Assessment of on-treatment platelet reactivity at high and low shear stress and platelet activation status after the addition of dipyridamole to aspirin in the early and late phases after TIA and ischaemic stroke.

BACKGROUND: Data are limited on the ability of dipyridamole to additionally inhibit platelet function/reactivity in ischaemic cerebrovascular disease (CVD) patients on aspirin. AIMS: To assess inhibition of platelet function/reactivity and platelet activation with dipyridamole in CVD. METHODS: This prospective, observational study assessed TIA/ischaemic stroke patients before (baseline; N = 60), at 14 ±7 days (14d, N = 39) and ≥ 90 days (90d, N = 31) after adding dipyridamole to aspirin. Platelet function/reactivity at high shear stress (PFA-100® C-ADP) and low shear stress (VerifyNow® P2Y12 and Multiplate® ADP assays), and platelet activation status (% expression of CD62P, CD63 and leucocyte-platelet complexes on whole blood flow cytometry) were quantified. 'Dipyridamole-high on-treatment platelet reactivity (HTPR)' was defined as failure to inhibit ADP-induced platelet aggregation +/- adhesion compared with the patient's baseline on aspirin monotherapy by more than twice the coefficient-of-variation of the assay after adding dipyridamole to aspirin. RESULTS: Dipyridamole-HTPR was identified in 71.4-75% of patients on PFA-100 C-ADP, 83.9-86.8% of patients on VerifyNow P2Y12, and 81.5-83.3% of patients on Multiplate ADP assays. There were no changes in CD62P/CD63 expression (P ≥ 0.18), or consistent changes in leucocyte-platelet complexes in CVD patients overall at 14d or 90d vs. baseline after commencing dipyridamole. Monocyte-platelet complexes increased in the patient subgroup with dipyridamole-HTPR at 14d and 90d on PFA-100, and at 14d on VerifyNow (P ≤ 0.04), but not in those without dipyridamole-HTPR. DISCUSSION: Additional antiplatelet effects of dipyridamole are detectable under high and low shear stress conditions with user-friendly platelet function/reactivity tests ex vivo. Increasing circulating monocyte-platelet complexes over time are associated with dipyridamole-HTPR.

Profile of reticulated platelets in the early, subacute and late phases after transient ischemic attack or ischemic stroke.

Information regarding the profile of reticulated platelets (RP) in ischemic cerebrovascular disease (CVD) patients is limited. Data from two prospective, observational, case-control studies were combined to compare the %RP using whole blood flow cytometry in patients ≤ 4 weeks of TIA/stroke onset (baseline, N = 210), and 14 ±7 days (14d, N = 182) and ≥ 90 days (90d, N = 145) after starting or changing antiplatelet therapy with healthy controls (N = 34). There were no differences in median %RP between the overall CVD patient population at baseline or 14d vs. controls (P ≥ 0.2). However, the median %RP was significantly higher in CVD patients overall at 90d (P = .036), and in the subgroup of patients with "lacunar" TIA/ischemic stroke at baseline (P = .04) and at 90d (P = .01), but not at 14d (P = .06) vs. controls. There were no significant differences in the median %RP between other TIA/stroke subgroups and controls (P ≥ 0.05). Elevated circulating reticulated platelets, as a marker of increased platelet production/turnover, may occur following an ischemic event in a well-phenotyped TIA/ischemic stroke population overall, but may precede symptom onset at least in the subgroup with small vessel occlusion. These data improve our understanding of the profile of reticulated platelets in CVD patients.

Relationship between 'on-treatment platelet reactivity', shear stress, and micro-embolic signals in asymptomatic and symptomatic carotid stenosis.

