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1.
Medicine (Baltimore) ; 99(1): e18613, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31895814

RESUMO

Postoperative fever in pediatric patients following reconstructive hip surgery is of unknown significance. This study identifies the prevalence of postoperative fever after corrective hip surgery, its relationship to infection, and whether preventative use of anti-pyretics affects patient outcomes.Overall, 222 patients who underwent a varus derotational osteotomy (VDRO) between 11/1/2004 to 8/1/2014 with minimum 6 months follow up were retrospectively identified. Variables included diagnosis, inpatient stay, daily maximum temperature, duration of fever, fever workup, and administration of scheduled anti-pyretics. Fever was defined as temperature ≥38°C.In total, 123/222 (55.4%) and 70/222 (31.5%) had postoperative fevers of ≥38°C and ≥38.5°C, respectively. Average inpatient stay was 2.7 days postoperatively. Temperature (mean = 38.0°C) was greatest on postoperative day 1 (POD1), and 43.7% of patients had T ≥38°C on POD1. Anti-pyretics did not influence the duration of fever. Anti-pyretics on the day of surgery (POD0) did not influence the incidence of fever. Acetaminophen on POD0 significantly reduced likelihood of fever on POD1 (P = .02). Average length of fevers ≥38°C and 38.5°C were 8.4 and 4.2 hours, respectively. 3/18 (16.7%) fever workups administered were positive. Postoperative fever did not predict infection. 9/222 (4/1%) patients had postoperative infection - 5/123 (4.1%) with fever ≥38°C and 4/70 (5.7%) with fever ≥38.5°C. Rates of infection in patients with and without fevers were not significantly different (P = .97 for T ≥38°C and P = .38, for T ≥38.5°C).Though common, postoperative fever does not increase risk of infection. The low prevalence of positive cultures indicates routine fever workups can safely be avoided in most patients.Level of Evidence: III, retrospective comparative study.


Assuntos
Coxa Vara/cirurgia , Febre/etiologia , Osteotomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Criança , Febre/epidemiologia , Humanos , Los Angeles/epidemiologia , Osteotomia/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores de Risco
2.
BJU Int ; 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31869527

RESUMO

OBJECTIVES: To evaluate the utility of kidney injury test (KIT) assay urinary biomarkers to detect kidney stones and quantify stone burden. PATIENTS AND METHODS: A total of 136 spot urine samples from 98 individuals, with and without kidney stone disease, were processed in a predefined assay to measure six DNA and protein markers in order to generate a risk score for the non-invasive detection of nephrolithiasis. From this cohort, 56 individuals had spot, non-timed urine samples collected at the time of radiographically confirmed kidney stones, and 54 demographically matched, healthy controls without kidney stone disease also provided spot, non-timed urine samples. Sixteen individuals with persistent stone disease had more than one urine sample. Using a proprietary microwell-based KIT assay, we measured cell-free DNA (cfDNA), methylated cfDNA, clusterin, creatinine, protein and CXCL10. A KIT stone score was computed across all markers using the prior locked KIT algorithm. The KIT stone score, with a scale of 0 to 100, was then correlated with demographic variables, kidney stone burden, obstructive kidney stone disease, and urine solutes in 24-h urine collections. RESULTS: The scaled KIT stone score, a composite of all six biomarkers, readily discriminated individuals with current or prior radiographically confirmed kidney stones from healthy controls without kidney stone disease (P < 0.001). In individuals with nephrolithiasis, KIT stone score also correlated with radiologically measured stone size (P = 0.017) and differentiated patients with a clinical radiological diagnosis of obstructive nephrolithiasis associated with upper renal tract dilatation (P = 0.001). Stone burden as assessed by KIT stone score, however, did not correlate with the any of the traditional measures of 24-h urine solutes or the 24-h urine supersaturation levels. In patients with persistent stone disease, where multiple urine samples were collected over time and after different interventions, the use of KIT stone score could non-invasively track stone burden over time through a spot urine, non-timed urine sample. CONCLUSIONS: A random, spot urine-based assay, KIT stone score, can non-invasively detect, quantify and monitor current stone burden, and may thus minimize radiographic exposure for kidney stone detection. The KIT stone score assay may also help monitor stone recurrence risk for patients with nephrolithiasis, without the requirement for 24-h urine collections.

