Notes

[Long-Term Recurrence-Free Emergency in a Individual Whom Gotten Chemotherapy pertaining to Numerous Metastases associated with Rectal Cancers Including the Lesser-Curvature Lymph Node Metastasis-A Circumstance Report].
Univariable or multivariable meta-regression and subgroup analyses will be conducted to compare elevated and non-elevated categories of cTn concentration. Sensitivity analyses will be used to assess the robustness of our results by removing each included study at one time to obtain and evaluate the remaining overall estimates of all-cause mortality or MAE.

In accordance with the Institutional Review Board/Independent Ethics Committee of Fuwai Hospital, ethical approval was waived for this systematic review protocol. This meta-analysis will be disseminated through a peer-reviewing process for journal publication and conference communication.

CRD42020216059.
CRD42020216059.
This study aimed to report the prevalence and clinical characteristics of adults with cerebral palsy (CP) in a geographically defined region of the UK.

Cross-sectional study using the Northern Ireland Cerebral Palsy Register (NICPR).

All validated cases known to the NICPR, born 1981-2001 and alive and resident in Northern Ireland at age 19 years were included.

The study included 1218 persons with CP aged 19-39 years, 46 of whom died in adulthood. The prevalence of CP was 2.38 per 1000. The majority of cases had spastic CP (n=1132/1218, 93%) and could walk (n=949/1218, 78%). Those that died in adulthood typically had bilateral spastic CP (n=39/46) and used a wheelchair (n=40/46).

The prevalence of CP in adults is similar to other common neurological conditions such as multiple sclerosis and Parkinson's disease. The needs of adults with CP vary widely with almost half having two or more associated impairments that may require multiprofessional and multiagency coordination. Results from this study can be used to inform transformation of health and care services for adults with CP.
The prevalence of CP in adults is similar to other common neurological conditions such as multiple sclerosis and Parkinson's disease. The needs of adults with CP vary widely with almost half having two or more associated impairments that may require multiprofessional and multiagency coordination. Results from this study can be used to inform transformation of health and care services for adults with CP.
Increasing urban populations have led to the growth of informal settlements, with contaminated environments linked to poor human health through a range of interlinked pathways. Here, we describe the design and methods for the Revitalising Informal Settlements and their Environments (RISE) study, a transdisciplinary randomised trial evaluating impacts of an intervention to upgrade urban informal settlements in two Asia-Pacific countries.

RISE is a cluster randomised controlled trial among 12 settlements in Makassar, Indonesia, and 12 in Suva, Fiji. Six settlements in each country have been randomised to receive the intervention at the outset; the remainder will serve as controls and be offered intervention delivery after trial completion. The intervention involves a water-sensitive approach, delivering site-specific, modular, decentralised infrastructure primarily aimed at improving health by decreasing exposure to environmental faecal contamination. Consenting households within each informal settlement sinments and human health and well-being.

Study protocols have been approved by ethics boards at Monash University, Fiji National University and Hasanuddin University.

ACTRN12618000633280; Pre-results.
ACTRN12618000633280; Pre-results.
This systematic review aimed to explore consultant attitudes towards teaching undergraduate medical students in the UK.

Systematic review.

Standard systematic review methodology was followed. MEDLINE, EMBASE and OpenGrey were searched from inception to August 2019 to identify studies exploring senior doctors' attitudes towards teaching undergraduate medical students. Two reviewers independently carried out key methodological steps including study screening/selection, quality assessment and data extraction. A narrative synthesis was undertaken.

Five studies were included in the review dating 2003-2015. Two studies used questionnaires, and three used focus groups/semistructured interviews. Key findings identified across all studies were consultants generally found teaching undergraduate medical students enjoyable, and consultants identified time constraints as a barrier to teaching. Other findings were consultants feeling there was a lack of recognition for time spent teaching, and a lack of training/guo longer as enthusiastic about teaching as they once were, but it is evident over the 12 years of these studies that enjoyment levels, and presumably enthusiasm, have not changed significantly.
Performing contractions with minimum force fluctuations is essential for everyday life as reduced force steadiness impacts on the precision of voluntary movements and functional ability. Several studies have investigated the effect of experimental or clinical musculoskeletal pain on force steadiness but with conflicting findings. The aim of this systematic review is to summarise the current literature to determine whether pain, whether it be clinical or experimental, influences force steadiness.

This protocol for a systematic review was informed and reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols and the Cochrane Handbook for Systematic Reviews of Interventions. Key databases will be searched from inception to 31 August 2020, including MEDLINE, EMBASE, PubMed, CINAHL Plus, ZETOC and Web of Science. Grey literature and key journals will be also reviewed. Risk of bias will be assessed with the Newcastle-Ottawa tool, and the quality of the cumulative evidence assessed with the Grading of Recommendations, Assessment, Development and Evaluation guidelines. If homogeneity exists between groups of studies, meta-analysis will be conducted. Otherwise, a narrative synthesis approach and a vote-counting method will be used, while the results will be presented as net increases or decreases of force steadiness.

The findings will be presented at conferences and the review will be also submitted for publication in a refereed journal. No ethical approval was required.

CRD42020196479.
CRD42020196479.
The purpose of this study is to explore the mediating effect of physical disability as well as the role of physical activity (PA) as a moderator in the relationship between physical frailty and health-related quality of life (HRQoL) among rural older adults in China.

Cross-sectional analysis.