BACKGROUND: Assessment of 'high on-treatment platelet reactivity (HTPR)' could enhance understanding of the pathophysiology of first or recurrent vascular events in carotid stenosis patients on antiplatelet therapy. METHODS: This prospective, multi-centre study assessed antiplatelet-HTPR status and its relationship with micro-emboli signals (MES) in asymptomatic vs. symptomatic ≥ 50-99% carotid stenosis. Platelet function/reactivity was assessed under 'moderately high shear stress' with the PFA-100® and 'low shear stress' with VerifyNow® and Multiplate® analysers. Bilateral 1-h transcranial Doppler ultrasound of the middle cerebral arteries classified patients as MES + ve or MES - ve. RESULTS: Data from 34 asymptomatic patients were compared with 43 symptomatic patients in the 'early phase' (≤ 4 weeks) and 37 patients in the 'late phase' (≥ 3 months) after TIA/ischaemic stroke. Median daily aspirin doses were higher in early symptomatic (225 mg; P < 0.001), but not late symptomatic (75 mg; P = 0.62) vs. asymptomatic patients (75 mg). There was a lower prevalence of aspirin-HTPR in early (28.6%; P = 0.028), but not late symptomatic (38.9%; P = 0.22) compared with asymptomatic patients (56.7%) on the PFA-100®, but not on the VerifyNow® or Multiplate® (P ≤ 0.53). Early symptomatic patients had a higher prevalence of aspirin-HTPR on the PFA-100® (28.6%) vs. VerifyNow® (9.5%; P = 0.049), but not Multiplate® assays (11.9%, P = 0.10). There was no difference in aspirin-HTPR prevalence between any symptomatic vs. asymptomatic MES + ve or MES - ve subgroup. DISCUSSION: Recently symptomatic moderate-severe carotid stenosis patients had a lower prevalence of aspirin-HTPR than their asymptomatic counterparts on the PFA-100®, likely related to higher aspirin doses. The prevalence of antiplatelet-HTPR was positively influenced by higher shear stress levels, but not MES status.

Safety aspects of riding with children: Descriptive analysis of adult riders' self-report.

Active transport, including cycling, is promoted as an effective way of increasing children's physical activity and health. Parents can support children's riding by riding with them and it is important to address relevant safety issues. Little is known about parents' experience of safety-relevant aspects of riding with children. Participants in the Safer Cycling Study in New South Wales, Australia, who reported that they had ridden with children in the last 12 months were questioned about how they ride with children, and their experience of safety issues and crashes. Among the 187 respondents who had ridden with children on their bicycle, the most common form of carrier was a rear-mounted seat (48%) followed by a trailer (29%). Many respondents (79%) identified risks specific to riding carrying children, including those linked with specific carrier types and with use of footpaths. Most (92%) indicated that they change their behaviour when carrying a child on their bicycle; for example, riding more slowly, more carefully, and away from roads. Among crashes with a child on the bicycle, most were falls. Among the 345 participants who had ridden to accompany a child on a bicycle, approximately three quarters identified risks specific to accompanying children, such as managing the child's limited skill, awareness and predictability. Ninety-seven percent reported behavioural changes including positioning themselves as a barrier for their child and caution crossing roads. Findings suggest strategies to support parents in riding safely with children.

Autosomal Dominant Gene Negative Frontotemporal Dementia-Think of SCA17.

SCA 17 is a rare, autosomal dominant disorder caused by TBP gene CAG/CAA repeat expansion. Ataxia and dementia are common. The presence of frontal dysfunction at outset of the disease may mimic frontotemporal dementia (FTD). Parkinsonism, chorea, dystonia, and pyramidal signs may occur. We report an Irish family with autosomal dominant partially penetrant frontal dementia with cerebellar atrophy due to SCA17 and present detailed neuropsychological assessment for the first time. A 44-year-old doctor presented with 18-month history of behavioral problems. She slowed down, became apathetic, and unable to multitask. She became more irritable and short tempered, and her work performance deteriorated. Brain MRI showed cerebellar atrophy and cerebellar hypometabolism was noted on FDG-PET. A sister developed personality changes at age 45 with apathy, and had problems with memory and social skills; another sister at age 39 became dysarthric and unsteady. A brother at age 52 demonstrated emotional lability, and became dysarthric, unsteady, and slowed down. Their mother aged 73 had an abnormal antalgic gait due to arthritis; their father was jocular and disinhibited. MAPT testing detected an exon 9 c.726C>T variant in the proband. Subsequent testing in nine siblings and both parents failed to show co-segregation with disease. SCA17 testing revealed a TBP gene 43 repeat expansion that co-segregated in all affected siblings and in the mother whose gait problems were initially attributed to arthritis. In over 80% of cases of FTD with clear autosomal dominant inheritance, causative gene defects involve MAPT, GRN, or C9orf72 mutations. A minority involves VCP, FUS, and CHMP2B. As evident from our case, SCA17 testing should also be considered, especially if cerebellar atrophy if found on imaging. Segregation analysis is crucial. MAPT variant (c.726C>T exon 9) detected in the family was deemed a polymorphism.