3.
Glob Adv Health Med ; 8: 2164956119887720, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31723480

RESUMO

Background: Fishman et al. reported that side plank poses asymmetrically strengthened the convex side of the curve and decreased primary Cobb angle by 49% among compliant patients with adolescent idiopathic scoliosis (AIS). Methods: AIS patients with curves of 10° to 45° were randomized into the front plank (control) or side plank group. The side plank was performed with their curve convex down. A weekly survey monitored compliance, defined by completing poses 4 or more times a week. Results: A total of 64 patients were enrolled; 34% (22 of 64) of patients (mean age = 13 years) were compliant. In the control group, there were 11 compliant patients with 6 undergoing brace treatment. At enrollment, they had a mean Cobb angle of 30° (range: 14°-40°) and mean scoliometer reading of 13°. At 6 months, they had a mean Cobb angle of 30° (range: 14°-42°) and mean scoliometer of 12°. In the side plank group, there were 11 compliant patients with 5 undergoing brace treatment. At enrollment, they had a mean Cobb angle of 32° (range: 21°-44°) and mean scoliometer reading of 12°. At 6 months, they had a mean Cobb angle of 31° (range: 17°-48°) and a mean scoliometer reading of 13°. There were no significant changes in either the control or side plank group in regards to primary Cobb angle (control: P = .53, side plank: P = .67) or scoliometer (control: P = .22, side plank: P = .45). Conclusion: There were no significant changes in primary Cobb angle or scoliometer after 6 months of side plank exercises. In contrast to a prior study, there was no improvement in curve magnitude in AIS patients performing side plank exercises.

4.
Genome Med ; 11(1): 64, 2019 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-31640730

RESUMO

Here, we present the Northeast Asian Reference Database (NARD), including whole-genome sequencing data of 1779 individuals from Korea, Mongolia, Japan, China, and Hong Kong. NARD provides the genetic diversity of Korean (n = 850) and Mongolian (n = 384) ancestries that were not present in the 1000 Genomes Project Phase 3 (1KGP3). We combined and re-phased the genotypes from NARD and 1KGP3 to construct a union set of haplotypes. This approach established a robust imputation reference panel for Northeast Asians, which yields the greatest imputation accuracy of rare and low-frequency variants compared with the existing panels. NARD imputation panel is available at https://nard.macrogen.com/ .

5.
Alzheimers Dement (N Y) ; 5: 627-636, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31660425

RESUMO

Introduction: Low blood-brain barrier (BBB) penetration and hematopoietic side effects limit the therapeutic development of erythropoietin (EPO) for Alzheimer's disease (AD). A fusion protein of EPO and a chimeric monoclonal antibody targeting the mouse transferrin receptor (cTfRMAb) has been engineered. The latter drives EPO into the brain via receptor-mediated transcytosis across the BBB and increases its peripheral clearance to reduce hematopoietic side effects of EPO. Our previous work shows the protective effects of this BBB-penetrating EPO in AD mice but hematologic effects have not been studied. Herein, we investigate the hematologic safety and therapeutic effects of chronic cTfRMAb-EPO dosing, in comparison to recombinant human EPO (rhu-EPO), in AD mice. Methods: Male APPswe PSEN1dE9 (APP/PS1) mice (9.5 months) were treated with saline (n = 11), and equimolar doses of cTfRMAb-EPO (3 mg/kg, n = 7), or rhu-EPO (0.6 mg/kg, n = 9) 2 days/week subcutaneously for 6 weeks, compared to saline-treated wild-type mice (n = 10). At 6 weeks, exploration and memory were assessed, and mice were sacrificed at 8 weeks. Spleens were weighed, and brains were evaluated for amyloid beta (Aß) load and synaptophysin. Blood was collected at 4, 6 and 8 weeks for a complete blood count and white blood cells differential. Results: cTfRMAb-EPO transiently increased reticulocyte counts after 4 weeks, followed by normalization of reticulocytes at 6 and 8 weeks. rhu-EPO transiently increased red blood cell count, hemoglobin and hematocrit, and significantly decreased mean corpuscular volume and reticulocytes at 4 weeks, which remained low at 6 weeks. At 8 weeks, a significant decline in red blood cell indices was observed with rhu-EPO treatment. Exploration and cognitive deficits were significantly worse in APP/PS1-rhu-EPO mice. Both cTfRMAb-EPO and rhu-EPO decreased 6E10-positive brain Aß load; however, cTfRMAb-EPO and not rhu-EPO selectively reduced brain Aß1-42 and elevated synaptophysin expression. Discussion: Chronic treatment with cTfRMAb-EPO results in better hematologic safety, behavioral, and therapeutic indices compared with rhu-EPO, supporting the development of this BBB-penetrable EPO analog for AD.

