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1.
J Adv Nurs ; 2024 Jun 12.
Article En | MEDLINE | ID: mdl-38864346

AIMS: To describe women's experiences with a range of bladder self-care practices. DESIGN: We conducted a secondary, directed content analysis of qualitative data from the Study of Habits, Attitudes, Realities and Experiences, a multisite focus group study designed to explore adolescent and adult women's experiences, perceptions, beliefs, knowledge and behaviours related to bladder health. This study was conducted by the National Institute of Diabetes and Digestive and Kidney Diseases' Prevention of Lower Urinary Tract Symptoms Research Consortium. Study methods were informed by the Consortium's conceptual framework, based on a social ecological model adapted from Glass and McAtee's Society-Behavior-Biology Nexus. METHODS: Participants were recruited at seven geographically diverse United States research centres between July 2017 and April 2018. Data for the current analysis were collected using a semi-structured discussion group with 36 focus groups involving 316 community-dwelling adult women aged 18-93 years. Coded text was re-examined according to eight self-care behavioural domains identified through literature review and expert opinion as potentially influencing bladder health. RESULTS: Participants described many self-care practices they had adopted to prevent bladder problems or manage existing symptoms and conditions. Eight themes were identified: 'Choosing fluids, foods and medications'; 'Dressing for bladder health'; 'Promoting bodily cleanliness'; 'Managing toileting environments'; 'Timing when to void'; 'Exercising pelvic floor muscles for bladder control'; 'Limiting physical activities that challenge the bladder' and 'Staying home and navigating when away'. Thirteen subthemes were derived from five of the eight themes. CONCLUSION: Women use a broad array of self-care practices related to their bladder health. Research is needed to examine the efficacy of self-care behaviours for preventing or managing bladder symptoms and conditions, and to discern potential risks. Results have important implications for development of bladder health promotion interventions and public health messaging around women's bladder health. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: This study provides a comprehensive framework for understanding women's bladder self-care practices, which can be used by clinicians and public health professionals in designing interventions to promote bladder health and function. IMPACT: Women with and without lower urinary tract symptoms use a broad range of self-care practices that may affect their bladder health, including some that may be harmful. Because of the high prevalence of bladder symptoms in women, this study may help patient assessment and counselling regarding self-care practices. REPORTING METHOD: This study was reported according to the Standards for Reporting Qualitative Research (SRQR). PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

2.
J Urol ; 212(1): 124-135, 2024 Jul.
Article En | MEDLINE | ID: mdl-38703067

PURPOSE: We aimed to estimate the prevalence of a wide range of lower urinary tract symptoms (LUTS) in US women, and explore associations with bother and discussion with health care providers, friends, and family. MATERIALS AND METHODS: We analyzed baseline data collected from May 2022 to December 2023 in the RISE FOR HEALTH study-a large, regionally representative cohort study of adult female community members. LUTS and related bother were measured by the 10-item Symptoms of Lower Urinary Tract Dysfunction Research Network Symptom Index, and discussion was assessed by a study-specific item. RESULTS: Of the 3000 eligible participants, 73% (95% CI 71%-74%) reported any storage symptoms, 52% (95% CI 50%-53%) any voiding or emptying symptoms, and 11% (95% CI 10%-13%) any pain with bladder filling, for an overall LUTS prevalence of 79% (95% CI 78%-81%). This prevalence estimate included 43% (95% CI 41%-45%) of participants with mild to moderate symptoms and 37% (95% CI 35%-38%) with moderate to severe symptoms. Over one-third of participants reported LUTS-related bother (38%, 95% CI 36%-39%) and discussion (38%, 95% CI 36%-40%), whereas only 7.1% (95% CI 6.2%-8.1%) reported treatment. Urgency and incontinence (including urgency and stress incontinence) were associated with the greatest likelihood of bother and/or discussion (adjusted prevalence ratios = 1.3-2.3), even at mild to moderate levels. They were also the most commonly treated LUTS. CONCLUSIONS: LUTS, particularly storage LUTS such as urgency and incontinence, were common and bothersome in the RISE study population, yet often untreated. Given this large burden, both prevention and treatment-related interventions are warranted to reduce the high prevalence and bother of LUTS.


