bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeted next-generation sequencing identifies novel variants in candidate genes for Parkinson’s disease in Black South African and Nigerian patients
Authors: Oluwole Oluwafemi G. , Kuivaniemi Helena , Abrahams Shameemah , Haylett William L. , Vorster Alvera A. , van Heerden Carel J. , Kenyon Colin P. , Tabb David L. , Fawale Michael B. , Sunmonu Taofiki A. , Ajose Abiodun , Olaogun Matthew O. , Rossouw Anastasia C. , van Hillegondsberg Ludo S. , Carr Jonathan , Ross Owen A. , Komolafe Morenikeji A. , Tromp Gerard , Bardien Soraya
Published: February 2020

Background

The prevalence of Parkinson’s disease (PD) is increasing in sub-Saharan Africa, but little is known about the genetics of PD in these populations. Due to their unique ancestry and diversity, sub-Saharan African populations have the potential to reveal novel insights into the pathobiology of PD. In this study, we aimed to characterise the genetic variation in known and novel PD genes in a group of Black South African and Nigerian patients.

Methods

We recruited 33 Black South African and 14 Nigerian PD patients, and screened them for sequence variants in 751 genes using an Ion AmpliSeq™ Neurological Research panel. We used bcftools to filter variants and annovar software for the annotation. Rare variants were prioritised using MetaLR and MetaSVM prediction scores. The effect of a variant on ATP13A2’s protein structure was investigated by molecular modelling.

Results

We identified 14,655 rare variants with a minor allele frequency ≤ 0.01, which included 2448 missense variants. Notably, no common pathogenic mutations were identified in these patients. Also, none of the known PD-associated mutations were found highlighting the need for more studies in African populations. Altogether, 54 rare variants in 42 genes were considered deleterious and were prioritized, based on MetaLR and MetaSVM scores, for follow-up studies. Protein modelling showed that the S1004R variant in ATP13A2 possibly alters the conformation of the protein.

Conclusions

We identified several rare variants predicted to be deleterious in sub-Saharan Africa PD patients; however, further studies are required to determine the biological effects of these variants and their possible role in PD. Studies such as these are important to elucidate the genetic aetiology of this disorder in patients of African ancestry.
Lifetime cost-effectiveness analysis of first-line dialysis modalities for patients with end-stage renal disease under peritoneal dialysis first policy
Authors: Wong Carlos K. H. , Chen Julie , Fung Samuel K. S. , Mok Maggie , Cheng Yuk lun , Kong Irene , Lo Wai Kei , Lui Sing Leung , Chan T. M. , Lam Cindy L. K.
Published: February 2020

Background

This study aimed to determine the lifetime cost-effectiveness of first-line dialysis modalities for end-stage renal disease (ESRD) patients under the “Peritoneal Dialysis First” policy.

Methods

Lifetime cost-effectiveness analyses from both healthcare provider and societal perspectives were performed using Markov modelling by simulating at age 60. Empirical data on costs and health utility scores collected from our studies were combined with published data on health state transitions and survival data to estimate the lifetime cost, quality-adjusted life-years (QALYs) and cost-effectiveness of three competing dialysis modalities: peritoneal dialysis (PD), hospital-based haemodialysis (HD) and nocturnal home HD.

Results

For cost-effectiveness analysis over a lifetime horizon from the perspective of healthcare provider, hospital-based HD group (lifetime cost USD$142,389; 6.58 QALYs) was dominated by the PD group (USD$76,915; 7.13 QALYs). Home-based HD had the highest effectiveness (8.37 QALYs) but with higher cost (USD$97,917) than the PD group. The incremental cost-effectiveness ratio (ICER) was USD$16,934 per QALY gained for home-based HD over PD. From the societal perspective, the results were similar and the ICER was USD$1195 per QALY gained for home-based HD over PD. Both ICERs fell within the acceptable thresholds. Changes in model parameters via sensitivity analyses had a minimal impact on ICER values.

Conclusions

This study assessed the cost-effectiveness of dialysis modalities and service delivery models for ESRD patients under “Peritoneal Dialysis First” policy. For both healthcare provider and societal perspectives, PD as first-line dialysis modality was cost-saving relative to hospital-based HD, supporting the existing PD First or favoured policy. When compared with PD, Nocturnal home Home-based HD was considered a cost-effective first-line dialysis modality for ESRD patients.
A decrease in brown adipose tissue activity is associated with weight gain during chemotherapy in early breast cancer patients
Authors: Ginzac Angeline , Barres Bertrand , Chanchou Marion , Gadéa Emilie , Molnar Ioana , Merlin Charles , Coudert Bruno , Thivat Emilie , Durando Xavier
Published: February 2020

Background

A decrease in thermogenesis is suspected to be implicated in the energy expenditure reduction during breast cancer treatment. This study aimed to investigate the impact of chemotherapy on the metabolic activity of brown adipose tissue (BAT) and the link with weight variation.

Methods

This was an ancillary analysis of a multicentre trial involving 109 HER2+ breast cancer patients treated with neoadjuvant chemotherapy. A centralised review of 18F-FDG uptake intensity (SUVmax) in specific BAT regions (cervical and supraclavicular) was conducted on two PET-CT scans for each patient (before and after the first course of chemotherapy).

