Editor's Choice - Short Term Cost Effectiveness of Radiofrequency Ablation and High Ligation and Stripping for Great Saphenous Vein Incompetence.

OBJECTIVE: Superficial venous incompetence (SVI) is a common disease that causes significant quality of life (QoL) impairment. There is a need for more health economic evaluations of SVI treatment. The aim of this study was to perform a cost effectiveness analysis in patients with great saphenous vein (GSV) incompetence comparing radiofrequency ablation (RFA), high ligation and stripping (HL/S), and no treatment or conservative treatment with one year follow up. METHODS: Randomised controlled trial economic analysis from an ongoing trial; 143 patients (156 limbs) with GSV incompetence (CEAP clinical class 2 - 6) were included. Treatment was performed with RFA or HL/S. Follow up was performed up to one year using duplex ultrasound, revised venous clinical severity score (r-VCSS), Aberdeen Varicose Vein Questionnaire (AVVQ), and EuroQol-5D-3L (EQ-5D-3L). RESULTS: Seventy-eight limbs were treated with RFA and HL/S respectively. No treatment or conservative treatment was assumed to have zero in treatment cost and no treatment benefit. In the RFA group, one limb had reflux in the GSV after one month and three limbs after one year. In HL/S, two limbs had remaining reflux in the treated area at one month and one year. Both disease severity (r-VCSS, p = .004) and QoL (AVVQ, p = .021 and EQ-5D-3L, p = .028) were significantly improved over time. The QALY gain was 0.21 for RFA and 0.17 for HL/S. The cost per patient was calculated as €1 292 for RFA and €2 303 for HL/S. The cost per QALY (compared with no treatment or conservative treatment) was €6 155 for RFA and €13 549 for HL/S. With added cost for days absent from work the cost per QALY was €7 358 for RFA and €24 197 for HL/S. The cost per QALY for both methods was well below the threshold suggested by Swedish National Board of Health. CONCLUSION: RFA is more cost effective than HL/S and no treatment or conservative treatment at one year follow up.

Quantifiable remaining reflux 1 year after treatment of superficial venous incompetence is associated with impaired clinical outcome.

OBJECTIVE: Remaining symptoms after treatment of superficial venous incompetence is a common problem. Duplex ultrasound is often used during follow-up, but does not permit an overall quantification of venous function. We have developed a plethysmographic method using occlusion cuffs for separation of superficial and deep venous reflux. By assessing the superficial component it is possible to quantify a potential suboptimal hemodynamic treatment in patients with superficial venous incompetence. The aim was to examine whether patients with hemodynamically quantifiable remaining reflux after treatment experience impaired clinical outcomes. METHODS: This single-center prospective cohort study evaluated 156 limbs with great saphenous vein incompetence treated with radiofrequency ablation or high ligation and stripping. Duplex ultrasound and strain-gauge plethysmography (SGP) with and without selective superficial occlusion were performed before and one-year after treatment. Time taken (seconds) to reach 50% of the venous volume (T50) was evaluated. A difference in the T50of >5 seconds between postoperative strain-gauge plethysmography with and without superficial occlusion was defined as remaining reflux. The Venous Clinical Severity Score (VCSS) and Aberdeen Varicose Vein Questionnaire (AVVQ) were evaluated and compared between patients with and without remaining reflux. Multivariable logistic regression was used to evaluate risk factors for remaining plethysmographic reflux. RESULTS: In all patients, median (25th, 75th percentile) T50 increased preoperatively from 7 seconds (3, 12 seconds) to 17 seconds (11, 28 seconds) (P < .001) 1 year after treatment. The VCSS and AVVQ were reduced (VCSS, 8.0 [6.0, 10.0] vs 3.0 [1.0, 5.0] [P < .001]; AVVQ, 21.8 [15.8, 32.1] vs 6.4 [2.2, 11.0] [P < .001]). Of the 156 limbs, 87 (56%) demonstrated remaining reflux 1 year after treatment. Patients with remaining plethysmographic reflux displayed higher median (25th, 75th percentile) VCSS (3.0 [2.0, 5.0] vs 2.0 [1.0, 4.0]; P = .012) and AVVQ (7.5 [2.7, 14.9] vs 4.7 [1.6, 9.2]; P = .025). Multivariate logistic regression showed that higher preoperative C in the Clinical Etiology Anatomy Pathophysiology classification (CEAP) (odds ratio [OR], 2.9 [95% confidence interval [CI], 1.34-6.46), age (OR, 1.03; 95% CI, 1.001-1.065), small saphenous vein incompetence (OR, 4.2; 95% CI, 1.30-13.73) and postoperative great saphenous vein reflux below the treated area (OR, 2.16; 95% CI, 1.02-4.56) were significant risk factors for remaining plethysmographic reflux. CONCLUSIONS: A majority of treated limbs showed quantifiable reflux 1 year after intervention and these patients displayed worse patient related outcomes assessed with the VCSS and AVVQ. Remaining plethysmographic reflux was associated with preoperative small saphenous vein incompetence and reflux below the treated area as well as advanced age and higher C in CEAP.

