RESUMEN
This article includes a thorough examination of the inhibitory potential of quinoline-based drugs on cancer cells, as well as an explanation of their modes of action. Quinoline derivatives, due to their various chemical structures and biological activity, have emerged as interesting candidates in the search for new anticancer drugs. The review paper delves into the numerous effects of quinoline-based chemicals in cancer progression, including apoptosis induction, cell cycle modification, and interference with tumor-growth signaling pathways. Mechanistic insights on quinoline derivative interactions with biological targets enlightens their therapeutic potential. However, obstacles such as poor bioavailability, possible off-target effects, and resistance mechanisms make it difficult to get these molecules from benchside to bedside. Addressing these difficulties might be critical for realizing the full therapeutic potential of quinoline-based drugs in cancer treatment.
Asunto(s)
Antineoplásicos , Neoplasias , Quinolinas , Humanos , Antineoplásicos/química , Neoplasias/tratamiento farmacológico , Muerte Celular , Ciclo Celular , Quinolinas/químicaRESUMEN
Chemical-based carotenoids have large implications to health as they may cause adverse side effects. Naturally occurring carotenoids mainly from microalgal sources are emerging as excellent substitute to combat cancer diseases. Astaxanthin is the most powerful antioxidant that derived from selected established microalgae with limited yield. Microalgal bioprospecting may provide the high-yielding sources for astaxanthin production. Hence, in the present research, freshwater microalgae Monoraphidium sp. (NCM no. 5585) and Scenedesmus obliquus (NCM no. 5586) were chosen to explore the unique potential of producing astaxanthin. Identification of bioactive metabolites in extracted carotenoid was analyzed through HPLC. Astaxanthin is identified as a major bioactive metabolite in both carotenoid fraction and ß carotene only in Scenedesmus obliquus. Antioxidant potential of microalgal carotenoids was obtained by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and Ferric-reducing antioxidant power (FRAP) assay. The anti-proliferation activity of the extracted carotenoid from Monoraphidium sp. and Scenedesmus obliquus was evaluated against hepatocellular liver carcinoma cell line HUH7 by 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) colorimetric assay. Higher astaxanthin in Monoraphidium sp. leads to boosted antioxidant and anti-proliferation activity contrary to Scenedesmus obliquus that possess both astaxanthin and ß carotene. Though freshwater microalgae have a huge potential to create beneficial metabolites like carotenoids, they are rarely studied in the pharmaceutical industry. This work was the first to investigate the anti-proliferative activity of Monoraphidium sp. and Scenedesmus obliquus carotenoid fraction on the HUH7 hepatocarcinoma cell line.
RESUMEN
Peritoneal dialysis (PD) catheter-related infections are important risk factors for catheter loss and peritonitis. The 2023 updated recommendations have revised and clarified definitions and classifications of exit site infection and tunnel infection. A new target for the overall exit site infection rate should be no more than 0.40 episodes per year at risk. The recommendation about topical antibiotic cream or ointment to catheter exit site has been downgraded. New recommendations include clarified suggestion of exit site dressing cover and updated antibiotic treatment duration with emphasis on early clinical monitoring to ascertain duration of therapy. In addition to catheter removal and reinsertion, other catheter interventions including external cuff removal or shaving, and exit site relocation are suggested.
Asunto(s)
Infecciones Relacionadas con Catéteres , Diálisis Peritoneal , Peritonitis , Humanos , Infecciones Relacionadas con Catéteres/etiología , Infecciones Relacionadas con Catéteres/prevención & control , Infecciones Relacionadas con Catéteres/tratamiento farmacológico , Diálisis Peritoneal/efectos adversos , Catéteres de Permanencia/efectos adversos , Antibacterianos/uso terapéutico , Factores de Riesgo , Peritonitis/tratamiento farmacológicoRESUMEN
Ugi-four component reaction (Ugi-4CR) is extremely attractive for diversity-oriented and step economical synthesis as evident from past applications. Here we report the synthesis of fused polycyclic ß-carboline derivatives by sequential Pictet-Spengler's and Ugi-4CR multi-component reaction followed by cascade cyclization. The post cyclisation of Ugi product provides conformationally stable heterocyclic molecule that is expected to be suitable for interaction with different biological targets. The methodology provides a simple and facile access to heterocycles embedded in polycyclic framework which otherwise seems difficult to synthesize by conventional methods. Synthesis of fused Polycyclic ß-Carboline Derivatives Using Ugi-4CR Followed by Cascade Cyclization.
