Associations between Socioeconomic Status and Urge Urinary Incontinence: An Analysis of NHANES 2005 to 2016.

PURPOSE: Urge urinary incontinence significantly impacts quality of life. We investigated the association between urge urinary incontinence and socioeconomic status in a nationally representative adult population. MATERIALS AND METHODS: We analyzed the 2005 to 2016 NHANES (National Health and Nutrition Examination Survey), a United States population based, cross-sectional study. Urge urinary incontinence was determined by self-report of leaking urine before reaching the toilet. Socioeconomic status was represented by the poverty income ratio, which reflects the family income relative to poverty thresholds specific to that year and household size. Survey weighted logistic regression models were used to analyze the relationship between socioeconomic status and the poverty income ratio. Multiplicative terms were applied to test for interaction in prespecified subgroups of interest. RESULTS: A total of 25,553 participants were included in the final analysis, representing 180 million people in the United States. Of the participants 19.4% reported any urge urinary incontinence, 4.2% reported weekly urge urinary incontinence and 1.6% reported daily urge urinary incontinence. In the fully adjusted multivariable models those with a poverty income ratio less than 2.00 showed significantly higher odds of any urge urinary incontinence compared to the group with a poverty income ratio of 2.00 or greater (OR 1.17, 95% CI 1.05-1.30, p=0.003). There was increasing strength of association for weekly and daily urge urinary incontinence (OR 1.31, 95% CI 1.12-1.55, p <0.001, and OR 1.60, 95% CI 1.23-2.09, p=0.001, respectively). Individual interaction analyses revealed no significant effect of female gender, age greater than 50 years, body mass index 30 kg/m2 or greater, or less than a high school education on the association of urge urinary incontinence with the poverty income ratio. CONCLUSIONS: This study revealed a significant association between urge urinary incontinence and socioeconomic status after meaningful adjustment for covariates. Health care interventions targeting low socioeconomic status individuals with urge urinary incontinence are needed to address this disparity.

Understanding the Link Between Gut Microbiome and Urinary Stone Disease.

PURPOSE OF REVIEW: With recent advances in sequencing technologies and increasing research into the gut microbiome (GMB), studies have revealed associations between the GMB and urinary stone disease (USD). We sought to determine whether the evidence pointed towards a few specific gut bacteria or the broader GMB network is seemingly responsible for this relationship. RECENT FINDINGS: Initially, Oxalobacter formigenes (OF) was pursued as the main link between GMB and USD given its ability to degrade oxalate in the gut. However, the latest studies consistently suggest that the entire GMB is much more likely to be involved in handling oxalate absorption and other risk factors for urinary stone formation, rather than just a few microbiota. The GMB has complex networks that are likely involved in the pathophysiology of USD, although the causal mechanisms remain unclear. With increasing interest and research, potential modalities that act on the GMB may help to prevent incidence of USD.

Micronutrient inadequacy and urinary stone disease: an analysis of the National Health and Nutrition Examination Survey 2007-2018.

Urinary stone disease is common and affects approximately 10% of the American adults. The role of diet in stone formation is well-recognized; however, the literature focus has been on dietary excess rather than micronutrient inadequacy. As patients with stones may be at risk for nutrient inadequacies, we investigated the role of micronutrient inadequacy in stone formation by performing a cross-sectional analysis of the National Health and Nutrition Examination Survey on adults who were not taking dietary supplements. Micronutrient intake was obtained from 24-h dietary recalls, and usual intake was calculated. Survey-weighted, adjusted logistic regression was used for an incident analysis on having any history of stones. An additional analysis on recurrent stone-formers was performed with the outcome being 2 or more stones passed. Finally, a sensitivity analysis using quasi-Poisson regression was performed with the outcome being number of stones passed. There were 9777 respondents representing 81,087,345 adults, of which 9.36% had a stone history. Our incident analysis revealed inadequate vitamin A intake to be associated with stone formation (OR 1.33, 95% CI: 1.03-1.71). Recurrent analysis did not find any significant associations, while our sensitivity analysis revealed inadequate vitamin A (IRR 1.96, 95% CI: 1.28-3.00) and pyridoxine (IRR 1.99, 95% CI: 1.11-3.55) to be associated with a higher number of recurrent stones. Hence, inadequate dietary intake of vitamin A and pyridoxine was associated with nephrolithiasis. Further research is needed to identify the roles of these micronutrients in stone-formers and the potential for evaluation and treatment.

