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Anand Shah

Publications and source records attributed to Anand Shah.

14 recordsLinked to original sources
PubMed2025

Multiplex PCR assay for the rapid detection of Klebsiella pneumoniae pathotypes.

Introduction. Klebsiella pneumoniae (Kp) is a major cause of nosocomial infections, with its evolving pathotypes including multidrug-resistant, hypervirulent (hvKp) and convergent strains posing significant diagnostic and treatment challenges due to combined antimicrobial resistance and virulence.Gap Statement. While there is a pressing requirement for thorough detection of Kp pathotypes, current assays in resource-limited environments are unable to effectively focus on essential carbapenemase and hypervirulence genes with the necessary reliability and precision.Aim. To develop and validate a multiplex PCR (m-PCR) assay capable of simultaneously detecting Kp isolates including those carrying partial or full virulence markers, alongside antimicrobial resistance.Methodology. In this study, an m-PCR assay was designed and optimized for the simultaneous detection of key biomarkers associated with hypervirulent (rmpA, rmpA2, iucA, peg344 and iroB), carbapenem-resistant (bla NDM, bla OXA-48-like and bla KPC) and convergent Kp pathotypes in clinical isolates. The assay was evaluated on clinical isolates and validated against whole-genome sequencing (WGS) data for accuracy, specificity and sensitivity.Results. The developed m-PCR assay exhibited 100% specificity when compared to WGS data, successfully detecting all target genes without cross-amplification in ATCC control strains. The assay demonstrated high sensitivity, efficiently amplifying bacterial genomes from minimal DNA input as low as 1 ng µl-1. Additionally, validation through sequencing confirmed the accuracy of detected amplicons.Conclusion. This m-PCR assay offers a rapid, sensitive and specific diagnostic tool for differentiating Kp pathotypes in clinical settings, aiding in timely intervention and improved infection control measures.

Klebsiella pneumoniae↗
PubMed2006

DADOS-Prospective: an open source application for Web-based prospective data collection.

BACKGROUND: Randomized, prospective trials involving multi-institutional collaboration have become a central part of clinical and translational research. However, data management and coordination of multi-center studies is a complex process that involves developing systems for data collection and quality control, tracking data queries and resolutions, as well as developing communication procedures. We describe DADOS-Prospective, an open-source Web-based application for collecting and managing prospective data on human subjects for clinical and translational trials. DADOS-Prospective not only permits users to create new clinical research forms (CRF) and supports electronic signatures, but also offers the advantage of containing, in a single environment, raw research data in downloadable spreadsheet format, source documentation and regulatory files stored in PDF format, and audit trails. RESULTS: Feedback from formal and field usability tests was used to guide the design and development of DADOS-Prospective. To date, DADOS-Prospective has been implemented in five prospective clinical studies at our institution. Four of these studies are still in the CRF creation phase and one study has been entirely launched. CONCLUSION: DADOS-Prospective has significant advantages over existing Web-based data collecting programs. At our institution, it has been demonstrated to be an efficient tool for prospective clinical studies.

Journal Article↗
PubMed2006

DADOS-Survey: an open-source application for CHERRIES-compliant Web surveys.

BACKGROUND: The Internet has been increasingly utilized in biomedical research. From online searching for literature to data sharing, the Internet has emerged as a primary means of research for many physicians and scientists. As a result, Web-based surveys have been employed as an alternative to traditional, paper-based surveys. We describe DADOS-Survey, an open-source Web-survey application developed at our institution that, to the best of our knowledge, is the first to be compliant with the Checklist for Reporting Results of Internet E-Surveys (CHERRIES). DADOS-Survey was designed with usability as a priority, allowing investigators to design and execute their own studies with minimal technical difficulties in doing so. RESULTS: To date, DADOS-Survey has been successfully implemented in five Institutional Review Board-approved studies conducted by various departments within our academic center. Each of these studies employed a Web-survey design as their primary methodology. Our initial experience indicates that DADOS-Survey has been used with relative ease by each of the investigators and survey recipients. This has been further demonstrated through formal and field usability testing, during which time suggestions for improvement were incorporated into the software design. CONCLUSION: DADOS-Survey has the potential to have an important role in the future direction of Web-survey administration in biomedical research. This CHERRIES-compliant application is tailored to the emerging requirements of quality data collection in medicine.

Academic Medical Centers↗
PubMed2006

Duke Surgery Research Central: an open-source Web application for the improvement of compliance with research regulation.

