Noninvasive Ocular Drug Delivery System of Dexamethasone Sodium Phosphate in the Treatment of Experimental Uveitis Rabbit.

PURPOSE: To investigate the efficacy and safety of dexamethasone sodium phosphate administered through Visulex system (DSP-Visulex) in treating experimental uveitis. METHODS: Uveitis was induced in rabbits by subcutaneous injections of complete Freund's adjuvant and an intravitreal injection of H37RA antigen. After induction, the animals of the control group received no treatment and the others received various treatment regimens of DSP-Visulex. Each regimen was different in DSP strength (4%, 8%, and 15%), application time, or treatment frequency. Efficacy and safety of DSP-Visulex were evaluated by ophthalmic observations and histopathological examinations for ocular inflammations and pathology. RESULTS: The control group exhibited panuveitis with significant inflammation in the vitreous, choroid, and retina, but less in the conjunctiva, cornea, and anterior chamber. The uveitis occurred within 24 h after induction and persisted throughout the study in the control group. All treatments showed some reduction in inflammation in the vitreous, choroid, and retina. The higher dose regimens generally showed more rapid and higher degree of resolution than the lower dose regimens. The posterior eye tissues of the 15% and 8% DSP-Visulex appeared normal with minimal or no inflammation, whereas the untreated eye and the 4% DSP-Visulex eyes showed minimal response. CONCLUSIONS: All DSP-Visulex regimens suppressed the signs of inflammation and were well tolerated over the course of a 29-day study. The 8% and 15% DSP-Visulex treatment regimens were safe and efficacious for anterior, intermediate, and posterior uveitis. On the other hand, the 4% DSP-Visulex regimen may only be considered for anterior and intermediate uveitis.

Evaluation of third-degree and fourth-degree laceration rates as quality indicators.

OBJECTIVE: To examine the patterns and predictors of third-degree and fourth-degree laceration in women undergoing vaginal delivery. METHODS: We identified a population-based cohort of women in the United States who underwent a vaginal delivery between 1998 and 2010 using the Nationwide Inpatient Sample. Multivariable log-linear regression models were developed to account for patient, obstetric, and hospital factors related to lacerations. Between-hospital variability of laceration rates was calculated using generalized log-linear mixed models. RESULTS: Among 7,096,056 women who underwent vaginal delivery in 3,070 hospitals, 3.3% (n=232,762) had a third-degree laceration and 1.1% (n=76,347) had a fourth-degree laceration. In an adjusted model for fourth-degree lacerations, important risk factors included shoulder dystocia and forceps and vacuum deliveries with and without episiotomy. Other demographic, obstetric, medical, and hospital variables, although statistically significant, were not major determinants of lacerations. Risk factors in a multivariable model for third-degree lacerations were similar to those in the fourth-degree model. Regression analysis of hospital rates (n=3,070) of lacerations demonstrated limited between-hospital variation. CONCLUSION: Risk of third-degree and fourth-degree laceration was most strongly related to operative delivery and shoulder dystocia. Between-hospital variation was limited. Given these findings and that the most modifiable practice related to lacerations would be reduction in operative vaginal deliveries (and a possible increase in cesarean delivery), third-degree and fourth-degree laceration rates may be a quality metric of limited utility.

Factors associated with 30-day hospital readmission after hysterectomy.

