Improving access to health care in a rural regional hospital in South Africa: Why do patients miss their appointments?

Background: Access to health services is one of the Batho Pele (‘people first’) values and principles of the South African government since 1997. This necessitated some changes around public service systems, procedures, attitudes and behaviour. The challenges of providing health care to rural geographically spread populations include variations in socio-economic status, transport opportunities, access to appointment information and patient perceptions of costs and benefits of seeking health care. George hospital, situated in a rural area, serves 5000 outpatient visits monthly, with non-attendance rates of up to 40%. Objectives: The aim of this research was to gain a greater understanding of the reasons behind non-attendance of outpatient department clinics to allow locally driven, targeted interventions. Methods: This was a descriptive study. We attempted to phone all patients who missed appointments over a 1-month period (n = 574). Only 20% were contactable with one person declining consent. Twenty-nine percent had no telephone number on hospital systems, 7% had incorrect numbers, 2% had died and 42% did not respond to three attempts. Results: The main reasons for non-attendance included unaware of appointment date (16%), out of area (11%), confusion over date (11%), sick or admitted to hospital (10%), family member sick or died (7%), appointment should have been cancelled by clerical staff (6%) and transport (6%). Only 9% chose to miss their appointment. The other 24% had various reasons. Conclusions: Improved patient awareness of appointments, adjustments in referral systems and enabling appointment cancellation if indicated would directly improve over two-thirds of reasons for non-attendance. Understanding the underlying causes will help appointment planning, reduce wasted costs and have a significant impact on patient care

Transcription factor NRF2 as a therapeutic target for chronic diseases: a systems medicine approach

Systems medicine has a mechanism-based rather than a symptom- or organ-based approach to disease and identifies therapeutic targets in a nonhypothesis-driven manner. In this work, we apply this to transcription factor nuclear factor (erythroid-derived 2)-like 2 (NRF2) by cross-validating its position in a protein-protein interaction network (the NRF2 interactome) functionally linked to cytoprotection in low-grade stress, chronic inflammation, metabolic alterations, and reactive oxygen species formation. Multiscale network analysis of these molecular profiles suggests alterations of NRF2 expression and activity as a common mechanism in a subnetwork of diseases (the NRF2 diseasome). This network joins apparently heterogeneous phenotypes such as autoimmune, respiratory, digestive, cardiovascular, metabolic, and neurodegenerative diseases, along with cancer. Importantly, this approach matches and confirms in silico several applications for NRF2-modulating drugs validated in vivo at different phases of clinical development. Pharmacologically, their profile is as diverse as electrophilic dimethyl fumarate, synthetic triterpenoids like bardoxolone methyl and sulforaphane, protein-protein or DNA-protein interaction inhibitors, and even registered drugs such as metformin and statins, which activate NRF2 and may be repurposed for indications within the NRF2 cluster of disease phenotypes. Thus, NRF2 represents one of the first targets fully embraced by classic and systems medicine approaches to facilitate both drug development and drug repurposing by focusing on a set of disease phenotypes that appear to be mechanistically linked. The resulting NRF2 drugome may therefore rapidly advance several surprising clinical options for this subset of chronic diseases

Cancer stem cells (CSCs) : metabolic strategies for their identification and eradication

Phenotypic and functional heterogeneity is one of the most relevant features of cancer cells within different tumor types and is responsible for treatment failure. Cancer stem cells (CSCs) are a population of cells with stem cell-like properties that are considered to be the root cause of tumor heterogeneity, because of their ability to generate the full rep- ertoire of cancer cell types. Moreover, CSCs have been invoked as the main drivers of metastatic dissemination and therapeutic resistance. As such, targeting CSCs may be a useful strategy to improve the effectiveness of classical anticancer therapies. Recently, metabolism has been considered as a relevant player in CSC biology, and indeed, onco- genic alterations trigger the metabolite-driven dissemination of CSCs. More interestingly, the action of metabolic pathways in CSC maintenance might not be merely a conse- quence of genomic alterations. Indeed, certain metabotypic phenotypes may play a causative role in maintaining the stem traits, acting as an orchestrator of stemness. Here, we review the current studies on the metabolic features of CSCs, focusing on the bio- chemical energy pathways involved in CSC maintenance and propagation. We provide a detailed overview of the plastic metabolic behavior of CSCs in response to microenvironment changes, genetic aberrations, and pharmacological stressors. In addition, we describe the potential of comprehensive metabolic approaches to identify and selectively eradicate CSCs, together with the possibility to ‘force’ CSCs within certain metabolic dependences, in order to effectively target such metabolic biochemical inflexibilities. Finally, we focus on targeting mitochondria to halt CSC dissemination and effectively eradicate cancer

