Real-world treatment patterns and disease control over one year in patients with inflammatory bowel disease in Brazil.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBDs) with a remission-relapsing presentation and symptomatic exacerbations that have detrimental impacts on patient quality of life and are associated with a high cost burden, especially in patients with moderate-to-severe disease. The Real-world Data of Moderate-to-Severe Inflammatory Bowel Disease in Brazil (RISE BR) study was a noninterventional study designed to evaluate disease control, treatment patterns, disease burden and health-related quality of life in patients with moderate-to-severe active IBD. We report findings from the prospective follow-up phase of the RISE BR study in patients with active UC or CD. AIM: To describe the 12-mo disease evolution and treatment patterns among patients with active moderate-to-severe IBD in Brazil. METHODS: This was a prospective, noninterventional study of adult patients with active Crohn's disease (CD: Harvey-Bradshaw Index ≥ 8, CD Activity Index ≥ 220), inadequate CD control (i.e., calprotectin > 200 µg/g or colonoscopy previous results), or active ulcerative colitis (UC: Partial Mayo score ≥ 5). Enrollment occurred in 14 centers from October 2016 to February 2017. The proportion of active IBD patients after 9-12 mo of follow-up, Kaplan-Meier estimates of the time to mild or no activity and a summary of treatment initiation, discontinuation and dose changes were examined. RESULTS: The study included 118 CD and 36 UC patients, with mean ± SD ages of 43.3 ± 12.6 and 44.9 ± 16.5 years, respectively. The most frequent drug classes at index were biologics for CD (62.7%) and 5-aminosalicylate derivates for UC patients (91.7%). During follow-up, 65.3% of CD and 86.1% of UC patients initiated a new treatment at least once. Discontinuations/dose changes occurred in 68.1% of CD patients [median 2.0 (IQR: 2-5)] and 94.3% of UC patients [median 4.0 (IQR: 3-7)]. On average, CD and UC patients had 4.4 ± 2.6 and 5.0 ± 3.3 outpatient visits, respectively. The median time to first mild or no activity was 319 (IQR: 239-358) d for CD and 320 (IQR: 288-358) d for UC patients. At 9-12 mo, 22.0% of CD and 20.0% of UC patients had active disease. CONCLUSION: Although a marked proportion of active IBD patients achieved disease control within one year, the considerable time to achieve this outcome represents an unmet medical need of the current standard of care in a Brazilian real-world setting.

Real-world disease activity and sociodemographic, clinical and treatment characteristics of moderate-to-severe inflammatory bowel disease in Brazil.

BACKGROUND: Understanding the treatment landscape of inflammatory bowel diseases (IBD) is essential for improving disease management and patient outcomes. Brazil is the largest Latin American country, and it presents socioeconomic and health care differences across its geographical regions. This country has the highest increase in IBD incidence and prevalence in Latin America, but information about the clinical and treatment characteristics of IBD is scarce. AIM: To describe the sociodemographic, clinical, and treatment characteristics of IBD outpatients in Brazil overall and in the Southeast, South and Northeast/Midwest regions. METHODS: Multicenter, cross-sectional study with a 3-year retrospective chart review component. Patients with moderate-to-severe Crohn's disease (CD) or ulcerative colitis (UC) were consecutively enrolled between October 2016 and February 2017. Active CD at enrollment was defined as a Harvey Bradshaw Index ≥ 8 or a CD Activity Index ≥ 220 or a calprotectin level > 200 µg/g or an active result based on colonoscopy suggestive of inadequate control during the previous year; active UC was defined as a partial Mayo score ≥ 5. Descriptive statistics were used to analyze all variables. RESULTS: In a total of 407 included patients, CD was more frequent than UC, both overall (264 CD/143 UC patients) and by region (CD:UC ratios of 2.1 in the Southeast, 1.6 in the South and 1.2 in the Northeast/Midwest). The majority of patients were female (54.2% of CD; 56.6% of UC), and the mean ages were 45.9 ± 13.8 years (CD) and 42.9 ± 13.0 years (UC). The median disease duration was 10.0 (range: 0.5-45) years for both IBD types. At enrollment, 44.7% [95% confidence interval (CI): 38.7-50.7] of CD patients and 25.2% (95%CI: 18.1-32.3) of UC patients presented with active disease. More than 95% of IBD patients were receiving treatment at enrollment; CD patients were commonly treated with biologics (71.6%) and immunosuppressors (67.4%), and UC patients were commonly treated with mesalazine [5-Aminosalicylic acid (5-ASA)] derivates (69.9%) and immunosuppressors (44.1%). More than 50% of the CD patients had ileocolonic disease, and 41.7% presented with stricturing disease. One-quarter of CD patients had undergone CD-related surgery in the past 3 years, and this proportion was lower in the Northeast/Midwest region (2.9%). CONCLUSION: In Brazil, there are regional variations in IBD management. CD outweighs UC in both frequency and disease activity. However, one-quarter of UC patients have active disease, and most are receiving 5-ASA treatment.

