bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving detection of JC virus by ultrafiltration of cerebrospinal fluid before polymerase chain reaction for the diagnosis of progressive multifocal leukoencephalopathy
Authors: Nakamichi Kazuo , Kawamoto Michi , Ishii Junko , Saijo Masayuki
Published: October 2019

Background

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disorder caused by JC virus (JCV). Although detecting JCV DNA in the cerebrospinal fluid (CSF) by real-time polymerase chain reaction (PCR) is useful, diagnosis is difficult when JCV concentrations are low. We therefore aimed to lower the detection limit of real-time PCR testing by enriching JCV in the CSF via ultrafiltration.

Methods

Virus suspensions and CSF specimens from 20 untreated patients with suspected PML were collected and total DNAs were extracted. The JCV large T gene was detected by quantitative real-time PCR under condition with and without prior centrifugal ultrafiltration.

Results

The JCV DNA was reliably detected to a lower limit of 10 copies/mL of virus suspension by real-time PCR with ultrafiltration. When using this method, the quantity of JCV DNA per PCR reaction increased 3.2- to 8.7-fold compared with the standard procedure. Seven patients were positive for JCV when using the standard procedure, and an additional patient was positive when using ultrafiltration. All JCV-positive patients had neurological features and magnetic resonance imaging findings compatible with PML.

Conclusions

The detection limit of JCV DNA by real-time PCR can be lowered by viral enrichment using ultrafiltration. Our simple protocol offers a valuable tool for PML diagnosis when extremely low copy numbers of JCV are released into the CSF or when brain biopsy is not feasible.
Female sex is associated with a lower risk of bone metastases and favourable prognosis in non-sex-specific cancers
Authors: Ma Wenjuan , Peltzer Karl , Qi Lisha , Xu Guijun , Liu Zheng , Wang Jingyi , Mao Min , Chekhonin Vladimir P. , Wang Xin , Zhang Chao
Published: October 2019

Background

The objectives were to investigate the disparity in the prevalence of bone metastases (BM) between the sexes and to assess the effect of female sex on the development and prognosis of BM.

Methods

Cases of invasive non-sex-specific cancers diagnosed between 2010 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) program were used. The prevalence of BM was calculated by combining the prevalence of BM among different cancers. Multivariable logistic regression and proportion hazard regression were conducted to investigate the effect of female sex, and the results were pooled by meta-analysis.

Results

The pooled prevalence of BM among male and female patients was 2.3% (95% CI: 1.6–3.2%) and 1.8% (95% CI: 1.2–2.6%), respectively. The pooled prevalence of BM dramatically decreased for patients aged 11–40 years old, plateaued for patients aged 41–90 years old and increased for patients aged > 90 years old in both male and female patients. Meta-analysis suggested that female sex had a protective effect on the development of BM (pooled OR = 0.80; 95% CI: 0.75–0.84; p < .001) and a favourable prognosis for respiratory system cancers (pooled HR = 0.81; 95% CI: 0.71–0.92; p < .001). However, no significant associations existed for other cancers. Male non-sex-specific cancer patients and those with male-leaning genetic variations or hormonal status have a greater likelihood of developing BM than female patients.

Conclusions

Female sex was associated with fewer BM in various non-sex-specific cancers, and the effect was constant with changes in age. Female sex showed a protective effect exclusively on the prognosis of respiratory system cancers.
lionessR: single sample network inference in R
Authors: Kuijjer Marieke L , Hsieh Ping-Han , Quackenbush John , Glass Kimberly
Published: October 2019

Background

In biomedical research, network inference algorithms are typically used to infer complex association patterns between biological entities, such as between genes or proteins, using data from a population. This resulting aggregate network, in essence, averages over the networks of those individuals in the population. LIONESS (Linear Interpolation to Obtain Network Estimates for Single Samples) is a method that can be used together with a network inference algorithm to extract networks for individual samples in a population. The method’s key characteristic is that, by modeling networks for individual samples in a data set, it can capture network heterogeneity in a population. LIONESS was originally made available as a function within the PANDA (Passing Attributes between Networks for Data Assimilation) regulatory network reconstruction framework. However, the LIONESS algorithm is generalizable and can be used to model single sample networks based on a wide range of network inference algorithms.

Results

In this software article, we describelionessR, an R implementation of LIONESS that can be applied to any network inference method in R that outputs a complete, weighted adjacency matrix. As an example, we provide a vignette of an application oflionessRto model single sample networks based on correlated gene expression in a bone cancer dataset. We show how the tool can be used to identify differential patterns of correlation between two groups of patients.

Conclusions

We developedlionessR, an open source R package to model single sample networks. We show howlionessRcan be used to inform us on potential precision medicine applications in cancer. ThelionessRpackage is a user-friendly tool to perform such analyses. The package, which includes a vignette describing the application, is freely available at:https://github.com/kuijjerlab/lionessRand at:http://bioconductor.org/packages/lionessR.
Risk factors of acute respiratory infections among under five children attending public hospitals in southern Tigray, Ethiopia, 2016/2017
Authors: Alemayehu Sielu , Kidanu Kalayou , Kahsay Tensay , Kassa Mekuria
Published: October 2019

Background

Acute Respiratory infection accounts for 94,037000 disability adjusted life years and 1.9 million deaths worldwide. Acute respiratory infections is the most common causes of under-five illness and mortality. The under five children gets three to six episodes of acute respiratory infections annually regardless of where they live. Disease burden due to acute respiratory infection is 10–50 times higher in developing countries when compared to developed countries. The aim of this study was to assess risk factors of acute respiratory infection among under-five children attending Public hospitals in Southern Tigray, Ethiopia 2016/2017.

