bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-world long-term efficacy and safety of erenumab in adults with chronic migraine: a 52-week, single-center, prospective, observational study
Authors: Cullum Christopher Kjaer , Do Thien Phu , Ashina Messoud , Bendtsen Lars , Hugger Sarah Sonja , Iljazi Afrim , Gusatovic Julia , Snellman Josefin , Lopez-Lopez Cristina , Ashina Håkan , Amin Faisal Mohammad
Published: June 2022

Background

Clinical trials have shown that erenumab is effective and well-tolerated for the preventive treatment of chronic migraine. To extend the results from clinical trials, we assessed the real-world efficacy and safety of erenumab in patients with chronic migraine from the outpatient clinic at the Danish Headache Center.

Methods

A 52-week, single-center, prospective, observation study of erenumab in adults with chronic migraine who are eligible for treatment with monoclonal antibodies against CGRP or its receptor in Denmark. The primary outcome was defined as proportion of patients who achieved ≥ 30% reduction in monthly migraine days (MMDs) from baseline to weeks 9–12.

Results

A total of 300 adult patients with chronic migraine were enrolled and received at least one dose of erenumab. At baseline, the mean (SD) number of monthly headache days was 23 ± 4.9 and mean number of MMDs was 16.8 ± 6.4. Of 300 enrolled patients, 273 (91.0%) patients completed 12 weeks of treatment, and 119 (39.7%) completed 52 weeks of treatment. The number of patients who achieved ≥ 30% reduction in MMDs from baseline to weeks 9–12 was 195 (71.4%) of 273 patients. Sustained ≥ 30% reduction in MMDs at all assessment periods throughout the 52-week treatment period was achieved by 102 (34%) of 300 patients. Adverse events occurred in 220 (73.3%) out of 300 patients. The most common adverse event was constipation. Treatment discontinuation due to lack of tolerability occurred in 41 (13.7%) patients.

Conclusions

Among adult patients with chronic migraine and previous failure of medications for migraine prevention, erenumab was found to be effective and well-tolerated.
Comprehensive analysis of cucumber C-repeat/dehydration-responsive element binding factor family genes and their potential roles in cold tolerance of cucumber
Authors: Li Jialin , Li Hongmei , Quan Xiaoyan , Shan Qiuli , Wang Wenbo , Yin Ning , Wang Siqi , Wang Zenghui , He Wenxing
Published: June 2022

Background

Cold stress is one of the main abiotic stresses limiting cucumber (Cucumis sativus L.) growth and production. C-repeat binding factor/Dehydration responsive element-binding 1 protein (CBF/DREB1), containing conserved APETALA2 (AP2) DNA binding domains and two characteristic sequences, are key signaling genes that can be rapidly induced and play vital roles in plant response to low temperature. However, the CBF family has not been systematically elucidated in cucumber, and the expression pattern of this family genes under cold stress remains unclear.

Results

In this study, three CsCBF family genes were identified in cucumber genome and their protein conserved domain, protein physicochemical properties, gene structure and phylogenetic analysis were further comprehensively analyzed. Subcellular localization showed that all three CsCBFs were localized in the nucleus. Cis-element analysis of the promoters indicated that CsCBFs might be involved in plant hormone response and abiotic stress response. Expression analysis showed that the three CsCBFs could be significantly induced by cold stress, salt and ABA. The overexpression of CsCBFs in cucumber seedlings enhanced the tolerance to cold stress, and importantly, the transcript levels of CsCOR genes were significantly upregulated in 35S:CsCBFs transgenic plants after cold stress treatment. Biochemical analyses ascertained that CsCBFs directly activated CsCOR genes expression by binding to its promoter, thereby enhancing plant resistance to cold stress.

Conclusion

This study provided a foundation for further research on the function of CsCBF genes in cold stress resistance and elucidating its mechanism.
Knowing the entire story – a focus group study on patient experiences with chronic Lyme-associated symptoms (chronic Lyme disease)
Authors: Baarsma M. E. , Claassen S. A. , van der Horst H. E. , Hovius J. W. , Sanders J. M.
Published: June 2022

Background

Healthcare providers frequently struggle to provide effective care to patients with chronic Lyme-associated symptoms (chronic Lyme disease, CLD), potentially causing these patients to feel misunderstood or neglected by the healthcare system. This study is the first to use a combined medical and communication science approach, and aims to assess patients’ experiences with CLD & CLD-related care, identify themes and repertories in these patients’ narrations, and provide potential ways to improve communication with them.

Methods

Informed by the principles of ‘clean language’, we conducted focus groups with self-identified CLD patients (N = 15). We asked participants about their experiences with CLD and CLD-related healthcare. We performed thematic analyses using a bottom-up approach based in discourse analysis. We also sought to identify specific types of verbalizations (repertoires) across themes.

Results

Participants thematised a heterogeneous set of CLD-associated symptoms, which they frequently labelled as ‘invisible’ to others. Their illness significantly affected their daily lives, impacting their work, social activities, relationships with loved ones, hobbies and other means of participating in society. Negative experiences with healthcare providers were near-universal, also in patients with short-lived CLD-associated symptoms. Verbalizations were notable for frequent use of communicative modes that implicitly create common ground between participants and that give a certain validity to personal experiences (impersonal ‘you’ and other forms of presupposition).

