Women with endometriosis have higher comorbidities: Analysis of domestic data in Taiwan

AbstractEndometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities

AIDS clinical trials group: Phase I/II study of combination 2′,3′-dideoxycytidine and zidovudine in patients with acquired immunodeficiency syndrome (AIDS) and advanced AIDS-related complex

The dideoxynucleosides 3′-azido-3′-deoxythymidine (zidovudine, AZT) and 2′,3′-dideoxycytidine (ddC) are potent inhibitors of human immunodeficiency virus (HIV) in vitro and improve surrogate measures of HIV infection in vivo. Long-term administration of AZT has been associated with significant hematologic toxicity and has resulted in virus with reduced in vitro susceptibility. Although ddC does not have significant hematologic toxicity and has not shown cross-resistance with AZT in vitro, ddC has been associated with a severe dose-related peripheral neuropathy. Given the independent activity of each agent, their non-overlapping toxicity profiles, and the absence of cross-resistance, it was hypothesized that concurrent administration of AZT and ddC in low doses might be at least as active as either drug given individually at higher doses in the treatment of HIV infection. It was further hypothesized that combined low doses of both drugs would reduce the incidence of serious side effects and the development of resistance. A phase I/II dose-finding trial of six different regimens of combination AZT and ddC in persons with acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex was initiated to test these hypotheses

Effect of Resiquimod 0.01% Gel on Lesion Healing and Viral Shedding When Applied to Genital Herpes Lesions▿

Resiquimod, a Toll-like receptor 7/8 agonist developed as a topical treatment to decrease recurrences of anogenital herpes, induces proinflammatory cytokines that may delay lesion healing. Adults with frequently recurring anogenital herpes were randomized within 24 h of onset of a recurrence to vehicle or resiquimod 0.01% gel two times per week for 3 weeks. Subjects underwent daily lesion assessments and sampling for herpes simplex virus DNA PCR for 21 days or until investigator-determined healing of lesion(s). Eighty-two subjects with a mean age of 39 ± 10.5 years and a median of seven recurrences per year were enrolled in the study. The qualifying recurrence was positive by PCR for herpes simplex virus in 68% of subjects. No difference was observed between the vehicle (39 subjects) and resiquimod (43 subjects) groups with respect to time to healing (median of 7.0 days versus median of 6.5 days, respectively; Cox proportional hazard model ratio of 1.229; 95% confidence interval, 0.778 to 1.942; P = 0.376). The distributions of maximum severity scores for any investigator-assessed local skin signs and for subject-assessed local symptoms were similar between treatment groups (P = 0.807 and P = 0.103, respectively). For subjects with at least one positive PCR result, no difference was observed for time to cessation of viral shedding (median of 7 days versus median of 5 days for vehicle and resiquimod groups, respectively; Cox proportional hazard model ratio of 1.471; 95% confidence interval, 0.786 to 2.754; P = 0.227). Application of resiquimod 0.01% two times per week for 3 weeks did not delay the healing of genital herpes lesions or reduce acute viral shedding

Safety and efficacy of midazolam nasal spray in the outpatient treatment of patients with seizure clusters—a randomized, double‐blind, placebo‐controlled trial

