Dr. MANMOHAN SINGHAL - Academia.edu (original) (raw)
Papers by Dr. MANMOHAN SINGHAL
Journal of Clinical Oncology, Jun 1, 2022
Background: BTC is associated with poor prognosis and limited treatment choices. There is limited... more Background: BTC is associated with poor prognosis and limited treatment choices. There is limited evidence on HCRU and costs among BTC patients receiving systemic treatments (ST). This study examined HCRU and total direct cost of care among BTC patients treated with ST to understand the disease burden in management of BTC. Methods: A retrospective cohort study of BTC patients who received first line (1L) ST was conducted, using US private payer Cancer Care Quality Program data and administrative claims from the HealthCore Integrated Research Database between 07/01/2014-03/31/ 2021. Patients with ampullary cancer, brain/ CNS metastases, other primary cancer before BTC diagnosis were excluded. Per patient per month (PPPM) costs in 2020 USD were calculated during 1L, 2L, and 3L treatments associated with HCRU from inpatient, emergency room, and outpatient visits as well as outpatient pharmacy dispensing. Results: Among 298 BTC patients (biliary tract, n=203; gallbladder, n=65; bile duct, n=30; stage IV, n=231; stage III, n=28; stage I/II, n=39) who received ST, mean (SD) age was 61.7 (9) years at 1L treatment initiation, and the majority were female (58%). Following 1L treatment, 44% received 2L treatment, and 16% received 3L treatment. Median follow-up was 7.6 months. Among 201 (67%) patients who had hospitalization in the follow-up period, mean (SD) number of hospitalizations was 2.5 (2), and the average length of stay was 7.0 (5) days. Total PPPM all-cause costs were the lowest during 1L treatment
PubMed, Apr 1, 2022
Adrenal insufficiency (AI) is well entrenched in medical constraints like septic shock, criticall... more Adrenal insufficiency (AI) is well entrenched in medical constraints like septic shock, critically ill and multi-morbid hemodynamically unstable patients but its exact prevalence or differences in the cases of chronic liver disease (CLD) at variable grades of severity has recently gained momentum. The eventuality of AI propounding in stable compensated and decompensated cirrhosis without sepsis or in early and late stages of liver desecration are the existing lacunae in popular literature that this study aims to address. Material: A prospective, analytical study was conducted from March 2021 to December 2021 encompassing 100 hemodynamically stable patients with cirrhosis without infection, admitted at SMS Medical College, Jaipur, who were assessed clinically, biochemically and for adrenal functions. Adrenal insufficiency was defined on multivariable approach including basal 8am cortisol levels, followed by giving 250mcg synthetic adrenocorticotrophic hormone IM injection and retaking serum cortisol levels post-hourly interval to delineate peak and delta cortisol variables. All samples were processed by chemoluminiscence based method on fully automatic immunoassay analyser. Observation: The study comprised 81 males and 19 females with the mean age being 45.4±12.92 years, with CLD etiology concentrating substantially around alcohol consumption (71%). Viral comorbidities viz. HBV, HCV, both viral and alcohol related and miscellaneous causes were documented in 23, 10, 14 and 12 patients respectively. AI surfaced in 38% patients with CLD being statistically significant with p< 0.001. Inclusively, 10.5% patients with Child-Turcotte-Pugh (CTP) class A, 57.89% with CTP class B and 31.57% cases with CTP class C developed adrenal insufficiency. No statistical differences were found in age, sex; mean arterial pressure, heart rate, HDL, cirrhosis etiology, degree of alcohol consumption and manifestations of portal hypertension between patients with or without AI. For prudence, serum albumin levels were lower (p<0.5) with INR raised (p<0.33) in patients with AI than their counterparts. However, multivariate analysis revealed no direct independent adrenal insufficiency predictor. ROC curve showed that the CTP score may be a good predictor for AI in liver cirrhosis patients as supplemented by significant negative correlations found between CTP score and peak cortisol levels (p=0.001). Conclusion: Adrenal insufficiency found frequent even in stable cirrhotic patients form an integral division of the CLD spectra and worsening glucocorticoid levels should be periodically assessed in such patients for preventing parallel comorbidities.
PubMed, Apr 1, 2022
Non-Alcoholic Fatty Liver Disease is an emerging epidemic in the face of the new generation. It i... more Non-Alcoholic Fatty Liver Disease is an emerging epidemic in the face of the new generation. It is considered the hepatic manifestation of the metabolic syndrome. With the increasing prevalence of obesity and metabolic syndrome, it has become a common sight in our outpatient department. We have investigated the echocardiographic parameters for systolic and diastolic dysfunction in the patients with NAFLD to evaluate its effects on the heart and hope our study could shine a light and provide us with a perspective into the various effects the metabolic syndrome has on our body. Material: We recruited 35 Normotensive, Non-Diabetic Non-Alcoholic Fatty Liver Disease Patients (NAFLD) of age ranging from 18 to 60 years of age diagnosed on the basis of ultrasound Abdomen and 35 Controls from both inpatient and outpatient department of Sawai Man Singh Medical College and Allied Hospitals from the month of August 2021 to October 2021 for the study. Every Patient underwent conventional transthoracic and Tissue Doppler Echocardiography along with their physical and metabolic parameters. All the patients of NAFLD were graded ultrasongraphically based on Hamaguchi et al criteria. Observation: NAFLD patients had higher Body Mass Indices, Abdominal circumferences, Systolic Blood pressures, Total Cholesterol levels and Low-Density Lipoprotein levels in comparison to their normal counterparts. On the Echocardiographic front, the patient underwent transthoracic 2D ECHO and we observed an increased interventricular septum thickness (0.99 ± 0.04 vs 0.78 ± 0.05, p <0.0001), posterior wall thickness (0.96±0.05 vs 0.75±0.04 p < 0.0001) and left ventricular Mass (173±22.6 vs 116±8.24 p < 0.0001). On Tissue Doppler Imaging (TDI) we observed a decreased E/A ratio (1.25 ± 0.17 vs 1.44 ± 0.22 p < 0.0001) which was suggestive of an increased Left ventricular Dysfunction. On correlational analysis, we had made an observation that there was a positive correlation of the grading of fatty liver with that of interventricular septum thickness (r= 0.5305 p = 0.001), posterior wall thickness (r = 0.4362 p= 0.088) and left ventricular mass (r = 0.6292, p = 0.0001) with the grade of fatty liver. Conclusion: From our study, it was imperative that NAFLD even in the absence of Hypertension or Diabetes has a role in the impairment of Systolic and Diastolic function of the left ventricle and its role in cardiovascular morbidity and mortality cannot be ignored.
