bluuebunny/crossref_metadata_2025 huggingface dataset:
A conceptual model of functional health literacy to improve chronic airway disease outcomes
Authors: Poureslami Iraj , Tregobov Noah , Shum Jessica , McMillan Austin , Akhtar Alizeh , Kassay Saron , Starnes Kassandra , Mahjoob Maryam , FitzGerald J. Mark
Published: January 2021

Background

Current conceptual models of health literacy (HL) illustrate the link between HL and health outcomes. However, these models fail to recognize and integrate certain elements of disease management, health system factors, and socio-demographic factors into their framework. This article outlines the development of Chronic Airway Disease (CAD) Management and Health Literacy (CADMaHL) conceptual model that integrates the aforementioned elements and factors into a single framework.

Methods

Information obtained during the following stages informed the development of our model: (1) a systematic review of existing CAD HL measurement tools that apply core HL domains; (2) patient-oriented focus group sessions to understand HL barriers to CAD self-management practices; (3) key-informant interviews to obtain potential strategies to mitigate CAD management barriers, and validate disease self-management topics; (4) elicited the perspectives of Canadian respirologist’s on the ideal functional HL skills for asthma and COPD patients.

Results

Throughout the study process many stakeholders (i.e., patients, key-informants, and an international HL advisory panel) contributed to and reviewed the model. The process enabled us to organize the CADMaHL model into 6 primary modules, including: INPUT, consisting of four HL core components (access, understand, communicate, evaluate,) and numeracy skills; OUTPUT, including application of the obtained information; OUTCOME, covering patient empowerment in performing self-management practices by applying HL skills; ASSESSMENT, consisting of information about functionality and relevancy of CADMaHL; IMPACT, including mediators between HL and health outcomes; CROSSCUTTING FACTORS, consisting of diverse socio-demographics and health-system factors with applicability across the HL domains.

Conclusions

We developed the CADMaHL model, with input from key-stakeholders, which addresses a knowledge gap by integrating various disease management, health-system and socio-demographic factors absent from previous published frameworks. We anticipate that our model will serve as the backbone for the development of a comprehensive HL measurement tool, which may be utilized for future HL interventions for CAD patients.

Trial registration

NCT01474928- Date of registration: 11/26/2017.
Pattern of Crimean-Congo hemorrhagic fever related high risk behaviors among Iranian butchers and its relation to perceived self-efficacy
Authors: Adham Davoud , Abazari Malek , Moradi-Asl Eslam , Abbasi-Ghahramanloo Abbas
Published: January 2021

Background

Crimean-Congo hemorrhagic fever (CCHF) is highly fatal to humans and an acute viral disease. The CCHF disease has been reported in occupations such as butchers, slaughterhouse butchers and workers. The aim of this study was to investigate the pattern of CCHF related high risk behaviors among butchers and determine the effects of perceived self-efficacy of the participants on their membership in latent classes.

Methods

The participants of this cross-sectional study were recruited from all the meat distribution centers in Ardabil Province in 2019–2020. The LCA approach was used to observe the CCFH related high risk behaviors patterns.

Results

The statistical significance level was assigned at P-value < 0.05 in all the analyses. Three latent classes were identified; namely, 1) low risk (16.1%), 2) high risk (53.6%), and 3) very high risk (30.2%). After adjusting for other possible confounders higher score of perceived self-efficacy significantly decrease the odds of membership in high risk class (OR = 0.74) and very high risk class (OR = 0.62) compared to the low risk class. Also, age (OR = 1.07) and experience (OR = 0.91) associate with very high risk class.

Conclusions

This study revealed the co-occurrence of CCHF related high risk behaviors in the majority of workers in the livestock and meat industry. It is necessary to provide butchers and slaughterhouse workers with general education, force them to use protective equipment and investigate the rate of tick bites in risky occupations.
Perianal and perineal rhabdomyosarcomas: a retrospective multicenter study of 35 cases
Authors: Guo Yaoyu , Hu Bang , Huang Dandan , Wang Xinhua , Li Juan , Zhang Di , Li Xueying , Chen Gong , Ren Donglin
Published: January 2021

Background

Perianal/perineal rhabdomyosarcomas (PRMS) are easily misdiagnosed soft tissue tumours with a poor prognosis. This study was designed to analyze the clinical, diagnostic, pathological and prognostic features of PRMS, and to explore currently available therapeutic modalities.

Methods

Clinical data of PRMS patients admitted to the Sixth Affiliated Hospital and the Cancer Center of Sun Yat-sen University and from related Chinese literature published from 1987 to 2018 were collected and analyzed. The Chi-square test was used to evaluate the differences between each group. The Kaplan–Meier methods were applied to estimate and compare survival rates.

Results

A total of 35 patients were included in this study; 20 identified within related Chinese literatures and 15 from our center admitted during the period of 1997–2019. Out of these cases, 34 presented with perianal masses and the remaining one manifested as an inguinal mass. Moreover, 20 patients complained of pain and 16 of them were misdiagnosed as perianal abscesses, in which the presence of pain contributed to the misdiagnosis (p < 0.05). The average time interval between symptom onset and pathological diagnosis was 3.1 months. Next, 13 cases were classified into IRS group III/IV and 20 cases into stages 3/4. Additionally, 14 and 9 cases received the pathological diagnoses of embryonal rhabdomyosarcoma and alveolar rhabdomyosarcoma, respectively. Regarding the patients’ survival rates, five patients survived for more than 2 years, and three of them survived for more than 5 years. The overall 2 years and 5 years survival rates were 32% and 24%, respectively. The symptom of pain and misdiagnosis both contributed to the poor prognosis in these patients (p < 0.05). MRI showed that the PRMS were closely related to external anal sphincter in 10 cases.

