Low rectal resection for low rectal endometriosis and rectal adenocarcinoma: Are we discussing the same risks?

OBJECTIVE: To evaluate the rate and risk factors for anastomosis leakage in patients undergoing colorectal resection with low anastomosis for rectal endometriosis and rectal adenocarcinoma. METHODS: A retrospective cohort study evaluating prospectively collected data was conducted. Patients undergoing colorectal resection for rectal endometriosis and rectal adenocarcinoma with low anastomosis (<7 cm from the anal verge [AV]) from September 2018 to January 2023 were included in the analysis. The main outcome was the rate of anastomosis leakage. A multivariate logistic regression was conducted to evaluate risk factors for anastomosis leakage in both groups. RESULTS: A total of 159 patients underwent colorectal resection with low anastomosis due to rectal endometriosis (n = 99) and rectal adenocarcinoma (n = 60). Patients with endometriosis were significantly younger than those with adenocarcinoma (35.7 ± 5.1 vs 63.7 ± 12.6; P = 0.001). The leakage rate was similar between the endometriosis (n = 12, 12.1%) and adenocarcinoma (n = 9, 15.0%) patients (P = 0.621). The anastomosis height less than 5 cm from the AV (adjusted odds ratio [aOR] 12.12, 95% confidence interval [CI] 2.24-23.54) was significantly associated with the anastomosis leakage. Protective stoma was associated with the decrease of the leakage risk (aOR 0.12, 95% CI 0.01-0.72). The type of disease (rectal endometriosis or adenocarcinoma) was not associated with the anastomosis leakage (aOR 2.87, 95% CI 0.34-21.23). CONCLUSIONS: Despite the different pathogenesis, the risk of anastomotic leakage was found to be similar between patients with low rectal endometriosis and those with rectal adenocarcinoma. These results must be considered by the gynecologist and colorectal surgeon to deliver proper information before rectal surgery for endometriosis.

Robotic Management of Recurrent Rectal Endometriosis After Previous Segmental Bowel Resection.

OBJECTIVE: To describe the management of recurrent bowel endometriosis after previous colorectal resection. DESIGN: Surgical video article. The local institutional board review was omitted due to the narration of surgical management. Patient consent was obtained. SETTING: A tertiary referral center. The patient first underwent segmental bowel resection for deep infiltrating endometriosis of the rectum in the ENDORE randomized controlled trial in 2012 and then received a total hysterectomy in 2018. Five years later, she presented with recurrent nodules in the rectovaginal, left parametrium, and abdominal wall after discontinuing medical suppressive treatment. INTERVENTION: Laparoscopic management using robotic assistance was employed to complete excision of the rectovaginal nodule. Disc excision was performed to remove rectal infiltration. The procedure started with rectal shaving and excision of vaginal infiltration . A traction stitch was placed over the limits of the rectal shaving area. The general surgeon placed a 28 mm circular anal stapler transanally and performed complete excision of the shaved rectal area. Anastomotic perfusion was checked with indocyanine green. A methylene blue enema test was conducted to rule out anastomotic leakage. Outcomes were favorable, with systematic self-catheterization during 5 postoperative weeks. No specific symptoms were related to the other 2 nodules, which were not removed. CONCLUSION: Rectal recurrences may occur long after colorectal resection and outside the limits of the previous surgery site. To accurately assess this risk, long-term follow-up of patients is mandatory.. Postoperative medical amenorrhea may play a role in recurrence prevention. Surgical management of recurrences may be challenging and focus on only those nodules responsible for symptoms so as to best preserve the organ's function and reduce postoperative morbidity.

Toward a strengths-based model for designing virtual reality learning experiences for autistic users.

LAY ABSTRACT: Virtual reality has been studied for its potential in supporting individuals with autism, but existing research often focuses on deficits and lacks consideration of individual preferences and strengths. This article introduces a framework that emphasizes the strengths and abilities of autistic individuals when designing virtual reality interventions. It builds upon an existing taxonomy of educational technology affordances and extends it to align with the unique needs of autistic individuals. The framework provides guidance for incorporating virtual reality technology that supports and amplifies autistic strengths, such as visual perception and response to positive feedback. The framework has implications for practice, research, and policy. For practitioners, it offers a tool for designing virtual reality experiences that cater to the strengths of autistic individuals, enhancing engagement and educational outcomes. Researchers can utilize the framework to guide the development of user-centered virtual reality interventions and expand our understanding of the potential benefits of virtual reality for autistic populations. Policymakers and educators can consider this framework when incorporating virtual reality into educational settings, ensuring that virtual reality technology is used in a way that aligns with the strengths and needs of autistic learners. Overall, the framework promotes a strengths-based approach in utilizing virtual reality technology for individuals with autism, fostering inclusivity and maximizing the benefits of immersive experiences.

