bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating the prognostic performance of a polygenic risk score for breast cancer risk stratification
Authors: Olsen Maria , Fischer Krista , Bossuyt Patrick M. , Goetghebeur Els
Published: December 2021

Background

Polygenic risk scores (PRS) could potentially improve breast cancer screening recommendations. Before a PRS can be considered for implementation, it needs rigorous evaluation, using performance measures that can inform about its future clinical value.

Objectives

To evaluate the prognostic performance of a regression model with a previously developed, prevalence-based PRS and age as predictors for breast cancer incidence in women from the Estonian biobank (EstBB) cohort; to compare it to the performance of a model including age only.

Methods

We analyzed data on 30,312 women from the EstBB cohort. They entered the cohort between 2002 and 2011, were between 20 and 89 years, without a history of breast cancer, and with full 5-year follow-up by 2015. We examined PRS and other potential risk factors as possible predictors in Cox regression models for breast cancer incidence. With 10-fold cross-validation we estimated 3- and 5-year breast cancer incidence predicted by age alone and by PRS plus age, fitting models on 90% of the data. Calibration, discrimination, and reclassification were calculated on the left-out folds to express prognostic performance.

Results

A total of 101 (3.33‰) and 185 (6.1‰) incident breast cancers were observed within 3 and 5 years, respectively. For women in a defined screening age of 50–62 years, the ratio of observed vs PRS-age modelled 3-year incidence was 0.86 for women in the 75–85% PRS-group, 1.34 for the 85–95% PRS-group, and 1.41 for the top 5% PRS-group. For 5-year incidence, this was respectively 0.94, 1.15, and 1.08. Yet the number of breast cancer events was relatively low in each PRS-subgroup. For all women, the model’s AUC was 0.720 (95% CI: 0.675–0.765) for 3-year and 0.704 (95% CI: 0.670–0.737) for 5-year follow-up, respectively, just 0.022 and 0.023 higher than for the model with age alone. Using a 1% risk prediction threshold, the 3-year NRI for the PRS-age model was 0.09, and 0.05 for 5 years.

Conclusion

The model including PRS had modest incremental performance over one based on age only. A larger, independent study is needed to assess whether and how the PRS can meaningfully contribute to age, for developing more efficient screening strategies.
ESR1 PvuII polymorphism: from risk factor to prognostic and predictive factor of the success of primary systemic therapy in advanced breast cancer
Authors: Karsono Ramadhan , Haryono Samuel J. , Karsono Bambang , Harahap Wirsma Arif , Pratiwi Yulia , Aryandono Teguh
Published: December 2021

Background

TheESR1gene encodes Estrogen Receptor alpha (ERα), which plays a role in the tumourigenesis of breast cancer. A single nucleotide polymorphism (SNP) in intron 1 of this gene calledESR1PvuII (rs2234693) has been reported to increase the risk of breast cancer. This study aimed to investigate theESR1PvuII polymorphism as a prognostic and predictive factor guiding the choice of therapy for advanced breast cancer.

Methods

This retrospective study was conducted in 104 advanced breast cancer patients at Dharmais Cancer Hospital from 2011 to 2018. TheESR1PvuII polymorphism was analysed by Sanger sequencing of DNA from primary breast tumour samples.

Results

The percentages of patients withESR1PvuII genotypes TT, TC, and CC were 42.3, 39.4, and 18.3%, respectively. Looking at prognosis, patients withESR1PvuII TC + CC had shorter overall survival than those with the TT genotype [HR = 1.79; 95% CI 1.05–3.04;p = 0.032]. As a predictive marker, TC + CC was associated with shorter survival (p = 0.041), but TC + CC patients on primary hormonal therapy had a median overall survival longer than TC + CC patients on primary chemotherapy (1072 vs 599 days).

Conclusion

TheESR1PvuII TC + CC genotypes confer poor prognosis in advanced breast cancer, but these genotypes could be regarded as a good predictor of the therapeutic effect of hormonal treatment.
Factors impacting cumulative dissipated energy levels and postoperative visual acuity outcome in cataract surgery
Authors: Bui Anh D. , Sun Zhimin , Wang Yunzhen , Huang Shengsong , Ryan Michael , Yu Yinxi , Ying Gui-Shuang , Ramanathan Saras , Singh Kuldev , Yang Yangfan , Han Ying
Published: December 2021

Purpose

To determine factors impacting cumulative dissipated energy (CDE) and postoperative best-corrected visual acuity (BCVA) in phacoemulsification.

Design

Review of 1102 cases at University of California, San Francisco (UCSF) and at Zhongshan Ophthalmic Center (ZOC), China.

Subjects

Patients who underwent cataract surgery at UCSF 03/2014–03/2019 and at ZOC 10/2018–05/2019.

Methods

Patient demographics, medical history, routine ocular examination, and surgical information, including disassembly method, complications, and surgeon training level were recorded. Univariable and multivariable regression models were used to determine factors associated with CDE and good postoperative BCVA (20/40 or better) at 1 month.

Outcome measures

CDE, postoperative BCVA.

