bluuebunny/crossref_metadata_2025 huggingface dataset:
Pseudomyxoma peritonei diagnosed 19 years after appendicectomy
Authors: Wrafter Paula F , Connelly Tara , Khan Jody Sultan Ali , Joyce William P
Published: October 2015

Pseudomyxoma peritonei (PMP) is an uncommon clinical finding describing the intraperitoneal accumulation of abundant mucinous, jelly-like material. This entity may represent a spectrum of diseases ranging from mucinous ascites, commonly associated with ruptured epithelial tumours of the appendix, to frank mucinous carcinomatosis. In cases of appendiceal origin, the patient may present with signs and symptoms of acute appendicitis, and thus careful diagnosis must be made in order to correctly and appropriately guide management. This may include a combination of surgical debulking with or without intraperitoneal or systemic chemotherapy. We present a 52-year-old woman with a 4-month history of abdominal pain and distension with a previous appendicectomy 19 years earlier. Radiological and pathological investigations diagnosed a probable PMP secondary to ruptured appendicitis many years ago. We describe her unique case, with emphasis on length of time to diagnosis and clinical management by surgical cytoreduction alone.
Freeman-Sheldon syndrome in a 29-year-old woman presenting with rare and previously undescribed features
Authors: Chamberlain Robert L , Poling Mikaela I , Portillo Augusto L , Morales Andrés , Ramirez Rigoberto RT , McCormick Rodger J
Published: October 2015

Described are previously unreported features presenting in a case of Freeman-Sheldon syndrome (FSS); these apparently unreported features may substantively inform current therapy and further research. While considered to be primarily a craniofacial syndrome, FSS is officially described as a myopathic distal arthrogryposis. Clinical diagnosis requires microstomia, whistling-face appearance (pursed lips), H-shaped chin dimpling, nasolabial folds, and two or more contractures of hands and feet. Spinal deformities, metabolic and gastroenterological problems, other dysmorphic craniofacial characteristics, and visual and auditory impairments are frequent findings. Differential diagnoses include: distal arthrogryposis type 1, 2B (Sheldon-Hall syndrome) and 3; arthrogryposis multiplex congenita and isolated non-syndromic deformities. Expression is frequently from new allelic variation. Important implications exist for geneticists, neonatologists, paediatricians, plastic surgeons and others to facilitate patients’ legitimate opportunity to meaningfully overcome functional limitations and become well. Despite complexities and complications, early craniofacial surgery and aggressive physiotherapy for limb contractures can achieve excellent outcomes for patients.
Pemphigus vulgaris: a rare cause of dysphagia
Authors: Al-Janabi Ali , Greenfield Simon
Published: October 2015

Pemphigus vulgaris is a rare autoimmune blistering disease of the skin and mucous membranes. The case reported presented unusually with dyspepsia that was not responsive to protein pump inhibitor (PPI) therapy. This progressed to severe dysphagia and odynophagia. An esophagogastroduodenoscopy showed extensive ulceration of the esophagus, and direct immunofluorescence of an esophageal biopsy showed bright intercellular staining with C3 and IgG, confirming the diagnosis of pemphigus vulgaris. Immunological remission was achieved after a number of courses of pulsed intravenous methylprednisolone and cyclophosphamide. The patient has remained in remission for 5 years, but has required regular dilation of esophageal strictures for symptom relief. During this period, a chronic lymphocytosis was incidentally noted on routine blood tests, and chronic lymphocytic leukaemia was diagnosed. It is essential to investigate PPI-resistant symptoms, dysphagia and odynophagia, as they may indicate a serious underlying cause.
Life-threatening ACE inhibitor-induced angio-oedema successfully treated with icatibant: a bradykinin receptor antagonist
Authors: Ostenfeld Sarah , Bygum Anette , Rasmussen Eva Rye
Published: October 2015

We present a case of a 75-year-old woman treated with an ACE inhibitor, who presented with angio-oedema of the tongue and had difficulty speaking. No symptoms of anaphylaxis or urticaria were present. The patient was treated intravenously with antihistamine and glucocorticoid in combination with adrenaline inhalations. After 6 h in the hospital the swelling progressed, and the patient was admitted to the intensive care unit and treated with one injection of icatibant—a bradykinin receptor antagonist. The patient reported subjective relief after 20–30 min and the swelling resolved within 2 h. Although the angio-oedema was potentially life threatening, the patient avoided intubation and mechanical ventilation. ACE inhibitor-induced angio-oedema is most likely caused by an accumulation of bradykinin and substance P. Consequently, a bradykinin receptor antagonist is the rational treatment of choice instead of antiallergic medications, which have no proven efficacy in this condition.
Rapid diagnostic pathways for suspected colorectal cancer: views of primary and secondary care clinicians on challenges and their potential solutions
Authors: Redaniel Maria Theresa , Ridd Matthew , Martin Richard M , Coxon Fareeda , Jeffreys Mona , Wade Julia
Published: October 2015

Objectives

To ascertain the challenges associated with implementation of the 2-week wait referral criteria and waiting time targets for colorectal cancer and to identify recommendations for improvements to the pathway.

Design

Qualitative research using semistructured interviews and applying thematic analysis using the method of constant comparison.

Setting

10 primary care surgeries and 6 secondary care centres from 3 geographical areas in the England.

Participants

Purposive sample of 24 clinicians (10 general practitioners (GPs), 7 oncologists and 7 colorectal surgeons).