Methods

Institution based case control study was conducted from Nov 2016 to June 2017. Interviewer administered structured questionnaire was used to collect data from a sample of 288 (96 cases and 192 controls) children under 5 years of age. Systematic random sampling was used to recruit study subjects and SPSS version 20 was used to analyze the data. Bivariate and multivariate analysis were employed to examine statistical association between the outcome variable and selected independent variables at 95% confidence level. Level of statistical Significance was declared at p < 0.05. Tables, figures and texts were used to present data.

Result

One hundred sixty (55.6%) and 128 (44.4%) of the participants were males and females respectively. Malnutrition (AOR = 2.89; 95%CI: 1.584–8.951; p = 0.039), cow dung use (AOR =2.21; 95%CI: 1.121–9.373; p = 0.014), presence of smoker in the family (AOR = 0.638; 95% CI: 0.046–0.980; p = 0.042) and maternal literacy (AOR = 3.098; 95%CI: 1.387–18.729; p = 0.021) were found to be significant predictors of acute respiratory infection among under five children.

Conclusion

According to this study maternal literacy, smoking, cow dung use and nutritional status were strongly associated with increased risk of childhood acute respiratory infection. Health care providers should work jointly with the general public, so that scientific knowledge and guidelines for adopting particular preventive measures for acute respiratory infection are disseminated.
Injury rate and risk factors among small-scale gold miners in Ghana
Authors: Nakua Emmanuel Kweku , Owusu-Dabo Ellis , Newton Samuel , Koranteng Adofo , Otupiri Easmon , Donkor Peter , Mock Charles
Published: October 2019

Background

To determine the potential risk factors for injury, estimate the annual injury rate and examine the safety perceptions, and use of personal protective equipment among small-scale gold miners in Ghana.

Methods

A cross-sectional survey was carried out with 494 small-scale gold miners from four major mining districts in Ghana. A household-based approach was used to obtain a representative sample of miners. The study was conducted from June 2015 to August 2016. A systematic sampling technique was used to select households and recruit respondents to interview. Miners were asked about any mining related injury that they had sustained in the past year. A logistics regression model was employed to examine the association between risk factors and injury. Data were analyzed with STATA version 14.0.

Results

The annual incidence rate of mining-related injury was 289 per 1000 workers. Injuries were mainly caused by machinery/tools 66(46.1%), followed by slip/falls 46(32.2%). The major risk factor for injury was underground work (adjusted odds ratio for injury 3.19; 95% CI = 1.42–7.20) compared with surface work. Higher education levels were protective, with adjusted odds ratios of 0.48 (95% CI = 0.24–0.99) for middle school education and 0.38 (95% CI 0.17–0.83) for secondary school compared with no schooling. Only 15(3.0%) of miners reported to have had safety training in the past year and 105(21.3%) indicated that there were safety regulations at their work place. A moderate number of workers reported using work boots 178(36.0%) and hand gloves 134(27.1%), but less than 10% of workers used other personal protective equipment.

Conclusion

The annual injury incidence rate among small-scale gold miners is high. Potential targets for improving safety include increasing safety training, increasing use of personal protective equipment, and better understanding potential changes that can be made in the machinery and tools used in small-scale mining, which were associated with almost half of all injuries.
Anemia prevalence and etiology among women, men, and children in Ethiopia: a study protocol for a national population-based survey
Authors: Tadesse Amare Worku , Hemler Elena C. , Andersen Christopher , Passarelli Simone , Worku Alemayehu , Sudfeld Christopher R. , Berhane Yemane , Fawzi Wafaie W.
Published: October 2019

Background

Anemia remains a public health challenge in Ethiopia, affecting an estimated 56% of children under age 5 years, 23% of women of reproductive age and 18% of adult men. However, anemia etiology and the relative contribution of underlying risk factors for anemia remains unclear and has hindered implementation of anemia control programs.

Methods/design

Anemia Etiology in Ethiopia (AnemEE) is a population-based cross-sectional survey of six regions of Ethiopia that includes children, women of reproductive age, and men from regionally representative households. The survey will include detailed assessment of anemia, iron, inflammatory and nutritional biomarkers, diet, comorbidities, and other factors. The objectives of AnemEE are 1) to generate evidence for decision-making on the etiology of anemia in Ethiopia among men, women and children and 2) to simulate the potential effect of iron fortification and other interventions on the prevalence of anemia and risk of iron overload.

Discussion

AnemEE will provide the most comprehensive evaluation of anemia etiology in Ethiopia to date due to its detailed assessment of diet, biomarkers, infections and other risk factors in a population-based sample. By generating evidence and simulating potential interventions, AnemEE will inform the development of high-impact anemia control programs and policies.

