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Approximately 476,000 cases of Lyme disease are diagnosed in the United States annually, yet comprehensive economic evaluations are lacking. In a prospective study among reported cases in Lyme disease-endemic states, we estimated the total patient cost and total societal cost of the disease. In addition, we evaluated disease and demographic factors associated with total societal cost. Participants had a mean patient cost of ≈$1,200 (median $240) and a mean societal cost of ≈$2,000 (median $700). Patients with confirmed disseminated disease or probable disease had approximately double the societal cost of those with confirmed localized disease. The annual, aggregate cost of diagnosed Lyme disease could be $345-968 million (2016 US dollars) to US society. Our findings emphasize the importance of effective prevention and early diagnosis to reduce illness and associated costs. These results can be used in cost-effectiveness analyses of current and future prevention methods, such as a vaccine.

Background: West Nile virus (WNV) is the leading cause of arboviral disease in the United States and is associated with significant morbidity and mortality. A previous analysis found that a vaccination program targeting persons aged ≥60 years was more cost-effective than universal vaccination, but costs remained high., Methods: We used a mathematical Markov model to evaluate cost-effectiveness of an age- and incidence-based WNV vaccination program. We grouped states and large counties (≥100 000 persons aged ≥60 years) by median annual WNV incidence rates from 2004 to 2017 for persons aged ≥60 years. We defined WNV incidence thresholds, in increments of 0.5 cases per 100 000 persons ≥60 years. We calculated potential cost per WNV vaccine-prevented case and per quality adjusted life-years (QALYs) saved., Results: Vaccinating persons aged ≥60 years in states with an annual incidence of WNV neuroinvasive disease of ≥0.5 per 100 000 resulted in approximately half the cost per health outcome averted compared to vaccinating persons aged ≥60 years in the contiguous United States. This approach could potentially prevent 37% of all neuroinvasive disease cases and 63% of WNV-related deaths nationally. Employing such a threshold at a county level further improved cost-effectiveness ratios while preventing 19% and 30% of WNV-related neuroinvasive disease cases and deaths, respectively., Conclusions: An age- and incidence-based WNV vaccination program could be a more cost-effective strategy than an age-based program while still having a substantial impact on lowering WNV-related morbidity and mortality., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

An estimated 300,000 cases of Lyme disease occur in the United States annually. Disseminated Lyme disease may result in carditis, arthritis, facial palsy or meningitis, sometimes requiring hospitalization. We describe the epidemiology and cost of Lyme disease-related hospitalizations. We analysed 2005-2014 data from the Truven Health Analytics MarketScan Commercial Claims and Encounters Databases to identify inpatient records associated with Lyme disease based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. We estimated the annual number and median cost of Lyme disease-related hospitalizations in the United States in persons under 65 years of age. Costs were adjusted to reflect 2016 dollars. Of 20,983,165 admission records contained in the inpatient databases during the study period, 2,823 (0.01%) met inclusion criteria for Lyme disease-related hospitalizations. Over half of the identified records contained an ICD-9-CM code for meningitis (n = 614), carditis (n = 429), facial palsy (n = 400) or arthritis (n = 377). Nearly 60% of hospitalized patients were male. The median cost per Lyme disease-related hospitalization was $11,688 (range: $140-$323,613). The manifestation with the highest median cost per stay was carditis ($17,461), followed by meningitis ($15,177), arthritis ($13,012) and facial palsy ($10,491). Median cost was highest among the 15- to 19-year-old age group ($12,991). Admissions occurring in January had the highest median cost ($13,777) for all study years. Based on extrapolation to the U.S. population, we estimate that 2,196 Lyme disease-related hospitalizations in persons under 65 years of age occur annually with an estimated annual cost of $25,826,237. Lyme disease is usually treated in an outpatient setting; however, some patients with Lyme disease require hospitalization, underscoring the need for effective prevention methods to mitigate these serious cases. Information from this analysis can aid economic evaluations of interventions that prevent infection and advances in disease detection., (Published 2020. This article is a U.S. Government work and is in the public domain in the USA.)