Value in Health, May 1, 2015
Acta Haematologica, 2022
Ruxolitinib is an FDA-approved treatment of intermediate- and high-risk myelofibrosis. In the pha... more Ruxolitinib is an FDA-approved treatment of intermediate- and high-risk myelofibrosis. In the phase 3 COMFORT studies, ruxolitinib reduced spleen volume in patients with myelofibrosis, with a median time to response of 3 months. However, nearly 20% of patients discontinued by month 4 with few treatment options available following discontinuation of ruxolitinib treatment. In this study, 2 independent patient care data sources were queried (Cardinal Health Oncology Provider Extended Network [OPEN] and HealthCore Integrated Research Environment [HIRE®]), and a retrospective review of medical charts was conducted. Patients aged ≥18 years with a diagnosis of myelofibrosis (primary or secondary), use of ruxolitinib for myelofibrosis, and documented physician-directed ruxolitinib interruption were included. Among 26 included patients, pre-interruption median (interquartile range [IQR]) ruxolitinib treatment duration was 123 (57–391, OPEN) and 110 (37–148, HIRE) days. Half the patients interrupted treatment within 3 months, commonly for adverse events (42% and 71%, respectively). After restarting ruxolitinib, median (IQR) re-treatment duration was 196 (54–553) and 166 (108–262) days, respectively. Consistent with previous reports, symptoms and spleen size improved in (OPEN/HIRE) 45%/43% and 40%/33% of evaluable patients, respectively. Further studies investigating the management of dose modifications and interruptions are needed to optimize benefit from ruxolitinib therapy.
Circulation, Nov 8, 2022
AHA estimated 10.3 million US adults with apparent treatment resistant hypertension (aTRH) in 201... more AHA estimated 10.3 million US adults with apparent treatment resistant hypertension (aTRH) in 2018; limited data exist regarding clinical outcomes for these patients. This retrospective cohort study assessed risk of major adverse cardiac events (MACE: stroke, myocardial infarction, heart failure hospitalization) and end stage renal disease (ESRD) among aTRH patients, comparing those with controlled blood pressure (CBP; SBP/DBP <130/80 mm Hg) vs uncontrolled blood pressure (UBP; ≥130/80 mm Hg), using linked IQVIA Ambulatory EMR- US and IQVIA PharMetrics® Plus claims data. Patients taking ≥3 antihypertensive (anti-HTN) classes within 30 days (index regimen) between 1/1/2015 and 6/30/2021, having ≥2 BP values post-index regimen (2 nd BP date = index date) with ≥12 months pre-index enrollment (baseline) were included. Unbalanced covariates were adjusted in the multivariable model. Cohorts consisted of 11,427 CBP and 22,333 UBP patients: mean (SD) age 62 (13) vs 60 (12) years, female (48% vs 46%), African-American (8% vs 12%), mean (SD) baseline SBP/DBP 118 (8)/70 (6) vs 141 (14)/82 (9) mm Hg, mean (SD) BMI 32 (8) vs 34 (10) kg/m 2 , respectively. The index regimen consisted of 3, 4, or ≥5 anti-HTN classes in 82% vs 79%, 15% vs 18%, and 2% vs 3% of CBP vs UBP patients, respectively (all p<0.001). Frequently observed baseline comorbidities in CBP vs UBP patients included hyperlipidemia (79% vs 76%), mild to moderate diabetes (43% vs 42%), chronic pulmonary disease (31% vs 25%), and congestive heart failure (27% vs 16%). Mean (SD) follow-up time was 2.7 (2.1) years for both cohorts. Patients with UBP were at 8% and 53% increased risk of developing MACE and ESRD, respectively, MACE risk was mainly driven by a 31% increased risk of stroke (figure). Despite being treated with 3+ anti-HTN classes, 66% of aTRH patients had UBP and demonstrated increased risk of MACE and ESRD compared to CBP patients. Development of future innovative treatment approaches can add value in the management of aTRH.
Journal of Clinical Oncology, Nov 1, 2013
124 Background: Improved outcomes with HER2-directed therapies highlight the importance of standa... more 124 Background: Improved outcomes with HER2-directed therapies highlight the importance of standardized testing for HER2 positivity. This study aimed to assess HER2 testing practices, rate of HER2+ disease, and trastuzumab use in early breast cancer (EBC) at the Huntsman Cancer Institute (HCI) a National Cancer Institute-Designated Center and member of the National Comprehensive Cancer Network. Methods: Included patients’ records from the HCI electronic data warehouse (EDW) and the HCI tumor registry were female, age ≥ 18 years, ≥ 2 visits in the EDW and a stage I to IIIa EBC diagnosis from 2005 to 2012. HER2 testing patterns were identified through chart review of pathology and clinical notes in the EDW. HER2+ was defined as either FISH+ or IHC3+. Patient characteristics, HER2+ rate, and trastuzumab use were evaluated descriptively. Discordance rate associated with reflex testing (IHC 2+ retested by FISH) was also evaluated. Results: A total of 1,459 women were included with stage I (49%, n=720), IIa (26%, n=374), IIb (14%, n=197), and IIIa (12%, n=168) EBC. Mean age was 57 years. HER2+ disease was identified in 243 (17%) tumors. Of HER2+ tumors, 104 (43%) were ER+/PR+, 33 (14%) ER+/PR-, 1 (&lt;1%) ER-/PR+, 79 (32%) ER-/PR-, and 26 (11%) unknown. Tumors were first tested for HER2 using: 1,192 (82%) IHC, 36 (3%) FISH, 227 (15%) unknown and 4 (&lt;1%) other tests. First IHC results were scored 0 (23%), 1+ (33%), 2+ (26%), 3+ (17%), and unknown (&lt;1%). Reflex testing within one month was performed in 301/308 (98%) of IHC 2+ tumors. The discordance rate of IHC/FISH was 10%. Trastuzumab was prescribed for 184/243 (76%) women whose tumors were considered HER2+ based on final interpretation and in 1 HER2 equivocal tumor. Documented reasons for lack of trastuzumab use in HER2+ patients (n=59) included low risk of recurrence based on stage or other treatments (n=18), loss to follow-up (n=13), unknown (n=11), not clinically appropriate due to age or comorbidity (n=10), and patient declined (n=7). Conclusions: This is one of few cancer registries assessing the rate of HER2+ disease in EBC. Reflex testing identified additional HER2+ tumors. The HER2+ rate was within range of previously published studies.
