Rini Vohra

Background and Objectives: Cardiovascular disease (CVD) is the leading cause of death globally and hypercholesterolemia is one of the major risk factors associated with CVD. Due to a growing body of research on side effects and long-term impacts of conventional CVD treatments, focus is shifting towards exploring alternative treatment approaches such as Ayurveda. However, because of a lack of strong scientific evidence, the safety and efficacy profiles of such interventions have not been well established. The current study aims to conduct a systematic review and meta-analyses to explore the strength of evidence on efficacy and safety of Ayurvedic herbs for hypercholesterolemia. Methods: Literature searches were conducted using databases including Medline, Cochrane Database, AMED, Embase, AYUSH research portal, and many others. All randomized controlled trials on individuals with hypercholesterolemia using Ayurvedic herbs (alone or in combination) with an exposure period of ≥ 3 weeks were included, with primary outcomes being total cholesterol levels, adverse events, and other cardiovascular events. The search strategy was determined with the help of the Cochrane Metabolic and Endocrine Disorders Group. Two researchers assessed the risk of each study individually and discrepancies were resolved by consensus or consultation with a third researcher. Meta-analysis was conducted using the inverse variance method and results are presented as forest plots and data summary tables using Revman v5.3. Results: A systematic review of 32 studies with 1386 participants found randomized controlled trials of three Ayurvedic herbs, Allium sativum (garlic), Commiphora mukul (guggulu), and Nigella sativa (black cumin) on hypercholesterolemia that met inclusion criteria. The average duration of intervention was 12 weeks. Meta-analysis of the trials showed that guggulu reduced total cholesterol and low-density lipoprotein levels by 16.78 mg/dL (95% C.I. 13.96 to 2.61; p-value = 0.02) and 18.78 mg/dL (95% C.I. 34.07 to 3.48; p = 0.02), respectively. Garlic reduced LDL-C by 10.37 mg/dL (95% C.I. −17.58 to −3.16; p-value = 0.005). Black cumin lowered total cholesterol by 9.28 mg/dL (95% C.I. −17.36, to −1.19, p-value = 0.02). Reported adverse side effects were minimal. Conclusion: There is moderate to high level of evidence from randomized controlled trials that the Ayurvedic herbs guggulu, garlic, and black cumin are moderately effective for reducing hypercholesterolemia. In addition, minimal evidence was found for any side effects associated with these herbs, positioning them as safe adjuvants to conventional treatments.

Study 1.;Background: Individuals with autism spectrum disorders (ASD) have extensive comorbidities. The current literature lacks documentation of prevalence of different types of comorbidities and their association with healthcare utilization and expenditures among adults with ASD as compared to adults without ASD.;Aim: To determine: 1) the differences in prevalence of psychiatric, non-psychiatric comorbidities, other health conditions, healthcare utilization, and expenditures among adults with and without ASD; and 2) the association of type of comorbidity with healthcare utilization and expenditures of adults with ASD.;Method: A retrospective cohort study using claims data from three state Medicaid Analytic eXtract was conducted. Adults aged 22--64 years with ASD (ICD9-CM code: 299.xx) with at least one inpatient or two outpatient claims on separate service dates who were continuously enrolled between January 1, 2000 to December 31, 2008 were identified. ASD cases were matched to no ASD controls by age, sex, and race using propensity score matching (1:3). Baseline and outcome differences across cases and controls were examined using bivariate analyses for categorical (chi-square) and continuous independent variables (t-tests). All cause health care utilization (outpatient visits, inpatient hospitalizations, emergency room, and prescription drug use), and associated health care costs were assessed during the follow-up year. Multivariate multinomial logistic regressions for healthcare utilization and generalized linear models with gamma distribution for expenditures were conducted to compare healthcare utilization and expenditures among adults with and without ASD. Association of type of comorbidity with healthcare utilization (binary and multinomial logistic regressions) and expenditures (generalized linear models with gamma distribution) were also analyzed among adults with ASD. Multivariate regression analyses were adjusted for state, identification year, patient socio-demographics, baseline prescription drug use, and county characteristics.;Study 2.;Background: The use of emergency department (ED) visits among adults with psychiatric needs is known to be high, yet there are no comprehensive studies that have characterized ED use among adults with ASD. Adults with ASD may be at substantial risk of high ED use and costs.;Objectives: 1) To examine the trends in ED visits and mean total ED charges for adults with ASD over a period of 6 years; 2) To examine and compare the types of ED use (psychiatric, non-psychiatric, and injury) among adults with and without ASD.;Methods: A cross-sectional study using discharge level data from the Nationwide Emergency Department Sample (NEDS; 2006--2011) was conducted to the examine trends and characteristics of ED visits among adults aged 22--64 years, with and without ASD (ICD9-CM