Retinoblastoma (RB) is a childhood eye tumor, caused by the RB1 gene mutation. Since RB is a rapidly proliferating tumor, the patient presents with a Group-D/E tumor at the time of diagnosis. Enucleation is preferred in most unilateral cases to prevent metastasis. Various cell lines have been established to study the tumor's growth pattern and target the cancer cells. The commonly used cell lines are WERI-Rb-1 and Y79, both isolated from the primary tumor of RB. Cell lines established from the metastatic site of RB have not been characterized before. In this study, we have characterized NCC-RbC-51, derived from RB tumor to cervical lymph node site and investigated its potential to represent a highly aggressive and metastatic tumor. We compared the proliferative and invasive properties of NCC-RbC-51 with a cell line isolated from the primary site, WERI-Rb-1. NCC-RbC-51 had higher rates of proliferation and apoptosis and had better invasive ability. Copy number variation analysis and the pathways predicted from these show that the pathways altered in NCC-RbC-51 could contribute to its metastatic nature. In all, the results suggest that NCC-RbC-51, a cell line isolated from metastatic site, could be a potential model to study aggressive/invasive RB.

Dengue is a mosquito-borne viral illness that causes a variety of health outcomes, from a mild acute febrile illness to potentially fatal severe dengue. Between 2005 and 2010, the annual number of suspected dengue cases reported to the Passive Dengue Surveillance System (PDSS) in Puerto Rico ranged from 2,346 in 2006 to 22,496 in 2010. Like other passive surveillance systems, PDSS is subject to under-reporting. To estimate the degree of under-reporting in Puerto Rico, we built separate inpatient and outpatient probability-based multiplier models, using data from two different surveillance systems-PDSS and the enhanced dengue surveillance system (EDSS). We adjusted reported cases to account for sensitivity of diagnostic tests, specimens with indeterminate results, and differences between PDSS and EDSS in numbers of reported dengue cases. In addition, for outpatients, we adjusted for the fact that less than 100% of medical providers submit diagnostic specimens from suspected cases. We estimated that a multiplication factor of between 5 (for 2010 data) to 9 (for 2006 data) must be used to correct for the under-reporting of the number of laboratory-positive dengue inpatients. Multiplication factors of between 21 (for 2010 data) to 115 (for 2008 data) must be used to correct for the under-reporting of laboratory-positive dengue outpatients. We also estimated that, after correcting for underreporting, the mean annual rate, for 2005-2010, of medically attended dengue in Puerto Rico to be between 2.1 (for dengue inpatients) to 7.8 (for dengue outpatients) per 1,000 population. These estimated rates compare to the reported rates of 0.4 (dengue outpatients) to 0.1 (dengue inpatients) per 1,000 population. The multipliers, while subject to limitations, will help public health officials correct for underreporting of dengue cases, and thus better evaluate the cost-and-benefits of possible interventions., Competing Interests: The authors have declared that no competing interests exist.

Background Anogeissus latifolia Wall. (A. latifolia) bark has been traditionally used in the treatment of various diseases which includes diabetes and general debility. The present study was aimed to investigate the comparative hypoglycemic and hypolipidemic activity of various extracts of A. latifolia bark in streptozotocin-induced type 1 diabetic rats. Methods Acute toxicity was carried out at 2 g/kg dose of petroleum ether extract of A. latifolia bark (PEALB), chloroform extract of A. latifolia bark (CEALB) and methanol extract of A. latifolia bark (MEALB) in rats. Diabetes was induced by streptozotocin (STZ, 60 mg/kg, i.p.) and it was confirmed at 72 h. Diabetic rats received above extracts at 100 and 200 mg/kg doses for 28 days. Body weight and blood glucose level were determined at every week after the treatment schedule. Serum biochemical parameters and lipid profile levels were estimated at the end of the study. Results PEALB, CEALB and MEALB were non-toxic and no death was observed at 2 g/kg dose. Administration of MEALB at 100 and 200 mg/kg showed significant (p< 0.01, p< 0.05) improvement in body weight and reduction in blood glucose at third and fourth week of treatment. Altered serum biochemical parameters and lipid profiles level were brought to near normal level significantly (p<0.001) compared to diabetic control rats after the administration of both doses of MEALB. However, PEALB and CEALB did not exhibit significant hypoglycemic and hypolipidemic activity. Conclusions Our findings revealed that long-term (28 days) treatment of MEALB possesses significant hypoglycemic and hypolipidemic activity compared to PEALB and CEALB in type 1 diabetic rats and given evidence to the traditional use of A. latifolia bark in diabetes.

