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1.
Arch Dis Child ; 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32198160

RESUMO

OBJECTIVE: Infections with multidrug-resistant organisms (MDROs) such as Gram-negative bacteria have high morbidity and mortality with limited treatment options. Colistin, an antibiotic active against MDRO, was rarely used due to frequent adverse effects, but its use has now been recommended among adults. In this study, we determined the efficacy of colistin for the treatment of sepsis in neonates. DESIGN/SETTING/PATIENTS/OUTCOMES: We conducted a retrospective record review of all neonates admitted to the neonatal intensive care unit of Aga Khan University Hospital, Karachi, Pakistan, between June 2015 and June 2018, who had sepsis and received colistin by intravenous, inhalation and/or intrathecal routes. Predictors of colistin efficacy, for neonatal survival and microbial clearance, were assessed using multiple logistic regression. RESULTS: 153 neonates received colistin; 120 had culture-proven sepsis; and 93 had MDR-GNB (84 colistin-sensitive). 111 (72.5%) neonates survived and were discharged from hospital; 82.6% had microbial clearance. Neonates with colistin-sensitive bacteria (adjusted OR (AOR)=3.2, 95% CI 2.8 to 4.0), and those in which colistin therapy started early (AOR=7.2, 95% CI 3.5 to 13.6) were more likely to survive. Neonates with increased gestational age (AOR=1.9, 95% CI 1.5 to 3.0), higher weight (AOR=5.4, 95% CI 3.3 to 11.8) and later onset of sepsis (AOR=4.3, 95% CI 2.0 to 9.0) had higher survival. Adverse events included nephrotoxicity in 5.2%; 13.7% developed seizures and 18.3% had electrolyte imbalance. CONCLUSIONS: Colistin therapy was associated with survival among neonates suffering from MDR-GNB sepsis. The frequency of side effects was moderate.

2.
Mol Cancer ; 19(1): 57, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32164715

RESUMO

Early-stage detection of leukemia is a critical determinant for successful treatment of the disease and can increase the survival rate of leukemia patients. The factors limiting the current screening approaches to leukemia include low sensitivity and specificity, high costs, and a low participation rate. An approach based on novel and innovative biomarkers with high accuracy from peripheral blood offers a comfortable and appealing alternative to patients, potentially leading to a higher participation rate.Recently, non-coding RNAs due to their involvement in vital oncogenic processes such as differentiation, proliferation, migration, angiogenesis and apoptosis have attracted much attention as potential diagnostic and prognostic biomarkers in leukemia. Emerging lines of evidence have shown that the mutational spectrum and dysregulated expression of non-coding RNA genes are closely associated with the development and progression of various cancers, including leukemia. In this review, we highlight the expression and functional roles of different types of non-coding RNAs in leukemia and discuss their potential clinical applications as diagnostic or prognostic biomarkers and therapeutic targets.

3.
Sci Rep ; 10(1): 3530, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32103043

RESUMO

Butea monosperma is one of the extensively used plants in traditional system of medicines for many therapeutic purposes. In this study, the antioxidant activity, α-glucosidase and α-amylase inhibition properties of freeze drying assisted ultrasonicated leaf extracts (hydro-ethanolic) of B. monosperma have been investigated. The findings revealed that 60% ethanolic fraction exhibited high phenolic contents, total flavonoid contents, highest antioxidant activity, and promising α-glucosidase and α-amylase inhibitions. The UHPLC-QTOF-MS/MS analysis indicated the presence of notable metabolites of significant medicinal potential including apigenin, apigenin C-hexoside C-pentoside, apigenin C-hexoside C-hexoside, apigenin-6,8-di-C-pentoside and genistin etc., in B. monosperma leave extract. Docking studies were carried out to determine the possible role of each phytochemical present in leaf extract. Binding affinity data and interaction pattern of all the possible phytochemicals in leaf extract of B. monosperma revealed that they can inhibit α-amylase and α-glucosidase synergistically to prevent hyperglycemia.