Student health and well-being in secondary schools: the role of school support staff alongside teaching staff.

A growing evidence base indicates that health and educational attainment are synergistic goals. Students' relationships with teachers and other students in the school environment are consistently predictive of a broad range of health and well-being outcomes. Despite the potential importance of relationships between students and a broad range of actors within a school, research tends to reduce 'school staff' to 'teachers'. Previous research has highlighted incongruence between the power imbalance within a teacher-student relationship and the dynamics required to address health and well-being-related issues. To date, there has been no investigation into how the nature of the relationships between students and support staff may differ from those with teaching staff. This article aims to conceptualise the role of support versus teaching staff in promoting health and well-being to understand how school system functioning may affect relationships between school staff and students. Semi-structured interviews were conducted to obtain the perceptions of staff, students and parents within four exploratory case study schools of differing socio-economic status, geographical location and size. In line with the Theory of Health Promoting Schools and Human Functioning, findings demonstrated that the prominence of well-being relies on provision of staffing structures which include a team of support staff to work alongside teaching staff to provide the time and space to deal with issues immediately and build trust and rapport in a one-to-one setting. Further mixed-methods research is required to investigate how staffing structures can facilitate the development of mutually trusting relationships between staff and students.

Health-related quality of life, surgical and aesthetic outcomes following microvascular free flap reconstructions: an 8-year institutional review.

INTRODUCTION: Microvascular free flap reconstruction has revolutionised the reconstruction of complex defects of traumatic, oncological, congenital and infectious aetiologies. Complications of microvascular free flap procedures impact negatively on patient post-operative course and outcome. METHODS: We performed a retrospective analysis of 102 consecutive patients undergoing 108 free flap procedures at a tertiary referral centre over an 8-year period. Logistic regression analysis was used to identify factors predictive of free flap complications. Health-related quality of life (HRQoL) and aesthetic outcomes were assessed using the Short Form 36 questionnaire and a satisfaction visual analogue scale respectively. RESULTS: In total, 108 free tissue transfers were performed; 23% were fasciocutaneous free flaps, 69% musculocutaneous and 8% osteoseptocutaneous. The overall flap success rate was 92.6%. Over a third of patients (34.3%) had flap-related complications ranging from minor wound dehiscence to total flap loss. ASA (American Society of Anesthesiologists) grade ≥2 (OR: 16.9, 95% CI: 15.3-18.1, p<0.009), history of smoking (OR: 6.1, 95% CI: 5.5-7.2, p<0.049), body mass index ≥25 kg/m(2) (OR: 21.3, 95% CI: 20.8-22.1, p<0.003), low albumin (odds ratio [OR]: 2.2, 95% confidence interval [CI]: 1.2-3.9, p<0.003) and peripheral vascular disease (OR: 6.9, 95% CI: 5.9-7.5, p<0.036) were identified as factors independently predictive of free flap complications. CONCLUSIONS: Patients undergoing uncomplicated free flap surgery and those reporting superior post-operative flap aesthesis have higher HRQoL scores. Microvascular free tissue transfer has revolutionised our approach to the reconstruction of complex defects, providing a safe, reliable procedure to restore functionality and quality of life for patients.

Hand weakness in Charcot-Marie-Tooth disease 1X.

