Delphine Hu

Prolonged Regional Nerve Blockade by Controlled Release of Local Anesthetic from a Biodegradable Polymer Matrix

Background:Prolonged nerve blockade is potentially useful in the management of many acute and chronic pain problems. Aside from infusions via an indwelling catheter, most currently available nondestructive techniques for prolonging local anesthetic action cannot provide more than 1–2 days of blockade. Bioerodible polymer matrixes have been used to deliver a variety of drugs in patients and animals for periods lasting weeks to years. Previously, dibucaine and bupivacaine were incorporated into copolymers of 1,3 bis(p-carboxyphenoxy) propane-sebacic acid anhydride (1:4), and demonstrated sustained release in vitro following incubation of the drug-polymer matrixes in phosphate-buffered solution (pH 7.4, 37° C). Methods:In the present study, cylindrical pellets made from polymer matrixes incorporated with buplvacaine-HCl were implanted surgically along the sciatic nerves of rats. Neural block was assessed by direct observation of motor skills and by leg-withdrawal latency to a hot surface. Biochemical and hlstologic examinations were performed 2 weeks after implantation. Results:Sensory and motor blockade was produced for periods ranging from 2 to 6 days. Contralateral control legs receiving polymer implants without drug showed no block. Blockade was reversible, and animals appeared to recover sensory and motor function normally. Biochemical indexes of nerve and muscle function were indistinguishable from contralateral controls. Conclusions:This biodegradable polymer system provides a promising new alternative for the delivery of local anesthetics to peripheral nerves to produce prolonged blockade for the management of acute and chronic pain.

The economic burden of noncervical human papillomavirus disease in the United States

OBJECTIVE The purpose of this study was (1) to estimate the direct medical costs of 7 major noncervical human papillomavirus (HPV)-related conditions that include genital cancers, mouth and oropharyngeal cancers, anogenital warts, and juvenile-onset recurrent respiratory papillomatosis, and (2) to approximate the economic burden of noncervical HPV disease. STUDY DESIGN For each condition, we synthesized the best available secondary data to produce lifetime cost per case estimates, which were expressed in present value. Using an incidence-based approach, we then applied these costs to develop an aggregate measure of economic burden. RESULTS The economic burden that was associated with noncervical HPV-6-, -11-, -16-, and -18-related conditions in the US population in the year 2003 approximates

Screening for Chlamydia trachomatis in Women 15 to 29 Years of Age: A Cost-Effectiveness Analysis

418 million (range,

neurologic Evaluation of Infant and Adult Rats before and after Sciatic Nerve Blockade

160 million to

Sciatic nerve blockade in infant, adolescent, and adult rats: a comparison of ropivacaine with bupivacaine.

1.6 billion). CONCLUSION The economic burden of noncervical HPV disease is substantial. Analyses that assess the value of investments in HPV prevention and control programs should take into account the costs and morbidity and mortality rates that are associated with these conditions.

Alternative Strategies to Reduce Maternal Mortality in India: A Cost-Effectiveness Analysis

Context Annual screening for Chlamydia trachomatis in sexually active women younger than 25 years of age is cost-effective, but the economic implications of more recent recommendations to expand screening to older women and to test more frequently in women with previous infection are unknown. Contribution The cost-effectiveness of annual screening in women 15 to 29 years of age followed by semiannual screening in those with previous infection is well within the range of other accepted health care interventions. In some scenarios, such as high-prevalence populations, screening was cost-saving. Implications Recently proposed screening recommendations for Chlamydia trachomatis are cost-effective. The Editors Genital infection with Chlamydia trachomatis is the most widespread bacterial sexually transmitted disease in the United States and is associated with annual costs that exceed

The Costs, Benefits, and Cost-Effectiveness of Interventions to Reduce Maternal Morbidity and Mortality in Mexico

