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.

Cost effectiveness of renal denervation therapy for the treatment of resistant hypertension in the UK.

BACKGROUND: Patients with resistant hypertension are at a high risk for developing serious cardiovascular events and renal complications. Catheter-based renal denervation (RDN) is a procedure with the potential to normalize systolic blood pressure (SBP). OBJECTIVE: The overall objective of the study was to estimate the cost effectiveness of RDN in the UK for patients with diagnosed resistant hypertension, expressed as a standard cost per quality-adjusted life-year (QALY) ratio. METHODS: A patient lifetime, economic, Markov heath-state model was developed, linking expected changes in SBP to reductions in risks for cardiovascular events and renal complications, using the Framingham, PROCAM, and other published risk equations. The model was developed from the perspective of the healthcare payer in the UK using relevant cost data from 2012. Clinical effectiveness for RDN (a mean reduction of 32 mmHg in SBP) was taken from the phase III Symplicity HTN-2 trial, in patients with a mean baseline SBP of 178 mmHg. HTN-2 was the largest, multicenter randomized controlled trial on the effectiveness of RDN therapy at the time of the model development. A systematic review identified UK-specific sources for utility, mortality, and cost parameter values, and included recently published UK guidelines for the clinical management of hypertension. RESULTS: RDN therapy resulted in an increase in health benefit over a patient's lifetime compared with anti-hypertensive pharmacological treatment alone (12.77 vs. 12.16 QALYs; discounted). Additional lifetime costs per patient were modeled at £2,961; equivalent to an incremental cost per additional QALY of £4,805. This result was robust to full probabilistic sensitivity and scenario analyses. CONCLUSION: RDN is an effective clinical procedure that offers patients a meaningful and cost-effective alternative for achieving SBP control, where traditional combination, anti-hypertensive pharmacologic strategies have been proven to be ineffective.

The effect of renal denervation added to standard pharmacologic treatment versus standard pharmacologic treatment alone in patients with resistant hypertension: rationale and design of the SYMPATHY trial.

The first studies on renal denervation (RDN) suggest that this treatment is feasible, effective, and safe in the short term. Presently available data are promising, but important uncertainties exist; therefore, SYMPATHY has been initiated. SYMPATHY is a multicenter, randomized, controlled trial in patients randomized to RDN in addition to usual care (intervention group) or to continued usual care (control group). Randomization will take place in a ratio of 2 to 1. At least 300 participants will be included to answer the primary objective. Sample size may be extended to a maximum of 570 to address key secondary objectives. The primary objective is to assess whether RDN added to usual care compared with usual care alone reduces blood pressure (BP) (ambulatory daytime systolic BP) in subjects with an average daytime systolic BP ≥135, despite use of ≥3 BP-lowering agents, 6 months after RDN. Key secondary objectives are evaluated at 6 months and at regular intervals during continued follow-up and include the effect of RDN on the use of BP-lowering agents, in different subgroups (across strata of estimated glomerular filtration rate and of baseline BP), on office BP, quality of life, and cost-effectiveness.

Similarities and differences between renal sympathetic denervation and carotid baroreceptor stimulation.

The two novel approaches recently introduced for the treatment of resistant hypertension, i.e. carotid baroreceptor stimulation and renal denervation, share a number of similarities but are also characterized by important differences. The similarities include the evidence that both interventions have as common pathophysiological background the state of sympathetic overdrive characterizing essential hypertension. In addition both procedures 1) are invasive, 2) exert in the short-term period clearcut blood pressure lowering effects and 3) still face a number of open questions, particularly related to the long-term blood pressure lowering effects, impact on end-organ damage and on cardiovascular events. The differences include the fact that two procedures act on distinct targets that trigger sympathetic activation and consequently blood pressure increase. In addition, only in the case of carotid baroreceptor stimulation the blood pressure effects can be easily assessed immediately following the implantation. Finally, the economic costs, metabolic effects and impact on vagal modulation of heart rate are different between the two interventions. This paper will provide a comparison of the background, effects and outcome of renal denervation and carotid baroreceptor stimulation, stressing whenever possible the clinical implications of the main features of the two interventions.

Hipertensión arterial resistente / Resistant hypertension

Mujer de 53 años de edad, con antecedentes patológicos de hipercolesterolemia tratada con estatinas, sin antecedentes de enfermedades cardiovasculares, remitida a la Unidad de Hipertensión Arterial (HTA) y Riesgo Vascular por presentar HTA resistente a 4 fármacos antihipertensivos a dosis plenas. En la exploración física destacaba obesidad con un índice de masa corporal de 36,3kg/m2, y presión arterial (PA) clínica de 162/102mmHg. La exploración física no mostró datos de interés. Analítica: glucemia 120mg/dl, Hb glucada 6,4%. Albuminuria 68mg/g creatinina, con función renal, estudio del eje renina angiotensina y resto de analítica dentro de la normalidad. Ecocardiograma: masa de ventrículo izquierdo, 131g/m2 (normal, <110g/m2). La HTA resistente se confirmó mediante monitorización ambulatoria de la presión arterial durante 24h (153/89mmHg). Se añadió al tratamiento espironolactona 25mg/día, que fue bien tolerada, sin cambios en la función renal y con caliemia tras el tratamiento dentro de la normalidad (4,1mmol/l). A las 8 semanas presentaba un buen control de PA clínica, 132/86mmHg, y de la PA de 24h, 128/78mmHg (AU)

