Measurement of breath acetone concentrations by selected ion flow tube mass spectrometry in type 2 diabetes

Selected ion flow tube-mass spectrometry (SIFT-MS) can measure volatile compounds in breath on-line in real time and has the potential to provide accurate breath tests for a number of inflammatory, infectious and metabolic diseases, including diabetes. Breath concentrations of acetone in type 2 diabetic subjects undertaking a long-term dietary modification programme were studied. Acetone concentrations in the breath of 38 subjects with type 2 diabetes were determined by SIFT-MS. Anthropomorphic measurements, dietary intake and medication use were recorded. Blood was analysed for beta hydroxybutyrate (a ketone body), HbA1c (glycated haemoglobin) and glucose using point-of-care capillary (fingerprick) testing. All subjects were able to undertake breath manoeuvres suitable for analysis. Breath acetone varied between 160 and 862 ppb (median 337 ppb) and was significantly higher in men (median 480 ppb versus 296 ppb, p = 0.01). In this cross-sectional study, no association was observed between breath acetone and either dietary macronutrients or point-of-care capillary blood tests. Breath analysis by SIFT-MS offers a rapid, reproducible and easily performed measurement of acetone concentration in ambulatory patients with type 2 diabetes. The high inter-individual variability in breath acetone concentration may limit its usefulness in cross-sectional studies. Breath acetone may nevertheless be useful for monitoring metabolic changes in longitudinal metabolic studies, in a variety of clinical and research settings.     

Combined anti-PD-1 and anti-CTLA-4 checkpoint blockade: Treatment of melanoma and immune mechanisms of action

Cytotoxic T-lymphocyte associated protein-4 (CTLA-4) and the Programmed Death Receptor 1 (PD-1) are immune checkpoint molecules that are well-established targets of antibody immunotherapies for the management of malignant melanoma. The monoclonal antibodies, Ipilimumab, Pembrolizumab, and Nivolumab, designed to interfere with T cell inhibitory signals to activate immune responses against tumors, were originally approved as monotherapy. Treatment with a combination of immune checkpoint inhibitors may improve outcomes compared to monotherapy in certain patient groups and these clinical benefits may be derived from unique immune mechanisms of action. However, treatment with checkpoint inhibitor combinations also present significant clinical challenges and increased rates of immune-related adverse events. In this review, we discuss the potential mechanisms attributed to single and combined checkpoint inhibitor immunotherapies and clinical experience with their use.     

Living with heart failure: An integrative review

Objectives

To conduct an integrative review that explores the experiences and perceptions of patients who have heart failure to find any commonality that might enhance care giving to this patient group and areas for future research.

Background

Patients are expected to take responsibility for much of the day-to-day management of their heart failure and modify their behaviour to maintain and improve their health. The degree of responsibility which patients can take is to a large extent dependant on how they see themselves in the context of their new situation. Limited research has been undertaken about how patients come to terms with their new condition and subsequent ‘new self’, but this has not been linked to patients’ ability to take more responsibility. This review will integrate this notion of self-care, personal responsibility and the implications of this for nursing care, as this is not identified in current guidelines.

Design and data sources

Using an integrative review method, Ovid MEDLINE (R), CINAHL, EMBASE, AMED, HMIC, BNI and PsycINFO databases were searched from January 1985 to May 2008. 18 papers were selected that most clearly reflected the concept of understanding the patient's experience of living with heart failure.

Results

Patients appear to undergo a process of taking on a new identity, ‘a new self’. From the review five conceptual categories emerge: diagnosis and manifestations of heart failure; perceptions of day-to-day life; coping behaviours; role of others and concept of self which influences all of the other categories. This maps a journey, as the individual experiences heart failure; their success or failure at adapting to this new sense of self, will influence self-care behaviours.

Conclusions

Literature that explores understanding the patient's experiences of living with heart failure, taking on a new identity and the influence of this on their self-care behaviour, is limited. The integration of the new condition with patient's sense of self is likely to a have a major impact on the effectiveness of treatments offered. An essential and ethical care component for patients with heart failure should be an ongoing assessment of their experience of the situation that they live with.     

Informing fieldwork design: Key elements to quality in fieldwork education for undergraduate occupational therapy students

Aim:  In this current climate of escalating student fees, students as paying consumers expect a quality fieldwork experience. However, the ability of universities to deliver quality fieldwork programs is compromised by the increasing pressure experienced by fieldwork educators to meet productivity targets in the face of diminishing resources. This paper details how one university, Monash University, sought input from stakeholders to design a fieldwork program.
Methods:  This qualitative study utilised focus groups to inform the researchers of stakeholders' perceptions of what constitutes quality fieldwork education. A total of five focus groups were held, involving 47 occupational therapists practising in Victoria.
Results:  The major findings include the need to provide ongoing professional development for fieldwork educators, the need to develop tangible strategies in recognition of their contribution towards fieldwork education, and the imperative for closer collaboration between universities and fieldwork educators.
Conclusions:  Based on literature and in response to the focus group discussions, Monash University has implemented a number of measures to ensure the successful implementation of quality fieldwork education. These include providing ongoing professional development for fieldwork educators to enhance their role, addressing fieldwork educators' concerns about project placements and supporting students with fieldwork relocation. Most importantly, this study demonstrates the need for educational institutions to take the lead in dialogue with the profession to enhance a collaborative response to constant changes in health-care directions. The importance of ongoing research to inform quality fieldwork education is critical to moving the profession forward.     

