bluuebunny/crossref_metadata_2025 huggingface dataset:
Restoration of dendritic cell homeostasis and Type I/Type III interferon levels in convalescent COVID-19 individuals
Authors: Rajamanickam Anuradha , Kumar Nathella Pavan , Pandiaraj Arul Nancy , Selvaraj Nandhini , Munisankar Saravanan , Renji Rachel Mariam , Venkatramani Vijayalakshmi , Murhekar Manoj , Thangaraj Jeromie Wesley Vivian , Kumar Muthusamy Santhosh , Kumar Chethrapilly Purushothaman Girish , Bhatnagar Tarun , Ponnaiah Manickam , Sabarinathan Ramasamy , Saravanakumar Velusamy , Babu Subash
Published: October 2022

Background

Plasmacytoid and myeloid dendritic cells play a vital role in the protection against viral infections. In COVID-19, there is an impairment of dendritic cell (DC) function and interferon secretion which has been correlated with disease severity.

Results

In this study, we described the frequency of DC subsets and the plasma levels of Type I (IFNα, IFNβ) and Type III Interferons (IFNλ1), IFNλ2) and IFNλ3) in seven groups of COVID-19 individuals, classified based on days since RT-PCR confirmation of SARS-CoV2 infection. Our data shows that the frequencies of pDC and mDC increase from Days 15–30 to Days 61–90 and plateau thereafter. Similarly, the levels of IFNα, IFNβ, IFNλ1, IFNλ2 and IFNλ3 increase from Days 15–30 to Days 61–90 and plateau thereafter. COVID-19 patients with severe disease exhibit diminished frequencies of pDC and mDC and decreased levels of IFNα, IFNβ, IFNλ1, IFNλ2 and IFNλ3. Finally, the percentages of DC subsets positively correlated with the levels of Type I and Type III IFNs.

Conclusion

Thus, our study provides evidence of restoration of homeostatic levels in DC subset frequencies and circulating levels of Type I and Type III IFNs in convalescent COVID-19 individuals.
Can passive leg raise predict the response to fluid resuscitation in ED?
Authors: Elwan MH , Roshdy A , Elsharkawy EM , Eltahan SM , Coats TJ
Published: October 2022

Objective

Passive leg raise (PLR) can be used as a reversible preload challenge to stratify patients according to preload response. We aim to evaluate the accuracy of PLR, monitored by a non-invasive cardiac output monitor in predicting to response to fluid resuscitation in emergency department (ED).

Methods

We recruited adult patients planned to receive a resuscitation fluid bolus. Patients were monitored using a thoracic electrical bioimpedance (TEB) cardiac output monitor (Niccomo, Medis, Germany). A 3-min PLR was carried out before and after fluid infusion. Stroke volume changes (ΔSV) were calculated and a positive response was defined as ≥ 15% increase.

Results

We recruited 39 patients, of which 37 were included into the analysis. The median age was 63 (50–77) years and 19 patients were females. 17 patients (46%) were fluid responders compared to 11 (30%) with positive response to PLR1. ΔSV with PLR1 and fluid bolus showed moderate correlation (r = 0.47, 95% confidence interval, CI 0.17–0.69) and 62% concordance rate. For the prediction of the response to a fluid bolus the PLR test had a sensitivity of 41% (95% CI 22–64) and specificity of 80% (95% CI 58–92) with an area under the curve of 0.59 (95% CI 0.41–0.78). None of the standard parameters showed a better predictive ability compared to PLR.

Conclusion

Using TEB, ΔSV with PLR showed a moderate correlation with fluid bolus, with a limited accuracy to predict fluid responsiveness. The PLR test was a better predictor of fluid responsiveness than the parameters commonly used in emergency care (such as heart rate and blood pressure). These data suggest the potential for a clinical trial in sepsis comparing TEB monitored, PLR directed fluid management with standard care.
Mapping between headache specific and generic preference-based health-related quality of life measures
Authors: Khan Kamran , Mistry Hema , Matharu Manjit , Norman Chloe , Petrou Stavros , Stewart Kimberley , Underwood Martin , Achana Felix
Published: October 2022

Background

The Headache Impact Test (HIT-6) and the Chronic Headache Questionnaire (CH-QLQ) measure headache-related quality of life but are not preference-based and therefore cannot be used to generate health utilities for cost-effectiveness analyses. There are currently no established algorithms for mapping between the HIT-6 or CH-QLQ and preference-based health-related quality-of-life measures for chronic headache population.

Methods

We developed algorithms for generating EQ-5D-5L and SF-6D utilities from the HIT-6 and the CHQLQ using both direct and response mapping approaches. A multi-stage model selection process was used to assess the predictive accuracy of the models. The estimated mapping algorithms were derived to generate UK tariffs and was validated using the Chronic Headache Education and Self-management Study (CHESS) trial dataset.