Prediction of Postoperative Delirium After Cardiac Surgery with A Quick Test of Cognitive Speed, Mini-Mental State Examination and Hospital Anxiety and Depression Scale.

Purpose: To evaluate if preoperative assessment with A Quick Test of Cognitive Speed (AQT) could increase the accuracy of predicting delirium after cardiac surgery compared to Mini-Mental State Examination (MMSE), and examine if a composite of variables, including cognitive function and depressive symptoms, could be useful to predict delirium. Patients and Methods: Cardiac surgery was performed in 218 patients (mean age 72 years). Preoperative evaluation involved AQT, MMSE and Hospital Anxiety And Depression Scale (HADS). Postoperative delirium was assessed using Nursing Delirium Screening Scale (Nu-DESC) and Confusion Assessment Method-ICU (CAM-ICU). Logistic regression was performed to detect predictors of postoperative delirium and receiver operator characteristic curves (ROC) with area under the curve (AUC) to determine the accuracy. Results: Postoperative delirium occurred in 47 patients (22%) who had lower MMSE scores (median (range), 27 (19-30) vs 28 (20-30), p=0.009) and slower AQT (median (range), 76 (48-181) vs 70 (40-182) seconds, p=0.030) than patients without delirium. Predictive power measured as AUC (95% CI) was 0.605 (0.51-0.70) for AQT and 0.623 (0.53-0.72) for MMSE. Logistic regression (OR, 95% CI) showed MMSE <27 points (2.72, 1.27-5.86), AQT >70 sec (2.26, 1.03-4.95), HADS-D >4 points (2.60, 1.21-5.58) and longer cardiopulmonary bypass-time (1.007, 1.002-1.013) to be associated with postoperative delirium. Combining these parameters yielded an AUC of 0.736 (0.65-0.82). Conclusion: The ability of predicting delirium using AQT was similar to MMSE, and only slightly higher by combining AQT and MMSE. Adding HADS-D and cardiopulmonary bypass-time to MMSE and AQT increased the predictive power to a borderline acceptable discriminatory value. Preoperative cognitive tests and screening for depressive symptoms may help identify patients at risk of postoperative delirium. Yet, there is still a need to establish useful preoperative tests.

Neoehrlichia mikurensis Causing Thrombosis and Relapsing Fever in a Lymphoma Patient Receiving Rituximab.

Neoehrlichia (N.) mikurensis, an intracellular tick-borne bacterium not detected by routine blood culture, is prevalent in ticks in Scandinavia, Central Europe and Northern Asia, and may cause long-standing fever, nightly sweats, migrating pain, skin rashes and thromboembolism, especially in patients treated with rituximab. The multiple symptoms may raise suspicion of both infection, inflammation and malignancy, and lead in most cases to extensive medical investigations across many medical specialist areas and a delay of diagnosis. We describe a complex, albeit typical, case of neoehrlichiosis in a middle-aged splenectomised male patient with a malignant lymphoma, receiving treatment with rituximab. The multifaceted clinical picture associated with this tick-borne disease is addressed, and longitudinal clinical and laboratory data, as well as imaging, are provided. Longstanding relapsing fever in combination with thrombosis in superficial and deep veins in an immunocompromised patient living in a tick-endemic region should raise the suspicion of the emerging tick-borne disease neoehrlichiosis. Given the varied clinical presentation and the risk of delay in diagnosis and treatment, we believe it is important to raise clinicians' awareness of this emerging infection, which is successfully treated with doxycycline.

Cerebrovascular Reserve Capacity as a Predictor of Postoperative Delirium: A Pilot Study.