Results

Overall, after one course of chemotherapy a significant decrease of 4.4% in 18F-FDG-uptake intensity was observed. It was not correlated to initial BMI, age or season. During chemotherapy, 10.1% (n = 11) of the patients lost weight (− 7.7 kg ± 3.8 kg; ie, − 9.4% ± 3.7%) and 29.4% (n = 32) gained weight (+ 5.1 kg ± 1.7 kg; ie, + 8.5% ± 2.6%). Among these subgroups, only the patients who had gained weight underwent a significant decrease (13.42%) in 18F-FDG uptake intensity (p = 0.042).

Conclusion

This study is the first to highlight in a large cohort of patients the negative impact of chemotherapy on brown adipose tissue activity. Weight gain during chemotherapy could thus potentially be explained in part by a decrease in brown adipose tissue activity.
Marijuana legalization and historical trends in marijuana use among US residents aged 12–25: results from the 1979–2016 National Survey on drug use and health
Authors: Yu Bin , Chen Xinguang , Chen Xiangfan , Yan Hong
Published: February 2020

Background

Marijuana is the most commonly used illicit drug in the United States. More and more states legalized medical and recreational marijuana use. Adolescents and emerging adults are at high risk for marijuana use. This ecological study aims to examine historical trends in marijuana use among youth along with marijuana legalization.

Method

Data (n = 749,152) were from the 31-wave National Survey on Drug Use and Health (NSDUH), 1979–2016. Current marijuana use, if use marijuana in the past 30 days, was used as outcome variable. Age was measured as the chronological age self-reported by the participants, period was the year when the survey was conducted, and cohort was estimated as period subtracted age. Rate of current marijuana use was decomposed into independent age, period and cohort effects using the hierarchical age-period-cohort (HAPC) model.

Results

After controlling for age, cohort and other covariates, the estimated period effect indicated declines in marijuana use in 1979–1992 and 2001–2006, and increases in 1992–2001 and 2006–2016. The period effect was positively and significantly associated with the proportion of people covered by Medical Marijuana Laws (MML) (correlation coefficients: 0.89 for total sample, 0.81 for males and 0.93 for females, all threepvalues < 0.01), but was not significantly associated with the Recreational Marijuana Laws (RML). The estimated cohort effect showed a historical decline in marijuana use in those who were born in 1954–1972, a sudden increase in 1972–1984, followed by a decline in 1984–2003.

Conclusion

The model derived trends in marijuana use were coincident with the laws and regulations on marijuana and other drugs in the United States since the 1950s. With more states legalizing marijuana use in the United States, emphasizing responsible use would be essential to protect youth from using marijuana.
Occupational stress and the risk of turnover: a large prospective cohort study of employees in Japan
Authors: Kachi Yuko , Inoue Akiomi , Eguchi Hisashi , Kawakami Norito , Shimazu Akihito , Tsutsumi Akizumi
Published: February 2020

Background

Although several studies have examined the association between occupational stress and turnover, these studies relied on cross-sectional designs, subjects’ self-report, healthcare workforce, or small sample sizes. This study aimed to confirm whether occupational stress increases the risk of turnover in a large-scale prospective cohort study using actual turnover data from company records.

Methods

The participants were 3892 male and 5765 female employees aged 20–49 years in a financial service company. We followed them from October 2012 until April 1, 2016 and used company records to identify employees who resigned. We identified employees with high and low stress using the Brief Job Stress Questionnaire. Hazard ratios for turnover in high-stress employees were estimated using Cox proportional hazards models, and population attributable risks were calculated separately for men and women.

Results

During 11,475,862 person-days, 122 men and 760 women resigned. After adjustment for age, length of service, job type, and position, the hazard ratios (95% confidence intervals) for turnover in high-stress employees were 2.86 (1.74–4.68) for men and 1.52 (1.29–1.78) for women. The corresponding population attributable risks for high stress were 8.2% for men and 8.3% for women. The component scores, i.e., job stressors, psychological/physical stress response, workplace social support, and job strain (the combination of high job demands and low job control) were also significantly associated with turnover (p < 0.05).

Conclusions

Occupational stress increases the risk of actual turnover. Measures to prevent occupational stress may be useful to prevent employee turnover.
High prevalence of human immunodeficiency virus, hepatitis B and C viral infections among people who inject drugs: a potential stumbling block in the control of HIV and viral hepatitis in Tanzania
Authors: Kawambwa Rahim H. , Majigo Mtebe V. , Mohamed Ahmed A. , Matee Mecky I.
Published: February 2020

Background

Tanzania has witnessed a significant decrease in the prevalence of human immunodeficiency virus (HIV) and viral hepatitis in the general population attributed to several interventional measures. It is uncertain whether this decline has also occurred among people who inject drugs (PWID). This study aimed to determine the seroprevalence of HIV, Hepatitis B and C viruses infection among PWID recruited from their hotspot sites in Dar es Salaam, Tanzania.

Methods

A cross-sectional study conducted between June and September 2017 recruited PWID from pre-identified hotspot sites using a snowball referral sampling technique. A structured questionnaire was used to obtain information regarding socio-demographic characteristics, behaviour and drug use. Blood was tested for the presence of IgG antibodies against HIV and Hepatitis C virus (HCV) and hepatitis B surface antigen (HBsAg). Data were entered in the computer using excel software and analysed using Statistical Package for Social Sciences version 20.