Rural households in Shandong of China (Rushan, Qufu, Laolin).

A survey was conducted among 3243 rural older adults. The data were collected using questionnaires measuring physical frailty, physical disability, HRQoL and PA. Bootstrap analyses were employed to explore the mediating effect of physical disability and also the moderating role of PA on physical frailty and HRQoL.

After controlling for age and education, physical disability partially mediated the effect of physical frailty on HRQoL (indirect effect=-0.143, 95% CI -0.175 to -0.113), with the mediating effect accounting for 33.71% of the total effect. PA moderated the relationship between physical frailty and physical disability as well as the relationfor older adults with physical frailty and physical disability problems.
People with anterior cruciate ligament (ACL) reconstruction (ACLR) are at high risk of sustaining a graft rupture and/or contra-lateral ACL injury. The main factors that may predispose individuals for subsequent ACL injuries are, however, not established. To reduce the risk of reinjuries, it is of particular interest to identify modifiable risk-factors, for instance, those related to sensorimotor control which are responsive to training. The aim of the current study protocol is to present the design of our prospective cohort study STOP Graft Rupture investigating sensorimotor function as predictors for graft rupture, contra-lateral ACL injury and/or failure to return to sport (RTS) within 3 years following ACLR.

We aim to recruit 200 individuals (15-35 years, ~50% women) with ACLR from Norrland University Hospital, Umeå and Lund University Hospital, Lund, Sweden. Participants will be assessed with a comprehensive test battery for sensorimotor muscle function, including hop performance, muscle strength, muscle activation, hip and ankle range of motion and postural orientation as well as patient-reported function 1 year after ACLR (baseline). For a subgroup of individuals (Umeå cohort), 3D kinematics and joint position sense will also be evaluated. At follow-up (≥3 years post-ACLR), the participants will be asked to answer questions related to new ACL injuries to either knee and about RTS. Separate logistic regression models, adjusting for possible confounders, will be used to evaluate the influence of the different sensorimotor predictors on the prospective outcomes (graft rupture, contra-lateral ACL injury, RTS).

This study was approved by the Swedish Ethical Review Board (Dnr 2016/319 and Dnr 2019-04037). The results will be published in international peer-reviewed scientific journals and presented at clinical and scientific congresses.

NCT04162613.
NCT04162613.
This study aimed to determine the frequency of mouthwash use and its association to oral sex practice in heterosexuals.

A cross-sectional study.

Data obtained from a sexual health clinic in Victoria, Australia, between March 2019 and April 2019.

Heterosexual men and women attending the sexual health clinic answered a survey using computer-assisted self-interview.

Univariable and multivariable logistic regression were performed to examine the association between frequent mouthwash use (ie, daily or weekly mouthwash use) and oral sex practices (including tongue kissing, fellatio, cunnilingus and insertive rimming).

There were 681 heterosexuals included in the analysis 315 (46.3%) men and 366 (53.7%) women. Of participants, 302 (44.3%) used mouthwash frequently, 173 (25.4%) used mouthwash infrequently and 206 (30.2%) never used mouthwash. There was no significant difference in the proportion of frequent mouthwash users between men and women (46.4% of men vs 42.6% of women; p=0.329). The proportion of frequent mouthwash users increased with increasing age groups (39.3% in ≤24 years, 45.2% in 25-34 years and 52.8% in ≥35 years or older; p
=0.039) with those aged ≥35 years having a 1.80 times (95% CI 1.12 to 2.89) higher odds of being a frequent mouthwash user than those aged ≤24 years. There were no significant associations between frequent mouthwash users had sexually transmitted infection (STI) risk after adjusting for age and country of birth.

Older heterosexuals are more likely to use mouthwash. Given the high proportion and associations of mouthwash use in heterosexuals, future investigations related to oral STIs in this group should include mouthwash use.
Older heterosexuals are more likely to use mouthwash. Given the high proportion and associations of mouthwash use in heterosexuals, future investigations related to oral STIs in this group should include mouthwash use.
As people living with HIV (PLWH) live longer, morbidity and mortality from non-AIDS comorbidities have emerged as major concerns. Our objective was to compare prevalence trends and age at diagnosis of nine chronic age-associated comorbidities between individuals living with and without HIV.

This population-based cohort study used longitudinal cohort data from all diagnosed antiretroviral-treated PLWH and 14 age-sex-matched HIV-negative individuals in British Columbia, Canada.

The study included 8031 antiretroviral-treated PLWH and 32 124 HIV-negative controls (median age 40 years, 82% men). Eligible participants were ≥19 years old and followed for ≥1 year during 2000 to 2012.

The presence of non-AIDS-defining cancers, diabetes, osteoarthritis, hypertension, Alzheimer's and/or non-HIV-related dementia, cardiovascular, kidney, liver and lung diseases were identified from provincial administrative databases. Beta regression assessed annual age-sex-standardised prevalence trends and Kruskal-Wallis tests c health data to measure prevalence and incidence, is reproducible to other settings.
PLWH experienced higher prevalence and earlier age at diagnosis of non-AIDS comorbidities than their HIV-negative controls. These results stress the need for optimised screening for comorbidities at earlier ages among PLWH, and a comprehensive HIV care model that integrates prevention and treatment of chronic age-associated conditions. Additionally, the robust methodology developed in this study, which addresses concerns on the use of administrative health data to measure prevalence and incidence, is reproducible to other settings.
To identify the advantages and disadvantages that group practices have on patients, physicians and healthcare systems.