How are Autistic People Involved in the Design of Extended Reality Technologies? A Systematic Literature Review.

The primary aim of this systematic review is to investigate the inclusion of autistic individuals in the design process of immersive technologies. This study follows the preferred reporting items for systematic reviews and meta-analyses standards for systematic literature reviews. To ensure the research questions and subsequent stages of the review incorporate pertinent parameters, the problem, interest, context framework has also been employed. Findings highlight that, while early proponents of immersive technology emphasized the importance of user involvement in design of new technology, immaturity of the technology often limited the implementation of direct user input to the design process. Nonetheless, analysis of the literature published between 2002-2022 identified 20 studies in which substantial influence of autistic individuals and stakeholders was found in the design process of immersive technologies. The roles of autistic individuals varied from active co-designers and co-creators to essential contributors in refining prototypes and providing critical feedback, ensuring the final products align with their needs and preferences. Results underscore the need to align research and design of immersive technologies more closely with the priorities and preferences of autistic individuals. Further is needed regarding actively involving autistic individuals in the design and implementation of immersive technology applications. On this basis, we maintain that more inclusive and effective deployment of immersive technologies is needed in order to ensure that resultant technologies are fit for purpose and address the actual needs of the autistic community.

Learning Experience Design of Project PHoENIX: Addressing the Lack of Autistic Representation in Extended Reality Design and Development.

This paper presents Project PHoENIX, which stands for Participatory, Human-centered, Equitable, Neurodiverse, Inclusive, eXtended reality. The project aims to co-produce research with autistic users to create a virtual reality (VR) environment that is highly usable, accessible, and sensitive to the needs and preferences of these individuals. Project PHoENIX utilizes participatory design within a learning experience design (LXD) frame to locate autistic people, their caregivers, and providers centrally in the processes of immersive technology design and development, as well as research design and execution. An overarching literature review on VR and autism and issues of limited design precedent of VR environments with autistic participants is provided, as well as details on the Project PHoENIX design framework, project description, and project design outcomes. Details are provided on how the online VR environment was co-designed and co-developed through collaborative research with autistic stakeholders while being sensitive to their needs and preferences. Research findings and implications are discussed regarding the design process, constraints, principles, and insights. The paper concludes by discussing lessons learned and how this project can provide much-needed design precedent for advancing the field towards a more inclusive, human-centered, and neurodiverse VR research and development paradigms.

A Nitrite Excipient Database: A Useful Tool to Support N-Nitrosamine Risk Assessments for Drug Products.

N-Nitrosamine risk assessment and control have become an integral part of pharmaceutical drug product development and quality evaluation. Initial reports of nitrosamine contamination were linked with the drug substance and its manufacturing process. Subsequently, the drug product and aspects of the formulation process have shown to be relevant. Regarding specific formulation contributions to nitrosamine content in a product, one risk lies in possible interactions between nitrosating agents, derived from nitrite in excipients, and vulnerable amines, either present as moieties of the active molecule or as impurities / degradants. However, the limited validated information on nitrite levels in excipients available until now, has been an obstacle for scientists to assess the risk of nitrosamine formation in pharmaceutical products. This has driven the creation of a database to store and share such validated information. The database, maintained by Lhasa Limited, constitutes a central platform to hold the data donated by the pharmaceutical company members on the nitrite concentrations in common excipients measured with validated analytical procedures. The goal of this data sharing initiative is to provide a common framework to contextualize and estimate the risk posed by presence of nitrites to contribute to the formation of nitrosamines in drug products. The major findings from the database analyses are: (1) average nitrite content and batch to batch variance differ among excipients, (2) for solid dosage forms, the nitrite contribution is dominated by the highest formula % excipients, e.g., the fillers (diluents), which are typically used in larger proportion, and are characterized by low nitrite levels and low variability, leading to an average value of 1 µg/g nitrite in a typical formulation, (3) substantial differences in average nitrite content in batches from different excipient vendors potentially reflecting differences in source materials or processing methods for excipient manufacturing. That final point suggests that future selection of raw materials or processing by excipient manufacturers may help reduce nitrite levels in finished drug product formulations, and thus the overall risk of nitrosamine formation in cases where the product contains vulnerable amines.

