Development of a patient-centered text message-based platform for the self-management of interstitial cystitis/bladder pain syndrome symptoms.

OBJECTIVE: To develop a patient-centered text message-based platform that promotes self-management of symptoms of interstitial cystitis/bladder pain syndrome (IC/BPS). METHODS: Adult women with IC/BPS interested in initiating a first- or second-line treatments per American Urological Association guidelines (recategorized as "behavioral/non-pharmacologic treatments" and "oral medicines" in the 2022 version) participated in rapid cycle innovation consisting of iterative cycles of contextual inquiry, prototype design and development. We delivered treatment modules and supportive messages using an algorithm-driven interactive messaging prototype through a HIPAA-compliant texting platform. Patients provided feedback through narrative text messages and an exit interview. Feedback was analyzed qualitatively and used to iteratively revise the platform until engagement ≥ 85% and accuracy ≥ 80% were achieved. The final version consisted of four treatment module categories (patient education and behavioral modification, cognitive behavioral therapy, pelvic floor physical therapy, and guided mindfulness practices) and supportive messages delivered through an automated algorithm over 6 weeks. RESULTS: Thirty IC/BPS patients with moderate symptom bother (median IC Problem Index score 9, range 6-12) participated in five cycles of contextual inquiry. Qualitative analysis identified three overarching concepts that informed the development of the platform: preference for patient centered terms, desire to gain self-efficacy in managing symptoms, and need for provider support. Patients preferred the term "interstitial cystitis" to "bladder pain syndrome" which carried the stigma of chronic pain. Patients reported greater self-efficacy in managing symptoms through improved access to mind-body and behavioral treatment modules that helped them to gain insight into their motivations and behaviors. The concept of provider support was informed by shared decision making (patients could choose preferred treatment modules) and reduced sense of isolation (weekly check in messages to check on symptom bother). CONCLUSION: A patient centered text message-based platform may be clinically useful in the self-management of IC/BPS symptoms.

Cognitive function following surgery for pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: Older women are at higher risk for cognitive dysfunction following surgery. We hypothesized that for women undergoing pelvic organ prolapse (POP) surgery, memory function would not be significantly different at delayed postoperative assessment compared to baseline. OBJECTIVE: We sought to compare performance on tests of various neurocognitive domains before and after surgery for POP. METHODS: A prospective cohort study was conducted with women, aged 60 years and older who were undergoing surgery for POP. A battery of highly sensitive neurocognitive tests was administered preoperatively (baseline), on postoperative day 1 (postoperative visit 1, POV1), and at the first postoperative clinic visit 4-6 weeks after surgery (postoperative visit 2, POV2). The test battery included the scene-encoding memory task, the n-back task, the Iowa gambling task, the balloon analogue risk task, and the psychomotor vigilance task. These tests assessed the neurocognitive subdomains of episodic memory, working memory, decision-making, risk-taking, and sustained attention. Two score comparisons were made: between baseline and POV1, and between baseline and POV2. RESULTS: In 29 women, performance on the scene-encoding memory task was worse at POV1 than at baseline (2.22 ± 0.4 vs. 2.45 ± 0.6, p < 0.05) but was better than baseline at POV2 (2.7 ± 0.7 vs. 2.45 ± 0.6, p < 0.05). Similarly, performance on the psychomotor vigilance test was worse at POV1 than at baseline (p < 0.01) but there was no difference at POV2. There was no difference in performance on the Iowa gambling test, n-back test, and balloon analogue risk tasks between baseline and any postoperative visit. CONCLUSION: Cognitive test scores did not worsen significantly between baseline and delayed postoperative assessments in older women undergoing surgery for POP.

Polyamine-stimulation of arsenic-transformed keratinocytes.

Tumor promotion is strongly associated with inflammation and increased polyamine levels. Our understanding of relevant mechanisms responsible for arsenic-induced cancer remains limited. Previous studies suggest that arsenic targets and dysregulates stem cell populations that remain dormant in the skin until promoted to be recruited out of the bulge stem cell region, thus giving rise to skin tumors. In this study, we explored a possible mechanism by which increased keratinocyte polyamine biosynthesis promotes tumorsphere formation and invasiveness of arsenic-transformed HaCaT keratinocytes (As-HaCaT). Unlike parental HaCaT cells, As-HaCaT cells were tumorigenic in athymic nude mice, and the CD45negative epithelial tumor cells had enriched expression of Toll-Like Receptor 4 (TLR4), CD34 and CXCR4 as did As-HaCaT tumorsphere cultures compared to As-HaCaT monolayer cultures. Ornithine decarboxylase (ODC) overexpressing keratinocytes (Ker/ODC) release increased levels of the alarmin high mobility group box 1 (HMGB1). Ker/ODC conditioned medium (CM) stimulated As-HaCaT but not parental HaCaT tumorsphere formation, and this was inhibited by glycyrrhizin, an inhibitor of HMGB1, and by TAK242, an inhibitor of the HMGB1 receptor TLR4. Compared to parental HaCaT cells, As-HaCaT cells demonstrated greater invasiveness across a Matrigel-coated filter using either fibroblast CM or SDF-1α as chemoattractants. Addition of Ker/ODC CM or HMGB1 dramatically increased As-HaCaT invasiveness. Glycyrrhizin and TAK242 inhibited this Ker/ODC CM-stimulated invasion of As-HaCaT cells but not HaCaT cells. These results show that polyamine-dependent release of HMGB1 promotes the expansion of stem cell-like subpopulations in arsenic-transformed keratinocytes while also increasing their invasiveness, suggesting that polyamines may be a potential therapeutic target for the prevention and treatment of arsenic-initiated skin cancers.