A scoping review was performed based on the methodology proposed by Arksey and O'Malley, and refined by Levac
. Titles and abstracts were screened by two reviewers. A quantitative analysis was performed to assess the type, year and region of publication, as well as the population studied. A qualitative descriptive analysis was performed to identify common themes.

MEDLINE, EMBASE and Cochrane databases were searched from database inception to October 2018 for papers which assessed outcomes relevant to the research question.

Our search strategy returned 2408 papers and 98 were included in the final analysis. Most papers were from the USA, were surveys and assessed physician outcomes. Advantages of group practices for patients included improved satisfaction and quality of care. Studies of physicians reported improved quality of life and income, while disadvantages included increased stress due to poor interpersonal relationships. Studies of healthcare systems reported improved efficiency and better utilisation of resources.

Group practices have many benefits for patients and physicians. However, further work needs to be done assessing patient outcomes and establishing the elements that make a group practice successful.
Group practices have many benefits for patients and physicians. However, further work needs to be done assessing patient outcomes and establishing the elements that make a group practice successful.
Occurrence of inaccurate or delayed diagnoses is a significant concern in patient care, particularly in emergency medicine, where decision making is often constrained by high throughput and inaccurate admission diagnoses. Artificial intelligence-based diagnostic decision support system have been developed to enhance clinical performance by suggesting differential diagnoses to a given case, based on an integrated medical knowledge base and machine learning techniques. The purpose of the study is to evaluate the diagnostic accuracy of Ada, an app-based diagnostic tool and the impact on patient outcome.

The eRadaR trial is a prospective, double-blinded study with patients presenting to the emergency room (ER) with abdominal pain. At initial contact in the ER, a structured interview will be performed using the Ada-App and both, patients and attending physicians, will be blinded to the proposed diagnosis lists until trial completion. Throughout the study, clinical data relating to diagnostic findings and types of therapy will be obtained and the follow-up until day 90 will comprise occurrence of complications and overall survival of patients. The primary efficacy of the trial is defined by the percentage of correct diagnoses suggested by Ada compared with the final discharge diagnosis. Further, accuracy and timing of diagnosis will be compared with decision making of classical doctor-patient interaction. Secondary objectives are complications, length of hospital stay and overall survival.

Ethical approval was received by the independent ethics committee (IEC) of the Goethe-University Frankfurt on 9 April 2020 including the patient information material and informed consent form. All protocol amendments must be reported to and adapted by the IEC. The results from this study will be submitted to peer-reviewed journals and reported at suitable national and international meetings.

DRKS00019098.
DRKS00019098.
To examine how often study funding and author conflicts of interest are stated in science and health press releases and in corresponding news; and whether disclosure in press releases is associated with disclosure in news. Second, to specifically examine disclosure rates in industry-funded studies.

Retrospective content analysis with two cohorts.

Press releases about health, psychology or neuroscience research from research universities and journals from 2011 (n=996) and 2015 (n=254) and their associated news stories (n=1250 and 578).

Mention of study funding and author conflicts of interest.

In our 2011 cohort, funding was reported in 94% (934/996) of journal articles, 29% (284/996) of press releases and 9% (112/1250) of news. The corresponding figures for 2015 were 84% (214/254), 52% (131/254) and 10% (58/578). A similar pattern was seen for the industry funding subset. If the press release reported study funding, news was more likely to 22% if in the press release versus 7% if not in the press release (2011), relative risk (RR) 3.1 (95% CI 2.1 to 4.3); for 2015, corresponding figures were 16% versus 2%, RR 6.8 (95% CI 2.2 to 17). In journal articles, 27% and 22% reported a conflict of interest, while less than 2% of press releases or news ever mentioned these.

Press releases and associated news did not frequently state funding sources or conflicts of interest. Funding information in press releases was associated with such information in news. Given converging evidence that news draws on press release content, including statements of funding and conflicts of interest in press releases may lead to increased reporting in news.
Press releases and associated news did not frequently state funding sources or conflicts of interest. Funding information in press releases was associated with such information in news. Given converging evidence that news draws on press release content, including statements of funding and conflicts of interest in press releases may lead to increased reporting in news.
This study estimates the prevalence of cancers that are categorised as treatable but not curable (TbnC) in England. It provides a quantification of the population and a framework to aid identification of this group to enable the design of tailored support services.

Through consultation with clinical and data experts an algorithmic definition of TbnC was developed. Using cancer registry data sets, with five other linked data sets held by the National Disease Registration Service, the algorithm was applied as part of this retrospective cohort study to estimate the size and characteristics of the TbnC population.

The health data records of 1.6 million people living with cancer in England in 2015, following a cancer diagnosis between 2001 and 2015, were retrospectively assessed for TbnC status.

An estimated 110 615 people in England were living with TbnC cancer at the end of 2015, following identification of TbnC cancer between 2012 and 2015. In addition, 51 946 people fit the initial search criteria but were found to have been in their last year of life at the end of 2015 and therefore considered separately here as end of life cases. A further 57 117 people in England were initially identified as being at high risk of recurrence or having their life being shortened by cancer but did not fit the TbnC conceptual framework and were excluded, but their results are also reported under 'group B'.

