http://hdl.handle.net/10468/453 2013-05-24T21:40:42Z http://hdl.handle.net/10468/890 Mapping the gene for autosomal dominant restless legs syndrome in an Irish family Skehan, Evelyn B. Restless Legs Syndrome (RLS) is a common neurological disorder affecting nearly 15% of the general population. Ironically, RLS can be described as the most common condition one has never heard of. It is usually characterised by uncomfortable, unpleasant sensations in the lower limbs inducing an uncontrollable desire to move the legs. RLS exhibits a circadian pattern with symptoms present predominantly in the evening or at night, thus leading to sleep disruption and daytime somnolence. RLS is generally classified into primary (idiopathic) and secondary (symptomatic) forms. Primary RLS includes sporadic and familial cases of which the age of onset is usually less than 45 years and progresses slowly with a female to male ratio of 2:1. Secondary forms often occur as a complication of another health condition, such as iron deficiency or thyroid dysfunction. The age of onset is usually over 45 years, with an equal male to female ratio and more rapid progression. Ekbom described the familial component of the disorder in 1945 and since then many studies have been published on the familial forms of the disorder. Molecular genetic studies have so far identified ten loci (5q, 12q, 14p, 9p, 20p, 16p, 19p, 4q, 17p). No specific gene within these loci has been identified thus far. Association mapping has highlighted a further five areas of interest. RLS6 has been found to be associated with SNPs in the BTBD9 gene. Four other variants were found within intronic and intergenic regions of MEIS1, MAP2K5/LBXCOR1, PTPRD and NOS1. The pathophysiology of RLS is complex and remains to be fully elucidated. Conditions associated with secondary RLS, such as pregnancy or end-stage renal disease, are characterised by iron deficiency, which suggests that disturbed iron homeostasis plays a role. Dopaminergic dysfunction in subcortical systems also appears to play a central role. An ongoing study within the Department of Pathology (University College Cork) is investigating the genetic characteristics of RLS in Irish families. A three generation RLS pedigree RLS3002 consisting of 11 affected and 7 unaffected living family members was recruited. The family had been examined for four of the known loci (5q, 12q, 14p and 9p) (Abdulrahim 2008). The aim of this study was to continue examining this Irish RLS pedigree for possible linkage to the previously described loci and associated regions. Using informative microsatellite markers linkage was excluded to the loci on 5q, 12q, 14p, 9p, 20p, 16p, 19p, 4q, 17p and also within the regions reported to be associated with RLS. This suggested the presence of a new unidentified locus. A genome-wide scan was performed using two microsatellite marker screening sets (Research Genetics Inc. Mapping set and the Applied Biosystems Linkage mapping set version 2.5). Linkage analysis was conducted under an autosomal dominant model with a penetrance of 95% and an allele frequency of 0.01. A maximum LOD score of 3.59 at θ=0.00 for marker D19S878 indicated significant linkage on chromosome 19p. Haplotype analysis defined a genetic region of 6.57 cM on chromosome 19p13.3, corresponding to 2.5 Mb. There are approximately 100 genes annotated within the critical region. Sequencing of two candidate genes, KLF16 and GAMT, selected on the assumed pathophysiology of RLS, did not identify any sequence variant. This study provides evidence of a novel RLS locus in an Irish pedigree, thus supporting the picture of RLS as a genetically heterogeneous trait. 2010-10-01T00:00:00Z http://hdl.handle.net/10468/465 Warfarin prevalence, indications for use and haemorrhagic events Ouirke, William; Cahill, Mary R.; Perera, Kanthi; Sargent, Jeremy; Conway, Jane Warfarin, the standard oral anticoagulant drug used in Ireland, is a widely prescribed medication, particularly in the elderly. A HSE Mid-Western Area wide audit was undertaken over a 12-month period to examine the prevalence and indications for warfarin use and haemorrhagic complications associated with the drug. Every patient receiving warfarin therapy over a 13-week period was included (2564). The age standardised rate varied from 0.09% of 35-39 year olds to 6.1% of 80-84 year olds. Atrial fibrillation was the most common indication (54%) in patients attending the Mid-Western Regional Hospital anticoagulation clinic. The annual cumulative incidence of adverse