4.
Arch Virol ; 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32103340

RESUMO

Oxidative stress is the process by which reactive molecules and free radicals are formed in cells. In this study, we report the blood-based gene expression profile of oxidative stress and antioxidant genes for identifying surrogate markers of liver tissue in chronic hepatitis C (CHC) patients by using real-time PCR. A total of 144 untreated patients diagnosed with CHC having genotype 3a and 20 healthy controls were selected for the present study. Liver biopsy staging and grading of CHC patients were performed using the METAVIR score. Total RNA was extracted from liver tissue and blood samples, followed by cDNA synthesis and real-time PCR. The relative expression of genes was calculated using the ΔΔCt method. The expression profile of 84 genes associated with oxidative stress and antioxidants was determined in liver tissue and blood samples. In liver tissue, 46 differentially expressed genes (upregulated, 27; downregulated, 19) were identified in CHC patients compared to normal samples. In blood, 61 genes (upregulated, 51; downregulated; 10) were significantly expressed in CHC patients. A comparison of gene expression in liver and whole blood showed that 20 genes were expressed in a similar manner in the liver and blood. The expression levels of commonly expressed liver and blood-based genes were also correlated with clinical factors in CHC patients. A receiver operating curve (ROC) analysis of oxidative stress genes (ALB, CAT, DHCR24, GPX7, PRDX5, and MBL2) showed that infections in patients with CHC can be distinguished from healthy controls. In conclusion, blood-based gene expression can reflect the behavior of oxidative stress genes in liver tissue, and this blood-based gene expression study in CHC patients explores new blood-based non-invasive biomarkers that represent liver damage.

6.
J Clin Anesth ; 62: 109729, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32006800

RESUMO

BACKGROUND: Childhood and adolescent obesity increased in recent decades, and caregivers face an increasing number of obese pediatric surgical patients. Some clinical and pharmacogenetic data suggest that obese patients have altered pain sensitivity and analgesic requirements. OBJECTIVE: To test the primary hypothesis that increased BMI in pediatric patients is associated with increased pain during the initial 48 postoperative hours. Secondarily, we tested whether BMI is associated with increased opioid consumption during the same period. DESIGN: Retrospective single-center cohort study. SETTING: Pediatric surgical wards in a tertiary medical center. PATIENTS: A total of 808 opioid naïve patients aged 8 to 18 years having elective non-cardiac surgery with hospital stay of at least 48 h in the Cleveland Clinic between 2010 and 2015. INTERVENTIONS: None. MEASUREMENTS: Using U.S. Centers for Disease Control definitions for childhood weight classifications, we retrospectively evaluated the association between body mass index (BMI) percentile and time-weighted average pain scores and opioid consumption. We used multivariable linear regression to test for an association with postoperative pain scores, and multivariable gamma regression to test for an association with postoperative opioid consumption (in mg morphine equivalents Kg-1). RESULTS: BMI was not associated with postoperative pain after general, orthopedic, or neuro-spinal surgeries. Pain increased by 0.07 [98.75% CI: (0.01, 0.13), Padj < 0.05] points per 5 percentile increase in BMI after neuro-cranial surgery. Higher BMI was associated with a decrease in postoperative opioid consumption (mean change [95% CI] -2.12% [-3.12%, -1.10%] in morphine equivalents Kg-1 per 5 percentile increase in BMI, P < 0.001). CONCLUSION: We found no clinically important increase in pain scores or opioid consumption in association with higher BMI in patients 8 to 18 years of age recovering from elective non-cardiac surgery.

7.
Front Immunol ; 11: 33, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32082315

RESUMO

Alpha-synuclein (αSynAgg) are pathological hallmarks of Parkinson's disease (PD) and other synucleinopathies that induce microglial activation and immune-mediated neurotoxicity, but the molecular mechanisms of αSynAgg-induced immune activation are poorly defined. We performed quantitative proteomics by mass spectrometry coupled with PCR, immunohistochemical and functional validations studies to define the molecular characteristics of alpha synuclein mediated microglial activation. In mouse microglia, αSynAgg induced robust pro-inflammatory activation (increased expression of 864 genes including Irg1, Ifit1, and Pyhin) and increased nuclear proteins involved in RNA synthesis, splicing, and anti-viral defense mechanisms. Conversely, αSynAgg decreased expression several proteins (including Cdc123, Sod1, and Grn), which were predominantly cytosolic and involved in metabolic, proteasomal and lysosomal mechanisms. Pathway analyses and confirmatory in vitro studies suggested that αSynAgg partly mediates its effects via Stat3 activation. As predicted by our proteomic findings, we verified that αSynAgg induces mitochondrial dysfunction in microglia. Twenty-six proteins differentially expressed by αSynAgg were also identified as PD risk genes in genome-wide association studies (upregulated: Brd2, Clk1, Siglec1; down-regulated: Memo1, Arhgap18, Fyn, and Pgrn/Grn). We validated progranulin (PGRN) as a lysosomal PD-associated protein that is downregulated by αSynAgg in microglia in-vivo and is expressed by microglia in post-mortem PD brain, congruent with our in vitro findings. Conclusion: Together, proteomics approach both reveals novel molecular insights into αSyn-mediated neuroinflammation in PD and other synucleinopathies.