Lower Urinary Tract Symptoms , Humans , Lower Urinary Tract Symptoms/epidemiology , Female , Prevalence , United States/epidemiology , Middle Aged , Aged , Adult , Cohort Studies
3.
Obstet Gynecol ; 143(4): 595-602, 2024 Apr 01.
Article En | MEDLINE | ID: mdl-38387036

OBJECTIVE: To develop evidence- and consensus-based clinical practice guidelines for management of high-tone pelvic floor dysfunction (HTPFD). High-tone pelvic floor dysfunction is a neuromuscular disorder of the pelvic floor characterized by non-relaxing pelvic floor muscles, resulting in lower urinary tract and defecatory symptoms, sexual dysfunction, and pelvic pain. Despite affecting 80% of women with chronic pelvic pain, there are no uniformly accepted guidelines to direct the management of these patients. METHODS: A Delphi method of consensus development was used, comprising three survey rounds administered anonymously via web-based platform (Qualtrics XM) to national experts in the field of HTPFD recruited through targeted invitation between September and December 2021. Eleven experts participated with backgrounds in urology, urogynecology, minimally invasive gynecology, and pelvic floor physical therapy (PFPT) participated. Panelists were asked to rate their agreement with rated evidence-based statements regarding HTPFD treatment. Statements reaching consensus were used to generate a consensus treatment algorithm. RESULTS: A total of 31 statements were reviewed by group members at the first Delphi round with 10 statements reaching consensus. 28 statements were reposed in the second round with 17 reaching consensus. The putative algorithm met clinical consensus in the third round. There was universal agreement for PFPT as first-line treatment for HTPFD. If satisfactory symptom improvement is reached with PFPT, the patient can be discharged with a home exercise program. If no improvement after PFPT, second-line options include trigger or tender point injections, vaginal muscle relaxants, and cognitive behavioral therapy, all of which can also be used in conjunction with PFPT. Onabotulinumtoxin A injections should be used as third line with symptom assessment after 2-4 weeks. There was universal agreement that sacral neuromodulation is fourth-line intervention. The largest identified barrier to care for these patients is access to PFPT. For patients who cannot access PFPT, experts recommend at-home, guided pelvic floor relaxation, self-massage with vaginal wands, and virtual PFPT visits. CONCLUSION: A stepwise approach to the treatment of HTPFD is recommended, with patients often necessitating multiple lines of treatment either sequentially or in conjunction. However, PFPT should be offered first line.


Pelvic Floor Disorders , Pelvic Floor , Humans , Female , Physical Therapy Modalities , Exercise Therapy , Pelvic Floor Disorders/therapy , Pelvic Pain/therapy , Pelvic Pain/drug therapy
4.
J Surg Educ ; 81(4): 556-563, 2024 Apr.
Article En | MEDLINE | ID: mdl-38383237

OBJECTIVE: Previous work has analyzed residency letters of recommendation for agentic and communal language, but this has not been applied to spoken language. Our objective was to analyze intraoperative spoken language by attending and resident surgeons for the use of agentic and communal language. DESIGN: We completed a linguistic inquiry and word count (LIWC) analysis on 16 operating room transcripts (total time 615 minutes) between attendings and resident surgeons for categories associated with agentic and communal speech. Wilcoxon signed rank and Mann-Whitney U tests were used to compare attending versus resident and male versus female speech patterns for word count; "I," clout, and power (agentic categories); and "we," authentic, social (communal categories). SETTING: Midwestern academic university teaching hospital. PARTICIPANTS: Sixteen male (9 attendings, 7 residents) and 16 female (7 attendings, 9 residents) surgeons, from 6 surgical specialties, most commonly from General Surgery. RESULTS: Attending surgeons used more words per minute than residents (40.01 vs 16.92, p < 0.01), were less likely to use "I" (3.18 vs 5.53, p < 0.01), and spoke more language of "clout" (75.82 vs 55.47, p < 0.01). There were no significant differences between attendings and residents in use of analytic speech (23.72 vs 24.67, p = 0.32), "causation" (1.20 vs 1.08, p = 0.72), or "cognitive processing" (10.20 vs 10.54, p = 0.74). Residents used more speech with "emotional tone" (92.91 vs 79.92, p = 0.03), "positive emotion" (4.98 vs 3.86, p = 0.04), more "assent" language (4.89 vs 3.09, p < 0.01), and more "informal" language (9.27 vs 6.77, p < 0.01). There were no gender differences, except for male residents speaking with greater certainty than female residents, although by less than 1% of the total word count. CONCLUSIONS: In the operating room, attending surgeons were more likely to use agentic language compared to resident surgeons based on LIWC analysis. These differences did not depend on gender and likely relate to surgeon experience and confidence, learning versus teaching, and power dynamics.


Internship and Residency , Surgeons , Humans , Male , Female , Operating Rooms , Linguistics , Learning
5.
J Wound Ostomy Continence Nurs ; 51(1): 53-60, 2024.
Article En | MEDLINE | ID: mdl-38215298

