Management of female stress urinary incontinence with single-incision mini-sling (Altis®): 36 month multicenter outcomes.

PURPOSE: To assess noninferiority of the safety and effectiveness of the Altis® Single Incision Sling (SIS) with standard midurethral transobturator and/or retropubic slings through 36 months in a prospective, longitudinal, nonrandomized US Food and Drug Administration (FDA) 522 cohort study. MATERIALS AND METHODS: Adult females with confirmed predominant stress urinary incontinence (UI) through cough stress test (CST) or urodynamics and failed two noninvasive incontinence therapies. Effectiveness endpoints included objective dryness, negative CST, adverse events, and revision/resurgery through 36 months. The primary effectiveness endpoint was reduction from baseline in 24-h pad weight of ≥50% at 6 months, as requested by the FDA, and is included as a study point in this paper. Primary safety endpoint was rate of related serious adverse events (SAE) through 36 months. Noninferiority margins of 15% and 10% were prespecified for the effectiveness and safety endpoints. Due to the observational nature of the cohort study, a propensity methodology was conducted to assess the effect of potential confounding variables on the primary endpoints between groups. RESULTS: Three hundred fifty-five women underwent the sling procedure (n = 184 Altis; n = 171 Comparator). One hundred fourty (76%) Altis subjects and 101 (59%) Comparator subjects completed follow-up through 36 months. At 36 months, for the effectiveness endpoint, the difference in proportions of -0.005 for Altis versus Comparator (95% confidence interval [CI]: -0.102 to 0.092) was statistically significant (p = 0.002), supporting the hypothesis that Altis is noninferior to Comparator. Furthermore, both groups demonstrated high objective efficacy; in the Altis arm n = 99 (81.8%) subjects were a success, and in the Comparator arm, n = 79 (82.3%) subjects were a success. Additionally, regarding the CST, Altis was found to be noninferior to the Comparator at every study visit, and the rate of negative CST remained above 80% for both groups (p < 0.001). At 36 months, Altis (n = 2; 1.1%) and Comparator (n = 4; 2.3%) subjects experienced a device and/or procedure-related SAE. The difference in proportions of 0.013 for Altis versus Comparator (95% CI: -0.023 to 0.048) was statistically significant (p < 0.001), demonstrating that Altis is noninferior to Comparator with respect to the primary safety endpoint throughout the study. There were 62 (36.3%) retropubic midurethral slings (RMUS), 96 (56.1%) transobturator midurethral slings (TMUS), and 13 (7.6%) SIS slings in the Comparator group. For the 36 month effectiveness endpoint, assessing the noninferiority of Altis versus RMUS and Altis versus TMUS, 99 (81.8%) Altis and 37 (90.2%) RMUS were a success, trending toward statistical significance, however, it cannot be determined to be noninferior (p = 0.092). Ninty-nine (81.8%) Altis and 33 (71.7%) TMUS were a success; this was statistically significant (p < 0.001), demonstrating Altis was noninferior to TMUS. Rates of negative CST were 122 (87.1%) Altis, 40 (93.0%) RMUS (p < 0.001), and 44 (91.7%) TMUS (p < 0.001). CST demonstrated that Altis was noninferior to RMUS and Altis was noninferior to TMUS at 36 months. CONCLUSION: Altis single-incision sling was noninferior to standard midurethral sling for treatment of stress UI, throughout the study and at 36 months. Furthermore, adverse event rates were low.

A Multicenter Prospective Study Evaluating Efficacy and Safety of a Single-incision Sling Procedure for Stress Urinary Incontinence.

