P. Tulikangas’s research while affiliated with Hartford Hospital and other places

In the United States, around 9 million women are affected by pelvic pain due to conditions such as interstitial cystitis/bladder syndrome, fibromyalgia, pelvic floor myalgias, chronic opioid use, or irritable bowel syndrome. Treatment options for concurrent pelvic floor disorders and pelvic pain can prove challenging due to the overall desire to avoid exacerbating overall pain while optimizing pelvic floor symptoms. The primary aim of this study was to compare both perioperative pelvic muscle training and vaginal reconstructive surgery among women who experienced or lacked preoperative pain and to inform better approaches to management of women with preoperative pain. The study was a secondary analysis of the Operations and Pelvic Muscle Training in the Management of Apical Support Loss (OPTIMAL) randomized clinical trial, as performed via the Pelvic Floor Disorders network. The main study's design was a 2 × 2 randomized factorial design with a surgical intervention and a perioperative behavioral intervention. The Eunice Kennedy Shriver National Institute of Child Health and Development data and specimen hub provided the data for this study. Included were 374 women undergoing surgery for both stress urinary incontinence and stage 2–4 pelvic organ prolapse from 2008 to 2013. All participants underwent vaginal prolapse repair and midurethral sling, and were randomized to either perioperative pelvic muscle therapy or usual care. The Pain scale, the Pelvic Floor Impact Questionnaire, the Pelvic Floor Distress Inventory, and the Patient Global Impression of Improvement were all completed by patients at baseline and repeated through month 24. The OPTIMAL trial had a primary outcome of surgical success as defined by anatomical success, but the primary outcome of this secondary analysis was a change in pain scale scores over 24 months after surgery. Three hundred seventy-four women participated in the original trial, with 368 in this secondary analysis. One hundred nine of the 368 women reported preoperative pain. Women with pelvic pain were more likely to be Hispanic, but there were no differences in surgical procedures performed, hospital stay, complications (ie, bladder injury, suture exposure, etc), or estimated blood loss in women with and without pelvic pain. Women with preoperative pain experienced greater pain at all time points, but also exhibited greater pain improvement at 24 months after surgery. Women with preoperative pain had worse baseline pelvic floor symptoms than those without pain. Although women with pain and women without pain had improvements in distress symptoms measured with the Pelvic Floor Distress Inventory, women with pain saw a greater improvement after surgery. All distress subscales improved significantly more in women with pain than women without pain. One additional interesting finding was that women randomized to sacrospinous suspension and pelvic muscle therapy had greater improvements in postoperative pain than those randomized to usual care. Notably, rates of surgical anatomic success and extent of Patient Global Impression of Improvement were not different between women with and without pain. Strengths of the study include its design as a secondary analysis of a large prospective multicenter randomized controlled trial. A substantial proportion of participants reported at least moderate pain at baseline but were not selected based on preoperative pain. Women in the trial were randomized to types of vaginal reconstructive surgery and pelvic muscle training, which allowed the authors to draw conclusions in categories of physical therapy treatments and surgeries for women with and without preoperative pain. Limitations of the study include a lack of preoperative pain data, pain diagnoses, and participant medications in the OPTIMAL trial. Furthermore, the study used no validated pain scale and was limited by OPTIMAL trial data collection intervals. Thankfully, data collected at numerous points over 24 months in some regard accounted for pain symptoms over time. The study found that, for patients with preoperative pain, significant improvement in pelvic floor symptoms and pain takes place after vaginal reconstructive surgery. Similar postoperative improvement rates were found. In addition, perioperative pelvic floor muscle training may be beneficial for patients with planned sacrospinous ligament fixation.

