acid and risk of incident chronic kidney disease: a national cohort study and updated meta-analysis
Authors: Wu Nianwei , Xia Jing , Chen Sen , Yu Chuan , Xu Ying , Xu Chengfu , Yan Tong , Li Ningxiu , Liu Yanjun , Pan Xiong-Fei
Published: October 2021

Background

We prospectively examined the association between serum uric acid (SUA) levels and chronic kidney disease (CKD) in China and updated the evidence through a comprehensive meta-analysis of prospective studies worldwide.

Methods

Our original analyses were based on data from the China Health and Retirement Longitudinal Study. The primary exposure of interest was SUA at baseline, and the main outcome was incident CKD. Logistic regression models were used to examine the association between SUA levels and incident CKD. A meta-analysis was performed to pool our effect estimate and those from other cohort studies.

Results

During a 4-year follow-up, 180 participants developed incident CKD. Participants in the highest SUA quartile were 2.73 times as likely to develop incident CKD compared to those in the lowest quartile (multivariable-adjusted OR, 2.73; 95% CI, 1.65–4.50). Each 1 mg/dL increment in the SUA levels was associated with a 49% increased risk of incident CKD (multivariable-adjusted OR, 1.49; 95% CI, 1.28–1.74). In the meta-analysis of 30 cohort studies (including the current study), pooled relative risks (95% CIs) of incident CKD were 1.15 (1.10–1.21) for SUA each 1 mg/dL increment, 1.22 (1.14–1.30) for the highest versus lowest SUA group, and 1.17 (1.12–1.23) for hyperuricemia versus no hyperuricemia.

Conclusions

Baseline SUA levels were associated with higher risk of incident CKD in middle-aged and elderly Chinese adults, and this positive association was confirmed in the meta-analysis of multiple cohort studies. Our findings may imply that SUA levels need to be routinely monitored for future CKD risk.
The patient experience of Wilson disease: a conceptual model based on qualitative research
Authors: Karantzoulis Stella , Heuer Karli , Sparling Nicole , Teynor Megan
Published: October 2021

Background

Wilson disease (WD) is a rare disease wherein copper accumulates in tissues, leading to hepatic degeneration, neurological impairments, and psychiatric symptoms. This study aimed to characterize the patient experience of WD and develop a conceptual model containing key symptoms and impacts of the disease.

Results

A targeted literature review was conducted to develop a preliminary conceptual model of WD that was subsequently refined through one-on-one interviews with 3 WD clinicians and finalized following concept elicitation interviews with 11 patients and 1 caregiver. The literature review returned 30 articles, from which 45 concepts (35 signs/symptoms and 10 impacts) were selected for inclusion in the preliminary conceptual model. After interviews with clinicians, the model was expanded to include 45 signs/symptoms and 14 impacts. The final comprehensive conceptual model developed after interviews with patients included 54 symptoms in total (n = 22 hepatic, n = 19 neurological, n = 13 psychiatric), and 21 impacts. Across symptoms, patients reported a high level of bother, with approximately 49% of symptoms reported by patients having an average peak bother rating of ≥ 7 out of 10 (10 = most bothersome). Patient interviews identified 2 subgroups of patients: those who experience neurological, psychiatric, and hepatic symptoms and those who experience mostly hepatic and some psychiatric symptoms, but no neurological symptoms.

Conclusions

This research underscores the substantial multisystemic symptoms and impacts that patients with WD describe as highly bothersome in their lives. Hepatic symptoms emerged as especially common and important to patients with WD, possibly beyond what is commonly understood in research and clinical practice. Further, the description of 2 distinct patient groups may help to inform patient management and support more targeted drug development processes.
Clinical and event-based outcomes of patients with mucopolysaccharidosis VI receiving enzyme replacement therapy in Turkey: a case series
Authors: İnci Aslı , Okur İlyas , Tümer Leyla , Biberoğlu Gürsel , Öktem Murat , Ezgü Fatih
Published: October 2021

Background

The objective of this study was to describe clinical manifestations and events of patients with mucopolysaccharidosis (MPS) VI in Turkey who are treated with galsulfase enzyme replacement therapy (ERT). Clinical data of 14 children with MPS VI who were followed up at the Department of Pediatrics of the Gazi University Faculty of Medicine in Ankara, Turkey were retrospectively collected from the patients’ medical records. Patients were selected based on availability of a pre-ERT baseline and follow-up clinical data for a similar period of time (1.9–3.2 years). Event data (occurrence of acute clinical events, onset of chronic events, surgeries) collected during hospital visits and telemedicine were available for up to 10 years after initiation of ERT (2.5–10 years).

