Biomedical subjects

John B Wong

Publications and source records attributed to John B Wong.

At least 19 recordsLinked to original sources

PubMed2007

Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025.

UNLABELLED: This study predicts the burden of incident osteoporosis-related fractures and costs in the United States, by sex, age group, race/ethnicity, and fracture type, from 2005 to 2025. Total fractures were >2 million, costing nearly $17 billion in 2005. Men account for >25% of the burden. Rapid growth in the disease burden is projected among nonwhite populations. INTRODUCTION: The aging of the U.S. population will likely lead to greater prevalence of osteoporosis. Policy makers require precise projections of the disease burden by demographic subgroups and skeletal sites to effectively target osteoporosis intervention and treatment programs. MATERIALS AND METHODS: A state transition Markov decision model was used to estimate total incident fractures and costs by age, sex, race/ethnicity, and skeletal site for the U.S. population 50 years of age for 2005-2025. RESULTS: More than 2 million incident fractures at a cost of $17 billion are predicted for 2005. Total costs including prevalent fractures are more than $19 billion. Men account for 29% of fractures and 25% of costs. Total incident fractures by skeletal site were vertebral (27%), wrist (19%), hip (14%), pelvic (7%), and other (33%). Total costs by fracture type were vertebral (6%), hip (72%), wrist (3%), pelvic (5%), and other (14%). By 2025, annual fractures and costs are projected to rise by almost 50%. The most rapid growth is estimated for people 65-74 years of age, with an increase>87%. An increase of nearly 175% is projected for Hispanic and other subpopulations. CONCLUSIONS: Osteoporosis prevention, treatment, and education efforts should address all skeletal sites, not just hip and vertebral, and appropriate attention is warranted for men and diverse race/ethnicity subgroups.

Cost of Illness↗

PubMed2006

The economics of hepatitis C virus.

Hepatitis C virus is a disease of major public health significance throughout the world in terms of overall morbidity and mortality and in its economic consequences and demands on medical resources. The global economic burden of this disease has yet to be fully realized. In this article the authors discuss the economic burden of hepatitis C, the economics of therapy, and the economics of its prevention and screening.

Antiviral Agents↗

PubMed2006

Analysis and optimization of the cationic lipid component of a lipid/peptide vector formulation for enhanced transfection in vitro and in vivo.

We have previously described a lipopolyplex formulation comprising a mixture of a cationic peptide with an integrin-targeting motif (K16GACRRETAWACG) and Lipofectin, a liposome consisting of DOTMA and DOPE in a 1:1 ratio. The high transfection efficiency of the mixture involved a synergistic interaction between the lipid/peptide components. The aim of this study was to substitute the lipid component of the lipopolyplex to optimize transfection further and to seek information on the structure-activity relationship of the lipids in the lipopolyplex. Symmetrical cationic lipids with diether linkages that varied in alkyl chain length were formulated into liposomes and then incorporated into a lipopolyplex by mixing with an integrin-targeting peptide and plasmid DNA. Luciferase transfections were performed of airway epithelial cells and fibroblasts in vitro and murine lung airways in vivo. The biophysical properties of lipid structures and liposome formulations and their potential effects on bilayer membrane fluidity were determined by differential scanning calorimetry and calcein-release assays. Shortening the alkyl tail from C18 to C16 or C14 enhanced lipopolyplex and lipoplex transfection in vitro but with differing effects. The addition of DOPE enhanced transfection when formulated into liposomes with saturated lipids but was more variable in its effects with unsaturated lipids. A substantial improvement in transfection efficacy was seen in murine lung transfection with unsaturated lipids with 16 carbon alkyl tails. The optimal liposome components of lipopolyplex and lipoplex vary and represent a likely compromise between their differing structural and functional requirements for complex formation and endosomal membrane destabilization.

Animals↗

PubMed2006

Hepatitis C: cost of illness and considerations for the economic evaluation of antiviral therapies.