OBJECTIVE: To evaluate the safety and efficacy of a novel formulation of midazolam administered as a single‐dose nasal spray (MDZ–NS) in the outpatient treatment of patients experiencing seizure clusters (SCs). METHODS: This was a phase III, randomized, double‐blind, placebo‐controlled trial (ClinicalTrials.gov NCT01390220) with patients age ≥12 years on a stable regimen of antiepileptic drugs. Following an in‐clinic test dose phase (TDP), patients entered an outpatient comparative phase (CP) and were randomized (2:1) to receive double‐blind MDZ–NS 5 mg or placebo nasal spray, administered by caregivers when they experienced an SC. The primary efficacy end point was treatment success (seizure termination within 10 minutes and no recurrence 10 minutes to 6 hours after trial drug administration). Secondary efficacy end points were proportion of patients with seizure recurrence 10 minutes to 4 hours, and time‐to‐next seizure >10 minutes after double‐blind drug administration. Safety was monitored throughout. RESULTS: Of 292 patients administered a test dose, 262 patients were randomized, and 201 received double‐blind treatment for an SC (n = 134 MDZ–NS, n = 67 placebo, modified intent‐to‐treat population). A significantly greater proportion of MDZ–NS‐ than placebo‐treated patients achieved treatment success (53.7% vs 34.4%; P = 0.0109). Significantly, fewer MDZ–NS‐ than placebo‐treated patients experienced seizure recurrence (38.1% vs 59.7%; P = 0.0043). Time‐to‐next seizure analysis showed early separation (within 30 minutes) between MDZ–NS and placebo that was maintained throughout the 24‐hour observation period (21% difference at 24 hours; P = 0.0124). Sixteen patients (5.5%) discontinued because of a treatment‐emergent adverse event (TEAE) during the TDP and none during the CP. During the CP, 27.6% and 22.4% of patients in the MDZ–NS and placebo groups, respectively, experienced ≥1 TEAE. SIGNIFICANCE: MDZ–NS was superior to placebo in providing rapid, sustained seizure control when administered to patients experiencing an SC in the outpatient setting and was associated with a favorable safety profile

Safety and efficacy of midazolam nasal spray in the outpatient treatment of patients with seizure clusters: An open‐label extension trial

To evaluate safety- and seizure-related outcomes with repeated intermittent use of a novel formulation of midazolam administered as a single-dose nasal spray (MDZ-NS) in the outpatient treatment of patients experiencing seizure clusters (SCs). In this open-label extension trial (ClinicalTrials.gov NCT01529034), patients aged ≥12 years and on a stable regimen of antiepileptic drugs who completed the original phase III, randomized controlled trial were enrolled. Caregivers administered MDZ-NS 5 mg when patients experienced SCs; a second dose could be given if seizures did not terminate within 10 minutes or recurred within 10 minutes-6 hours. Patients were monitored for treatment-emergent adverse events (TEAEs) throughout, and the main seizure-related outcome was treatment success, defined as seizure termination within 10 minutes and no recurrence 10 minutes-6 hours after drug administration. Of 175 patients enrolled, 161 (92.0%) received ≥1 MDZ-NS dose, for a total of 1998 SC episodes. Median time spent by patients in the trial was 16.8 months (range = 1-55.7 months). TEAEs were experienced by 40.4% of patients within 2 days of drug administration and 57.1% overall. TEAEs reported by most patients (within 2 days and overall) were nasal discomfort (12.4%) and somnolence (9.3%). One patient each discontinued due to treatment-related nasal discomfort and somnolence. There were no patients with treatment-related respiratory depression, and none with TEAEs indicative of drug abuse or dependence. Treatment success criteria were met in 55% (1108/1998) of SC episodes after administration of a single 5-mg dose and in 80.2% (617/769) with the second dose. Treatment success was consistent over treated episode number. Repeated, intermittent, acute treatment of patients experiencing SCs with MDZ-NS in the outpatient setting was well tolerated over an extended period, with maintenance of efficacy suggesting lack of development of tolerance

Role for Plasmacytoid Dendritic Cells in the Immune Control of Recurrent Human Herpes Simplex Virus Infection▿

Plasmacytoid dendritic cells (pDC) are an important component of the innate immune response, producing large amounts of alpha interferon in response to viral stimulation in vitro. Under noninflammatory conditions, pDC are not found in the skin and are restricted in location to the blood and lymph nodes. Therefore, their role in mucosal and cutaneous herpes simplex virus (HSV) infection has not been well-defined. In this study we show a role for human pDC in the immune response to HSV infection. First, by confocal microscopy we showed that pDC infiltrate the dermis of recurrent genital herpes simplex lesions at early and late phases, often at the dermo-epidermal junction. We then showed that pDC in vitro are resistant to HSV infection despite expressing the entry receptors CD111, CD112, and HVE-A. Within the lesions, pDC were found closely associated with CD3+ lymphocytes and NK cells, especially those which were activated (CD69+). Furthermore, these HSV-exposed pDC were able to stimulate virus-specific autologous T-lymphocyte proliferation. We conclude from this work that pDC may contribute to the immune control of recurrent herpes virus infection in vivo