Deep Vein Thrombosis in Europe-Health-Related Quality of Life and Mortality.

OBJECTIVES: Deep vein thrombosis (DVT) is a major health-care burden in Europe, but exact estimates are lacking. This study reports results from the PREFER venous thromboembolism (VTE) study concerning health-related quality of life (HrQoL) and mortality of patients with DVT. METHODS: PREFER VTE was a prospective, observational study, conducted in 7 European countries, designed to provide data concerning treatment patterns, resource utilization, mortality, and QoL. First-time or recurrent patients with DVT were followed at 1, 3, 6, and 12 months. Health-related QoL-as measured by the EuroQoL 5-Dimension 5-Level instrument ( EQ-5D-5L)-was analyzed using Tobit regression with repeated measures, assessing the impact of baseline characteristics stratified by cancer activity. Mortality was analyzed using logistic regression. RESULTS: At baseline, patients with DVT had a 0.14 lower EQ-5D-5L index score (0.72 for total sample) compared to the reference UK population (0.85). The EQ-5D-5L index score improved from baseline to 12 months in patients with active cancer (from 0.70 to 0.79) and those without (0.72-0.87); 7.3% died within a year, a 5.2% excess mortality compared to the age- and gender-adfjusted general population. The 12-month mortality rate of DVT varied between 2.9% in the pooled data from Germany, Switzerland, or Austria and 15.4% in Italy. Furthermore, the mortality rate differed between patients with active cancer and those without (42.9% vs 4.7%). CONCLUSIONS: Deep vein thrombosis is associated with a substantial burden of illness in terms of HrQoL at baseline, which following treatment normalizes after 12 months and has a significant mortality rate. In addition, active cancer has a significant impact on mortality and the HrQoL of patients with DVT.

Deep-vein thrombosis in Europe - Burden of illness in relationship to healthcare resource utilization and return to work.

OBJECTIVES: Deep-vein thrombosis (DVT) forms a major healthcare burden in Europe, but exact estimates concerning the economic burden on society are lacking. This study reports results from the PREFER in VTE study concerning resource utilization and absence from work in DVT patients. METHODS: The PREFER in VTE registry was a prospective, observational, multicenter study carried out in Europe (France, Italy, Spain, the UK, and DACH [Germany, Switzerland and Austria]), designed to provide data concerning treatment patterns, resource utilization, mortality and quality of life. Patients with a first-time and/or recurrent DVT, were recruited and followed for 12 months. Data about resource utilization concerns resource utilization related to DVT. Specifically, treatment pattern, re-hospitalization rate, length of hospital stay, ambulatory/office visit, and proportion of patients returning to work, were analyzed and presented. Subgroup analysis by country and active cancer were also conducted. The length of hospital stay was analyzed as a function of demographics, previous events and co-morbidities using zero-inflated binomial negative regression. Similarly, time until return to work was analyzed using Cox regression. RESULTS: A total of 2056 patients with DVT were recruited, with an average age of 60 years. Patients with active cancer were mostly treated with heparin (83.9%), while patients without active cancer were treated with combinations of heparin, VKA and DOACs. DOACs were less often used in Spain and Italy (<7.0%). Following the management of their initial DVT 20.5% of the patients with and 12.2% of patients without active cancer (n = 88; n = 1462) were hospitalized for on average 8.2 and 10.1 days, respectively. The hospitalization-rate was highest in Italy (16.7%) and lowest in France (7.7%). Furthermore, the average length of stay was highest in Italy (16.6 days) and lowest in DACH (5.2 days). Physician visits were highest in DACH (9.3), lowest in the UK (2.6). Of those working, 50% returned to work at 1 month; >30% did not return to work within the year. CONCLUSIONS: Medical treatment of DVT differed between patients with active cancer and those without. Post-VTE or VTE-related resource utilization differs remarkably between countries. Work-loss seems high, but questions may be raised concerning the causality due to the presence of co-morbidities.

Cost-effectiveness analysis of exenatide once-weekly versus dulaglutide, liraglutide, and lixisenatide for the treatment of type 2 diabetes mellitus: an analysis from the UK NHS perspective.

