Experience with botulinum toxin therapy for axillary hyperhidrosis and comparison to modelled data for endoscopic thoracic sympathectomy - A quality of life and cost effectiveness analysis.

AIM: To estimate cost-effectiveness of botulinum toxin therapy for axillary hyperhidrosis compared to the standard surgical intervention of endoscopic thoracic sympathectomy (ETS). METHODS: The validated dermatology life quality index questionnaire was given to patients attending for treatment over a 4 month period, to assess their quality of life (QoL) over the preceding week (n = 44). Follow-up was performed 4-6 weeks later by telephone using the same questionnaire to validate the effectiveness of the treatment. The duration of effect of the botulinum toxin treatment was also recorded and this data was used as the basis for cost effectiveness analysis. Using HIPE data, the baseline cost for single intervention using botulinum toxin and ETS was retrieved. Using figures provided by HIPE and expert opinion of the costs of complications, a stochastic model for 10,000 patients was used to evaluate the total costs for ETS including the complications. RESULTS: The results from the QoL analysis show that botulinum toxin therapy is a successful therapy for improvement of symptoms. It was revealed that the mean interval before recurrence of original symptoms after botulinum toxin therapy was 5.6 months. The baseline cost for both treatments are €389 for botulinum toxin and €9389 for uncomplicated ETS. The stochastic model yields a mean cost of €11,390 for ETS including complications. CONCLUSIONS: Treatments reached cost equivalence after 13.3 years. However, given the efficacy of the botulinum toxin therapy and the low risk we propose that botulinum toxin therapy for hyperhidrosis should be considered the gold standard.

Frequency of inter-specialty consensus decisions and adherence to advice following discussion at a weekly neurovascular multidisciplinary meeting.

BACKGROUND/AIMS: Data are limited on the frequency of 'consensus decisions' between sub-specialists attending a neurovascular multidisciplinary meeting (MDM) regarding management of patients with extracranial carotid/vertebral stenoses and post-MDM 'adherence' to such advice. METHODS: This prospective audit/quality improvement project collated prospectively-recorded data from a weekly Neurovascular/Stroke Centre MDM documenting the proportion of extracranial carotid/vertebral stenosis patients in whom 'consensus management decisions' were reached by neurologists, vascular surgeons, stroke physicians-geriatricians and neuroradiologists. Adherence to MDM advice was analysed in asymptomatic carotid stenosis (ACS), symptomatic carotid stenosis (SCS), 'indeterminate symptomatic status stenosis' (ISS) and vertebral artery stenosis (VAS) patients, including intervals between index event to MDM + / - intervention. RESULTS: One hundred fifteen patients were discussed: 108 with carotid stenosis and 7 with VAS. Consensus regarding management was noted in 96.5% (111/115): 100% with ACS and VAS, 96.2% with SCS and 92.9% with ISS. Adherence to MDM management advice was 96.4% (107/111): 100% in ACS, ISS and VAS patients; 92% (46/50) in SCS patients. The median interval from index symptoms to revascularisation in 50-99% SCS patients was 12.5 days (IQR: 9-18.3 days; N = 26), with a median interval from MDM to revascularisation of 5.5 days (IQR: 1-7 days). Thirty patients underwent revascularisation. Two out of twenty-nine patients (6.9%) with either SCS or ISS had a peri-procedural ipsilateral ischaemic stroke, with no further strokes/deaths during 3-months follow-up. CONCLUSIONS: The high frequency of inter-specialty consensus regarding management and adherence to proposed treatment supports a collaborative/multidisciplinary model of care in patients with extracranial arterial stenoses. Service development should aim to shorten times between MDM discussion-intervention and optimise prevention of stroke/death.

Re-amputation and survival following toe amputation: outcome data from a tertiary referral centre.

PURPOSE: Toe amputation is a commonly performed procedure for irreversible foot sepsis. However, outcome and predictors of outcome are poorly understood. Our aim was to determine survival and rate of progression to further amputation following index toe amputation. METHODS: Consecutive patients between 2010 and 2015 were included. Progression to further minor amputation, major amputation or death was recorded. Multivariable Cox regression analyses were undertaken to determine independent predictors of outcome and survival. RESULTS: One hundred forty-six patients were included, with mean age of 65 years. Fifty-five (37.7%) patients underwent hallux amputation, while 91 (62.3%) underwent amputation of non-hallux digit(s). Following index toe amputation, 63 (43.2%) patients progressed to further minor or major ipsilateral amputation, median time to which was 36 months. Twenty-one patients (14.4%) progressed to major ipsilateral amputation. Patients undergoing index non-hallux amputation were significantly more likely to require further minor amputation (P = 0.050); however, the rate of major amputation between hallux (14.5%) and non-hallux (14.3%) groups was similar. Overall, 5-year ipsilateral amputation-free (iAFS) was 39.6 ± 4.1%, ipsilateral major amputation-free (iMAFS) was 55.9 ± 4.1% and overall survival (OS) was 64.3 ± 4.0% and did not differ between index amputation sites. CONCLUSION: Almost half of patients undergoing toe amputation required further digital amputation. However, limb preservation rates are high, and a majority of patients are alive at 5-year follow-up. There was no significant difference in outcome between patients undergoing hallux and non-hallux primary procedures. Overall, increasing age remains the only independent predictor of iMAFS and OS.

