Efficacy and Safety of Natalizumab in Crohn’s Disease Patients Treated at 6 Boston Academic Hospitals

BACKGROUND: Despite trials demonstrating its efficacy, many physicians harbor concerns regarding the use of natalizumab in the treatment of patients with refractory Crohn's disease (CD). The purpose of this study was to perform a descriptive analysis of a series of CD patients not currently enrolled in a clinical trial. METHODS: A retrospective case review of patients treated with natalizumab at 6 sites in Massachusetts: Boston Medical Center, Beth Israel Deaconess Medical Center, Brigham & Women's Hospital, Lahey Clinic, Massachusetts General Hospital, and UMass Medical Center. RESULTS: Data on 69 CD patients on natalizumab were collected. At the start of treatment, patients' disease duration was 12 years. A high proportion of patients were women (68%), presented with perianal disease (65%) and upper gastrointestinal tract involvement (14%). Prior nonbiologic therapies were steroids (96%), thiopurines (94%), antibiotics (74%), methotrexate (58%), and at least two anti-tumor necrosis factor agent failures (81%). Sixty-nine percent (44 of 64 patients) with available medical evaluation had a partial or complete clinical response. Loss of response was 13% after an average of 1 year of treatment. Adverse events were infusion reactions, headaches, fever, and infections. No case of progressive multifocal leukoencephalopathy was observed. CONCLUSIONS: In our clinical experience outside the context of a clinical trial, natalizumab is largely reserved for CD patients with extensive ileocolonic disease who have failed conventional immunosuppressants and of at least 2 anti-tumor necrosis factor agents. This drug is, however, well tolerated and offers significant clinical improvement for more than a year in one-third of these difficult-to-treat CD patients.

Ultrasound-guided proximal paravertebral anaesthesia in cattle

OBJECTIVE To develop and evaluate a method for ultrasound-guidance in performing the proximal paravertebral block for flank anaesthesia in cattle through a cadaveric study, followed by clinical application. STUDY DESIGN prospective experimental cadaveric study and clinical series. ANIMALS Previously frozen lumbar sections of cows without known spinal abnormalities were used. The clinical case group comprised of ten animals for which a right flank laparotomy was indicated. METHODS Twenty cow cadavers were used to perform ultrasound-guided bilateral injections of 1.0 mL dye (1.0 mL 1% Toluidine Blue in 1% Borax) at the intervertebral foramen at the level of T13, L1 and L2 spinal nerves. Distance and depth of injection, staining of the dorsal and ventral nerve branches, and deviation from the target were evaluated. The investigator's confidence as to visualisation and expected success at staining the nerve was assessed. Ten clinical cases received the ultrasound-guided proximal paravertebral anaesthesia. Analgesic success was evaluated using a 4-grade scoring system at 10 minutes after the injection and during surgery, respectively. Categorical variables were described using frequencies and proportions. RESULTS Both dorsal and ventral branches of the spinal nerves T13, L1 or L2 were at least partially stained in 41% of injections, while in 77% of injections one of the branches was stained. Five out of ten clinical cases had a satisfactory anaesthesia. There was no significant association between confidence at injection and either staining or analgesic success. CONCLUSION Results from the cadaveric and clinical study suggest no significant improvement using ultrasound guidance to perform proximal paravertebral block in cows compared to our previous clinical experience and to references in the literature using the blind method. CLINICAL RELEVANCE Further research should be conducted to improve the ultrasound-guided technique described in this study.

Indication and timing of soft tissue augmentation at maxillary and mandibular incisors in orthodontic patients. A systematic review.