Results

A total of 219 PWID were recruited, the majority of whom were males (74.9%), unmarried (60.7%), had low education (62.6%) and low income (57.1%). The median age was 39 years, with an inter-quartile range of 35–43. Approximately 32.0% had a history of drug injection for more than 3 years, 79.9% were injecting drugs more than 3 times per day and 47.5% were sharing needles. The overall prevalence of HIV, HBsAg, and HCV was 33.8, 7.8, and 50.2%, respectively. There was serologic evidence of at least one infection for 68.9%, while 22.4% had two or more infections. HIV infection was independently associated with being married, while HCV was associated with injecting drugs for more than 3 years and unprotected sex.

Conclusion

Over two-third of PWID had serologic evidence of infection with at least one virus while 22.4% having at least two infections. The high prevalence of HIV and viral hepatitis infections among PWID may hamper initiatives of ending HIV and viral hepatitis epidemics in Tanzania.
Food insecurity among women of reproductive age in Nepal: prevalence and correlates
Authors: Pandey Shanta , Fusaro Vincent
Published: February 2020

Background

Food insecurity is widely prevalent in certain sections of society in low and middle-income countries. The United Nations has challenged all member countries to eliminate hunger for all people by 2030. This study examines the prevalence and correlates of household food insecurity among women, especially Dalit women of reproductive age in Nepal.

Methods

Data came from2016 Nepal Demographic Health Survey,a cross-sectional, nationally representative survey that included 12,862 women between 15 and 49 years of age of which 12% were Dalit. Descriptive analysis was used to assess the prevalence of household food insecurity while logistic regression examined the relationship between women’s ethnicity and the risk of food insecurity after accounting for demographic, economic, cultural, and geo-ecological characteristics.

Results

About 56% of all women and 76% of Dalit women had experienced food insecurity. Ethnicity is strongly related to food insecurity. Dalit women were most likely to be food insecure, even after accounting for factors such as education and wealth. They were 82, 85, 89 and 92% more vulnerable to food insecurity than Muslims, Brahmin/Chhetri,TeraiIndigenous, and Hill Indigenous populations, respectively. Education was a protective factor—women with secondary education (6th to 10th grade) were 39% less likely to be food insecure compared to their counterparts without education. With a more than 10th grade education, women were 2.27 times more likely to be food secure compared to their counterparts without education. Marriage was also protective. Economically, household wealth is inversely correlated with food insecurity. Finally, residence in the Mid-Western, Far-Western and Central Development regions was correlated with food insecurity.

Conclusion

To reduce food insecurity in Nepal, interventions should focus on improving women’s education and wealth, especially among Dalit and those residing in the Far- and Mid-Western regions.
Health system factors influencing uptake of Human Papilloma Virus (HPV) vaccine among adolescent girls 9-15 years in Mbale District, Uganda
Authors: Nabirye Juliet , Okwi Livex Andrew , Nuwematsiko Rebecca , Kiwanuka George , Muneza Fiston , Kamya Carol , Babirye Juliet N.
Published: February 2020

Background

Globally, cervical cancer is the fourth most common cancer in women with more than 85% of the burden in developing countries. In Uganda, cervical cancer has shown an increase of 1.8% per annum over the last 20 years. The availability of the Human Papillomavirus (HPV) vaccine presents an opportunity to prevent cervical cancer. Understanding how the health system influences uptake of the vaccine is critical to improve it. This study aimed to assess how the health systems is influencing uptake of HPV vaccine so as to inform policy for vaccine implementation and uptake in Mbale district, Eastern Uganda.

Methods

We conducted a cross sectional study of 407 respondents, selected from 56 villages. Six key informant interviews were conducted with District Health Officials involved in implementation of the HPV vaccine. Quantitative data was analyzed using Stata V.13. Prevalence ratios with their confidence intervals were reported. Qualitative data was audio recorded, transcribed verbatim and analyzed using MAXQDA V.12, using the six steps of thematic analysis developed by Braun and Clarke.

Results

Fifty six (14%) of 407 adolescents self-reported vaccine uptake. 182 (52.3%) of 348 reported lack of awareness about the HPV vaccine as the major reason for not having received it. Receiving vaccines from outreach clinics (p = 0.02), having many options from which to receive the vaccine (p = 0.02), getting an explanation on possible side-effects (p = 0.024), and receiving the vaccine alongside other services (p = 0.024) were positively associated with uptake.

Key informants reported inconsistency in vaccine supply, inadequate training on HPV vaccine, and the lack of a clear target for HPV vaccine coverage as the factors that contribute to low uptake.

Conclusion

We recommend training of health workers to provide adequate information on HPV vaccine, raising awareness of the vaccine in markets, schools, and radio talk shows, and communicating the target to health workers.