Asunto(s)
Carbolinas , CiclizaciónRESUMEN
A rigorous exploration of microbial diversity has revealed its presence on Earth, deep oceans, and vast space. The presence of microbial life in diverse environmental conditions, ranging from moderate to extreme temperature, pH, salinity, oxygen, radiations, and altitudes, has provided the necessary impetus to search for them by extending the limits of their habitats. Microbiology started as a distinct science in the mid-nineteenth century and has provided inputs for the betterment of mankind during the last 150 years. As beneficial microbes are assets and pathogens are detrimental, studying both have its own merits. Scientists are nowadays working on illustrating the microbial dynamics in Earth's subsurface, deep sea, and polar regions. In addition to studying the role of microbes in the environment, the microbe-host interactions in humans, animals and plants are also unearthing newer insights that can help us to improve the health of the host by modulating the microbiota. Microbes have the potential to remediate persistent organic pollutants. Antimicrobial resistance which is a serious concern can also be tackled only after monitoring the spread of resistant microbes using disciplines of genomics and metagenomics The cognizance of microbiology has reached the top of the world. Space Missions are now looking for signs of life on the planets (specifically Mars), the Moon and beyond them. Among the most potent pieces of evidence to support the existence of life is to look for microbial, plant, and animal fossils. There is also an urgent need to deliberate and communicate these findings to layman and policymakers that would help them to take an adequate decision for better health and the environment around us. Here, we present a glimpse of recent advancements by scientists from around the world, exploring and exploiting microbial diversity.
RESUMEN
AIMS: COVID-19 has currently emerged as the major global pandemic affecting the lives of people across the globe. It broke out from Wuhan Province of China, first reported to WHO on 31st December 2019 as "Pneumonia of unknown cause". Over time more people were infected with this virus, and the only tactic to ensure safety was to take precautionary measures due to the lack of any effective treatment or vaccines. As a result of unavailability of desired efficacy for previously repurposed drugs, exploring novel scaffolds against the virus has become the need of the hour. MAIN METHODS: In the present study, 23 new annomontine analogues were designed representing ß-Carboline based scaffolds. A hypothesis on its role as an effective ligand was laid for target-specific binding in SARS-CoV-2. These molecules were used for molecular docking analysis against the multiple possible drug targets using the Maestro Interface. To ensure the drug safety of these molecules ADME/Tox analysis was also performed. KEY FINDINGS: The molecular docking analysis of the 23 novel molecules indicated the efficiency of these derivates against COVID-19. The efficiency of molecules was computed by the summation of the docking score against each target defined as LigE Score and compared against Hydroxycholoquine as a standard. Based on the docking score, the majority of the annomontine derivatives were found to have increased binding affinity with targets as compared to hydroxycholoquine. SIGNIFICANCE: Due to the lack of efficiency, effectiveness, and failure of already repurposed drugs against the COVID-19, the exploration of the novel scaffold that can act as effective treatment is much needed. The current study hence emphasizes the potential of Annomontine based - ß- Carboline derivatives as a potential drug candidate against COVID-19.
RESUMEN
Malaria is a major parasitic disease in tropical and sub-tropical regions. Pertaining to the sustaining resistance in malarial parasite against the available drugs, novel treatment options are the need of the hour. In this resolve recently, focus has shifted to finding the natural alternatives that possess anti-plasmodial activity for combatting malaria. Drawing on the text written in ancient scriptures and Ayurveda, natural compounds are now being screened for their therapeutic properties. Indole is one such natural compound, present in all living organisms, it displays a range of therapeutic activities including anticancer, anti-inflammatory, antimalarial etc. In this review, we have discussed various indole scaffold as well as the semi-synthetic drugs containing indole moiety that have been synthesized for malaria treatment.