Results

Several models were developed that reasonably accurately predict health utilities in this context. The best performing model for predicting EQ-5D-5L utility scores from the HIT-6 scores was a Censored Least Absolute Deviations (CLAD) (1) model that only included the HIT-6 score as the covariate (mean squared error (MSE) 0.0550). The selected model for CH-QLQ to EQ-5D-5L was the CLAD (3) model that included CH-QLQ summary scores, age, and gender, squared terms and interaction terms as covariates (MSE 0.0583). The best performing model for predicting SF-6D utility scores from the HIT-6 scores was the CLAD (2) model that included the HIT-6 score and age and gender as covariates (MSE 0.0102). The selected model for CH-QLQ to SF-6D was the OLS (2) model that included CH-QLQ summary scores, age, and gender as covariates (MSE 0.0086).

Conclusion

The developed algorithms enable the estimation of EQ-5D-5L and SF-6D utilities from two headache-specific questionnaires where preference-based health-related quality of life data are missing. However, further work is needed to help define the best approach to measuring health utilities in headache studies.
Bidirectional relationship between nocturnal subjective sleep duration and cognitive performance in Chinese over 45 years old: a national representative longitudinal study
Authors: Li Chao , Min Xianying , Cheng Gang , Yan Yan , Li Zexuan
Published: October 2022

Introduction

Previous studies have inconsistent associations between changes in sleep duration and cognitive function and have not separated interindividual effects from intraindividual effects. This study aimed to examine the bidirectional associations between subjective night sleep duration and cognitive function while differing intraindividual and interindividual effects.

Methods

A national representative sample was obtained from China Health and Retirement Longitudinal Study during 2011–2018. Night sleep duration and potential confounders were assessed and collected by questionnaires. Cognition was assessed in three categories (orientation, executive function, and memory), and z scores were used for global cognitive performance. The random intercept cross-lagged panel model was used to examine the temporal associations during 2011–2018.

Results

Across 9404 participants over 45, at interindividual level, moderate (β= -0.014) and long sleepers (β= -0.06) had positive association between sleep duration and cognitive decline after adjusted covariates, but short sleepers had negative associations between sleep duration and cognitive decline (β = 0.87). At intraindividual level, prolonged sleep duration predicted better cognition for short (β= -0.021 at wave2-3; β= -0.04 at wave3-4) and moderate (β= -0.017 at wave3-4) sleepers.

Conclusion

For short sleepers, longer subjective nocturnal sleep duration predicted better cognitive performance; but moderate and long sleepers showed opposite results—short and moderate sleepers with prolonged subjective nocturnal sleep duration would have later cognitive decline. Our findings tentatively suggested that an increased subjective night sleep duration and subjective long sleep duration could be regarded as useful tools for identifying middle- and old adults at higher risks of progressing to cognitive decline.
A family carer decision support intervention for people with advanced dementia residing in a nursing home: a study protocol for an international advance care planning intervention (mySupport study)
Authors: Harding Andrew J E , Doherty Julie , Bavelaar Laura , Walshe Catherine , Preston Nancy , Kaasalainen Sharon , Sussman Tamara , van der Steen Jenny T , Cornally Nicola , Hartigan Irene , Loucka Martin , Vlckova Karolina , Di Giulio Paola , Gonella Silvia , Brazil Kevin ,   On behalf of the mySupport Study Group, Achterberg Wilco P. , Visser Mandy , Buckley Catherine , Fitzgerald Serena , Foley Tony , Fox Siobhan , Connolly Alan , O’Caoimh Ronan , O’Connell Selena , Sweeney Catherine , Timmons Suzanne , Wilson Christine Brown , Carter Gillian , Cousins Emily , De Vries Kay , Dixon Josie , Harrison Dening Karen , Henderson Catherine , McCann Adrienne
Published: October 2022

Background

Where it has been determined that a resident in a nursing home living with dementia loses decisional capacity, nursing home staff must deliver care that is in the person's best interests. Ideally, decisions should be made involving those close to the person, typically a family carer and health and social care providers. The aim of the Family Carer Decisional Support intervention is to inform family carers on end-of-life care options for a person living with advanced dementia and enable them to contribute to advance care planning. This implementation study proposes to; 1) adopt and apply the intervention internationally; and, 2) train nursing home staff to deliver the family carer decision support intervention.

Methods

This study will employ a multiple case study design to allow an understanding of the implementation process and to identify the factors which determine how well the intervention will work as intended. We will enrol nursing homes from each country (Canada n = 2 Republic of Ireland = 2, three regions in the UK n = 2 each, The Netherlands n = 2, Italy n = 2 and the Czech Republic n = 2) to reflect the range of characteristics in each national and local context. The RE-AIM (reach, effectiveness, adoption, implementation, maintenance) framework will guide the evaluation of implementation of the training and information resources. Our mixed methods study design has three phases to (1) establish knowledge about the context of implementation, (2) participant baseline information and measures and (3) follow up evaluation.

Discussion

The use of a multiple case study design will enable evaluation of the intervention in different national, regional, cultural, clinical, social and organisational contexts, and we anticipate collecting rich and in-depth data. While it is hoped that the intervention resources will impact on policy and practice in the nursing homes that are recruited to the study, the development of implementation guidelines will ensure impact on wider national policy and practice. It is our aim that the resources will be sustainable beyond the duration of the study and this will enable the resources to have a longstanding relevance for future advance care planning practice for staff, family carers and residents with advanced dementia.
Perineal stress as a predictor of performing episiotomy in primiparous women: a prospective observational study
Authors: Xu Binbin , Luo Qi , Wu Rongrong , Lu Ying , Ying Hongjun , Xu Yanan , Lu Zhaie
Published: October 2022

Background

Episiotomy is a surgical solution to relieve perineal stress, resulting in an easily repairable incision, in comparison to the risks of serious vaginal trauma during delivery. The midwife typically adopts such a clinical decision, on experience and subjective judgment. However, the association between perineal stress and episiotomy is poorly characterized. Our aim was to identify a threshold value for perineal stress leading to episiotomy, which eventually may be employed as a clinical tool for assessing whether an episiotomy is required or not.