Excision of Deep Rectovaginal Endometriosis Nodules with Large Infiltration of Both Rectum and Vagina: What Is a Reasonable Rate of Preventive Stoma? A Comparative Study.

STUDY OBJECTIVE: To compare postoperative complications and rectovaginal fistula rate in women undergoing excision of large rectovaginal endometriosis requiring concomitant excision of rectum and vagina during 2 time periods with differing policies for preventive stoma confection. DESIGN: Retrospective before-and-after comparative cohort study on data prospectively recorded in a database. Patients managed from September 2018 to March 2020 (first period) were compared with those managed from April 2020 to June 2022 (second period). SETTING: Endometriosis Institute. PATIENTS: One hundred sixty-eight patients presenting with deep endometriosis infiltrating the rectum and vagina, with lesions more than 3 cm in diameter during 2 consecutive time periods with differing policies regarding use of preventive stoma. INTERVENTIONS: Rectal disc excision or colorectal resection, concomitantly with large vaginal excision. MEASUREMENTS AND MAIN RESULTS: A total of 87 and 81 women received surgery during the first and the second period, respectively, during which the rate of preventive stoma was, respectively, 32.2% and 8.6%. Deep rectovaginal nodule characteristics were comparable. The mean height (SD) of rectal sutures after disc excision and colorectal resection were, respectively, 6.5 cm (2.3 cm) and 7.2 cm (3.8 cm). Rectovaginal fistula was recorded in 17 patients, corresponding to an overall rate of 10.1%. The rates of rectovaginal fistula in the group of patients with and without preventive stoma, regardless of the period in which surgery was performed, were 11.4% and 9.8%, respectively (p = .76). The rates of fistula recorded during the first and the second period were, respectively, 9.2% and 11.1% (p = .80), and that of overall early main complications were 31% and 29.6% (p = .84). Regression logistic model identified an independent relationship between smoking and rectovaginal fistula (adjusted odds ratio [OR] 3.9, 95% confidence interval [CI] 1.1-14) after adjustment for the period (adjusted OR 1.4, 95% CI 0.4-4.9 related to the second period), stoma confection (adjusted OR 1.8, 95% CI 0.5-7.1 related to stoma confection), robotic surgery (adjusted OR 1.7, 95% CI 0.3-10.1 related to robotic assistance), and type of rectal surgery (adjusted OR 0.4, 95% CI 0.1-1.4 related to disc excision when compared with colorectal resection). CONCLUSION: No statistically significant differences were found concerning risk of rectovaginal fistula in women with rectovaginal endometriosis requiring large rectal and vaginal excision after a decision to no longer routinely perform preventive stoma.

Disk Excision Using End-to-End Anastomosis Circular Stapler for Deep Endometriosis of the Rectum: A 492-Patient Continuous Prospective Series.

STUDY OBJECTIVE: To report a large series including women managed by disk excision using end-to-end anastomosis (EEA) circular transanal stapler to assess the feasibility of the technique, the features of nodules suitable for removal by disk excision, and the rate of major early complications. DESIGN: Retrospective study on data prospectively recorded in 2 databases. SETTING: Two tertiary referral centers. PATIENTS: A total of 492 patients undergoing surgery for rectal endometriosis from May 2011 to June 2022. INTERVENTIONS: Rectal disk excision using the EEA stapler. MEASUREMENT AND MAIN RESULTS: Disk excision using EEA was performed in 492 patients (24.2%) of 2,029 women receiving surgery for deep endometriosis infiltrating the rectum during the 11-year study period. Deep endometriosis involved low rectum in 11% and mid rectum in 55.3%. The diameter of rectal nodules exceeded 3 cm in 65.9%. Mean operative time was 2 hours, mean diameter of rectal patches removed was 41 ± 11 mm, and the mean rectal suture height was 9.2 ± 5.5 cm. The presence of microscopic foci on the edges of rectal patches was identified in 30.2% of cases. Rectal fistula was recorded in 20 patients (4%). The distance from the anal verge was significantly lower in patients with fistula than women with no fistula (5.9 ± 2 cm vs 9.2 ± 5.6 cm, p = .027). Follow-up ranged from 1 to 120 months, with a median value of 36 months. Magnetic resonance imaging in 3 patients during follow-up revealed a recurrent nodule infiltrating the previous stapled line (0.6%) after a postoperative delay of, respectively, 36, 48, and 84 months. CONCLUSION: Disk excision using the EEA stapler is suitable in nodules >3 cm if surgeons ensure deep shaving of the rectum, to allow complete inclusion of the shaved area into the stapler jaws. Postoperative rectal recurrences seem incidental, whereas bowel leakage rate is comparable with that after colorectal resection. This technique is suitable in almost a quarter of patients managed for rectal endometriosis nodules and is therefore a valuable technique that warrants more widespread use.