2 billion (1-3). Women sustain the most severe consequences of untreated infection, including pelvic inflammatory disease, chronic pelvic pain, ectopic pregnancy, and tubal infertility (1, 4). Since most chlamydial infections are asymptomatic, screening and early treatment are the most promising public health interventions to prevent serious sequelae (5-7). The availability of nucleic acid amplification technology to detect C. trachomatis that can be used on urine, as well as cervical and vaginal specimens (8-10), has enhanced the enthusiasm for screening by making it more feasible in nonclinical settings (11-13). Although early guidelines advised annual C. trachomatis screening for all sexually active women younger than 25 years of age (14-16), reports of high recurrence rates have led to suggestions for more frequent testing in previously infected women (17-21). In fact, the Centers for Disease Control and Prevention (CDC) now advocates a follow-up test in women who have tested positive for C. trachomatis (16). While annual C. trachomatis screening for sexually active adolescent and young adult women is cost-effective (22-24), the costs and clinical benefits of selectively targeting women with a history of chlamydial infection for more intensive screening have not been evaluated. Furthermore, most guidelines specifically target women between 15 and 25 years of age; however, recent reports of substantial risk in older women have prompted questions about the potential value of extending the upper age limit to 30 years (24-26). We sought to use the best available data in a decision analytic model to assess the cost-effectiveness of new C. trachomatis screening policies. Methods Analytic Overview We developed a computer-based mathematical model (by using DATA 4.0, TreeAge Software, Inc., Williamstown, Massachusetts) to simulate screening, diagnosis, and treatment of chlamydial infection in a representative cohort of sexually active U.S. women, incorporating infection severity, treatment setting, and risk for long-term complications. Strategies were 1) no screening; 2) annual screening for all women; 3) annual screening for all women followed by 1 repeated test within 3 to 6 months after a positive test result; and 4) annual screening for all women except those with a history of at least 1 infection, who are rescreened every 6 months. We evaluated the implications of targeting these strategies to 3 specific age groups (15 to 19 years, 15 to 24 years, and 15 to 29 years) in the base case and the possibility of extending the upper age limit of screening to 39 years in the sensitivity analysis. Model outcomes include intermediate events (for example, pelvic inflammatory disease, chronic pelvic pain, ectopic pregnancy, and infertility) and long-term outcomes (for example, average per-person lifetime costs, life expectancy, and quality-adjusted life expectancy). Following the reference case recommendations of the Panel of Cost-Effectiveness in Health and Medicine (27), we measured the comparative performance of alternate strategies by using the incremental cost-effectiveness ratio (defined as the additional cost of a specific screening strategy divided by its additional clinical benefit compared with the next least expensive strategy). In addition to deterministic 1-way and 2-way sensitivity analyses, we conducted probabilistic sensitivity analyses by using a second-order Monte Carlo simulation. Finally, we analyzed the indirect effects of an effective screening program on the reduced force of infection (that is, the per-susceptible rate of infection). We reassessed the cost-effectiveness of alternative screening strategies by using a dynamic framework that permits the probability of infection in uninfected women to be a function of the number of infectious individuals in the population at that time. Model Health states in the model are defined to reflect important characteristics that affect prognosis, quality of life, and resource use. The time horizon incorporates a womans entire lifetime and is divided into equal 6-month increments (that is, cycles) during which women transition from one health state to another. A cohort of 100000 sexually active nonpregnant women enters the model at 15 years of age. In each cycle, uninfected women have an age-specific probability of developing an acute C. trachomatis infection that may be symptomatic or asymptomatic. We assume that women with symptomatic infections seek care and are treated according to the most recent CDC guidelines (16). Women with asymptomatic infection (or treatment failure) may be spontaneously cured, remain persistently infected (defined as a detectable infection for more than 6 months after the initial acute infection), or develop pelvic inflammatory disease. In our model, spontaneous cure refers to lower genital tract infection that, despite treatment failure or the absence of treatment, resolves spontaneously (does not progress to pelvic inflammatory disease or persist in the lower genital tract as subclinical infection) because of a successful immune response against the organism. A proportion of patients with pelvic inflammatory disease may develop long-term complications (such as infertility, ectopic pregnancy, and chronic pelvic pain), may remain chronically but asymptomatically (subclinically) infected, or may be cured by effective treatment. Once cured of infection, a woman may subsequently become reinfected. To estimate the effect of screening, the model distinguishes between detected and undetected acute infection. We assume that all eligible women are offered and adhere to screening in the base-case analysis, but we examine alternative assumptions in the sensitivity analysis. In a designated screening cycle, a woman with a positive test result moves temporarily to a detected state and is offered treatment (16). If a woman with a true-positive result returns for and adheres to treatment, she may be cured, although she will retain her history of infection. Women treated for acute infection are subject to the risk and costs of medication side effects. Women who develop long-term sequelae (such as chronic pelvic pain) are no longer considered part of the general screening cohort. Data Table 1 presents selected model variables and their plausible ranges (1, 4, 6, 8, 9, 22, 28-63). When several estimates were available, we considered the strength of the study design, sample size, presence of control group, similarity of patient populations, and comparability of outcomes measurements. A wide plausible range was established for each variable by using the highest and lowest values reported in the literature. Table 1. Model Variables: Baseline Values and Ranges Used in Sensitivity Analyses The annual incidence of acute chlamydial infection varies widely depending on the age group, population, and clinical setting (1, 28-30). We assumed an annual incidence of 6% in women 15 to 19 years of age (28, 29), which was reduced by 13% per year beginning at age 20 years to reflect the age-related decrease in infection risk (31-33). We assumed that 80% of women who were notified of a positive test result (determined by using nucleic acid amplification technology on a urine sample) would return for treatment (34, 35) and 96% of women treated with azithromycin would be cured, in accordance with a 1996 randomized, controlled trial comparing cure rates for C. trachomatis infection in persons treated with azithromycin versus doxycycline (36). We estimated that 30% of women with untreated or uncured acute chlamydial infection would remain persistently infected (37-39), 40% would be spontaneously cured of infection (38, 39), and 30% would develop acute pelvic inflammatory disease within 6 months of an initial infection (1, 4, 6). These estimates translate to an average duration of infection of 0.93 year, which closely approximates the estimate of 0.96 year cited by Groseclose and colleagues (2) and Buhaug and colleagues (32). Women with a history of C. trachomatis infection have a relative risk for reinfection approximately twice that of women with first-time acute infection. In women 15 to 19 years of age, this translates to a reinfection risk of 12%, which is in agreement with values (9% to 13%) reported in published studies (18, 64). On the basis of studies of women with untreated C. trachomatis infection, 28% to 50% of women have positive results on follow-up tests (range, 45 days to 16 months) (38, 39). Because of the potential for misclassification bias, the degree to which repeated test positivity represents persistent infection versus reinfection in these studies is uncertain, and we examined the effect of this uncertainty in a 2-way sensitivity analysis. Because chlamydia prevalence has substantially decreased in regions with large-scale screening programs (65, 66), we analyzed the indirect effects of an effective 10-year screening program on the reduced force of infection. For this analysis, the probability of infection in uninfected women (that is, per-susceptible rate of infection) is