Background: West Nile virus (WNV) is the leading cause of domestically-acquired arboviral disease in the United States. Several WNV vaccines are in various stages of development. We estimate the cost-effectiveness of WNV vaccination programs targeting groups at increased risk for severe WNV disease., Methods: We used a mathematical model to estimate costs and health outcomes of vaccination with WNV vaccine compared to no vaccination among seven cohorts, spaced at 10year intervals from ages 10 to 70years, each followed until 90-years-old. U.S. surveillance data were used to estimate WNV neuroinvasive disease incidence. Data for WNV seroprevalence, acute and long-term care costs of WNV disease patients, quality-adjusted life-years (QALYs), and vaccine characteristics were obtained from published reports. We assumed vaccine efficacy to either last lifelong or for 10years with booster doses given every 10years., Results: There was a statistically significant difference in cost-effectiveness ratios across cohorts in both models and all outcomes assessed (Kruskal-Wallis test p<0.0001). The 60-year-cohort had a mean cost per neuroinvasive disease case prevented of $664,000 and disability averted of $1,421,000 in lifelong model and $882,000 and $1,887,000, respectively in 10-year immunity model; these costs were statistically significantly lower than costs for other cohorts (p<0.0001). Vaccinating 70-year-olds had the lowest cost per death averted in both models at around $4.7 million (95%CI $2-$8 million). Cost per disease case averted was lowest among 40- and 50-year-old cohorts and cost per QALY saved lowest among 60-year cohorts in lifelong immunity model. The models were most sensitive to disease incidence, vaccine cost, and proportion of persons developing disease among infected., Conclusions: Age-based WNV vaccination program targeting those at higher risk for severe disease is more cost-effective than universal vaccination. Annual variation in WNV disease incidence, QALY weights, and vaccine costs impact the cost effectiveness ratios., (Published by Elsevier Ltd.)

National surveillance provides important information about Lyme disease (LD) but is subject to underreporting and variations in practice. Information is limited about the national epidemiology of LD from other sources. Retrospective analysis of a nationwide health insurance claims database identified patients from 2005-2010 with clinician-diagnosed LD using International Classification of Diseases, Ninth Revision, Clinical Modification, codes and antimicrobial drug prescriptions. Of 103,647,966 person-years, 985 inpatient admissions and 44,445 outpatient LD diagnoses were identified. Epidemiologic patterns were similar to US surveillance data overall. Outpatient incidence was highest among boys 5-9 years of age and persons of both sexes 60-64 years of age. On the basis of extrapolation to the US population and application of correction factors for coding, we estimate that annual incidence is 106.6 cases/100,000 persons and that ≈329,000 (95% credible interval 296,000-376,000) LD cases occur annually. LD is a major US public health problem that causes substantial use of health care resources.

There are no published data on the economic burden for specific West Nile virus (WNV) clinical syndromes (i.e., fever, meningitis, encephalitis, and acute flaccid paralysis [AFP]). We estimated initial hospital and lost-productivity costs from 80 patients hospitalized with WNV disease in Colorado during 2003; 38 of these patients were followed for 5 years to determine long-term medical and lost-productivity costs. Initial costs were highest for patients with AFP (median $25,117; range $5,385-$283,381) and encephalitis (median $20,105; range $3,965-$324,167). Long-term costs were highest for patients with AFP (median $22,628; range $624-$439,945) and meningitis (median $10,556; range $0-$260,748). Extrapolating from this small cohort to national surveillance data, we estimated the total cumulative costs of reported WNV hospitalized cases from 1999 through 2012 to be $778 million (95% confidence interval $673 million-$1.01 billion). These estimates can be used in assessing the cost-effectiveness of interventions to prevent WNV disease.