Trial registration

ClinicalTrials.gov,NCT04002466. Registered on 28 June 2019. Retrospectively registered.
The relationships between health-related behaviours in the Canadian adult population
Authors: Mudryj Adriana N. , Riediger Natalie D. , Bombak Andrea E.
Published: October 2019

Background

Health-related behaviours such as physical inactivity, low fruit and vegetable intake, smoking, alcohol use, and inadequate sleep are significant predictors of adverse health outcomes. Health promotion strategies often focus on one behavior, though research suggests health-related behaviours tend to co-occur. The purpose of this study is to describe the relationships between health-related behaviours in the Canadian adult population.

Methods

Data from cycles 3 (2012–2013) and 4 (2014–2015) of the Canadian Health Measures Survey were pooled to describe health-related behaviours (current smoking status, high-risk alcohol use, fruit and vegetable intake, inadequate sleep, and physical activity) among adults according to sex, age group, household education, and income adequacy. Logistic regression was used to test for relationships between health-related behaviours.

Results

Findings indicated that adverse health-related behaviours co-occur frequently, with approximately half of Canadians reporting two or more adverse health-related behaviours. Overall, Canadian men were more likely to report adverse health-related behaviours compared to women, with the exception of inadequate sleep. Smoking status, fruit and vegetable intake, sleep and physical activity exhibited an income and education gradient. Sex-based patterns in grouping of behaviours were present such that adverse health-related behaviours were associated with current smoking among men and with high-risk alcohol use among women.

Conclusion

Our findings suggest that health-related behaviours should be considered in both isolation and combination when designing intervention strategies. Sex-specific patterns of how these behaviours co-occur must also be taken into account.
Time spent cycling, walking, running, standing and sedentary: a cross-sectional analysis of accelerometer-data from 1670 adults in the Copenhagen City Heart Study
Authors: Johansson Melker Staffan , Korshøj Mette , Schnohr Peter , Marott Jacob Louis , Prescott Eva Irene Bossano , Søgaard Karen , Holtermann Andreas
Published: October 2019

Background

Information about how much time adults spend cycling, walking and running can be used for planning and evaluating initiatives for active, healthy societies. The objectives of this study were to describe how much time adult Copenhageners cycle, walk, run, stand and spend sedentary using accelerometers, and to describe differences between population groups.

Methods

In the fifth examination of the Copenhagen City Heart Study, 2335 individuals gave consent to wear accelerometers (skin-attached; right thigh and iliac crest; 24 h/day, 7 consecutive days) of which 1670 fulfilled our inclusion criteria (≥16 h/day for ≥5 days; median wear time: 23.8 h/day). Daily time spent cycling, walking, running, standing and sedentary was derived from accelerometer-based data using the Acti4 software, and differences between sex, age groups, level of education and BMI were investigated using Kruskal-Wallis rank sum tests.

Results

Among those cycling (61%), the median cycling time was 8.3 min/day. The median time walking, running, standing and sedentary was 82.6, 0.1, 182.5 and 579.1 min/day, respectively. About 88% walked fast (i.e., ≥100 steps/min) ≥30 min/day. The shortest duration and lowest prevalence of cycling, walking and running were found among older individuals, those with a low level of education, and individuals being overweight or obese.

Conclusions

We found a long duration and high prevalence of cycling and walking, but also that many adult Copenhageners spent much time sedentary. Population groups with low participation in physical activities such as cycling and walking should be targeted in future initiatives towards an active, healthy society.
The prevalence of cardiometabolic multimorbidity and its association with physical activity, diet, and stress in Canada: evidence from a population-based cross-sectional study
Authors: Sakakibara Brodie M. , Obembe Adebimpe O. , Eng Janice J.
Published: October 2019

Background

Cardiometabolic multimorbidity (CM) is defined as having a diagnosis of at least two of stroke, heart disease, or diabetes, and is an emerging health concern, but the prevalence of CM at a population level in Canada is unknown. The objectives of this study were to quantify the: 1) prevalence of CM in Canada; and 2) association between CM and lifestyle behaviours (e.g., physical activity, consumption of fruits and vegetables, and stress).

Methods

Using data from the 2016 Canadian Community Health Survey, we estimated the overall and group prevalence of CM in individuals aged ≥50 years (n = 13,226,748). Multiple logistic regression was used to quantify the association between CM and lifestyle behaviours compared to a group without cardiometabolic conditions.

Results

The overall prevalence of CM was 3.5% (467,749 individuals). Twenty-two percent (398,755) of people with diabetes reported having another cardiometabolic condition and thus CM, while the same was true for 32.2% (415,686) of people with heart disease and 48.4% (174,754) of stroke survivors. 71.2% of the sample reported eating fewer than five servings of fruits and vegetables per day. The odds of individuals with CM reporting zero minutes of physical activity was 2.35 [95% CI = 1.87 to 2.95] and having high stress was 1.89 [95% CI = 1.49 to 2.41] times the odds of the no cardiometabolic condition reference group. The odds of individuals with all three cardiometabolic conditions reporting zero minutes of physical activity was 4.31 [95% CI = 2.21 to 8.38] and having high stress was 3.93 [95% CI = 2.03 to 7.61].

