Ophthalmic adverse drug reactions to systemic drugs: a systematic review

PURPOSE: To perform a comprehensive and systematic review regarding ophthalmic adverse drug reactions (ADRs) to systemic drugs to: (i) systematically summarize existing evidence, (ii) identify areas, ophthalmic ADRs or drugs that lacked systematization or assessment (namely drugs with original studies characterizing specific ophthalmic ADRs but without causality assessment nor without meta-analysis). METHODS: Systematic review of several electronic databases (last search 1/7/2012): Medline, SCOPUS, ISI web of knowledge, ISI Conference Proceedings, International Pharmaceutical Abstracts and Google scholar. Search query included: eye, ocular, ophthalmic, ophthalmology, adverse and reaction. Inclusion criteria were: (i) Primary purpose was to assess an ophthalmic ADR to a systemic medication; (ii) Patient evaluation performed by an ophthalmologist; (iii) Studies that specified diagnostic criteria for an ocular ADR. Different types of studies were included and analyzed separately. Two independent reviewers assessed eligibility criteria, extracted data and evaluated risk of bias. RESULTS: From 562 studies found, 32 were included (1 systematic review to sildenafil, 11 narrative reviews, 1 trial, 1 prospective study, 6 transversal studies, 6 spontaneous reports and 6 case series). Drugs frequently involved included amiodarone, sildenafil, hydroxychloroquine and biphosphonates. Frequent ophthalmic ADRs included: keratopathy, dry eye and retinopathy. CONCLUSIONS: To increase evidence about ophthalmic ADRs, there is a need for performing specific systematic reviews, applying strictly the World Health Organization's (WHO) definition of ADR and WHO causality assessment of ADRs. Some ophthalmic ADRs may be frequent, but require ophthalmological examination; therefore, ophthalmologists' education and protocols of collaboration between other specialties whenever they prescribe high-risk drugs are suggestions for the future

Antagonizing the spindle assembly checkpoint silencing enhances paclitaxel and Navitoclax-mediated apoptosis with distinct mechanistic

Antimitotic drugs arrest cells in mitosis through chronic activation of the spindle assembly checkpoint (SAC), leading to cell death. However, drug-treated cancer cells can escape death by undergoing mitotic slippage, due to premature mitotic exit. Therefore, overcoming slippage issue is a promising chemotherapeutic strategy to improve the effectiveness of antimitotics. Here, we antagonized SAC silencing by knocking down the MAD2-binding protein p31comet, to delay mitotic slippage, and tracked cancer cells treated with the antimitotic drug paclitaxel, over 3 days live-cell time-lapse analysis. We found that in the absence of p31comet, the duration of mitotic block was increased in cells challenged with nanomolar concentrations of paclitaxel, leading to an additive effects in terms of cell death which was predominantly anticipated during the first mitosis. As accumulation of an apoptotic signal was suggested to prevent mitotic slippage, when we challenged p31comet-depleted mitotic-arrested cells with the apoptosis potentiator Navitoclax (previously called ABT-263), cell fate was shifted to accelerated post-mitotic death. We conclude that inhibition of SAC silencing is critical for enhancing the lethality of antimitotic drugs as well as that of therapeutic apoptosis-inducing small molecules, with distinct mechanisms. The study highlights the potential of p31comet as a target for antimitotic therapies.The authors gratefully acknowledge CESPU—Cooperativa de Ensino Superior Politécnico e Universitário, which financed this work under the projects “ComeTarget_CESPU_2017” and “ComeTax”. Ana C. Henriques acknowledge FCT-Fundação para a Ciência e a Tecnologia for financial support (Grant SFRH/BD/116167/2016)

Early cyclosporine a withdrawal in kidney-transplant recipients receiving sirolimus prevents progression of chronic pathologic allograft lesions

BACKGROUND: Nephrotoxicity of calcineurin inhibitors (CNIs) is partially responsible for the development of chronic allograft nephropathy (CAN). Sirolimus has demonstrated its potential to substitute for CNIs because it lacks significant nephrotoxicity and shows a short-term immunosuppressive capacity comparable with that of cyclosporine. This results in the maintenance of better renal function when cyclosporine is eliminated, but it has not been demonstrated whether this benefit is associated with an improvement in the pathologic substrate and a reduction in CAN. METHODS: We analyzed pretransplant and 1-year renal-allograft biopsies from 64 patients enrolled in a multicenter trial. Patients received cyclosporine and sirolimus during the first 3 months after transplant and were then randomly assigned to continue with cyclosporine or have it withdrawn. Histologic chronic allograft lesions were compared between groups. RESULTS: The percentage of patients in whom chronic pathologic lesions progressed was lower in the group of cyclosporine elimination. Significant differences were observed in chronic interstitial and tubular lesions (70% vs. 40.9% [P<0.05] and 70% vs. 47.8% [P<0.05], respectively), whereas no differences were observed in acute lesions (subclinical rejection). Prevalence of CAN at 1 year was lower in this group, as was the severity and incidence of new cases (P<0.05). CONCLUSIONS: Early cyclosporine withdrawal associated with sirolimus administration is followed by an improvement in renal function, a reduction in the progression of chronic pathologic allograft lesions, and a lower incidence of new cases and severity of CAN during the first year after transplantation. This benefit may result in better long-term graft outcome