PURPOSE: Although maternal depression is associated with adverse outcomes in women and children, its relationship with lower urinary tract symptoms (LUTS) in offspring is less well-characterized. We examined the association between prenatal and postpartum maternal depression and LUTS in primary school-age daughters. DESIGN: Observational cohort study. SUBJECTS AND SETTING: The sample comprised 7148 mother-daughter dyads from the Avon Longitudinal Study of Parents and Children. METHOD: Mothers completed questionnaires about depressive symptoms at 18 and 32 weeks' gestation and 21 months postpartum and their children's LUTS (urinary urgency, nocturia, and daytime and nighttime wetting) at 6, 7, and 9 years of age. Multivariable logistic regression models were used to estimate the association between maternal depression and LUTS in daughters. RESULTS: Compared to daughters of mothers without depression, those born to mothers with prenatal and postpartum depression had higher odds of LUTS, including urinary urgency (adjusted odds ratio [aOR] range = 1.99-2.50) and nocturia (aOR range = 1.67-1.97) at 6, 7, and 9 years of age. Additionally, daughters born to mothers with prenatal and postpartum depression had higher odds of daytime wetting (aOR range = 1.81-1.99) and nighttime wetting (aOR range = 1.63-1.95) at 6 and 7 years of age. Less consistent associations were observed for depression limited to the prenatal or postpartum periods only. CONCLUSIONS: Exposure to maternal depression in the prenatal and postpartum periods was associated with an increased likelihood of LUTS in daughters. This association may be an important opportunity for childhood LUTS prevention. Prevention strategies should reflect an understanding of potential biological and environmental mechanisms through which maternal depression may influence childhood LUTS.


Depression, Postpartum , Lower Urinary Tract Symptoms , Nocturia , Pregnancy , Child , Female , Humans , Cohort Studies , Depression, Postpartum/complications , Depression, Postpartum/epidemiology , Longitudinal Studies , Depression/complications , Depression/epidemiology , Nuclear Family , Nocturia/complications , Nocturia/epidemiology , Lower Urinary Tract Symptoms/complications , Lower Urinary Tract Symptoms/epidemiology , Schools
6.
Int Urogynecol J ; 35(1): 215-225, 2024 Jan.
Article En | MEDLINE | ID: mdl-38133837

INTRODUCTION AND HYPOTHESIS: Pelvic floor myofascial pain (PFMP) is a common but underrecognized component of chronic pelvic pain and pelvic floor disorders symptoms with limited, well-studied treatment modalities. Our objective was to determine the effect of vaginal cryotherapy on PFMP with palpation. METHODS: Following a standardized PFMP screening examination, individuals with a pain score ≥4/10 in ≥1 of four muscle groups were invited to participate in a randomized controlled trial comparing patients undergoing vaginal cryotherapy with controls. Participants in both arms could choose to participate in a single in-office treatment; a 2-week, at-home daily treatment; or both. RESULTS: Between March 2019 and September 2021, a total of 163 participants were enrolled and randomized: 80 to cryotherapy, and 83 to the control group. Sixty-three (28 cryotherapy; 35 controls) completed in-office treatment and 56 (32 cryotherapy; 24 controls) completed at-home therapy. In the in-office comparison, mean pain scores decreased significantly in both arms: cryotherapy (5.13 vs 4.10; p=0.02) and controls (5.60 vs 4.72; p<0.01), with a similar magnitude of reduction between arms (p=0.75). In the at-home comparison, mean pain scores decreased significantly in the cryotherapy arm (6.34 vs 4.75; p<0.01), and nonsignificantly in the control arm (5.41 vs 4.66; p=0.07), resulting in a nonsignificant difference between arms (p=0.14). CONCLUSIONS: Pelvic floor myofascial pain with palpation improved following both a single cryotherapy session and 2 weeks of daily cryotherapy. Interestingly, pain scores also improved with room temperature therapy. Whether these findings reflect a therapeutic effect of both cold and room temperature intravaginal therapy or a placebo effect is unclear but should be explored in larger studies.


Myofascial Pain Syndromes , Pelvic Floor , Female , Humans , Pilot Projects , Myofascial Pain Syndromes/therapy , Cryotherapy , Pain
7.
Neurourol Urodyn ; 42(5): 1036-1054, 2023 06.
Article En | MEDLINE | ID: mdl-36626146

OBJECTIVE: The Prevention of Lower Urinary Tract Symptoms (PLUS) research consortium launched the RISE FOR HEALTH (RISE) national study of women's bladder health which includes annual surveys and an in-person visit. For the in-person exam, a standardized, replicable approach to conducting a pelvic muscle (PM) assessment was necessary. The process used to develop the training, the products, and group testing results from the education and training are described. METHODS: A comprehensive pelvic muscle assessment (CPMA) program was informed by literature view and expert opinion. Training materials were prepared for use on an electronicLearning (e-Learning) platform. An in-person hands-on simulation and certification session was then designed. It included a performance checklist assessment for use by Clinical Trainers, who in collaboration with a gynecology teaching assistant, provided an audit and feedback process to determine Trainee competency. RESULTS: Five discrete components for CPMA training were developed as e-Learning modules. These were: (1) overview of all the clinical measures and PM anatomy and examination assessments, (2) visual assessment for pronounced pelvic organ prolapse, (3) palpatory assessment of the pubovisceral muscle to estimate muscle integrity, (4) digital vaginal assessment to estimate strength, duration, symmetry during PM contraction, and (5) pressure palpation of both myofascial structures and PMs to assess for self-report of pain. Seventeen Trainees completed the full CPMA training, all successfully meeting the a priori certification required pass rate of 85% on checklist assessment. CONCLUSIONS: The RISE CPMA training program was successfully conducted to assure standardization of the PM assessment across the PLUS multicenter research sites. This approach can be used by researchers and healthcare professionals who desire a standardized approach to assess competency when performing this CPMA in the clinical or research setting.