Asunto(s)
Antimaláricos/farmacología , Malaria/tratamiento farmacológico , Plasmodium/efectos de los fármacos , Animales , Antimaláricos/síntesis química , Antimaláricos/química , HumanosRESUMEN
BACKGROUND: Peritoneal dialysis (PD) can offer patients more autonomy and flexibility compared with in-center hemodialysis (HD). However, burnout - defined as mental, emotional, or physical exhaustion that leads to thoughts of discontinuing PD - is associated with an increased risk of transfer to HD. We aimed to describe the perspectives of burnout among patients on PD and their caregivers. METHODS: In this focus group study, 81 patients and 45 caregivers participated in 14 focus groups from 9 dialysis units in Australia, Hong Kong, and the United States. Transcripts were analyzed thematically. RESULTS: We identified two themes. Suffering an unrelenting responsibility contributed to burnout, as patients and caregivers felt overwhelmed by the daily regimen, perceived their life to be coming to a halt, tolerated the PD regimen for survival, and had to bear the burden and uncertainty of what to expect from PD alone. Adapting and building resilience against burnout encompassed establishing a new normal, drawing inspiration and support from family, relying on faith and hope for motivation, and finding meaning in other activities. CONCLUSIONS: For patients on PD and their caregivers, burnout was intensified by perceiving PD as an unrelenting, isolating responsibility that they had no choice but to endure, even if it held them back from doing other activities in life. More emphasis on developing strategies to adapt and build resilience could prevent or minimize burnout.
Asunto(s)
Cuidadores , Diálisis Peritoneal , Australia , Agotamiento Psicológico , Hong Kong/epidemiología , Humanos , Diálisis Peritoneal/efectos adversos , Diálisis RenalRESUMEN
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder that may be treated with non-ablative light-based devices; however, no systematic reviews on the topic exist to date. We conducted a systematic review and meta-analysis to determine efficacy of non-ablative light-based devices in treating HS. Specifically, a systematic review was conducted using MEDLINE, EMBASE, Web of Science and CINAHL. We analyzed the use of non-ablative light-based devices in the treatment of HS. At least two investigators performed title/abstract review and data extraction. Meta-analysis was conducted using comprehensive meta-analysis software. 5 RCTs and 11 case reports/series were included (n = 211 unique patients). No observational studies were found. For Nd:YAG laser, meta-analysis of 3 RCTs reported improvement in modified HS Lesion Area and Severity Index (HS-LASI) when compared to control subjects. In addition, three case reports/series reported HS-LASI, Physician Global Assessment (PGA) scores and number-of-lesion improvements in treated patients. For intense pulsed light (IPL), two RCTs reported HS-LASI and Dermatology Life Quality Index (DLQI) score improvements. For Alexandrite laser, one case report showed lesion improvement. In conclusion, meta-analysis of Nd:YAG laser in HS patients suggests significant improvement in HS-LASI scores. For IPL, evidence is limited, but suggests improvement in HS-LASI and DLQI scores. For Alexandrite laser, evidence precludes conclusions. Given small sample sizes and inconsistent reporting scales, larger RCTs are required to better determine the efficacy of these modalities in treating HS.
