Sudhakar Manne | DePaul University (original) (raw)

Papers by Sudhakar Manne

JGH open, Aug 23, 2018

Background and Aim: Postoperative infection (POI) is a major source of morbidity and prolongation... more Background and Aim: Postoperative infection (POI) is a major source of morbidity and prolongation of hospitalization in inflammatory bowel disease (IBD) patients. This large observational study was conducted to further describe risk factors and to quantify the proportion of POIs that are preventable. Methods: We conducted a retrospective cohort analysis of the Optum US health insurance claims database. The study population included adults with ulcerative colitis (UC) or Crohn's disease (CD) who underwent lower gastrointestinal (GI) surgery of small intestine, colon, rectum, or anus during September 2014 to September 2016. Multiple logistic regression was used to identify and quantify risk factors and determine the proportion of infections that are preventable. Results: A total of 3360 adult IBD patients with lower GI surgery were included in the study. Their mean age was 51 years, 52.5% were women, and 59.5% had CD. The 30-day POI incidence was 15.1% (95% confidence interval: 14.0-16.4%). We identified the following nonmodifiable or procedural risk factors: history of POI, open procedure, red blood cell transfusion within 6 months, preoperative hospital stay of at least 4 days, lower GI ostomy surgery, lower GI resection surgery, and a history of chronic obstructive pulmonary disease. Modifiable risk factors included corticosteroid use and anemia prior to surgery, but few infections were attributable to these modifiable factors. Conclusions: This large, observational, real-world evidence study from the US found that the majority of the observed risk factors were nonmodifiable or procedure-related. Corticosteroid use and anemia before surgery were identified as modifiable risk factors.

Gastroenterology, May 1, 2019

Figure 1. a) Frame 2 (of 9) of RGG (radionuclide gastrogram) of representative patient. b) Mid-an... more Figure 1. a) Frame 2 (of 9) of RGG (radionuclide gastrogram) of representative patient. b) Mid-antrum and pre-pyloric TACs from RGG of Figure 1a. Mid-antrum ROI #4 (yellow dashed curve) demonstrates the largest effective fractional reduction in luminal diameter compared to the neighboring antral slices.

Organometallics, 2006

A general, two-step procedure is reported for the modular synthesis of a series of palladium comp... more A general, two-step procedure is reported for the modular synthesis of a series of palladium complexes of chelating Chugaev-type diaminocarbene ligands via metal-templated addition of hydrazines to alkylisocyanides. This method afforded high yields of (dicarbene)palladium dihalide complexes with methyl, isopropyl, cyclohexyl, and tert-butyl substituents by addition of hydrazine to the corresponding alkylisocyanide, and analogous backbone-substituted complexes were prepared by palladium-templated addition of methylhydrazine to methylisocyanide. The complexes were fully characterized by IR, 1 H NMR, and 13 C NMR spectroscopies. X-ray crystallographic analyses of four (dicarbene)palladium dibromide complexes revealed structural similarities with complexes of imidizole-based N-heterocyclic carbenes (NHCs), characterizing these chelating ligands as strongly donating, resonance-stabilized diaminocarbenes. To examine whether these ligands are amenable to cross-coupling catalyst optimization via systematic ligand modification, a set of 10 (dicarbene)palladium dihalide complexes was tested as precatalysts in the Suzuki-Miyaura coupling of bromobenzene with phenylboronic acid. Substantial variations in catalytic activity were observed, and a backbone-substituted palladium dicarbene complex derived from methylhydrazine was identified as the most active precatalyst. Catalyst activities did not correlate with ligand sterics, and subtle electronic perturbation of carbene donor ability by the alkyl groups is proposed to be the origin of the differences in activity. The optimized catalyst was found to give high yields in Suzuki-Miyaura cross-couplings of electron-poor aryl chlorides and a range of aryl bromides, although elevated temperatures (120°C) were necessary. Coupling reactions conducted open to air showed little formation of homocoupling byproduct and minimal loss of yield in most cases, identifying the optimized system as a rare example of an air-tolerant Suzuki-Miyaura catalyst. This study highlights the importance of a modular ligand design in fine-tuning the activity of a homogeneous catalyst.

