Repurposing of parenterally administered active substances used to treat pain both systemically and locally

Pain is a constant in our lives. The efficacy of drug therapy administered by the parenteral route is often limited either by the physicochemical characteristics of the drug itself or its adsorption–distribution–metabolism–excretion (ADME) mechanisms. One promising alternative is the design of innovative drug delivery systems that can improve the pharmacokinetics |(PK) and/or reduce the toxicity of traditionally used drugs. In this review, we discuss several products that have been approved by the main regulatory agencies (i.e., nano- and microsystems, implants, and oil-based solutions), highlighting the newest technologies that govern both locally and systemically the delivery of drugs. Finally, we also discuss the risk assessment of the scale-up process required, given the impact that this approach could have on drug manufacturing.Teaser: The management of pain by way of the parenteral route can be improved using complex drug delivery systems (e.g., micro- and nanosystems) which require high-level assessment and shorten the regulatory pathway.     

Hepatitis B and circadian rhythm of the liver

The circadian rhythm in humans is determined by the central clock located in the hypothalamus’s suprachiasmatic nucleus, and it synchronizes the peripheral clocks in other tissues. Circadian clock genes and clock-controlled genes exist in almost all cell types. They have an essential role in many physiological processes, including lipid metabolism in the liver, regulation of the immune system, and the severity of infections. In addition, circadian rhythm genes can stimulate the immune response of host cells to virus infection. Hepatitis B virus (HBV) infection is the leading cause of liver disease and liver cancer globally. HBV infection depends on the host cell, and hepatocyte circadian rhythm genes are associated with HBV replication, survival, and spread. The core circadian rhythm proteins, REV-ERB and brain and muscle ARNTL-like protein 1, have a crucial role in HBV replication in hepatocytes. In addition to influencing the virus’s life cycle, the circadian rhythm also affects the pharmacokinetics and efficacy of antiviral vaccines. Therefore, it is vital to apply antiviral therapy at the appropriate time of day to reduce toxicity and improve the effectiveness of antiviral treatment. For these reasons, understanding the role of the circadian rhythm in the regulation of HBV infection and host responses to the virus provides us with a new perspective of the interplay of the circadian rhythm and anti-HBV therapy. Therefore, this review emphasizes the importance of the circadian rhythm in HBV infection and the optimization of antiviral treatment based on the circadian rhythm-dependent immune response.     

Geographic Characteristics of Various Cancers in Yogyakarta Province,Indonesia: A Spatial Analysis at the Community Level

Background: Cancer remains a significant public health problem in Indonesia and worldwide. Yogyakarta Province has the largest number of cancer cases in Indonesia. Maps of the distribution of cancer cases are useful tools for stratification of cancer risk and for selective prevention strategies. The aim of this study was to determine the spatial distribution of cancer cases in Yogyakarta Province. Methods: Cancer patient data registered by the Yogyakarta Provincial Health Office during 2019-2020 were analysed in this study (n=9,933). To evaluate cancer pattern distributions, ArcGIS 10.2 and Excel 2016 software were used. Results: The mean participant age (± standard deviation) was 55.08 ± 15.46 years, and 79.40% were female. Breast and cervical cancer were the most frequently diagnosed, and the majority of patients were located in Sleman district. The incidence of all cancer types varied by county-level. The majority of cancer patients lived below the poverty line. Cancer screening rates were low, and screening was limited to breast and cervical cancer. Conclusion: Various types of cancers were identified in Yogyakarta, Indonesia; of them, breast and cervical cancer predominated. Most of the cancer patients were from Sleman district and economically poor areas. Geospatial techniques are useful for identifying environmental factors related to cancer and improving cancer control strategies and resource allocation.     

流动人口基层医疗卫生机构首诊现状及影响因素分析

目的:了解流动人口基层首诊现状及其影响因素,为推进流动人口分级诊疗提供实证参考依据。方法:基于2017年全国流动人口动态监测调查数据中82734名最近1次患病(负伤)流动人口数据,利用SPSS 25.0统计软件分析其基层首诊情况及影响因素。结果:82734名最近1次患病(负伤)流动人口中首选到基层医疗卫生机构就诊15936人,基层首诊率仅为19.3%;二分类logistic回归分析结果显示:年龄≥65岁、农业户口、流动时间0~5年、患慢性病、至少参加1项医疗保险,居住地到最近医疗服务机构所需时间≤15 min的流动人口患病后更愿意选择到基层首诊。学历大专及以上、家庭月均收入>10000元、市跨县、东北地区、不愿意落户、自评健康状况为不健康的流动人口患病后更不愿意选择到基层首诊。结论:流动人口患病(负伤)后选择到基层首诊率较低,年龄、受教育程度、户口类型、家庭月均总收入、流动时间、流动范围、流入地区域、落户意愿、自评健康状况、是否患慢性病、有无参加医疗保险、居住地到最近医疗服务机构所需时间是影响流动人口患病(负伤)后选择到基层首诊的主要因素。     

MR-safety in clinical practice at 7T: Evaluation of a multistep screening process in 1819 subjects

