Harnessing the law to advance equitable cancer care in South Africa: exploring the feasibility, desirability and added value of a dedicated national cancer act.

Background: The 2017 World Health Assembly resolution on integrated cancer prevention and control provided clear guidance on creating an enabling environment for cancer care. Through a variety of mechanisms, including civil society advocacy, some countries have secured overarching legislation in the form of national cancer acts to promote equitable access and outcomes for cancer patients. In South Africa, cancer incidence is set to double by 2030; and, while existing legislative and policy frameworks do address cancer prevention and control, these are fragmented, poorly implemented and have had limited success. Methods: This study assessed the feasibility and potential impact of promulgating a dedicated national cancer act in South Africa through exploratory in-depth interviews with 25 purposively selected key informants from various stakeholder groups, including cancer survivors; legal scholars; human rights advocates; health care providers; public health specialists and academicians. Findings: Following thematic analysis, three key themes were identified: the content of a dedicated national cancer act, the socio-political leveragability of an act and accountability mechanisms that would support such an act. Conclusion: While most respondents had not considered the possibility of a dedicated national cancer act, they were open to the concept for South Africa. Concerns about widening inequities, duplication, funding and accountability would need to be addressed against the current backdrop of health inequities and limited human rights leveraging for health.

Framework for Adoption of Next-Generation Sequencing (NGS) Globally in the Oncology Area.

Radical new possibilities of improved treatment of cancer are on offer from an advanced medical technology already demonstrating its significance: next-generation sequencing (NGS). This refined testing provides unprecedentedly precise diagnoses and permits the use of focused and highly personalized treatments. However, across regions globally, many cancer patients will continue to be denied the benefits of NGS as long as some of the yawning gaps in its implementation remain unattended. The challenges at the regional and national levels are linked because putting the solutions into effect is highly dependent on cooperation between regional- and national-level cooperation, which could be hindered by shortfalls in interpretation or understanding. The aim of the paper was to define and explore the necessary conditions for NGS and make recommendations for effective implementation based on extensive exchanges with policy makers and stakeholders. As a result, the European Alliance for Personalised Medicine (EAPM) developed a maturity framework structured around demand-side and supply-side issues to enable interested stakeholders in different countries to self-evaluate according to a common matrix. A questionnaire was designed to identify the current status of NGS implementation, and it was submitted to different experts in different institutions globally. This revealed significant variability in the different aspects of NGS uptake. Within different regions globally, to ensure those conditions are right, this can be improved by linking efforts made at the national level, where patients have needs and where care is delivered, and at the global level, where major policy initiatives in the health field are underway or in preparation, many of which offer direct or indirect pathways for building those conditions. In addition, in a period when consensus is still incomplete and catching up is needed at a political level to ensure rational allocation of resources-even within individual countries-to enable the best ways to make the necessary provisions for NGS, a key recommendation is to examine where closer links between national and regional actions could complement, support, and mutually reinforce efforts to improve the situation for patients.

Empowering quality data - the Gordian knot of bringing real innovation into healthcare system.

OBJECTIVES: The introduction of Personalised Medicine (PM) into healthcare systems could benefit from a clearer understanding of the distinct national and regional frameworks around the world. Recent engagement by international regulators on maximising the use of real-world evidence (RWE) has highlighted the scope for improving the exploitation of the treasure-trove of health data that is currently largely neglected in many countries. The European Alliance for Personalised Medicine (EAPM) led an international study aimed at identifying the current status of conditions. METHODS: A literature review examined how far such frameworks exist, with a view to identifying conducive factors - and crucial gaps. This extensive review of key factors across 22 countries and 5 regions revealed a wide variety of attitudes, approaches, provisions and conditions, and permitted the construction of a comprehensive overview of the current status of PM. Based on seven key pillars identified from the literature review and expert panels, the data was quantified, and on the basis of further analysis, an index was developed to allow comparison country by country and region by region. RESULTS: The results show that United States of America is leading according to overall outcome whereas Kenya scored the least in the overall outcome. CONCLUSIONS: Still, common approaches exist that could help accelerate take-up of opportunities even in the less prosperous parts of the world.

