Safety and efficacy of candesartan versus valsartan combined with amlodipine on peripheral and central blood pressure / Seguridad y eficacia de candesartán frente a valsartán combinado con amlodipino sobre la presión arterial periférica y central

Introduction: “Amlodipine/valsartan” or “amlodipine/candesartan” combinations represent two effective antihypertensive agents with complementary mechanisms of action. Nevertheless, a study has yet to be done to evaluate the effect of amlodipine/candesartan on central blood pressure and compare it with amlodipine/valsartan combination. To see how “amlodipine plus candesartan combination” reduces peripheral and central blood pressure compared to the most studied combination, “amlodipine plus valsartan”. Material and methods: Eighty-six patients were randomized in an open-label, prospective study by 1:1 ratio to two groups. Group I (n=42) received the amlodipine and valsartan combination, and group II (n=44) received the amlodipine and candesartan combination. Peripheral and central blood pressure (CBP) was measured at baseline, at 6 and 12 weeks of follow-up. Discussion: Both treatment groups reduced peripheral systolic, diastolic, and mean blood pressure. There was no significant difference between and within both groups. The amlodipine/candesartan combination showed more reduction in peripheral systolic blood pressure (PSBP) after 12 weeks of treatment (p=<0.001). Both groups decreased CBP without significant differences between groups. The amlodipine/candesartan combination showed additional efficacy in decreasing CSBP after 12 weeks (p=<0.001). The two treatment groups did not exert significant efficacy in lowering heart rate (HR) and augmentation index% (AIx%). Conclusion: To conclude, the amlodipine 10mg/candesartan 16mg combination was non-inferior to the amlodipine 10mg/valsartan 160mg combination in terms of reducing peripheral and CBP over time.(AU)

Introducción: «Las combinaciones de amlodipino/valsartán» o «amlodipino/candesartán» representan 2 agentes antihipertensivos efectivos con mecanismos de acción complementarios. Sin embargo, aún no se ha realizado un estudio para evaluar el efecto del amlodipino/candesartán en la presión arterial central y compararlo con la combinación amlodipino/valsartán. En este estudio, se comparó la reducción de la presión arterial periférica y central entre estas 2 combinaciones. Materiales y métodos: Ochenta y seis pacientes fueron asignados aleatoriamente a 2 grupos: el Grupo I (n=42) recibió amlodipino y valsartán, y el Grupo II (n=44) recibió amlodipino y candesartán. Se midió la presión arterial periférica y central al inicio, a las 6 y 12 semanas de seguimiento. Discusión: Ambos grupos redujeron la presión arterial periférica de manera similar, pero la combinación amlodipino/candesartán mostró una mayor reducción en la presión arterial sistólica periférica después de 12 semanas de tratamiento. Ambas combinaciones también disminuyeron la presión arterial central, pero nuevamente, la combinación amlodipino/candesartán tuvo una mayor eficacia en la reducción de la presión arterial sistólica central después de 12 semanas. No se observaron diferencias significativas en la frecuencia cardíaca ni en el índice de aumento entre los grupos. Conclusión: En conclusión, la combinación de amlodipino 10mg/candesartán 16mg demostró ser tan efectiva como la combinación de amlodipino 10mg/valsartán 160mg en la reducción tanto de la presión arterial periférica como central a lo largo del tiempo.(AU)

Tranexamic acid in patients with traumatic brain injury: a meta-analysis.

BACKGROUND: We performed a meta-analysis to assess the effectiveness and safety of tranexamic acid in patients with traumatic brain injury (TBI). METHODS: We searched the literature for articles evaluating the effectiveness and safety of tranexamic acid (TXA) in TBI published between January 2012 and January 2021, and identified 8 studies with a total of 10860 patients: 5660 received TXA and 5200 served as controls. We used a dichotomous or continuous approach with a random or fixed-effect model to assess the efficacy and safety of TXA in TBI, and calculated the mean difference (MD) and odds ratio (OR) with the corresponding 95% confidence interval. RESULTS: In patients with TBI, early administration of TXA was associated with a greater relative benefit (MD -2.45; 95% CI = -4.78 to -0.12; p=0.04) and less total haematoma expansion (MD - 2.52; 95% CI = -4.85 to -0.19; p=0.03) compared to controls. There were no statistically significant differences in mortality (OR 0.94; 95% CI=0.85-1.03; p=0.18), presence of progressive haemorrhage (OR 0.75; 95% CI=0.56-1.01; p=0.06), need for neurosurgery (OR 1.15; 95% CI=0.66-1.98; p=0.63), high Disability Rating Scale score (OR 0.90; 95% CI=0.56-1.45; p=0.68), and incidence of ischaemic or thromboembolic complications (OR 1.34; 95% CI=0.33-5.46; p=0.68) between TBI patients treated with TXA and controls. CONCLUSIONS: Early administration of TXA in TBI patients may have a greater relative benefit and may inhibit haematoma expansion. There were no significant differences in mortality, presence of progressive haemorrhage, need for neurosurgery, high Disability Rating Scale score, and incidence of ischaemic or thromboembolic complications between TBI patients treated with TXA and controls. Further studies are needed to validate these results.

Safety and efficacy of candesartan versus valsartan combined with amlodipine on peripheral and central blood pressure.

