Factores de riesgo, manejo y supervivencia del cáncer vesical después de trasplante renal / Risk factors, management, and survival of bladder cancer after kidney transplantation

Introducción y objetivos: El trasplante renal se asocia a un mayor riesgo de cáncer de vejiga; sin embargo, no existen directrices sobre el tratamiento del cáncer de vejiga tras el trasplante renal.Materiales y métodosSe realizó una revisión sistemática de la literatura utilizando PubMed y siguiendo las directrices PRISMA para identificar estudios relacionados con la prevalencia y la supervivencia del cáncer de vejiga después del trasplante de riñón. También se revisaron y discutieron los factores de riesgo y el tratamiento de la enfermedad en este contexto.ResultadosSe identificaron un total de 41 estudios publicados entre 1996 y 2018, que incluían datos primarios sobre el cáncer de vejiga después del trasplante de riñón. Se observó una marcada heterogeneidad en términos de la prevalencia del cáncer vesical, el tiempo hasta el diagnóstico, la prevalencia del cáncer vesical no músculoinvasivo/músculoinvasivo, y la supervivencia. Se identificaron 4 estudios, publicados entre 2003 y 2017, que incluían datos primarios sobre el cáncer de vejiga tratado con el bacilo de Calmette-Guérin (BCG) después del trasplante de riñón. La supervivencia libre de enfermedad, la supervivencia específica del cáncer y la supervivencia global, fueron similares entre los estudios de BCG (75-100%).ConclusionesLa exposición a carcinógenos causante de ERET, VBK y VPH, los agentes inmunosupresores y el estado de inmunosupresión probablemente contribuyen a un mayor riesgo de cáncer de vejiga después del trasplante renal. La enfermedad no músculoinvasiva debe tratarse con resección transuretral. (AU)

Introduction and objectives: Kidney transplantation is associated with an increased risk of bladder cancer; however guidelines have not been established on the management of bladder cancer after kidney transplantation.Materials and methodsA systematic literature review using PubMed was performed in accordance with the PRISMA statement to identify studies concerning the prevalence and survival of bladder cancer after kidney transplantation. The risk factors and management of bladder cancer after kidney transplantation were also reviewed and discussed.ResultsA total of 41 studies, published between 1996 and 2018, reporting primary data on bladder cancer after kidney transplantation were identified. Marked heterogeneity in bladder cancer prevalence, time to diagnosis, non-muscle invasive/muscle-invasive bladder cancer prevalence, and survival was noted. Four studies, published between 2003 and 2017, reporting primary data on bladder cancer treated with Bacillus Calmette-Guérin (BCG) after kidney transplantation were identified. Disease-free survival, cancer-specific survival, and overall survival were similar between BCG studies (75-100%).ConclusionsCarcinogen exposure that led to ESRD, BKV, HPV, immunosuppressive agents, and the immunosuppressed state likely contribute to the increased risk of bladder cancer after renal transplantation. Non-muscle invasive disease should be treated with transurethral resection. BCG can be safely used in transplant recipients and likely improves the disease course. Muscle-invasive disease should be treated with radical cystectomy, with special consideration to the dissection and urinary diversion choice. Chemotherapy and immune checkpoint inhibitors can be safely used in regionally advanced bladder cancer with potential benefit. mTOR inhibitors may reduce the risk of developing bladder cancer, and immunosuppression medications should be reduced if malignancy develops. (AU)

Risk factors, management, and survival of bladder cancer after kidney transplantation.

