bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimizing microbiome sequencing for small intestinal aspirates: validation of novel techniques through the REIMAGINE study
Authors: Leite Gabriela Guimaraes Sousa , Morales Walter , Weitsman Stacy , Celly Shreya , Parodi Gonzalo , Mathur Ruchi , Sedighi Rashin , Barlow Gillian M. , Rezaie Ali , Pimentel Mark
Published: November 2019

Background

The human small intestine plays a central role in the processes of digestion and nutrient absorption. However, characterizations of the human gut microbiome have largely relied on stool samples, and the associated methodologies are ill-suited for the viscosity and low microbial biomass of small intestine samples. As part of the REIMAGINE study to examine the specific roles of the small bowel microbiome in human health and disease, this study aimed to develop and validate methodologies to optimize microbial analysis of the small intestine.

Results

Subjects undergoing esophagogastroduodenoscopy without colon preparation for standard of care were prospectively recruited, and ~ 2 ml samples of luminal fluid were obtained from the duodenum using a custom sterile aspiration catheter. Samples of duodenal aspirates were either untreated (DA-U,N = 127) or pretreated with dithiothreitol (DA-DTT,N = 101), then cultured on MacConkey agar for quantitation of aerobic gram-negative bacteria, typically from the class Gammaproteobacteria, and on blood agar for quantitation of anaerobic microorganisms. DA-DTT exhibited 2.86-fold greater anaerobic bacterial counts compared to DA-U (P = 0.0101), but were not statistically different on MacConkey agar.

DNA isolation from DA-U (N = 112) and DA-DTT (N = 43) samples and library preparation for 16S rRNA gene sequencing were also performed using modified protocols. DA-DTT samples exhibited 3.81-fold higher DNA concentrations (P = 0.0014) and 4.18-fold higher 16S library concentrations (P < 0.0001) then DA-U samples. 16S rRNA gene sequencing revealed increases in the detected relative abundances of obligate and facultative anaerobes in DA-DTT samples, including increases in the generaClostridium(false discovery rate (FDR)P = 4.38E-6),Enterococcus(FDRP = 2.57E-8),Fusobacterium(FDRP = 0.02) andBacteroides(FDRP = 5.43E-9). Detected levels of Gram-negative enteropathogens from the phylumProteobacteria, such asKlebsiella(FDRP = 2.73E-6) andProvidencia(FDRP < 0.0001) (familyEnterobacteriaceae) andPseudomonas (familyPseudomonadaceae) (FDRP = 0.04), were also increased in DA-DTT samples.

Conclusions

This study validates novel DTT-based methodology which optimizes microbial culture and 16S rRNA gene sequencing for the study of the small bowel microbiome. The microbial analyses indicate increased isolation of facultative and obligate anaerobes from the mucus layer using these novel techniques.
A phase Ib study of capecitabine and ziv-aflibercept followed by a phase II single-arm expansion cohort in chemotherapy refractory metastatic colorectal cancer
Authors: Strickler John H. , Rushing Christel N. , Niedzwiecki Donna , McLeod Abigail , Altomare Ivy , Uronis Hope E. , Hsu S. David , Zafar S. Yousuf , Morse Michael A. , Chang David Z. , Wells James L. , Blackwell Kimberly L. , Marcom P. Kelly , Arrowood Christy , Bolch Emily , Haley Sherri , Rangwala Fatima A. , Hatch Ace J. , Nixon Andrew B. , Hurwitz Herbert I.
Published: November 2019

Background

Patients with chemotherapy refractory metastatic colorectal cancer (CRC) have a poor prognosis and limited therapeutic options. In this phase Ib/II clinical trial, we established the maximum tolerated dose (MTD) and recommended phase II dose (RPTD) for the combination of capecitabine and ziv-aflibercept, and then we evaluated the efficacy of the combination in patients with chemotherapy refractory metastatic CRC.

Methods

All patients were required to have a Karnofsky Performance Status > 70% and adequate organ function. The phase Ib dose escalation cohort included patients with advanced solid tumors who had progressed on all standard therapies. Using a standard 3 + 3 design, we identified the MTD and RPTD for the combination. Fifty patients with metastatic CRC who had progressed on or were intolerant of a fluoropyrimidine, oxaliplatin, irinotecan, and bevacizumab were then enrolled in a single-arm phase II expansion cohort, and were treated at the RPTD. Prior EGFR antibody therapy was required for subjects with RAS wildtype tumors. The primary endpoint for the expansion cohort was progression-free survival (PFS) at two months. Secondary endpoints included objective response rate (ORR) and overall survival (OS).

Results

A total of 63 patients were enrolled and evaluable for toxicity (13 dose escalation; 50 expansion). The MTD and RPTD were: capecitabine 850 mg/m2, P.O. bid, days 1–14, and ziv-aflibercept 6 mg/kg I.V., day 1, of each 21-day cycle. In the expansion cohort, 72% of patients were progression-free at two months (95% confidence interval [CI], 60–84%). Median PFS and OS were 3.9 months (95% CI, 2.3–4.5) and 7.1 months (95% CI: 5.8–10.0), respectively. Among all patients evaluable for toxicity, the most common treatment related adverse events (all grade [%]; grade ≥ 3 [%]) included palmar-plantar erythrodysesthesia (41%; 6%), hypertension (33%; 22%), and mucositis (19%; 5%). RNA was isolated from archived tumor specimens and gene expression analyses revealed no association between angiogenic biomarkers and clinical outcomes.

