Background and Aims: South Africa is a middle-income country with high levels of income inequality and a rapidly aging population and increasing dementia prevalence. Little is known about which risk factors for dementia are important and how they differ by social determinants of health as well as key demographic characteristics such as sex and wealth. We sought to calculate the population attributable risks (PARs) for established potentially modifiable risk factors for dementia among these different groups. Methods: We obtained risk factor prevalence from population-based surveys for established dementia risk factors (diabetes, midlife hypertension, midlife obesity, physical inactivity, depression, smoking, low educational attainment, social isolation). We used relative risk estimates reported in previous meta-analyses and estimated PARs using Levin's formula and accounting for communality. We tested for one-way and two-way interactions by sex and wealth using Pearson's χ2. In stratified analyses, we performed tests for trend using logistic regression. Results: The prevalence of established risk factors for dementia ranged from 5% for depression to 64% for low education. After accounting for communality, the risk factors contributing the greatest PAR were low education (weighted PAR 12%, 95% CI 7% to 18%), physical inactivity (9, 5-14%), and midlife hypertension (6, 5-14%). Together, 45% of dementia cases may be attributable to modifiable risk factors (95% CI 25-59%). We found significant interactions (p < 0.005) between sex, wealth, or both (sex ^* wealth) and each risk factor except social isolation and physical activity. Low education was inversely associated with wealth in both male and female. The PAR for midlife hypertension, obesity, and diabetes was associated with increasing wealth, and was higher in female. In contrast, the PAR for smoking was higher in male (8% vs. 2%) and was associated with increasing wealth among female only. We found that either a strategy of large reductions in selected risk factors with the highest PAR (midlife hypertension, smoking, physical inactivity) or small reductions across all risk factors could potentially reduce dementia cases by as many as 250,000 by 2050. Discussions: The potential impact on dementia risk by decreasing exposure to established dementia risk factors is large and differs by sex and social determinants of health like wealth. Risk factor PAR should inform national and local health policy dementia initiatives in South Africa including which risk factors to target in the whole population and which to target in high-risk groups for maximum public health benefit.

Objectives

To systematically review risks and summarize reported complication rates associated with the performance of endoscopic retrograde cholangiopancreatography (ERCP) in children during the past 2 decades.

Study design

A systematic literature search of MEDLINE, Embase, and Web of Science from January 1995 to January 2016 was conducted for observational studies published in English. Studies reporting ERCP complications in patients <21 years without history of liver transplant or cholecystectomy were included. A summary estimate of the proportion of children who experienced complications following ERCP was derived via a random effects meta-analysis.

Results

Thirty-two studies involving 2612 children and 3566 procedures were included. Subjects' ages ranged from 3 days to 21 years. Procedures were performed for biliary (54%), pancreatic (38%), and other (8%) indications; 56% of ERCPs were interventional. The pooled complication rate was 6% (95% CI 4%- 8%). Procedural complications included post-ERCP pancreatitis (166, 4.7%), bleeding (22, 0.6%), and infections (27, 0.8%). The pooled estimate of post-ERCP pancreatitis was 3% (95% CI 0.02-0.05), and other complications were 1% (95% CI 0.02-0.05). In the subgroup with neonatal cholestasis, the pooled complication rate was 3% (95% CI 0.01-0.07). Adult and pediatric gastroenterologists and surgeons performed the ERCPs. Available data limited the ability to report differences between pediatric-trained and other endoscopists.

Conclusions

Complications associated with pediatric ERCP range widely in severity and are reported inconsistently. Our review suggests 6% of pediatric ERCPs have complications. Further studies that use systematic and standardized methodologies are needed to determine the frequency and risk factors for ERCP-related complications.

