Peptide immunotherapy for allergic disease

The only disease-modifying treatment available for IgE-mediated disease is specific immunotherapy, but the retention of B cell epitopes in whole allergen preparations confers a risk of IgE-mediated systemic reactions to their administration. Compelling evidence for the central role of T cells in allergic disease suggests that IgE-binding epitopes could be removed from such therapy, improving safety without affecting efficacy. Short, allergen-derived peptides lack the conformational determinants required for IgE crosslinking and are, therefore, an attractive therapeutic possibility. However, human leukocyte antigen (HLA) polymorphism means that T cell peptide epitopes present a huge diversity, which makes the design of peptide-based vaccines problematic. Over the past 10 years, advances in our understanding of epitope selection and major histocompatibility complex (MHC)-peptide-T cell receptor interactions have taken this therapy forward to early clinical trials with human volunteers.     

Peptide immunotherapy for allergic disease

The only disease-modifying treatment available for IgE-mediated disease is specific immunotherapy, but the retention of B cell epitopes in whole allergen preparations confers a risk of IgE-mediated systemic reactions to their administration. Compelling evidence for the central role of T cells in allergic disease suggests that IgE-binding epitopes could be removed from such therapy, improving safety without affecting efficacy. Short, allergen-derived peptides lack the conformational determinants required for IgE crosslinking and are, therefore, an attractive therapeutic possibility. However, human leukocyte antigen (HLA) polymorphism means that T cell peptide epitopes present a huge diversity, which makes the design of peptide-based vaccines problematic. Over the past 10 years, advances in our understanding of epitope selection and major histocompatibility complex (MHC)–peptide–T cell receptor interactions have taken this therapy forward to early clinical trials with human volunteers.     

Specific immunotherapy in pollen allergy

Pollen allergy affects at least 10% of the global population, and up to one-third of the affected individuals displaying hay fever symptoms will later develop allergic asthma. The efficacy of allergen-specific immunotherapy (SIT) in seasonal allergic rhinitis has been confirmed in many clinical studies using grass, ragweed, and birch pollen extracts. SIT prevents the onset of new sensitizations to different allergens, and reduces the development of asthma in patients with allergic rhinitis caused by inhaled allergens, including pollen. Several rational approaches are being developed to improve the efficacy of SIT by reducing immunoglobulin (Ig)E-mediated adverse reactions. The use of chemically modified, recombinant or genetically engineered allergens is being explored, in addition to the investigation of novel adjuvants and alternative routes of administration. The first clinical trials using recombinant allergens provided encouraging results, suggesting that allergen extracts can be successfully substituted by molecule-based formulations. These new formulations, for use in the routine management of pollen allergies, should become available in the near future.     

Primary care oncology: addressing the challenges

The last decade has seen an emerging clinical discipline known as 'primary care oncology' that describes the involvement of general practitioners (GPs) in preventing, diagnosing, treating and following up patients with cancer. This paper reports the experience of our team in investigating the information required to develop a shared electronic care record system to link GPs and cancer specialists in Wales in order to facilitate information sharing between them in a timely and effective manner. It identifies a potential minimum dataset that can provide the basis for the development of a Welsh primary care cancer dataset. It also addresses the associated challenges to be overcome at implementation, namely information, technical, cultural/organisational and management challenges. This work is a collaboration between the Department of Computer Science at Cardiff University and Velindre NHS Trust, the South East Wales Cancer Centre.     

Opportunities and challenges in translational science

The mission of translational science is to bring predictivity and efficiency to the development and dissemination of interventions that improve human health. Ten years ago this year, the National Center for Advancing Translational Sciences was founded to embody, conduct, and support this new discipline. The Center’s first decade has brought substantial progress across a broad range of translational areas, from diagnostic and drug development to clinical trials to implementation science to education. The origins of the translational science and advances to this point are reviewed here and allow the establishment of an ambitious future research agenda for the field.     

Dendritic cell-based immunotherapy for cancer and relevant challenges for transfusion medicine

The encouraging results from dendritic cell-related cancer immunotherapy have created tremendous interest for its broad clinical application. Dendritic cells are the most potent antigen-presenting cells. In cancer patients, dendritic cell production and function along with other antitumor immune defenses are compromised. Autologous dendritic cells enriched and sensitized in vitro with tumor-associated antigens can effectively elicit host cellular immunity against cancer and result in clinical antitumor responses through either direct injection or ex vivo generation of antitumor T lymphocytes. In small group studies, clinical response rates have reached 50% in patients with advanced stage of cancer. These cellular products caused minimal side effects and were well tolerated. The isolation and preparation of clinical grade dendritic cells have been driven by transfusion medicine specialists who are well versed in similar processes for hematopoietic stem-cell preparation. The purpose of this article is to review the mechanisms of tumor immune surveillance and the biology of dendritic cells relevant to tumor antigen presentation, sensitization, and T-lymphocyte stimulation. Information on tumor-associated antigens and clinical trial results with dendritic cell-based cancer immunotherapy are summarized. The potential challenges for blood banking/transfusion medicine involving both technical and regulatory issues are discussed.     