RESUMEN
RATIONALE & OBJECTIVE: Home dialysis has been underused in the United States, especially among minority groups. We investigated whether adjustment for socioeconomic factors would attenuate racial/ethnic differences in the initiation of home dialysis. STUDY DESIGN: Retrospective observational cohort study. SETTING & POPULATION: Adult patients in the US Renal Data System who initiated dialysis on day 1 with either in-center hemodialysis (HD), home HD (HHD), or peritoneal dialysis (PD) from 2005 to 2013. PREDICTOR: Race/ethnicity: non-Hispanic white, Hispanic, black, or Asian. OUTCOME: Initiating dialysis with PD versus in-center HD and HHD versus in-center HD for each minority group compared with non-Hispanic whites. ANALYTICAL APPROACH: Odds ratios and 95% CIs estimated by logistic regression. RESULTS: Of 523,526 patients, 55% were white, 28% were black, 13% were Hispanic, and 4% were Asian; 8% started dialysis on PD, and 0.1%, on HHD. In unadjusted analyses, blacks and Hispanics were 30% and 19% less likely and Asians were 31% more likely to start on PD than whites. The differences narrowed when fully adjusted for demographic, medical, and socioeconomic factors. Adjustment for socioeconomic factors reduced these differences between white and black, Hispanic, and Asian patients by 13%, 28%, and 1%, respectively. Blacks were just as likely and Hispanics and Asians were less likely to start on HHD than whites. This did not change appreciably when fully adjusted for demographic, medical, and socioeconomic factors. LIMITATIONS: No data for physician and patient preferences or modality education. CONCLUSIONS: Black and Hispanic patients are less likely to start on PD than white patients, attributable partly, though not completely, to socioeconomic factors. Hispanics and Asians are less likely to start on HHD than whites. This was materially unaffected by socioeconomic factors. More research is needed to determine whether urgent-start PD programs and transitional care units in socioeconomically disadvantaged areas might reduce these disparities and increase home dialysis use among all groups.
RESUMEN
BACKGROUND AND OBJECTIVES: We investigated whether the recent growth in home dialysis use was proportional among all racial/ethnic groups and also whether there were changes in racial/ethnic differences in home dialysis outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This observational cohort study of US Renal Data System patients initiating dialysis from 2005 to 2013 used logistic regression to estimate racial/ethnic differences in home dialysis initiation over time, and used competing risk models to assess temporal changes in racial/ethnic differences in home dialysis outcomes, specifically: (1) transfer to in-center hemodialysis (HD), (2) mortality, and (3) transplantation. RESULTS: Of the 523,526 patients initiating dialysis from 2005 to 2013, 55% were white, 28% black, 13% Hispanic, and 4% Asian. In the earliest era (2005-2007), 8.0% of white patients initiated dialysis with home modalities, as did a similar proportion of Asians (9.2%; adjusted odds ratio [aOR], 0.95; 95% confidence interval [95% CI], 0.86 to 1.05), whereas lower proportions of black [5.2%; aOR, 0.71; 95% CI, 0.66 to 0.76] and Hispanic (5.7%; aOR, 0.83; 95% CI, 0.86 to 0.93) patients did so. Over time, home dialysis use increased in all groups and racial/ethnic differences decreased (2011-2013: 10.6% of whites, 8.3% of blacks [aOR, 0.81; 95% CI, 0.77 to 0.85], 9.6% of Hispanics [aOR, 0.94; 95% CI, 0.86 to 1.00], 14.2% of Asians [aOR, 1.04; 95% CI, 0.86 to 1.12]). Compared with white patients, the risk of transferring to in-center HD was higher in blacks, similar in Hispanics, and lower in Asians; these differences remained stable over time. The mortality rate was lower for minority patients than for white patients; this difference increased over time. Transplantation rates were lower for blacks and similar for Hispanics and Asians; over time, the difference in transplantation rates between blacks and Hispanics versus whites increased. CONCLUSIONS: From 2005 to 2013, as home dialysis use increased, racial/ethnic differences in initiating home dialysis narrowed, without worsening rates of death or transfer to in-center HD in minority patients, as compared with white patients.