Conclusion

The combination of capecitabine and ziv-aflibercept at the RPTD demonstrated acceptable safety and tolerability. PFS at 2 months in patients with chemotherapy refractory metastatic CRC was significantly greater than that in historical controls, indicating that this combination warrants further study.

Trial registration

This clinical trial was registered in the www.clinicaltrials.gov system as NCT01661972 on July 31, 2012.
Dietary-phytochemical mediated reversion of cancer-specific splicing inhibits Warburg effect in head and neck cancer
Authors: Yadav Sandhya , Bhagat Somnath D. , Gupta Amit , Samaiya Atul , Srivastava Aasheesh , Shukla Sanjeev
Published: November 2019

Background

The deregulated alternative splicing of key glycolytic enzyme, Pyruvate Kinase muscle isoenzyme (PKM) is implicated in metabolic adaptation of cancer cells. The splicing switch from normal PKM1 to cancer-specific PKM2 isoform allows the cancer cells to meet their energy and biosynthetic demands, thereby facilitating the cancer cells growth. We have investigated the largely unexplored epigenetic mechanism of PKM splicing switch in head and neck cancer (HNC) cells. Considering the reversible nature of epigenetic marks, we have also examined the utility of dietary-phytochemical in reverting the splicing switch from PKM2 to PKM1 isoform and thereby inhibition of HNC tumorigenesis.

Methods

We present HNC-patients samples, showing the splicing-switch from PKM1-isoform to PKM2-isoform analyzed via immunoblotting and qRT-PCR. We performed methylated-DNA-immunoprecipitation to examine the DNA methylation level and chromatin-immunoprecipitation to assess the BORIS (Brother of Regulator of Imprinted Sites) recruitment and polII enrichment. The effect of dietary-phytochemical on the activity of denovo-DNA-methyltransferase-3b (DNMT3B) was detected by DNA-methyltransferase-activity assay. We also analyzed the Warburg effect and growth inhibition using lactate, glucose uptake assay, invasion assay, cell proliferation, and apoptosis assay. The global change in transcriptome upon dietary-phytochemical treatment was assayed using Human Transcriptome Array 2.0 (HTA2.0).

Results

Here, we report the role of DNA-methylation mediated recruitment of the BORIS at exon-10 of PKM-gene regulating the alternative-splicing to generate the PKM2-splice-isoform in HNC. Notably, the reversal of Warburg effect was achieved by employing a dietary-phytochemical, which inhibits the DNMT3B, resulting in the reduced DNA-methylation at exon-10 and hence, PKM-splicing switch from cancer-specific PKM2 to normal PKM1. Global-transcriptome-analysis of dietary-phytochemical-treated cells revealed its effect on alternative splicing of various genes involved in HNC.

Conclusion

This study identifies the epigenetic mechanism of PKM-splicing switch in HNC and reports the role of dietary-phytochemical in reverting the splicing switch from cancer-specific PKM2 to normal PKM1-isoform and hence the reduced Warburg effect and growth inhibition of HNC. We envisage that this approach can provide an effective way to modulate cancer-specific-splicing and thereby aid in the treatment of HNC.
Tumor budding outperforms ypT and ypN classification in predicting outcome of rectal cancer after neoadjuvant chemoradiotherapy
Authors: Trotsyuk Iryna , Sparschuh Halina , Müller Alice Josephine , Neumann Konrad , Kruschewski Martin , Horst David , Elezkurtaj Sefer
Published: November 2019

Background

Budding is a complementary prognostic factor for colorectal cancer. In this study, we aimed to clarify the role of tumor budding in rectal cancer patients after preoperative chemoradiotherapy.

Methods

A total of 124 patients with rectal cancer treated with neoadjuvant chemoradiotherapy and consecutive surgery were included. Surgical specimens were evaluated for budding and routine clinicopathological features. Budding was evaluated on hematoxylin and eosin (H&E)-stained slides and by cytokeratin immunohistochemical (IHC) staining.

Results

A budding rate of 36.9% (n = 38) by H&E and 55.6% (n = 55) by IHC was observed. Budding was significantly associated with a high ypT and ypN status, poor differentiation, and low degrees of tumor regression. Moreover, budding was strongly predictive of a worse patient outcome, as measured by tumor recurrence or death. In multivariate analyses, budding remained the only significant parameter for overall survival and was even superior to the ypT and ypN status (budding in H&E: hazard ratio (HR) 2.72, 95% confidence interval (95% CI) 1.15–6.44,p = 0.023; budding in IHC: HR 5.19, 95% CI 1.62–16.61,p = 0.006).

Conclusion

Budding is a strong prognostic predictor of survival in rectal cancer patients after neoadjuvant therapy. A standardized evaluation of tumor budding after neoadjuvant therapy may thus aid in risk stratification and guide the clinical management of patients with rectal cancer. Immunostaining can help to enhance the diagnostic accuracy and prognostic significance.
Ex vivo tissue slice culture system to measure drug-response rates of hepatic metastatic colorectal cancer
Authors: Martin Steve Z. , Wagner Daniel C. , Hörner Nina , Horst David , Lang Hauke , Tagscherer Katrin E. , Roth Wilfried
Published: November 2019

Background

The lack of predictive biomarkers or test systems contributes to high failure rates of systemic therapy in metastasized colorectal carcinoma, accounting for a still unfavorable prognosis. Here, we present an ex vivo functional assay to measure drug-response based on a tissue slice culture approach.

