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#1
06.12.2005, 21:54
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Фарматекс-только контрацепция?
Уважаемые коллеги!!
Имела неострожность при ответе на вопрос пациентки упомянуть о бактерицидном эффекте фарматекса. Это вызвало бурю негодования со стороны других врачей и участников форума. К сожалению ни одного гинеколога там не побывало. Поэтому выношу эту тему на обсуждение здесь. Может быть это действительно миф и заблуждение российских гинекологов(как говорит Е.Е.Студенцов). Коллеги!! Хотелось бы услышать ваше мнение. 
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#2
06.12.2005, 22:08
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Цитата:
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#3
06.12.2005, 22:22
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Цитата:
DA Grimes, L Lopez, EG Raymond, V Halpern, K Nanda, KF Schulz The Cochrane Database of Systematic Reviews 2005 Issue 4 (Status: New) Copyright © 2005 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. DOI: 10.1002/14651858.CD005218.pub2 This version first published online: 19 October 2005 in Issue 4, 2005 Date of Most Recent Substantive Amendment: 15 June 2005 This record should be cited as: Grimes DA, Lopez L, Raymond EG, Halpern V, Nanda K, Schulz KF. Spermicide used alone for contraception. The Cochrane Database of Systematic Reviews 2005, Issue 4. Art. No.: CD005218. DOI: 10.1002/14651858.CD005218.pub2. -------------------------------------------------------------------------------- Abstract Background Spermicides have been used as contraceptives for thousands of years. Despite this long use, only recently have studies examined the comparative efficacy and acceptability of these vaginal medications. Spermicides contain an active ingredient (most commonly nonoxynol-9) and a formulation used to disperse the product, such as foam or vaginal suppository. Objectives This review examined all known randomized controlled trials of a spermicide used alone for contraception. Search strategy We searched the following computerized databases from inception to July 2004 for randomized controlled trials of spermicides for contraception: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, POPLINE, LILACS, and EMBASE. We examined the reference list of each trial found as well as that of review articles and textbook chapters. Selection criteria We included any trial of a commercial product used alone for contraception. Each included trial must have provided sufficient information to determine pregnancy rates. We located reports from 14 trials. Data collection and analysis Two reviewers independently extracted information from the trials identified. We did not conduct a meta-analysis, since most trials had large losses to follow-up. We entered the data into tables and presented the results descriptively. Main results In the largest trial to date, the gel (Advantage S) containing the lowest dose of nonoxynol-9 (52.5 mg) was significantly less effective in preventing pregnancy than were gels with higher doses of the same agent (100 mg and 150 mg). Probabilities of pregnancy by six months were 22% for the 52.5 mg gel, 16% for the 100 mg dose, and 14% for the 150 mg dose. In the same trial, the three different vehicles with 100 mg of nonoxynol-9 had similar efficacy. Interpretation of these figures is limited, since 39% of participants discontinued the method or were lost from the trial. Few important differences in efficacy emerged in other trials. Authors' conclusions The probability of pregnancy varied widely in reported trials. A gel containing nonoxynol-9 52.5 mg was inferior to two other products tested in the largest trial. Aside from this finding, personal characteristics and behavior of users may be more important than characteristics of the spermicide products in determining the probability of pregnancy. Gel was liked more than the film or vaginal suppository in the largest trial. Spermicide trials have the dual challenges of difficult recruitment and high discontinuation rates; the latter threatens trial validity. Synopsis Because of poor trial quality, how well various spermicides work in preventing pregnancy is unclear. Vaginal spermicides have been used by women for several thousand years. This review compared the effectiveness of different spermicide products when used alone for contraception. The largest trial compared five different spermicides. The gel with the smallest amount of nonoxynol-9 was less effective in preventing pregnancy than were products containing more of the same ingredient. Women liked the gel better than the film or suppository. These trials had problems recruiting women into the studies and then keeping them in the studies until the planned end. Implications for practice Most trials to date were so poorly done that drawing conclusions about the comparative ef_cacy of spermicides is not possible. The pregnancy probabilities varied widely in reported trials, but have been as high as 28% over six months of use (Raymond 1999a). Few important differences emerged between products, although a gel containing nonoxynol-9 52.5 mg was inferior to two other products tested in one trial (Raymond 2004a). Aside from this one product, personal characteristics and behavior of users may be more important than characteristics of the spermicide products themselves in determining the likelihood of pregnancy. Gel may be a more acceptable spermicide formulation than film or vaginal suppository (Raymond 2005). In general use outside of research settings, spermicides fall into the bottom tier of contraceptive effectiveness (Steiner 2003). On the other hand, advantages of spermicides for women at low risk of HIV infection include easy availability, moderate cost, absence of systemic effects, and control by the woman.
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#4
06.12.2005, 22:32
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Цитата:
Кстати производитель упоминает об этом свойстве весьма осторожно - in vitro (а не in vivo) - чтобы избежать последующих возможных судебных исков.
