Identifying risks related to road traffic accidents among vulnerable population in Moneragala district, Sri Lanka

Objectives: To identify individual and environmental risks related to road traffic accidents(RTA) among elderly (>60years) and disabled people (>5years living with physical, sensory or mobility impairment) in Moneragala district.Methods: Study was designed as community based participatory research. Participants were vulnerable road users (elderly and disabled). Eight focus group discussions (8-10 in each) were conducted with elderly and disabled to identify local and regional destinations that were most important to access, perceived risks related to RTA and needs/suggestions for road safety. Participants were encouraged to photograph the environment barriers and facilitators for road safety. ‘Photovoice’ is increasingly used as valuable adjunct in participatory research-a voice better heard through.Results: Frequently visited places identified by older people were the hospital, temple, village houses, community hall and bank. For disabled it varied by age, as vocational training centre, special needs school and community hall. Mostly used travel modes were public bus, three wheeled-vehicles or walking. Transportation barriers for the elderly were identified as poor road conditions, lack of disability-friendly transportation system, financial constraints and negative human factors. Disabled found accessibility to public places a major barrier. These facts were supported by photographs. Suggestions for improvement included awareness programs among people involved in transportation, cost effective transportation modes, mass media acknowledgments of rights of elderly and disabled, more effective legislation and improved road infrastructure.Conclusions: It is evident that many places the study population frequently travels are located in the city. They face many risks when travelling to these destinations. It is proposed to improve road conditions, modify modes of transportation, rigorous law enforcement and awareness programs among public to minimize the road related risks faced by disabled and elderl

The clinical utility of molecular diagnostic testing for primary immune deficiency disorders: a case based review

Primary immune deficiency disorders (PIDs) are a group of diseases associated with a genetic predisposition to recurrent infections, malignancy, autoimmunity and allergy. The molecular basis of many of these disorders has been identified in the last two decades. Most are inherited as single gene defects. Identifying the underlying genetic defect plays a critical role in patient management including diagnosis, family studies, prognostic information, prenatal diagnosis and is useful in defining new diseases. In this review we outline the clinical utility of molecular testing for these disorders using clinical cases referred to Auckland Hospital. It is written from the perspective of a laboratory offering a wide range of tests for a small developed country

Patient-identified information and communication needs in the context of major trauma

Background: Navigating complex health care systems during the multiple phases of recovery following major trauma entails many challenges for injured patients. Patients’ experiences communicating with health professionals are of particular importance in this context. The aim of this study was to explore seriously injured patients’ perceptions of communication with and information provided by health professionals in their first 3-years following injury. Methods: A qualitative study designed was used, nested within a population-based longitudinal cohort study. Semi-structured telephone interviews were undertaken with 65 major trauma patients, aged 17 years and older at the time of injury, identified through purposive sampling from the Victorian State Trauma Registry. A detailed thematic analysis was undertaken using a framework approach. Results: Many seriously injured patients faced barriers to communication with health professionals in the hospital, rehabilitation and in the community settings. Key themes related to limited contact with health professionals, insufficient information provision, and challenges with information coordination. Communication difficulties were particularly apparent when many health professionals were involved in patient care, or when patients transitioned from hospital to rehabilitation or to the community. Difficulties in patient-health professional engagement compromised communication and exchange of information particularly at transitions of care, e.g., discharge from hospital. Conversely, positive attributes displayed by health professionals such as active discussion, clear language, listening and an empathetic manner, all facilitated effective communication. Most patients preferred communication consistent with patient-centred approaches, and the use of multiple modes to communicate information. Conclusions: The communication and information needs of seriously injured patients were inconsistently met over the course of their recovery continuum. To assist patients along their recovery trajectories, patient-centred communication approaches and considerations for environmental and patients’ health literacy are recommended. Additionally, assistance with information coordination and comprehensive multimodal information provision should be available for injured patients.Sandra Braaf, Shanthi Ameratunga, Andrew Nunn, Nicola Christie, Warwick Teague, Rodney Judson and Belinda J. Gabb

