bluuebunny/crossref_metadata_2025 huggingface dataset:
Hip Resurfacing: History, Current Status, and Future
Authors: Amstutz Harlan C. , Le Duff Michel J.
Published: June 2015

Hip resurfacing arthroplasty (HRA) presents several advantages over conventional total hip arthroplasty (THA), including conservation and preservation of bone, reduced risk of dislocation, easy replication of hip biomechanics and easy revision if needed. It is a particularly appealing procedure for young patients. HRA has been performed for over 40 years following the same technological advances as THA. The bearing material used by most designs is metal-on-metal (MoM), which has the best compromise between strength and wear properties. However, MoM HRA has a specific set of possible complications. Aseptic femoral failures were initially the most prevalent cause for revision but progress in patient selection and surgical technique seem to have resolved this problem. Wear-related failures (high metal ion levels and adverse local tissue reactions) are now the main concern, and are essentially associated with poor acetabular component design and orientation, to which MoM is more sensitive than other bearing materials. The concept of functional coverage is key to understanding how MoM bearings are affected by edge wear. Only a 3-D assessment of cup position (e.g. the contact patch to rim distance) provides the necessary information to determine the role of cup positioning in relationship with abnormal bearing wear. The concept of hip resurfacing is more valid today than ever as the age of the patients in need of hip arthroplasty keeps getting lower. The recent publication of several excellent long-term survivorship results suggests that selection of a well-designed resurfacing system and accuracy in the placement of the cup can achieve long-term durability.
A Novel Photocrosslinkable and Cytocompatible Chitosan Coating for Ti6Al4V Surfaces
Authors: Zujur Denise , Moret Josnell , Rodriguez Dubrasvka , Cruz Lauren , Lira Joaquin , Gil Linda , Dominguez Ernic , Alvarez-Barreto Jose
Published: June 2015

Background

In this work, chitosan (CH) was used to produce a novel coating for Ti6Al4V, the most widely used alloy in orthopedic implants, so as to improve the biological tissue response at the metallic surface.

Methods

The Ti6Al4V surface was sandblasted with alumina particles. CH was chemically modified, via carbodiimide chemistry, using lactobionic and 4-azidebenzoic acid to make it soluble at physiological pH and photocrosslinkable, respectively. The reaction was verified by FTIR, NMR and UV/vis spectroscopy. Ti6Al4V surfaces were coated with solutions of the modified CH and exposed to UV light, causing polymer crosslinking and formation of a hydrogel on the surface. The crosslinking reaction was monitored by FTIR at different exposure times. Coating morphology was observed by SEM. The coating's cytocompatibility was determined in vitro through the culture of rat bone marrow mesenchymal stem cells, using an MTT assay, with their morphology assessed by SEM.

Results

The developed coating behaved as a hydrogel on the Ti6Al4V and was stable on the surface. FTIR and NMR confirmed the crosslinking mechanism, based on an arile ring expansion, and subsequent reaction with the CH amine groups. Furthermore, the coating was able to support cell proliferation and osteogenic differentiation.

Conclusions

UV crosslinking of CH is easy to apply and has potential for future metallic implant surface modifications. Due to its nature as a hydrogel, the coating could be used for further studies in the encapsulation of bioactive molecules to improve osteogenic potential at the tissue–implant interface.
HER family Receptor Expression and Prognosis in Pancreatic Cancer
Authors: Bittoni Alessandro , Mandolesi Alessandra , Andrikou Kalliopi , Santoni Matteo , Alfonsi Simona , Lanese Andrea , Loretelli Cristian , Pellei Chiara , Piva Francesco , Scarpelli Marina , Cascinu Stefano
Published: June 2015

Background

HER family receptors play a key role in tumor progression in several malignancies, such as colorectal, lung or breast cancer. The aims of this study were to investigate expression of HER-1, HER-2 and HER-3 in pancreatic cancer (PC) samples and evaluate the association between HER-family receptor expression and patients’ clinical outcomes.

Methods

Tissue samples from 91 PC patients were subjected to immunohistochemical staining to assess the expression of HER-1, HER-2 and HER-3. Semiquantitative scores of zero (no staining or staining in less than 10% of cancer cells), 1+, 2+ or 3+ were assigned to each sample based on the intensity of staining for HER receptors. Scores of 2+ or 3+ were defined as positive staining.

Results

HER-1 overexpression was observed in 41 out of 91 samples (45.1%), while HER-2 was not overexpressed in any of the analyzed samples. HER-3 was overexpressed in 37 samples (40.7%) and was found to be associated with advanced TNM stage. In particular, HER-3 was overexpressed in 12 out of 16 stage IV patients (75%) compared with only 33.3% of stage I-III patients (p = 0.02). Among 79 patients with available survival data, the 6 patients with strong HER-3 expression (score 3+) had a shorter survival compared with remaining patients (median overall survival 6.9 months vs. 12.3 months, respectively).

Conclusions

HER-1 and HER-3 were found to be expressed in a significant proportion of PC patients. Strong HER-3 expression represents an indicator of poor prognosis in PC patients, being associated with advanced stage and shorter survival.
Endometriosis as an Epiphenomenon in a Patient with Nonobstructive Primary Amenorrhea: A Case Report
Authors: Cavaco-Gomes João , Oliveira João P. , Costa Ana R. , Beires Jorge
Published: June 2015

Introduction

The pathophysiology of endometriosis is not well established. Different theories have been proposed to explain endometriosis, but none alone is able to explain all of the cases described.