haemorrhagic events in patients with a recorded INR > or = 5.0 episode was 16.6%. The incidence of major and minor haemorrhagic events per INR > or = 5.0 episode was 1.3% and 15.3% respectively. The most common sites of haemorrhage were genitourinary (39%) and gastrointestinal (27%). No fatal or intracranial haemorrhage relating to episodes of over-anticoagulation were reported during the audit period. The most frequent reason for over-anticoagulation was drug interaction (43%). In 74% of patients, the elevated INR was reversed by omitting or reducing warfarin dose. In 17% of cases, vitamin K was administered. Only 3% of incidents were treated with fresh frozen plasma or prothrombin complex concentrates.Warfarin, the standard oral anticoagulant drug used in Ireland, is a widely prescribed medication, particularly in the elderly. A HSE Mid-Western Area wide audit was undertaken over a 12-month period to examine the prevalence and indications for warfarin use and haemorrhagic complications associated with the drug. Every patient receiving warfarin therapy over a 13-week period was included (2564). The age standardised rate varied from 0.09% of 35-39 year olds to 6.1% of 80-84 year olds. Atrial fibrillation was the most common indication (54%) in patients attending the Mid-Western Regional Hospital anticoagulation clinic. The annual cumulative incidence of adverse haemorrhagic events in patients with a recorded INR > or = 5.0 episode was 16.6%. The incidence of major and minor haemorrhagic events per INR > or = 5.0 episode was 1.3% and 15.3% respectively. The most common sites of haemorrhage were genitourinary (39%) and gastrointestinal (27%). No fatal or intracranial haemorrhage relating to episodes of over-anticoagulation were reported during the audit period. The most frequent reason for over-anticoagulation was drug interaction (43%). In 74% of patients, the elevated INR was reversed by omitting or reducing warfarin dose. In 17% of cases, vitamin K was administered. Only 3% of incidents were treated with fresh frozen plasma or prothrombin complex concentrates. 2007-03-01T00:00:00Z http://hdl.handle.net/10468/469 Writing to patients: a randomised controlled trial O'Reilly, Máire; Cahill, Mary R.; Perry, Ivan J. It has been suggested that consultants should consider writing directly to patients with a summary of their outpatient consultation. In a controlled trial involving consecutive new referrals to a haematology outpatient clinic, we randomised patients to receive either a personal letter from their consultant summarising their consultation (n = 77) or a brief note thanking them for attending the clinic (n = 73). Patients were assessed for recall of and satisfaction with the consultation by a single independent observer, using standardised methods. At the second visit to outpatients, the patients' median percentage recall of items discussed during the consultation was 67% (IQ range 50-80%) in the intervention group, versus 57% (IQ range 43-76%) in the control group (p = 0.3). Strongly positive views on the personal letter were expressed by patients and referring clinicians. The findings suggest that although personal letters do not substantially improve recall of the clinical encounter, they are feasible, highly valued by patients and acceptable to referring clinicians. 2006-03-01T00:00:00Z http://hdl.handle.net/10468/92 Writing to patients: 'putting the patient in the picture' O'Reilly, Máire; Cahill, Mary R.; Perry, Ivan J. We have explored consultant, general practitioner and patient attitudes towards the proposal that following an outpatient consultation, consultants should consider communicating directly with patients in the form of a summary letter, with a copy to the referring general practitioner or other professionals as appropriate. We conducted in-depth interviews with a purposive sample of 20 consultants, 16 patients and 12 general practitioners. The consultants and general practitioners were both involved in the care of participating patients. Patients highlighted the likely value of summary letters including, increased knowledge, improvement recall of the clinical encounter, and reassurance. Clinicians were concerned that patients would not understand letters from consultants. Additional concerns included the impact of letter on consultant-general practitioner relationship and medico-legal issues. These findings reflect fundamental differences in expectations about the nature and quality of communications between doctors and their patients. 2005-02-01T00:00:00Z