Recent Research Publications- March 2023
Stephens-Shields AJ, Lai HH, Landis JR, Kreder K, Rodriguez LV, Naliboff BD, Afari N, Sutcliffe S, Moldwin R, Griffith JW, Clemens JQ, Bradley CS, Quallich S, Gupta P, Harte SE, Farrar JT.
J Urol. 2023 Feb 27:101097JU0000000000003394. doi: 10.1097/JU.0000000000003394. Epub ahead of print. PMID: 36848118.
Objectives: Symptom heterogeneity in interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome, collectively termed urologic chronic pelvic pain syndrome (UCPPS), has resulted in difficulty in defining appropriate clinical trial endpoints. We determine clinically important differences (CIDs) for 2 primary symptom measures, Pelvic Pain Severity (PPS) and Urinary Symptom Severity (USS), and evaluate subgroup differences.
Methods: The Multidisciplinary Approach to the Study of Chronic Pelvic Pain Symptom Patterns Study enrolled individuals with UCPPS. We defined CIDs by associating changes in PPS and USS over 3 to 6 months with marked improvement on a global response assessment using regression and receiver operating characteristic curves. We evaluated CIDs for absolute and percent change and examined differences in CIDs by sex-diagnosis, presence of Hunner lesions, pain type, pain widespreadness, and baseline symptom severity.
Results: An absolute change of -4 was clinically important in PPS among all patients, but CID estimates differed by pain type, presence of Hunner lesions, and baseline severity. PPS CID estimates for percent change were more consistent across subgroups and ranged from 30 to 57 percent. The absolute change USS CID was -3 for female participants and -2 for male participants with CP/CPPS only. Patients with greater baseline severity required larger decreases in symptoms to feel improved. Estimated CIDs had lower accuracy among participants with low baseline symptoms.
Conclusion: A reduction of 30-50% in PSS is a clinically meaningful endpoint for future therapeutic trials in UCPPS. USS CIDs are more appropriately defined separately for male and female participants.
Urinary Biomarkers and Overactive Bladder Symptoms Before and After Prolapse Surgery.
Maetzold EC, Santillan DA, Kenne KA, Bradley CS, Ten Eyck P, Wendt L, Funk M, Kowalski JT.
Urogynecology (Hagerstown). 2023 Feb 1;29(2):266-272. doi: 10.1097/SPV.0000000000001316. PMID: 36735443.
Importance: Women with pelvic organ prolapse (POP) have increased prevalence of overactive bladder (OAB) and the evaluation of urinary biomarkers associated with OAB in the setting of POP is limited.
Objective: The objective is to determine whether associations exist between urinary biomarkers measured before POP surgery with postoperative OAB symptoms.
Study design: In this prospective cohort study, women with anterior and/or apical POP beyond the hymen undergoing POP surgery were assessed using the OAB Questionnaire Short Form (OAB-q SF) and the Urogenital Distress Inventory 6 (UDI-6) preoperatively and 3 months postoperatively. A first morning voided urine specimen was collected preoperatively and 3 months postoperatively. Urinary biomarkers for inflammation, neuroinflammation, and tissue remodeling were measured. Univariate generalized linear models measured the relationship between biomarkers and symptoms. Between- and within-cohort assessments were made using 2-sample paired and unpaired t tests, respectively.
Results: Seventy-seven participants with OAB (n = 67, 87.0%) and without OAB (n = 10, 13.0%) were enrolled. Seventy-four participants (96%) completed 3-month follow up. The OAB-q SF and UDI-6 scores significantly improved between preoperative and postoperative measures. Preoperative urinary biomarkers did not demonstrate significant correlations with postoperative OAB-q SF or UDI-6 scores. No significant differences were measured in preoperative biomarkers between patients with and without OAB or when comparing preoperative and postoperative biomarkers in patients with OAB.
Conclusions: Urinary biomarkers for tissue remodeling, inflammation, and neuroinflammation were not significantly correlated with OAB symptoms in a population of patients with OAB and POP.
Pelvic Pain and Pelvic Floor Muscle Dysfunction in Women Seeking Treatment for Prolapse.
Gore A, Kenne KA, Kowalski JT, Bradley CS.
Urogynecology (Hagerstown). 2023 Feb 1;29(2):225-233. doi: 10.1097/SPV.0000000000001323. PMID: 36735438.
Importance: Pelvic floor muscle dysfunction (PFMD) can cause pelvic pain, but its associations with pelvic organ prolapse (POP) and POP treatment outcomes are poorly understood.
