Five-year Results from the Prospective, Multicenter, Observational SOUNDS Study of Patients with Overactive Bladder Treated with the InterStim System for Sacral Neuromodulation.

BACKGROUND: Although sacral neuromodulation (SNM) for overactive bladder (OAB) is an established therapy, there is a lack of high-quality, long-term data on real-life practice. OBJECTIVE: To report on real-life therapeutic effectiveness, quality of life (QoL), disease severity, and safety as well as patient-reported symptom bother after approximately 5 yr of follow-up. DESIGN, SETTING, AND PARTICIPANTS: A total of 291 OAB patients were enrolled at 25 French sites according to local standard of care. Sacral neuromOdUlation with InterStim therapy for intractable lower uriNary tract DySfunctions (SOUNDS) enrolled both de novo and replacement patients, and a total of 229 patients were permanently implanted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Over the course of the study, patients were followed up six times with two follow-ups in the year after implantation and annually thereafter. Of the patients, 154 completed the final follow-up after a mean of 57.7 ± 3.9 mo. RESULTS AND LIMITATIONS: The mean number of daily leaks in urinary urge incontinence (UI) patients was reduced from 4.4 ± 3.3 at baseline to 1.8 ± 2.6 after 5 yr in de novo and from 5.4 ± 4.9 to 2.2 ± 3.0 in replacement patients (both p < 0.001). Likewise, the number of voids in urinary frequency patients was reduced compared with baseline (de novo: reduced from 12.6 ± 4.0 [baseline] to 9.6 ± 4.3 [5 yr]; replacements: reduced from 11.5 ± 4.3 [baseline] to 9.2 ± 3.1 [5 yr]; both p < 0.05). Complete continence rates after 5 yr were 44% (25/57) in de novo and 33% (5/15) in replacement UI patients, and 68% (39/57) and 67% (10/15) of UI patients were categorized as therapy responders by showing a >50% improvement in leaks. Disease severity (Urinary Symptom Profile domain 2), Numeric Rating Scale-based symptom bother, and disease-specific QoL (Ditrovie) improved significantly in both groups at all visits (p < 0.001). Adverse events related to device or procedure occurred in 51% (140/274) of patients, with 66% (152/229) of the events being classified as minor (Clavien-Dindo grade I and II). Surgical revisions were reported in 39% (89/229), which include permanent explants in 15% (34/229) of patients. CONCLUSIONS: SOUNDS demonstrates the sustained effectiveness and QoL improvements of SNM in OAB patients after 5 yr in real-world conditions while maintaining an acceptable safety profile consistent with literature. PATIENT SUMMARY: This study confirmed that French overactive bladder patients had a sustained symptom and bother reduction, and improvements in quality of life up to 5 yr after sacral neuromodulation device implantation.

Sacral Neuromodulation with the InterStim System for Overactive Bladder: 3-Year Results from the French Prospective, Multicenter, Observational SOUNDS Study.

BACKGROUND: SOUNDS strengthens the evidence basis of sacral neuromodulation (SNM) for overactive bladder (OAB) through real-world data. OBJECTIVE: To analyze diary-based effectiveness, quality of life (QoL), disease severity, symptom bother, and safety data for SNM with the InterStim system up to 3 yr after implantation. DESIGN, SETTING, AND PARTICIPANTS: Twenty-five representative French sites enrolled 291 patients with OAB followed according to the local standard of care. Overall, 229 patients received a de novo or replacement InterStim implant and had four follow-up visits, two within the first yr and annually thereafter. A total of 190 patients completed the fourth follow-up visit after a mean of 33.7 ± 3.7 mo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The effectiveness outcomes measured were changes in daily voids and leaks and the therapy responder rates. Other outcomes included validated QoL data (Ditrovie and EuroQol 5-dimension 5-level questionnaires), disease severity (Urinary Symptom Profile [USP]), symptom bother rated using a numeric rating scale (NRS), and safety data. Follow-up data were compared to baseline results using the Wilcoxon signed-rank test. RESULTS AND LIMITATIONS: Average daily voids and leaks were significantly reduced at all time points up to 3 yr after implantation (p < 0.05) except for voids at 21 mo in the group receiving a replacement device. The therapeutic response for urinary urge incontinence at the fourth follow-up was 72% for the de novo group and 86% for the replacement group. Disease-specific QoL (Ditrovie), OAB-specific symptom severity (USP domain 2), and NRS-rated disease bother were significantly improved at all visits (p < 0.001). Device- or procedure-related adverse events occurred in 49% of patients, with 68% of the events classified as minor (Clavien-Dindo grade I or II). Surgical revisions were performed in 33% of patients, including permanent removal in 13%, over a mean exposure time of 44.4 ± 15.3 mo. CONCLUSIONS: This study confirms the safety and effectiveness of SNM for OAB and improvements in QoL and disease bother in real life. PATIENT SUMMARY: Our study in French patients with overactive bladder showed that disease symptoms and bother were significantly reduced and quality of life was significantly improved over a study duration of approximately 3 yr after implantation of a device to stimulate nerves that control the bladder. This trial is registered at ClinicalTrials.gov as NCT02186041.