After pelvic reconstructive surgery for pelvic organ prolapse, postoperative stress urinary incontinence (SUI) commonly occurs, which leads many women to choose to have a midurethral sling placed at the time of surgery, even in cases without symptomatic preoperative urinary incontinence. Approximately 27.3% of women with a sling had de novo SUI despite this intervention. Full evaluation of the societal and economic implications brought by a midurethral sling placement attempting to prevent postoperative de novo SUI at the time of a pelvic reconstructive surgery have yet to be evaluated. This study aimed to evaluate the 1-year cost-effectiveness of a midurethral sling in the prevention of SUI at the time of prolapse surgery. This assessment was a randomized controlled trial based on patient resource utilization and patient-reported effectiveness. Study data were obtained via the OPUS randomized clinical trial, which was performed through the Pelvic Floor Disorders Network (a cooperative agreement network sponsored through the National Institute of Child Health and Human Development). A total of 337 women with anterior vaginal prolapse and without SUI symptoms set to undergo treatment from May 2007 to January 2011 were included in the study. Patients were randomly assigned to receive either sham incisions or a midurethral sling during vaginal prolapse surgery. Follow-up occurred at 3, 6, and 12 months postsurgery, with surveys, physical examinations, and medical history. Cost data were collected, and overall health utility in quality-adjusted life-years (QALYs) was calculated. Secondary outcomes were urinary incontinence-specific quality of life and cases of urinary incontinence, as defined by bothersome incontinence symptoms and positive cough stress tests. Initial surgical procedures and subsequent urinary incontinence-related health care were all used for recording health care sector costs. Total costs for study participants were collected via health care resource utilization data, including office visits, additional surgical procedures, and related procedures. The incremental cost-effectiveness ratio was the difference between the sham incision and midurethral sling groups in mean cost, divided by difference in mean QALYs. Data for health care resource utilization were collected during the trial period. Questionnaires at baseline, 3, 6, 9, and 12 months were used to collect other costs. At 1 year, one-way sensitivity analysis was performed for assessing the varying effectiveness of midurethral slings at 1 year, by noting the urinary incontinence-associated patient costs and by using varied QALY for the sling group. Results were taken from a study population of 337 women who underwent randomization to be included in the analysis of cost-effectiveness. No great variance of characteristics existed between groups. One year after surgery, a lower rate of urinary incontinence existed for those in the midurethral sling group. Notably, QALYs were not statistically different between midurethral sling and sham incision groups at baseline, but at 12 months, there was an improvement in both the UDI stress subscale and an overall reduction in the Incontinence Severity Index for the midurethral sling group. In conclusion, although prophylactic midurethral sling placements during vaginal prolapse surgery does reduce the rate of de novo SUI, based on this analysis of date from the OPUS trial, it is not a cost-effective intervention. The decision to place a sling in this setting is often driven by cost savings on the patient side, whereas midurethral sling health care costs are higher than when sling is not done.

Importance: The impact of preoperative pain on outcomes can guide counseling. Objective: The objective of this study was to compare outcomes after vaginal reconstructive surgery and pelvic muscle training between women with and without preoperative pain. Study design: This is a secondary analysis of the Operations and Pelvic Muscle Training in the Management of Apical Support Loss (OPTIMAL) trial, which randomized patients to a surgical intervention (sacrospinous ligament fixation versus uterosacral vaginal vault suspension) and a perioperative behavioral intervention (pelvic floor muscle training vs usual care). Preoperative pain was defined as a response of "5" or greater on the pain scale or answering "moderately" or "quite a bit" on the Pelvic Floor Distress Inventory question "Do you usually experience pain in the lower abdomen or genital area?" Results: The OPTIMAL trial included 109 women with preoperative pain and 259 without pain. Although women with pain had worse pain scores and pelvic floor symptoms at baseline and postoperatively, they had greater improvement on pain scores (-2.3 ± 2.4 vs -0.2 ± 1.4, P < 0.001), as well as Pelvic Floor Distress Inventory and Pelvic Floor Impact Questionnaire scores. Among women with pain who underwent a sacrospinous ligament fixation, those who received pelvic floor muscle training had a greater reduction in pain compared with those in the usual care group (-3.0 ± 2.3 vs -1.3 ± 2.1, P = 0.008). Persistent or worsening pain was present at 24 months in 5 (16%) women with preoperative pain. Conclusions: Women with preoperative pain experience significant improvements in pain and pelvic floor symptoms with vaginal reconstructive surgery. Pelvic floor muscle training perioperatively may be beneficial for select patients.

