The potential economic value of a 'universal' (multi-year) influenza vaccine

Please cite this paper as: Lee et al. (2011) The potential economic value of a ‘universal’ (multi‐year) influenza vaccine. Influenza and Other Respiratory Viruses 6(3), 167–175. Background Limitations of the current annual influenza vaccine have led to ongoing efforts to develop a ‘universal’ influenza vaccine, i.e., one that targets a ubiquitous portion of the influenza virus so that the coverage of a single vaccination can persist for multiple years. Objectives To estimate the economic value of a ‘universal’ influenza vaccine compared to the standard annual influenza vaccine, starting vaccination in the pediatric population (2–18 year olds), over the course of their lifetime. Patient/Methods Monte Carlo decision analytic computer simulation model. Results Universal vaccine dominates (i.e., less costly and more effective) the annual vaccine when the universal vaccine cost ≤$100/dose and efficacy ≥75% for both the 5‐ and 10‐year duration. The universal vaccine is also dominant when efficacy is ≥50% and protects for 10 years. A $200 universal vaccine was only cost‐effective when ≥75% efficacious for a 5‐year duration when annual compliance was 25% and for a 10‐year duration for all annual compliance rates. A universal vaccine is not cost‐effective when it cost $200 and when its efficacy is ≤50%. The cost‐effectiveness of the universal vaccine increases with the duration of protection. Conclusions Although development of a universal vaccine requires surmounting scientific hurdles, our results delineate the circumstances under which such a vaccine would be a cost‐effective alternative to the annual influenza vaccine.     

Ablation of perimitral flutter following catheter ablation of atrial fibrillation: impact on outcomes from a randomized study (PROPOSE)

MVI Block vs Trigger Ablation in PMFL . Introduction: Patients with previous ablation for atrial fibrillation (AF) may experience recurrence of perimitral flutter (PMFL). These arrhythmias are usually triggered from sources that may also induce AF. This study aims at determining whether ablation of triggers or completing mitral valve isthmus (MVI) block prevents more arrhythmia recurrences. Methods and Results: Sixty‐five patients with recurrent PMFL after initial ablation of long standing persistent AF were included in this study. Thirty‐two patients were randomized to MVI ablation only (Group 1) and 33 were randomized to cardioversion and repeat pulmonary vein (PV) isolation plus ablation of non‐PV triggers (Group 2). MVI bidirectional block was achieved in all but 1 patient from Group 1. In Group 2, reconnection of 17 PVs was detected in 14 patients (42%). With isoproterenol challenge, 44 non‐PV trigger sites were identified in 28 patients (85%, 1.57 sites per patient). At 18‐month follow‐up, 27 patients (84%) from Group 1 had recurrent atrial tachyarrhythmias, of whom 15 remained on antiarrhythmic drug (AAD); however, 28 patients from Group 2 (85%, P < 0.0001 vs Group 1) were free from arrhythmia off AAD. The ablation strategy used in Group 2 was associated with a lower risk of recurrence (hazard ratio = 0.10, 95% CI 0.04–0.28, P < 0.001) and an improved arrhythmia‐free survival (log rank P < 0.0001). Conclusion: In patients presenting with PMFL after ablation for longstanding persistent AF, MVI block had limited impact on arrhythmia recurrence. On the other hand, elimination of all PV and non‐PV triggers achieved higher freedom from atrial arrhythmias at follow‐up. (J Cardiovasc Electrophysiol, Vol. 23, pp. 137‐144, February 2012)     

Aberrant medial sural artery causing popliteal vein entrapment syndrome

Isolated popliteal venous entrapment is unusual and often caused by variation or aberrant origins of the gastrocnemius muscle, thickened perivenous fascia or an abnormal vascular bundle. We report a unique case of a fit and well 35-year-old man with popliteal venous entrapment after presenting to the vascular unit with symptomatic varicose veins. The cause of the entrapment was found to be an aberrant medial sural artery on operative exploration. The artery was ligated, releasing the entrapped vein. The patient made an uneventful recovery with resolution of symptoms of venous insufficiency without evidence of muscle ischaemia.     

Computer-based interventions for sexual health promotion: systematic review and meta-analyses

This systematic review was conducted to determine the effects of self-help interactive computer-based interventions (ICBIs) for sexual health promotion. We searched 40 databases for randomized controlled trials (RCTs) of computer-based interventions, defining 'interactive' as programmes that require contributions from users to produce personally relevant material. We conducted searches and analysed data using Cochrane Collaboration methods. Results of RCTs were pooled using a random-effects model with standardized mean differences for continuous outcomes and odds ratios (ORs) for binary outcomes, with heterogeneity assessed using the I(2) statistic. We identified 15 RCTs of ICBIs (3917 participants). Comparing ICBIs to minimal interventions, there were significant effects on sexual health knowledge (standardized mean difference [SMD] 0.72, 95% confidence interval [CI] 0.27-1.18); safer sex self-efficacy (SMD 0.17, 95% CI 0.05-0.29); safer-sex intentions (SMD 0.16, 95% CI 0.02-0.30); and sexual behaviour (OR 1.75, 95% CI 1.18-2.59). ICBIs had a greater impact on sexual health knowledge than face-to-face interventions did (SMD 0.36, 95% CI 0.13-0.58). ICBIs are effective tools for learning about sexual health, and show promising effects on self-efficacy, intention and sexual behaviour. More data are needed to analyse biological outcomes and cost-effectiveness.     