Results

Age at initiation of ERT ranged from 2.8 to 15.8 years (mean age 7.5 years). All patients presented with reduced endurance and skeletal abnormalities (dysostosis multiplex) on radiography. Other common clinical manifestations were cardiac valve disease (N = 13), short stature (N = 11), cranial abnormalities on MRI (N = 10), spinal abnormalities on MRI (N = 7), and mild cognitive impairment (N = 6). School attendance was generally poor, and several patients had urinary incontinence. After 1.9 to 3.2 years of ERT, most patients showed improvements in endurance in the 6-min walk test and 3-min stair climb tests; the frequency of urinary incontinence decreased. ERT did not seem to prevent progression of cardiac valve disease, eye disorders, hearing loss, or bone disease. Long-term event-based data showed a high incidence of respiratory tract infections, adenotonsillectomy/adenoidectomy, reduced sleep quality, sleep apnea, and depression before initiation of ERT. The number of events tended to remain stable or decrease in all patients over 2.5–10 years follow-up. However, the nature of the events shifted over time, with a reduction in the frequency of respiratory tract infections and sleep problems and an increase in ophthalmologic events, ear tube insertions, and depression.

Conclusions

This case series shows the high disease burden of the MPS VI population in Turkey and provides a unique insight into their clinical journey based on real-life clinical and event-based data collected before and after initiation of ERT.
Association between warfarin and COVID-19-related outcomes compared with direct oral anticoagulants: population-based cohort study
Authors:   The OpenSAFELY Collaborative, Wong Angel Y. S. , Tomlinson Laurie A. , Brown Jeremy P. , Elson William , Walker Alex J. , Schultze Anna , Morton Caroline E. , Evans David , Inglesby Peter , MacKenna Brian , Bhaskaran Krishnan , Rentsch Christopher T. , Powell Emma , Williamson Elizabeth , Croker Richard , Bacon Seb , Hulme William , Bates Chris , Curtis Helen J. , Mehrkar Amir , Cockburn Jonathan , McDonald Helen I. , Mathur Rohini , Wing Kevin , Forbes Harriet , Eggo Rosalind M. , Evans Stephen J. W. , Smeeth Liam , Goldacre Ben , Douglas Ian J.
Published: October 2021

Background

Thromboembolism has been reported as a consequence of severe COVID-19. Although warfarin is a commonly used anticoagulant, it acts by antagonising vitamin K, which is low in patients with severe COVID-19. To date, the clinical evidence on the impact of regular use of warfarin on COVID-19-related thromboembolism is lacking.

Methods

On behalf of NHS England, we conducted a population-based cohort study investigating the association between warfarin and COVID-19 outcomes compared with direct oral anticoagulants (DOACs). We used the OpenSAFELY platform to analyse primary care data and pseudonymously linked SARS-CoV-2 antigen testing data, hospital admissions and death records from England. We used Cox regression to estimate hazard ratios (HRs) for COVID-19-related outcomes comparing warfarin with DOACs in people with non-valvular atrial fibrillation. We also conducted negative control outcome analyses (being tested for SARS-CoV-2 and non-COVID-19 death) to assess the potential impact of confounding.

Results

A total of 92,339 warfarin users and 280,407 DOAC users were included. We observed a lower risk of all outcomes associated with warfarin versus DOACs [testing positive for SARS-CoV-2, HR 0.73 (95% CI 0.68–0.79); COVID-19-related hospital admission, HR 0.75 (95% CI 0.68–0.83); COVID-19-related deaths, HR 0.74 (95% CI 0.66–0.83)]. A lower risk of negative control outcomes associated with warfarin versus DOACs was also observed [being tested for SARS-CoV-2, HR 0.80 (95% CI 0.79–0.81); non-COVID-19 deaths, HR 0.79 (95% CI 0.76–0.83)].