Chronic hepatitis C virus (HCV) infection affects 170 million individuals worldwide. As it is detected incidentally through the evaluation of liver function tests or at the time of blood donor testing, it is usually clinically silent until the advanced stages of liver disease have occurred, when treatment is less effective and shortages of donor liver organs limit the therapeutic options. Combination therapy with ribavirin and pegylated interferon has resulted in sustained viral negative response rates of 54-61%. Because treatment is expensive and not uniformly effective, and because not all chronically infected patients will develop complications, concerns have arisen regarding the cost effectiveness of combination therapy. This paper reviews the public health and individual implications of HCV infections. Because of the latency of infection, numerous country-specific population analyses suggest that HCV will cause an increasing number of liver-related deaths over the next 10 years, despite the dramatic drop in incidence over the past 10-15 years. These deaths will be related to prevalent HCV infection from transfusion and injection drug use prior to identification of the virus and availability of screening tests in the late 1980s and early 1990s. HCV can reduce life expectancy and impair quality of life, yet not all patients will develop progressive liver disease, and antiviral treatment may have associated adverse effects. Finally, to assess the value of antiviral drugs for HCV infection, this paper reviews studies examining the costs of antiviral drugs and of the disease itself along with response to antiviral therapy and the cost effectiveness of antiviral therapy. Although antiviral therapy appears to be expensive, when also considering the likelihood of sustained viral response to therapy, and the cost savings, quality-of-life improvement and prolongation of life expectancy from the prevention of HCV complications, antiviral treatment for HCV appears to be cost effective when compared with other well accepted medical interventions.

Antiviral Agents↗

PubMed2005

Empirical anti-Candida therapy among selected patients in the intensive care unit: a cost-effectiveness analysis.

BACKGROUND: Mortality from invasive candidiasis is high. Low culture sensitivity and treatment delay contribute to increased mortality, but nonselective early therapy may result in excess costs and drug resistance. OBJECTIVE: To determine the cost-effectiveness of anti-Candida strategies for high-risk patients in the intensive care unit (ICU). DESIGN: Cost-effectiveness decision model. DATA SOURCES: Published data to 10 May 2005, identified from MEDLINE and Cochrane Library searches, ICU databases, expert estimates, and actual hospital costs. TARGET POPULATION: Patients in the ICU with suspected infection who have not responded to antibacterial therapy. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTIONS: Fluconazole, caspofungin, amphotericin B, or lipid formulation of amphotericin B given as either empirical or culture-based therapy and no anti-Candida therapy. OUTCOME MEASURES: Incremental life expectancy and incremental cost per discounted life-year (DLY) saved. RESULTS OF BASE-CASE ANALYSIS: Ten percent of the target population will have invasive candidiasis. Empirical caspofungin therapy is the most effective strategy but is expensive (295,115 dollars per DLY saved). Empirical fluconazole therapy is the most reasonable strategy (12,593 dollars per DLY saved) and decreases mortality from 44.0% to 30.4% in patients with invasive candidiasis and from 22.4% to 21.0% in the overall target cohort. RESULTS OF SENSITIVITY ANALYSIS: Empirical fluconazole therapy is reasonable for likelihoods of invasive candidiasis greater than 2.5% or fluconazole resistance less than 24.0%. For higher resistance levels, empirical caspofungin therapy is preferred. For low prevalences of invasive candidiasis, culture-based fluconazole is reasonable. For prevalences exceeding 60%, empirical caspofungin therapy is reasonable. For caspofungin to be reasonable at a prevalence of 10%, its cost must be reduced by 58%. LIMITATIONS: Less severe illness and limited use of broad-spectrum antimicrobial agents, typical of smaller hospitals, could result in a lower risk for invasive candidiasis. CONCLUSIONS: In patients in the ICU with suspected infection who have not responded to antibiotic treatment, empirical fluconazole should reduce mortality at an acceptable cost. The use of empirical strategies in low-risk patients is not justified.

Amphotericin B↗

PubMed2005

Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials.