Enhanced ex vivo inhibition of platelet function following addition of dipyridamole to aspirin after transient ischaemic attack or ischaemic stroke: first results from the TRinity AntiPlatelet responsiveness (TrAP) study.

Ex vivo dipyridamole 'non-responsiveness' has not been extensively studied in ischaemic cerebrovascular disease. Platelet surface marker expression, leucocyte-platelet complex formation and inhibition of platelet function at high shear stress as detected by the PFA-100® Collagen-Adenosine-diphosphate (C-ADP) and Collagen-Epinephrine cartridges was assessed in 52 patients within 4 weeks of transient ischaemic attack (TIA) or ischaemic stroke on aspirin, and then 14 d (14 d) and >90 d (90 d) after adding dipyridamole. A novel definition of 'Dipyridamole non-responsiveness' was used. The median C-ADP closure time increased following addition of dipyridamole, remained elevated at 90 d (P ≤ 0·03), and was unaffected by aspirin dose. 59% at 14 d and 56% at 90 d were 'dipyridamole non-responders' on the PFA-100. The proportion of non-responders at 14 and 90 d was similar (P= 0·9). Compared with baseline (4·6%), median monocyte-platelet complexes increased at 14 d (5·0%, P= 0·03) and 90 d (4·9%, P= 0·04). Low C-ADP closure times were associated with increased monocyte-platelet complexes at 14 d (r= -0·32, P= 0·02) and 90 d (r= -0·33, P = 0·02). Monocyte-platelet complexes increased in the subgroup of dipyridamole non-responders on the PFA-100 (P≤ 0·045), but not in responders (P ≥ 0·5), at 14 and 90 d versus baseline. Additional inhibition of platelet function has been detected with the PFA-100 when dipyridamole is added to aspirin. Elevated monocyte-platelet complexes may contribute to ex vivo dipyridamole non-responsiveness.

von Willebrand Factor Antigen, von Willebrand Factor Propeptide, and ADAMTS13 in Carotid Stenosis and Their Relationship with Cerebral Microemboli.

BACKGROUND: The relationship between von Willebrand factor antigen (VWF:Ag), VWF propeptide (VWFpp), VWFpp/VWF:Ag ratio, ADAMTS13 activity, and microembolic signal (MES) status in carotid stenosis is unknown. METHODS: This prospective, multicenter study simultaneously assessed plasma VWF:Ag levels, VWFpp levels and ADAMTS13 activity, and their relationship with MES in asymptomatic versus symptomatic moderate-to-severe (≥50-99%) carotid stenosis patients. One-hour 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 transient ischemic attack (TIA)/ischemic stroke. VWF:Ag levels were higher (p = 0.049) and VWFpp/VWF:Ag ratios lower (p = 0.006) in early symptomatic than in asymptomatic patients overall, and in early symptomatic versus asymptomatic MES-ve subgroups (p ≤0.02). There were no intergroup differences in VWFpp expression or ADAMTS13 activity (p ≥0.05). VWF:Ag levels and ADAMTS13 activity decreased (p ≤ 0.048) and VWFpp/VWF:Ag ratios increased (p = 0.03) in symptomatic patients followed up from the early to late phases after TIA/stroke. Although there were no differences in the proportions of symptomatic and asymptomatic patients with blood group O, a combined analysis of early symptomatic and asymptomatic patients revealed lower median VWF:Ag levels in patients with blood group O versus those without blood group O (9.59 vs. 12.32 µg/mL, p = 0.035). DISCUSSION: VWF:Ag expression, a marker of endothelial ± platelet activation, is enhanced in recently symptomatic versus asymptomatic carotid stenosis patients, including in MES-ve patients, and decreases with ADAMTS13 activity over time following atherosclerotic TIA/ischemic stroke.