STUDY OBJECTIVE: The aim of the Altis 522 study was to compare the safety and efficacy of the Altis Single-Incision Sling System (SIS) (Coloplast, Minneapolis, MN) with standard midurethral transobturator and/or retropubic slings through 36 months. In this report, we present data through 12 months of follow-up. DESIGN: Postmarket, prospective, multicenter, nonrandomized cohort design. SETTING: The study was performed at 23 hospitals in the United States and Canada. PATIENTS: Adult female patients with stress urinary incontinence (SUI) clinically indicated for an incontinence sling were treated (n = 355). INTERVENTIONS: Altis SIS was compared with any Food and Drug Administration-cleared transobturator or retropubic sling. MEASUREMENTS AND MAIN RESULTS: Collected measures included device- and/or procedure-related serious adverse events, relevant nonserious and all adverse events, and revision surgery. Objective efficacy measures included 24-hour pad weight, dryness (defined as pad weight ≤4.0 g), and cough stress test. Subjective outcome measures included patient global impression of improvement, urogenital distress inventory, Incontinence Impact Questionnaire-Short Form, Surgical Satisfaction Questionnaire, and visual analog scale for pain. At 12 months, 24-hour pad weight success (≥50% reduction), negative cough stress test, patient global impression of improvement, urogenital distress inventory, and Incontinence Impact Questionnaire-Short Form appeared similar between groups. Through 12 months, 2 subjects in the Altis group and 3 subjects in the comparator group experienced a serious device- and/or procedure-related adverse event. In the Altis group, 1 subject (0.5%) experienced a device revision, and 1 subject (0.5%) had the device explanted. In the comparator group, 7 subjects (4.1%) experienced a device revision, and 1 device (0.6%) was explanted before the 12-month visit. The occurrence of relevant nonserious procedure and/or device-related adverse events was similar between groups. CONCLUSION: At 12-months follow-up, safety and efficacy appeared similar between Altis SIS and standard transobturator and retropubic midurethral slings.

Food systems for sustainable development: proposals for a profound four-part transformation.

Evidence shows the importance of food systems for sustainable development: they are at the nexus that links food security, nutrition, and human health, the viability of ecosystems, climate change, and social justice. However, agricultural policies tend to focus on food supply, and sometimes, on mechanisms to address negative externalities. We propose an alternative. Our starting point is that agriculture and food systems' policies should be aligned to the 2030 Agenda for Sustainable Development. This calls for deep changes in comparison with the paradigms that prevailed when steering the agricultural change in the XXth century. We identify the comprehensive food systems transformation that is needed. It has four parts: first, food systems should enable all people to benefit from nutritious and healthy food. Second, they should reflect sustainable agricultural production and food value chains. Third, they should mitigate climate change and build resilience. Fourth, they should encourage a renaissance of rural territories. The implementation of the transformation relies on (i) suitable metrics to aid decision-making, (ii) synergy of policies through convergence of local and global priorities, and (iii) enhancement of development approaches that focus on territories. We build on the work of the "Milano Group," an informal group of experts convened by the UN Secretary General in Milan in 2015. Backed by a literature review, what emerges is a strategic narrative linking climate, agriculture and food, and calling for a deep transformation of food systems at scale. This is critical for achieving the Sustainable Development Goals and the Paris Agreement. The narrative highlights the needed consistency between global actions for sustainable development and numerous local-level innovations. It emphasizes the challenge of designing differentiated paths for food systems transformation responding to local and national expectations. Scientific and operational challenges are associated with the alignment and arbitration of local action within the context of global priorities.

Assessing effects of PCB exposure on American mink (Mustela vison) abundance in Portland Harbor.