OBJECTIVE To assess the indication and timing of soft tissue augmentation for prevention or treatment of gingival recession when a change in the inclination of the incisors is planned during orthodontic treatment. MATERIALS AND METHODS Electronic database searches of literature were performed. The following electronic databases with no restrictions were searched: MEDLINE, EMBASE, Cochrane, and CENTRAL. Two authors performed data extraction independently using data collection forms. RESULTS No randomized controlled trial was identified. Two studies of low-to-moderate level of evidence were included: one of prospective and retrospective data collection and one retrospective study. Both implemented a periodontal intervention before orthodontics. Thus, best timing of soft tissue augmentation could not be assessed. The limited available data from these studies appear to suggest that soft tissue augmentation of bucco-lingual gingival dimensions before orthodontics may yield satisfactory results with respect to the development or progression of gingival recessions. However, the strength of the available evidence is not adequate in order to change or suggest a possible treatment approach in the daily practice based on solid scientific evidence. CONCLUSIONS Despite the clinical experience that soft tissue augmentation of bucco-lingual gingival dimensions before orthodontic treatment may be a clinically viable treatment option in patients considered at risk, this treatment approach is not based on solid scientific evidence. Moreover, the present data do not allow to draw conclusions on the best timing of soft tissue augmentation when a change in the inclination of the incisors is planned during orthodontic treatment and thus, there is a stringent need for randomized controlled trials to clarify these open issues.

How does the ascending aorta geometry change when it dissects?

OBJECTIVES The purpose of this study is to delineate changes in aortic geometry and diameter due to dissection. BACKGROUND Aortic diameter is the major criterion for elective ascending aortic replacement for dilated ascending aortas to prevent aortic dissection. However, recommendations are made on the basis of clinical experience and observation of diameters of previously dissected aortas. METHODS Six tertiary centers on 2 continents reviewed their acute aortic dissection type A databases, which contained 1,821 patients. Included were all non-Marfan patients with nonbicuspid aortic valves who had undergone computed tomography angiography <2 years before and within 12 h after aortic dissection onset. Aortic geometry before and after dissection onset were compared. RESULTS Altogether, 63 patients were included (27 spontaneous and 36 retrograde dissections, median age 68 [57; 77] years; 54% were men). In all but 1 patient, maximum ascending aortic diameter was <55 mm before aortic dissection onset. The largest increase in diameter and volume induced by the dissection were observed in the ascending aorta (40.1 [36.6; 45.3] mm vs. 52.9 [46.1; 58.6] mm, +12.8 mm; p < 0.001; 124.0 [90.8; 162.5] cm(3) vs. 171.0 [147.0; 197.0] cm(3), +47 cm(3); p < 0.001). Mean aortic arch diameter increased from 39.8 (30.5; 42.6) mm to 46.4 (42.0; 51.6) mm (+6.6 mm; p < 0.001) and descending thoracic aorta diameter from 31.2 (27.0; 33.3) mm to 34.9 (30.9; 39.5) mm (+3.7 mm; p < 0.001). Changes in thoracic aorta geometry were similar for spontaneous and retrograde etiology. CONCLUSIONS Geometry of the thoracic aorta is affected by aortic dissection, leading to an increase in diameter that is most pronounced in the ascending aorta. Both spontaneous and retrograde dissection result in similar aortic geometry changes.

The pre- and post-somatic segments of the human type I spiral ganglion neurons--structural and functional considerations related to cochlear implantation.

Human auditory nerve afferents consist of two separate systems; one is represented by the large type I cells innervating the inner hair cells and the other one by the small type II cells innervating the outer hair cells. Type I spiral ganglion neurons (SGNs) constitute 96% of the afferent nerve population and, in contrast to other mammals, their soma and pre- and post-somatic segments are unmyelinated. Type II nerve soma and fibers are unmyelinated. Histopathology and clinical experience imply that human SGNs can persist electrically excitable without dendrites, thus lacking connection to the organ of Corti. The biological background to this phenomenon remains elusive. We analyzed the pre- and post-somatic segments of the type I human SGNs using immunohistochemistry and transmission electron microscopy (TEM) in normal and pathological conditions. These segments were found surrounded by non-myelinated Schwann cells (NMSCs) showing strong intracellular expression of laminin-β2/collagen IV. These cells also bordered the perikaryal entry zone and disclosed surface rugosities outlined by a folded basement membrane (BM) expressing laminin-β2 and collagen IV. It is presumed that human large SGNs are demarcated by three cell categories: (a) myelinated Schwann cells, (b) NMSCs and (c) satellite glial cells (SGCs). Their BMs express laminin-β2/collagen IV and reaches the BM of the sensory epithelium at the habenula perforata. We speculate that the NMSCs protect SGNs from further degeneration following dendrite loss. It may give further explanation why SGNs can persist as electrically excitable monopolar cells even after long-time deafness, a blessing for the deaf treated with cochlear implantation.

