Mehmet Genc

A Cost-effectiveness Analysis of Screening and Treatment for Chlamydia trachomatis Infection in Asymptomatic Women

In recent decades, Chlamydia trachomatis has been recognized as one of the most widespread sexually transmitted organisms [1]. In women, it can cause urethritis, cervicitis, pelvic inflammatory disease (for example, endometritis and salpingitis), and the sequelae of these conditions, such as infertility, ectopic pregnancy, and chronic pelvic pain. In men, C. trachomatis infection can cause urethritis and epididymitis, which may rarely result in urethral strictures and decreased fertility. Neonates passing through the birth canal of an infected woman can become infected, leading to chlamydial conjunctivitis and pneumonia. Chlamydial infections of the genital tract do not invariably cause symptoms that would prompt a person to seek medical aid. Identification and treatment of infected persons is important not only for their own well-being but also to prevent the spread of C. trachomatis in society. We assess the cost-effectiveness of some commonly used diagnostic tests and treatment regimens, including the recently introduced DNA amplification assays and a single oral dose of azithromycin, for identifying and treating asymptomatic female carriers of C. trachomatis. Methods Eligible Patients We considered a cohort of 1000 sexually active, nonpregnant women of reproductive age who had no clinical signs or symptoms of a genital tract infection. We assumed that these women attend youth, gynecology, and family planning clinics for either contraceptive advice or routine gynecologic care. We derived the assumptions on their demographic characteristics from the Swedish Womens Health Study [2], which focused on the same group of women considered in our analysis. These assumptions include the following: The mean age of the women is 26 years (range, 15 to 48 years); most are nonparous (68%), are either married or cohabiting (52%), have a steady partner (85%), and have had some training beyond the compulsory 9 years of education (88%); they have had a mean of 11 sex partners; and the prevalence of genital tract infection with C. trachomatis and Neisseria gonorrhoeae is 8.5% and 0.1%, respectively. We believe that these women are representative of the general Swedish female population who are of reproductive age and are at moderate risk for chlamydial infections of the genital tract. Intervention We compared a no-screening strategy with tissue cell culture, confirmed enzyme immunoassay, and DNA amplification assays that were based on either polymerase chain reaction (Amplicor C. trachomatis, Roche Diagnostic Systems, Elizabeth, New Jersey) or ligase chain reaction (LCR Assay C. trachomatis, Abbott Diagnostics, North Chicago, Illinois) for screening asymptomatic chlamydial infections of the genital tract. We assumed that all samples with positive or equivocal enzyme immunoassay results would be tested with a blocking assay [3]. Positive results that become blocked would be reported as confirmed positive, and equivocal results that become blocked would be further evaluated with a direct fluorescent assay. If chlamydial elementary bodies are found in the pellet obtained by centrifugation of the sample tested by enzyme immunoassay, the result would again be reported as confirmed positive. In the screening strategies, endocervical samples are collected from women during a pelvic examination. Any woman with laboratory-confirmed chlamydial infection is referred to a disease intervention specialist, who attempts to confidentially notify infected women and arrange a visit to the clinic. Notification efforts include telephone calls, letters, and visits to the patients residence. When the patient returns to the clinic, an antibiotic regimen is prescribed, and counseling regarding the disease and its treatment as well as notification of the patients partner are done. Partner notification is mandatory by law in Sweden; the disease intervention specialist informs the index patient of the importance of revealing her sex partner or partners and interviews her extensively to obtain the names, addresses, and telephone numbers of her sex partners. The disease intervention specialist then contacts these partners to motivate them to be examined at the clinic. This procedure is repeated until the partner comes to the clinic for examination. At this visit, the same steps are followed as with the index patient: physical examination, partner notification, counseling, and prescription of an antibiotic regimen for empiric treatment of uncomplicated chlamydial genital infection. In our analysis, we assumed that a 7-day, twice-daily course of doxycycline was prescribed to treat uncomplicated chlamydial genital tract infection in both women and their sex partners. We also evaluated the effect of administering a single oral 1-g dose of azithromycin under supervision in the clinic on the outcomes of the screening strategies. We assumed that only persons who seek medical help because of