Case presentation

We report a case of a woman with a congenital polymalformative syndrome, early puberty and primary amenorrhea, in whom an asymptomatic right adnexal nodule was detected at 14 years of age. When she was 18 years old, a laparoscopy was performed, and an ovoid lesion in the right uterine tube was identified and salpingectomy was performed. The pathological examination revealed endometriosis in the muscular layer of the tube.

Conclusions

Endometriosis can start early in puberty, even before menarche and in the absence of an obstructive disorder.
Endometriosis in a Twin Pregnancy Leading to Massive Hemoperitoneum and Intrauterine Death: A Case Report
Authors: Loh Michelle J.M. , Wee Jonathan Y.S. , Teo Steven B.L.
Published: June 2015

Endometriosis, defined as ectopic endometrium-like glands outside the uterus, is well known to be the main cause of infertility. It is commonly thought to become quiescent during pregnancy. In recent years, however, new breakthroughs in the area of assisted reproductive technology (ART) have resulted in a rise in women with endometriosis conceiving. An association between endometriosis and preterm births, small for gestation age (SGA) babies, higher caesarean section rates, antepartum hemorrhage and preeclampsia have been described in the literature. It is thus imperative for heightened antenatal surveillance in women with surgically confirmed severe endometriosis and for the risks as mentioned above to be made known to these women. We present a case report on the disastrous outcomes (massive hemoperitoneum and intrauterine death) of endometriosis in a twin pregnancy.
Effects of Preoperative and Perioperative Administration of Wobenzym Vital on Minimal-Mild Endometriosis
Authors: Giannini Andrea , Palla Giulia , Goglia Lorenzo , Genazzani Andrea R. , Genazzani Alessandro , Simoncini Tommaso
Published: June 2015

Background

Endometriosis is an estrogen-dependent chronic inflammatory disease associated with pelvic pain, inflammation and infertility. Drugs that modulate the release of chemokines and angiogenic and inflammatory molecules are under evaluation. The aim of the present randomized, double-blind, placebo-controlled study was to investigate the effects of Wobenzym Vital, an enzyme-flavonoids combination supplement with antiinflammatory activity, as supportive treatment in patients affected by minimal-moderate endometriosis selected for surgery.

Methods

Thirty women suspected for endometriosis stage I-II were randomly assigned to receive Wobenzym Vital or placebo for a period of 40-60 days before surgery and 60 days thereafter. Visual analog scale (VAS) scores for pain at enrollment, time of surgery and 7 and 60 days afterwards were evaluated. Blood samples were taken at the same times for the assay of several inflammatory, angiogenic and growth factors and growth factor regulators.

Results

Treatment with Wobenzym Vital was associated with lower VAS scores before surgery and perioperatively. Surgery further reduced VAS scores in all patients. Patients receiving placebo underwent increases in plasmatic concentrations of sCD40L, EGF, IGFBP-1, IL-6, IL-8, TGF-α and TNF-α in the perioperative period, while this was not noted in patients with active treatment. A trend for lower concentrations of several of the tested analytes in the peritoneal fluid was found in patients treated with Wobenzym Vital.

Conclusions

In symptomatic patients affected by minimal-mild endometriosis undergoing surgery, preoperative and postoperative treatment with Wobenzym Vital results in reduced pain and lower concentrations of inflammatory and angiogenic factors in peripheral blood and the peritoneal cavity.
Endothelial Nitric Oxide Synthase Gene Polymorphism among Endometriotic Females in Egypt
Authors: Hassan Mostafa M.M.
Published: June 2015

Background

Endometriosis is one of the most common benign gynecological diseases, causing pain and infertility in women of reproductive age. The etiology of the disorder is complex but probably involves the interaction of several environmental factors with different gene loci. The aim of this study was to investigate the possible association between Glu298Asp polymorphism of the endothelial nitric oxide synthase (eNOS) gene and the pathogenesis of endometriosis.

Methods

Fifty-eight women with an endoscopic diagnosis of endometriosis and 40 age-matched normal females were included in this study.

Results

The study showed an absence of statistically significant differences as regards genotype distribution of the Glu298Asp polymorphism between women with and without endometriosis.

Conclusions

This study showed the absence of association between Glu298Asp polymorphism of the eNOS gene and risk of endometriosis in the Egyptian population.
Relationships between Plasma Pentraxin 3 Levels and Inflammation Markers Patients with Tunneled Permanent Catheter in Hemodialysis
Authors: Yigit Irem Pembegul , Dogukan Ayhan , Taskapan Hulya , Comert Melda , Ilhan Necip , Ulu Ramazan , Aygen Bilge
Published: June 2015

Purpose

Vascular access (VA) devices may contribute to chronic inflammation in hemodialysis (HD). Pentraxin 3 (PTX3) is a recently discovered acute phase protein that responds more rapidly than other inflammatory markers. This study compared PTX3 and other markers between HD patients and healthy controls.

Methods

The study population included 30 patients with tunneled permanent catheter (TPC), 30 patients with arteriovenous fistula (AVF) and 30 healthy controls. Hemogram, biochemical assays, ferritin, high sensitive C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α) and PTX3 were evaluated in all groups.

