Porphyrin-lipid stabilized paclitaxel nanoemulsion for combined photodynamic therapy and chemotherapy.

BACKGROUND: Porphyrin-lipids are versatile building blocks that enable cancer theranostics and have been applied to create several multimodal nanoparticle platforms, including liposome-like porphysome (aqueous-core), porphyrin nanodroplet (liquefied gas-core), and ultrasmall porphyrin lipoproteins. Here, we used porphyrin-lipid to stabilize the water/oil interface to create porphyrin-lipid nanoemulsions with paclitaxel loaded in the oil core (PLNE-PTX), facilitating combination photodynamic therapy (PDT) and chemotherapy in one platform. RESULTS: PTX (3.1 wt%) and porphyrin (18.3 wt%) were loaded efficiently into PLNE-PTX, forming spherical core-shell nanoemulsions with a diameter of 120 nm. PLNE-PTX demonstrated stability in systemic delivery, resulting in high tumor accumulation (~ 5.4 ID %/g) in KB-tumor bearing mice. PLNE-PTX combination therapy inhibited tumor growth (78%) in an additive manner, compared with monotherapy PDT (44%) or chemotherapy (46%) 16 days post-treatment. Furthermore, a fourfold reduced PTX dose (1.8 mg PTX/kg) in PLNE-PTX combination therapy platform demonstrated superior therapeutic efficacy to Taxol at a dose of 7.2 mg PTX/kg, which can reduce side effects. Moreover, the intrinsic fluorescence of PLNE-PTX enabled real-time tracking of nanoparticles to the tumor, which can help inform treatment planning. CONCLUSION: PLNE-PTX combining PDT and chemotherapy in a single platform enables superior anti-tumor effects and holds potential to reduce side effects associated with monotherapy chemotherapy. The inherent imaging modality of PLNE-PTX enables real-time tracking and permits spatial and temporal regulation to improve cancer treatment.

Therapeutic living donor nephrectomy.

Therapeutic living donor nephrectomy is defined as a nephrectomy that is performed as therapy for an underlying medical condition. The patient directly benefits from having their kidney removed, but the kidney is deemed transplantable. The kidney is subsequently used as an allograft for an individual with advanced renal disease. Therapeutic donor nephrectomy can be successfully utilized for a heterogenous cohort of disease processes as both treatment for the donor and to increase the number of suitable organs available for transplantation. We describe four cases of therapeutic donor nephrectomy that were performed at our institution. Of the four cases, two patients elected to undergo therapeutic donor nephrectomy as treatment for loin pain hematuria syndrome; one after blunt abdominal trauma that resulted in complete proximal ureteral avulsion; and the fourth after being diagnosed with a small renal mass. Based on our data presented to the United Network for Organ Sharing Board of Directors (UNOS) in December 2015, living donor evaluation has been made simpler for patients electing to undergo therapeutic donor nephrectomy. UNOS eliminated the requirement for a psychosocial evaluation for these patients. As the organ shortage continues to limit transplantation, therapeutic donor nephrectomy should be considered when appropriate.

Pharmacological and residual effects in randomized placebo-controlled trials. A structural causal modelling approach.

BACKGROUND: Distinguishing between pharmacological and residual effects, this paper considers the problem of causal assessment in the case of a particular model, namely a Sure Outcome of Random Events (SORE) model developed for the analysis of data from a randomized placebo-controlled double-blind trial of a drug. METHOD: This model takes into account two kinds of observable effects, a therapeutic effect and a side-effect. For each observable effect, two latent factors are considered, i.e. a pharmacological (or explained) factor and a residual (or unexplained) one. RESULTS: The model presents a plausible mechanism generating the observed and latent outcomes, recursively decomposed into an ordered sequence of sub-mechanisms. CONCLUSIONS: The characteristics of this model leads to a novel assessment of causality that evaluates the effect of latent variables and of the bias resulting from ignoring the structural features of the data generating process. This approach is illustrated by a numerical example, along with a case study based on a secondary analysis of real data.

Experimental and Computational Studies to Characterize and Evaluate the Therapeutic Effect of Albizia lebbeck (L.) Seeds in Alzheimer's Disease.

Background and Objectives: Alzheimer's disease (AD) is a neurodegenerative disorder that deteriorates daily life due to loss of memory and cognitive impairment. It is believed that oxidative stress and cholinergic deficit are the leading causes of AD. Disease-modifying therapies for the treatment of AD are a challenging task for this century. The search for natural and synthetic agents has attracted the attention of researchers. The objective of this study was a scientific approach to search for most suitable remedy for AD by exploiting the potential of Albizia lebbeck (L.) seeds. Materials and Methods: Hydromethanolic extract of Albizia lebbeck seeds (ALE) was prepared by maceration. The plant was characterized by physico-chemical, phyto-chemical, and high-performance liquid chromatography (HPLC). Thirty-six Wistar albino rats were used in this study and divided into six groups (n = 6). Group I: normal control; Group II: disease control (AlCl3; 100 mg/Kg); Group III: standard control (galantamine; 0.5mg/Kg); Groups IV-VI were treated ALE at 100, 200 and 300 mg/Kg dose levels, respectively. All the treatments were given orally for 21 consecutive days. Y-maze, T-maze, Morris water maze, hole board, and open field behavioral tests were performed to analyze the cognitive impairment. Biochemical, histological, and computational studies were performed to support the results of behavioral tests. Results: HPLC analysis indicated the presence of quercetin, gallic acid, m-coumaric acid, and sinapic acid. ALE significantly improved the memory and cognitive impairments. Endogenous antioxidant stress biomarker levels and histopathological outcomes supported the therapeutic potential of A. lebbeck in AD. Cholinergic deficits were also ameliorated by ALE co-administration, possibly by the inhibition of hyperactive acetylcholinesterase (AChE). Docking studies supported the potential of ALE against AD. Conclusions: The data suggested that ALE has neuroprotective potential that can be exploited for beneficial effects to treat AD.