Results

GPs and specialists highlighted delays in patient help-seeking, difficulties applying the colorectal cancer referral criteria due to their low predictive value, and concerns about the stringent application of targets because of potential impact on individual care and associated penalties for breaching. Promoting patient awareness and early presentation, clarifying predictive symptoms, allowing flexibility, optimising resources and maximising care coordination were suggested as improvements.

Conclusions

Challenges during diagnosis and treatment persist, with guidelines and waiting time targets producing the perception of unintended harms at individual and organisational levels. This has led to variations in how guidelines are implemented. These require urgent evaluation, so that effective practices can be adopted more widely.
QUASI-EXPERIMENTAL STUDY OF A LEARNING COLLABORATIVE TO IMPROVE PUBLIC PRESCHOOL QUALITY AND CHILDREN'S LANGUAGE OUTCOMES IN CHILE
Authors: Arbour MaryCatherine , Yoshikawa Hirokazu , Atwood Sidney , Duran Francis Romina , Godoy Felipe , Trevino Ernesto , Snow Catherine E
Published: October 2015

Background

Decades of research shows that early childhood interventions can positively impact children's short- and long-term health, academic and economic outcomes, but that interventions' effectiveness depend on their quality. Interest in continuous quality improvement (CQI) methods is rising among early childhood clinicians, educators and policymakers. We report on a study that integrated CQI into an existing professional development program that aimed to improve the quality of preschool education in Chile and the outcomes of participating children.

Objectives

To analyze how CQI methods can be applied in education to impact child development, in the context of a project centered on literacy instructional strategies supported by health, socio-emotional skills and family involvement.

Methods

Teachers from 40 low-income classrooms received training in instructional strategies. A subset of 18 early adopters participated in a Collaborative that taught CQI methods and facilitated shared learning. Children's language skills were assessed at the beginning and end of a 2 year period using an internationally validated test. Quasi-experimental methods (propensity scores and inverse-propensity weighting) were used to estimate the impact of professional development in instructional strategies combined with CQI methods versus professional development in instructional strategies alone.

Results

Children in classrooms whose teachers received professional development in language instruction plus CQI methods had larger increases in language skills (vocabulary, effect size 0.31, p<0.05) than children whose teachers received language instructional strategies alone.

Conclusions

CQI may be a valuable addition to promote change via professional development in low-income schools in Chile and warrant further examination for early childhood interventions in diverse contexts globally.
IDENTIFYING PRIORITIES FOR IMPROVED CHILD HEALTHCARE: A MIXED METHODS ANALYSIS OF SAFETY INCIDENT REPORTS
Authors: Rees Philippa , Edwards Adrian , Powell Colin , Williams Huw , Hibbert Peter , Makeham Meredith , Luff Donna , Parry Gareth , Sheikh Aziz , Donaldson Liam , Carson-Stevens Andrew
Published: October 2015

Background

Globally children are failed on numerous indicators of care quality, most of which is provided in the primary care setting. There is a paucity of research and development to explain iatrogenic harm in the primary care setting, not least safety events involving children.

Objectives

We identified priority issues (by frequency and level of harm) reported by clinicians from the England and Wales National Reporting and Learning System (NRLS). The concepts and content within reports empirically informed a systems-level Driver diagram for improvement of child health.

Methods

We undertook a retrospective cross-sectional mixed methods study of safety incident reports from primary care involving ‘unwell’ children between 2003–2013. We classified incident types, contributory factors, and harm outcomes. Data underwent exploratory analysis to explore the relationship between variables, and thematic analysis provided in-depth contextual insights. Subject matter experts identified key drivers for improvement.

Results

Of 2191 incidents identified, priority improvement areas included: medication provision in the community pharmacy setting; diagnosis, assessment, and timely referral of acutely unwell children in out of hours care settings; and communication with and about the child. Reported causes are outlined in the attached Ishikawa diagrams (figures 1–3) and the related Driver diagram (figure 4) summarises opportunities to mitigate priority concepts.

Conclusions

Analysis of incident reports can be used to inform national-level improvement initiatives when there is a paucity of existing available evidence. Further validation and development of the proposed designs are needed with the clinical teams responsible for care delivery.

Figure 1

Ishikawa diagram illustrating the factors and incidents frequently reported as contributing to medication incidents.

Figure 2

Ishikawa diagram illustrating the factors and incidents frequently reported as contributed to diagnosis, assessment, and referral incidents.

Figure 3

Ishikawa diagram illustrating the factors and incidents frequently reported as contributing to communication incidents.

Figure 4

Driver diagram illustrating opportunities to improve the safety of primary care for children.
TRAVELLING WITH THE SYSTEMS QUALITY IMPROVEMENT MODEL IN LACS HEALTH DISTRICT IN TOGO TO REDUCE TUBERCULOSIS DEATHS
Authors: Afanvi Kossivi , Kassankogno Yao , Ekouevi Koumavi
Published: October 2015

Background

The ultimate goal of every tuberculosis (TB) treatment program is a high treatment success rate. Treatment success is extremely important because, when the rate is high, it significantly contributes to declining numbers of new cases by reducing the number and period of infectious cases, TB morbidity and mortality, and prevents the emergence of resistant strains.

Objectives

Decrease TB mortality by increasing pulmonary TB patients' treatment success rate to at least 85% in Lacs Health District by the end of July 2014.

Methods

A systems and dialogic analysis of the public health system related to TB patients' treatment revealed that it was not performing well; we found weak coverage and quality of TB services, a poorly-functioning TB health information system, poor-performing health workforce, poor availability of HIV tests and antiretroviral for TB patients, and low degree of patients' participation in their care. We redesigned the system to correct those weaknesses. The effectiveness of these changes was monitored using plan, do, study, act (PDSA) cycles.