6.
Global Health ; 15(1): 57, 2019 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533850

RESUMO

In 2015, the World Health Organization (WHO) Expert Committee approved the addition of 16 cancer medicines to the WHO Model List of Essential Medicines (EML), bringing the total number of cancer medicines on the list to 46. This change represented the first major revision to the EML oncology section in recent history and reinforces international recognition of the need to ensure access and affordability for cancer treatments. Importantly, many low and middle-income countries rely on the EML, as well as the children's EML, as a guide to establish national formularies, and moreover use these lists as tools to negotiate medicine pricing. However, EML inclusion is only one component that impacts cancer treatment access. More specifically, factors such as intellectual property rights and international trade agreements can interact with EML inclusion, drug pricing, and accessibility. To better understand this dynamic, we conducted an interdisciplinary review of the patent status of EML cancer medicines compared to other EML noncommunicable disease medicines using the 17th, 18th, 19th, 20th, and 21st editions of the list. We also explored the interaction of intellectual property rights with the international trade regime and how trade agreements can and do impact cancer treatment access and affordability. Based on this analysis, we conclude that patent status is simply one factor in the complex international environment of health systems, IPR policies, and trade regimes and that aligning these oftentimes disparate interests will require shared global governance across the cancer care continuum.


Assuntos
Antineoplásicos , Comércio/organização & administração , Medicamentos Essenciais , Propriedade Intelectual , Cooperação Internacional , Políticas , Antineoplásicos/economia , Antineoplásicos/provisão & distribução , Custos e Análise de Custo , Medicamentos Essenciais/economia , Medicamentos Essenciais/provisão & distribução , Acesso aos Serviços de Saúde , Humanos , Neoplasias/tratamento farmacológico , Organização Mundial da Saúde
7.
Int J Mol Sci ; 20(18)2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31510053

RESUMO

Standard methods for detecting and monitoring of IgA nephropathy (IgAN) have conventionally required kidney biopsies or suffer from poor sensitivity and specificity. The Kidney Injury Test (KIT) Assay of urinary biomarkers has previously been shown to distinguish between various kidney pathologies, including chronic kidney disease, nephrolithiasis, and transplant rejection. This validation study uses the KIT Assay to investigate the clinical utility of the non-invasive detection of IgAN and predicting the progression of renal damage over time. The study design benefits from longitudinally collected urine samples from an investigator-initiated, multicenter, prospective study, evaluating the efficacy of corticosteroids versus Rituximab for preventing progressive IgAN. A total of 131 urine samples were processed for this study; 64 urine samples were collected from 34 IgAN patients, and urine samples from 64 demographically matched healthy controls were also collected; multiple urinary biomarkers consisting of cell-free DNA, methylated cell-free DNA, DMAIMO, MAMIMO, total protein, clusterin, creatinine, and CXCL10 were measured by the microwell-based KIT Assay. An IgA risk score (KIT-IgA) was significantly higher in IgAN patients as compared to healthy control (87.76 vs. 14.03, p < 0.0001) and performed better than proteinuria in discriminating between the two groups. The KIT Assay biomarkers, measured on a spot random urine sample at study entry could distinguish patients likely to have progressive renal dysfunction a year later. These data support the pursuit of larger prospective studies to evaluate the predictive performance of the KIT-IgA score in both screening for non-invasive diagnosis of IgAN, and for predicting risk of progressive renal disease from IgA and utilizing the KIT score for potentially evaluating the efficacy of IgAN-targeted therapies.

8.
Spine Deform ; 7(5): 729-733, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31495472

RESUMO

STUDY DESIGN: Prospective, single center. OBJECTIVE: To compare maximal voluntary ventilation (MVV) and forced vital capacity (FVC) testing in the outpatient scoliosis clinic to determine their relative feasibility and sensitivity in assessing pulmonary function in the AIS population. SUMMARY OF BACKGROUND DATA: Evidence of compromised pulmonary function in patients with severe AIS is well established. The American Thoracic Society (ATS) has established criteria for the reliability and accuracy of pulmonary function tests (PFTs), including MVV and FVC. METHODS: A total of 91 AIS patients with thoracic curves of 20° or greater were enrolled in the orthopedic clinic. Patients performed PFTs using the CareFusion MicroLoop Spirometer. MVV and FVC values were collected. Results were considered reliable or "passing" when ATS spirometer guidelines were met. RESULTS: Eighty-seven of the 91 patients (96%) met ATS criteria for the MVV test and 43 of the 91 patients (47%) met criteria for the FVC test. Both MVV (r = -0.41, p < .01) and FVC (r = -0.37, p = .01) were significantly correlated with thoracic Cobb angle. The percentile predicted (%predicted) MVV (r = -0.24, p = .03) and %predicted FVC (r = -0.32, p = .04) were also significantly correlated with thoracic Cobb angle. Of those who passed both tests (42/91 patients), 26% had abnormal MVV results with normal FVC results, and 5% had abnormal FVC results with normal MVV results. CONCLUSION: MVV and FVC correlated closely with Cobb angle. Twice as many AIS patients could perform an MVV test compared with an FVC test. MVV seems to be a more practical and sensitive PFT than FVC for assessing the pulmonary function of AIS patients in the orthopedic clinic setting. LEVEL OF EVIDENCE: Level II.