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#5
06.12.2005, 22:51
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In Vitro and In Vivo: The Story of Nonoxynol 9
[Review Article] Hillier, Sharon L PhD*; Moench, Thomas MD†; Shattock, Robin PhD Summary: There is an urgent need to expand the range of interventions to prevent HIV transmission and acquisition, especially those that can be controlled by women. Microbicides, defined as antimicrobial products that can be applied topically for the prevention of HIV and other sexually transmitted infections, may offer one of the most promising preventive interventions, because they could be inexpensive, readily available, and widely acceptable. The first microbial product to be clinically evaluated contained Nonoxynol-9 (nonylpenoxypolyethoxyethanol [N-9]), a nonionic surfactant, as the active agent. This article presents a review of the in vitro, ex vivo, and animal model data on the safety of N-9 and a critical analysis of their predictive power based on the results of multiple safety and efficacy trials. CONCLUSION Recent clinical studies have clearly indicated that N-9 should no longer be considered a candidate microbicide. Nevertheless, the wealth of nonclinical and clinical data available from these studies represents an important opportunity to assess the predictive value of these data in relation to clinical outcome. What lessons can we learn from the in vitro, in vivo, and human studies conducted with N-9 that can inform the clinical development of safe microbicides? In vitro studies demonstrate that N-9 displays antiviral activity at doses that are cytotoxic for lymphocytes and primary epithelial cells. This cytotoxicity is influenced by the concentration, duration, and number of exposures. N-9 also shows substantial toxicity in vivo in the genital tract of mice, rats, rabbits, and non-human primates. Data obtained from N-9 studies in animal models correlate well with data that have been accumulating in women exposed to N-9.46,47,50 The epithelial disruption, inflammatory infiltrate in tissue and cervicovaginal secretions, increase in expression of cellular factors that promote HIV replication, and apparent increase in susceptibility to HIV that are observed in women after N-9 use are similar to the physical characteristics observed in those animal models; they argue against the pursuit of N-9 as a microbicide and likewise against the further study of other candidate microbicides that have similar toxicities. Thus, an important lesson learned is that although N-9 has been historically used as a negative control, the level of toxicity observed after N-9 exposure in the RVI test should become a positive toxicity control or marker for an unacceptable degree of toxicity. Additionally, new products that have toxicity profiles similar to N-9 should probably not move forward into clinical trials. N-9 was never subjected to the extensive in vitro preclinical evaluation that is now required of all candidates before clinical testing. In the current scientific environment, it is highly unlikely that N-9 would have progressed further than early in vitro evaluation. In vitro, in vivo, and clinical studies have suggested the potential ability of N-9 to exert an influence on inflammatory processes. These findings have started a debate on what is the best method to detect vaginal inflammation in clinical trials of microbicidal candidates. Evaluating cervical lesions has been a routine part of clinical safety assessments for microbicide trials; however, little is known about more subtle changes in the cervical and vaginal epithelium, including induction of subepithelial inflammation and interference with normal host defense mechanisms. The lack of correlation in clinical studies of inflammation, cervical lesions, and symptomology suggests that we need to address this issue further in all future trials. N-9 has provided us with an invaluable learning experience in microbicide preclinical development. The lessons learned from N-9 studies have and should continue to be in force in the design of protocols to test other candidate microbicides. The most critical aspect of this experience has been to recognize the paramount importance of safety in microbicide development.
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#6
08.12.2005, 19:31
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Цитата:
James Trussella, , and Rosalie Dominikb Received 25 May 2005; accepted 28 June 2005. Available online 24 August 2005. Abstract Objective To evaluate the effect of adherence and condom use on apparent efficacy of microbicides. Design Hypothetical trial designs and scenarios. Methods Mathematical calculations of effectiveness. Results In a randomized trial of a candidate microbicide and a placebo, nonuse of the microbicide will result in underestimation of microbicide efficacy, with the magnitude of this difference between effectiveness and efficacy increasing directly with the level of microbicide nonuse. Adding condoms to the trial will not change this expected result as long as use of condoms and microbicide is independent, and microbicide use is the same in the trials with and without condoms. However, if microbicide use is lower in the trial with condoms, then effectiveness will be lower than in the trial without condoms, with the magnitude of the difference between effectiveness and efficacy being even greater. Moreover, condom and microbicide use may not be independent. If participants tend to use condoms rather than nothing, the trial result will more closely approximate microbicide efficacy. If, however, participants substitute condom use for microbicide use, then the expected estimate of effectiveness will less closely approximate microbicide efficacy and could be closer to or further away from the expected estimate of effectiveness than in the trial without condoms. In another trial design, where there is either simultaneous use of microbicide and condoms or no use of either (guaranteed when condoms are packaged with either a microbicidal or a placebo gel), expected effectiveness will fall short of microbicide efficacy. If nonuse is the same in a trial without condoms and a trial with microbicidally lubricated condoms, then the trial with condoms will produce an estimate of effectiveness that less closely approximates microbicide efficacy than would the trial without condoms. If there is less nonuse in the trial with condoms, then the expected estimate of effectiveness will more closely approximate microbicide efficacy and could be closer to or further away from the expected estimate of effectiveness than in the trial without condoms. Conclusions We have shown that both microbicide nonadherence and some patterns of condom use may seriously impair our ability to identify an effective microbicide. Under many plausible assumptions, effectiveness results of typical trials will substantially underestimate the efficacy of the candidate microbicide product being studied. Therefore, we could have a microbicide that is highly efficacious but not be able to tell that from our trials. The underestimation of effectiveness cannot be resolved merely by increasing the size of the trials; to do that would increase the precision of the trial result, but it would not change the magnitude of the expected point estimate of effectiveness. We can try to minimize noncompliance by providing counseling, memory aids, frequent resupply, and other measures. The level of condom use will not affect the expected estimate of effectiveness if condom use and microbicide use are independent. But even if use of the microbicides and condoms is independent, high condom use will affect these trials by lowering the overall HIV incidence rate among the study population, and thus requiring larger samples sizes to detect the microbicide effects. Of course, we cannot deliberately limit use of condoms. Although we may choose to conduct our trials at locations where we believe that people are likely to refuse to use condoms, current ethical standards require that we use every reasonable means to convince them to change their minds. This situation is not hopeless. If a trial does show evidence of effectiveness, we can in most cases reasonably conclude that the microbicide itself works to prevent infection. However, we are unlikely to be able to determine how well it works. Microbicide researchers and developers should consider these issues in determining their strategies for the development of new products and while interpreting trial results.
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Линейный вид