Hyperparathyroidism is an endocrine disorder caused by one or more hyperfunctioning parathyroid glands. Current imaging consisting of ultrasound and ^99mTc-sestamibi is imprecise, making localization difficult. ¹⁸F-fluorocholine (¹⁸F-FCH) PET has recently shown promise in presurgical localization of parathyroid adenomas. The primary aim of this study was to summarize the sensitivities and specificities of studies using ¹⁸F-FCH PET to localize hyperparathyroidism. A secondary aim was to summarize a subset of studies in which ^99mTc-sestamibi scans were also used and to compare the performance of the 2 modalities. Methods: We searched the MEDLINE and EMBASE databases following the PRISMA (Preferred Reporting Items for Systematic Review and Metaanalysis) statement. Quality was assessed using the QUADAS-2 tool (Quality Assessment of Diagnostic Accuracy Studies). Twenty studies were included for quantitative assessment in our metaanalysis. A random-effects model and a hierarchic summary receiver-operating-characteristic model was used to summarize the sensitivity of ¹⁸F-FCH PET in detecting abnormal parathyroid adenomas. We used the same methodology to assess sensitivity of ^99mTc-sestamibi, as a comparison to ¹⁸F-FCH PET. Results: ¹⁸F-FCH PET had a high sensitivity, 0.97 (range, 0.96-0.98), for the detection of abnormal parathyroid adenomas. In the subpopulation for which both ¹⁸F-FCH and ^99mTc-sestamibi were reported, ¹⁸F-FCH also had a higher sensitivity, 0.96 (0.94-0.98), than the 0.54 (0.29-0.79) reported for ^99mTc-sestamibi (P < 0.001). Conclusion: ¹⁸F-FCH PET demonstrates high localization accuracy in patients with hyperparathyroidism. This metaanalysis supports the use of ¹⁸F-FCH over ^99mTc-sestamibi in patients with hyperparathyroidism.

⁶⁸Ga-PSMA-11 PET is used to stage patients with prostate cancer. We performed an updated metaanalysis that separates imaging at the time of diagnosis and at the time of biochemical recurrence and focuses on pathology correlation in both populations. Methods: We searched the MEDLINE and EMBASE databases using the PRISMA statement. Quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool 2. In total, 1,811 studies were screened, 58 were analyzed, 41 were included for qualitative synthesis, and 29 were included for quantitative analysis. A random-effect model and a hierarchical summary receiver-operating-characteristic model were used to summarize the sensitivity, specificity, positive predictive value (PPV), negative predictive value, and accuracy for pelvic lymph nodes in initial staging compared with pathology at prostatectomy and the PPV for lesions with pathologic correlation in those with biochemical recurrence. We also summarized the detection rate of ⁶⁸Ga-PSMA-11 in those with biochemical recurrence stratified by prostate-specific antigen (PSA) at the time of imaging. Results: The metaanalysis of ⁶⁸Ga-PSMA-11 at initial staging demonstrated a sensitivity and specificity of 0.74 (95% confidence interval [95% CI], 0.51-0.89) and 0.96 (95% CI, 0.85-0.99), respectively, using nodal pathology at prostatectomy as a gold standard. At biochemical recurrence, the PPV was 0.99 (95% CI, 0.96-1.00). The detection rate was 0.63 (95% CI, 0.55-0.70), with a PSA of less than 2.0 and 0.94 (95% CI, 0.91-0.96) with a PSA of more than 2.0. Conclusion: ⁶⁸Ga-PSMA-11 performed well for the localization of metastatic prostate cancer at initial staging and at the time of biochemical recurrence.

Aim

To measure resilience and identify associated demographic and clinical factors in individuals with spina bifida.

Method

An anonymous survey was distributed via Facebook advertising to individuals with congenital urological conditions. Respondents 18 years or older with spina bifida were included in this study. Resilience was measured with the 10-item Connor-Davidson Resilience Scale. Mean resilience levels in the study population and a US general population sample were compared with Student's t-test. Multiple linear regression assessed demographic and clinical factors associated with resilience.

Results

The mean resilience score for participants (n=195; 49 males, 146 females; mean age 40y 2mo [SD 12y 7mo] range 18-74y) was 27.2 (SD 7.5), which differed from a mean of 31.8 (SD 5.4) for a US general population sample (p<0.01). Multiple linear regression demonstrated significant positive associations between resilience and older age (p=0.04), prior urological surgeries (p=0.03), higher household education (p<0.01), and higher physical function (p<0.01).

Interpretation

Resilience in individuals with spina bifida is moderately poor, relative to the general population, and is associated with certain demographic and clinical factors. As a modifiable construct with positive effects on quality of life, psychological well-being, and health-related behaviors, resilience is a promising target for intervention in individuals with spina bifida. What this paper adds Resilience in individuals with spina bifida is moderately poor. Resilience is lower in individuals with spina bifida than the general population. Resilience is associated with age, household education, physical function, and urological surgery.

Objective

To evaluate the impact of body mass index (BMI) on perioperative outcomes and radiation exposure for ultrasound (US)-guided percutaneous nephrolithotomy (PCNL).

Patients and methods

Data were prospectively collected for consecutive patients who underwent PCNL at the University of California, San Francisco, from July 2013 to November 2015. Patients were divided into 3 groups according to their BMI: <25 (normal weight), 25-29.9 (overweight), and >30 (obese) kg/m². Perioperative outcomes were compared between patients who underwent US-guided vs fluoroscopy-guided PCNL.