Anaphylaxis to hyperallergenic functional foods

<p>Abstract</p> <p>Background</p> <p>Food allergy can cause life threatening reactions. Currently, patients with severe food allergy are advised to avoid foods which provoke allergic reactions. This has become increasingly difficult as food proteins are being added to a broader range of consumer products.</p> <p>Patients and methods</p> <p>Here we describe our investigations into the allergenicity of a new drink when two cow's milk allergic children suffered anaphylaxis after consuming <it>Wh</it>_<it>2</it><it>ole</it>^®.</p> <p>Results</p> <p>Our studies have shown that in comparison with cow's milk, <it>Wh</it>_<it>2</it><it>ole</it>^®contains at least three times the concentration of β-lactoglobulin. β-lactoglobulin is one of the dominant allergens in bovine milk.</p> <p>Conclusions</p> <p>These studies have shown that modern technology allows the creation of "hyperallergenic" foods. These products have the potential to cause severe reactions in milk allergic persons. Avoiding inadvertent exposure is the shared responsibility of allergic consumers, regulatory authorities and the food industry.</p

A Phase 1, Dose Escalation Study of Guadecitabine (SGI-110) in Combination with Pembrolizumab in Patients with Solid Tumours

Background: Data suggest that immunomodulation induced by DNA hypomethylating agents can sensitize tumors to immune checkpoint inhibitors. We conducted a phase 1 dose-escalation trial (NCT02998567) of guadecitabine and pembrolizumab in patients with advanced solid tumors. We hypothesized that guadecitabine will overcome pembrolizumab resistance. Methods: Patients received guadecitabine (45 mg/m 2 or 30 mg/m 2, administered subcutaneously on days 1-4), with pembrolizumab (200 mg administered intravenously starting from cycle 2 onwards) every 3 weeks. Primary endpoints were safety, tolerability and maximum tolerated dose; secondary and exploratory endpoints included objective response rate (ORR), changes in methylome, transcriptome, immune contextures in pre-treatment and on-treatment tumor biopsies. Results: Between January 2017 and January 2020, 34 patients were enrolled. The recommended phase II dose was guadecitabine 30 mg/m 2, days 1-4, and pembrolizumab 200 mg on day 1 every 3 weeks. Two dose-limiting toxicities (neutropenia, febrile neutropenia) were reported at guadecitabine 45 mg/m 2 with none reported at guadecitabine 30 mg/m 2. The most common treatment-related adverse events (TRAEs) were neutropenia (58.8%), fatigue (17.6%), febrile neutropenia (11.8%) and nausea (11.8%). Common, grade 3+ TRAEs were neutropaenia (38.2%) and febrile neutropaenia (11.8%). There were no treatment-related deaths. Overall, 30 patients were evaluable for antitumor activity; ORR was 7% with 37% achieving disease control (progression-free survival) for ≥24 weeks. Of 12 evaluable patients with non-small cell lung cancer, 10 had been previously treated with immune checkpoint inhibitors with 5 (42%) having disease control ≥24 weeks (clinical benefit). Reduction in LINE-1 DNA methylation following treatment in blood (peripheral blood mononuclear cells) and tissue samples was demonstrated and methylation at transcriptional start site and 5' untranslated region gene regions showed enriched negative correlation with gene expression. Increases in intra-tumoural effector T-cells were seen in some responding patients. Patients having clinical benefit had high baseline inflammatory signature on RNAseq analyses. Conclusions: Guadecitabine in combination with pembrolizumab is tolerable with biological and anticancer activity. Reversal of previous resistance to immune checkpoint inhibitors is demonstrated

Phase 1, dose-escalation study of guadecitabine (SGI-110) in combination with pembrolizumab in patients with solid tumors

