Transcatheter aortic valve implantation (TAVI) for treatment of aortic valve stenosis: an evidence update.

BACKGROUND: One-year mortality outcomes in the PARTNER trial showed that transcatheter aortic valve implantation (TAVI) was noninferior to surgical aortic valve replacement (sAVR) in patients who were eligible for sAVR (cohort A), and superior to standard treatment in patients who were ineligible for sAVR (cohort B). OBJECTIVE: To update a previous report on the safety, effectiveness, and cost-effectiveness of TAVI, published in 2012. DATA SOURCES: A literature search was performed on September 11, 2012, using OVID MEDLINE, OVID MEDLINE In-Process and Other Non-Indexed Citations, OVID EMBASE, EBSCO Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Wiley Cochrane Library, and the Centre for Reviews and Dissemination database, for studies published from January 1, 2011, until September 11, 2012. REVIEW METHODS: Randomized controlled trials investigating TAVI in comparison to sAVR or standard treatment were included for analysis. Results were summarized descriptively. RESULTS: At 2-year follow-up, mortality in cohort A was similar between the TAVI and sAVR groups. Rates of stroke/transient ischemic attack, major vascular complications, and moderate/severe paravalvular aortic regurgitation were significantly higher in the TAVI group, but rate of major bleeding was significantly higher in the sAVR group. Mortality in cohort B was significantly lower with transfemoral (TF) TAVI than with standard treatment, but rate of stroke was significantly higher with TF TAVI. TF TAVI resulted in a more rapid improvement in quality of life scores than sAVR, but this difference was not sustained at 6 and 12 months. Patients who underwent transapical TAVI did not have a greater early improvement in quality of life compared to sAVR patients. Compared to standard treatment, TF TAVI resulted in a greater improvement in quality of life scores at all time points. Incremental cost-effectiveness ratios were in favour of TAVI for inoperable patients in the base-case analysis, but varied widely for operable patients. CONCLUSIONS: The findings of the 2-year follow-up with respect to mortality and adverse events were consistent with those of the 1-year follow-up. TAVI was also associated with improvement in quality of life, although results varied by cohort. Consistent with the 2012 report, TAVI may be cost-effective for patients who are not candidates for surgery.

Transcatheter aortic valve implantation (TAVI) for treatment of aortic valve stenosis: an evidence-based Analysis (part B).

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has become an alternative to surgical aortic valve replacement (sAVR) for patients at high risk for surgery. OBJECTIVE: To evaluate the safety, effectiveness, and cost-effectiveness of TAVI for treatment of aortic valve stenosis in symptomatic older adults. REVIEW METHODS: A literature search was performed on September 6, 2011, for studies published from January 1, 2007, to September 6, 2011. A combined decision tree and Markov model was developed to compare costs, life years, and quality-adjusted life-years (QALYs) of all treatment options in their respective patient populations over a 20-year time horizon. RESULTS: Two studies from the PARTNER trial were identified. The first study compared TAVI to sAVR in patients who were candidates for sAVR. The second study compared TAVI to standard treatment in patients who were not eligible for sAVR. The first study showed that TAVI and sAVR had similar mortality rates at 1 year. The second study showed a significant improvement in patient survival in those undergoing TAVI. However, in both studies, the TAVI group had significantly higher rates of stroke/transient ischemic attack, and major vascular complications. Rates of major bleeding were significantly higher in sAVR group in the first study and significantly higher in TAVI group in the second study. The base-case cost-effectiveness of TAVI was $48,912 per QALY, but the incremental cost-effectiveness ratio ranged from $36,000 to $291,000 per QALY depending on the assumptions made in the longer-term prediction portion of the model (i.e., beyond the follow-up period of the PARTNER trial). CONCLUSIONS: TAVI improves survival in patients who cannot undergo surgery. For those who are candidates for surgery, TAVI has a mortality rate similar to sAVR, but it is associated with significant adverse effects. TAVI may be cost-effective for patients who cannot undergo surgery, but is not cost-effective for patients who can.

Metal-on-metal hip resurfacing arthroplasty: an analysis of safety and revision rates.