Computer-Assisted Instruction , Pelvic Organ Prolapse , Urinary Bladder Diseases , Female , Humans , Muscle Contraction/physiology , Muscles , Exercise Therapy
8.
Am J Obstet Gynecol ; 228(5): 559.e1-559.e9, 2023 05.
Article En | MEDLINE | ID: mdl-36627074

BACKGROUND: The American College of Obstetricians and Gynecologists recommends offering a vaginal pessary to women seeking treatment of pelvic organ prolapse. However, single-institution series have suggested that a sizable proportion of women fitted with a pessary will transition to surgery within the first year. OBJECTIVE: This study aimed to estimate the proportion of female US Medicare beneficiaries with pelvic organ prolapse who undergo surgery after pessary fitting, to describe the median time to surgery from pessary fitting, and to identify factors associated with the transition from pessary to surgery. STUDY DESIGN: The Medicare 5% Limited Data Set was queried from 2011 to 2016 for women aged ≥65 years with a diagnosis of prolapse who underwent pessary fitting. Cases with at least 3 years of follow-up in the Medicare Data Set were followed longitudinally for the primary outcome of surgery for prolapse. The cumulative incidence of prolapse surgery following index pessary fitting was calculated. Characteristics of women who underwent surgery and those who did not were compared using time-varying Cox regression analysis. RESULTS: Among 2032 women fitted with a pessary, 608 underwent surgery within 7 years. The median time to surgery was 496 days (interquartile range, 187-1089 days). The cumulative incidence of prolapse surgery was 12.2% at 1 year and 30.9% at 7 years. After adjusting for covariates, factors significantly associated with the transition to surgery included previous prolapse surgery (adjusted hazard ratio, 1.50; 1.09-2.07) and a diagnosis of urinary incontinence at the time of pessary fitting (adjusted hazard ratio, 1.20; 0.62-0.99). Factors associated with a lower hazard of surgery included age (adjusted hazard ratio, 0.96 per year; 95% confidence interval, 0.95-0.97), dual Medicare/Medicaid eligibility (adjusted hazard ratio, 0.75; 95% confidence interval, 0.56-1.00), and pessary fitting by a nongynecologist (adjusted hazard ratio, 0.78; 95% confidence interval, 0.62-0.99). CONCLUSION: In this population of Medicare beneficiaries, within 7 years of pessary fitting, almost one-third of women aged >65 years underwent surgery for prolapse. These results add to our current understanding of the demographics of pessary use in an older population and may aid in counseling older patients presenting for treatment of symptomatic pelvic organ prolapse.


Medicare , Pelvic Organ Prolapse , Aged , Female , Humans , United States/epidemiology , Pessaries/adverse effects , Pelvic Organ Prolapse/surgery , Pelvic Organ Prolapse/etiology , Regression Analysis , Proportional Hazards Models , Seizures/etiology
9.
Neurourol Urodyn ; 42(5): 1011-1021, 2023 06.
Article En | MEDLINE | ID: mdl-36573845

OBJECTIVES: To describe the methods for the in-person assessment of the RISE FOR HEALTH (RISE) study, a population-based multicenter prospective cohort study designed to identify factors that promote bladder health and/or prevent lower urinary tract symptoms in adult women, conducted by the Prevention of Lower Urinary Tract Symptoms Research Consortium (PLUS). METHODS AND RESULTS: A subset of RISE participants who express interest in the in-person assessment will be screened to ensure eligibility (planned n = 525). Eligible consenting participants are asked to complete 15 physical assessments in addition to height and weight, to assess pelvic floor muscle function, musculoskeletal (MSK) status, and pain, and to provide urogenital microbiome samples. Pelvic floor muscle assessments include presence of prolapse, strength, levator attachment integrity (tear) and myofascial pain. MSK tests evaluate core stability, lumbar spine, pelvic girdle and hip pain and function. Participants are asked to complete the Short Physical Performance Battery to measure balance, lower extremity strength, and functional capacity. All participants are asked to provide a voided urine sample and a vaginal swab for microbiome analyses; a subset of 100 are asked to contribute additional samples for feasibility and validation of a home collection of urinary, vaginal, and fecal biospecimens. RESULTS: Online and in-person training sessions were used to certify research staff at each clinical center before the start of RISE in-person assessments. Standardized protocols and data collection methods are employed uniformly across sites. CONCLUSIONS: The RISE in-person assessment is an integral portion of the overall population-based RISE study and represents an innovative approach to assessing factors hypothesized to promote bladder health and/or prevent lower urinary tract symptoms. Data collected from this assessment will be used to prioritize future research questions and prevention strategies and interventions. This description of the assessment methods is intended to provide methodologic transparency and inform other researchers who join efforts to understand and improve bladder health.