Is The Allergen Really Needed in Allergy Immunotherapy?

Immunotherapy for type I allergies is well established and is regarded to be the most efficient treatment option besides allergen avoidance. As of today, different forms of allergen preparations are used in this regard, as well as different routes of application. Virus-like particles (VLPs) represent a potent vaccine platform with proven immunogenicity and clinical efficacy. The addition of toll-like receptor ligands and/or depot-forming adjuvants further enhances activation of innate as well as adaptive immune responses. CpG motifs represent intensively investigated and potent direct stimulators of plasmacytoid dendritic cells and B cells, while T cell responses are enhanced indirectly through increased antigen presentation and cytokine release. This article will focus on the function of VLPs loaded with DNA rich in nonmethylated CG motifs (CpGs) and the clinical experience gained in the treatment of allergic rhinitis, demonstrating clinical efficacy also if administered without allergens. Several published studies have demonstrated a beneficial impact on allergic symptoms by treatment with CpG-loaded VLPs. Subcutaneous injection of VLPs loaded with CpGs was tested with or without the adjuvant alum in the presence or absence of an allergen. The results encourage further investigation of VLPs and CpG motifs in immunotherapy, either as a stand-alone product or as adjuvants for allergen-specific immunotherapy.

Impact of different magnification levels on visual caries detection with ICDAS

OBJECTIVES The aim of this in vitro study was to examine the effect of different levels of magnification on the accuracy and reliability of visual caries detection using ICDAS criteria. METHODS Occlusal surfaces of 100 extracted molars were assessed by 14 examiners (3rd and the 4th year dental students and dentists) using no magnification aids, a 2.5× Galilean loupe, a 4.5× Keplerian loupe, or a surgical microscope with 10× magnification. The assessments were repeated on a different day. Sensitivity, specificity, AUC and reliabilities were calculated according to the gold standard of histology. RESULTS We found that with increasing magnification, the number of surfaces rated as "sound" (ICDAS code 0) decreased, while the number of surfaces with a localized enamel breakdown (ICDAS code 3) increased. While the sensitivities increased, the values of the specificities decreased to an unacceptably low level irrespective of the clinical experience of the examiners. CONCLUSIONS ICDAS seems to be optimized for natural vision up to 2.0× magnification and not for high magnifications. The use of powerful magnification in visual caries detection involves the risk of unnecessary and premature invasive treatment. CLINICAL SIGNIFICANCE This paper discusses when it does and does not make sense to use magnification devices for visual caries detection using ICDAS criteria. Strong magnifications should be refrained from for this purpose.

Single crowns versus conventional fillings for the restoration of root-filled teeth.