Importance: The relative cost per improvement in quality of life can help guide decisions about adding a midurethral sling at the time of prolapse surgery. Objective: This study aimed to assess the cost-effectiveness of prophylactic midurethral slings placed at the time of prolapse surgery to reduce de novo urinary incontinence based on a randomized controlled trial. Study design: Costs and effectiveness were collected as part of a planned secondary analysis from the Outcomes following vaginal Prolapse repair and mid Urethral Sling (OPUS) trial, where 337 women without symptomatic stress urinary incontinence were randomly assigned to a midurethral sling or sham incisions during vaginal prolapse surgery. Within-trial cost-effectiveness analysis was performed from the societal perspective. Effectiveness was measured in quality-adjusted life-years (QALYs) and de novo urinary incontinence. We calculated incremental cost-effectiveness ratios and cost-effectiveness acceptability curves. Results: Within-trial societal costs were higher for the sling group than for the control group ($18,170 [95$16,420-$19,920] vs$15,700 [95% CI, $14,110-$17300], P = 0.041). The changes in QALY were 0.04 (95% CI, 0.02-0.06) versus 0.03 (95% CI, 0.02-0.05; P = 0.54). The incremental cost-effectiveness ratio for prophylactic sling was $309,620/QALY. This is above the generally accepted range of willingness-to-pay thresholds of$50,000 to $150,000/QALY. At 1 year, urinary incontinence was more common in the control group, and the cost to prevent 1 case was$91. The probability that prophylactic sling is cost-effective is 24%. Conclusions: Prophylactic sling placed during vaginal prolapse surgery reduced the rate of de novo urinary incontinence, but was not cost-effective.

Objective: To assess the cost effectiveness of performing routine concurrent apical support procedures at the time of hysterectomy for benign indications. Methods: We developed a Markov decision model from the health care sector perspective to compare concurrent apical support (ie, McCall culdoplasty) at the time of hysterectomy for benign indications compared with hysterectomy alone. We modeled Markov transitions between asymptomatic, prolapse without treatment, and treated prolapse states for 3 years. Our primary outcome was incremental cost-effectiveness ratio, defined as the difference between groups in mean cost (2019 U.S. dollars) divided by the difference in mean quality-adjusted life-years (QALYs). Model parameter estimates were taken from the published medical literature. Cost estimates were obtained from Medicare reimbursement rates and the literature. One-way, two-way, and probabilistic sensitivity analyses were performed. Results: We assumed a base-case scenario of 13% posthysterectomy prolapse after hysterectomy alone and 2.1% after concurrent apical support, 5.8% and 0.9% undergoing subsequent surgical treatment for prolapse, respectively. Concurrent apical support at the time of hysterectomy had higher costs ($1,667 vs$1,423) but was more effective (2.34 vs 2.31 QALYs) than hysterectomy alone. Concurrent apical support was cost effective with an incremental cost-effectiveness ratio of $11,988/QALY, compared with general willingness-to-pay ranges of$50,000-150,000/QALY. In sensitivity analyses, concurrent apical support remained cost effective as long as the rate of posthysterectomy prolapse after concurrent apical support remained less than 8.7%. Monte Carlo simulation showed that concurrent apical support was cost effective in more than 60% of the simulated iterations. Conclusion: Apical support at the time of hysterectomy for benign indications is cost effective compared with hysterectomy alone from the health care sector perspective at 3 years. Our results suggest that encouraging concurrent apical support procedures at time of hysterectomy is a cost-effective strategy in preventing posthysterectomy vaginal prolapse.

Objective: To evaluate objective and subjective outcomes of patients who underwent sacrocolpopexy using autologous rectus fascia to provide more data regarding non-mesh alternatives in pelvic organ prolapse surgery. Design: Ambispective cohort study with retrospective and prospective data. Setting: A single academic medical center. Population: Women who underwent abdominal sacrocolpopexy using autologous rectus fascia between January 2010 and December 2019 METHODS: Patients were recruited for a follow-up visit including completing the Pelvic Floor Distress Inventory (PFDI) and Pelvic Organ Prolapse Quantification (POPQ) exam. Demographic and clinical characteristics were collected. Main outcome measures: Composite failure, anatomic failure, symptomatic failure, and retreatment. Results: During the study period, 132 women underwent sacrocolpopexy using autologous rectus fascia. Median follow-up time was 2.2 years. Survival analysis showed that composite failure was 0.8% (CI 0.1-5.9%) at 12 months, 3.5% (CI 1.1-10.7%) at 2 years, 13.2% (CI 7.0-24.3%) at 3 years, and 28.3% (CI 17.0-44.8%) at 5 years. Anatomic failure was 0% at 12 months, 1.4% (CI 0.2-9.2%) at 2 years, 3.1% (CI 0.8-12.0%) at 3 years, and 6.8% (CI 2.0-22.0%) at 5 years. Symptomatic failure rate was 0% at 12 months, 1.3% (CI 0.2-9.0%) at 2 years, 2.9% (CI 0.7-11.3%) at 3 years, and 13.1% (CI 5.3-30.3%) at 5 years. Retreatment rate was 0.8% (CI 0.1-5.9%) at 12 months and 2 years, 9.4% (CI 4.2-20.3%) at 3 years, and 13.0% (CI 6.0-27.2%) at 5 years. Conclusions: Autologous rectus fascia sacrocolpopexy may be considered a safe and effective alternative for patients who desire to avoid synthetic mesh.