8.
BMJ Case Rep ; 13(1)2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31919061

RESUMO

A 60-year-old woman was presented in emergency department with abdominal pain and vomiting for 1 day. She was known to have seropositive rheumatoid arthritis. Importantly, she was treated surgically for complex jejunal atresia and duplication surgery, when she was 6 days old. CT scan showed intestinal obstruction secondary to intussception. Patient had lapartomy and operative findings revealed side-to-side anastomosis with gut duplication 10 cm distal to duodenal jejunum junction (due to her previous surgery during infancy). Redundant part of the loop dilated up to 300 mL with large hard stone (4×3.5 cm) was excised. Patient recovered well postoperatively and was discharged to go home. To our knowledge, this is the first case report to show formation of large stone 60 years after surgical treatment of complex jejunal atresia and duplication surgery in infancy.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31976579

RESUMO

BACKGROUND: Despite increased research using large administrative databases to identify determinants of maternal morbidity and mortality, the extent to which these databases capture obstetric co-morbidities is unknown. OBJECTIVE: To evaluate the impact that the time window used to assess obstetric co-morbidities has on the completeness of ascertainment of those co-morbidities. METHODS: We conducted a five-year analysis of inpatient hospitalisations of pregnant women from 2010-2014 using the Nationwide Readmissions Database. For each woman, using discharge diagnoses, we identified 24 conditions used to create the Obstetric Comorbidity Index. Using various assessment windows for capturing obstetric co-morbidities, including the delivery hospitalisation only and all weekly windows from 7 to 280 days, we calculated the frequency and rate of each co-morbidity and the degree of underascertainment of the co-morbidity. Under each scenario, and for each co-morbidity, we also calculated the all-cause, 30-day readmission rate. RESULTS: There were over 3 million delivery hospitalisations from 2010 to 2014 included in this analysis. Compared with a full 280-day window, assessment of obstetric co-morbidities using only diagnoses made during the delivery hospitalisation would result in failing to identify over 35% of cases of chronic renal disease, 28.5% cases in which alcohol abuse was documented during pregnancy, and 23.1% of women with pulmonary hypertension. For seven other co-morbidities, at least 1 in 20 women with that condition would have been missed with exclusive reliance on the delivery hospitalisation for co-morbidity diagnoses. Not only would reliance on delivery hospitalisations have resulted in missed cases of co-morbidities, but for many conditions, estimates of readmission rates for women with obstetric co-morbidities would have been underestimated. CONCLUSIONS: An increasing proportion of maternal and child health research is based on large administrative databases. This study provides data that facilitate the assessment of the degree to which important obstetric co-morbidities may be underascertained when using these databases.

10.
Am J Hosp Palliat Care ; 37(2): 136-141, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31337229

RESUMO

OBJECTIVE: To characterize the use of palliative care for patients with metastatic prostate cancer and identify its associations with costs, hospital course, and discharge. MATERIALS AND METHODS: Using the National Inpatient Sample database from 2012 to 2013, we identified 99 070 patients with metastatic prostate cancer and analyzed the data from their hospital admissions using descriptive statistics, χ2 analysis, and regression modeling. RESULTS: Palliative care services were consulted in 10.4% (10 300) of metastatic prostate cancer admissions. These admissions were associated with nonelective origin, acute complications, and reduced surgical procedures and chemotherapy. Patients in private, investor-owned hospitals had a 51.6% less consultations (P < .001), while nonprofit and government, nonfederal hospitals had 4.7% and 7.8% more consultations (P < .001). Median costs and charges were only marginally less (2.1% and 5.6%, respectively, P < .001), length of stay was 22% higher (P < .001), and in-house mortality was 147.2% higher in the consultation group (P < .001). Controlling for other factors, patients seen by palliative care were more likely to have do-not-resuscitate orders (odds ratio [OR]: 5.25, P < .001) and be transferred to another facility like hospice (OR: 3.90, P < .001) or to home health (OR: 3.85, P < .001). CONCLUSIONS: Palliative care consultation could improve care for patients with metastatic prostate cancer in a different manner than observed in other diseases. With our characterization of the incidence and patient and hospital factors, we can conclude that there is room to expand palliative care's role beyond uninsured patients in large, urban teaching hospitals.