Methods

In total, 245 nulliparous women were investigated for perineal stress during non-instrumental vaginal delivery in Ningbo Women & Children’s Hospital. During the second stage of labor, a flexible membrane stress sensor was placed between the fetal head and perineal wall above the anal fissure. Once the entire fetal head pressed against the sensor, real-time perineal stress was measured, and the peak value was recorded. Cases were divided into non-episiotomy group (n = 173) and episiotomy group (n = 72). The correlations between perineal stress and episiotomy was assessed through logistic regression with adjustment for maternal age, estimated birthweight, duration of second stage of labor, maternal body mass index, and presence of analgesia. Midwives were blinded to all stress measurement values. The predictive value of perineal stress on performing episiotomy was evaluated, together with the ideal cut-off perineal stress value for performing episiotomy. A ROC analysis was also performed.

Results

The episiotomy group had significantly higher levels of perineal stress in comparison to the non-episiotomy group (140.50 ± 16.03 N versus 118.37 ± 19.21 N, p < 0.01). The episiotomy group was linked to significantly higher perineal stress in comparison to the non-episiotomy group (140.50 ± 16.03 VS 118.37 ± 19.21 N, p < 0.01). ROC analysis between perineal stress and episiotomy revealed a high area under the curve (AUC 0.81, 95% CI 0.75–0.86) and a cut-off value for perineal stress of 124.49 N was identified for episiotomy decision.

Conclusion

The level of perineal stress was an independent predictor of performing episiotomy in nulliparous women during non-instrumental vaginal delivery. Perineal stress exceeding 124.49 N was identified as the cut-off prompting midwives to perform episiotomy.
Process evaluation methods and results from the Health in Pregnancy and Postpartum (HIPP) randomized controlled trial
Authors: Wilcox Sara , Dahl Alicia A. , Boutté Alycia K. , Liu Jihong , Day Kelsey , Turner-McGrievy Gabrielle , Wingard Ellen
Published: October 2022

Background

Excessive gestational weight gain has increased over time and is resistant to intervention, especially in women living with overweight or obesity. This study described the process evaluation methods and findings from a behavioral lifestyle intervention for African American and white women living with overweight and obesity that spanned pregnancy (≤ 16 weeks gestation) through 6 months postpartum.

Methods

The Health in Pregnancy and Postpartum (HIPP) study tested a theory-based behavioral intervention (vs. standard care) to help women (N = 219; 44% African American, 29.1 ± 4.8 years) living with overweight or obesity meet weight gain guidelines in pregnancy and lose weight in postpartum. Participants completed process evaluation surveys at 32 weeks gestation (n = 183) and 6 months postpartum (n = 168) regarding their perceptions of most and least helpful aspects of the intervention. A database tracked delivery and receipt of intervention components (in-depth counseling session, telephone calls, podcasts). Descriptive statistics are used to report fidelity, dose, and participants’ perceptions. We also tested whether dose of behavioral intervention components was associated with gestational weight gain and 6-month postpartum weight retention with linear regression models controlling for baseline age and gestational weeks, receipt of Medicaid, race, parity, and marital status. A content analysis was used to code and analyze responses to open-ended survey questions.

Results

Over 90% of participants (both groups) would recommend the program to a friend. Implementation fidelity was moderately high and greater in pregnancy than postpartum for all intervention components. Dose received and participants’ ratings of the in-depth counseling session and telephone calls were more favorable than podcasts. The Facebook group was not perceived to be very helpful, likely because of low participant interaction. Although podcasts were created to reinforce call topics, this redundancy was viewed negatively by some. More calls completed and more podcasts downloaded related to lower gestational weight gain (p < .05).

Conclusion

Study findings underscore challenges in engaging this important but busy population, especially during the postpartum period.

Trial registration:

The study was registered at clinicaltrials.gov (NCT02260518) on 10/09/2014. https://clinicaltrials.gov/ct2/show/NCT02260518.
Nomogram for predicting spontaneous pregnancy after microscopic varicocelectomy in infertile men with normal hormone
Authors: Liu Lina , Li Jia , Liu Gang , Pan Chunyu , Bai Song , Zhan Yunhong , Shan Liping
Published: October 2022

Introduction

The current challenge for the treatment of varicocele is identifying patients who could benefit the most from surgery. We aimed to develop and validate a nomogram for predicting spontaneous pregnancy following microscopic varicocelectomy in infertile men, based on a large cohort.