Conclusions

Overall, this study shows no evidence of harmful effects of warfarin on severe COVID-19 disease.
Effect of acupuncture for diminished ovarian reserve: study protocol for a randomized controlled trial
Authors: Xu Huanfang , Hao Mingzhao , Zheng Chensi , Yang Huisheng , Yin Yaqian , Yang Li , Fang Yigong
Published: October 2021

Background

Diminished ovarian reserve (DOR) is a condition in which the ovary loses its normal reproductive potential, compromising fertility. Although the prevalence and incidence of DOR is increasing, there are currently no effective treatments for this condition. Acupuncture has been reported as an alternative therapy for female infertility. The purpose of this study is to investigate the effect of acupuncture for women with DOR.

Methods/design

In this randomized controlled trial, a total of 120 women with DOR will be randomly assigned to receive either acupuncture or sham acupuncture for 12 weeks. The primary outcome will be determined by the mean change from baseline in the antral follicle count (AFC) at week 12. Secondary outcomes include serum levels of FSH, LH, E2, and AMH, the length of menstrual cycle, and the score of Self-Rating Anxiety Scale (SAS).

Discussion

This study is expected to investigate the effectiveness of acupuncture versus sham acupuncture in improving ovarian reserve for women with DOR.

Trial registration

Acupuncture-Moxibustion Clinical Trial Registry ChiCTR1800014988. Registered on 6 February 2018
Functional implication of heat shock protein 70/90 and tubulin in cold stress of Dermacentor silvarum
Authors: Agwunobi Desmond O. , Wang Tongxuan , Zhang Meng , Wang Tianhong , Jia Qingying , Zhang Miao , Shi Xinyue , Yu Zhijun , Liu Jingze
Published: October 2021

Background

The tick Dermacentor silvarum Olenev (Acari: Ixodidae) is a vital vector tick species mainly distributed in the north of China and overwinters in the unfed adult stage. The knowledge of the mechanism that underlies its molecular adaptation against cold is limited. In the present study, genes of hsp70 and hsp90 cDNA, named Dshsp70 and Dshsp90, and tubulin were cloned and characterized from D. silvarum, and their functions in cold stress were further evaluated.

Methods

The genome of the heat shock proteins and tubulin of D. silvarum were sequenced and analyzed using bioinformatics methods. Each group of 20 ticks were injected in triplicate with Dshsp90-, Dshsp70-, and tubulin-derived dsRNA, whereas the control group was injected with GFP dsRNA. Then, the total RNA was extracted and cDNA was synthesized and subjected to RT-qPCR. After the confirmation of knockdown, the ticks were incubated for 24 h and were exposed to − 20 °C lethal temperature (LT50), and then the mortality was calculated.

Results

Results indicated that Dshsp70 and Dshsp90 contained an open reading frame of 345 and 2190 nucleotides that encoded 114 and 729 amino acid residues, respectively. The transcript Dshsp70 showed 90% similarity with that identified from Dermacentor variabilis, whereas Dshsp90 showed 85% similarity with that identified from Ixodes scapularis. Multiple sequence alignment indicates that the deduced amino acid sequences of D. silvarum Hsp90, Hsp70, and tubulin show very high sequence identity to their corresponding sequences in other species. Hsp90 and Hsp70 display highly conserved and signature amino acid sequences with well-conserved MEEVD motif at the C-terminal in Hsp90 and a variable C-terminal region with a V/IEEVD-motif in Hsp70 that bind to numerous co-chaperones. RNA interference revealed that the mortality of D. silvarum was significantly increased after injection of dsRNA of Dshsp70 (P = 0.0298) and tubulin (P = 0.0448), whereas no significant increases were observed after the interference of Dshsp90 (P = 0.0709).

Conclusions

The above results suggested that Dshsp70 and tubulin play an essential role in the low-temperature adaptation of ticks. The results of this study can contribute to the understanding of the survival and acclimatization of overwintering ticks.

Graphical abstract
A discussion concerning the existence results for the Sobolev-type Hilfer fractional delay integro-differential systems
Authors: Kavitha K. , Nisar Kottakkaran Sooppy , Shukla Anurag , Vijayakumar Velusamy , Rezapour Shahram
Published: October 2021

The goal of this study is to propose the existence results for the Sobolev-type Hilfer fractional integro-differential systems with infinite delay. We intend to implement the outcomes and realities of fractional theory to obtain the main results by Monch’s fixed point technique. Moreover, we show the existence and controllability of the thought about the fractional system with the nonlocal condition. In addition, an application to illustrate the outcomes is also included.