Long-term Outcomes of Sacral Nerve Stimulation on the Treatment of Fecal Incontinence: A Systematic Review.

INTRODUCTION: Sacral nerve stimulation (SNS) has now been used as a treatment for fecal incontinence (FI) for >20 years. The aim of this systematic review was to determine the long-term efficacy of SNS on the treatment of FI. MATERIALS AND METHODS: A comprehensive search of the MEDLINE, Embase, and Cochrane Central data bases was performed to find publications, excluding case reports, reporting outcomes of SNS treatment for FI in adults with ≥36 months of follow-up. Bias was assessed using the Risk of Bias in Non-randomized Studies-of Interventions tool. Data were summarized per reported FI-related outcomes for symptom severity and quality of life. RESULTS: In total, 3326 publications were identified, and 36 studies containing 3770 subjects were included. All studies had a serious risk of bias. Success was variably defined by each publication and ranged from 59.4% to 87.5% for per-protocol analyses and 20.9% to 87.5% for intention-to-treat analyses. All studies reporting bowel diary data, St Mark's scores, and Cleveland Clinic Incontinence Scores indicated significant improvement with SNS treatment in the long term. Studies that evaluated quality-of-life outcomes also all showed improvements in quality of life as measured by the Fecal Incontinence Quality of Life Scale. The aggregate revision rate was 35.2%, and the explantation rate was 19.7%. CONCLUSIONS: Improvements in objective and subjective outcomes at ≥36 months support using SNS for the long-term treatment of FI. Interpretation of these data is limited by a lack of comparative trials and heterogeneity of the included studies.

How Clinicians Discuss Medications During Primary Care Encounters Among Older Adults with Cognitive Impairment.

BACKGROUND: People with cognitive impairment experience high rates of polypharmacy and potentially inappropriate medication use. How clinicians communicate about medications may affect to what extent patients and family companions understand and participate in decisions about medication use. OBJECTIVE: To characterize how primary care clinicians discuss medications during encounters with older adults with cognitive impairment and their companions. DESIGN: Qualitative content analysis of audio-recorded clinical encounters from SAME Page, a randomized controlled trial to examine the effects of a patient-family agenda setting checklist on primary care visit communication among patients with cognitive impairment. Visits occurred between August 2016 and August 2017. PARTICIPANTS: Patients were 65 or older, had > 1 incorrect answer on a cognitive screener, and attended visits with a relative or unpaid companion. Clinicians were physicians, nurse practitioners, or physician assistants at participating practices. APPROACH: The encounters were transcribed verbatim. We used qualitative content analysis to identify major themes. KEY RESULTS: Patients were on average 79.9 years of age. The average MMSE score was 21.6. About half of clinicians reported practicing for 15 or more years (n = 8). We identified three major themes. First, we found numerous instances in which primary care clinicians introduced patients and companions to key principles of optimal prescribing and deprescribing. Second, clinicians used a variety of approaches to foster shared decision-making about medication use. Third, several challenges prevented clinicians from working together with patients and companions to optimize prescribing and deprescribing. CONCLUSIONS: This study offers insight into key language clinicians can use to initiate discussions about optimizing prescribing, as well as barriers they face in doing so. Examples identified in these transcripts should be tested with patients and caregivers to examine how such communications are received and interpreted. Future research should develop and test interventions that seek to overcome obstacles to optimizing prescribing for older adults with cognitive impairment.

A Comparison of Spinal Anesthesia Versus Monitored Anesthesia Care With Local Anesthesia in Minimally Invasive Fetal Surgery.

BACKGROUND: Minimally invasive fetal surgery is commonly performed to treat twin-to-twin transfusion syndrome with selective fetoscopic laser photocoagulation and twin-reversed arterial perfusion sequence using radiofrequency ablation. Although an increasing number of centers worldwide are performing these procedures, anesthetic management varies. Both neuraxial anesthesia and monitored anesthesia care with local anesthesia are used at different institutions. We sought to determine the efficacy and outcomes of these 2 anesthetic techniques for fetal procedures at our institution. METHODS: All patients undergoing minimally invasive fetal surgery for twin-to-twin transfusion syndrome or twin-reversed arterial perfusion sequence over a 6-year time period (2011-2016) were reviewed. Patients receiving monitored anesthesia care with local anesthesia were compared with those receiving spinal anesthesia in both selective fetoscopic laser photocoagulation and radiofrequency ablation fetal procedures. The primary outcome examined between the monitored anesthesia care and spinal anesthesia groups was the difference in conversion to general anesthesia using a noninferiority design with a noninferiority margin of 5%. Secondary outcome measures included use of vasopressors, procedure times, intraoperative fluids administered, maternal complications, and unexpected fetal demise within 24 hours of surgery. RESULTS: The difference in failure rate between monitored anesthesia care and spinal was -0.5% (95% CI, -4.8% to 3.7%). Patients receiving monitored anesthesia care plus local anesthesia were significantly less likely to need vasopressors, had a shorter presurgical operating room time, and received less fluid (P < .001). Operative time did not differ significantly. CONCLUSIONS: Monitored anesthesia care plus local anesthesia is a reliable and safe anesthetic choice for minimally invasive fetal surgery. Furthermore, it decreases maternal hemodynamic instability and reduces preincision operating room time.