Lower Urinary Tract Symptoms , Pelvic Floor , Adult , Humans , Female , Prospective Studies , Urinary Bladder , Pain
10.
Neurourol Urodyn ; 42(5): 1022-1035, 2023 06.
Article En | MEDLINE | ID: mdl-36403285

OBJECTIVES: To describe the methods for the in-person musculoskeletal (MSK) assessment of the RISE FOR HEALTH (RISE) study, a population-based multicenter prospective cohort study designed to identify factors associated with bladder health (BH) conducted by the Prevention of Lower Urinary Tract Symptoms Research Consortium (PLUS). METHODS: A subset of RISE participants who express interest in the in-person assessment are screened to ensure eligibility (planned n = 525). Eligible consenting participants are asked to complete a standardized MSK assessment to evaluate core stability (four component core stability test, lumbar spine pain (seated slump test), pelvic girdle pain, (sacroiliac joint, anterior superior iliac spine, pubic symphysis tenderness, and pelvic girdle pain provocation test), hip pain (flexion, abduction, internal rotation and flexion, adduction and external rotation) and pelvic girdle function (active straight leg raise). Participants are also asked to complete the Short Physical Performance Battery to measure balance, gait speed, lower extremity strength, and functional capacity. RESULTS: Detailed online and in-person MSK training sessions led by physical therapy were used to certify research staff at each clinical center before the start of RISE in-person assessments. All evaluators exceeded the pre-specified pass rates. CONCLUSIONS: The RISE in-person MSK assessment will provide further insight into the role of general body MSK health and dysfunction and the spectrum of BH.


Low Back Pain , Pelvic Girdle Pain , Humans , Prospective Studies , Sacroiliac Joint
11.
Int Urogynecol J ; 34(6): 1261-1270, 2023 06.
Article En | MEDLINE | ID: mdl-36125508

INTRODUCTION AND HYPOTHESIS: Pelvic floor myofascial pain (PFMP) is associated with lower urinary tract symptoms (LUTS). The objective of this study was to test movement-based pelvic floor physical therapy (PT) for patients with PFMP and LUTS. We hypothesized that movement-based PT designed to target PFMP would result in significant improvement in both PFMP and concomitant LUTS. METHODS: This pilot trial enrolled patients with moderate-to-severe PFMP on palpation who were referred to movement-based PT to diagnose and treat pelvic floor dysfunction in the context of body alignment and movement patterns. The primary outcome was change in Urogenital Distress Inventory (UDI) scores after PT. Factors associated with PT attendance were also measured. We aimed to enroll 55 participants to achieve 80% power to detect a difference in 11 points on the UDI scores with an alpha-level of 0.05, accounting for a 10% loss to follow-up. The sample size was increased to 65 owing to a higher-than-expected loss-to-follow-up rate. RESULTS: Sixty-five patients were enrolled and 62 analyzed. Thirty-eight (61.3%) attended PT, and 30 (48.4%) completed a follow-up PT Attendance (PTA) survey. Overall, UDI score and irritative, obstructive, and stress subscales (p<0.0001) improved in participants who attended PT as well as mean myofascial examination scores at each site. CONCLUSIONS: Participants who attended movement-based PT demonstrated an improvement in LUTS. Future studies should extend our findings by: first, confirming whether the myofascial pain-directed elements of PT improved LUTS; second, investigating whether movement-based PT improves prolapse symptoms; and third, including a non-PT control arm to rule out the possible influence of a placebo effect and behavioral modifications on LUTS and PFMP.


Lower Urinary Tract Symptoms , Myofascial Pain Syndromes , Humans , Pelvic Floor , Pilot Projects , Myofascial Pain Syndromes/therapy , Myofascial Pain Syndromes/complications , Lower Urinary Tract Symptoms/complications , Physical Therapy Modalities , Pain
12.
J Womens Health Phys Therap ; 46(2): 100-108, 2022.
Article En | MEDLINE | ID: mdl-35757164