Background Vaginal epithelial abnormalities (VEA) are a common complication associated with pessary use. The objective of this study was to determine if there is a host pro-inflammatory response associated with pessary use and VEA.Methods Patients wearing pessaries for at least two weeks for the management of pelvic organ prolapse and/or urinary incontinence were screened for eligibility. Vaginal swabs were collected from women with VEA (cases) and without VEA (controls). Cases were matched to controls in a 1:3 ratio. Cytokine analysis of the collected samples was performed using multiplex analysis to determine the concentrations of interleukin (IL)6, interferon alpha 2 (IFNα2), tumor necrosis factor alpha (TNFα) and IL1β. A cross-sectional analysis was performed, comparing vaginal cytokine concentrations in women with and without VEA.ResultsWe enrolled 211 patients in this analysis: 50 cases and 161 controls. The median concentrations (pg/mL) of the four cytokines for cases and controls respectively were; IL6: 6.7 (IQR <2.9 [the lower limit of detection, LLD]-14.2) and < 2.9 (LLD) (IQR <2.9 [LLD]-5.5), IFNα2: 8.2 (IQR 6.1–13.9) and 7.9 (IQR 3.9–13.6), TNFα: 15.2 (IQR 6.1–30.4) and 4.68 (IQR <2.3 [LLD]-16.3), IL1β 195.7 (IQR 54.5–388.6) and 38.5 (IQR 6.7–154.9). The differences in median cytokine levels were statistically higher in cases for IL6, TNFα, and IL1β (all p < 0.001) compared to controls. Older age (OR: 1.062, 95% CI, 1.015–1.112), lower BMI (OR: 0.910, 95% CI, 0.839–0.986) and presence of VEA at last check (OR: 5.377, 95% CI, 2.049–14.108) were associated with higher odds of having VEA on multivariate analysis.Conclusion Pro-inflammatory cytokines, specifically IL6, TNFα, and IL1β, are elevated in pessary-wearing patients who have VEA. Additional prospective studies are needed to assess baseline vaginal inflammatory profiles before and after pessary placement to understand VEA formation in pessary patients.

Objective: To evaluate objective and subjective outcomes of patients who underwent sacrocolpopexy using autologous rectus fascia to provide more data regarding non-mesh alternatives in pelvic organ prolapse surgery. Design: Cohort study with retrospective and prospective data. Setting: A single academic medical center. Population: Women who underwent abdominal sacrocolpopexy using autologous rectus fascia between January 2010 and December 2019 Methods: Patients were recruited for a follow-up visit including completing the Pelvic Floor Distress Inventory (PFDI) and Pelvic Organ Prolapse Quantification (POPQ) exam. Demographic and clinical characteristics were collected. Main Outcome Measures: Composite failure, anatomic failure, symptomatic failure, and retreatment. Results: During the study period, 132 women underwent sacrocolpopexy using autologous rectus fascia. Median follow-up time was 2.2 years. Survival analysis showed that composite failure was 0.8% (CI 0.1-5.9%) at 12 months, 3.5% (CI 1.1-10.7%) at 2 years, 13.2% (CI 7.0-24.3%) at 3 years, and 28.3% (CI 17.0-44.8%) at 5 years. Anatomic failure was 0% at 12 months, 1.4% (CI 0.2-9.2%) at 2 years, 3.1% (CI 0.8-12.0%) at 3 years, and 6.8% (CI 2.0-22.0%) at 5 years. Symptomatic failure rate was 0% at 12 months, 1.3% (CI 0.2-9.0%) at 2 years, 2.9% (CI 0.7-11.3%) at 3 years, and 13.1% (CI 5.3-30.3%) at 5 years. Retreatment rate was 0.8% (CI 0.1-5.9%) at 12 months and 2 years, 9.4% (CI 4.2-20.3%) at 3 years, and 13.0% (CI 6.0-27.2%) at 5 years. Conclusions: Autologous rectus fascia sacrocolpopexy may be considered a safe and effective alternative for patients who desire to avoid synthetic mesh.