11.
Environ Sci Pollut Res Int ; 27(5): 5620-5629, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31858417

RESUMO

The aim of the present paper is to determine residential energy environmental Kuznets curve (EKC) in Next-11 and BRICS countries with the specific consideration on the role of economic growth, renewable energy consumption, and financial development from an era of 1990-2015. In order to determine the cross-section independence and to control the heterogeneity between cross-sections in the paper, we have applied unique and advanced techniques of econometrics panel data. Moreover, the following tests have been applied which are the CIPS unit root test, co-integration test, fully modified ordinary least square (FMOLS), and heterogeneous panel causality technique. The outcomes revealed that in the long run, all the variables are co-integrated. Moreover, there is a significant and positive influence of residential energy consumption, economic growth, and financial development on environmental degradation. However, in the reduction of carbon dioxide (CO2) emissions, essential role is performed by renewable energy. On the other hand, findings show great support for the residential energy EKC hypothesis in emerging countries.

13.
Nat Commun ; 10(1): 5448, 2019 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-31784514

RESUMO

Amphisomes are organelles of the autophagy pathway that result from the fusion of autophagosomes with late endosomes. While biogenesis of autophagosomes and late endosomes occurs continuously at axon terminals, non-degradative roles of autophagy at boutons are barely described. Here, we show that in neurons BDNF/TrkB traffick in amphisomes that signal locally at presynaptic boutons during retrograde transport to the soma. This is orchestrated by the Rap GTPase-activating (RapGAP) protein SIPA1L2, which connects TrkB amphisomes to a dynein motor. The autophagosomal protein LC3 regulates RapGAP activity of SIPA1L2 and controls retrograde trafficking and local signaling of TrkB. Following induction of presynaptic plasticity, amphisomes dissociate from dynein at boutons enabling local signaling and promoting transmitter release. Accordingly, sipa1l2 knockout mice show impaired BDNF-dependent presynaptic plasticity. Taken together, the data suggest that in hippocampal neurons, TrkB-signaling endosomes are in fact amphisomes that during retrograde transport have local signaling capacity in the context of presynaptic plasticity.

14.
Nutr Neurosci ; : 1-12, 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31814540

RESUMO

Introduction: Phytoestrogens are non-steroidal estrogen analogues and are found primarily in soy products. They have received increasing attention as dietary supplements for estrogen deficiency and as modulators of endogenous estrogen functions, including cognition and emotion. In addition to modifying the levels of circulating sex hormones, phytoestrogens also exert direct effects on estrogen and androgen receptors in the brain and thus effectively modulate the neural circuit functions.Objective: The aim of this study was to investigate the long-term effects of low phytoestrogen intake (∼6 weeks) on the hippocampal plasticity and hippocampus-dependent memory formation in the adult C57BL/6 male mice.Methods and Results: In comparison to mice on a diet with normal phytoestrogen content, mice on low phytoestrogen diet showed a significant reduction in the phosphorylation of NR2B subunit, a molecular correlate of plasticity in the Schaffer collateral-CA1 synapse. We observed a profound decrease in long-term potentiation (LTP) in the ventral hippocampus, whereas no effect on plasticity was evident in its dorsal portion. Furthermore, we demonstrated that acute perfusion of slices with an estrogen analogue equol, an isoflovane metabolized from daidzein produced by the bacterial flora in the gut, was able to rescue the observed LTP deficit. Examining potential behavioral correlates of the plasticity attenuation, we found that mice on phytoestrogen-free diet display decreased contextual fear memory at remote but not at recent time points after training.Conclusions: Our data suggests that nutritional phytoestrogens have profound effects on the plasticity in the ventral hippocampus and ventral hippocampus-dependent memory.