Background: Women with urgency/frequency predominant lower urinary tract symptoms (UF-LUTS) may have elevated pelvic floor muscle (PFM) position at rest and limited mobility with PFM contraction and bearing down, but this has not been quantified. Objectives: To compare PFM position and mobility using transperineal ultrasound (TPUS) at rest, maximal PFM contraction (perineal elevation), and bearing down (perineal descent) in women with and without UF-LUTS. We hypothesized that women with UF-LUTS would demonstrate elevated resting position and decreased excursion of pelvic landmarks during contraction and bearing down as compared to women without UF-LUTS. Study Design: Case-control study. Methods: Women with UF-LUTS were matched 1:1 on age, body mass index and vaginal parity to women without UF-LUTS. TPUS videos were obtained during 3 conditions: rest, PFM contraction, and bearing down. Levator plate angle (LPA) and puborectalis length (PR length), were measured for each condition. Paired t-tests or Wilcoxon signed rank tests compared LPA and PR length between cases and controls. Results: 21 case-control pairs (42 women): Women with UF-LUTS demonstrated greater LPA at rest (66.8 ± 13.2 degrees vs 54.9 ± 9.8 degrees; P=0.006), and less PR lengthening from rest to bearing down (0.2 ± 3.1 mm vs 2.1 ± 2.9 mm; P=.03). Conclusion: Women with UF-LUTS demonstrated more elevated (cranioventral) position of the PFM at rest and less PR muscle lengthening with bearing down. These findings highlight the importance of a comprehensive PFM examination and possible treatment for women with UF-LUTS to include PFM position and mobility.

13.
Blood Adv ; 6(12): 3611-3624, 2022 06 28.
Article En | MEDLINE | ID: mdl-35298613

Lipid raft-associated proteins play a vital role in membrane-mediated processes. The lipid microdomain-associated protein flotillin 2 (FLOT2), which has a scaffolding function, is involved in polarization, as well as in actin cytoskeletal organization of primitive and mature hematopoietic cells and has been associated with different malignancies. However, its involvement in myeloid leukemias is not well studied. Using murine transplantation models, we show here that the absence of FLOT2 from leukemia-initiating cells (LICs) altered the disease course of BCR-ABL1+ chronic myeloid leukemia (CML), but not of MLL-AF9-driven acute myeloid leukemia (AML). While FLOT2 was required for expression of the adhesion molecule CD44 on both CML- and AML-LIC, a defect in the cytoskeleton, cell polarity, and impaired homing ability of LIC was only observed in FLOT2-deficient BCR-ABL1+ compared with MLL-AF9+ cells. Downstream of CD44, BCR-ABL1 kinase-independent discrepancies were observed regarding expression, localization, and activity of cell division control protein 42 homolog (CDC42) between wild-type (WT) and FLOT2-deficient human CML and AML cells. Inhibition of CDC42 by ML141 impaired the homing of CML LIC and, thereby, CML progression. This suggested that alteration of both CD44 and CDC42 may be causative of impaired CML progression in the absence of FLOT2. In summary, our data suggest a FLOT2-CD44-CDC42 axis, which differentially regulates CML vs AML progression, with deficiency of FLOT2 impairing the development of CML.


Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Leukemia, Myeloid, Acute , Animals , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/pathology , Membrane Microdomains/metabolism , Membrane Microdomains/pathology , Membrane Proteins/genetics , Membrane Proteins/metabolism , Mice
14.
J Womens Health Phys Therap ; 45(3): 126-134, 2021.
Article En | MEDLINE | ID: mdl-34366727

BACKGROUND: Urgency and frequency are common lower urinary tract symptoms (UF-LUTS) in women. There is limited evidence to guide physical therapist-led treatment. OBJECTIVES: To compare hip and pelvic floor muscle strength between women with and without UF-LUTS. We hypothesized women with UF-LUTS would demonstrate 1) diminished hip external rotator and abductor strength and 2) equivalent pelvic floor strength and diminished endurance compared to controls. STUDY DESIGN: A matched case-control study. METHODS: Women with UF-LUTS (cases) and controls were matched on age, body mass index (BMI), vaginal parity. Examiner measured participants' 1) hip external rotator and abductor strength via dynamometry (maximum voluntary effort against fixed resistance) and 2) pelvic floor muscle strength (peak squeeze pressure) and endurance (squeeze pressure over a 10 second hold) via vaginal manometry. Values compared between cases and controls with paired-sample t-tests (hip) or Wilcoxon signed rank tests (pelvic floor). RESULTS: 21 pairs (42 women): Hip external rotation (67.0 ± 19.0 N vs 83.6 ± 21.5 N; P=0.005) and hip abduction strength (163.1 ± 48.1 N vs 190.1 ± 53.1 N; P=0.04) were significantly lower in cases than controls. There was no significant difference in pelvic floor strength (36.8 ± 19.9 cmH20 vs 41.8 ± 21.0 cmH20; P=0.40) or endurance (234.0 ± 149.6 cmH20*seconds vs 273.4 ± 149.1 cmH20*seconds; P=0.24). CONCLUSION: Women with UF-LUTS had weaker hip external rotator and abductor muscles, but similar pelvic floor strength and endurance compared to controls. Hip strength may be important to assess in patients with UF-LUTS, further research is needed.