Therapeutic effect of monophosphoryl lipid A administration on Paracoccidioides brasiliensis-infected mice.

The lack of antifungals with low toxicity and short-term therapy for patients with paracoccidioidomycosis (PCM) led us to evaluate adjuvants in immunotherapeutic intervention. We have previously shown complete Freund's adjuvant (CFA) to be therapeutic on experimental PCM. Owing to CFA toxicity, here we tested adjuvants approved for clinical use or in preclinical phase in experimental mouse PCM. Of all, only monophosporyl lipid A (MPLA) demonstrates a beneficial effect, by reducing the fungal burden and increasing the concentrations of IFN-γ and TNF-α, which are immunoprotective in PCM. These results suggest that MPLA might improve intervention in PCM.

Therapeutic Effect of Recombinant Mutated Interleukin 11 in the Mouse Model of Tuberculosis.

Earlier we demonstrated that blocking of interleukin 11 (IL-11) by systemic administration of anti-IL-11 antibodies attenuates severity of Mycobacterium tuberculosis infection in mice. The substitution W147A in the IL-11 molecule creates the form of cytokine capable to disrupt gp130/IL11R signaling complex formation, thus serving as a high-affinity specific antagonist of IL-11-mediated signaling. We hypothesized that this mutant form of IL-11 may serve as an effective tool for inhibition of native IL-11 activity in vivo. We established the recombinant W147A mutant form of IL-11 in an optimized Escherichia coli expression system and administered it as the aerosol in the lungs of M. tuberculosis-susceptible I/St mice infected with M. tuberculosis Our results show that this therapeutic approach markedly inhibits tuberculous inflammation in lungs, increases the survival time of infected animals, and decreases expression of key inflammatory factors at the RNA and protein levels. These findings are a step toward clinical evaluation of the anti-IL-11 therapy for tuberculosis.

Reconstruction Algorithm-Based Computed Tomography Image Feature for Evaluating the Effect of Internal Administration and Medicated Bath of Liangxue Xiaoyin Decoction on Psoriasis Vulgaris.

Skin computed tomography (CT) image based on improved marching cubes (MC) algorithm was explored to evaluate the therapeutic effect of internal administration of Liangxue Xiaoyin decoction combined with medicated bath in the treatment of psoriasis vulgaris. 712 patients with psoriasis vulgaris blood heat syndrome in hospital were recruited as the research object, which were randomly divided into observation group (TCM oral therapy combined with medicinal bath) and control group (TCM oral therapy), each with 356 cases. Psoriasis area and severity index (PASI), pruritus degree, and clinical treatment effect were compared. The results showed that the reconstruction time of median method was greatly shorter, and the algorithm efficiency was improved by 40.6290%. After treatment, the psoriasis area and severity index (PASI) score of the observation group was 5.61 ± 1.15, ΔPASI = (22.64 ± 2.15). ΔPASI% = 80.14%, which were greatly higher than the control group ((9.41 + 1.56) points, ΔPASI = (18.84 + 1.65) points, ΔPASI% = 66.69%) (P < 0.05). After treatment, the itching degree of the observation group was 3.03 ± 1.01 points, which was lower than that of the control group ((3.71 ± 1.06) points), and the itching degree of the observation group was greater than that of the control group, with substantial difference (P < 0.05). The total effective rate of observation group (88.76%) was higher than that of control group (71.07%) (P < 0.05). Therefore, skin CT image based on the improved MC algorithm can evaluate the therapeutic effect of internal administration of Liangxue Xiaoyin decoction combined with medicated bath in the treatment of psoriasis vulgaris. The internal administration of Liangxue Xiaoyin decoction combined with medicated bath had a good effect on the treatment of psoriasis vulgaris and was of certain clinical application value.

BICEPP: an example-based statistical text mining method for predicting the binary characteristics of drugs.

BACKGROUND: The identification of drug characteristics is a clinically important task, but it requires much expert knowledge and consumes substantial resources. We have developed a statistical text-mining approach (BInary Characteristics Extractor and biomedical Properties Predictor: BICEPP) to help experts screen drugs that may have important clinical characteristics of interest. RESULTS: BICEPP first retrieves MEDLINE abstracts containing drug names, then selects tokens that best predict the list of drugs which represents the characteristic of interest. Machine learning is then used to classify drugs using a document frequency-based measure. Evaluation experiments were performed to validate BICEPP's performance on 484 characteristics of 857 drugs, identified from the Australian Medicines Handbook (AMH) and the PharmacoKinetic Interaction Screening (PKIS) database. Stratified cross-validations revealed that BICEPP was able to classify drugs into all 20 major therapeutic classes (100%) and 157 (of 197) minor drug classes (80%) with areas under the receiver operating characteristic curve (AUC) > 0.80. Similarly, AUC > 0.80 could be obtained in the classification of 173 (of 238) adverse events (73%), up to 12 (of 15) groups of clinically significant cytochrome P450 enzyme (CYP) inducers or inhibitors (80%), and up to 11 (of 14) groups of narrow therapeutic index drugs (79%). Interestingly, it was observed that the keywords used to describe a drug characteristic were not necessarily the most predictive ones for the classification task. CONCLUSIONS: BICEPP has sufficient classification power to automatically distinguish a wide range of clinical properties of drugs. This may be used in pharmacovigilance applications to assist with rapid screening of large drug databases to identify important characteristics for further evaluation.