Conclusion

Central themes found in CLD patients’ communication are 1. the experience of significant symptoms, 2. for which adequate relief is only rarely found from conventional medical practitioners, and 3. that are largely invisible to the outside world. Verbalizing these themes, patients use various repertoires for their shared experiences, such as a feeling of abandonment or not being heard by the medical system, feelings of loss with respect to their previous health, and the idea that they might have been better off had they been diagnosed sooner. Working with these repertoires will enable healthcare providers to establish a shared perspective with their CLD patients, thus engaging in more fruitful doctor-patient communication. We hypothesize that these findings are not unique to CLD, but may also be applicable to other conditions with an uncertain aetiology, such as Long COVID.
The association between health anxiety, physical disease and cardiovascular risk factors in the general population – a cross-sectional analysis from the Tromsø study: Tromsø 7
Authors: Norbye Anja Davis , Abelsen Birgit , Førde Olav Helge , Ringberg Unni
Published: June 2022

Background

Health anxiety (HA) is defined as a worry of disease. An association between HA and mental illness has been reported, but few have looked at the association between HA and physical disease.

Objective

To examine the association between HA and number of diseases, different disease categories and cardiovascular risk factors in a large sample of the general population.

Methods

This study used cross-sectional data from 18,432 participants aged 40 years or older in the seventh survey of the Tromsø study. HA was measured using a revised version of the Whiteley Index-6 (WI-6-R). Participants reported previous and current status regarding a variety of different diseases. We performed exponential regression analyses looking at the independent variables 1) number of diseases, 2) disease category (cancer, cardiovascular disease, diabetes or kidney disease, respiratory disease, rheumatism, and migraine), and 3) cardiovascular risk factors (high blood pressure or use of cholesterol- or blood pressure lowering medication).

Results

Compared to the healthy reference group, number of diseases, different disease categories, and cardiovascular risk factors were consistently associated with higher HA scores. Most previous diseases were also significantly associated with increased HA score. People with current cancer, cardiovascular disease, and diabetes or kidney disease had the highest HA scores, being 109, 50, and 60% higher than the reference group, respectively.

Conclusion

In our general adult population, we found consistent associations between HA, as a continuous measure, and physical disease, all disease categories measured and cardiovascular risk factors.
Two differentially methylated region networks in nonalcoholic fatty liver disease, viral hepatitis, and hepatocellular carcinoma
Authors: Kurokawa Suguru , Yoneda Masato , Ogawa Yuji , Honda Yasushi , Kessoku Takaomi , Imajo Kento , Saito Satoru , Nakajima Atsushi , Hotta Kikuko
Published: June 2022

Background

We previously reported that two differentially methylated region (DMR) networks identified by DMR and co-methylation analyses are strongly correlated with the fibrosis stages of nonalcoholic fatty liver disease (NAFLD). In the current study, we examined these DMR networks in viral hepatitis and hepatocellular carcinoma (HCC).

Methods

We performed co-methylation analysis of DMRs using a normal dataset (GSE48325), two NAFLD datasets (JGAS000059 and GSE31803), and two HCC datasets (GSE89852 and GSE56588). The dataset GSE60753 was used for validation.

Results

One DMR network was clearly observed in viral hepatitis and two HCC populations. Methylation levels of genes in this network were higher in viral hepatitis and cirrhosis, and lower in HCC. Fatty acid binding protein 1 (FABP1), serum/glucocorticoid regulated kinase 2 (SGK2), and hepatocyte nuclear factor 4 α (HNF4A) were potential hub genes in this network. Increased methylation levels of the FABP1 gene may be correlated with reduced protection of hepatocytes from oxidative metabolites in NAFLD and viral hepatitis. The decreased methylation levels of SGK2 may facilitate the growth and proliferation of HCC cells. Decreased methylation levels of HNF4A in HCC may be associated with tumorigenesis. The other DMR network was observed in NAFLD, but not in viral hepatitis or HCC. This second network included genes involved in transcriptional regulation, cytoskeleton organization, and cellular proliferation, which are specifically related to fibrosis and/or tumorigenesis in NAFLD.

Conclusions

Our results suggest that one DMR network was associated with fibrosis and tumorigenesis in both NAFLD and viral hepatitis, while the other network was specifically associated with NAFLD progression. Furthermore, FABP1, SGK2, and HNF4A are potential candidate targets for the prevention and treatment of HCC.
Gut microbiota and atopic dermatitis in children: a scoping review
Authors: Liu Yue , Du Xiaofan , Zhai Shujie , Tang Xiaodong , Liu Cuiling , Li Weihong
Published: June 2022

Background

Gut microbiota plays an important role in the development of atopic dermatitis (AD). We aimed to elucidate research trends in gut microbiota and AD in children, to provide evidence and insights to the clinical prevention and treatment of AD in children.

Methods

A scoping literature review on the studies of gut microbiota and AD were conducted. Two authors independently searched Pubmed et al. databases for studies focused on gut microbiota and AD in children up to January 15, 2022. The literatures were screened and analyzed by two reviewers.

Results

A total of 44 reports were finally included and analyzed. Current researches have indicated that abnormal human microecology is closely associated with AD, and the disturbance of intestinal microbiota plays an important role in the occurrence and development of AD. Probiotics can correct the microbiota disorder, have the functions of regulating immunity, antioxidant, and help to restore the microecological homeostasis. However, there is still a lack of high-quality research reports on the efficacy and safety of probiotics in the prevention and treatment of AD in children.

