Adiposity is related to gender differences in impaired stress-induced pressure natriuresis

The purpose of this study was to determine if there are gender differences in stress-induced pressure natriuresis and to examine the effects of adiposity on these differences. The subjects were 151 boys and 141 girls 15 to 18 years of age who underwent a 5-hour stress protocol (2-hour prestress, 1-hour stress, 2-hour poststress) after being brought into similar levels of sodium balance. The gender-by-condition interaction was significant for systolic and diastolic blood pressure (P=0.001 for both), and the effect of condition was significant for sodium excretion (P=0.001). Systolic blood pressure was higher for boys throughout the protocol (P=0.001 for each) and correlated with body mass index at each condition (range in r=0.28 to 0.35; P<0.001 for each). Hemodynamically, in boys body mass index was correlated with cardiac output during stress (r=0.23; P=0.006), which was correlated with systolic blood pressure (r=0.21; P=0.01). With respect to natriuresis, body mass index was inversely correlated with sodium excretion during stress (r=-0.22; P=0.008) and positively correlated with angiotensin II in a subsample of boys (n=89: r=0.31; P=0.003). The inverse correlation between angiotensin II and sodium excretion during stress approached significance (r=-0.17; P<0.06). Similar results were not observed for girls. In conclusion, gender differences in stress-induced pressure natriuresis appear to be related to the influence of adiposity on both blood pressure and natriuresis.     

Transmission of drug-resistant tuberculosis among treated patients in Shanghai, China

We sought to determine whether patients who had therapy failure with increasingly drug-resistant strains of tuberculosis had primary or acquired drug resistance, by genotyping the initial and subsequent drug-resistant clinical isolates of Mycobacterium tuberculosis collected from patients by the Shanghai Centers for Disease Control and Prevention over the course of a 5-year period. The vast majority of patients (27/32) had primary drug resistance, indicating transmission of a drug-resistant strain of M. tuberculosis. Only 16% (5/32) had acquired drug resistance because of a poor treatment regimen or nonadherence to an adequate regimen. Our findings highlight the urgency of increasing efforts to interrupt the transmission of drug-resistant tuberculosis in communities and facilities in Shanghai, China.     

The effect of age on short-term outcomes after abdominal surgery for pelvic organ prolapse

OBJECTIVES: To compare perioperative morbidity and 1-year outcomes of older and younger women undergoing surgery for pelvic organ prolapse (POP). DESIGN: Prospective ancillary analysis. SETTING: Academic medical centers in National Institutes of Health, National Institute of Child Health and Human Development Colpopexy and Urinary Reduction Study. PARTICIPANTS: Women with POP and no symptoms of stress incontinence. INTERVENTION: Abdominal sacrocolpopexy with randomization to receive Burch colposuspension for treatment of possible occult incontinence or not. MEASUREMENTS: Perioperative complications and Pelvic Organ Prolapse Quantification and quality-of-life (QOL) questionnaires (Pelvic Floor Distress Inventory, Pelvic Floor Impact Questionnaire, and Medical Outcomes Study Short-Form Health Survey (SF-36) preoperatively, immediately postoperatively, and 6 weeks and 3 and 12 months postoperatively). RESULTS: Three hundred twenty-two women aged 31 to 82 (21% aged > or =70), 93% white. Older women had higher baseline comorbidity (P<.001) and more severe POP (P=.003). Controlling for prolapse stage and whether Burch was performed, there were no age differences in complication rates. Older women had longer hospital stays (3.1+/-1.0 vs 2.7+/-1.5 days, P=.02) and higher prevalence of incontinence at 6 weeks (54.7% vs 37.2%, P=.005). At 3 and 12 months, there were no differences in self-reported incontinence, stress testing for incontinence, or prolapse stage. Improvements from baseline were significant on all QOL measures but with no age differences. CONCLUSION: Outcomes of prolapse surgery were comparable between older and younger women except that older women had slightly longer hospital stays.     

Gastrointestinal Tract Pathology in a BALB/c Niemann–Pick Disease Type C1 Null Mouse Model

Background

Niemann–Pick disease, type C (NPC) is a rare lysosomal storage disorder characterized by progressive neurodegeneration, splenomegaly, hepatomegaly, and early death. NPC is caused by mutations in either the NPC1 or NPC2 gene. Impaired NPC function leads to defective intracellular transport of unesterified cholesterol and its accumulation in late endosomes and lysosomes. A high frequency of Crohn disease has been reported in NPC1 patients, suggesting that gastrointestinal tract pathology may become a more prominent clinical issue if effective therapies are developed to slow the neurodegeneration. The Npc1 ^nih mouse model on a BALB/c background replicates the hepatic and neurological disease observed in NPC1 patients. Thus, we sought to characterize the gastrointestinal tract pathology in this model to determine whether it can serve as a model of Crohn disease in NPC1.

Methods

We analyzed the gastrointestinal tract and isolated macrophages of BALB/cJ cNctr-Npc1m1N/J (Npc1^?/?) mouse model to determine whether there was any Crohn-like pathology or inflammatory cell activation. We also evaluated temporal changes in the microbiota by 16S rRNA sequencing of fecal samples to determine whether there were changes consistent with Crohn disease.