Quality of life, work productivity impairment and healthcare resources in inflammatory bowel diseases in Brazil.

BACKGROUND: Inflammatory bowel diseases (IBD) have been associated with a low quality of life (QoL) and a negative impact on work productivity compared to the general population. Information about disease control, patient-reported outcomes (PROs), treatment patterns and use of healthcare resources is relevant to optimizing IBD management. AIM: To describe QoL and work productivity and activity impairment (WPAI), treatment patterns and use of healthcare resources among IBD patients in Brazil. METHODS: A multicenter cross-sectional study included adult outpatients who were previously diagnosed with moderate to severe Crohn's disease (CD) or ulcerative colitis (UC). At enrolment, active CD and UC were defined as having a Harvey Bradshaw Index ≥ 8 or a CD Activity Index ≥ 220 or calprotectin > 200 µg/g or previous colonoscopy results suggestive of inadequate control (per investigator criteria) and a 9-point partial Mayo score ≥ 5, respectively. The PRO assessment included the QoL questionnaires SF-36 and EQ-5D-5L, the Inflammatory Bowel Disease Questionnaire (IBDQ), and the WPAI questionnaire. Information about healthcare resources and treatment during the previous 3 years was collected from medical records. Chi-square, Fisher's exact and Student's t-/Mann-Whitney U tests were used to compare PROs, treatment patterns and the use of healthcare resources by disease activity (α = 0.05). RESULTS: Of the 407 patients in this study (CD/UC: 64.9%/35.1%, mean age 42.9/45.9 years, 54.2%/56.6% female, 38.3%/37.1% employed), 44.7%/25.2% presented moderate-to-severe CD/UC activity, respectively, at baseline. Expressed in median values for CD/UC, respectively, the SF-36 physical component was 46.6/44.7 and the mental component was 45.2/44.2, the EQ-visual analog scale score was 80.0/70.0, and the IBDQ overall score was 164.0/165.0. Moderate to severe activity, female gender, being unemployed, a lower educational level and lower income were associated with lower QoL (P < 0.05). Median work productivity impairment was 20% and 5% for CD and UC patients, respectively, and activity impairment was 30%, the latter being higher among patients with moderate to severe disease activity compared to patients with mild or no disease activity (75.0% vs 10.0%, P < 0.001). For CD/UC patients, respectively, 25.4%/2.8% had at least one surgery, 38.3%/19.6% were hospitalized, and 70.7%/77.6% changed IBD treatment at least once during the last 3 years. The most common treatments at baseline were biologics (75.3%) and immunosuppressants (70.9%) for CD patients and 5-ASA compounds (77.5%) for UC patients. CONCLUSION: Moderate to severe IBD activity, especially among CD patients, is associated with a substantial impact on QoL, work productivity impairment and an increased number of IBD surgeries and hospitalizations in Brazil.

Nano-Computed Tomography: Technique and Applications.

UNLABELLED: Nano-computed tomography (nano-CT) is an emerging, high-resolution cross-sectional imaging technique and represents a technical advancement of the established micro-CT technology. Based on the application of a transmission target X-ray tube, the focal spot size can be decreased down to diameters less than 400 nanometers (nm). Together with specific detectors and examination protocols, a superior spatial resolution up to 400 nm (10 % MTF) can be achieved, thereby exceeding the resolution capacity of typical micro-CT systems. The technical concept of nano-CT imaging as well as the basics of specimen preparation are demonstrated exemplarily. Characteristics of atherosclerotic plaques (intraplaque hemorrhage and calcifications) in a murine model of atherosclerosis (ApoE (-/-)/LDLR(-/-) double knockout mouse) are demonstrated in the context of superior spatial resolution in comparison to micro-CT. Furthermore, this article presents the application of nano-CT for imaging cerebral microcirculation (murine), lung structures (porcine), and trabecular microstructure (ovine) in contrast to micro-CT imaging. This review shows the potential of nano-CT as a radiological method in biomedical basic research and discusses the application of experimental, high resolution CT techniques in consideration of other high resolution cross-sectional imaging techniques. KEY POINTS: Nano-computed tomography is a high resolution CT-technology for 3D imaging at sub-micrometer resolution. The technical concept bases on a further development of the established ex-vivo-micro-CT technology. By improvement of the spatial resolution, structures at a cellular level become visible (e.g. osteocyte lacunae).