BACKGROUND: Although regulatory compliance in academic research is enforced by law to ensure high quality and safety to participants, its implementation is frequently hindered by cost and logistical barriers. In order to decrease these barriers, we have developed a Web-based application, Duke Surgery Research Central (DSRC), to monitor and streamline the regulatory research process. RESULTS: The main objective of DSRC is to streamline regulatory research processes. The application was built using a combination of paper prototyping for system requirements and Java as the primary language for the application, in conjunction with the Model-View-Controller design model. The researcher interface was designed for simplicity so that it could be used by individuals with different computer literacy levels. Analogously, the administrator interface was designed with functionality as its primary goal. DSRC facilitates the exchange of regulatory documents between researchers and research administrators, allowing for tasks to be tracked and documents to be stored in a Web environment accessible from an Intranet. Usability was evaluated using formal usability tests and field observations. Formal usability results demonstrated that DSRC presented good speed, was easy to learn and use, had a functionality that was easily understandable, and a navigation that was intuitive. Additional features implemented upon request by initial users included: extensive variable categorization (in contrast with data capture using free text), searching capabilities to improve how research administrators could search an extensive number of researcher names, warning messages before critical tasks were performed (such as deleting a task), and confirmatory e-mails for critical tasks (such as completing a regulatory task). CONCLUSION: The current version of DSRC was shown to have excellent overall usability properties in handling research regulatory issues. It is hoped that its release as an open-source application will promote improved and streamlined regulatory processes for individual academic centers as well as larger research networks.

Academic Medical Centers↗
PubMed2006

Chairperson and faculty gender in academic emergency medicine departments.

OBJECTIVES: Despite the influx of female physicians in academic medicine departments, there are a small number of women in faculty and departmental leadership positions in emergency medicine (EM). The objective of this study was to determine if the gender of the chairperson of an academic EM department is associated with the gender of the residency program director (RPD) and gender proportion of its faculty. METHODS: This was a retrospective analysis of 133 academic EM departments using the Society for Academic Emergency Medicine online residency catalog, program Web site, or e-mail. Main outcome measures were proportion of female EM faculty and gender of the RPD. RESULTS: Data were available for 133 academic departments. Women chaired 7.5% (n = 10) of departments and comprised 22.3% of all faculty and 15.0% (n = 20) of RPD positions. EM departments that were chaired by women had a significantly higher percentage of female faculty compared with those led by men (31% vs. 22%; p = 0.01). Similarly, departments that were chaired by women had a significantly higher proportion of female RPDs compared with those chaired by men (50% vs. 12%; p < 0.01). Compared with departments chaired by men, the RPD was 5.0 times (95% confidence interval = 1.9 to 27.8; p < 0.01) more likely to be a woman if the chairperson was also a woman. CONCLUSIONS: An academic EM department was more likely to have a higher proportion of female faculty and a female RPD when the department chairperson was female.

Emergency Medicine↗
PubMed2005

Fibroblast growth factor-23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease.

Hyperphosphatemia, calcitriol deficiency, and secondary hyperparathyroidism (SHPT) are common complications of chronic kidney disease (CKD). Fibroblast growth factor-23 (FGF-23) is a novel phosphaturic hormone that also inhibits renal 1alpha-hydroxylase activity and thus may be involved in the pathogenesis of SHPT. Several hypotheses were tested: that FGF-23 increases as renal function declines; is linearly associated with serum phosphate levels; is associated with increased phosphaturia independent of parathyroid hormone (PTH); and is associated with decreased calcitriol levels independent of renal function, hyperphosphatemia, and vitamin D stores. FGF-23, PTH, 25(OH)D3, calcitriol, calcium, phosphate, and urinary fractional excretion of phosphate (Fe(PO4)) were measured in 80 CKD patients. Multiple linear regression was used to test the hypotheses. FGF-23 and PTH were inversely associated with estimated GFR (eGFR), whereas calcitriol levels were linearly associated with eGFR. Hyperphosphatemia and hypocalcemia were present in only 12 and 6% of patients, respectively, all of whose eGFR was <30. Increased Fe(PO4) was associated with decreased eGFR, and both increased FGF-23 and PTH were independently associated with increased Fe(PO4). Increased FGF-23 and decreased 25(OH)D3 were independent predictors of decreased calcitriol, but the effects on calcitriol levels of renal function itself and hyperphosphatemia were completely extinguished by adjusting for FGF-23. It is concluded that FGF-23 levels increase early in CKD before the development of serum mineral abnormalities and are independently associated with serum phosphate, Fe(PO4), and calcitriol deficiency. Increased FGF-23 may contribute to maintaining normal serum phosphate levels in the face of advancing CKD but may worsen calcitriol deficiency and thus may be a central factor in the early pathogenesis of SHPT.