BACKGROUND: Metal-on-metal (MOM) hip resurfacing arthroplasty (HRA) is in clinical use as an appropriate alternative to total hip arthroplasty in young patients. In this technique, a metal cap is placed on the femoral head to cover the damaged surface of the bone and a metal cup is placed in the acetabulum. OBJECTIVES: The primary objective of this analysis was to compare the revision rates of MOM HRA using different implants with the benchmark set by the National Institute of Clinical Excellence (NICE). The secondary objective of this analysis was to review the literature regarding adverse biological effects associated with implant material. REVIEW METHODS: A literature search was performed on February 13, 2012, to identify studies published from January 1, 2009, to February 13, 2012. RESULTS: The revision rates for MOM HRA using 6 different implants were reviewed. The revision rates for MOM HRA with 3 implants met the NICE criteria, i.e., a revision rate of 10% or less at 10 years. Two implants had short-term follow-ups and MOM HRA with one of the implants failed to meet the NICE criteria. Adverse tissue reactions resulting in failure of the implants have been reported by several studies. With a better understanding of the factors that influence the wear rate of the implants, adverse tissue reactions and subsequent implant failure can be minimized. Many authors have suggested that patient selection and surgical technique affect the wear rate and the risk of tissue reactions. The biological effects of high metal ion levels in the blood and urine of patients with MOM HRA implants are not known. Studies have shown an increase in chromosomal aberrations in patients with MOM articulations, but the clinical implications and long-term consequences of this increase are still unknown. Epidemiological studies have shown that patients with MOM HRA implants did not have an overall increase in mortality or risk of cancer. There is insufficient clinical data to confirm the teratogenicity of MOM implants in humans. CONCLUSIONS: Metal-on-metal HRA can be beneficial for appropriately selected patients, provided the surgeon has the surgical skills required for performing this procedure.

Collagen cross-linking using riboflavin and ultraviolet-a for corneal thinning disorders: an evidence-based analysis.