OBJECTIVE: To analyze factors associated with 30-day readmission among women who underwent hysterectomy for uterine cancer and benign indications. METHODS: We used the National Surgical Quality Improvement Project database to perform a cohort study of women who underwent hysterectomy from 2011 to 2012. Patients were stratified by surgical indication (uterine cancer or benign indications). Multivariable logistic regression models were constructed to determine factors associated with 30-day readmission. Model fit statistics were used to evaluate the importance of demographic factors, preoperative comorbidities, and postoperative complications on readmission. RESULTS: The rate of 30-day readmission was 6.1% among 4,725 women with uterine cancer and 3.4% after hysterectomy for benign gynecologic disease in 36,471 patients. In a series of multivariable models, postoperative complications including wound complications, infections, and pulmonary emboli and myocardial infarctions were the factors most strongly associated with readmission. Compared with women without a complication, complications increased the readmission rate from 2.5 to 20.3% for women with uterine cancer and from 1.5 to 15.1% for those without cancer. Among women with uterine cancer, postoperative complications explained 34.3% of the variance in readmission compared with 5.9% for demographic factors and 2.2% for preoperative comorbidities. For patients with benign diseases, complications accounted for 32.1%, preoperative conditions 1.2%, and demographic factors 2.5% of the variance in readmission. CONCLUSION: Efforts to reduce readmission should be directed at initiatives to reduce complications and improve the care of women who experience a complication.

Thromboembolism incidence and prophylaxis during vaginal delivery hospitalizations.

OBJECTIVE: Although major international guidelines recommend venous thromboembolism (VTE) prophylaxis during vaginal delivery hospitalization for women with additional risk factors, US guidelines recommend prophylaxis for a very small number of women who are at particularly high risk for an event. The purpose of this study was to characterize practice patterns of VTE prophylaxis in the United States during vaginal delivery hospitalizations and to determine VTE incidence in this population. STUDY DESIGN: A population-level database was used to analyze VTE incidence and use of VTE prophylaxis during vaginal delivery hospitalizations in the United States between 2006 and 2012 (n = 2,673,986). We evaluated whether patients received either pharmacologic or mechanical prophylaxis. Hospital-level factors and patient characteristics were included in multivariable regression analysis that evaluated prophylaxis administration. RESULTS: We identified 2,673,986 women who underwent vaginal delivery. Incidence of VTE increased during the study period from 15.6-29.8 events per 100,000 delivery hospitalizations. Within the cohort, 2.6% of patients (n = 68,835) received VTE prophylaxis. Pharmacologic prophylaxis was rare; <1% of women received unfractionated or low-molecular-weight heparin. Although patients with thrombophilia or a previous VTE event were likely to receive prophylaxis (60.8% and 72.8%, respectively), patients with risk factors for VTE such as obesity, smoking, and heart disease were unlikely to receive prophylaxis (rates of 5.9%, 3.3%, and 6.2%, respectively). CONCLUSION: Our findings demonstrate that the administration of VTE prophylaxis outside a small group of women at extremely high risk for VTE is rare during vaginal delivery hospitalization. Given that VTE incidence is rising in this population, further research to determine whether broadening prophylaxis for VTE may reduce severe maternal morbidity and death is indicated.

Comparative effectiveness of robotically assisted compared with laparoscopic adnexal surgery for benign gynecologic disease.

OBJECTIVE: To perform a population-based analysis to compare the complications and cost of laparoscopic and robotically assisted adnexal surgery. METHODS: A nationwide database was used to analyze the use and outcomes of robotically assisted adnexal surgery from 2009 to 2012. Multivariable mixed effects regression models were developed to examine predictors of use of robotic surgery. After propensity score matching, complications and cost were compared between robotically assisted and laparoscopic surgery. RESULTS: Eighty-seven thousand five hundred fourteen women were identified. From 2009 to 2012, performance of robotic-assisted oophorectomy increased from 3.5% (95% confidence interval [CI] 3.2-3.8%) to 15.0% (95% CI 14.4-15.6%), whereas robotically assisted cystectomy rose from 2.4% (95% CI 2.0-2.7%) to 12.9% (95% CI 12.2-13.5%). The overall complication rate was 7.1% (95% CI 4.0-10.2%) for robotically assisted compared with 6.0% (95% CI 2.9-9.1%) for laparoscopic oophorectomy (odds ratio [OR] 1.20, 95% CI 1.00-1.45; P=.052). Robotic-assisted oophorectomy was associated with a higher rate of intraoperative complications (3.4% compared with 2.1%, OR 1.60, 95% CI 1.21-2.13). The overall complication rate was 3.7% (95% CI -0.8 to 8.2%) after robotically assisted compared with 2.7% (95% CI -1.8 to 7.2%) for laparoscopic cystectomy (OR 1.38, 95% CI 0.95-1.99). The intraoperative complication rate was higher for robotically assisted cystectomy (2.0% compared with 0.9%, OR 2.40, 95% CI 1.31-4.38). Compared with laparoscopy, robotically assisted oophorectomy was associated with $2,504 (95% CI $2,356-2,652) increased total costs and robotically assisted cystectomy $3,310 (95% CI $3,082-3,581) higher costs. CONCLUSION: Use of robotically assisted adnexal surgery increased rapidly. Compared with laparoscopic surgery, robotically assisted adnexal surgery is associated with substantially greater costs and a small, but statistically significant, increase in intraoperative complications.