9.
J Pediatr Orthop ; 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31403990

RESUMO

BACKGROUND: Recently, there have been several reports of using an enhanced discharge pathway following posterior spinal fusion (PSF) in patients with adolescent idiopathic scoliosis (AIS). No previous studies have prospectively examined patient satisfaction of patients with AIS using an enhanced discharge pathway. The purpose of this study was to evaluate patient satisfaction with an enhanced discharge pathway for PSF and whether patients felt that their length of stay was appropriate. METHODS: Patients with AIS undergoing PSF were prospectively enrolled. At their first postoperative clinic visit, patients were administered a survey regarding their experience. RESULTS: Of the 46 patients enrolled (mean age, 14 y), 1 was discharged on postoperative day (POD) 2, 33 were discharged on POD 3, 9 were discharged on POD 4, and 3 were discharged on POD 5. Eighty (37/46) of patients felt that they were discharged at an appropriate time, whereas 20% (9/46) felt they were discharged too early. Patients who felt they were discharged at an appropriate time (mean, 3.2 d) had a trend toward shorter stays than those who felt they were discharged too early (mean, 3.7 d). Overall patient satisfaction of hospital stay was high with a mean of 9 on a 10-point scale (range, 1 to 10). There was no correlation between length of stay and patient satisfaction (P=0.723). Patients who felt they were discharged early had a significantly higher mean FACES pain scores than those who felt they were discharged about right both as inpatients (mean, 4.8 vs. 3.4; P=0.0319) and at their first postoperative clinic visit (5.4 vs. 2.9; P=0.004). CONCLUSIONS: Eighty percent of patients with AIS who underwent PSF felt that the time of discharge was appropriate with an enhanced discharge pathway. There was no correlation between patient satisfaction and length of stay. LEVEL OF EVIDENCE: Level II.

10.
PLoS One ; 14(7): e0220052, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31365568

RESUMO

A Common Rejection Module (CRM) consisting of 11 genes expressed in allograft biopsies was previously reported to serve as a biomarker for acute rejection (AR), correlate with the extent of graft injury, and predict future allograft damage. We investigated the use of this gene panel on the urine cell pellet of kidney transplant patients. Urinary cell sediments collected from patients with biopsy-confirmed acute rejection, borderline AR (bAR), BK virus nephropathy (BKVN), and stable kidney grafts with normal protocol biopsies (STA) were analyzed for expression of these 11 genes using quantitative polymerase chain reaction (qPCR). We assessed these 11 CRM genes for their abundance, autocorrelation, and individual expression levels. Expression of 10/11 genes were elevated in AR when compared to STA. Psmb9 and Cxcl10could classify AR versus STA as accurately as the 11-gene model (sensitivity = 93.6%, specificity = 97.6%). A uCRM score, based on the geometric mean of the expression levels, could distinguish AR from STA with high accuracy (AUC = 0.9886) and correlated specifically with histologic measures of tubulitis and interstitial inflammation rather than tubular atrophy, glomerulosclerosis, intimal proliferation, tubular vacuolization or acute glomerulitis. This urine gene expression-based score may enable the non-invasive and quantitative monitoring of AR.

11.
J Clin Med ; 8(4)2019 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-31013714

RESUMO

The current standard of care measures for kidney function, proteinuria, and serum creatinine (SCr) are poor predictors of early-stage kidney disease. Measures that can detect chronic kidney disease in its earlier stages are needed to enable therapeutic intervention and reduce adverse outcomes of chronic kidney disease. We have developed the Kidney Injury Test (KIT) and a novel KIT Score based on the composite measurement and validation of multiple biomarkers across a unique set of 397 urine samples. The test is performed on urine samples that require no processing at the site of collection and without target sequencing or amplification. We sought to verify that the pre-defined KIT test, KIT Score, and clinical thresholds correlate with established chronic kidney disease (CKD) and may provide predictive information on early kidney injury status above and beyond proteinuria and renal function measurements alone. Statistical analyses across six DNA, protein, and metabolite markers were performed on a subset of residual spot urine samples with CKD that met assay performance quality controls from patients attending the clinical labs at the University of California, San Francisco (UCSF) as part of an ongoing IRB-approved prospective study. Inclusion criteria included selection of patients with confirmed CKD and normal healthy controls; exclusion criteria included incomplete or missing information for sample classification, logistical delays in transport/processing of urine samples or low sample volume, and acute kidney injury. Multivariate logistic regression of kidney injury status and likelihood ratio statistics were used to assess the contribution of the KIT Score for prediction of kidney injury status and stage of CKD as well as assess the potential contribution of the KIT Score for detection of early-stage CKD above and beyond traditional measures of renal function. Urine samples were processed by a proprietary immunoprobe for measuring cell-free DNA (cfDNA), methylated cfDNA, clusterin, CXCL10, total protein, and creatinine. The KIT Score and stratified KIT Score Risk Group (high versus low) had a sensitivity and specificity for detection of kidney injury status (healthy or CKD) of 97.3% (95% CI: 94.6-99.3%) and 94.1% (95% CI: 82.3-100%). In addition, in patients with normal renal function (estimated glomerular filtration rate (eGFR) ≥ 90), the KIT Score clearly identifies those with predisposing risk factors for CKD, which could not be detected by eGFR or proteinuria (p < 0.001). The KIT Score uncovers a burden of kidney injury that may yet be incompletely recognized, opening the door for earlier detection, intervention and preservation of renal function.