Results

In multivariable analysis, patient age at time of surgery, diabetes, degree of nuclear sclerosis (NS), white-to-white corneal diameter, disassembly method, preoperative BCVA, surgeon training level, and surgical center were significantly associated with CDE. Log10CDE increased by 0.20–0.31 for patient age ≥ 70 years, by 0.07 if the patient had diabetes, by 0.12–0.41 for NS grade ≥ 2, by 0.48 per 10 mm increase in white-to-white corneal diameter, by 0.34–0.47 for disassembly method other than non-stop chop, by 0.16 per unit increase in preoperative logMAR BCVA, and by > 0.09 when phacoemulsification was performed by residents early in their training. Log10CDE was 0.33 higher at UCSF than ZOC. In multivariable analysis, worse baseline visual acuity and age above 90 years at time of surgery decreased the odds of good BCVA (OR = 0.26 per unit increase in preoperative logMAR BCVA; OR = 0.12 for age > 90); comorbid retinal issues decreased the odds of good postoperative BCVA (OR = 0.13–0.39); greater anterior chamber depth (ACD) or shorter axial length (AL), increased the odds of good postoperative outcome (OR = 2.64 per 1 mm increase ACD, OR = 0.84 per 1 mm increase AL).

Conclusions

Cataract grade determined by slit lamp exam and, for the first time, older patient age, were noted to be important predictors of high CDE. CDE was not a risk factor for postoperative BCVA measured at postoperative 1 month. When surgery was performed by trainees under supervision, lower training level was associated with higher CDE, but not with worse postoperative BCVA.
IgG4-related chronic sclerosing sialadenitis in a child with recurrent parotitis: a case report
Authors: Timeus Fabio , Calvo Mario Michele , Caci Anna Maria , Gallone Giorgio Oliviero , Vittone Federico
Published: December 2021

Background

IgG4-related disease (IgG4-RD) includes a group of immune-mediated diseases histologically characterized by lymphoplasmacytic infiltrate with a prevalence of IgG4-positive plasma cells, storiform fibrosis and obliterative phlebitis. Autoimmune pancreatitis, sialadenitis, dacryoadenitis and retroperitoneal fibrosis are the most frequent manifestations. IgG4-related sialadenitis usually affects submandibular glands and is very rare in children.

Here we report the case of IgG4-related sialadenitis in a six-year-old patient previously diagnosed as juvenile recurrent parotitis.

Case presentation

A six-year-old patient was referred to our Centre for left parotid swelling of 4 × 3 cm, that was tender, soft in consistency, with overlying red and warm skin. His general condition was good but he was subfebrile; general examination revealed mild enlargement of left cervical lymph nodes. In the last 2 years he had had five episodes of parotitis, diagnosed by another pediatric Center as juvenile recurrent parotitis.

On ultrasound examination the left parotid gland appeared enlarged, inhomogeneous, with a colliquative intraparotid lymph node and no evidence of sialolithiasis. Laboratory tests showed an increase of white blood cells and anti-VCA IgM and IgG positivity, with anti-EBNA e anti-EA I negativity.

The patient was initially treated with oral antibiotics, but after 10 days the parotid became fluctuating, requiring surgical biopsy and drainage. Postoperative course was regular, with complete remission under oral antibiotic and steroid therapy. Microbiological tests, including cultures for aerobic and anaerobic bacteria, mycobacteria and Bartonella, were negative.

Surprisingly, histology showed marked fibrosis and histiocytic and lymphoplasmacellular infiltrate with polyclonal plasma cells mostly expressing IgG4 immunoglobulins. Thus, the diagnosis of IgG4 related chronic sialadenitis in recurrent parotitis and recent EBV infection was made.

Conclusions

IgG4-related sialadenitis is very unusual in children. Histology plays a key role in diagnosis, considering that up to 30% of patients have normal serum IgG4 levels, as shown in our case.

The lack of previous histological data makes it impossible to attribute our patient’s previous episodes of parotitis to IgG4-RD, though it is a very consistent possibility.
Effectiveness of exercise interventions on mental health and health-related quality of life in women with polycystic ovary syndrome: a systematic review
Authors: Patten Rhiannon K. , Pascoe Michaela C. , Moreno-Asso Alba , Boyle Russell A. , Stepto Nigel K. , Parker Alexandra G.
Published: December 2021

Background

Polycystic ovary syndrome (PCOS) is a complex condition, impacting cardio-metabolic and reproductive health, mental health and health-related quality of life. The physical health benefits of exercise for women with PCOS are well-established and exercise is increasingly being recognised as efficacious for improving psychological wellbeing. The aim of this review was to summarise the evidence regarding the effectiveness of exercise interventions on mental health outcomes in women with PCOS.

Methods

A systematic search of electronic databases was conducted in March of 2020. Trials that evaluated the effect of an exercise intervention on mental health or health-related quality of life outcomes in reproductive aged women with diagnosed PCOS were included. Methodological quality was assessed using the modified Downs and Black checklist. Primary outcomes included symptoms of depression and anxiety, and health-related quality of life.

Results

Fifteen articles from 11 trials were identified and deemed eligible for inclusion. Exercise demonstrated positive improvements in health-related quality of life in all of the included studies. Half of included studies also reported significant improvements in depression and anxiety symptoms. There was large variation in methodological quality of included studies and in the interventions utilised.