This article presents an integrated analysis using a Monte Carlo exposure model, dose­response effects model and habitat,and population dynamics models, all of which allow us to quantitatively estimate the effects of polychlorinated biphenyl (PCB)exposure on American mink (Mustela vison) abundance at the Portland Harbor Superfund Site (Site), and the associated uncertainties. The Site extends from river mile 1.9 of the Lower Willamette River, near its confluence with the Columbia River, to river mile 11.8, just downstream of downtown Portland, Oregon. The potential effects of PCBs on the American mink population were evaluated in the Baseline Ecological Risk Assessment (BERA) due to the historical presence of mink in the are a and because mink are known to be highly sensitive to the effects of PCBs. Hazard quotients (HQs) calculated in the BERA indicated that PCB concentrations measured in Portland Harbor fish were above levels known to cause reproductive effects in mink. Further analysis was needed to evaluate the potential magnitude of effects on the Site mink population. The integrated analysis presented herein demonstrates that if an effect of PCB exposure is a less than 30% reduction in kit production, then PCB remediation is not expected to have any effect on mink abundance. This is a Site­specific conclusion that depends on the quality, abundance, and distribution of mink habitat in Portland Harbor. The PCB dose associated with a 30% reduction in kit production was calculated as 101 mg/kg bw/d (90% CI » 69­146 mg/kg bw/d). The mink PCB dose estimates from the Portland Harbor BERA indicate that if mink are present, their baseline exposure levels probably exceed 101 mg/kg bw/d. Therefore, some level of reduction in PCB exposure could be beneficial to the species if the study area provides sufficient habitat to support a mink population. This analysis demonstrates that risk analysis for population­level assessment endpoints benefits from analyses beyond those that calculate exposure and predict organism­level effects. Evaluation of population­level impacts provides risk managers with a richer perspective within which to evaluate the environmental protectiveness and cost effectiveness of feasibility study alternatives across a range of potential remediation goals.

Neutrophils, not monocyte/macrophages, are the major splenic source of postburn IL-10.

Burn induces myeloid-derived suppressor cells (MDSCs), a heterogeneous population of immature polymorphonuclear neutrophils (PMNs) and monocytes, which protect against infection. Previous work from our laboratory demonstrated that inflammatory monocytes (iMos) were the major MDSC source of TNF-α in the postburn spleen, and we hypothesized that they were also the major source of postburn IL-10. To test this hypothesis, we examined cytokine production by postburn CCR2 knockout (KO) mice, which have fewer iMos than burn wild-type (WT) splenocytes, but equal numbers of PMNs and F4/80 macrophages. Using cell sorting and/or intracellular cytokine techniques, we examined IL-10 production by postburn PMNs and iMos. Finally, we compared IL-10 production by postburn PMNs and iMos with culture-derived MDSCs. Splenocytes from postburn CCR2 KO mice produced less IL-6 and TNF-α than WT burn splenocytes in response to LPS, but KO and WT burn splenocytes produced equal amounts of IL-10 in response to peptidoglycan. Depletion of PMNs from postburn splenocytes led to reductions in IL-10 and increases in IL-6 and TNF-α in response to peptidoglycan, but not in response to LPS. Sorting or intracellular cytokine techniques gave consistent results: Burn PMNs made more IL-10 than sham PMNs and also more IL-10 than burn or sham iMos. Polymorphonuclear neutrophil and iMos subpopulations from culture-derived MDSCs produced the same cytokine profiles in response to LPS and peptidoglycan as did the PMNs and iMos from postburn spleens: PMNs made IL-10, whereas iMos made IL-6. Finally, LPS-induced mortality of burn mice was made worse by anti-Gr-1 depletion of all PMNs and 66% of iMos from burn mice. This suggests that PMNs play a primarily anti-inflammatory role in vitro and in vivo.

Alcohol mortality: a comparison of spatial clustering methods.

The identification of spatial clusters of alcohol mortality can be a key tool in identifying locations that are suffering from alcohol-related problems or are at risk of experiencing those types of problems. This study compares two methods for identifying statistically significant spatial clusters of county-level alcohol mortality rates in New York. One method utilizes a local indicator of spatial association to determine which groups of neighboring counties have rates that are significantly related to each other. The other method is a spatial scan technique that calculates a maximum likelihood ratio of cases relative to the underlying population to identify the group of counties that rejects the null hypothesis of "no clustering". The results show that because each technique bases its cluster detection on its own criteria, different counties are selected by each method. However, the overlap of the selections indicates that the two analytic methods illustrate different elements of the same clusters. Consequently, these spatial analytic techniques are seen as complimentary and are best used in tandem rather than individually. These findings suggest that multiple methods are a preferred approach to identifying clusters of alcohol-related mortality at the county level.