bluuebunny/crossref_metadata_2025 huggingface dataset:
What Early Intervention Looks Like in Child Care Settings: Stories From Providers
Authors: Weglarz-Ward Jenna M. , Santos Rosa Milagros , Hayslip Loretta A.
Published: November 2019

As more families enroll their infants and toddlers with disabilities in child care programs, early intervention (EI) services are being delivered in these natural environments. This article presents the findings of a study on infants and toddlers with disabilities in child care settings from the perspectives of professionals. Twenty-four child care and EI providers participated in eight focus groups across one state to discuss their experiences with EI services in child care settings. Using thematic analysis, major themes emerged, including Participant Experiences With EI in Child Care with six unique codes. Results suggest that the great variability of experiences across children, professionals, and programs contributed to an uncertainty of professional roles and responsibilities, challenges to communication among providers, and alignment to professional recommended practices. In addition, differences in specific location of services (i.e., in a separate room) and delivery model led to EI visits being viewed as disruptive and carrying over strategies into child care routines difficult. Recommendations for future research, policy, and practice are included.
Caregiver Stress, Coping Strategies, and Support Needs of Mothers Caring for their Children Who Are Undergoing Active Cancer Treatments
Authors: Tan Rebekah , Koh Serena , Wong Min En , Rui Ma , Shorey Shefaly
Published: November 2019

The diagnosis of childhood cancer not only affects the life of the child but also impacts the lives of the caregivers as well. This study aims to explore the caregiving stress, coping strategies, and support needs of mothers caring for children/adolescents with cancer during the active treatment phase. Individual semi-structured interviews were conducted, and two authors independently and thematically analyzed data. Caregiving mothers went through a process of emotional changes and a change in lifestyles when their children were diagnosed with cancer and undergoing treatments. It is important to ensure that caregiving mothers of children/adolescents with cancer are well supported by family, friends, and healthcare professionals. Healthcare professionals can develop informational booklets on cancer treatment protocols and work together with mothers. Parent support groups and plans for psychoeducational and spiritual care programs for mothers as forms of informational and emotional support may also be established.
Community pharmacists as catalysts for deprescribing: An exploratory study using quality improvement processes
Authors: Farrell Barbara , Clarkin Chantalle , Conklin James , Dolovich Lisa , Irving Hannah , McCarthy Lisa , Raman-Wilms Lalitha
Published: November 2019

Background:

There is growing international emphasis on deprescribing, involving the monitored reduction or stopping of medications that are no longer needed or that cause more harm than benefits, especially for the elderly. Community pharmacists are well positioned to partner with patients and their other health care providers in facilitating deprescribing activities.

Objective:

To build community pharmacists’ capacity to integrate deprescribing into their daily practices through training and workflow strategies.

Methods:

This study used an exploratory mixed-methods (primarily qualitative) design. Staff at 4 Ontario pharmacies were trained to use deprescribing guidelines. Qualitative data were collected through field observations, notes from advisory group meetings and documented Plan-Do-Study-Act (PDSA) plans. Quantitative data were derived from process and output measures reported by the pharmacies. Iterative PDSA cycles allowed the project team to appraise and accelerate process improvements over time and to summarize findings on facilitators, barriers and the adaptation of processes.

Results:

All 4 pharmacies identified individual and common goals related to deprescribing; however, drugs targeted and use of professional services to identify and address deprescribing opportunities varied. Each demonstrated that deprescribing activities could be integrated into daily practice and workflow. Common themes characterized approaches taken by each pharmacy: (1) processes used for capacity building among staff to identify patients for possible deprescribing, (2) approaches for preliminary interactions with patients, (3) in-depth medication reviews and (4) follow-up and monitoring. Approaches changed over time.

Conclusion:

Deprescribing appears to be feasible in community pharmacies. Data derived to populate a business model canvas informs the development of an in-depth business model for deprescribing. Can Pharm J (Ott) 2019;152:xx-xx.
Assessing fatigue in multiple sclerosis: Psychometric properties of the five-item Modified Fatigue Impact Scale (MFIS-5)
Authors: Meca-Lallana Virginia , Brañas-Pampillón María , Higueras Yolanda , Candeliere-Merlicco Antonio , Aladro-Benito Yolanda , Rodríguez-De la Fuente Ofir , Salas-Alonso Elisa , Maurino Jorge , Ballesteros Javier
Published: November 2019

Fatigue in multiple sclerosis is a key symptom associated with work-related problems and poor quality of life outcomes. The five-item Modified Fatigue Impact Scale is a brief self-assessment tool for measuring the impact of fatigue on cognitive, physical and psychosocial function. A non-interventional, cross-sectional study was conducted to assess dimensionality and item characteristics of the five-item Modified Fatigue Impact Scale in multiple sclerosis. A total of 302 subjects were studied. Mokken analysis found the five-item Modified Fatigue Impact Scale is a strong one-dimensional scale (overall scalability index H = 0.67) with high reliability (Cronbach’s alpha = 0.90). The confirmatory factor analysis model confirmed the one-dimensional structure (comparative fit index = 1.0, root-mean-square error of approximation = 0.035). Samejima’s model fitted well as an unconstrained model with different item difficulties. The five-item Modified Fatigue Impact Scale shows appropriate psychometric characteristics and may constitute a valuable and easy-to-implement addition to measure the impact of fatigue in clinical practice.
Genetic Implication and Dental Consideration in Syndromes with Benign and Malignant Oral Neoplastic Component: A Narrative Review
Authors: Singh Saurabh , Gupta Khushboo , Pendalya Siva Kumar , Kondreddy Kameswari
Published: November 2019