Methods

Two hundred eighty-two consecutive patients who underwent microscopic varicocelectomy from January 2018 to December 2020 were enrolled as participants in the study. Xiang Hua center (206 patients) as a development cohort. Hu Nan center (76 patients) as a validation cohort. Patient clinicopathologic data were recorded. Multivariate logistic regression was used to build a predictive model with regression coefficients. Then, backward stepwise selection was applied, and the likelihood ratio test with Akaike’s information criterion was used as the stopping rule. The performance of this predictive model was assessed for discrimination, calibration, and clinical usefulness.

Results

Predictors of this model included the age of female partners, diameter of veins, initial and increased total progressively motile sperm count. The model demonstrated good discrimination with an AUROC of 0.925 (p < 0.001) and calibration (Unreliability test, p = 0.522) in the validation cohort. Furthermore, the model was clinically useful, according to decision curve analysis.

Conclusions

Our findings indicated that younger female partners, larger diameter of veins, higher initial and increased total progressively motile sperm count were significant predictors of spontaneous pregnancy in infertile men, post microscopic varicocelectomy. This nomogram may assist in individual decision-making on the treatment strategy of varicocele preoperatively and improve the treatment outcome.
Socio-demographic determinants of cervical cancer screening uptake among women of child-bearing age in Mangochi, Malawi: a facility-based cross-sectional study
Authors: Mpachika-Mfipa Felistas , Kululanga Lucy Ida , Kazembe Abigail , Mfipa Dumisani
Published: October 2022

Background

Cervical cancer (CC) is the number one leading cause of death among women in Malawi. However, it is generally viewed as preventable and treatable if diagnosed in an early stage. Despite the burden, Malawi registers low uptake of cervical cancer screening (CCS). This study examined the socio-demographic determinants of CCS uptake among women of child-bearing age (WCBA) in Mangochi district.

Methods

A cross-sectional quantitative study was conducted in five health facilities. A total of 482 women between the ages of 18–49 participated and were sampled using a multi-stage sampling method. An interviewer administered structured questionnaire was used to collect data from June to July, 2019. Multivariate logistic regression model was used to identify determinants of CCS uptake among WCBA.

Results

Few respondents (13.1%) had ever done CCS. Compared to respondents in the age-group of 18–24 years, those in the age-groups of 25–35 years and 36–49 years were 2.63 and 3.90 times more likely to undergo CCS (AOR = 2.63, 95% CI 1.30–5.31 and AOR = 3.90, 95% CI 1.62–9.38), respectively. Respondents who practiced Christianity were 2.77 times more likely to undergo CCS than those who practiced Islam (AOR = 2.77, 95% CI 1.23–6.22). Respondents of the Chewa ethnic group were 71% less likely to undergo CCS as compared to those of Yao ethnicity (AOR = 0.29, 95% CI 0.09–0.95). Respondents who lived in semi-urban areas were 2.57 times more likely to go for CCS than those who were village residents (AOR = 2.57, 95% CI 1.19–5.55).

Conclusion

Our study showed that CCS uptake was low in Mangochi and the results suggested that age, religion, ethnicity and place of residence were determinants of CCS uptake. We recommend that comprehensive health education on CC should specifically target the young women and Muslim women in places where they meet. We call upon the district health authorities to scale up CCS provision in all Antiretroviral Therapy (ART) and outreach clinics to improve CCS uptake among women residing in the villages and those of the Chewa ethnicity. We, further, call upon all CC program implementers to design programs that address the highlighted socio-demographic determinants of CCS uptake among WCBA in the district.
COVID-19 case counts and COVID-19 related Emergency Department visits: differences by immigration status, March-December 2020
Authors: Ro Annie , Huynh Michael Pham , Bruckner Tim A. , Du Senxi , Young Andrew
Published: October 2022

Background

Undocumented immigrants face barriers to health care access, which may have been exacerbated during the early days of the COVID-19 pandemic. We test whether undocumented immigrants in Los Angeles County accessed COVID-19 related medical care by examining their Emergency Department (ED) patterns through high and low periods of COVID-19 infection. If undocumented immigrants were underutilizing or foregoing health care, we expect null or weaker associations between COVID-19 cases and COVID-19 related ED visits relative to Medi-Cal patients.

Methods

We analyzed all ED visits to the Los Angeles County + University of Southern California (LAC + USC) Medical Center between March - December 2020 (n = 85,387). We conducted logistic regressions with Los Angeles County weekly COVID-19 case counts as our main independent variable and an interaction between case counts and immigration status, stratified by age (over and under 65 years).

Results

We found that undocumented immigrants under 65 years old had a higher odds for a COVID-19 related ED visit compared to Medi-Cal patients and that both undocumented and Medi-Cal patients had higher odds of a COVID-19 related ED visit as COVID-19 cases in Los Angeles County increased. For patients over 65 years, Medi-Cal patients actually had a weaker association between ED visits and county COVID-19 counts; as COVID-19 case counts rose, the odds of a COVID-19 related ED visit increased for the undocumented patients.