INTRODUCTION AND OBJECTIVES: Kidney transplantation is associated with an increased risk of bladder cancer; however guidelines have not been established on the management of bladder cancer after kidney transplantation. MATERIALS AND METHODS: A systematic literature review using PubMed was performed in accordance with the PRISMA statement to identify studies concerning the prevalence and survival of bladder cancer after kidney transplantation. The risk factors and management of bladder cancer after kidney transplantation were also reviewed and discussed. RESULTS: A total of 41 studies, published between 1996 and 2018, reporting primary data on bladder cancer after kidney transplantation were identified. Marked heterogeneity in bladder cancer prevalence, time to diagnosis, non-muscle invasive/muscle-invasive bladder cancer prevalence, and survival was noted. Four studies, published between 2003 and 2017, reporting primary data on bladder cancer treated with Bacillus Calmette-Guérin (BCG) after kidney transplantation were identified. Disease-free survival, cancer-specific survival, and overall survival were similar between BCG studies (75-100%). CONCLUSIONS: Carcinogen exposure that led to ESRD, BKV, HPV, immunosuppressive agents, and the immunosuppressed state likely contribute to the increased risk of bladder cancer after renal transplantation. Non-muscle invasive disease should be treated with transurethral resection. BCG can be safely used in transplant recipients and likely improves the disease course. Muscle-invasive disease should be treated with radical cystectomy, with special consideration to the dissection and urinary diversion choice. Chemotherapy and immune checkpoint inhibitors can be safely used in regionally advanced bladder cancer with potential benefit. mTOR inhibitors may reduce the risk of developing bladder cancer, and immunosuppression medications should be reduced if malignancy develops.

Resilience capacities of health systems: Accommodating the needs of Palestinian refugees from Syria.

Resilience is increasingly recognised as a key process mitigating the impact of shocks and stressors on functioning. The literature on individual and community resilience is being extended to address characteristics of resilient service delivery systems in contexts of adversity. The validity and utility of a capacity-oriented resilience framework (including absorption, adaptation and transformation) is examined with respect to the functioning of United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) health systems in Lebanon and Jordan in the context of the Syrian crisis. We completed 62 semi-structured interviews (30 in Lebanon in November-December 2016, and 32 in Jordan in January 2017) with professionals at primary care, area, and country management levels. Participants reflected on changes in population health status and health service delivery during the Syrian crisis, notably with respect to the influx of refugees from Syria. Interviews were analysed through inductive thematic analysis and used to critically interrogate health systems resilience against a pro-capacities framework. We find that UNRWA systems in Lebanon and Jordan were broadly resilient, deploying diverse strategies to address health challenges and friction between host and refugee populations. Absorptive capacity was evidenced by successful accommodation of increased patient numbers across most service areas. Adaptive capacities were reflected in broadening of collaboration and reconfiguration of staff roles to enhance service delivery. Transformative capacities were demonstrated in the revision of the service packages provided. While manifest as technical capacities, these clearly drew upon solidarity and commitment linked to the political context of the Palestinian experience. The study adds to the limited literature on health system and organizational resilience and indicates that capacity-oriented framings of resilience are valuable in extracting generalizable lessons for health systems facing adversity. The proposed resilience framework promises to guide strategies for sustained care delivery in these contexts.

The Use of Complementary and Alternative Medicine among Lebanese Adults: Results from a National Survey.

Objective. To examine the prevalence and correlates of Complementary and Alternative Medicine (CAM) use in Lebanon. Methods. A cross-sectional survey was conducted through face to face interviews on a nationally representative sample of 1,475 Lebanese adults. The survey questionnaire explored the sociodemographic and health related characteristics as well as the types and modes of CAM use. The main outcome in this study was the use of CAM during the last 12 months. Results. Prevalence of CAM use was 29.87% with "folk herbs" being the most commonly used (75%). Two out of five CAM users indicated using it as alternative to conventional therapies and only 28.4% of users disclosed the use of CAM to their physician. CAM use was significantly associated with higher income, presence of a chronic disease, and lack of access to needed health care. Lower odds of CAM use were observed among older adults and those with a higher education level. Conclusions. This study revealed a high prevalence of CAM use in Lebanon. Health policy and decision makers need to facilitate proper regulation and integration of CAM into mainstream medicine and educate health care providers and the public alike on the safe and effective use of CAM therapies.

Population pharmacokinetic modelling and evaluation of different dosage regimens for darunavir and ritonavir in HIV-infected individuals.