Conclusions

The available evidence indicates that exercise is effective for improving health-related quality of life and PCOS symptom distress. Exercise also shows some efficacy for improving symptoms and/or prevalence of depression and anxiety in women with PCOS. However, due to large heterogeneity of included studies, conclusions could not be made regarding the impact of exercise intervention characteristics. High-quality trials with well reported exercise intervention characteristics and outcomes are required in order to determine effective exercise protocols for women with PCOS and facilitate translation into practice.
Health indices for the evaluation and monitoring of health in children and adolescents in prevention and health promotion: a scoping review
Authors: Selmani Albulena , Coenen Michaela , Voss Stephan , Jung-Sievers Caroline
Published: December 2021

Background

Health indicators are used in different settings to monitor health outcomes. Child and adolescent health is arguably one of the most important areas for the application of indices and indicators in prevention and health promotion. Although single health indicators may be better suited to display the complexity of the health status and its determinants, a selected set of indicators will still offer a complex picture. Therefore, it is argued that a group of indicators combined into an index may offer a pragmatic tool that is easier to use in order to inform stakeholders.

Methods

A scoping review was conducted to identify and describe health indices that monitor and evaluate health of children and adolescents and to appraise the quality and value of the identified indices that may guide the further applications of these indices in particular settings. The three bibliographic databases MEDLINE, EMBASE and PsycINFO were searched and a double screening of titles and abstracts as well as double screening of full texts was performed. Indices contained in these studies were analysed in terms of focus and composition and evaluated in terms of quality criteria.

Results

The scoping review identified 36 eligible studies with 18 health indices in six thematic categories. Of the identified indices, seven indices focus on anthropometrical variables, three indices focus on special aspects of newborns and five indices focus on oral health. One index assesses “healthy lifestyle” and one “functional ability” whereas one index a combination of different aspects. Most indices are calculated by using primary health data.

Conclusions

Alone or in combination with single sets of indicators, indices in six major thematic domains may be used as pragmatic tools for monitoring children’s and adolescents´ health and the evaluation of interventions in health promotion and prevention settings.
Acute respiratory infection symptoms and COVID-19 testing behaviour: results based on South Australian health surveys
Authors: Joshi S. , D’Onise K. , Nolan R. , Davis S. , Glass K. , Lokuge K.
Published: December 2021

Background

Effective syndromic surveillance alongside COVID-19 testing behaviours in the population including in higher risk and hard to reach subgroups is vital to detect re-emergence of COVID-19 transmission in the community. The aim of this paper was to identify the prevalence of acute respiratory infection symptoms and coronavirus testing behaviour among South Australians using data from a population based survey.

Methods

We used cross-sectional data from the 2020 state-wide population level health survey on 6857 respondents aged 18 years and above. Descriptive statistics were used to explore the risk factors and multivariable logistic regression models were used to assess the factors associated with the acute respiratory infection symptoms and coronavirus testing behaviour after adjusting for gender, age, household size, household income, Aboriginal and/or Torres Strait Islander status, SEIFA, Country of birth, number of chronic diseases, wellbeing, psychological distress, and mental health.

Results

We found that 19.3% of respondents reported having symptoms of acute respiratory infection and the most commonly reported symptoms were a runny nose (11.2%), coughing (9.9%) and sore throat (6.2%). Fever and cough were reported by 0.8% of participants. Of the symptomatic respondents, 32.6% reported seeking health advice from a nurse, doctor or healthcare provider. Around 18% (n = 130) of symptomatic respondents had sought testing and a further 4.3% (n = 31) reported they intended to get tested. The regression results suggest that older age, larger household size, a higher number of chronic disease, mental health condition, poor wellbeing, and psychological distress were associated with higher odds of ARI symptoms. Higher household income was associated with lower odds of being tested or intending to be tested for coronavirus after adjusting for other explanatory variables.

Conclusions

There were relatively high rates of self-reported acute respiratory infection during a period of very low COVID-19 prevalence and low rate of coronavirus testing among symptomatic respondents. Ongoing monitoring of testing uptake, including in higher-risk groups, and possible interventions to improve testing uptake is key to early detection of disease.
Fatal congenital lobar emphysema in a puerpera: a case report and literature review
Authors: Gan Fanyi , Xia Liang , Yang Yushang , Pu Qiang , Liu Lunxu
Published: December 2021

Background

Congenital lobal emphysema (CLE) is a developmental lung abnormality usually diagnosed in the neonatal period and is rarely observed in adults. Adults with CLE are usually asymptomatic and only a small fraction may present with coughing, recurrent pneumonia and respiratory distress. In imaging studies, the most frequently affected lobe of CLE is the left upper lobe, followed by the right middle lobe. However, multilobar involvement with severe mediastinal shift is extremely rare.

Case presentation

We report a case of fatal CLE in a 28-year-old puerpera with postpartum respiratory failure. Chest computed tomography (CT) revealed emphysema of the right upper, middle and lower lobes resulting in adjacent atelectasis. Hyperinflation of the right upper lobe crossed the midline, leading to a deviation of the mediastinal structure to the left hemithorax and severe compression of the left lung.

Conclusions

Early and timely diagnosis of CLE with routine follow-up is necessary for patients. CLE, especially with multilobar involvement or mediastinal shift, could be life-threatening and should be promptly and aggressively treated to prevent severe complications.
Expression signature, prognosis value and immune characteristics of cathepsin F in non-small cell lung cancer identified by bioinformatics assessment
Authors: Song Liyuan , Wang Xianhui , Cheng Wang , Wu Yi , Liu Min , Liu Ruizi , Zhang Shenyi , Xia Hong , Liu Hao , Tai Xuejiao , Zhao Huzi , Li Xihua , Ji Fuyun
Published: December 2021

Background

In recent years, immunotherapies and targeted therapies contribute to population-level improvement in NSCLC cancer-specific survival, however, the two novel therapeutic options have mainly benefit patients containing mutated driven genes. Thus, to explore other potential genes related with immunity or targeted therapies may provide novel options to improve survival of lung cancer patients without mutated driven genes. CTSF is unique in human cysteine proteinases. Presently, CTSF has been detected in several cell lines of lung cancer, but its role in progression and prognosis of lung cancer remains unclear.