Fighting Cancer around the World: A Framework for Action.

Tackling cancer is a major challenge right on the global level. Europe is only the tip of an iceberg of cancer around the world. Prosperous developed countries share the same problems besetting Europe-and the countries and regions with fewer resources and less propitious conditions are in many cases struggling often heroically against a growing tide of disease. This paper offers a view on these geographically wider, but essentially similar, challenges, and on the prospects for and barriers to better results in this ceaseless battle. A series of panels have been organized by the European Alliance for Personalised Medicine (EAPM) to identify different aspects of cancer care around the globe. There is significant diversity in key issues such as NGS, RWE, molecular diagnostics, and reimbursement in different regions. In all, it leads to disparities in access and diagnostics, patients' engagement, and efforts for a better understanding of cancer.

Absorption of irrigation fluid during XPS™ GreenLight laser vaporization of the prostate: results from a prospective breath ethanol monitoring study.

PURPOSE: To assess whether and to what extent irrigation fluid absorption occurs during laser vaporization (LV) of the prostate using the 180 W XPS™ GreenLight laser. METHODS: This prospective investigation was performed in a tertiary care center with a consecutive series of patients undergoing 180 W LV of the prostate. Intraoperative irrigation was performed with isotonic saline containing 1 % ethanol. The volume of irrigation fluid absorption was calculated from periodically performed breath ethanol measurements during LV. Additionally, intraoperative changes in biochemical and hematological blood parameters were assessed. RESULTS: Positive breath ethanol tests were detectable in 22 of 54 patients. The median absorption volume in these patients was 950 ml (range 208-4579 ml). Ten patients absorbed more than 2000 ml. Absorbers had smaller prostates, more capsular perforations and injuries to venous sinuses, and more total energy was applied with higher output power. Five patients had transient symptoms potentially related to fluid absorption. A significant drop in hemoglobin, hematocrit, venous pH and bicarbonate and an increase in chloride were detectable in the absorber group. These changes were significantly different in the non-absorber group. CONCLUSIONS: Absorption of irrigation fluid did occur in a relevant proportion of patients undergoing XPS™ GreenLight LV. High-volume absorption (≥2000 ml), which might be clinically relevant, was detectable in almost 20 % of all procedures. Absorption of saline irrigation fluid does not result in a classical TUR syndrome, but fluid and chloride overload can lead to serious complications, particularly in cardiovascular high-risk patients. Thus, patients with symptoms potentially related to fluid absorption should be monitored carefully.

Management of patients on chemotherapeutic treatment for advanced cancer with acute conditions in the emergency department.

BACKGROUND: Chemotherapy is increasingly used in people with advanced cancer to palliate symptoms and improve survival. New Zealand provides medical oncology services in a Hub and Spoke model, with an increasing emphasis on delivering treatment at out-patient spoke services, where after hours and urgent care is provided by the Emergency Department (ED). This study sought to describe the factors that influenced the care and clinical decision-making of this group of patients in the ED. METHODS: Semi-structured telephone interviews were held with five ED nurses from three hospitals at the spoke. Raw data was thematically analysed via an exploratory descriptive approach. RESULTS: Care of the oncology patient in ED is determined by the presentation itself, and differs little to the care delivered to other patient groups. That the patient is on chemotherapy may have little influence on the interventions provided. Challenges arise through patient complexity, lack of oncology specialist availability and low volumes preclude the maintenance of specialist skills and knowledge. Clinical decisions are influenced by local Hospice teams rather than Oncology team providing cancer treatment. CONCLUSION: A more collaborative relationship between Oncology and ED nurses may support the provision of emergency care within the context of active cancer treatment.

Role of community nurses in the prevention of tuberculosis in the Tshwane Health District of Gauteng.