Results

PTX levels were highest in HD patients with TPC, intermediated in HD patients with AVF and lowest in healthy controls (5.2 + 2.4 vs. 3.1 + 1.3 vs. 1.8 + 0.7, p<0.001 for all comparisons). PTX3 levels correlated strongly to hs-CRP (r = 0.857) and moderately to TNF-α, NLR, ferritin and total neutrophil count. PTX3 and albumin levels had a negative correlation. PTX3 levels were higher in patients with 8 months of TPC than those with 7 months or less.

Conclusions

PTX3 levels are significantly elevated in all patients on HD, but presence and extended duration of TPC are associated with incrementally higher levels of PTX3 and other inflammatory markers. PTX3 and NLR may be useful in assessing chronic inflammatory states in HD.
Patterns of Superficial Veins of the Middle Upper Extremity in Caucasian Population
Authors: Vučinić Nikola , Erić Mirela , Macanović Milica
Published: June 2015

Purpose

Superficial veins of the middle upper extremity are frequently variable in existence and arrangement. The superficial veins are clinically important in many revascularization procedures, particularly reconstructive microsurgery and arterial bypass surgery as well as intravenous injection or therapy. The aim of this study was to assess the patterns of superficial veins of middle upper extremity in healthy volunteers.

Methods

We examined both arms of 169 people. A tourniquet was applied at the mid-arm and a drawing made of the pattern of veins. It took about 1-3 min for each arm. We then examined the 338 drawings looking for similar patterns. The study took place in Department of Anatomy, Faculty of Medicine in Novi Sad, Serbia.

Results

We found nine patterns of middle upper extremity veins. The most common was an ‘M’-shaped pattern (115/338, 34%) followed by an ‘N’-shaped pattern (97/338, 29%).

Conclusions

There are only nine basic patterns of middle upper extremity venous anatomy. Some are more common than others. This knowledge should help those needing venous access for medical procedures (venepuncture, transfusion, infusion, cardiac catheterization, placement of dialysis access).
Optimizing Outcomes in the Elderly with End-Stage Renal Disease—Live Long and Prosper
Authors: Masengu Agnes , Hanko Jennifer B. , Maxwell Alexander P.
Published: June 2015

Background

The elderly form an expanding proportion of patients with chronic kidney disease and end-stage renal disease worldwide. The increased physiological frailty and functional morbidity associated with the aging process pose unique challenges when planning optimal management of an older patient needing renal replacement therapy (RRT).

Aims

This position paper discusses current evidence regarding the optimal management of end-stage renal disease in the elderly with an emphasis on hemodialysis since it is the most common modality used in older patients. Further research is needed to define relevant patient-reported outcome measures for end-stage renal disease including functional assessments and psychological impacts of various forms of RRT. For those older patients who have opted for dialysis treatment, it is important to study the strategies that encourage greater uptake of home-based dialysis therapies and optimal vascular access.

Conclusions

The management of advanced chronic kidney disease in the elderly can be challenging but also extremely rewarding. The key issue is adopting a patient-focused and individualized approach that seeks to achieve the best outcomes based on a comprehensive holistic assessment of what is important to the patient.
Tokio Rationale and Protocol: A Phase II Study to Evaluate the Activity and Safety of Third-line Tyrosine Kinase Inhibitor after 2 Tyrosine Kinase Inhibitors in Patients with Metastatic Renal Cell Carcinoma
Authors: Verzoni Elena , Grassi Paolo , Montone Rosanna , Galli Giulia , Necchi Andrea , Procopio Giuseppe
Published: June 2015

Aims and Background

The introduction of agents targeting vascular endothelial growth factor has radically changed the approach to metastatic renal cell carcinoma (mRCC): sunitinib and pazopanib are now the standard first-line therapy in mRCC. At sunitinib failure, second-line axitinib or everolimus or sorafenib should be considered to improve the clinical outcome. No data are available for a third-line tyrosine kinase inhibitor (TKI) after 2 previous lines of therapy with TKIs. At pazopanib failure, no prospective data are available.

Study Design

The TOKIO study was designed to evaluate progression-free survival, safety, and efficacy of third-line therapy with TKI in 44 patients already treated with 2 previous lines of TKIs in 10 Italian centers, and relapsed from sunitinib-axitinib (group A) or pazopanib-sorafenib (group B). Standard treatment is sorafenib in group A and sunitinib in group B, administered until disease progression or unacceptable toxicity. Secondary endpoints include the evaluation of overall survival, safety, and quality of life.
Sarcomatoid Mesothelioma: Future Advances in Diagnosis, Biomolecular Assessment, and Therapeutic Options in a Poor-Outcome Disease
Authors: Galetta Domenico , Catino Annamaria , Misino Andrea , Logroscino Antonio , Fico Maria
Published: June 2015