Natural Orifice Specimen Extraction Colorectal Resection for Deep Endometriosis: A 50 Case Series.

STUDY OBJECTIVE: To describe our experience with the use of natural orifice specimen extraction (NOSE) technique for segmental bowel resection in patients with colorectal endometriosis. DESIGN: A retrospective, observational study. SETTING: A single tertiary referral center. PATIENTS: A total of 50 consecutive patients undergoing NOSE colectomy for colorectal endometriosis in our center, between March 2021 and November 2021. INTERVENTIONS: NOSE colectomy for colorectal endometriosis with removal of the excised colorectal specimen through the vagina or the anus. MEASUREMENT AND MAIN RESULTS: A total of 45 procedures were performed laparoscopically and 5 procedures were performed robotically. All interventions were performed by 3 endometriosis surgeons in a multidisciplinary fashion, with involvement of a colorectal surgeon. There were no cases of conversion to laparotomy. Concomitant surgical procedures were performed in all cases. Eleven patients had concomitant interventions on the digestive tract. Five patients had concomitant interventions on the sacral plexus or sciatic nerve. All anastomoses were lateroterminal. The mean height of colorectal anastomosis was 12 cm (standard deviation [SD] ± 4), and the mean length of the excised colorectal specimen was 9 cm (SD ± 4). In 29 cases, the specimen was extracted through the vagina and in 21 cases through the anus. A total of 5 patients required a reoperation in the early postoperative period: We identified 1 case of anastomotic leak, 1 case of postoperative bowel obstruction, 1 case of hemorrhage and 2 cases of pelvic collection (no macroscopic evidence of pus). No patient received blood transfusion. The mean operative time was 158 minutes (SD ± 70) and mean hospital stay was 4 days (SD ± 1). CONCLUSION: NOSE colectomy is a reproducible surgical technique for the management of colorectal endometriosis. The complication rate appears comparable with the conventional (minilaparotomy) surgical approach. In experienced hands, this technique has a short learning curve, both in laparoscopy and in robotic surgery.

Adjuncts to the Management of Graft Aorto-Enteric Erosion and Fistula with in situ Reconstruction.

OBJECTIVE: The objective of this retrospective single centre study was to determine whether different enteric reconstruction methods and adjuncts confer a benefit after in situ reconstructions (ISRs) of graft aorto-enteric erosion (AEnE) and fistula (AEnF). METHODS: Primary endpoints were in hospital mortality and AEnE/F recurrence. Survival was estimated using the Kaplan-Meier method and explanatory factors were searched for using uni- ± multivariable Cox regression analysis. In 2013, a multidisciplinary team meeting was convened and since then the primary operator has always been a senior surgeon. RESULTS: Sixty-six patients were treated for AEnE (n = 38) and AEnF (n = 28, 42%) from 2004 to 2020. All patients with AEnF presented with gastrointestinal bleeding (vs. 0 for AEnE; p < .001). Signs of infection were seen in 50 patients (76% [37 for AEnE vs. 13 for AEnF]; p < .001). Referrals for endograft infection increased over time (n = 15, 23%; one before 2013 vs. 14 after; p = .002). Most patients underwent complete graft excision (n = 52, 79%) with increasing suprarenal cross clamping (n = 21, 32%; four before 2013 vs. 17 after; p = .015). Complex visceral reconstructions decreased over time (n = 31, 47%; 17 before 2013 vs. 14 after; p = .055), while "open abdomens" (OAs) increased (one before 2013 vs. 22 after; p < .001), reducing operating time (p = .012). In hospital mortality reached 42% (n = 28). Estimated survival reached 47.6% (95% confidence interval [CI] 35.0 - 59.1) at one year and 45.6% (95% CI 33.0 - 57.3) at three years and was higher for AEnE than for AEnF (log rank p = .029). AEnE/F recurrence was noted in 12 patients (18%). Older age predicted in hospital mortality in multivariable analysis (p = .034). AEnE/F recurrence decreased with the presence of a primary senior surgeon (vs. junior; p = .003) and OA (1 [4.4%] vs. 11 [26%] for primary fascial closure; p = .045) in univariable analysis. CONCLUSION: Mortality and recurrence rates remain high after ISR of AEnE/F. Older age predicted in hospital mortality. Primary closure of enteric defects ≤ 2 cm in diameter reduced operating time without increasing the recurrence of AEnF.