Conclusion

The number of Canadians with CM or at risk of CM is high and these individuals have lifestyle behaviours that are associated with adverse health outcomes. Lifestyle behaviours tend to diminish with increasing onset of cardiometabolic conditions. Lifestyle modification interventions focusing on physical activity and stress management for the prevention and management CM are warranted.
Gender differential secular trend in lifetime smoking prevalence among adolescents: an age-period-cohort analysis
Authors: Hwang Jun Hyun , Park Soon-Woo
Published: October 2019

Background

There has been a gender difference in adolescents’ lifetime smoking prevalence trends over the last 10 years. This study aimed to explain the gender differential secular trend in adolescents’ lifetime smoking prevalence using age-period-cohort (APC) analysis and suggests possible causes for this trend, including Korean tobacco control policies during the last 10 years.

Methods

We utilized the 2006–2017 Korea Youth Risk Behavior Web-based Survey enrolling grades 7 to 12. Using year of survey and year of entry into middle school, we classified 859,814 students who had ever smoked into 6 age groups, 12 periods, and 17 school admission cohorts. Using APC analysis with the intrinsic estimator method, the effects of age, period, and school admission cohort on lifetime smoking prevalence were analyzed according to gender.

Results

Overall, there was a similar tendency of all the three effects on lifetime smoking prevalence between genders: an increasing age effect with grade, negative period effect with survey period, and similar pattern of school admission cohort groups. However, compared to boys, girls experienced reduction in the increasing age effect in the 12th grade, consistent and steeper decreasing trend in the period effect from 2006 to 2016, and shorter and lower school admission cohort effect.

Conclusions

Gender differential response to chronological changes in lifetime smoking prevalence was measured by the APC effect, which affected the gender differential secular trend in lifetime smoking prevalence. Therefore, considering the APC effect could help us understand the trend in smoking rates, as well as the contextual factors that affect it.
Management of Juvenile Hallux Valgus Deformity: the role of combined Hemiepiphysiodesis
Authors: Chiang Ming-Hung , Wang Ting-Ming , Kuo Ken N. , Huang Shier-Chieg , Wu Kuan-Wen
Published: October 2019

Background

This study aimed to investigate the efficacy of percutaneous hemiepiphysiodesis for gradual correction of symptomatic juvenile hallux valgus (HV) deformity.

Methods

Between 2012 to 2014, 24 patients with symptomatic juvenile HV were treated by combined percutaneous medial drilling hemiepiphysiodesis of the first proximal phalanx and lateral transphyseal screw hemiepiphysiodesis of the first metatarsal at our institution. Twenty-one of 24 patients fulfilled inclusion criteria had a complete radiological and clinical follow-up of at least 2 years. Preoperative and postoperative radiographs of the feet were reviewed for measurements of hallux valgus angle (HVA), intermetatarsal angle (IMA), proximal metatarsal articular angle (PMAA), proximal phalangeal articular angle (PPAA), and metatarsal length ratio (MTLR). Clinical outcomes were assessed using the AOFAS hallux metatarsophalangeal-interphalangeal score.

Results

The study included 21 consecutive patients (37 ft) for analysis. The mean age at surgery was 12.0 years (SD = 1.3) and mean follow-up after surgery was 35.1 months (SD = 6.0). With the data available, the HV deformity improved in terms of the reduction of HVA by a mean of 4.7 degrees (P < .001) and the reduction of IMA by 2.2 degrees (P < .001). The PMAA and PPAA also improved significantly in the anteroposterior plane; however, the PMAA difference was insignificant in lateral plane as expected. The mean difference in the MTLR was 0.00 (P = .216) which was indicative of no length discrepancy between first and second metatarsals. The AOFAS score increased from 68.7 to 85.2 (P < .001). In correlation analysis, time to physeal closure was significantly correlated with the final HVA change (r = −.611,P = .003).

Conclusion

Although combined hemiepiphysiodesis does not create a large degree of correction as osteotomy, yet it did improve HV deformity with adequate growth remaining in our series. It is a procedure that can be of benefit to patients with symptomatic juvenile HV from this minimal operative approach before skeletal maturity.

Level of evidence

Level IV, retrospective case series.
Surgical treatment strategy for esophagogastric junction cancers based on the tumor diameter
Authors: Hoshino Isamu , Gunji Hisashi , Ishige Fumitaka , Iwatate Yosuke , Takiguchi Nobuhiro , Ikeda Atsushi , Soda Hiroaki , Tonooka Toru , Sato Nami , Kawahara Kenji , Nabeya Yoshihiro
Published: October 2019

Background

The number of patients with esophagogastric junction (EGJ) cancers has tended to increase. However, no clear consensus on the optimum treatment policy has yet been reached.

Methods

This study included patients diagnosed with adenocarcinoma of Sievert type II in whom resection was performed in our hospital. We performed a clinicopathological examination, and patients were divided into two groups by the tumor size: L group, tumor size ≥4 cm; and S group, tumor size < 4 cm. The clinical factors, such as nodal dissection and recurrence pattern, were then analyzed.