Results

We increased TB patient success rate from 80% to 95% between February 2012 and July 2014.The mortality rate dropped from 13% to 3% and the failure to follow-up rate dropped from 3% to 2%.

Conclusions

Health systems performance depends on the closeness of services to population; skilled workforce; the ability to collect and analyze data and use information for action; population empowerment, and good management and improvement capabilities of management team especially public health directors. It is highly important that every district health management team member develops improvement capabilities.

Figure 1

Systems Quality Improvement Model (SQIM) conceptual framework.

Figure 2

TB treatment success rate P chart.

Figure 3

TB mortality rate P chart.

Figure 4

TB treatment failure to follow-up rate P chart.
COMMUNITY COLLABORATION IMPROVES CARE AND REDUCES REHOSPITALIZATIONS FOR HEART FAILURE PATIENTS
Authors: Thompson Christine , Kell Charlene , Banerjee Dipanjan
Published: October 2015

Background

HF is a leading cause of hospitalization for adults, with highest readmission rates occurring 30 days post-discharge. Hospitals are instituting evidence-based strategies to improve patient transitions from hospital to home and reduce 30-day all-cause readmissions. Impacting 90-day readmissions poses a greater challenge. Incorporating community partners into care transitions is critical for successful outcomes, particularly considering new bundled payment models. Patients discharging to skilled nursing facilities (SNFs) or with home health agency (HHA) services are often more vulnerable and at heightened risk.

Objectives

Create a collaborative partnership between one medical center and local SNFs and home health agencies (HHA) to improve sustained HF patient outcomes and reduce hospital readmissions.

Methods

Monthly multidisciplinary meetings were held with local SNF and HHA participants. Collaborative goals included identifying gaps in patient transitions between care settings and creating an evidence-based community standard for HF patient care. Corollary aims were to align quality care practices, share outcomes data and create solutions for identified barriers to optimal care transitions.

Results

Comparing baseline data (476 HF discharges) to a year post-implementation of our intervention bundle (412 discharges), overall 30-day readmissions reduced from 19% to 9% while 90-day readmissions improved from 31% to 19%. 30-day rehospitalizations for SNF patients declined from and were decreased for patients who discharged with home health services by 26%.

Conclusions

Building relationships fostering communication and collaboration among community partners is a key strategy to reduce avoidable rehospitalizations and sustain improved patient outcomes.

Figure 1

Primary Diagnosis HF Patient Readmissions by Index Disposition (pre/post interventions).
CAN ORGANISATIONAL RESTRUCTURING OF HOSPITALS IMPROVE QUALITY AND SAFETY? THE EXPERIENCE AT SYDNEY CHILDREN'S HOSPITALS NETWORK
Authors: Farrow Glen
Published: October 2015

Background

In New South Wales serious publicised adverse events in 2006 brought quality and safety to community attention. The Garling external review of 2008 made 139 recommendations, including the creation a single children's hospital. This was addressed by the creation of the Sydney Children's Hospitals Network (SCHN) in June 2010. SCHN brought together the boards and management structures of Sydney Children's Hospital Randwick and the Children's Hospital at Westmead.

Objectives

In business, restructures are often implemented to improve performance, safety and customer satisfaction, but improvement has been difficult to demonstrate in healthcare. This study asks whether quality and safety have been improved by the formation of SCHN in June 2010.

Methods

Quality data within IHI domains of quality (safe, effective, patient-centred, timely, efficient) has been compared pre and post SCHN. Results are analysed in split control charts, with Chi squared analysis, P scores and benchmarking with data from the Clinical Excellence Commission NSW, and “Solutions For Patient Safety” a North American collaboration of 80 children's hospitals. Restructuring of clinical governance was based on the principals of alignment, networks and improving situational awareness.

Results

Significant improvement was seen in several parameters of quality and safety including fewer serious incidents, fewer medico legal cases, fewer medication errors, better access to emergency departments, fewer complaints and maintaining readmission rates despite a 20% increase in activity.

Conclusions

At SCHN organisational restructuring has improved quality and safety performance. Structural alignment within agreed quality standards, network roles that share learnings between facilities and better situational awareness are thought to be responsible.

Figure 1

SCHN inpatient activity including day cases 2005–2014.

Figure 2

SCHN SAC 1 and 2 incidents as a % of separation.

Figure 3

Total incidents reported SCHN as a percentage of separations.

Figure 4

Total incidents reported at CHW increased p<0.05.

Figure 5

Total incidents reported at SCH decreased p<0.05.

Figure 6

SAC 1s at CHW: harm is reduced.

Figure 7

Time delay in medicolegal notifications.

Figure 8

SCHN Medicolegal cases reduced (p<0.05).

Figure 9

SCHN CVAD infections: benchmarking with North America.

Figure 10

SCHN medication errors: benchmarking with North America.

Figure 11

SCHN medication errors 2009–2014.

Figure 12

Total number of ward arrests: benchmarking with Cincinnati Children's Medical Centre.

Figure 13

SCHN readmission rates increased at 28 days.

Figure 14

SCHN “Did not wait” significantly reduced (p<0.01).