A Comprehensive Evaluation of the Performance of the Test Strip Technology for OneTouch Verio Glucose Meter Systems

Abstract Background: OneTouch(?) Verio(?) test strips (LifeScan Inc., Milpitas, CA) are designed to minimize error when used in blood glucose monitoring systems. These strips have a specialized architecture and incorporate a sophisticated waveform and proprietary algorithm. Materials and Methods: Performance of OneTouch Verio test strips was assessed in the laboratory in the presence of a wide range of patient, environmental, and pharmacologic factors. A clinical evaluation was conducted in which 296 patients and healthcare professionals (HCPs) performed glucose testing using OneTouch Verio test strips and OneTouch VerioIQ meters. Results: In the laboratory study, OneTouch Verio test strip results achieved a high level of performance over a wide range of hematocrit (19-61%), temperature (5-45(°)C), humidity (10-90% relative humidity), and altitude (0-3,048?m) conditions. Performance was not affected by 22 of 23 chemical compounds. In the clinical study, 100% (31/31) of lay-user test results were within ±10?mg/dL of reference values for blood glucose <75?mg/dL. At blood glucose ≥75?mg/dL, 99.2% (243/245) were within ±15% of reference values. A feature of the VerioIQ meter, PatternAlert(?) Technology, was correctly used and positively evaluated by >98% of lay users. Conclusions: OneTouch Verio test strips are accurate and precise over a wide range of patient, environmental, and pharmacologic conditions. In addition, lay-users were able to successfully use the OneTouch VerioIQ PatternAlert Technology without HCP training.     

The nature and severity of urinary incontinence in post-natal women

This study investigated the frequency, nature and experience of urinary incontinence in post-natal women. Surveys were completed by 224 women, 50% of whom indicated that they had experienced accidental urine loss. The majority of women who had experienced any symptoms were moderately to greatly bothered by them. A variety of strategies were used to manage the problem; however, 42% of the women who experienced accidental urine loss had taken no action to ease the problem. Women received information about urinary incontinence and pelvic floor exercises from a variety of health care professionals, but this was not consistently provided. The implications of these findings are discussed.     

Cytopenia induction by 5-fluorouracil identifies thrombopoietic mutants in sensitized ENU mutagenesis screens

The ability of random mutagenesis techniques to annotate the mammalian genome can be hampered due to genetic redundancy and compensatory pathways that mask heterozygous mutations under homeostatic conditions. The objective of this study was to devise a pharmacologically sensitized screen using the chemotherapeutic drug, 5-fluorouracil (5FU), to induce cytopenia. 5FU dose was optimized in the 129/SvImJ, C57BL/6J, BALB/cJ, and C3H/HeJ strains of laboratory mice. N-ethyl-N-nitrosourea (ENU) mutagenesis was performed on 129/SvImJ males and phenotypic variants were identified by backcrossing on to the C57BL/6J background. G1 animals were challenged with 100 μg/g 5FU and phenodeviants with altered platelet recovery were monitored. Of 546 G1 animals tested, 15 phenodeviants were identified that displayed increased baseline platelet number, a platelet overshoot, or delayed platelet recovery, thereby demonstrating the utility of this approach for uncovering mutations in megakaryocyte and platelet development. Four G1 mice were selected for further analysis. The phenotypes were heritable in all four strains and genetic mapping identified a chromosome location in two of the three G2 lines tested. In conclusion, our group has developed a sensitized random mutagenesis screen utilizing 5FU and has shown that the strain combination of 129/SvImJ × C57BL/6J is robust for identification of founder lines with defects in megakaryocyte and platelet development.     

Antihypertensive drug treatment: a comparison of usual care with self blood pressure measurement

Blood pressure self-measurement is increasing in most communities and yet its role in the management of hypertension is poorly understood. This study was devised to evaluate the behaviour of doctors in general practice when treating patients with poorly controlled essential hypertension who use self-measurement. Patients, most of whom were already taking antihypertensive medications were commenced on perindopril or indapamide at their doctor's discretion and were randomly allocated to self-measurement (SM) using an OMRON HEM706 oscillometric device or a continuation of their usual care (UC) over an 8-week period. This was an observational study without any specific or set treatment goals for the doctor to follow. Sixty of 62 subjects completed the study and the two groups were equally matched for age, body mass index, gender, and blood pressure (BP). While additional perindopril or indapamide produced a significant fall in BP in both groups over the study period, the systolic pressure remained significantly higher in the SM group (sitting 148 +/- 3 compared with 142 +/- 3; 145 +/- 3 compared with 138 +/- 3 mm Hg respectively; P < 0.05). Twenty-four hour and daytime ambulatory monitor systolic pressures were also significantly higher in the SM group. Differences in diastolic BP were not statistically significant. Furthermore, SM patients were less likely to have their medications increased and more likely to have them reduced or ceased. Doctors and patients found self-measurement convenient and useful. This study suggests that doctors prescribing decisions are influenced by evidence from self-measurement of BP with consequential increases in office BP related to reduced drug use. While self-BP measurement can offer reassurance about adequacy of control when away from a physicians office, our best evidence of understanding target blood pressures comes from large randomised studies using office blood pressures as an end-point. There is an urgent need for further study to provide arbitration between self-measurement and office blood pressures although each measurement must contribute to the management of hypertension.     