Background and Objective:

The presence of an internal and often occult malignancy may be forewarned by various oral manifestations. Several of these findings are preferentially localized to the head and neck region, including the oral cavity. This places the dental practitioner in a unique position to detect these signs and symptoms of occult neoplastic involvement. Because they may be present before an established syndrome or cancer diagnosis, even representing the initial expression of disease in some cases, early recognition by a dentist may lead to timely diagnosis and management of these syndromes. Thus, the aim of this narrative review was literature search and gathering data of such syndromes.

Materials and Methods:

A Medline–PubMed search was conducted of the literature using the keywords “syndrome,” “dental management,” “Cowden’s syndrome,” “Peutz–Jeghers syndrome,” “malignant component,” “Gardner’s syndrome,” “Gorlin–Goltz syndrome,” and “McCune–Albright syndrome.” The search strategy was limited to human studies (case reports and case series), full-text English articles published from January 1, 2000, to mid-2019. Irrelevant articles or articles with inadequate information were omitted.

Results:

A total of 36 pieces of literature were reviewed, of which 13 were literature reviews, 15 case reports, 3 expert committee guides and updates, and 4 original research papers, and 1 was a book.

Conclusion:

These syndromes pose risk during dental practice, which necessitates extra awareness and caution to prevent potential complications. Although, the multidisciplinary approach in treating these cases is not well documented, any related information may be helpful in understanding the pathogenesis and the nature of these syndromes.
Social Change and the Changing Indian Voter: Consolidation of the BJP in India’s 2019 Lok Sabha Election
Authors: Suri K. C.
Published: November 2019

This article is about the changing voter in a changing India in the context of India’s Lok Sabha election held in the year 2019. Positing a two-way relationship between social change and electoral politics, this article analyses the sources for the success of the Bharatiya Janata Party (BJP) in mobilizing massive support among various Hindu social groups. It examines the claims of the BJP leaders that the 2019 election has breached the barriers of caste and class. It takes the view that the social change over the decades after independence, especially after the 1990s, led to the emergence of a new elite composed of members from different social groups with shared values and social life willing to join hands for political purposes and that led to the massive victory of the BJP in the absence of any other viable alternative.
Behavioral Engagement Shifts Among At-Risk High School Students Enrolled in Online Courses
Authors: Darling-Aduana Jennifer
Published: November 2019

Academic behaviors such as attendance are highly associated with academic outcomes. High schools are also increasingly turning to online courses to educate their most marginalized students. In this study, I explored the extent to which enrollment in an online course improved engagement and allowed students to make course progress online outside the traditional school day by examining within-student changes in academic behaviors. Students completed their online course in fewer class periods than required to complete a comparable course in a traditional, face-to-face instructional setting. At the same time, students attended, on average, three additional days of school when enrolled in an online course as when enrolled in solely face-to-face courses, indicating a potentially positive spillover effect. Results have implications for practitioners and policy makers interested in online learning and understanding what programs might be most effective in reengaging students at risk of course failure or dropping out of high school.
Medical Students’ Knowledge and Attitudes Toward Shared Decision Making: Results From a Multinational, Cross-Sectional Survey
Authors: Yen Renata W. , Barr Paul J. , Cochran Nan , Aarts Johanna W. , Légaré France , Reed Malcolm , O’Malley A. James , Scalia Peter , Painchaud Guérard Geneviève , Backer Grant , Reilly Clifford , Elwyn Glyn , Durand Marie-Anne
Published: November 2019

Introduction. We aimed to conduct a multinational cross-sectional online survey of medical students’ attitudes toward, knowledge of, and experience with shared decision making (SDM). Methods. We conducted the survey from September 2016 until May 2017 using the following: 1) a convenience sample of students from four medical schools each in Canada, the United States, and the Netherlands ( n = 12), and 2) all medical schools in the United Kingdom through the British Medical School Council ( n = 32). We also distributed the survey through social media. Results. A total of 765 students read the information sheet and 619 completed the survey. Average age was 24, 69% were female. Mean SDM knowledge score was 83.6% (range = 18.8% to 100%; 95% confidence interval [CI] = 82.8% to 84.5%). US students had the highest knowledge scores (86.2%, 95% CI = 84.8% to 87.6%). The mean risk communication score was 57.4% (range = 0% to 100%; 95% CI = 57.4% to 60.1%). Knowledge did not vary with age, race, gender, school, or school year. Attitudes were positive, except 46% believed SDM could only be done with higher educated patients, and 80.9% disagreed that physician payment should be linked to SDM performance (increased with years in training, P < 0.05). Attitudes did not vary due to any tested variable. Students indicated they were more likely than experienced clinicians to practice SDM (72.1% v. 48.8%). A total of 74.7% reported prior SDM training and 82.8% were interested in learning more about SDM. Discussion. SDM knowledge is high among medical students in all four countries. Risk communication is less well understood. Attitudes indicate that further research is needed to understand how medical schools deliver and integrate SDM training into existing curricula.
Integrated transcriptomic analysis reveals hub genes involved in diagnosis and prognosis of pancreatic cancer
Authors: Zhou Yang-Yang , Chen Li-Ping , Zhang Yi , Hu Sun-Kuan , Dong Zhao-Jun , Wu Ming , Chen Qiu-Xiang , Zhuang Zhi-Zhi , Du Xiao-Jing
Published: November 2019

Background

The hunt for the molecular markers with specificity and sensitivity has been a hot area for the tumor treatment. Due to the poor diagnosis and prognosis of pancreatic cancer (PC), the excision rate is often low, which makes it more urgent to find the ideal tumor markers.