Malignant pleural mesothelioma (MPM) is the most frequent pleural neoplasm, with asbestos exposure as one of the recognized carcinogen agents, causative in 80% of cases. The prognosis is poor; median survival of untreated cases is 6-9 months, with fewer than 5% of patients surviving 5 years. Sarcomatoid mesothelioma (SM) represents the subtype with the worst outcome and median survival ranging from 3.5 to 8 months. In the last few years, an accurate differentiation between the subtypes of MPM has become a crucial issue, due to differences in chemosensitivity and clinical outcome, and several studies have evaluated different immunohistochemical markers to better define the diagnosis. The different and worse outcome of patients with SM and, in general, nonepithelioid subtypes makes it intriguing to select these cases to better study the biomolecular profile in order to find factors linked to prognosis and/or predictive of therapeutic response. Considering recent studies on miRNA and genetic mapping, further investigation of this rare subtype might represent a field for basic and clinical-translational research providing for more tailored therapies.
Stability of Spinal Bone Metastases and Survival Analysis in Renal Cancer after Radiotherapy
Authors: Schlampp Ingmar , Lang Helge , Förster Robert , Wolf Robert , Bostel Tilman , Bruckner Thomas , Debus Jürgen , Rief Harald
Published: June 2015

Purpose

This retrospective analysis evaluated the outcome of patients with spinal bone metastases of renal cell cancer after radiotherapy (RT) in terms of stability and survival, using a validated scoring system for spinal stability assessment.

Materials and Methods

The survival rates of 155 patients with bone metastases of renal cancer treated from January 2000 to January 2012 were determined. The stability of irradiated osteolytic lesions of the thoracic and lumbar spine was evaluated retrospectively using the Taneichi score and analyzed for predictive factors. The effects of therapy in terms of changes in neurological signs and tumor-related pain were recorded.

Results

Follow-up with regular computed tomography (CT) was available for 28 patients, 14 with unstable metastases. One hundred thiry-two patients (85%) died during follow-up. RT could not improve the stability of vertebral bodies after 3 and 6 months. Consequently, none of the examined predictive factors such as age, number of bone metastases and systemic therapy showed a significant correlation with stability 6 months after RT. The median survival of all 155 patients after diagnosis of bone metastases was 12.9 months. Improvement of pain and neurological deficits occurred in 60%, and in 24% of the respective affected in all patients.

Conclusions

RT was unable to improve the stability of vertebral metastases, probably due to the short overall survival, which resulted in an insufficient number of patients with evaluable follow-up. RT allowed reduction of pain and neurological deficits. A short fractionation schedule may be preferred in this situation.
Surgical Treatment of Renal Carcinoma with Atrial Tumor Thrombus Avoiding Cardiopulmonary Bypass: Step-by-Step Description
Authors: Guglielmo Nicola , Melandro Fabio , Montalto Gioacchino , Poli Luca , Pietra Fatima Della , Rossi Massimo , Mazzesi Giuseppe , Berloco Pasquale
Published: June 2015

Tumor thrombus in the inferior vena cava (IVC) occurs in 4–10% of patients with renal cell carcinoma (RCC) and poses a challenge for the surgical team. Because there is no systemic therapy available to significantly reduce tumor burden, surgical intervention is the only treatment. However, the surgical approach is associated with significant morbidity and mortality. When the thrombus extends above the diaphragm, the use of cardiopulmonary bypass (CPB) and accompanying deep hypothermic circulatory arrest (DHCA) has usually been advocated. However, complications inherent to CPB and DHCA, such as coagulopathy and central nervous system complications, have led us to search for an alternative surgical approach to these tumors. The purpose of this study is to describe the surgical technique used in five patients with large RCC with tumor thrombus extending into the supradiaphragmatic IVC and Right atrium (RA), Right atrium, who underwent extensive resection without CPB and DHCA.
First Bahraini adolescent with anti-NMDAR-Ab encephalitis
Authors: Almuslamani Ahood , Mahmood Fatima
Published: June 2015

Anti-N-methyl-D-aspartate-receptor (NMDA-R) encephalitis is a new autoimmune, often paraneoplastic disorder that presents with complex neuropsychiatric symptoms. It was first described in 2007 by Dalmau et al. Our patient presented with headache, behavioral changes and then seizures with hallucinations. She was initially misdiagnosed to have schizophrenia and was prescribed antipsychotics. She deteriorated and developed further seizures with hypoventilation and choreoathetosis. Her blood investigations were positive for mycoplasma IGM. Her CSF studies showed high white cell counts, predominantly lymphocytes, and high anti-NMDA-R titre. Her brain MRI scans showed high T2 and FLAIR intensities in the grey and white matter of the left cerebellar hemisphere suggestive of acute disseminated encephalomyelitis. She responded to treatment with antibiotics, multiple antiepileptics, steroids and needed five sessions of plasmapheresis. There was no underlying malignancy on repeated scanning of the abdomen. She needed around one year for full recovery with intensive rehabilitation. The objective of this paper was to highlight the occurrence of this fairly new, challenging, easily missed, not-so-rare form of encephalitis often occurring in the absence of fever.
The prevalence of psychological impact on caregivers of hospitalized patients: The forgotten part of the equation
Authors: Al-Zahrani Rahma , Bashihab Rahaf , Ahmed Anwar E. , Alkhodair Reem , Al-Khateeb Sultan
Published: June 2015