the presence of signs and symptoms of chlamydial diseases and their sequelae receive medical care in the no-screening strategy. Decision-Analysis Model We used two decision trees to graphically structure our decision-analysis model (Figure 1 and Figure 2). The branches in the decision trees represent the strategies of screening and no screening. The square at the point of branching indicates a decision node: a point at which a decision must be madefor example, whether or not to screen a woman. The nodes represented by circles are used if subsequent outcomes occur by chancefor example, if the physician cannot control the results of the test, which therefore branch from a chance node. We used the Bayes theorem to assign probabilities within the ranges presented in Table 1 to the chance nodes of the decision trees. We varied the prevalence of C. trachomatis among women from 0% to 100% to determine the prevalence above which one strategy is preferred to another [break-even analysis] Figure 1, node 1). Figure 1. Decision tree showing the outcomes of screening strategies for Chlamydia trachomatis among women and the outcomes of no screening. Figure 2. Decision tree showing the outcomes of tracing and treating contacts of women with a diagnosis of chlamydial infection of the genital tract and the outcomes of no contact tracing. Table 1. Ranges of Probabilities Assigned to the Chance Nodes of the Decision Trees We derived the estimates on the sensitivity and specificity of the laboratory tests from multicenter clinical evaluations in which a positive diagnosis was made when tissue cell culture was positive or when the results of one nonculture test (enzyme immunoassay, direct fluorescence assay, polymerase chain reaction assay, or ligase chain reaction assay) verified those of another. The estimates on follow-up rates for women with positive results and their partners were derived from data obtained from medical centers in North America and Sweden, which do follow-up procedures similar to those considered in our analysis. We obtained data on the prevalence of infection in male partners of women infected with C. trachomatis from studies in which tissue cell culture or the polymerase chain reaction assay was used for diagnosis. Compliance with a 7-day, twice-daily course of doxycycline is nearly 100% among Swedish patients but may be as low as 50% in other countries. We assumed that administering a single dose of azithromycin ensures full compliance and that noncompliance is synonymous with treatment failure. We also assumed that each woman would disclose one or two male sex partners [13]. Case-finding and partner notification yielded six groups of male partners (Figure 2, node 8). The probabilities for these outcomes were obtained from the probabilities of the corresponding outcomes of screening in women (Figure 1). In the no-screening strategy, the partners can be divided into two groups: contacts of infected women and contacts of healthy women. The probability of a man having an infected female partner is the same as that of a woman being infected (Figure 2, node 9). Costs Table 2 presents the direct and indirect cost estimates associated with medical services used in our analysis. Direct costs included salaries of health care personnel and costs of hospitals, drugs, equipment, and so forth; indirect costs were lost wages and lost value of household management due to participation in a health care program or sickness. We obtained these cost estimates from reported calculations that were based on average salaries and costs of medical care in Sweden [15, 21]. Using upper and lower limits for input salaries and costs, we made these calculations yield the widest range of monetary value for each cost category. The ranges of direct costs were extended in either direction by 20% to include any regional differences in medical care costs. The cost of sample collection, which included the cost of the sample collection materials, wages of the personnel collecting the endocervical swabs, and the cost of storing and transporting the specimens to the laboratory, were added to the cost of doing a diagnostic test. Table 2. Cost Assumptions Used in the Decision Analysis* We included no cost for the womans initial clinic visit because the test was not the primary reason for consultation. We assumed that the cost of informing a patient of her test result and arranging a visit to the clinic included the salary of a disease intervention specialist plus the cost of equipment and the setting. Because patient follow-up may be difficult and time-consuming in certain settings, we estimated that a disease intervention specialist spends an average of 30 minutes for the follow-up of each patient. The cost of medical care for uncomplicated genital chlamydial infection includes those of a physicians appointment, antibiotic treatment, a 1-week course of clotrimazole for the 20% of female patients who develop moniliasis from antibiotic therapy, and partner notification. We obtained the average cost of an unt