12.
J Clin Med ; 8(2)2019 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-30781765

RESUMO

Standard methods for detecting chronic lung allograft dysfunction (CLAD) and rejection have poor sensitivity and specificity and have conventionally required bronchoscopies and biopsies. Plasma cell-free DNA (cfDNA) has been shown to be increased in various types of allograft injury in transplant recipients and CXCL10 has been reported to be increased in the lung tissue of patients undergoing CLAD. This study used a novel cfDNA and CXCL10 assay to evaluate the noninvasive assessment of CLAD phenotype and prediction of survival from bronchoalveolar lavage (BAL) fluid. A total of 60 BAL samples (20 with bronchiolitis obliterans (BOS), 20 with restrictive allograft syndrome (RAS), and 20 with stable allografts (STA)) were collected from 60 unique lung transplant patients; cfDNA and CXCL10 were measured by the ELISA-based KIT assay. Median cfDNA was significantly higher in BOS patients (6739 genomic equivalents (GE)/mL) versus STA (2920 GE/mL) and RAS (4174 GE/mL) (p < 0.01 all comparisons). Likelihood ratio tests revealed a significant association of overall survival with cfDNA (p = 0.0083), CXCL10 (p = 0.0146), and the interaction of cfDNA and CXCL10 (p = 0.023) based on multivariate Cox proportional hazards regression. Dichotomizing patients based on the median cfDNA level controlled for the mean level of CXCL10 revealed an over two-fold longer median overall survival time in patients with low levels of cfDNA. The KIT assay could predict allograft survival with superior performance compared with traditional biomarkers. These data support the pursuit of larger prospective studies to evaluate the predictive performance of cfDNA and CXCL10 prior to lung allograft failure.

13.
Spine Deform ; 7(5): 729-733, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31975205

RESUMO

STUDY DESIGN: Prospective, single center. OBJECTIVE: To compare maximal voluntary ventilation (MVV) and forced vital capacity (FVC) testing in the outpatient scoliosis clinic to determine their relative feasibility and sensitivity in assessing pulmonary function in the AIS population. Evidence of compromised pulmonary function in patients with severe AIS is well established. The American Thoracic Society (ATS) has established criteria for the reliability and accuracy of pulmonary function tests (PFTs), including MVV and FVC. METHODS: A total of 91 AIS patients with thoracic curves of 20° or greater were enrolled in the orthopedic clinic. Patients performed PFTs using the CareFusion MicroLoop Spirometer. MVV and FVC values were collected. Results were considered reliable or "passing" when ATS spirometer guidelines were met. RESULTS: Eighty-seven of the 91 patients (96%) met ATS criteria for the MVV test and 43 of the 91 patients (47%) met criteria for the FVC test. Both MVV (r = -0.41, p < .01) and FVC (r = -0.37, p = .01) were significantly correlated with thoracic Cobb angle. The percentile predicted (%predicted) MVV (r = -0.24, p = .03) and %predicted FVC (r = -0.32, p = .04) were also significantly correlated with thoracic Cobb angle. Of those who passed both tests (42/91 patients), 26% had abnormal MVV results with normal FVC results, and 5% had abnormal FVC results with normal MVV results. CONCLUSION: MVV and FVC correlated closely with Cobb angle. Twice as many AIS patients could perform an MVV test compared with an FVC test. MVV seems to be a more practical and sensitive PFT than FVC for assessing the pulmonary function of AIS patients in the orthopedic clinic setting. LEVEL OF EVIDENCE: Level II.