Diabetes, Jun 22, 2018
This study compared HbA1c control, treatment patterns, and costs in adults with T2DM initiated on... more This study compared HbA1c control, treatment patterns, and costs in adults with T2DM initiated on CANA or a GLP-1 based on administrative claims data from the HealthCore Integrated Research Database (4/2013-02/2016) augmented with laboratory data. The analysis included adult patients with ≥1 HbA1c result at baseline (BL) and in the 12-month follow-up period; statistical analysis was performed at 3-month intervals. Inverse probability of treatment weighting (IPTW) accounted for differences in BL characteristics. From 12 months pre- to 12 months post-index (Figure), there were no significant differences in HbA1c at each 3-month interval in patients initiated on CANA (n = 750) or GLP-1 (n = 2417); results were consistent regardless of BL HbA1c (≥7%, ≥8%, or ≥9%) (data not shown). A greater proportion of patients were adherent to index medication (proportion of days covered ≥80%) over 12 months with CANA vs. GLP-1 (47.5% vs. 37.5%; P <0.001). The likelihood of discontinuation from index medication was lower with CANA than GLP-1 (49.6% vs. 57.4%; HR [95% CI]: 0.78 [0.70, 0.88]). Continuous 12-month pharmacy costs were $1,421 lower with CANA vs. GLP-1. In summary, CANA initiation resulted in similar HbA1c values, greater adherence, less discontinuation, and lower treatment cost compared to GLP-1 in T2DM patients. Disclosure M. Singhal: Other Relationship; Self; Janssen Scientific Affairs, LLC. H. Tan: Other Relationship; Self; Janssen Scientific Affairs, LLC. C.I. Coleman: Research Support; Self; Janssen Pharmaceuticals, Inc., Boehringer Ingelheim Pharmaceuticals, Inc. W.H. Herman: Other Relationship; Self; Merck Sharp & Dohme Corp., Lexicon Pharmaceuticals, Inc.. Consultant; Self; Janssen Scientific Affairs, LLC.. Research Support; Spouse/Partner; Nestlé. Other Relationship; Self; American Diabetes Association. Advisory Panel; Self; National Committee for Quality Assurance (NCQA). J. Cai: Employee; Self; Janssen Scientific Affairs, LLC. M. Han: Employee; Self; Janssen Scientific Affairs, LLC. M. Ingham: Employee; Self; Janssen Scientific Affairs, LLC..
Value in Health, May 1, 2014
Objectives: This study was conducted to compare health and cost outcomes utilizing either Ticagre... more Objectives: This study was conducted to compare health and cost outcomes utilizing either Ticagrelor versus Plavix in the management of acute coronary syndrome (ACS) patients, and impact of generic Clopidogrel used in Hong Kong. MethOds: A decision analytic model was used to perform a cost-effectiveness analysis of treating ACS patients for one year with Ticagrelor plus aspirin strategy compared with Plavix (or generic Clopidogrel) plus aspirin strategy from Hong Kong health care provider perspective. To estimate discounted (3%) lifetime costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). The health states in the model included patient in ACS without event, myocardial infarction (MI), and death from vascular cause. The model simulates a cohort of 45-year-old patients with ACS, and Markov cycle is one year. The time horizon was lifetime (85 years old). Event rates were adopted from the PLATO study, and the ACS registry in the Prince of Wales Hospital (PWH) in Hong Kong. Probabilistic sensitivity analyses using Monte Carlo simulations were conducted to assess parameter uncertainty. Results: Compared with the Plavix (or generic Clopidogrel) treatment strategy, the Ticagrelor treatment strategy for ACS, STEMI, and UA / NSTEMI patients were associated with
Value in Health, May 1, 2015
Clinical Therapeutics, Dec 1, 2016
Purpose: Data comparing real-world effectiveness of the glucagon-like peptide-1 receptor agonists... more Purpose: Data comparing real-world effectiveness of the glucagon-like peptide-1 receptor agonists (GLP-1RAs) exenatide once weekly (QW) and liraglutide in the treatment of type 2 diabetes (T2D) are limited. Furthermore, there is limited information on exenatide QW or liraglutide response by glycemic control and insulin use status. This study identifies 1-year glycosylated hemoglobin (HbA 1c) and weight outcomes with exenatide QW and liraglutide in the real-world setting overall and in insulin-naive patients with uncontrolled T2D. Methods: This retrospective cohort study using national electronic medical record data compared 1-year HbA 1c and weight outcomes in patients with T2D prescribed exenatide QW or liraglutide. Included patients were adults (Z18 years old) with T2D who were GLP-1RA naive when newly prescribed exenatide QW or liraglutide between January 1, 2012, and March 31, 2013 (index date). Outcomes were reported descriptively overall and in subsets of insulinnaive patients with baseline HbA 1c Z7.0% or Z9.0%. Multivariable linear regression analyses were performed to estimate adjusted change in HbA 1c and weight. Findings: The study included 808 exenatide QW and 4333 liraglutide patients. Mean (SD) age was 57 (11) years in both groups. Mean baseline HbA 1c was 8.3% (1.5%) in exenatide QW patients and 8.4% (1.6%) in liraglutide patients (P ¼ 0.66); 16 (2%) of the exenatide QW and 1099 (25.4%) of the liraglutide patients were newly prescribed insulin on the index date (P o 0.001). Adjusted mean HbA 1c change at 1 year was À0.37% (95% CI, À0.53% to À0.21%) for exenatide QW and À0.37% (95% CI, À0.55% to À0.18%) for liraglutide. Adjusted HbA 1c reduction was more pronounced in insulin-naive patients with baseline HbA 1c Z7.0% (À0.71% and À0.80% for the exenatide QW and liraglutide patients, respectively, P 4 0.05) and Z9.0% (À1.73% and À1.57% for exenatide QW and liraglutide patients, respectively, P 4 0.05). Mean (adjusted) weight loss was À2.22 kg (95% CI, À3.06 to À1.37 kg) with exenatide QW and À2.21 kg (95% CI, À3.18 to À1.23 kg) with liraglutide. Implications: Exenatide QW and liraglutide lead to similar HbA 1c and weight reductions at 1 year in the real-world setting. Greater HbA 1c reductions occurred in insulin-naive patients with baseline HbA 1c Z7.0%. Both agents are appropriate options for patients needing antidiabetes therapy to lower HbA 1c while promoting weight loss.