Results

Relative to controls, Npc1 mutant mice demonstrate increased inflammation and crypt abscesses in the gastrointestinal tract; however, the observed pathological changes are significantly less than those observed in other Crohn disease mouse models. Analysis of Npc1 mutant macrophages demonstrated an increased response to lipopolysaccharides and delayed bactericidal activity; both of which are pathological features of Crohn disease. Analysis of the bacterial microbiota does not mimic what is reported in Crohn disease in either human or mouse models. We did observe significant increases in cyanobacteria and epsilon-proteobacteria. The increase in epsilon-proteobacteria may be related to altered cholesterol homeostasis since cholesterol is known to promote growth of this bacterial subgroup.

Conclusions

Macrophage dysfunction in the BALB/c Npc1^?/? mouse is similar to that observed in other Crohn disease models. However, neither the degree of pathology nor the microbiota changes are typical of Crohn disease. Thus, this mouse model is not a good model system for Crohn disease pathology reported in NPC1 patients.

     

Integrating research and system-wide practice in public health to enhance the evidence-base of interventions: lessons learnt from Better Start Bradford

Background

Many interventions that are delivered within public health services have little evidence of effectiveness. An efficient way to improve the evidence-base of public health interventions is to integrate research into system-wide practice, and to evaluate interventions in partnership with stakeholders and the local community. Evaluation of interventions that are being delivered as a part of usual practice offers valuable opportunities to contribute to the evidence base but also generates challenges. We aimed to develop innovative methods and pragmatic strategies to overcome these challenges and achieve relevant and robust evaluations within a complex and changing system.

Mothers’ Selection of Future Primary Caregivers in Rural West Java,Indonesia

This study analyzes mothers’ preference of a future primary caregiver by using within-family analysis approach in the context of Sundanese population in rural West Java, Indonesia. This is a cross-sectional study involving healthy mothers (60–69 years old) with a perfect score of Instrumental Activity of Daily Living (IADL), and who had at least two living children. The within-family analysis of a selection of future caregivers was conducted based on the report from 177 mothers of their 904 children using multilevel modeling with binomial outcome. Being a daughter, older, emotionally the closest to the mother, having supported the mother in the past, being perceived as future bequest receiver, and being geographically closer to mother increased the chance of being selected as preferred future primary caregivers. There were also cross-level effects of socioeconomic status (SES) on the selection of future primary caregivers by mothers, where poor mothers tend to pick poor children as their future primary caregivers. The results were contrasted to the findings from a similar study conducted in the United States. In addition, the importance of knowledge about future care preference and its implications for intervention is discussed.     

Association of Dialysis Modality and Cardiovascular Mortality in Incident Dialysis Patients

Background and objectives: The aim of the investigation presented here was to compare the rates, causes, and timing of cardiovascular (CV) death in incident peritoneal dialysis (PD) and hemodialysis (HD) patients.Design, setting, participants, & measurements: The study included all adult Australian and New Zealand patients commencing dialysis between January 1, 1997 and December 31, 2007. Rates of and times to CV death were compared by incident rate ratios, cumulative incidence, and multivariable Cox proportional hazards model analyses. Dialysis modality was included in the model as a time-varying covariate, and a competing risks approach was used to obtain cause-specific hazard ratios.Results: Of the 24,587 patients who commenced dialysis (first treatment PD n = 6521; HD n = 18,066) during the study, 5669 (21%) died from CV causes [PD 2044 (28%) versus HD 3625 (21%)]. The incidence rates of CV mortality in PD and HD patients were 9.99 and 7.96 per 100 patient-years, respectively (incidence rate ratio PD versus HD, 1.25; 95% confidence interval 1.12 to 1.32). PD was consistently associated with an increased hazard of CV death compared with HD after 1 yr of treatment. This increased risk in PD patients was largely accounted for by an increased risk of death due to myocardial infarction.Conclusions: Dialysis modality is significantly associated with the risk, causes, and timing of CV death experienced by ESRD patients in Australia and New Zealand.Cardiovascular disease (CVD) represents the leading cause of death in dialysis patients, accounting for up to 40% of deaths in Australia, New Zealand, and the United States (1,2). Individuals with chronic kidney disease (CKD) have up to a 10- to 20-fold greater risk of cardiac death than age- and sex-matched controls without CKD (3,4). Once dialysis patients develop cardiac events, they are significantly less likely to receive important interventions and are far more likely to die than patients without CKD (5).The increased incidence of CVD in dialysis patients is only partially explained by an increased prevalence of traditional risk factors, such as hypertension, diabetes mellitus, dyslipidemia, smoking, obesity, and physical inactivity (6,7). Additional risk may be conferred by nontraditional factors that are frequently observed in advanced CKD, such as hyperhomocysteinemia, anemia, abnormal calcium/phosphate metabolism, inflammation, malnutrition, oxidative stress, and elevated lipoprotein(s) (6,8–11).There is limited evidence that dialysis modality may also influence CVD risk. Bleyer et al. (12) observed an increased risk of cardiac death in hemodialysis (HD) patients immediately after weekends, possibly related to the more frequent occurrence of hyperkalemia and fluid overload at this time. In contrast, the continuous nature of peritoneal dialysis (PD) may potentially minimize cardiovascular risk related to fluctuations in body fluid and electrolyte compositions. HD patients may also be exposed to a greater risk of CVD compared with PD patients as a result of more rapid loss of residual renal function (13,14) and more hyperdynamic circulation conferred by the presence of an arteriovenous fistula and extracorporeal circulation (15). On the other hand, PD patients are exposed to greater amounts of glucose in dialysate, leading to a much higher prevalence of insulin resistance, dyslipidemia, and metabolic syndrome (16). There is also evidence that PD patients exhibit greater coagulability, possibly related to dyslipidemia (17). Despite observed differences in known CVD risk factors between PD and HD patients, there has been little study to date of the influence of dialysis modality on CVD risk. Kennedy et al. (6) observed that PD was of borderline statistical significance (P = 0.06) as an independent predictor of carotid atherosclerosis in stage 5 CKD. Previous registry studies have shown conflicting results with respect to the influence of dialysis modality on all-cause mortality (reviewed in reference 18), but none have specifically examined cardiovascular mortality. Moreover, many of these studies have suffered from serious limitations, such as inclusion of prevalent patients, use of proportional versus nonproportional hazards models, single-center design, data coding ambiguity, use of outdated data, dialysis modality selection bias, lack of adjustment for demographic and clinical variables, and residual confounding (18). The aim of the study presented here was to evaluate the effects of dialysis modality on the frequency, types, and causes of cardiovascular mortality in a large, incident, ESRD population.     