14.
Arch Public Health ; 76: 57, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30349691

RESUMO

Background: In response to the growing awareness and use of electronic nicotine delivery systems (ENDS), or e-cigarettes, the U.S. Food and Drug Administration asserted its regulatory authority over ENDS in May 2016. Federal, state, and local regulatory action on ENDS may have significant and unique impacts on specialty ENDS retailers, including tobacco and vape shops. The purpose of this study is to describe the commercial motivations of vape shops in minority communities as business entities whose financial interests and actions may be particularly impacted by regulation of ENDS. Methods: Specialty tobacco and vape retail stores in three minority communities were identified through an online search and community canvassing. Key informant interviews were conducted with tobacco and vape shop owners or managers discussing the business interests and tactics of selling ENDS for their store. Interview data were coded and analyzed for major themes. Results: Interviews with 18 tobacco shops and 9 vape shops were completed. Tobacco shops' reasons for carrying e-cigarettes were business oriented, focused on maintaining their customer base. In comparison, vape shops opened because of the owner's positive experiences with e-cigarettes and belief in the potential of e-cigarettes to help people quit or reduce smoking. Tobacco shops mainly see their customers as using e-cigarettes to quit smoking whereas vape shops reported their customers using e-cigarettes for more varied reasons. Tobacco shops are much more limited in their marketing than vape shops, which rely heavily on social media and experimentation with other forms of marketing. Conclusions: Tobacco shops and vape shops differ in their rationale and approaches to the business of e-cigarettes. Vape shops engage in a wide range of activities that stabilize their financial interest and increase their influence with customers and within the vape community. In order for regulatory policymaking and tobacco control interventions to maximize effectiveness, the actions of vape shops in promoting ENDS use and influencing policy debates must be taken into account.

15.
PLoS One ; 13(10): e0205107, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30289917

RESUMO

RATIONALE: Recent studies suggest that similar injury mechanisms are in place across different solid organ transplants, resulting in the identification of a common rejection module (CRM), consisting of 11 genes that are overexpressed during acute and, to a lesser extent, chronic allograft rejection. OBJECTIVES: We wanted to evaluate the usefulness of the CRM module in identifying acute rejection (AR) and different phenotypes of chronic lung transplant rejection (CLAD), i.e., bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS), using transbronchial brushings, broncho-alveolar lavage (BAL) samples, and explant tissue. METHODS: Gene expression measurements for the 11 CRM genes (CD6, TAP1, CXCL10, CXCL9, INPP5D, ISG20, LCK, NKG7, PSMB9, RUNX3, and BASP1) were performed via qRT-PCR in 14 transbronchial brushings (AR, n = 4; no AR, n = 10), 32 BAL samples (stable, n = 13; AR, n = 8; BOS, n = 9; RAS, n = 10), and 44 tissue specimens (unused donor lungs, n = 15; BOS, n = 13; RAS, n = 16). A geometric mean score was calculated to quantitate overall burden of immune injury and a new computational model was built for the most significant genes in lung transplant injury. RESULTS: Acute rejection showed a significant difference in almost every gene analysed, validating previous observations from microarray analysis. RAS tissue demonstrated a higher geometric mean score (6.35) compared to donor tissue (4.09, p = 0.018). Analysis of individual CRM genes showed an increased expression of ISG20, CXCL10 and CXCL9 in RAS. In BAL samples, no differences were detected in gene expression or geometric mean scores between the various groups (stable, 5.15; AR, 5.81; BOS, 5.62; RAS, 7.31). A newly modelled 2-gene tissue CRM score did not demonstrate any difference between BOS and RAS (p>0.05). However, the model was able to discriminate RAS from BOS tissue (AUC = 0.75, 95% CI = 0.55-0.94, p = 0.025). CONCLUSION: Transcriptional tissue analysis for CRM genes in CLAD can identify acute rejection and distinguish RAS from BOS. The immune activation in RAS seems similar to acute rejection after kidney/liver/heart transplantation.


Assuntos
Rejeição de Enxerto/metabolismo , Transplante de Pulmão , Adulto , Aloenxertos/metabolismo , Biomarcadores/metabolismo , Lavagem Broncoalveolar , Doença Crônica , Estudos de Coortes , Simulação por Computador , Feminino , Expressão Gênica , Humanos , Pulmão/metabolismo , Pulmão/cirurgia , Masculino , Pessoa de Meia-Idade , Transcriptoma , Transplante Homólogo , Adulto Jovem
16.
Spine Deform ; 6(6): 699-703, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30348346