Representation of Minority Groups in Key Pelvic Floor Disorder Trials.

BACKGROUND: Multicenter randomized clinical trials on pelvic floor disorders (PFDs) support evidence-based care. However, many of these studies include homogenous study populations lacking diversity. Heterogeneous sampling allows for greater generalizability while increasing knowledge regarding specific subgroups. The racial/ethnic makeup of key pelvic floor disorder (PFD) trials has not been examined. OBJECTIVE: This study aimed to investigate racial/ethnic representation in major PFD clinical trials in comparison to racial/ethnic distribution of PFD in the National Health and Nutritional Examination Survey (NHANES). METHODS: Demographic data were extracted from completed PFD Network (PFDN) and Urinary Incontinence Treatment Network studies, which have resulted in nearly 200 publications. Prevalence of PFD by race/ethnicity was obtained from the NHANES. A representative index (Observed "n" by PFD study/Expected "n" based on the NHANES-reported prevalence) was calculated as a measure of representation. Meta-analyses were performed for each outcome and overall with respect to race/ethnicity. RESULTS: Eighteen PFDN/Urinary Incontinence Treatment Network studies were analyzed. White women comprised 70%-89% of PFD literature; Black women, 6%-16%; Hispanic women, 9%-15%; Asians, 0.5%-6%; and American Indians, 0%-2%. Representation of White women was higher in 13 of 18 PFDN studies compared with the NHANES prevalence data. Representation of Black women was either decreased or not reported in 10 of 18 index studies compared with the NHANES prevalence data. Hispanic women were absent or underrepresented in 7 of 18 PFDN studies compared with the prevalence data. CONCLUSIONS: Our examination of PFDN and other landmark trials demonstrates inconsistent reporting of minority subgroups, limiting applicability with respect to minority populations. Our study suggests that PFD research would benefit from targeted sampling of minority groups.

Kidney stone formation and the gut microbiome are altered by antibiotics in genetic hypercalciuric stone-forming rats.

Antibiotics can alter the gut microbiome (GMB), which may be associated with stone disease. We sought to determine the effect that antibiotics have on the GMB, urine ion excretion and stone formation in genetic hypercalciuric stone-forming (GHS) rats. 116th generation GHS rats were fed a fixed amount of a normal calcium (1.2%) and phosphate (0.65%) diet, and divided into three groups (n = 10): control (CTL) diet, or supplemented with ciprofloxacin (Cipro, 5 mg/day) or Bactrim (250 mg/day). Urine and fecal pellets were collected over 6, 12 and 18 weeks. Fecal DNA was amplified across the 16S rRNA V4 region. At 18 weeks, kidney stone formation was visualized by Faxitron and blindly assessed by three investigators. After 18 weeks, urine calcium and oxalate decreased with Bactrim compared to CTL and Cipro. Urine pH increased with Bactrim compared to CTL and Cipro. Urine citrate increased with Cipro compared to CTL and decreased by half with Bactrim. Calcification increased with Bactrim compared to CTL and Cipro. Increased microbial diversity correlated with decreased urinary oxalate in all animals (R = - 0.46, p = 0.006). A potential microbial network emerged as significantly associated with shifts in urinary pH. Bactrim and Cipro differentially altered the GMB of GHS rats. The Bactrim group experienced a decrease in urine calcium, increased CaP supersaturation and increased calcification. The GMB is likely a contributing factor to changes in urine chemistry, supersaturation and stone risk. Further investigation is required to fully understand the association between antibiotics, the GMB and kidney stone formation.

High fractional excretion of glycation adducts is associated with subsequent early decline in renal function in type 1 diabetes.