Methods

Tumor tissue slices of hepatic metastases of nine patients suffering from colorectal carcinoma were cultivated for 72 h and treated with different concentrations of the clinically relevant drugs Oxaliplatin, Cetuximab and Pembrolizumab. Easy to use, objective and automated analysis routines based on the Halo platform were developed to measure changes in proliferative activity and the morphometric make-up of the tumor. Apoptotic indices were assessed semiquantitatively.

Results

Untreated tumor tissue slices showed high morphological comparability with the original “in vivo”-tumor, preserving proliferation and stromal-tumor interactions. All but one patients showed a dosage dependent susceptibility to treatment with Oxaliplatin, whereas only two patients showed responses to Cetuximab and Pembrolizumab, respectively. Furthermore, we identified possible non-responders to Cetuximab therapy in absence of RAS-mutations.

Conclusions

This is the first time to demonstrate feasibility of the tissue slice culture approach for metastatic tissue of colorectal carcinoma. An automated readout of proliferation and tumor-morphometry allows for quantification of drug susceptibility. This strongly indicates a potential value of this technique as a patient-specific test-system of targeted therapy in metastatic colorectal cancer. Co-clinical trials are needed to customize for clinical application and to define adequate read-out cut-off values.
Associations of sociodemographic and clinical factors with perinatal depression among Israeli women: a cross-sectional study
Authors: Adler Limor , Tsamir Judith , Katz Rachel , Koren Gideon , Yehoshua Ilan
Published: November 2019

Background

Perinatal depression is a common problem that affects about 18% of women worldwide, though the heterogeneity between countries is great. The aims of this study were to assess the prevalence of perinatal depressive symptoms in a national sample of women in Israel, and to investigate associations of these symptoms with demographic, medical and lifestyle factors.

Methods

The study included all members of Maccabi Health Services, the second largest health maintenance organization in Israel, who filled the Edinburgh Postnatal Depression Scale (EPDS) during 2015–2016. Crude odds ratios (ORs) and adjusted ORs (aORs) are presented for associations of sociodemographic, medical and lifestyle factors with perinatal depressive symptoms, according to a score ≥ 10 on the EPDS.

Results

Of 27,520 women who filled the EPDS, 1346 (4.9%) met the criteria for perinatal depression. In a logistic regression analysis we found the following factors associated with perinatal depression: the use of antidepressant medications (aOR = 2.34, 95% CI 1.94–2.82, P < 0.001 and aOR = 3.44; 95% CI 2.99–3.97, P < 0.001 for ≤3 months and > 3 months respectively), a diagnosis of chronic diabetes mellitus (aOR = 2.04; 95% CI 1.22–3.43, P = 0.007), Arab background (aOR = 2.28; 95% CI 1.82–2.86, P < 0.001), current and past smoking (aOR = 1.62; 95% CI 1.35–1.94, P < 0.001 and aOR = 1.36; 95% CI 1.05–1.76, P = 0.021, respectively), and anaemia (aOR = 1.17; 95% CI 1.04–1.32, P = 0.011). Orthodox Jewish affiliation and residence in the periphery of the country were associated with lower perinatal depression (aOR = 0.48; 95% CI 0.36–0.63, P < 0.001 and aOR = 0.72; 95% CI 0.57–0.92, P = 0.007, respectively).

Conclusions

The prevalence of perinatal depression in this study was 4.9%. Perinatal depression was associated with a number of demographic, medical and lifestyle factors, including the use of antidepressant medication, chronic diabetes mellitus, Arab background, current or past smoking, and anaemia. These risk factors may help identify women at risk of perinatal depression.
Sense it and use it: interoceptive accuracy and sensibility in suicide ideators
Authors: Forkmann Thomas , Volz-Sidiropoulou Eftychia , Helbing Trientje , Drüke Barbara , Mainz Verena , Rath Dajana , Gauggel Siegfried , Teismann Tobias
Published: November 2019

Background

Interoceptive deficits have been found to be associated with suicidal ideation and behavior. However, an objective measure of interoceptive accuracy has not been investigated in participants with suicide ideation, by now. This study aimed at investigating interoceptive accuracy and sensibility in persons with and without suicide ideation (SI) while controlling for severity of depressive symptoms.

Method

Ninety-five participants (age: M = 34.8, SD = 11.6, n = 56 female [58.9%]; n = 51 patients with a Major Depressive Disorder and n = 44 healthy participants) were assessed for interoceptive accuracy and sensibility, depression and SI.

Results

Twenty-five participants (26%) reported SI. They showed interoceptive accuracy comparable to persons without SI (t = −.81, p = .422), but significantly lower interoceptive sensibility. After controlling for severity of depressive symptoms in a hierarchical linear regression analysis, most associations between interoceptive sensibility and SI disappeared.

Conclusion

Results suggest that suicide ideators do not lack the ability to perceive their own bodily signals but they feel less able to use them in a way that is advantageous for them. Differences between suicide ideators and non-ideators appear to be largely driven by depressive symptoms (depression bias).
Trajectories of clinical and parenting outcomes following admission to an inpatient mother-baby unit
Authors: Reilly Nicole , Brake Elloise , Briggs Nancy , Austin Marie-Paule
Published: November 2019

Background

This study aimed to examine trajectories of clinical and parenting outcomes following admission to a mother-baby unit (MBU), and to explore factors associated with these trajectories.