A population living with TbnC cancer can be identified using data currently collected on a national scale in England. This large population living with TbnC cancer requires personalised treatment and support.
A population living with TbnC cancer can be identified using data currently collected on a national scale in England. This large population living with TbnC cancer requires personalised treatment and support.
Patients who present in primary care with chronic functional somatic symptoms (FSS) have reduced quality of life and increased health care costs. Recognising these early is a challenge. The aim is to develop and internally validate a clinical prediction rule for repeated consultations with FSS.

Records from the longitudinal population-based ('Lifelines') cohort study were linked to electronic health records from general practitioners (GPs).

We included patients consulting a GP with FSS within 1 year after baseline assessment in the Lifelines cohort.

The outcome is repeated consultations with FSS, defined as ≥3 extra consultations for FSS within 1 year after the first consultation. Multivariable logistic regression, with bootstrapping for internal validation, was used to develop a risk prediction model from 14 literature-based predictors. Model discrimination, calibration and diagnostic accuracy were assessed.

18 810 participants were identified by database linkage, of whom 2650 consulted a GP with Fmodel. Moreover, this model mostly included general predictors of increased risk of repeated consultations among patients with FSS. The model discrimination and positive predictive values were insufficient and preclude clinical implementation.
Approximately 60 000 (9/100) infants are born into water annually in the UK and this is likely to increase. Case reports identified infants with water inhalation or sepsis following birth in water and there is a concern that women giving birth in water may sustain more complex perineal trauma. There have not been studies large enough to show whether waterbirth increases these poor outcomes. The POOL Study (ISRCTN13315580) plans to answer the question about the safety of waterbirths among women who are classified appropriate for midwifery-led intrapartum care.

A cohort study with a nested qualitative component. Objectives will be answered using retrospective and prospective data captured in electronic National Health Service (NHS) maternity and neonatal systems. The qualitative component aims to explore factors influencing pool use and waterbirth; data will be gathered via discussion groups, interviews and case studies of maternity units.

The protocol has been approved by NHS Wales Research Ethics Committee (18/WA/0291) the transfer of identifiable data has been approved by Health Research Authority Confidentiality Advisory Group (18CAG0153).Study findings and innovative methodology will be disseminated through peer-reviewed journals, conferences and events. Results will be of interest to the general public, clinical and policy stakeholders in the UK and will be disseminated accordingly.
The protocol has been approved by NHS Wales Research Ethics Committee (18/WA/0291) the transfer of identifiable data has been approved by Health Research Authority Confidentiality Advisory Group (18CAG0153).Study findings and innovative methodology will be disseminated through peer-reviewed journals, conferences and events. Results will be of interest to the general public, clinical and policy stakeholders in the UK and will be disseminated accordingly.
India has an overall neonatal mortality rate of 28/1000 live births, with higher rates in rural India. Approximately 3.5 million pregnancies in India are affected by preterm birth (PTB) annually and contribute to approximately a quarter of PTBs globally. Embedded within the PROMISES study (which aims to validate a low-cost salivary progesterone test for early detection of PTB risk), we present a mixed methods explanatory sequential feasibility substudy of the salivary progesterone test.

A pretraining and post-training questionnaire to assess Accredited Social Health Activists (ASHAs) (n=201) knowledge and experience of PTB and salivary progesterone sampling was analysed using the McNemar test. Descriptive statistics for a cross-sectional survey of pregnant women (n=400) are presented in which the acceptability of this test for pregnant women is assessed. Structured interviews were undertaken with ASHAs (n=10) and pregnant women (n=9), and were analysed using thematic framework analysis to explore the barriers and facilitators influencing the use of this test in rural India.

Before training, ASHAs' knowledge of PTB (including risk factors, causes, postnatal support and testing) was very limited. After the training programme, there was a significant improvement in the ASHAs' knowledge of PTB. All 400 women reported the salivary test was acceptable with the majority finding it easy but not quick or better than drawing blood. For the qualitative aspects of the study, analysis of interview data with ASHAs and women, our thematic framework comprised of three main areas implementation of intervention; networks of influence and access to healthcare. Qualitative data were stratified and presented as barriers and facilitators.

This study suggests support for ongoing investigations validating PTB testing using salivary progesterone in rural settings.
This study suggests support for ongoing investigations validating PTB testing using salivary progesterone in rural settings.
To identify and synthesise available evidence on the impact of transitional care interventions with both predischarge and postdischarge elements on readmission rates in older medical patients.

A systematic review.

Inclusion criteria were medical patients ≥65 years or mean age in study population of ≥75 years; interventions were transitional care interventions between hospital and home with both predischarge and postdischarge components; outcome was hospital readmissions. Studies were excluded if they included other patient groups than medical patients, included patients with only one diagnosis or patients with only psychiatric disorders. PubMed, The Cochrane Library, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Web of Science were searched from January 2008 to August 2019. Study selection at title level was undertaken by one author; the remaining selection process, data extraction and methodological quality assessment were undertaken by two authors independently. A narra.
CRD42019121795.
The aim of this study was to investigate the impact of age on the diagnostic properties of typical symptoms of urinary tract infection (UTI) in women presenting in general practice with symptoms suggestive of UTI with significant bacteriuria as the reference standard.

Diagnostic accuracy study.

General practice, Copenhagen, Denmark.

Adult 15 years or older. Women presenting in general practice with symptoms suggestive of UTI where urine was collected for investigation.

Accuracy of four symptoms of UTI (dysuria, frequency, urge and abdominal pain) in six different age groups.