Objectives: The objectives of this study were to determine (1) if pelvic pain is associated with PFMD in women seeking POP treatment and (2) if baseline PFMD in women seeking management of POP is associated with improvement in pelvic pain at 12 months.
Study design: This was an ambispective cohort study of women enrolled at one site of the Pelvic Floor Disorders Registry. Pelvic floor muscle dysfunction was identified if tenderness was reported on a standardized pelvic floor muscle examination at baseline. Outcomes included a pelvic pain questionnaire (score 0-70, assessed pain in the past 24 hours in 7 pelvic locations) and the Global Health-10 overall average pain rating (0-10).
Results: One hundred forty-four women planning surgery (118) or pessary (26) were included. Twenty (13.9%) had baseline PFMD. Women with PFMD versus no PFMD had greater baseline Pelvic Pain scores (median [IQR], 9.7 [4-23] vs 2.5 [0-7], P < 0.001) and overall average pain (4 [3-6] vs 1 [0-3], P < 0.001). In 107 women with 12-month treatment outcomes, those with PFMD at baseline had greater improvement in pelvic pain compared with those without PFMD (change score -6.5 [-15.2 to 0] vs 0 [-3 to 0] respectively, P = 0.03). Overall pain improved after treatment in the no PFMD group but not in the PFMD group.
Conclusions: Patients with baseline PFMD vs none undergoing treatment for prolapse had higher baseline pelvic pain and greater improvement in pelvic pain at 12 months.
Bypassing of nearest labor & delivery unit is contingent on rurality, wealth, and race.
Carrel M, Keino BC, Novak NL, Ryckman KK, Radke S.
Birth. 2023 Mar;50(1):5-10. doi: 10.1111/birt.12712. Epub 2023 Feb 8. PMID: 36752116.
Patient decisions to bypass the closest labor & delivery (L&D) facility in favor of other birthing locations can have consequences for the provision of health care in rural and micropolitan areas as patient volumes decline and payer mixes change. Among 220 589 uncomplicated births in Iowa, we document characteristics of birth parents who bypass their closest birthing facility, show how this bypassing behavior results in changed travel times to delivery facilities across the rural/urban divide, and indicate the parts of the state where bypassing behavior is most prevalent. From 2013 to 2019, 55.2% of deliveries occurred in facilities that were further from birthing parents' residences than the closest L&D facility. Bypassing is associated with White, non-Hispanic race/ethnicity, and private insurance status. Although bypassing is least common among micropolitan birth parents, this group has the greatest travel burden to birthing facilities and exhibits increasing rates of bypassing over time. Perinatal quality improvement programs can target locations and populations where low-risk birthing parents can be encouraged to deliver close to home if medically appropriate, particularly in small towns and rural areas. This can potentially alleviate the risk of obstetric deserts by ensuring L&D units maintain patient volumes necessary to continue operations.
Garand M, Huang SSY, Goessling LS, Wan F, Santillan DA, Santillan MK, Brar A, Wylie TN, Wylie KM, Eghtesady P
Microorganisms. 2023 Jan 19;11(2):262. doi: 10.3390/microorganisms11020262. PMID: 36838226; PMCID: PMC9963073.
Background: We have previously shown coxsackievirus B (CVB) to be a potent inducer of congenital heart disease (CHD) in mice. The clinical relevance of these findings in humans and the roles of other viruses in the pathogenesis of CHD remain unknown.
Methods: We obtained plasma samples, collected at all trimesters, from 89 subjects (104 pregnancies), 73 healthy controls (88 pregnancies), and 16 with CHD-affected birth (16 pregnancies), from the Perinatal Family Tissue Bank (PFTB). We performed CVB IgG/IgM serological assays on plasma. We also used ViroCap sequencing and PCR to test for viral nucleic acid in plasma, circulating leukocytes from the buffy coat, and in the media of a co-culture system.
Results: CVB IgG/IgM results indicated that prior exposure was 7.8 times more common in the CHD group (95% CI, 1.14-54.24, adj. p-value = 0.036). However, the CVB viral genome was not detected in plasma, buffy coat, or co-culture supernatant by molecular assays, although other viruses were detected.
Conclusion: Detection of viral nucleic acid in plasma was infrequent and specifically no CVB genome was detected. However, serology demonstrated that prior CVB exposure is higher in CHD-affected pregnancies. Further studies are warranted to understand the magnitude of the contribution of the maternal blood virome to the pathogenesis of CHD.