Uptake of the HPV vaccine was lower than the Ministry of Health target of 80%. We recommend training of health workers to clearly provide adequate information on HPV vaccine, increasing awareness about the vaccine to the adolescents and increasing access for girls in and out of school.
RECOVER-E – a mobile app for patients undergoing total knee or hip replacement: study protocol
Authors: Stauber Anja , Schüßler Nadine , Palmdorf Sarah , Schürholz Nina , Bruns David , Osterbrink Jürgen , Nestler Nadja
Published: February 2020

Background

Total knee replacement (TKR) or total hip replacement (THR) are common and effective procedures in patients with osteoarthritis (OA) to restore physical function and reduce joint related pain. Patient education plays an important role in the treatment process aiming to develop necessary self-management skills to facilitate recovery and ensure long-term success. We have developed a mobile app (RECOVER-E) for iOS and Android smartphones which provides important information on the preoperative phase, surgery and recovery. The concomitant study will determine the efficacy of RECOVER-E on patients’ surgical outcomes.

Methods/design

This study is a non-randomized, multi-centre (4 sites), double-arm, controlled trial with 1:1 assignment. 160 patients undergoing primary TKR or THR will be recruited from January until October 2019 in 4 German hospitals. Both groups will receive standard care. Additionally, the intervention group will use the app RECOVER-E. Measurements will be taken 4–6 weeks before surgery, on the day of admission to the hospital, on the first and 7th postoperative day and 3 months post-surgery. Primary outcome will be self-reported physical function measured on the activities of daily living (ADL) subscale of the Knee injury and Osteoarthritis Outcome Score (KOOS) and the Hip disability and Osteoarthritis Outcome Score (HOOS) for patients with knee and hip osteoarthritis, respectively.

Secondary outcomes include the subscales for pain, symptoms, function in sport and recreation and knee/hip-related quality of life of the HOOS and KOOS, preoperative anxiety, measured by the Hospital Anxiety and Depression Scale (HADS), as well as, pain at rest and pain during activity measured by a numerical rating scale (NRS). Primary endpoint is 3 months post-surgery.

Discussion

Mobile Health (mHealth) has become increasingly important in patient-centred health care aiming to enhance patient involvement and self-management capabilities. To our knowledge this is the first study to investigate the effect of an evidence-based mobile app on patient reported outcomes after joint replacement. This study should provide evidence supporting the use of mHealth to facilitate recovery and open up new possibilities for patient care in joint replacement.

Trial registration

DRKS Data Management retrospectively registered. DRKS-ID: DRKS00012744.
In vitro comparison of cyclic fatigue resistance of TruNatomy in single and double curvature canals compared with different nickel-titanium rotary instruments
Authors: Elnaghy Amr M. , Elsaka Shaymaa E. , Mandorah Ayman O.
Published: February 2020

Background

The purpose of this study was to compare the cyclic fatigue resistance of newly developed TruNatomy instruments (TRN) in single and double (S-shaped) curvature canals with HyFlex CM (HCM), Vortex Blue (VB) and RaCe (RC) instruments.

Methods

Size 20/.04 taper and size 25/0.04 of HCM, VB and RC were used. For TRN instruments, size 20/.04 taper (small) and size 26/.04 taper (prime) were used. The instruments were tested in artificial canals with double curvature (coronal curve; 60° curvature, 5 mm radius and apical curve; 70° curvature and 2 mm radius) and single curvature (60° curvature, 5 mm radius). The number of cycles to failure (NCF) was recorded. Data were statistically analyzed by Kruskal-Wallis and Dunn’s multiple comparison tests. Weibull analysis was performed on NCF data. Statistical significant was set atp < 0.05.

Results

TRN and HCM revealed higher NCF compared with the other instruments for both tested sizes in single and double curvature canals (p < 0.05). TRN and HCM showed no statistically significant difference in the NCF (p > 0.05). The probability of survival was higher for HCM and TRN instruments than VB and RC instruments.

Conclusions

HCM and TRN instruments were more resistant to cyclic fatigue than VB and RC instruments in single and double curvature canals. HCM and TRN instruments were anticipated to survive with higher number of cycles than the other tested instruments. RC instrument had the lowest fatigue resistance than the other instruments.
Are we preparing for collaboration, advocacy and leadership? Targeted multi-site analysis of collaborative intrinsic roles implementation in medical undergraduate curricula
Authors:   on behalf of the Collaborators of the MERlin Mapping Group, Griewatz Jan , Yousef Amir , Rothdiener Miriam , Lammerding-Koeppel Maria
Published: February 2020

Background

The Collaborator, Health Advocate and Leader/Manager roles are highly relevant for safe patient management and optimization of healthcare system in rehabilitation and prevention. They are defined in competency-based frameworks and incorporate competencies empowering physicians to master typical daily tasks in interdisciplinary, interprofessional and institutional collaboration. However, appropriate implementation of roles remains difficult in undergraduate medical education (UME) and needs to be closely monitored. The aim of this cross-institutional mapping study was to examine for the roles of Collaborator, Health Advocate and Leader/Manager: (1) To what extent do German UME programs explicitly meet the given standards after 5 years of study? (2) Which information may be obtained from multi-site mapping data for evidence-based reflection on curricula and framework?

Methods

In a joint project of eight German UME programs, 80 to 100% of courses were mapped from teachers’ perspective against given national standards: (sub-)competency coverage, competency level attainment and assessment. All faculties used a common tool and consented procedures for data collection and processing. The roles’ representation was characterized by the curricular weighting of each role content expressed by the percentage of courses referring to it (citations). Data were visualized in a benchmarking approach related to a general mean of the intrinsic roles as reference line.