There have been suggestions from previous studies that patients with Charcot-Marie-Tooth disease (CMT) have weaker dominant hand muscles. Since all studies to date have included a heterogeneous group of CMT patients we decided to analyse hand strength in 43 patients with CMT1X. We recorded handedness and the MRC scores for the first dorsal interosseous and abductor pollicis brevis muscles, median and ulnar nerve compound motor action potentials and conduction velocities in dominant and non-dominant hands. Twenty-two CMT1X patients (51%) had a weaker dominant hand; none had a stronger dominant hand. Mean MRC scores were significantly higher for first dorsal interosseous and abductor pollicis brevis in non-dominant hands compared to dominant hands. Median nerve compound motor action potentials were significantly reduced in dominant compared to non-dominant hands. We conclude that the dominant hand is weaker than the non-dominant hand in patients with CMT1X.

Frequency of mutations in the genes associated with hereditary sensory and autonomic neuropathy in a UK cohort.

The hereditary sensory and autonomic neuropathies (HSAN, also known as the hereditary sensory neuropathies) are a clinically and genetically heterogeneous group of disorders, characterised by a progressive sensory neuropathy often complicated by ulcers and amputations, with variable motor and autonomic involvement. To date, mutations in twelve genes have been identified as causing HSAN. To study the frequency of mutations in these genes and the associated phenotypes, we screened 140 index patients in our inherited neuropathy cohort with a clinical diagnosis of HSAN for mutations in the coding regions of SPTLC1, RAB7, WNK1/HSN2, FAM134B, NTRK1 (TRKA) and NGFB. We identified 25 index patients with mutations in six genes associated with HSAN (SPTLC1, RAB7, WNK1/HSN2, FAM134B, NTRK1 and NGFB); 20 of which appear to be pathogenic giving an overall mutation frequency of 14.3%. Mutations in the known genes for HSAN are rare suggesting that further HSAN genes are yet to be identified. The p.Cys133Trp mutation in SPTLC1 is the most common cause of HSAN in the UK population and should be screened first in all patients with sporadic or autosomal dominant HSAN.

Health-related quality of life and functional outcomes following nerve transfers for traumatic upper brachial plexus injuries.

We report the patient-scored Health-Related Quality of Life (HRQoL) and functional outcomes of a cohort of 21 consecutive patients undergoing nerve transfer surgery for traumatic upper brachial plexus injuries. Outcomes were assessed using the British Medical Research Council power grading system, Short-Form 36, Disability of Arm, Shoulder and Hand questionnaire, and Pain Visual Analogue Scale (PVAS). The mean age of our cohort was 29.8 years (range 18-53 years), with a mean follow-up period of 42.9 months. At follow-up, elbow flexion ≥ M3 strength was achieved in 17/21 patients. Shoulder abduction ≥ M3 was achieved in 14/19 patients. External rotation ≥ M3 strength was achieved in 11/15 patients. Delayed surgical repair correlated negatively with HRQoL outcomes. Higher injury severity scores and smoking were associated with higher PVAS scores. These findings provide key prognostic information for patients and peripheral nerve surgeons embarking upon this intensive pathway to potential recovery.

Image-guided transnasal cryoablation of a recurrent nasal adenocarcinoma in a dog.

An eight-year-old female spayed Airedale terrier with rapid recurrence of a nasal adenocarcinoma following image-guided intensity-modulated radiation therapy was treated with transnasal, image-guided cryotherapy. Ice ball size and location were monitored real-time with computed tomography-fluoroscopy to verify that the entire tumour was enveloped in ice. Serial computed tomography scans demonstrated reduction in and subsequent resolution of the primary tumour volume corresponding visually with the ice ball imaged during the ablation procedure. Re-imaging demonstrated focallysis of the cribriform plate following ablation that spontaneously resolved by 13 months. While mild chronic nasal discharge developed following cryoablation, no other clinical signs of local nasal neoplasia were present. Twenty-one months after nasal tumour cryoablation the dog was euthanased as a result of acute haemoabdomen. Image-guided cryotherapy may warrant further investigation for the management of focal residual or recurrent tumours in dogs, especially in regions where critical structures preclude surgical intervention.