A 53 year old woman with hypercholesterolemia treated with statins, with no history of cardiovascular disease, was referred to the Hypertension and Vascular Risk Unit for management of hypertension resistant to 4 antihypertensive agents at full doses. The patient had obesity, with a body mass index of 36.3kg/m2 and office blood pressure 162/102mm Hg. Physical examination showed no data of interest. Analysis: glucose 120mg/dl, glycated Hb: 6.4%, albuminuria 68mg/g, kidney function and study of the renin angiotensin system and other biochemical parameters were normal. Echocardiography: left ventricular mass, 131g/m2 (normal, <110g/m2). True resistant hypertension was confirmed by ambulatory monitoring of blood pressure during 24h (153/89mm Hg). Spironolactone treatment (25mg/day) was added and was well tolerated, with no change in renal function and kaliemia within normal (4.1mmol/l) following the treatment. After 8 weeks, blood pressure was well controlled: office blood pressure 132/86mm Hg and 24h-ambulatory blood pressure: 128/79mm Hg (AU)

Renal denervation - a clinical update and future directions.

The aim of this review is to give a contemporary update on renal denervation therapy focusing particularly on the scientific background and present literature as well as on different technical approaches and potential future directions.

Potential lifetime cost-effectiveness of catheter-based renal sympathetic denervation in patients with resistant hypertension.

AIMS: Recent studies have demonstrated the safety and efficacy of catheter-based renal sympathetic denervation (RDN) for the treatment of resistant hypertension. We aimed to determine the cost-effectiveness of this approach separately for men and women of different ages. METHODS AND RESULTS: A Markov state-transition model accounting for costs, life-years, quality-adjusted life-years (QALYs), and incremental cost-effectiveness was developed to compare RDN with best medical therapy (BMT) in patients with resistant hypertension. The model ran from age 30 to 100 years or death, with a cycle length of 1 year. The efficacy of RDN was modelled as a reduction in the risk of hypertension-related disease events and death. Analyses were conducted from a payer's perspective. Costs and QALYs were discounted at 3% annually. Both deterministic and probabilistic sensitivity analyses were performed. When compared with BMT, RDN gained 0.98 QALYs in men and 0.88 QALYs in women 60 years of age at an additional cost of €2589 and €2044, respectively. As the incremental cost-effectiveness ratios increased with patient age, RDN consistently yielded more QALYs at lower costs in lower age groups. Considering a willingness-to-pay threshold of €35 000/QALY, there was a 95% probability that RDN would remain cost-effective up to an age of 78 and 76 years in men and women, respectively. Cost-effectiveness was influenced mostly by the magnitude of effect of RDN on systolic blood pressure, the rate of RDN non-responders, and the procedure costs of RDN. CONCLUSION: Renal sympathetic denervation is a cost-effective intervention for patients with resistant hypertension. Earlier treatment produces better cost-effectiveness ratios.

Cost-effectiveness and clinical effectiveness of catheter-based renal denervation for resistant hypertension.

OBJECTIVES: The purpose of this study was to assess cost-effectiveness and long-term clinical benefits of renal denervation in resistant hypertensive patients. BACKGROUND: Resistant hypertension affects 12% of hypertensive persons. In the Symplicity HTN-2 randomized controlled trial, catheter-based renal denervation (RDN) lowered systolic blood pressure by 32 ± 23 mm Hg from 178 ± 18 mm Hg at baseline. METHODS: A state-transition model was used to predict the effect of RDN and standard of care on 10-year and lifetime probabilities of stroke, myocardial infarction, all coronary heart disease, heart failure, end-stage renal disease, and median survival. We adopted a societal perspective and estimated an incremental cost-effectiveness ratio in U.S. dollars per quality-adjusted life-year, both discounted at 3% per year. Robustness and uncertainty were evaluated using deterministic and probabilistic sensitivity analyses. RESULTS: Renal denervation substantially reduced event probabilities (10-year/lifetime relative risks: stroke 0.70/0.83; myocardial infarction 0.68/0.85; all coronary heart disease 0.78/0.90; heart failure 0.79/0.92; end-stage renal disease 0.72/0.81). Median survival was 18.4 years for RDN versus 17.1 years for standard of care. The discounted lifetime incremental cost-effectiveness ratio was $3,071 per quality-adjusted life-year. Findings were relatively insensitive to variations in input parameters except for systolic blood pressure reduction, baseline systolic blood pressure, and effect duration. The 95% credible interval for incremental cost-effectiveness ratio was cost-saving to $31,460 per quality-adjusted life-year. CONCLUSIONS: The model suggests that catheter-based renal denervation, over a wide range of assumptions, is a cost-effective strategy for resistant hypertension that might result in lower cardiovascular morbidity and mortality.