The Need for Robust, Consistent Methods in Societal Exergy Accounting

© 2017 The AuthorsStudies of societal exergy use have the common aim of tracing the flow of exergy along society, and are used to gain insights into the efficiency of energy use and linkages to economic growth. However, their methodological approaches vary greatly, with significant impacts on results. Therefore, we make a review of past studies to identify, synthesize and discuss methodological differences, to contribute to a more consistent and robust approach to societal exergy accounting. Issues that should be taken into account when making methodological options are discussed and key insights are presented: (1) For mapping of primary inputs and useful exergy categories, the inclusion of all natural resources is more consistent but it has the cost of not being able to distinguish the various energy end-uses in the production of materials. (2) To estimate primary electricity, none of the methods currently used is able to capture simultaneously the efficiency of the renewable energy sector, the environmental impact and the efficiency of energy use in society. (3) To estimate final-to-useful exergy conversion efficiencies, standard thermodynamic definitions should be used because the use of proxies fails to distinguish between increases in exergy efficiency and increases in the efficiency of providing energy services

Autopsy in adults with congenital heart disease (ACHD).

The adult congenital heart diseases (ACHD) population is exceeding the pediatric congenital heart diseases (CHD) population and is progressively expanding each year, representing more than 90% of patients with CHD. Of these, about 75% have undergone surgical and/or percutaneous intervention for palliation or correction. Autopsy can be a very challenging procedure in ACHD patients. The approach and protocol to be used may vary depending on whether the pathologists are facing native disease without surgical or percutaneous interventions, but with various degrees of cardiac remodeling, or previously palliated or corrected CHD. Moreover, interventions for the same condition have evolved over the last decades, as has perioperative myocardial preservations and postoperative care, with different long-term sequelae depending on the era in which patients were operated on. Careful clinicopathological correlation is, thus, required to assist the pathologist in performing the autopsy and reaching a diagnosis regarding the cause of death. Due to the heterogeneity of the structural abnormalities, and the wide variety of surgical and interventional procedures, there are no standard methods for dissecting the heart at autopsy. In this paper, we describe the most common types of CHDs that a pathologist could encounter at autopsy, including the various types of surgical and percutaneous procedures and major pathological manifestations. We also propose a practical systematic approach to the autopsy of ACHD patients

Healthy excessive weight in Portuguese women 4years after delivery of a liveborn

OBJECTIVE: To quantify the prevalence of healthy excessive weight and determinants of metabolic profile, considering women's reproductive life. METHODS: We evaluated 1847 mothers of a birth cohort assembled after delivery and reevaluated 4years later. A healthy profile was defined as the absence of hypertension, diabetes, dyslipidemia, C-reactive protein <3mg/l and being below the second tertile of HOMA-IR. Adjusted odds ratios (OR) and confidence intervals (95% CI) were computed using multinomial logistic regression, taking women with normal BMI as the reference category of the outcome. RESULTS: Four years after delivery, 47% of women had normal BMI, 33% were overweight and 20% obese. In each BMI class, 61%, 33% and 12% presented a healthy metabolic profile, respectively. Family history of CVD/cardiometabolic risk factors was associated with a higher probability of obesity with a not healthy metabolic profile (OR=1.39 95% CI: 0.98-1.98). Women who breastfed the enrolled child for >26weeks and practiced physical exercise were less likely to be obese and metabolically unhealthy (OR=0.39 95% CI: 0.23-0.68; OR=0.48 95% CI: 0.33-0.70, respectively), with no effect on healthy excessive weight. CONCLUSIONS: These results support the existence of a healthy excessive weight phenotype in women after motherhood, influenced by anthropometrics, genetic and lifestyles characteristics