Methods

CTSF expression and clinical datasets of lung cancer patients were obtained from GTEx, TIMER, CCLE, THPA, and TCGA, respectively. Association of CTSF expression with clinicopathological parameters and prognosis of lung cancer patients was analyzed using UALCAN and Kaplan–Meier Plotter, respectively. LinkedOmics were used to analyze correlation between CTSF and CTSF co-expressed genes. Protein–protein interaction and gene–gene interaction were analyzed using STRING and GeneMANIA, respectively. Association of CTSF with molecular markers of immune cells and immunomodulators was analyzed with Immunedeconv and TISIDB, respectively.

Results

CTSF expression was currently only available for patients with NSCLC. Compared to normal tissues, CTSF was downregulated in NSCLC samples and high expressed CTSF was correlated with favorable prognosis of NSCLC. Additionally, CTSF expression was correlated with that of immune cell molecular markers and immunomodulators both in LUAD and LUSC. Noticeably, high expression of CTSF-related CTLA-4 was found to be associated with better OS of LUAD patients. Increased expression of CTSF-related LAG-3 was related with poor prognosis of LUAD patients while there was no association between CTSF-related PD-1/PD-L1 and prognosis of LUAD patients. Moreover, increased expression of CTSF-related CD27 was related with poor prognosis of LUAD patients while favorable prognosis of LUSC patients.

Conclusions

CTSF might play an anti-tumor effect via regulating immune response of NSCLC.
The effectiveness of exercise therapy and education plus cognitive behavioral therapy, alone or in combination with total knee arthroplasty in patients with knee osteoarthritis – study protocol for the MultiKnee trial
Authors: Lindberg Maren Falch , Aamodt Arild , Badawy Mona , Bergvad Ingvild B. , Borchgrevink Petter , Furnes Ove , Gay Caryl , Heir Stig , Holm Inger , Indrekvam Kari , Kise Nina , Lau Bjørn , Magnussen Jon , Nerhus Tor Kjetil , Rognsvåg Turid , Rudsengen Daniil E. , Rustøen Tone , Skou Søren T. , Stubberud Jan , Småstuen Milada S. , Lerdal Anners
Published: December 2021

Background

One in five patients report chronic pain following total knee arthroplasty (TKA) and are considered non-improvers. Psychological interventions such as cognitive behavioral therapy (CBT), combined with exercise therapy and education may contribute to reduced pain an improved function both for patients with OA or after TKA surgery, but the evidence for the effectiveness of such interventions is scarce. This randomized controlled trial with three arms will compare the clinical effectiveness of patient education and exercise therapy combined with internet-delivered CBT (iCBT), evaluated either as a non-surgical treatment choice or in combination with TKA, in comparison to usual treatment with TKA in patients with knee OA who are considered candidates for TKA surgery.

Methods

The study, conducted in three orthopaedic centers in Norway will include 282 patients between ages 18 and 80, eligible for TKA. Patients will be randomized to receive the exercise therapy + iCBT, either alone or in combination with TKA, or to a control group who will undergo conventional TKA and usual care physiotherapy following surgery. The exercise therapy will include 24 one hour sessions over 12 weeks led by a physiotherapist. The iCBT program will be delivered in ten modules. The physiotherapists will receive theoretical and practical training to advise and mentor the patients during the iCBT program. The primary outcome will be change from baseline to 12 months on the pain sub-scale from the Knee Injury and Osteoarthritis Outcome Score (KOOS). Secondary outcomes include the remaining 4 sub-scales from the KOOS (symptoms, function in daily living, function in sports and recreation, and knee-related quality of life), EQ-5D-5L, the Pain Catastrophizing Scale, the 30-s sit-to-stand test, 40-m walking test and ActiGraph activity measures. A cost-utility analysis will be performed using QALYs derived from the EQ-5D-5L and registry data.

Discussion

This is the first randomized controlled trial to investigate the effectiveness of exercise therapy and iCBT with or without TKA, to optimize outcomes for TKA patients. Findings from this trial will contribute to evidence-based personalized treatment recommendations for a large proportion of OA patients who currently lack an effective treatment option.

Trial registration

Clinicaltrials.gov: NCT03771430. Registered: Dec 11, 2018.
The effect of age on short-term and mid-term outcomes after thoracoscopic Ivor Lewis esophagectomy: a propensity score-matched analysis
Authors: Martin Friederike , Kröll Dino , Knitter Sebastian , Hofmann Tobias , Raakow Jonas , Denecke Christian , Pratschke Johann , Biebl Matthias
Published: December 2021

Background

The number of elderly patients diagnosed with esophageal cancer rises. Current information about outcomes in elderly patients undergoing thoracoscopic Ivor Lewis esophagectomy is limited. The objective of this study was to evaluate the influence of age on short-and mid-term outcomes after thoracoscopic Ivor Lewis esophagectomy.

Methods

A retrospective review of 188 patients with esophageal cancer undergoing thoracoscopic Ivor Lewis esophagectomy between August 2014 and July 2019 was performed. Patients were divided into patients aged > 75 years (elderly group (EG), n = 37) and patients ≤ 75 years (younger group (YG), n = 151) and matched using propensity-score matching. Baseline characteristics, length of hospital stay, mortality and major postoperative complications (Clavien-Dindo ≥ grade III) were compared.

