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ABSTRACT: Studies of determinants of recurrent disease often give unexpected results. In particular, well-established risk factors may seem not to have much influence on the recurrence risk. Recently, it has been argued that such paradoxical findings may be because of the bias caused by the selection of patients based on the occurrence of an earlier episode of the disease. This bias was referred to as index event bias. Here, we give a theoretical quantitative example of index event bias, showing that, as a result of selection of patients on the basis of previous disease: (1) risk factors become inversely associated when they are not in the unselected population, and (2) the crude association between the risk factor of interest and disease becomes biased toward the null.
Journal of clinical epidemiology 02/2013; 66(2):192-6. · 2.96 Impact Factor
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ABSTRACT: Purpose: To assess the prevalence of end-of-life visual impairment in patients followed for glaucoma. Methods: Data of 122 patients followed for glaucoma who had died between July 2008 and July 2010 and who had visited the ophthalmology outpatient department of a large non-academic Dutch hospital were collected from the medical files. Sixty-one patients had open-angle glaucoma (OAG), and 61 patients were suspect for glaucoma or had ocular hypertension (OHT). Visual impairment was defined as a mean deviation value <-15 dB or a Snellen visual acuity <0.3 (20/60) of the better eye. We determined the number of patients with visual impairment on the last patient visit before death and investigated its main explanations. Results: Overall, the mean age at death was 81.8 years after a mean follow-up period of 9.2 years. Seventy-three per cent of all patients had their last visit in the year preceding death. In OAG, 16 patients (26%) had an end-of-life visual impairment. In nine patients (15%), this was caused by glaucoma. Eight of them had substantial visual loss at the initial visit. Six (10%) impaired OAG cases were mainly explained by ocular comorbidity, and there was an equal contribution of comorbidity and glaucoma in one case. Five glaucoma suspects or patients with OHT (8%) were visually impaired at death and these were all caused by ocular comorbidity. Conclusion: The prevalence of end-of-life visual impairment is considerable in patients with OAG. Substantial visual loss at baseline is an important contributing factor. In glaucoma suspects or patients with OHT, the prevalence is lower and can be attributed to ocular comorbidity.
Acta ophthalmologica 12/2012; · 2.44 Impact Factor
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ABSTRACT: PURPOSE: To examine which prognostic factors are associated with glaucomatous visual field progression. DESIGN: Knowledge of prognostic factors helps clinicians to select patients at risk of glaucomatous visual field progression and intensify their treatment. METHODS: By consulting relevant databases, we identified 2733 articles published up to September 2010, of which 85 articles investigating prognostic factors for visual field progression in patients with open-angle glaucoma (OAG) were eligible. We summarized results for each factor in tables, noting the direction of the association between the prognostic factor and progression, and the accompanying P value. Four authors, working blind to the factors, independently judged the extent to which a prognostic factor was associated with glaucomatous visual field progression. If there were different associations for normal-tension glaucoma (NTG) studies, they were judged separately. Consensus was reached during group meetings. MAIN OUTCOME MEASURES: The Main Outcome Measure of this review article is the ranking of a factor in the list of 103 presumed prognostic factors for glaucomatous visual field progression. These outcomes have been reported in the Results section of the Abstract. RESULTS: A total of 103 different prognostic factors were investigated in 85 articles. The following factors were clearly associated with glaucomatous visual field progression: age, disc hemorrhages (for NTG), baseline visual field loss, baseline intraocular pressure (IOP), and exfoliation syndrome. An association was unlikely for family history of glaucoma, atherosclerosis, systemic hypertension, visual acuity, sex (for NTG), systolic blood pressure, myopic refractive error (for NTG), and Raynaud's phenomenon. CONCLUSIONS: The factors we found clearly associated with progression could be used in clinical practice and for developing clinical prediction models. For many other factors, further research is necessary. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Ophthalmology 12/2012; · 5.45 Impact Factor
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ABSTRACT: Primary treatment for patients with intermittent claudication is exercise therapy. Diabetes mellitus (DM) is a frequently occurring comorbidity in patients with intermittent claudication, and in these patients, exercise tolerance is decreased. However, there is little literature about the increase in walking distance after supervised exercise therapy (SET) in patients with both intermittent claudication and DM. The objective of this study was to determine the effectiveness of SET for intermittent claudication in patients with DM.