Methods

Robust Rank Aggreg (RRA) methods was firstly applied to identify the differentially expressed genes (DEGs) between PC tissues and normal tissues from GSE28735, GSE15471, GSE16515, and GSE101448. Among these DEGs, the highly correlated genes were clustered using WGCNA analysis. The co-expression networks and molecular complex detection (MCODE) Cytoscape app were then performed to find the sub-clusters and confirm 35 candidate genes. For these genes, least absolute shrinkage and selection operator (lasso) regression model was applied and validated to build a diagnostic risk score model. Cox proportional hazard regression analysis was used and validated to build a prognostic model.

Results

Based on integrated transcriptomic analysis, we identified a 19 gene module (SYCN, PNLIPRP1, CAP2, GNMT, MAT1A, ABAT, GPT2, ADHFE1, PHGDH, PSAT1, ERP27, PDIA2, MT1H, COMP, COL5A2, FN1, COL1A2, FAP and POSTN) as a specific predictive signature for the diagnosis of PC. Based on the two consideration, accuracy and feasibility, we simplified the diagnostic risk model as a four-gene model: 0.3034*log2(MAT1A)-0.1526*log2(MT1H) + 0.4645*log2(FN1) -0.2244*log2(FAP), log2(gene count). Besides, a four-hub gene module was also identified as prognostic model = − 1.400*log2(CEL) + 1.321*log2(CPA1) + 0.454*log2(POSTN) + 1.011*log2(PM20D1), log2(gene count).

Conclusion

Integrated transcriptomic analysis identifies two four-hub gene modules as specific predictive signatures for the diagnosis and prognosis of PC, which may bring new sight for the clinical practice of PC.
ProtRank: bypassing the imputation of missing values in differential expression analysis of proteomic data
Authors: Medo Matúš , Aebersold Daniel M. , Medová Michaela
Published: November 2019

Background

Data from discovery proteomic and phosphoproteomic experiments typically include missing values that correspond to proteins that have not been identified in the analyzed sample. Replacing the missing values with random numbers, a process known as “imputation”, avoids apparent infinite fold-change values. However, the procedure comes at a cost: Imputing a large number of missing values has the potential to significantly impact the results of the subsequent differential expression analysis.

Results

We propose a method that identifies differentially expressed proteins by ranking their observed changes with respect to the changes observed for other proteins. Missing values are taken into account by this method directly, without the need to impute them. We illustrate the performance of the new method on two distinct datasets and show that it is robust to missing values and, at the same time, provides results that are otherwise similar to those obtained with edgeR which is a state-of-art differential expression analysis method.

Conclusions

The new method for the differential expression analysis of proteomic data is available as an easy to use Python package.
Complete chloroplast genomes of all six Hosta species occurring in Korea: molecular structures, comparative, and phylogenetic analyses
Authors: Lee Soo-Rang , Kim Kyeonghee , Lee Byoung-Yoon , Lim Chae Eun
Published: November 2019

Background

The genus Hosta is a group of economically appreciated perennial herbs consisting of approximately 25 species that is endemic to eastern Asia. Due to considerable morphological variability, the genus has been well recognized as a group with taxonomic problems. Chloroplast is a cytoplasmic organelle with its own genome, which is the most commonly used for phylogenetic and genetic diversity analyses for land plants. To understand the genomic architecture of Hosta chloroplasts and examine the level of nucleotide and size variation, we newly sequenced four (H. clausa, H. jonesii, H. minor, and H. venusta) and analyzed six Hosta species (including the four, H. capitata and H. yingeri) distributed throughout South Korea.

Results

The average size of complete chloroplast genomes for the Hosta taxa was 156,642 bp with a maximum size difference of ~ 300 bp. The overall gene content and organization across the six Hosta were nearly identical with a few exceptions. There was a single tRNA gene deletion in H. jonesii and four genes were pseudogenized in three taxa (H. capitata, H. minor, and H. jonesii). We did not find major structural variation, but there were a minor expansion and contractions in IR region for three species (H. capitata, H. minor, and H. venusta). Sequence variations were higher in non-coding regions than in coding regions. Four genic and intergenic regions including two coding genes (psbA and ndhD) exhibited the largest sequence divergence showing potential as phylogenetic markers. We found compositional codon usage bias toward A/T at the third position. The Hosta plastomes had a comparable number of dispersed and tandem repeats (simple sequence repeats) to the ones identified in other angiosperm taxa. The phylogeny of 20 Agavoideae (Asparagaceae) taxa including the six Hosta species inferred from complete plastome data showed well resolved monophyletic clades for closely related taxa with high node supports.

