Adverse treatment outcomes in multidrug resistant tuberculosis go beyond the microbe-drug interaction: Results of a multiple correspondence analysis. / Los resultados adversos en el tratamiento de la tuberculosis resistente a múltiples fármacos sobrepasan la relación fármaco-microorganismo: resultados de un análisis de correspondencia múltiple

INTRODUCTION: Multidrug-resistant tuberculosis treatment is effective in 50% of patients due to several factors including antibiotic susceptibility of the microorganism, adverse treatment reactions, social factors, and associated comorbidities. OBJECTIVES: In this study, we describe the demographics, clinical characteristics, and factors associated with treatment outcomes in multidrug-resistant tuberculosis (MDR-TB) patients in Medellín, Colombia. MATERIALS AND METHODS: We conducted a retrospective analysis using data from patients diagnosed with MDR-TB attending Hospital La María in Medellín, Colombia, for treatment between 2010 and 2015. Patients were categorized as having successful (cured) or poor (failure, lost to follow-up, and death) treatment outcomes. Associations between demographic, clinical factors, laboratory results, treatment outcomes, and follow-up information were evaluated by univariate, multivariate, and multiple correspondence analyses. RESULTS: Of the 128 patients with MDR-TB, 77 (60%) had successful outcomes. Of those with poor outcomes, 26 were lost to follow-up, 15 died, and 10 were treatment failures. Irregular treatment, the presence of comorbidities, and positive cultures after more than two months of treatment were associated with poor outcomes compared to successful ones (p<0.05 for all). The multiple correspondence analyses grouped patients who were lost to follow-up, had HIV, and drug addiction, as well as patients with treatment failure, irregular treatment, and chronic obstructive pulmonary disease. CONCLUSION: The recognition of factors affecting treatment is essential and was associated with treatment outcomes in this series of patients. Early identification of these factors should increase the rates of treatment success and contribute to MDR-TB control.

Introducción. El tratamiento de la tuberculosis multirresistente tiene una efectividad del 50 %, afectado por múltiples factores como la sensibilidad del microorganismo, las reacciones secundarias, los factores sociales y las comorbilidades existentes. Objetivos. Describir la demografía, las características clínicas y los factores pronósticos asociados con los resultados del tratamiento en pacientes multirresistentes (TB-MDR) de Medellín, Colombia. Métodos. Se hizo un análisis retrospectivo de los datos de los pacientes con TB-MDR atendidos en el Hospital La María de Medellín, Colombia, que fueron tratados entre el 2010 y el 2015. Los pacientes se categorizaron con tratamiento exitoso (curados) o con tratamiento fallido (falla en el tratamiento, pérdida durante el seguimiento y muerte). Se determinó la asociación entre las características demográficas y clínicas, los resultados de los exámenes de laboratorio, los desenlaces del tratamiento y la información del seguimiento, utilizando análisis univariado, multivariado y de correspondencia múltiple. Resultados. De 128 pacientes con TB-MDR, 77 (60 %) tuvieron un tratamiento exitoso. De los que tuvieron un tratamiento fallido, 26 pacientes se perdieron en el seguimiento, 15 murieron y 10 tuvieron falla en el tratamiento. El tratamiento irregular, las comorbilidades y los cultivos positivos más allá de 2 meses de tratamiento se asociaron significativamente con los tratamientos fallidos (p<0,05). El análisis de correspondencia múltiple agrupó los pacientes con pérdida en el seguimiento, con HIV y tratamientos irregulares, y los pacientes con tratamientos irregulares y enfermedad pulmonar obstructiva crónica con falla en el tratamiento y muerte. Conclusión. El reconocimiento temprano de los factores que afectan el desenlace del tratamiento de los pacientes con TB-MDR es esencial; la identificación de dichos factores debería incrementar el éxito del tratamiento y contribuir al adecuado control de la TB-MDR.