The objectives of this study were to identify the role of community nurses in the prevention of tuberculosis (TB) and to identify problems experienced by them when fulfilling this role in the Tshwane Health District of Gauteng. A non-experimental, descriptive, quantitative research design method was used to collect data from community nurses. The sample included 59 registered nurses who voluntarily agreed to participate in the study. A questionnaire was used to collect data and quantitative data analysis methods were employed. Various opinions and ideas on the role of community nurses in the prevention of TB and the problems experienced were identified. Based on the results of this research, measures to protect community nurses from contracting TB whilst on duty should be a priority. Government should support TB programmes by providing money to non-governmental organisations and direct observed treatment short course (DOTS) supporters to make follow-up visits to patients possible, thus reducing the number of defaulters. Stringent measures should be taken at all border points to ensure that foreigners are screened for TB, multidrug-resistant TB and extensively drug-resistant TB. This study was limited to community nurses in the Tshwane Health District of Gauteng who were registered with the South African Nursing Council (SANC) and therefore this study could not be generalised to registered nurses in the hospital setting or even to clinics in the rest of South Africa.

Oligomeric coiled-coil adhesin YadA is a double-edged sword.

Yersinia adhesin A (YadA) is an essential virulence factor for the food-borne pathogens Yersinia enterocolitica and Yersinia pseudotuberculosis. Surprisingly, it is a pseudogene in Yersinia pestis. Even more intriguing, the introduction of a functional yadA gene in Y. pestis EV76 was shown to correlate with a decrease in virulence in a mouse model. Here, we report that wild type (wt) Y. enterocolitica E40, as well as YadA-deprived E40 induced the synthesis of neutrophil extracellular traps (NETs) upon contact with neutrophils, but only YadA-expressing Y. enterocolitica adhered to NETs and were killed. As binding seemed to be a prerequisite for killing, we searched for YadA-binding substrates and detected the presence of collagen within NETs. E40 bacteria expressing V98D,N99A mutant YadA with a severely reduced ability to bind collagen were found to be more resistant to killing, suggesting that collagen binding contributes significantly to sensitivity to NETs. Wt Y. pestis EV76 were resistant to killing by NETs, while recombinant EV76 expressing YadA from either Y. pseudotuberculosis or Y. enterocolitica were sensitive to killing by NETs, outlining the importance of YadA for susceptibility to NET-dependent killing. Recombinant EV76 endowed with YadA from Y. enterocolitica were also less virulent for the mouse than wt EV76, as shown before. In addition, EV76 carrying wt YadA were less virulent for the mouse than EV76 expressing YadA(V98D,N99A). The observation that YadA makes Yersinia sensitive to NETs provides an explanation as for why evolution selected for the inactivation of yadA in the flea-borne Y. pestis and clarifies an old enigma. Since YadA imposes the same cost to the food-borne Yersinia but was nevertheless conserved by evolution, this observation also illustrates the duality of some virulence functions.

Cervical cancer attitudes and beliefs-a Cape Town community responds on World Cancer Day.

BACKGROUND: Attitudes and beliefs affect women's cervical cancer screening behavior. Methods. We surveyed 228 women in Cape Town, South Africa about their screening history, knowledge, beliefs, and access barriers regarding Papanicolaou (Pap) smears and cervical cancer. RESULTS: More than half of the participants had never had a Pap smear or had 1 more than 10 years ago. One third did not know what a Pap smear was. Lengthy wait times and fatalistic beliefs also affected screening behavior. Ethnicity was associated with differences in beliefs. CONCLUSIONS: Opportunistic cancer screening events are an effective way that women can obtain Pap smears and cancer education.

Prevalence of Capnocytophaga canimorsus in dogs and occurrence of potential virulence factors.

Capnocytophaga canimorsus is a Gram-negative commensal of dog's mouth causing severe human infections. A strain isolated from a human fatal infection was recently shown to have a sialidase, to inhibit the bactericidal activity of macrophages and to block the release of nitric oxide by LPS-stimulated macrophages. The present study aimed at determining the prevalence of C. canimorsus in dogs and the occurrence of these hypothetical virulence factors. C. canimorsus could be retrieved from the saliva of 61 dogs out of 106 sampled. Like in clinical isolates, all dog strains had a sialidase and 60% blocked the killing of phagocytosed Escherichia coli by macrophages. In contrast, only 6.5% of dog strains blocked the release of nitric oxide by LPS-challenged macrophages, suggesting that this property might contribute to virulence. The comparative analysis of 69 16S rDNA sequences revealed the existence of C. canimorsus strains that could be misdiagnosed.