BACKGROUND Endodontic treatment involves removal of the dental pulp and its replacement by a root canal filling. Restoration of root filled teeth can be challenging due to structural differences between vital and non-vital root-filled teeth. Direct restoration involves placement of a restorative material e.g. amalgam or composite, directly into the tooth. Indirect restorations consist of cast metal or ceramic (porcelain) crowns. The choice of restoration depends on the amount of remaining tooth, and may influence durability and cost. The decision to use a post and core in addition to the crown is clinician driven. The comparative clinical performance of crowns or conventional fillings used to restore root-filled teeth is unknown. This review updates the original, which was published in 2012. OBJECTIVES To assess the effects of restoration of endodontically treated teeth (with or without post and core) by crowns versus conventional filling materials. SEARCH METHODS We searched the following databases: the Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE via OVID, EMBASE via OVID, CINAHL via EBSCO, LILACS via BIREME. We also searched the reference lists of articles and ongoing trials registries.There were no restrictions regarding language or date of publication. The search is up-to-date as of 26 March 2015. SELECTION CRITERIA Randomised controlled trials (RCTs) or quasi-randomised controlled trials in participants with permanent teeth that have undergone endodontic treatment. Single full coverage crowns compared with any type of filling materials for direct restoration or indirect partial restorations (e.g. inlays and onlays). Comparisons considered the type of post and core used (cast or prefabricated post), if any. DATA COLLECTION AND ANALYSIS Two review authors independently extracted data from the included trial and assessed its risk of bias. We carried out data analysis using the 'treatment as allocated' patient population, expressing estimates of intervention effect for dichotomous data as risk ratios, with 95% confidence intervals (CI). MAIN RESULTS We included one trial, which was judged to be at high risk of performance, detection and attrition bias. The 117 participants with a root-filled, premolar tooth restored with a carbon fibre post, were randomised to either a full coverage metal-ceramic crown or direct adhesive composite restoration. None experienced a catastrophic failure (i.e. when the restoration cannot be repaired), although only 104 teeth were included in the final, three-year assessment. There was no clear difference between the crown and composite group and the composite only group for non-catastrophic failures of the restoration (1/54 versus 3/53; RR 0.33; 95% CI 0.04 to 3.05) or failures of the post (2/54 versus 1/53; RR 1.96; 95% CI 0.18 to 21.01) at three years. The quality of the evidence for these outcomes is very low. There was no evidence available for any of our secondary outcomes: patient satisfaction and quality of life, incidence or recurrence of caries, periodontal health status, and costs. AUTHORS' CONCLUSIONS There is insufficient evidence to assess the effects of crowns compared to conventional fillings for the restoration of root-filled teeth. Until more evidence becomes available, clinicians should continue to base decisions about how to restore root-filled teeth on their own clinical experience, whilst taking into consideration the individual circumstances and preferences of their patients.

The hundred most cited articles in bariatric surgery

BACKGROUND Many studies quantitatively analyzing scientific papers have appeared in the last 2 years. Citation analysis is a commonly used bibliometric method. In spite of some limitations, it remains a good measure of the impact an article has on a specific field, specialty, or a journal. The aim of this study was to analyze the qualities and characteristics of the 100 most cited articles in the field of bariatric surgery. METHODS The Thomson Reuters Web of Knowledge was used to list all bariatric surgery-related articles (BSRA) published from 1945 to 2014. The top 100 most cited BSRA in 354 surgical and high impact general journals were selected for further analysis. RESULTS Most of the articles were published in the 2000s (60%). The top 100 most cited were published in 17 of the 354 journals. Leading countries were USA followed by Canada and Australia. Most of the articles published (76%) were clinical experience articles. The most common level of evidence was IV (42%). CONCLUSIONS Many of the milestone papers in bariatric surgery have been included in this bibliometric study. A huge increase in research activity during the last decade is clearly visible in the field. It is apparent that the number of citations of an article is not related to its level of evidence; a fact that is increasingly being emphasized in surgical research.

The State of the University of Connecticut Health Center

Academic medical centers represent the integration of education, namely schools of medicine and dental medicine, research, often through a biomedical sciences graduate program, and a clinical experience, often supplied with an onsite hospital. These medical centers involve an intricate mix of individuals and personalities, making their operation a difficult and sometimes daunting task. The University of Connecticut Health Center (UCHC) financial struggles have created a new opportunity, an affiliation with Hartford Healthcare, which will equip the UCHC with a major tertiary care University Hospital. This thesis intends to provide an analysis of the challenges and potential benefits of such a partnership. It is focused on the impact to the medical school’s academic mission and involves a comprehensive look at John Dempsey Hospital (JDH) finances, governance, and employee matters. The research concludes that such an affiliation is necessary to change the healthcare landscape of the region and transform the UCHC into a top medical driver of the Connecticut economy. It intends to show how the status quo is no longer an acceptable option.

