Efficacy of ketoconazole gel-flakes in treatment of vaginal candidiasis: Formulation, in vitro and clinical evaluation.

Candida albicans, as the main causative fungus of vaginal candidiasis, is currently a global issue of concern due to its high prevalence, biofilm formation and emergence of resistance. Ketoconazole (KTZ), an antifungal drug, which has poor water-solubility and penetration capacity, is ineffective against deep-seated Candida infection. Considering these issues, this work aimed to develop a novel multifunctional carrier for KTZ via encapsulation of KTZ/ß-cyclodextrin (ß-CD) co-ground mixture into chitosan/gellan gum gel-flakes (threadlike and polygonal structures). Analytical studies revealed existence of electrostatic-derived complexes between negatively charged gellan gum and positively charged chitosan. Gel-flakes were then loaded in in situ gel of pluronic F-127 (PF-127). Based on gelation temperature (Tgel), viscosity and release studies; selected formulation was further evaluated, showing significant in vitro anti-candida activity. Despite reduced dosage regimen (50 mg/daily/three days), KTZ flakes in situ gel was as effective as Gynoconazol vaginal cream® (80 mg terconazole/daily/three days) in improving patient complaints and Candida eradication. Multifunctionality of KTZ carrier was based on efficient spreading and coating of the vagina due to free-flowing properties during application, flakes entanglement within folded vaginal epithelia, sustained release and increased penetration capacity of KTZ to reach deep-seated infections. In conclusion, flakes in situ gel could be considered as a highly promising KTZ delivery option for treatment of vaginal candidiasis.

Maternal mortality in an academic institution in Upper Egypt.

Maternal mortality is a worldwide problem. Measuring maternal mortality and identifying its causes is essential, and should be assessed regularly for the purpose of planning, monitoring and evaluation of provided maternal health care. Quality of care indicators such as case fatality rate is used to measure the facility performance, in particular, quality and promptness of care. This descriptive study aimed to calculate maternal mortality ratio, quality of care indicators such as maternal mortality index, case fatality and direct obstetric case fatality rate for the Women's Health Hospital and identify causes of maternal mortality, and the main deficits in medical records. The Maternal mortality ratio was alarmingly high in Women's Health Hospital, Assiut University, Egypt reaching 225/100,000, however, those who delivered in the hospital, the MMR was 100.5/100,000. The leading causes of maternal death were obstetric haemorrhage (38.3%), complications of caesarean sections (27.7%) and pre-eclampsia/eclampsia (23.4%). Nearly half (42%) of the deaths occurred during vacations. Quality indicators revealed poor quality of health care.

Low-Molecular-Weight Heparin for the Treatment of Unexplained Recurrent Miscarriage With Negative Antiphospholipid Antibodies: A Randomized Controlled Trial.

BACKGROUND: Recurrent miscarriage (RM) is one of the most common clinical problems in reproduction with no definite cause in about 50% of the cases. The study aims to evaluate the effect of low-molecular-weight heparin (LMWH) in the treatment of women with RM negatively tested for antiphospholipid antibodies (APAs). METHODS: An open-labeled registered randomized controlled study (NCT 01608347) included women who attended the outpatient clinic in Assiut Women Health Hospital and Nag-Hamady Central Hospital, Egypt, with 3 or more unexplained RM. Eligible participants were randomly assigned into 2 groups. The study group included 150 patients receiving LMWH (Tinzaparin sodium 4500 IU) subcutaneous daily injection with 500 µg folic acid once daily orally started once positive pregnancy test till the 20th week of gestation. The control group included 150 patients receiving the same dose of folic acid alone. The primary outcome of the study was the rate of continuation of a viable pregnancy after 20 weeks of gestation. RESULTS: There was no significant difference between both groups as regards age, parity, or number of previous miscarriages. There was a significant increase in women who continued their pregnancy beyond 20 weeks in the study group compared to the control group (73.3% vs 48%, respectively; P = .002). The take-home baby rate was also significantly higher in the LMWH group compared to the control group ( P = .001). CONCLUSION: Early start of LMWH decreases the incidence of miscarriage in the first 20 weeks of pregnancy in women with unexplained RM negative for APAs.

Tactile Electrosurgical Ablation: A Technique for the Treatment of Intractable Heavy and Prolonged Menstrual Bleeding.