Vascular endothelial growth factor (VEGF), tyrosine kinase (TK) and mechanistic target of rapamycin kinase (mTOR) inhibitors are common first-line (1 L) treatments for metastatic renal cell carcinoma (mRCC). Despite treatment availability, the 5-year survival rate in patients diagnosed at the metastatic stage is only ≈ 10%. To gain contemporary insights into RCC treatment trends that may inform clinical, scientific and payer considerations, treatment patterns and adverse events (AEs) associated with 1 L therapy were examined in a retrospective, longitudinal, population-based, observational study of patients with mRCC. US administrative claims data (Truven Health MarketScan Commercial Databases) were used to assess trends in 1 L treatment initiation in mRCC (2006–2015) and characterize patterns of individual 1 L treatments, baseline characteristics, comorbidities and treatment-related AEs from 2011 through 2015. Outcomes were evaluated by drug class and route of administration. Ten-year trend analysis (n = 4270) showed that TK/VEGF-directed therapy rapidly became more common than mTOR-directed therapy, and oral treatments were favored over intravenous (IV) treatments. Overall, 1992 eligible patients initiated 1 L treatment for mRCC from 2011 through 2015: 1752 (88%) received TK/VEGF-directed agents and 233 (12%) received mTOR-directed agents; 1674 (84%) received oral treatments, and 318 (16%) received IV treatments. The most common 1 L treatment was sunitinib (n = 849), followed by pazopanib (n = 631), temsirolimus (n = 157) and bevacizumab (n = 154). Patient characteristics and comorbidities, including age, diabetes and congestive heart failure, were independent predictors of 1 L mRCC treatment choice. The three most common potentially 1 L treatment–related AEs were nausea/vomiting (128.2 per 100 patient-years [PY]), hypertension (69 per 100 PY) and renal insufficiency (44.6 per 100 PY). A wide variety of agents were used as second-line (2 L) therapy. Substantial latency of onset was observed for several potentially treatment-related toxicities in patients treated with TK/VEGF- or mTOR-directed agents. In the US, 1 L TK/VEGF inhibitor uptake in recent years appears largely in line with national approvals and guidelines, with varied 2 L agent use. Although retrospective evaluation of claims data cannot assess underlying causality, insights from these real-world RCC treatment and AE patterns will be useful in informing medical and payer decisions.

Background A lack of gold standard treatment for autism spectrum disorders (ASD), no clear ASD management guidelines, and lack of evidence-based pharmacological interventions other than aripiprazole and risperidone elevate the risk of off-label prescribing and adverse effects among individuals with ASD, more so among adults. Objective The aim of this study was to identify and compare the types of prescription drug use, rates of polypharmacy, and characteristics associated with polypharmacy among adults with and without ASD in a retrospective cross-sectional analysis of a three-state Medicaid Analytic eXtract database (2000–2008). Methods Adults aged 22–64 years with ASD (ICD9-CM code: 299.xx) were propensity score-matched to ‘no ASD’ controls by age, sex, and race. General polypharmacy (≥6 unique classes of prescription drugs in a year) and psychotropic polypharmacy (≥3 unique prescription drug classes of psychotropic medications within a 90-day period) were the main study outcomes. Chi-square tests for rates, t tests for mean number of claims, and multivariate logistic regressions for likelihood of prescription drug use and polypharmacy were run. Results Annually, almost 75% of adults with ASD had >20 prescription drug claims compared with 33% of adults without ASD. Around 85% of adults with ASD used at least one psychotropic drug class compared with 42% of adults without ASD. Highly common psychotropics were antipsychotics (66%_ASD vs 20%_noASD), anticonvulsants (59%_ASD vs 20%_noASD), and anxiolytics/hypnotics/sedatives (21%_ASD vs 11%_noASD). Other than psychotropics, many adults with ASD used medical prescription drugs such as antimicrobials (47%), dermatologic agents (48%), respiratory agents (38%), gastrointestinal agents (31%), alternative medications (25%), antiparkinsonian agents (22.6%), antihyperlipidemics/statins (7.3%), and immunologics (2.0%). Rates of general (48%_ASD vs 32%_noASD) and psychotropic polypharmacy (19%_ASD vs 6%_noASD) were significantly higher in the ASD group. Conclusion Prescription drug use and polypharmacy rates among adults with ASD are substantially higher than those in an age-, sex-, and race-matched cohort of adults without ASD. Adults with ASD frequently use therapeutic treatments other than psychotropics. Healthcare providers, who usually report low confidence in treating patients with ASD, should play an active role in constant monitoring of prescription drug use patterns and patient response to interventions. Prescribers and caregivers are encouraged to make decisions after weighing the benefits and risks associated with a pharmacological treatment. Further investigations into the common use of any alternative treatments that can affect a patient’s response to core treatments should also be conducted.

A retrospective data analysis using 2000–2008 three state Medicaid Analytic eXtract was conducted to examine the prevalence and association of comorbidities (psychiatric and non-psychiatric) with healthcare utilization and expenditures of fee-for-service enrolled adults (22–64 years) with and without autism spectrum disorders (International Classification of Diseases, Ninth Revision–clinical modification code: 299.xx). Autism spectrum disorder cases were 1:3 matched to no autism spectrum disorder controls by age, gender, and race using propensity scores. Study outcomes were all-cause healthcare utilization (outpatient office visits, inpatient hospitalizations, emergency room, and prescription drug use) and associated healthcare expenditures. Bivariate analyses (chi-square tests and t-tests), multinomial logistic regressions (healthcare utilization), and generalized linear models with gamma distribution (expenditures) were used. Adults with autism spectrum disorders (n = 1772) had significantly higher rates of psychiatric comorbidity (81%), epilepsy (22%), infections (22%), skin disorders (21%), and hearing impairments (18%). Adults with autism spectrum disorders had higher mean annual outpatient office visits (32 _ASD vs 8 _noASD ) and prescription drug use claims (51 _ASD vs 24 _noASD ) as well as higher mean annual outpatient office visits (US$4375 _ASD vs US$824 _noASD ), emergency room (US$15,929 _ASD vs US$2598 _noASD ), prescription drug use (US$6067 _ASD vs US$3144 _noASD ), and total expenditures (US$13,700 _ASD vs US$8560 _noASD ). The presence of a psychiatric and a non-psychiatric comorbidity among adults with autism spectrum disorders increased the annual total expenditures by US$4952 and US$5084, respectively.