Conclusions

The changes of gut microbiota are essential to the development of AD in children, which may be an effective target for the prevention and treatment of AD. Future studies with larger sample size and rigorous design are needed to elucidate the effects and safety of probiotics in AD.
Cognitive behavioural group therapy as addition to psychoeducation and pharmacological treatment for adolescents with ADHD symptoms and related impairments: a randomised controlled trial
Authors: Haugan Anne-Lise Juul , Sund Anne Mari , Young Susan , Thomsen Per Hove , Lydersen Stian , Nøvik Torunn Stene
Published: June 2022

Background

Cognitive behavioural therapy (CBT) is recommended for attention-deficit/hyperactivity-disorder (ADHD) in adolescents. However, all CBTs are not created equal, and the guidelines do not specify which CBT interventions are the most effective for this patient group. This study examines the efficacy of a group CBT without parent involvement as follow-up treatment compared to no additional CBT in adolescents with persistent and impairing ADHD symptoms after a short psychoeducational intervention and medical treatment.

Methods

The authors conducted a two-arm parallel randomized controlled trial in two child and adolescent mental health outpatient clinics in Norway. One hundred patients aged 14–18 years with a diagnosis of ADHD (66%) or subthreshold ADHD (34%) were randomized to either a 12-week group CBT program (N = 50) or a non-CBT control condition (N = 50). Assessments were made at admission to the clinic, two weeks before and two weeks after treatment. The primary outcomes were parent-, teacher- and self-ratings of ADHD symptoms (ADHD Rating Scale-IV), and the secondary outcomes were ratings of ADHD symptom severity, executive function, functional impairment, and emotional problems. Evaluators blinded to group allocation rated ADHD symptom severity with the Clinical Global Impression Scale for Severity (CGI-S) at baseline and post-treatment.

Results

Analyses using mixed-effects models showed no difference between the treatment arms from baseline to post treatment in primary and secondary outcomes.

Conclusions

Contrary to our hypothesis, we found no incremental treatment effect on the part of a group CBT as follow-up to psychoeducation and pharmacological treatment on ADHD symptoms and accompanying impairments. Limitations with the CBT was the large number and low dosage of treatment components, causing restricted time for practice. Unlike evidence-based, individualized targeted CBTs with parent involvement, a group CBT directed solely at the adolescents with no parent involvement does not appear effective for treating ADHD.

Trial registration

NCT02937142, 18/10/2016.
COVID-19 lockdown – who cares? The first lockdown from the perspective of relatives of people with severe mental illness
Authors: Mork Erlend , Aminoff Sofie R. , Barrett Elizabeth Ann , Simonsen Carmen , Hegelstad Wenche ten Velden , Lagerberg Trine Vik , Melle Ingrid , Romm Kristin Lie
Published: June 2022

Background

Informal care is vital to many people with severe mental illness under normal circumstances. Little is known about how extraordinary circumstances affect relatives with a family member with mental illness. This study investigated the consequences of the first COVID-19 lockdown in Norway from the perspective of relatives of persons with psychotic- and/or bipolar disorders: What were the challenges and for whom?

Method

Relatives were invited to complete an online survey shortly after the first lockdown was initiated. Both quantitative and qualitative data were collected concerning experiences of relatives’ own and their affected family members’ health and situation. Two hundred and seventy-nine relatives completed the survey, mostly mothers and partners.

Results

One-third of the relatives reported considerable deterioration in their family members’ mental health, and a substantial minority worried about severe self-harm or suicide. Main themes in the qualitative analyses were “Isolation and its effects on mental health”, “Worrying about the pandemic and its consequences”, “Increased symptomatology” and “Suicide”. Being a relative during the lockdown put heavy strain on the relatives’ own health, in particular disturbance of sleep, concentration, and the ability to take care of others in the family. Relatives of family members with psychotic bipolar disorder, not currently in treatment, or living with their family experienced the situation especially challenging.

Conclusions

Many relatives found the first lockdown hard for their family. Efforts to integrate relatives’ perspectives in health care and contingency plans under normal circumstances could potentially alleviate some of the extra burden experienced by families during extraordinary circumstances.
Prospective cohort of cryobiopsy in interstitial lung diseases: a single center experience
Authors: Ribeiro Neto Manuel L. , Arrossi Andrea Valeria , Yadav Ruchi , Culver Daniel A. , Mukhopadhyay Sanjay , Parambil Joseph G. , Southern Brian D. , Tolle Leslie , Pande Aman , Almeida Francisco A. , Sahoo Debasis , Glennie Jessica , Ahmad Usman , Mehta Atul C. , Gildea Thomas R.
Published: June 2022

Rationale

Transbronchial cryobiopsy has been increasingly used to diagnose interstitial lung diseases. However, there is uncertainty regarding its accuracy and risks, mainly due to a paucity of prospective or randomized trials comparing cryobiopsy to surgical biopsy.

Objectives

To evaluate the diagnostic yield and complications of cryobiopsy in patients selected by multidisciplinary discussion.

Methods

This was a prospective cohort from 2017 to 2019. We included consecutive patients with suspected interstitial lung diseases being considered for lung biopsy presented at our multidisciplinary meeting.