Conclusion

PRMS are easily misdiagnosed lesions, which often leads to an unfavourable outcome in affected patients. Patients with painful perianal masses should be evaluated to exclude PRMS. MRI revealed that PRMS are closely related to the external anal sphincter. Multidisciplinary management is recommended in the treatment of PRMS.
Risk factors for the development of tubo-ovarian abscesses in women with ovarian endometriosis: a retrospective matched case–control study
Authors: Gao Yang , Qu Pengpeng , Zhou Yang , Ding Wei
Published: January 2021

Background

The purpose of this study was to assess the risk factors associated with the development of tubo-ovarian abscesses in women with ovarian endometriosis cysts.

Methods

This retrospective single-center study included 176 women: 44 with tubo-ovarian abscesses associated with ovarian endometriosis and 132 age-matched (1:3) patients with ovarian endometriosis but without tubo-ovarian abscesses. Diagnoses were made via surgical exploration and pathological examination. The potential risk factors of tubo-ovarian abscesses associated with ovarian endometriosis were evaluated using univariate analysis. The results (p ≤ 0.05) of these parameters were analyzed using a multivariate model.

Results

Five factors were included in the multivariate conditional logistic regression model, including in vitro fertilization, presence of an intrauterine device, lower genital tract infection, spontaneous rupture of ovarian endometriosis cysts, and diabetes mellitus. The presence of a lower genital tract infection (odds ratio 5.462, 95% CI 1.772–16.839) and spontaneous rupture of ovarian endometriosis cysts (odds ratio 2.572, 95% CI 1.071–6.174) were found to be statistically significant risk factors for tubo-ovarian abscesses associated with ovarian endometriosis.

Conclusions

Among the factors investigated, genital tract infections and spontaneous rupture of ovarian endometriosis cysts were found to be involved in the occurrence of tubo-ovarian abscesses associated with ovarian endometriosis. Our findings indicate that tubo-ovarian abscesses associated with ovarian endometriosis may not be linked to in vitro fertilization as previously thought.
Modeling successive birth interval of women in Ethiopia: application of parametric shared frailty and accelerated failure time model
Authors: Mustefa Nuru Muhammed , Belay Denekew Bitew
Published: January 2021

Background

Both short and long birth intervals are associated with many risk factors and about 29% of births are short birth intervals in Ethiopia. The purpose of this study is to model the birth intervals of adult women aged 15–49 years using accelerated failure time and shared frailty models in order to analyze the birth intervals of Ethiopian women.

Methods

The data was obtained from the 2016 Ethiopian Demographic and Health Survey (EDHS). Accelerated failure time with different baseline and shared frailty models are used for the analysis to identify important demographic and socio-economic factors affecting the length of birth intervals and correlates of the birth intervals respectively.

Results

The data consists of 9147 women, of which about 7842 (85.5%) are closed interval and the rest of 1323(14.5%) are open interval. Accelerated failure time (AFT) result revealed that women education level, husbands education level, age at first birth, marital status, religion and family wealth index are significant factors affecting birth interval of women in Ethiopia.

Conclusion

Women with closely spaced births tend to have larger family sizes when compared with women with longer inter-birth interval. Longer successive birth interval tends to reduce the total fertility rate of women. Furthermore, improvements in socio-economic status and level of education of women associate with reduced fertility, improved maternal and child wellbeing, and longer birth interval.
Talking about quality: how ‘quality’ is conceptualized in nursing homes and homecare
Authors: Aase Ingunn , Ree Eline , Johannessen Terese , Strømme Torunn , Ullebust Berit , Holen-Rabbersvik Elisabeth , Thomsen Line Hurup , Schibevaag Lene , van de Bovenkamp Hester , Wiig Siri
Published: January 2021

Background

The delivery of high-quality service in nursing homes and homecare requires collaboration and shared understanding among managers, employees, users and policy makers from across the healthcare system. However, conceptualizing healthcare professionals’ perception of quality beyond hospital settings (e.g., its perspectives, defining attributes, quality dimensions, contextual factors, dilemmas) has rarely been done. This study therefore explores the meaning of “quality” among healthcare managers and staff in nursing homes and homecare.

Methods

The study applies a cross-sectional qualitative design with focus groups and individual interviews, to capture both depth and breadth of conceptualization of quality from healthcare professionals in nursing homes and homecare. We draw our data from 65 managers and staff in nursing homes and homecare services in Norway and the Netherlands. The participants worked as managers (n = 40), registered nurses (RNs) or assistant nurses (n = 25).

Results

The analysis identified the two categories and four sub-categories: “Professional issues: more than firefighting” (subcategories “professional pride” and “competence”) and “patient-centered approach: more than covering basic needs” (subcategories “dignity” and “continuity”). Quality in nursing homes and homecare is conceptualized as an ongoing process based on having the “right competence,” good cooperation across professional groups, and patient-centered care, in line with professional pride and dignity for the patients.