Journal of Clinical Hypertension, Jul 17, 2023
Patients with apparent treatment‐resistant hypertension (aTRH) are at increased risk of end‐organ... more Patients with apparent treatment‐resistant hypertension (aTRH) are at increased risk of end‐organ damage and cardiovascular events. Little is known about the effects of blood pressure (BP) control in this population. Using a national claims database integrated with electronic medical records, the authors evaluated the relationships between uncontrolled BP (UBP; ≥130/80 mmHg) or controlled BP (CBP; <130/80 mmHg) and risk of major adverse cardiovascular events plus (MACE+; stroke, myocardial infarction, heart failure requiring hospitalization) and end‐stage renal disease (ESRD) in adult patients with aTRH (taking ≥3 antihypertensive medication classes concurrently within 30 days between January 1, 2015 and June 30, 2021). MACE+ components were also evaluated separately. Multivariable regression models were used to adjust for baseline differences in demographic and clinical characteristics, and sensitivity analyses using CBP <140/90 mmHg were conducted. Patients with UBP (n = 22 333) were younger and had fewer comorbidities at baseline than those with CBP (n = 11 427). In the primary analysis, which adjusted for these baseline differences, UBP versus CBP patients were at an 8% increased risk of MACE+ (driven by a 31% increased risk of stroke) and a 53% increased risk of ESRD after 2.7 years of follow‐up. Greater MACE+ (22%) and ESRD (98%) risk increases with UBP versus CBP were seen in the sensitivity analysis. These real‐world data showed an association between suboptimal BP control in patients with aTRH and higher incidence of MACE+ and ESRD linked with UBP despite the use of multidrug regimens. Thus, there remains a need for improved aTRH management.
Value in Health, May 1, 2016
BMJ open diabetes research & care, Nov 1, 2019
What is already known about this subject? ► The glycemic efficacy of sodium glucose cotransporter... more What is already known about this subject? ► The glycemic efficacy of sodium glucose cotransporter 2 (SGLT2) inhibitors versus glucagon-like peptide-1 (GLP-1) receptor agonists has not been compared in head-to-head clinical trials of patients with type 2 diabetes mellitus (T2DM); previous realworld studies based on electronic medical records data have shown similar HbA1c reductions with the SGLT2 inhibitor canagliflozin and GLP-1 receptor agonists in patients with T2DM. What are the new findings? ► After initiating canagliflozin 300 mg versus any dose of a GLP-1 receptor agonist, there were no significant differences in mean HbA1c levels at 3-month intervals for up to 12 months (primary outcome), with similar or better achievement of HbA1c<8.0% and <9.0% and better adherence, less discontinuation, and lower drug acquisition costs when adherent. How might these results change the focus of research or clinical practice? ► These findings provide comparative effectiveness data for canagliflozin 300 mg versus any dose of a GLP-1 receptor agonist in the absence of headto-head clinical trial results and corroborate results from previous real-world studies.
Peritoneal Dialysis International, 1999
2023 IEEE Statistical Signal Processing Workshop (SSP)
The Journal of Sexual Medicine
BackgroundTreatment with phosphodiesterase type 5 inhibitors (PDE-5is) is effective in treating e... more BackgroundTreatment with phosphodiesterase type 5 inhibitors (PDE-5is) is effective in treating erectile dysfunction (ED).AimThe objective of this study was to determine the effect of PDE-5is on the incidence of major adverse cardiovascular (CV) events (MACE; composite outcome of CV death, hospitalization for myocardial infarction, coronary revascularization, stroke, heart failure, and unstable angina pectoris) and overall mortality.MethodsA retrospective observational cohort study was conducted in a large US claims database in men with ≥1 diagnosis of ED without prior MACE within 1 year, from January 1, 2006, to October 31, 2020. The exposed group had ≥1 claim for PDE-5i and the unexposed group had no claims for PDE-5i, and the groups were matched up to 1:4 on baseline risk variables.OutcomeThe primary outcome was MACE and the secondary outcomes were overall mortality and individual components of MACE, determined by multivariable Cox proportional hazard modeling.ResultsMatched plus...
Circulation: Cardiovascular Quality and Outcomes
Background: Phosphodiesterase type 5 inhibitor (PDE-5i) medications are effective in treating Ere... more Background: Phosphodiesterase type 5 inhibitor (PDE-5i) medications are effective in treating Erectile Dysfunction (ED) for tens of millions of men in the US and worldwide. The objective of this study was to determine the effect of PDE-5is on the incidence of major adverse cardiovascular events (MACE) (composite outcome of cardiovascular (CV) death, hospitalization for myocardial infarction, coronary revascularization, stroke, heart failure, or unstable angina pectoris) and all-cause death. Methods: A retrospective observational cohort study was conducted in a large US commercial and Medicare insurance claims database in men with ≥1 diagnosis of ED without prior MACE hospitalization within 1 year from Jan 2006 to Oct 2020. The exposed group had ≥1 claim for PDE-5i; the unexposed group had no claims for PDE-5i and were matched 2:1 on baseline risk variables. The primary outcome was MACE and secondary outcome was all-cause death, determined by multivariate Cox proportional hazard mode...
International Journal of Research in Medical Sciences, 2022
Background: The COVID-19 pandemic, in its omnipresence, descended an unprecedented blow on the re... more Background: The COVID-19 pandemic, in its omnipresence, descended an unprecedented blow on the reeling facilities nationwide, which at its stabilising junction posed another threat – mucormycosis. Potentially immunodeficient cases, diabetes and excessive rampancy of steroids propagated this neo-epidemic, currently challenging the fretting mortality rate. Aim of the study was to analyse the clinical profile elaborating the recent illnesses and progression in patients admitted with mucormycosis in a dedicated ‘mucor-care’ centre.Methods: Total 195 admitted patients were evaluated based on their COVID protocol management and oxygen therapy administered with special emphasis on hygiene maintenance in view of mask support, oral care and hospitalisation course with duration and medications provided. Type and duration of glucocorticoids, injectable or oral, dispensed to the patients were duly logged and analysed.Results: Half cases (50%) were found COVID reverse transcriptase-polymerase ch...