Measurements and main results

Of 112 patients, we recommended no biopsy in 31, transbronchial forceps biopsy in 16, cryobiopsy in 54 and surgical biopsy in 11. By the end of the study, 34 patients had had cryobiopsy and 24 patients, surgical biopsy. Overall pathologic and multidisciplinary diagnostic yield of cryobiopsy was 47.1% and 61.8%, respectively. The yield increased over time for both pathologic (year 1: 28.6%, year 2: 54.5%, year 3: 66.7%, p = 0.161) and multidisciplinary (year 1: 50%, year 2: 63.6%, year 3: 77.8%, p = 0.412) diagnosis. Overall rate of grade 4 bleeding after cryobiopsy was 11.8%. Cryobiopsy required less chest tube placement (11.8% vs 100%, p < 0.001) and less hospitalizations compared to surgical biopsy (26.5% vs 95.7%, p < 0.001), but hospitalized patients had a longer median hospital stay (2 days vs 1 day, p = 0.004).

Conclusions

Diagnostic yield of cryobiopsy increased over time but the overall grade 4 bleeding rate was 11.8%.
3D analysis of the distal ulna with regard to the design of a new ulnar head prosthesis
Authors: Furrer Pascal Raffael , Nagy Ladislav , Reissner Lisa , Schweizer Andreas
Published: June 2022

Study design

A retrospective, single center, data analysis.

Objective

Persistent pain and instability are common complications after distal ulnar head arthroplasty. One main reason may be the insufficient representation of the anatomical structures with the prosthesis. Some anatomical structures are neglected such as the ulnar head offset and the ulnar torsion which consequently influences the wrist biomechanics.

Methods

CT scans of the ulnae of forty healthy and asymptomatic patients were analyzed in a three-dimensional surface calculation program. In the best fit principle, cylinders were fitted into the medullary canal of the distal ulna and the ulnar head to determine their size. The distance between the central axes of the two cylinders was measured, which corresponds to the ulnar offset, and also their rotational orientation was measured, which corresponds to the ulnar torsion.

Results

The mean medullary canal diameter was 5.8 mm (±0.8), and the ulnar head diameter was 15.8 mm (±1.5). The distance between the two cylinder axes was 3.89 mm (±0.78). The orientation of this offset was at an average of 8.63° (±15.28) of supination, reaching from 23° pronation to 32° supination.

Conclusion

With these findings, a novel ulnar head prosthesis should have different available stem and head sizes but also have an existing but variable offset between these two elements. A preoperative three-dimensional analysis is due to the high variation of offset orientation highly recommended. These findings might help to better represent the patients natural wrist anatomy in the case of an ulnar head arthroplasty.

Level of Evidence

III.
Feasibility and advantages analyses of wedge resection without mesentery detached approach applied to closure of loop ileostomy
Authors: Qin Hai-Quan , Liao Jian-Kun , Wang Wen-Tao , Meng Ling-Hou , Huang Zi-Gao , Mo Xian-Wei
Published: June 2022

Objectives

To evaluate the feasibility and advantages of wedge resection plus transverse suture without mesentery detached approach applied to loop ileostomy closure by analyzing the surgical data and the incidence of postoperative complications of patients undergoing this procedure.

Methods

We performed a retrospective analysis of the hospitalization data of patients who underwent ileostomy closure surgery and met the research standards from January 2017 to April 2021 in Guangxi Medical University Cancer Hospital; all surgeries were performed by the same surgeon. The perioperative data were statistically analyzed by grouping.

Results

In total, 65 patients were enrolled in this study, with 12 in the wedge resection group, 35 in the stapler group, and 18 in the hand suture group. There was no significant difference in operation time between the wedge resection group and stapler group (P > 0.05), but both groups had shorter operation time than that in the hand suture group (P < 0.05). The postoperative exhaustion time of wedge resection group was earlier than that of the others, and cost of surgical consumables in the wedge resection group was significantly lower than that in the stapler group, all with statistically significant differences (P < 0.05). By contrast, there were no statistically significant differences in postoperative complication incidences among the three groups.

Conclusions

The wedge resection plus transverse suture without mesentery detached approach is safe and easy for closure of loop ileostomy in selected patients, and the intestinal motility recovers rapidly postoperatively. It costs less surgical consumables, and is particularly suitable for the currently implemented Diagnosis-Related Groups payment method.
Improving transitions and outcomes of sepsis survivors (I-TRANSFER): a type 1 hybrid protocol
Authors: O’Connor Melissa , Kennedy Erin E. , Hirschman Karen B. , Mikkelsen Mark E. , Deb Partha , Ryvicker Miriam , Hodgson Nancy A. , Barrón Yolanda , Stawnychy Michael A. , Garren Patrik A. , Bowles Kathryn H.
Published: June 2022

Background

This protocol is based on home health care (HHC) best practice evidence showing the value of coupling timely post-acute care visits by registered nurses and early outpatient provider follow-up for sepsis survivors. We found that 30-day rehospitalization rates were 7 percentage points lower (a 41% relative reduction) when sepsis survivors received a HHC nursing visit within 2 days of hospital discharge, at least 1 more nursing visit the first week, and an outpatient provider follow-up visit within 7 days compared to those without timely follow-up. However, nationwide, only 28% of sepsis survivors who transitioned to HHC received this timely visit protocol. The opportunity exists for many more sepsis survivors to benefit from timely home care and outpatient services. This protocol aims to achieve this goal. 