Introduction:Despite the large number of caregivers suffering from various psychiatric disorders, research on psychological symptoms among caregivers of hospitalized patients is lacking in Saudi populations.Objectives:The objective of this study is to determine the prevalence of depression, anxiety and stress among caregivers of hospitalized Saudi patients.Methods:A cross-sectional study of depression, anxiety and stress among caregivers of hospitalized patients was conducted. Arabic speaking caregivers (n = 353) between the ages of 14 and 80 years were included in the study. The Depression Anxiety Stress Scales (DASS-21) test (Arabic version) was used to measure the three psychological symptoms.Results:The study has shown high rates of depression, anxiety and stress among caregivers (72.8%, 76.5%, and 61.5%, respectively). Depression was found to be associated with long-term hospital stay (81.4% vs. 69.3%; p-value = 0.021) and family caregivers (75.4% vs. 46.9%, p-value = 0.001). Anxiety was found to be associated with family caregivers (78.8% vs. 53.1%; p-value = 0.001). The three psychological symptoms were higher among those with an age above 20 years old (p-value < 0.05). Multivariate logistic models show the risk of the psychological symptoms increased with low-income, higher education, immediate relation to the patient, and older caregivers.Conclusions:The findings suggest that the prevalence of depression, anxiety and stress symptoms were very common among caregivers. The results showed that approximately 8 out of 10 caregivers suffer from at least one psychiatric disorder. Older, low socioeconomic status, and well-educated caregivers were identified as being at higher risk of developing psychiatric symptoms.
Violência obstétrica e prevenção quaternária: o que é e o que fazer
Authors: Tesser Charles Dalcanale , Knobel Roxana , Andrezzo Halana Faria de Aguiar , Diniz Simone Grilo
Published: June 2015

O objetivo deste artigo é justificar a necessidade de prevenção quaternária frente à 'violência obstétrica' (VO), terminologia que agrupa todas as formas de violência e danos originados no cuidado obstétrico profissional, bem como discutir estratégias e ações de prevenção quaternária a serem realizadas pelos médicos de família e comunidade (MFC), pelas equipes de atenção primária à saúde (APS) e suas entidades associativas. A prevalência de violência obstétrica no Brasil é alta: ¼ das mulheres relata terem sofrido maus-tratos durante o atendimento ao parto, além de excesso de intervenções desnecessárias (como venóclise, ocitocina de rotina e episiotomia) e privação de uma assistência baseada em boas práticas, tais como parto em posição vertical, possibilidade de se alimentar e de se movimentar durante o trabalho de parto e presença de um acompanhante. Destaca-se o excesso crônico de cesarianas (55,6% do total de nascimentos) no Brasil, mais prevalente no setor privado (85%) do que no público (40%). Ações de prevenção quaternária dirigidas à VO são propostas e discutidas, como: (1) a elaboração (individual e coletiva) de planos de parto orientados pelas equipes de APS no pré-natal (para os quais se oferece um roteiro); (2) a introdução de outros profissionais qualificados no cuidado ao parto de risco habitual (incluindo MFC capacitados); e (3) a participação dos MFC e profissionais da APS e suas associações no movimento social e político pela “humanização” do parto, com apoio às mudanças nas maternidades já em funcionamento e às novas iniciativas de serviços de cuidado ao parto.
Attention-deficit hyperactivity disorder: preventing overdiagnosis and overtreatment
Authors: St-Onge Jean-Claude
Published: June 2015

The first part of this article focuses on the wide variations in the diagnosis of attention-deficit hyperactivity disorder (ADHD) that are observed between countries and between regions within the same country. Diagnosing ADHD is more problematic than is commonly thought. For instance, younger American children in the same grade at school are 64% more likely to receive the diagnosis; symptoms can result from many underlying causes. Furthermore, ADHD can be confused with many other health issues. As a result it is largely overdiagnosed and overtreated. The second part of the article reviews recent studies showing that anti-ADHD drugs lack long-term effectiveness and come with important adverse events. Overall, and in the long run, the pharmacologic treatment of ADHD is likely to cause more harm than good.
Teaching and learning quaternary prevention
Authors: Gomes Luís Filipe , Gusso Gustavo , Jamoulle Marc
Published: June 2015

This article presents an overview of different techniques and skills necessary for teaching and learning quaternary prevention (P4). It adopts the Expertise Model that defines the competences required in P4 for each level: novice, competent, proficient, and expert. This framework should be used as a step-wise roadmap for teachers in order to achieve high levels of performance. This proposal is complemented by a list of methods applied in teaching and assessment of learners’ performance and competence. By covering a range of learning and teaching issues, those who aim to teach quaternary prevention can explore the proposed framework. Quaternary prevention is a research and teaching fertile medical field that entails the integration of different areas such as health service organisation, epidemiology, communication skills, and andragogy either at the macro or the micro levels of health related activities.
Unnecessary Overtreatment Index: a useful tool in family practice
Authors: Pezeshki Mohammad Zakaria , Pezeshki Sina
Published: June 2015

One of the most important aspects of quaternary prevention is avoiding the exposure of the patients to unnecessary overtreatment.  In this commentary we explain how a valid and reliable double blinded randomized controlled clinical trial (RCT) with a good external validity may help a physician to estimate the magnitude of unnecessary overtreatment.
¿Overscreening o prevención a escala humana? Tamizaje excesivo
Authors: Pizzanelli Miguel
Published: June 2015