Journal of Clinical Oncology, Jun 1, 2022
Background: BTC is associated with poor prognosis and limited treatment choices. There is limited... more Background: BTC is associated with poor prognosis and limited treatment choices. There is limited evidence on HCRU and costs among BTC patients receiving systemic treatments (ST). This study examined HCRU and total direct cost of care among BTC patients treated with ST to understand the disease burden in management of BTC. Methods: A retrospective cohort study of BTC patients who received first line (1L) ST was conducted, using US private payer Cancer Care Quality Program data and administrative claims from the HealthCore Integrated Research Database between 07/01/2014-03/31/ 2021. Patients with ampullary cancer, brain/ CNS metastases, other primary cancer before BTC diagnosis were excluded. Per patient per month (PPPM) costs in 2020 USD were calculated during 1L, 2L, and 3L treatments associated with HCRU from inpatient, emergency room, and outpatient visits as well as outpatient pharmacy dispensing. Results: Among 298 BTC patients (biliary tract, n=203; gallbladder, n=65; bile duct, n=30; stage IV, n=231; stage III, n=28; stage I/II, n=39) who received ST, mean (SD) age was 61.7 (9) years at 1L treatment initiation, and the majority were female (58%). Following 1L treatment, 44% received 2L treatment, and 16% received 3L treatment. Median follow-up was 7.6 months. Among 201 (67%) patients who had hospitalization in the follow-up period, mean (SD) number of hospitalizations was 2.5 (2), and the average length of stay was 7.0 (5) days. Total PPPM all-cause costs were the lowest during 1L treatment
PubMed, Apr 1, 2022
Adrenal insufficiency (AI) is well entrenched in medical constraints like septic shock, criticall... more Adrenal insufficiency (AI) is well entrenched in medical constraints like septic shock, critically ill and multi-morbid hemodynamically unstable patients but its exact prevalence or differences in the cases of chronic liver disease (CLD) at variable grades of severity has recently gained momentum. The eventuality of AI propounding in stable compensated and decompensated cirrhosis without sepsis or in early and late stages of liver desecration are the existing lacunae in popular literature that this study aims to address. Material: A prospective, analytical study was conducted from March 2021 to December 2021 encompassing 100 hemodynamically stable patients with cirrhosis without infection, admitted at SMS Medical College, Jaipur, who were assessed clinically, biochemically and for adrenal functions. Adrenal insufficiency was defined on multivariable approach including basal 8am cortisol levels, followed by giving 250mcg synthetic adrenocorticotrophic hormone IM injection and retaking serum cortisol levels post-hourly interval to delineate peak and delta cortisol variables. All samples were processed by chemoluminiscence based method on fully automatic immunoassay analyser. Observation: The study comprised 81 males and 19 females with the mean age being 45.4±12.92 years, with CLD etiology concentrating substantially around alcohol consumption (71%). Viral comorbidities viz. HBV, HCV, both viral and alcohol related and miscellaneous causes were documented in 23, 10, 14 and 12 patients respectively. AI surfaced in 38% patients with CLD being statistically significant with p< 0.001. Inclusively, 10.5% patients with Child-Turcotte-Pugh (CTP) class A, 57.89% with CTP class B and 31.57% cases with CTP class C developed adrenal insufficiency. No statistical differences were found in age, sex; mean arterial pressure, heart rate, HDL, cirrhosis etiology, degree of alcohol consumption and manifestations of portal hypertension between patients with or without AI. For prudence, serum albumin levels were lower (p<0.5) with INR raised (p<0.33) in patients with AI than their counterparts. However, multivariate analysis revealed no direct independent adrenal insufficiency predictor. ROC curve showed that the CTP score may be a good predictor for AI in liver cirrhosis patients as supplemented by significant negative correlations found between CTP score and peak cortisol levels (p=0.001). Conclusion: Adrenal insufficiency found frequent even in stable cirrhotic patients form an integral division of the CLD spectra and worsening glucocorticoid levels should be periodically assessed in such patients for preventing parallel comorbidities.
PubMed, Apr 1, 2022
Non-Alcoholic Fatty Liver Disease is an emerging epidemic in the face of the new generation. It i... more Non-Alcoholic Fatty Liver Disease is an emerging epidemic in the face of the new generation. It is considered the hepatic manifestation of the metabolic syndrome. With the increasing prevalence of obesity and metabolic syndrome, it has become a common sight in our outpatient department. We have investigated the echocardiographic parameters for systolic and diastolic dysfunction in the patients with NAFLD to evaluate its effects on the heart and hope our study could shine a light and provide us with a perspective into the various effects the metabolic syndrome has on our body. Material: We recruited 35 Normotensive, Non-Diabetic Non-Alcoholic Fatty Liver Disease Patients (NAFLD) of age ranging from 18 to 60 years of age diagnosed on the basis of ultrasound Abdomen and 35 Controls from both inpatient and outpatient department of Sawai Man Singh Medical College and Allied Hospitals from the month of August 2021 to October 2021 for the study. Every Patient underwent conventional transthoracic and Tissue Doppler Echocardiography along with their physical and metabolic parameters. All the patients of NAFLD were graded ultrasongraphically based on Hamaguchi et al criteria. Observation: NAFLD patients had higher Body Mass Indices, Abdominal circumferences, Systolic Blood pressures, Total Cholesterol levels and Low-Density Lipoprotein levels in comparison to their normal counterparts. On the Echocardiographic front, the patient underwent transthoracic 2D ECHO and we observed an increased interventricular septum thickness (0.99 ± 0.04 vs 0.78 ± 0.05, p <0.0001), posterior wall thickness (0.96±0.05 vs 0.75±0.04 p < 0.0001) and left ventricular Mass (173±22.6 vs 116±8.24 p < 0.0001). On Tissue Doppler Imaging (TDI) we observed a decreased E/A ratio (1.25 ± 0.17 vs 1.44 ± 0.22 p < 0.0001) which was suggestive of an increased Left ventricular Dysfunction. On correlational analysis, we had made an observation that there was a positive correlation of the grading of fatty liver with that of interventricular septum thickness (r= 0.5305 p = 0.001), posterior wall thickness (r = 0.4362 p= 0.088) and left ventricular mass (r = 0.6292, p = 0.0001) with the grade of fatty liver. Conclusion: From our study, it was imperative that NAFLD even in the absence of Hypertension or Diabetes has a role in the impairment of Systolic and Diastolic function of the left ventricle and its role in cardiovascular morbidity and mortality cannot be ignored.