OBJECTIVES: Darunavir is a protease inhibitor that is administered with low-dose ritonavir to enhance its bioavailability. It is prescribed at standard dosage regimens of 600/100 mg twice daily in treatment-experienced patients and 800/100 mg once daily in naive patients. A population pharmacokinetic approach was used to characterize the pharmacokinetics of both drugs and their interaction in a cohort of unselected patients and to compare darunavir exposure expected under alternative dosage regimens. METHODS: The study population included 105 HIV-infected individuals who provided darunavir and ritonavir plasma concentrations. Firstly, a population pharmacokinetic analysis for darunavir and ritonavir was conducted, with inclusion of patients' demographic, clinical and genetic characteristics as potential covariates (NONMEM(®)). Then, the interaction between darunavir and ritonavir was studied while incorporating levels of both drugs into different inhibitory models. Finally, model-based simulations were performed to compare trough concentrations (Cmin) between the recommended dosage regimen and alternative combinations of darunavir and ritonavir. RESULTS: A one-compartment model with first-order absorption adequately characterized darunavir and ritonavir pharmacokinetics. The between-subject variability in both compounds was important [coefficient of variation (CV%) 34% and 47% for darunavir and ritonavir clearance, respectively]. Lopinavir and ritonavir exposure (AUC) affected darunavir clearance, while body weight and darunavir AUC influenced ritonavir elimination. None of the tested genetic variants showed any influence on darunavir or ritonavir pharmacokinetics. The simulations predicted darunavir Cmin much higher than the IC50 thresholds for wild-type and protease inhibitor-resistant HIV-1 strains (55 and 550 ng/mL, respectively) under standard dosing in >98% of experienced and naive patients. Alternative regimens of darunavir/ritonavir 1200/100 or 1200/200 mg once daily also had predicted adequate Cmin (>550 ng/mL) in 84% and 93% of patients, respectively. Reduction of darunavir/ritonavir dosage to 600/50 mg twice daily led to a 23% reduction in average Cmin, still with only 3.8% of patients having concentrations below the IC50 for resistant strains. CONCLUSIONS: The important variability in darunavir and ritonavir pharmacokinetics is poorly explained by clinical covariates and genetic influences. In experienced patients, treatment simplification strategies guided by drug level measurements and adherence monitoring could be proposed.

Pharmacogenetics-based population pharmacokinetic analysis of efavirenz in HIV-1-infected individuals.

Besides CYP2B6, other polymorphic enzymes contribute to efavirenz (EFV) interindividual variability. This study was aimed at quantifying the impact of multiple alleles on EFV disposition. Plasma samples from 169 human immunodeficiency virus (HIV) patients characterized for CYP2B6, CYP2A6, and CYP3A4/5 allelic diversity were used to build up a population pharmacokinetic model using NONMEM (non-linear mixed effects modeling), the aim being to seek a general approach combining genetic and demographic covariates. Average clearance (CL) was 11.3 l/h with a 65% interindividual variability that was explained largely by CYP2B6 genetic variation (31%). CYP2A6 and CYP3A4 had a prominent influence on CL, mostly when CYP2B6 was impaired. Pharmacogenetics fully accounted for ethnicity, leaving body weight as the only significant demographic factor influencing CL. Square roots of the numbers of functional alleles best described the influence of each gene, without interaction. Functional genetic variations in both principal and accessory metabolic pathways demonstrate a joint impact on EFV disposition. Therefore, dosage adjustment in accordance with the type of polymorphism (CYP2B6, CYP2A6, or CYP3A4) is required in order to maintain EFV within the therapeutic target levels.

Effect of alpha-stat vs. pH-stat strategies on cerebral oximetry during moderate hypothermic cardiopulmonary bypass.