IntroductionMR facilities must implement and maintain adequate screening and safety procedures to ensure safety during MR examinations. The aim of this study was to evaluate a multi-step MR safety screening process used at a 7T facility regarding incidence of different types of safety risks detected during the safety procedure.MethodsSubjects scheduled for an MR examination and having entered the 7T facility during 2016–2019 underwent a pre-defined multi-step MR safety screening process. Screening documentation of 1819 included subjects was reviewed, and risks identified during the different screening steps were compiled. These data were also related to documented decisions made by a 7T MR safety committee and reported MR safety incidents.ResultsPassive or active implants (n = 315) were identified in a screening form and/or an additional documented interview in 305 subjects. Additional information not previously self-reported by the subject, regarding implants necessitating safety decisions performed by the staff was revealed in the documented interview in 102 subjects (106 items). In total, the 7T MR safety committee documented a decision in 36 (2%) of the included subjects. All of these subjects were finally cleared for scanning.ConclusionA multi-step screening process allows a thorough MR screening of subjects, avoiding safety incidents. Different steps in the process allow awareness to rise and items to be detected that were missed in earlier steps.Implications for practiceSafety questions posed at a single timepoint during an MR screening process might not reveal all safety risks. Repetition and rephrasing of screening questions leads to increased detection of safety risks. This could be effectively mitigated by a multi-step screening process. A multi-disciplinary safety committee is efficient at short notice responding to unexpected safety issues.     

Comparing Radiomics features of tumour and healthy liver tissue in a limited CT dataset: A machine learning study

IntroductionLiver cancer lesions on Computed Tomography (CT) withholds a great amount of data, which is not visible to the radiologists and radiographer. Radiomics features can be extracted from the lesions and used to train Machine Learning (ML) algorithms to predict between tumour and liver tissue. The purpose of this study was to investigate and classify Radiomics features extracted from liver tumours and normal liver tissue in a limited CT dataset.MethodsThe Liver Tumour Segmentation Benchmark (LiTS) dataset consisting of 131 CT scans of the liver with segmentations of tumour tissue and healthy liver was used to extract Radiomic features. Extracted Radiomic features included size, shape, and location extracted with morphological and statistical techniques according to the International Symposium on Biomedical Imaging manual. Relevant features was selected with chi2 correlation and principal component analysis (PCA) with tumour and healthy liver tissue as outcome according to a consensus between three experienced radiologists. Logistic regression, random forest and support vector machine was used to train and validate the dataset with a 10-fold cross-validation method and the Grid Search as hyper-parameter tuning. Performance was evaluated with sensitivity, specificity and accuracy.ResultsThe performance of the ML algorithms achieved sensitivities, specificities and accuracy ranging from 96.30% (95% CI: 81.03%–99.91%) to 100.00% (95% CI: 86.77%–100.00%), 91.30% (95% CI: 71.96%–98.93%) to 100.00% (95% CI: 83.89%–100.00%)and 94.00% (95% CI: 83.45%–98.75%) to 100.00% (95% CI: 92.45%–100.00%), respectively.ConclusionML algorithms classifies Radiomics features extracted from healthy liver and tumour tissue with perfect accuracy. The Radiomics signature allows for a prognostic biomarker for hepatic tumour screening on liver CT.Implications for practiceDifferentiation between tumour and liver tissue with Radiomics ML algorithms have the potential to increase the diagnostic accuracy, assist in the decision-making of supplementary multiphasic enhanced medical imaging, as well as for developing novel prognostic biomarkers for liver cancer patients.     

A case of sudden cardiac death due to mitochondrial disease

A 25-year-old, emaciated man without medical treatment was found to have died suddenly at home by his mother. At autopsy, there were no injuries to his body, but significant circulatory insufficiency was observed. Electron microscopy revealed abnormal mitochondria in cells of the cardiac conduction system. The conduction system was filled with mitochondrial size abnormalities and mitochondrial cristae abnormalities. No notable abnormal findings were observed in other organs. Genetic examination of the blood revealed the mitochondrial pathogenetic variant m.3243A>G. Epileptic seizures, diabetic ketoacidosis, and hyperosmolar hyperglycemic state were unlikely to be the cause of sudden death. The cause of death was diagnosed as arrhythmia possibly induced by the failure of the cardiac conduction system due to mitochondrial disease. This is a rare case of sudden death caused by an accumulation of abnormal mitochondria in the cardiac conduction system.     

Modification of an extended total temporomandibular joint replacement (eTMJR) classification system

The aims of this paper were to validate a modification of an extended total temporomandibular joint replacement (eTMJR) classification system and develop a classification schematic for ease of reference. High-volume TMJ surgeons were asked to score 20 separate eTMJR devices using the updated classification system, and inter-rater variability was calculated. Using the modified classification system developed, a Conger’s kappa (κ) coefficient of 0.53 was returned, suggesting moderate to good levels of agreement. The final classification system was then developed in a series of standardised graphic illustrations as visual representations of the different subcategories of eTMJR devices.