Results

After matching 74 patients remained (n = 37 in each group). Postoperatively, no significant differences in major and overall complications, intra-hospital and 30-day mortality, disease-free or overall survival up to 3 years after surgery were noted. The incidence of pulmonary complications (65% vs. 38%) and pneumonia (54% vs. 30%) was significantly higher and the median hospital length of stay (12 vs. 14 days) significantly longer in the EG versus YG.

Conclusion

Thoracoscopic Ivor Lewis esophagectomies resulted in acceptable postoperative major morbidity and mortality without compromising 3-years overall and disease-free survival in elderly compared to younger patients with esophageal cancer. However, the incidence of postoperative pulmonary complications was higher in patients aged over 75 years.
Expression, purification and characterisation of a human anti-CDK4 single-chain variable fragment antibody
Authors: Zhao Jialiang , Xu Jingjing , Yang Tianbin , Yu Xinze , Cheng Cheng , Zhang Tong , Ren Ze , Li Na , Yang Fang , Li Guiying
Published: December 2021

Background

Cyclin-dependent kinase 4 (CDK4) when hyperactivated drives development and maintenance of most tumour types, thus prompting its use as an essential cancer treatment target and a diagnostic tool. Target-binding molecules, such as single-chain variable fragment (scFv) antibodies, hold tremendous potential for use in a wide range of cancer diagnostic and therapeutic applications.

Results

A human anti-CDK4 scFv antibody (AK2) derived from a human phage display library was expressed in soluble form in Escherichia coli and shown to be secreted into the culture supernatant. Next, soluble AK2 within culture supernatant was successfully purified using affinity chromatography then was shown, using enzyme-linked immunosorbent assays, to bind to recombinant human CDK4 with high affinity and specificity. Further analyses of AK2 interactions with intracellular components demonstrated that AK2 recognised and interacted specifically with endogenous CDK4 and thus could be useful for detection of CDK4 within tumour cells.

Conclusions

A novel anti-CDK4 scFv antibody that can recognise and interact specifically with recombinant human CDK4 and endogenous CDK4 in tumour cells was expressed and purified successfully. These results suggest that the anti-CDK4 scFv antibody may serve as a new and promising tool for achieving CDK4-targeted diagnosis, prognosis and treatment of numerous types of cancers.
Women empowerment in reproductive health: a systematic review of measurement properties
Authors: Vizheh Maryam , Muhidin Salut , Behboodi Moghadam Zahra , Zareiyan Armin
Published: December 2021

Introduction

There is a considerable dearth of official metrics for women empowerment, which is pivotal to observe universal progress towards Sustainable Development Goals 5, targeting "achieve gender equality and empower all women and girls.” This study aimed to introduce, critically appraise, and summarize the measurement properties of women empowerment scales in sexual and reproductive health.

Methods

A comprehensive systematic literature search through several international electronic databases, including PubMed, Scopus, Embase, ProQuest, and Science Direct was performed on September 2020, without a time limit. All studies aimed to develop and validate a measurement of women empowerment in sexual and reproductive health were included. The quality assessment was performed through a rating scale addressing the six criteria, including: a priori explicit theoretical framework, evaluating content validity, internal consistency, and factor analysis to assess structural validity.

Results

Of 5234 identified studies, fifteen were included. The majority of the studies were conducted in the United States. All studies but one used a standardized measure. Total items of each scale ranged from 8 to 23. The most common domains investigated were decision-making, freedom of coercion, and communication with the partner. Four studies did not use any conceptual framework. The individual agency followed by immediate relational agency were the main focus of included studies. Of the included studies, seven applied either literature review, expert panels, or empirical methods to develop the item pool. Cronbach's alpha coefficient reported in nine studies ranged from α = 0.56 to 0.87. Most of the studies but three lack reporting test–retest reliability ranging r = 0.69–0.87. Nine studies proved content validity. Six criteria were applied to scoring the scales, by which nine of fifteen articles were rated as medium quality, two rated as poor quality, and four rated as high quality.

Conclusion

Most scales assessed various types of validity and Internal consistency for the reliability. Applying a theoretical framework, more rigorous validation of scales, and assessing the various dimensions of women empowerment in diverse contexts and different levels, namely structural agency, are needed to develop effective and representing scales.
Cancer screening simulation models: a state of the art review
Authors: Bespalov Aleksandr , Barchuk Anton , Auvinen Anssi , Nevalainen Jaakko
Published: December 2021

Background

Nowadays, various simulation approaches for evaluation and decision making in cancer screening can be found in the literature. This paper presents an overview of approaches used to assess screening programs for breast, lung, colorectal, prostate, and cervical cancers. Our main objectives are to describe methodological approaches and trends for different cancer sites and study populations, and to evaluate quality of cancer screening simulation studies.

Methods

A systematic literature search was performed in Medline, Web of Science, and Scopus databases. The search time frame was limited to 1999–2018 and 7101 studies were found. Of them, 621 studies met inclusion criteria, and 587 full-texts were retrieved, with 300 of the studies chosen for analysis. Finally, 263 full texts were used in the analysis (37 were excluded during the analysis). A descriptive and trend analysis of models was performed using a checklist created for the study.