Value in Health, May 1, 2015
Acta Haematologica, 2022
Ruxolitinib is an FDA-approved treatment of intermediate- and high-risk myelofibrosis. In the pha... more Ruxolitinib is an FDA-approved treatment of intermediate- and high-risk myelofibrosis. In the phase 3 COMFORT studies, ruxolitinib reduced spleen volume in patients with myelofibrosis, with a median time to response of 3 months. However, nearly 20% of patients discontinued by month 4 with few treatment options available following discontinuation of ruxolitinib treatment. In this study, 2 independent patient care data sources were queried (Cardinal Health Oncology Provider Extended Network [OPEN] and HealthCore Integrated Research Environment [HIRE®]), and a retrospective review of medical charts was conducted. Patients aged ≥18 years with a diagnosis of myelofibrosis (primary or secondary), use of ruxolitinib for myelofibrosis, and documented physician-directed ruxolitinib interruption were included. Among 26 included patients, pre-interruption median (interquartile range [IQR]) ruxolitinib treatment duration was 123 (57–391, OPEN) and 110 (37–148, HIRE) days. Half the patients interrupted treatment within 3 months, commonly for adverse events (42% and 71%, respectively). After restarting ruxolitinib, median (IQR) re-treatment duration was 196 (54–553) and 166 (108–262) days, respectively. Consistent with previous reports, symptoms and spleen size improved in (OPEN/HIRE) 45%/43% and 40%/33% of evaluable patients, respectively. Further studies investigating the management of dose modifications and interruptions are needed to optimize benefit from ruxolitinib therapy.
Circulation, Nov 8, 2022
AHA estimated 10.3 million US adults with apparent treatment resistant hypertension (aTRH) in 201... more AHA estimated 10.3 million US adults with apparent treatment resistant hypertension (aTRH) in 2018; limited data exist regarding clinical outcomes for these patients. This retrospective cohort study assessed risk of major adverse cardiac events (MACE: stroke, myocardial infarction, heart failure hospitalization) and end stage renal disease (ESRD) among aTRH patients, comparing those with controlled blood pressure (CBP; SBP/DBP <130/80 mm Hg) vs uncontrolled blood pressure (UBP; ≥130/80 mm Hg), using linked IQVIA Ambulatory EMR- US and IQVIA PharMetrics® Plus claims data. Patients taking ≥3 antihypertensive (anti-HTN) classes within 30 days (index regimen) between 1/1/2015 and 6/30/2021, having ≥2 BP values post-index regimen (2 nd BP date = index date) with ≥12 months pre-index enrollment (baseline) were included. Unbalanced covariates were adjusted in the multivariable model. Cohorts consisted of 11,427 CBP and 22,333 UBP patients: mean (SD) age 62 (13) vs 60 (12) years, female (48% vs 46%), African-American (8% vs 12%), mean (SD) baseline SBP/DBP 118 (8)/70 (6) vs 141 (14)/82 (9) mm Hg, mean (SD) BMI 32 (8) vs 34 (10) kg/m 2 , respectively. The index regimen consisted of 3, 4, or ≥5 anti-HTN classes in 82% vs 79%, 15% vs 18%, and 2% vs 3% of CBP vs UBP patients, respectively (all p<0.001). Frequently observed baseline comorbidities in CBP vs UBP patients included hyperlipidemia (79% vs 76%), mild to moderate diabetes (43% vs 42%), chronic pulmonary disease (31% vs 25%), and congestive heart failure (27% vs 16%). Mean (SD) follow-up time was 2.7 (2.1) years for both cohorts. Patients with UBP were at 8% and 53% increased risk of developing MACE and ESRD, respectively, MACE risk was mainly driven by a 31% increased risk of stroke (figure). Despite being treated with 3+ anti-HTN classes, 66% of aTRH patients had UBP and demonstrated increased risk of MACE and ESRD compared to CBP patients. Development of future innovative treatment approaches can add value in the management of aTRH.
Journal of Clinical Oncology, Nov 1, 2013
124 Background: Improved outcomes with HER2-directed therapies highlight the importance of standa... more 124 Background: Improved outcomes with HER2-directed therapies highlight the importance of standardized testing for HER2 positivity. This study aimed to assess HER2 testing practices, rate of HER2+ disease, and trastuzumab use in early breast cancer (EBC) at the Huntsman Cancer Institute (HCI) a National Cancer Institute-Designated Center and member of the National Comprehensive Cancer Network. Methods: Included patients’ records from the HCI electronic data warehouse (EDW) and the HCI tumor registry were female, age ≥ 18 years, ≥ 2 visits in the EDW and a stage I to IIIa EBC diagnosis from 2005 to 2012. HER2 testing patterns were identified through chart review of pathology and clinical notes in the EDW. HER2+ was defined as either FISH+ or IHC3+. Patient characteristics, HER2+ rate, and trastuzumab use were evaluated descriptively. Discordance rate associated with reflex testing (IHC 2+ retested by FISH) was also evaluated. Results: A total of 1,459 women were included with stage I (49%, n=720), IIa (26%, n=374), IIb (14%, n=197), and IIIa (12%, n=168) EBC. Mean age was 57 years. HER2+ disease was identified in 243 (17%) tumors. Of HER2+ tumors, 104 (43%) were ER+/PR+, 33 (14%) ER+/PR-, 1 (&lt;1%) ER-/PR+, 79 (32%) ER-/PR-, and 26 (11%) unknown. Tumors were first tested for HER2 using: 1,192 (82%) IHC, 36 (3%) FISH, 227 (15%) unknown and 4 (&lt;1%) other tests. First IHC results were scored 0 (23%), 1+ (33%), 2+ (26%), 3+ (17%), and unknown (&lt;1%). Reflex testing within one month was performed in 301/308 (98%) of IHC 2+ tumors. The discordance rate of IHC/FISH was 10%. Trastuzumab was prescribed for 184/243 (76%) women whose tumors were considered HER2+ based on final interpretation and in 1 HER2 equivocal tumor. Documented reasons for lack of trastuzumab use in HER2+ patients (n=59) included low risk of recurrence based on stage or other treatments (n=18), loss to follow-up (n=13), unknown (n=11), not clinically appropriate due to age or comorbidity (n=10), and patient declined (n=7). Conclusions: This is one of few cancer registries assessing the rate of HER2+ disease in EBC. Reflex testing identified additional HER2+ tumors. The HER2+ rate was within range of previously published studies.