Objective. To study the efficacy and safety of tactile electrosurgical ablation (TEA) in stopping a persistent attack of abnormal uterine bleeding not responding to medical and hormonal therapy. Methods. This is a case series of 19 cases with intractable abnormal uterine bleeding, who underwent TEA at the Women's Health Center of Assiut University. The outcomes measured were; patient's acceptability, operative time, complications, menstrual outcomes, and reintervention. Results. None of the 19 counseled cases refused the TEA procedure which took 6-10 minutes without intraoperative complications. The procedure was successful in the immediate cessation of bleeding in 18 out of 19 cases. During the 24-month follow-up period, 9 cases developed amenorrhea, 5 had scanty menstrual bleeding, 3 were regularly menstruating, 1 case underwent repeat TEA ablation, and one underwent a hysterectomy. Conclusions. TEA represents a safe, inexpensive, and successful method for management of uterine bleeding emergencies with additional long-term beneficial effects. However, more studies with more cases and longer follow-up periods are warranted.

Patterns of Candida biofilm on intrauterine devices.

Biofilms are colonies of microbial cells encased in a self-produced organic polymeric matrix and represent a common mode of microbial growth. Microbes growing as biofilm are highly resistant to commonly used antimicrobial drugs. We aimed to screen and characterize biofilm formation by different isolates of Candida on removed intrauterine devices (IUDs), to perform experimental biofilm formation with isolated strains, and to examine biofilm by the crystal violet and XTT reduction assays and scanning electron microscopy (SEM). A total of 56 IUDs were examined for biofilm formation using Sabouraud's dextrose chloramphenicol agar. Suspected colonies were identified by different methods. Antifungal susceptibility testing with fluconazole (FLU) and amphotericin B for the isolated strains and in vitro experimental biofilm formation was carried out. The biofilm was quantified by crystal violet, XTT reduction assay and SEM. Among the 56 IUDs investigated, 26 were Candida positive (46.4 %). Candida albicans was recovered from 15 isolates. The biofilm MIC of FLU was increased 64 to 1000 times compared to the MIC for planktonic cells. The XTT method results were dependent on the Candida species; biofilm formation was highest in Candida krusei and Candida glabrata strains, followed by C. albicans and Candida tropicalis. SEM of Candida biofilm revealed a heterogeneous thick biofilm with a mixture of micro-organisms. The main conclusion from this study was non-albicans Candida represents more than a half of the Candida biofilm. Better understanding of Candida biofilms may lead to the development of novel therapeutic approaches for the treatment of fungal infections, especially resistant ones among IUD users.

Modified cervicopexy: a novel, less-invasive technique for Stages III and IV uterine prolapse.

OBJECTIVE: To evaluate modified anterior abdominal wall cervicopexy (AWC) as a less invasive (via 3-cm minilaparotomy) and more augmented (via securing posterior vaginal wall to uterosacral ligaments) technique. METHODS: Case series of 30 women with Stages III and IV apical uterine prolapse assessed by the pelvic organ prolapse quantification system. RESULTS: The modified AWC procedure was performed successfully for 17 cases with Stage III uterovaginal prolapse and 13 cases with Stage IV uterovaginal prolapse. The procedure was conducted safely with no operative or postoperative complications, apart from two cases with postoperative urinary retention. Operative time ranged from 45 to 70min. Follow-up was available for 1-3 years. Overall, 27 cases were satisfied with the procedure, and three cases developed recurrence after caesarean section due to cutting the supporting sutures. CONCLUSIONS: The modified AWC procedure is less invasive, simple and effective for Stages III and IV uterine prolapse.

Trichloroacetic acid application versus spray monopolar diathermy for treating benign cervical lesions: a randomized controlled clinical trial.