Graphing and reporting heterogeneous treatment effects through reference classes.

BACKGROUND: Exploration and modelling of heterogeneous treatment effects as a function of baseline covariates is an important aspect of precision medicine in randomised controlled trials (RCTs). Randomisation generally guarantees the internal validity of an RCT, but heterogeneity in treatment effect can reduce external validity. Estimation of heterogeneous treatment effects is usually done via a predictive model for individual outcomes, where one searches for interactions between treatment allocation and important patient baseline covariates. However, such models are prone to overfitting and multiple testing and typically demand a transformation of the outcome measurement, for example, from the absolute risk in the original RCT to log-odds of risk in the predictive model. METHODS: We show how reference classes derived from baseline covariates can be used to explore heterogeneous treatment effects via a two-stage approach. We first estimate a risk score which captures on a single dimension some of the heterogeneity in outcomes of the trial population. Heterogeneity in the treatment effect can then be explored via reweighting schemes along this axis of variation. This two-stage approach bypasses the search for interactions with multiple covariates, thus protecting against multiple testing. It also allows for exploration of heterogeneous treatment effects on the original outcome scale of the RCT. This approach would typically be applied to multivariable models of baseline risk to assess the stability of average treatment effects with respect to the distribution of risk in the population studied. CASE STUDY: We illustrate this approach using the single largest randomised treatment trial in severe falciparum malaria and demonstrate how the estimated treatment effect in terms of absolute mortality risk reduction increases considerably in higher risk strata. CONCLUSIONS: 'Local' and 'tilting' reweighting schemes based on ranking patients by baseline risk can be used as a general approach for exploring, graphing and reporting heterogeneity of treatment effect in RCTs. TRIAL REGISTRATION: ISRCTN clinical trials registry: ISRCTN50258054. Prospectively registered on 22 July 2005.

The efficacy of jade moxibustion in knee osteoarthritis.

INTRODUCTION: This study aims to compare clinical effect between Jade moxibustion and traditional moxibustion, and to determine the clinical effect of Jade moxibustion on knee osteoarthritis (KOA). METHODS/DESIGN: This is a 2-parallel-group, randomized controlled trial. A total of 148 subjects with KOA (Kellgren-Lawrence grade II or III) will be recruited and randomized to receive Jade moxibustion treatment or a traditional moxibustion treatment in a 1:1 ratio. Jade moxibustion group: The affected knee of the subjects will be covered with jade kneepad. Traditional moxibustion group: Chosen the ST35, ST34, EX-LE4, SP10 and Ashi points at the affected knee. The subjects will receive treatment three times a week, altogether 12 times in 4 weeks. The main outcomes are WOMAC knee pain score, knee function score and SF-36 quality of life questionnaire changes at the 4th week. Secondary outcomes include WOMAC knee pain score and knee function score, overall clinical efficacy evaluation, medication, safety evaluation at the 2nd, 12th, and 24th week, and cytokines related to osteoarthritis in serum. DISCUSSION: This randomized controlled trial used traditional moxibustion as a control group to provide rigorous evidence for the clinical efficacy and safety of Jade moxibustion in treatment of KOA. TRIAL REGISTRATION: ISRCTN registry, No 21174552. Registered on 28 February 2020.

International Experience in Therapeutic Value and Value-Based Pricing: A Rapid Review of the Literature.

OBJECTIVES: To characterize at a global level the concept of therapeutic value (TV) and describe the experience of value-based pricing (VBP) policies in 6 reference countries. METHODS: We conducted a rapid review of the literature that addressed 2 exploratory research questions. A systematic and exhaustive search was carried out up to July 2018 in MEDLINE (Ovid), Embase, Scopus, and Web of Science. RESULTS: The concepts of TV and VBP are related; value frameworks for medicines should include social preferences, comparative effectiveness, safety, adoption viability, social impact, high quality of evidence, severity of illness, and innovation. The added therapeutic value (ATV) is the manner of measuring the therapeutic advantages of new medicines compared with existing ones in terms of comparative effectiveness and safety. There are variations in the mechanisms of reimbursement and drug pricing regulation between the countries of study. CONCLUSION: In a VBP system it is essential to establish the TV and ATV of a new medicine. Although there are no methodological guidelines for the implementation of VBP policies, the process implies from the beginning the definition of TV categories that will be included in the drug pricing and reimbursement systems. Agreements between the pharmaceutical industry and governments have become a useful tool as a negotiating mechanism in most countries.

Quantitative Proteomics and Metabolomics Reveal Biomarkers of Disease as Potential Immunotherapy Targets and Indicators of Therapeutic Efficacy.

Quantitative mass spectrometry (MS) continues to deepen our understanding of the immune system, quickly becoming the gold standard for obtaining high-throughput, quantitative data on biomolecules. The development of targeted and multiplexed assays for biomarker quantification makes MS an attractive tool both for diagnosing diseases and for quantifying the effects of immunotherapeutics. Because of its accuracy, the use of MS for identifying biomarkers of disease reduces the potential for misdiagnosis and overtreatment. Advances in workflows for sample processing have drastically reduced processing time and complexities due to sample preparation, making MS a more accessible technology. In this review, we present how recent developments in proteomics and metabolomics make MS an essential component of enhancing and monitoring the efficacy of immunotherapeutic treatments.