Diabetes, Jun 22, 2018
This study compared HbA1c control, treatment patterns, and costs in adults with T2DM initiated on... more This study compared HbA1c control, treatment patterns, and costs in adults with T2DM initiated on CANA or a GLP-1 based on administrative claims data from the HealthCore Integrated Research Database (4/2013-02/2016) augmented with laboratory data. The analysis included adult patients with ≥1 HbA1c result at baseline (BL) and in the 12-month follow-up period; statistical analysis was performed at 3-month intervals. Inverse probability of treatment weighting (IPTW) accounted for differences in BL characteristics. From 12 months pre- to 12 months post-index (Figure), there were no significant differences in HbA1c at each 3-month interval in patients initiated on CANA (n = 750) or GLP-1 (n = 2417); results were consistent regardless of BL HbA1c (≥7%, ≥8%, or ≥9%) (data not shown). A greater proportion of patients were adherent to index medication (proportion of days covered ≥80%) over 12 months with CANA vs. GLP-1 (47.5% vs. 37.5%; P <0.001). The likelihood of discontinuation from index medication was lower with CANA than GLP-1 (49.6% vs. 57.4%; HR [95% CI]: 0.78 [0.70, 0.88]). Continuous 12-month pharmacy costs were $1,421 lower with CANA vs. GLP-1. In summary, CANA initiation resulted in similar HbA1c values, greater adherence, less discontinuation, and lower treatment cost compared to GLP-1 in T2DM patients. Disclosure M. Singhal: Other Relationship; Self; Janssen Scientific Affairs, LLC. H. Tan: Other Relationship; Self; Janssen Scientific Affairs, LLC. C.I. Coleman: Research Support; Self; Janssen Pharmaceuticals, Inc., Boehringer Ingelheim Pharmaceuticals, Inc. W.H. Herman: Other Relationship; Self; Merck Sharp & Dohme Corp., Lexicon Pharmaceuticals, Inc.. Consultant; Self; Janssen Scientific Affairs, LLC.. Research Support; Spouse/Partner; Nestlé. Other Relationship; Self; American Diabetes Association. Advisory Panel; Self; National Committee for Quality Assurance (NCQA). J. Cai: Employee; Self; Janssen Scientific Affairs, LLC. M. Han: Employee; Self; Janssen Scientific Affairs, LLC. M. Ingham: Employee; Self; Janssen Scientific Affairs, LLC..
Value in Health, May 1, 2014
Objectives: This study was conducted to compare health and cost outcomes utilizing either Ticagre... more Objectives: This study was conducted to compare health and cost outcomes utilizing either Ticagrelor versus Plavix in the management of acute coronary syndrome (ACS) patients, and impact of generic Clopidogrel used in Hong Kong. MethOds: A decision analytic model was used to perform a cost-effectiveness analysis of treating ACS patients for one year with Ticagrelor plus aspirin strategy compared with Plavix (or generic Clopidogrel) plus aspirin strategy from Hong Kong health care provider perspective. To estimate discounted (3%) lifetime costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). The health states in the model included patient in ACS without event, myocardial infarction (MI), and death from vascular cause. The model simulates a cohort of 45-year-old patients with ACS, and Markov cycle is one year. The time horizon was lifetime (85 years old). Event rates were adopted from the PLATO study, and the ACS registry in the Prince of Wales Hospital (PWH) in Hong Kong. Probabilistic sensitivity analyses using Monte Carlo simulations were conducted to assess parameter uncertainty. Results: Compared with the Plavix (or generic Clopidogrel) treatment strategy, the Ticagrelor treatment strategy for ACS, STEMI, and UA / NSTEMI patients were associated with
Value in Health, May 1, 2015
Clinical Therapeutics, Dec 1, 2016
Purpose: Data comparing real-world effectiveness of the glucagon-like peptide-1 receptor agonists... more Purpose: Data comparing real-world effectiveness of the glucagon-like peptide-1 receptor agonists (GLP-1RAs) exenatide once weekly (QW) and liraglutide in the treatment of type 2 diabetes (T2D) are limited. Furthermore, there is limited information on exenatide QW or liraglutide response by glycemic control and insulin use status. This study identifies 1-year glycosylated hemoglobin (HbA 1c) and weight outcomes with exenatide QW and liraglutide in the real-world setting overall and in insulin-naive patients with uncontrolled T2D. Methods: This retrospective cohort study using national electronic medical record data compared 1-year HbA 1c and weight outcomes in patients with T2D prescribed exenatide QW or liraglutide. Included patients were adults (Z18 years old) with T2D who were GLP-1RA naive when newly prescribed exenatide QW or liraglutide between January 1, 2012, and March 31, 2013 (index date). Outcomes were reported descriptively overall and in subsets of insulinnaive patients with baseline HbA 1c Z7.0% or Z9.0%. Multivariable linear regression analyses were performed to estimate adjusted change in HbA 1c and weight. Findings: The study included 808 exenatide QW and 4333 liraglutide patients. Mean (SD) age was 57 (11) years in both groups. Mean baseline HbA 1c was 8.3% (1.5%) in exenatide QW patients and 8.4% (1.6%) in liraglutide patients (P ¼ 0.66); 16 (2%) of the exenatide QW and 1099 (25.4%) of the liraglutide patients were newly prescribed insulin on the index date (P o 0.001). Adjusted mean HbA 1c change at 1 year was À0.37% (95% CI, À0.53% to À0.21%) for exenatide QW and À0.37% (95% CI, À0.55% to À0.18%) for liraglutide. Adjusted HbA 1c reduction was more pronounced in insulin-naive patients with baseline HbA 1c Z7.0% (À0.71% and À0.80% for the exenatide QW and liraglutide patients, respectively, P 4 0.05) and Z9.0% (À1.73% and À1.57% for exenatide QW and liraglutide patients, respectively, P 4 0.05). Mean (adjusted) weight loss was À2.22 kg (95% CI, À3.06 to À1.37 kg) with exenatide QW and À2.21 kg (95% CI, À3.18 to À1.23 kg) with liraglutide. Implications: Exenatide QW and liraglutide lead to similar HbA 1c and weight reductions at 1 year in the real-world setting. Greater HbA 1c reductions occurred in insulin-naive patients with baseline HbA 1c Z7.0%. Both agents are appropriate options for patients needing antidiabetes therapy to lower HbA 1c while promoting weight loss.