Clinical Lymphoma Myeloma and Leukemia

BMJ Open, 2021

ObjectiveTo examine age, gender, and temporal differences in baseline characteristics and clinica... more ObjectiveTo examine age, gender, and temporal differences in baseline characteristics and clinical outcomes of adult patients hospitalised with COVID-19.DesignA cohort study using deidentified electronic medical records from a Global Research Network.Setting/Participants67 456 adult patients hospitalised with COVID-19 from the USA; 7306 from Europe, Latin America and Asia-Pacific between February 2020 and January 2021.ResultsIn the US cohort, compared with patients 18–34 years old, patients ≥65 had a greater risk of intensive care unit (ICU) admission (adjusted HR (aHR) 1.73, 95% CI 1.58 to 1.90), acute respiratory distress syndrome(ARDS)/respiratory failure (aHR 1.86, 95% CI 1.76 to 1.96), invasive mechanical ventilation (IMV, aHR 1.93, 95% CI, 1.73 to 2.15), and all-cause mortality (aHR 5.6, 95% CI 4.36 to 7.18). Men appeared to be at a greater risk for ICU admission (aHR 1.34, 95% CI 1.29 to 1.39), ARDS/respiratory failure (aHR 1.24, 95% CI1.21 to 1.27), IMV (aHR 1.38, 95% CI 1.3...

Blood, 2020

Background Maintenance therapy improves PFS in NDMM pts. Additional active, well-tolerated treatm... more Background Maintenance therapy improves PFS in NDMM pts. Additional active, well-tolerated treatment options that are suitable for long-term administration are required. The international, multicenter, double-blind, placebo-controlled, phase 3 TOURMALINE-MM4 trial (NCT02312258) of the oral PI ixazomib as maintenance therapy post-induction in non-transplant NDMM pts met its primary endpoint of PFS. Ixazomib demonstrated a significant and clinically meaningful benefit vs placebo, with a manageable and well-tolerated toxicity profile. Feasible, tolerable options for long-term therapy are particularly important in this setting, as pts are often elderly and/or frail. We report herein a subgroup analysis of TOURMALINE-MM4 according to age and frailty status. Methods Pts who achieved ≥partial response (PR) after 6-12 months of standard-of-care induction therapy were randomized 3:2 to ixazomib or placebo maintenance for up to 24 months. The sum of 4 components - age (<75 vs 75-80 vs >...

Gut, 2020

ObjectiveTo generate real-world evidence for the epidemiology of gastroparesis in the UK, we eval... more ObjectiveTo generate real-world evidence for the epidemiology of gastroparesis in the UK, we evaluated the prevalence, incidence, patient characteristics and outcomes of gastroparesis in the Clinical Practice Research Datalink (CPRD) database.DesignThis was a retrospective, cross-sectional study. Prevalence and incidence of gastroparesis were evaluated in the CPRD database, with linkage to Hospital Episodes Statistics Admitted Patient Care and Office for National Statistics mortality data. Prevalence and incidence were age and sex standardised to mid-2017 UK population estimates. Descriptive analyses of demographics, aetiologies, pharmacological therapies and mortality were conducted.ResultsStandardised prevalence of gastroparesis, as documented in general practice records, was 13.8 (95% CI 12.6 to 15.1) per 100 000 persons in 2016, and standardised incidence of gastroparesis rose from 1.5 (95% CI 1.1 to 1.8) per 100 000 person-years in 2004 to 1.9 (95% CI 1.4 to 2.3) per 100 000 pe...

INQUIRY: The Journal of Health Care Organization, Provision, and Financing, 2019

Application of selective algorithms to administrative health claims databases allows detection of... more Application of selective algorithms to administrative health claims databases allows detection of specific patients and disease or treatment outcomes. This study identified and applied different algorithms to a single data set to compare the numbers of patients with different inflammatory bowel disease classifications identified by each algorithm. A literature review was performed to identify algorithms developed to define inflammatory bowel disease patients, including ulcerative colitis, Crohn’s disease, and inflammatory bowel disease unspecified in routinely collected administrative claims databases. Based on the study population, validation methods, and results, selected algorithms were applied to the Optum Clinformatics® Data Mart database from June 2000 to March 2017. The patient cohorts identified by each algorithm were compared. Three different algorithms were identified from literature review and selected for comparison (A, B, and C). Each identified different numbers of pat...