Increased protein glycation, oxidation and nitration is linked to the development of diabetic nephropathy. We reported levels of serum protein glycation, oxidation and nitration and related hydrolysis products, glycation, oxidation and nitration free adducts in patients with type 1 diabetes (T1DM) during onset of microalbuminuria (MA) from the First Joslin Kidney Study, a prospective case-control study of patients with T1DM with and without early decline in GFR. Herein we report urinary excretion of the latter analytes and related fractional excretion values, exploring the link to MA and early decline in GFR. We recruited patients with T1DM and normoalbuminuria (NA) (n = 30) or new onset MA with and without early GFR decline (n = 22 and 33, respectively) for this study. We determined urinary protein glycation, oxidation and nitration free adducts by stable isotopic dilution analysis liquid chromatography-tandem mass spectrometry (LC-MS/MS) and deduced fractional excretion using reported plasma levels and urinary and plasma creatinine estimates. We found urinary excretion of pentosidine was increased ca. twofold in patients with MA, compared to normoalbuminuria (0.0442 vs 0.0103 nmol/mg creatinine, P < 0.0001), and increased ca. threefold in patients with early decline in GFR, compared to patients with stable GFR (0.0561 vs 0.0176 nmol/mg creatinine, P < 0.01). Urinary excretion of all other analytes was unchanged between the study groups. Remarkably, fractional excretions of 6 lysine and arginine-derived glycation free adducts were higher in patients with early decline in GFR, compared to those with stable GFR. Impaired tubular reuptake of glycation free adducts by lysine and arginine transporter proteins in patients with early GFR decline is likely involved. We conclude that higher fractional excretions of glycation adducts are potential biomarkers for early GFR decline in T1DM and MA. Measurement of these analytes could provide the basis for identifying patients at risk of early decline in renal function to target and intensify renoprotective treatment.

Exploring the Association of Asthma with Urinary Stone Disease: Results from the National Health and Nutrition Examination Survey 2007-2014.

BACKGROUND: The prevalence of urinary stone disease (USD) and asthma is rising and has recently been associated in a pediatric population. OBJECTIVE: To investigate the association between asthma and USD in a nationally representative adult population. DESIGN, SETTING, AND PARTICIPANTS: We analyzed the National Health and Nutrition Examination Survey 2007-2014, a US population-based cross-sectional study. A history of asthma and USD was obtained by self-report to questionnaires. USD severity was represented by graded stratification into non-stone formers, single stone formers, and recurrent stone formers (>2 stones). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Odds ratios (ORs) for asthma were calculated for respondents with USD and separately for the graded USD groups. Survey-weighted logistic regression models included adjustments for demographics (model A), medical information (model B), and for relevant medications (model C). RESULTS AND LIMITATIONS: A total of 20 906 participants aged ≥20 yr were included in the analysis. Of these, 9.2% reported of having a history of kidney stones. Logistic regression analysis adjusted for demographics, medical conditions, and medications showed that stone formers had significantly increased odds of asthma (odds ratio=1.23; 95% confidence interval: 1.03-1.47; p=0.023). Separate logistic regression analysis demonstrated a graded association between single and recurrent stone formers and the odds of having asthma (p=0.01), which remained significant in the 20-50-yr-old population and the diabetic population, especially for recurrent stone formers. Causal relationships were limited by cross-sectional nature of the study. CONCLUSIONS: Increasing severity of USD is associated with an increase in odds for asthma among American adults, providing impetus for future studies into the mechanisms explaining this phenomenon. PATIENT SUMMARY: In this report, we looked at self-reported histories of asthma and urinary stone disease (USD) using information from a large US population. We found that asthma was associated with USD; however, further studies are needed to elucidate this relationship.

Ubiquitous antigen-specific T regulatory type 1 cells variably suppress hepatic and extrahepatic autoimmunity.