Journal of Clinical Hypertension, Jul 17, 2023
Patients with apparent treatment‐resistant hypertension (aTRH) are at increased risk of end‐organ... more Patients with apparent treatment‐resistant hypertension (aTRH) are at increased risk of end‐organ damage and cardiovascular events. Little is known about the effects of blood pressure (BP) control in this population. Using a national claims database integrated with electronic medical records, the authors evaluated the relationships between uncontrolled BP (UBP; ≥130/80 mmHg) or controlled BP (CBP; <130/80 mmHg) and risk of major adverse cardiovascular events plus (MACE+; stroke, myocardial infarction, heart failure requiring hospitalization) and end‐stage renal disease (ESRD) in adult patients with aTRH (taking ≥3 antihypertensive medication classes concurrently within 30 days between January 1, 2015 and June 30, 2021). MACE+ components were also evaluated separately. Multivariable regression models were used to adjust for baseline differences in demographic and clinical characteristics, and sensitivity analyses using CBP <140/90 mmHg were conducted. Patients with UBP (n = 22 333) were younger and had fewer comorbidities at baseline than those with CBP (n = 11 427). In the primary analysis, which adjusted for these baseline differences, UBP versus CBP patients were at an 8% increased risk of MACE+ (driven by a 31% increased risk of stroke) and a 53% increased risk of ESRD after 2.7 years of follow‐up. Greater MACE+ (22%) and ESRD (98%) risk increases with UBP versus CBP were seen in the sensitivity analysis. These real‐world data showed an association between suboptimal BP control in patients with aTRH and higher incidence of MACE+ and ESRD linked with UBP despite the use of multidrug regimens. Thus, there remains a need for improved aTRH management.
Value in Health, May 1, 2016
BMJ open diabetes research & care, Nov 1, 2019
What is already known about this subject? ► The glycemic efficacy of sodium glucose cotransporter... more What is already known about this subject? ► The glycemic efficacy of sodium glucose cotransporter 2 (SGLT2) inhibitors versus glucagon-like peptide-1 (GLP-1) receptor agonists has not been compared in head-to-head clinical trials of patients with type 2 diabetes mellitus (T2DM); previous realworld studies based on electronic medical records data have shown similar HbA1c reductions with the SGLT2 inhibitor canagliflozin and GLP-1 receptor agonists in patients with T2DM. What are the new findings? ► After initiating canagliflozin 300 mg versus any dose of a GLP-1 receptor agonist, there were no significant differences in mean HbA1c levels at 3-month intervals for up to 12 months (primary outcome), with similar or better achievement of HbA1c<8.0% and <9.0% and better adherence, less discontinuation, and lower drug acquisition costs when adherent. How might these results change the focus of research or clinical practice? ► These findings provide comparative effectiveness data for canagliflozin 300 mg versus any dose of a GLP-1 receptor agonist in the absence of headto-head clinical trial results and corroborate results from previous real-world studies.
Peritoneal Dialysis International, 1999
2023 IEEE Statistical Signal Processing Workshop (SSP)
The Journal of Sexual Medicine
BackgroundTreatment with phosphodiesterase type 5 inhibitors (PDE-5is) is effective in treating e... more BackgroundTreatment with phosphodiesterase type 5 inhibitors (PDE-5is) is effective in treating erectile dysfunction (ED).AimThe objective of this study was to determine the effect of PDE-5is on the incidence of major adverse cardiovascular (CV) events (MACE; composite outcome of CV death, hospitalization for myocardial infarction, coronary revascularization, stroke, heart failure, and unstable angina pectoris) and overall mortality.MethodsA retrospective observational cohort study was conducted in a large US claims database in men with ≥1 diagnosis of ED without prior MACE within 1 year, from January 1, 2006, to October 31, 2020. The exposed group had ≥1 claim for PDE-5i and the unexposed group had no claims for PDE-5i, and the groups were matched up to 1:4 on baseline risk variables.OutcomeThe primary outcome was MACE and the secondary outcomes were overall mortality and individual components of MACE, determined by multivariable Cox proportional hazard modeling.ResultsMatched plus...
Circulation: Cardiovascular Quality and Outcomes
Background: Phosphodiesterase type 5 inhibitor (PDE-5i) medications are effective in treating Ere... more Background: Phosphodiesterase type 5 inhibitor (PDE-5i) medications are effective in treating Erectile Dysfunction (ED) for tens of millions of men in the US and worldwide. The objective of this study was to determine the effect of PDE-5is on the incidence of major adverse cardiovascular events (MACE) (composite outcome of cardiovascular (CV) death, hospitalization for myocardial infarction, coronary revascularization, stroke, heart failure, or unstable angina pectoris) and all-cause death. Methods: A retrospective observational cohort study was conducted in a large US commercial and Medicare insurance claims database in men with ≥1 diagnosis of ED without prior MACE hospitalization within 1 year from Jan 2006 to Oct 2020. The exposed group had ≥1 claim for PDE-5i; the unexposed group had no claims for PDE-5i and were matched 2:1 on baseline risk variables. The primary outcome was MACE and secondary outcome was all-cause death, determined by multivariate Cox proportional hazard mode...
International Journal of Research in Medical Sciences, 2022
Background: The COVID-19 pandemic, in its omnipresence, descended an unprecedented blow on the re... more Background: The COVID-19 pandemic, in its omnipresence, descended an unprecedented blow on the reeling facilities nationwide, which at its stabilising junction posed another threat – mucormycosis. Potentially immunodeficient cases, diabetes and excessive rampancy of steroids propagated this neo-epidemic, currently challenging the fretting mortality rate. Aim of the study was to analyse the clinical profile elaborating the recent illnesses and progression in patients admitted with mucormycosis in a dedicated ‘mucor-care’ centre.Methods: Total 195 admitted patients were evaluated based on their COVID protocol management and oxygen therapy administered with special emphasis on hygiene maintenance in view of mask support, oral care and hospitalisation course with duration and medications provided. Type and duration of glucocorticoids, injectable or oral, dispensed to the patients were duly logged and analysed.Results: Half cases (50%) were found COVID reverse transcriptase-polymerase ch...