BICC1 Interacts with PKD1 and PKD2 to Drive Cystogenesis in ADPKD.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is primarily of adult-onset and caused by pathogenic variants in PKD1 or PKD2 . Yet, disease expression is highly variable and includes very early-onset PKD presentations in utero or infancy. In animal models, the RNA-binding molecule Bicc1 has been shown to play a crucial role in the pathogenesis of PKD. Methods: To study the interaction between BICC1, PKD1 and PKD2 we combined biochemical approaches, knockout studies in mice and Xenopus, genetic engineered human kidney cells as well as genetic association studies in a large ADPKD cohort. Results: We first demonstrated that BICC1 physically binds to the proteins Polycystin-1 and -2 encoded by PKD1 and PKD2 via distinct protein domains. Furthermore, PKD was aggravated in loss-of-function studies in Xenopus and mouse models resulting in more severe disease when Bicc1 was depleted in conjunction with Pkd1 or Pkd2 . Finally, in a large human patient cohort, we identified a sibling pair with a homozygous BICC1 variant and patients with very early onset PKD (VEO-PKD) that exhibited compound heterozygosity of BICC1 in conjunction with PKD1 and PKD2 variants. Genome editing demonstrated that these BICC1 variants were hypomorphic in nature and impacted disease-relevant signaling pathways. Conclusions: These findings support the hypothesis that BICC1 cooperates functionally with PKD1 and PKD2 , and that BICC1 variants may aggravate disease severity highlighting RNA metabolism as an important new concept for disease modification in ADPKD.

Triangulation of a Needs Assessment on High-Tone Pelvic Floor Dysfunction.

IMPORTANCE: High-tone pelvic floor dysfunction is a complex condition that is challenging to manage effectively. Pelvic floor physical therapy (PFPT) is often used in the treatment and relies on a coordinated effort between the physician, patient, and physical therapist. Collaboration is crucial for therapy success, but there is limited research that includes personal perspectives from these individuals. OBJECTIVE: The objective of this qualitative study was to gain further insight from these groups to identify areas for improvement in patient counseling and understanding of the diagnosis of high-tone pelvic floor dysfunction and the role of physical therapy. STUDY DESIGN: The following participants were recruited: urogynecologists, pelvic floor physical therapists, and patients. Semistructured interviews were conducted exploring participant experiences with therapy and management of the condition and surrounding phenomena. RESULTS: Participants interviewed included 5 urogynecologists, 5 pelvic floor physical therapists, and 15 patients. Similarities in key themes were identified: (1) the usefulness of pelvic models and illustrations in counseling, (2) appropriate descriptions of therapy, (3) motivating factors for patients, and (4) patient barriers to completing therapy. Several emergent themes revealed a misalignment in perspectives, including (1) patients reporting an unclear understanding of PFPT, (2) patient unawareness of the intimacy of therapy, and (3) reports of unsupportive and unempathetic physician providers. CONCLUSIONS: There are both similarities and discrepancies in the perspectives among physicians, pelvic floor physical therapists, and patients regarding high-tone pelvic floor dysfunction and PFPT. Acknowledging these comparisons and adapting practices could facilitate patient-centered care and improve patient understanding of their diagnosis.

Vaginal Hysterectomy Rates Before and After Implementation of a Multiple-Tier Intervention.

OBJECTIVE: To assess a multiple-tier intervention to increase vaginal hysterectomy rates. METHODS: We performed a cohort study assessing hysterectomy performance before and after implementation of a multiple-tier intervention to increase vaginal hysterectomy rates at a single tertiary care medical center. This intervention involved resident and attending education and simulation, professional development, design of a clinical pathway to assist in hysterectomy decision making, and development of a surgical mentorship program. RESULTS: Data from 698 hysterectomies (253 preintervention and 445 postintervention) were included. The preintervention time period extended from January 1, 2016, to December 31, 2017 (24 months), and the postintervention period from January 1, 2018, to February 28, 2020 (26 months). The intervention was implemented over the month of December 2017 but was not complete until January 1, 2018. The preintervention and postintervention cohorts were similar in most demographic and clinical aspects. Postintervention, the proportion of vaginal hysterectomies was higher (26.5% vs 5.5%, odds ratio 6.2, 95% CI 3.52-11.35), including in those performed for reasons other than prolapse (6.8% vs 0%, P<.001). Logistic regression revealed that prolapse, uterine weight less than 250 g, and surgery during the postintervention cohort were significantly associated with vaginal hysterectomy. Operative complications did not differ significantly by hysterectomy type. CONCLUSION: Implementation of a multiple-tier intervention was associated with an increase in vaginal hysterectomies.

Epigenetic Therapy Augments Classic Chemotherapy in Suppressing the Growth of 3D High-Grade Serous Ovarian Cancer Spheroids over an Extended Period of Time.

Recurrent high-grade serous ovarian cancer (HGSC) is clinically very challenging and prematurely shortens patients' lives. Recurrent ovarian cancer is characterized by high tumor heterogeneity; therefore, it is susceptible to epigenetic therapy in classic 2D tissue culture and rodent models. Unfortunately, this success has not translated well into clinical trials. Utilizing a 3D spheroid model over a period of weeks, we were able to compare the efficacy of classic chemotherapy and epigenetic therapy on recurrent ovarian cancer cells. Unexpectedly, in our model, a single dose of paclitaxel alone caused the exponential growth of recurrent high-grade serous epithelial ovarian cancer over a period of weeks. In contrast, this effect is not only opposite under treatment with panobinostat, but panobinostat reverses the repopulation of cancer cells following paclitaxel treatment. In our model, we also demonstrate differences in the drug-treatment sensitivity of classic chemotherapy and epigenetic therapy. Moreover, 3D-derived ovarian cancer cells demonstrate induced proliferation, migration, invasion, cancer colony formation and chemoresistance properties after just a single exposure to classic chemotherapy. To the best of our knowledge, this is the first evidence demonstrating a critical contrast between short and prolonged post-treatment outcomes following classic chemotherapy and epigenetic therapy in recurrent high-grade serous ovarian cancer in 3D culture.