Benefits of Catheter Thrombectomy during Carotid Stenting: A Preliminary Study

Despite the use of distal embolic protection devices (DEPs) in carotid artery (CA) stenting, an appreciable risk of stroke exists, particularly in symptomatic patients. The mechanism of embolic events is possibly related to microembolization of atherothrombotic débris that remains or forms on the stent struts. This study evaluated the safety of using thrombus-extraction catheters in the setting of CA stenting.From August 2006 through June 2008, 43 symptomatic and asymptomatic patients with severe CA stenosis (>90%) underwent CA stenting with DEPs. After stenting and before removal of the DEP, an extraction catheter was passed through the stented segment. The extracted volume and the filtered extracted volume were visually examined for débris. The primary outcome was a composite of stroke and death at 30 days. Outcomes were compared with those in a control population of 783 patients who underwent CA stenting with a DEP, but without prophylactic thrombus aspiration. Retrospective analysis was performed on prospectively gathered data.Substantial amounts of atherothrombotic débris were extracted from the stented segment in all 43 thrombectomy patients, none of whom died or experienced periprocedural stroke. In the control group, 3.9% of patients experienced these outcomes. Differences in primary outcome did not reach statistical significance.We conclude that the prophylactic use of extraction catheters is safe and does not incur periprocedural events. The results of this preliminary study are encouraging, although larger, randomized trials (optimally using diffusion-weighted magnetic resonance imaging) are needed in order to evaluate this technique''s potential benefits in reducing neurologic complications.Key words: Angioplasty, balloon/instrumentation/methods; atherosclerosis/therapy; balloon dilatation/instrumentation/methods; carotid arteries/surgery; carotid stenosis/complications/therapy; catheterization; equipment design; stents; stroke/prevention & control; survival rate; treatment outcomeAdvances in the endovascular treatment of carotid arterial (CA) occlusive disease have led to a reduction in treatment-related adverse events. Distal embolic protection devices (DEPs), lower-profile sheaths and stent-delivery systems, and more aggressive periprocedural antiplatelet therapy have all contributed to this improvement.^1,2Despite the improved procedural safety afforded by these technical advances, the risk of periprocedural stroke consequent to CA stenting is not negligible.³ This risk is particularly high in symptomatic patients, in octogenarians, and in subsets of patients with certain lesions, such as those with critical stenosis and ulcerated lesions.^3,4 Observational data from a prospective multicenter registry that was compiled in order to assess outcomes of CA stenting revealed that 4.8% of the patients who underwent neuroprotected carotid stenting experienced a stroke.⁵ In addition to symptomatic strokes, subclinical microinfarctions after CA stenting range from 22% to as high as 41.5%.^6–8 During intermediate-term follow-up, these microinfarctions have been associated with cognitive decline.⁹ Observational data also suggest that most neurologic events (77%) occur after the procedure has been completed.⁵ The mechanisms that underlie late occurrence of neurologic events remain undefined; however, they may be secondary to embolization of atherothrombotic débris after a DEP has been removed. Consequently, we surmised that the use of an aspiration catheter might reduce distal embolization of atherothrombotic material after stenting, via the aspiration of friable atherothrombotic débris from the stent struts while the DEP is still deployed.We sought to investigate the safety of this novel technique by using the PRONTO® Extraction catheter (Vascular Solutions, Inc.; Minneapolis, Minn) or the QuickCat™ Extraction Catheter (Kensey Nash Corporation; Exton, Pa) as an adjunct to filter-based DEPs in the setting of CA stenting.