Background: Data suggest that immunomodulation induced by DNA hypomethylating agents can sensitize tumors to immune checkpoint inhibitors. We conducted a phase 1 dose-escalation trial (NCT02998567) of guadecitabine and pembrolizumab in patients with advanced solid tumors. We hypothesized that guadecitabine will overcome pembrolizumab resistance. Methods: Patients received guadecitabine (45 mg/m 2 or 30 mg/m 2, administered subcutaneously on days 1-4), with pembrolizumab (200 mg administered intravenously starting from cycle 2 onwards) every 3 weeks. Primary endpoints were safety, tolerability and maximum tolerated dose; secondary and exploratory endpoints included objective response rate (ORR), changes in methylome, transcriptome, immune contextures in pre-treatment and on-treatment tumor biopsies. Results: Between January 2017 and January 2020, 34 patients were enrolled. The recommended phase II dose was guadecitabine 30 mg/m 2, days 1-4, and pembrolizumab 200 mg on day 1 every 3 weeks. Two dose-limiting toxicities (neutropenia, febrile neutropenia) were reported at guadecitabine 45 mg/m 2 with none reported at guadecitabine 30 mg/m 2. The most common treatment-related adverse events (TRAEs) were neutropenia (58.8%), fatigue (17.6%), febrile neutropenia (11.8%) and nausea (11.8%). Common, grade 3+ TRAEs were neutropaenia (38.2%) and febrile neutropaenia (11.8%). There were no treatment-related deaths. Overall, 30 patients were evaluable for antitumor activity; ORR was 7% with 37% achieving disease control (progression-free survival) for ≥24 weeks. Of 12 evaluable patients with non-small cell lung cancer, 10 had been previously treated with immune checkpoint inhibitors with 5 (42%) having disease control ≥24 weeks (clinical benefit). Reduction in LINE-1 DNA methylation following treatment in blood (peripheral blood mononuclear cells) and tissue samples was demonstrated and methylation at transcriptional start site and 5' untranslated region gene regions showed enriched negative correlation with gene expression. Increases in intra-tumoural effector T-cells were seen in some responding patients. Patients having clinical benefit had high baseline inflammatory signature on RNAseq analyses. Conclusions: Guadecitabine in combination with pembrolizumab is tolerable with biological and anticancer activity. Reversal of previous resistance to immune checkpoint inhibitors is demonstrated

Children admitted to hospital following unintentional injury: perspectives of health service providers in Aotearoa/New Zealand

<p>Abstract</p> <p>Background</p> <p>Unintentional injuries are the leading cause of death and hospitalisation among New Zealand children, with indigenous Māori and ethnic minority Pacific children significantly over represented in these statistics. International research has shown that many children hospitalised for injury, as well as their families experience high levels of stress, and ethnic disparities in the quality of trauma care are not uncommon. The research on which this paper is based sought to identify key issues and concerns for New Zealand's multi-ethnic community following hospitalisation for childhood injury in order to inform efforts to improve the quality of trauma services. This paper reports on service providers' perspectives complementing previously published research on the experiences of families of injured children.</p> <p>Methods</p> <p>A qualitative research design involving eleven in-depth individual interviews and three focus groups was used to elicit the views of 21 purposefully selected service provider key informants from a range of professional backgrounds involved in the care and support of injured children and their families in Auckland, New Zealand. Interviews were transcribed and data were analysed using thematic analysis.</p> <p>Results</p> <p>Key issues identified by service providers included limited ability to meet the needs of children with mild injuries, particularly their emotional needs; lack of psychological support for families; some issues related to Māori and Pacific family support services; lack of accessible and comprehensive information for children and families; poor staff continuity and coordination; and poor coordination of hospital and community services, including inadequacies in follow-up plans. There was considerable agreement between these issues and those identified by the participant families.</p> <p>Conclusions</p> <p>The identified issues and barriers indicate the need for interventions for service improvement at systemic, provider and patient levels. Of particular relevance are strategies that enable families to have better access to information, including culturally appropriate oral and written sources; improve communication amongst staff and between staff and families; and carefully developed discharge plans that provide care continuity across boundaries between hospital and community settings. Māori and Pacific family support services are important and need better resourcing and support from an organisational culture responsive to the needs of these populations.</p