Developing a community facilitator‐led participatory learning and action women's group intervention to improve infant feeding,care and dental hygiene practices in South Asian infants: NEON programme

IntroductionThe Nurture Early for Optimal Nutrition (NEON) study is a multiphase project that aims to optimize feeding, care and dental hygiene practices in South Asian children <2 years in East London, United Kingdom. The multiphase project uses a participatory learning and action (PLA) approach facilitated by a multilingual community facilitator. In this paper, we elaborate on the process and results of the Intervention Development Phase in the context of the wider NEON programme.MethodsQualitative community‐based participatory intervention codevelopment and adaptation.SettingCommunity centres in East London and online (Zoom) meetings and workshops.ParticipantsIn total, 32 participants registered to participate in the Intervention Development Phase. Four Intervention Development workshops were held, attended by 25, 17, 20 and 20 participants, respectively.ResultsCollaboratively, a culturally sensitive NEON intervention package was developed consisting of (1) PLA group facilitator manual, (2) picture cards detailing recommended and nonrecommended feeding, care and dental hygiene practices with facilitators/barriers to uptake as well as solutions to address these, (3) healthy infant cultural recipes, (4) participatory Community Asset Maps and (5) list of resources and services supporting infant feeding, care and dental hygiene practices.ConclusionThe Intervention Development Phase of the NEON programme demonstrates the value of a collaborative approach between researchers, community facilitators and the target population when developing public health interventions. We recommend that interventions to promote infant feeding, care and dental hygiene practices should be codeveloped with communities. Recognizing and taking into account both social and cultural norms may be of particular value for infants from ethnically diverse communities to develop interventions that are both effective in and accepted by these communities.Patient and Public Involvement and EngagementConsiderable efforts were placed on Patient/Participant and Public Involvement and Engagement. Five community facilitators were identified, each of which represented one ethnic/language group: (i) Bangladeshi/Bengali and Sylheti, (ii) Pakistani/Urdu, (iii) Indian/Gujrati, (iv) Indian/Punjabi and (v) Sri Lankan/Tamil. The community facilitators were engaged in every step of the study, from the initial drafting of the protocol and study design to the Intervention Development and refinement of the NEON toolkit, as well as the publication and dissemination of the study findings. More specifically, their role in the Intervention Development Phase of the NEON programme was to:

• 1.Support the development of the study protocol, information sheets and ethics application.
• 2.Ensure any documents intended for community members are clear, appropriate and sensitively worded.
• 3.Develop strategies to troubleshoot any logistical challenges of project delivery, for example, recruitment shortfalls.
• 4.Contribute to the writing of academic papers, in particular reviewing and revising drafts.
• 5.Develop plain language summaries and assist in dissemination activities, for example, updates on relevant websites.
• 6.Contribute to the development of the NEON intervention toolkit and recruitment of the community members.
• 7.Attend and contribute to Intervention Development workshops, ensuring the participant''s voices were the focus of the discussion and workshop outcomes.

     

Type 1 Diabetes Development Requires Both CD4+ and CD8+ T cells and Can Be Reversed by Non-Depleting Antibodies Targeting Both T Cell Populations

Type 1 diabetes development in NOD mice appears to require both CD4⁺ and CD8⁺ T cells. However, there are some situations where it has been suggested that either CD4⁺ or CD8⁺ T cells are able to mediate diabetes in the absence of the other population. In the case of transgenic mice, this may reflect the numbers of antigen-specific T cells able to access the pancreas and recruit other cell types such as macrophages leading to a release of high concentrations of damaging cytokines. Previous studies examining the requirement for CD8⁺ T cells have used antibodies specific for CD8α. It is known that CD8α is expressed not only on αβ T cells, but also on other cell types, including a DC population that may be critical for presenting islet antigen in the pancreatic draining lymph nodes. Therefore, we have re-examined the need for both CD4⁺ and CD8⁺ T cell populations in diabetes development in NOD mice using an antibody to CD8β. Our studies indicate that by using highly purified populations of T cells and antibodies specific for CD8⁺ T cells, there is indeed a need for both cell types. In accordance with some other reports, we found that CD4⁺ T cells appeared to be able to access the pancreas more readily than CD8⁺ T cells. Despite the ability of CD4⁺ T cells to recruit CD11b class II positive cells, diabetes did not develop in the absence of CD8⁺ T cells. These studies support the observation that CD8⁺ T cells may be final effector cells. As both T cell populations are clearly implicated in diabetes development, we have used a combination of non-depleting antibodies to target both CD4-positive and CD8-positive cells and found that this antibody combination was able to reverse diabetes onset in NOD mice as effectively as anti-CD3 antibodies.