Results

One hundred thirty-five patients were enrolled; 93 cases were performed under US and 42 under fluoroscopic guidance. US successfully guided renal access in 76.9% of normal weight, 79.0% of overweight, and 45.7% of obese patients (P < .05). Mean fluoroscopic screening time and radiation exposure dose were reduced for US compared to fluoroscopy cases across all BMI categories (P < .05). As BMI increased, radiation exposure dose rose disproportionately faster compared to screening time (P < .001). No significant differences among the BMI groups were found with regard to complication rate, hospital stay, and stone-free status.

Conclusion

US-guided PCNL may be more difficult in obese patients, but with its use, the overweight and obese experience the largest absolute reduction in radiation exposure. Because these patients are inherently at greater risk for radiation exposure compared to normal weight patients, they may benefit the most from adoption of US for PCNL.

Background: Interferon-gamma (IFN-γ) is a key mediator of sarcoidosis-related granulomatous inflammation. Previous findings of IFN-γ-producing Th17 cells in bronchoalveolar lavage fluid from sarcoidosis patients invokes the transition of Th17.0 cells to Th17.1 cells in the disease's pathogenesis. Since the T-bet transcription factor is crucial for this transition, the goal of this study was to determine if T-bet expression in Th17.0 cells reflects the extent of granulomatous inflammation in sarcoidosis patients as assessed by clinical outcomes. Methods: Using a case-control study design, we identified two groups of sarcoidosis subjects (total N = 43) with pulmonary function tests (PFTs) that either (1) changed (increased or decreased) longitudinally or (2) were stable. We used flow cytometry to measure the transcription factors T-bet and RORγt in Th1, Th17.0, and Th17.1 cell subsets defined by CCR6, CCR4 and CXCR3 in blood samples. We compared the percentages of T-bet⁺ cells in RORγt⁺Th17.0 cells (defined as CCR6⁺CCR4⁺CXCR3^-) based on subjects' PFT group. We also assessed the relationship between the direction of change in PFTs with the changes in %T-bet⁺ frequencies using mixed effects modeling. Results: We found that T-bet expression in subjects' RORγt⁺Th17.0 cells varied based on clinical outcome. The T-bet⁺ percentage of RORγt⁺Th17.0 cells was higher in the cases (subject group with PFT changes) as compared to controls (stable group) (27 vs. 16%, p = 0.0040). In comparisons before and after subjects' PFT changes, the T-bet⁺ frequency of RORγt⁺Th17.0 cells increased or decreased in the opposite direction of the PFT change. The percentage of these T-bet⁺ cells was also higher in those with greater numbers of involved organs. Serum levels of interferon-γ-induced chemokines, CXCL9, CXCL10, and CXCL11, and whole blood gene expression of IFN-γ-related genes including GBP1, TAP1, and JAK2 were independently positively associated with the T-bet⁺ frequencies of RORγt⁺Th17.0 cells. Conclusions: These data suggest that expression of T-bet in Th17.0 cells could reflect the extent of granulomatous inflammation in sarcoidosis patients because they represent a transition state leading to the Th17.1 cell phenotype. These findings indicate that Th17 plasticity may be part of the disease paradigm.

Background

Variability in imaging protocols and techniques has resulted in a lack of consensus regarding the incorporation of perfusion imaging into stroke triage and treatment. The objective of our study was to evaluate the available scientific evidence regarding the utility of perfusion imaging in determining treatment eligibility in patients with acute stroke and in predicting their clinical outcome.

Methods

We performed a systematic review of the literature using PubMed, Web of Science, and Cochrane Library focusing on themes of medical imaging, stroke, treatment, and outcome (CRD42016037817). We included randomized controlled trials, cohort studies, and case-controlled studies published from 2011 to 2016. Two independent reviewers conducted the study appraisal, data abstraction, and quality assessments of the studies.

Results

Our literature search yielded 13 studies that met our inclusion criteria. In total, 994 patients were treated with the aid of perfusion imaging compared with 1819 patients treated with standard care. In the intervention group 51.1% of patients had a favorable outcome at 3 months compared with 45.6% of patients in the control group (p=0.06). Subgroup analysis of studies that used multimodal therapy (IV tissue plasminogen activator, endovascular thrombectomy) showed a significant benefit of perfusion imaging (OR 1.89, 95% CI 1.43 to 2.51, p<0.01).

Conclusions

Perfusion imaging may represent a complementary tool to standard radiographic assessment in enhancing patient selection for reperfusion therapy, with a subset of patients having up to 1.9 times the odds of achieving independent functional status at 3 months. This is particularly important as patients selected based on perfusion status often included individuals who did not meet the current treatment eligibility criteria.