CONTEXT: The role and dose of oral vitamin D supplementation in nonvertebral fracture prevention have not been well established. OBJECTIVE: To estimate the effectiveness of vitamin D supplementation in preventing hip and nonvertebral fractures in older persons. DATA SOURCES: A systematic review of English and non-English articles using MEDLINE and the Cochrane Controlled Trials Register (1960-2005), and EMBASE (1991-2005). Additional studies were identified by contacting clinical experts and searching bibliographies and abstracts presented at the American Society for Bone and Mineral Research (1995-2004). Search terms included randomized controlled trial (RCT), controlled clinical trial, random allocation, double-blind method, cholecalciferol, ergocalciferol, 25-hydroxyvitamin D, fractures, humans, elderly, falls, and bone density. STUDY SELECTION: Only double-blind RCTs of oral vitamin D supplementation (cholecalciferol, ergocalciferol) with or without calcium supplementation vs calcium supplementation or placebo in older persons (> or =60 years) that examined hip or nonvertebral fractures were included. DATA EXTRACTION: Independent extraction of articles by 2 authors using predefined data fields, including study quality indicators. DATA SYNTHESIS: All pooled analyses were based on random-effects models. Five RCTs for hip fracture (n = 9294) and 7 RCTs for nonvertebral fracture risk (n = 9820) met our inclusion criteria. All trials used cholecalciferol. Heterogeneity among studies for both hip and nonvertebral fracture prevention was observed, which disappeared after pooling RCTs with low-dose (400 IU/d) and higher-dose vitamin D (700-800 IU/d), separately. A vitamin D dose of 700 to 800 IU/d reduced the relative risk (RR) of hip fracture by 26% (3 RCTs with 5572 persons; pooled RR, 0.74; 95% confidence interval [CI], 0.61-0.88) and any nonvertebral fracture by 23% (5 RCTs with 6098 persons; pooled RR, 0.77; 95% CI, 0.68-0.87) vs calcium or placebo. No significant benefit was observed for RCTs with 400 IU/d vitamin D (2 RCTs with 3722 persons; pooled RR for hip fracture, 1.15; 95% CI, 0.88-1.50; and pooled RR for any nonvertebral fracture, 1.03; 95% CI, 0.86-1.24). CONCLUSIONS: Oral vitamin D supplementation between 700 to 800 IU/d appears to reduce the risk of hip and any nonvertebral fractures in ambulatory or institutionalized elderly persons. An oral vitamin D dose of 400 IU/d is not sufficient for fracture prevention.

Aged↗

PubMed2005

Using competence network collaboration and decision-analytic modeling to assess the cost-effectiveness of interferon alpha-2b plus ribavirin as initial treatment of chronic hepatitis C in Germany.

The objective of this study was to translate and apply a decision-analytic model for chronic hepatitis C (CHC) to the German health care context using competence network collaboration. The German Hepatitis C Model (GEHMO) competence network used a systematic multistep approach to identify and transfer a high quality Markov model for CHC to the German health care context. GEHMO was used to project lifetime clinical and economic outcomes and to determine the cost-effectiveness of initial antiviral therapy with interferon a-2b plus ribavirin from a societal perspective. In 40-year-old patients combination therapy for 24 and 48 weeks increased life expectancy by 1.6 and 2.3 years, respectively, compared with interferon alone for 48 weeks. The discounted incremental cost-utility ratios (ICUR) for combination therapy were euro 5,500 per quality-adjusted life-year gained (QALY) for 24 weeks and euro 6,800/QALY for 48 weeks of treatment. ICUR was euro 9,800/QALY for moving from 24 to 48 weeks of treatment. Combination therapy remained cost-effective in sensitivity analyses. In conclusion, combination therapy with interferon alpha-2b and ribavirin is effective and cost-effective compared with other well-accepted medical treatments. Competence network collaboration and decision modeling provide a useful and efficient approach to combine evidence from international studies with country-specific parameters.

Adult↗

PubMed2005

Estimating the proportion of patients infected with HIV who will die of comorbid diseases.

PURPOSE: Effective antiretroviral therapies have improved the prognosis for patients infected with the human immunodeficiency virus (HIV). We aimed to estimate the likelihood that HIV-infected patients would die of comorbid disease. METHODS: A probabilistic simulation of antiretroviral-naïve HIV-infected patients in the United States was calibrated with data from an observational cohort (N = 3545) and validated with data from a separate patient cohort (N = 12574). The simulation explicitly represents the 2 main determinants of treatment failure and subsequent death from HIV-related causes: nonadherence to combination therapy and accumulation of phenotypic resistance to combination therapy. The likelihood of deaths not directly attributable to HIV was estimated from the Collaborations in HIV Outcomes Research-US (CHORUS) cohort. RESULTS: For patients with newly diagnosed HIV infections, CD4 counts of 500 cells/mm3, and viral loads of 10000 copies/mL, the median estimated survival was 26.8 years for 30-year-olds, 24.4 years for 40-year-olds and 14.6 years for 50-year-olds. The proportion of deaths not directly attributable to HIV was 36% for 30-year-olds, 53% for 40-year-olds, and 72% for 50-year-olds. For patients with characteristics similar to CHORUS participants, the median estimated survival approached 20.4 years, the mean age at death approached 60.4 years, and 41% died of illnesses not directly attributable to HIV. These estimates of non-HIV mortality were likely conservative. CONCLUSION: As HIV-infected patients live longer, our results suggest they will experience increasing mortality from causes not directly attributable to HIV. The projected risk from comorbid disease has clinical and policy implications for future delivery of care to HIV-infected patients.

