Biologic therapies for refractory juvenile dermatomyositis: five years of experience of the Childhood Arthritis and Rheumatology Research Alliance in North America.

BACKGROUND: The prognosis of children with juvenile dermatomyositis (JDM) has improved remarkably since the 1960's with the use of corticosteroid and immunosuppressive therapy. Yet there remain a minority of children who have refractory disease. Since 2003 the sporadic use of biologics (genetically-engineered proteins that usually are derived from human genes) for inflammatory myositis has been reported. In 2011-2016 we investigated our collective experience of biologics in JDM through the Childhood Arthritis and Rheumatology Research Alliance (CARRA). METHODS: The JDM biologic study group developed a survey on the CARRA member experience using biologics for Juvenile DM utilizing Delphi consensus methods in 2011-2012. The survey was completed online by the CARRA members interested in JDM in 2012. A second survey was similarly developed that provided more opportunity to describe their experiences with biologics in JDM in detail and was completed by CARRA members in Feb 2013. During three CARRA meetings in 2013-2015, nominal group techniques were used for achieving consensus on the current choices of biologic drugs. A final survey was performed at the 2016 CARRA meeting. RESULTS: One hundred and five of a potential 231 pediatric rheumatologists (42%) responded to the first survey in 2012. Thirty-five of 90 had never used a biologic for Juvenile DM at that time. Fifty-five of 91 (denominators vary) had used biologics for JDM in their practice with 32%, 5%, and 4% using rituximab, etanercept, and infliximab, respectively, and 17% having used more than one of the three drugs. Ten percent used a biologic as monotherapy, 19% a biologic in combination with methotrexate (mtx), 52% a biologic in combination with mtx and corticosteroids, 42% a combination of a biologic, mtx, corticosteroids (steroids), and an immunosuppressive drug, and 43% a combination of a biologic, IVIG and mtx. The results of the second survey supported these findings in considerably more detail with multiple combinations of drugs used with biologics and supported the use of rituximab, abatacept, anti-TNFα drugs, and tocilizumab in that order. One hundred percent recommended that CARRA continue studying biologics for JDM. The CARRA meeting survey in 2016 again supported the study and use of these four biologic drug groups. CONCLUSIONS: Our CARRA JDM biologic work group developed and performed three surveys demonstrating that pediatric rheumatologists in North America have been using multiple biologics for refractory JDM in numerous scenarios from 2011 to 2016. These survey results and our consensus meetings determined our choice of four biologic therapies (rituximab, abatacept, tocilizumab and anti-TNFα drugs) to consider for refractory JDM treatment when indicated and to evaluate for comparative effectiveness and safety in the future. Significance and Innovations This is the first report that provides a substantial clinical experience of a large group of pediatric rheumatologists with biologics for refractory JDM over five years. This experience with biologic therapies for refractory JDM may aid pediatric rheumatologists in the current treatment of these children and form a basis for further clinical research into the comparative effectiveness and safety of biologics for refractory JDM.

Cardiovascular events associated with second-line anti-diabetes treatments: analysis of real-world Korean data.

AIM: To compare the risks of cardiovascular disease (CVD) and all-cause mortality associated with sulfonylurea (SU), dipeptidyl peptidase-4 inhibitor (DPP4i) and thiazolidinedione (TZD) as add-on medications to metformin (MET) therapy in people with Type 2 diabetes. METHODS: We identified 40 263 individuals who used SU (n = 11 582), DPP4i (n = 26 623) or TZD (n = 2058) in addition to MET between January 2013 and June 2015 from the database of the Korean National Health Insurance, the single-payer healthcare system in South Korea. Cox proportional hazard models were used to estimate hazard ratios for major CVD event (coronary artery disease, heart failure, stroke or transient ischaemic attack) development and all-cause mortality by second-line anti-diabetes medication type. Age, sex, duration of MET monotherapy, calendar year and comorbid conditions were adjusted as potential confounders. RESULTS: The observed numbers of CVD events (total observed person-time) were 485 (18 778 person-years) for MET + SU, 744 (40 374 person-years) for MET + DPP4i and 60 (3014 person-years) for MET + TZD users. Compared with MET + SU users, the fully adjusted hazard ratios for CVD events were 0.79 [95% confidence interval (CI): 0.71-0.89] for MET + DPP4i users and 0.85 (95% CI: 0.65-1.11) for MET + TZD users. The corresponding hazard ratios for all-cause mortality were 0.84 (95% CI: 0.66-1.07) for MET + DPP4i users and 0.67 (95% CI: 0.35-1.28) for MET + TZD users. CONCLUSION: Analysis of Korea National Health Insurance database showed that MET + DPP4i treatment for diabetes had a lower CVD risk than MET + SU treatment.