High speed e-beam lithography for gold nanoarray fabrication and use in nanotechnology.

E-beam lithography has been used for reliable and versatile fabrication of sub-15 nm single-crystal gold nanoarrays and led to convincing applications in nanotechnology. However, so far this technique was either too slow for centimeter to wafer-scale writing or fast enough with the so-called dot on the fly (DOTF) technique but not optimized for sub-15 nm dots dimension. This prevents use of this technology for some applications and characterization techniques. Here, we show that the DOTF technique can be used without degradation in dots dimension. In addition, we propose two other techniques. The first one is an advanced conventional technique that goes five times faster than the conventional one. The second one relies on sequences defined before writing which enable versatility in e-beam patterns compared to the DOTF technique with same writing speed. By comparing the four different techniques, we evidence the limiting parameters for the writing speed. Wafer-scale fabrication of such arrays with 50 nm pitch allowed XPS analysis of a ferrocenylalkyl thiol self-assembled monolayer coated gold nanoarray.

Characterization of drug-resistant influenza virus A(H1N1) and A(H3N2) variants selected in vitro with laninamivir.

Neuraminidase inhibitors (NAIs) play a major role for managing influenza virus infections. The widespread oseltamivir resistance among 2007-2008 seasonal A(H1N1) viruses and community outbreaks of oseltamivir-resistant A(H1N1)pdm09 strains highlights the need for additional anti-influenza virus agents. Laninamivir is a novel long-lasting NAI that has demonstrated in vitro activity against influenza A and B viruses, and its prodrug (laninamivir octanoate) is in phase II clinical trials in the United States and other countries. Currently, little information is available on the mechanisms of resistance to laninamivir. In this study, we first performed neuraminidase (NA) inhibition assays to determine the activity of laninamivir against a set of influenza A viruses containing NA mutations conferring resistance to one or many other NAIs. We also generated drug-resistant A(H1N1) and A(H3N2) viruses under in vitro laninamivir pressure. Laninamivir demonstrated a profile of susceptibility that was similar to that of zanamivir. More specifically, it retained activity against oseltamivir-resistant H275Y and N295S A(H1N1) variants and the E119V A(H3N2) variant. In vitro, laninamivir pressure selected the E119A NA substitution in the A/Solomon Islands/3/2006 A(H1N1) background, whereas E119K and G147E NA changes along with a K133E hemagglutinin (HA) substitution were selected in the A/Quebec/144147/2009 A(H1N1)pdm09 strain. In the A/Brisbane/10/2007 A(H3N2) background, a large NA deletion accompanied by S138A/P194L HA substitutions was selected. This H3N2 variant had altered receptor-binding properties and was highly resistant to laninamivir in plaque reduction assays. Overall, we confirmed the similarity between zanamivir and laninamivir susceptibility profiles and demonstrated that both NA and HA changes can contribute to laninamivir resistance in vitro.

Ultracompact optical filter based on a stub resonator in GaInAsP/InP optical wire technology.

We report on the fabrication and characterization of a very compact filtering structure based on a resonant stub fabricated using optical wire technology in the InP material line. The stub length is close to 1.6 microm and has been designed to get a resonance wavelength close to 1550 nm. The characterization showed a resonance frequency at 1520 nm with a 12 dB resonance peak.

Design, optimization and fabrication of an optical mode filter for integrated optics.