Examination of the influence of behavioral, normative and control beliefs on the adherence to a prescribed renal diet among elderly populations with chronic to end-stage renal disease

The 1999-2004 prevalence of chronic kidney disease in adults 20 year or older (15.5 million) is an estimated 7.69%. The risk of developing CKD is exacerbated by diabetes, hypertension and/or a family history of kidney disease. African Americans, Hispanics, Pacific Islanders, Native Americans, and the elderly are more susceptible to higher incidence of CKD. The challenges of aging coupled with co-morbidities such as kidney disease raises the potential for malnutrition among elderly (for the purpose of this study 55 years or older) populations. Lack of adherence to prescribed nutrition guidelines specific to renal failure jeopardizes body homeostasis and increases the likelihood of future morbidity and resultant mortality. The relationship and synergy that exists between diet and disease is evident. Clinical experience with renal patients has indicated the importance of adherence to diet therapy specific to kidney disease. Extension investigation of diet adherence among endstage renal disease patients revealed a sizeable dearth in the current literature. This thesis study was undertaken to help reduce that void. The study design is qualitative and descriptive. Support, cooperation, and collaboration were provided by the University of Texas Nephrology Department, University of Texas Physicians, and DaVita Dialysis Centers. Approximately 105 male and female chronic to end-stage kidney disease patients were approached to participate in elicitation interviews in dialysis treatment facilities regarding their present diet beliefs and practices. Eighty-five were recruited and agreed to participate. Inclusion criteria required individuals to be between 35-90 years of age; capable of completing a 5-10 minute interview; and English speaking. Each kidney patient was asked seven (7) non-leading questions developed from the constructs of the Theory of Planned Behavior. The study presents a descriptive comparison of behavioral, normative, and control beliefs that influence adherence to renal diets by age, race, and gender. The study successfully concluded that behavioral, normative, and control beliefs of chronic to end-stage renal patients promoted execution and adherence to prescribed nutrition. This study provides valuable information for dietitians, technicians, nurses, and physicians to assess patient compliance toward prescribed nutrition and the means to support or improve that performance. ^

Endocoronas de resina compuesta : presentación de un caso clínico

Las restauraciones de inserción rígidas, tanto incrustaciones como coronas, cuentan con el aval de una amplia experiencia clínica. En nuestra práctica diaria se nos presentan a menudo casos en los que no podemos resolver el problema de una gran destrucción coronaria con ninguno de estos tratamientos. En este trabajo se presenta un caso clínico solucionado mediante la confección de una endocorona de resina compuesta debido a la contraindicación clínica de las restauraciones tradicionales, ya que el elemento a ser tratado presentaba una perforación en el piso de la cámara pulpar con un pronóstico de sobrevida reservado.

A data-globe and immersive virtual reality environment for upper limb rehabilitation after spinal cord injury

While a number of virtual data-gloves have been used in stroke, there is little evidence about their use in spinal cord injury (SCI). A pilot clinical experience with nine SCI subjects was performed comparing two groups: one carried out a virtual rehabilitation training based on the use of a data glove, CyberTouch combined with traditional rehabilitation, during 30 minutes a day twice a week along two weeks; while the other made only conventional rehabilitation. Furthermore, two functional indexes were developed in order to assess the patient’s performance of the sessions: normalized trajectory lengths and repeatability. While differences between groups were not statistically significant, the data-glove group seemed to obtain better results in the muscle balance and functional parameters, and in the dexterity, coordination and fine grip tests. Related to the indexes that we implemented, normalized trajectory lengths and repeatability, every patient showed an improvement in at least one of the indexes, either along Y-axis trajectory or Z-axis trajectory. This study might be a step in investigating new ways of treatments and objective measures in order to obtain more accurate data about the patient’s evolution, allowing the clinicians to develop rehabilitation treatments, adapted to the abilities and needs of the patients.

Interferon-β gene therapy inhibits tumor formation and causes regression of established tumors in immune-deficient mice

Despite the potential of type 1 interferons (IFNs) for the treatment of cancer, clinical experience with IFN protein therapy of solid tumors has been disappointing. IFN-β has potent antiproliferative activity against most human tumor cells in vitro in addition to its known immunomodulatory activities. The antiproliferative effect, however, relies on IFN-β concentrations that cannot be achieved by parenteral protein administration because of rapid protein clearance and systemic toxicities. We demonstrate here that ex vivo IFN-β gene transduction by a replication-defective adenovirus in as few as 1% of implanted cells blocked tumor formation. Direct in vivo IFN-β gene delivery into established tumors generated high local concentrations of IFN-β, inhibited tumor growth, and in many cases caused complete tumor regression. Because the mice were immune-deficient, it is likely that the anti-tumor effect was primarily through direct inhibition of tumor cell proliferation and survival. Based on these studies, we argue that local IFN-β gene therapy with replication-defective adenoviral vectors might be an effective treatment for some solid tumors.

