Biomedical subjects

Nitin Jain

Publications and source records attributed to Nitin Jain.

12 recordsLinked to original sources

PubMed2026

Final phase 2 study results of acalabrutinib in treatment-naive and relapsed/refractory chronic lymphocytic leukemia.

Acalabrutinib is a selective, covalent Bruton tyrosine kinase inhibitor approved for marketing in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). We report final, long-term phase 1/2 study results in 99 patients with treatment-naive (TN) and 134 with relapsed/refractory (R/R) CLL/SLL. At final data cutoff, 71% and 31% of patients in the TN and R/R cohorts, respectively, remained on acalabrutinib treatment (median follow-up of 73.7 and 52.6 months). Among the events of clinical interest (any grade) in the TN and R/R cohorts, atrial fibrillation was reported in 6.1% and 9.0%, hypertension in 29.3% and 23.1%, other malignancies (excluding nonmelanoma skin cancer) in 14.1% and 17.2%, and major bleeding in 8.1% and 8.2% of patients, respectively. The incidence of the most common adverse events decreased over time. Overall response rates were 97.0% and 94.8% in the TN and R/R cohorts, respectively, with similar response findings among patients with standard and high-risk genomic features. In the TN cohort, median progression-free survival (PFS) was not reached and the 72-month PFS rate was 86.7% (95% confidence interval [CI], 77.0-92.5). For the R/R cohort, median PFS was 66.1 months (range, 0.4-87.8) and the 72-month PFS rate was 45.1% (95% CI, 35.6-54.1). This final analysis extends the duration of benefit observed with acalabrutinib, demonstrates that no new safety signals are apparent with longer follow-up, and confirms the safety and tolerability of acalabrutinib monotherapy for patients with CLL/SLL. This trial was registered at www.clinicaltrials.gov as #NCT02029443.

Humans↗

PubMed2006

Correlation of antibacterial activity of some N-[5-(2-furanyl)-2-methyl-4-oxo-4H-thieno[2,3-d]pyrimidin-3-yl]-carboxamide and 3-substituted-5-(2-furanyl)-2-methyl-3H-thieno[2,3-d]pyrimidin-4-ones with topological indices using Hansch analysis.

The antimicrobial activity of the N-[5-(2-furanyl)-2-methyl-4-oxo-4H-theino[2,3-d]pyrimidin-3-y1]-carboxamides and 3-substituted-5-(2-furanyl)-2-methyl-3H-thieno[2,3-d]pyrimidin-4-ones was correlated with different topological indices using Hansch analysis. Good correlations were obtained through a simple regression equation with third order molecular connectivity index (3chi). The developed QSAR models were crossvalidated by leave-one-out technique.

Animals↗

PubMed2006

Insulin and glucose play a role in foam cell formation and function.

BACKGROUND: Foam cell formation in diabetic patients often occurs in the presence of high insulin and glucose levels. To test whether hyperinsulinemic hyperglycemic conditions affect foam cell differentiation, we examined gene expression, cytokine production, and Akt phosphorylation in human monocyte-derived macrophages incubated with two types of oxidized low density lipoprotein (LDL), minimally modified LDL (mmLDL) and extensively oxidized LDL (OxLDL). METHODS AND RESULTS: Using Affymetrix GeneChip arrays, we found that several genes directly related to insulin signaling were changed. The insulin receptor and glucose-6-phosphate dehydrogenase were upregulated by mmLDL and OxLDL, whereas insulin-induced gene 1 was significantly down-regulated. In hyperinsulinemic hyperglycemic conditions, modified LDL upregulated Akt phosphorylation and expression of the insulin-regulated aminopeptidase. The level of proinflammatory cytokines, IL-lbeta, IL-12, and IL-6, and of a 5-lipoxygenase eicosanoid, 5-hydroxyeicosatetraenoic acid (5-HETE), was also increased. CONCLUSION: These results suggest that the exposure of macrophages to modified low density lipoproteins in hyperglycemic hyperinsulinemic conditions affects insulin signaling and promotes the release of proinflammatory stimuli, such as cytokines and eicosanoids. These in turn may contribute to the development of insulin resistance.

Cell Differentiation↗

PubMed2005

Rank-invariant resampling based estimation of false discovery rate for analysis of small sample microarray data.