Adult↗
PubMed2005

Mechanisms of reactive oxygen species-dependent downregulation of insulin receptor substrate-1 by angiotensin II.

OBJECTIVE: Angiotensin II has been implicated in the pathogenesis of the vascular complications of insulin resistance. Recently, serine phosphorylation and degradation of insulin receptor substrate-1 (IRS-1) were shown to inhibit Akt activation and reduce glucose uptake. Therefore, we examined the effects of chronic angiotensin II treatment on IRS-1 phosphorylation and protein expression in vascular smooth muscle cells (VSMCs). METHODS AND RESULTS: Using Western analysis, we found that angiotensin II (100 nmol/L; 18 hours) caused a 61+/-5% degradation of IRS-1 and abolished insulin-induced activation of Akt. Phosphorylation of IRS-1 on Ser307, which leads to subsequent IRS-1 degradation, was stimulated by angiotensin II. This phosphorylation was blocked by the Src inhibitor PP1 and by the antioxidants N-acetylcysteine and ebselen. Stable overexpression of catalase abrogated angiotensin II-induced IRS-1 phosphorylation and IRS-1 degradation. Similarly, a mutant phosphoinositide-dependent kinase-1 (PDK1) that cannot associate with Src abolished IRS-1 phosphorylation and degradation induced by angiotensin II. Proteasome inhibitors also prevented IRS-1 degradation. CONCLUSIONS: Thus, angiotensin II decreases IRS-1 protein levels in VSMCs via Src, PDK1, and reactive oxygen species-mediated phosphorylation of IRS-1 on Ser307 and subsequent proteasome-dependent degradation. These events impair insulin signaling and provide a molecular basis for understanding the clinical observation that angiotensin II type 1 receptor antagonists improve insulin resistance and its associated vasculopathies.

Angiotensin II↗
PubMed2005

Circulating levels of the antiangiogenic marker sFLT-1 are increased in first versus second pregnancies.

Preeclampsia is far more common in women's first pregnancy but the mechanism of this association is unknown. Altered angiogenesis, marked by increased levels of circulating soluble fms-like tyrosine kinase (sFlt-1), an inhibitor of placental growth factor (PlGF) and vascular endothelial growth factor, has been implicated in the pathogenesis of preeclampsia. We tested the hypothesis that nulliparous women demonstrate increased sFlt-1 levels compared with multiparous women, suggesting an overall increase in relative antiangiogenesis during first pregnancies. We measured sFlt-1 and PlGF levels in early pregnancy serum samples from the first 2 completed pregnancies of 97 women who participated in the MOMS cohort study. Repeated measures analyses demonstrated that sFlt-1 levels were significantly increased in first compared with second pregnancies (877+/-598 pg/mL vs 728+/-399 pg/mL; P=.01) but there was no significant difference in PlGF levels (45.3+/-40.7 pg/mL vs 40.1+/-31.9 pg/mL; P=.14). After adjusting for age, gestational age, blood pressure, body mass index, smoking, and the interpregnancy time interval, the residual decrease in sFlt-1 levels from the first to the second pregnancy remained significant at 107 pg/mL (P=.04). Significant interaction between ethnicity and pregnancy order on sFlt-1 levels was observed such that Hispanic women demonstrated greater sFlt-1 levels than white women during their first pregnancy but lower levels in their second pregnancies. Increased sFlt-1 secretion in first versus second pregnancies may account in part for the increased risk of preeclampsia among nulliparous women. Additional studies are needed to verify these findings and to further examine ethnic differences in angiogenesis factors and their potential impact on the incidence of preeclampsia.

Adult↗
PubMed2004

Differential risk of hypertensive disorders of pregnancy among Hispanic women.