Resistance of Capnocytophaga canimorsus to killing by human complement and polymorphonuclear leukocytes.

Capnocytophaga canimorsus is a bacterium of the canine oral flora known since 1976 to cause rare but severe septicemia and peripheral gangrene in patients that have been in contact with a dog. It was recently shown that these bacteria do not elicit an inflammatory response (H. Shin, M. Mally, M. Kuhn, C. Paroz, and G. R. Cornelis, J. Infect. Dis. 195:375-386, 2007). Here, we analyze their sensitivity to the innate immune system. Bacteria from the archetype strain Cc5 were highly resistant to killing by complement. There was little membrane attack complex (MAC) deposition in spite of C3b deposition. Cc5 bacteria were as resistant to phagocytosis by human polymorphonuclear leukocytes (PMNs) as Yersinia enterocolitica MRS40, endowed with an antiphagocytic type III secretion system. We isolated Y1C12, a transposon mutant that is hypersensitive to killing by complement via the antibody-dependent classical pathway. The mutation inactivated a putative glycosyltransferase gene, suggesting that the Y1C12 mutant was affected at the level of a capsular polysaccharide or lipopolysaccharide (LPS) structure. Cc5 appeared to have several polysaccharidic structures, one being altered in Y1C12. The structure missing in Y1C12 could be purified by classical LPS purification procedures and labeled by tritiated palmitate, indicating that it is more likely to be an LPS structure than a capsule. Y1C12 bacteria were also more sensitive to phagocytosis by PMNs than wild-type bacteria. In conclusion, a polysaccharide structure, likely an LPS, protects C. canimorsus from deposition of the complement MAC and from efficient phagocytosis by PMNs.

Capnocytophaga canimorsus resists phagocytosis by macrophages and blocks the ability of macrophages to kill other bacteria.

Capnocytophaga canimorsus is a commensal bacterium from the canine oral flora, which can cause septicemia or meningitis in humans upon bite wound infections. C. canimorsus 5 (Cc5), a strain isolated from a patient with fatal septicemia, was used to investigate the interaction between C. canimorsus and J774.1 mouse macrophages. J774.1 cells infected at high multiplicity with Cc5 did not phagocytose nor kill Cc5 within 120 min of infection, unless the bacteria were opsonized with specific antibodies. Opsonization with complement, however, did not increase phagocytosis. Moreover, infection of J774.1 cells with live Cc5 led to the release of a soluble factor, which interfered with the ability of macrophages to kill other phagocytosed bacteria. These results provide an example of how C. canimorsus neutralizes the innate immune system.

The discovery of SycO highlights a new function for type III secretion effector chaperones.

Bacterial injectisomes deliver effector proteins straight into the cytosol of eukaryotic cells (type III secretion, T3S). Many effectors are associated with a specific chaperone that remains inside the bacterium when the effector is delivered. The structure of such chaperones and the way they interact with their substrate is well characterized but their main function remains elusive. Here, we describe and characterize SycO, a new chaperone for the Yersinia effector kinase YopO. The chaperone-binding domain (CBD) within YopO coincides with the membrane localization domain (MLD) targeting YopO to the host cell membrane. The CBD/MLD causes intrabacterial YopO insolubility and the binding of SycO prevents this insolubility but not folding and activity of the kinase. Similarly, SycE masks the MLD of YopE and SycT covers an aggregation-prone domain of YopT, presumably corresponding to its MLD. Thus, SycO, SycE and most likely SycT mask, inside the bacterium, a domain needed for proper localization of their cognate effector in the host cell. We propose that covering an MLD might be an essential function of T3S effector chaperones.