Consecutive patients with intermittent claudication who started SET were included. Exclusion criteria were Rutherford stage 4 to 6 and the inability to perform the standardized treadmill test. SET was administered according to the guidelines of the Royal Dutch Society for Physiotherapy. At baseline and at 1, 3, and 6 months of follow-up, a standardized treadmill exercise test was performed. The primary outcome measurement was the absolute claudication distance (ACD).
We included 775 patients, of whom 230 had DM (29.7%). At 6 months of follow-up, data of 440 patients were available. Both ACD at baseline and at 6 months of follow-up were significantly lower in patients with DM (P < 0.001). However, increase in ACD after 6 months of SET did not differ significantly (P = 0.48) between the DM group and the non-DM group (270 m and 400 m, respectively).
In conclusion, SET for patients with intermittent claudication is equally effective in improving walking distance for both patients with and without DM, although ACD remains lower in patients with DM.
Annals of Vascular Surgery 08/2012; 26(7):957-63. · 1.03 Impact Factor
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ABSTRACT: Screening with ankle-brachial index (ABI) measurement could be clinically relevant to avoid cardiovascular events in subjects with asymptomatic atherosclerosis. To assess the practical impact of guidelines regarding the use of ABI as a screening tool in general practice, the corresponding number needed to screen, including the required time investment, and the feasibility of ABI performance, was assessed.
An observational study was performed in the setting of 955 general practices in the Netherlands. Overall, 13,038 subjects of ≥55 years presenting with symptoms of intermittent claudication and/or presenting with ≥ one vascular risk factor were included. Several guidelines recommend the ABI as an additional measurement in selected populations for risk assessment for cardiovascular morbidity.
Screening of the overall population of ≥50 years results in ≈862 subjects per general practice who should be screened, resulting in a time-requirement of approximately 6 weeks of full time work. Using an existing clinical prediction model, 247 patients per general practice should be screened for PAD by ABI measurement.
Screening the entire population of ≥50 years will in our opinion not be feasible in general practice. A more rationale and efficient approach might be screening of subsets of the population of ≥55 years based on a clinical prediction model.
BMC Cardiovascular Disorders 07/2012; 12:59. · 1.52 Impact Factor
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Harry R Büller, Martin H Prins,
Anthonie W A Lensin,
Hervé Decousus,
Barry F Jacobson,
Erich Minar,
Jaromir Chlumsky,
Peter Verhamme,
Phil Wells,
Giancarlo Agnelli,
Alexander Cohen,
Scott D Berkowitz,
Henri Bounameaux,
Bruce L Davidson,
Frank Misselwitz,
Alex S Gallus,
Gary E Raskob,
Sebastian Schellong,
Annelise Segers
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ABSTRACT: A fixed-dose regimen of rivaroxaban, an oral factor Xa inhibitor, has been shown to be as effective as standard anticoagulant therapy for the treatment of deep-vein thrombosis, without the need for laboratory monitoring. This approach may also simplify the treatment of pulmonary embolism.
In a randomized, open-label, event-driven, noninferiority trial involving 4832 patients who had acute symptomatic pulmonary embolism with or without deep-vein thrombosis, we compared rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily) with standard therapy with enoxaparin followed by an adjusted-dose vitamin K antagonist for 3, 6, or 12 months. The primary efficacy outcome was symptomatic recurrent venous thromboembolism. The principal safety outcome was major or clinically relevant nonmajor bleeding.