Preeclampsia and gestational hypertension are leading complications of pregnancy that also portend increased risk of future chronic hypertension. Although rates of chronic hypertension differ between non-Hispanic Caucasian and Hispanic women, few studies examined their relative rates of hypertensive disorders of pregnancy. The purpose of this study was to compare the risk of preeclampsia and gestational hypertension in a prospective cohort of normotensive, nulliparous Hispanic (n = 863) and non-Hispanic Caucasian women (n = 2,381). Compared with non-Hispanic Caucasian women, Hispanic women demonstrated a significantly decreased incidence of gestational hypertension (1.6% versus 8.5%; P < 0.01), but a similar incidence of preeclampsia (3.8% versus 3.7%; P = 0.9). Adjusting for age, smoking, diabetes, BP, body mass index (BMI), and multiple gestation uncovered an increased relative risk (RR) for preeclampsia among Hispanic women (RR 1.9; 95% CI, 1.1 to 3.3; P = 0.01), while their relative risk for gestational hypertension remained significantly decreased (RR 0.39; 95% CI, 0.22 to 0.72; P < 0.01). Among women who initially presented with hypertension during pregnancy, Hispanic women were over threefold (hazard ratio 3.3; 95% CI, 1.9 to 6.0; P < 0.01) more likely to develop preeclampsia than non-Hispanic Caucasian women. Besides Hispanic ethnicity, baseline BP, BMI, diabetes, and multiple gestation were independent risk factors for preeclampsia, whereas only baseline BP and BMI were associated with gestational hypertension. Socioeconomic status and access to prenatal care were not associated with either disorder. Hispanic ethnicity is independently associated with increased risk for preeclampsia and decreased risk for gestational hypertension. The initial presentation of hypertension during pregnancy in Hispanic women most likely represents early preeclampsia.

Adult↗
PubMed2004

Inflammation and glucose intolerance: a prospective study of gestational diabetes mellitus.

OBJECTIVE: Increased leukocyte count is a marker of inflammation that has been associated with the development of type 2 diabetes in prospective studies. Although gestational diabetes mellitus (GDM) and type 2 diabetes share certain pathophysiological mechanisms, few studies have examined inflammation and risk of GDM. RESEARCH DESIGN AND METHODS: We prospectively examined routine leukocyte counts collected at the first prenatal visit in a cohort of 2,753 nulliparous euglycemic women, 98 (3.6%) of whom were later diagnosed with GDM. Subjects were divided into quartiles of leukocyte count, and the results of third-trimester glucose screening tests and the incidence of GDM among these quartiles were compared. Logistic regression was used to calculate univariate and multivariable-adjusted relative risks (RRs) of GDM according to leukocyte quartiles. RESULTS: Leukocyte counts were increased among women who subsequently developed GDM compared with those who remained free of GDM (10.5 +/- 2.2 vs. 9.2 +/- 2.2 x 10(3) cells/ml; P < 0.01). There was a linear increase in postloading mean glucose levels (P for trend <0.01), the area under the glucose tolerance test curves (P for trend <0.01), and the incidence of GDM (quartile 1, 1.1; quartile 2, 2.5; quartile 3, 4.2; and quartile 4, 6.4%; P for trend <0.01) with increasing leukocyte quartiles. In the multivariable-adjusted analysis, the linear trend in the RR of GDM with increasing leukocyte quartiles remained statistically significant (quartile 1, reference; quartile 2, RR 2.3 [95% CI 0.9-5.7]; quartile 3, 3.3 [1.4-7.8]; quartile 4, 4.9 [2.1-11.2]; P for trend <0.01). CONCLUSIONS: Increased leukocyte count early in pregnancy is independently and linearly associated with the results of GDM screening tests and the risk of GDM. Although overlap in the leukocyte count distributions precludes it from being a clinically useful biomarker, these data suggest that inflammation is associated with the development of GDM and may be another pathophysiological link between GDM and future type 2 diabetes.

Adult↗
PubMed2003

Clinical spectrum and prevalence of neurologic events provoked by tilt table testing.

BACKGROUND: Motor activity occurring during neurocardiogenic syncope can mimic true neurologic events. OBJECTIVE: To assess the prevalence and type of apparent neurologic events associated with tilt table testing. METHODS: The records of consecutive patients undergoing tilt table testing for the evaluation of syncope were reviewed. Patients underwent a 70 degrees upright tilt for 40 minutes, followed by a 20-minute tilt while receiving isoproterenol hydrochloride. The results of tilt table tests were considered positive when clinical symptoms were reproduced in association with a decline in blood pressure. Clinical variables and neurologic events were analyzed. RESULTS: Tilt table tests were performed on 694 patients during the study period, and the results were positive in 222 of them. Eighteen patients (8%) had apparent neurologic events during tilt table testing. Eleven patients (5%) had apparent tonic-clonic seizure-like activity, and 7 patients (3%) had non-tonic-clonic neurologic events, including focal seizures (n = 3), dysarthria or aphasia (n = 2), unilateral extremity dysesthesia (n = 1), and reproduction of temporal lobe epilepsy symptoms (n = 1). The patients with tonic-clonic seizure-like activity had a significantly lower systolic blood pressure reading at the termination of tilt table testing than all other patients whose tilt table test results were positive (P =.04). The heart rate at the time of test termination was significantly lower in the patients with tonic-clonic seizure-like activity and non-tonic-clonic neurologic events (P<.01) than in those with positive test results and no provoked neurologic events, and asystole was provoked more frequently in these 2 patient populations (P =.03). CONCLUSIONS: Neurologic events are common during episodes of neurocardiogenic syncope, and this diagnosis should be considered in the evaluation of unexplained seizure-like activity.