Conclusion

Based on the understanding of quality among the healthcare professionals in our study, quality should encompass the softer dimensions of professional pride and competence, as well as a patient-centered approach to care. These dimensions should be factors in improvement activities and in daily practice.
Correction to: Long‑term outcomes of medical therapy versus successful recanalisation for coronary chronic total occlusions in patients with and without type 2 diabetes mellitus
Authors: Guo Lei , Wang Junjie , Ding Huaiyu , Meng Shaoke , Zhang Xiaoyan , Lv Haichen , Zhong Lei , Wu Jian , Xu Jiaying , Zhou Xuchen , Huang Rongchong
Published: January 2021

An amendment to this paper has been published and can be accessed via the original article.
Long-term prognosis of chronic total occlusion treated by successful percutaneous coronary intervention in patients with or without diabetes mellitus: a systematic review and meta-analysis
Authors: Zhu Yong , Meng Shuai , Chen Maolin , Liu Kesen , Jia Ruofei , Li Hong , Zhu Huagang , Jin Zening
Published: January 2021

Background

Diabetes mellitus (DM) is highly prevalent among patients undergoing percutaneous coronary intervention (PCI) for chronic total occlusion (CTO). Therefore, the purpose of our study was to investigate the clinical outcomes of CTO-PCI in patients with or without DM.

Methods

All relevant articles published in electronic databases (PubMed, Embase, and the Cochrane Library) from inception to August 7, 2020 were identified with a comprehensive literature search. Additionally, we defined major adverse cardiac events (MACEs) as the primary endpoint and used risk ratios (RRs) with 95% confidence intervals (CIs) to express the pooled effects in this meta-analysis.

Results

Eleven studies consisting of 4238 DM patients and 5609 non-DM patients were included in our meta-analysis. For DM patients, successful CTO-PCI was associated with a significantly lower risk of MACEs (RR = 0.67, 95% CI 0.55–0.82, p = 0.0001), all-cause death (RR = 0.46, 95% CI 0.38–0.56, p < 0.00001), and cardiac death (RR = 0.35, 95% CI 0.26–0.48, p < 0.00001) than CTO-medical treatment (MT) alone; however, this does not apply to non-DM patients. Subsequently, the subgroup analysis also obtained consistent conclusions. In addition, our study also revealed that non-DM patients may suffer less risk from MACEs (RR = 1.26, 95% CI 1.02–1.56, p = 0.03) than DM patients after successful CTO-PCI, especially in the subgroup with a follow-up period of less than 3 years (RR = 1.43, 95% CI 1.22–1.67, p < 0.0001).

Conclusions

Compared with CTO-MT alone, successful CTO-PCI was found to be related to a better long-term prognosis in DM patients but not in non-DM patients. However, compared with non-DM patients, the risk of MACEs may be higher in DM patients after successful CTO-PCI in the drug-eluting stent era, especially during a follow-up period shorter than 3 years.
Usage of and satisfaction with Integrated Community Case Management care in western Uganda: a cross-sectional survey
Authors: Miller James S. , Patel Palka , Mian-McCarthy Sara , Wesuta Andrew Christopher , Matte Michael , Ntaro Moses , Bwambale Shem , Kenney Jessica , Stone Geren S. , Mulogo Edgar Mugema
Published: January 2021

Background

In some areas of Uganda, village health workers (VHW) deliver Integrated Community Case Management (iCCM) care, providing initial assessment of children under 5 years of age as well as protocol-based treatment of malaria, pneumonia, and diarrhoea for eligible patients. Little is known about community perspectives on or satisfaction with iCCM care. This study examines usage of and satisfaction with iCCM care as well as potential associations between these outcomes and time required to travel to the household’s preferred health facility.

Methods

A cross-sectional household survey was administered in a rural subcounty in western Uganda during December 2016, using a stratified random sampling approach in villages where iCCM care was available. Households were eligible if the household contained one or more children under 5 years of age.

Results

A total of 271 households across 8 villages were included in the final sample. Of these, 39% reported that it took over an hour to reach their preferred health facility, and 73% reported walking to the health facility; 92% stated they had seen a VHW for iCCM care in the past, and 55% had seen a VHW in the month prior to the survey. Of respondents whose households had sought iCCM care, 60% rated their overall experience as “very good” or “excellent,” 97% stated they would seek iCCM care in the future, and 92% stated they were “confident” or “very confident” in the VHW’s overall abilities. Longer travel time to the household’s preferred health facility did not appear to be associated with higher propensity to seek iCCM care or higher overall satisfaction with iCCM care.

Conclusions

In this setting, community usage of and satisfaction with iCCM care for malaria, pneumonia, and diarrhoea appears high overall. Ease of access to facility-based care did not appear to impact the choice to access iCCM care or satisfaction with iCCM care.
Physician-perceived utility of the EORTC QLQ-GINET21 questionnaire in the treatment of patients with gastrointestinal neuroendocrine tumours: a multicentre, cross-sectional survey (QUALINETS)
Authors: Benavent Marta , Sastre Javier , Escobar Ignacio García , Segura Angel , Capdevila Jaume , Carmona Alberto , Sevilla Isabel , Alonso Teresa , Crespo Guillermo , García Lourdes , Canal Neus , de la Cruz Guillermo , Gallego Javier
Published: January 2021

Background and objective

Patient-reported outcome measures can provide clinicians with valuable information to improve doctor-patient communication and inform clinical decision-making. The aim of this study was to evaluate the physician-perceived utility of the QLQ-GINET21 in routine clinical practice in patients with gastrointestinal neuroendocrine tumours (GI-NETs). Secondary aims were to explore the patient, clinician, and/or centre-related variables potentially associated with perceived clinical utility.