Methods

Women admitted to an MBU completed the Edinburgh Postnatal Depression Scale (EPDS), Depression, Anxiety and Stress Scale (DASS-21), Karitane Parenting Confidence Scale (KPCS) and Maternal Postnatal Attachment Scale (MPAS) at admission, discharge and 3 months following discharge. Questions assessing psychosocial risk and adult attachment style were also completed at admission, and information relating to service engagement in the time since discharge was collected at follow-up. Additional clinical and demographic information was extracted from the patient medical record.

Results

Seventy-five women participated in the study. Overall, significant improvements in mean scores on measures of anxiety and parenting confidence were maintained 3-months following discharge. However, the majority of women (93.3%) followed trajectories that were characterised by deterioration in self-reported mother-infant attachment following discharge. 62.9 and 34.6% of women followed trajectories of increased symptoms of depression and stress between discharge and follow-up, respectively. Across measures, the least optimal trajectories, or least optimal scores, at follow-up were associated with less secure maternal attachment style (associated with more anxiety symptoms, poorer parenting confidence and maternal-infant attachment), older maternal age (more depressive symptoms) and increased psychosocial risk (more anxiety symptoms).

Conclusions

The findings of this study highlight the clinical implications of anxious attachment style for the mental health and parenting outcomes of women admitted to an MBU and the importance of incorporating mother-infant therapy as part of an ongoing management plan. Comprehensive discharge planning and transitional care to help ensure women discharged from an MBU are best supported in the longer term is recommended.
Prevalence and correlates of depressive symptoms among adults living with HIV in rural Kilifi, Kenya
Authors: Nyongesa Moses K. , Mwangi Paul , Wanjala Stanley W. , Mutua Agnes M. , Newton Charles R. J. C. , Abubakar Amina
Published: November 2019

Background

Published research on depression among people living with HIV/AIDS (PLWHA) from Africa is increasing, but data from Kenya remains scarce. This cross-sectional study measured the prevalence and correlates of depressive symptoms among PLWHA in rural Kilifi, on the Kenyan coast.

Methods

Between February and April 2018, we consecutively recruited and interviewed 450 adults living with HIV and on combination antiretroviral therapy (cART). Depressive symptoms were assessed with the 9-item Patient Health Questionnaire (PHQ-9), with a positive depression screen defined as PHQ-9 score ≥ 10. Measures of psychosocial, health, and treatment characteristics were also administered.

Results

The overall prevalence of depressive symptoms was 13.8% (95% Confidence Interval (95%CI): 10.9, 17.3). Multivariable logistic regression analysis identified current comorbid chronic illness (adjusted Odds Ratio (aOR) 5.72, 95% CI: 2.28, 14.34; p < 0.001), cART regimen (aOR 6.93, 95%CI: 2.34, 20.49; p < 0.001), perceived HIV-related stigma (aOR 1.10, 95%CI: 1.05, 1.14, p < 0.001) and difficulties accessing HIV care and treatment services (aOR 2.37, 95%CI: 1.14, 4.91; p = 0.02) as correlates of depressive symptoms.

Conclusion

The prevalence of depressive symptoms among adults living with HIV on the Kenyan coast is high. Those at high risk for elevated depressive symptoms (e.g., with comorbid chronic illnesses, on second-line cART, experiencing perceived HIV-stigma or with problems accessing HIV care) may benefit from early identification, treatment or referral, which requires integration of mental health programmes into HIV primary care.
Ecological niche modelling to estimate the distribution of Culicoides, potential vectors of bluetongue virus in Senegal
Authors: Ciss Mamadou , Biteye Biram , Fall Assane Gueye , Fall Moussa , Gahn Marie Cicille Ba , Leroux Louise , Apolloni Andrea
Published: November 2019

Background

Vector-borne diseases are among the leading causes of morbidity and mortality in humans and animals. In the Afrotropical region, some are transmitted by Culicoides, such as Akabane, bluetongue, epizootic haemorrhagic fever and African horse sickness viruses. Bluetongue virus infection has an enormous impact on ruminant production, due to its high morbidity and mortality rates.

Methods

A nationwide Culicoides trapping campaign was organized at the end of the 2012 rainy season in Senegal. A Maximum Entropy approach (MaxEnt), Boosted Regression Tree (BRT) method and Ecological Niche Factor Analysis (ENFA) were used to develop a predictive spatial model for the distribution of Culicoides, using bio-climatic variables, livestock densities and altitude.

Results

The altitude, maximum temperature of the warmest month, precipitation of the warmest quarter, mean temperature of the wettest quarter, temperature seasonality, precipitation of the wettest quarter and livestock density were among the most important factors to predict suitable habitats of Culicoides. Culicoides occurrences were, in most of the cases, positively correlated to precipitation variables and livestock densities; and negatively correlated to the altitude and temperature indices. The Niayes area and the Groundnut basin were the most suitable habitats predicted.