90 practices included 1178 adult women. The prevalence of bacteriuria varied between 30% in women aged 30-44 years and 67% in women aged 75-89 years. The likelihood ratios for dysuria varied between age groups with the best performance in women aged 15-29 (positive likelihood ratio (pLR) 1.62 (1.30-1.94), negative likelihood ratio (nLR) 0.36 (0.19-0.54)) and women aged 30-44 (pLR 1.74 (1.30-2.17), nLR 0.48 (0.27-0.68)). CIs included or approximated one for the remaining symptoms in most age groups. When symptoms were combined to calculate post-test probabilities, the combined effect of the varying prevalence of bacteriuria and the varying diagnostic values resulted in a large variation of the post-test probabilities between age groups.

The diagnostic value of symptoms of UTI as well as the prevalence of bacteriuria in women presenting to general practice with suspected UTI vary between age groups with considerable clinical implications. Diagnostic studies should take demographics such as age into consideration.

ClinicalTrials.gov NCT02698332.
ClinicalTrials.gov NCT02698332.
The aims of this study are to describe area deprivation levels and changes that occur during residential moves involving New Zealand children from birth to their fourth birthday, and to assess whether these changes vary by ethnicity.

Longitudinal administrative data.

Children born in New Zealand from 2004 to 2018.

All (565 689) children born in New Zealand with at least one recorded residential move.

A longitudinal data set was created containing lifetime address histories for our cohort. This was linked to the New Zealand Deprivation Index, a measure of small area deprivation. Counts of moves from each deprivation level to each other deprivation level were used to construct transition matrices.

Children most commonly moved to an area with the same level of deprivation. This was especially pronounced in the most and least deprived areas. The number of moves observed also increased with deprivation. Māori and Pasifika children were less likely to move to, or remain in low-deprivation areas, and more likely to move to high-deprivation areas. They also had disproportionately high numbers of moves.

While there was evidence of mobility between deprivation levels, the most common outcome of a move was no change in area deprivation. The most deprived areas had the highest number of moves. Māori and Pasifika children were over-represented in high-deprivation areas and under-represented in low-deprivation areas. They also moved more frequently than the overall population of 0 to 3 year olds.
While there was evidence of mobility between deprivation levels, the most common outcome of a move was no change in area deprivation. The most deprived areas had the highest number of moves. Māori and Pasifika children were over-represented in high-deprivation areas and under-represented in low-deprivation areas. They also moved more frequently than the overall population of 0 to 3 year olds.
Acute-on-chronic liver failure (ACLF) is a clinical syndrome with high short-term mortality, unclear mechanism and controversial diagnosis criteria. The Chinese Acute-on-Chronic Liver Failure (CATCH-LIFE) study has been conducted in China to fill the gaps. In the first phase (the CATCH-LIFE investigation cohort), 2600 patients were continuously recruited from 14 national nationwide liver centres from 12 different provinces of China in 2015-2016, and a series of important results were obtained. To validate the preliminary results, we designed and conducted this multicentre prospective observational cohort (the CATCH-LIFE validation cohort).

Patients diagnosed with chronic liver disease and hospitalised for acute decompensation (AD) or acute liver injure were enrolled, received standard medical therapy. We collected the participants' demographics, medical history, laboratory data, and blood and urine samples during their hospitalisation.

From September 2018 to March 2019, 1370 patients (73.4% men) aged from 15 to 79 years old were enrolled from 13 nationwide liver centres across China. Of these patients, 952 (69.5%) had chronic hepatitis B, 973 (71.1%) had cirrhosis and 1083 (79.1%) complicated with AD at admission. The numbers and proportions of enrolled patients from each participating centre and the patients' baseline characteristics are presented.

A total of 12 months is required for each participant to complete follow-up. Outcome information (survival, death or receiving liver transplantation) collection and data cleansing will be done before June 2020. The data in the CATCH-LIFE validation cohort will be used for comparison between the new ACLF diagnostic criteria derivated from the CATCH-LIFE investigation cohort with existing ones. Moreover, future proteomic and metabolic omics analyses will provide valuable insights into the mechanics of ACLF, which will promote the development of specific therapy that leads to decrease patients' mortality.

NCT03641872.
NCT03641872.
The literature shows that selective carious tissue removal (SCTR) decreases the number and diversity of bacteria, stops the caries process and reduces the risk of pulp exposure. However, no consensus exists on which pulp liner would be suitable for teeth undergoing SCTR. So, this study will verify the in vivo response of dentine-pulp complex after SCTR in primary teeth with or without pulp liner material.

A randomised clinical trial, double-blinded, parallel-group and allocation concealment will be conducted with the enrolment of 384 patients from 5 to 9 years, with one maxillary/mandibular first/second primary molars with deep occlusal/occlusoproximal cavities. The remaining dentine will be lined with calcium hydroxide cement-group 1; mineral trioxide aggregate-group 2 and without liner-group 3. The primary outcome will be success of the of dentine-pulp complex evaluated clinically and radiographically at 6, 12 and 24 months, while the secondary outcomes will be the measurement of the dentine barrier on periapical radiographs. During all study, two trained and calibrated examiners will evaluate the treated teeth clinically and radiographically. Interexaminer and intraexaminer reliability will be verified by casual and systematic error. The Kolmogorov-Smirnov test will be adopted to test the normality of continuous variables. Comparisons among groups will be performed by using the χ
test and anaylsis of variance, followed by Tukey test (p<0.05). The logistic regression will be applied, and the degrees of this association will be measured using the OR and 95% CI.