Rivaroxaban was noninferior to standard therapy (noninferiority margin, 2.0; P=0.003) for the primary efficacy outcome, with 50 events in the rivaroxaban group (2.1%) versus 44 events in the standard-therapy group (1.8%) (hazard ratio, 1.12; 95% confidence interval [CI], 0.75 to 1.68). The principal safety outcome occurred in 10.3% of patients in the rivaroxaban group and 11.4% of those in the standard-therapy group (hazard ratio, 0.90; 95% CI, 0.76 to 1.07; P=0.23). Major bleeding was observed in 26 patients (1.1%) in the rivaroxaban group and 52 patients (2.2%) in the standard-therapy group (hazard ratio, 0.49; 95% CI, 0.31 to 0.79; P=0.003). Rates of other adverse events were similar in the two groups.
A fixed-dose regimen of rivaroxaban alone was noninferior to standard therapy for the initial and long-term treatment of pulmonary embolism and had a potentially improved benefit-risk profile. (Funded by Bayer HealthCare and Janssen Pharmaceuticals; EINSTEIN-PE ClinicalTrials.gov number, NCT00439777.).
New England Journal of Medicine 04/2012; 366(14):1287-97. · 53.30 Impact Factor
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ABSTRACT: Purpose: To determine the cost-effectiveness of ocular hypertension (OH) treatment initiated with latanoprost compared to timolol.Methods: Two strategies for OH therapy are modelled, (1) ‘starting with timolol’ and (2) ‘starting with latanoprost’. Therapy can be maintained or changed dependent on the achieved intraocular pressure (IOP) and side-effects. Adjustments of therapy to reach a target pressure involve monotherapy, combination therapy and laser. Four drugs are used: latanoprost, timolol, brimonidine and dorzolamide. Once the adjustments of therapy are completed, lifelong follow-up with IOP-dependent conversion to glaucoma and progression to blindness are modelled. Direct medical costs are assigned. The IOP-lowering effect of drugs is based on meta-analyses and applied by Monte Carlo simulation to a hypothetical cohort of patients with OH. The characteristics of the cohort, including the initial IOP distribution, are based on data of 1000 patients.Results: The IOP decreased from 25,4 mm Hg (mean) to 16.7 (±0.017) mm Hg (strategy 1) and to 16.5 (±0.013) mm Hg (strategy 2). Costs per patient within 15 months of therapy were € 367 and € 469, respectively. Lifetime blindness and costs were 0.0334 years and € 3 514 (strategy 1) and 0.0318 years and € 4 397 (strategy 2). Incremental costs per year of vision saved for strategy (2) in comparison with strategy (1) amount to, given the uncertainties in the model, approximately € 537 000.Conclusion: For saving 1 year of vision, high costs are needed when OH therapy is initiated with latanoprost compared to timolol, when the cost price of latanoprost remains high.
Acta ophthalmologica 02/2012; 90(2):146 - 154. · 2.44 Impact Factor
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ABSTRACT: The percentage of time within the target INR range 2.0 to 3.0 (TTR) in patients treated with vitamin K antagonists varies considerably among efficacy-studies of novel anticoagulants. In order to properly asses the quality of anticoagulant control in upcoming cost-effectiveness studies and real life registries this systematic review reports a benchmark of TTR for different treatment durations in patients with venous thromboembolism and discusses ways to calculate TTR.
Medline and Embase were searched for studies published between January 1990 and May 2012. Randomized controlled trials and cohort studies reporting the TTR in patients with objectively confirmed venous thromboembolism treated with vitamin K antagonists (VKA) were eligible. Duplicate reports, studies only reporting INR during initial treatment or with VKA treatment less than 3 months were excluded. Three authors assessed trials for inclusion and extracted data independently. Discrepancies were resolved by discussion between the reviewers. A meta-analysis was performed by calculating a weighted mean, based on the number of participants in each included study, for each time-period in which the TTR was measured since the confirmation of the diagnosis of VTE.
Forty studies were included (26064 patients). The weighted means of TTR were 54.0% in the first month since the start of treatment, 55.6% in months 1 to 3, 60.0% in months 2 to 3, 60.0% in the months1 to 6+ and 75.2% in months 4 to 12+. Five studies reported TTR in classes. The INR in these studies was ≥67% of time in therapeutic range in 72.0% of the patients.