Cuando se aplica un método de tamizaje de modo excesivo, abusivo o innecesario los daños provocados pueden superar a los beneficios. Para desarrollar el concepto de tamizaje excesivo, fueron consideradas algunas categorías: tamizaje innecesario, sin indicación médica, inducido, obligatorio, por frecuencia inadecuada. Existen sesgos de interpretación que no permiten determinar de forma objetiva el balance daño beneficio de los programas de tamizaje relacionados al exceso de diagnóstico. Evitar el daño producido por tamizajes excesivos (overscreening) requiere llevar recomendaciones y pautas genéricas al terreno de la práctica clínica con casos particulares. La prevención cuaternaria, fundada conceptualmente en los cuidados de salud centrados en la persona, permite considerar las creencias, inquietudes, opciones individuales, haciendo posible llevar a la prevención a una escala humana.
Philosophical roots of Quaternary Prevention
Authors: Widmer Daniel
Published: June 2015

This article explores two philosophical dimensions of quaternary prevention since it represents the family doctors’ response to overmedicalization. The first dimension refers to the theory of knowledge and the second to the theory of action. Despite their interconnectedness, they are addressed separately. Firstly, in the theories of knowledge (Epistemology) we argue that the positivism of Evidence-Based Medicine (EBM), so useful to select good practices, should be balanced against critical vision of the use of EBM coupled with a constructivist view through the narrative-based medicine. Secondly, in the theory of action (Ethics) we argue that the non-maleficence principle (primum non nocere) needs to be balanced by the beneficence principle. The latter is the primary medical obligation and doctors should cultivate this practical wisdom. Finally, some aspects of P4’s future challenges are discussed such as health inequalities, interprofessional collaboration, responsibility, managerialism, and the integrative medicine, where a philosophical position should be considered.
Filosofia da cultura e escrita da história: Notas sobre as relações entre os projetos de uma genealogia da cultura em Foucault e Nietzsche
Authors: Giacoia Júnior Oswaldo
Published: June 2015

Este artigo tem como finalidade discutir alguns aspectos da leitura e da interpretação que Foucault fez de Nietzsche. Não se trata de examinar o conjunto da recepção foucaultiana de Nietzsche e nem a pertinência das conclusões que Foucault tira delas, para saber se as mesmas são legítimas ou fiéis ao pensamento desse último, mas de, a partir das reflexões de Foucault sobre a relação entre genealogia e escrita da história em Nietzsche, mostrar quais elementos são privilegiados por Foucault, assim como quais ele silenciou e deixou na sombra. Com isso, pretendemos mostrar de que maneira o pensamento de Nietzsche se tornou indispensável para a crítica de Foucault à subjetividade moderna.
Hippocampal place cells construct reward related sequences through unexplored space
Authors: Ólafsdóttir H Freyja , Barry Caswell , Saleem Aman B , Hassabis Demis , Spiers Hugo J
Published: June 2015

Dominant theories of hippocampal function propose that place cell representations are formed during an animal's first encounter with a novel environment and are subsequently replayed during off-line states to support consolidation and future behaviour. Here we report that viewing the delivery of food to an unvisited portion of an environment leads to off-line pre-activation of place cells sequences corresponding to that space. Such ‘preplay’ was not observed for an unrewarded but otherwise similar portion of the environment. These results suggest that a hippocampal representation of a visible, yet unexplored environment can be formed if the environment is of motivational relevance to the animal. We hypothesise such goal-biased preplay may support preparation for future experiences in novel environments.
Dynamics of preventive vs post-diagnostic cancer control using low-impact measures
Authors: Akhmetzhanov Andrei R , Hochberg Michael E
Published: June 2015

Cancer poses danger because of its unregulated growth, development of resistance, and metastatic spread to vital organs. We currently lack quantitative theory for how preventive measures and post-diagnostic interventions are predicted to affect risks of a life threatening cancer. Here we evaluate how continuous measures, such as life style changes and traditional treatments, affect both neoplastic growth and the frequency of resistant clones. We then compare and contrast preventive and post-diagnostic interventions assuming that only a single lesion progresses to invasive carcinoma during the life of an individual, and resection either leaves residual cells or metastases are undetected. Whereas prevention generally results in more positive therapeutic outcomes than post-diagnostic interventions, this advantage is substantially lowered should prevention initially fail to arrest tumour growth. We discuss these results and other important mitigating factors that should be taken into consideration in a comparative understanding of preventive and post-diagnostic interventions.
ATF4 licenses C/EBPβ activity in human mesenchymal stem cells primed for adipogenesis
Authors: Cohen Daniel M , Won Kyoung-Jae , Nguyen Nha , Lazar Mitchell A , Chen Christopher S , Steger David J
Published: June 2015

A well-established cascade of transcription factor (TF) activity orchestrates adipogenesis in response to chemical cues, yet how cell-intrinsic determinants of differentiation such as cell shape and/or seeding density inform this transcriptional program remain enigmatic. Here, we uncover a novel mechanism licensing transcription in human mesenchymal stem cells (hMSCs) adipogenically primed by confluence. Prior to adipogenesis, confluency promotes heterodimer recruitment of the bZip TFs C/EBPβ and ATF4 to a non-canonical C/EBP DNA sequence. ATF4 depletion decreases both cell-density-dependent transcription and adipocyte differentiation. Global profiling in hMSCs and a novel cell-free assay reveals that ATF4 requires C/EBPβ for genomic binding at a motif distinct from that bound by the C/EBPβ homodimer. Our observations demonstrate that C/EBPβ bridges the transcriptional programs in naïve, confluent cells and early differentiating pre-adipocytes. Moreover, they suggest that homo- and heterodimer formation poise C/EBPβ to execute diverse and stage-specific transcriptional programs by exploiting an expanded motif repertoire.
Registered report: BET bromodomain inhibition as a therapeutic strategy to target c-Myc
Authors: Kandela Irawati , Jin Hyun Yong , Owen Katherine ,   Reproducibility Project: Cancer Biology
Published: June 2015