15.
J Pediatr Urol ; 17(4): 452-462, 2021 08.
Article En | MEDLINE | ID: mdl-34090791

BACKGROUND: Lower urinary tract symptoms (LUTS) are common in children and adolescents. Non-invasive tests evaluating bladder function are generally preferred over invasive tests, yet few studies have explored the range of normative values for these tests in healthy, asymptomatic children. OBJECTIVE: To define normative reference ranges for non-invasive tests of bladder function in healthy, asymptomatic girls and adolescents. STUDY DESIGN: A comprehensive search strategy was performed in seven electronic databases through October 2019. English-language studies reporting data on voiding frequency, voided and postvoid residual volumes (PVR) and uroflowmetry results in healthy, asymptomatic girls (mean age ≥ 5 years) were included. Two independent reviewers performed study review, data extraction, and quality assessment. Overall mean estimates and 95% confidence intervals for each bladder function parameter were calculated using random effects models, and 95% normative reference values were estimated. RESULTS: Ten studies met eligibility criteria for the meta-analysis (n = 2143 girls, age range: 3-18). Mean estimates of maximum voided volume and PVR were 233.4 ml (95% CI 204.3-262.6; n = 1 study) and 8.6 ml (95% CI 4.8-12.4; n = 2 studies) respectively. Pooled mean estimates for uroflowmetry parameters were: 21.5 ml/s (95% CI 20.5-2.5) for maximum flow rate (n = 6 studies), 12.5 ml/s (95% CI 11.2-13.8) for mean flow rate (n = 6 studies), 6.8 s (95% CI 4.4-9.3) for time to maximum flow (n = 3 studies), 15.7 s (95% CI 13.0-18.5) for flow time (n = 3 studies), and 198.7 ml (95% CI 154.2-234.2) for voided volume (n = 9 studies). No studies reported estimates of voiding frequency. Between-study heterogeneity was high (89.0-99.6%). CONCLUSIONS: Although we were able to calculate pooled mean estimates for several parameters, the small number of included studies and the wide age ranges of participants preclude generalization of reference values to all healthy girls. Further research is needed to determine normative reference values within specific age groups.


Lower Urinary Tract Symptoms , Urinary Bladder , Adolescent , Child , Child, Preschool , Female , Humans , Urination , Urodynamics , Urologic Surgical Procedures
17.
Female Pelvic Med Reconstr Surg ; 27(1): e39-e44, 2021 01 01.
Article En | MEDLINE | ID: mdl-31725016

OBJECTIVES: Vaginal estrogen therapy (VET) has been shown to decrease the risk of recurrent urinary tract infections (UTIs) in postmenopausal women, but the mechanism of action has not been fully described. Our objectives were to assess whether the postmenopausal urine inflammatory profile changes in response to VET. METHODS: We prospectively enrolled postmenopausal patients into 3 groups: (1) currently using VET without a history of recurrent UTIs (rUTIs); (2) history of UTIs, currently using VET; and (3) history of rUTIs, not using VET but willing to start. We followed patients over 6 to 19 months and collected urine samples at 3 time points. We performed comprehensive cytopathologic analysis, quantitative urine inflammatory scoring, and enzyme-linked immunosorbent assay for interleukin 6. RESULTS: Seventy patients were recruited (group 1, n = 30; group 2, n = 20; group 3, n = 20). Urine from patients in groups 2 and 3 demonstrated increased inflammatory cells, debris, and exfoliated urothelial cells. Quantitative urine inflammatory scores and interleukin 6 were significantly higher in postmenopausal patients with rUTIs not on VET (0.12 vs 0.93, P < 0.05) and decreased significantly after initiating VET (0.93 vs 0.38, P < 0.05). CONCLUSIONS: Postmenopausal women with rUTIs on VET demonstrate decreased cell shedding, reduced urine inflammatory scores, and decreased urine interleukin 6. Modulation of the genitourinary inflammatory profile may represent one mechanism through which VET helps prevent rUTIs in postmenopausal women.


Estrogens/therapeutic use , Postmenopause , Urinary Tract Infections/prevention & control , Urothelium/drug effects , Aged , Aged, 80 and over , Estrogens/pharmacology , Female , Humans , Interleukin-6/urine , Prospective Studies , Recurrence , Urinary Tract Infections/microbiology
18.
Female Pelvic Med Reconstr Surg ; 27(1): e152-e160, 2021 01 01.
Article En | MEDLINE | ID: mdl-32301801

OBJECTIVES: The aims of the study were to systematically review the literature and to synthesize the evidence for the effectiveness of botulinum toxin injection to the pelvic floor muscles for treating pelvic floor myofascial pain in female patients. METHODS: This systematic literature search was performed in February 2018 and updated in September 2019. Articles were screened based on predefined criteria: (1) adult population, (2) female patients, (3) treatment of pelvic pain by transvaginal botulinum toxin injection into the pelvic floor, (4) published in English or English translation available, (5) study design including randomized controlled trials, cohort studies, and case series with more than 10 participants, and (6) quantitative report of pain scores. Nine studies were included in the primary analysis, and an unpublished study was included in a sensitivity analysis. A random effects model with robust variance estimation was used to estimate the pooled mean difference in patient-reported pain scores after botulinum toxin injection. RESULTS: A statistically significant reduction in patient-reported pain scores was noted at 6 weeks after botulinum toxin injection (mean difference, 20.3; 95% confidence interval, 11.7-28.9) and continued past 12 weeks (mean difference, 19.4; 95% confidence interval, 14.6-24.2). Significant improvement was noted in secondary outcomes including dyspareunia, dyschezia, and quality of life. CONCLUSIONS: This systematic review and meta-analysis support the conduct of future, large-scale randomized controlled trials to determine the efficacy and optimize administration of botulinum toxin injections for treatment of pelvic floor myofascial pain and associated symptoms in women.