Conclusion

While the overall likelihood of undocumented patients having a COVID-19 related ED visit varies compared to Medi-Cal patients - for younger patients, the odds is higher; for older patients, the odds is lower - it does not appear that undocumented patients underutilized the ED during the early COVID-19 pandemic relative to Medi-Cal patients. The ED may be a viable source of contact for this high-risk population for future outreach.
Barriers and facilitators of domain-specific physical activity: a systematic review of reviews
Authors: Garcia Leandro , Mendonça Gerfeson , Benedetti Tânia R. Bertoldo , Borges Lucélia Justino , Streit Inês Amanda , Christofoletti Marina , Silva-Júnior Fernando Lopes e , Papini Camila Bosquiero , Binotto Maria Angélica
Published: October 2022

Background

Knowing what facilitates and hinders physical activity behaviour across domains (leisure, travel, work or education, and household) is central for the development of actions for more active lifestyles. Thus, the aim of this systematic review of reviews was to summarize the evidence on barriers and facilitators of domain-specific physical activity.

Methods

We included systematic reviews with or without meta-analysis that investigated the association between modifiable barriers and facilitators and levels of domain-specific physical activity. Reviews published until September 2020 were retrieved from PubMed, ISI Web of Science, Scopus, Regional Library of Medicine (BIREME), and PsycNET, and from the reference list of selected articles. Each review was screened by two independent reviewers for eligibility. Data extracted from selected papers included methodological aspects (number of primary studies, study designs, and age groups); physical activity domains and barriers and facilitators investigated; and direction of association. For each pair of barrier/facilitator and domain-specific physical activity, we recorded the number of positive, negative, and null associations reported across reviews. Quality assessment of each systematic review was performed using the AMSTAR-2 tool.

Results

Forty-four systematic reviews were selected. The evidence base was largest for leisure-time followed by travel-related physical activity. A very small number of reviews included physical activity in work, educational and domestic settings. Across all physical activity domains, factors related to the built environment were more abundant in the reviews than intra and interpersonal factors. Very consistent positive associations were observed between a range of intrapersonal factors and leisure-time physical activity, as well as moderately consistent evidence of positive association for general social support and support from family members. Evidence of moderate consistency was found for the positive association between transport-related physical activity and positive beliefs about consequences, walkability, and existence of facilities that support active travel. Evidence on barriers and facilitators for physical activity at work, educational, and domestic settings was limited in volume and consistency.

Conclusions

Efforts and resources are required to diversify and strength the evidence base on barriers and facilitators of domain-specific physical activity, as it is still limited and biased towards the leisure domain and built environment factors.

Trial registration

PROSPERO CRD42020209710.
Combination therapy with budesonide and N-acetylcysteine ameliorates LPS-induced ALI by attenuating neutrophil recruitment through the miR-196b-5p/Socs3 molecular axis
Authors: Li Yang , Yu Huimin , Lv Meifen , Li Qiaofen , Zou Kaiwen , Lv Shaokun
Published: October 2022

Background

Neutrophil infiltration accelerates the inflammatory response and is highly correlated to the development of acute lung injury (ALI). Budesonide (BUD) and N-acetylcysteine (NAC) both inhibit the inflammatory response to alleviate ALI, so we further investigated whether their combination is better for ALI.

Methods

In this study, we investigated the effect and mechanism of Combined BUD and NAC therapy on LPS-induced ALI. Rat ALI model and neutrophil abnormal activation model were established by lipopolysaccharide (LPS). BUD and NAC were treated alone or in combination, or cells were transfected with miR-196b-5p mimic or si-Socs3 to evaluate the efficacy and mechanism of BUD and NAC alone or in combination. Histopathological observation of lungs was performed by Hematoxylin Eosin (HE) staining. The quantity of neutrophils and inflammatory factors level in bronchoalveolar lavage fluid (BALF) were determined by Richter-Gimza complex stain and Enzyme-Linked Immunosorbnent Assay (ELISA), respectively. ReverseTranscription-PolymeraseChainReaction (RT–qPCR) was utilized to assess miR-196b-5p and inflammatory factor mRNA levels. The expression level of Socs3 was detected by immunohistochemistry or Western Blot.

Results

BUD and NAC combined treatment had a better effect on neutrophil recruitment and inflammatory response in LPS-induced ALI than did BUD and NAC alone. Transfection of the miR-196b-5p mimic reversed the effect of combined BUD and NAC. In conclusion, the combination of BUD and NAC is a better treatment for ALI.

Conclusions

Combination therapy with BUD and NAC ameliorates LPS-induced ALI by attenuating neutrophil recruitment through the miR-196b-5p/Socs3 molecular axis.
Mechanisms of action of Zishen Yutai pills in treating premature ovarian failure determined by integrating UHPLC-Q-TOF-MS and network pharmacology analysis
Authors: Dang Lei , Zhang Chunbo , Su Biru , Ning Na , Huang Qiuling , Zhou Su , Wu Meng , Ma Wenqing , Wang Man , Cui Pengfei , Li Yan , Wang Shixuan
Published: October 2022

Background

Zishen Yutai (ZSYT) pill, a patent Chinese medicine, has been widely used in the treatment of infertility, abortion, and adjunctive treatment of in vitro fertilization (IVF) for decades. Recently, the results of clinical observations showed that premature ovarian failure (POF) patients exhibited improved expression of steroids and clinical symptoms associated with hormone disorders after treatment with Zishen Yutai pills. However, the pharmacological mechanism of action of these pills remains unclear.