Simultaneous assessment of plaque morphology, cerebral micro-embolic signal status and platelet biomarkers in patients with recently symptomatic and asymptomatic carotid stenosis.

The relationship between plaque morphology, cerebral micro-embolic signals (MES) and platelet biomarkers in carotid stenosis patients warrants investigation.We combined data from two prospective, observational studies to assess carotid plaque morphology and relationship with cerebral MES and platelet biomarkers in patients with recently symptomatic (≤4 weeks of transient ischaemic attack (TIA)/ischaemic stroke) versus asymptomatic carotid stenosis. Plaque morphology on ultrasound was graded with Grey-Scale Median (GSM) and Gray-Weale (GW) scoring. Bilateral transcranial Doppler ultrasound classified patients as 'MES+ve' or 'MES-ve'. Full blood counts were analysed and flow cytometry quantified CD62P and CD63 expression, leucocyte-platelet complexes and reticulated platelets.Data from 42 recently symptomatic carotid stenosis patients were compared with those from 36 asymptomatic patients. There were no differences in median GSM scores between symptomatic and asymptomatic patients (25 vs. 30; P = 0.31) or between MES+ve vs. MES-ve symptomatic patients (36 vs. 25; P = 0.09). Symptomatic patients with GSM-echodense plaques (GSM ≥25) had higher platelet counts (228 vs. 191 × 109/L), neutrophil-platelet (3.3 vs. 2.7%), monocyte-platelet (6.3 vs. 4.55%) and lymphocyte-platelet complexes (2.91 vs. 2.53%) than 'asymptomatic patients with GSM-echodense plaques' (P ≤ 0.03).Recently, symptomatic carotid stenosis patients with 'GSM-echodense plaques' have enhanced platelet production/secretion/activation compared with their asymptomatic counterparts. Simultaneous assessment with neurovascular imaging and platelet biomarkers may aid risk-stratification in carotid stenosis.

A systematic review and meta-analysis of comparative studies comparing nonthermal versus thermal endovenous ablation in superficial venous incompetence.

OBJECTIVE: Endovenous thermal ablation (TA) offers an effective initial treatment option for superficial venous incompetence of the lower limb. These techniques offer lower complication rates with similar efficacy to traditional open surgery. In recent years, nonthermal ablation (NTA) in the form of mechanochemical ablation and cyanoacrylate vein ablation has been suggested to further reduce perioperative morbidity. This study aimed to compare the use of both thermal and nonthermal endovenous ablative techniques in the management of superficial venous incompetence. METHODS: A search of online databases including MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, and Cochrane database was last performed in January 2019. Comparative studies comparing NTA with TA were included. The primary outcome was technical success. Secondary outcomes included operative pain, complications, modification of disease severity, and quality of life. RESULTS: Six studies describing the outcomes of 1236 participants and 1256 truncal ablations were included for analysis. Follow-up ranged from 6 weeks to 36 months. With regard to overall technical success, 458 of 483 (94.8%) receiving NTA and 521 of 553 (94.2%) undergoing TA had successful truncal ablation on follow-up ultrasound imaging at the study end point (pooled risk ratio, 1.01; 95% confidence interval [CI], 0.99-1.04). Subgroup analysis identified no difference in success between groups during immediate, 6-month, 12-month, or >12-month follow-up periods. Postprocedural pain was generally lower in those undergoing NTA with a mean difference of -18.11 (95% CI, -36.7 to 0.48). Techniques experienced significatly lower rates of ecchymosis (risk ratio, 0.43; 95% CI, 0.23-0.78), with no difference identified with regard to rates of paresthesia, phlebitis, and skin pigmentation. Further assessment of quality of life (mean difference, -0.27; 95% CI, -0.57 to 0.04) and Venous Clinical Severity Score (-0.52; 95% CI, -1.05 to 0.01) revealed no difference between groups. Included data were deemed of moderate methodologic quality. CONCLUSIONS: Nonthermal techniques are as effective as standard TA in the first year and, in some studies, may be associated with less procedural pain. These data suggest that NTA offers an alternative and safe means to treat superficial venous disease. There is, however, a need for further powered trials with larger numbers of patients and longer follow-up to definitively examine this hypothesis.

Increased Leucocyte-Platelet Complex Formation in Recently Symptomatic versus Asymptomatic Carotid Stenosis Patients and in Micro-emboli Negative Subgroups.