Inflammatory Bowel Diseases, 2019

Background The latest estimate of the prevalence of inflammatory bowel disease (IBD) in the Unite... more Background The latest estimate of the prevalence of inflammatory bowel disease (IBD) in the United States was based on 2009 data, which indicates a need for an up-to-date re-estimation. The objectives of this study were to investigate the prevalence of all forms of IBD including ulcerative colitis (UC), Crohn’s disease (CD), and IBD unspecified (IBDU). Methods Pediatric (age 2–17) and adult (age ≥18) IBD patients were identified from 2 large claims databases. For each year between 2007 and 2016, prevalence was calculated per 100,000 population and standardized based on the 2016 national Census. A fixed-effects meta-analytical model was used for overall prevalence. Results The pediatric prevalence of IBD overall increased by 133%, from 33.0/100,000 in 2007 to 77.0/100,000 in 2016. Among children, CD was twice as prevalent as UC (45.9 vs 21.6). Prevalence was higher in boys than girls for all forms of IBD, in contrast to the adult population where the prevalence was higher in women th...

American Journal of Gastroenterology, 2018

Introduction: It is well known that patients with inflammatory bowel disease (IBD) are at higher ... more Introduction: It is well known that patients with inflammatory bowel disease (IBD) are at higher risk to develop osteoporosis. IBD can affect bone mineralization in multiple pathways including malabsorption, recurrent steroids use and increased inflammatory response. However, IBD patients have many potential confounders that also cause osteoporosis independent from IBD. Therefore we conducted this study to establish if IBD is an independent risk factor for the development of osteoporosis. Methods: Using data from the National Inpatient Sample (NIS) database between 2002 and 2014, we identified patients who were diagnosed with IBD and were compared to patients without IBD. We performed multivariate logistic regression analysis for the association between IBD and osteoporosis. Results: The total population was comprised of 101,020,258 patients, of which 704868 (0.69%) were diagnosed with IBD. IBD patients were older (50 vs 48) with more females (58.4% vs 57.3%) and more African American patients (14.4% vs 10%) (P < 0.001). In addition, IBD patients had less alcohol abuse (2.3% vs 3.4%), obesity (6% vs 6.9%) and renal disease (5.8% vs 7.2%) (P < 0.001 for all). However, IBD patients were more likely to smoke (12.9% vs 9.5%) and have thyroid disease (8.8% vs 8.2%) (P < 0.001 for all). Using Multivariate logistic regression, and after adjusting for potential confounding factors, IBD was a statistically significant risk factor for osteoporosis (Odds Ratio [OR], 1.869, 95% confidence interval [CI], 1.843-1.895, P < 0.001) compared with patients without IBD. Conclusion: IBD patients are at significant risk to develop osteoporosis. Hence, early screening for osteoporosis and appropriate treatment is essential to prevent fractures in IBD patients.

Medicine, 2017

Primary sclerosing cholangitis (PSC) is a rare obliterative fibrotic condition of the bile ducts.... more Primary sclerosing cholangitis (PSC) is a rare obliterative fibrotic condition of the bile ducts. We assessed PSC epidemiology and natural history within the UK Clinical Practice Research Datalink (CPRD). Incidence and natural history of PSC were evaluated in a retrospective cohort study using linkage of CPRD, Hospital Episode Statistics, and Office for National Statistics data. Data from age, sex, and general practice-matched population controls provided a context for the incident PSC patients. Liver disease other than PSC was defined as autoimmune hepatitis, hepatitis, hepatomegaly, liver failure, cirrhosis, portal hypertension, cholangiocarcinoma, or hepatobiliary cancer. The age-standardized incidence of PSC was 0.68 (95% confidence interval [CI] 0.45-0.99) per 100,000 person-years and the agestandardized prevalence was 5.58 (95% CI 4.82-7.35) per 100,000 during 1998 to 2014. In all, 250 incident PSC patients met the inclusion criteria and each was matched with 5 controls (mean age 54 ± 18 years, men 63.2%). A higher percentage of PSC patients had a history of inflammatory bowel disease (54% vs 2%) and liver disease other than PSC (22% vs 1%) than controls (standardized difference weighted >0.1). During a median follow-up of 5 years, PSC patients were more likely to develop adverse health outcomes. The mortality rate per 1000 person-years was 3-fold higher in PSC than population controls (49.5 vs 16.1; incidence rate ratio 3.1, 95% CI 2.2-4.2). The incidence and prevalence of PSC observed in the UK CPRD were either comparable with or higher than previous studies. Compared with the general population, PSC patients had worse health outcomes including PSC disease progression, complications, and higher mortality.