Recommendations on the use of biosimilars by the Brazilian Society of Rheumatology, Brazilian Society of Dermatology, Brazilian Federation of Gastroenterology and Brazilian Study Group on Inflammatory Bowel Disease--Focus on clinical evaluation of monoclonal antibodies and fusion proteins used in the treatment of autoimmune diseases.

The Brazilian Societies of Rheumatology (SBR) and Dermatology (SBD), the Brazilian Federation of Gastroenterology (FBG) and the Brazilian Study Group on Inflammatory Bowel Disease (GEDIIB) gathered a group of their respective specialists on the topic of interest to discuss the most relevant issues regarding the clinical use of biosimilar medicines in Brazil. The main aim of that meeting was to prepare a document with recommendations to guide medical specialists and to help the national regulatory and policy-making agencies as concerns the authorization for marketing biosimilars used in autoimmune diseases, such as rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, Crohn's disease, juvenile idiopathic arthritis and ulcerative colitis. In addition to considerations on the typical differences between innovator medicines and biosimilars, the specialists established a set of seven recommendations on regulatory advances related to clinical studies, indication extrapolation, nomenclature, interchangeability, automatic substitution and pharmacovigilance.

Retocolite ulcerativa não complicada / Ulcerative colitis not complicated

Retocolite ulcerativa inespecífica (RCU) e doença de Crohn (DC) são consideradas as principais doenças inflamatórias intestinais idiopáticas (DIIs). De etiologia ainda desconhecida, evoluem, clinicamente, por surtos recorrentes, intercalando episódios de atividade inflamatória, acompanhados de manifestações digestivas e extradigestivas, com períodos de remissão, ambos imprevisíveis...

Nonspecific ulcerative recolitis (NUC) and Chron's Disease (CD) are considered the mainly idiopathic inflammatory bowel disease (IBD). Etiology unknown, the nonspecific ulcerative recolitis has a clinical proceed, by recurrent outbreaks, episodes of intercalated inflammatory activity, following by digestive and extra digestive symptoms, with period of remission, both of them are unpredictable...

Dual energy CT myelography after lumbar osteosynthesis.

PURPOSE: The purpose of this study was to evaluate the benefits of CT myelography in the DE technique in patients with lumbar osteosynthesis. MATERIALS AND METHODS: In 30 patients a DE-CT scan of the spine with tube voltages of 80 kV and 140 kV was performed and a virtual monochromatic series of 120 kV was generated after intrathecal contrast injection. The impact of metal artifacts on the spinal canal and the spinal foramina was evaluated. The visualization of nerve roots was compared between a VRT series of the dural sac and conventional myelography. RESULTS: With tube voltages of 140 kV, the artifacts were least pronounced. As no overlay disturbance was present, VRT visualization of the nerve roots was more reliable than conventional myelography. CONCLUSION: In patients after osteosynthesis, CT in the DE technique provides minimal artifact disturbance using a tube voltage of 140 kV. "Virtual myelography" seems to be superior to conventional myelography for the evaluation of nerve roots. This could reduce additional conventional radiography, may shorten the entire examination and radiation time and diminish unnecessary painful movements for the patient.

Doença de Crohn estenosante / Stuttering crohn's disease

As estenoses são uma das mais graves complicações da doença de Crohn (DC), por pressuporem indicação de ressecção cirúrgica de segmentos intestinais e, como consequência,um novo desenho anatômico do canal alimentar, na maioria das vezes com perda dos eu estado fisiológico, objetivo insistentemente perseguido pelo tratamento medicamentoso desse processo inflamatório. Surgem tanto primariamente em áreas doentes do intestino delgado ou cólon quanto em anastomoses de cirurgias prévias.

Diverticulose, doença diverticular e diverticulite / Diverticulosis, diverticulitis and diverticular disease

Os autores revisaram um dos assuntos mais relevantes dentro da Gastroenterologia: diverticulose cólica, doença diverticular, diverticulite e outras complicações relacionadas com os divertículos cólicos, como o sangramento diverticular. São apresentados, extensivamente, dados epidemiológicos, fatores de risco, quadro clínico e os métodos diagnósticos mais atuais relativos à doença diverticular, diverticulite e outras complicações. Nos últimos anos, a abordagem terapêutica, particularmente nos casos não complicados de doença diverticular, evoluiu consideravelmente com o uso de mesalazina e probióticos, assuntos que mereceram uma análise crítica por parte dos autores, no contexto dos novos itens fisiopatológicos.