INTRODUCTION: Cerebral micro-embolic signals (MES) predict risk of stroke in carotid stenosis patients. However, MES-negative 'recently symptomatic patients' also have a higher stroke risk than 'asymptomatic patients'. Differences in platelet activation status may contribute to this disparity in risk. METHODS: This prospective, observational study assessed platelet biomarkers and their relationship with MES in asymptomatic versus symptomatic moderate (≥50-69%) or severe (≥70-99%) carotid stenosis patients. Full blood count parameters were measured and whole-blood flow cytometry was used to quantify platelet surface CD62P and CD63 expression and leucocyte-platelet complex formation. Bilateral simultaneous transcranial Doppler ultrasound of the middle cerebral arteries classified patients as 'MES positive' or 'MES negative'. RESULTS: Data from 34 asymptomatic patients were compared with those from 43 symptomatic patients in the 'early phase' (≤ 4 weeks) and 37 of these symptomatic patients in the 'late phase' (≥ 3 months) after transient ischaemic attack/ischaemic stroke. There were no differences in %CD62P or %CD63 expression between early or late symptomatic and asymptomatic patients overall (p > 0.05). The percentage of lymphocyte-platelet complexes was higher in early symptomatic than in asymptomatic patients (2.8 vs. 2.16%; p < 0.001). MES were more commonly observed in early symptomatic (31.4%; p = 0.027) but not in late symptomatic (6.7%; p = 0.996) versus asymptomatic patients (7.1%). The percentage of lymphocyte-platelet complexes was higher in early symptomatic than in asymptomatic MES-negative patients (2.7 vs. 2.17%; p = 0.02). CONCLUSION: These data add to the evidence that leucocyte-platelet complex formation/platelet activation is increased in recently symptomatic versus asymptomatic patients, and may contribute to the pathogenesis of first and subsequent strokes in carotid stenosis patients, including those who are MES negative.

Mortality rates of patients undergoing emergency laparotomy in an Irish university teaching hospital.

INTRODUCTION: Emergency laparotomy (EL) is a commonly performed operation with increased morbidity and mortality. Currently, there is a lack of published outcomes following emergency laparotomy within an Irish population. The aim of this study was to assess our outcomes and compare these to predefined outcomes from NELA. METHODS: A review of a prospectively maintained database of all patients who underwent an emergency laparotomy between January 1st 2015 and October 31st 2016 was performed. Patient demographics, operative indication and procedures, preoperative lactate, time of surgery, admission to high dependency unit (HDU) and mortality (30- and 90-day mortality) were included. Statistical analysis was performed using Minitab V18 with p < 0.05 considered significant. RESULTS: One hundred twenty-four emergency operations were performed on 120 patients. The median age was 60 years. Indications for surgery included the following (%): peritonitis (32.45%), obstruction (22.5%), complicated hernia (19.1%), mesenteric ischaemia (15%), trauma (4.1%), and acute haemorrhage (3.3%). A consultant surgeon and consultant anaesthetist were present at 79 and 78% of EL carried out, respectively. Reported 30- and 90-day mortality were 6.66 and 11.6%, respectively. Thirty-day mortality was 20% in octogenarians. Index lactate did not correlate with mortality (p = 0.43). A significant proportion of mortalities had procedures carried out between 6 pm and midnight with the highest mortality rate in patients with mesenteric ischaemia (p < 0.05). CONCLUSION: EL is associated with high mortality rates. Our mortality figures compare favourably with the NELA data. We support the development of a national database to facilitate improvements in the quality of care delivered to this high-risk cohort.

Assessment of 'on-treatment platelet reactivity' and relationship with cerebral micro-embolic signals in asymptomatic and symptomatic carotid stenosis.

INTRODUCTION: The relationship between on-treatment platelet reactivity and cerebral micro-embolic signals (MES) is unknown, and has not been previously simultaneously assessed in asymptomatic and symptomatic carotid stenosis patients. METHODS: Consecutive eligible patients with ≥50% asymptomatic or recently symptomatic carotid stenosis (≤4weeks following TIA/ischaemic stroke) were recruited to this pilot study. Symptomatic patients were followed up to the 'late' phase (≥3months) following symptom onset or carotid intervention; longitudinal data were analysed from symptomatic patients with data available at both time-points. Platelet function/reactivity was assessed with the PFA-100® to measure collagen-ADP (C-ADP) and collagen-epinephrine (C-EPI) closure times in citrate-anticoagulated whole blood. Bilateral simultaneous 1-hour transcranial Doppler ultrasound (TCD) monitoring of the middle cerebral arteries was performed to classify patients as MES +ve or MES -ve. RESULTS: 31 patients with ≥50% asymptomatic and 46 with early symptomatic carotid stenosis or occlusion were included. 35 symptomatic patients were followed up to the late phase (23 following carotid intervention). Prevalence of 'high on-treatment platelet reactivity' (HTPR) on the C-EPI cartridge did not differ between asymptomatic and symptomatic patients overall, but was lower in 'symptomatic post-intervention' than asymptomatic patients on aspirin monotherapy (10% vs. 50%; p=0.03). The prevalence of HTPR on the C-EPI cartridge decreased between the early and late phases in symptomatic patients (63% vs. 34%; p=0.017), including those on aspirin monotherapy (p=0.016). There were no significant differences in HTPR status between asymptomatic vs. early or late symptomatic MES +ve or MES -ve patients. DISCUSSION: Carotid interventional treatment, presumably in combination with resolution of the acute phase response, may decrease the prevalence of HTPR in patients with recently symptomatic carotid stenosis over time. Preliminary subgroup analysis suggests that successful intervention may reduce the prevalence of aspirin-HTPR in symptomatic patients to lower levels than asymptomatic medically-treated patients on aspirin monotherapy. Larger, longitudinal studies are warranted to reassess the impact of more intensive secondary preventive treatment on ex vivo platelet function at different levels of shear stress in carotid stenosis patients.