Introduction: Postoperative delirium is a common complication after cardiac surgery with cardiopulmonary bypass (CPB). Compromised regulation of the cerebral circulation may be a predisposing factor for delirium. However, the potential relationship between cerebrovascular reserve capacity and delirium is unknown. The aim of this study was to investigate if impaired cerebrovascular reserve capacity was associated with postoperative delirium. Methods: Forty-two patients scheduled for cardiac surgery with CPB were recruited consecutively. All patients underwent preoperative transcranial Doppler (TCD) ultrasound with calculation of breath-hold index (BHI). BHI < 0.69 indicated impaired cerebrovascular reserve capacity. In addition, patients were examined with preoperative neuropsychological tests such as MMSE (Mini Mental State Examination) and AQT (A Quick Test of cognitive speed). Postoperative delirium was assessed using Nursing Delirium Screening Scale (Nu-DESC) in which a score of ≥2 was considered as delirium. Results: Six patients (14%) scored high for postoperative delirium and all demonstrated impaired preoperative cerebrovascular reserve capacity. Median (25th-75th percentile) BHI in patients with postoperative delirium was significantly lower compared to the non-delirium group [0.26 (-0.08-0.44) vs. 0.83 (0.57-1.08), p = 0.002]. Preoperative MMSE score was lower in patients who developed postoperative delirium (median, 25th-75th percentile; 26.5, 24-28 vs. 28.5, 27-29, p = 0.024). Similarly, patients with postoperative delirium also displayed a slower performance during the preoperative cognitive speed test AQT color and form (mean ± SD; 85.8 s ± 19.3 vs. 69.6 s ± 15.8, p = 0.043). Conclusion: The present findings suggest that an extended preoperative ultrasound protocol with TCD evaluation of cerebrovascular reserve capacity and neuropsychological tests may be valuable in identifying patients with increased risk of developing delirium after cardiac surgery.

Impact on venous haemodynamics after treatment of great saphenous vein incompetence using plethysmography and duplex ultrasound.

OBJECTIVES: To evaluate postoperative venous haemodynamics and quality of life after treatment of great saphenous vein (GSV) incompetence. METHODS: Radiofrequency ablation and high ligation and stripping were performed in 62 patients (65 limbs) and 58 (65 limbs), respectively. Phlebectomies were performed in both modalities. Strain-gauge plethysmography on the foot combined with superficial venous occlusion was used to measure refilling time after knee bends. Strain-gauge plethysmography, duplex ultrasound and quality of life were assessed before and one month after treatment. RESULTS: Duplex ultrasound displayed successful intervention in all but two limbs. Refilling time increased similar in radiofrequency ablation and high ligation and stripping after treatment (p < 0.001). Postoperatively, strain-gauge plethysmography detected remaining reflux in 71% of the patients. Multivariate analysis showed that two or more incompetent calf branches were associated with remaining reflux (OR 4.82 (95% CI: 1.33-17.5), p = 0.02). No difference in quality of life was seen in patients with remaining reflux. CONCLUSIONS: Despite successful treatment, a majority of the limbs showed remaining reflux, in which incompetent calf branches appear to play an important role.Clinicaltials.gov: Lower Limb Venous Insufficiency and the Effect of Radiofrequency Treatment Versus Open Surgery. Nr: NCT02397226.

Reduced compensatory responses to maintain central blood volume during hypovolemic stress in women with vasovagal syncope.

Although vasovagal syncope (VVS) is a common clinical condition, the underlying pathophysiology is not fully understood. A decrease in cardiac output has recently been suggested as a factor in orthostatic VVS. The aim was to investigate compensatory mechanisms to maintain central blood volume and venous return during hypovolemic stress in women with VVS. Fourteen VVS women (25.7 ± 5.0 yr) and 15 matched controls (22.8 ± 3.2 yr) were investigated. Single-step and graded lower body negative pressure (LBNP) to presyncope were used to create hypovolemic stress. Peripheral mobilization of venous blood from the arm (capacitance response and net capillary fluid absorption) and lower limb blood pooling (calf capacitance response) were evaluated using a volumetric technique. Cardiovascular responses and plasma norepinephrine (P-NE) were measured. Resting P-NE was elevated in VVS women (P < 0.01). Despite a similar hypovolemic stimulus, the increase in P-NE was blunted (P < 0.01) and the maximal percent increase in total peripheral resistance was reduced (P < 0.05) during graded LBNP in VVS women. The arm capacitance response was slower (P < 0.05) and reduced in VVS women at higher levels of LBNP (P < 0.05). Capillary fluid absorption from extra- to intravascular space was reduced by ∼40% in VVS women (P < 0.05). Accordingly, the reduction in cardiac output was more pronounced (P < 0.05). In conclusion, in VVS women, mobilization of peripheral venous blood and net fluid absorption from tissue to blood during hypovolemic stress were decreased partly as a result of an attenuated vasoconstrictor response. This may seriously impede maintenance of cardiac output during hypovolemic stress and could contribute to the pathogenesis of VVS.