Figure 15

SCHN formal complaints reduced (p<0.1).
INCREASING TRICHOMONAS TESTING IN THE PEDIATRIC EMERGENCY DEPARTMENT
Authors: Stukus Kristin , Cripe Timothy , Cohen Daniel , Craig Farah , Sawicki Laura , Weisbecker Lindsey , Hollar Jessica , Kurtovic Kelli , Buckingham Don
Published: October 2015

Background

Trichomonas is a common adolescent sexually transmitted infection (STI), causing vaginal pain, discharge and dysuria. Affected individuals are more likely to have co-occurrence of other STIs as well, including HIV. Improving the Trichomonas testing process in the ED may result in a higher, targeted testing rate and thus improved detection and treatment.

Objectives

To increase Trichomonas testing in the ED among high-risk adolescent patients from 40% in July 2014 to 100% by March 31,2015 and sustain through 2015.

Methods

A team of MDs, CRNPs, RNs and QI professionals assembled in 2014 to address this need. Six months data was collected to define the baseline rate of testing. Deploying the IHI Model for Improvement, the team formulated an aim statement and identified key drivers. Using root cause analysis, interventions were proposed for each problem area. A series of PDSA cycles were undertaken, and the results of each were monitored using a control chart. These interventions included increasing awareness and education for clinical staff; combined test availability; use of order sets for STI; and adding Licensed Professional Initiated Protocol to nurse ordering practice. This was all done in conjunction with feedback for individual missed cases.

Results

Over an 18 month period, the rate of Trichomonas testing in the ED rose with each intervention: from 25% (January 2014) to 98% (March 2015) which has been sustained through August of 2015.

Conclusions

Improving the process of Trichomonas testing of symptomatic adolescents in the ED, results in higher screening rates among ED pediatric providers.

Figure 1

Trichomonas testing in the ED.

Figure 2

Adolescents with STD and Trichomonas testing.
Improving venous thromboembolism risk assessment compliance using the electronic tool in admitted medical patients
Authors: Taha, MD Haytham , J. Raji, RN Salama , Ellahham, MD Samer , Bashir, MD Nihal , Al hanaee, MD Manar , Boharoon, MD Hessa , AlFalahi, MD May
Published: October 2015

Sheikh Khalifa Medical City (SKMC) in Abu Dhabi is the main tertiary care referral hospital in the United Arab Emirates (UAE) with 560 bed capacity that is fully occupied most of the time.

SKMC senior management has made a commitment to make quality and patient safety a top priority. Venous thromboembolism (VTE) risk assessment has been identified as a critical patient safety measure and key performance indicator. The electronic VTE risk assessment form a computerized decision support tool was introduced to improve adherence with deep venous thrombosis (DVT) prophylaxis recommendations. A multidisciplinary task force team was formed and led this quality improvement project. The purpose of this publication is to indicate the quality improvement interventions implemented to enhance compliance with VTE risk assessment and the outcomes of those interventions.

We chose to conduct the pilot study in General Medicine as it is the busiest department in the hospital. The study period was from April 2014 till August 2015.The lessons learned were disseminated throughout the hospital. Our aim was to improve VTE risk assessment compliance by using the electronic form in order to ensure patient safety and reduce preventable harm. VTE risk assessment compliance improved in general medicine from 4% to 98%, and overall SKMC compliance from 21% to above 90%.
Interview with Prof. Emmanuel Tsesmelis and Prof. Albert De Roeck from CERN
Authors:   APPN Editorial Team
Published: October 2015

Professor Emmanuel Tsesmelis: is an experimental particle physicist with a career spanning scientific research, academic teaching, science communication, international relations and management at CERN and at several universities. He is a Senior Physicist and Deputy Head of International Relations in CERN's Director-General Unit and a Visiting Professor in Particle and Accelerator Physics at the University of Oxford. He is an elected Fellow of the Australian Institute of Physics and a supernumerary member of Jesus College, Oxford.

Professor Albert De Roeck: is a senior research scientist and staff member at CERN. He is also a professor at the University of Antwerp (Belgium) and a visiting professor at the Institute of Particle Physics and Phenomenology in Durham (UK). He obtained his PhD at the university of Antwerp on an experiment at CERN, studying the multiparticle dynamics in hadron-hadron interactions, by colliding meson beams on protons and nuclear targets. After his PhD, Albert spent 10 years at the German particle physics laboratory, DESY, where he and his team made very precise measurements of the quark and gluon structure of the proton. In the late 90's his interest turned to the possibility to discover new physics, in particular Supersymmetry and Extra Dimensions, and he returned to CERN and joined an experiment at the large electron-positron collider LEP. Albert is now one the leaders of the physics program and preparation for physics analysis at the CMS experiment at the LHC.
IUPAP Office Moved from London to Singapore
Authors:   APPN Editorial Team
Published: October 2015

The International Union of Pure and Applied Physics (IUPAP) was established in 1922 in Brussels with 13 member countries. Its aim is to support and promote Physics and Physics learning worldwide. The Union is governed by its General Assembly which meets every three years. The Council is its top executive body, supervising the activities of the 19 specialized International Commissions and 4 Affiliated Commissions.
Left ventricular remodeling during and after 60 days of sedentary head-down bed rest
Authors: Westby Christian M. , Martin David S. , Lee Stuart M. C. , Stenger Michael B. , Platts Steven H.
Published: October 2015