Adaptação cultural e validação da Compliance with Standard Precautions Scale (CSPS) para enfermeiros brasileiros

Introdução: As precauções-padrão (PP) constituem um conjunto de medidas que têm como finalidade minimizar o risco de transmissão ocupacional de patógenos, sendo indispensável sua utilização por profissionais de saúde, sobretudo pelos enfermeiros. No entanto, a não adesão às PP constitui problemática amplamente discutida em todo o mundo. Embora haja diversos estudos brasileiros que visem avaliar a adesão às PP , ainda tem-se observado grande fragilidade no processo de construção e de validação dos instrumentos utilizados para avaliação deste construto. Objetivo: Realizar a adaptação cultural e validação da Compliance with Standard Precautions Scale (CSPS) para enfermeiros brasileiros. Metodologia: Trata-se de um estudo metodológico para a adaptação e validação da CSPS. Essa escala é composta por 20 itens com quatro opções de respostas, e destina-se a avaliar a adesão às PP. O processo de adaptação consistiu em Tradução, Consenso entre Juízes, Retrotradução e Validação Semântica. A primeira etapa foi a tradução do idioma original para o português do Brasil. Após foi realizado um comitê composto por sete juízes, a versão de consenso obtida na etapa anterior foi traduzida novamente para o idioma de origem. Foram avaliadas as propriedades psicométricas do instrumento, considerando-se as validades de face e de conteúdo, a validade de construto e a confiabilidade. A versão para o Português do Brasil da CSPS (CSPS-PB) foi aplicada em uma amostra de 300 enfermeiros que atuam na assistência a pacientes em um hospital localizado na cidade de São Paulo/SP. A confiabilidade foi avaliada por meio da consistência interna (alfa de Cronbach) e teste reteste (coeficiente de correlação intraclasse - ICC). Para a validação de construto, foi utilizada a comparação entre grupos diferentes, análise fatorial exploratória e análise fatorial confirmatória, segundo o Modelo de Equações Estruturais (SEM). Utilizou-se o software IBM® SPSS, 19.0. Para a análise fatorial confirmatória foi utilizado o módulo específico Analysis of Moment Structures (IBM® SPSS AMOS). Para a análise paralela utilizou-se o programa RanEigen Syntax. O nível de significância adotado foi ? = 0,05. Todos os aspectos éticos foram contemplados. Resultados: A tradução realizada por tradutores juramentados garantiu qualidade a esse processo. A validação de face e de conteúdo possibilitou a realização de modificações pertinentes e imperativas a fim de atender aos critérios de equivalências conceituais, idiomáticas, culturais e semânticas. Obteve-se ?=0,61 na avaliação da consistência interna, indicando confiabilidade satisfatória. O ICC indicou uma correlação de 0,87 quase perfeita para o teste reteste duas semanas após a primeira abordagem, conferindo estabilidade satisfatória. A validade de construto mostrou que a CSPS-PB foi capaz de discriminar as médias de adesão às PP entre grupos distintos referente à idade (F=5,15 p<=0,01), ao tempo de experiência clínica (F = 8,9 p<= 0,000) e a ter recebido treinamento (t = 2,48 p<=0,01). Na análise fatorial confirmatória, o modelo foi subidentificado. A análise fatorial exploratória indicou que todos os itens apresentaram cargas fatoriais adequadas (>=0,30), sendo identificados quatro fatores pela análise paralela. O total de variância explicada foi de 35,48%. Conclusão: A CSPS-PB, trata-se de um instrumento adequado, confiável e válido para medir a adesão às PP entre enfermeiros brasileiros