Reduced venous compliance: an important determinant for orthostatic intolerance in women with vasovagal syncope.

The influence of lower limb venous compliance on orthostatic vasovagal syncope (VVS) is uncertain. The most widespread technique to calculate venous compliance uses a nonphysiological quadratic regression equation. Our aim was therefore to construct a physiologically derived venous wall model (VWM) for calculation of calf venous compliance and to determine the effect of venous compliance on tolerance to maximal lower body negative pressure (LBNP). Venous occlusion plethysmography was used to study calf volume changes in 15 women with VVS (25.5 ± 1.3 yr of age) and 15 controls (22.8 ± 0.8 yr of age). The fit of the VWM and the regression equation to the experimentally induced pressure-volume curve was examined. Venous compliance was calculated as the derivative of the modeled pressure-volume relationship. Graded LBNP to presyncope was used to determine the LBNP tolerance index (LTI). The VWM displayed a better fit to the experimentally induced pressure-volume curve (P < 0.0001). Calf blood pooling was similar in the groups and was not correlated to the LTI (r = 0.204, P = 0.30). Venous compliance was significantly reduced at low venous pressures in women with VVS (P = 0.042) and correlated to the LTI (r = 0.459, P = 0.014) in the low pressure range. No correlation was found between venous compliance at high venous pressures and the LTI. In conclusion, the new VWM accurately adopted the curvilinear pressure-volume curve, providing a valid characterization of venous compliance. Reduced venous compliance at low venous pressures may adversely affect mobilization of peripheral venous blood to the central circulation during hypovolemic circulatory stress in women with VVS.

Visualization of oxidative stress in ex vivo biopsies using electron paramagnetic resonance imaging.

PURPOSE: The purpose of this study was to develop an X-Band electron paramagnetic resonance imaging protocol for visualization of oxidative stress in biopsies. METHODS: The developed electron paramagnetic resonance imaging protocol was based on spin trapping with the cyclic hydroxylamine spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine and X-Band EPR imaging. Computer software was developed for deconvolution and back-projection of the EPR image. A phantom containing radicals of known spatial characteristic was used for evaluation of the developed protocol. As a demonstration of the technique electron paramagnetic resonance imaging of oxidative stress was performed in six sections of atherosclerotic plaques. Histopathological analyses were performed on adjoining sections. RESULTS: The developed computer software for deconvolution and back-projection of the EPR images could accurately reproduce the shape of a phantom of known spatial distribution of radicals. The developed protocol could successfully be used to image oxidative stress in six sections of the three ex vivo atherosclerotic plaques. CONCLUSIONS: We have shown that oxidative stress can be imaged using a combination of spin trapping with the cyclic hydroxylamine spin probe cyclic hydroxylamine spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine and X-Band EPR imaging. A thorough and systematic evaluation on different types of biopsies must be performed in the future to validate the proposed technique.

Single-dose tranexamic acid in advanced ovarian cancer surgery reduces blood loss and transfusions: double-blind placebo-controlled randomized multicenter study.

OBJECTIVE: To determine whether single-dose tranexamic acid given intravenously immediately before surgery for presumed advanced ovarian cancer reduces perioperative blood loss and blood transfusions. DESIGN: A randomized double-blind, placebo-controlled multicenter study. SETTING: Two university hospitals and two central hospitals in the southeast health region of Sweden. POPULATION: One hundred women with presumed advanced ovarian cancer scheduled for radical debulking surgery between March 2008 and May 2012 who complied with inclusion/exclusion criteria were randomized; 50 were allocated to receive tranexamic acid and 50 to receive placebo. Analysis was performed according to intention-to-treat principles. METHODS: The volume of tranexamic acid (15 mg/kg body weight, 100 mg/mL tranexamic acid) or the same volume of placebo (0.9% NaCl) was added to a 100-mL saline solution plastic bag. The study medication was given immediately before the start of surgery. Data were analyzed by means of non-parametric statistics and multivariate models adjusted for confounding factors. MAIN OUTCOME MEASURES: Blood loss and red blood cell transfusions. RESULTS: The total blood loss volume and transfusion rate were significantly lower in the tranexamic acid group compared with the placebo group. Median total blood loss was 520 and 730 mL, respectively (p = 0.03). Fifteen (30%) and 22 (44%), respectively received transfusions (odds ratio 0.44; upper 95% CI 0.97; p = 0.02). CONCLUSION: A single dose of tranexamic acid given immediately before surgery reduces blood loss and transfusion rates significantly in advanced ovarian cancer surgery. Tranexamic acid may be recommended as standard prophylactic treatment in advanced ovarian cancer surgery.