Coupling AAV-mediated promoterless gene targeting to SaCas9 nuclease to efficiently correct liver metabolic diseases.

Non-integrative AAV-mediated gene therapy in the liver is effective in adult patients, but faces limitations in pediatric settings due to episomal DNA loss during hepatocyte proliferation. Gene targeting is a promising approach by permanently modifying the genome. We previously rescued neonatal lethality in Crigler-Najjar mice by inserting a promoterless human uridine glucuronosyl transferase A1 (UGT1A1) cDNA in exon 14 of the albumin gene, without the use of nucleases. To increase recombination rate and therapeutic efficacy, here we used CRISPR/SaCas9. Neonatal mice were transduced with two AAVs: one expressing the SaCas9 and sgRNA, and one containing a promoterless cDNA flanked by albumin homology regions. Targeting efficiency increased ~26-fold with an eGFP reporter cDNA, reaching up to 24% of eGFP-positive hepatocytes. Next, we fully corrected the diseased phenotype of Crigler-Najjar mice by targeting the hUGT1A1 cDNA. Treated mice had normal plasma bilirubin up to 10 months after administration, hUGT1A1 protein levels were ~6-fold higher than in WT liver, with a 90-fold increase in recombination rate. Liver histology, inflammatory markers, and plasma albumin were normal in treated mice, with no off-targets in predicted sites. Thus, the improved efficacy and reassuring safety profile support the potential application of the proposed approach to other liver diseases.

Therapeutic effects of human monoclonal PSMA antibody-mediated TRIM24 siRNA delivery in PSMA-positive castration-resistant prostate cancer.

Background and Aims: Prostate specific membrane antigen (PSMA) is specifically expressed on prostate epithelial cells and markedly overexpressed in almost all prostate cancers. TRIM24 is also up-regulated from localized prostate cancer to metastatic castration-resistant prostate cancer (CRPC). Because of the high relevance of TRIM24 for cancer development and the universal expression of PSMA in CPRC, we investigated the efficacy of human monoclonal PSMA antibody (PSMAb)-based platform for the targeted TRIM24 siRNA delivery and its therapeutic efficacy in CRPC in vivo and in vitro. Methods: The therapeutic complexes were constructed by conjugating PSMAb and sulfo-SMCC-protamine, and encapsulating TRIM24 siRNA. Flow cytometry, immunofluorescence, and fluorescence imaging were performed to detect the receptor-binding, internalization, and targeted delivery of PSMAb-sulfo-SMCC-protamine (PSP)-FAM-siRNA complex (PSPS) in vitro and in vivo. CCK-8, plate-colony formation, apoptosis, cell cycle, and Transwell assays were performed to evaluate the therapeutic potential of the PSP-TRIM24 siRNA complex in vitro, whereas the in vivo therapeutic efficacy was monitored by small animal imaging, radiography, and micro CT. Results: We confirmed that PSP could efficiently protect siRNA from enzymatic digestion, enable targeted delivery of siRNA, and internalize and release siRNA into PSMA-positive (PSMA+) prostate cancer cells in vitro and in vivo. Silencing TRIM24 expression by the PSP-TRIM24 siRNA complex could dramatically suppress proliferation, colony-formation, and invasion of PSMA+ CRPC cells in vitro, and inhibit tumor growth of PSMA+ CRPC xenografts and bone loss in PSMA+ CRPC bone metastasis model without obvious toxicity at therapeutic doses in vivo. Conclusion: PSMAb mediated TRIM24 siRNA delivery platform could significantly inhibit cell proliferation, colony-formation, and invasion in PSMA+ CRPC in vitro and suppressed tumor growth and bone loss in PSMA+ CRPC xenograft and bone metastasis model.

Psicoterapia breve operacionalizada na adaptação de mulheres com câncer de mama: coletânea de casos / Brief psychotherapy operationalized in adaptation of women with breast cancer: case selection / Psicoterapia breve operacionalizada en la adaptación de mujeres con cáncer de mama: recopilación de casos

O objetivo deste estudo foi investigar os efeitos terapêuticos da Psicoterapia Breve Operacionalizada (PBO) na adaptação de mulheres diagnosticadas com câncer de mama e em tratamento oncológico. O câncer de mama mostra-se mobilizador de sofrimento psíquico para as mulheres tanto no diagnóstico quanto no tratamento, o que justifica identificar intervenções psicológicas adequadas para essa população. As participantes foram 17 mulheres com idade entre 30 e 65 anos. A Escala Diagnóstica Adaptativa Operacionalizada (EDAO) foi o instrumento utilizado para avaliação da adaptação em quatro setores: afetivo-relacional, produtividade, orgânico e sociocultural. Referida avaliação foi feita em três momentos: antes e após a intervenção breve, e no follow-up . A PBO foi a intervenção breve utilizada. Os resultados mostraram que o setor orgânico foi o mais comprometido, seguido do afetivo-relacional, com soluções pouquíssimo adequadas. Como foco da psicoterapia breve, a situação-problema mais recorrente se relacionava ao câncer de mama, que, na compreensão psicodinâmica, mostrou-se associada ao intenso desamparo egóico diante do adoecimento e tratamento oncológico. Na avaliação adaptativa final e follow-up , 82,4% das participantes apresentaram evolução de grupo adaptativo. Concluímos que, neste estudo, a intervenção com a PBO possibilitou efeitos terapêuticos na adaptação, reverberando na solução das situações-problema e na crise adaptativa por perda.(AU)