Obstipação intestinal na mulher / Constipation in women

Constipação intestinal crônica é uma disfunção digestiva que acomete de 20.

[Impact of functional restoration programs on fears, avoidance and beliefs in chronic low back pain patients]. / Impact de programmes de restauration fonctionnelle sur les peurs, croyances et conduites d'évitement du lombalgique chronique.

OBJECTIVE: To assess the impact of functional restoration programs on fears, avoidance and beliefs in chronic low back pain. METHODS: Open prospective study in eight spine centers. Seventy patients enrolled in several restoration programs were evaluated before and at the end of the program. Variables recorded were pain (VAS), disability (Quebec back pain disability scale), handicap (VAS), anxiety and depression (HAD scale), and fears, avoidance and beliefs (FABQ). RESULTS: All variables recorded significantly improved at the end of the programs except for fears about professional activities (FABQ1) and lumbar mobility. Fears about physical activities (FABQ2) significantly decreased after these programs. Variations in FABQ1 and FABQ2 scores were not correlated with variations in scores of outcome measures assessing impairment, disability, and handicap. CONCLUSION: Functional restoration programs in their current form in France do not decrease fears and beliefs about professional activities in chronic low back pain patients. Adding psychosocial intervention at the work place to the functional restoration programs may lead to a better impact on fears about work thus reducing work loss.

Managing chronic headaches in the clinic.

Chronic daily headache (CDH), which is often linked to a history of migraine, tension-type headache and the abuse of headache medications, and cluster headache are the best known of the chronic headaches. These headaches may not be well recognised or well treated in primary care. This article outlines the development of management algorithms for these headache subtypes, designed for use by the primary care physician with an interest in headache. Principles of care for chronic headaches include implementation of screening procedures, differential diagnosis, tailoring of management to the individual's needs, proactive follow-up and a team approach to care. These principles can be customised to the headache subtype by the selection of appropriate therapies. The optimal treatments for CDH include physical therapy to the neck if there is any stiffness there, withdrawal of abused medications and treatment of any subsequent withdrawal symptoms and headache prophylaxis, together with the provision of acute medications as rescue therapy. Optimal treatments for cluster headache include short- and long-term prophylaxis to prevent the headaches developing and acute medications for use as rescue. If treatment is ineffective, alternative medications can be provided at follow-up, with the possibility of referral for refractory patients.

Establishing principles for migraine management in primary care.

Published guidelines for the management of migraine in primary care were evaluated by an international advisory board of headache specialists, to establish evidence-based principles of migraine management that could be recommended for international use. Twelve principles of migraine management were identified, covering screening, diagnosis, management and treatments: Almost all headaches are benign/primary and can be managed by all practising clinicians. Use questions/a questionnaire to assess the impact on daily living and everyday activities, for diagnostic screening and to aid management decisions. Share migraine management between the clinician and the patient. Provide individualised care for migraine and encourage patients to manage their migraine. Follow up patients, preferably with migraine calendars or diaries. Regularly re-evaluate the success of therapy using specific outcome measures and monitor the use of acute and prophylactic medications regularly. Adapt migraine management to changes that occur in the illness and its presentation over the years. Provide acute medication to all migraine patients and recommend it is taken at the appropriate time, during the attack. Provide rescue medication/symptomatic treatment for when the initial therapy fails. Offer to prescribe prophylactic medications, as well as lifestyle changes, to patients who have four or more migraine attacks per month or who are resistant to acute medications. Consider concurrent co-morbidities in the choice of appropriate prophylactic medication. Work with the patient to achieve comfort with mutually agreed upon treatment and ensure that it is practical for their lifestyle and headache presentation. Using these principles, practising clinicians can screen and diagnose their headache patients effectively and manage their migraine patients over the long-term natural history of the migraine process. In this way, the majority of migraine patients can be well treated in primary care, ensuring a structured and individualised approach to headache management, and conserving valuable healthcare resources.

New guidelines for the management of migraine in primary care.

Despite repeated initiatives over the past decade, migraine remains under-recognised, under-diagnosed and under-treated in everyday clinical practice. The Migraine in Primary Care Advisors (MIPCA) group has produced new guidelines for migraine management to attempt to rectify this situation. MIPCA is a group of physicians, nurses, pharmacists and other healthcare professionals dedicated to the improvement of headache management in primary care, who have also worked closely with the Migraine Action Association (the UK patients' group) in the development of these guidelines. The principles of the new MIPCA guidelines are: To arrange specific consultations for headache. To institute a system of detailed history taking, patient education and buy-in at the outset of the consultation. To utilise a new screening algorithm for the differential diagnosis of headache, which can be confirmed by further questioning, if necessary. To institute a process of management that is individualised for each patient, using a new algorithm. Assessing the impact on the patient's daily life is a key aspect of diagnosis and management. To prescribe only treatments that have objective evidence of favourable efficacy and tolerability. To utilise prospective follow-up procedures to monitor the success of treatment. To organise a team approach to headache management in primary care.