Methods

Guided by the Consolidated Framework for Implementation Research, this Type 1 hybrid pragmatic study will test the effectiveness of the Improving Transitions and Outcomes of Sepsis Survivors (I-TRANSFER) intervention compared to usual care on 30-day rehospitalization and emergency department use among sepsis survivors receiving HHC. The study design includes a baseline period with no intervention, a six-month start-up period followed by a one-year intervention period in partnership with five dyads of acute and HHC sites. In addition to the usual care/control periods from the dyad sites, additional survivors from national data will serve as control observations for comparison, weighted to produce covariate balance. The hypotheses will be tested using generalized mixed models with covariates guided by the Andersen Behavioral Model of Health Services. We will produce insights and generalizable knowledge regarding the context, processes, strategies, and determinants of I-TRANSFER implementation.

Discussion

As the largest HHC study of its kind and the first to transform this novel evidence through implementation science, this study has the potential to produce new knowledge about the impact of timely attention in HHC to alleviate symptoms and support sepsis survivor’s recovery at home. If effective, the impact of this intervention could be widespread, improving the quality of life and health outcomes for a growing, vulnerable population of sepsis survivors. A national advisory group will assist with widespread results dissemination.
Predictors of evidence-based practice competency among Tunisian nursing students
Authors: Tlili Mohamed Ayoub , Aouicha Wiem , Tarchoune Syrine , Sahli Jihene , Ben Dhiab Mohamed , Chelbi Souad , Mtiraoui Ali , Ajmi Thouraya , Ben Rejeb Mohamed , Mallouli Manel
Published: June 2022

Background

Evidence-based practice (EBP) is an important competency of undergraduate nursing students which should be cultivated before graduation by increasing future healthcare providers’ knowledge, skills and attitudes towards EBP. This study aimed to describe nursing students’ competencies (attitudes, knowledge, skills) in Evidence-based practice (EBP) and to determine factors predicting EBP competency.

Methods

A descriptive cross-sectional study was conducted at the Higher School of Health Sciences and Techniques of Sousse (Tunisia) among 365 nursing students. Data were collected using the validated Evidence Based Practice Competencies Questionnaire (EBP-COQ). Multiple linear regression was performed to determine factors predicting EBP competencies.

Results

The overall score of EBP-COQ questionnaire was 3.26 ± 0.53 out of 5. The attitude, skills and knowledge subscales received 4.04 ± 0.41; 3.05 ± 0.77 and 2.70 ± 0.74 as mean scores respectively. Multiple linear regression analysis (table 4) revealed that significant related factors were academic level (β = 0.271, p = 0.001), English-language reading skills (β = 0.435, p < 0.001), facing staff resistance in implementing a new evidence-based procedure (β = − 0.081, p = 0.035) difficulties in obtaining full-text papers (β = − 0.127, p < 0.001) and training in methodology (β = 0.232, p < 0.001) and also in statistics (β = 0.205, p < 0.001).

Conclusions

These results help to understand students’ attitudes, knowledge and skills in EBP and can be therefore a starting point to develop effective strategies for EBP curricula.
Medical students’ learning experience and participation in communities of practice at municipal emergency care units in the primary health care system: a qualitative study
Authors: Giske Solveig , Kvangarsnes Marit , Landstad Bodil J. , Hole Torstein , Dahl Berit Misund
Published: June 2022

Background

Medical education has been criticised for not adapting to changes in society, health care and technology. Internationally, it is necessary to strengthen primary health care services to accommodate the growing number of patients. In Norway, emergency care patients are increasingly treated in municipal emergency care units in the primary health care system. This study explores medical students’ learning experience and how they participated in communities of practice at two municipal emergency care units in the primary health care system.

Methods

In this qualitative study, we collected data from March to May 2019 using semi-structured individual interviews and systematic observations of six ninth-semester medical students undergoing two-week clerkships at municipal emergency care units. The interview transcripts were thematically analysed with a social constructivist approach. A total of 102 systematic observations were used to triangulate the findings from the thematic analysis.

Results

Three themes illuminated what the medical students learned and how they participated in communities of practice: (i) They took responsibility for emergency care patients while participating in the physicians’ community of practice and thus received intensive training in the role of a physician. (ii) They learned the physician’s role in interprofessional collaboration. Collaborating with nursing students and nurses led to training in clinical procedures and insight into the nurses’ role, work tasks, and community of practice. (iii) They gained in-depth knowledge through shared reflections when time was allocated for that purpose. Ethical and medical topics were elucidated from an interprofessional perspective when nursing students, nurses, and physicians participated.

Conclusions

Our findings suggest that this was a form of clerkship in which medical students learned the physician’s role by taking responsibility for emergency care patients and participating in multiple work tasks and clinical procedures associated with physicians’ and nurses’ communities of practice. Participating in an interprofessional community of practice for professional reflections contributed to in-depth knowledge of ethical and medical topics from the medical and nursing perspectives.
Public legitimacy of healthcare resource allocation committees: lessons learned from assessing an Israeli case study
Authors: Assor Yael , Greenberg Dan
Published: June 2022

Background

The National Health Insurance Law enacted in 1995 stipulates a list of health services to which all Israeli residents are entitled. For the past 20 years, the list has been updated annually, as a function of a predetermined budget, according to recommendations from the Public National Advisory Committee (PNAC), which evaluates and prioritizes candidate technologies. We assessed the legitimacy of this resource-allocation process as reflected in Israeli public discourse and its congruence with the accountability for reasonableness (A4R) framework.