Epidemiología de la lepra en la región del Norte Araguaia, MT, Brasil, en el período entre 2001 y 2012 (parte III) / No disponible

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Office and ambulatory blood pressure control in hypertensive patients treated with different two-drug and three-drug combinations.

There is scarce information regarding ambulatory blood pressure (BP) achieved in daily practice with a wide range of antihypertensive drug combinations. We looked for differences in office and ambulatory BP among major drug combinations of two and three antihypertensive agents from a different drugs class. A total of 17187 patients treated with six types of two-drug combinations and 9724 treated with six types of three-drug combinations from the Spanish ABPM Registry were analyzed. We compared achieved office and ambulatory BP, as well as office (< 140/90 mmHg) and ambulatory (24-hour BP < 130/80; day BP < 135/85, and night BP < 120/70 mmHg) BP control among groups. The combination of renin-angiotensin system (RAS) blockers with diuretics and the triple combination of RAS blockers with diuretics and calcium channel blockers (CCB) were associated with lower values of 24-hour, daytime and nighttime BP, as well as more pronounced nocturnal BP dip. Compared with such combinations (reference), other double combinations had lower rates of ambulatory BP control. Moreover, triple combinations containing alpha blockers also had lower rates of ambulatory BP control. We conclude that even with similar office BP control, differences exist among antihypertensive two-drug and three-drug combinations with respect to ambulatory BP control achieved during treatment, with RAS blockers/diuretics and RAS blockers/CCBs/diuretics obtaining better control rates. This can help physicians choose among drug combinations in order to obtain further ambulatory BP reductions.

Caso clínico de seguimiento farmacoterapéutico comunitario en dolor oncológico / No disponible

Se trata de un caso en el que el farmacéutico acompaña al paciente a lo largo de todo su proceso oncológico, de 1 año de duración, revisando la medicación y fomentando su adherencia y uso adecuado, intentando buscar los mejores resultados posibles

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Effectiveness of antiepileptic drug combination therapy for partial-onset seizures based on mechanisms of action.

IMPORTANCE: To our knowledge, the current study is the first to describe antiepileptic drug (AED) combination therapy patterns according to their mechanism of action (MOA) in a real-world setting and to evaluate the differences in outcomes comparing different-MOA combination therapy with same-MOA combination therapy for patients with partial-onset seizure. OBJECTIVE: To compare treatment persistence and health care use with AED combinations categorized by MOA in patients with partial-onset seizures. DESIGN, SETTING, AND PARTICIPANTS: Using the Truven Health MarketScan Commercial Claims Database containing 96 million covered lives from July 1, 2004, through March 31, 2011, adults with concomitant use of 2 different AEDs and a recent partial-onset seizure diagnosis were selected. Antiepileptic drugs were categorized by MOA: sodium channel blockers (SC), gamma-aminobutyric acid analogs (G), synaptic vesicle protein 2A binding (SV2), and multiple mechanisms (M). Patients were assigned a combination category based on their concomitant AED use. MAIN OUTCOMES AND MEASURES: Treatment persistence was measured from the start of AED combination therapy until the end of the combination. Health care resource use was measured during the combination treatment duration. Multivariate analyses evaluated AED discontinuation risk and health care use according to MOA combinations. RESULTS: Distribution of 8615 selected patients by combination was 3.3% for G+G, 7.5% for G+SV2, 8.6% for G+M, 13.9% for SC+SC, 19.0% for G+SC, 21.5% for SC+M, and 26.3% for SC+SV2. The same-MOA (G+G and SC+SC) combinations had the shortest persistence (mean [SD], 344 [345] days and 513 [530] days, respectively) and greater hazard of discontinuation compared with different-MOA combinations. Patients with different-MOA G combinations had a significantly lower risk for inpatient admission (odds ratio, 0.716; 95% CI, 0.539-0.952; P = .02) compared with G+G combinations. Patients with different-MOA SC combinations had significantly lower risks for emergency department visits (odds ratio, 0.853; 95% CI, 0.742-0.980; P = .03) compared with SC+SC combinations. CONCLUSIONS AND RELEVANCE: The findings suggest that AED combinations with different MOAs have greater effectiveness as measured by treatment persistence and lower risks for hospitalization and emergency department visits. Further research is needed to more fully understand the role of the MOA in achieving optimal outcomes.

Predictors of tuberculosis treatment outcomes.