The present protocol was submitted and approved by the Ethical Committee of the University of São Paulo, Bauru, São Paulo, Brazil (CAAE 79123517.0.0000.5417). Consent for publication will be obtained from all parents or legal guardians. Results of this study will be reported in full through peer-reviewed journals.

RBR-9fsxnn.
RBR-9fsxnn.
Acral melanomas (AM) represent a rare subgroup of melanomas with poor clinical outcomes and are enriched in Asian populations. Recent advances in next generation sequencing have provided opportunities to apply precision medicine to AM.

Here, we present a series of 13 patients with melanomas from Taiwan and Singapore, including 8 patients with AM profiled using whole exome sequencing and summarize the recent studies on the genomic landscape of AM.

We identified mutually exclusive mutations in BRAF, NRAS, HRAS, NF1 and KIT in 6 AM cases. In addition, recurrent copy number gains in CCND1 and CDK4, as well as recurrent deletions in CDKN2A/CDKN2B, ATM and RAD51 were observed, supporting the potential use of CDK4/6 or PARP inhibitors in the treatment of these patients.

The genomic landscape of AM provides an important resource for applying novel targeted therapies in this rare disease.
The genomic landscape of AM provides an important resource for applying novel targeted therapies in this rare disease.
Fusion of histone-lysine N-methyltransferase 2A gene (KMT2A) with the Rho guanine nucleotide exchange factor 12 gene (ARHGEF12), both located in 11q23, was reported in some leukemic patients. We report a KMT2A-ARHGEF12 fusion occurring during treatment of a pediatric acute myeloid leukemia (AML) with topoisomerase II inhibitors leading to a secondary acute lymphoblastic leukemia (ALL).

Multiple genetic analyses were performed on bone marrow cells of a girl initially diagnosed with AML.

At the time of diagnosis with AML, the t(9;11)(p21;q23)/KMT2A-MLLT3 genetic abnormality was found. After chemotherapy resulting in AML clinical remission, a 2 Mb deletion in 11q23 was found generating a KMT2A-ARHGEF12 fusion gene. When the patient later developed B lineage ALL, a t(14;19)(q32;q13), loss of one chromosome 9, and KMT2A-ARHGEF12 were detected.

The patient sequentially developed AML and ALL with three leukemia-specific genomic abnormalities in her bone marrow cells, two of which were KMT2A-rearrangements.
The patient sequentially developed AML and ALL with three leukemia-specific genomic abnormalities in her bone marrow cells, two of which were KMT2A-rearrangements.
Prognosis of advanced stages of laryngeal squamous cell carcinoma (LSCC) remains poor. To clarify therapeutic targets and improve survival rate, identification of new specific and prognostic biomarkers of LSCC is required. The study aimed to evaluate the impact of IL-10rs1800871, rs1800872, rs1800896 single nucleotide polymorphisms (SNPs), and IL-10 serum levels on LSCC development and determine associations of selected SNPs with patient survival rate.

A total of 300 LSCC patients and 533 controls were included in the study. Genotyping was carried out using RT-PCR; IL-10 serum levels were analyzed by ELISA.

Significant associations were identified between IL-10 rs1800871 variants and advanced stage of LSCC patient group in the codominant, recessive and additive models (OR=0.473, p=0.027; OR=0.510, p=0.040; and OR=0.733; p=0.037). Significant variants of IL-10 rs1800872 were determined in the codominant, recessive and additive models (OR=0.473, p=0.027; OR=0.510, p=0.040; and OR=0.733, p=0.037). The distribution of IL-10 SNPs genotypes did not impact LSCC patient survival rate (respectively, p=0.952; p=0.952; p=0.991).

IL-10rs1800871 and rs1800872 SNPs are associated with advanced stage of LSCC. The genotypic distribution of IL-10 SNPs does not influence the survival rate of LSCC patients.
IL-10rs1800871 and rs1800872 SNPs are associated with advanced stage of LSCC. The genotypic distribution of IL-10 SNPs does not influence the survival rate of LSCC patients.Numerous cancer drivers have been identified, but they are specific to a given cancer type and condition; universal cancer drivers and universal cancer mechanisms still remain largely unclear. Here, we identified the deadliest universal drivers for all cancers via developing algorithms to analyze massive RNAseqs and clinical data from The Cancer Genome Atlas (TCGA). In general, noncoding RNAs primarily serve as the most important inducers and suppressors for all types of cancers. In particular, pseudogenes are primary inducers, and specifically the antisense RNA RP11-335K5.2 serves as the most universal cancerous driver, independently of the cancer type and condition. Therefore, noncoding RNAs, instead of proteins as conventionally thought, primarily drive cancer, which establishes a novel field for future cancer research and therapy.
Opisthorchis viverrini (Ov) infection-induced cholangiocarcinoma (CCA) is a major public health problem in northeastern Thailand. Praziquantel was shown to prevent CCA development in an Ov-infected hamster model; however, the molecular mechanism remains unknown.

In this study, we used a hamster model with Ov and N-nitrosodimethylamine-induced CCA to study the mechanisms of praziquantel action. The liver tissues from the hamsters with and without praziquantel treatment were analyzed using
H nuclear magnetic resonance spectroscopy.

A total of 14 metabolites were found to be significantly different between the two groups. Furthermore, the combination of acetate, inosine and sarcosine was shown to exert an anti-inflammatory effect through interleukin-6 inhibition in a macrophage cell line, suggesting a mechanism by which praziquantel may prevent inflammation caused by Ov, cholangiocyte transformation and further CCA develpoment.