Conclusion

We present ecological niche models for different Culicoides species, namely C. imicola, C. oxystoma, C. enderleini and C. miombo, potential vectors of bluetongue virus, on a nationwide scale in Senegal. Through our modelling approach, we were able to determine the effect of bioclimatic variables on Culicoides habitats and were able to generate maps for the occurrence of Culicoides species. This information will be helpful in developing risk maps for disease outbreaks.
Effectiveness and cost-effectiveness of a multicomponent intervention to implement a clinical practice guideline for systemic lupus erythematosus: protocol for a cluster-randomized controlled trial
Authors:   SLE-CPG-Implementation Group, Trujillo-Martín María M. , Ramallo-Fariña Yolanda , del Pino-Sedeño Tasmania , Rúa-Figueroa Íñigo , Trujillo-Martín Elisa , Vallejo-Torres Laura , Imaz-Iglesia Iñaki , Sánchez-de-Madariaga Ricardo , de Pascual-Medina Ana M. , Serrano-Aguilar Pedro
Published: November 2019

Background

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with significant potential morbidity and mortality. Substantial gaps have been documented between the development and dissemination of clinical practice guidelines (CPG) and their implementation in practice. The aim of this study is to assess the effectiveness and cost-effectiveness of a multi-component knowledge transfer intervention to implement a CPG for the management of SLE (CPG-SLE).

Methods

The study is an open, multicentre, controlled trial with random allocation by clusters to intervention or control. Clusters are four public university hospitals of the Canary Islands Health Service where rheumatologists are invited to participate. Patients diagnosed with SLE at least one year prior to recruitment are selected. Rheumatologists in intervention group receive a short educational group programme to both update their knowledge about SLE management according to CPG-SLE recommendations and to acquire knowledge and training on use of the patient-centred approach, a decision support tool embedded in the electronic clinical record and a quarterly feedback report containing information on management of SLE patients. Primary endpoint is change in self-perceived disease activity. Secondary endpoints are adherence of professionals to CPG-SLE recommendations, health-related quality of life, patient perception of their participation in decision making, attitudes of professionals towards shared decision making, knowledge of professionals about SLE and use of healthcare resources. Calculated sample size is 412 patients. Data will be collected from questionnaires and clinical records. Length of follow-up will be 18 months. Multilevel mixed models with repeated time measurements will be used to analyze changes in outcomes over time. Cost-effectiveness, from both social and healthcare services perspectives, will be analyzed by measuring effectiveness in terms of quality-adjusted life years gained. Deterministic and probabilistic sensitivity analyses are planned.

Discussion

Impact of CPGs in clinical practice could be improved by applying proven value interventions to implement them. The results of this ongoing trial are expected to generate important scientifically valid and reproducible information not only on clinical effectiveness but also on cost-effectiveness of a multi-component intervention for implementation of a CPG based on communication technologies for chronic patients in the hospital setting.

Trial registration

ClinicalTrial.gov NCT03537638. Registered on 25 May 2018.
Can income-based co-payment rates improve disparity? The case of the choice between brand-name and generic drugs
Authors: Ito Yuki , Hara Konan , Yoo Byung-Kwang , Tomio Jun , Kobayashi Yasuki
Published: November 2019

Background

Higher income population tend to prefer brand-name to generic drugs, which may cause disparity in access to brand-name drugs among income groups. A potential policy that can resolve such disparity is imposing a greater co-payment rate on high-income enrollees. However, the effects of such policy are unknown. We examined how patients’ choice between brand-name and generic drugs are affected by the unique income-based co-payment rates in Japan; 10% for general enrollees and 30% for those with high income among the elderly aged 75 and over.

Methods

We drew on cross-sectional price variation among commonly prescribed 311 drugs using health insurance claims data from a large prefecture in Japan between October 2013 and September 2014 to identify between-income-group differences in responses to differentiated payments.

Results

Running 311 multivariate logistic regression models controlling individual demographics, the median estimate indicated that high-income group was 3% (odds ratio = 0.97) less likely to choose a generic drug than the general-income group and the interquartile estimates ranged 0.92–1.02. The multivariate feasible generalized least squares model indicated high-income group’s higher likelihood to choose brand-name drugs than the general-income group without co-payment rate differentiation (p < 0.001). Such gap in the likelihood was attenuated by 0.4% (p = 0.027) with an US$1 increase in the difference in additional payment/month for brand-name drugs between income groups — no gap with US$10 additional payment/month. This attenuation was observed in drugs for chronic diseases only, not for acute diseases.

Conclusions

Income-based co-payment rates appeared to reduce disparity in access to brand-name drugs across income groups, in addition to reducing total medical expenditure among high-income group who shifted from brand-name drugs to generic ones due to larger drug price differences.
The acceptance and applicability of a patient-reported experience measurement tool in oncological care: a descriptive feasibility study in northern Germany
Authors: Rudolph Christiane , Petersen Gitte Stentebjerg , Pritzkuleit Ron , Storm Hans , Katalinic Alexander
Published: November 2019

Background

Patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs) are tools for assessing outcomes of and experiences with health care from the patient’s perspective. In Germany, PROMs are widely used in research for evaluating patient outcomes and quality of care. However, the application of PREMs is rather scant, especially in oncology. The study aimed to assess the feasibility of patient-centred quality evaluation in oncological care in Germany using the German adaptation of the Danish National Cancer Patient Questionnaire. This questionnaire is a PREM/PROM-tool addressing patients of all cancer sites and covering the entire cancer patient pathway.