Methods

The compounds of Zishen Yutai pills found in blood circulation were identified via ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) technique in the serum of POF mice after oral administration of Zishen Yutai pills. The potential targets of compounds were screened using Traditional Chinese Medicine Systems Pharmacology Database, Traditional Chinese Medicine Database@Taiwan, Drugbank Database, PubChem, HIT, Pharmapper, and Swiss Target Prediction. The target genes associated with POF were collected from Online Mendelian Inheritance in Man Database, PharmGkb, Genecards, Therapeutic Target Database, and Genetic Association Database. The overlapping genes between the potential targets of Zishen Yutai pills’ compounds and the target genes associated with POF were clarified via protein-protein interaction (PPI), pathway, and network analysis.

Results

Nineteen compounds in Zishen Yutai pills were detected in the serum of POF mice after oral administration. A total of 695 Zishen Yutai (ZSYT) pill-related targets were screened, and 344 POF-related targets were collected. From the results of Zishen Yutai (ZSYT) pill-POF PPI analysis, CYP19A1, AKR1C3, ESR1, AR, and SRD5A2 were identified as key targets via network analysis, indicating their core role in the treatment of POF with Zishen Yutai pills. Moreover, the pathway enrichment results suggested that Zishen Yutai pills treated POF primarily by regulating neuroactive ligand-receptor interaction, steroid hormone biosynthesis, and ovarian steroidogenesis.

Conclusions

Via virtual screening, we found that regulation of neuroactive ligand-receptor interaction, steroid hormone biosynthesis, and ovarian steroidogenesis was the potential therapeutic mechanism of Zishen Yutai pills in treating POF. Our study suggested that combining the analysis of Zishen Yutai pills’ compounds in blood in vivo in the POF model and network pharmacology prediction might offer a tool to characterize the mechanism of Zishen Yutai pills in the POF.
Educating physicians on strong opioids by descriptive versus simulated-experience formats: a randomized controlled trial
Authors: Wegwarth Odette , Spies Claudia , Ludwig Wolf-Dieter , Donner-Banzhoff Norbert , Jonitz Günther , Hertwig Ralph
Published: October 2022

Background

Long-term prescriptions of strong opioids for chronic noncancer pain—which are not supported by scientific evidence—suggest miscalibrated risk perceptions among those who prescribe, dispense, and take opioids. Because risk perceptions and behaviors can differ depending on whether people learn about risks through description or experience, we investigated the effects of descriptive versus simulated-experience educative formats on physicians’ risk perceptions of strong opioids and their prescription behavior for managing chronic noncancer pain.

Methods

Three hundred general practitioners and 300 pain specialists in Germany—enrolled separately in two independent exploratory randomized controlled online trials—were randomly assigned to either a descriptive format (fact box) or a simulated-experience format (interactive simulation).

Primary endpoints

Objective risk perception (numerical estimates of opioids’ benefits and harms), actual prescriptions of seven therapy options for managing chronic pain.

Secondary endpoint

Implementation of intended prescriptions of seven therapy options for managing chronic pain.

Results

Both formats improved the proportion of correct numerical estimates of strong opioids’ benefits and harms immediately after intervention, with no notable differences between formats. Compared to description, simulated experience led to significantly lower reported actual prescription rates for strong and/or weak opioids, and was more effective at increasing prescription rates for non-drug-based therapies (e.g., means of opioid reduction) from baseline to follow-up for both general practitioners and pain specialists. Simulated experience also resulted in a higher implementation of intended behavior for some drug-based and non-drug-based therapies.

Conclusions

The two formats, which recruit different cognitive processes, may serve different risk-communication goals: If the goal is to improve exact risk perception, descriptive and simulated-experience formats are likely to be equally suitable. If, however, the goal is to boost less risky prescription habits, simulated experience may be the better choice.

Trial registration

DRKS00020358 (German Clinical Trials Register, first registration: 07/01/2020).
Responsibility driven learning in primary care: a qualitative evaluation of a medical student COVID-19 volunteering programme
Authors: Coster Samantha , Parekh Ravi , Moula Zoe , Kumar Sonia
Published: October 2022

Background

During the first wave of the pandemic when clinical placements were suspended, a UK medical student volunteering programme was developed to support local GP practices. This study aimed to explore the impact that volunteering in primary care had on students’ learning and professional development to inform the design of future service-learning curricula innovations.

Methods

Seventy medical students across all years volunteered across forty-five GP practices in north-west London. Ten volunteer students and six GPs who had hosted students volunteered to participate in remotely conducted, semi-structured interviews with a researcher. Transcriptions were independently coded by two researchers and analysed by thematic analysis using service learning and communities of practice as sensitising concepts.

Results

Analysis showed a strong alignment between the views of students and GPs in terms of perceived learning. Our analysis of both sets of interviews resulted in five themes describing student outcomes from the volunteering scheme: developing as a doctor, understanding the complexity of medicine, responsibility driven learning, a meaningful role in a community of practice, and seeing behind the scenes in primary care.