RESUMO

STUDY DESIGN: Prospective, randomized control study. OBJECTIVES: To determine whether the SRS-22r (SRS-22) has a negative effect on the body image of females with adolescent idiopathic scoliosis (AIS) using the Body Appreciation Scale (BAS). SUMMARY: The SRS-22 is a validated questionnaire designed by the Scoliosis Research Society (SRS) to assess outcomes of scoliosis patients. Parents and nursing staff have expressed concern that the questionnaire may incite body image concerns when administered to teenagers with AIS. METHODS: Female AIS patients were prospectively enrolled and randomly assigned to the study or control group. Patients were being observed, braced, or planning operative intervention. Patients in the study group were administered the SRS-22, followed by the BAS. Patients in the control group were administered only the BAS. The BAS is scored from 13 to 65, with higher scores indicating a more positive body image. RESULTS: 45 females were enrolled and assigned to study group (n = 24, SRS-22+BAS) or control group (n = 21, BAS only). There were no differences between the groups in age (p = .55) or Cobb angle (p = .21). There were no differences in overall BAS scores between study (mean = 55.9, range 31-65) and control group participants (mean = 54.2, range 42-64, p = .56). SRS-22 questions and BAS scores had multiple correlations. A higher BAS score is associated with the following SRS-22 questions: being a happy person in the last 6 months, feeling calm and peaceful during the past 6 months, and feeling attractive with one's current back condition. A lower BAS score is associated with the following SRS-22 questions: being down in the dumps, feeling downhearted and blue, and feeling that one's back condition affects personal relationships. CONCLUSION: Similar BAS scores were observed between the study and control group. Despite concerns regarding the potential negative impact of the SRS-22, taking the questionnaire was not observed to negatively affect patients' body image. LEVEL OF EVIDENCE: Level II.


Assuntos
Imagem Corporal/psicologia , Escoliose/psicologia , Inquéritos e Questionários , Adolescente , Criança , Feminino , Humanos
17.
Global Health ; 14(1): 66, 2018 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-29980215

RESUMO

BACKGROUND: Non-communicable diseases (NCDs) account for over two-thirds of deaths worldwide, and global efforts to address NCDs have accelerated. Current prevention and control efforts rely primarily on individual behavior/lifestyle approaches that place the onus of responsibility for health on the individual. These approaches, however, have not stopped the increasing trend of NCDs worldwide. Thus, there is urgent need for exploring alternative approaches in order to attain the aim of reducing global premature NCDs mortality by 25% by 2025, and meeting the NCD reduction objective in the Sustainable Development Goals. DISCUSSION: We suggest the need for a structural approach to addressing the NCDs epidemic that integrates social science and public health theories. We evaluate two overarching principles (empowerment and human rights) and three social determinants of health (labor and employment, trade and industry, and macroeconomics) addressed in the 2013 Global Action Plan for the Prevention and Control of NCDs to demonstrate how a structural approach to NCDs can be incorporated into existing NCD interventions. For each area considered, theoretical considerations for structural thinking are provided and conclude with recommended actions. CONCLUSION: Achieving the global health agenda goals of reducing NCDs mortality will require a shift to a paradigm that embraces concerted efforts to address both behavioral/lifestyle factors and structural dimensions of NCDs.


Assuntos
Saúde Global/estatística & dados numéricos , Política de Saúde , Doenças não Transmissíveis/prevenção & controle , Metas , Humanos , Mortalidade Prematura , Doenças não Transmissíveis/mortalidade , Determinantes Sociais da Saúde
18.
Biol Reprod ; 99(3): 639-649, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29668838

RESUMO

Endocrine disrupting chemicals (EDCs) are pollutants found throughout the environment that disrupt normal endocrine processes. In mice, penis development is thought to be most susceptible to EDCs during a critical developmental window occurring on embryonic days (E) 15.5-17.5. However, androgen signaling begins on E13.5 when androgen receptor (AR) protein is found in the genitalia and testosterone is circulating. We hypothesize that disrupting androgen signaling prior to the established critical window sensitizes the penis to future androgen disruption. To test this hypothesis, CD1 dams were exposed to vinclozolin or a corn oil solvent control on E13.5 and E14.5 and AR levels were measured with immunohistochemistry on E14.5. Early antiandrogen exposure reduced AR within nuclei and decreased intensity of AR expression within E14.5 genitalia. To evaluate the influence of antiandrogen exposure before the known critical window of penis development, two groups of pregnant dams (n = 3) were exposed to vinclozolin starting at either E13.5 or E14.5 and continued exposure through E16.5. Histology and M.O.U.S.E. scoring were used to quantify penis abnormalities. To account for differences in total doses mice experienced due to differences in length of dosing time, we compared animals that received the same total doses. Exposure to antiandrogens on E13.5 exacerbated malformations when exposure was continued through sexually dimorphic development. Both exposure time and vinclozolin dose are important for severity of vinclozolin-induced penis abnormalities in mice. This work shows that antiandrogen exposure prior to sensitive periods can exacerbate the effects of later antiandrogen exposure on reproductive development.