Patterns of use and predictors of receipt of antibiotics in women undergoing cesarean delivery.

OBJECTIVE: Perioperative antibiotics are recommended during cesarean delivery to reduce the risk of postoperative infections and resulting maternal morbidity. We examined the patterns of use and predictors of receipt of antibiotics in women undergoing cesarean delivery. METHODS: We identified a national cohort of women who underwent a cesarean delivery between 2003 and 2010 using a commercial hospitalization database. Women who received antibiotics on the day of cesarean delivery were classified as having received perioperative antibiotics. Multivariable regression models were developed to account for patient, obstetric, physician, and hospital factors on receipt of antibiotics. Between-hospital variation was calculated using generalized linear mixed models. RESULTS: Among 1,137,804 women who underwent cesarean delivery, 59.5% received perioperative antibiotics. The proportion of patients receiving antibiotics increased over time from 52.5% in 2003 to 63.1% in 2010 (P<.001) and varied significantly by geographic region. Women who did not labor were more likely to receive antibiotics than those who had a cesarean delivery after labor (66% compared with 44%, P<.001). Age, race, and insurance status were not major determinants of the use of perioperative antibiotics. CONCLUSION: Among women undergoing cesarean delivery, compliance with the recommendation for universal perioperative antibiotic prophylaxis is poor. Coordinated efforts are needed to enhance use of guideline-based perioperative antibiotic prophylaxis for women undergoing cesarean delivery. LEVEL OF EVIDENCE: III.

Safety and tolerance of radical hysterectomy for cervical cancer in the elderly.

BACKGROUND: Despite institutional studies that suggest that radical hysterectomy for cervical cancer is well tolerated in the elderly, little population-level data are available on the procedure's outcomes in older women. We performed a population-based analysis to determine the morbidity, mortality, and resource utilization of radical hysterectomy in elderly women with cervical cancer. METHODS: Patients recorded in the Nationwide Inpatient Sample with invasive cervical cancer who underwent abdominal radical hysterectomy between 1998 and 2010 were analyzed. Patients were stratified by age: <50, 50-59, 60-69, and ≥70 years. We examined the association between age and the outcomes of interest using chi square tests and multivariable generalized estimating equations. RESULTS: A total of 8199 women were identified, including 768 (9.4%) women age 60-69 and 462 (5.6%) women ≥70 years of age. All cause morbidity increased from 22.1% in women <50, to 24.7% in those 50-59 years, 31.4% in patients 60-69 years and 34.9% in women >70years of age (P<0.0001). Compared to women<50, those >70 were more likely to have intraoperative complications (4.8% vs. 9.1%, P=0.0003), surgical site complications (10.9% vs. 17.5%, P<0.0001), and medical complications (9.9% vs. 19.5%, P<0.0001). The risk of non-routine discharge (to a nursing facility) was 0.5% in women <50 vs. 12.3% in women ≥70 (P<0.0001). Perioperative mortality women ≥70 years of age was 30 times greater than that of women <50 (P<0.0001). CONCLUSION: Perioperative morbidity and mortality are substantially greater in elderly women who undergo radical hysterectomy for cervical cancer. Non-surgical treatments should be considered in these patients.