OBJECTIVE: To assess the cost-effectiveness of exenatide 2 mg once-weekly (EQW) compared to dulaglutide 1.5 mg QW, liraglutide 1.2 mg and 1.8 mg once-daily (QD), and lixisenatide 20 µg QD for the treatment of adult patients with type 2 diabetes mellitus (T2DM) not adequately controlled on metformin. METHODS: The Cardiff Diabetes Model was applied to evaluate cost-effectiveness, with treatment effects sourced from a network meta-analysis. Quality-adjusted life years (QALYs) were calculated with health-state utilities applied to T2DM-related complications, weight changes, hypoglycemia, and nausea. Costs (GBP £) included drug treatment, T2DM-related complications, severe hypoglycemia, nausea, and treatment discontinuation due to adverse events. A 40-year time horizon was used. RESULTS: In all base-case comparisons, EQW was associated with a QALY gain per patient; 0.046 vs dulaglutide 1.5 mg; 0.102 vs liraglutide 1.2 mg; 0.043 vs liraglutide 1.8 mg; and 0.074 vs lixisenatide 20 µg. Cost per patient was lower for EQW than for liraglutide 1.8 mg (-£2,085); therefore, EQW dominated liraglutide 1.8 mg. The cost difference per patient between EQW and dulaglutide 1.5 mg, EQW and liraglutide 1.2 mg, and EQW and lixisenatide 20 µg was £27, £103, and £738, respectively. Cost per QALY gained with EQW vs dulaglutide 1.5 mg, EQW vs liraglutide 1.2 mg, and EQW vs lixisenatide 20 µg was £596, £1,004, and £10,002, respectively. In the probabilistic sensitivity analysis, the probability that EQW is cost-effective ranged from 76-99%. CONCLUSION: Results suggest that exenatide 2 mg once-weekly is cost-effective over a lifetime horizon compared to dulaglutide 1.5 mg QW, liraglutide 1.2 mg QD, liraglutide 1.8 mg QD, and lixisenatide 20 µg QD for the treatment of T2DM in adults not adequately controlled on metformin alone.

Cost effectiveness of surgical versus non-surgical treatment of adults with displaced fractures of the proximal humerus: economic evaluation alongside the PROFHER trial.

AIMS: A pragmatic multicentre randomised controlled trial (PROFHER) was conducted in United Kingdom National Health Service (NHS) hospitals to evaluate the clinical effectiveness and cost effectiveness of surgery compared with non-surgical treatment for displaced fractures of the proximal humerus involving the surgical neck in adults. METHODS: A cost utility analysis from the NHS perspective was performed. Differences between surgical and non-surgical treatment groups in costs and quality adjusted life years (QALYs) at two years were used to derive an estimate of the cost effectiveness of surgery using regression methods. RESULTS: Patients randomised to receive surgical intervention accumulated mean greater costs and marginally lower QALYs than patients randomised to non-surgery. The surgical intervention cost a mean of £1758 more per patient (95% confidence intervals (CI) £1126 to £2389). Total QALYs for the surgical group were smaller than those for non-surgery -0.0101 (95% CI -0.13 to 0.11). The probability of surgery being cost effective was less than 10% given the current NICE willingness to pay at a threshold of £20 000 for an additional QALY. The results were robust to sensitivity analyses. DISCUSSION: The results suggest that current surgical treatment is not cost effective for the majority of displaced fractures of the proximal humerus involving the surgical neck in the United Kingdom's NHS. TAKE HOME MESSAGE: The results of this trial do not support the trend of increased surgical treatment for patients with displaced fractures of the proximal humerus involving the surgical neck within the United Kingdom NHS.

Multimodal imaging including spectral-domain optical coherence tomography and confocal near-infrared reflectance for characterization of lacquer cracks in highly myopic eyes.

PURPOSE: To compare multimodal imaging in detecting lacquer cracks in highly myopic eyes, and to correlate these findings with those of spectral-domain optical coherence tomography (SD-OCT). METHODS: An observational case series study. Patients with a refractive error worse than -8 diopters and lacquer cracks were recruited. The rates of detection of the lacquer cracks using multimodal imaging including near-infrared reflectance (NIR) imaging, fundus autofluorescence (FAF) imaging, and fluorescence angiography (FA) were compared. The characteristic findings of multimodal imaging were correlated with those of SD-OCT. RESULTS: NIR imaging was more sensitive (92.9%) in detecting lacquer cracks than either FAF (12.5%) or FA (67.9%). Lacquer cracks showed hyperreflectance on NIR, and they were consistently associated with a continuous retinal pigment epithelium-Bruch's membrane complex, thinner choroid, and acoustic shadows on SD-OCT. CONCLUSIONS: NIR imaging is superior to blue laser light (FAF and FA) imaging in detecting lacquer cracks. SD-OCT in combination with NIR located primary pathological lacquer cracks in the intact retinal pigment epithelium-Bruch's membrane complex as well as thinner choroid. These findings indicate that multimodal cSLO and SD-OCT imaging allow for detecting of lacquer cracks in highly myopic eyes.