Results

(Sub-)competencies of the Health Advocate are consistently well-integrated in curricula with a wide range of generally high curricular weightings. The Collaborator reveals average curricular representation, but also signs of ongoing curricular development in relevant parts and clear weaknesses regarding assessment and achieved outcomes. The Leader/Manager displays consistently lowest curricular weightings with several substantial deficiencies in curricular representation, constructive alignment and/or outcome level. Our data allow identifying challenges to be considered by local curriculum developers or framework reviewers (e.g. non-achievement of competency levels, potential underrepresentation, lacking constructive alignment).

Conclusion

Our non-normative, process-related benchmarking approach provides a differentiated crosscut snapshot to compare programs in the field of others, thus revealing shortcomings in role implementation, especially for Leader/Manager and Collaborator. The synopsis of multi-site data may serve as an external reference for program self-assessment and goal-oriented curriculum development. It may also provide practical data for framework review.
Disclosure to genetic relatives without consent – Australian genetic professionals’ awareness of the health privacy law
Authors: Meggiolaro Natalia , Barlow-Stewart Kristine , Dunlop Kate , Newson Ainsley J. , Fleming Jane
Published: February 2020

Background

When a genetic mutation is identified in a family member (proband), internationally, it is usually the proband’s or another responsible family member’s role to disclose the information to at-risk relatives. However, both active and passive non-disclosure in families occurs: choosing not to communicate the information or failing to communicate the information despite intention to do so, respectively. The ethical obligations to prevent harm to at-risk relatives and promote the duty of care by genetic health professionals (GHPs) is in conflict with Privacy laws and professional regulations that prohibits disclosure of information to a third party without the consent of the proband (duty of confidentiality). In New South Wales (NSW), Australia, amendments to Privacy legislation permits such disclosure to living genetic relatives with the process defined under guidelines although there is no legal duty to warn. This study assessed NSW GHP’s awareness and experience of the legislation and guidelines.

Methods

An online survey collected demographics; theoretical knowledge; clinical scenarios to assess application knowledge; attitudes; confidence; experience with active non-disclosure. A link to correct answers was provided after completion. Knowledge scores above the median for non-parametric data or above the mean for parametric data were classified as ‘good’ or ‘poor’. Chi square tests assessed associations between confidence and knowledge scores.

Results

While many of the 37 participants reported reading the guidelines, there was limited awareness of their scope and clinical application; that there is no legal duty to warn; and that the threat does not need to be imminent to warrant disclosure. No association between confidence and ‘good’ theoretical or applied clinical knowledge was identified. Uncertainty of their professional responsibility was identified and in the several case examples of active non-disclosure that were reported this uncertainty reflected the need for further understanding of the guidelines in regard to the processes required before disclosure was initiated.

Conclusions

There is a need for further education and training about the guidelines associated with the legislation that would be relevant to support disclosure. The findings may inform future strategies to support introduction of policy changes in other jurisdictions where similar regulatory regimes are introduced.
Educating health professionals to optimise falls screening in hospitals: protocol for a mixed methods study
Authors: Shaw L. , Kiegaldie D. , Morris M. E.
Published: February 2020

Background

Falls in hospitals remain a major challenge to patient safety. All hospitalised adults are at risk of falling during their inpatient stay, though this risk is not always realised by patients and clinicians. This study will evaluate the outcomes of a hospital clinician education program that teaches clinicians how to screen for falls risk and assign mitigation strategies using clinical reasoning, rather than relying on a standardised falls risk assessment tool (FRAT). The education program aims to increase clinician knowledge, motivation and confidence in screening falls risk and selecting individual falls prevention interventions. Perceptions of the education intervention will also be examined.

Methods

Participants will be a sample of convenience of nurses and allied health professionals from five Australian hospitals. For each hospital there will be two cohorts. Cohort 1 will be clinical leaders who shall receive a three-hour education program on the latest evidence in hospital falls risk assessment and how to implement a new falls screening and management tool. They will also be taught practical skills to enable them to deliver an effective one-hour in-service training session to Cohort 2. Cohort 2 will be recruited from the workforce as a whole and include nurses and other health professionals involved in routine hospital falls screening and prevention.

The investigation will be framed on Keller’s Model of Motivational Design and Kirkpatrick’s evaluation framework. It will involve a mixed methods pre and post-test questionnaire design inclusive of semi-structured telephone interviews, to triangulate the data from multiple approaches.

Discussion

This study will quantify the outcomes of a high-quality clinician education program to increase knowledge of evidence-based practice for falls prevention. It is predicted that positive behavioural changes will occur in health professionals, leading to organisational change and improved patient outcomes. Furthermore, the findings from the study will inform the future refinement of educational delivery to health professionals across hospital sites.

Trial registration

The study has also been approved by the Australian New Zealand Clinical Trials Registry: Preventing Hospital Falls: Optimal Screening UTN U1111-1225-8450.

Universal Trial Number (UTN): U1111–1228-0041 (obtained 5/2/19).

Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12619000200189 (obtained 12/2/19).
Impact, challenges and limits of inpatient palliative care consultations – perspectives of requesting and conducting physicians
Authors: Coym Anja , Oechsle Karin , Kanitz Alena , Puls Nora , Blum David , Bokemeyer Carsten , Ullrich Anneke
Published: February 2020

Background

Inpatient palliative care consultation (IPCC) teams have been established to improve care for patients with specialist palliative care (PC) needs throughout all hospital departments. The objective is to explore physicians’ perceptions on the impact of IPCC, its triggers, challenges and limits, and their suggestions for future service improvements.

Methods

A Qualitative study drawing on semi-structured interviews with 10 PC specialists of an IPCC team and nine IPCC requesting physicians from oncology and non-oncological departments of a university hospital. Analysis was performed using qualitative content analysis.

Results

PC specialists and IPCC requesting physicians likewise considered organization of further care and symptom-burden as main reasons for IPCC requests. The main impact however was identified from both as improvement of patients’ (and their caregivers’) coping strategies and relief of the treating team. Mostly, PC specialists emphasized a reduction of symptom burden, and improvement of further care. Challenges in implementing IPCC were lack of time for both. PC specialists addressed requesting physicians’ skepticism towards PC. Barriers for realization of IPCC included structural aspects for both: limited time, staff capacities and setting. PC specialists saw problems in implementing recommendations like disagreement towards their suggestions. All interviewees considered education in PC a sensible approach for improvement.

Conclusions

IPCC show various positive effects in supporting physicians and patients, but are also limited due to structural problems, lack of knowledge, insecurity, and skepticism by the requesting physicians. To overcome some of these challenges implementation of PC education programs for all physicians would be beneficial.
Social value of a set of proposals for the ideal approach of multiple sclerosis within the Spanish National Health System: a social return on investment study
Authors: Moral Torres Ester , Fernández Fernández Óscar , Carrascal Rueda Pedro , Ruiz-Beato Elena , Estella Pérez Elvira , Manzanares Estrada Rita , Gómez-García Teresa , Jiménez Margarita , Hidalgo-Vega Álvaro , Merino María
Published: February 2020

Background

Multiple Sclerosis (MS) is a chronic inflammatory, demyelinating and neurodegenerative disease that in many cases produces disability, having a high impact in patients’ lives, reducing significantly their quality of life. The aim of this study was to agree on a set of proposals to improve the current management of MS within the Spanish National Health System (SNHS) and apply the Social Return on Investment (SROI) method to measure the potential social impact these proposals would create.

Methods

A Multidisciplinary Working Team of nine experts, with representation from the main stakeholders regarding MS, was set up to agree on a set of proposals to improve the management of MS. A forecast SROI analysis was carried out, with a one-year timeframe. Data sources included an expert consultation, a narrative literature review and a survey to 532 MS patients. We estimated the required investment of a hypothetical implementation, as well as the potential social value that it could create. We calculated outcomes in monetary units and we measured intangible outcomes through financial proxies.

Results

The proposed ideal approach revealed that there are still unmet needs related to MS that can be addressed within the SNHS. Investment would amount to 148 million € and social return to 272 million €, so each euro invested could yield almost €2 of social return.

Conclusions

This study could guide health interventions, resulting in money savings for the SNHS and increases in patients’ quality of life.
Epigenetics dysfunction in morbid obesity with or without obstructive sleep apnoea: the EPIMOOSA study
Authors: Lázaro Javier , Clavería Paloma , Cabrejas Carmen , Fernando José , Daga Berta , Ordoñez Beatriz , Segura Silvia , Sanz - Rubio David , Marín José M.
Published: February 2020

Background

Obstructive sleep apnoea (OSA) and morbid obesity (MO), defined by a body mass index ≥35 kg/m2, are two closely related conditions. Recent studies suggest that circulating microRNA (miRNA) plays a potential role in the physiopathology of both conditions. To date, circulating miRNA expression has been studied separately in both conditions, but never jointly. The primary treatment of OSA is continuous positive airway pressure (CPAP), whereas bariatric surgery (BS) is the treatment of choice for MO. We have thus initiated the Epigenetics modification in Morbid Obesity and Obstructive Sleep Apnoea (EPIMOOSA) study (ClinicalTrials.gov identifier: NCT03995836).

Methods/design

EPIMOOSA is a prospective non-interventional cohort study aiming to recruit 45 MO patients who are candidates for BS. Three groups will be formed: MO without OSA, MO with OSA without CPAP and MO with OSA and CPAP. All of them will be followed up in 4 visits: baseline, 6 months prior to BS and 3, 6 and 12 months post-BS. At baseline, OSA status will be assessed by home sleep polygraphy (HSP), and CPAP will be adopted according to national guidelines. A specific standardized questionnaire (including medical conditions and AOS-related symptoms) and anthropometrical examination will be performed at each visit. Blood samples will be obtained at each visit for immediate standard biochemistry, haematology and inflammatory cytokines. For bio-banking, serum, plasma, and circulating exosomes will also be obtained. Twenty-four hours of blood pressure and electrocardiogram (ECG) Holter monitoring will be performed at all visits. A new HSP will be performed at the last visit. Finally, the three groups will be sex- and age- matched with participants in the EPIOSA study, an ongoing study aimed at understanding epigenetic changes in non-obese OSA patients.