These findings might avail the development of a preventive strategy for CCA in high-risk populations.
These findings might avail the development of a preventive strategy for CCA in high-risk populations.
Metastasis to cervical lymph nodes of oral squamous cell carcinoma (OSCC) leads to a poor prognosis. The present study aimed at investigating the pathways and molecules associated with OSCC metastasis.

The transcriptome between HSC-3 cells and their highly metastatic subline, HSC-3-M3 cells, was examined using gene expression microarray. Gene enrichment analyses and Ingenuity Pathway Analysis were performed. Kaplan-Meier plot analysis using a publicly available dataset was conducted to assess whether candidate molecules are prognosticators.

A total of 1,018 genes were differentially expressed, and the inflammatory pathway and NF-kB were predicted to be activated in HSC-3-M3 cells. CSF2 was suggested to be an indicator of poor prognosis in head and neck cancers.

Inflammation and NF-kB may be involved in the metastasis of OSCC, and CSF2 is a promising diagnostic and therapeutic molecule. Moreover, HSC-3-M3 cells are a useful cell line model for studying OSCC progression.
Inflammation and NF-kB may be involved in the metastasis of OSCC, and CSF2 is a promising diagnostic and therapeutic molecule. Moreover, HSC-3-M3 cells are a useful cell line model for studying OSCC progression.The annual death toll for gastric cancer is in the range of 700,000 worldwide. Even in patients with early-stage gastric cancer recurrence within five years has been observed after surgical resection and following chemotherapy with therapy-resistant features. Therefore, the identification of new targets and treatment modalities for gastric cancer is of paramount importance. In this review we focus on the role of microRNAs with documented efficacy in preclinical xenograft models with respect to growth of human gastric cancer cells. We have identified 31 miRs (-10b, -19a, -19b, -20a, -23a/b, -25, -27a-3p, -92a, -93, -100, -106a, -130a, -135a, -135b-5p, -151-5p, -187, -199-3p, -215, -221-3p, -224, -340a, -382, -421, -425, -487a, -493, -532-3p, -575, -589, -664a-3p) covering 26 different targets which promote growth of gastric cancer cells in vitro and in vivo as xenografts. Five miRs (miRs -10b, 151-5p, -187, 532-3p and -589) additionally have an impact on metastasis. Thirteen of the identified miRs (-19b, -20a/b, -25, -92a, -106a, -135a, -187, -221-3p, -340a, -421, -493, -575 and -589) have clinical impact on worse prognosis in patients.
The infectious coronavirus disease 2019 (COVID-19) pandemic is an ongoing global healthcare challenge. Up to one-third of hospitalised patients develop severe pulmonary complications and acute respiratory distress syndrome. Pulmonary outcomes following COVID-19 are unknown.

The Swiss COVID-19 lung study is a multicentre prospective cohort investigating pulmonary sequelae of COVID-19. We report on initial follow-up 4 months after mild/moderate or severe/critical COVID-19 according to the World Health Organization severity classification.

113 COVID-19 survivors were included (mild/moderate n=47, severe/critical n=66). We confirmed several comorbidities as risk factors for severe/critical disease. Severe/critical disease was associated with impaired pulmonary function,
diffusing capacity of the lung for carbon monoxide (

) % predicted, reduced 6-min walk distance (6MWD) and exercise-induced oxygen desaturation. After adjustment for potential confounding by age, sex and body mass index (BMI), patientrus 2 infection, severe/critical COVID-19 was associated with significant functional and radiological abnormalities, potentially due to small-airway and lung parenchymal disease. A systematic follow-up for survivors needs to be evaluated to optimise care for patients recovering from COVID-19.
Data from the INMARK trial were used to investigate the feasibility and validity of home spirometry as a measure of lung function decline in patients with idiopathic pulmonary fibrosis (IPF).

Subjects with IPF and preserved forced vital capacity (FVC) were randomised to receive nintedanib or placebo for 12 weeks followed by open-label nintedanib for 40 weeks. Clinic spirometry was conducted at baseline and weeks 4, 8, 12, 16, 20, 24, 36 and 52. Subjects were asked to perform home spirometry at least once a week and ideally daily. Correlations between home- and clinic-measured FVC and rates of change in FVC were assessed using Pearson correlation coefficients.

In total, 346 subjects were treated. Mean adherence to weekly home spirometry decreased over time but remained above 75% in every 4-week period. Over 52 weeks, mean adherence was 86%. Variability in change from baseline in FVC was greater when measured by home rather than clinic spirometry. Strong correlations were observed between home- and clinic-measured FVC at all time-points (r=0.72-0.84), but correlations between home- and clinic-measured rates of change in FVC were weak (r=0.26 for rate of decline in FVC over 52 weeks).

Home spirometry was a feasible and valid measure of lung function in patients with IPF and preserved FVC, but estimates of the rate of FVC decline obtained using home spirometry were poorly correlated with those based on clinic spirometry.
Home spirometry was a feasible and valid measure of lung function in patients with IPF and preserved FVC, but estimates of the rate of FVC decline obtained using home spirometry were poorly correlated with those based on clinic spirometry.
Asthma exacerbations are major contributors to asthma morbidity and mortality. They are usually managed with bronchodilators and oral corticosteroids (OCS), but clinical trial evidence suggests that antibiotics could be beneficial. We aimed to assess whether treatment of asthma exacerbations with antibiotics in addition to OCS improved outcomes in larger, more representative routine-care populations.