Results

A total of 48 patients were diagnosed with ECJ cancers. The average tumor size was 55.1 mm, and 32 cases (66.7%) had tumors ≥4 cm. Metastasis to the mediastinum was noted in 4 cases (12.5%) in the L group but none in the S group. Recurrence in the upper or middle mediastinum lymph nodes was noted in 3 cases (9.4%) in the L group. The 5-year overall survival rates were 49.7 and 83.9% in the L and S groups, respectively.

Conclusions

As the tumor grows large, it is difficult to accurately judge EGJ on the image, and as a result it is difficult to understand the exact esophageal invasion distance of the tumor. Therefore, lymph node dissection including the upper mediastinum is considered vital, regardless of the degree of esophageal invasion.
A survey of caregiver acculturation and acceptance of silver diamine fluoride treatment for childhood caries
Authors: Kumar Anjali , Cernigliaro Dana , Northridge Mary E. , Wu Yinxiang , Troxel Andrea B. , Cunha-Cruz Joana , Balzer Jay , Okuji David M.
Published: October 2019

Background

Interest in aqueous silver diamine fluoride (SDF) has been growing as a treatment for caries arrest. A cross-sectional study was conducted to identify factors associated with caregiver acceptance of SDF treatment for children presenting with caries at 8 Federally Qualified Health Centers. The study purpose was to examine associations between caregiver acceptance of SDF treatment for children with caries and (1) sociodemographic and acculturation characteristics of caregivers and (2) clinical assessments of the children by dentists.

Methods

A caregiver survey collected information on: sociodemographic characteristics; acculturation characteristics, measured using the validated Short Acculturation Scale for Hispanics (SASH); perceived benefits and barriers of SDF treatment, including caregiver comfort; and perceived health-related knowledge. Chart reviews were conducted to assess: the medical / dental insurance of pediatric patients; cumulative caries experience, measured using decayed, missing, filled teeth total scores (dmft / DMFT); whether operating room treatment was needed; and a record of caregiver acceptance of SDF treatment (the outcome measure). Standard logistic regression models were developed for caregiver acceptance of SDF treatment for their children as the binary outcome of interest (yes / no) to calculate unadjusted odds ratios (OR) and adjusted ORs for covariates of interest.

Results

Overall, 434 of 546 caregivers (79.5%) accepted SDF treatment for their children. A U-shaped relationship between caregiver odds of accepting SDF treatment and age group of pediatric patients was present, where caregivers were most likely to accept SDF treatment for their children who were either < 6 years or 9–14 years, and least likely to accept SDF treatment for children 6 to < 9 years. The relationship between acculturation and caregiver acceptance of SDF treatment depended upon whether or not caregivers were born in the United States: greater acculturation was associated with caregiver acceptance of SDF treatment among caregivers born in this country, and lower acculturation was associated with caregiver acceptance of SDF treatment among caregivers born elsewhere.

Conclusions

Caregiver acceptance of SDF treatment is high; child’s age and caregiver comfort are associated with acceptance. Providers need to communicate the risks and benefits of evidence-based dental treatments to increasingly diverse caregiver and patient populations.
A predictive model for non-completion of an intensive specialist obesity service in a public hospital: a case-control study
Authors: Atlantis Evan , Lin Fang , Anandabaskaran Sulak , Fahey Paul , Kormas Nic
Published: October 2019

Background

Despite the growing evidence base supporting intensive lifestyle and medical treatments for severe obesity, patient engagement in specialist obesity services is difficult to achieve and poorly understood. To address this knowledge gap, we aimed to develop a model for predicting non-completion of a specialist multidisciplinary service for clinically severe obesity, termed the Metabolic Rehabilitation Programme (MRP).

Method

Using a case-control study design in a public hospital setting, we extracted data from medical records for all eligible patients with a body mass index (BMI) of ≥35 kg/m2 with either type 2 diabetes or fatty liver disease referred to the MRP from 2010 through 2015. Non-completion status (case definition) was coded for patients whom started but dropped-out of the MRP within 12 months. Using multivariable logistic regression, we tested the following baseline predictors hypothesised in previous research: age, gender, BMI, waist circumference, residential distance from the clinic, blood pressure, obstructive sleep apnoea (OSA), current continuous positive airway pressure (CPAP) therapy, current depression/anxiety, diabetes status, and medications. We used receiver operating characteristics and area under the curve to test the performance of models.

Results

Out of the 219 eligible patient records, 78 (35.6%) non-completion cases were identified. Significant differences between non-completers versus completers were: age (47.1 versus 54.5 years, p < 0.001); residential distance from the clinic (21.8 versus 17.1 km, p = 0.018); obstructive sleep apnoea (OSA) (42.9% versus 56.7%, p = 0.050) and CPAP therapy (11.7% versus 28.4%, p = 0.005). The probability of non-completion could be independently associated with age, residential distance, and either OSA or CPAP. There was no statistically significant difference in performance between the alternate models (69.5% versus 66.4%, p = 0.57).