Adult↗

PubMed2005

The cost effectiveness of infliximab for severe treatment-resistant rheumatoid arthritis in the UK.

OBJECTIVE: To estimate the cost effectiveness (from the UK NHS and personal social service perspectives) of infliximab plus methotrexate (MTX) compared with MTX alone, in the treatment of patients with severe rheumatoid arthritis (RA) who were not adequately controlled on disease-modifying antirheumatic drugs and who were resistant to MTX. METHOD: Clinical data for the first year of therapy were taken from the ATTRACT (Anti-Tumour Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy) and a Markov model developed to assess costs and consequences in the longer term. Transition probabilities and health state valuations for the model were estimated based on the ARAMIS (Arthritis, Rheumatism, and Aging Medical Information System) cohort, and resource use and costs ( 2,000 pounds values) obtained from various sources in the UK. Univariate sensitivity analyses were conducted to test the robustness of the results. RESULTS: The primary analysis suggested that infliximab plus MTX had an ICER of 33,618 pounds per QALY gained. Alternative modelling assumptions and various other sensitivity analyses were applied, but the ICER always remained within the range for interventions typically funded by the NHS. CONCLUSION: This model suggests, with its underlying assumptions and data, that the combination of infliximab and MTX may be a cost-effective treatment (from the UK NHS and personal social service perspectives) for patients experiencing RA that cannot be maintained on MTX alone.

Antibodies, Monoclonal↗

PubMed2004

Effect of Vitamin D on falls: a meta-analysis.

CONTEXT: Falls among elderly individuals occur frequently, increase with age, and lead to substantial morbidity and mortality. The role of vitamin D in preventing falls among elderly people has not been well established. OBJECTIVE: To assess the effectiveness of vitamin D in preventing an older person from falling. DATA SOURCES: MEDLINE and the Cochrane Controlled Trials Register from January 1960 to February 2004, EMBASE from January 1991 to February 2004, clinical experts, bibliographies, and abstracts. Search terms included trial terms: randomized-controlled trial or controlled-clinical trial or random-allocation or double-blind method, or single-blind method or uncontrolled-trials with vitamin D terms: cholecalciferol or hydroxycholecalciferols or calcifediol or dihydroxycholecalciferols or calcitriol or vitamin D/aa[analogs & derivates] or ergocalciferol or vitamin D/bl[blood]; and with accidental falls or falls, and humans. STUDY SELECTION: We included only double-blind randomized, controlled trials (RCTs) of vitamin D in elderly populations (mean age, 60 years) that examined falls resulting from low trauma for which the method of fall ascertainment and definition of falls were defined explicitly. Studies including patients in unstable health states were excluded. Five of 38 identified studies were included in the primary analysis and 5 other studies were included in a sensitivity analysis. DATA EXTRACTION: Independent extraction by 3 authors using predefined data fields including study quality indicators. DATA SYNTHESIS: Based on 5 RCTs involving 1237 participants, vitamin D reduced the corrected odds ratio (OR) of falling by 22% (corrected OR, 0.78; 95% confidence interval [CI], 0.64-0.92) compared with patients receiving calcium or placebo. From the pooled risk difference, the number needed to treat (NNT) was 15 (95% CI, 8-53), or equivalently 15 patients would need to be treated with vitamin D to prevent 1 person from falling. The inclusion of 5 additional studies, involving 10 001 participants, in a sensitivity analysis resulted in a smaller but still significant effect size (corrected RR, 0.87; 95% CI, 0.80-0.96). Subgroup analyses suggested that the effect size was independent of calcium supplementation, type of vitamin D, duration of therapy, and sex, but reduced sample sizes made the results statistically nonsignificant for calcium supplementation, cholecalciferol, and among men. CONCLUSIONS: Vitamin D supplementation appears to reduce the risk of falls among ambulatory or institutionalized older individuals with stable health by more than 20%. Further studies examining the effect of alternative types of vitamin D and their doses, the role of calcium supplementation, and effects in men should be considered.

Accidental Falls↗

PubMed2004

Asymmetric synthesis of dialkyloxy-3-alkylammonium cationic lipids.