Short periods of weightlessness are associated with reduced stroke volume and left ventricular (LV) mass that appear rapidly and are thought to be largely dependent on plasma volume. The magnitude of these cardiac adaptations are even greater after prolonged periods of simulated weightlessness, but the time course during and the recovery from bed rest has not been previously described. We collected serial measures of plasma volume (PV, carbon monoxide rebreathing) and LV structure and function [tissue Doppler imaging, three-dimensional (3-D) and 2-D echocardiography] before, during, and up to 2 wk after 60 days of 6° head down tilt bed rest (HDTBR) in seven healthy subjects (four men, three women). By 60 days of HDTBR, PV was markedly reduced (2.7 ± 0.3 vs. 2.3 ± 0.3 liters, P < 0.001). Resting measures of LV volume and mass were ∼15% ( P < 0.001) and ∼14% lower ( P < 0.001), respectively, compared with pre-HDTBR values. After 3 days of reambulation, both PV and LV volumes were not different than pre-HDTBR values. However, LV mass did not recover with normalization of PV and remained 12 ± 4% lower than pre-bed rest values ( P < 0.001). As previously reported, decreased PV and LV volume precede and likely contribute to cardiac atrophy during prolonged LV unloading. Although PV and LV volume recover rapidly after HDTBR, there is no concomitant normalization of LV mass. These results demonstrate that reduced LV mass in response to prolonged simulated weightlessness is not a simple effect of tissue dehydration, but rather true LV muscle atrophy that persists well into recovery.
Sulforaphane mitigates muscle fibrosis inmdxmice via Nrf2-mediated inhibition of TGF-β/Smad signaling
Authors: Sun Chengcao , Li Shujun , Li Dejia
Published: October 2015

Sulforaphane (SFN), an activator of NF-E2-related factor 2 (Nrf2), has been found to have an antifibrotic effect on liver and lung. However, its effects on dystrophic muscle fibrosis remain unknown. This work was undertaken to evaluate the effects of SFN-mediated activation of Nrf2 on dystrophic muscle fibrosis. Male mdx mice (age 3 mo) were treated with SFN by gavage (2 mg/kg body wt per day) for 3 mo. Experimental results demonstrated that SFN remarkably attenuated skeletal and cardiac muscle fibrosis as indicated by reduced Sirius Red staining and immunostaining of the extracellular matrix. Moreover, SFN significantly inhibited the transforming growth factor-β (TGF-β)/Smad signaling pathway and suppressed profibrogenic gene and protein expressions such as those of α-smooth muscle actin (α-SMA), fibronectin, collagen I, plasminogen activator inhibitor-1 (PAI-1), and tissue inhibitor metalloproteinase-1 (TIMP-1) in an Nrf2-dependent manner. Furthermore, SFN significantly decreased the expression of inflammatory cytokines CD45, TNF-α, and IL-6 in mdx mice. In conclusion, these results show that SFN can attenuate dystrophic muscle fibrosis by Nrf2-mediated inhibition of the TGF-β/Smad signaling pathway, which indicates that Nrf2 may represent a new target for dystrophic muscle fibrosis.
Molecular Imaging with MRI: Potential Application in Pancreatic Cancer
Authors: Chen Chen , Wu Chang Qiang , Chen Tian Wu , Tang Meng Yue , Zhang Xiao Ming
Published: October 2015

Despite the variety of approaches that have been improved to achieve a good understanding of pancreatic cancer (PC), the prognosis of PC remains poor, and the survival rates are dismal. The lack of early detection and effective interventions is the main reason. Therefore, considerable ongoing efforts aimed at identifying early PC are currently being pursued using a variety of methods. In recent years, the development of molecular imaging has made the specific targeting of PC in the early stage possible. Molecular imaging seeks to directly visualize, characterize, and measure biological processes at the molecular and cellular levels. Among different imaging technologies, the magnetic resonance (MR) molecular imaging has potential in this regard because it facilitates noninvasive, target-specific imaging of PC. This topic is reviewed in terms of the contrast agents for MR molecular imaging, the biomarkers related to PC, targeted molecular probes for MRI, and the application of MRI in the diagnosis of PC.
Mechanisms and Clinical Applications of Genome Instability in Multiple Myeloma
Authors: Cagnetta Antonia , Lovera Davide , Grasso Raffaella , Colombo Nicoletta , Canepa Letizia , Ballerini Filippo , Calvio Marino , Miglino Maurizio , Gobbi Marco , Lemoli Roberto , Cea Michele
Published: October 2015

Ongoing genomic instability represents a hallmark of multiple myeloma (MM) cells, which manifests largely as whole chromosome- or translocation-based aneuploidy. Importantly, although it supports tumorigenesis, progression and, response to treatment in MM patients, it remains one of the least understood components of malignant transformation in terms of molecular basis. Therefore these aspects make the comprehension of genomic instability a pioneering strategy for novel therapeutic and clinical speculations to use in the management of MM patients. Here we will review mechanisms mediating genomic instability in MM cells with an emphasis placed on pathogenic mutations affecting DNA recombination, replication and repair, telomere function and mitotic regulation of spindle attachment, centrosome function, and chromosomal segregation. We will discuss the mechanisms by which genetic aberrations give rise to multiple pathogenic events required for myelomagenesis and conclude with a discussion of the clinical applications of these findings in MM patients.
High-Dose FOLFIRI plus Bevacizumab in the Treatment of Metastatic Colorectal Cancer Patients with Two Different UGT1A1 Genotypes: FFCD 0504 Study
Authors: Manfredi Sylvain , Bouché Olivier , Rougier Philippe , Dahan Laetitia , Loriot Marie Anne , Aparicio Thomas , Etienne Pierre Luc , Lafargue Jean Pierre , Lécaille Cedric , Legoux Jean Louis , Le Malicot Karine , Maillard Emilie , Lecomte Thierry , Khemissa Faiza , Breysacher Gilles , Michel Pierre , Mitry Emmanuel , Bedenne Laurent
Published: October 2015