BACKGROUND: The evaluation of statistical significance has become a critical process in identifying differentially expressed genes in microarray studies. Classical p-value adjustment methods for multiple comparisons such as family-wise error rate (FWER) have been found to be too conservative in analyzing large-screening microarray data, and the False Discovery Rate (FDR), the expected proportion of false positives among all positives, has been recently suggested as an alternative for controlling false positives. Several statistical approaches have been used to estimate and control FDR, but these may not provide reliable FDR estimation when applied to microarray data sets with a small number of replicates. RESULTS: We propose a rank-invariant resampling (RIR) based approach to FDR evaluation. Our proposed method generates a biologically relevant null distribution, which maintains similar variability to observed microarray data. We compare the performance of our RIR-based FDR estimation with that of four other popular methods. Our approach outperforms the other methods both in simulated and real microarray data. CONCLUSION: We found that the SAM's random shuffling and SPLOSH approaches were liberal and the other two theoretical methods were too conservative while our RIR approach provided more accurate FDR estimation than the other approaches.

Algorithms↗

PubMed2005

Combined size and density segregation and mixing in noncircular tumblers.

Flowing granular materials segregate due to differences in particle size (driven by percolation) and density (driven by buoyancy). For noncircular tumblers the additional interaction between the segregation mechanisms and chaotic advection complicates the physics. Experiments are performed using a bi-disperse mixture of equal volumes of different sizes of steel and glass beads in a quasi-two-dimensional square tumbler. Mixing is observed instead of segregation when the denser beads are larger than the lighter beads so that the ratio of particle sizes is greater than the ratio of particle densities. This can be expressed in terms of the particle diameters and masses as d(heavy)/d(light) >(m(heavy)/m(light))(1/4) . Segregation patterns vary from a semicircular core when the fill level is below 50% to more complicated patterns including lobes and streaks for fill levels above 50%. Temporal evolution of segregated patterns is quantified in terms of a "segregation index" (based on the area of the segregated pattern) to capture both the rate and extent of segregation at different particle properties. The circular and noncircular tumblers have no significant difference in the segregation index, even though the segregation patterns differ significantly.

Journal Article↗

PubMed2005

Creeping motion in granular flow.

The core of a quasi-two-dimensional rotating cylinder filled more than half full with glass beads rotates slightly faster than the cylinder itself and decreases in radius over time. Core precession depends linearly on the number of tumbler revolutions while core erosion varies logarithmically. Both processes serve to quantify the slow granular motion in the "fixed" bed and depend on the filling fraction and the tumbler rotation rate. A simple model, based on experimental observations of an exponential decrease in velocity parallel to the free surface, captures the primary features of the core dynamics.

Journal Article↗

PubMed2004

Effect of provider volume on resource utilization for surgical procedures of the knee.

Operating-room time and patient disposition on discharge are important determinants of healthcare resource utilization and cost. We examined the relation between these determinants and hospital/surgeon volume for anterior cruciate ligament (ACL) reconstruction and meniscectomy procedures. Patients undergoing ACL reconstruction (18,390 cases) and meniscectomy (123,012 cases) were extracted from the State Ambulatory Surgery Databases for the years 1997-2000. Surgeon and hospital volume were divided into low-, intermediate-, and high-volume categories. Multivariate logistic regression models were used to estimate the adjusted association between surgeon and hospital volume and patient discharge status and operating-room time. Patients undergoing ACL reconstruction or meniscectomy performed by low-volume surgeons were significantly more likely to be non-routinely discharged as compared to high-volume surgeons (adjusted odds ratio 3.5, 95% confidence interval 1.7-7.2 for ACL reconstruction; adjusted odds ratio 2.0, 95% confidence interval 1.6-2.3 for meniscectomy). The mean operating-room time for performing ACL reconstruction or meniscectomy was significantly higher in low- and intermediate-volume surgeons and hospitals as compared to high-volume surgeons and hospitals (p < or = 0.001). High-volume providers utilize healthcare resources more efficiently. Our findings may help surgeons and hospitals in optimizing resource utilization and cost for routinely-performed ambulatory surgery procedures.

Adult↗

PubMed2004

Insurance status and race represent independent predictors of undergoing laparoscopic surgery for appendicitis: secondary data analysis of 145,546 patients.