The cationic diether-linked cytofectin DOTMA (available commercially as a mixture, Lipofectin comprised of DOTMA:DOPE, 1:1) and analogues including DIMRIE and DORIE are frequently used for in vitro and in vivo transfections. Despite this wide usage direct synthetic routes to the optical isomers have received little attention to date. Here we describe strategies to synthesize enantiomers of DOTMA and analogues, including an extremely concise procedure to the trimethylammonium salts. One strategy utilized N-protection, as the imine, with concomitant ether formation and deprotection during the workup. Methylation of the 1-amino-2,3-dialkyloxypropane then generated the trimethylammonium cationic lipids directly. This methodology was extended to synthesize a novel headgroup functionalized lipid. A second route was also developed using an alternative chiral synthon.

Cations↗

PubMed2004

Expanded criteria donor grafts for deceased donor liver transplantation under the MELD system: a decision analysis.

Expanded criteria donor (ECD) liver grafts have a higher likelihood of primary graft failure (PGF) compared with standard criteria donor (SCD) grafts. Given a choice between an available ECD graft versus waiting for an SCD graft that may not always become available, what should liver transplant candidates do? The study's aim was to estimate 1-year survival comparing immediate ECD liver grafting with waiting for an SCD organ. Using UNOS data, published literature estimates, and expert opinion, we constructed a Markov decision analytic model to estimate survival while waiting for an SCD transplant and survival with immediate ECD transplant. Sensitivity analyses were performed by varying model parameters individually and simultaneously with a second-order Monte Carlo simulation. For all patients with MELD scores >20, survival was higher with immediate ECD transplant despite the additional increased risk for PGF. Survival was better with an immediate ECD transplant unless the probability of PGF exceeded 23%, 72%, and 88% for recipients with MELD scores of 11-20, 21-25, and 26-30 respectively. For patients with MELD scores >30, the survival benefit with the immediate ECD strategy persisted at even higher rates of PGF. In conclusion, our results suggest that, despite the higher risk for PGF, transplantation with an available ECD graft should be preferred over waiting for an SCD organ for patients with advanced MELD scores. At less advanced MELD scores, the survival benefit depends on the risk of PGF associated with the ECD organ.

Cadaver↗

PubMed2004

Is it influenza or anthrax? A decision analytic approach to the treatment of patients with influenza-like illnesses.

STUDY OBJECTIVE: We analyze the risks and benefits of alternative treatment strategies for non-septic-appearing febrile patients with influenza-like illnesses and possible exposure to anthrax. METHODS: We used a decision analytic model to evaluate 6 testing and treatment strategies in an emergency department. Patients were non-septic-appearing and had influenza-like illnesses but low likelihood of exposure to anthrax. The following interventions were used: (1) no empiric antibiotics; (2) blood culture and treatment only if the result was positive; (3) rapid testing for influenza and, for those who tested negative, treatment with 60 days of ciprofloxacin; (4) a two-test strategy in which all patients were first tested for influenza; those who tested negative had a blood culture test and were treated empirically with ciprofloxacin for 3 days while waiting for blood culture results; (5) culture test for all patients and treatment with ciprofloxacin for up to 3 days while waiting for blood culture results; and (6) treatment of all patients with ciprofloxacin empirically for 60 days. Main outcome measures were deaths, complications from anthrax, adverse events from ciprofloxacin, and ciprofloxacin patient-days. RESULTS: For nonzero probabilities of anthrax, patient mortality was always lowest in the strategies in which all patients were treated empirically for anthrax either for 60 days or for 3 days pending blood culture results. These strategies, however, were associated with more morbidity (more ciprofloxacin patient-days and more antibiotic adverse events) than were strategies without empiric treatment. The numbers of adverse events and antibiotic patient-days were reduced substantially with the two-test strategy, in which patients with influenza were identified early and not treated. In general, for probabilities of anthrax equaling or exceeding 2%, treating all patients empirically for 60 days was best, but for probabilities between 0.1% and 2%, the sensitivity of blood culture for anthrax determined the optimal strategy: when the sensitivity exceeded 95%, a short course of empiric ciprofloxacin until blood culture results became available was best, but for sensitivities below 95%, more aggressive empiric antibiotics use was warranted. The proportion of patients with influenza in the community affected the choice of strategy, so that seasonal variation exists. CONCLUSION: During influenza season, our findings support rapid testing for influenza, followed by empiric treatment for anthrax pending blood culture results for those who test negative for influenza. Our results help to highlight the importance of developing rapid and sensitive tests for anthrax and of developing improved surveillance and methods to calculate the previous probability of attacks.