OBJECTIVE: To analyze tuberculosis treatment outcomes and their predictors. METHODS: This was a retrospective longitudinal cohort study involving tuberculosis patients treated between 2004 and 2006 at the Instituto de Pesquisa Evandro Chagas, in the city of Rio de Janeiro. We estimated adjusted risk ratios (ARRs) for the predictors of treatment outcomes. RESULTS: Among 311 patients evaluated, the rates of cure, treatment abandonment, treatment failure, and mortality were 72%, 19%, 2%, and 6%, respectively. Changes in the treatment regimen due to adverse events occurred in 8%. The factors found to reduce the probability of cure were alcoholism (ARR, 0.30), use of the streptomycin+ethambutol+ofloxacin (SEO) regimen (ARR, 0.32), HIV infection without the use of antiretroviral therapy (ART; ARR, 0.36), and use of the rifampin+isoniazid+pyrazinamide+ethambutol regimen (ARR, 0.58). Being younger and being alcoholic both increased the probability of abandonment (ARR, 3.84 and 1.76, respectively). It was impossible to determine the ARR for the remaining outcomes due to their low prevalence. However, using the relative risk (RR), we identified the following potential predictors of mortality: use of the SEO regimen (RR, 11.43); HIV infection without ART (RR, 9.64); disseminated tuberculosis (RR, 9.09); lack of bacteriological confirmation (RR, 4.00); diabetes mellitus (RR, 3.94); and homosexual/bisexual behavior (RR, 2.97). Low income was a potential predictor of treatment failure (RR, 11.70), whereas disseminated tuberculosis and HIV infection with ART were potential predictors of changes in the regimen due to adverse events (RR, 3.57 and 2.46, respectively). CONCLUSIONS: The SEO regimen should not be used for extended periods. The data confirm the importance of ART and suggest the need to use it early.

Preditores dos desfechos do tratamento da tuberculose / Predictors of tuberculosis treatment outcomes

OBJETIVO: Analisar os desfechos do tratamento da tuberculose e seus preditores. MÉTODOS: Estudo longitudinal de coorte de pacientes com tuberculose tratados entre 2004 e 2006 no Instituto de Pesquisa Evandro Chagas, na cidade do Rio de Janeiro. As razões de risco ajustadas (RRa) dos preditores foram estimadas. RESULTADOS: Foram incluídos 311 pacientes. As taxas de cura, de abandono, de mortalidade e de falha terapêutica foram, respectivamente, 72 por cento, 19 por cento, 6 por cento e 2 por cento. A troca de regime terapêutico por eventos adversos foi necessária em 8 por cento. O alcoolismo (RRa, 0,30), uso do regime estreptomicina+etambutol+ofloxacina (SEO; RRa, 0,32), infecção por HIV sem tratamento antirretroviral (TARV; RRa, 0,36) e o uso do regime rifampicina+isoniazida+pirazinamida+etambutol (RRa, 0,58) reduziram a probabilidade de cura. A faixa etária mais jovem (RRa, 3,84) e o alcoolismo (RRa, 1,76) aumentaram a probabilidade do abandono. Não foi possível determinar as RRa para os demais desfechos devido a suas baixas prevalências. Entretanto, medidas do risco relativo (RR) identificaram os seguintes potenciais preditores do óbito: uso de esquema SEO (RR, 11,43), infecção pelo HIV sem TARV (RR, 9,64), forma clínica disseminada (RR, 9,09), ausência de confirmação bacteriológica (RR, 4,00), diabetes mellitus (RR, 3,94) e comportamento homo/bissexual (RR, 2,97). A baixa renda (RR, 11,70) foi potencial preditor para falha terapêutica, ao passo que infecção pelo HIV com uso de TARV (RR, 2,46) e forma clínica disseminada (RR, 3,57) foram potenciais preditores para troca do esquema por evento adverso. CONCLUSÕES: O esquema SEO deve ser utilizado transitoriamente quando possível. Os dados confirmam a importância de TARV e sugerem a necessidade de seu início precoce.

OBJECTIVE: To analyze tuberculosis treatment outcomes and their predictors. METHODS: This was a retrospective longitudinal cohort study involving tuberculosis patients treated between 2004 and 2006 at the Instituto de Pesquisa Evandro Chagas, in the city of Rio de Janeiro. We estimated adjusted risk ratios (ARRs) for the predictors of treatment outcomes. RESULTS: Among 311 patients evaluated, the rates of cure, treatment abandonment, treatment failure, and mortality were 72 percent, 19 percent, 2 percent, and 6 percent, respectively. Changes in the treatment regimen due to adverse events occurred in 8 percent. The factors found to reduce the probability of cure were alcoholism (ARR, 0.30), use of the streptomycin+ethambutol+ofloxacin (SEO) regimen (ARR, 0.32), HIV infection without the use of antiretroviral therapy (ART; ARR, 0.36), and use of the rifampin+isoniazid+pyrazinamide+ethambutol regimen (ARR, 0.58). Being younger and being alcoholic both increased the probability of abandonment (ARR, 3.84 and 1.76, respectively). It was impossible to determine the ARR for the remaining outcomes due to their low prevalence. However, using the relative risk (RR), we identified the following potential predictors of mortality: use of the SEO regimen (RR, 11.43); HIV infection without ART (RR, 9.64); disseminated tuberculosis (RR, 9.09); lack of bacteriological confirmation (RR, 4.00); diabetes mellitus (RR, 3.94); and homosexual/bisexual behavior (RR, 2.97). Low income was a potential predictor of treatment failure (RR, 11.70), whereas disseminated tuberculosis and HIV infection with ART were potential predictors of changes in the regimen due to adverse events (RR, 3.57 and 2.46, respectively). CONCLUSIONS: The SEO regimen should not be used for extended periods. The data confirm the importance of ART and suggest the need to use it early.