Sacral neuromodulation with the InterStim™ system for faecal incontinence: results from a prospective French multicentre observational study.

AIM: The aim of this work was to evaluate the effectiveness, patient satisfaction and quality of life (QoL) and the safety of sacral neuromodulation (SNM) with the InterStimTM system for the treatment of faecal incontinence (FI) and establish whether results published predominantly by expert sites are generalisable. METHOD: This is a prospective, multicentre, observational study that invited all French sites treating FI with the InterStim™ system to enrol subjects indicated for an SNM therapy evaluation. Data were collected at three follow-up visits within 1 and 15 months. Therapeutic effectiveness was evaluated by the reduction in leakages per week and improvements over time in the ability to defer defaecation and QoL (as measured with the Faecal Incontinence Quality of Life score). Safety was assessed through reported adverse events. RESULTS: A total of 221 subjects with a mean age of 62.1 years were tested (184 women) and 178 received a permanent implant. For all implanted subjects with diary data at baseline and follow-up, a reduction in leakage of more than 50% was observed in 80%, 76% and 83% at 1-3, 4-8 and 9-15 months, respectively. The mean number of leakage episodes and urgency improved significantly compared with the baseline (p < 0.0001). Subjects showed improvements in QoL and time to defer defaecation and were generally satisfied with their therapy. The main device-related adverse event was the requirement to undertake reprogramming (in 52% of subjects with actions following an event). The rates of infection (in 6% of subjects) and surgical revision (in 10% of subjects) were in agreement with literature reports. CONCLUSION: This study confirms the clinical effectiveness, safety and positive effect of SNM on QoL as well as high patient satisfaction for the treatment of FI in real-life.

Sacral Neuromodulation with the InterStim™ System for Intractable Lower Urinary Tract Dysfunctions (SOUNDS): Results of Clinical Effectiveness, Quality of Life, Patient-Reported Outcomes and Safety in a French Multicenter Observational Study.

BACKGROUND: Real-world data that support the use of sacral neuromodulation (SNM) for lower urinary tract dysfunctions are of continued interest. OBJECTIVE: To evaluate the effectiveness, quality of life (QoL), patient-reported outcomes (PROs), and safety of SNM with the InterStim™ system in real life during 1-yr postimplant. DESIGN, SETTING, AND PARTICIPANTS: This is a prospective, multicenter, observational study at 25 representative public and private French sites. Eligible patients received SNM therapy for overactive bladder (OAB) and non-obstructive urinary retention based on local standard of care. Overall, 320 patients were enrolled; 247 received permanent implant or replacement; 204 implanted patients completed second follow-up after mean of 10.0±3.8 mo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Effectiveness outcomes were change in voids, leaks, and catheterizations/day. Other outcomes included validated QoL and disease severity scores as well as PROs and adverse event data. Outcomes at follow-ups were compared with baseline using the Wilcoxon signed-rank test. RESULTS AND LIMITATIONS: Voids in urinary frequency (UF) and leaks/day in urinary urge incontinence (UI) patients were significantly reduced after 10 mo in both de novo (mean baseline voids/day UF de novo: 12.7 vs 8.6 after 10 mo; p<0.001; mean baseline leaks/day UI de novo: 4.3 vs 1.1 after 10 mo; p<0.001) and replacement patients (mean baseline voids/day UF replacement: 11.5 vs 7.9 after 10 mo; p<0.001; mean baseline leaks/day UI replacement: 5.4 vs 1.0 after 10 mo; p<0.001). Disease bother, Urinary Symptom Profile score, and Ditrovie questionnaire score were also significantly improved. Revisions postimplant occurred in 20% of patients including in 9% due to permanent explantation during a mean exposure time of 24.3 mo. CONCLUSIONS: Through a real-life study, SOUNDS (Sacral neuromOdUlation with InterStim™ therapy for intractable lower uriNary tract DySfunctions) confirms the clinical effectiveness, safety, and positive effect of SNM on QoL and PROs for the treatment of OAB patients. PATIENT SUMMARY: These analyses on French patients who received sacral neuromodulation (SNM) for retention or OAB during a 10-mo period showed that SNM improved OAB symptoms, quality of life, and reduced disease bother. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02186041.

