Long- and short-term outcomes in renal allografts with deceased donors: A large recipient and donor genome-wide association study.

Improvements in immunosuppression have modified short-term survival of deceased-donor allografts, but not their rate of long-term failure. Mismatches between donor and recipient HLA play an important role in the acute and chronic allogeneic immune response against the graft. Perfect matching at clinically relevant HLA loci does not obviate the need for immunosuppression, suggesting that additional genetic variation plays a critical role in both short- and long-term graft outcomes. By combining patient data and samples from supranational cohorts across the United Kingdom and European Union, we performed the first large-scale genome-wide association study analyzing both donor and recipient DNA in 2094 complete renal transplant-pairs with replication in 5866 complete pairs. We studied deceased-donor grafts allocated on the basis of preferential HLA matching, which provided some control for HLA genetic effects. No strong donor or recipient genetic effects contributing to long- or short-term allograft survival were found outside the HLA region. We discuss the implications for future research and clinical application

Oral vancomycin desensitisation to treat Clostridium difficile infection in a vancomycin allergic patient

The prevalence of Clostridium difficile infection (CDI) is increasing worldwide. Oral vancomycin is an effective and frequently used treatment. However, patients with CDI who are allergic to intravenous vancomycin cannot receive oral vancomycin due to the risk of anaphylaxis if given the oral form.We present a case where oral vancomycin desensitisation was used to successfully treat a vancomycin allergic patient with recurrent CDI. Keywords: Allergy, Anaphylaxis, Desensitisation, Vancomycin, Clostridium difficil

Measurement of serum immunoglobulins: a national survey of practice

Aim  To survey how serum immunoglobulins (IgG, IgA, IgM) are measured and reported across public hospitals in Ireland.  Methods  We developed a seven-point questionnaire to elicit the methodology, reporting and reference intervals of serum immunoglobulins. It was distributed electronically by email to sixteen laboratory managers of Irish public hospitals.  Results  A total of twelve questionnaires were completed. The test method was the same in each laboratory, whilst the analyser and source of the reference intervals varied. In some institutions, the reference interval differed within the adult age population and for sex. The IgG parameter contained the highest spread of results. The lower reference limit ranged 5.4-8.0 g/L, with a standard deviation of 0.81, and the upper reference limit ranged 14.9-18.2 g/L (SD 1.04).  Conclusion  Considerable variation exists in the reference intervals of serum immunoglobulins within different Irish public hospitals. This has important implications for users of the test, patients and referral patterns.</p

Undertaking a Collaborative Rapid Realist Review to Investigate What Works in the Successful Implementation of a Frail Older Person’s Pathway

We addressed the research question “what factors enable the successful development and implementation of a frail older person’s pathway within the acute setting”. A rapid realist review (RRR) was conducted by adopting the RAMESES standards. We began with a sample of 232 articles via database searches supplemented with 94 additional records including inputs from a twitter chat and a hospital site visit. Our final sample consisted of 18 documents. Following review and consensus by an expert panel we identified a conceptual model of context-mechanism-(resources)-outcomes. There was overall agreement frailty should be identified at the front door of the acute hospital. Significant challenges identified related to organisational boundaries both within the acute setting and externally, the need to shift outcomes to patient orientated ones, to support staff to sustain the pathway by providing ongoing education and by providing role clarity. RRRs can support research such as the systematic approach to improving care for frail older adults (SAFE) study by producing accounts of what works based on a wide range of sources and innovative engagement with stakeholders. It is evident from our provisional model that numerous factors need to combine and interact to enable and sustain a successful frail older person’s pathway

Cytomegalovirus Infection in Ireland: Seroprevalence, HLA Class I Alleles, and Implications

Cytomegalovirus (CMV) infections occur worldwide and primary infection usually occurs in early childhood and is often asymptomatic whereas primary infection in adults may result in symptomatic illness. CMV establishes a chronic latent infection with intermittent periods of reactivation. Primary infection or reactivation associate with increased mortality and morbidity in those who are immunocompromised. Transplacental transmission may result in significant birth defects or long-term sensorineural hearing loss. We performed a study to determine the CMV seroprevalence and the association between HLA Class I alleles and frequency of CMV infection in Ireland. The presence of CMV IgG, a marker of previous CMV infection, was determined for a cohort of 1849 HLA typed solid organ transplant donors between 1990 and 2013. The presence of CMV IgG was correlated with HLA type. The CMV seroprevalence in solid organ transplant donors was 33.4% (range 22–48% per annum) over the time period 1990 to 2013. Multivariate logistic regression analysis showed that both age and HLA alleles were associated with CMV seropositivity. A significant and positive relationship between age and CMV seropositivity was observed (OR = 1.013, P < 0.001, CI [1.007, 1.019]). Chi-square analysis revealed that the female gender was independently associated with CMV seropositivity (P < 0.01). Seroprevalence in women of reproductive age (20–39 years) was significantly higher than men of the same age (37% vs 26%, P < 0.01). The frequencies of HLA-A1, HLA-A2, and HLA-A3 in our cohort were 40.8%, 48.8%, and 25.9%, respectively. Logistic regression analysis showed that the presence of HLA-A1 but not HLA-A2 or HLA-A3 was independently associated with CMV seronegativity (P < 0.01). Interestingly, individuals who co-expressed HLA-A2 and HLA-A3 alleles were significantly more likely to be CMV seropositive (P < 0.02). The frequencies of HLA-B5, HLA-B7, and HLA-B8 in our cohort were 6.1%, 31.2%, and 30.8%, respectively. The presence of the most common inherited haplotype in the Irish population, HLA-A1, B8 was significantly associated with CMV seronegativity (OR = 1.278, P < 0.001, CI [1.049, 1.556]). CMV seroprevalence is lower in Ireland compared with other countries. The high frequency of HLA-A1 in the Irish population may, in part, have a role in the reduced susceptibility to CMV infection