Outpatient thoracic surgical programme in 300 patients: clinical results and economic impact.

OBJECTIVE: To evaluate clinical aspects, results and the economic impact of the outpatient thoracic surgery programme (OTSP) developed in our Department. METHODS: Prospective study of 300 patients who entered in the OTSP from April 2001 to March 2005. The procedures performed were video-mediastinoscopy (MC), video-thoracoscopic lung biopsy (LB) and video-thoracoscopic bilateral thoracic sympathectomy (TS). All procedures were performed under general anaesthesia and patients were discharged in 4-6h. We analyse demographic data, the substitution index (SI), the admission rate (AR) and readmission rate (RR) after the procedure. We calculate the economic impact of stay expenses on our hospital and on other Spanish hospitals. RESULTS: The female/male ratio of the 300 patients was 83/217, with a mean age of 58.1 years (range: 15-85 years). There were no deaths. Mediastinoscopy was performed as outpatient procedure in 210 patients (mean age: 65.6 years) out of 244 total MC (SI=86.1%). Two patients were admitted (AR=0.95%) to observe a minimal pneumothorax and because of late night end. There were no readmissions after MC (RR=0%). We included 32 ambulatory patients for lung biopsy (mean age: 61.5 years) out of 64 total LB (SI=50.0%). One patient was admitted because of air leak (AR=3.1%) and there were no readmissions after LB (RR=0%). Fifty-eight patients were included in the OTSP for bilateral sympathectomy (mean age: 27.1 years) out of 83 total TS (SI=69.9%); there were no admissions (AR=0%) and one patient was readmitted after 9 days because of a hemothorax (RR=1.7%). Sixty-four patients out of the 91 not included in the OTSP were included in an 'afternoon surgical programme' and dismissed the morning after surgery, without contraindication for their inclusion in the OTSP. The hospital's total stay saving was 12,668 euros (88,226 euros if performed elsewhere), 42 euros per patient (294 euros per patient if performed elsewhere). CONCLUSION: Video-assisted mediastinoscopy, lung biopsy and bilateral sympathectomy can be included safely in outpatient thoracic surgical programmes. The impact of the economic benefit of OTSP over the conventional hospitalisation depends on the Department's previous policy on hospital stays. Further experience is needed to increase the substitution index and expand the OTSP to other procedures.

Temporary sympathectomy in the treatment of chronic refractory angina.

The aim of this study was to investigate the safety and efficacy of the two most commonly practiced temporary sympathectomy techniques in the treatment of chronic refractory angina. Fifty-nine consecutive refractory angina patients commencing outpatient temporary sympathectomy from November 1, 2000 to November 1, 2002, were prospectively audited for duration of pain relief and procedural complications over a two-year period. A total of 227 stellate ganglion blockades (SGB) and 100 paravertebral blockades (PVB) were performed on 59 chronic refractory angina (CRA) patients naïve to sympathectomy. The mean period of pain relief obtained following SGB was 3.48 weeks (SD 3.38) and the mean relief following PVB was 2.80 weeks (SD 2.00). Mild, fully reversible complications occurred in 3% of SGB and 3% of PVB procedures, with one patient requiring overnight hospitalization. This study demonstrates that temporary sympathectomy may provide a safe and effective outpatient procedure in refractory angina patients when applied as part of holistic care.

Thoracodorsal sympathectomy for severe hyperhydrosis: posterior bilateral versus unilateral staged sympathectomy.

The aim of this study was to compare the results of simultaneous bilateral thoracodorsal sympathectomy in the prone position with those of anterolateral sympathectomy performed in two staged, separate procedures for the treatment of bilateral excessive sweating of the hands and axillae, and to describe our technique for bilateral, simultaneous thoracodorsal sympathectomy. From July 1995 to March 2001, 202 thoracodorsal sympathectomies were done in 101 patients for severe hyperhydrosis. There were 79 females (age range 20-46) and 22 males (age range 19-65). In 52 patients, anterolateral sympathectomies were performed in the supine position, using unilateral lung collapse, with both sides operated on in two separate, staged procedures. In 49 patients, bilateral sympathectomy was conducted during a single procedure, in the prone position, without using unilateral lung collapse. In comparing the results from these two methods, we concluded that simultaneous bilateral thoracodorsal posterior sympathectomy, has comparable safety, may improve outcome, decreases in half the number of hospital admissions, and produces a significant overall reduction in cost when compared with staged anterolateral sympathectomy for the treatment of severe hyperhydrosis.