High-dose FOLFIRI has an acceptable safety profile and promising efficacy. UDP-glucuronosyltransferase: (UGT1A1) polymorphism may be predictive of toxicity and efficacy of irinotecan. This phase II study aimed to evaluate the combination of high-dose FOLFIRI plus bevacizumab in patients with previously untreated metastatic colorectal cancer (MCRC) based on their UGT1A1 genotype. Patients with the UGT1A1 *1/*1 (group 1) or *1/*28 (group 2) genotype received bevacizumab plus high-dose FOLFIRI every 2 weeks. Using the Bryant and Day design with objective response rate and toxicity as the primary endpoints, 54 patients in each group were required with a planned interim analysis after inclusion of 17 patients per group. We planned to stop the trial at the interim analysis if ≤7 patients exhibited an objective response (OR) and/or ≥3 patients exhibited severe toxicity. At the interim analysis, ORs were higher than the number expected: 52.9% (group 1) and 58.8% (group 2). More than three toxic events occurred in both groups and, according to the interim analysis rule, the trial was closed due to unacceptable toxicity. Recruitment was stopped when 86 patients were included and an analysis on overall population was done for overall survival (OS) and progression-free survival (PFS). The median PFS was 10.7 months (group 1) and 10.4 months (group 2). The median OS was 25.5 months (group 1) and 23.9 months (group 2). This trial does not support the use of the intensive treatment with HD-FOLFIRI plus bevacizumab combination for MCRC in patients with the UGTA1*1/UGT1A1*1 or UGT1A1*1/UGT1A1*28 genotype. Mol Cancer Ther; 14(12); 2782–8. ©2015 AACR.
Apolipoprotein E e4 and Cognitive Function: A Modifiable Association? Results from Two Independent Cohort Studies
Authors: Perna Laura , Mons Ute , Rujescu Dan , Kliegel Matthias , Brenner Hermann
Published: October 2015

Background: The apolipoprotein E (APOE) e4 genetic polymorphism is a major risk factor for Alzheimer' s disease, hence the possible prevention of its detrimental effects on cognition is of high relevance. Methods: We used linear regression models to assess associations of APOE e4 with cognitive performance in a population-based cohort study (n = 1,434) and in a cohort of patients with coronary heart disease (n = 366), and restricted cubic splines to explore dose-response relationships between serum cholesterol levels and cognition depending on APOE polymorphism. Results: The association of APOE e4 with cognitive function was strongly amplified in the presence of hypercholesterolemia and cardiovascular disease in both independent cohorts; hypercholesterolemia was associated with cognitive function only among APOE e4 carriers in the presence of cardiovascular disease. The interaction effect between APOE genotype and hypercholesterolemia was statistically significant in both cohorts. Conclusions: The detrimental effects of APOE e4 polymorphism on cognition may strongly depend on modifiable risk factors.
Intervention Associated Acute Kidney Injury and Long-Term Cardiovascular Outcomes
Authors: Saratzis Athanasios , Harrison Seamus , Barratt Jonathan , Sayers Robert D. , Sarafidis Pantelis A. , Bown Matthew J.
Published: October 2015

Background: Acute kidney injury (AKI) has been associated with all-cause short- and long-term mortality. However, its association with cardiovascular (CV) events remains unclear. We sought to investigate this in patients undergoing open (OAR) or endovascular (EVAR) abdominal aortic aneurysm repair, as they are likely to develop both AKI and CV morbidity. A meta-analysis was subsequently performed to confirm this in other CV-interventions. Methods: AKI-incidence was assessed in a multicentre-cohort of 1,068 patients undergoing EVAR (947 individuals) or OAR electively using the ‘Acute Kidney Injury Network' criteria. A composite-endpoint was used, consisting of non-fatal myocardial infarction (MI), stroke, vascular event, hospitalisation due to heart failure and CV death. A systematic literature review identified studies reporting AKI-incidence and CV events. Risk ratios (RRs) at 1 and 5 years were combined using meta-analysis. Results: During a median follow-up of 62 months (range 11-121), AKI was associated with CV events on adjusted (for CV risk-factors) analyses (Incidence 36% of EVAR, 32% of OAR patients; hazard ratio 1.73, 95% CI 1.06-3.39, p = 0.03) for the overall population. In the meta-analysis, 7 studies reported incidence of MI on 23,936 patients 1-year after coronary intervention (PCI) with a pooled RR of 1.76 (95% CI 1.45-2.83, p < 0.001); at 2 years, 3 studies reported MI incidence on 17,773 patients after PCI with a pooled RR of 1.34 (95% CI 1.10-1.63, p = 0.003). MI-incidence was reported 5 years after cardiac surgery by 3 studies (33,701 patients) with a pooled RR of 1.60 (95% CI 1.43-1.81). Conclusion: AKI is associated with long-term CV events after surgery or endovascular intervention.
A Trial of Lifestyle Modification on Cardiopulmonary, Inflammatory, and Metabolic Effects among Obese with Chronic Kidney Disease
Authors: Navaneethan Sankar D. , Fealy Ciaran E. , Scelsi Amanda C. , Arrigain Susana , Malin Steven K. , Kirwan John P.
Published: October 2015