Intramedullary screw fixation for simple displaced olecranon fractures

PURPOSE: Olecranon fractures are common and typically require surgical fixation due to displacement generated by the pull of the triceps muscle. The most common techniques for repairing olecranon fractures are tension-band wiring or plate fixation, but these methods are associated with high rates of implant-related soft-tissue irritation. Another treatment option is fixation with an intramedullary screw, but less is known about surgical results using this strategy. Thus, the purpose of this study was to report the clinical and functional outcomes of olecranon fractures treated with an intramedullary cannulated screw. METHODS: We identified 15 patients (average age at index procedure 44 years, range 16-83) with a Mayo type I or IIA olecranon fracture who were treated with an intramedullary cannulated screw at a single level 2 trauma center between 2012 and 2017. The medical record was reviewed to assess radiographic union, postoperative range of motion and complications (including hardware removal). Patient-reported outcome was evaluated using the Disabilities of the Arm, Shoulder and Hand (DASH) score. Average follow-up was 22 months (range 8-36 months). RESULTS: By the 6th month post-operative visit, 14 patients had complete union of their fracture and 1 patient had an asymptomatic non-union that did not require further intervention. Average flexion was 145° (range 135-160) and the average extension lag was 11° (range 0-30). Implants were removed in 5 patients due to soft-tissue irritation. Average DASH score (± standard deviation) by final follow-up was 16 ± 10. CONCLUSIONS: Fixation of simple olecranon fractures with an intramedullary screw is a safe and easy fixation method in young patients, leading to good functional and radiological results. Compared to available data, less hardware removal is necessary than with tension-band wiring or plate fixation

ABC-Transporter Expression Does Not Correlate with Response to Irinotecan in Patients with Metastatic Colorectal Cancer

Background: Active efflux of irinotecan by ATP-binding cassette (ABC)-transporters, in particular ABCB1 and ABCG2, is a well-established drug resistance mechanism in vitro and in pre-clinical mouse models, but its relevance in colorectal cancer (CRC) patients is unknown. Therefore, we assessed the association between ABC-transporter expression and tumour response to irinotecan in patients with metastatic CRC. Methods: Tissue microarrays of a large cohort of metastatic CRC patients treated with irinotecan in a prospective study (CAIRO study; n=566) were analysed for expression of ABCB1 and ABCG2 by immunohistochemistry. Kaplan-Meier and Cox proportional hazard regression analyses were performed to assess the association of ABC transporter expression with irinotecan response. Gene expression profiles of 17 paired tumours were used to assess the concordance of ABCB1/ABCG2 expression in primary CRC and corresponding metastases. Results: The response to irinotecan was not significantly different between primary tumours with positive versus negative expression of ABCB1 (5.8 vs 5.7 months, p=0.696) or ABCG2 (5.7 vs 6.1 months, p=0.811). Multivariate analysis showed neither ABCB1 nor ABCG2 were independent predictors for progression free survival. There was a mediocre to poor concordance between ABC-transporter expression in paired tumours. Conclusion: In metastatic CRC, ABC-transporter expression in the primary tumour does not predict irinotecan response

Cancer stem cell metabolism

Cancer is now viewed as a stem cell disease. There is still no consensus on the metabolic characteristics of cancer stem cells, with several studies indicating that they are mainly glycolytic and others pointing instead to mitochondrial metabolism as their principal source of energy. Cancer stem cells also seem to adapt their metabolism to microenvironmental changes by conveniently shifting energy production from one pathway to another, or by acquiring intermediate metabolic phenotypes. Determining the role of cancer stem cell metabolism in carcinogenesis has become a major focus in cancer research, and substantial efforts are conducted towards discovering clinical targets