Conclusions

Our study provides detailed information on the chloroplast genome of the Hosta taxa. We identified nucleotide diversity hotspots and characterized types of repeats, which can be used for developing molecular markers applicable in various research area.
Low pre-transplant levels of mannose-binding lectin are associated with viral infections and mortality after haematopoietic allogeneic stem cell transplantation
Authors:   on behalf of SCT team, Puente M. , Fariñas-Alvarez C. , Moreto A. , Sánchez-Velasco P. , Ocejo-Vinyals J. G. , Fariñas M. C.
Published: November 2019

Background

Mannose-binding lectin (MBL) is a key component of innate immunity. Low serum MBL levels, related to promoter polymorphism and structural variants, have been associated with an increased risk of infection. The aim of this work was to analyse the incidence and severity of infections and mortality in relation to the MBL2 genotype and MBL levels in patients underwent allogeneic haematopoietic stem cell transplantation (Allo-HSCT).

Results

This was a prospective cohort study of 72 consecutive patients underwent Allo-HSCT between January 2007 and June 2009 in a tertiary referral centre. Three periods were considered in the patients’ follow-up: the early period (0–30 days after Allo-HSCT), the intermediate period (30–100 days after Allo-HSCT) and the late period (> 100 days after Allo-HSCT). A commercial line probe assay for MBL2 genotyping and an ELISA Kit were used to measure MBL levels. A total of 220 episodes of infection were collected in the 72 patients. No association between donor or recipient MBL2 genotype and infection was found. The first episode of infection presented earlier in patients with pre-transplant MBL levels of < 1000 ng/ml (median 6d vs 8d, p = 0.036). MBL levels < 1000 ng/ml in the pre-transplant period (risk ratio (RR) 2.48, 95% CI 1.00–6.13), neutropenic period (0–30 days, RR 3.28, 95% CI 1.53–7.06) and intermediate period (30–100 days, RR 2.37, 95% CI 1.15–4.90) were associated with increased risk of virus infection. No association with bacterial or fungal disease was found. Mortality was associated with pre-transplant MBL levels < 1000 ng/ml (hazard ratio 5.55, 95% CI 1.17–26.30, p = 0.03) but not with MBL2 genotype.

Conclusions

Patients who underwent Allo-HSCT with low pre-transplant MBL levels presented the first episode of infection earlier and had an increased risk of viral infections and mortality in the first 6 months post-transplant. Thus, pre-transplant MBL levels would be important in predicting susceptibility to viral infections and mortality and might be considered a biomarker to be included in the pre-transplantation risk assessment.
Antibiotics resistance and toxin profiles of Bacillus cereus-group isolates from fresh vegetables from German retail markets
Authors: Fiedler Gregor , Schneider Carmen , Igbinosa Etinosa O. , Kabisch Jan , Brinks Erik , Becker Biserka , Stoll Dominic A. , Cho Gyu-Sung , Huch Melanie , Franz Charles M. A. P.
Published: November 2019

Background

This study aimed to evaluate the safety of raw vegetable products present on the German market regarding toxin-producing Bacillus cereus sensu lato (s.l.) group bacteria.

Results

A total of 147 B. cereus s.l. group strains isolated from cucumbers, carrots, herbs, salad leaves and ready-to-eat mixed salad leaves were analyzed. Their toxinogenic potential was assessed by multiplex PCR targeting the hemolysin BL (hbl) component D (hblD), non-hemolytic enterotoxin (nhe) component A (nheA), cytotoxin K-2 (cytK-2) and the cereulide (ces) toxin genes. In addition, a serological test was used to detect Hbl and Nhe toxins. On the basis of PCR and serological results, none of the strains were positive for the cereulide protein/genes, while 91.2, 83.0 and 37.4% were positive for the Hbl, Nhe and CytK toxins or their genes, respectively. Numerous strains produced multiple toxins. Generally, strains showed resistance against the β-lactam antibiotics such as penicillin G and cefotaxim (100%), as well as amoxicillin/clavulanic acid combination and ampicillin (99.3%). Most strains were susceptible to ciprofloxacin (99.3%), chloramphenicol (98.6%), amikacin (98.0%), imipenem (93.9%), erythromycin (91.8%), gentamicin (88.4%), tetracycline (76.2%) and trimethoprim/sulfamethoxazole combination (52.4%). The genomes of eight selected strains were sequenced. The toxin gene profiles detected by PCR and serological test mostly agreed with those from whole-genome sequence data.

Conclusions

Our study showed that B. cereus s.l. strains encoding toxin genes occur in products sold on the German market and that these may pose a health risk to the consumer if present at elevated levels. Furthermore, a small percentage of these strains harbor antibiotic resistance genes. The presence of these bacteria in fresh produce should, therefore, be monitored to guarantee their safety.
Molecular cloning and metabolomic characterization of the 5-enolpyruvylshikimate-3-phosphate synthase gene from Baphicacanthus cusia
Authors: Yu Jian , Zhang Yihan , Ning Shuju , Ye Qi , Tan Hexin , Chen Ruibing , Bu Qitao , Zhang Rui , Gong Peimin , Ma Xiaoli , Zhang Lei , Wei Daozhi
Published: November 2019

Background

Indigo alkaloids, such as indigo, indirubin and its derivatives, have been identified as effective antiviral compounds in Baphicacanthus cusia. Evidence suggests that the biosynthesis of indigo alkaloids in plants occurs via the shikimate pathway. The enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) is involved in plant metabolism; however, its underlying putative mechanism of regulating the production of indigo alkaloids is currently unknown.