Adverse treatment outcomes in multidrug resistant tuberculosis go beyond the microbe-drug interaction: Results of a multiple correspondence analysis / Los resultados adversos en el tratamiento de la tuberculosis resistente a múltiples fármacos sobrepasan la relación fármaco-microorganismo: resultados de un análisis de correspondencia múltiple

Abstract . Introduction: Multidrug-resistant tuberculosis treatment is effective in 50% of patients due to several factors including antibiotic susceptibility of the microorganism, adverse treatment reactions, social factors, and associated comorbidities. Objectives: In this study, we describe the demographics, clinical characteristics, and factors associated with treatment outcomes in multidrug-resistant tuberculosis (MDR-TB) patients in Medellín, Colombia. Materials and methods: We conducted a retrospective analysis using data from patients diagnosed with MDR-TB attending Hospital La María in Medellín, Colombia, for treatment between 2010 and 2015. Patients were categorized as having successful (cured) or poor (failure, lost to follow-up, and death) treatment outcomes. Associations between demographic, clinical factors, laboratory results, treatment outcomes, and follow-up information were evaluated by univariate, multivariate, and multiple correspondence analyses. Results: Of the 128 patients with MDR-TB, 77 (60%) had successful outcomes. Of those with poor outcomes, 26 were lost to follow-up, 15 died, and 10 were treatment failures. Irregular treatment, the presence of comorbidities, and positive cultures after more than two months of treatment were associated with poor outcomes compared to successful ones (p<0.05 for all). The multiple correspondence analyses grouped patients who were lost to follow-up, had HIV, and drug addiction, as well as patients with treatment failure, irregular treatment, and chronic obstructive pulmonary disease. Conclusion: The recognition of factors affecting treatment is essential and was associated with treatment outcomes in this series of patients. Early identification of these factors should increase the rates of treatment success and contribute to MDR-TB control.

Resumen . Introducción. El tratamiento de la tuberculosis multirresistente tiene una efectividad del 50 %, afectado por múltiples factores como la sensibilidad del microorganismo, las reacciones secundarias, los factores sociales y las comorbilidades existentes. Objetivos. Describir la demografía, las características clínicas y los factores pronósticos asociados con los resultados del tratamiento en pacientes multirresistentes (TB-MDR) de Medellín, Colombia. Métodos. Se hizo un análisis retrospectivo de los datos de los pacientes con TB-MDR atendidos en el Hospital La María de Medellín, Colombia, que fueron tratados entre el 2010 y el 2015. Los pacientes se categorizaron con tratamiento exitoso (curados) o con tratamiento fallido (falla en el tratamiento, pérdida durante el seguimiento y muerte). Se determinó la asociación entre las características demográficas y clínicas, los resultados de los exámenes de laboratorio, los desenlaces del tratamiento y la información del seguimiento, utilizando análisis univariado, multivariado y de correspondencia múltiple. Resultados. De 128 pacientes con TB-MDR, 77 (60 %) tuvieron un tratamiento exitoso. De los que tuvieron un tratamiento fallido, 26 pacientes se perdieron en el seguimiento, 15 murieron y 10 tuvieron falla en el tratamiento. El tratamiento irregular, las comorbilidades y los cultivos positivos más allá de 2 meses de tratamiento se asociaron significativamente con los tratamientos fallidos (p<0,05). El análisis de correspondencia múltiple agrupó los pacientes con pérdida en el seguimiento, con HIV y tratamientos irregulares, y los pacientes con tratamientos irregulares y enfermedad pulmonar obstructiva crónica con falla en el tratamiento y muerte. Conclusión. El reconocimiento temprano de los factores que afectan el desenlace del tratamiento de los pacientes con TB-MDR es esencial; la identificación de dichos factores debería incrementar el éxito del tratamiento y contribuir al adecuado control de la TB-MDR.

Blocking the RAAS at different levels: an update on the use of the direct renin inhibitors alone and in combination.

The renin-angiotensin-aldosterone system (RAAS), an important regulator of blood pressure and mediator of hypertension-related complications, is a prime target for cardiovascular drug therapy. Angiotensin-converting enzyme inhibitors (ACEIs) were the first drugs to be used to block the RAAS. Angiotensin II receptor blockers (ARBs) have also been shown to be equally effective for treatment. Although these drugs are highly effective and are widely used in the management of hypertension, current treatment regimens with ACEIs and ARBs are unable to completely suppress the RAAS. Combinations of ACEIs and ARBs have been shown to be superior than to either agent alone for some, but certainly not all, composite cardiovascular and kidney outcomes, but dual RAAS blockade with the combination of an ACEI and an ARB is sometimes associated with an increase in the risk for adverse events, primarily hyperkalemia and worsening renal function. The recent introduction of the direct renin inhibitor, aliskiren, has made available new combination strategies to obtain a more complete blockade of the RAAS with fewer adverse events. Renin system blockade with aliskiren and another RAAS agent has been, and still is, the subject of many large-scale clinical trials and furthermore, is already available in some countries as a fixed combination.