This study aimed to investigate the therapeutic effects of Operationalized Brief Psychotherapy (PBO) so women diagnosed with breast cancer could adapt to treatment. Breast cancer has mobilized psychological suffering for women during diagnosis and treatment, justifying the identification of the appropriate psychological interventions for this population. Participants included 17 women aged 30 to 65 years. Adaptative Operational Diagnostic Scale (EDAO) was used to evaluated adaptation in four sectors: affective-relational, productivity, organic, and sociocultural before and after a brief psychological intervention and follow-up. The PBO was used as the brief intervention. Results showed that the organic sector was the most compromised, followed by the affective-relational one, which showed very little adequate solutions. As a focus of brief psychotherapy, the most recurring problem-situation was related to breast cancer, which, in yjr psychodynamic understanding, was associated with the intense helplessness of the ego in the face of illness and treatment. In the final adaptative evaluation and follow-up, 82.4% of participants showed evolution in the adaptive group. This study concluded that the intervention with PBO enabled therapeutic effects in these participants' adaptation, reverberating in the solution of problem-situation and in the adaptive crisis by loss.(AU)

El propósito de este estudio fue investigar los efectos terapéuticos de la psicoterapia breve operacionalizada (PBO) en la adaptación de mujeres diagnosticadas con cáncer de mama y en tratamiento oncológico. El cáncer de mama moviliza sufrimiento psicológico para las mujeres tanto en el diagnóstico como en el tratamiento, lo que justifica identificar intervenciones psicológicas adecuadas para esta población. Participaron 17 mujeres de entre 30 y 65 años. El instrumento utilizado fue la Escala de Diagnóstico Adaptativo Operacionalizada (EDAO) para la evaluación adaptativa en cuatro sectores: afectivo-relacional, productividad, orgánico y sociocultural. La evaluación se realizó en tres momentos: antes, después de la intervención breve y en el seguimiento. La PBO fue la intervención breve utilizada. Los resultados mostraron que el sector orgánico fue el más comprometido, seguido por el afectivo-relacional con soluciones poquísimas adecuadas. Como foco de la psicoterapia breve, la situación-problema más recurrente estuvo relacionada con el cáncer de mama, que en la comprensión psicodinámica resultó estar asociada a un intenso desamparo ante la enfermedad y el tratamiento oncológico. En la evaluación adaptativa final y el seguimiento, el 82,4% de las participantes tuvieron evolución grupal adaptativa. Se concluye que la intervención con PBO permitió efectos terapéuticos en la adaptación de estos participantes, repercutiendo en la solución de situaciones-problema y en la crisis adaptativa por pérdida.(AU)

Usefulness of the intravenous flecainide challenge test before oral flecainide treatment in a patient with Andersen-Tawil syndrome.

Andersen-Tawil syndrome (ATS) is an inherited disorder characterised by the triad of ventricular arrhythmias (VAs), periodic paralysis and dysmorphic features. A 31-year-old woman diagnosed with ATS caused by a KCNJ2 mutation (p.R228ins) was urgently admitted to our hospital following an episode of syncope during exercise. Electrocardiography revealed frequent premature ventricular complexes and non-sustained ventricular tachycardias (VTs) with pleomorphic QRS patterns. During the intravenous flecainide test (30 mg), the frequent VAs were inhibited completely. After oral flecainide (100 mg) was started, VAs, except for a brief bigeminy, were suppressed during the exercise test. On 24-hour Holter recordings, the VAs decreased from 50 133 to 13 363 beats/day (-73%). Sustained VT and syncope were not observed during a 3-year follow-up period. Intravenous flecainide challenge test may be useful in predicting the efficacy of oral flecainide treatment for patients with ATS.

Retrospective review of medicine utilization for noncommunicable diseases in three public sector pharmacies in Jamaica / Revisión retrospectiva del uso de medicamentos para enfermedades no transmisibles en tres farmacias del sector público de Jamaica / Revisão retrospectiva do uso de medicamentos para doenças não transmissíveis em três farmácias da rede pública na Jamaica

[ABSTRACT]. Objective. The rational use of medicines offers a cost-saving strategy to maximize therapeutic outcomes for developing and developed countries. The aim of this study was to evaluate the rational use of medicines for selected noncommunicable diseases (NCDs) at three pharmacies at public hospitals in Jamaica using the World Health Organization’s (WHO’s) prescribing indicators. Methods. In this retrospective cross-sectional study, prescriptions for adult outpatients containing at least one medicine for cardiovascular disease, diabetes, cancer, chronic obstructive pulmonary disease or asthma that were filled between January and July 2019 were reviewed using WHO’s prescribing indicators for the rational use of medicines. Data were analyzed and expressed as descriptive and inferential statistics. For all analyses conducted, significance was determined at P < 0.05. Results. A total of 1500 prescriptions covering 5979 medicines were reviewed; prescriptions were mostly written for female patients aged 42–60 years. Polypharmacy was observed in 35.6% (534) of prescriptions, and there was an average of 4 medicines per prescription, with a maximum of 17. Most of the prescriptions at each site were filled, with the main reason for not dispensing a medicine being that it was out of stock. Generic prescribing was high for all sites, accounting for more than 95% (5722) of prescribed medicines. There was full compliance with prescribing according to the WHO Model List of Essential Medicines at two of the sites, but it was just off the target at Site 1, by 1.4%. Conclusions. The WHO guidelines for the rational use of medicines were followed with respect to the proportion of medicines prescribed from the WHO Model List and the proportion of antibiotics prescribed. The number of medicines per prescription and the proportion of medicines prescribed by generic name did not meet the WHO criteria. However, prescribing was aligned with treatment guidelines for the selected NCDs.