Stent design favorably influences the vascular response in normal porcine coronary arteries

OBJECTIVES: The purpose of this study was to compare the arterial response following implantation of a stainless-steel, balloon-expandable, tubular slotted stent with that of a novel computer-designed, multi-cellular stent in normal porcine coronary arteries. BACKGROUND: Intracoronary stent placement has evolved into the primary strategy for percutaneous revascularization of symptomatic coronary arterial lesions. Presently there is intense interest in developing new stent designs to improve stent delivery and biocompatability. METHODS: Computer-assisted design was utilized to develop a balloon-expandable stent with symmetric expansion properties, uniform arterial wall coverage, longitudinal flexibility and radial strength. Quantitative coronary angiography and histological assessment of the stented arteries was used to evaluate the acute and chronic vascular responses to a stainless-steel, balloon-expandable, tubular slotted stent as compared to the computer-designed BX stent in the normolipemic swine. RESULTS: Forty stents (24 BX, 16 tubular slotted) were implanted in 19 miniature swine at a mean inflation pressure of 9 atm using identical delivery systems. Eight of the BX and none of the tubular slotted stents were post-dilated with a non-compliant balloon at 12-14 atm. The mean stent-to-artery ratio was similar for the BX (1.03 +/- 0.06) and tubular slotted (1.04 +/- 0.11; p = 0.59) designs. Protrusion or asymmetric radial flaring of a strut at the stent margin was present in 1 of 23 BX stents (4.3%) and 10 of 15 tubular slotted stents (66.7%; p < 0.0001). The mean arterial injury score was significantly less for the BX stent (0.2 +/- 0.2) as compared with the tubular slotted stents (0.4 +/- 0.4; p = 0.025). At 3 days, thrombus area was similar for the BX and tubular slotted designs (0.42 +/- 0.16 mm2 versus 0.44 +/- 0.18 mm2, respectively; p = 0.88). The mean neointimal area was significantly less for the BX at 2 months (1.09 +/- 0.25 mm2 versus 2.93 +/- 2.26 mm2 in the tubular slotted stent) and at 6 months (1.10 +/- 0.26 mm2 versus 2.07 +/- 0.65 mm2 in the tubular slotted stent; p = 0.01), resulting in approximately 50% less in-stent stenosis. CONCLUSIONS: The arterial response to a balloon-expandable stent can be favorably influenced by computer-assisted modification of design in an experimental model. Further study is warranted to determine the impact of stent design upon clinical in-stent restenosis.     

Progression of mitral regurgitation: a prospective Doppler echocardiographic study.

OBJECTIVES: This study was performed to define the rates and determinants of progression of organic mitral regurgitation (MR). BACKGROUND: Severe MR has major clinical consequences, but the rates and determinants of progression of the degree of regurgitation are unknown. Quantitative Doppler echocardiographic methods allow the quantitation of regurgitant volume (RVol), regurgitant fraction (RF) and effective regurgitant orifice (ERO) to define progression of MR. METHODS: In a prospective study of MR progression, 74 patients had two quantitative Doppler echocardiographic examinations of MR (with at least two methods) 561 +/- 423 days apart without an intervening event. RESULTS: Progression of MR was observed, with increase in RVol (77 +/- 46 ml vs. 65 +/- 40 ml, p < 0.0001), RF (47 +/- 16% vs. 43% +/- 15%, p < 0.0001), and ERO (50 +/- 35 mm2 vs. 41 +/- 28 mm2, p < 0.0001). Annual rates (95% confidence interval) were, respectively, 7.4 ml/year (5.1, 9.7), 2.9%/year (1.9, 3.9) and 5.9 mm2/year (3.9, 7.8). However, wide individual variation was observed, and regression and progression of RVol >8 ml was found in 11% and 51%, respectively. In multivariate analysis, independent predictors of progression of RVol were progression of the lesions, particularly a new flail leaflet (p = 0.0003), and progression of mitral annulus diameter (p = 0.0001). Regression of MR was associated with marked changes in afterload, particularly decreased blood pressure (p = 0.008). No significant effect of treatment was detected. CONCLUSIONS: Organic MR tends to progress over time with increase in volume overload (RVol) due to increase in ERO. Progression of MR is variable and determined by progression of lesions or mitral annulus size. These data should help plan follow up of patients with organic MR and future intervention trials.