Discussion and conclusion

Results from this study highlighted how a meaningful service-led role and responsibility in primary care can empower and motivate students to learn beyond the traditional medical curriculum and assessments. Adopting these new ‘pro-active’ roles within general practices led volunteers, particularly those in the early years of study, to develop a better understanding of primary care and medical complexity. It also enhanced their professional skills, attitudes and behaviours, while having a beneficial impact on patient care during the pandemic.
Influencing mechanism of the use behavior of clinical practice guidelines on antimicrobials: evidence from the integration of theory of reasoned action and organizational readiness for change
Authors: Huang Junbin , Liu Wenbin , Huang Yimin
Published: October 2022

Background

To confront the serious challenge of antimicrobial resistance, using clinical practice guidelines (CPGs) standardizing the prescription behavior is vital. However, the overall mechanisms remains largely unknown as to how guidelines' use behavior can be improved. This study aimed to identify the determinants and investigate their relationship to bridge the knowledge gap of overall influencing mechanism of the use behavior of CPGs on antimicrobials.

Methods

By integrating theory of reasoned action (TRA) and organizational readiness for change (ORC), a structured questionnaire was developed to cover potential determinants that affect physicians’ use behaviors of CPGs on antimicrobials at the individual-level (attitude, subjective norm, and behavioral intention) and organizational-level (top management support and organizational resource allocation). A multi-stage random sampling was implemented to collect data from physicians in secondary and tertiary hospitals from eastern, central and western China. Structural equation model (SEM) was used to test the proposed hypotheses, and to analyze the relationship and mechanism among the factors.

Result

In total, 815 physicians were included. Most physicians demonstrated a positive tendency toward the use of CPGs on antimicrobials, with a mean score of 3.95 (SD = 0.70). The reliability and validity analysis showed the questionnaire constructed from the integrated theoretical model of TRA and ORC was acceptable. The SEM validation results also showed that the top management support (β = 0.688, P < 0.001), organizational resource allocation (β = 0.129, P < 0.001), individual attitudes (β = 0.164, P < 0.001), subjective norms (β = 0.322, P < 0.001), and behavioral intentions (β = 0.424, P < 0.001) were positively associated with physicians’ use behaviors of CPGs on antimicrobials. Besides, top management support, organizational resource allocation, attitudes and subjective norms showed their mediating effects on regarding use behavior, which was 0.305, 0.129, 0.164 and 0.201, respectively.

Conclusions

This study revealed the influence mechanism of the use of CPGs on antimicrobials from the individual and organizational perspectives. These findings will not only help formulate future strategies to promote the use of CPGs on antimicrobials, but also provide clues for more effective prescription interventions.
Nurses experience increased clinical and organisational competence by working with a medical quality register, RevNatus – a qualitative study
Authors: Bjørngaard Hilde , Koksvik Hege Svean , Jakobsen Bente , Grønning Kjersti
Published: October 2022

Background

RevNatus is a consent-based, nationwide medical quality register that collects data on patients with inflammatory rheumatic diseases during pregnancy and one year postpartum. The entering of data takes place in outpatient clinics in rheumatology wards in hospitals. The aim of this study is to explore how rheumatology nurses experience organizing and working with the medical quality register RevNatus in addition to their normal clinical patient-care tasks.

Methods

Qualitative focus group interviews and individual in-depth interviews were conducted in 2018 to gain insights into how nurses organize performing quality register work and clinical work simultaneously. Data were analysed using systematic text condensation.

Results

The informants represented seven different rheumatology outpatient clinics in Norway. The analyses showed that working with RevNatus increased the nurses’ knowledge about pregnancy and rheumatic diseases, improved the content of their nurse consultations and found the ‘register form’ as a useful template to structure the nurse consultations. The nurses took the main responsibility for RevNatus, but lack of routines and uncoordinated collaboration with the rheumatologists and secretaries made the nurses spend too much time verifying the accuracy of data or post-registering missing data.

Conclusion

The nurses experienced work with RevNatus as time-consuming, but the register work increased both their clinical and organisational competences. Routines and collaboration within the registry team are important to ensure the data quality and reduce the workload.
Interdisciplinary collaboration across secondary and primary care to improve medication safety in the elderly (The IMMENSE study) – a randomized controlled trial
Authors: Johansen Jeanette Schultz , Halvorsen Kjell H. , Svendsen Kristian , Havnes Kjerstin , Robinson Eirin Guldsten , Wetting Hilde Ljones , Haustreis Stine , Småbrekke Lars , Kamycheva Elena , Garcia Beate Hennie
Published: October 2022

Background

Suboptimal medication use contributes to a substantial proportion of hospitalizations and emergency department visits in older adults. We designed a clinical pharmacist intervention to optimize medication therapy in older hospitalized patients. Based on the integrated medicine management (IMM) model, the 5-step IMMENSE intervention comprise medication reconciliation, medication review, reconciled medication list upon discharge, patient counselling, and post discharge communication with primary care. The objective of this study was to evaluate the effects of the intervention on healthcare use and mortality.

Methods

A non-blinded parallel group randomized controlled trial was conducted in two internal medicine wards at the University Hospital of North Norway. Acutely admitted patients ≥ 70 years were randomized 1:1 to intervention or standard care (control). The primary outcome was the rate of emergency medical visits (readmissions and emergency department visits) 12 months after discharge.