Facts and myths on recurrent vulvovaginal candidosis-a review on epidemiology, clinical manifestations, diagnosis, pathogenesis and therapy.

Approximately three-quarters of all women will experience an episode of vulvovaginal candidosis at least once in their life and 5-10% of them will have more than one attack. Women suffering from three to four attacks within 12 months will be diagnosed with recurrent vulvovaginal candidosis (RVVC). This review covers the large number of proposed aetiological factors for RVVC. The diagnosis of the condition made by conventional means by health providers is often false and is also often misdiagnosed by the affected woman herself. The review covers various methods of diagnosing RVVC and the current knowledge on potential pathogenetic mechanisms proposed for genital candida infections. Treatment of RVVC, including local and systemic antimicrobial therapy and behaviour modification to decrease the risk of recurrences, are discussed. Recent knowledge on drug resistance in candida is also included.

Ethnic differences of polymorphisms in cytokine and innate immune system genes in pregnant women

OBJECTIVE: Investigations of the possible role of polymorphic genes in pregnancy outcome may be influenced by ethnic variations in genotype or allele frequencies. Differences in allelic carriage of immune system-related genes among white, black, and Hispanic pregnant women living in New York City and Boston were evaluated. METHODS: DNA was extracted from buccal or vaginal epithelial cells collected from 198 white, 75 black, and 114 Hispanic pregnant women who delivered at term and who had no history of a preterm birth. Genetic polymorphisms in the immunoregulatory genes encoding interleukin (IL)-1β, tumor necrosis factor-α, IL-4, IL-10, IL-1 receptor antagonist (IL-1ra), mannose-binding lectin, toll-like receptor-4, and the 70-kDa heat shock protein were determined. RESULTS: Allele 2 of the IL-1ra gene (IL1RN*2) and IL-4 –590C homozygosity were 4-fold less common in blacks than in whites or Hispanics (P < .001). The IL-4 −590T allele was almost 2-fold more common in Hispanics than in whites (P < .001). The frequency of the 70-kDa heat shock protein 1267G allele was at least 1.4 times greater in blacks compared with whites (P < .001) or Hispanics (P = .002), whereas the homozygous mannose-binding lectin codon 54G allele was observed at least 4.5 times more often in Hispanics compared with whites (P = .007) or blacks (P = .02). CONCLUSION: Investigations of the role of genetic factors affecting pregnancy outcome must be cognizant of ethnic variations when enrolling case and control subjects for studies on allele and genotype frequencies. LEVEL OF EVIDENCE: III

Vaginal nitric oxide in pregnant women with bacterial vaginosis.

To evaluate vaginal nitric oxide (NO) production in response to alterations in the vaginal microbial flora.

Innate immune system gene polymorphisms in maternal and child genotype and risk of preterm delivery

Abstract Objective. There is little information about the combination of genetic variability in pregnant women and their children in relation to the risk of preterm delivery (PTD). In a sub-cohort of 487 non-Hispanic white and 288 African-American mother/child pairs, the Pregnancy Outcomes and Community Health Study assessed 10 functional polymorphisms in 9 genes involved in innate immune function. Methods. Race-stratified weighted logistic regression models were used to calculate odds ratios for genotype and PTD/PTD subtypes. Polymorphisms significantly associated with PTD/PTD subtypes were tested for mother/child genotype interactions. Results. Three maternal polymorphisms (IL-1 receptor antagonist intron two repeat (IL-1RN), matrix metalloproteinase- −C1562T, and TNF receptor two M196R (TNFR2)) and three child polymorphisms (IL1-RN, tumor necrosis factor-alpha −G308A, and TNFR2) were associated with PTD, but associations varied by PTD subtype and race. Two interactions were detected for maternal and child genotype. Among non-Hispanic white women, the odds of PTD was higher when both mother and child carried the IL-1RN allele two (additive interaction p < 0.05). Among African-American women, the odds of PTD were higher when both mother and child carried the TNFR2 R allele (multiplicative interaction p < 0.05). Conclusion. These results highlight the importance of assessing both maternal and child genotype in relation to PTD risk.

Optimized amniotic fluid analysis in patients suspected of intrauterine infection/inflammation.

Abstract Objective: To determine the combination of amniotic fluid (AF) tests with the best diagnostic accuracy for predicting intrauterine infection/inflammation (IUI) in patients with clinical suspicion of chorioamnionitis. Study design: This is a retrospective study of 34 pregnant women who presented with uterine tenderness, maternal fever, maternal tachycardia, and/or fetal tachycardia and underwent AF analysis. IUI diagnosis was based on placental histology, positive AF bacterial cultures, and/or Gram stain. Result: Logistic regression analysis revealed a significant relationship between IUI and AF glucose. Glucose is more sensitive than culture or Gram stain (64% vs. 40% and 20%, [iw-0.3]respectively). Culture and glucose combined achieved the best diagnostic accuracy (sensitivity, 71%; specificity, 100%; positive and negative predictive values, 100–83%, respectively). Conclusion: Positive AF Gram stain or glucose <15 mg/dL strongly suggests IUI in symptomatic patients. If both tests are negative, the result of culture should aid the management.

Differential utilization of expanded genetic screening tests in patients of reproductive ages from private and academic practices.

Abstract Objective: We sought to evaluate the types of genetic screening tests that are performed in women of childbearing ages in New Jersey. Method: Data from patients who had a reproductive genetics consultation between January 1, 2012, and July 31, 2012, were stratified according to the referring providers, i.e., those from academic or private practices, and descriptive analyses performed. Unconventional genetic screening was defined as any test ordered by the referring health care provider outside the recommendations from the American Congress of Obstetricians and Gynecologists or the American College of Medical Genetics and Genomics. Results: Overall, 30% of 371 patients referred for a genetic consultation underwent unconventional screening. As compared to patients from academic practices, the relative rate of unconventional screening was 10-fold higher among patients from private practices, resulting in a relative 34-fold increase in the estimated cost in genetic screening (P<0.01). Conclusion: This set of preliminary observations highlight the need for further state, nationwide, and international studies to understand the financial, personal, and societal impact that this discrepancy health care system in the use of genetic carrier screening portends.