Assessment of childhood allergy for the primary care practitioner

PURPOSE: To update the primary care practitioner on the assessment of common childhood allergic illnesses. DATA SOURCES: Relevant scientific literature and published clinical practice guidelines. CONCLUSIONS: Atopic children often develop symptoms that occur in a predictable progression from atopic dermatitis to gastrointestinal disturbances, chronic serous otitis media, rhinitis, and asthma. Evaluation of allergic symptoms should be based on their chronicity, family history of atopy, and knowledge of how the information will change patient management. Both skin and blood testing are accurate and useful tools in establishing a diagnosis of allergic disease. Management includes avoidance/environmental control, medications, and, when necessary, referral to specialists. IMPLICATIONS FOR PRACTICE: As the incidence of allergic disease increases, the human and monetary costs associated with allergies place a major burden on our healthcare system. Early identification of allergies and appropriate intervention are important to prevent progression to more significant disease. The use of objective diagnostic testing aids in implementing appropriate evidence-based medical management.     

Peanut allergy: Beyond the oral immunotherapy plateau

BackgroundThere are a lack of disease‐modifying treatments for peanut allergy, which is lifelong in most instances. Oral immunotherapy has remained at the forefront of prospective treatments, though its efficacy is consistently undermined by the risk of adverse reactions and meager sustained effects.AimThis review discusses the current state of oral immunotherapy, its strengths and limitations, and the future of therapeutics for the treatment of peanut allergy.ConclusionThe persistence of peanut allergy is currently attributed to reservoirs of peanut‐specific memory B cells and Th2 cells, though the cellular and molecular interplay that facilitates the replenishment of peanut‐specific IgE remains elusive. Uncovering these events will prove critical for identification of novel targets as we forge ahead to a new age of peanut allergy treatment with biotherapeutics.     

Diagnostic challenges in childhood sarcoidosis

The aim of our clinical image was to emphasize the value of a careful skin examination in the diagnosis of early‐onset sarcoidosis in children.     

Developing person-centred care: addressing contextual challenges through practice development

Developing person-centred care is not a one-time event; rather it requires a sustained commitment from organisations to the ongoing facilitation of developments, a commitment both in clinical teams and across organizations. Contextual factors pose the greatest challenge to person-centredness and the development of cultures that can sustain person-centred care. We will begin with a general comment on 'context' and its meaning before exploring three particular factors that influence the practice context, namely, workplace culture, learning culture, and the physical environment. Next we explore a particular approach to developing person-centred care through emancipatory practice development. We highlight the importance of facilitation through emancipatory practice development programmes and describe how person-centred care can be developed through the presentation of a case study that illustrates the principles and processes of emancipatory practice development as well as the outcomes achieved. We conclude with an application to clinical practice. A key consideration for all organisations in the development of person-centred care is to move from what we suggest are 'person-centred moments' (individual, ad hoc experiences of person-centredness) to 'person-centred care' as an underpinning culture of teams and organisations.     

Advances in addressing technical challenges of point-of-care diagnostics in resource-limited settings

The striking prevalence of HIV, TB and malaria, as well as outbreaks of emerging infectious diseases, such as influenza A (H7N9), Ebola and MERS, poses great challenges for patient care in resource-limited settings (RLS). However, advanced diagnostic technologies cannot be implemented in RLS largely due to economic constraints. Simple and inexpensive point-of-care (POC) diagnostics, which rely less on environmental context and operator training, have thus been extensively studied to achieve early diagnosis and treatment monitoring in non-laboratory settings. Despite great input from material science, biomedical engineering and nanotechnology for developing POC diagnostics, significant technical challenges are yet to be overcome. Summarized here are the technical challenges associated with POC diagnostics from a RLS perspective and the latest advances in addressing these challenges are reviewed.     

Parental perceptions of the schools' role in addressing childhood obesity.

As childhood obesity has increased, schools have struggled with their role in this epidemic. Parents with a school-age child in a suburban latchkey program were surveyed regarding their perceptions of childhood obesity, body mass index, and the school's role in prevention and treatment of obesity. More than 80% of participants identified inactivity, poor eating behavior, lack of parental control in what children eat, and eating too much as the main causes of childhood obesity. Parents preferred receiving information about their child's body mass index from the school via a letter from the school nurse. Participants agreed that physical education classes, as well as units on nutrition and weight control, should be present in schools. Parents also supported eliminating junk food machines and offering special low-calorie meals. By supporting these strategies, parents indicated that schools should have a role in childhood obesity. School nurses can advocate for parental preferences in their school district.     

Cancer immunotherapy and heat-shock proteins: promises and challenges

Recent mechanistic studies on the role of heat-shock proteins (HSPs) to induce innate and adaptive immune responses have resulted in conflicting reports. Whereas some groups reported that HSPs have direct immunological function, others emphasised the endotoxin contamination of HSP preparations and questioned the antigen-specificity of HSP vaccines. The present review will discuss these issues and suggest that HSPs have diverse and distinct immunological functions that could be superimposed on effects resulting from endotoxin contamination or misunderstood by using experimental procedures with inadequate controls. To understand the actual function of HSPs in their interaction with the immune system, methods and procedures need to be optimised and appropriate controls need to be used. These points should also clarify the conflicting findings about HSPs and promote our knowledge about other immuologically important components that may be present in HSP preparations.     

Case study of a transtheoretical case management approach to addressing childhood obesity

Childhood obesity is an increasing health concern that is strongly associated with chronic health problems persisting into adulthood. Obesity in childhood is resistant to interventions that involve only recommendations to decrease caloric intake and to increase caloric expenditure. The challenge with this approach to childhood obesity is twofold: It is neither theoretically based nor does it consider the children's or their parent's perceptions of their health problems. Of significance, this traditional approach also ignores the transition along the stages of behavioral change. Case management has proven to be successful in managing various chronic health problems in both adults and children. This case study will present a new intervention model to treat childhood obesity based on the transtheoretical framework utilizing case management in a primary care setting.