A retrospective comparative effectiveness study into managing asthma exacerbations with OCS alone
OCS plus antibiotics was conducted using the Optimum Patient Care Research Database. The dataset included 28 637 patients; following propensity score matching 20 024 adults and 4184 children were analysed.

Antibiotics in addition to OCS were prescribed for the treatment of asthma exacerbations in 45% of adults and 32% of children. Compared to OCS alone, OCS plus antibiotics was associated with reduced risk of having an asthma/wheeze consultation in the following 2 weeks (children hazard ratio (HR) 0.84 (95% tibiotic overuse.
Patients with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) demonstrate high rates of co-infection with respiratory viruses, including influenza A (IAV), suggesting pathogenic interactions.

We investigated how IAV may increase the risk of COVID-19 lung disease, focusing on the receptor angiotensin-converting enzyme (ACE)2 and the protease TMPRSS2, which cooperate in the intracellular uptake of SARS-CoV-2.

We found, using single-cell RNA sequencing of distal human nondiseased lung homogenates, that at baseline, ACE2 is minimally expressed in basal, goblet, ciliated and secretory epithelial cells populating small airways. We focused on human small airway epithelial cells (SAECs), central to the pathogenesis of lung injury following viral infections. Primary SAECs from nondiseased donor lungs apically infected (at the air-liquid interface) with IAV (up to 3×10
 pfu; ∼1 multiplicity of infection) markedly (eight-fold) boosted the expression of ACanslational changes in ACE2 by IAV may increase vulnerability to lung injury such as acute respiratory distress syndrome during viral co-infections. These findings support efforts in the prevention and treatment of influenza infections during the COVID-19 pandemic.
The goal of this study is to evaluate the long-term outcomes of patients with takotsubo syndrome and assess factors associated with death or recurrence.

This is a retrospective population-based cohort study of consecutive patients who presented to an integrated health system in Southern California with takotsubo syndrome between 2006 and 2016. Medical records were manually reviewed to confirm diagnosis and to identify predisposing factors, medication treatment and long-term outcomes. Factors associated with death or recurrent takotsubo syndrome were tested using Cox regression models.

Between 2006 and 2016, there were 519 patients with a confirmed diagnosis of takotsubo syndrome. Patients were followed for 5.2 years (IQR 3.0-7.2). During the follow-up period, 39 (7.5%) had recurrent takotsubo syndrome and 84 (16.2%) died. In multivariate modelling, factors associated with higher risk of recurrence or death were age (HR 1.56 per 10-year increase, 95% CI 1.29 to 1.87), male sex (HR 2.52, 95% CI 1.38 to 4.60), diabetes (HR 1.6, 95% CI 1.06 to 2.43), pulmonary disease (HR 2.0, 95% CI 1.37 to 2.91) and chronic kidney disease (HR 1.58, 95% CI 1.01 to 2.47). Treatment with beta-blockers were associated with lower risk of recurrence or death (HR 0.46, 95% CI 0.29 to 0.72). No association was observed between treatment with ACE inhibitors or angiotensin-receptor blockers and recurrence or death (HR 0.92, 95% CI 0.59 to 1.42).

Recurrent takotsubo syndrome occurred in a minor subset of patients. Treatment with beta-blocker was associated with higher event-free survival.
Recurrent takotsubo syndrome occurred in a minor subset of patients. Treatment with beta-blocker was associated with higher event-free survival.
It remains unknown whether patient socioeconomic factors affect interventions and survival after out-of-hospital cardiac arrest (OHCA), and whether a socioeconomic effect on bystander interventions affects survival. Therefore, this study examined patient socioeconomic disparities in prehospital factors and survival.

From the Danish Cardiac Arrest Registry, patients with OHCA ≥30 years were identified, 2001-2014, and divided into quartiles of household income (highest, high, low, lowest). Associations between income and bystander cardiopulmonary resuscitation (CPR) and 30-day survival with bystander CPR as mediator were analysed by logistic regression and mediation analysis in private witnessed, public witnessed, private unwitnessed and public unwitnessed arrests, adjusted for confounders.

We included 21 480 patients. Highest income patients were younger, had higher education and were less comorbid relative to lowest income patients. They had higher odds for bystander CPR with the biggest difference in ps and survival after OHCA that was not explained by patient or cardiac arrest-related factors.
Tricuspid regurgitation (TR) is a common valvular heart disease with unsatisfactory medical therapeutics and high surgical mortality. The present study aims to evaluate the safety and effectiveness of transcatheter tricuspid valve replacement (TTVR) in high-risk patients with severe TR.

This was a compassionate multicentre study. Between September 2018 and November 2019, 46 patients with TR who were not suitable for surgery received compassionate TTVR under general anaesthesia and the guidance of trans-oesophageal echocardiography and fluoroscopy in four institutions. Access to the tricuspid valve was obtained via a minimally invasive thoracotomy and transatrial approach. Patients' data at baseline, before discharge, 30 days and 6 months after the procedure were collected.

All patients had severe TR with vena contracta width of 12.6 (11.0, 14.5) mm. Procedural success (97.8%) was achieved in all but one case with right ventricle perforation. The procedural time was 150.0 (118.8, 180.0) min. Intensive care unit time was 2.
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