Methods

A qualitative analysis of public discourse documents (articles in the print media, court rulings and parliamentary debates (N = 119) was conducted to assess the perceived legitimacy by the Israeli public of the PNAC. Further content analysis of these documents and semi-structured interviews with stakeholders (N = 70) revealed the mainstays and threats to its legitimacy. Based on these data sources, on governmental documents specifying PNAC's procedures, and on data from participant observations, we assessed its congruence with A4R’s four conditions: publicity, relevance, revision and appeals, regulation.

Results

The PNAC enjoys ongoing support for its legitimacy in Israeli public discourse, which stem from its perceived professional focus and transparency. These strengths are consistent with the A4R’s emphasis on the publicity and the relevance conditions. The three major threats to PNAC's legitimacy pertain to: (1) the composition of the committee; (2) its operating procedures; (3) its guiding principles. These perceived shortcomings are also consistent with incongruencies between PNAC's work model and A4R. These findings thus further support the empirical validity of the A4R.

Conclusion

The analysis of the fit between the PNAC and A4R points to refinements in all four conditions that could make the A4R a more precise evaluative framework. Concurrently, it highlights areas that the PNAC should improve to increase its legitimacy, such as incorporating cost-effectiveness analyses and including patient representatives in the decision-making process.

Hebrew and Arabic abstracts for this article are available as an additional file.
Accelerating problem-solving capacities of sub-national public health professionals: an evaluation of a digital immunization training intervention
Authors: Watkins Karen E. , Sandmann Lorilee R. , Dailey Cody Aaron , Li Beixi , Yang Sung-Eun , Galen Robert S. , Sadki Reda
Published: June 2022

Background

This article reports an evaluation of the Immunization Training Challenge Hackathons (ITCH), invented by The Geneva Learning Foundation (TGLF) for national and sub-national immunization staff who strive to develop the knowledge and capacity of others to improve immunization program performance. ITCH, a fully-digital program focused on networked collaborative problem-solving between peers, provided an “opt-in” activity for learners in the Teach to Reach (T2R) Accelerator Program designed to improve training effectiveness in the immunization sphere.

Methods

Conducted by a team from the University of Georgia, this mixed method evaluation consisted of thematic analysis of recorded sessions and open-ended comments; and statistical analyses of application and follow-up survey data. The evaluation focused on what was learned and how ITCH participants implemented what they learned. Key stakeholder interviews provided supplemental data about program intent and results. ITCH consisted of 17 30-min sessions held in 2020, in English and French, with 581 participating at least once out of 1,454 enrolled in the overall program. Challenge owners and respondents came from 15 African and Asian countries and spanned different roles with differing scope.

Results

Over 85% [n = 154] of survey respondents [n = 181, a 31% response rate] indicated they were able to implement what they learned from the ITCH sessions. A majority [n = 139, 76.7%] reported finding the sessions useful. Issues with poor connectivity and the timing of the live meetings impeded some in their ability to participate, a problem compounded by consequences of the pandemic. The ITCH process constituted of learning or coming to consciousness simultaneously of four types of learning — participants realizing how much they could learn from each other (peer learning), experiencing the power of defying distance to solve problems together (remote learning), and feeling a growing sense of belonging to a community (social learning), emergent across country borders and health system levels (networked learning).

Conclusions

Based on evaluation findings, it was concluded that ITCH demonstrated an effective scalable, informal, non-didactic, experience-led, fast-paced, peer learning design. A focus on community engagement and developing brokering skills was recommended.
The impact of referral letter quality on timely access to specialised mental health care: a quantitative study of the reliability of patient triage
Authors: Nymoen Marit , Biringer Eva , Hetlevik Øystein , Thorsen Olav , Assmus Jörg , Hartveit Miriam
Published: June 2022

Background

Patients referred to specialised mental health care are usually triaged based on referral information provided by general practitioners. However, knowledge about this system’s ability to ensure timely access to and equity in specialised mental health care is limited. We aimed to investigate to the degree to which patient triage, based on referral letter information, corresponds to triage based on a hospital specialist’s consultation with the patient, and whether the degree of correspondence is affected by the quality of the referral letter.

Methods

We gathered information from three specialised mental health centres in Norway regarding patients that were referred and offered health care (N = 264). Data consisted of triage decisions for each patient (i.e., the hospital specialist’s assessment of maximum acceptable waiting time), which were determined on the basis of a) referral information and b) meeting the patient. Referral letter quality was evaluated using the Quality of Referral information-Mental Health checklist. The reliability of priority setting and the impact of referral letter quality on this measure were investigated using descriptive analyses, binary logistic regression and Nadaraya-Watson kernel regression.

Results

In 143 (54%) cases, the triage decision based on referral information corresponded with the decision based on patient consultation. In 70 (27%) cases, the urgency of need for treatment was underestimated when based on referral information compared with that based on information from patient consultation. Referral letter quality could not explain the differences between the two triage decisions. However, when a cut-off value of 7 on the Quality of Referral information-Mental Health scale was used, low-quality letters were found more frequently among patients whose urgency of need was underestimated, compared with those whose need was overestimated.