Anthrax↗

PubMed2004

Should beta-blockers be given to patients with heart disease and peanut-induced anaphylaxis? A decision analysis.

BACKGROUND: Beta-blocker therapy postmyocardial infarction is generally recommended because it reduces mortality. However, beta-blockers may increase anaphylaxis mortality in the growing population of patients with peanut-induced anaphylaxis. OBJECTIVE: We sought to assess the risks and benefits of beta-blocker therapy among patients with peanut allergy and heart disease. METHODS: We created a Markov model for patients with heart disease at risk for peanut-induced anaphylaxis to compare life expectancy with the following strategies: (1) beta-blocker and (2) no beta-blocker. Meta-analysis and a literature review were used to estimate model parameters. We performed sensitivity analysis to explore parameter uncertainty. RESULTS: For peanut-allergic patients who are postmyocardial infarction or who have congestive heart failure, the heart disease benefit of beta-blockers outweighs the increased likelihood of dying from anaphylaxis, increasing life expectancy by 9.4 and 17.4 months, respectively. Beta-blocker was preferred unless (1) the annual rate of moderate to severe anaphylaxis exceeded 6.0% for postmyocardial infarction and 15% for congestive heart failure patients; (2) beta-blocker therapy increased the incidence of moderate to severe anaphylaxis >2.5-fold for postmyocardial infarction and >5.8-fold for congestive heart failure patients; (3) anaphylaxis case fatality exceeded 6.5% postmyocardial infarction; or (4) beta-blocker therapy increased anaphylaxis case fatality >25-fold postmyocardial infarction. CONCLUSION: Our results suggest that for patients postmyocardial infarction or with congestive heart failure who are at risk for peanut-induced anaphylaxis, beta-blocker use should still improve survival. However, the epidemiology of anaphylaxis and effects of beta-blocker therapy on anaphylaxis incidence and mortality require further study.

Adrenergic beta-Antagonists↗

PubMed2004

Comparing the public health burden of chronic hepatitis C and HIV infection in France.

BACKGROUND/AIMS: In France, the prevalence of hepatitis C virus (HCV) exceeds that of HIV, but in the absence of treatment, HIV infection progresses more rapidly than HCV. More HIV-infected patients, however, have received treatment. Using reported public health data in France and natural history models, we applied the back-calculation method to project future mortality from HCV and HIV incorporating current therapies. METHODS: The HCV model was based on literature data for the natural history of HCV and reports of hepatocellular carcinoma mortality. The HIV model used estimates from the French Hospital Database on HIV and reported AIDS cases and deaths. RESULTS: Peak annual mortality from HIV at 5000 occurred in 1994 and was 1000 in 1998, but HCV mortality likely increased through the 1990s and reached 3000 in 1998. Considering only HCV infections occurring until 1998 and currently available therapy, our model suggested that annual HCV-related mortality would continue to rise and would reach 4500 deaths in 2022. In contrast, AIDS-related deaths began to decrease in 1997. CONCLUSIONS: The public health burden of HCV is likely on the rise, while the burden of HIV, given the fairly widespread use of effective medications, may be on the decline. These results may help health policymakers in planning their responses to these epidemics.

Acquired Immunodeficiency Syndrome↗

PubMed2004

Systematic review of outcomes after surgical management of venous disease incorporating subfascial endoscopic perforator surgery.

INTRODUCTION: In the United States more than 6 million persons have chronic venous insufficiency and more than 500,000 have venous ulcers. Patients in whom conservative therapies fail may improve after surgical treatment of superficial and perforating venous disease, but the degree of this benefit is uncertain. PURPOSE: We performed a systematic review of health outcomes in patients with severe chronic venous insufficiency treated with surgical management that incorporated subfascial endoscopic perforator surgery (SEPS), to quantify the overall rates of surgical outcomes. METHODS: Published studies in English reporting venous ulcer healing and recurrence outcomes after SEPS were obtained from a MEDLINE search. Data regarding patient characteristics and surgical outcomes were abstracted from each study, and the outcomes were combined by using a random effects model. RESULTS: Our search identified 20 studies, 1 randomized trial and 19 case series, involving 1140 treated limbs. CEAP classification was secondary cause (E(S)) in 36%, deep venous involvement (A(D))in 56%, and obstructive (P(O)) in 12%. Overall, after surgical treatment including SEPS, with or without concomitant superficial venous ablation, ulcers in 88% of limbs healed. Ulcers recurred in 13%, at mean time of 21 months. Risk factors for nonhealing and recurrence included postoperative incompetent perforator veins, pathophysiologic obstruction, secondary cause, and ulcer diameter greater than 2 cm. Complications and their overall rates after surgical treatment including SEPS were wound infection (6%), hematoma (9%), neuralgia (7%), and deep venous thrombosis (1%). CONCLUSION: Our results suggest that surgical management of venous ulcer including SEPS, with or without saphenous ablation, leads to an 88% chance of ulcer healing and a 13% chance of ulcer recurrence over the short term. Randomized controlled trials are needed to discern the contributions of compression therapy, superficial venous surgery, and SEPS in the treatment of venous ulcer disease.