Adrenergic beta-Agonists↗
PubMed2003

Current in vivo and in vitro screens for inhalant allergy.

Screening for inhalant allergy requires the use of a rapid, accurate, cost-effective methodology for the detection of the presence or absence of allergic responsiveness. In vivo and in vitro methods have been demonstrated to be sensitive and specific in the diagnosis of inhalant allergy, even with panels as small as seven or eight antigens. There is good concurrence between skin testing techniques and various serum measures of specific IgE, and both methods can be used effectively for screening inhalant allergy, although per-test costs for in vitro methods remain higher than comparable costs for skin testing [28]. Although the rapidity of both methods is acceptable, skin testing allows immediate observation and interpretation of test results, whereas all in vitro methods involve serum processing that delays results for hours to days. In general, both in vitro methods and epicutaneous testing with a device such as the Multi-Test II offer the clinician effective techniques in screening for inhalant allergy. Each technique has benefit and can be used in both primary care practices and in specialists' offices. The choice of the primary technique to be used for screening depends on the type of practice, the practice's familiarity with skin testing, the geographic region, and the relevant payer mix. A review of the relevant research on allergy screening suggests that the number of antigens used should be in the range of 8 to 12 and should include representative allergens from all the significant classes for the specific geographic [table: see text] region. This screen would probably contain one or two grasses, weeds, and trees, two or three molds, cat allergen, and one dust mite allergen. A sample panel is demonstrated in Box 6. It is important to recognize that the diagnosis and treatment of inhalant allergy is a fluid process. In patients who have negative allergy screens but for whom suspicion of inhalant allergy remains high, additional testing with ID techniques is sometimes indicated. This procedure might be suggested in patients for whom there is a high suspicion of mold allergy or who have unusual inhalant exposures. These individuals may represent a failure of the screening process and require additional testing. In these unusual cases, the judgment of the otolaryngic allergist is critical in guiding this further diagnostic work-up. The use of screening procedures for the diagnosis of inhalant allergy provides a rapid, accurate, and cost-effective method for evaluating patients with a history suggestive of allergic disease. Research suggests that a screening panel has strong clinometric properties and has both sensitivity and specificity in excess of 95%. It is statistically unlikely that a patient with negative findings to an allergy screen will demonstrate clinically significant inhalant allergy.

Humans↗
PubMed2002

Insulin resistance but not inflammation is associated with gestational hypertension.

Hypertensive disorders of pregnancy, including gestational hypertension and preeclampsia, are leading causes of pregnancy-associated morbidity. Although insulin resistance and inflammation contribute to preeclampsia, prospective data regarding mechanisms of gestational hypertension are sparse. We conducted a prospective, nested case-control study to test the hypotheses that insulin resistance, marked by reduced sex hormone-binding globulin (SHBG) levels, and inflammation, marked by increased C-reactive protein levels, are similarly associated with gestational hypertension. We measured first-trimester C-reactive protein and SHBG levels in 51 women who subsequently developed gestational hypertension and 102 randomly selected normotensive pregnant controls. Compared with controls, first-trimester SHBG levels were significantly reduced among women who later developed gestational hypertension (176+/-73 versus 203+/-79 nmol/L; P=0.03), but there was no difference in C-reactive protein levels. There was statistically significant interaction among nulliparity, first-trimester SHBG levels, and risk of gestational hypertension, such that increasing SHBG levels were associated with significantly reduced risk of gestational hypertension among nulliparous women (odds ratio, 0.64 per 50-nmol/L increase; 95% confidence interval, 0.46, 0.90; P<0.01) but not among multiparous women. This association remained significant after adjusting for potential confounders (odds ratio, 0.55; 95% confidence interval, 0.31, 0.98; P=0.04). We conclude that insulin resistance, but not inflammation, is an independent risk factor for gestational hypertension among nulliparous women. Furthermore, important mechanistic differences exist in the pathogenesis of gestational hypertension comparing nulliparous and multiparous women.

Adult↗