[RESUMEN]. Objetivo. El uso racional de los medicamentos proporciona una estrategia de ahorro de costos para maximizar los resultados terapéuticos tanto en los países en desarrollo como en los países desarrollados. El objetivo de este estudio fue evaluar el uso racional de medicamentos para algunas enfermedades no transmisibles (ENT) seleccionadas en tres farmacias de hospitales públicos de Jamaica, usando los indicadores de prescripción de la Organización Mundial de la Salud (OMS). Métodos. En este estudio transversal retrospectivo se examinaron las prescripciones realizadas a pacientes ambulatorios adultos que incluían al menos un medicamento para enfermedades cardiovasculares, diabetes, cáncer, enfermedad pulmonar obstructiva crónica o asma, dispensadas entre enero y julio del 2019, utilizando los indicadores de prescripción para el uso racional de medicamentos de la OMS. Los datos se analizaron y expresaron mediante estadística descriptiva e inferencial. Para todos los análisis realizados se estableció un nivel de significación de p <0,05. Resultados. Se examinó un total de 1 500 prescripciones que incluían 5 979 medicamentos; la mayor parte de ellas correspondían a pacientes de sexo femenino de 42 a 60 años. Se observó que había polimedicación en el 35,6% (534) de las prescripciones, con un promedio de 4 y un máximo de 17 medicamentos por receta. En todos los centros se dispensó la mayor parte de los medicamentos prescritos, y el motivo principal para no hacerlo fue la falta de existencias del medicamento en cuestión. La prescripción de genéricos fue elevada en todos los centros y supuso más del 95% (5 722) de los medicamentos prescritos. En dos centros la prescripción se realizó en su totalidad de acuerdo con la Lista Modelo de Medicamentos Esenciales de la OMS, pero en el centro 1 no se alcanzó el objetivo por un 1,4%. Conclusiones. Se siguieron las directrices de la OMS para el uso racional de medicamentos en cuanto a la proporción de medicamentos prescritos de la Lista Modelo de la OMS y la proporción de antibióticos prescritos. El número de medicamentos por receta y la proporción de medicamentos prescritos mediante su nombre genérico no cumplieron con los criterios de la OMS. Sin embargo, las prescripciones estaban en consonancia con las directrices de tratamiento de las enfermedades no transmisibles seleccionadas.

[RESUMO]. Objetivo. O uso racional de medicamentos é uma estratégia de contenção de custos para maximizar os resultados terapêuticos em países desenvolvidos e em desenvolvimento. O objetivo deste estudo foi avaliar o uso racional de medicamentos para algumas doenças não transmissíveis selecionadas em três farmácias de hospitais públicos na Jamaica a partir dos indicadores de prescrição preconizados pela Organização Mundial da Saúde (OMS). Métodos. Estudo transversal retrospectivo que avaliou receitas médicas de pacientes ambulatoriais adul- tos contendo pelo menos um medicamento prescrito para doença cardiovascular, diabetes, câncer, doença pulmonar obstrutiva crônica ou asma e dispensadas entre janeiro e julho de 2019. A avaliação foi realizada a partir dos indicadores de prescrição preconizados pela OMS para o uso racional de medicamentos. Os dados obtidos foram analisados por meio de estatísticas descritivas e inferenciais. O nível de significância de p <0,05 foi adotado em todas as análises. Resultados. Ao todo, foram analisadas 1 500 receitas médicas compreendendo 5 979 medicamentos. Em sua maioria, as receitas foram prescritas para pacientes do sexo feminino com idades entre 42 e 60 anos. A polifarmácia foi observada em 35,6% (534) das receitas; em média, foram prescritos 4 medicamentos, até um máximo de 17. As farmácias estudadas dispensaram a maior parte dos medicamentos receitados. O principal motivo para não fornecer algum medicamento foi o desabastecimento. O percentual de medicamentos genéricos foi alto em todos os locais, representando mais de 95% (5 722) do volume receitado. Houve plena observância da Lista Modelo de Medicamentos Essenciais da OMS nas receitas analisadas em dois dos locais estudos, e observância quase completa (diferença de 1,4%) no local 1. Conclusões. As diretrizes da OMS de uso racional de medicamentos foram cumpridas no que se refere ao percentual de medicamentos receitados de acordo com a Lista Modelo da OMS e o percentual de antibióticos receitados. Os critérios da OMS não foram cumpridos quanto ao número de medicamentos por receita e ao percentual receitado usando o nome genérico. Porém, os medicamentos foram receitados de acordo com as diretrizes terapêuticas para as doenças não transmissíveis selecionadas.

Phytochemical profile and biological activities of Bromelia antiacantha extracts / Perfil fitoquímico e atividades biológicas de extratos de Bromelia antiacantha

Reports from popular medicine usually act as a basis for the development of new drugs from natural compounds with therapeutic actions for serious diseases and prevalence such as cancer. Bromelia antiacantha Bertol. is a species of the Bromeliaceae family, considered an unconventional food plant, found in the south and midwest regions of Brazil. Despite the high nutritional content and pharmacological potential of its fruits, few scientific studies report its biological actions. Thus, this study evaluates the phytochemical profile of aqueous and ethanol extracts obtained from B. antiacantha fruits, as well as their possible antioxidant, antitumor, and cytotoxic activities. The aqueous extract exhibited phenolic compounds and flavonoids, while ethanol extracts indicated the presence of flavonoids and coumarin in their composition, regardless of the region of collection. The ethanolic extract demonstrated a more promising antioxidant effect than the aqueous extract and also induced a significant inhibition in the viability of human cervical cancer cells of the SiHa strain. In addition, treatment with both extracts did not alter the viability of non-tumor cells of the immortalized human keratinocyte lineage (HaCaT). These results bring new data about extracts obtained from a native plant, edible and traditionally used in popular medicine, opening new perspectives for its possible therapeutic application.