BACKGROUND AND OBJECTIVES: This study was undertaken to compare the effect of alpha-stat vs. pH-stat strategies for acid-base management on regional cerebral oxygen saturation (RsO2) in patients undergoing moderate hypothermic haemodilution cardiopulmonary bypass (CPB). METHODS: In 14 adult patients undergoing elective coronary artery bypass grafting, an awake RsO2 baseline value was monitored using a cerebral oximeter (INVOS 5100). Cerebral oximetry was then monitored continuously following anaesthesia and during the whole period of CPB. Mean +/- SD of RsO2, CO2, mean arterial pressure and haematocrit were determined before bypass and during the moderate hypothermic phase of the CPB using the alpha-stat followed by pH-stat strategies of acid-base management. Alpha-stat was then maintained throughout the whole period of CPB. RESULTS: The mean baseline RsO2 in the awake patient breathing room air was 59.6 +/- 5.3%. Following anaesthesia and ventilation with 100% oxygen, RsO2 increased up to 75.9 +/- 6.7%. Going on bypass, RsO2 significantly decreased from a pre-bypass value of 75.9 +/- 6.7% to 62.9 +/- 6.3% during the initial phase of alpha-stat strategy. Shifting to pH-stat strategy resulted in a significant increase of RsO2 from 62.9 +/- 6.3% to 72.1 +/- 6.6%. Resuming the alpha-stat strategy resulted in a significant decrease of RsO2 to 62.9 +/- 7.8% which was similar to the RsO2 value during the initial phase of alpha-stat. CONCLUSION: During moderate hypothermic haemodilutional CPB, the RsO2 was significantly higher during the pH-stat than during the alpha-stat strategy. However, the RsO2 during pH-stat management was significantly higher than the baseline RsO2 value in the awake patient breathing room air, denoting luxury cerebral perfusion. In contrast, the RsO2 during alpha-stat was only slightly higher than the baseline RsO2, suggesting that the alpha-stat strategy avoids luxury perfusion, but can maintain adequate cerebral oxygen supply-demand balance during moderate hypothermic haemodilutional CPB.

Effect of low-dose dexmedetomidine or clonidine on the characteristics of bupivacaine spinal block.

BACKGROUND: The purpose of this study was to compare the onset and duration of sensory and motor block, as well as the hemodynamic changes and level of sedation, following intrathecal bupivacaine supplemented with either dexmedetomidine or clonidine. METHODS: In a prospective, double-blind study, 60 patients undergoing transurethral resection of prostate or bladder tumor under spinal anesthesia were randomly allocated to one of three groups. Group B received 12 mg of hyperbaric bupivacaine, group D received 12 mg of bupivacaine supplemented with 3 microg of dexmedetomidine and group C received 12 mg of bupivacaine supplemented with 30 microg of clonidine. The onset times to reach peak sensory and motor levels, and the sensory and motor regression times, were recorded. Hemodynamic changes and the level of sedation were also recorded. RESULTS: Patients in groups D and C had a significantly shorter onset time of motor block and significantly longer sensory and motor regression times than patients in group B. The mean time of sensory regression to the S1 segment was 303 +/- 75 min in group D, 272 +/- 38 min in group C and 190 +/- 48 min in group B (B vs. D and B vs. C, P < 0.001). The regression of motor block to Bromage 0 was 250 +/- 76 min in group D, 216 +/- 35 min in group C and 163 +/- 47 min in group B (B vs. D and B vs. C, P < 0.001). The onset and regression times were not significantly different between groups D and C. The mean arterial pressure, heart rate and level of sedation were similar in the three groups intra-operatively and post-operatively. CONCLUSIONS: Dexmedetomidine (3 microg) or clonidine (30 microg), when added to intrathecal bupivacaine, produces a similar prolongation in the duration of the motor and sensory block with preserved hemodynamic stability and lack of sedation.

National survey of blindness and low vision in Lebanon.

AIMS: To survey level of blindness and low vision in Lebanon. METHODS: A population survey was undertaken in 10,148 individuals to measure the prevalence and identify the causes of blindness in Lebanon. RESULTS: The prevalence of blindness was 0.6% and that of low vision 3.9%. The major causes of blindness were cataract (41.3%) and uncorrected large refractive error (12.6%). CONCLUSION: Most causes of blindness in Lebanon can be controlled by various educational and medical programmes.