The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by replicating selected results from a substantial number of high-profile papers in the field of cancer biology published between 2010 and 2012. This Registered report describes the proposed replication plan of key experiments from ‘BET bromodomain inhibition as a therapeutic strategy to target c-Myc’ by Delmore and colleagues, published in Cell in 2011 (Delmore et al., 2011). The key experiments that will be replicated are those reported in Figures 3B and 7C-E. Delmore and colleagues demonstrated that treatment with JQ1, a small molecular inhibitor targeting BET bromodomains, resulted in the transcriptional down-regulation of the c-Myc oncogene in vitro (Figure 3B; Delmore et al., 2011). To assess the therapeutic efficacy of JQ1 in vivo, mice bearing multiple myeloma (MM) lesions were treated with JQ1 before evaluation for tumor burden and overall survival. JQ1 treatment significantly reduced disease burden and increased survival time (Figure 7C-E; Delmore et al., 2011). The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange and the results of the replications will be published in eLife.
Osteopathic Manipulative Therapy in Women With Postpartum Low Back Pain and Disability: A Pragmatic Randomized Controlled Trial
Authors: Schwerla Florian , Rother Katrin , Rother Denis , Ruetz Michaela , Resch Karl-Ludwig
Published: June 2015

Context: Persistent low back pain (LBP) is a common complaint among women during and after pregnancy, and its effects on quality of life can be disabling.

Objective: To evaluate the effectiveness of osteopathic manipulative therapy (OMTh; manipulative care provided by foreign-trained osteopaths) in women with persistent LBP and functional disability after childbirth.

Methods: A pragmatic randomized controlled trial was conducted among a sample of women with a history of pregnancy-related LBP for at least 3 months after delivery. Participants were identified from the general population in Germany. By means of external randomization, women were allocated to an OMTh group and a waitlist control group. Osteopathic manipulative therapy was provided 4 times at intervals of 2 weeks, with a follow-up after 12 weeks. The OMTh was tailored to each participant and based on osteopathic principles. The participants allocated to the control group did not receive OMTh during the 8-week study; rather, they were put on a waiting list to receive OMTh on completion of the study. Further, they were not allowed to receive any additional treatment (ie, medication, physical therapy, or other sources of pain relief) during the study period. The main outcome measures were pain intensity as measured by a visual analog scale and the effect of LBP on daily activities as assessed by the Oswestry Disability Index (ODI).

Results: A total of 80 women aged between 23 and 42 years (mean [SD], 33.6 [4.5] years) were included in the study, with 40 in the OMTh group and 40 in the control group. Pain intensity decreased in the OMTh group from 7.3 to 2.0 (95% CI, 4.8-5.9; P<.001) and in the control group from 7.0 to 6.5 (95% CI, -0.2 to -0.9; P=.005). The between-group comparison of changes revealed a statistically significant improvement in pain intensity in the OMTh group (between-group difference of means, 4.8; 95% CI, 4.1-5.4; P<.001) and level of disability (between-group difference of means, 10.6; 95% CI, 9.9-13.2; P<.005). The follow-up assessment in the OMTh group (n=38) showed further improvement.

Conclusion: During 8 weeks, OMTh applied 4 times led to clinically relevant positive changes in pain intensity and functional disability in women with postpartum LBP. Further studies that include prolonged follow-up periods are warranted. (German Clinical Trials Register: DRKS00006280.)
Diabetes Mellitus Coding Training for Family Practice Residents
Authors: Urse Geraldine N.
Published: June 2015

Context: Although physicians regularly use numeric coding systems such as the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) to describe patient encounters, coding errors are common. One of the most complicated diagnoses to code is diabetes mellitus. The ICD-9-CM currently has 39 separate codes for diabetes mellitus; this number will be expanded to more than 50 with the introduction of ICD-10-CM in October 2015.

Objective: To assess the effect of a 1-hour focused presentation on ICD-9-CM codes on diabetes mellitus coding.

Methods: A 1-hour focused lecture on the correct use of diabetes mellitus codes for patient visits was presented to family practice residents at Doctors Hospital Family Practice in Columbus, Ohio. To assess resident knowledge of the topic, a pretest and posttest were given to residents before and after the lecture, respectively. Medical records of all patients with diabetes mellitus who were cared for at the hospital 6 weeks before and 6 weeks after the lecture were reviewed and compared for the use of diabetes mellitus ICD-9 codes.

Results: Eighteen residents attended the lecture and completed the pretest and posttest. The mean (SD) percentage of correct answers was 72.8% (17.1%) for the pretest and 84.4% (14.6%) for the posttest, for an improvement of 11.6 percentage points (P≤.035). The percentage of total available codes used did not substantially change from before to after the lecture, but the use of the generic ICD-9-CM code for diabetes mellitus type II controlled (250.00) declined (58 of 176 [33%] to 102 of 393 [26%]) and the use of other codes increased, indicating a greater variety in codes used after the focused lecture.