Economic evaluation of a randomized controlled trial of ultrasound therapy for hard-to-heal venous leg ulcers.

BACKGROUND: A pragmatic, multicentre randomized controlled trial (VenUS III) was conducted to determine whether low-dose ultrasound therapy increased the healing rate of hard-to-heal leg ulcers. This study was a cost-effectiveness analysis of the trial data. METHODS: Cost-effectiveness and cost-utility analyses were conducted alongside the VenUS III trial, in which patients were randomly allocated to either ultrasound treatment administered weekly for 12 weeks along with standard care, or standard care alone. The time horizon was 12 months and based on the UK National Health Service (NHS) perspective. RESULTS: The base-case analysis showed that ultrasound therapy added to standard care was likely to be more costly and provide no extra benefit over standard care alone. Individuals who received ultrasound treatment plus standard care took a mean of 14.7 (95 per cent confidence interval - 32.7 to 56.8) days longer to heal, had 0.009 (-0.042 to 0.024) fewer quality-adjusted life years and had higher treatment costs by £ 197.88 (-35.19 to 420.32). Based on these point estimates, ultrasound therapy plus standard care for leg ulcers was dominated by standard care alone. The analysis of uncertainty showed that this treatment strategy is unlikely to be cost-effective. CONCLUSION: Ultrasound treatment was not cost-effective for hard-to-heal leg ulcers and should not be recommended for adoption in the NHS.

VenUS III: a randomised controlled trial of therapeutic ultrasound in the management of venous leg ulcers.

OBJECTIVES: To compare the clinical effectiveness and cost-effectiveness of low-dose ultrasound delivered in conjunction with standard care against standard care alone in the treatment of hard-to-heal venous ulcers. DESIGN: A multicentre, pragmatic, two-armed randomised controlled trial with an economic evaluation. SETTING: Community nurse services; community leg ulcer clinics; hospital outpatient leg ulcer clinics, among both urban and rural settings in England, Scotland, Northern Ireland and Ireland. PARTICIPANTS: Patients with a venous leg ulcer of > 6 months' duration or > 5 cm2 and an ankle-brachial pressure index of ≥ 0.8. In total, 337 patients were recruited to the study. INTERVENTIONS: Participants in the intervention group received low-dose ultrasound (0.5 W/cm2) delivered at 1 MHz, pulsed pattern of 1 : 4, applied to periulcer skin (via a water-based contact gel) weekly for up to 12 weeks alongside standard care. Standard care consisted of low-adherent dressings and compression therapy, renewed as recommended by the patient's nurse and modified if required to reflect changes in ulcer and skin condition. The output of the ultrasound machines was checked every 3 months to confirm intervention fidelity. MAIN OUTCOME MEASURES: The primary end point was time to healing of the largest eligible ulcer (reference ulcer). Secondary outcomes were time to healing of all ulcers, proportion of patients healed, percentage and absolute change in ulcer size, proportion of time patients were ulcer free, cost of treatments, health-related quality of life (HRQoL), adverse events, withdrawal and loss to follow-up. RESULTS: There was a small, and statistically not significant, difference in the median time to complete ulcer healing of all ulcers in favour of standard care [median 328 days, 95% confidence interval (CI) 235 days, inestimable] compared with ultrasound (median 365 days, 95% CI 224 days, inestimable). There was no difference between groups in the proportion of patients with ulcers healed at 12 months (72/168 in ultrasound vs 78/169 standard care), nor in the change in ulcer size at 4 weeks. There was no evidence of a difference in recurrence of healed ulcers. There was no difference in HRQoL [measured using the Short Form questionnaire-12 items (SF-12)] between the two groups. There were more adverse events with ultrasound than with standard care. Ultrasound therapy as an adjuvant to standard care was found not to be a cost-effective treatment when compared with standard care. The mean cost of ultrasound was £197.88 (bias-corrected 95% CI -£35.19 to £420.32) higher than standard care per participant per year. There was a significant relationship between ulcer healing and area and duration at baseline. In addition, those centres with high recruitment rates had the highest healing rates. CONCLUSIONS: Low-dose ultrasound, delivered weekly during dressing changes, added to the package of current best practice (dressings, compression therapy) did not increase ulcer healing rates, affect quality of life (QoL) or reduce recurrence. It was associated with higher costs and more adverse events. There is no evidence that adding low-dose ultrasound to standard care for 'hard-to-heal' ulcers aids healing, improves QoL or reduces recurrence. It increases costs and adverse events. The relationship between ulcer healing rates and patient recruitment is worthy of further study. TRIAL REGISTRATION: Current Controlled Trials ISRCTN21175670. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 15, No. 13. See the HTA programme website for further project information.