Peptide MHC class II-based (pMHCII-based) nanomedicines trigger the formation of multicellular regulatory networks by reprogramming autoantigen-experienced CD4+ T cells into autoimmune disease-suppressing T regulatory type 1 (TR1) cells. We have shown that pMHCII-based nanomedicines displaying liver autoimmune disease-relevant yet ubiquitously expressed antigens can blunt various liver autoimmune disorders in a non-disease-specific manner without suppressing local or systemic immunity against infectious agents or cancer. Here, we show that such ubiquitous autoantigen-specific T cells are also awakened by extrahepatic tissue damage and that the corresponding TR1 progeny can suppress experimental autoimmune encephalomyelitis (EAE) and pancreatic ß cell autoreactivity. In mice having EAE, nanomedicines displaying either ubiquitous or CNS-specific epitopes triggered the formation and expansion of cognate TR1 cells and their recruitment to the CNS-draining lymph nodes, sparing their liver-draining counterparts. Surprisingly, in mice having both liver autoimmunity and EAE, liver inflammation sequestered these ubiquitous or even CNS-specific TR1 cells away from the CNS, abrogating their antiencephalitogenic activity. In these mice, only the ubiquitous antigen-specific TR1 cells suppressed liver autoimmunity. Thus, the scope of antigen spreading in autoimmune disorders is larger than previously anticipated, involving specificities expected to be silenced by mechanisms of tolerance; the regulatory activity, but not the retention of autoreactive TR1 cells, requires local autoantigen expression.

Diurnal Glycemic Patterns during an 8-Week Open-Label Proof-of-Concept Trial of Empagliflozin in Type 1 Diabetes.

BACKGROUND: We recently reported improved glycemic control with reduced insulin dose in subjects with type 1 diabetes treated with the sodium glucose co-transporter-2 inhibitor empagliflozin. To further characterize the effects, we analyzed diurnal glycemic patterns by continuous glucose monitoring (CGM). METHODS: In an 8-week single-arm open-label pilot study of empagliflozin, we compared ambulatory glucose profiles produced from CGM data during 2-week intervals in a placebo run-in baseline period, end-of-treatment, and post-treatment. Change in glycemic exposure was evaluated by area under the median curve according to time of day (AUCTOTAL 12:00am-11:55pm; AUCDAY 7:05am-10:55pm, AUCNIGHT 11:00pm-7:00am), as well as glycemic variability, glycemic stability and time-in-target (≥70 to ≤140mg/dL). RESULTS: The 40 patients (26 on insulin pump) were aged 24±5 years and BMI 24.5±3.2 kg/m2. Consistent with the observed HbA1c decrease (8.0±0.9% to 7.6±0.9%, p<0.0001), normalized AUCTOTAL CGM decreased from 153.7±25.4 to 149.0±30.2mg/dL∙h at end-of-treatment (p = 0.31), and significantly increased post-treatment (164.1±29.5mg/dL∙h, p = 0.02). The numerical decrease in normalized AUCNIGHT (152.0±36.6 to 141.9±34.4mg/dL∙h, p = 0.13) exceeded AUCDAY (154.5±24.5 to 152.6±30.4mg/dL∙h, p = 0.65). Trends toward lower glycemic variability (83.1±18.9 to 75.6±28.6mg/dL, p = 0.06) and little change in glycemic stability (10.8±3.6 to 10.3±4.5mg/dL/h, p = 0.51) were observed. When empagliflozin was discontinued, these worsened relative to baseline (89.3±19.3mg/dL, p = 0.04 and 11.8±3.7mg/dL/hr, p = 0.08). Time-in-target numerically increased (40.2±11.9 to 43.1±13.5%, p = 0.69) at end-of-treatment but reversed post-treatment. Findings were similar on stratification of pump and MDI subjects. CONCLUSIONS: We observed that empagliflozin was associated with patterns of improved nighttime glycemia more prominent than daytime. TRIAL REGISTRATION: Clinicaltrials.gov NCT01392560.

Durable medical equipment: types and indications.

There are various treatments for musculoskeletal-related conditions, including the use of durable medical equipment (DME). Numerous DME devices are currently available. This article addresses several of the common DME devices used for treating upper and lower extremity orthopedic conditions.

Reliability and validity of a point-of-care sural nerve conduction device for identification of diabetic neuropathy.