Conclusions

Deciding the urgency of patient need for specialised mental health care based on referral information is a reliable system in many situations. However, the possibility of under- and overestimation is present, implying risks to patient safety and inappropriate use of resources. Improving the content of referral letters does not appear to reduce this risk when the letters are of acceptable quality.

Trial registration

NCT01374035.
Adiposity and grip strength: a Mendelian randomisation study in UK Biobank
Authors: Pinto Pereira Snehal M. , Garfield Victoria , Farmaki Aliki-Eleni , Tomlinson David J. , Norris Thomas , Fatemifar Ghazaleh , Denaxas Spiros , Finan Chris , Cooper Rachel
Published: June 2022

Background

Muscle weakness, which increases in prevalence with age, is a major public health concern. Grip strength is commonly used to identify weakness and an improved understanding of its determinants is required. We aimed to investigate if total and central adiposity are causally associated with grip strength.

Methods

Up to 470,786 UK Biobank participants, aged 38–73 years, with baseline data on four adiposity indicators (body mass index (BMI), body fat percentage (BF%), waist circumference (WC) and waist-hip-ratio (WHR)) and maximum grip strength were included. We examined sex-specific associations between each adiposity indicator and grip strength. We explored whether associations varied by age, by examining age-stratified associations (< 50 years, 50–59 years, 60–64 years,65 years +). Using Mendelian randomisation (MR), we estimated the strength of the adiposity–grip strength associations using genetic instruments for each adiposity trait as our exposure.

Results

In males, observed and MR associations were generally consistent: higher BMI and WC were associated with stronger grip; higher BF% and WHR were associated with weaker grip: 1-SD higher BMI was associated with 0.49 kg (95% CI: 0.45 kg, 0.53 kg) stronger grip; 1-SD higher WHR was associated with 0.45 kg (95% CI:0.41 kg, 0.48 kg) weaker grip (covariate adjusted observational analyses). Associations of BMI and WC with grip strength were weaker at older ages: in males aged < 50 years and 65 years + , 1-SD higher BMI was associated with 0.93 kg (95% CI: 0.84 kg, 1.01 kg) and 0.13 kg (95% CI: 0.05 kg, 0.21 kg) stronger grip, respectively. In females, higher BF% was associated with weaker grip and higher WC was associated with stronger grip; other associations were inconsistent.

Conclusions

Using different methods to triangulate evidence, our findings suggest causal links between adiposity and grip strength. Specifically, higher BF% (in both sexes) and WHR (males only) were associated with weaker grip strength.
Comparative profiling of agr locus, virulence, and biofilm-production genes of human and ovine non-aureus staphylococci
Authors: Azara Elisa , Longheu Carla Maria , Attene Sonia , Sanna Silvana , Sale Marco , Addis Maria Filippa , Tola Sebastiana
Published: June 2022

Background

In a collaboration between animal and human health care professionals, we assessed the genetic characteristics shared by non-aureus staphylococci (NAS) infecting humans and dairy ewes to investigate their relatedness in a region concentrating half of the total National sheep stock. We examined by PCR 125 ovine and 70 human NAS for biofilm production, pyrogenic toxins, adhesins, autolysins genes, and accessory gene regulator (agr) locus. The microtiter plate assay (MPA) was used for the phenotypic screening of biofilm production. Ovine NAS included S. epidermidis, S. chromogenes, S. haemolyticus, S. simulans, S. caprae, S. warneri, S. saprophyticus, S. intermedius, and S. muscae. Human NAS included S. haemolyticus, S. epidermidis, S. hominis, S. lugdunensis, S. capitis, S. warneri, S. xylosus, S. pasteuri, and S. saprophyticus subsp. bovis.

Results

Phenotypically, 41 (32.8%) ovine and 24 (34.3%) human isolates were characterized as biofilm producers. Of the ovine isolates, 12 were classified as biofilm-producing while the remaining 29 as weak biofilm-producing. All 24 human isolates were considered weak biofilm-producing. Few S. epidermidis isolates harbored the icaA/D genes coding for the polysaccharide intercellular adhesin (PIA), while the bhp, aap, and embp genes coding biofilm accumulation proteins were present in both non-producing and biofilm-producing isolates. Fifty-nine sheep NAS (all S. epidermidis, 1 S. chromogenes, and 1 S. haemolyticus) and 27 human NAS (all S. epidermidis and 1 S. warneri) were positive for the agr locus: agr-3se (57.8%) followed by agr-1se (36.8%) predominated in sheep, while agr-1se (65.4%), followed by agr-2se (34.6%) predominated in humans.

Concerning virulence genes, 40, 39.2, 47.2%, 52.8, 80 and 43.2% of the sheep isolates carried atlE, aae, sdrF, sdrG, eno and epbS respectively, against 37.1, 42.8, 32.8, 60, 100 and 100% of human isolates. Enterotoxins and tsst were not detected.