Results

One gene encoding EPSPS was isolated from B. cusia. Quantitative real-time PCR analysis revealed that BcEPSPS was expressed at the highest level in the stem and upregulated by methyl jasmonate (MeJA), salicylic acid (SA) and abscisic acid (ABA) treatment. The results of subcellular localization indicated that BcEPSPS is mainly expressed in both the plastids and cytosol, which has not been previously reported. An enzyme assay revealed that the heterogeneously expressed BcEPSPS protein catalysed the generation of 5-enolpyruvyl shikimate-3-phosphate. The overexpression of BcEPSPS in Isatis indigotica hairy roots resulted in the high accumulation of indigo alkaloids, such as indigo, secologanin, indole and isorhamnetin.

Conclusions

The function of BcEPSPS in catalysing the production of EPSP and regulating indigo alkaloid biosynthesis was revealed, which provided a distinct view of plant metabolic engineering. Our findings have practical implications for understanding the effect of BcEPSPS on active compound biosynthesis in B. cusia.
A prospective observational study testing liquid crystal phase change type thermometer placed on skin against oesophageal/pharyngeal placed thermometers in participants undergoing general anesthesia
Authors: Simpson G. , Rodseth R. N.
Published: November 2019

Abstracts

Background

Patient outcomes are influenced by intraoperative temperature management. Oesophageal/pharyngeal temperature monitoring is the standard of care at our institute but is not well tolerated in awake patients. Many non-invasive temperature monitors have been studied. Only the TraxIt® Wearable Children’s Underarm Thermometer which contains liquid crystals that undergo phase changes according to temperature is available at our institution. We tested these non-invasive monitors against our standard of care which is the oesophageal/pharyngeal temperature monitor.

Methods

We conducted a prospective observational study of 100 patients receiving general anaesthesia for elective surgery. Patients were eligible for inclusion if they were ≥ 18 years old, were planned to have a general anaesthetic > 60 min during which no body cavity (chest or abdomen) would be opened. Patient temperature was measured with an oesophageal/pharyngeal thermistor probe and skin surface temperature monitors placed over the forehead, in the axilla, over the sternum, and behind the ear (over major vessels to the brain). Temperatures were recorded and then analysed using Altman-Bland plots. Pre-determined clinically relevant limits of agreement were set at −/+ 0.5 °C.

Results

From the 100 patients we collected 500 data points for each monitor with an average monitoring time of 102 min (30–300 min) across a range of surgical procedures. None of the skin surface temperature monitors achieved the pre-determined limits of agreement and results were impacted by the use of a forced air warmer.

Conclusion

The TraxIt® Wearable Children’s Underarm Thermometers are not suitable for temperature monitoring during general anaesthesia.
Does the implementation of a care pathway for patients with hip or knee osteoarthritis lead to fewer diagnostic imaging and referrals by general practitioners? A pre-post-implementation study of claims data
Authors: van den Bogaart Esther H. A. , Kroese Mariëlle E. A. L. , Spreeuwenberg Marieke D. , Ottenheijm Ramon P. G. , Deckers Patrick , Ruwaard Dirk
Published: November 2019

Background

The Dutch care for hip and knee osteoarthritis (OA) is of good quality, but there is room for improvement regarding the efficient use of diagnostic imaging and conservative treatment. Therefore a stepped-care approach, in the shape of the care pathway ‘Better exercise in osteoarthritis’, was implemented to reduce the number of diagnostic imaging requested by GPs and referrals of GPs to orthopaedic care.

Methods

In 2015, the pathway is implemented with the use of educational meetings, distributing guidelines and incorporating reminders in the GPs’ referral application. To evaluate the effect of the pathway on the diagnostic and referral behaviour of GPs, hip and knee related health insurance claims are used together with claims of other joints and of a control region for comparison. The average number of claims and the percentage change in the post-implementation period are described. Binary logistic regression analysis is used to examine the interaction between region (intervention and control) and period (pre- and post-implementation). Using random sampling of patient records, information about the practical application of the pathway and the number of hip or knee arthroplasties is added.

Results

In both regions, the number of diagnostic imaging decreased and the number of initial orthopaedic consultations increased during the post-implementation period. Significant interaction effects were found in knee-related diagnostics (p ≤ 0.001) and diagnostics of other joints (p = 0.039). No significant interaction effects were found in hip-related diagnostics (p = 0.060) and in initial orthopaedic consultation claims of hip (p = 0.979), knee (p = 0.281), and other joints (p = 0.464). Being referred according to the pathway had no significant effect on the probability of undergoing arthroplasty.

Conclusion

The implementation of the pathway had a positive effect on GPs diagnostic behaviour related to the knee, but not to the hip. The referral behaviour of GPs to orthopaedic care needs attention for future interventions and research, since an increase (instead of a desired decrease) in the number of initial orthopaedic consultations was found. Focusing on the entire width of care for hip and knee OA could be helpful.
Indirect costs associated with ulcerative colitis: a systematic literature review of real-world data
Authors: Constantin Joelle , Atanasov Petar , Wirth Daniel , Borsi Andras
Published: November 2019

Background

The economic burden of ulcerative colitis (UC), specifically related to indirect costs, is not extensively documented. Understanding and quantifying it is required by health care decision makers.