Results

Currently, the most common methodological approaches in modeling cancer screening were individual-level Markov models (34% of the publications) and cohort-level Markov models (41%). The most commonly evaluated cancer types were breast (25%) and colorectal (24%) cancer. Studies on cervical cancer evaluated screening and vaccination (18%) or screening only (13%). Most studies have been conducted for North American (42%) and European (39%) populations. The number of studies with high quality scores increased over time.

Conclusions

Our findings suggest that future directions for cancer screening modelling include individual-level Markov models complemented by screening trial data, and further effort in model validation and data openness.
A clinical decision support system is associated with reduced loss to follow-up among patients receiving HIV treatment in Kenya: a cluster randomized trial
Authors: Oluoch Tom , Cornet Ronald , Muthusi Jacques , Katana Abraham , Kimanga Davies , Kwaro Daniel , Okeyo Nicky , Abu-Hanna Ameen , de Keizer Nicolette
Published: December 2021

Background

Loss to follow-up (LFTU) among HIV patients remains a major obstacle to achieving treatment goals with the risk of failure to achieve viral suppression and thereby increased HIV transmission. Although use of clinical decision support systems (CDSS) has been shown to improve adherence to HIV clinical guidance, to our knowledge, this is among the first studies conducted to show its effect on LTFU in low-resource settings.

Methods

We analyzed data from a cluster randomized controlled trial in adults and children (aged ≥ 18 months) who were receiving antiretroviral therapy at 20 HIV clinics in western Kenya between Sept 1, 2012 and Jan 31, 2014. Participating clinics were randomly assigned, via block randomization. Clinics in the control arm had electronic health records (EHR) only while the intervention arm had an EHR with CDSS. The study objectives were to assess the effects of a CDSS, implemented as alerts on an EHR system, on: (1) the proportion of patients that were LTFU, (2) LTFU patients traced and successfully linked back to treatment, and (3) time from enrollment on the study to documentation of LTFU.

Results

Among 5901 eligible patients receiving ART, 40.6% (n = 2396) were LTFU during the study period. CDSS was associated with lower LTFU among the patients (Adjusted Odds Ratio—aOR 0.70 (95% CI 0.65–0.77)). The proportions of patients linked back to treatment were 25.8% (95% CI 21.5–25.0) and 30.6% (95% CI 27.9–33.4)) in EHR only and EHR with CDSS sites respectively. CDSS was marginally associated with reduced time from enrollment on the study to first documentation of LTFU (adjusted Hazard Ratio—aHR 0.85 (95% CI 0.78–0.92)).

Conclusion

A CDSS can potentially improve quality of care through reduction and early detection of defaulting and LTFU among HIV patients and their re-engagement in care in a resource-limited country. Future research is needed on how CDSS can best be combined with other interventions to reduce LTFU.

Trial registration NCT01634802. Registered at www.clinicaltrials.gov on 12-Jul-2012. Registered prospectively.
Effects of an educational intervention to strengthen humanistic practice on haemodialysis nurses’ caring attitudes and behaviours and quality of working life: a cluster randomised controlled trial
Authors: Antonini Matteo , Bellier-Teichmann Tanja , O’reilly Louise , Cara Chantal , Brousseau Sylvain , Weidmann Jean , Roulet-Schwab Delphine , Ledoux Isabelle , Konishi Mario , Pasquier Jérôme , Delmas Philippe
Published: December 2021

Background

Nurses are trained to establish a trusting relationship with patients to create an environment promoting patients’ quality of life. However, in tech-heavy care settings, such as haemodialysis units, dehumanising practices may emerge and take root for various reasons to the potential detriment of both patients and nurses. For patients, this may lead to a deterioration of quality of life and, ultimately, of health status. For nurses, it may cause a deterioration of the work environment and, in turn, of quality of working life. Based on Watson’s Theory of Human Caring, we developed a brief educational intervention for haemodialysis nurses to strengthen their humanistic practice in the aim of improving the nurse-patient relationship and nurse quality of working life.. The intervention was tested by way of an experimental design.

Methods

One hundred and one haemodialysis nurses, recruited in ten hospitals in French-speaking Switzerland, were randomised into an experimental group that received the intervention and a control group. The nurse-patient relationship was measured with the Caring Nurse-Patient Interaction Scale (EIIP-70) and nurse quality of life at work was measured with the Quality of Work Life Questionnaire at four time points: pre-intervention, intervention completion, and six-month and one-year follow-ups. Random intercept regression analysis was used to evaluate change over time in the two variables under study.

Results

The intervention appeared to reinforce nurse attitudes and behaviours geared to a more humanistic practice. The effect seemed to fade over time but, 1 year post-intervention, six dimensions of the nurse-patient relationship (hope, sensibility, helping relationship, expression of emotions, problem solving, teaching) scored above baseline. Nurse quality of working life, too, seemed positively impacted. The cultural dimension of nurse quality of working life, that is, the degree to which everyday work activities attune with personal and cultural values, seemed positively impacted, as well, with improvement stable throughout the year following the intervention.

Conclusions

Results support a positive effect of the intervention over both the short term and the medium-to-long term. A brief intervention of the sort may constitute an effective means to improve the nurse-patient relationship by preventing or reducing dehumanising practices.

Trial registration

NCT03283891.
Going above and beyond: a qualitative study on the experiences and perspectives of HIV healthcare providers in Greece
Authors: Kyrou Dimitrios , Vrontaras Nikolaos , Karamanidou Christina
Published: December 2021

Background

This study concerns the experiences and perceptions of healthcare providers (HCPs) in Greece, as they respond to the changing health and psychosocial needs of people living with HIV (PLHIV) in unfavorable conditions, within a healthcare system encumbered by a decade of austerity measures.