Methods

The Danish National Cancer Patient Questionnaire was translated into German via forward-backward translation. Face-validity was tested among three cancer patients in a conventional pre-test. The German adaptation contains 99 questions. A pilot test was carried out among 245 newly diagnosed breast and colorectal cancer patients in the German federal state Schleswig-Holstein. Patients were recruited via clinics participating in the Oncological Care Registry (12 specialised units in seven hospitals) and contacted six to nine months after diagnosis. Response behaviour and response patterns were compared to the Danish study population (n = 1964).

Results

The willingness among clinicians to support patient recruitment as well as the response rate of patients to the questionnaire was high (65%). Moreover, response behaviour and response patterns of German and Danish patients were consistent. Despite the generally good response behaviour of patients to the single items, the authors observed that questions assessing the diagnostic process did not fully capture German pathways. Only 19.3% of the German patients stated that their diagnostic process was initiated by a visit to a general practitioner (GP) in contrast to 52% in Denmark. The assessment of patient experiences in the diagnostic phase heavily focuses on experiences in general practice, which does not seem appropriate in the German health care setting.

Conclusion

The translation was successful, and the feasibility of a future large-scale study within existing structures is given. However, some modifications of questions heavily related to the Danish health care system, especially referring to the diagnostic phase, are necessary.
Effects of a comprehensive reservation service for non-emergency registration on appointment registration rate, patient waiting time, patient satisfaction and outpatient volume in a tertiary hospital in China
Authors: Xie Wanhua , Yang Xiufeng , Cao Xiaojun , Liu Peiying
Published: November 2019

Background

In China, a long waiting time for registration is a common occurrence in many tertiary hospitals. This study aimed to analyze the effects of a comprehensive reservation service for non-emergency registration on appointment registration rate, patient waiting time, patient satisfaction and outpatient volume at the Guangzhou Women and Children’s Medical Center.

Methods

This was a cross-sectional study. This study investigated the effects of a comprehensive reservation service for non-emergency registration in Guangzhou Women and Children’s Medical Center in China starting in October 2015. In total, 2194 patients completed a satisfaction survey administered by the Guangdong Situation Research Center. The content of the questionnaire consisted of six aspects: general impression, service attitude, service quality, hospital environment, price perception and medical ethics. A Likert 5-point rating scale was used in the questionnaire; answers were classified as “very satisfied”, “relatively satisfied”, “neutral”, “unsatisfied” and “very unsatisfied”. The method of application was paper-based. T-tests were used to compare the sample means, and chi-square tests were used to compare the rates. A multiple-test procedure was performed to evaluate the differences in the reservation rates during a 12-month period.

Results

After the implementation of the comprehensive reservation service for non-emergency registration in our hospital, which has an annual outpatient volume of approximately 4 million, the monthly appointment registration rate increased from (34.95 ± 2.91)% to(89.13 ± 3.12)%,P < 0.01. The patient waiting time was significantly reduced (P < 0.01), and the proportion of patients who believed that the waiting time required improvement was decreased significantly (P < 0.01). Moreover, the third-party evaluation result of outpatient satisfaction significantly improved (P < 0.01). The total hospital outpatient volume decreased(P < 0.01). The outpatient volume of the Department of General Pediatrics decreased.

Conclusion

The implementation of the comprehensive reservation service for non-emergency registration in the hospital shortened patient waiting time and improved patient satisfaction, and the outpatient volume was effectively controlled. These results indicated that this program obtained the desired results in a Grade 3A hospital in China.
The immune response of young turkeys to haemorrhagic enteritis virus infection at different levels and sources of methionine in the diet
Authors: Tykałowski Bartłomiej , Śmiałek Marcin , Koncicki Andrzej , Ognik Katarzyna , Zduńczyk Zenon , Jankowski Jan
Published: November 2019

Background

Haemorrhagic enteritis (HE) of turkeys was first described in 1937 in the USA, while in Poland it was first diagnosed in 1987. Polish haemorrhagic enteritis virus (HEV) isolates are usually low pathogenic and trigger a subclinical disease. Unfortunately, even the low- pathogenic HEV strains cause severe immunosuppression leading to secondary bacterial infections and huge economic losses. The objective of this study was to evaluate if the influence of Met on HEV infected turkeys immune response can be differentiated by both its level and source. Met is one of the amino acids that not only play a nutritional role but also participate in and regulate key metabolic pathways and immune response. In our study, the birds were assigned to 4 dietary treatments which differed in Met levels (0.55 and 0.78% in weeks 1–4 of age and 0.45 and 0.65% in weeks 5–8 of age, respectively) and sources (DL-methionine (DLM) or DL-methionine hydroxy analogue (MHA)).

Results

The HEV added the percentage of CD4+ cells and decreased the percentage of IgM+ cells in the blood, spleen and caecal tonsils (CTs) of turkeys. In addition, it increased the percentage of CD4+CD25+ cells in blood, and interleukin-6 (IL-6) level in plasma. The higher dose of Met led to a significant decrease in the percentages of CD4+, CD8+ and CD4+IL-6+ cell subpopulations in the blood of HEV-infected and uninfected turkeys and to an increase in the percentage of IgM+ B cells in CTs. Turkeys administered feeds with an increased Met content displayed a decrease in plasma IL-6 levels and an increase in plasma IgA levels.