Aim

To assess the impact of indirect costs of UC in observation studies.

Method

A systematic literature search was conducted in MEDLINE®, Embase® and Cochrane Library to capture all relevant publications reporting outcomes on absenteeism, presenteeism and productivity losses in moderate to severe UC. Eligibility criteria for inclusion into the review were established using a predefined PICOS scheme. All costs were adjusted to 2017 currency values (USD dollars, $).

Results

In total, 18 studies reporting data on indirect costs were included in the analysis. Absenteeism costs were classified into three categories: sick leave, short-term and long-term disability. Most of the studies captured absenteeism costs related specifically to sick leave, which was experienced on average by 10 to 24% patients with UC. Only three studies captured presenteeism costs, as these are difficult to measure, however costs ranged from 1602 $ to 2947 $ per patient year. The proportion of indirect costs accounted for 35% of total UC costs (Total UC costs were defined as the sum of healthcare costs, productivity costs and out-of-pocket costs).

Discussion

A limited number of studies were identified describing the indirect costs in patients with moderate to severe UC. Insufficient data on different components of costs allowed a limited analysis on the impact of indirect costs in patients with UC. Further studies are needed to gain an understanding of the influence of UC on patients’ functional abilities.
Mumps: MMR vaccination and genetic diversity of mumps virus, 2007–2011 in Catalonia, Spain
Authors:   the Working Group for the Study for Mumps in Catalonia, Barrabeig Irene , Antón Andrés , Torner Núria , Pumarola Tomàs , Costa Josep , Domínguez Àngela
Published: November 2019

Background

Mumps is a vaccine-preventable disease but outbreaks have been reported in persons vaccinated with two doses of MMR vaccine.

The objective was to describe the demographic features, vaccination effectiveness and genetic mumps virus diversity among laboratory-confirmed cases between 2007 and 2011 in Catalonia.

Methods

Cases and outbreaks of mumps notified to the notifiable diseases system of Catalonia between 2007 and 2011 retrospectively registered were included. Public health care centres provided written immunization records to regional public health staff to determine the vaccination history.

Saliva and serum specimens were collected from suspected cases for laboratory-confirmation using real-time reverse-transcriptase PCR (rtRT-PCR) or serological testing.

Phylogenetic analysis of the complete SH gene (316 nucleotides) and complete coding HN protein (1749 nucleotides) sequences was made.

Categorical variables were compared using the Chi-square or Fisher’s tests and continuous variables using the Student test. Vaccination effectiveness by number of MMR doses was estimated using the screening method.

Results

During the study period, 581 confirmed cases of mumps were notified (incidence rate 1.6 cases/100,000 persons-year), of which 60% were male. Three hundred sixty-four laboratory-confirmed cases were reported, of which 44% were confirmed by rtRT-PCR. Of the 289 laboratory-confirmed cases belonging to vaccination cohorts, 33.5% (97) had received one dose of MMR vaccine and 50% (145) two doses.

Based on phylogenetic analyses of 316-nucleotide and 174-nucleotide SH sequences, the viruses belonging to viral genotypes were: genotype G (126), genotype D (23), genotype H (2), genotype F (2), genotype J (1), while one remained uncharacterized.

Amino acid differences were detected between circulating strains and the Jeryl Lynn vaccine strains, although the majority of amino acid substitutions were genotype-specific.

Fifty-one outbreaks were notified that included 324 confirmed mumps cases. Genotype G was the most frequent genotype detected. The family (35%), secondary schools (25%) and community outbreaks (18%) were the most frequent settings.

Conclusions

Our study shows that genotype G viruses are the most prevalent in Catalonia. Most cases occurred in people who had received two doses of MMR, suggesting inadequate effectiveness of the Jeryl Lynn vaccine strain. The possible factors related are discussed.
A case report of long treatment with Itraconazole in a patient with chronic Chagas disease
Authors: Bosch-Nicolau Pau , Salvador Fernando , Sánchez-Montalvá Adrián , Sulleiro Elena , Burgos Joaquín , Molina Israel
Published: November 2019

Background

Current available treatments (benznidazole and nifurtimox) for Chagas disease (CD) show limited efficacy in chronic phase and frequent undesirable effects. Ergosterol synthesis inhibitors (ESI) had been considered as promising drugs for CD treatment and despite its recent poor results in several clinical trials, different strategies have been proposed to optimize its role in this infection.

Case presentation

We present a case of chronic Chagas disease in patient diagnosed with HIV who received treatment for histoplasmosis with itraconazol during twelve months. Even though T. cruzi rt-PCR was persistently negative during treatment, when itraconazol was stopped she presented with a positive blood rt-PCR.