Methods

To this end, semi-structured interviews were conducted with 20 HCPs in six HIV units throughout Greece. The data were analyzed employing reflexive thematic analysis, under a critical realist approach.

Results

Three main themes were generated from the analysis of the data: 1) Care Beyond Medicine, 2) Compensating System Barriers Towards Optimized Care and 3) Role Appraisal. According to HCPs’ perspectives, 1) their role extends beyond medicine, as they provide care for vulnerable groups and respond to their psychosocial difficulties. 2) Struggling to overcome structural barriers, HCPs often manage to provide privileged care to PLHIV. 3) In doing so, they become excessively involved. Despite the fulfillment experienced, HCPs often feel invalidated by the hospital setting, and frustrated, when they cannot manage to respond to the pressing needs of PLHIV.

Conclusions

HCPs are forced to pull together their personal resources in order to coordinate care and respond to PLHIV’s psychosocial difficulties and health issues, as there is no formal model of coordination of care for PLHIV in Greece. Considering these findings, the development of case management protocols and integrated care pathways in Greece is being proposed.
Assessment of anti-PD-(L)1 for patients with coexisting malignant tumor and tuberculosis classified by active, latent, and obsolete stage
Authors: Su Shan , Ye Mei-Feng , Cai Xiao-Ting , Bai Xue , Huang Zhi-Hao , Ma Si-Cong , Zou Jian-Jun , Wen Yu-Xiang , Wu Li-Juan , Guo Xue-Jun , Zhang Xian-Lan , Cen Wen-Chang , Su Duo-Hua , Huang Hui-Yi , Dong Zhong-Yi
Published: December 2021

Background

It is not a rare clinical scenario to have patients presenting with coexisting malignant tumor and tuberculosis. Whether it is feasible to conduct programmed death-(ligand) 1 [PD-(L)1] inhibitors to these patients, especially those with active tuberculosis treated with concurrent anti-tuberculosis, is still unknown.

Methods

This study enrolled patients with coexisting malignancy and tuberculosis and treated with anti-PD-(L)1 from Jan 2018 to July 2021 in 2 institutions. The progression-free survival (PFS), objective response rate (ORR), and safety of anti-PD-(L)1 therapy, as well as response to anti-tuberculosis treatment, were evaluated.

Results

A total of 98 patients were screened from this cohort study, with 45 (45.9%), 21 (21.4%), and 32 (32.7%) patients diagnosed with active, latent, and obsolete tuberculosis, respectively. The overall ORR was 36.0% for anti-PD-(L)1 therapy, with 34.2%, 35.5%, and 41.2% for each subgroup. Median PFS was 8.0 vs 6.0 vs 6.0 months (P=0.685) for each subgroup at the time of this analysis. For patients with active tuberculosis treated with concurrent anti-tuberculosis, median duration of anti-tuberculosis therapy was 10.0 (95% CI, 8.01–11.99) months. There were 83.3% (20/24) and 93.3% (42/45) patients showing sputum conversion and radiographic response, respectively, after anti-tuberculosis therapy, and two patients experienced tuberculosis relapse. Notably, none of the patients in latent and only one patient in obsolete subgroups showed tuberculosis induction or relapse after anti-PD-(L)1 therapy. Treatment-related adverse events (TRAEs) occurred in 33 patients (73.3%) when treated with concurrent anti-PD-(L)1 and anti-tuberculosis. Grade 3 or higher TRAEs were hematotoxicity (n = 5, 11.1%), and one patient suffered grade 3 pneumonitis leading to the discontinuation of immunotherapy.

Conclusions

This study demonstrated that patients with coexisting malignant tumor and tuberculosis benefited equally from anti-PD-(L)1 therapy, and anti-tuberculosis response was unimpaired for those with active tuberculosis. Notably, the combination of anti-PD-(L)1 and anti-tuberculosis therapy was well-tolerated without significant unexpected toxic effects.
Identification of a novel KAT6A variant in an infant presenting with facial dysmorphism and developmental delay: a case report and literature review
Authors: Bae Soyoung , Yang Aram , Kim Jinsup , Lee Hyun Ju , Park Hyun Kyung
Published: December 2021

Background

Arboleda-Tham syndrome (ARTHS), caused by a pathogenic variant of KAT6A, is an autosomal dominant inherited genetic disorder characterized by various degrees of developmental delay, dysmorphic facial appearance, cardiac anomalies, and gastrointestinal problems.

Case presentation

A baby presented multiple facial deformities including a high arched and cleft palate, with philtral ridge and vermilion indentation, a prominent nasal bridge, a thin upper lip, low-set ears, an epicanthal fold, and cardiac malformations. Whole exome sequencing (WES) revealed a heterozygous nonsense mutation in exon 8 of the KAT6A gene (c.1312C>T, p.[Arg438*]) at 2 months of age. After a diagnosis of ARTHS, an expressive language delay was observed during serial assessments of developmental milestones.