Methods

Non-interventional, cross-sectional, multicentre study conducted at 34 hospitals in Spain and Portugal (NCT02853422). Patients diagnosed with GI-NETs completed two health-related quality of life (HRQoL) questionnaires (QLQ-C30, QLQ-GINET21) during a single routine visit. Physicians completed a 14-item ad hoc survey to rate the clinical utility of QLQ-GINET21 on three dimensions: 1)therapeutic and clinical decision-making, 2)doctor-patient communication, 3)questionnaire characteristics.

Results

A total of 199 patients at 34 centres were enrolled by 36 participating clinicians. The highest rated dimension on the QLQ-GINET21 was questionnaire characteristics (86.9% of responses indicating “high utility”), followed by doctor-patient communication (74.4%), and therapeutic and clinical decision-making (65.8%). One physician-related variable (GI-NET patient volume > 30 patients/year) was associated with high clinical utility and two variables (older age/less experience treating GI-NETs) with low clinical utility.

Conclusions

Clinician-perceived clinical utility of QLQ-GINET21 is high. Clinicians valued the instruments’ capacity to provide a better understanding of patient perspectives and to identify the factors that had the largest influence on patient HRQoL.
Surgical outcomes of pulmonary metastasectomy in hepatocellular carcinoma patients according to approach method: thoracoscopic versus open approach
Authors: Lee Han Pil , Yun Jae Kwang , Jung Hee Suk , Moon Duk Hwan , Lee Geun Dong , Choi Sehoon , Kim Yong-Hee , Kim Dong Kwan , Park Seung Il , Kim Hyeong Ryul
Published: January 2021

Background

The role of surgical intervention as a treatment for pulmonary metastasis (PM) from hepatocellular carcinoma (HCC) has not been established. In this study, we investigated the clinical outcomes of pulmonary metastasectomy. Using propensity score matching (PSM) analysis, we compared the results according to the surgical approach: video-assisted thoracic surgery (VATS) versus the open method.

Methods

A total of 134 patients (115 men) underwent pulmonary metastasectomy for isolated PM of HCC between January 1998 and December 2010 at Seoul Asan Medical Center. Of these, 84 underwent VATS (VATS group) and 50 underwent thoracotomy or sternotomy (open group). PSM analysis between the groups was used to match them based on the baseline characteristics of the patients.

Results

During the median follow-up period of 33.4 months (range, 1.8–112.0), 113 patients (84.3%) experienced recurrence, and 100 patients (74.6%) died of disease progression. There were no overall survival rate, disease-free survival rate, and pulmonary-specific disease-free survival rate differences between the VATS and the open groups (p = 0.521, 0.702, and 0.668, respectively). Multivariate analysis revealed local recurrence of HCC, history of liver cirrhosis, and preoperative alpha-fetoprotein level as independent prognostic factors for overall survival (hazard ratio, 1.729/2.495/2.632, 95% confidence interval 1.142–2.619/1.571–3.963/1.554–4.456; p = 0.010/< 0.001/< 0.001, respectively).

Conclusions

Metastasectomy can be considered a potential alternative for selected patients. VATS metastasectomy had outcomes comparable to those of open metastasectomy.
Geriatric nutritional risk index predicts cancer prognosis in patients with local advanced rectal cancer undergoing chemoradiotherapy followed by curative surgery
Authors: Ide Shozo , Okugawa Yoshinaga , Omura Yusuke , Yamamoto Akira , Ichikawa Takashi , Kitajima Takahito , Shimura Tadanobu , Imaoka Hiroki , Fujikawa Hiroyuki , Yasuda Hiromi , Yokoe Takeshi , Okita Yoshiki , Ohi Masaki , Toiyama Yuji
Published: January 2021

Aim

The clinical significance of the geriatric nutritional risk index (GNRI) in locally advanced rectal cancer (LARC) patients undergoing preoperative chemoradiotherapy (CRT) followed by curative surgery has not been comprehensively evaluated.

Methods

This retrospective study enrolled 93 LARC patients diagnosed with clinical lymph node metastasis. The GNRI formula was as follows: 1.489 × albumin (g/l) + 41.7 × current weight/ideal weight. Patients were categorized as GNRI low (GNRI < 104.25) or high (GNRI > 104.25) according to the receiver operating characteristic (ROC) curve for survival analysis. The impact of GNRI status on the prognostic outcomes of curative surgery for LARC was examined.

Results

There were 55 (59.14%) and 38 (40.86%) patients in the GNRI high and low groups, respectively. Of the investigated demographic factors, age, pathological tumor invasion, and presence of recurrence were significantly associated with the GNRI value. In Kaplan–Meier analysis, overall survival (OS) and disease-free survival (DFS) were significantly shorter in the GNRI low group (OS: p = 0.00020, DFS: p = 0.0044, log-rank test). Multivariate analysis using a Cox proportional hazards model showed that a low GNRI was an independent risk factor for poor OS (hazard ratio (HR) = 3.22; 95% confidence interval (CI), 1.37–8.23; p = 0.0068) and DFS (HR = 2.32; 95%CI = 1.15–4.79; p = 0.018). Although use of adjuvant therapy has no impact on prognosis (OS: p = 0.26, DFS: p = 0.29), low GNRI showed shorter OS and DFS in patients with pathological lymph node metastasis [ypN(+)] (OS: p = 0.033, DFS: p = 0.032, log-rank test).