Linking otolith microchemistry and surface water contamination from natural gas mining.

Unconventional natural gas drilling and the use of hydraulic fracturing technology have expanded rapidly in North America. This expansion has raised concerns of surface water contamination by way of spills and leaks, which may be sporadic, small, and therefore difficult to detect. Here we explore the use of otolith microchemistry as a tool for monitoring surface water contamination from generated waters (GW) of unconventional natural gas drilling. We exposed Brook Trout in the laboratory to three volumetric concentrations of surrogate generated water (SGW) representing GW on day five of drilling. Transects across otolith cross-sections were analyzed for a suite of elements by LA-ICP-MS. Brook Trout exposed to a 0.01-1.0% concentration of SGW for 2, 15, and 30 days showed a significant (p < 0.05) relationship of increasing Sr and Ba concentrations in all but one treatment. Analyses indicate lesser concentrations than used in this experiment could be detectable in surface waters and provide support for the use of this technique in natural habitats. To our knowledge, this is the first demonstration of how trace elements in fish otoliths may be used to monitor for surface water contamination from GW.

Evolving Federal and State Health Care Policy: Toward a More Integrated and Comprehensive Care-Delivery System for Children With Medical Complexity.

Irrespective of any future changes in federal health policy, the momentum to shift from fee-for-service to value-based payment systems is likely to persist. Public and private payers continue to move toward alternative payment models that promote novel care-delivery systems and greater accountability for health outcomes. With a focus on population health, patient-centered medical homes, and care coordination, alternative payment models hold the potential to promote care-delivery systems that address the unique needs of children with medical complexity (CMC), including nonmedical needs and the social determinants of health. Notwithstanding, the implementation of care systems with meaningful quality measures for CMC poses unique and substantive challenges. Stakeholders must view policy options for CMC in the context of transformation within the overall health system to understand how broader health system changes impact care delivery for CMC.

Maternally involved galanin neurons in the preoptic area of the rat.

Recent selective stimulation and ablation of galanin neurons in the preoptic area of the hypothalamus established their critical role in control of maternal behaviors. Here, we identified a group of galanin neurons in the anterior commissural nucleus (ACN), and a distinct group in the medial preoptic area (MPA). Galanin neurons in ACN but not the MPA co-expressed oxytocin. We used immunodetection of phosphorylated STAT5 (pSTAT5), involved in prolactin receptor signal transduction, to evaluate the effects of suckling-induced prolactin release and found that 76 % of galanin cells in ACN, but only 12 % in MPA were prolactin responsive. Nerve terminals containing tuberoinfundibular peptide 39 (TIP39), a neuropeptide that mediates effects of suckling on maternal motivation, were abundant around galanin neurons in both preoptic regions. In the ACN and MPA, 89 and 82 % of galanin neurons received close somatic appositions, with an average of 2.9 and 2.6 per cell, respectively. We observed perisomatic innervation of galanin neurons using correlated light and electron microscopy. The connection was excitatory based on the glutamate content of TIP39 terminals demonstrated by post-embedding immunogold electron microscopy. Injection of the anterograde tracer biotinylated dextran amine into the TIP39-expressing posterior intralaminar complex of the thalamus (PIL) demonstrated that preoptic TIP39 fibers originate in the PIL, which is activated by suckling. Thus, galanin neurons in the preoptic area of mother rats are innervated by an excitatory neuronal pathway that conveys suckling-related information. In turn, they can be topographically and neurochemically divided into two distinct cell groups, of which only one is affected by prolactin.

A Thalamo-Hypothalamic Pathway That Activates Oxytocin Neurons in Social Contexts in Female Rats.