Conclusions

Non-completion of intensive specialist obesity management services is most common among younger patients, with fewer complex care needs, and those living further away from the clinic. Clinicians should be aware of these potential risk factors for dropping out early when managing outpatients with severe obesity, whereas policy makers might consider strategies for increasing access to specialist obesity management services.
Comparing methods to estimate incremental inpatient costs and length of stay due to methicillin-resistant Staphylococcus aureus in Alberta, Canada
Authors: Kirwin Erin , Varughese Marie , Waldner David , Simmonds Kimberley , Joffe A. Mark , Smith Stephanie
Published: October 2019

Background

Methicillin-resistant Staphylococcus aureus (MRSA) is an opportunistic bacterial organism resistant to first line antibiotics. Acquisition of MRSA is often classified as either healthcare-associated or community-acquired. It has been shown that both healthcare-associated and community-acquired infections contribute to the spread of MRSA within healthcare facilities. The objective of this study was to estimate the incremental inpatient cost and length of stay for individuals colonized or infected with MRSA. Common analytical methods were compared to ensure the quality of the estimate generated. This study was performed at Alberta Ministry of Health (Edmonton, Alberta), with access to clinical MRSA data collected at two Edmonton hospitals, and ministerial administrative data holdings.

Methods

A retrospective cohort study of patients with MRSA was identified using a provincial infection prevention and control database. A coarsened exact matching algorithm, and two regression models (semilogarithmic ordinary least squares model and log linked generalized linear model) were evaluated. A MRSA-free cohort from the same facilities and care units was identified for the matched method; all records were used for the regression models. Records span from January 1, 2011 to December 31, 2015, for individuals 18 or older at discharge.

Results

Of the models evaluated, the generalized linear model was found to perform the best. Based on this model, the incremental inpatient costs associated with hospital-acquired cases were the most costly at $31,686 (14,169 – 60,158) and $47,016 (23,125 – 86,332) for colonization and infection, respectively. Community-acquired MRSA cases also represent a significant burden, with incremental inpatient costs of $7397 (2924 – 13,180) and $14,847 (8445 – 23,207) for colonization and infection, respectively. All costs are adjusted to 2016 Canadian dollars. Incremental length of stay followed a similar pattern, where hospital-acquired infections had the longest incremental stays of 35.2 (16.3–69.5) days and community-acquired colonization had the shortest incremental stays of 3.0 (0.6–6.3) days.

Conclusions

MRSA, and in particular, hospital-acquired MRSA, places a significant but preventable cost burden on the Alberta healthcare system. Estimates of cost and length of stay varied by the method of analysis and source of infection, highlighting the importance of selecting the most appropriate method.
A framework for cross-cultural development and implementation of complex interventions to improve palliative care in nursing homes: the PACE steps to success programme
Authors:   on behalf of PACE, Hockley Jo , Froggatt Katherine , Van den Block Lieve , Onwuteaka-Philipsen Bregje , Kylänen Marika , Szczerbińska Katarzyna , Gambassi Giovanni , Pautex Sophie , Payne Sheila Alison
Published: October 2019

Background

The PACE Steps to Success programme is a complex educational and development intervention to improve palliative care in nursing homes. Little research has investigated processes in the cross-cultural adaptation and implementation of interventions in palliative care across countries, taking account of differences in health and social care systems, legal and regulatory policies, and cultural norms. This paper describes a framework for the cross-cultural development and support necessary to implement such an intervention, taking the PACE Steps to Success programme as an exemplar.

Methods

The PACE Steps to Success programme was implemented as part of the PACE cluster randomised control trial in seven European countries. A three stage approach was used, a) preparation of resources; b) training in the intervention using a train-the-trainers model; and c) cascading support throughout the implementation. All stages were underpinned by cross-cultural adaptation, including recognising legal and cultural norms, sensitivities and languages. This paper draws upon collated evidence from minutes of international meetings, evaluations of training delivered, interviews with those delivering the intervention in nursing homes and providing and/or receiving support.

Results

Seventy eight nursing homes participated in the trial, with half randomized to receive the intervention, 3638 nurses/care assistants were identified at baseline. In each country, 1–3 trainers were selected (total n = 16) to deliver the intervention. A framework was used to guide the cross-cultural adaptation and implementation. Adaptation of three English training resources for different groups of staff consisted of simplification of content, identification of validated implementation tools, a review in 2 nursing homes in each country, and translation into local languages. The same training was provided to all country trainers who cascaded it into intervention nursing homes in local languages, and facilitated it via in-house PACE coordinators. Support was cascaded from country trainers to staff implementing the intervention.

Conclusions

There is little guidance on how to adapt complex interventions developed in one country and language to international contexts. This framework for cross-cultural adaptation and implementation of a complex educational and development intervention may be useful to others seeking to transfer quality improvement initiatives in other contexts.
Three myths about risk thresholds for prediction models
Authors:   on behalf of the Topic Group ‘Evaluating diagnostic tests and prediction models’ of the STRATOS initiative, Wynants Laure , van Smeden Maarten , McLernon David J. , Timmerman Dirk , Steyerberg Ewout W. , Van Calster Ben
Published: October 2019

Background

Clinical prediction models are useful in estimating a patient’s risk of having a certain disease or experiencing an event in the future based on their current characteristics. Defining an appropriate risk threshold to recommend intervention is a key challenge in bringing a risk prediction model to clinical application; such risk thresholds are often defined in an ad hoc way. This is problematic because tacitly assumed costs of false positive and false negative classifications may not be clinically sensible. For example, when choosing the risk threshold that maximizes the proportion of patients correctly classified, false positives and false negatives are assumed equally costly. Furthermore, small to moderate sample sizes may lead to unstable optimal thresholds, which requires a particularly cautious interpretation of results.