Conclusions

GNRI is a useful marker for LARC patients diagnosed with clinical lymph node metastasis and treated by preoperative CRT followed by curative surgery. GNRI is a useful tool to identify high risk of recurrence for improving the survival in LARC patients.
Application of ultrasound-guided intranodal lymphangiography and embolisation in cancer patients with postoperative lymphatic leakage
Authors: Sun Xingwei , Zhou Feng , Bai Xuming , Yuan Qiang , Zhang Mingqing , Ma Liang , Jin Yong
Published: January 2021

Background

Traumatic lymphatic leakage is a rare but potentially life-threatening complication. The purpose of this study was to introduce ultrasound-guided intranodal lymphangiography and embolisation techniques for postoperative lymphatic leakage in patients with cancer.

Methods

From January 2018 through June 2020, seven cancer patients (three males, four females, aged 59–75 years [mean 67.57 ± 6.11 years]) developed lymphatic leakage after abdominal or pelvic surgery, with drainage volumes ranging from 550 to 1200 mL per day. The procedure and follow-up of ultrasound-guided intranodal lymphangiography and embolisation were recorded. This study retrospectively analysed the technical success rate, operative time, length of hospital stay, clinical efficacy, and complications.

Results

The operation was technically successful in all patients. Angiography revealed leakage, and embolisation was performed in all seven patients (7/7, 100%). The operative time of angiography and embolisation was 41 to 68 min, with an average time of 53.29 ± 10.27 min. The mean length of stay was 3.51 ± 1.13 days. Lymph node embolisation was clinically successful in five patients (5/7, 71.43%), who had a significant reduction in or disappearance of chylous ascites. The other two patients received surgical treatment 2 weeks later due to poor results after embolisation. All patients were followed for 2 weeks. No serious complications or only minor complications were found in all the patients.

Conclusions

Ultrasound-guided intranodal lymphangiography and embolisation were well tolerated by the patients, who experienced a low incidence of complications. Early intervention is recommended for cancer patients with postoperative lymphatic leakage.
Smoking and inequalities in mortality in 11 European countries: a birth cohort analysis
Authors: Long Di , Mackenbach Johan , Martikainen Pekka , Lundberg Olle , Brønnum-Hansen Henrik , Bopp Matthias , Costa Giuseppe , Kovács Katalin , Leinsalu Mall , Rodríguez-Sanz Maica , Menvielle Gwenn , Nusselder Wilma
Published: January 2021

Purpose

To study the trends of smoking-attributable mortality among the low and high educated in consecutive birth cohorts in 11 European countries.

Methods

Register-based mortality data were collected among adults aged 30 to 79 years in 11 European countries between 1971 and 2012. Smoking-attributable deaths were estimated indirectly from lung cancer mortality rates using the Preston-Glei-Wilmoth method. Rate ratios and rate differences among the low and high-educated were estimated and used to estimate the contribution of inequality in smoking-attributable mortality to inequality in total mortality.

Results

In most countries, smoking-attributable mortality decreased in consecutive birth cohorts born between 1906 and 1961 among low- and high-educated men and high-educated women, but not among low-educated women among whom it increased. Relative educational inequalities in smoking-attributable mortality increased among both men and women with no signs of turning points. Absolute inequalities were stable among men but slightly increased among women. The contribution of inequality in smoking-attributable mortality to inequality in total mortality decreased in consecutive generations among men but increased among women.

Conclusions

Smoking might become less important as a driver of inequalities in total mortality among men in the future. However, among women, smoking threatens to further widen inequalities in total mortality.
Are there subgroups of chronic fatigue syndrome? An exploratory cluster analysis of biological markers
Authors: Asprusten Tarjei Tørre , Sletner Line , Wyller Vegard Bruun Bratholm
Published: January 2021

Background

Chronic fatigue syndrome (CFS) is defined according to subjective symptoms only, and several conflicting case definition exist. Previous research has discovered certain biological alterations. The aim of the present study was to explore possible subgroups based on biological markers within a widely defined cohort of adolescent CFS patients and investigate to what extent eventual subgroups are associated with other variables.

Methods

The Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial (NorCAPITAL) has previously performed detailed investigation of immunological, autonomic, neuroendocrine, cognitive and sensory processing functions in an adolescent group of CFS patients recruited according to wide diagnostic criteria. In the present study, hierarchical cluster analyses (Ward’s method) were performed using representative variables from all these domains. Associations between clusters and constitutional factors (including candidate genetic markers), diagnostic criteria, subjective symptoms and prognosis were explored by standard statistical methods.

Results

A total of 116 patients (26.7% males, mean age 15.4 years) were included. The final cluster analyses revealed six clusters labelled pain tolerant & good cognitions, restored HPA dynamics, orthostatic intolerance, low-grade inflammation, pain intolerant & poor cognitions, and high vagal (parasympathetic) activity, respectively. There was substantial overlap between clusters. The pain intolerant & poor cognitions-cluster was associated with low functional abilities and quality of life, and adherence to the Canada 2003 diagnostic criteria for CFS. No other statistically significant cluster associations were discovered.

Conclusion

Within a widely defined cohort of adolescent CFS patients, clusters could be delineated, but no distinct subgroups could be identified. Associations between clusters and constitutional factors, subjective symptoms and prognosis were scarce. These results question the clinical usefulness of searching for CFS subgroups, as well as the validity of the most “narrow” CFS diagnostic criteria.