INTRODUCTION: "Amlodipine/valsartan" or "amlodipine/candesartan" combinations represent two effective antihypertensive agents with complementary mechanisms of action. Nevertheless, a study has yet to be done to evaluate the effect of amlodipine/candesartan on central blood pressure and compare it with amlodipine/valsartan combination. To see how "amlodipine plus candesartan combination" reduces peripheral and central blood pressure compared to the most studied combination, "amlodipine plus valsartan". MATERIAL AND METHODS: Eighty-six patients were randomized in an open-label, prospective study by 1:1 ratio to two groups. Group I (n=42) received the amlodipine and valsartan combination, and group II (n=44) received the amlodipine and candesartan combination. Peripheral and central blood pressure (CBP) was measured at baseline, at 6 and 12 weeks of follow-up. DISCUSSION: Both treatment groups reduced peripheral systolic, diastolic, and mean blood pressure. There was no significant difference between and within both groups. The amlodipine/candesartan combination showed more reduction in peripheral systolic blood pressure (PSBP) after 12 weeks of treatment (p=<0.001). Both groups decreased CBP without significant differences between groups. The amlodipine/candesartan combination showed additional efficacy in decreasing CSBP after 12 weeks (p=<0.001). The two treatment groups did not exert significant efficacy in lowering heart rate (HR) and augmentation index% (AIx%). CONCLUSION: To conclude, the amlodipine 10mg/candesartan 16mg combination was non-inferior to the amlodipine 10mg/valsartan 160mg combination in terms of reducing peripheral and CBP over time.

Enhanced pharmaceutical recovery as postoperative standard care after radical cystectomy: A meta-analysis.

INTRODUCTION: We performed a meta-analysis to evaluate the effect of enhanced pharmaceutical recovery as postoperative standard care after radical cystectomy. METHODS: A systematic literature search up to April 2021 was done and 33 studies included 6596 subjects submitted to surgery for radical cystectomy at the start of the study; 3143 of them received enhanced pharmaceutical recovery after surgery and 3453 were controls. The studies reported relationships about the effects of enhanced pharmaceutical recovery as postoperative standard care after radical cystectomy. We calculated the odds ratio (OR) and mean difference (MD) with 95% confidence intervals (CIs) to assess the effects of enhanced pharmaceutical recovery as postoperative standard care after radical cystectomy using the dichotomous and continuous methods with a random or fixed-effect model. RESULTS: Enhanced pharmaceutical recovery after surgery had significantly lower length of hospital stay (MD, -2.78; 95% CI, -3.59 to -1.97, p < 0.001), complications (OR, 0.75; 95% CI, 0.60-0.94, p = 0.01), readmission within 30 days (OR, 0.80; 95% CI, 0.69-0.94, p = 0.007), and time to defecation (MD, -1.30; 95% CI, -2.22 to -0.37, p = 0.006) compared to control in subjects submitted to radical cystectomy. CONCLUSIONS: Enhanced pharmaceutical recovery after surgery may reduce the length of hospital stay, complications, readmission within 30 days, and time to first bowel movement compared to control in subjects with surgery for radical cystectomy. Furthers studies are required to validate these findings.

Dose emission and aerodynamic characterization of the terbutaline sulphate dose emitted from a Turbuhaler at low inhalation flow.

Previously, dose emission below 30 L min(-1) through DPI has not been routinely determined. However, during routine use some patients do not achieve 30 L min(-1) inhalation flows. Hence, the aim of the present study was to determine dose emission characteristics for low inhalation flows from terbutaline sulphate Turbuhaler. Total emitted dose (TED), fine particle dose (FPD) and mass median aerodynamic diameter (MMAD) of terbutaline sulphate Turbuhaler were determined using inhalation flows of 10-60 L min(-1) and inhaled volume of 4 L. TED and FPD increase significantly with the increase of inhalation flows (p <0.05). Flows had more pronounced effect on FPD than TED, thus, faster inhalation increases respirable amount more than it increases emitted dose. MMAD increases with decrease of inhalation flow until flow of 20L min(-1) then it decreases. In vitro flow dependent dose emission has been demonstrated previously for Turbuhaler for flow rates above 30 L min(-1) but is more pronounced below this flow. Minimal FPD below 30 L min(-1) suggests that during routine use at this flow rate most of emitted dose will impact in mouth. Flow dependent dose emission results suggest that Pharmacopoeias should consider the use variety of inhalation flows rather than one that is equivalent to pressure drop of 4 KPa.

The relative lung and systemic bioavailability of terbutaline following nebulisation in non-invasively ventilated patients.

Nebulising a bronchodilator during non-invasive ventilation (NIV) is effective but there is a lack of consensus on the system to use because comparator in vivo studies in these patients are difficult. Urinary pharmacokinetic methodology post inhalation could provide this information. Chronic obstructive pulmonary disease patients requiring NIV received randomised study doses of either 2mg terbutaline nebulised from an Aeroneb Pro (AERO) or 5mg from a Sidestream (SIDE) on days 1 and 3 of admission. Urine samples were provided at 30 min then pooled up to 24h post inhalation and amounts of urinary terbutaline (UTER0.5 and UTER24; indices of relative lung and systemic bioavailability, respectively) were determined. Twelve consenting patients receiving NIV mean (SD) age and weight of 74.8 (8.2) years and 61.0 (10.7)kg completed the study. The mean (SD) UTER0.5 following AERO and SIDE was 9.4 (3.7) and 10.4 (4.1) µg with a mean ratio (90% confidence interval) of 89.7 (87.8, 92.3)%. UTER24 was 192.3 (52.4) and 205.3 (58.0)mcg with a mean ratio (90% CI) of 93.7 (113.5, 77.3)%. This urinary pharmacokinetic method to identity relative lung and systemic bioavailability between two nebuliser systems was easy to perform and is a useful and simple in vivo method to compare different nebulisers in patients receiving non-invasive ventilation.