Oxytocin is released from neurons in the paraventricular hypothalamic nucleus (PVN) in mothers upon suckling and during adult social interactions. However, neuronal pathways that activate oxytocin neurons in social contexts are not yet established. Neurons in the posterior intralaminar complex of the thalamus (PIL), which contain tuberoinfundibular peptide 39 (TIP39) and are activated by pup exposure in lactating mothers, provide a candidate projection. Innervation of oxytocin neurons by TIP39 neurons was examined by double labeling in combination with electron microscopy and retrograde tract-tracing. Potential classic neurotransmitters in TIP39 neurons were investigated by in situ hybridization histochemistry. Neurons activated after encounter with a familiar conspecific female in a familiar environment were mapped with the c-Fos technique. PVN and the supraoptic nucleus oxytocin neurons were closely apposed by an average of 2.0 and 0.4 TIP39 terminals, respectively. Asymmetric (presumed excitatory) synapses were found between TIP39 terminals and cell bodies of oxytocin neurons. In lactating rats, PIL TIP39 neurons were retrogradely labeled from the PVN. TIP39 neurons expressed vesicular glutamate transporter 2 but not glutamic acid decarboxylase 67. PIL contained a markedly increased number of c-Fos-positive neurons in response to social encounter with a familiar conspecific female. Furthermore, the PIL received ascending input from the spinal cord and the inferior colliculus. Thus, TIP39 neurons in the PIL may receive sensory input in response to social interactions and project to the PVN to innervate and excite oxytocin neurons, suggesting that the PIL-PVN projection contributes to the activation of oxytocin neurons in social contexts.

Effect of prebiotics on the fecal microbiota of elderly volunteers after dietary supplementation of Bacillus coagulans GBI-30, 6086.

In advancing age, gut populations of beneficial microbes, notably Bifidobacterium spp., show a marked decline. This contributes to an environment less capable of maintaining homoeostasis. This in vitro investigation studied the possible synergistic effects of probiotic supplementation in modulating the gut microbiota enabling prebiotic therapy to in elderly persons. Single stage batch culture anaerobic fermenters were used and inoculated with fecal microbiota obtained from volunteers after taking a 28 day treatment of Bacillus coagulans GBI-30, 6086 (GanedenBC30 (BC30)) or a placebo. The response to prebiotic supplements fructooligosaccharides (FOS) and galactooligosaccharides (GOS) in the fermenters was assessed. Bacterial enumeration was carried out using fluorescent in situ hybridisation and organic acids measured by gas chromatography. Baseline populations of Faecalibacterium prausnitzii, Clostridium lituseburense and Bacillus spp. were significantly higher in those having consumed BC30 compared to the placebo. Both prebiotics increased populations of several purportedly beneficial bacterial groups in both sets of volunteers. Samples from volunteers having ingested the BC30 also increased populations of C. lituseburense, Eubacterium rectale and F. prausnitzii more so than in persons who had consumed the placebo, this also resulted in significantly higher concentrations of butyrate, acetate and propionate. This shows that consumption of BC30 and subsequent use of prebiotics resulted in elevated populations of beneficial genres of bacteria as well as organic acid production.

Osteopathic manipulative treatment for the treatment of hospitalized premature infants with nipple feeding dysfunction.

Premature newborns and infants are usually required to successfully transition from gavage to nipple feeding using breast or bottle before discharge from the hospital. This transition is frequently the last discharge skill attained. Delayed acquisition of this skill may substantially prolong hospital length of stay. The authors describe a case of hospitalized premature twins who had considerable delays in attaining nipple-feeding skills. Because of their inability to take all feedings by nipple, preparation for surgical placement of gastrostomy tubes was initiated. Before the surgeries were scheduled, the inpatient osteopathic manipulative medicine service was consulted, and the twins received a series of evaluations and osteopathic manipulative treatment (OMT) sessions. During the OMT course, the twins' nipple feeding skills progressed to full oral feeding, which allowed them to be discharged to home without placement of gastrostomy tubes. The authors also review the literature and discuss the development of nipple feeding in premature newborns and infants and the use of OMT in the management of nipple feeding dysfunction.

Reversible control of free energy and topography of nanostructured surfaces.

We describe a facile method for the formation of dynamic nanostructured surfaces based on the modification of porous anodic aluminum oxide with poly(N-isopropyl acrylamide) (PNIPAAm) via surface-initiated atom transfer radical polymerization. The dynamic structure of these surfaces was investigated by atomic force microscopy (AFM), which showed dramatic changes in the surface nanostructure above and below the aqueous lower critical solution temperature of PNIPAAm. These changes in surface structure are correlated with changes in the macroscopic wettability of the surfaces, which was probed by water contact angle measurements. Principal component analysis was used to develop a quantitative correlation between AFM image intensity histograms and macroscopic wettability. Such correlations and dynamic nanostructured surfaces may have a variety of uses.