The impact of natural history parameters on the cost-effectiveness of Chlamydia trachomatis screening strategies.

Background: Only limited data exist comparing differences in sensory function and responses to neural blockade in infant and adult rats. Therefore, the authors sought (1) to compare baseline thermal, proprioceptive, and postural responses in infant, adolescent, and adult rats; and (2) to compare the effects of sciatic nerve blockade on thermal, proprioceptive, and postural responses in infant, adolescent, and adult rats. Methods: Infant, adolescent, and adult rats were evaluated for proprioceptive, thermal, and mechanical nociceptive and motor function before and after sciatic blockade using a detailed neurologic examination. Results: Mechanical and thermal nociception were present in all rats, starting from age 1 day. The withdrawal reflex latency to pinch was rapid at all ages, whereas that reaction to thermal stimulus depended on both age and temperature. In contrast, the tactile placing response and hopping response were absent at birth and developed completely during the first 10 days of life. The extensor postural thrust was absent in the first 2 weeks of life and developed variably during the first 50 days of life. Sciatic blockade duration is shorter in infant rats than in adult rats receiving the same dose per kilogram. A brief halothane general anesthetic at the time of sciatic injection in infant or adult rats does not alter the duration of blockade. Conclusions: Infant rats show increased sensitivity to noxious thermal stimuli and similar response to deep mechanical stimuli compared with adult rats. Their proprioceptive and motor responses develop during the first 2 weeks of life. When doses are scaled by body weight, block duration is shorter in infant than in adult rats.

Cost-effectiveness analysis of alternative first-trimester pregnancy termination strategies in Mexico City

Background Ropivacaine is a newly introduced local anesthetic. anesthetic. No data are available regarding its safety, efficacy, or sensory‐selectivity in children. The sciatic block duration and systemic toxicity of bupivacaine and ropivacaine were compared compared among infant, adolescent, and adult rats. Methods Infant, adolescent, and adult rats received blocks with ropivacaine or bupivacaine. Nociceptive, proprioceptive, and motor blockade were assessed. Systemic effects (contralateral leg analgesia, seizures, respiratory distress, apnea) were quantified. Plasma local anesthetic concentrations were measured at terminal apnea. Results Nerve blockade for a given absolute dose lasted longer in infants than in older rats for both drugs. Block duration duration from ropivacaine generally was the same as or slightly shorter than bupivacaine. There was no difference in sensory‐selectivity between the drugs. Doses required to induce all systemic toxicity indices were inversely related to age (e.g., the lethal dose in 50% of animals [LD50] of ropivacaine in infants is 155 mg/kg; in adults it is 54 mg/kg). All indices of toxicity occurred at higher doses per kilogram for ropivacaine than bupivacaine, at all ages (e.g., the LD50 of bupivacaine in infants is 92 mg/kg; in adults it is 30 mg/kg). Plasma concentrations at terminal apnea were higher for ropivacaine than for bupivacaine at all ages, and were higher in infants than in older rats. Conclusions Ropivacaine resembles bupivacaine in its local anesthetic effects but has a greater margin of safety. For a given absolute dose, sciatic blockade in infant rats lasts longer than in adolescents or adults. Although the doses (in milligrams per kilogram) causing toxicity were much higher in infants than in adults, this probably does not correspond to a wider therapeutic index.

Cost-effectiveness analysis of unsafe abortion and alternative first-trimester pregnancy termination strategies in Nigeria and Ghana.

A cost-effectiveness study by Sue Goldie and colleagues finds that better family planning, provision of safe abortion, and improved intrapartum and emergency obstetrical care could reduce maternal mortality in India by 75% in 5 years.