15.
Saudi J Kidney Dis Transpl ; 30(5): 1144-1150, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31696854

RESUMO

This descriptive observational study was conducted at the Department of Nephrology, Bahawal Victoria Hospital, Bahawalpur, Pakistan, from January 2012 to April 2018, to study the pattern of biopsy-proven kidney diseases in that region as a part to establish a national renal biopsy registry. All adult patients who underwent renal biopsy at the Bahawal Victoria Hospital, Bahawalpur, Pakistan, from January 2012 to April 2018, were included in the study. All the biopsies were evaluated by light microscopy and immunofluorescence. All the patients underwent urine dipstick, microscopic examination, and quantification of proteinuria. Hepatitis B surface antigen, anti-hepatitis C virus, human immunodeficiency virus, and serology (antinuclear antibody, anti-ds DNA, and C3 and C4) were checked in all the patients. There were a total of 195 patients, with a mean age of 30.5 ± 12.8 years. Females were comparatively younger than males (P = 0.0154). Primary glomerulonephritis (GN) accounted for 77% (155) of all the patients, whereas secondary GN contributed 15.8%. Focal and segmental glomerulosclerosis (FSGS) was the most common diagnosis (28.2%) followed by membranous nephropathy (MN) (18.9%). Lupus nephritis was the third-most common pathology, and it predominated among females (P= 0.0026). Out of the eight diabetic patients, one each had FSGS and crescentic GN. In conclusion, primary glomerular diseases were the predominant biopsy-proven kidney diseases, and FSGS and MN were the most common glomerular diseases. This pattern in South Punjab closely resembles that in southern and northern parts of the country.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31768252

RESUMO

Background: The inappropriate use of antibiotics in hospitals increases resistance, morbidity, and mortality. Little is currently known about appropriate antibiotic use among hospitals in Lahore, the capital city of Pakistan. Methods: Longitudinal surveillance was conducted over a period of 2 months among hospitals in Lahore, Pakistan. Antibiotic treatment was considered inappropriate on the basis of a wrong dosage regimen, wrong indication, or both based on the British National Formulary. Results: A total of 2022 antibiotics were given to 1185 patients. Out of the total prescribed, approximately two-thirds of the study population (70.3%) had at least one inappropriate antimicrobial. Overall, 27.2% of patients had respiratory tract infections, and out of these, 62.8% were considered as having inappropriate therapy. Cephalosporins were extensively prescribed among patients, and in many cases, this was inappropriate (67.2%). Penicillins were given to 283 patients, out of which 201 (71.0%) were prescribed for either the wrong indication or dosage or both. Significant variations were also observed regarding inappropriate prescribing for several antimicrobials including the carbapenems (70.9%), aminoglycosides (35.8%), fluoroquinolones (64.2%), macrolides (74.6%) and other antibacterials (73.1%). Conclusion: Educational interventions, institutional guidelines, and antimicrobial stewardship programs need to be developed to enhance future appropriate antimicrobial use in hospitals in Pakistan. Policies by healthcare and Government officials are also needed to minimize inappropriate antibiotic use.

17.
Polim Med ; 49(1): 35-43, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31769938

RESUMO

BACKGROUND: Poorly water-soluble drugs do not dissolve well in aqueous-based gastrointestinal fluid; therefore, they are not well absorbed. Thus, employing a suitable solubility enhancing technique is necessary for such a drug. Drug/HP­ß­CD complexation is a promising way to improve solubility and dissolution of a poorly water-soluble drug. Levodropropizine was used as a model drug in this study. OBJECTIVES: The purpose of this research was to enhance the aqueous solubility and dissolution rate of levodropropizine by employing the inclusion complexation technique. MATERIAL AND METHODS: A microparticle formulation was prepared from levodropropizine and hydroxypropyl-ß-cyclodextrin (HP­ß­CD) in a 1:1 molar ratio through the spray-drying technique. The host-guest relationship between levodropropizine and HP­ß­CD was also investigated using the molecular docking computational methodology. The aqueous solubility and dissolution rate of levodropropizine in formulations were assessed and compared with those of the drug alone. X-ray diffraction (XRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR) were applied for the solid-state characterization of the prepared samples. RESULTS: According to the research outcomes, the levodropropizine/HP­ß­CD formulation had enhanced the aqueous solubility (351.12 ±13.26 vs 92.76 ±5.00 mg/mL) and dissolution rate (97.83 ±3.36 vs 3.12 ±1.76% in 10 min) of levodropropizine, compared to the plain drug powder. The levodropropizine/ HP­ß­CD formulation had converted the crystalline drug into its amorphous counterpart. Furthermore, no covalent interaction was found to exist between levodropropizine and HP­ß­CD. The spray-dried particles were discrete. Each particle had a shriveled appearance. CONCLUSIONS: The levodropropizine/HP­ß­CD formulation is, therefore, recommended for the more effective administration of levodropropizine through the oral route.