OBJECTIVE: The main objectives for this evidence-based analysis were to determine the safety and effectiveness of photochemical corneal collagen cross-linking with riboflavin (vitamin B(2)) and ultraviolet-A radiation, referred to as CXL, for the management of corneal thinning disease conditions. The comparative safety and effectiveness of corneal cross-linking with other minimally invasive treatments such as intrastromal corneal rings was also reviewed. The Medical Advisory Secretariat (MAS) evidence-based analysis was performed to support public financing decisions. SUBJECT OF THE EVIDENCE-BASED ANALYSIS: The primary treatment objective for corneal cross-linking is to increase the strength of the corneal stroma, thereby stabilizing the underlying disease process. At the present time, it is the only procedure that treats the underlying disease condition. The proposed advantages for corneal cross-linking are that the procedure is minimally invasive, safe and effective, and it can potentially delay or defer the need for a corneal transplant. In addition, corneal cross-linking does not adversely affect subsequent surgical approaches, if they are necessary, or interfere with corneal transplants. The evidence for these claims for corneal cross-linking in the management of corneal thinning disorders such as keratoconus will be the focus of this review. The specific research questions for the evidence review were as follows: TECHNICAL: How technically demanding is corneal cross-linking and what are the operative risks? SAFETY: What is known about the broader safety profile of corneal cross-linking?Effectiveness - Corneal Surface Topographic Affects:What are the corneal surface remodeling effects of corneal cross-linking?Do these changes interfere with subsequent interventions, particularly corneal transplant known as penetrating keratoplasty (PKP)?Effectiveness -Visual Acuity:What impacts does the remodeling have on visual acuity?Are these impacts predictable, stable, adjustable and durable?Effectiveness - Refractive Outcomes: What impact does remodeling have on refractive outcomes?Effectiveness - Visual Quality (Symptoms): What impact does corneal cross-linking have on vision quality such as contrast vision, and decreased visual symptoms (halos, fluctuating vision)?Effectiveness - Contact lens tolerance: To what extent does contact lens intolerance improve after corneal cross-linking?Vision-Related QOL: What is the impact of corneal cross-linking on functional visual rehabilitation and quality of life?PATIENT SATISFACTION: Are patients satisfied with their vision following the procedure?Disease Process:What impact does corneal cross-linking have on the underling corneal thinning disease process?Does corneal cross-linking delay or defer the need for a corneal transplant?What is the comparative safety and effectiveness of corneal cross-linking compared with other minimally invasive treatments for corneal ectasia such as intrastromal corneal rings? CLINICAL NEED: TARGET POPULATION AND CONDITION Corneal ectasia (thinning) disorders represent a range of disorders involving either primary disease conditions, such as keratoconus (KC) and pellucid marginal corneal degeneration, or secondary iatrogenic conditions, such as corneal thinning occurring after laser in situ keratomileusis (LASIK) refractive surgery. Corneal thinning is a disease that occurs when the normally round dome-shaped cornea progressively thins causing a cone-like bulge or forward protrusion in response to the normal pressure of the eye. The thinning occurs primarily in the stroma layers and is believed to be a breakdown in the collagen process. This bulging can lead to irregular astigmatism or shape of the cornea. Because the anterior part of the cornea is responsible for most of the focusing of the light on the retina, this can then result in loss of visual acuity. The reduced visual acuity can make even simple daily tasks, such as driving, watching television or reading, difficult to perform. Keratoconus is the most common form of corneal thinning disorder and involves a noninflammatory chronic disease process of progressive corneal thinning. Although the specific cause for the biomechanical alterations in the corneal stroma is unknown, there is a growing body of evidence suggesting that genetic factors may play an important role. Keratoconus is a rare disease (< 0.05% of the population) and is unique among chronic eye diseases because it has an early onset, with a median age of 25 years. Disease management for this condition follows a step-wise approach depending on disease severity. Contact lenses are the primary treatment of choice when there is irregular astigmatism associated with the disease. Patients are referred for corneal transplants as a last option when they can no longer tolerate contact lenses or when lenses no longer provide adequate vision. Keratoconus is one of the leading indications for corneal transplants and has been so for the last 3 decades. Despite the high success rate of corneal transplants (up to 20 years) there are reasons to defer it as long as possible. Patients with keratoconus are generally young and a longer-term graft survival of at least 30 or 40 years may be necessary. The surgery itself involves lengthy time off work and postsurgery, while potential complications include long-term steroid use, secondary cataracts, and glaucoma. After a corneal transplant, keratoconus may recur resulting in a need for subsequent interventions. Residual refractive errors and astigmatism can remain challenges after transplantation, and high refractive surgery and regraft rates in KC patients have been reported. Visual rehabilitation or recovery of visual acuity after transplant may be slow and/or unsatisfactory to patients. DESCRIPTION OF TECHNOLOGY/THERAPY: Corneal cross-linking involves the use of riboflavin (vitamin B(2)) and ultraviolet-A (UVA) radiation. A UVA irradiation device known as the CXL® device (license number 77989) by ACCUTECH Medical Technologies Inc. has been licensed by Health Canada as a Class II device since September 19, 2008. An illumination device that emits homogeneous UVA, in combination with any generic form of riboflavin, is licensed by Health Canada for the indication to slow or stop the progression of corneal thinning caused by progressive keratectasia, iatrogenic keratectasia after laser-assisted in situ keratomileusis (LASIK) and pellucid marginal degeneration. The same device is named the UV-X® device by IROCMedical, with approvals in Argentina, the European Union and Australia. UVA devices all use light emitting diodes to generate UVA at a wavelength of 360-380 microns but vary in the number of diodes (5 to 25), focusing systems, working distance, beam diameter, beam uniformity and extent to which the operator can vary the parameters. In Ontario, CXL is currently offered at over 15 private eye clinics by refractive surgeons and ophthalmologists. The treatment is an outpatient procedure generally performed with topical anesthesia. The treatment consists of several well defined procedures. The epithelial cell layer is first removed, often using a blunt spatula in a 9.0 mm diameter under sterile conditions. This step is followed by the application of topical 0.1% riboflavin (vitamin B(2)) solution every 3 to 5 minutes for 25 minutes to ensure that the corneal stroma is fully penetrated. A solid-state UVA light source with a wavelength of 370 nm (maximum absorption of riboflavin) and an irradiance of 3 mW/cm(2) is used to irradiate the central cornea. Following treatment, a soft bandage lens is applied and prescriptions are given for oral pain medications, preservative-free tears, anti-inflammatory drops (preferably not nonsteroidal anti-inflammatory drugs, or NSAIDs) and antibiotic eye drops. Patients are recalled 1 week following the procedure to evaluate re-epithelialization and they are followed-up subsequently. EVIDENCE-BASED ANALYSIS METHODS: A literature search was conducted on photochemical corneal collagen cross-linking with riboflavin (vitamin B(2)) and ultraviolet-A for the management of corneal thinning disorders using a search strategy with appropriate keywords and subject headings for CXL for literature published up until April 17, 2011. The literature search for this Health Technology Assessment (HTA) review was performed using the Cochrane Library, the Emergency Care Research Institute (ECRI) and the Centre for Reviews and Dissemination. The websites of several other health technology agencies were also reviewed, including the Canadian Agency for Drugs and Technologies in Health (CADTH) and the United Kingdom's National Institute for Clinical Excellence (NICE). The databases searched included OVID MEDLINE, MEDLINE IN-Process and other Non-Indexed Citations such as EMBASE. As the evidence review included an intervention for a rare condition, case series and case reports, particularly for complications and adverse events, were reviewed. A total of 316 citations were identified and all abstracts were reviewed by a single reviewer for eligibility. For those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any additional relevant studies not identified through the search. (ABSTRACT TRUNCATED)