BACKGROUND: Studies have shown that racial and socioeconomic differences lead to inequality in access to health care. It is unknown whether insurance status and race affect the choice of surgical treatment for patients presenting with appendicitis. STUDY DESIGN: Patients with primary ICD-9 procedure codes for laparoscopic and open appendectomy were selected from the 1998, 1999, and 2000 Nationwide (US) Inpatient Samples. The primary predictor variables were insurance status (private, Medicare, Medicaid, other) and race (Caucasian, African American, Hispanic, other). Multiple logistic regression models were used to assess whether insurance status and race are associated with the choice of surgical procedure for patients presenting with appendicitis. RESULTS: Discharge abstracts of 145,546 patients were used for our analyses. There were 32,407 patients (22.3%) who underwent laparoscopic appendectomy and 113,139 patients (77.7%) who had open appendectomy. Although 24.2% of privately insured patients underwent laparoscopic appendectomy, only 16.9% of Medicare patients, 17.4% of Medicaid patients, and 19.6% of patients in the "other" insurance category were treated using the laparoscopic procedure (p < 0.001). Caucasian patients underwent laparoscopic surgery in 24.8%, African Americans in 18.6%, Hispanics in 19.6%, and other ethnicities in 18.8% of patients (p < 0.001). Compared with the Medicaid subset, and after adjusting for potential confounders such as age, gender, race, patient comorbidity, median ZIP code income, hospital location and teaching status, and presence of abscess or perforation, privately insured patients (odds ratio [OR] = 1.26, 95% [CI [1.20, 1.33], p < 0.001) and Medicare patients (OR = 1.17, 95% CI [1.05, 1.30], p = 0.004) were significantly more likely to undergo laparoscopic surgery. Caucasian patients (OR = 1.42, 95% CI [1.33, 1.51], p < 0.001) and Hispanics (OR = 1.12, 95% CI [1.04, 1.20], p = 0.002) were significantly more likely to have laparoscopic appendectomy, compared with African Americans, even after adjusting for the previously mentioned confounders and insurance status. CONCLUSIONS: Even after adjusting for potential confounders, insurance status and race are marked independent predictors of having laparoscopic surgery in patients treated for appendicitis in this sample.

Adult↗

PubMed2004

Laparoscopic appendectomy in the elderly.

BACKGROUND: Evidence suggests that laparoscopic appendectomy (LA) has advantages over open appendectomy (OA) in the treatment of appendicitis. It remains, however, unclear whether LA is indicated in the elderly patient population. METHODS: Patients with primary International Classification of Diseases, revision 9, procedure codes for LA (n=32406 patients) and OA (n=112884 patients) were selected from the 1998, 1999, and 2000 Nationwide Inpatient Samples. The end points that were under investigation were the length of hospital stay, the rate of routine discharge, and in-hospital morbidity and mortality rates. Multiple linear and logistic regression analyses were performed to assess the risk-adjusted association between the surgery type and the patient outcomes. Stratified analyses were performed according to age (65 years and older; less than 65 years old) and to the presence of appendiceal perforation or abscess. RESULTS: After risk adjustment, patients who underwent LA had a significantly shorter mean length of stay (LA, 2.45 days; OA, 3.71 days; P <. 0001), higher rate of routine discharge (odds ratio, 2.80; P <.0001), lower overall complication rate (odds ratio, 0.92; P=.03), and mortality rate (odds ratio, 0.23; P=.001) compared with OA patients. Similar benefits of LA were found in the strata of patients who were less than 65 years old, in elderly patients, and in patients with appendiceal perforation or abscess. CONCLUSION: LA has statistically significant advantages over OA with respect to the length of hospital stay, the rate of routine discharge, and postoperative morbidity and mortality rates for patients who are less than 65 years old, in elderly patients, and in patients with appendiceal abscess or perforation.

Abdominal Abscess↗

PubMed2004

The relationship between surgeon and hospital volume and outcomes for shoulder arthroplasty.