Main text

We discuss how three common myths about risk thresholds often lead to inappropriate risk stratification of patients. First, we point out the contexts of counseling and shared decision-making in which a continuous risk estimate is more useful than risk stratification. Second, we argue that threshold selection should reflect the consequences of the decisions made following risk stratification. Third, we emphasize that there is usually no universally optimal threshold but rather that a plausible risk threshold depends on the clinical context. Consequently, we recommend to present results for multiple risk thresholds when developing or validating a prediction model.

Conclusion

Bearing in mind these three considerations can avoid inappropriate allocation (and non-allocation) of interventions. Using discriminating and well-calibrated models will generate better clinical outcomes if context-dependent thresholds are used.
Canine non-B, non-T NK lymphocytes have a potential antibody-dependent cellular cytotoxicity function against antibody-coated tumor cells
Authors: Kim Yoseop , Lee Soo-Hyeon , Kim Cheol-Jung , Lee Je-Jung , Yu Dohyeon , Ahn Soomin , Shin Dong-Jun , Kim Sang-Ki
Published: October 2019

Background

The antibody-dependent cellular cytotoxicity (ADCC) is a cell-mediated immune defense mechanism in which effector immune cells actively lyse antibody-coated target cells. The ADCC of tumor cells is employed in the treatment of various cancers overexpressing unique antigens, and only natural killer (NK) cells are known to be major effectors of antibody mediated ADCC activity. Canine NK cells are still defined as non-B, non-T large granular lymphocytes because of the lack of information regarding the NK cell-restricted specific marker in dogs, and it has never been demonstrated that canine NK cells have ADCC ability against tumor cells. In the present study, we investigated whether canine non-B, non-T NK cells have ADCC ability against target antibody-coated tumor cells, using cetuximab and trastuzumab, the only human antibodies reported binding to canine cancer cells.

Results

Activated canine non-B, non-T NK cells (CD3−CD21−CD5−TCRαβ−TCRγδ−) for 13~17 days ex vivo showed ADCC ability against trastuzumab- or cetuximab-coated target tumor cells expressing various levels of human epidermal growth factor receptor 2 (HER-2) and epidermal growth factor receptor (EGFR). Trastuzumab and cetuximab induced significant ADCC responses of canine NK cells even in CMT-U334 and CF41.Mg cells expressing low levels of HER-2 and/or EGFR, as well as in SKBR3 and DU145 cells overexpressing HER-2 and/or EGFR. The trastuzumab-mediated ADCC activity of NK cells was significantly enhanced by treatment with rcIL-21.

Conclusions

The results of this study suggest that canine non-B, non-T NK lymphocytes have a potential ADCC function and that combinational strategies of monoclonal antibodies with either cytokines, which activate NK cells in vivo, or adoptive transfer of NK cells may be a feasible method for amplifying the efficacy of immunotherapy against malignant cancers even with very low expression of target molecules in dogs.
Toxoplasma gondii oocyst-driven infection in pigs, chickens and humans in northeastern China
Authors: Liu Xiao-Yi , Wang Ze-Dong , El-Ashram Saeed , Liu Quan
Published: October 2019

Background

Toxoplasma gondii, an intracellular apicomplexan protozoan parasite, can infect almost all warm-blooded animals. The aim of the present study was to investigate T. gondii oocyst-driven infection in pigs, chickens and humans in Jilin province, northeastern China.

Results

The serum samples of pigs, chickens and humans were sampled and tested by indirect enzyme-linked immunosorbent assays (ELISAs) using dense granule antigen GRA7, oocyst-specific protein OWP8, and sporozoite-specific protein CCp5A, respectively. Results showed a prevalence of 16.7% by GRA7-ELISA, and 12.2% by OWP8- and CCp5A-ELISA in pigs; 10.4% by GRA7-ELISA, 13.5% by OWP8-ELISA, and 9.4% by CCp5A-ELISA in chickens; and 14.2% by GRA7-ELISA, 3.6% by OWP8-ELISA, and 3.0% by CCp5A-ELISA in humans. No significant differences were observed between T. gondii seroprevalence in pigs and chickens among the three antigens-based ELISAs (P > 0.05). However, there were significant differences between T. gondii seroprevalence rates in humans (P < 0.05). These findings demonstrated a low prevalence of T. gondii oocyst-driven infection in humans, a medium prevalence in pigs, and a high prevalence in chickens.

Conclusions

The present study demonstrated that different oocyst-driven infection rates in different animal species, which would help to design effective strategies to prevent T. gondii transmission. To our knowledge, this is the first study to differentiate T. gondii infective forms in pigs, chickens and humans in China.
The relationship between plasma β-hydroxybutyric acid and conjugated linoleic acid in milk as a biomarker for early diagnosis of ketosis in postpartum Polish Holstein-Friesian cows
Authors: Puppel Kamila , Gołębiewski Marcin , Solarczyk Paweł , Grodkowski Grzegorz , Slósarz Jan , Kunowska-Slósarz Małgorzata , Balcerak Marek , Przysucha Tomasz , Kalińska Aleksandra , Kuczyńska Beata
Published: October 2019

Background

The aim of this study was to investigate the association between plasma β-hydroxybutyric acid (BHBA) and conjugated linoleic acid in postpartum Polish Holstein-Friesian (PHF) cows. The experiment was carried out at an experimental dairy farm, where a herd of approximately 350 cows was kept. Samples were taken at six time points: between days 5–7, 8–14, 15–21, 22–28, 29–35, and 36–42, resulting in 510 samples of both milk and blood. The cows involved in the experiment were divided into two groups – ketotic and healthy – by taking into account general health symptoms, blood serum BHBA, and non-esterified fatty acids (NEFA) concentration at 5–7 days postpartum.