Discussion

EPIMOOSA will evaluate changes in circulating miRNA in MO with or without OSA for the first time. In addition, EPIMOOSA will be able to elucidate the influence of OSA in MO patients and how specific and combined treatments alter miRNA expression.
Long non-coding RNA SOX2OT promotes the stemness phenotype of bladder cancer cells by modulating SOX2
Authors: Zhan Yonghao , Chen Zhicong , He Shiming , Gong Yanqing , He Anbang , Li Yifan , Zhang Lianghao , Zhang Xuepei , Fang Dong , Li Xuesong , Zhou Liqun
Published: February 2020

Background

Accumulating evidence indicates that long non-coding RNAs (lncRNAs) are potential biomarkers and key regulators of tumour development and progression. SOX2 overlapping transcript (SOX2OT) is a novel lncRNA that acts as a potential biomarker and is involved in the development of cancer and cancer stem cells. However, the clinical significance and molecular mechanism of SOX2OT in bladder cancer are still unknown.

Methods

The expression level of SOX2OT was determined by RT-qPCR in a total of 106 patients with urothelial bladder cancer and in different bladder cancer cell (BCC) lines. Bladder cancer stem cells (BCSCs) were isolated from BCCs using flow cytometry based on the stem cell markers CD44 and ALDH1. Loss-of-function experiments were performed to investigate the biological roles of SOX2OT in the stemness phenotype of BCSCs. Comprehensive transcriptional analysis, RNA FISH, dual-luciferase reporter assays and western blots were performed to explore the molecular mechanisms underlying the functions of SOX2OT.

Results

SOX2OT was highly expressed in bladder cancer, and increased SOX2OT expression was positively correlated with a high histological grade, advanced TNM stage and poor prognosis. Further experiments demonstrated that knockdown of SOX2OT inhibited the stemness phenotype of BCSCs. Moreover, inhibition of SOX2OT delayed xenograft tumour growth and decreased metastases in vivo. Mechanistically, we found that SOX2OT was mainly distributed in the cytoplasm and positively regulated SOX2 expression by sponging miR-200c. Furthermore, SOX2 overexpression reversed the SOX2OT silencing-induced inhibition of the BCSC stemness phenotype.

Conclusion

This study is the first to demonstrate that SOX2OT plays an important regulatory role in BCSCs and that SOX2OT may serve as a potential diagnostic biomarker and therapeutic target in bladder cancer.
The association of serum total bile acid with non-alcoholic fatty liver disease in Chinese adults: a cross sectional study
Authors: Zhang Ziyu , Dai Wen , Weng Shuwei , Luo Mengdie , Fu Jiahao , Zadroga John A. , Spolitu Stefano , Peng Daoquan
Published: February 2020

Background

Non-alcoholic fatty liver disease (NAFLD) is currently the major cause of chronic liver disease globally. Bile acids (BAs) have emerged as relevant signaling molecules that are associated with NAFLD development. This study was aimed to examine the association of serum total bile acids (TBAs) with NAFLD in a large population of Chinese subjects.

Methods

This cross sectional study recruited 152,336 participants from the Second Xiangya Hospital, China. NAFLD was diagnosed based on the presence of hepatic steatosis on ultrasonography, without significant alcohol consumption and other known causes for chronic liver disease. A multivariate logistic regression model was used to test for the association of serum TBAs with NAFLD, adjusting for conventional risk factors of NAFLD.

Results

A total of 27.4% of the participants had NAFLD. Patients with NAFLD had slightly higher TBA levels than those without, 3.4 vs. 3.0 μmol/L (p < 0.001). However, TBA levels were not associated with NAFLD in the multivariate logistic regression model, which adjusted for age, gender and other acknowledged risk factors for NAFLD (OR = 1.00. 95% CI: 1.00–1.00, p = 0.797).

Conclusions

We found that the serum TBA levels were not associated with NAFLD. Future studies in a large population, focusing on serum BA composition may improve the understating of the role of BAs in NAFLD.
IRGS: an immune-related gene classifier for lung adenocarcinoma prognosis
Authors: Shi Xiaoshun , Li Ruidong , Dong Xiaoying , Chen Allen Menglin , Liu Xiguang , Lu Di , Feng Siyang , Wang He , Cai Kaican
Published: February 2020

Background

Tumour cells interfere with normal immune functions by affecting the expression of some immune-related genes, which play roles in the prognosis of cancer patients. In recent years, immunotherapy for tumours has been widely studied, but a practical prognostic model based on immune-related genes in lung adenocarcinoma comparable to existing model has not been established and reported.

Methods

We first obtained publicly accessible lung adenocarcinoma RNA expression data from The Cancer Genome Atlas (TCGA) for differential gene expression analysis and then filtered immune-related genes based on the ImmPort database. By using the lasso algorithm and multivariate Cox Proportional-Hazards (CoxPH) regression analysis, we identified candidate genes for model development and validation. The robustness of the model was further examined by comparing the model with three established gene models.