Relatos da medicina popular costumam atuar como referencial para o desenvolvimento de novos fármacos a partir de moléculas naturais com ações terapêuticas para doenças de alta gravidade e prevalência como o câncer. Bromelia antiacantha Bertol. é uma espécie da família Bromeliaceae, considerada uma planta alimentícia não convencional (PANC), encontrada nas regiões sul e centro-oeste do Brasil. Apesar do alto teor nutritivo e potencial farmacológico de seus frutos, poucos estudos científicos relatam suas ações biológicas. Desta forma, este estudo avalia o perfil fitoquímico de extratos aquoso e etanólico obtidos de frutos de B. antiacantha, bem como a sua possível ação antioxidante, antitumoral e citotóxica. O extrato aquoso apresentou compostos fenólicos e flavonoides, enquanto os extratos etanólicos apontam a presença de flavonóides e cumarina em sua composição, independente da região de coleta. O extrato etanólico demonstrou efeito antioxidante mais promissor do que o extrato aquoso e também induziu uma inibição significativa na viabilidade de células humanas de câncer cervical da linhagem SiHa. Além disso, o tratamento com ambos extratos não alterou a viabilidade de células não tumorais da linhagem de queratinócitos humanos imortalizados (HaCaT). Estes dados trazem novas informações sobre extratos obtidos de uma espécie vegetal nativa, comestível e já utilizada tradicionalmente, mas abrindo novas perspectivas quanto a possíveis aplicações terapêuticas.

Direct costs of treating men with prostate cancer with High Intensity Focused Ultrasound / Costos directos del tratamiento de hombres con cáncer de próstata con el uso de High Intensity Focused Ultrasound / Custos diretos do tratamento de homens com câncer de próstata via High Intensity Focused Ultrasound

ABSTRACT Objective: To analyze the direct costs of materials, medicines/solutions and healthcare professionals required to treat men with prostate cancer using High Intensity Focused Ultrasound. Method: Quantitative, exploratory-descriptive research, single case study type. Data were collected from electronic medical records/printed documentation from the Operating Room of a public teaching and research hospital. Health professionals estimated the respective time spent on activities in the following stages: "Before anesthetic induction", "Before performing thermal ablation", "During thermal ablation" and "After performing thermal ablation". Costs were calculated by multiplying the (estimated) time spent by the unit cost of direct labor, adding to the measured cost of materials, medicines/solutions. Results: The measured costs with materials corresponded to US$851.58 (SD = 2.17), with medicines/solutions to US$72.13 (SD = 25.84), and estimated personnel costs to US$196.03, totaling US$1119.74/procedure. Conclusion: The economic results obtained may support hospital managers in the decision-making process regarding the adoption of the High Intensity Focused Ultrasound for the treatment of prostate cancer.

RESUMEN Objetivo: Analizar los costos directos de materiales, medicamentos/soluciones y profesionales de la salud necesarios para tratar a hombres con cáncer de próstata a través de High Intensity Focused Ultrasound. Método: Investigación cuantitativa, exploratoria-descriptiva, tipo estudio de caso único. Los datos se obtuvieron de registros médicos electrónicos/documentación impresa del Centro Quirúrgico de un hospital público de enseñanza e investigación. Los profesionales de la salud estimaron el tiempo respectivo dedicado a las actividades en las siguientes etapas: "Antes de la inducción anestésica", "Antes de realizar la ablación térmica", "Durante la realización de la ablación térmica" y "Después de realizar la ablación térmica". Los costos se calcularon multiplicando el tiempo (estimado) invertido por el costo unitario de la mano de obra directa, sumándolo al costo medido de materiales, medicamentos/soluciones. Resultados: Los costos medidos con materiales correspondieron a US$851,58 (DE = 2,17), con medicamentos/soluciones a US$72,13 (DE = 25,84) y los costos de personal estimados a US$196,03, totalizando US$1119,74/procedimiento. Conclusión: Los resultados económicos obtenidos podrán apoyar a los gestores hospitalarios en el proceso de toma de decisiones respecto a la adopción del High Intensity Focused Ultrasound para el tratamiento del cáncer de próstata.

RESUMO Objetivo: Analisar os custos diretos com materiais, medicamentos/soluções e profissionais de saúde requeridos à realização do tratamento de homens com câncer de próstata via High Intensity Focused Ultrasound. Método: Pesquisa quantitativa, exploratória-descritiva, do tipo estudo de caso único. Coletaram-se os dados em prontuários eletrônicos/documentações impressas do Centro Cirúrgico de um hospital público de ensino e pesquisa. Profissionais de saúde estimaram os respectivos tempos despendidos em atividades constantes das etapas: "Antes da indução anestésica", "Antes da execução da termoablação", "Durante a execução da termoablação" e "Após a execução da termoablação". Calcularam-se os custos multiplicando-se o tempo (estimado) despendido pelo custo unitário da mão de obra direta, somando-se ao custo mensurado dos materiais, medicamentos/soluções. Resultados: Os custos mensurados com materiais corresponderam a US$851,58 (DP = 2,17), com medicamentos/soluções a US$72,13 (DP = 25,84) e os custos estimados com pessoal a US$196,03, totalizando US$1119,74/procedimento. Conclusão: Os resultados econômicos obtidos poderão subsidiar os gestores hospitalares no processo decisório quanto à adoção do High Intensity Focused Ultrasound para o tratamento do câncer de próstata.