Results

In the first week of lactation, at 5–7 day in milk (DIM), the study showed a 53% lower level of C18:2 cis-9 trans-11 (CLA9) and an 80% lower level of C18:2 trans-10 cis-12 (CLA10) in cows with diagnosed ketosis compared to healthy cows. In the second week of lactation (8–14 DIM), a 34% lower level of CLA9 and a 54% lower level of CLA10 was found in the group of cows with BHBA levels > 1.2 mmol/L. Additionally, Pearson correlation analysis showed significant negative correlation between BHBA x CLA9 and BHBA x CLA10 in the first week of lactation: − 0.732and − 0.821, respectively.

Conclusion

The study shows that that both CLA9 and CLA10 can be used as markers for the early diagnosis of elevated blood levels of BHBA in postpartum Polish Holstein-Friesian cows.
Whole-genome bisulfite sequencing in systemic sclerosis provides novel targets to understand disease pathogenesis
Authors: Lu Tianyuan , Klein Kathleen Oros , Colmegna Inés , Lora Maximilien , Greenwood Celia M. T. , Hudson Marie
Published: October 2019

Background

Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease whose pathogenesis remains incompletely understood. Increasing evidence suggests that both genetic susceptibilities and changes in DNA methylation influence pivotal biological pathways and thereby contribute to the disease. The role of DNA methylation in SSc has not been fully elucidated, because existing investigations of DNA methylation predominantly focused on nucleotide CpGs within restricted genic regions, and were performed on samples containing mixed cell types.

Methods

We performed whole-genome bisulfite sequencing on purified CD4+ T lymphocytes from nine SSc patients and nine controls in a pilot study, and then profiled genome-wide cytosine methylation as well as genetic variations. We adopted robust statistical methods to identify differentially methylated genomic regions (DMRs). We then examined pathway enrichment associated with genes located in these DMRs. We also tested whether changes in CpG methylation were associated with adjacent genetic variation.

Results

We profiled DNA methylation at more than three million CpG dinucleotides genome-wide. We identified 599 DMRs associated with 340 genes, among which 54 genes exhibited further associations with adjacent genetic variation. We also found these genes were associated with pathways and functions that are known to be abnormal in SSc, including Wnt/β-catenin signaling pathway, skin lesion formation and progression, and angiogenesis.

Conclusion

The CD4+ T cell DNA cytosine methylation landscape in SSc involves crucial genes in disease pathogenesis. Some of the methylation patterns are also associated with genetic variation. These findings provide essential foundations for future studies of epigenetic regulation and genome-epigenome interaction in SSc.
Impact of free fatty acids on prognosis in coronary artery disease patients under different glucose metabolism status
Authors: Jin Jing-Lu , Cao Ye-Xuan , Liu Hui-Hui , Zhang Hui-Wen , Guo Yuan-Lin , Wu Na-Qiong , Zhu Cheng-Gang , Xu Rui-Xia , Gao Ying , Sun Jing , Dong Qian , Li Jian-Jun
Published: October 2019

Background

The aim of the present study is to examine the effects of free fatty acids (FFAs) on major cardiovascular events (MACEs) in patients with stable coronary artery disease (CAD) and different glucose metabolism status.

Methods

In this study, we consecutively enrolled 5443 patients from March 2011 to May 2015. Patients were categorized according to both status of glucose metabolism status [diabetes mellitus (DM), pre-diabetes (Pre-DM), normal glycaemia regulation (NGR)] and FFAs levels. All subjects were followed up for the occurrence of the MACEs.

Results

During a median of 6.7 years’ follow-up, 608 MACEs occurred. A twofold higher FFAs level was independently associated with MACEs after adjusting for confounding factors [Hazard Ratio (HR): 1.242, 95% confidence interval (CI) 1.084–1.424,pvalue = 0.002]. Adding FFAs to the Cox model increased the C-statistic by 0.015 (0.005–0.027). No significant difference in MACEs was observed between NGR and Pre-DM groups (p > 0.05). When patients were categorized by both status of glucose metabolism and FFAs levels, medium and high FFAs were associated with significantly higher risk of MACEs in Pre-DM [1.736 (1.018–2.959) and 1.779 (1.012–3.126), all p-value < 0.05] and DM [2.017 (1.164–3.494) and 2.795 (1.619–4.824), all p-value < 0.05].

Conclusions

The present data indicated that baseline FFAs levels were associated with the prognosis in DM and Pre-DM patients with CAD, suggesting that FFAs may be a valuable predictor in patients with impaired glucose metabolism.