Reported quality of VKA treatment is highly dependent on the time-period since the start of treatment, with TTR ranging from approximately 56% in studies including the 1(st) month to 75% in studies excluding the first 3 months.
PLoS ONE 01/2012; 7(9):e42269. · 4.09 Impact Factor
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Geert-Jan Geersing,
Petra M G Erkens,
Wim A M Lucassen,
Harry R Büller,
Hugo Ten Cate,
Arno W Hoes,
Karel G M Moons, Martin H Prins,
Ruud Oudega,
Henk C P M van Weert,
Henri E J H Stoffers
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ABSTRACT: To validate the use of the Wells clinical decision rule combined with a point of care D-dimer test to safely exclude pulmonary embolism in primary care.
Prospective cohort study.
Primary care across three different regions of the Netherlands (Amsterdam, Maastricht, and Utrecht).
598 adults with suspected pulmonary embolism in primary care.
Doctors scored patients according to the seven variables of the Wells rule and carried out a qualitative point of care D-dimer test. All patients were referred to secondary care and diagnosed according to local protocols. Pulmonary embolism was confirmed or refuted on the basis of a composite reference standard, including spiral computed tomography and three months' follow-up.
Diagnostic accuracy (sensitivity and specificity), proportion of patients at low risk (efficiency), number of missed patients with pulmonary embolism in low risk category (false negative rate), and the presence of symptomatic venous thromboembolism, based on the composite reference standard, including events during the follow-up period of three months.
Pulmonary embolism was present in 73 patients (prevalence 12.2%). On the basis of a threshold Wells score of ≤4 and a negative qualitative D-dimer test result, 272 of 598 patients were classified as low risk (efficiency 45.5%). Four cases of pulmonary embolism were observed in these 272 patients (false negative rate 1.5%, 95% confidence interval 0.4% to 3.7%). The sensitivity and specificity of this combined diagnostic approach was 94.5% (86.6% to 98.5%) and 51.0% (46.7% to 55.4%), respectively.
A Wells score of ≤4 combined with a negative qualitative D-dimer test result can safely and efficiently exclude pulmonary embolism in primary care.
BMJ (Clinical research ed.). 01/2012; 345:e6564.
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Paolo Prandoni,
Franco Noventa,
Roberto Quintavalla,
Carlo Bova,
Benilde Cosmi,
Sergio Siragusa,
Eugenio Bucherini,
Francesco Astorri,
Stefano Cuppini,
Fabio Dalla Valle,
Anthonie W A Lensing, Martin H Prins,
Sabina Villalta
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ABSTRACT: Although below-knee compression elastic stockings (CES) are effective for the prevention of the postthrombotic syndrome (PTS), a substantial number of patients with deep venous thrombosis still develop PTS. In the present open-label, randomized clinical trial, we compared thigh-length with below-knee CES for the prevention of PTS. A total of 267 patients with the first episode of proximal deep venous thrombosis were randomized to wear either thigh-length or below-knee CES for 2 years. After 3, 6, 12, 18, 24, and 36 months, they were assessed for PTS manifestations according to the Villalta scale. PTS developed in 44 (32.6%) of the 135 patients randomized to thigh-length CES and in 47 (35.6%) of the 132 allocated to below-knee CES, for an adjusted hazard ratio of 0.93 (95% confidence interval, 0.62-1.41). Severe PTS developed in 3 patients in each group. CES-related side effects developed in 55 (40.7%) of the 135 patients allocated to thigh-length CES and in 36 (27.3%) of those randomized to the below-knee group (P = .017), and led to premature discontinuation of their use in 29 (21.5%) and 18 (13.6%) patients, respectively. We conclude that thigh-length CES do not offer a better protection against PTS than below-knee CES and are less well tolerated.