Trial registration: Clinical Trials NCT01040429
The effect of fingolimod on regulatory T cells in a mouse model of brain ischaemia
Authors: Malone Kyle , Diaz Diaz Andrea C. , Shearer Jennifer A. , Moore Anne C. , Waeber Christian
Published: January 2021

Background

The role of the immune system in stroke is well-recognised. Fingolimod, an immunomodulatory agent licensed for the management of relapsing-remitting multiple sclerosis, has been shown to provide benefit in rodent models of stroke. Its mechanism of action, however, remains unclear. We hypothesised fingolimod increases the number and/or function of regulatory T cells (Treg), a lymphocyte population which promotes stroke recovery. The primary aim of this study was to rigorously investigate the effect of fingolimod on Tregs in a mouse model of brain ischaemia. The effect of fingolimod in mice with common stroke-related comorbidities (ageing and hypercholesteremia) was also investigated.

Methods

Young (15–17 weeks), aged C57BL/6 mice (72–73 weeks), and ApoE−/−mice fed a high-fat diet (20–21 weeks) underwent permanent electrocoagulation of the left middle cerebral artery. Mice received either saline or fingolimod (0.5 mg/kg or 1 mg/kg) at 2, 24, and 48 h post-ischaemia via intraperitoneal injection. Another cohort of young mice (8–9, 17–19 weeks) received short-term (5 days) or long-term (10 days) fingolimod (0.5 mg/kg) treatment. Flow cytometry was used to quantify Tregs in blood, spleen, and lymph nodes. Immunohistochemistry was used to quantify FoxP3+ cell infiltration into the ischaemic brain.

Results

Fingolimod significantly increased the frequency of Tregs within the CD4+ T cell population in blood and spleen post-ischaemia in all three mouse cohorts compared to untreated ischemic mice. The highest splenic Treg frequency in fingolimod-treated mice was observed in ApoE−/−mice (9.32 ± 1.73% vs. 7.8 ± 3.01% in young, 6.09 ± 1.64% in aged mice). The highest circulating Treg frequency was also noted in ApoE−/−mice (8.39 ± 3.26% vs. 5.43 ± 2.74% in young, 4.56 ± 1.60% in aged mice). Fingolimod significantly increased the number of FoxP3+ cells in the infarct core of all mice. The most pronounced effects were seen when mice were treated for 10 days post-ischaemia.

Conclusions

Fingolimod increases Treg frequency in spleen and blood post-ischaemia and enhances the number of FoxP3+ cells in the ischaemic brain. The effect of fingolimod on this regulatory cell population may underlie its neuroprotective activity and could be exploited as part of future stroke therapy.
Microglia as target for anti-inflammatory approaches to prevent secondary brain injury after subarachnoid hemorrhage (SAH)
Authors: Heinz Rebecca , Brandenburg Susan , Nieminen-Kelhä Melina , Kremenetskaia Irina , Boehm-Sturm Philipp , Vajkoczy Peter , Schneider Ulf C.
Published: January 2021

Background

Microglia-driven cerebral spreading inflammation is a key contributor to secondary brain injury after SAH. Genetic depletion or deactivation of microglia has been shown to ameliorate neuronal cell death. Therefore, clinically feasible anti-inflammatory approaches counteracting microglia accumulation or activation are interesting targets for SAH treatment. Here, we tested two different methods of interference with microglia-driven cerebral inflammation in a murine SAH model: (i) inflammatory preconditioning and (ii) pharmacological deactivation.

Methods

7T-MRI-controlled SAH was induced by endovascular perforation in four groups of C57Bl/6 mice: (i) Sham-operation, (ii) SAH naïve, (iii) SAH followed by inflammatory preconditioning (LPS intraperitoneally), and (iv) SAH followed by pharmacological microglia deactivation (colony-stimulating factor-1 receptor-antagonist PLX3397 intraperitoneally). Microglia accumulation and neuronal cell death (immuno-fluorescence), as well as activation status (RT-PCR for inflammation-associated molecules from isolated microglia) were recorded at day 4 and 14. Toll-like receptor4 (TLR4) status was analyzed using FACS.

Results

Following SAH, significant cerebral spreading inflammation occurred. Microglia accumulation and pro-inflammatory gene expression were accompanied by neuronal cell death with a maximum on day 14 after SAH. Inflammatory preconditioning as well as PLX3397-treatment resulted in significantly reduced microglia accumulation and activation as well as neuronal cell death. TLR4 surface expression in preconditioned animals was diminished as a sign for receptor activation and internalization.

Conclusions

Microglia-driven cerebral spreading inflammation following SAH contributes to secondary brain injury. Two microglia-focused treatment strategies, (i) inflammatory preconditioning with LPS and (ii) pharmacological deactivation with PLX3397, led to significant reduction of neuronal cell death. Increased internalization of inflammation-driving TLR4 after preconditioning leaves less receptor molecules on the cell surface, providing a probable explanation for significantly reduced microglia activation. Our findings support microglia-focused treatment strategies to overcome secondary brain injury after SAH. Delayed inflammation onset provides a valuable clinical window of opportunity.
Changes of blood-brain-barrier function and transfer of amyloid beta in rats with collagen-induced arthritis
Authors: Lai Po-Hsuan , Wang Ting-Hsuan , Zhang Nai-You , Wu Kuo-Chen , Yao Chung-Chen Jane , Lin Chun-Jung
Published: January 2021

Background

Rheumatoid arthritis (RA) is characterized by synovial inflammation, cartilage damage, and systemic inflammation. RA is also associated with the occurrence of neuroinflammation and neurodegenerative diseases. In this study, the impacts of RA on the function of the blood-brain barrier (BBB) and the disposition of amyloid beta (Aβ), including BBB transport and peripheral clearance of Aβ, were investigated in rats with collagen-induced arthritis (CIA), an animal model with similarity to clinical and pathological features of human RA.