Botulinum Toxins, Type A/therapeutic use , Myofascial Pain Syndromes/drug therapy , Neuromuscular Agents/therapeutic use , Pelvic Floor , Female , Humans , Treatment Outcome
19.
Female Pelvic Med Reconstr Surg ; 27(7): 421-426, 2021 07 01.
Article En | MEDLINE | ID: mdl-32701766

OBJECTIVE: The objective of this study was to determine factors associated with performance of concomitant apical support procedures (ASPs) with benign hysterectomy at a regional medical system. METHODS: Benign hysterectomies performed within 1 regional medical system from January 2011 to November 2017 were identified using International Classification of Diseases, Ninth and 10th Revision, and Current Procedural Terminology codes. Primary outcome was performance of concomitant ASP. χ2 Tests compared categorical variables. Multivariable logistic regression analysis was performed to determine factors associated with performance of concomitant ASP. RESULTS: A total of 12,345 benign hysterectomies were performed during the study period. Uterovaginal prolapse was the primary diagnosis in 924 (7.48%) hysterectomies and an associated diagnosis in 1180 (9.56%) hysterectomies. A total of 686 patients (5.56%) had concurrent ASPs: 119 (17.3%) in patients without a diagnosis of prolapse and 567 (82.7%) with prolapse. Using multivariable logistic regression, controlling for age, race, insurance type, hospital type, procedure year, hysterectomy route, and surgeon training in patients with a diagnosis of prolapse, older age, supracervical hysterectomy, and surgeon training were associated with performance of ASPs. CONCLUSIONS: Even in patients with a preoperative diagnosis of uterovaginal prolapse, ASPs are not routinely performed at time of hysterectomy. Fellowship-trained surgeons were more likely to perform ASPs. Ongoing educational efforts during training and postgraduate at the national and regional level on the importance of reestablishing apical vaginal support at time of hysterectomy is needed to prevent incident and recurrent post-hysterectomy vaginal vault prolapse.


Hysterectomy/methods , Practice Patterns, Physicians'/statistics & numerical data , Uterine Prolapse/surgery , Adolescent , Adult , Aged , Aged, 80 and over , Female , Gynecology/education , Humans , Hysterectomy/statistics & numerical data , Middle Aged , Obstetrics/education , Retrospective Studies , Uterine Prolapse/epidemiology , Young Adult
20.
Leukemia ; 34(8): 2087-2101, 2020 08.
Article En | MEDLINE | ID: mdl-32439895

Therapy resistance in leukemia may be due to cancer cell-intrinsic and/or -extrinsic mechanisms. Mutations within BCR-ABL1, the oncogene giving rise to chronic myeloid leukemia (CML), lead to resistance to tyrosine kinase inhibitors (TKI), and some are associated with clinically more aggressive disease and worse outcome. Using the retroviral transduction/transplantation model of CML and human cell lines we faithfully recapitulate accelerated disease course in TKI resistance. We show in various models, that murine and human imatinib-resistant leukemia cells positive for the oncogene BCR-ABL1T315I differ from BCR-ABL1 native (BCR-ABL1) cells with regards to niche location and specific niche interactions. We implicate a pathway via integrin ß3, integrin-linked kinase (ILK) and its role in deposition of the extracellular matrix (ECM) protein fibronectin as causative of these differences. We demonstrate a trend towards a reduced BCR-ABL1T315I+ tumor burden and significantly prolonged survival of mice with BCR-ABL1T315I+ CML treated with fibronectin or an ILK inhibitor in xenogeneic and syngeneic murine transplantation models, respectively. These data suggest that interactions with ECM proteins via the integrin ß3/ILK-mediated signaling pathway in BCR-ABL1T315I+ cells differentially and specifically influence leukemia progression. Niche targeting via modulation of the ECM may be a feasible therapeutic approach to consider in this setting.


Imatinib Mesylate/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Animals , Drug Resistance, Neoplasm , Fibronectins/analysis , Fibronectins/metabolism , Focal Adhesion Protein-Tyrosine Kinases/physiology , Fusion Proteins, bcr-abl/analysis , Fusion Proteins, bcr-abl/physiology , Humans , Imidazoles/pharmacology , Integrin beta3/physiology , Mice , Protein Serine-Threonine Kinases/antagonists & inhibitors , Protein Serine-Threonine Kinases/physiology , Pyridazines/pharmacology
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