The trauma of a recession.

Employment in construction in Ireland fell by 10% from nearly 282,000 in the second quarter of 2007 to 255,000 in the same period of 2008. Our study looks at the differences in soft tissue upper limb trauma dynamics of a pre- and post-recession Ireland. Construction accounted for 330 patients (27%) of all hand injuries in 2006, but only 18 (3%) in 2009. Our data shows a significant drop in hand injuries related to the construction industry, and more home/DIY cases and deliberate self-harm presenting in their stead.

Contribution of isoprene-derived organosulfates to free tropospheric aerosol mass.

Recent laboratory studies have demonstrated that isoprene oxidation products can partition to atmospheric aerosols by reacting with condensed phase sulfuric acid, forming low-volatility organosulfate compounds. We have identified organosulfate compounds in free tropospheric aerosols by single particle mass spectrometry during several airborne field campaigns. One of these organosulfates is identified as the sulfate ester of IEPOX, a second generation oxidation product of isoprene. The patterns of IEPOX sulfate ester in ambient data generally followed the aerosol acidity and NO(x) dependence established by laboratory studies. Detection of the IEPOX sulfate ester was most sensitive using reduced ionization laser power, when it was observed in up to 80% of particles in the tropical free troposphere. Based on laboratory mass calibrations, IEPOX added > 0.4% to tropospheric aerosol mass in the remote tropics and up to 20% in regions downwind of isoprene sources. In the southeastern United States, when acidic aerosol was exposed to fresh isoprene emissions, accumulation of IEPOX increased aerosol mass by up to 3%. The IEPOX sulfate ester is therefore one of the most abundant single organic compounds measured in atmospheric aerosol. Our data show that acidity-dependent IEPOX uptake is a mechanism by which anthropogenic SO(2) and marine dimethyl sulfide emissions generate secondary biogenic aerosol mass throughout the troposphere.

Unnecessary inter-hospital referral of minor hand injuries: a continuing problem.

BACKGROUND: Trauma patients are a burden on resources in terms of personnel, operating time and bed occupancy. The plastic surgery trauma clinic was established in January 1999 and has been running Monday to Friday mornings from 9 am to 1 pm since its establishment. AIM: To analyse and compare referral patterns to the Plastic Surgery trauma clinic over three time periods. METHOD: Three time groups were analysed and compared: data from this initial study (2000-2001), a retrospective chart review (2002-2003), as well as a prospective study (2006-2007). RESULTS: Numbers of attendances at the Trauma Clinic seem to be increasing every year despite encouragement by letter after the initial study for local centres to treat many of the minor injuries not requiring plastic surgical skills. CONCLUSION: Admission rates have remained below 50% of the patients seen in the clinic; however 50% of patients required only local anaesthetic procedures performed in the clinic, or no treatment at all (27.6% of patients in 2003, 35.3% in 2006).

Counting the cost of complementary and alternative therapies in an Irish neurological clinic.

BACKGROUND AND PURPOSE: Complementary and alternative therapy (CAT) use is frequent in patients with the common neurological disorders despite little scientific evidence of its efficacy. Little is known about the cost of regular CAT use. The purposes of this study were to determine the frequency and cost of CAT use in patients attending a neurology out-patient clinic and to determine whether neurological diagnosis affects CAT use. METHODS: All patients attending the neurology out-patient clinic were asked to complete a structured questionnaire which included demographic information, details on the underlying neurological diagnosis, use and cost of CAT. RESULTS: Six hundred and seventy-one patients completed the questionnaire. Over 60% of the patients had used CAT, and 25% used CAT on a regular basis. Only 25% of patients using CAT had informed their doctor. Rates of CAT use varied with neurological diagnosis. Of those using CAM on a regular basis, the mean annual cost was Euro 1351. CONCLUSION: Patients attending our neurology out-patient department use CAT frequently and often do not inform their doctor. Patients spend a significant amount of personal income on CAT. Given the implications, including potential interactions with prescribed medication, these findings should prompt doctors to ask every patient about CAT use.