Role of valsartan, amlodipine and hydrochlorothiazide fixed combination in blood pressure control: an update.

The treatment of moderate or severe hypertension in most cases requires the contemporaneous use of multiple antihypertensive agents. The most available two-drug combinations have an agent that addresses renin secretion and another one that is statistically more effective in renin-independent hypertension. The practice of combining agents that counteract different mechanisms is the most likely explanation for the fact that most available two-drug combinations have an agent that addresses renin secretion (beta-blocker, angiotensin converting enzyme inhibitor, angiotensin II receptor blocker or direct renin inhibitor) and another one that is more effective in renin-independent hypertension (diuretic, dihydropyridine or non-dihydropyridine calcium channel blocker). Based on these considerations, addition of hydrochlorothiazide to the combination of an antagonist of the renin-angiotensin system with a calcium channel blocker would constitute a logical approach. Inclusion of a diuretic in the triple combination is based on the evidence that these agents are effective and cheap, enhance the effect of other antihypertensive agents, and add a specific effect to individuals with salt-sensitivity of blood pressure. The benefit of triple combination therapy with amlodipine, valsartan and hydrochlorothiazide over its dual component therapies has been demonstrated, and the use of a single pill will simplify therapy resulting in better blood pressure control.

New strategies and drugs in the treatment of hypertension: monotherapy or combination?

Hypertension is one of the major risk factors associated with cardiovascular diseases. A range of blood pressure-lowering agents is available including diuretics, alpha- and beta-blockers, aldosterone antagonists, calcium-channel blockers (CCB), angiotensin-converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB) and direct renin inhibitors (DRI). Most patients require two or more medications to control their blood pressures within normal ranges. When high blood pressure cannot be controlled by low-dose monotherapy, physicians employ either high-dose monotherapy or combination therapy. High-dose ARB monotherapy is more effective for reducing proteinuria against low-dose ARB monotherapy or CCBs. Combination therapy is recommended for hypertension patients to facilitate prompt maintenance of blood pressure. Single-pill combination therapy simplifies treatment and optimizes long-term compliance. Thiazide diuretics such as hydrochlorothiazide (HCTZ), alone or in combination are still widely used as first-line hypertension treatment. Recent studies have shown that double (CCB+ARBs) or triple (CCB+ARBs+HCTZ) combination therapies have a greater lowering efficacy and are better tolerated. Moreover, the use of DRIs has been patented and proven effective in selected categories of hypertensive patients with or without concomitant target organ damage (TOD).

Olmesartan medoxomil: recent clinical and experimental acquisitions.

Angiotensin II is a vasoactive hormone of the renin-angiotensin system and plays an important role in the pathophysiology of several organ damages. Angiotensin II receptor blockers have been shown to be effective in treating both hypertension and connected organ damages. It is well known that although the angiotensin II receptor blockers have structural and pharmacokinetic differences, few pharmacological differences separate them. One of these is the degree of binding to the angiotensin II receptor type 1 compared with the angiotensin II receptor type 2; olmesartan medoxomil exhibits more than a 12,500-fold greater affinity for the angiotensin II receptor type 1 receptor than for the angiotensin II receptor type 2, making it theoretically the second most potent agent. However, olmesartan's excellent receptor interaction is based on the combination of several specific pharmacokinetic factors. Potential advantages of this drug include once-daily dosing, a very low incidence of significant adverse reactions and/or events and a well-tolerated side effect profile. Nowadays, we have a lot of information about the pharmacology, antihypertensive efficacy and safety of olmesartan medoxomil, to further extend many clinical studies are still continuing to evaluate the potential benefits of high dosages and/or combination of this molecule.