Blood 12/2011; 119(6):1561-5. · 9.90 Impact Factor
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ABSTRACT: Treatment of pulmonary embolism with low-molecular-weight heparin and vitamin K antagonists, such as warfarin, is not ideal. We aimed to assess non-inferiority of idrabiotaparinux, a reversible longlasting indirect inhibitor of activated factor X, to warfarin in patients with acute symptomatic pulmonary embolism.
In our randomised, double-blind, double-dummy, non-inferiority trial, we enrolled adults with objectively documented acute symptomatic pulmonary embolism attending 291 centres in 37 countries. We excluded patients who were pregnant, had active bleeding, kidney failure, or malignant hypertension, or were at high risk of death, bleeding, or adverse reactions to study drugs. We randomly allocated patients to receive 5-10 days' enoxaparin 1·0 mg/kg twice daily followed by subcutaneous idrabiotaparinux (starting dose 3·0 mg) or adjusted-dose warfarin (target international normalised ratio 2·0-3·0); regimens lasted 3 months or 6 months dependent on clinical presentation. Block randomisation was done with a central interactive computerised system, stratified by study centre and intended treatment duration. The primary efficacy outcome was recurrent venous thromboembolism at 99 days after randomisation. We estimated the odds ratio and 95% CI with a Mantel-Haenzsel χ(2) analysis (non-inferiority margin 2·0) in the intention-to-treat population. The main safety outcome was clinically relevant bleeding (major or non-major) in all patients at day 99. This study is registered with ClinicalTrials.gov, number NCT00345618.
Between Aug 1, 2006, and Jan 31, 2010, we enrolled 3202 patients aged 18-96 years. 34 (2%) of 1599 patients randomly allocated to receive enoxaparin-idrabiotaparinux and 43 (3%) of 1603 patients randomly allocated to receive enoxaparin-warfarin had recurrent venous thromboembolism (odds ratio 0·79, 95% CI 0·50-1·25; p(non-inferiority)=0·0001). 72 (5%) of 1599 patients in the enoxaparin-idrabiotaparinux group and 106 (7%) of 1603 patients in the enoxaparin-warfarin group had clinically relevant bleeding (0·67, 0·49-0·91; p(superiority)=0·0098). We noted similar differences in outcomes in those patients treated to 6 months.
Idrabiotaparinux could provide an attractive alternative to warfarin for the long-term treatment of pulmonary embolism, and seems to be associated with reduced bleeding.
Sanofi-Aventis (Paris, France).
The Lancet 11/2011; 379(9811):123-9. · 38.28 Impact Factor
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ABSTRACT: A large number of methods have been developed for assessing glaucomatous visual field progression, but their properties have not yet been systematically evaluated. In this systematic literature review, we summarize the evidence base for selecting a method by providing answers to ten relevant questions on the variety, validity and reproducibility of methods. In total, we found 301 different methods in 412 articles. The majority of studies (54%) used the Humphrey Field Analyzer. No data have been published about the reproducibility of methods. Although there is no gold standard to assess glaucomatous visual field progression, we found evidence on validity for 48 different methods. Some methods were less capable of distinguishing between progressive and nonprogressive patients. Choosing among twelve methods is supported by some evidence of their validity. These methods still differ in sensitivity, specificity and predictive values of test results within studies comparing several methods. In conclusion, the current evidence base is not perfect. A selection should be made from a limited number of methods, according to the clinical purpose of progression assessment. Methods that quantify the rate of visual field progression seem to be the most appropriate for guiding subsequent medical actions in individual patients. Future studies should investigate whether using one method to monitor patients is superior to another method in preventing loss of quality of life.