Asunto(s)
Hemodiálisis en el Domicilio/economía , Hemodiálisis en el Domicilio/estadística & datos numéricos , Utilización de Procedimientos y Técnicas/economía , Utilización de Procedimientos y Técnicas/estadística & datos numéricos , Sistema de Pago Prospectivo , Adulto , Negro o Afroamericano , Anciano , Asiático , Estudios de Cohortes , Etnicidad , Femenino , Hispánicos o Latinos , Humanos , Masculino , Persona de Mediana Edad , Estados Unidos , Población BlancaRESUMEN
BACKGROUND: Despite growing need, treatment for end-stage renal disease is limited in low- and middle-income countries due to resource restraints. We describe the development of an educational curriculum and quality improvement program to support continuous ambulatory peritoneal dialysis (CAPD) performed primarily by non-nephrology providers in Sri Lanka. METHODS: We developed a program of education, outcome tracking, and expert consultation to support providers in Kandy, Sri Lanka. Education included videos and in-person didactics covering core topics in CAPD. Event-tracking sheets recorded root causes and management of infections and hospitalizations. Conferences reviewed clinical cases and overall clinic management. We evaluated the patient census, peritonitis rates, and root causes and management of infections over 1 year. RESULTS: The curriculum was published through the International Society of Nephrology online academy. High provider turnover limited curriculum assessments. The CAPD patient census rose from 63 to 116 during the year. The peritonitis rate declined significantly, from 0.8 episodes per patient-year in the first 6 months to 0.4 in the latter 6 months, though the most common root causes of peritonitis, related to contamination events and hygiene, persisted. The appropriate ascertainment of culture data and prescription of antibiotics also increased. CONCLUSIONS: Our project supported the expansion of a CAPD program in a resource-limited setting, while also improving peritonitis outcomes. Ongoing challenges include ensuring a durable educational system for rotating providers, tracking outcomes beyond peritonitis, and formalizing management protocols. Our program can serve as an example of how established dialysis programs can support the burgeoning work of providers in resource-limited setting.
Asunto(s)
Educación a Distancia/métodos , Fallo Renal Crónico/terapia , Educación del Paciente como Asunto/métodos , Diálisis Peritoneal Ambulatoria Continua/economía , Mejoramiento de la Calidad , Adulto , Anciano , Femenino , Humanos , Fallo Renal Crónico/economía , Masculino , Persona de Mediana Edad , Factores Socioeconómicos , Sri Lanka , Grabación en Video , Adulto JovenRESUMEN
Background: Brain concentrations of omega-3 docosahexaenoic acid (DHA, 22:6n-3) have been reported to positively correlate with seizure thresholds in rodent seizure models. It is not known whether brain DHA depletion, achieved by chronic dietary omega-3 polyunsaturated fatty acid (PUFA) deficiency, lowers seizure thresholds in rats. Objective: The present study tested the hypothesis that lowering brain DHA concentration with chronic dietary n-3 PUFA deprivation in rats will reduce seizure thresholds, and that compared to injected oleic acid (OA), injected DHA will raise seizure thresholds in rats maintained on n-3 PUFA adequate and deficient diets. Methods: Rats (60 days old) were surgically implanted with electrodes in the amygdala, and subsequently randomized to the AIN-93G diet containing adequate levels of n-3 PUFA derived from soybean oil or an n-3 PUFA-deficient diet derived from coconut and safflower oil. The rats were maintained on the diets for 37 weeks. Afterdischarge seizure thresholds (ADTs) were measured every 4-6 weeks by electrically stimulating the amygdala. Between weeks 35 and 37, ADTs were assessed within 1 h of subcutaneous OA or DHA injection (600 mg/kg). Seizure thresholds were also measured in a parallel group of non-implanted rats subjected to the maximal pentylenetetrazol (PTZ, 110 mg/kg) seizure test. PUFA composition was measured in the pyriform-amygdala complex of another group of non-implanted rats sacrificed at 16 and 32 weeks. Results: Dietary n-3 PUFA deprivation did not significantly alter amygdaloid seizure thresholds or latency to PTZ-induced seizures. Acute injection of OA did not alter amygdaloid ADTs of rats on the n-3 PUFA adequate or deficient diets, whereas acute injection of DHA significantly increased amygdaloid ADTs in rats on the n-3 PUFA adequate control diet as compared to rats on the n-3 PUFA deficient diet (P < 0.05). Pyriform-amygdala DHA percent composition did not significantly differ between the groups, while n-6 docosapentaenoic acid, a marker of n-3 PUFA deficiency, was significantly increased by 2.9-fold at 32 weeks. Conclusion: Chronic dietary n-3 PUFA deficiency does not alter seizure thresholds in rats, but may prevent the anti-seizure effects of DHA.