Results

Of the 1510 patients assessed for eligibility, 662 patients were asked to participate, and 516 were enrolled. After withdrawal of consent and deaths in hospital, the modified intention-to-treat population comprised 480 patients with a mean age of 83.1 years (SD: 6.3); 244 intervention patients and 236 control patients. The number of emergency medical visits in the intervention and control group was 497 and 499, respectively, and no statistically significant difference was observed in rate of the primary outcome between the groups [adjusted incidence rate ratio of 1.02 (95% CI: 0.82–1.27)]. No statistically significant differences between groups were observed for any of the secondary outcomes, neither in subgroups, nor for the per-protocol population.

Conclusions

We did not observe any statistical significant effects of the IMMENSE intervention on the rate of emergency medical visits or any other secondary outcomes after 12 months in hospitalized older adults included in this study.

Trial registration

The trial was registered in clinicaltrials.gov on 28/06/2016, before enrolment started (NCT02816086).
Analysis and enhancement of risk management for ethnic differences in antineoplastic drugs in Japan
Authors: Uzu Shinobu , Sato Jun , Wakao Rika , Nonaka Takahiro
Published: October 2022

Background

Risk management in the post-marketing phase is crucial to minimize health problems caused by drugs. Because ethnic factors may affect drug safety, the objective of this study was to explore concrete approaches to reflecting ethnic factors in risk management under multi-regional drug development.

Methods

We assessed Pharmaceuticals and Medical Devices Agency (PMDA) review reports on antineoplastic drugs approved as new molecular entities in the last 10 years to identify any differences in the incidence of adverse drug reactions (ADRs) related to myelosuppression, hepatic impairment, renal impairment, and interstitial lung disease between Japanese and non-Japanese populations. In addition, we investigated how those ADRs were handled in the labeling of each drug.

Results

In total, 44 drugs were available for comparing the incidence of ADRs between Japanese and non-Japanese populations. Of these, 32 drugs had a higher incidence of ADRs in the Japanese population. However, the incidence of ADRs in the Japanese population was described in the labeling for 7 drugs, and only the incidence in the overall population in multi-regional phase III trials was described in the labeling for the remaining 25 drugs. Of these 25 drugs, two drugs were immediately placed under emergency safety control measures after approval because of the high incidence of ADRs in Japanese patients.

Conclusions

For drugs that might cause serious ADRs and with a higher incidence in the Japanese population, information should be provided on the incidence in the Japanese population as well as in the overall population.
Effects of dabigatran versus warfarin on 2-year cognitive outcomes in old patients with atrial fibrillation: results from the GIRAF randomized clinical trial
Authors: Caramelli Bruno , Yu Pai Ching , Cardozo Francisco A. M. , Magalhães Iuri R. , Spera Raphael R. , Amado Daniel K. , Escalante-Rojas Maria C. , Gualandro Danielle M. , Calderaro Daniela , Tavares Caio A. M. , Borges-Junior Flavio A. , Pastana Adriana F. , Matheus Mariana G. , Brucki Sonia M. D. , Rodrigues Ana Carolina O. , Nitrini Ricardo , Caramelli Paulo
Published: October 2022

Background

Observational studies support a role for oral anticoagulation to reduce the risk of dementia in atrial fibrillation patients, but conclusive data are lacking. Since dabigatran offers a more stable anticoagulation, we hypothesized it would reduce cognitive decline when compared to warfarin in old patients with atrial fibrillation.

Methods

The GIRAF trial was a 24-month, randomized, parallel-group, controlled, open-label, hypothesis generating trial. The trial was done in six centers including a geriatric care unit, secondary and tertiary care cardiology hospitals in São Paulo, Brazil. We included patients aged ≥ 70 years and CHA2DS2-VASc score > 1. The primary endpoint was the absolute difference in cognitive performance at 2 years. Patients were assigned 1:1 to take dabigatran (110 or 150 mg twice daily) or warfarin, controlled by INR and followed for 24 months. Patients were evaluated at baseline and at 2 years with a comprehensive and thorough cognitive evaluation protocol of tests for different cognitive domains including the Montreal Cognitive Assessment (MoCA), Mini-Mental State Exam (MMSE), a composite neuropsychological test battery (NTB), and computer-generated tests (CGNT).

Results

Between 2014 and 2019, 5523 participants were screened and 200 were assigned to dabigatran (N = 99) or warfarin (N = 101) treatment. After adjustment for age, log of years of education, and raw baseline score, the difference between the mean change from baseline in the dabigatran group minus warfarin group was − 0.12 for MMSE (95% confidence interval [CI] − 0.88 to 0.63; P = 0.75), 0.05 (95% CI − 0.07 to 0.18; P = 0.40) for NTB, − 0.15 (95% CI − 0.30 to 0.01; P = 0.06) for CGNT, and − 0.96 (95% CI − 1.80 to 0.13; P = 0.02) for MoCA, with higher values suggesting less cognitive decline in the warfarin group.

Conclusions

For elderly patients with atrial fibrillation, and without cognitive compromise at baseline that did not have stroke and were adequately treated with warfarin (TTR of 70%) or dabigatran for 2 years, there was no statistical difference at 5% significance level in any of the cognitive outcomes after adjusting for multiple comparisons.

Trial registration

Cognitive Impairment Related to Atrial Fibrillation Prevention Trial (GIRAF), NCT01994265.