Acta ophthalmologica 08/2011; 90(2):101-8. · 2.44 Impact Factor
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ABSTRACT: Current guidelines discourage combined oral contraceptive (COC) use in women with hereditary thrombophilic defects. However, qualifying all hereditary thrombophilic defects as similarly strong risk factors might be questioned. Recent studies indicate the risk of venous thromboembolism (VTE) of a factor V Leiden mutation as considerably lower than a deficiency of protein C, protein S, or antithrombin. In a retrospective family cohort, the VTE risk during COC use and pregnancy (including postpartum) was assessed in 798 female relatives with or without a heterozygous, double heterozygous, or homozygous factor V Leiden or prothrombin G20210A mutation. Overall, absolute VTE risk in women with no, single, or combined defects was 0.13 (95% confidence interval 0.08-0.21), 0.35 (0.22-0.53), and 0.94 (0.47-1.67) per 100 person-years, while these were 0.19 (0.07-0.41), 0.49 (0.18-1.07), and 0.86 (0.10-3.11) during COC use, and 0.73 (0.30-1.51), 1.97 (0.94-3.63), and 7.65 (3.08-15.76) during pregnancy. COC use and pregnancy were independent risk factors for VTE, with highest risk during pregnancy postpartum, as demonstrated by adjusted hazard ratios of 16.0 (8.0-32.2) versus 2.2 (1.1-4.0) during COC use. Rather than strictly contraindicating COC use, we advocate that detailed counseling on all contraceptive options, including COCs, addressing the associated risks of both VTE and unintended pregnancy, enabling these women to make an informed choice.
Blood 06/2011; 118(8):2055-61; quiz 2375. · 9.90 Impact Factor
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ABSTRACT: To determine whether a percutaneous vascular intervention (PVI) combined with supplemental supervised exercise therapy (SET) is more effective than a PVI alone in improving walking ability in patients with symptomatic peripheral arterial disease (PAD).
In this prospective randomized trial, patients with PAD treated with a PVI were eligible. Exclusion criteria were major amputation or tissue loss, comorbidity preventing physical activity, insufficient knowledge of the Dutch language, no insurance for SET, and prior participation in a SET program. All patients received a PVI and subsequently were randomly assigned to either the PVI alone group (n = 35) or the PVI + SET group (n = 35). The primary outcome parameter was the absolute claudication distance (ACD). This trial was registered at Clinical trials.gov, NCT00497445.
The study included 70 patients, most of whom were treated for an aortoiliac lesion. The mean difference in ACD at 6 months of follow-up was 271.3 m (95% confidence interval [CI] 64.0-478.6, P = .011) in favor of additional SET. In the PVI alone group, 1 (3.7%) patient finished the complete treadmill test compared with 11 (32.4%) patients in the PVI + SET group (P = .005). Physical health-related quality-of-life score was 44.1 ± 7.8 in the PVI alone group compared with 41.9 ± 9.5 in the PVI + SET group, which was a nonsignificant difference (P = .34).
SET following a PVI is more effective in increasing walking distance compared with a PVI alone. These data indicate that SET is a useful adjunct to a PVI for the treatment of PAD.
Journal of vascular and interventional radiology: JVIR 05/2011; 22(7):961-8. · 1.81 Impact Factor
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ABSTRACT: Some patients with acute VTE who may previously have been exposed to heparin products have unrecognized antibodies implicated in heparin-induced thrombocytopenia (HIT). Antibody prevalence and patient consequences upon exposure to heparin, low-molecular-weight heparin, and fondaparinux are uncertain.
In this secondary analysis, we tested patients in the Matisse VTE studies at study entry for heparin-dependent antibodies and further tested patients with enzyme-linked immunosorbent assay (ELISA)-positive results for platelet-activating antibodies. We compared the risk of HIT (> 50% fall in platelet count, heparin-dependent antibodies, no contradicting features) between patients treated with heparin (either unfractionated or low molecular weight [enoxaparin]) vs those who received fondaparinux. Comparison groups for thrombocytopenia occurrence comprised patients with ELISA-positive, platelet-activating, antibody-positive results; ELISA-positive, but platelet-activating antibody-negative results; and randomly selected antibody-negative results.
A total of 127 of 3,994 patients (3.2%) had ELISA-positive results at baseline, but only 14 (0.4%; 95% CI, 0.2%-0.6%) had platelet-activating antibodies. Among these 14, four treated with unfractionated or low-molecular-weight heparin developed HIT compared with zero of 10 fondaparinux-treated patients (OR, 95; 95% CI, 8-1,123; P < .001). This frequency (four of four, 100%) significantly differed from that of both heparin-treated patients whose results were ELISA positive but platelet-activating antibody negative and from heparin-treated antibody-negative control subjects (zero of 15 and zero of 27, respectively; P < .001 for both).