Obesity Science & Practice, 2016

To describe the characteristics of real-world patients potentially eligible for adjunctive pharma... more To describe the characteristics of real-world patients potentially eligible for adjunctive pharmacotherapy for weight loss. Methods Patients from the GE Centricity electronic medical record database were selected if they had body mass index (BMI) ≥30 or ≥27 to <30 kg m À2 with ≥1 obesity-associated comorbidity (hypertension, dyslipidemia, or type 2 diabetes) from 2002-2011; were aged ≥18 years and had ≥12 months of continuous enrollment before and after the date of first eligible BMI recorded (index date). Descriptive statistics and logistic regression were used for analysis. Results Of the 1,835,541 patients with overweight or obesity included, comorbidities were common (hypertension [55.4%], dyslipidemia [36.1%] and type 2 diabetes [13.4%]). The percentage of patients who received pharmacotherapy for weight loss was 0.7% within 12 months after the index date. Patients who received pharmacotherapy had higher BMI (median, 33.6 vs. 31.3 kg m À2), were younger (median, 42 vs. 52 years), primarily women (84.3 vs. 58.2%), commercially insured (70.1 vs. 50.4%) and had more frequent use of antidepressants (30.8 vs. 14.1%) and non-steroidal anti-inflammatory drugs (21.7 vs. 12.0%) than those who did not at baseline (all P values < 0.0001). Conclusions Few eligible patients received pharmacotherapy for weight loss. Patients who received pharmacotherapy tended to be heavier, younger, female, commercially insured, and used more antidepressants and non-steroidal anti-inflammatory drugs.

Gastroenterology, 2016

La prevención de la violencia en la infancia y la adolescencia. Una aproximación conceptual integ... more La prevención de la violencia en la infancia y la adolescencia. Una aproximación conceptual integral Violence prevention in childhood and adolescence. A conceptual and integral appro a c h José Manuel MORALES GONZÁLEZ* Miguel COSTA CABANILLAS** RESUMEN La comprensión del fenómeno de la violencia que afecta a niños y adolescentes sigue siendo una difícil tarea para los investigadores y los profesionales. Esta revisión intenta o f recer un modelo holístico de las medidas preventivas de acuerdo con los actuales estudios publicados en revistas nacionales e intemacionales. A pesar de que la definición de la violencia está afectada por un juicio social y cultural, los investigadores han intentado establecer criterios operativos que faciliten análisis comparativos entre los diferentes fact o res estructurales e interpersonales. Los autores se han centrado en la agresión interpersonal y han descrito cómo múltiples factores de riesgo y de protección interactúan e n t re sí. Diferentes programas preventivos han sido desarrollados durante los últimos años, mostrando muchos de ellos una alta eficacia para prevenir la violencia en niños y adolescentes cuando éstos han sido conducidos dentro del ámbito familiar y escolar. Por ello, el principal objetivo de este artículo fue exponer las diferentes estrategias basadas en la prevención primaria y secundaria de acuerdo con los recientes estudios publicados durante los últimos años.