Controlo da asma infantil: principais fatores associados

Introdu??o: A asma apresenta-se como uma doen?a cr?nica e inflamat?ria das vias a?reas caracterizada por epis?dios de obstru??o br?nquica revers?vel podendo ser desencadeada por diversos fatores. Constitui-se como a doen?a infantil mais comum, uma importante causa de internamento hospitalar e um problema de sa?de p?blica. As diretrizes internacionais sobre a gest?o da asma reconhecem que o tratamento reside no controlo atual e no risco de exacerba??es, sendo baseados na gest?o de sintomas. Relativamente ? perce??o do controlo da asma infantil, existem discrep?ncias entre a perce??o dos cuidadores e as indica??es internacionais. Objetivos: Descrever e analisar os dados cl?nicos, sociodemogr?ficos e fatores associados ao controlo da asma infantil. Metodologia: Estudo metodol?gico, quantitativo e transversal, numa amostra de crian?as, entre os 6 e os 11 anos, com asma e cuidadores. O controlo da asma foi avaliado pelo instrumento Childhood Asthma Control Test. Resultados: A amostra foi composta por 60 crian?as e cuidadores. 12% (n=7) das crian?as apresentam asma n?o controlada e 53% (n=32) asma parcialmente controlada. Em 38% (n=23) dos cuidadores existiram discrep?ncias entre o grau classificado mediante as guidelines internacionais e a sua perce??o. A an?lise de Regress?o Log?stica confirma que as crian?as com necessidades de terap?utica inalat?ria de resgate apresentam 7 vezes maior probabilidade da asma estar n?o controlada. Conclus?o: Torna-se perent?rio a necessidade de apreens?o da complexidade dos fatores que interferem no controlo da asma, existindo necessidade de programas de interven??o de gest?o de sintomas centrados nos cuidadores, na crian?a e nas necessidades identificadas.991B-C3B6-3D4F | Salete Soaresinfo:eu-repo/semantics/publishedVersio

Cardiovascular risk profile of mothers of a Portuguese birth cohort: a survey 4 years after delivery

Objectives: The aim of this study is to estimate the prevalence of smoking, low fruit and vegetable intake, sedentariness, overweight/obesity, abdominal obesity, hypertension, dyslipidemia and diabetes mellitus in mothers of a Portuguese birth cohort, 4 years after delivery. Methods: A birth cohort was assembled at public maternities of Porto (2005–2006). Children and mothers were reevaluated 4 years later. In this analysis, 5435 women were included. Socioeconomic characteristics, smoking, diet and exercise were self-reported. Anthropometrics and blood pressure were measured. A subgroup of 2483 randomly selected women provided a fasting venous blood sample for lipid and glucose measurements. Results: Overall, 25.3% women smoked, 71.5% consumed < 5 portions of fruit and vegetables per day, 81.3% were sedentary, 31.4% were overweight, 21.3% obese and 31.8% had abdominal obesity. The prevalence of hypertension, dyslipidemia and diabetes mellitus was 8.7%, 18.5% and 0.9%, respectively. At least one risk factor from each of the 3 groups (adverse lifestyles, adiposity and cardiometabolic comorbidities) was observed in 17.4% of women. Except for smoking, all risk factors were associated with unemployment, lower education and lower income. Conclusions: The high prevalence of unfavorable lifestyles and adiposity, and the aggregation of risk factors emphasize the adverse cardiovascular risk profile at a young age

Oxidative Stress in Kidney Transplantation: Malondialdehyde Is an Early Predictive Marker of Graft Dysfunction

Background Oxidative stress is one of the most important components of the ischemia-reperfusion process after kidney transplantation (KTx) and increases with graft dysfunction. Methods This prospective study was conducted on 40 consecutive KTx recipients to evaluate time-dependent changes in oxidative stress-related parameters within the first week after KTx and to assess their performance in predicting delayed graft function (DGF=dialysis requirement during initial posttransplant week) and graft function at 1 year. Blood samples were collected before (day 0) and after KTx (days 1, 2, 4, and 7). Total antioxidant capacity, plasma levels of malondialdehyde (MDA), and activities of glutathione peroxidase, glutathione reductase and superoxide dismutase were measured. Multivariable linear mixed and linear regression models, receiver-operating characteristic (ROC), and areas under ROC curves (AUC-ROC) were used. Results At all time points after KTx, mean MDA levels were significantly higher in patients developing DGF (n=18). Shortly after KTx (8–12 hr), MDA values were higher in DGF recipients (on average, +0.16 μmol/L) and increased further on following day, contrasting with prompt functioning recipients. Day 1 MDA levels accurately predicted DGF (AUC-ROC=0.90), with a performance higher than SCr (AUC-ROC=0.73) and similar to cystatin C (AUC-ROC=0.91). Multivariable analysis revealed that MDA levels on day 7 represented an independent predictor of 1-year graft function. Antioxidant enzyme activities were not significantly changed during the study period and were not predictors of 1-year graft function. Conclusions Increased MDA levels on day 1 after KTx might be an early prognostic indicator of DGF, and levels on day 7 might represent a useful predictor of 1-year graft function