Medical history of hypercholesterolaemia adversely affects the outcome of out-of-hospital cardiopulmonary resuscitation; the 'Shahal' experience in Israel.

AIMS: To evaluate the impact selected risk factors for cardiac death may have on the success rate in a large cohort of subscribers to 'SHAHAL' who were resuscitated from out-of-hospital cardiac arrest. METHODS AND RESULTS: In this medical facility currently serving 50 000 subscribers, data were prospectively gathered from between 1987-1998. The information retrieved from the patients' medical records included a medical history of hypertension, diabetes, hypercholesterolaemia (>220.mg. dl(-1)) smoking, angina, previous myocardial infarction, and congestive heart failure. A total of 998 patients aged 74+/-12 years (mean+/-1 SD) were included. Death was announced at the scene for 659 (66%) victims, while 339 (34%) patients were taken to hospital. Of these 140 (14% of the total cohort) survived and were discharged from the hospital. A comparison of various selected parameters between survivors and non-survivors of resuscitation revealed that survivors were younger, had a higher rate of pulseless ventricular tachycardia/ventricular fibrillation, more were among the arrests witnessed by the 'SHAHAL' team, and that more had a shorter time lag to initiation of cardiopulmonary resuscitation than non-survivors. None of the studied risk factors predicted the outcome of cardiopulmonary resuscitation, with the exception of hypercholesterolaemia, which carried a significantly worse prognosis for cardiopulmonary resuscitation (P=0.009). CONCLUSIONS: A medical history of hypercholesterolaemia appears to be an important risk factor which adversely affects the outcome of cardiopulmonary resuscitation.

Effect of viral infections on the ability of human endothelium for interferon, tumor necrosis factor and interleukin 6 production.

We have reported that cultured human umbilical cord vein endothelial cells (HUVEC) differ from endothelium present on vein surface of organ culture (OC) in production of cytokines and susceptibility to viral infections. In this paper we present the effect of viral infections on interferon (IFN), tumor necrosis factor (TNF), and interleukin 6 (IL-6) production in two culture systems: HUVEC and OC. Infection of 24-48 h HUVEC with herpes simplex type 1 (HSV-1) and vesicular stomatitis virus (VSV) reduced the amounts of IL-6 and TNF produced in comparison to those released spontaneously by uninfected cells. No IFN was detected in media from infected and uninfected HUVEC. Limited viral infections of 3-h-HUVEC and OC usually diminished their efficiency of IL-6 and TNF production. In the case of IL-6 synthesis by OC, effect of viral infection depended, however, on the constitutive synthesis of the cytokine. When spontaneous production was high (> 800 U/ml), VSV and HSV-1 infection reduced IL-6 level by 2-50 times; in the case of low production (< 150 U/ml) the stimulation effect (2-4 fold) was observed. OC released spontaneously some IFN activity (2-32 U/ml). HSV-1 infection of OC reduced IFN level, while VSV in single cases slightly upregulated IFN synthesis.

Antiviral nonspecific immunity of human placenta at term: possible role of endogenous tumor necrosis factors and interferons.

The antiviral immunity of human placenta and amniotic membrane in an organ culture (OC) system was studied. Freshly isolated explants of most of the placentas at term and the amniotic membranes were found to be relatively resistant to herpes simplex virus type 1 (HSV-1), encephalomyocarditis virus (EMCV), and vesicular stomatitis virus (VSV) infections. After in vitro aging, however, the OC acquired the sensitivity to the viruses. In about 66%-90% of placentas, resistance of freshly isolated explants to the infection was observed. This indicates that the placentas displayed a constitutive immunity against the viruses. To study the role of endogenous cytokines in antiviral immunity, we added specific antibodies neutralizing IFN and TNF activities to VSV-infected OC and checked their influence on viral replication. Increases of 10-fold to 100-fold of VSV replication in the OC treated with anti-TNF-alpha, anti-IFN-alpha, anti-IFN-gamma or anti-IFN-beta sera were observed. The results indicate the importance of the endogenous cytokines in placental and amniotic membrane immunity. However, we did not observe a simple correlation between the spontaneous IFN and TNF production and the level of resistance against viruses. In view of the results, the participation of TNF and IFN in the constitutively expressed immunity of human placenta is of a more complex nature.