Conclusion: After a focused lecture on diabetes mellitus coding, resident coding knowledge improved. Review of medical record data did not reveal an overall change in the number of diabetic codes used after the lecture but did reveal a greater variety in the codes used.
Heart Failure With Preserved Ejection Fraction
Authors: Rogers Felix J. , Gundala Teja , Ramos Jahir E. , Serajian Asif
Published: June 2015

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical condition. Initially called diastolic heart failure, it soon became clear that this condition is more than the opposite side of systolic heart failure. It is increasingly prevalent and lethal. Currently, HFpEF represents more than 50% of heart failure cases and shares a 90-day mortality and readmission rate similar to heart failure with reduced ejection fraction. Heart failure with preserved ejection fraction is best considered to be a systemic disease. From a cardiovascular standpoint, it is not just a stiff ventricle. A stiff ventricle combined with a stiff arterial and venous system account for the clinical manifestations of flash pulmonary edema and the marked changes in renal function or systemic blood pressure with minor changes in fluid volume status. No effective pharmacologic treatments are available for patients with HFpEF, but an approach to the musculoskeletal system has merit: the functional limitations and exercise intolerance that patients experience are largely due to abnormalities of peripheral vascular function and skeletal muscle dysfunction. Regular exercise training has strong objective evidence to support its use to improve quality of life and functional capacity for patients with HFpEF. This clinical review summarizes the current evidence on the pathophysiologic aspects, diagnosis, and management of HFpEF.
Identification and Complications of Cosmetic Fillers
Authors: Wortsman Ximena
Published: June 2015

Cosmetic fillers are frequently used these days for enhancing beauty and to treat wrinkles or sagging skin. However, information on the history of injections may be difficult to obtain, and there is a growing number of reports on complications with these agents. In contrast to other imaging techniques, sonography has been successfully used for detecting and identifying common types of cosmetic fillers and has become the first‐line imaging modality to deal with these exogenous components.
Utility of Sonoelastography in Differentiating Ruptured From Unruptured Epidermal Cysts and Implications for Patient Care
Authors: Park Joonsoo , Chae In Soo , Kwon Dong Rak
Published: June 2015

Objectives

This study aimed to evaluate the correlation of sonoelastographic features between ruptured and unruptured epidermal cysts.

Methods

We performed a prospective survey of 27 patients with clinically suspected epidermal cysts diagnosed by excisional biopsy with prebiopsy sonography and real‐time sonoelastography. We statistically evaluated the correlation between elastographic and histopathologic features. To measure the relative hardness on elastography, the Rinside/Routside ratio was used to show the ratio of the elasticity inside and outside the cyst, where the random value R was defined as the median red pixel intensity/(median red pixel intensity + median green pixel intensity + median blue pixel intensity).

Results

Only 24 of the 27 patients were enrolled. Among the 24 diagnosed epidermal cysts, 13 were unruptured cysts, and 11 were ruptured cysts based on histopathologic examination. There was no correlation between sonographically and histopathologically measured cyst diameters. The Rinside/Routside ratio was significantly higher in unruptured cysts than ruptured cysts (mean ± SD, 1.16 ± 0.15 versus 1.04 ± 0.13; P = .047). All values below the cutoff point were considered to indicate ruptured cysts, and the cutoff value was set to 1.0919, which afforded sensitivity of 83.3% and specificity of 66.7%.

Conclusions

Real‐time sonoelastography is able to detect differences in tissue elasticity between ruptured and unruptured epidermal cysts. This study shows the utility of real‐time sonoelastography, which has important implications for treatment planning.
Interobserver Reliability of Quantitative Muscle Sonographic Analysis in the Critically Ill Population
Authors: Sarwal Aarti , Parry Selina M. , Berry Michael J. , Hsu Fang-Chi , Lewis Marc T. , Justus Nicholas W. , Morris Peter E. , Denehy Linda , Berney Sue , Dhar Sanjay , Cartwright Michael S.
Published: June 2015

Objectives

There is growing interest in the use of quantitative high‐resolution neuromuscular sonography to evaluate skeletal muscles in patients with critical illness. There is currently considerable methodological variability in the measurement technique of quantitative muscle analysis. The reliability of muscle parameters using different measurement techniques and assessor expertise levels has not been examined in patients with critical illness. The primary objective of this study was to determine the interobserver reliability of quantitative sonographic measurement analyses (thickness and echogenicity) between assessors of different expertise levels and using different techniques for selecting the region of interest.

Methods

We conducted a cross‐sectional observational study in neurocritical care and mixed surgical‐medical intensive care units from 2 tertiary referral hospitals.

Results

Twenty diaphragm and 20 quadriceps images were evaluated. Images were obtained by using standardized imaging acquisition techniques. Quantitative sonographic measurements included muscle thickness and echogenicity analysis (either by the trace or square technique). All images were analyzed twice independently by 4 assessors of differing expertise levels. Excellent interobserver reliability was obtained for all measurement techniques regardless of expertise level (intraclass correlation coefficient, >0.75 for all comparisons). There was less variability between assessors for echogenicity values when the square technique was used for the quadriceps muscle and the trace technique for the diaphragm.

Conclusions

Excellent interobserver reliability exists regardless of expertise level for quantitative analysis of muscle parameters on sonography in the critically ill population. On the basis of these findings, it is recommended that echogenicity analysis be performed using the square technique for the quadriceps and the trace technique for the diaphragm.