OBJECTIVE: This study aimed to compare efficacy, tolerability, and safety of trichloroacetic acid (TCA) painting versus monopolar spray coagulation of the cervix for treating persistent benign cervical lesions. MATERIALS AND METHODS: A prospective randomized controlled trial was done in a tertiary care referral facility and university hospital. A total of 246 cases with objective evidence of benign cervical lesions were divided into 2 groups according to the line of management. Group A was composed of 126 cases subjected to spray monopolar coagulation, whereas group B was composed of 120 cases subjected to TCA application. Cervical smearing and colposcopy with or without cervical biopsy were performed to exclude underlying malignant lesions. Trichloroacetic acid painting or spray monopolar coagulation of the benign cervical lesion(s) was also performed. Follow-up was performed to assess relief of symptoms and cervical morphology for 1 month. Main outcome measures include success of management tool, relief of symptoms, and normal cervical morphology after 1 month of therapy. RESULTS: A statistically significant cure rate of cervical lesions after treatment in both groups without significant difference between both groups was reported. Failure rate was reported more in group B than group A mainly owing to hypertrophied ectopy and cervical polyp. Patient in group A reported low satisfaction (26.9%) and poor tolerability rate (44.5%) as compared with patients in group B, who reported high satisfaction (77.5%) and good tolerability rate (77.5%), this difference was statistically significant. CONCLUSIONS: Both topical application of 70% TCA and monopolar spray coagulation offer considerable efficacy, acceptable success rates, and minimal complications. Spray coagulation is significantly superior in terms of less persistent or incompletely healed lesions. Nevertheless, topical application of 70% TCA has the advantages of simplicity, higher patient tolerability, and safety, which can be widely used by gynecologists who have limited experience with surgical procedures. It is highly recommended if the cervical lesion is ectopy or nonspecific cervicitis but not hypertrophic lesion such as hypertrophic ectopy or polyp.

Reliability of unaided naked-eye examination as a screening test for cervical lesions in a developing country setup.

OBJECTIVE: This study aimed to test the reliability of unaided naked-eye examination (UNEE) of the cervix as a sole cervical cancer screening test in a developing country setup compared with the standard cervical cytology. MATERIALS AND METHODS: A total of 3,500 nonpregnant women aged between 25 and 55 years were included. An unlubricated bivalve speculum was inserted into the vagina under good light to visualize the cervix. A thorough UNEE of the cervix was done to detect any apparent lesions. Cervical smears were obtained using the long tip of an Ayre spatula. An additional endocervical sample was obtained by cytobrush. Women with abnormal Pap smears or visible cervical lesions by UNEE were scheduled for colposcopic examination. A biopsy specimen was obtained in every abnormal colposcopic examination. RESULTS: Of 3,500 cases, there were 9 (2.57%) preinvasive cervical lesions (cervical intraepithelial neoplasia 1-3) diagnosed with various diagnostic tools used in the study and confirmed by histopathologic examination. Of 3,500 cases, invasive cervical lesions were diagnosed in 6 (1.71%). The sensitivity of UNEE is much better than that of Pap smear (80% vs 60%) but less than that of colposcopy (86.7%). However, the specificity of UNEE (100%) is lower than that of Pap smear (91.16%) and better than that colposcopy (83.12%). The UNEE has a poor positive predictive value (3.75%) when compared with Pap smear (100%) and colposcopy (20%). The negative predictive values of the 3 tests were nearly comparable. CONCLUSIONS: Whenever access to Pap smear is limited, UNEE performed by general gynecologists and well-trained nurses is an acceptable alternative for detecting cervical premalignant or malignant lesions especially in low-resource settings.

Early amniotomy after vaginal misoprostol for induction of labor: a randomized clinical trial.

OBJECTIVES: To test the effectiveness and safety of early amniotomy after vaginal misoprostol for the induction of labor. STUDY DESIGN: A randomized clinical trial that included 320 women with medical or obstetric indication for labor induction. They were randomly assigned into two equal groups, amniotomy group and control group. Each participant received vaginal misoprostol 50 µg every 6 h for induction of labor. In amniotomy group, amniotomy was done in the early active phase of labor while in the control group, the membranes were left to rupture spontaneously or as judged by the senior resident in the duty. RESULTS: More subjects in the amniotomy group achieved vaginal delivery within 24 h than in the control group [117 (73.13 %) vs. 105 (65.63 %)]. Subjects in the amniotomy group reported shorter induction to delivery interval (09.72 ± 4.61 h vs. 13.61 ± 5.61, P = .002), and better neonatal outcome compared to the control group. There were no statistically significant differences between both group with regard to number of doses of misoprostol, need for oxytocin, Cesarean Section indication and maternal side effects. CONCLUSION: Early amniotomy after vaginal misoprostol for labor induction is associated with higher successful vaginal delivery rate, shorter labor duration and better neonatal outcome.