RESUMEN
BACKGROUND: Although angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-II receptor blockers (ARB) have been shown to preserve residual kidney function in a select group of Asian patients undergoing continuous ambulatory peritoneal dialysis (PD) in two small randomized clinical trials, the effectiveness of these drugs has yet to be demonstrated in a more diverse population of patients with multiple comorbid conditions. We investigated the association between ACEI/ARB use and development of recorded anuria in a cohort of patients initiating PD in the U.S. METHODS: We conducted a retrospective observational cohort study using the US Renal Data System and electronic health records data from a large national dialysis provider. We identified adult patients who initiated PD from 2007 to 2011. Only patients who participated in the federal prescription drug benefit program, Medicare Part D, for the first 90 days of dialysis were included. Patients who filled a prescription for an ACEI or ARB during those 90 days were considered users. We applied Cox proportional hazards models to an inverse probability of treatment-weighted (IPTW) cohort to estimate the hazard ratio (HR) for anuria (24-h urine volume < 200 ml) in ACEI/ARB users vs. non-users. RESULTS: Among 886 patients, 389 (44%) used an ACEI/ARB. Almost a third of these patients were black or Hispanic, and more than a quarter had comorbidities that would have excluded them from the randomized clinical trials of ACEI/ARB. Two hundred eighty patients reached anuria over 840 person-years of follow-up, for a composite event rate of 33 events per 100 person-years. We found no clear association between ACEI/ARB use and progression to anuria [HR: 0.86, 95% CI: 0.73-1.02]. CONCLUSIONS: ACEI/ARB use is common in patients initiating PD in the U.S. but was not associated with a lower risk of anuria. Residual confounding by unmeasured variables is an important limitation of this observational study. Still, these findings suggest that pragmatic clinical trials are warranted to test the effectiveness of ACEI/ARB in slowing the decline of residual kidney function in a diverse population of peritoneal dialysis patients with multiple comorbid conditions.
Asunto(s)
Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Riñón/efectos de los fármacos , Diálisis Peritoneal/tendencias , Insuficiencia Renal Crónica/terapia , Sistema Renina-Angiotensina/efectos de los fármacos , Anciano , Anciano de 80 o más Años , Antagonistas de Receptores de Angiotensina/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Anuria/fisiopatología , Anuria/terapia , Estudios de Cohortes , Femenino , Humanos , Riñón/fisiología , Masculino , Persona de Mediana Edad , Insuficiencia Renal Crónica/fisiopatología , Sistema Renina-Angiotensina/fisiología , Estudios RetrospectivosRESUMEN
BACKGROUND: Data on the effectiveness of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in reducing cardiovascular (CV) risk in patients undergoing peritoneal dialysis (PD) are limited. We investigated the association between ACEI/ARB use and CV outcomes in patients initiating PD. METHODS: In this observational cohort study, we identified from the United States Renal Data System all adult patients who initiated PD from 2007 to 2011 and participated in Medicare Part D, a federal prescription drug benefits program, for the first 90 days of dialysis. Patients who filled a prescription for an ACEI or ARB in those 90 days were considered users. We applied Cox regression to an inverse probability of treatment weighted cohort to estimate the hazard ratios (HRs) for the combined outcome of death, ischemic stroke or myocardial infarction (MI) and each outcome individually. RESULTS: Among 4879 patients, 2063 (42%) used an ACEI/ARB. Patients were followed up for a median of 1.2 years. We recorded 1771 events, for a composite rate of 25 events per 100 person-years. ACEI/ARB use (versus nonuse) was associated with a reduced risk of the composite outcome {HR 0.84 [95% confidence interval (CI) 0.76-0.93]}, all-cause mortality [HR 0.83 (95% CI 0.75-0.92)] and CV death [HR 0.74 (95% CI 0.63-0.87)], but not MI [HR 0.88 (95% CI 0.69-1.12)] or ischemic stroke [HR 1.06 (95% CI 0.79-1.43)]. Results were similar in as-treated analyses. In a subgroup analysis, we did not find any effect modification by residual renal function. CONCLUSIONS: ACEI/ARB use is common in patients initiating PD and is associated with a lower risk of fatal CV outcomes.