BACKGROUND: As far as we know, no previous study has determined the relationship between volume and outcomes for shoulder arthroplasty. We hypothesized that surgeons and hospitals with higher caseloads of total shoulder arthroplasties and hemiarthroplasties have better outcomes as measured by decreased mortality rate, shorter length of stay in the hospital, reduced postoperative complications, and routine disposition of patients on discharge. METHODS: Data on patients undergoing shoulder arthroplasty were extracted from the Nationwide Inpatient Sample databases for the years 1988 through 2000. Logistic regression with generalized estimating equations and multiple linear regression models were used to estimate the adjusted association between surgeon and hospital volume and outcomes for total shoulder arthroplasty and hemiarthroplasty after adjusting for comorbidity, age, race, household income, and sex. RESULTS: The mortality rates for patients who had a total shoulder arthroplasty performed by surgeons who did fewer than two procedures per year (0.36%) or who did between two and fewer than four procedures per year (0.32%) were higher than those for patients who had a total shoulder arthroplasty performed by surgeons who did four procedures or more per year (0.20%). The risk-adjusted rate of postoperative complications after hemiarthroplasty was significantly higher for patients managed by surgeons who performed fewer than two procedures per year (1.68%) than for those managed by surgeons with a volume of five procedures or more per year (0.97%). The possibility of postoperative complications when total shoulder arthroplasty was performed in hospitals with a volume of fewer than five procedures (1.44%) or in those with a volume of five to ten procedures per year (1.45%) was significantly higher than that in hospitals where ten procedures or more were performed every year (0.64%). The mean lengths of stay in the hospital after total shoulder arthroplasty and hemiarthroplasty were significantly longer when the operations were performed by surgeons who did fewer than two procedures per year or when they were done in hospitals with a volume of fewer than five procedures per year or with a volume of five to fewer than ten procedures per year than when they were done in hospitals or by surgeons in the highest volume category (p < 0.001). CONCLUSIONS: Patients who have a total shoulder arthroplasty or hemiarthroplasty performed by a high-volume surgeon or in a high-volume hospital are more likely to have a better outcome. LEVEL OF EVIDENCE: Therapeutic study, Level III-2 (retrospective cohort study). See Instructions to Authors for a complete description of levels of evidence.

Aged↗

PubMed2003

Local-pooled-error test for identifying differentially expressed genes with a small number of replicated microarrays.

MOTIVATION: In microarray studies gene discovery based on fold-change values is often misleading because error variability for each gene is heterogeneous under different biological conditions and intensity ranges. Several statistical testing methods for differential gene expression have been suggested, but some of these approaches are underpowered and result in high false positive rates because within-gene variance estimates are based on a small number of replicated arrays. RESULTS: We propose to use local-pooled-error (LPE) estimates and robust statistical tests for evaluating significance of each gene's differential expression. Our LPE estimation is based on pooling errors within genes and between replicate arrays for genes in which expression values are similar. We have applied our LPE method to compare gene expression in naïve and activated CD8+ T-cells. Our results show that the LPE method effectively identifies significant differential-expression patterns with a small number of replicated arrays. AVAILABILITY: The methodology is implemented with S-PLUS and R functions available at http://hesweb1.med.virginia.edu/bioinformatics

Algorithms↗

PubMed2003

Laparoscopic vs open colectomy: outcomes comparison based on large nationwide databases.

HYPOTHESIS: Laparoscopic colectomy has significant advantages over open colectomy in the treatment of diverticular disease with respect to the length of hospital stay, routine hospital discharge, and postoperative morbidity and mortality. DESIGN: Retrospective secondary data analysis. PATIENTS AND SETTING: Patients with primary International Classification of Diseases, Ninth Revision, Clinical Modification procedure codes for laparoscopic (709 patients [3.8%]) and open sigmoid resection (17 735 patients [96.2%]) were selected from the 1998, 1999, and 2000 Nationwide Inpatient Samples. These databases represent 20% stratified probability samples of all US community hospital discharges. Sampling weights were used to allow generalization of the study findings to the overall US population. Multiple linear and logistic regression analyses were performed to assess the risk-adjusted association between the surgery type and patient outcomes. MAIN OUTCOME MEASURES: Length of hospital stay, in-hospital complications, in-hospital mortality, and the rate of routine discharge. RESULTS: The patients had a mean age of 59.8 years; they were preponderantly white (89.1%) and female (54.0%). After adjusting for other covariates, laparoscopic sigmoidectomy was associated with a shorter mean hospital stay (laparoscopic sigmoidectomy vs open sigmoidectomy, 7.47 vs 9.37 days; P<.001), fewer gastrointestinal tract complications (odds ratio, 0.57; 95% confidence interval, 0.35-0.93; P =.03), a lower overall complication rate (odds ratio, 0.64; 95% confidence interval, 0.47-0.88; P =.007), and a higher routine hospital discharge rate (odds ratio, 2.21; 95% confidence interval, 1.51-3.21; P<.001). CONCLUSION: Laparoscopic sigmoid resection in patients with diverticular disease has statistically and clinically significant advantages over open sigmoid resection with respect to the length of hospital stay, rate of routine hospital discharge, and postoperative in-hospital morbidity.

Age Distribution↗