BMJ Open Diabetes Research & Care, 2015

Care Excellence (NICE) guideline on diabetes recommends at least annual monitoring of patients wi... more Care Excellence (NICE) guideline on diabetes recommends at least annual monitoring of patients with type 2 diabetes mellitus (T2DM) for proteinuria. To date, little has been published on the frequency of proteinuria monitoring in T2DM, and its association with risk factors for renal complications. We aimed to describe proteinuria monitoring in patients with T2DM. Design: This study identified patients with T2DM aged 40 years or older with the first antidiabetic drug use in 2007-2012 (cohort entry) in the UK Clinical Practice Research Datalink. At least 1 year of registration before and after cohort entry was required. A test was considered undertaken if a medical or laboratory code indicated a urinary albumin or protein test. The percentage of patients with at least one test performed was obtained in 1 year after cohort entry and any time during follow-up. A Cox proportional hazards model was used to estimate the HRs of patients having the first screening test while adjusting for baseline covariates. Results: 65 790 patients (mean age 63.0 years, men 57.5%, mean follow-up 41.0 months) were included, of whom 49 707 (75.6%) patients had at least one test in 1 year after antidiabetic drug initiation and 59 400 (90.3%) had at least one test any time during follow-up. Proteinuria monitoring decreased with time since initiation of antidiabetic drug therapy and with number of treatment changes and was independently associated with age, sex, smoking status, and year of antidiabetic drug initiation. 12.3% of patients with T2DM tested had a positive proteinuria test for the first screening performed in 1 year after initiation of antidiabetic drug therapy. Conclusions: The findings suggested suboptimal compliance with the NICE guideline on proteinuria monitoring in patients with T2DM and that level of monitoring appeared to depend on multiple clinical factors.

Diabetes Care, 2014

OBJECTIVE To compare the risk of subsequent myocardial infarction (MI) between patients with and ... more OBJECTIVE To compare the risk of subsequent myocardial infarction (MI) between patients with and without type 2 diabetes mellitus (T2DM) in a retrospective cohort study. RESEARCH DESIGN AND METHODS Patients with their first MI recorded in the U.K. General Practice Research Database in 1997–2008 were classified as T2DM, diagnosed before or within 28 days after the date of the first recorded MI (i.e., the index date), or non-T2DM. Patients diagnosed within 28 days after the index date were assumed to have developed T2DM at baseline (i.e., before the index date). The primary outcome was the first subsequent MI. The secondary outcomes were all-cause death and a composite of all-cause death or subsequent MI. Cox proportional hazards models were fit to obtain hazard ratios (HRs) for all outcomes. RESULTS A total of 7,411 T2DM (median age 72 years; men 63.4%) and 48,726 non-T2DM patients (median age 69 years; men 65.3%) were included. The crude incidences (per 1,000 patient-years) in T2DM ...

Clinical Drug Investigation, 2013

Background Diabetes is an important global disease, associated with significant morbidity and an ... more Background Diabetes is an important global disease, associated with significant morbidity and an increased risk of death due to chronic end-organ complications. The thiazolidinediones, used mainly as third-line agents in type 2 diabetes mellitus (T2DM), have been associated with some safety concerns, such as an increased risk of bladder cancer, an increased risk of bone fracture and heterogeneous effects on cardiovascular events. Objective This study aimed to evaluate safety data on pioglitazone for several outcomes and examine them in context with each other as well as with insulin, another third-line treatment for T2DM. Methods This retrospective cohort study extracted data from May 1, 2000 until June 30, 2010, from the i3 InVision Data Mart TM database. To adjust for the testing of multiple hypotheses, the Holm method was applied to endpoints representing potential harm from pioglitazone treatment, separately from those representing potential benefit from pioglitazone. The study population included patients with T2DM C 45 years old who were new users of either pioglitazone or insulin. Key outcomes were incident cases of a composite of myocardial infarction (MI) or stroke requiring hospitalization; bone fracture requiring hospitalization; bladder cancer; and a composite of nine other selected cancers. Kaplan-Meier curves were generated and hazard ratios

Dendrimers are polymers with chemically well-defined hyper-branched three-dimensional architectur... more Dendrimers are polymers with chemically well-defined hyper-branched three-dimensional architectures. Metallodendrimers offer attractive advantages over their polymeric counterparts due to their unique properties, which make them suitable for a number of biomedical and industrial applications. Catalysis based on transition metals combine the advantages of both homogeneous and heterogeneous catalytic systems such as selectivity and recyclability. Herein we report a more controlled approach for a covalent attachment of chelating ligands to poly (propylene imine) dendrimer (PPI), followed by complexation with Palladium. PPI dendrimers of three successive generations have been successfully functionalized with covalently attached bipyridyl ligands on the surface of the dendrimer in a single step reaction. A novel series of metal-chelating dendrimers has been synthesized upon complexation of chelating bipyridyl ligands with palladium. Metallodendrimers have also been successfully character...