Conclusion

Several studies using different ESI had been published for CD treatment. Either in vitro or in vivo assays demonstrated activity against T. cruzi of the different triazole derivatives so different clinical trials had been carried out to evaluate its efficacy and safety. Despite contradictory evidence in the animal model, longer treatments along with other treatment strategies previously proposed suggests that ESI failure rates in positive peripheral blood rt-PCR are higher than that obtained with the current treatments of choice.
A novel missense in GLI3 possibly affecting one of the zinc finger domains may lead to postaxial synpolydactyly: case report
Authors: Zou Qianqian , Tian Zhigang , Zheng Jie , Zhi Xiufang , Du Xiaojie , Shu Jianbo , Cai Chunquan
Published: November 2019

Background

Polydactyly is one of the most common congenital hand/foot malformations in humans. Mutations in GLI3 have been reported to cause syndromic and non-syndromic forms of preaxial and postaxial polydactylies.

Case presentation

The patient was a 2-year-old boy who underwent surgery in our hospital. The right hand and left foot of the patient were labelled as postaxial polydactyly type B, and there was cutaneous webbing between the 3rd and 4th fingers of the left hand. We identified a novel c. 1622C > T variant in GLI3 leading to an isolated postaxial synpolydactyly.

Conclusions

The patient carries a novel autosomal dominant heterozygous missense mutation. This mutation c.1622C > T;p.(Thr541Met) in the GLI3 gene may affect the normal function of the zinc finger domain (ZFD) in a different way. However, it seems that more research is needed to determine the exact effects of this mutation.
Copy number variation is highly correlated with differential gene expression: a pan-cancer study
Authors: Shao Xin , Lv Ning , Liao Jie , Long Jinbo , Xue Rui , Ai Ni , Xu Donghang , Fan Xiaohui
Published: November 2019

Background

Cancer is a heterogeneous disease with many genetic variations. Lines of evidence have shown copy number variations (CNVs) of certain genes are involved in development and progression of many cancers through the alterations of their gene expression levels on individual or several cancer types. However, it is not quite clear whether the correlation will be a general phenomenon across multiple cancer types.

Methods

In this study we applied a bioinformatics approach integrating CNV and differential gene expression mathematically across 1025 cell lines and 9159 patient samples to detect their potential relationship.

Results

Our results showed there is a close correlation between CNV and differential gene expression and the copy number displayed a positive linear influence on gene expression for the majority of genes, indicating that genetic variation generated a direct effect on gene transcriptional level. Another independent dataset is utilized to revalidate the relationship between copy number and expression level. Further analysis show genes with general positive linear influence on gene expression are clustered in certain disease-related pathways, which suggests the involvement of CNV in pathophysiology of diseases.

Conclusions

This study shows the close correlation between CNV and differential gene expression revealing the qualitative relationship between genetic variation and its downstream effect, especially for oncogenes and tumor suppressor genes. It is of a critical importance to elucidate the relationship between copy number variation and gene expression for prevention, diagnosis and treatment of cancer.
Pattern of renal amyloidosis in South Africa
Authors: Hassen Muhammed , Bates William , Moosa Mohammed Rafique
Published: November 2019

Background

Kidney disease is a serious manifestation of systemic amyloidosis and a major cause of morbidity and mortality. Tuberculosis (TB) occurs up to 27 times more commonly in human immunodeficiency virus (HIV) infected patients and is also an important cause of renal amyloid; there are however no reports of renal amyloidosis in South Africa in the HIV era.

Methods

This was a retrospective record review of cases of amyloidosis diagnosed on renal biopsies at our tertiary referral hospital between January 1985 and December 2016.

Results

Forty-six cases of amyloidosis were identified over the study period. The calculated biopsy prevalence was 1.38 per 100 non-transplant renal biopsies (95% Confidence Interval 1.02–1.86). AL amyloidosis was identified in 26 (57%) cases and AA in 20 (43%). The median age at presentation was 51 years and 52% of cases were female. Patients with AA amyloidosis were significantly younger compared to their AL counterparts (age 42 years vs. 58 years,p = < 0.001) and were all significantly non-white. The main clinical presentation was nephrotic syndrome (85%) and 52% of cases also had a serum creatinine value of greater than 120 μmol/L. Of the 20 cases of AA amyloidosis, 12 (60%) were associated with tuberculosis. HIV infection was noted in only two (10%) of the 20 AA cases. Median survival after diagnosis was 2 months.

Conclusion

Amyloidosis is a rare cause of kidney disease and typically presents with nephrotic syndrome. A similar number of AA and AL types were observed, and outcomes are worse in cases of AA amyloid. While TB remains the major underlying disease in this type, HIV infection was infrequent in cases of AA renal amyloidosis.
Optimal treatment for elderly patients with resectable proximal gastric carcinoma: a real world study based on National Cancer Database
Authors: Wang Xuefei , Zhao Junjie , Fairweather Mark , Yang Tingsong , Sun Yihong , Wang Jiping
Published: November 2019

Background

High perioperative morbidity, mortality, and uncertain outcome of surgery in octogenarians with proximal gastric carcinoma (PGC) pose a dilemma for both patients and physicians. We aim to evaluate the risks and survival benefits of different strategies treated in this group.

Methods

Octogenarians (≥80 years) with resectable proximal gastric carcinoma who were recommended for surgery were identified from National Cancer Database during 2004–2013.