Pattern of hepatitis virus infection among pregnant women and their newborns at the Women's Health Center of Assiut University, Upper Egypt.

OBJECTIVE: To determine the prevalence, risk factors, and rate of vertical transmission of HBV and/or HCV infection among pregnant women in Upper Egypt, and assess the preventive efficacy of administering hepatitis B immunoglobulin and vaccine to newborns on their carrier status at 8 months. METHODS: Five hundred pregnant women were screened for HCV and HBV serum markers by enzyme-linked immunoassay. Those testing positive had their status confirmed by polymerase chain reaction and their levels of liver enzymes and interferon gamma were evaluated. The newborns of HBV-positive women received hepatitis B immunoglobulin and vaccine and were followed up to assess the rates of vertical transmission and carrier status among the newborns. RESULTS: Of the 500 pregnant women, 6.4% were HCV positive, 4.0% were HBV positive, and 1.0% were both. The vertical transmission rate was 3.1% for HCV, 30.0% for HBV, and 20.0% for a combined infection. The carrier rate of the infants at the end of their eighth month was 10.8% for those with HCV and 8% for those with HBV. CONCLUSION: Infection with HBV and/or HCV is highly prevalent among pregnant women in Upper Egypt. The rate of vertical transmission was also high. Administering hepatitis B vaccine and immunoglobulin resulted in a 92% reduction in carrier status among newborns.

Sublingual versus vaginal misoprostol for induction of labor at term: a randomized prospective placebo-controlled study.

AIMS: To assess the effectiveness and safety of sublingual misoprostol (50 microg), compared with the same dose administered vaginally every 6 h for cervical ripening and labor induction in women with a viable fetus in the third trimester of pregnancy. METHODS: This double-blind randomized prospective placebo-controlled trial included 480 women with medical or obstetric indications for labor induction and undilated, uneffaced cervices. The patients were assigned randomly to receive 50 microg of sublingual or 50 microg of vaginal misoprostol every 6 h for 24 h. Maternal and neonatal outcome were analyzed. RESULTS: A total of 169 (70.4%) patients delivered vaginally in the sublingual group compared to 160 (66.7%) in the vaginal group. The main indications for cesarean section in both groups were fetal distress (33/71 [46.4%] vs 38/80 [47.5%]), followed by failure of labor progress. Thirty three (13.8%) patients in the sublingual group had meconium staining of the amniotic fluid compared to 39 (16.3%) in the vaginal group. There was no difference between the groups regarding the induction-to-delivery interval, duration of labor, neonatal outcome or maternal side-effects. CONCLUSION: Sublingual misoprostol is as effective as vaginal misoprostol for induction of labor at term. Moreover, the sublingual route is associated with a significantly higher patient satisfaction rate than vaginal misoprostol.

Adding phytoestrogens to clomiphene induction in unexplained infertility patients--a randomized trial.

This study investigated the role of oral phytoestrogens in improving pregnancy rate and cycle outcomes with clomiphene citrate. Patients with unexplained infertility and recurrent clomiphene citrate induction failure, were randomly divided into two groups: group I (n = 60) and group II (n = 59). Both groups received clomiphene citrate 150 mg per day (days 3 to 7). Group I received additional oral phytoestrogen (Cimicifuga racemosa) 120 mg/day from days 1 to 12. Human chorionic gonadotrophin (HCG) injection (10,000 IU i.m.) was given and timed intercourse was recommended when a leading follicle reached >17 mm and serum oestradiol exceeded 200 (pg/ml). There was a non-significant shortening of induction cycles in group I. Oestradiol and LH concentrations were higher in group I compared with group II. Endometrial thickness, serum progesterone and clinical pregnancy rate were significantly higher in group I (8.9 +/- 1.4 mm versus 7.5 +/- 1.3 mm, P < 0.001; 13.3 +/- 3.1 ng/ml versus 9.3 +/- 2.0 ng/ml, P < 0.01; 36.7% versus 13.6%, P < 0.01, respectively). It is concluded that adding C. racemosa rhizome dry extract to clomiphene citrate induction can improve the pregnancy rate and cycle outcomes in these couples.