Estudio reológico de emulsiones semisólidas de aplicación cutánea / Rheological study of semisolid emulsions for percutaneous application

En la formulacion de formas farmaceuticas de aplicacion percutanea, una de las caracteristicas mas importantes a estudiar son las propiedades reologicas, ya que estas tienen repercusion en la extensibilidad del preparado sobre la piel, su facilidad de aplicacion y su adherencia sobre la misma. Todo ello contribuye a la aceptacion por parte del paciente de la formulacion empleada. En este articulo se realiza el estudio reologico de tres formulaciones semisolidas (emulsiones A,B y C) para ver las posibles diferencias que existan entre ellas. La composicion de las mismas es similar, solo difieren en el agente emulsificante, que en el caso de las emulsiones A y B es Tefose 63„µ y en la emulsion C es Tween 80„µ y, en el componente de la fase oleosa, que en las emulsiones A y C es vaselina filante (solida) y en la emulsion B es vaselina liquida. Todas las emulsiones llevan acido salicilico (1%) como componente activo. Para ver las posibles diferencias reologicas que presentan entre ellas se realiza, a temperatura ambiente, la determinacion de la viscosidad del preparado utilizando, para ello, un viscosimetro Brookfield de cilindros concentricos (modelo RTV), aplicando todas las velocidades de cizalla (G) al semisolido. En todos los casos, los resultados indican que el coeficiente de viscosidad depende de la velocidad de cizalla aplicada. Estas determinaciones se llevan a cabo en las emulsiones recien preparadas (tiempo 0), a la semana y al mes de su elaboracion, con el fin de observar, no solo la influencia de los componentes de la formulacion en las propiedades reologicas, sino tambien, la posible influencia del almacenamiento en dichas propiedades. Con los datos obtenidos se deduce que, de las tres emulsiones ensayadas, la A es la mas estable (AU)

In the formulation of pharmaceutical forms of percutaneous application, rheological properties are amongst the most important characteristics to be studied, be- cause of its influence upon extensibility, easiness of application, and adherence to the skin, all of which contribute best to patient compliance. A rheological study on three semisolid formulations (emulsions A, B and C) is carried out in this paper to try to find out possible (rheological) differences between them. The composition of all three emulsions being similar, they nevertheless differ on the surfactant agent, Tefose 63 in emulsion A and B and Tween 80 in emulsion C, and on the oil agent, white soft Vaseline in emulsions A and C and mineral oil in emul- sion B. The active ingredient added to the formulations is salicylic acid (1%). Viscosity determinations are implemented by using a concentric cylinder Brookfield-RTV viscosimeter and then applying at room temperature all shear rates (G) to the semisolide. In all cases, the results indicate that the coefficient of viscosity de- pends on the share rate applied. Viscosity determinations are carried out at emulsion storage times 0 (fresh emulsion), 1 week and 1 month at room temperature in order to find out whether not only the composition of the emulsion, even the storage time has an influence on rheological properties. From the data, emulsion A was found out to be the most stable of the three (AU)

Management guidelines for Helicobacter pylori infection: utilization by paediatric gastroenterologists in Australasia.

OBJECTIVE: Although there are published guidelines representing the consensus of several large groups, it is unclear whether these are used by practitioners in the management of Helicobacter pylori infection in children and if the guidelines are relevant to particular regions of the world. The aim of this study was to answer these questions in regard to the Australasian region. METHODS: An email-based questionnaire was circulated to Australasian paediatric gastroenterologists to ascertain aspects of practice related to H. pylori infection in children and to review practitioner awareness and use of the guidelines. RESULTS: Twenty-five (78%) of 32 questionnaires were completed. Current practice reported by the respondents followed the principles of the published guidelines. However, only 15 gastroenterologists were aware of the guidelines: a number of these practitioners were uncomfortable adapting the published guidelines to their local situation. CONCLUSIONS: Although widely distributed in the paediatric gastroenterology literature, guidelines for management of H. pylori infection may not be utilized fully by individual practitioners. As these guidelines are updated, based upon current developments in the understanding of H. pylori disease, attempts should be made to ensure that such documents are widely distributed to practitioners and that they reflect regional variations in disease patterns.