Results

Patients age ≥ 80 years with PGC were less likely to be recommended or eventually undergo surgery compared to younger patients. Patients with surgery had a significantly better survival than those without surgery (5-year OS: 26% vs. 7%, p < 0.001), especially in early stage patients. However, additional chemotherapy (HR: 0.94, 95% CI: 0.82–1.08, P = 0.36) or radiotherapy (HR: 0.97, 95% CI: 0.84–1.13, P = 0.72) had limited benefits. On multivariate analysis, surgery (HR: 0.66, 95% CI: 0.51–0.86, P = 0.002) was a significant independent prognostic factor, while extensive surgery had no survival benefit (Combined organ resection: HR: 1.88, 95% CI: 1.22–2.91, P = 0.004; number of lymph nodes examined: HR: 0.99, 95% CI: 0.97–1.00, P = 0.10). Surgery performed at academic and research (AR) medical center had the best survival outcome (5-year OS: 30% in AR vs. 18–27% in other programs, P < 0.001) and lowest risk (30-day mortality: 1.5% in AR vs. 3.6–6.6% in other programs, P < 0.001; 90-day mortality: 6.2% in AR vs. 13.6–16.4% in other programs, P < 0.001) compared to other facilities.

Conclusions

Less-invasive approach performed at academic and research medical center might be the optimal treatment for elderly patients aged ≥80 yrs. with early stage resectable PGC.
Visual impairment in children with a brain tumor: a prospective nationwide multicenter study using standard visual testing and optical coherence tomography (CCISS study)
Authors: Nuijts M. A. , Degeling M. H. , Stegeman I. , Schouten-van Meeteren A. Y. N. , Imhof S. M.
Published: November 2019

Background

Children with a brain tumor have a high risk of impaired vision. Up to now, visual acuity measurement, visual field testing and orthoptic testing are the most informative diagnostic investigations for the assessment of visual function. Evaluating vision in children can be challenging given the challenges in cooperation, concentration and age-dependent shifts in visual tests. Since visual loss due to a brain tumor can be progressive and irreversible, we must aim to detect visual impairment as early as possible. Several studies have shown that optical coherence tomography facilitates discovery of nerve fiber damage caused by optic nerve glioma. Consequently, early detection of potential ocular damage will effect treatment decisions and will provide timely referral to visual rehabilitation centers.

Methods/design

The CCISS study is a prospective, observational, multicenter cohort study in The Netherlands. Patients aged 0–18 years with a newly diagnosed brain tumor are invited for inclusion in this study. Follow-up visits are planned at 6, 12, 18 and 24 months. Primary endpoints are visual acuity, visual field and optical coherence tomography parameters (retinal nerve fiber layer thickness and ganglion cell layer – inner plexiform layer thickness). Secondary endpoints include the course of visual function (measured by visual acuity, visual field and optical coherence tomography at different follow-up visits), course of the disease and types of treatment.

Discussion

The CCISS study will heighten the awareness of visual impairment in different types of brain tumors in children. This study will show whether optical coherence tomography leads to earlier detection of visual impairment compared to standard ophthalmological testing (i.e. visual acuity, visual field testing) in children with a brain tumor. Furthermore, the systematic approach of ophthalmological follow-up in this study will give us insight in the longitudinal relation between the course of visual function, course of the disease and types of treatment in children with a brain tumor.

Trial registration

The CCISS study is prospectively registered in the Netherlands Trial Register (NTR) since April 2019. Identifier: NL7697.
A randomised, double-blind, placebo-controlled clinical trial assessing the efficacy of bedtime buddy® for the treatment of nocturnal enuresis in children
Authors: Schloss Janet , Ryan Kimberley , Reid Rebecca , Steel Amie
Published: November 2019

Background

Nocturnal enuresis (NE), or ‘bedwetting’, is a form of night-time urinary incontinence occurring in younger children. A diagnosis of NE can be socially disruptive and psychologically stressful for a child. The most common strategies used by parents to manage NE are waking the child during the night to use the bathroom and limiting the child’s water intake before going to bed. Behavioural or educational therapies for NE such as urotherapy or bladder retraining are widely accepted and considered as a mainstream treatment option for non-neurogenic lower urinary tract dysfunction in children. Pharmacotherapy also plays an ancillary role. However, there is no gold standard therapy or intervention to effectively manage NE.

Methods

This study aims to determine the efficacy of a herbal combination in the treatment of NE in children. The target population for this study is 80 children aged between 6 and 14 years old (males and females) who have primary nocturnal enuresis ≥3 per week (wet nights). The active group will receive one or two capsules per day containing 420 mg of a proprietary blend of Urox® (Seipel Group, Brisbane, Australia) containing Cratevox™ (Crataeva nurvalaL; Capparidaceae; Varuna) stem bark extract standardised for 1.5% lupeol: non-standardisedEquisetum arvenseL. (Equisetaceae; Horsetail) stem extract; and, non-standardisedLindera aggregataSims. The primary outcome for this study is the frequency of nocturia. Secondary outcomes include safety, quality of life, and daytime incontinence. Each participation will be involved in the trial for 32 weeks including contact with the research team every 2 weeks for the first 8 weeks and then every 8 weeks until trial completion.

Discussion

This study examines a novel treatment for an under-researched health condition affecting many children. Despite the availability of several therapies for NE, there is insufficient evidence to support the use of any one intervention and as such this randomised placebo-controlled phase II trial will be an important contribution to understanding potential new treatments for this condition.

Trial registration

Australian and New Zealand Clinical Trials Registration Number:12618000288224.

Protocol: 23 February 2018, version 1.1.