Of patients with VTE, 0.4% had pathologic platelet-activating heparin-dependent antibodies rather than the 3.2% detected by the recommended cutoff of the commercial ELISA. Among study patients with acute VTE who had platelet-activating antibodies, treatment with fondaparinux reduced the risk of precipitating rapid-onset HIT.
Chest 03/2011; 140(2):366-73. · 5.25 Impact Factor
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British Journal of Haematology 01/2011; 153(1):134-6. · 4.94 Impact Factor
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ABSTRACT: To assess the impact of 2 strategies for initiating therapy in ocular hypertension (OH) on drug use, intraocular pressure (IOP), and blindness caused by glaucoma.
Using a simulation model, initiating therapy with timolol (strategy 1) and with latanoprost (strategy 2) was simulated for a hypothetic cohort of ocular hypertension patients with an initial IOP distribution (data of 1000 patients). Adjustment of therapy within 15 months and a subsequent lifelong follow-up, with an IOP dependent conversion to glaucoma, were modeled. The IOP lowering effect of medication (based on a meta-analysis) was applied by Monte Carlo simulation. Therapy could be maintained or changed, depending on the achieved IOP and side effects. Four drugs (latanoprost, timolol, brimonidine, dorzolamide) were used as monotherapy or in combination. Glaucoma conversion rate was based on literature.
Treatment goal was achieved in both strategies in 90% by monotherapy. This was 60% for patients with initial IOP's of 30 mm Hg. The originally prescribed medication was maintained in 66% (1) and in 77% (2). IOP decreased with approximately 34%, from 25.4 mm Hg (mean) to 16.7 mm Hg (1) and to 16.5 mm Hg (2) Blindness per person within 18.7 years of life expectancy was 0.0923 years (1) and 0.0870 years (2), which corresponds to approximately 1 month. The difference between strategies was 2 days spent in blindness per patient.
The difference in clinical effects of the strategies is small. This is largely owing to the key concept of a target pressure, which underlies both strategies.
Journal of glaucoma 01/2011; 20(1):30-6. · 1.74 Impact Factor
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Rupert Bauersachs,
Scott D Berkowitz,
Benjamin Brenner,
Harry R Buller,
Hervé Decousus,
Alex S Gallus,
Anthonie W Lensing,
Frank Misselwitz, Martin H Prins,
Gary E Raskob,
Annelise Segers,
Peter Verhamme,
Phil Wells,
Giancarlo Agnelli,
Henri Bounameaux,
Alexander Cohen,
Bruce L Davidson,
Franco Piovella,
Sebastian Schellong
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ABSTRACT: Rivaroxaban, an oral factor Xa inhibitor, may provide a simple, fixed-dose regimen for treating acute deep-vein thrombosis (DVT) and for continued treatment, without the need for laboratory monitoring.
We conducted an open-label, randomized, event-driven, noninferiority study that compared oral rivaroxaban alone (15 mg twice daily for 3 weeks, followed by 20 mg once daily) with subcutaneous enoxaparin followed by a vitamin K antagonist (either warfarin or acenocoumarol) for 3, 6, or 12 months in patients with acute, symptomatic DVT. In parallel, we carried out a double-blind, randomized, event-driven superiority study that compared rivaroxaban alone (20 mg once daily) with placebo for an additional 6 or 12 months in patients who had completed 6 to 12 months of treatment for venous thromboembolism. The primary efficacy outcome for both studies was recurrent venous thromboembolism. The principal safety outcome was major bleeding or clinically relevant nonmajor bleeding in the initial-treatment study and major bleeding in the continued-treatment study.