A sensitive and high-throughput LC-MS/MS method has been developed and validated for the combined determination of esomeprazole and naproxen in human plasma with ibuprofen as internal standard. Solid-phase extraction was used to extract both analytes and internal standard from human plasma. Chromatographic separation was achieved in 4.0 min on XBridge C18 column using acetonitrile-25 mM ammonium formate (70:30, v/v) as mobile phase. Mass detection was achieved by ESI/MS/MS in negative ion mode, monitoring at m/z 344.19 → 194.12, 229.12 → 169.05 and 205.13 → 161.07 for esomeprazole, naproxen and IS, respectively. The calibration curves were linear from 3.00 to 700.02 ng/mL for esomeprazole and 0.50 to 150.08 ng/mL for naproxen. The intra- and inter-batch precision and accuracy across four quality control levels met established criteria of US Food and Drug Administration guidelines. The assay is suitable for measuring accurate esomeprazole and naproxen plasma concentrations in human bioequivalence study following combined administration., (Copyright © 2013 John Wiley & Sons, Ltd.)

Vitamin A (all-trans retinol) is an important antioxidant whose role in embryo development in vitro and in vivo is well established. Oxidative stress is a major cause of defective embryo development. This study evaluated the effects of all-trans retinol supplementation to maturation and embryo culture media under different gaseous environments on the development of ovine oocytes and embryos in vitro. The percentages of cleavage, morula and blastocyst, total cell count and comet assay were taken as indicators of developmental competence of embryos. In experiments I and II, all-trans retinol at concentrations of 0, 2, 4, 6, 8 and 10 μM were supplemented to the oocyte maturation medium and cultured in an environment of 5% or 20% O2 respectively. All-trans retinol supplementation (6 μM) to the maturation medium at 5% O2 levels significantly increased blastocyst yield and total cell number (P < 0.05). Maturation of oocytes in a 20% O2 environment bettered cleavage rates in the 6 μM supplemented group compared with the control group (P < 0.05). In experiments III and IV, all-trans retinol, at the aforesaid concentrations was supplemented to embryo culture media under a 5% or 20% O2 environment, respectively. All-trans retinol supplementation to the embryo culture medium at 5% O2 levels did not yield any significant result whereas the culture at 20% O2 levels gave significantly higher blastocyst yield in the 6 μM supplemented group compared with the control group (P < 0.01).

Purpose: To determine the effects of α-tocopherol supplementation to oocyte maturation media and embryo culture media on the yield of ovine embryos., Methods: α-tocopherol, at concentrations of 0, 50, 100, 200, 400 and 500 µM was supplemented to ovine oocyte or embryo culture media and cultured at 5% or 20% O(2) levels. Percentages of cleavage, morula and blastocyst, total cell count and comet assay were taken as indicators of developmental competence of embryos., Results: 200 µM α-tocopherol in embryo culture medium at 20% O(2) level significantly increased the rates of cleavage (P < 0.05), morulae (P < 0.05) and blastocyst (P < 0.01) formation and blastocyst total cell number (P < 0.01) when compared with control. The rates of blastocyst formation were also significantly higher in 100 µM (P < 0.01) and 400 µM (P < 0.05) supplemented groups than control., Conclusion: α-tocopherol supplementation may enhance the in vitro developmental competence of ovine embryos by protecting them from oxidative damage.

Objectives: To assess the cost-effectiveness of screening for refractive error and fitting with glasses in India., Methods: We populated a decision tree with the costs of screening and spectacles, prevalence of varying levels of presenting and best corrected visual acuity (BCVA) from two studies, and sensitivity and specificity of screening. We calculated dollars spent per disability adjusted life year (DALY) averted separately in urban and rural areas for school-based screening (SBS) and primary eye care (PEC) programs that fit spectacles to individuals presenting for care. We conducted a series of univariate and probabilistic sensitivity analyses. An intervention was inferred to be highly cost-effective if the incremental cost-effectiveness ratio (ICER) was less than the gross domestic product (GDP) per capita and moderately cost-effective if the ICER was less than three times this level., Results: Compared with no screening, urban SBS was highly cost-effective; rural SBS was moderately cost-effective for ages 5-15 and highly cost-effective for ages 7-15. Both urban and rural PEC were moderately cost-effective in comparison to SBS. Probabilistic sensitivity analysis suggested that SBS is likely the most cost-effective solution for refractive error in India if the 5-15 year old age group is targeted; primary eye care is the best choice if a high value is placed on DALYs and the 7-15 year old age group is targeted., Conclusion: Both SBS and PEC Interventions for refractive error can be considered cost-effective in India. Which is the more cost-effective depends on the choice of targeted age group and area of the intervention.