A traumatic macular hole secondary to a high-energy Nd:YAG laser.

A case is reported of a traumatic macular hole caused by a high-energy Nd:YAG laser. The initial ocular examination revealed an explosive, crater-shaped, full-thickness macular hole surrounded by local edema and detachment. By the 12th day after the injury, the hole had shrunk progressively and was covered by a thin fibrin-like membrane. A thick epiretinal membrane covered the injured area 1 month after the injury. Nine months after the injury, the macular hole closed spontaneously with a partially detached epiretinal membrane. This case demonstrates one of the natural healing processes of a traumatic macular hole. Although the hole finally closed, the patient did not regain his vision because of the severe damage to the photoreceptors, retinal pigment epithelium, and choroid.

Endogenous Klebsiella pneumoniae endophthalmitis associated with prostate abscess: case report.

A young alcoholic and heavy smoker was admitted because of Klebsiella pneumoniae bacteremia. The abdominal and pelvic computed tomography with enhancement revealed an abscess in the right prostate. He experienced blurred vision of his left eye on the third day during admission. Initial ocular examination revealed mild reaction in the anterior chamber and vitreous as well as multiple Roth's spots in the retina. The administration of empirical antibiotics including cefazolin and gentamicin intravenously was changed to ceftriaxone and amikacin after ophthalmologic consultation. After parenteral antibiotics for 3 weeks, the systemic condition was controlled, and the vision remained stable. During the past decades, many cases of endogenous Klebsiella pneumoniae endophthalmitis associated with liver abscess were reported in Taiwan. However, documented reports of this condition associated with a prostate abscess are rare. This case, classified as posterior focal endogenous endophthalmitis, had good prognosis under appropriate antibiotic treatment. Early diagnosis and prompt therapy are important for control of sepsis and restoration of vision.

Evaluation of peribulbar anesthesia in encircling scleral buckle surgery and its postoperative pain course.

BACKGROUND: Retrobulbar anesthesia is considered effective in ocular surgery but it can give rise to serious complications. We used peribulbar anesthesia with sub-Tenon's irrigation to perform encircling scleral buckling for retinal detachment, as it could reduce the complications caused by retrobulbar anesthesia. We also recorded the course of pain for 72 hours after surgery. METHODS: Thirty patients who were diagnosed with rhegmatogenous retinal detachment were treated with an encircling scleral buckle. The surgery was performed with peribulbar anesthesia with occasional sub-Tenon's irrigation. We evaluated the patient's pain with a visual analogue scale after surgery at 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 12 hours, 24 hours, 48 hours, and 72 hours. RESULTS: In 24 cases (80%), the anesthesia was complete with the peribulbar block. Only 6 patients (20%) needed sub-Tenon's irrigation and four of them felt no pain after augmentation. Although all the surgical procedures proceeded without problem, two of the patients felt pain and were uncomfortable during the surgery. No serious complications occurred. The course of pain peaked 6 hours after surgery when 26 patients (86.7%) felt pain and 12 patients (40%) were uncomfortable (pain score > or = 5). Forty-eight hours after surgery, 9 patients (30%) still felt pain but no one felt uncomfortable. CONCLUSION: Peribulbar anesthesia can be used safely in encircling scleral buckling for retinal detachment. The postoperative pain is maximal 6 hours after surgery and becomes mild (pain score < or = 4) after 48 hours.