Conclusions

Considerable variation in biofilm formation ability was observed among NAS isolates from ovine and human samples. S. epidermidis was the best biofilm producer with the highest prevalence of adhesin-encoding genes.
Construction and characterization of BsGDH-CatIB variants and application as robust and highly active redox cofactor regeneration module for biocatalysis
Authors: Küsters Kira , Saborowski Ronja , Wagner Christian , Hamel Rebecca , Spöring Jan-Dirk , Wiechert Wolfgang , Oldiges Marco
Published: June 2022

Background

Catalytically active inclusion bodies (CatIBs) are known for their easy and cost efficient production, recyclability as well as high stability and provide an alternative purely biological technology for enzyme immobilization. Due to their ability to self-aggregate in a carrier-free, biodegradable form, no further laborious immobilization steps or additional reagents are needed. These advantages put CatIBs in a beneficial position in comparison to traditional immobilization techniques. Recent studies outlined the impact of cooperative effects of the linker and aggregation inducing tag on the activity level of CatIBs, requiring to test many combinations to find the best performing CatIB variant.

Results

Here, we present the formation of 14 glucose dehydrogenase CatIB variants of Bacillus subtilis, a well-known enzyme in biocatalysis due to its capability for substrate coupled regeneration of reduced cofactors with cheap substrate glucose. Nine variants revealed activity, with highest productivity levels for the more rigid PT-Linker combinations. The best performing CatIB, BsGDH-PT-CBDCell, was characterized in more detail including long-term storage at −20 °C as well as NADH cofactor regeneration performance in repetitive batch experiments with CatIB recycling. After freezing, BsGDH-PT-CBDCell CatIB only lost approx. 10% activity after 8 weeks of storage. Moreover, after 11 CatIB recycling cycles in repetitive batch operation 80% of the activity was still present.

Conclusions

This work presents a method for the effective formation of a highly active and long-term stable BsGDH-CatIB as an immobilized enzyme for robust and convenient NADH regeneration.
Association between hypertriglyceridemic-waist phenotype and non-alcoholic fatty liver disease: a general population-based study
Authors: Yang Ming , Xu Yaqin , Hu Chong , Zhang Shuhua , Kuang Maobin , Zou Yang
Published: June 2022

Background

Hypertriglyceridemic-waist (HTGW) phenotype has been proposed as a practical tool for screening the risk of cardiovascular diseases and glycemic metabolic disease. This study sought to investigate the relationship between HTGW phenotype and non-alcoholic fatty liver disease (NAFLD).

Methods

A total of 14,251 subjects who took part in health screening were enrolled in the study and NAFLD was diagnosed by abdominal ultrasound. According to triglyceride (TG) and waist circumference, the study population was divided into four phenotypes, in which HTGW phenotype was defined as TG ≥ 1.7 mmol/L and male waist circumference ≥ 90 cm or female waist circumference ≥ 80 cm. Multivariate logistic regression analysis was used to evaluate the relationship between HTGW phenotype and NAFLD.

Results

In the current study, 2.43% of the subjects had HTGW phenotype, while the prevalence of NAFLD in subjects with HTGW phenotype was 77.81%. After full adjustment for covariates, compared with people with normal waist circumference and TG levels, the risk of NAFLD in people with normal TG levels but enlarged waist circumference increased by 39% [OR:1.39, 95%CI: 1.15, 1.68], in people with normal waist circumference but elevated TG levels increased by 96% [OR:1.96, 95%CI: 1.65, 2.33], and in subjects with HTGW phenotype increased by 160% [OR:2.60, 95%CI: 1.88, 3.58]. Additionally, further analysis suggested that there were significant interactions between age, height, BMI and NAFLD risk associated with TGW phenotypes. Receiver operating characteristic curves analysis suggested that the combination of TG and waist circumference further improved the diagnostic value for NAFLD.

Conclusions

HTGW phenotype is associated with NAFLD risk in the general population, which may be a novel and accessible indicator for NAFLD screening.
A comprehensive review about immune responses and exhaustion during coronavirus disease (COVID-19)
Authors: Mohammed Rebar N. , Tamjidifar Rozita , Rahman Heshu Sulaiman , Adili Ali , Ghoreishizadeh Shadi , Saeedi Hossein , Thangavelu Lakshmi , Shomali Navid , Aslaminabad Ramin , Marofi Faroogh , Tahavvori Mina , Danshina Svetlana , Akbari Morteza , Ercan Gülinnaz
Published: June 2022

Coronavirus disease (COVID-19) is a viral infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The infection was reported in Wuhan, China, in late December 2019 and has become a major global concern due to severe respiratory infections and high transmission rates. Evidence suggests that the strong interaction between SARS-CoV-2 and patients' immune systems leads to various clinical symptoms of COVID-19. Although the adaptive immune responses are essential for eliminating SARS-CoV-2, the innate immune system may, in some cases, cause the infection to progress. The cytotoxic CD8+ T cells in adaptive immune responses demonstrated functional exhaustion through upregulation of exhaustion markers. In this regard, humoral immune responses play an essential role in combat SARS-CoV-2 because SARS-CoV-2 restricts antigen presentation through downregulation of MHC class I and II molecules that lead to the inhibition of T cell-mediated immune response responses. This review summarizes the exact pathogenesis of SARS-CoV-2 and the alteration of the immune response during SARS-CoV-2 infection. In addition, we’ve explained the exhaustion of the immune system during SARS-CoV-2 and the potential immunomodulation approach to overcome this phenomenon.