Asunto(s)
Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Enfermedades Cardiovasculares/prevención & control , Fallo Renal Crónico/terapia , Diálisis Peritoneal , Adolescente , Adulto , Anciano , Enfermedades Cardiovasculares/epidemiología , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: There is evidence that angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-II receptor blockers (ARB) may reduce cardiovascular (CV) risk in patients undergoing peritoneal dialysis (PD), but no studies have compared the effectiveness between these drug classes. In this observational cohort study, we compared the association of ARB vs. ACEI use on CV outcomes in patients initiating PD. METHODS: We identified from the US Renal Data System all adult patients who initiated PD from 2007 to 2011 and participated in Medicare Part D, a federal prescription drug benefits program, for the first 90 days of dialysis. Patients who filled a prescription for an ACEI or ARB in those 90 days were considered users. We excluded patients who used both ACEI and ARB. We applied Cox proportional hazards regression to an inverse probability of treatment-weighted cohort to estimate the hazard ratios (HR) for the combined outcome of all-cause death, ischemic stroke, or myocardial infarction; all-cause mortality; and CV death. RESULTS: Among 1892 patients using either drug class, 39 % were ARB users. We observed 624 events over 2,898 person-years of follow-up, for a composite event rate of 22 events per 100 person-years. We observed no differences between ARB vs. ACEI users: composite outcome HR 0.94, 95 % confidence interval (CI) 0.79-1.11; all-cause mortality HR 0.92, 95 % CI 0.76-1.10; CV death HR: 1.06, 95 % CI 0.80-1.41. CONCLUSION: We identified no significant difference in the risks of CV events or death between users of ARBs vs. ACEIs in patients initiating PD, thus supporting their mostly interchangeable use in this population.
Asunto(s)
Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Enfermedades Cardiovasculares/prevención & control , Fallo Renal Crónico/terapia , Diálisis Peritoneal , Sistema Renina-Angiotensina/efectos de los fármacos , Anciano , Anciano de 80 o más Años , Antagonistas de Receptores de Angiotensina/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/mortalidad , Investigación sobre la Eficacia Comparativa , Bases de Datos Factuales , Femenino , Humanos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/fisiopatología , Masculino , Medicare Part D , Diálisis Peritoneal/efectos adversos , Diálisis Peritoneal/mortalidad , Modelos de Riesgos Proporcionales , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Estados UnidosRESUMEN
INTRODUCTION: Cytological examination of serous effusions helps in staging, prognostication and management of patients with malignancy. The method has disadvantage of lower sensitivity in differentiating reactive atypical mesothelial cells from malignant cells. AIM: The aim of this study is to compare the cytological features of pleural and peritoneal exudative fluids by conventional smear (CS) method and cell block (CB) method and also to assess the utility of a combined approach for cytodiagnosis of these effusions. MATERIALS AND METHODS: One hundred and fifty-three pleural and peritoneal exudative fluid samples were subjected to evaluation by both CS and CB methods over a period of 2 years. Cellularity, architecture patterns, morphological features and yield for malignancy were compared, using the two methods. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy for diagnosing malignancy were calculated by both methods, using histology as a gold standard. RESULTS: CB method provided higher cellularity, better architectural patterns and additional yield for malignancy as compared to CS method (P < 0.005). Sensitivity, specificity, PPV, NPV, and accuracy by CS method were 69.2%, 95%, 56.25%, 97.08% and 92.8%, while by CB method were 92.30%, 99.2%, 92.30%, 99.28% and 98.6%. CONCLUSION: The present study shows that it is advisable to routinely make CBs before discarding specimens that are suspicious for malignancy by smear examination.