Chronic Disease↗

PubMed2004

All dysuria is local. A cost-effectiveness model for designing site-specific management algorithms.

OBJECTIVE: To determine the cost-effectiveness of management strategies for dysuria in different office settings. DESIGN: Decision and cost-effectiveness analyses, assuming the payer's perspective. Data on disease prevalence, test characteristics, treatment efficacy, and adverse effects were drawn from the English language literature using medline searches and bibliographies. SETTING: Hypothetical primary care practice. PATIENTS: Otherwise healthy, nonpregnant women with symptoms of dysuria, urgency, and frequency. INTERVENTIONS: All reasonable combinations of urinalysis, urine culture, pelvic examination, chlamydia and gonorrhea cultures, and empiric treatment with trimethoprim-sulfamethoxazole. RESULTS: The cost-effectiveness of strategies varied substantially among different patient settings. In all settings, empiric trimethoprim-sulfamethoxazole for all patients was least expensive and least effective. Most testing increased both cost and effectiveness. Compared to empiric antibiotics, performing pelvic examination and urine culture for women with normal urinalyses had a marginal cost-effectiveness ratio of $4 to $32 per symptom-day avoided (SDA). Adding urine culture for patients with pyuria had a marginal cost of $34 to $107 per SDA, which fell to $40/SDA when the prevalence of resistance to trimethoprim-sulfamethoxazole exceeded 40%. Pelvic examination and urine culture for all patients regardless of urinalysis results achieved the greatest benefit but at the highest cost (>$300 per SDA). CONCLUSIONS: In otherwise healthy women with symptoms of dysuria and no vaginal complaints, performing pelvic exam and urine culture based on urinalysis offers a reasonable alternative to empiric therapy. Other testing may be warranted, depending on antibiotic resistance and the value of avoiding a day of dysuria.

Acute Disease↗

PubMed2003

A meta-analysis of randomized controlled trials comparing coronary artery bypass graft with percutaneous transluminal coronary angioplasty: one- to eight-year outcomes.

OBJECTIVES: We performed a meta-analysis of randomized trials comparing coronary artery bypass graft surgery (CABG) with percutaneous transluminal coronary angioplasty (PTCA) for the treatment of coronary artery disease, incorporating new trials and examining long-term outcomes. BACKGROUND: Previous meta-analyses of trials comparing CABG with PTCA have reported short- and intermediate-term outcomes, but since then longer term follow-up and newer trials have been published. METHODS: We performed a meta-analysis of 13 randomized trials on 7,964 patients comparing PTCA with CABG. RESULTS: We found a 1.9% absolute survival advantage favoring CABG over PTCA for all trials at five years (p < 0.02), but no significant advantage at one, three, or eight years. In subgroup analysis of multivessel disease, CABG provided significant survival advantage at both five and eight years. Patients randomized to PTCA had more repeat revascularizations at all time points (risk difference [RD] 24% to 38%, p < 0.001); with stents, this RD was reduced to 15% at one and three years. Stents also resulted in a significant decrease in nonfatal myocardial infarction at three years when compared with CABG. For diabetic patients, CABG provided a significant survival advantage over PTCA at 4 years but not at 6.5 years. CONCLUSIONS: Our results suggest that, when compared with PTCA, CABG is associated with a lower five-year mortality, less angina, and fewer revascularization procedures. For patients with multivessel disease, CABG provided a survival advantage at five to eight years, and for diabetics, a survival advantage at four years. The addition of stents reduced the need for repeat revascularization by about half.

Angioplasty, Balloon, Coronary↗