Conclusions

In this study, we describe a case with a novel KAT6A variant first identified in Korea. This case broadens the scope of clinical features of ARTHS and emphasizes that WES is necessary for early diagnosis in patients with dysmorphic facial appearances, developmental delay, and other congenital abnormalities.
The overexpression of GDNF in nucleus accumbens suppresses alcohol-seeking behavior in group-housed C57Bl/6J female mice
Authors: Koskela Maryna , Piepponen T. Petteri , Lindahl Maria , Harvey Brandon K. , Andressoo Jaan-Olle , Võikar Vootele , Airavaara Mikko
Published: December 2021

Background

Craving for alcohol, in other words powerful desire to drink after withdrawal, is an important contributor to the development and maintenance of alcoholism. Here, we studied the role of GDNF (glial cell line-derived neurotrophic factor) and BDNF (brain-derived neurotrophic factor) on alcohol-seeking behavior in group-housed female mice.

Methods

We modeled alcohol-seeking behavior in C57Bl/6J female mice. The behavioral experiments in group-housed female mice were performed in an automated IntelliCage system. We conducted RT-qPCR analysis of Gdnf, Bdnf, Manf and Cdnf expression in different areas of the female mouse brain after alcohol drinking conditioning. We injected an adeno-associated virus (AAV) vector expressing human GDNF or BDNF in mouse nucleus accumbens (NAc) after ten days of alcohol drinking conditioning and assessed alcohol-seeking behavior. Behavioral data were analyzed by two-way repeated-measures ANOVA, and statistically significant effects were followed by Bonferroni’s post hoc test. The student’s t-test was used to analyze qPCR data.

Results

The RT-qPCR data showed that Gdnf mRNA level in NAc was more than four times higher (p < 0.0001) in the mice from the sweetened alcohol group compared to the water group. Our data showed a more than a two-fold decrease in Manf mRNA (p = 0.04) and Cdnf mRNA (p = 0.02) levels in the hippocampus and Manf mRNA in the VTA (p = 0.04) after alcohol consumption. Two-fold endogenous overexpression of Gdnf mRNA and lack of CDNF did not affect alcohol-seeking behavior. The AVV-GDNF overexpression in nucleus accumbens suppressed alcohol-seeking behavior while overexpression of BDNF did not.

Conclusions

The effect of increased endogenous Gdnf mRNA level in female mice upon alcohol drinking has remained unknown. Our data suggest that an increase in endogenous GDNF expression upon alcohol drinking occurs in response to the activation of another mesolimbic reward pathway participant.
Oscillatory mechanics at birth for identifying infants requiring surfactant: a prospective, observational trial
Authors: Lavizzari Anna , Veneroni Chiara , Beretta Francesco , Ottaviani Valeria , Fumagalli Claudia , Tossici Marta , Colnaghi Mariarosa , Mosca Fabio , Dellacà Raffaele L.
Published: December 2021

Background

Current criteria for surfactant administration assume that hypoxia is a direct marker of lung-volume de-recruitment. We first introduced an early, non-invasive assessment of lung mechanics by the Forced Oscillation Technique (FOT) and evaluated its role in predicting the need for surfactant therapy.

Objectives

To evaluate whether lung reactance (Xrs) assessment by FOT within 2 h of birth identifies infants who would need surfactant within 24 h; to eventually determine Xrs performance and a cut-off value for early detection of infants requiring surfactant.

Methods

We conducted a prospective, observational, non-randomized study in our tertiary NICU in Milan. Eligible infants were born between 27+0 and 34+6 weeks’ gestation, presenting respiratory distress after birth. Exclusion criteria: endotracheal intubation at birth, major malformations participation in other interventional trials, parental consent denied. We assessed Xrs during nasal CPAP at 5 cmH2O at 10 Hz within 2 h of life, recording flow and pressure tracing through a Fabian Ventilator for off-line analysis. Clinicians were blinded to FOT results.

Results

We enrolled 61 infants, with a median [IQR] gestational age of 31.9 [30.3; 32.9] weeks and birth weight 1490 [1230; 1816] g; 2 infants were excluded from the analysis for set-up malfunctioning. 14/59 infants received surfactant within 24 h. Xrs predicted surfactant need with a cut-off − 33.4 cmH2O*s/L and AUC-ROC = 0.86 (0.76–0.96), with sensitivity 0.85 and specificity 0.83. An Xrs cut-off value of − 23.3 cmH2O*s/L identified infants needing surfactant or respiratory support > 28 days with AUC-ROC = 0.89 (0.81–0.97), sensitivity 0.86 and specificity 0.77. Interestingly, 12 infants with Xrs < − 23.3 cmH2O*s/L (i.e. de-recruited lungs) did not receive surfactant and subsequently required prolonged respiratory support.

Conclusion

Xrs assessed within 2 h of life predicts surfactant need and respiratory support duration in preterm infants. The possible role of Xrs in improving the individualization of respiratory management in preterm infants deserves further investigation.
E-cadherin on epithelial–mesenchymal transition in thyroid cancer
Authors: Zhu Xiaoyu , Wang Xiaoping , Gong Yifei , Deng Junlin
Published: December 2021

Thyroid carcinoma is a common malignant tumor of endocrine system and head and neck. Recurrence, metastasis and high malignant expression after routine treatment are serious clinical problems, so it is of great significance to explore its mechanism and find action targets. Epithelial–mesenchymal transition (EMT) is associated with tumor malignancy and invasion. One key change in tumour EMT is low expression of E-cadherin. Therefore, this article reviews the expression of E-cadherin in thyroid cancers (TC), discuss the potential mechanisms involved, and outline opportunities to exploit E-cadherin on regulating the occurrence of EMT as a critical factor in cancer therapeutics.