BACKGROUND: Confirmation of diabetic sensorimotor polyneuropathy (DSP) relies on standard nerve conduction studies (NCS) performed in specialized clinics. We explored the utility of a point-of-care device (POCD) for DSP detection by nontechnical personnel and a validation of diagnostic thresholds with those observed in a normative database. RESEARCH DESIGN AND METHODS: 44 subjects with type 1 and type 2 diabetes underwent standard NCS (reference method). Two nontechnical examiners measured sural nerve amplitude potential (SNAP) and conduction velocity (SNCV) using the POCD. Reliability was determined by intraclass correlation coefficients (ICC [2], [1]). Validity was determined by Bland-Altman analysis and receiver operating characteristic curves. RESULTS: The 44 subjects (50% female) with mean age 56 ± 18 years had mean SNAP and SNCV of 8.0 ± 8.6 µV and 41.5 ± 8.2 m/s using standard NCS and 8.0 ± 8.2 µV and 49.9 ± 11.1 m/s using the POCD. Intrarater reproducibility ICC values were 0.97 for SNAP and 0.94 for SNCV while interrater reproducibility values were 0.83 and 0.79, respectively. Mean bias of the POCD was -0.1 ± 3.6 µV for SNAP and +8.4 ± 6.4 m/s for SNCV. A SNAP of ≤6 µV had 88% sensitivity and 94% specificity for identifying age-and height-standardized reference NCS values, while a SNCV of ≤48 m/s had 94% sensitivity and 82% specificity [corrected].. Abnormality in one or more of these thresholds was associated with 95% sensitivity and 71% specificity for identification of DSP according to electrophysiological criteria. CONCLUSIONS: The POCD demonstrated excellent reliability and acceptable accuracy. Threshold values for DSP identification validated those of published POCD normative values. We emphasize the presence of measurement bias--particularly for SNCV--that requires adjustment of threshold values to reflect those of standard NCS.

Effect of prostaglandin E2 injection on the structural properties of the rat patellar tendon.

BACKGROUND: Increased tendon production of the inflammatory mediator prostaglandin E2 (PGE2) has been suggested to be a potential etiologic agent in the development of tendinopathy. Repeated injection of PGE2 into tendon has been proposed as a potential animal model for studying treatments for tendinopathy. In contrast, nonsteroidal anti-inflammatory drugs (NSAIDs) which inhibit PGE2 production and are commonly prescribed in treating tendinopathy have been shown to impair the healing of tendon after acute injury in animal models. The contradictory literature suggests the need to better define the functional effects of PGE2 on tendon. Our objective was to characterize the effects of PGE2 injection on the biomechanical and biochemical properties of tendon and the activity of the animals. Our hypothesis was that weekly PGE2 injection to the rat patellar tendon would lead to inferior biomechanical properties. METHODS: Forty rats were divided equally into four groups. Three groups were followed for 4 weeks with the following peritendinous injection procedures: No injection (control), 4 weekly injections of saline (saline), 4 weekly injections of 800 ng PGE2 (PGE2-4 wks). The fourth group received 4 weekly injections of 800 ng PGE2 initially and was followed for a total of 8 weeks. All animals were injected bilaterally. The main outcome measurements included: the structural and material properties of the patellar tendon under tensile loading to failure, tendon collagen content, and weekly animal activity scores. RESULTS: The ultimate load of PGE2-4 wks tendons at 4 weeks was significantly greater than control or saline group tendons. The stiffness and elastic modulus of the PGE2 injected tendons at 8 weeks was significantly greater than the control or saline tendons. No differences in animal activity, collagen content, or mean fibril diameter were observed between groups. CONCLUSIONS: Four weekly peritendinous injections of PGE2 to the rat patellar tendon were not found to be an effective model of clinical tendinopathy. In contrast, improved structural and material properties of the patellar tendon were found after PGE2 injection. While PGE2 has been thought to have a contributory role in the development of tendinopathy and anti-inflammatory medications remain a common treatment, our results suggest a positive role of PGE2 in tendon remodeling in some circumstances.