Taurolidine attenuates the hemodynamic and respiratory changes associated with endotoxemia.

The purpose of this study was to determine if prereatment with taurolidine, a known anti-endotoxin agent, would attenuate the hemodynamic and respiratory responses associated with endotoxin induced lung injury in a large animal model in a randomized controlled study under license from the Department of Health. All animals underwent a general anesthetic. Vascular catheters were placed in the femoral artery and in the femoral vein. A Swan-Ganz Catheter was inserted for measurement of pulmonary artery pressure. Animals were randomized into three groups: Control, with measurements taken at baseline and half hourly up to 90 min; Endotoxin, receiving 5microg/Kg E. coli endotoxin intravenously after baseline measurements; and Endotoxin + Taurolidine, receiving 5g of taurolidine via intraperitoneal infusion 1 h before endotoxin administration. Main outcome measures were mean systemic arterial pressure (MAP), mean pulmonary arterial pressure (MPAP), arterial oxygen tension (pO2), serum endotoxin concentration, and pulmonary myeloperoxidase. Endotoxin induced a significant lung injury characterized by an increase in pulmonary artery pressure, hypoxia, and systemic hypotension. Pretreatment with intraperitoneal taurolidine significantly attenuated these hemodynamic and respiratory changes. Serum endotoxin concentration was also significantly reduced as was lung myeloperoxidase. The data suggest that taurolidine may have a therapeutic role in preventing the lung injury seen in endotoxemia.

Neovascularization: an "innocent bystander" in recurrent varicose veins.

OBJECTIVE: Varicose vein recurrence after surgery occurs in up to 60% of patients. A variety of technical factors have been implicated, but biological factors such as neovascularization have more recently been proposed. The objective of this study was to characterize the relative contribution of technical and biological factors to recurrence in a large prospective series of recurrent varicose veins. METHODS: Duplex and operative findings were recorded prospectively in a consecutive series of 500 limbs undergoing surgery for recurrent varicose veins between 1995 and 2005 in a university teaching hospital. Only limbs with previous saphenofemoral junction surgery were included. All limbs had preoperative duplex mapping by an accredited vascular technician who assessed the status of the great saphenous vein (GSV) in the thigh and groin, sought sonographic evidence of neovascularization, and reported on the presence of reflux in the short saphenous vein and perforator sites (typical and atypical). All operations were performed with an attending vascular surgeon as the lead operator. RESULTS: Primary GSV surgery was incomplete in 83.2% of limbs. A completely intact GSV system was present in 17.4% of limbs. An incompetent thigh saphenous vein was present in 44.2% of limbs, 37.6% had GSV stump incompetence with one or more intact tributaries, and 16% had both a residual thigh GSV and an incompetent stump with intact tributaries. Non-GSV sites of reflux were identified in 25% of limbs. Neovascularization was identified on duplex scanning in 41 (8.2%) limbs. However, in 27 of these, surgical exploration revealed a residual GSV stump with 1 or more significant tributaries. Each of the remaining 14 (2.8%) limbs had a residual incompetent thigh GSV. CONCLUSIONS: Despite reports to the contrary, neovascularization occurs in a relatively small proportion of patients with recurrent varicose veins. All recurrent varicose veins associated with duplex-diagnosed neovascularization are also associated with persistent reflux in the GSV stump tributaries, thigh GSV, or both. Recurrence after primary varicose vein surgery is associated with inadequate primary surgery or progression of disease, and neovascularization alone is not a cause of recurrent varicose veins.