Background: The feasibility and benefits of lifestyle intervention in chronic kidney disease (CKD) patients who are obese has not been well studied. We examined the early effects of an exercise plus weight loss intervention on body composition, exercise capacity, metabolic parameters and kidney function in obese subjects with CKD. Methods: Nine subjects (median age 57 years, body mass index (BMI) 43.9) underwent a lifestyle intervention program that included supervised aerobic exercise (i.e. ∼85% maximum heart rate) and dietary counseling (500 kcal reduction in daily caloric intake). Body composition (iDXA), exercise capacity (maximal oxygen consumption), quality of life, insulin resistance (Matsuda index), inflammation (high sensitivity C-reactive protein), adipokines (leptin and total adiponectin) and kidney function (iothalamate glomerular filtration rate) were measured at baseline and after 12 weeks of the intervention. Changes in parameters were compared using the Wilcoxon signed-rank test. Results: After 12 weeks of intervention, there was a significant decrease in BMI and fat mass (median -4.9 kg (25th-75th percentile -5.9 to -3.0)). There was a significant increase in exercise capacity (3.7 ml/kg/min (3.0-4.7)), along with improvements in insulin sensitivity (0.55 (0.43-1.2)), total adiponectin (780.9 μg/ml (262.1-1,497.1)) and leptin (-5.1 ng/ml (-14.5 to -3.3)). There were improvements in biomarkers of kidney disease very quality of life measures, but kidney function remained unchanged. Conclusion: Lifestyle modification is feasible in obese patients with CKD and produces weight loss that is related to improvements in exercise capacity, insulin resistance and adipokines. Whether lifestyle-induced weight loss and fitness can be sustained and whether it will mediate improvements in kidney function over time merits further investigation.
Association Analysis of the Reticulon 1 Gene in End-Stage Kidney Disease
Authors: Bonomo Jason A. , He John Cijiang , Fan Ying , Hicks Pamela J. , Lea Janice P. , Okusa Mark D. , Bowden Donald W. , Freedman Barry I.
Published: October 2015

Background: The reticulon 1 gene (RTN1) encodes reticulons, endoplasmic reticulum stress proteins recently implicated in kidney disease progression. Methods:RTN1 single nucleotide polymorphisms (SNPs) were tested for association with type 2 diabetes (T2D)-associated end-stage kidney disease (ESKD) in African Americans (AAs) and European Americans (EAs), and AAs with non-diabetic ESKD. RTN1 SNPs that were associated with T2D-ESKD in AA cases compared to non-nephropathy controls were identified from a discovery genome-wide association study (n = 1,797), then tested for replication in 1,847 additional AA T2D-ESKD cases and controls. Results: Three intronic RTN1 variants were nominally associated with T2D-ESKD in both discovery and replication analyses: rs1952034, rs12431381 and rs12434215 (additive models); combined T2D-ESKD (discovery + replication) p values were 0.015-3.0 × 10-4 (ORs 0.67-0.77; minor alleles protective). In addition, rs12434215 was weakly associated with T2D-ESKD in 557 EA T2D-ESKD cases contrasted with 753 EA non-nephropathy controls (p = 0.019; OR 0.69, dominant model). Nominal association extended to non-diabetic causes of ESKD in 1,459 additional AA cases (rs12431381 and rs12434215 p values 0.014-0.015; OR 0.77). An all-cause ESKD association analysis contrasted the 3,594 AA ESKD cases with 1,489 AA non-nephropathy controls and detected association with rs12434215 (p = 6.7 × 10-4, OR 0.73) and rs12431381 (p = 7.5 × 10-4, OR 0.75) in dominant models. Of the 3 SNPs, only rs12434215 was weakly associated with T2D per se when contrasting T2D non-nephropathy cases with non-diabetic controls (additive model p = 0.032 AAs; p = 0.048 EAs). Conclusions: These results suggest evidence of genetic association between common variants in RTN1 and ESKD in AAs and EAs.
Comparison of Two Different Ultrasound Systems for the Evaluation of Tissue Doppler Velocities in Fetuses
Authors: Cruz-Lemini Mónica , Valenzuela-Alcaraz Brenda , Figueras Francesc , Sitges Marta , Gómez Olga , Martínez Josep María , Bijnens Bart , Gratacós Eduard , Crispi Fátima
Published: October 2015

Introduction: Recent studies have reported variations of up to 30% between different ultrasound machines for tissue Doppler imaging (TDI), a problem that can significantly impact clinical diagnosis, patient management and research studies. The objective of this study was to assess repeatability and agreement between fetal myocardial peak velocities evaluated by TDI with two different ultrasound systems. Materials and Methods: Systolic (S'), early (E') and late (A') diastolic myocardial peak velocities at mitral and tricuspid annuli as well as at the basal septum were evaluated by spectral TDI in 150 fetuses using two different ultrasound systems: Siemens Antares (Siemens Medical Systems, Malvern, Pa., USA) and Vivid Q (General Electric Healthcare, Horten, Norway). A method comparison study was performed, calculating intraclass correlation coefficients (ICC), and agreement was assessed by Bland-Altman plots. Results: Annular peak velocities showed lower values when measured by Vivid Q compared to values measured by Siemens Antares. ICC ranged from 0.07 (septal S') to 0.33 (right A'), showing very poor repeatability for clinical application. Agreement between the two systems was also poor, with high coefficients of variation for all measurements. Conclusions: Fetal annular peak velocities obtained with different ultrasound systems are not directly comparable. This is consistent with previous data in adults and warrants the need of system-specific reference values, suggesting that the same ultrasound machine should be used for longitudinal follow-up.
Capsule Endoscope Aspiration after Repeated Attempts for Ingesting a Patency Capsule
Authors: Mannami Tomohiko , Ikeda Genyo , Seno Satoru , Sonobe Hiroshi , Fujiwara Nobukiyo , Komoda Minori , Edahiro Satoru , Ohtawa Yasuyuki , Fujimoto Yoshimi , Sato Naohiro , Kambara Takeshi , Waku Toshihiko
Published: October 2015