Methods

CIA was induced in female Lewis rats. In addition to neuroinflammation, the integrity and function of the BBB were examined. The expression of Aβ-transporting proteins at brain blood vessels was measured. Blood-to-brain influx and plasma clearance of Aβ were determined.

Results

Both microgliosis and astrogliosis were significantly increased in the brain of CIA rats, compared with controls. In terms of BBB function, the BBB permeability of sodium fluorescein, a marker compound for BBB integrity, was significantly increased in CIA rats. Moreover, increased expression of matrix metalloproteinase-3 (MMP-3) and MMP-9 and decreased expression of tight junction proteins, zonula occludens-1 (ZO-1) and occludin, were observed in brain microvessels of CIA rats. In related to BBB transport of Aβ, protein expression of the receptor of advanced glycation end product (RAGE) and P-glycoprotein (P-gp) was significantly increased in brain microvessels of CIA rats. Notably, much higher expression of RAGE was identified at the arterioles of the hippocampus of CIA rats. Following an intravenous injection of human Aβ, significant higher brain influx of Aβ was observed in the hippocampus of CIA rats.

Conclusions

Neuroinflammation and the changes of BBB function were observed in CIA rats. The increased RAGE expression at cerebral blood vessels and enhanced blood-to-brain influx of Aβ indicate the imbalanced BBB clearance of Aβ in RA.
Combination gene therapy for HIV using a conditional suicidal gene with CCR5 knockout
Authors: Mehmetoglu-Gurbuz Tugba , Yeh Rose , Garg Himanshu , Joshi Anjali
Published: January 2021

Background

Gene therapy approaches using hematopoietic stem cells to generate an HIV resistant immune system have been shown to be successful. The deletion of HIV co-receptor CCR5 remains a viable strategy although co-receptor switching to CXCR4 remains a major pitfall. To overcome this, we designed a dual gene therapy strategy that incorporates a conditional suicide gene and CCR5 knockout (KO) to overcome the limitations of CCR5 KO alone.

Methods

A two-vector system was designed that included an integrating lentiviral vector that expresses a HIV Tat dependent Thymidine Kinase mutant SR39 (TK-SR39) and GFP reporter gene. The second non-integrating lentiviral (NIL) vector expresses a CCR5gRNA-CRISPR/Cas9 cassette and HIV Tat protein.

Results

Transduction of cells sequentially with the integrating followed by the NIL vector allows for insertion of the conditional suicide gene, KO of CCR5 and transient expression of GFP to enrich the modified cells. We used this strategy to modify TZM cells and generate a cell line that was resistant to CCR5 tropic viruses while permitting infection of CXCR4 tropic viruses which could be controlled via treatment with Ganciclovir.

Conclusions

Our study demonstrates proof of principle that a combination gene therapy for HIV is a viable strategy and can overcome the limitation of editing CCR5 gene alone.
The relation between low carbohydrate diet score and psychological disorders among Iranian adults
Authors: Sangsefidi Zohreh Sadat , Salehi-Abarghouei Amin , Sangsefidi Zahra Sadat , Mirzaei Masoud , Hosseinzadeh Mahdieh
Published: January 2021

Background

Since evidence regarding to low carbohydrate diet (LCD) and psychiatric disorders is little and controversial, this study aimed to assess relation between LCD score and psychological disorders including depression, anxiety, and stress among a large representative sample of Iranian adult population in Yazd city, Iran.

Methods

This cross-sectional analysis was conducted on data of 7165 persons who participated in the recruitment phase of Yazd Health Study (YaHS) and Taghzieh Mardom-e-Yazd (TAMIZ) study. Dietary intakes were evaluated by a validated semi-quantitative food frequency questionnaire. LCD score was calculated for each person according to summing up assigned scores to deciles of percentages of energy from macronutrients. Assessment of psychological disorders was also conducted by the validated Iranian version of depression, anxiety and stress scale questionnaire (DASS 21). Eventually, association between adherence to LCD and psychological disorders was evaluated via logistic regression.

Results

After adjusting the confounders, women in the third quartile of LCD score might had 38% lower chance of depression versus those in the first quartile (odds ratio (OR) = 0.62, confidence interval (CI) = 0.42–0.93). However, no significant relationship was observed for other psychological disorders.

Conclusions

More adherences to LCD might be associated with lower chance of depression only among women. Further studies special prospective studies are required to validate these results.
Specific considerations for research on the effectiveness of multisectoral collaboration: methods and lessons from 12 country case studies
Authors: Hinton Rachael , Armstrong Corinne , Asri Eriana , Baesel Klaus , Barnett Sarah , Blauvelt Carla , Buang Saidatul Norbaya Bt , Bury Louise , Das Jai K. , Franz-Vasdeki Jennifer , Milman Helia Molina , Murray John , Palma Susana , Renner Ilona , Roche Marion , Saint Victoria , Simpson Sarah , Singh Lucy , McGhie Diana Vaca , Ukhova Daria , van Dijk Jetske , Xinico Silvia , Fogstad Helga , Graham Wendy , Kuruvilla Shyama
Published: February 2021

Background

The success of the Sustainable Development Goals (SDGs) is predicated on multisectoral collaboration (MSC), and the COVID-19 pandemic makes it more urgent to learn how this can be done better. Complex challenges facing countries, such as COVID-19, cut across health, education, environment, financial and other sectors. Addressing these challenges requires the range of responsible sectors and intersecting services – across health, education, social and financial protection, economic development, law enforcement, among others – transform the way they work together towards shared goals. While the necessity of MSC is recognized, research is needed to understand how sectors collaborate, inform how to do so more efficiently, effectively and equitably, and ascertain similarities and differences across contexts. To answer these questions and inform practice, research to strengthen the evidence-base on MSC is critical.