Aspectos da abordagem terapêutica sobre candidíase vulvovaginal / Aspects of the therapeutic approach to vulvovaginal candidiasis / Aspectos del abordaje terapéutico de la candidiasis vulvovaginal

A candidíase vulvovaginal, é uma infecção da vulva e vagina causada por vários tipos de Candida spp. Essa patologia afeta 75% de todas as mulheres pelo menos uma vez durante a vida, ocorrendo com mais frequência durante a idade fértil. A transmissão dessa infeção fúngica ocorre por meio de contato com mucosas e secreções em pele de portadores ou doentes, contato sexual, água contaminada e transmissão vertical. Alguns outros sintomas característicos mais vistos em casos de CVV, são lesões brancas, cremosas e planas, sendo mais intensos no período pré-menstrual, quando a acidez vaginal aumenta. numerosos antifúngicos estão disponíveis no mercado, os quais são encontrados para administração oral na forma de comprimidos ou, para uso tópico, na forma de cremes, loções, comprimidos vaginais, supositórios e tampões revestidos. O objetivo geral do trabalho foi analisar através da revisão de literatura, tratamentos convencionais e alternativos para abordagem terapêutica da Candidíase Vulvovaginal contextuando a mesma, utilizando definições, dados epidemiológicos e sua sintomatologia frente à sociedade. O presente trabalho é uma revisão integrativa, que teve a coleta de dados realizada de março de 2021 a outubro de 2021 nas bases de dados Lilacs, Scielo, Google acadêmico, A busca resultou em 902 artigos, dos quais 14 atenderam ao critério de inclusão. A busca por tratamentos frente a candidíase vulvovaginal tem se mostrado ampla de acordo com os artigos selecionadas. Concluímos que a patologia candidíase vulvovaginal, vem apresentando resistência em algumas abordagens terapêuticas, assim como algumas mulheres não aderem há algum tipo de tratamento, devido à falta de conhecimento sobre a patologia.

Vulvovaginal candidiasis is an infection of the vulva and vagina caused by various types of Candida spp. This condition affects 75% of all women at least once in their lifetime, occurring more frequently during their childbearing years. The transmission of this fungal infection occurs through contact with mucous membranes and secretions on the skin of patients or patients, sexual contact, contaminated water and vertical transmission. Some other characteristic symptoms more seen in cases of VVC are white, creamy and flat lesions, being more intense in the premenstrual period, when the vaginal acidity increases. numerous antifungals are available on the market which are available for oral administration in tablet form or, for topical use, in the form of creams, lotions, vaginal tablets, suppositories and coated tampons. The general objective of the work was to analyze, through a literature review, conventional and alternative treatments for the therapeutic approach of Vulvovaginal Candidiasis in its context, using definitions, epidemiological data and its symptoms in society. The present work is an integrative review, which had data collection carried out from March 2021 to October 2021 in the Lilacs, Scielo, Google academic databases. The search resulted in 902 articles, of which 14 met the inclusion criteria. The search for treatments against vulvovaginal candidiasis has been shown to be wide according to the selected articles. We conclude that the vulvovaginal candidiasis pathology has been showing resistance in some therapeutic approaches, as well as some women do not adhere to any type of treatment, due to lack of knowledge about the pathology.

La candidiasis vulvovaginal es una infección de la vulva y la vagina cau- sada por diversos tipos de Candida spp. Esta afección afecta al 75% de las mujeres al menos una vez en la vida, siendo más frecuente durante la edad fértil. La transmisión de esta infección fúngica se produce por contacto con mucosas y secreciones de la piel de pacientes o enfermos, contacto sexual, agua contaminada y transmisión vertical. Otros síntomas característicos más observados en los casos de CVV son las lesiones blancas, cremosas y planas, siendo más intensas en el período premenstrual, cuando aumenta la acidez vaginal. Existen en el mercado numerosos antifúngicos disponibles para adminis- tración oral en forma de comprimidos o, para uso tópico, en forma de cremas, lociones, comprimidos vaginales, supositorios y tampones recubiertos. El objetivo general del tra- bajo fue analizar, a través de una revisión bibliográfica, los tratamientos convencionales y alternativos para el abordaje terapéutico de la Candidiasis Vulvovaginal en su contexto, utilizando definiciones, datos epidemiológicos y su sintomatología en la sociedad. El pre- sente trabajo es una revisión integradora, que tuvo recolección de datos realizada de marzo de 2021 a octubre de 2021 en las bases de datos académicas Lilacs, Scielo, Google. La búsqueda resultó en 902 artículos, de los cuales 14 cumplieron los criterios de inclu- sión. La búsqueda de tratamientos contra la candidiasis vulvovaginal se ha mostrado am- plia según los artículos seleccionados. Concluimos que la patología de la candidiasis vul- vovaginal viene mostrando resistencia en algunos abordajes terapéuticos, así como algu- nas mujeres no se adhieren a ningún tipo de tratamiento, debido al desconocimiento de la patología.