This paper describes validated HPLC and HPTLC methods for simultaneous determination of alprazolam (ALP) and fluoxetine hydrochloride (FXT) in pure powder and formulation. The HPLC separation was achieved on a Nucleosil C8 column (150 mm length, 4.6 mm id, 5 microm particle size) using acetonitrile-phosphate buffer pH 5.5 (45 + 55, v/v) as the mobile phase at a flow rate of 1.0 mL/min at ambient temperature. The HPTLC separation was achieved on an aluminum-backed layer of silica gel 60F254 using acetone-toluene-ammonia (6.0 + 3.5 + 0.5, v/v/v) as the mobile phase. Quantification in the HPLC method was achieved with UV detection at 230 nm over the concentration range 4-14 microg/mL for both drugs, with mean recovery of 99.95 +/- 0.38 and 99.85 +/- 0.56% for ALP and FXT, respectively. Quantification in the HPTLC method was achieved with UV detection at 230 nm over the concentration range of 400-1400 ng/spot for both drugs, with mean recovery of 99.32 +/- 0.45 and 99.78 +/- 0.81% for ALP and FXT, respectively. These methods are simple, precise, and sensitive, and they are applicable for the simultaneous determination of ALP and FXT in pure powder and formulations.

This paper describes validated high-performance column liquid chromatographic (HPLC) and high-performance thin-layer chromatographic (HPTLC) methods for simultaneous estimation of acetylsalicylic acid (ASA) and clopidogrel bisulfate (CLP) in pure powder and formulations. The HPLC separation was achieved on a Nucleosil C8 column (150 mm length x 4.6 mm id, 5 microm particle size) using acetonitrile-phosphate buffer, pH 3.0 (55 + 45, v/v) mobile phase at a flow rate of 1.0 mL/min at ambient temperature. The HPTLC separation was achieved on an aluminum-backed layer of silica gel 60F254 using ethyl acetate-methanol-toluene-glacial acetic acid (5.0 + 1.0 + 4.0 + 0.1, v/v/v/v) mobile phase. Quantitation was achieved with UV detection at 235 nm over the concentration range 4-24 microg/mL for both drugs, with mean recoveries of 99.98 +/- 0.28 and 100.16 +/- 0.66% for ASA and CLP, respectively, using the HPLC method. Quantitation was achieved with UV detection at 235 nm over the concentration range of 400-1400 ng/spot for both drugs, with mean recoveries of 99.93 +/- 0.55 and 100.21 +/- 0.83% for ASA and CLP, respectively, using the HPTLC method. These methods are simple, precise, and sensitive, and they are applicable for the simultaneous determination of ASA and CLP in pure powder and formulations.

Two simple and accurate methods of analysis to determine pioglitazone hydrochloride (PIO) and mefformin hydrochloride (MET) in combined dosage forms were developed using second-derivative spectrophotometry and reversed-phase liquid chromatography (LC). PIO and MET in combined preparations (tablets) were quantified using the second-derivative responses at 227.55 nm for PIO and 257.25 nm for MET in spectra of their solutions in a mixture of methanol and acetonitrile (30 + 70). The calibration curves were linear [correlation coefficient (r) = 0.9984 for PIO and 0.9986 for MET] in the concentration range of 8-40 microg/mL for PIO and 4-12 microg/mL for MET. In the LC method, analysis was performed on a Hypersil ODS-C18 column with 5 microm particle size using the mobile phase acetonitrile-water-acetic acid (75 + 25 + 0.3), adjusted to pH 5.5 with liquor ammonia, at a flow rate of 0.5 mL/min. Measurement was made at a wavelength of 230 nm. Both the drugs were well resolved on the stationary phase, and the retention times were 8.5 min for PIO and 16.0 min for MET. The calibration curves were linear (r = 0.9933 for PIO and 0.9958 for MET) in the concentration range of 4-20 microg/mL for PIO and MET. Both methods were validated, and the results were compared statistically. They were found to be accurate, precise, and specific. The methods were successfully applied to the estimation of PIO and MET in combined tablet formulations.