Methods

This paper draws on a 12-country study series on MSC for health and sustainable development, in the context of the health and rights of women, children and adolescents. It is written by core members of the research coordination and country teams. Issues were analyzed during the study period through ‘real-time’ discussions and structured reporting, as well as through literature reviews and retrospective feedback and analysis at the end of the study.

Results

We identify four considerations that are unique to MSC research which will be of interest to other researchers, in the context of COVID-19 and beyond: 1) use theoretical frameworks to frame research questions as relevant to all sectors and to facilitate theoretical generalizability and evolution; 2) specifically incorporate sectoral analysis into MSC research methods; 3) develop a core set of research questions, using mixed methods and contextual adaptations as needed, with agreement on criteria for research rigor; and 4) identify shared indicators of success and failure across sectors to assess MSCs.

Conclusion

In responding to COVID-19 it is evident that effective MSC is an urgent priority. It enables partners from diverse sectors to effectively convene to do more together than alone. Our findings have practical relevance for achieving this objective and contribute to the growing literature on partnerships and collaboration. We must seize the opportunity here to identify remaining knowledge gaps on how diverse sectors can work together efficiently and effectively in different settings to accelerate progress towards achieving shared goals.
A consensus statement for trauma surgery capacity building in Latin America
Authors:   On behalf of the Cartagena Consensus, Dasari Mohini , Johnson Erica D. , Montenegro Jorge H. , Griswold Dylan P. , Jiménez Maria Fernanda , Puyana Juan Carlos , Rubiano Andres M.
Published: January 2021

Background

Trauma is a significant public health problem in Latin America (LA), contributing to substantial death and disability in the region. Several LA countries have implemented trauma registries and injury surveillance systems. However, the region lacks an integrated trauma system. The consensus conference’s goal was to integrate existing LA trauma data collection efforts into a regional trauma program and encourage the use of the data to inform health policy.

Methods

We created a consensus group of 25 experts in trauma and emergency care with previous data collection and injury surveillance experience in the LA. region. Experts participated in a consensus conference to discuss the state of trauma data collection in LA. We utilized the Delphi method to build consensus around strategic steps for trauma data management in the region. Consensus was defined as the agreement of ≥ 70% among the expert panel.

Results

The consensus conference determined that action was necessary from academic bodies, scientific societies, and ministries of health to encourage a culture of collection and use of health data in trauma. The panel developed a set of recommendations for these groups to encourage the development and use of robust trauma information systems in LA. Consensus was achieved in one Delphi round.

Conclusions

The expert group successfully reached a consensus on recommendations to key stakeholders in trauma information systems in LA. These recommendations may be used to encourage capacity building in trauma research and trauma health policy in the region.
Comparison of two different ways to apply a circular plaster cast for distal radius fractures: biomechanical study
Authors: Espejo-Reina Alejandro , Carrascal-Morillo María T. , Delgado-Martínez Alberto D.
Published: January 2021

Introduction

Although conservative treatment with circular plaster cast is the most commonly used method in distal radius fractures, the best method to apply it remains unclear.

Material and methods

Two frequently used configurations of circular plaster cast (with and without a splint) were selected to compare. Group C was applied only with circular bandages (three units) and group S with a splint (one unit) and over it, a circular bandage (two units). Both configurations had the same weight. Five prototypes of each group were built and mechanically tested. Three-point flexural tensile strength and maximum deflection were measured and compared.

Results

The previously splinted prototypes (group S) obtained higher tensile strength with the same weight (p< 0.05).

Discussion

No other study regarding strength and configuration of circular casts for distal radius fractures immobilization has been previously published, leading to a high variability in construction among orthopedic surgeons. Data confirms that applying a splint before circular bandage offers more mechanical resistance to the cast in flexion, with the same weight.

Conclusion

Applying a splint before circular bandage for plaster casts used for distal radius fractures make them more resistant to usual forces.
Building a trusted framework for uncertainty assessment in rare diseases: suggestions for improvement (Response to “TRUST4RD: tool for reducing uncertainties in the evidence generation for specialised treatments for rare diseases”)
Authors: Grimm Sabine E. , Pouwels Xavier , Ramaekers Bram L. T. , Wijnen Ben , Knies Saskia , Grutters Janneke , Joore Manuela A.
Published: February 2021

The aim of this letter to the editor is to provide a comprehensive summary of uncertainty assessment in Health Technology Assessment, with a focus on transferability to the setting of rare diseases. The authors of “TRUST4RD: tool for reducing uncertainties in the evidence generation for specialised treatments for rare diseases” presented recommendations for reducing uncertainty in rare diseases. Their article is of great importance but unfortunately suffers from a lack of references to the wider uncertainty in Health Technology Assessment and research prioritisation literature and consequently fails to provide a trusted framework for decision-making in rare diseases. In this letter to the editor we critique the authors’ tool and provide pointers as to how their proposal can be strengthened. We present references to the literature, including our own tool for uncertainty assessment (TRUST; unrelated to the authors’ research), and provide a broader perspective on uncertainty and risk management in rare diseases, including a detailed research agenda.