Results

Gene expression data from a total of 524 lung adenocarcinoma patients from TCGA were used for model development. We identified four biomarkers (MAP3K8, CCL20, VEGFC, and ANGPTL4) that could predict overall survival in lung adenocarcinoma (HR = 1.98, 95% CI 1.48 to 2.64, P = 4.19e−06) and this model could be used as a classifier for the evaluation of low-risk and high-risk groups. This model was validated with independent microarray data and was highly comparable with previously reported gene expression signatures for lung adenocarcinoma prognosis.

Conclusions

In this study, we identified a practical and robust four-gene prognostic model based on an immune gene dataset with cross-platform compatibility. This model has potential value in improving TNM staging for survival predictions in patients with lung adenocarcinoma.

Impact

The study provides a method of immune relevant gene prognosis model and the identification of immune gene classifier for the prediction of lung adenocarcinoma prognosis with RNA sequencing and microarray compatibility.
Amyloid beta and diabetic pathology cooperatively stimulate cytokine expression in an Alzheimer’s mouse model
Authors: Sankar Sitara B. , Infante-Garcia Carmen , Weinstock Laura D. , Ramos-Rodriguez Juan Jose , Hierro-Bujalance Carmen , Fernandez-Ponce Cecilia , Wood Levi B. , Garcia-Alloza Monica
Published: February 2020

Background

Diabetes is a risk factor for developing Alzheimer’s disease (AD); however, the mechanism by which diabetes can promote AD pathology remains unknown. Diabetes results in diverse molecular changes in the brain, including dysregulation of glucose metabolism and loss of cerebrovascular homeostasis. Although these changes have been associated with increased Aβ pathology and increased expression of glial activation markers in APPswe/PS1dE9 (APP/PS1) mice, there has been limited characterization, to date, of the neuroinflammatory changes associated with diabetic conditions.

Methods

To more fully elucidate neuroinflammatory changes associated with diabetes that may drive AD pathology, we combined the APP/PS1 mouse model with either high-fat diet (HFD, a model of pre-diabetes), the genetic db/db model of type 2 diabetes, or the streptozotocin (STZ) model of type 1 diabetes. We then used a multiplexed immunoassay to quantify cortical changes in cytokine proteins.

Results

Our analysis revealed that pathology associated with either db/db, HFD, or STZ models yielded upregulation of a broadprofileof cytokines, including chemokines (e.g., MIP-1α, MIP-1β, and MCP-1) and pro-inflammatory cytokines, including IL-1α, IFN-γ, and IL-3. Moreover, multivariate partial least squares regression analysis showed that combined diabetic-APP/PS1 models yielded cooperatively enhanced expression of the cytokine profile associated with each diabetic model alone. Finally, in APP/PS1xdb/db mice, we found that circulating levels of Aβ1-40, Aβ1-42, glucose, and insulin all correlated with cytokine expression in the brain, suggesting a strong relationship between peripheral changes and brain pathology.

Conclusions

Altogether, our multiplexed analysis of cytokines shows that Alzheimer’s and diabetic pathologies cooperate to enhance profiles of cytokines reported to be involved in both diseases. Moreover, since many of the identified cytokines promote neuronal injury, Aβ and tau pathology, and breakdown of the blood-brain barrier, our data suggest that neuroinflammation may mediate the effects of diabetes on AD pathogenesis. Therefore, strategies targeting neuroinflammatory signaling, as well as metabolic control, may provide a promising strategy for intervening in the development of diabetes-associated AD.
Nutrition therapy in critical illness: a review of the literature for clinicians
Authors: Lambell Kate J. , Tatucu-Babet Oana A. , Chapple Lee-anne , Gantner Dashiell , Ridley Emma J.
Published: February 2020

Nutrition therapy during critical illness has been a focus of recent research, with a rapid increase in publications accompanied by two updated international clinical guidelines. However, the translation of evidence into practice is challenging due to the continually evolving, often conflicting trial findings and guideline recommendations. This narrative review aims to provide a comprehensive synthesis and interpretation of the adult critical care nutrition literature, with a particular focus on continuing practice gaps and areas with new data, to assist clinicians in making practical, yet evidence-based decisions regarding nutrition management during the different stages of critical illness.
Fluorescence-based method is more accurate than counting-based methods for plotting growth curves of adherent cells
Authors: Pereira Túlio Felipe , Levin Gabriel , DeOcesano-Pereira Carlos , Caodaglio Amanda Schiersner , Fujita André , Tonso Aldo , Sogayar Mari Cleide
Published: February 2020

Objective

Cell growth curves constitute one of the primary assays employed to analyze cell proliferation dynamics of in vitro cultured cells under specific culture conditions. From the cell growth curve, it is possible to assess the behavior of proliferating cells under different conditions, such as drug treatment and genomic editions. Traditionally, growth curves for adherent cells are obtained by seeding the cells in multiple-well plates and counting the total number of cells at different time points. Here, we compare this traditional method to the fluorescence-based method, which is based on the CFSE fluorescence decay over time.

Results

The fluorescence-based method is not dependent on the determination of the total number of cells, but rather is approached by assessing the fluorescence of a sample of single cells from a cell population at different time points after plating. Therefore, this method is not biased due to either cell loss during harvesting or to the presence of cellular debris and cell clumps. Moreover, the fluorescence-based method displays lower variation among different measurements of the same time point, which increases the reliability on the determination of lag, log and stationary phase transitions.