Assuntos
Antagonistas de Androgênios/farmacologia , Oxazóis/farmacologia , Pênis/anormalidades , Pênis/crescimento & desenvolvimento , Anormalidades Induzidas por Medicamentos/patologia , Androgênios/metabolismo , Animais , Relação Dose-Resposta a Droga , Disruptores Endócrinos/farmacologia , Feminino , Masculino , Camundongos , Gravidez , Receptores Androgênicos/efeitos dos fármacos , Receptores Androgênicos/metabolismo
19.
Spine (Phila Pa 1976) ; 43(13): 890-894, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29049087

RESUMO

STUDY DESIGN: Multicenter prospective. OBJECTIVE: To assess the effect of intraoperative interventions in restoring intraoperative neuromonitoring (IONM) signals in pediatric spine surgery. SUMMARY OF BACKGROUND DATA: No prior studies have prospectively examined the rate of return of IONM signals by increasing blood pressure (BP) alone. METHODS: Patients undergoing posterior spinal deformity surgery were enrolled at their preoperative appointment. Surgeons completed an intraoperative data form on patients who experienced an IONM change defined as a 50% or greater decrease in either transcranial motor evoked potentials or somatosensory evoked potentials. RESULTS: Four hundred fifty two patients were enrolled with 30 (7%) having IONM change. Thirty patients met inclusion criteria (mean age, 12 yrs, range, 5-19) and had the following diagnoses: idiopathic scoliosis (43%), neuromuscular scoliosis (13%), congenital scoliosis (10%), early onset scoliosis (7%), and other (27%). 20% (6/30) had return of signals due to an increase in BP alone with no other interventions (mean arterial pressure [MAP] increased from mean of 68 [range, 58-76] to 86 mmHg [range, 75-95]). Signals returned to baseline after mean of 16 minutes (range, 2-45). In 60% of patients (18/30), MAP was raised from a mean of 72 mmHg (range, 55-84) to 86 mmHg (range, 75-100) in conjunction with other interventions and had mean return of signals in 37 minutes (range, 8-210). Six (20%) of patients had signals return to baseline after a mean of 6 minutes (range, 3-13) in which MAP did not change appreciably. All patients had return of signals at the conclusion of the procedure with one patient having postoperative neurological sequale. CONCLUSION: In this prospective study of 452 pediatric spinal deformity surgeries, raising MAPs above 85 mmHg should be considered the first step in response to IONM signal changes, as this alone was successful in 20% of patients without sacrificing deformity correction. LEVEL OF EVIDENCE: 2.


Assuntos
Pressão Arterial/fisiologia , Complicações Intraoperatórias/fisiopatologia , Monitorização Neurofisiológica Intraoperatória/métodos , Escoliose/fisiopatologia , Escoliose/cirurgia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Complicações Intraoperatórias/diagnóstico por imagem , Masculino , Estudos Prospectivos , Escoliose/diagnóstico por imagem , Adulto Jovem
20.
Spine Deform ; 6(1): 38-42, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29287815

RESUMO

STUDY DESIGN: Multicenter retrospective review. OBJECTIVE: To assess the effectiveness of using the stable sagittal vertebra (SSV) for selecting the lowest instrumented vertebrae (LIV) to prevent distal junctional kyphosis (DJK) in selective thoracic fusions. SUMMARY OF BACKGROUND DATA: Cho et al. reported that including the SSV in a fusion decreased the rate of DJK in thoracic hyperkyphosis. METHODS: A retrospective review was performed of patients from two pediatric hospitals with adolescent idiopathic scoliosis who underwent selective posterior thoracic fusion with the LIV at L2 or above from 2000 to 2012. Patients with less than 2 years' follow-up were excluded. The primary outcome measure was DJK, defined radiographically as ≥10° between the superior end plate of the LIV and the inferior end plate of the vertebra below on a standing lateral radiograph. We investigated the SSV, which was defined as the vertebral level at which 50% of the vertebral body was in front of the posterior sacral vertical line (PSVL) on a standing lateral radiograph. This particular definition was referred to as SSV. RESULTS: A total of 113 patients met the inclusion criteria. Mean age was 14.4 years. Mean Cobb angle was 58°. The overall rate of DJK was 7% (8/113). When the LIV was superior to SSV, the rate of DJK was 17% (8/46) versus 0% (0/67) when the LIV was at or inferior to SSV (p=.01). The rates of DJK for patients with the LIV one, two, and three levels above SSV were 17% (4/24), 7% (1/14), and 43% (3/7), respectively. There was no significant association between preoperative or postoperative maximum kyphosis, thoracic kyphosis, thoracolumbar kyphosis, pelvic incidence, sagittal balance or coronal balance, and development of DJK. CONCLUSION: Although LIV selection is complex, choosing the LIV at or below the SSV is a simple rule that minimizes the risk of DJK. LEVEL OF EVIDENCE: Level IV.


Assuntos
Cifose/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Sacro/cirurgia , Escoliose/cirurgia , Fusão Vertebral/métodos , Adolescente , Feminino , Humanos , Cifose/diagnóstico por imagem , Cifose/etiologia , Masculino , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Radiografia , Estudos Retrospectivos , Escoliose/complicações , Fusão Vertebral/instrumentação , Vértebras Torácicas/cirurgia , Resultado do Tratamento
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