Conclusions

The results of this study indicate that HEV infection impairs the immune function in turkeys. Met content in the feed has a moderate effect on the immune response in HEV-infected turkeys. The source of this amino acid appears not be as important as its dose, because value of the analysed parameters did not differ significantly between turkeys receiving feeds with DLM or MHA. In the uninfected turkeys, the higher by 40% (than recommended by NRC) level of Met in the feeds had a positive effect on humoral immunity parameters.
Over-expression of Nav1.6 channels is associated with lymph node metastases in colorectal cancer
Authors: Lin Shuiquan , Lv Yangbo , Xu Jianguang , Mao Xinglong , Chen Zhenhong , Lu Wuguang
Published: November 2019

Background and objectives

Lymph node metastasis is a key factor in predicting and determining the prognosis of patients with colorectal cancer (CRC). Sodium channels are highly expressed in a variety of tumors and are closely related to tumor development, metastasis, and invasion. We investigated the relationship between the expressions of different subtypes of Nav channels and lymph node metastasis of CRC.

Methods

Real-time PCR (RT-qPCR) was carried out to measure the expressions of different sodium channel subtypes, chemokine receptors (CCR2, CCR4, CCR7), and lymphocyte infiltration-related biomarkers (CD3e, CD8a, IL-2RA) in CRC tissues from 97 patients. The expressions of Nav1.5 and Nav1.6 in surgically isolated lymph nodes were detected by immunohistochemistry. Correlation analysis between expressions of different genes and lymph node metastasis was performed by two-tailed t test.

Results

Nav1.1 and Nav1.6 were highly expressed in CRC tissues and positively correlated with CRC lymph node metastasis. Nav1.6 was also highly expressed in metastatic lymph nodes. Further analysis showed that the high expression of Nav1.6 was closely related to the one of CCR2\CCR4 in tumor lymph node metastasis.

Conclusions

These results suggested that Nav1.6 might be a novel marker for CRC lymph node metastasis.
Remote estimation of rice LAI based on Fourier spectrum texture from UAV image
Authors: Duan Bo , Liu Yating , Gong Yan , Peng Yi , Wu Xianting , Zhu Renshan , Fang Shenghui
Published: November 2019

Background

The accurate estimation of rice LAI is particularly important to monitor rice growth status. Remote sensing, as a non-destructive measurement technology, has been proved to be useful for estimating vegetation growth parameters, especially at large scale. With the development of unmanned aerial vehicles (UAVs), this novel remote sensing platform has been widely used to provide remote sensing images which have much higher spatial resolution. Previous reports have shown that the spectral feature of remote sensing images could be an effective indicator to estimate vegetation growth parameters. However, the texture feature of high-resolution remote sensing images is rarely employed for this purpose. Besides, the physical mechanism between the texture feature and vegetation growth parameters is still unclear.

Results

In this study, a Fourier spectrum texture based on the UAV Image was developed to estimate rice LAI. And the relationship between Fourier spectrum texture and rice LAI was also analyzed. The results showed that Fourier spectrum texture could improve the accuracy of rice LAI estimation.

Conclusions

In conclusion, the texture feature of high-resolution remote sensing images may be more effective in rice LAI estimation than the spectral feature.
Dispatcher-assisted cardiopulmonary resuscitation for traumatic patients with out-of-hospital cardiac arrest
Authors: Lu Chien-Hsin , Fang Pin-Hui , Lin Chih-Hao
Published: November 2019

Background

Resuscitation efforts for traumatic patients with out-of-hospital cardiac arrest (OHCA) are not always futile. Dispatcher-assisted cardiopulmonary resuscitation (DA-CPR) during emergency calls could increase the rate of bystander cardiopulmonary resuscitation (CPR) and thus may enhance survival and neurologic outcomes of non-traumatic OHCA. This study aimed to examine the effectiveness of DA-CPR for traumatic OHCA.

Methods

A retrospective cohort study was conducted using an Utstein-style population database with data from January 1, 2014, to December 31, 2016, in Tainan City, Taiwan. Voice recordings of emergency calls were retrospectively retrieved and reviewed. The primary outcome was an achievement of sustained (≥2 h) return of spontaneous circulation (ROSC); the secondary outcomes were prehospital ROSC, ever ROSC, survival at discharge and favourable neurologic status at discharge. Statistical significance was set at a p-value of less than 0.05.

Results

A total of 4526 OHCA cases were enrolled. Traumatic OHCA cases (n = 560, 12.4%), compared to medical OHCA cases (n = 3966, 87.6%), were less likely to have bystander CPR (10.7% vs. 31.7%, p < 0.001) and initially shockable rhythms (7.1% vs. 12.5%, p < 0.001). Regarding DA-CPR performance, traumatic OHCA cases were less likely to have dispatcher recognition of cardiac arrest (6.3% vs. 42.0%, p < 0.001), dispatcher initiation of bystander CPR (5.4% vs. 37.6%, p < 0.001), or any dispatcher delivery of CPR instructions (2.7% vs. 20.3%, p < 0.001). Stepwise logistic regression analysis showed that witnessed cardiac arrests (aOR 1.70, 95% CI 1.10–2.62; p = 0.017) and transportation to level 1 centers (aOR 1.99, 95% CI 1.27–3.13; p = 0.003) were significantly associated with achievement of sustained ROSC in traumatic OHCA cases, while DA-CPR-related variables were not (All p > 0.05).