The study of rivaroxaban for acute DVT included 3449 patients: 1731 given rivaroxaban and 1718 given enoxaparin plus a vitamin K antagonist. Rivaroxaban had noninferior efficacy with respect to the primary outcome (36 events [2.1%], vs. 51 events with enoxaparin-vitamin K antagonist [3.0%]; hazard ratio, 0.68; 95% confidence interval [CI], 0.44 to 1.04; P<0.001). The principal safety outcome occurred in 8.1% of the patients in each group. In the continued-treatment study, which included 602 patients in the rivaroxaban group and 594 in the placebo group, rivaroxaban had superior efficacy (8 events [1.3%], vs. 42 with placebo [7.1%]; hazard ratio, 0.18; 95% CI, 0.09 to 0.39; P<0.001). Four patients in the rivaroxaban group had nonfatal major bleeding (0.7%), versus none in the placebo group (P=0.11).
Rivaroxaban offers a simple, single-drug approach to the short-term and continued treatment of venous thrombosis that may improve the benefit-to-risk profile of anticoagulation. (Funded by Bayer Schering Pharma and Ortho-McNeil; ClinicalTrials.gov numbers, NCT00440193 and NCT00439725.).
New England Journal of Medicine 12/2010; 363(26):2499-510. · 53.30 Impact Factor
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ABSTRACT: The first-line intervention for intermittent claudication is usually supervised exercise therapy (SET). The literature describes a range of exercise programs varying in setting, duration, and content. The purpose of the present study was to examine the exercise protocols offered and to identify the impact of the intensity of the SET programs (in terms of frequency, duration, and type of exercise) on improvements in walking distance (response) in the first 3 months. The present study is part of the Exercise Therapy in Peripheral Arterial Disease (EXITPAD) study, a multicenter randomized clinical trial comparing the effects of SET provided by regional physiotherapists, with or without daily feedback, on the level of activities with the effects of walking advice.
The analysis included patients randomized to receive SET with or without feedback. The physical therapists administering the SET were asked to fill out therapy evaluation sheets stating frequency, duration, and type of exercises. The relationship between training volume and the impact on walking distance was explored by dividing training volume data into tertiles and relating them to the median change in maximum walking distance at 3 and 12 months.
Data of 169 patients were included in the analysis. A SET program consisting of at least two training sessions per week each lasting over 30 minutes, during the first 3 months of a 1-year program tailored to individual patients' needs led to better results in terms of walking distance after 3 and 12 months than the other variants. The results of our analysis dividing training volume into tertiles suggest that there is a relationship between training volume and improvement in walking distance and that at least 590 minutes of training should be offered in the first 3 months. No differences were found between program involving only walking and a combination of exercises, nor between individual and group training.
A SET programs consisting of at least two training sessions a week, each lasting over 30 minutes, should be offered during the first 3 months of the SET program to optimize improvement in terms of maximum walking distance.
Journal of vascular surgery: official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter 11/2010; 52(5):1226-33. · 3.52 Impact Factor
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ABSTRACT: Basal cell carcinoma (BCC) is a slowly growing nonmelanoma type of skin cancer that often is located on the face. Different therapies are available to treat BCC, of which surgical excision (SE) and Mohs micrographic surgery (MMS) are the most frequently used surgical procedures.
To examine which attributes of a surgical treatment the general public values as important and to determine the incremental willingness to pay for MMS versus SE.
A discrete-choice experiment (DCE) was conducted among members of the general public to examine which attributes of a surgical treatment for primary BCC are valued as important. In addition, based on the attributes included in the experiment, the willingness to pay for MMS versus SE was determined.
Respondents (N=312) preferred a treatment with a lower recurrence rate, shorter surgery time, shorter travelling time, shorter waiting time, no risk for re-excision, and lower cost. The incremental willingness to pay for MMS was 847 euro ($1,203).
Results from this DCE indicate that, when outcome and process attributes are considered from a societal perspective, MMS is preferred over SE for primary BCC. The authors have indicated no significant interest with commercial supporters.
Dermatologic Surgery 11/2010; 36(12):1950-5. · 1.80 Impact Factor