Capsule endoscope aspiration into the respiratory tract is a rare complication of capsule endoscopy. Despite the potential seriousness of this complication, no accepted methods exist to accurately predict and therefore prevent it. We describe the case of an 85-year-old male who presented for evaluation of iron deficiency anemia. He complained of dysphagia while ingesting a patency capsule, with several attempts over a period of 5 min before he was successful. Five days later, he underwent capsule endoscopy, where he experienced similar symptoms in swallowing the capsule. The rest of the examination proceeded uneventfully. On reviewing the captured images, the capsule endoscope was revealed to be aspirated, remaining in the respiratory tract for approximately 220 s before images of the esophagus and stomach appeared. To our knowledge, this is the first documented case of a patient who experienced capsule endoscope aspiration after ingestion of a patency capsule. This case suggests that repeated attempts required for ingesting the patency capsule can predict capsule endoscope aspiration. We presume that paying sufficient attention to the symptoms of a patient who ingests a patency capsule could help us prevent serious complications such as aspiration of the capsule endoscope. In addition, this experience implies the potential risk for ingesting the patency capsule. We must be aware that the patency capsule could also be aspirated and there may be more unrecognized aspiration cases.
СТРАТЕГІЯ СТВОРЕННЯ ТА ОЦІНЮВАННЯ ФУНКЦІОНУВАННЯ СИСТЕМ УПРАВЛІННЯ ЯКІСТЮ МЕДИЧНОЇ ОСВІТИ. ДРУГЕ ПОВІДОМЛЕННЯ. ТРАНСФОРМАЦІЯ ІДЕЙ УПРАВЛІННЯ ЯКІСТЮ НА ОСНОВІ ПРИНЦИПУ «ДУАЛЬНИХ СИСТЕМ»
Authors: Mintser O. P. , Tolstanov O. K. , Zahoriy H. V.
Published: October 2015

It was proposed an assessment methodology functioning of the quality management systems of medical education. For quality evaluation system of postgraduate medical education the principle of dual control was appllied.

It was also considered the possibility of using of quadrupole model. The model consists of four clusters, each containing four quality management systems of medical education evaluation criteria and relevant indicators for the analysis of these criteria.

 
РОЗРОБКА ПЛАТФОРМИ СИСТЕМИ ПІДТРИМКИ ПРИЙНЯТТЯ РІШЕННЯ ДЛЯ МЕДИЧНОЇ ІНФОРМАЦІЙНОЇ СИСТЕМИ З ВІДКРИТИМ КОДОМ OPENEMR
Authors: Semenets A. V. , Martsenyuk V. P.
Published: October 2015

Introduction
An importance of Medical Information Systems (MIS) in medical practice and education is displayed. The wide usage of the Electronic Medical Records (EMR) software is signed.
Current state. The open source EMR-systems usage
The importance and alternative approaches to the implementation of the MIS in the Ukraine healthcare system are discussed. The situation on the MIS development in Ukraine is presented. The benefits of the open-source MIS usage are shown.

Effectiveness of the Clinical Decision Support Systems (CDSS) application in the medical decision making process are introduced. The CDSS capabilities in diagnostic of the pregnancy pathologies are considered.
The CDSS platform development implementation
The step-by-step results of the CDSS platform development as the plugin for the open-source MIS OpenEMR are presented.

The open-source MIS OpenEMR developer tools and software API are reviewed.

The information model of the CDSS database was proposed and developed. The Model-View-Controller (MVC) based approach to the CDSS architecture is proposed. The CDSS dialog subsystem implementation according to the MIS OpenEMR programming API is developed. The administrative module of the CDSS platform based on the Yii2 php-framework is created.

An approach to the decision making process which is based on the decision tree algorithm usage is proposed. An implementation of the given above approach as separate web-service based won the Google App Engine (GAE) capabilities is presented. The data exchanging formats and methods which OpenEMR CDSS module and DecissionTree GAE service interaction establish are developed.
ОБҐРУНТУВАННЯ ЕФЕКТИВНОСТІ ВИКОРИСТАННЯ E-LEARNING У СУЧАСНІЙ ВИЩІЙ МЕДИЧНІЙ ОСВІТІ
Authors: Bagrii-Zayats O. A.
Published: October 2015

The article is devoted to the consideration of the actual questions of e-learning development in both Ukraine and Western countries. The analysis of the contemporary stage of e-learning development has been made and the research of the main factors influencing on success and effectiveness of implementing in future has been conducted.
АВТОМАТИЗАЦІЯ РОБОЧОГО МІСЦЯ ЛІКАРЯ-БІОХІМІКА ГЕНЕТИКА
Authors: Stetsyuk V. Z. , Savytskyi A. Y. , Ivanova T. P. , Olkhovych N. V. , Kyryachenko S. P. , Horbenko A. O. , Kovtunovych R. H.
Published: October 2015

In the laboratory of medical genetics NCSH «OKHMATDYT» to identify the reliability of laboratory results and control the number and frequency of errors, carry out internal quality control. In order to evaluate the results of measurements of samples and eliminate harmful analytical errors developed and introduced software that allows you to build a calibration curve and process the results of biochemical research activity of lysosomal enzymes.