Conclusions

DA-CPR was not associated with better outcomes for traumatic OHCA in achieving a sustained ROSC. The DA-CPR program for traumatic OHCAs needs further studies to validate its effectiveness and practicability, especially in the communities where rules for the termination of resuscitation in prehospital settings do not exist.
Parental Mental Health, Fathers’ Involvement and Bedtime Resistance in Infants
Authors: Ragni Benedetta , De Stasio Simona , Barni Daniela , Gentile Simonetta , Giampaolo Rosaria
Published: November 2019

Background

Around the age of 6 months, difficulties in settling to sleep and frequent night awakenings are generally occurring in 20 to 30% of infants. According to the transactional model parental factors can play a significant role in influencing infant sleep development. The purpose of the current study was to explore the combined effect of infants’ factors (temperament and sleep onset problems), and parental factors (parental mental health in terms of post-partum affective disorders, consistent bedtime routines and fathers’ involvement at bedtime), on infant bedtime difficulties (e.g. fussing, crying or protesting), including both maternal and paternal perspectives.

Methods

Sixty Italian intact two-parent families of infants (34 boys and 26 girls) ageing from 8 to 12 months (M = 10.73, SD = 2.54) were enrolled in the study. The parents filled out self-report questionnaires to measure the aforementioned variables. To investigate which infant and parental factors predicted infants’ bedtime difficulties, two multiple linear regressions (MR), one for fathers and one for mothers, and relative weight analyses (RWA) were conducted.

Results

With regard to infants’ bedtime difficulties reported by fathers (R2 = .35) they were explained by infant involvement in constant bedtime routines (β = −.35,p = .030) and paternal involvement at bedtime (β = −.45,p = .007). Instead infants’ bedtime difficulties reported by mothers (R2 = .32) were explained by minutes the child taken to fall asleep (β = .24,p = .04), infant involvement in constant bedtime routines (β = −.31,p = .01) and bedtime paternal involvement (β = −.27,p = .05).

Conclusions

The main results of this study emphasized the protective role of consistent bedtime routines and bedtime paternal involvement in reducing infants’ bedtime difficulties perceived both from mothers and fathers. Future research could help to raise awareness and improve understanding of the familial influences on children’s sleep, providing recommendations for educating families, school professionals, healthcare providers, and the general public on risk and protective factors that could play a meaningful role in infants and children’s developing sleep patterns.
Design, planning and implementation lessons learnt from a surgical multi-centre randomised controlled trial
Authors: Biggs Katie , Hind Daniel , Bradburn Mike , Swaby Lizzie , Brown Steve
Published: November 2019

Background

Increasingly, pragmatic randomised controlled trials are being used to evaluate surgical interventions, although they present particular difficulties in regards to recruitment and retention.

Methods

Procedures and processes related to implementation of a multi-centre pragmatic surgical randomised controlled trial are discussed. In this surgical trial, forecasting of consent rates based on similar trials and micro-costing of study activities with research partners were undertaken and a video was produced targeting recruiting staff with the aim of aiding recruitment. The baseline assessments were reviewed to ensure the timing did not impact on the outcome. Attrition due to procedure waiting time was monitored and data were triangulated for the primary outcome to ensure adequate follow-up data.

Results

Forecasting and costing ensured that the recruitment window was of adequate length and adequate resource was available for study procedures at multiple clinics in each hospital. Recruiting staff found the recruitment video useful. The comparison of patient-reported data collected prior to randomisation and prior to treatment provided confidence in the baseline data. Knowledge of participant dropout due to delays in treatment meant we were able to increase the recruitment target in a timely fashion, and along with the triangulation of data sources, this ensured adequate follow-up of randomised participants.

Conclusions

This paper provides a range of evidence-based and experience-based approaches which, collectively, resulted in meeting our study objectives and from which lessons may be transferable.

Trial registration

ISRCTN, ISRCTN41394716. Registered on 10 May 2012.

UKCRN Study ID: 12486.
Direct qPCR is a sensitive approach to detect Mycoplasma contamination in U937 cell cultures
Authors: Baaity Zain , Breunig Sven , Önder Kamil , Somogyvári Ferenc
Published: November 2019

Objective

We aim to directly detectMycoplasmaDNA in a U937 suspension cell culture without using DNA purification. In order to makeMycoplasmacontamination monitoring easier, we optimized a commercially available quantitative PCR (qPCR)-based detection kit. We compared the sensitivity of direct qPCR against qPCR with a purified DNA template.

Results

Our findings indicate that qPCR worked optimally with a 6 μl sample volume and a 52 °C annealing-extension temperature. We were able to decrease the annealing-extension step time from 60 to 20 s without any major decrease in reaction sensitivity. The total cycle time of optimized direct qPCR was 65 min. The optimized qPCR protocol was used to detectMycoplasmaDNA before and after DNA purification. Our findings indicate that direct qPCR had a higher sensitivity than regular qPCR. Ct levels produced by direct qPCR with 6 μl templates were almost identical to Ct levels produced by regular qPCR with DNA purified from a 60 μl cell culture sample (23.42 vs 23.49 average Ct levels, respectively). The optimized direct qPCR protocol was successfully applied to monitor the elimination ofMycoplasmacontamination from U937 cell cultures.