Genomic Diagnosis of Rare Pediatric Disease in the United Kingdom and Ireland.

BACKGROUND: Pediatric disorders include a range of highly penetrant, genetically heterogeneous conditions amenable to genomewide diagnostic approaches. Finding a molecular diagnosis is challenging but can have profound lifelong benefits. METHODS: We conducted a large-scale sequencing study involving more than 13,500 families with probands with severe, probably monogenic, difficult-to-diagnose developmental disorders from 24 regional genetics services in the United Kingdom and Ireland. Standardized phenotypic data were collected, and exome sequencing and microarray analyses were performed to investigate novel genetic causes. We developed an iterative variant analysis pipeline and reported candidate variants to clinical teams for validation and diagnostic interpretation to inform communication with families. Multiple regression analyses were performed to evaluate factors affecting the probability of diagnosis. RESULTS: A total of 13,449 probands were included in the analyses. On average, we reported 1.0 candidate variant per parent-offspring trio and 2.5 variants per singleton proband. Using clinical and computational approaches to variant classification, we made a diagnosis in approximately 41% of probands (5502 of 13,449). Of 3599 probands in trios who received a diagnosis by clinical assertion, approximately 76% had a pathogenic de novo variant. Another 22% of probands (2997 of 13,449) had variants of uncertain significance in genes that were strongly linked to monogenic developmental disorders. Recruitment in a parent-offspring trio had the largest effect on the probability of diagnosis (odds ratio, 4.70; 95% confidence interval [CI], 4.16 to 5.31). Probands were less likely to receive a diagnosis if they were born extremely prematurely (i.e., 22 to 27 weeks' gestation; odds ratio, 0.39; 95% CI, 0.22 to 0.68), had in utero exposure to antiepileptic medications (odds ratio, 0.44; 95% CI, 0.29 to 0.67), had mothers with diabetes (odds ratio, 0.52; 95% CI, 0.41 to 0.67), or were of African ancestry (odds ratio, 0.51; 95% CI, 0.31 to 0.78). CONCLUSIONS: Among probands with severe, probably monogenic, difficult-to-diagnose developmental disorders, multimodal analysis of genomewide data had good diagnostic power, even after previous attempts at diagnosis. (Funded by the Health Innovation Challenge Fund and Wellcome Sanger Institute.).

Pharmacists and nurses as independent prescribers: exploring the patient's perspective.

BACKGROUND: Little is known about patients' opinions upon the development of non-medical prescribing (NMP). OBJECTIVE: To explore the opinions of patients on the development of NMP. METHODS: In-depth interviews using qualitative methodology (Interpretative Phenomological Analysis). Eighteen interviews were undertaken in Bristol (Sites 1 and 3), Swindon (Site 2) and Brighton (Site 4). [Site 1 = primary care, GP prescriber (n = 5), Site 2 = secondary care, consultant prescriber (n = 5), Site 3 = primary care (n = 5) and Site 4 = secondary care (n = 3) (both pharmacist supplementary prescribers.] Participants (n = 18) were randomly sampled from patients under the care of the participating prescriber. Participants were aged between 42 and 81 years of age (n = 11 male and n = 7 female). Interviews took place between January and August 2006. RESULTS: Participants expressed concerns about clinical governance, privacy and whether sufficient space were available to provide the service in community pharmacies. Participants acknowledged the expert drug knowledge of pharmacists and their accessibility. These factors enhanced acceptability of this role for pharmacists. Nurses were highly regarded, accepted and preferred as prescribers with few concerns. CONCLUSIONS: The results indicate support for pharmacists and nurses as prescribers, which aid successful implementation. Further research may be needed to evaluate the level of understanding that the public has of NMP and their views of the service once NMP is more widely established. Stakeholders should be mindful that the public may be hesitant regarding the professionalism, quality and clinical governance standards of clinics in community pharmacies in particular.

Supplementary prescribing by pharmacists in England.

PURPOSE: The implementation of supplementary prescribing by pharmacists within primary care trusts (PCTs) and secondary care trusts (SCTs) in England was studied. METHODS: A survey was developed and sent to pharmacists in PCTs and SCTs in England who would oversee the implementation of supplementary prescribing by pharmacists. RESULTS: The response rate was 68% for both surveys. The majority of SCTs and PCTs intended to implement supplementary prescribing by pharmacists by the end of 2005 (57% and 56%, respectively). The majority of SCT respondents did not believe that it would be more difficult to recruit designated medical practitioners to supervise supplementary prescribing training for pharmacists as opposed to nurses (67%, n = 43), whereas the largest group of PCT pharmacists believed it would be (47%, n = 86). Within secondary care, the clinical areas in which pharmacists were intending to work as supplementary prescribers were those where they already had established roles. Within primary care, the main clinical areas for pharmacists were influenced by those areas in the new General Medical Services contract Quality and Outcomes Framework for general practitioners. CONCLUSION: A survey investigating the implementation of supplementary prescribing by pharmacists in England found that there were significantly more barriers to its establishment within primary care than secondary care settings. Within primary care, supplementary prescribing is being implemented to develop new services. Within secondary care, the supplementary prescribing model is more often used to legitimize services already being provided.