We present the design, optimization, fabrication and characterization of an optical mode filter, which attenuates the snaking behavior of light caused by a lateral misalignment of the input optical fiber relative to an optical circuit. The mode filter is realized as a bottleneck section inserted in an optical waveguide in front of a branching element. It is designed with Bézier curves. Its effect, which depends on the optical state of polarization, is experimentally demonstrated by investigating the equilibrium of an optical splitter, which is greatly improved however only in TM mode. The measured optical losses induced by the filter are 0.28 dB.

Development of a long-acting injectable formulation with nanoparticles of rilpivirine (TMC278) for HIV treatment.

Long-acting parenteral formulations of antiretrovirals could facilitate maintenance and prophylactic treatment in HIV. Using the poorly water- and oil-soluble non-nucleoside reverse transcriptase inhibitor (NNRTI) TMC278 (rilpivirine) as base or hydrochloride (HCl), nanosuspensions were prepared by wet milling (Elan NanoCrystal technology) in an aqueous carrier. Laser diffraction showed that the average particles size were (1) close to the targeted size proportionality (200-400-800 nm), with increasing distributions the larger the average particle size, and (2) were stable over 6 months. Following single-dose administration, the plasma concentration profiles showed sustained release of TMC278 over 3 months in dogs and 3 weeks in mice. On comparison of intramuscular and subcutaneous injection of 5mg/kg (200 nm) in dogs, the subcutaneous route resulted in the most stable plasma levels (constant at 25 ng/mL for 20 days, after which levels declined slowly to 1-3 ng/mL at 3 months); 200 nm nanosuspensions achieved higher and less variable plasma concentration profiles than 400 and 800 nm nanosuspensions. In mice, the pharmacokinetic profiles after a single 20mg/kg dose (200 nm) were similar with two different surfactants used (poloxamer 338, or d-alpha-tocopheryl polyethylene glycol 1000 succinate). In conclusion, this study provides proof-of-concept that 200-nm sized TMC278 nanosuspensions may act as long-acting injectable.

Pharmacokinetics of tipifarnib after oral and intravenous administration in subjects with advanced cancer.

The primary objective of this study was to identify intravenous regimens of tipifarnib that would mimic the systemic exposure obtained after the current twice-daily oral administration of tipifarnib. After determination of an intravenous dose that 6 subjects with advanced cancer could tolerate, another 26 subjects were randomly assigned to receive 3 consecutive 4-day regimens of tipifarnib with different treatment sequences: a 100-mg 2-hour intravenous infusion, 200-mg oral administration twice daily, and a 200-mg/d continuous intravenous infusion. The systemic exposure to tipifarnib was comparable among these 3 regimens. The plasma concentration-time profile of 2-hour intravenous infusion more closely resembled the oral administration than did the continuous infusion. Glucuronidation is a metabolic pathway for tipifarnib with concentrations of the glucuronide conjugate greatly exceeding the parent compound after oral and intravenous administration. Analysis of plasma metabolites indicated that tipifarnib also undergoes dealkylation and loss of the imidazole group.

A mucoadhesive, cyclodextrin-based vaginal cream formulation of itraconazole.

The development of vaginal medications, especially antifungal medications, requires that the drug is solubilized as well as retained at or near the mucosa for sufficient periods of time to ensure adequate bioavailability. Itraconazole is a broad-spectrum antifungal agent, which has been used for some time orally and intravenously but for which a vaginal formulation has not yet been developed. We present here a novel itraconazole formulation intended for vaginal use based on hydroxypropyl-beta-cyclodextrin (HPbetaCD), a functional excipient that increases drug solubility and generates a mucoadhesive system in the presence of other ingredients. An aqueous phase was prepared by solubilizing itraconazole with HCl in the presence of propylene glycol and then adding an aqueous solution of HPbetaCD. After pH adjustment, the itraconazole/HPbetaCD solution was added to the oil phase (paraffin oil, trihydroxystearate, and cetyl dimethicon copolyol) and the desired cream containing 1%, 2%, and 2.5% drug obtained by homogenization. Primary irritation studies and subchronic toxicity studies using a rabbit vaginal model indicated that the formulation was safe, well tolerated, and retained in the vaginal space. Clinical investigations indicated that application of 5 g of a 2% cream was very well tolerated and itraconazole was not systemically absorbed. Additional studies in women found that the itraconazole cream was highly effective in reducing or eliminating fungal cultures with few adverse effects. These studies suggested that an HPbetaCD-based, emulsified wax cream formulation was a useful and effective dosage form for treating vaginal candidiasis.