Systematic review: impact of non-adherence to 5-aminosalicylic acid products on the frequency and cost of ulcerative colitis flares.

BACKGROUND: Ulcerative colitis (UC) can be maintained in remission with 5-aminosalicylic acid (5-ASA) medications, but frequent non-adherence by patients who are feeling well has been associated with more frequent flares of colitis. AIM: To perform a systematic review of the published literature and unpublished randomized clinical trials (RCTs) regarding the impact of non-adherence with 5-ASA medications on the incidence of UC flares and costs of care. METHODS: A search of MEDLINE, EMBASE and the Cochrane databases was performed. Prospective studies of UC maintenance with 5-ASAs in adults were selected if they included data on adherence and disease flares. Studies using insurance claims data to estimate the impact of non-adherence on cost of care were included. Data from unpublished RCTs were obtained from the FDA with a request under the Freedom of Information Act. RESULTS: The relative risk for flare in non-adherent vs. adherent patients ranged from 3.65 to infinity. Data were obtained from six unpublished 5-ASA RCTs, but none measured the impact of adherence on disease activity. The comorbidity-adjusted annual costs of care in adherent patients were 12.5% less than in non-adherent patients, despite increased medication expenditures. CONCLUSIONS: A substantial proportion of UC flares and medical costs of UC are attributable to 5-ASA non-adherence. As non-adherence to 5-ASA medications is common, cost-effective strategies to improve adherence are needed. The impact of adherence on disease activity should be measured in RCTs of all inflammatory bowel disease treatments.

A systematic review of the safety of topical therapies for atopic dermatitis.

BACKGROUND: The safety of topical therapies for atopic dermatitis (AD), a common and morbid disease, has recently been the focus of increased scrutiny, adding confusion as how best to manage these patients. OBJECTIVES: The objective of these systematic reviews was to determine the safety of topical therapies for AD. METHODS: Databases searched included: OVID Medline, Medline In-Process and Other Non-Indexed Citations, Embase, and the Cochrane Central Register of Controlled Trials. In addition to the articles identified by this search, investigators were also referred to a list of links (most recently updated 25 September 2005) to recent Food and Drug Administration (FDA) studies, reports and meetings regarding the topical calcineurin inhibitors for further potential references. Only fully published papers available in English and data obtained from FDA sites were included. Furthermore, the criteria for inclusion and exclusion for each systematic review were further evaluated at a meeting of all of the content and evidence-based medicine experts participating in this process and alteration of the inclusion criteria was done at that time when it was felt necessary to avoid inclusion of lower-quality data in the review. Qualitative review of the abstracted data was performed and reviewed at a meeting of all of the content and evidence-based medicine experts. RESULTS: While systemic exposure to these topical agents does occur, physiological changes appear to be uncommon and systemic complications rare and have only been found with use of topical corticosteroids. CONCLUSIONS: Based on the data that are available the overall safety of AD therapies appears to be good with the only documented systemic side-effects of therapy those occasionally seen with use of topical corticosteroids.

Spontaneous arterial embolization after thrombolytic therapy for acute myocardial infarction: the role of transesophageal echocardiography.

Arterial embolization from thrombolytic therapy for acute myocardial infarction is rare. We report two cases of spontaneous arterial embolization following the use of tissue plasminogen activator for acute myocardial infarction. Transesophageal echocardiography was able to identify the source of embolism as mobile atherosclerotic debris within the thoracic aorta. This information was of value in the management of these patients, in that femoral catheterization which could have precipitated further embolization was avoided.