Assuntos
Propilenoglicóis , beta-Ciclodextrinas , 2-Hidroxipropil-beta-Ciclodextrina , Varredura Diferencial de Calorimetria , Microscopia Eletrônica de Varredura , Simulação de Acoplamento Molecular , Propilenoglicóis/química , Propilenoglicóis/farmacologia , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , beta-Ciclodextrinas/química , beta-Ciclodextrinas/farmacologia
18.
ACR Open Rheumatol ; 1(9): 542-545, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31777837

RESUMO

Objective: The optimal strategy to detect the development of tuberculosis (TB) in subjects receiving biologic agents is not clear. The recommendations vary because there is wide variation in the reported rate of seroconversion in various parts of the world. There is a scarcity of long-term studies regarding seroconversion of TB in the United States among these patients. Methods: This is a retrospective study among veteran populations with rheumatic diseases who received various biologic agents between 2003 and 2014. Subjects who had repeated TB screening tests and adequate follow-up periods were considered for the study. Results: Out of 298 subjects who received biologic agents, 123 were considered for the study. After the initial negative screening test by tuberculin skin test (TST), patients were screened on an average of 1.2 years for 4.3 to 12 years. A total of 420 tests were performed, which were combination of TST and QuantiFERON-TB gold in-Tube assay. Only 1 out of 123 subjects (0.8%) seroconverted to latent TB and was treated with isoniazid for 9 months. Conclusion: Our results are in line with a few other studies reported from the United States. We conclude that in areas with low prevalence of TB the seroconversion rate is extremely low and annual testing is unnecessary in low-risk patient populations.

19.
J Grad Med Educ ; 11(5): 580-584, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31636829

RESUMO

Background: Residency program prestige is an important variable medical students consider when creating their rank list. Doximity Residency Navigator is a ranking system that previous reports have shown significantly influences medical student application decisions. Doximity's use of peer nomination as a central component of its methodology for determining program rank has drawn criticism for its lack of objectivity. Doximity has not published information regarding how peer nomination and more objective measures are statistically weighted in reputation calculation. Objective: This study assesses whether a strong negative correlation exists between residency program size and Doximity ranking. Methods: A cross-sectional study of Doximity residency rankings from the 2018-2019 academic year was conducted. Data extracted from Doximity included program rank, size, and age. Data were additionally collected from the Blue Ridge Institute for Medical Research, National Institutes of Health, funding in 2018 and the US News & World Report Best Medical Schools 2019-2020. A multivariable linear regression model was used that included Doximity ranking as the outcome variable and residency program size as the predictor variable with adjustment for the aforementioned variables. Results: Sixteen of the 28 specialties on Doximity were included in the analysis, representing 3388 unique residency programs. After adjustment for covariates, residency program size was a significant predictor of Doximity ranking (ß = -1.84; 95% CI -2.01 to -1.66, P < .001). Conclusions: These findings support the critique that the Doximity reputation ranking system may favor larger residency programs. More transparency for Doximity reputation ranking algorithm is warranted.

20.
Can J Urol ; 26(5): 9938-9944, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31629443

RESUMO

INTRODUCTION: To evaluate the overall survival and pathologic downstaging effect of neoadjuvant chemotherapy for upper tract urothelial cell carcinoma. MATERIALS AND METHODS: The National Cancer Database (NCDB) was queried for patients with stage II-IV upper tract urothelial cell carcinoma undergoing definitive surgical resection (nephroureterectomy) from 2004-2015. Patients with metastatic disease were excluded. Cohorts were stratified by receipt of neoadjuvant chemotherapy (NAC). Kaplan-Meier analysis and Cox regression were used to evaluate overall survival. Logistic regression was used to predict the odds of pathologic downstaging to non-invasive disease (< pT2). Propensity score matched analysis was performed between groups. RESULTS: A total of 3634 patients were identified with non-metastatic stage II-IV disease undergoing surgical resection; 3364 received no chemotherapy and 270 received NAC. Patients undergoing NAC had a 10.9% rate of downstaging to non-invasive disease (OR 6.35, p < 0.001). Moreover, on Kaplan-Meier analysis, median survival was 27.3 months and 44.8 months for no chemotherapy versus NAC, respectively (log-rank, p = 0.001). Cox regression for death also revealed benefits for receiving NAC (HR 0.67, p < 0.001). Findings were confirmed on propensity score matching (532 matched patients). After matching, Cox regression for death noted improvement with neoadjuvant as compared to no chemotherapy (HR 0.61, p < 0.001). CONCLUSION: Neoadjuvant chemotherapy increases likelihood of downstaging to non-invasive disease in patients with upper tract urothelial cell carcinoma. Chemotherapy also provides an overall survival benefit in patients undergoing nephroureterectomy.

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