Digits-in-Noise Test as an Assessment Tool for Hearing Loss and Hearing Aids.

The aim of this study was to examine the relationship between an American English Digits in Noise (DIN) test and commonly used audiological measures to evaluate the DIN test's ability to detect hearing loss and validate hearing aid fitting. QuickSIN and DIN tests were completed by participants with untreated hearing loss (n = 46), prescription hearing aids (n = 15), and over-the-counter (OTC) hearing aids (n = 12). Performance on the QuickSIN showed moderate positive correlations with DIN for untreated hearing loss participants and prescription hearing aid users, but not for OTC hearing aid users. For untreated hearing loss participants, both QuickSIN and DIN tests showed positive moderate to strong correlations with high frequency puretone averages. In OTC users, DIN scores did not significantly change over a 6-month time period and were better when conducted remotely compared to in-person testing. Our results suggest that the DIN test may be a feasible monitoring option for individuals with hearing loss and those fitted with hearing aids. However, due to small sample size in this pilot study, future research is needed to examine DIN test's utility for fitting and validating OTC hearing aids.

Cost effective and reliable cell based ELISA as an alternative method of flow cytometry for assessment of binding activity of Vedolizumab.

Vedolizumab is a humanized monoclonal antibody used for inflammatory bowel disease treatment. Vedolizumab binds to the α4ß7 integrin complex and inhibits its binding to mucosal addressin cell adhesion molecule-1 (MAdCAM-1). To evaluate the binding efficacy and quality control check of Vedolizumab, flow cytometry is performed by using HuT78 cells. As we know, flow cytometer is costly and require high equipment maintenance with a designated technical manpower to handle it. In this regard, the aim of study was to develop and validate an economical, simple and efficient cell based ELISA assay for potency estimation of Vedolizumab which has not been reported in any pharmacopoeia. The proposed bioassay method was optimized by investigating Vedolizumab binding to α4ß7 integrin which is expressed by HuT78 cells. The validation of this method was done at different parameters including specificity, linearity, range, repeatability, precision, and accuracy. The Vedolizumab binding by ELISA results were found specific for Vedolizumab with linearity (R2 = 0.99) and precision (%Geometric Coefficient of variance) observed for repeatability and intermediate precision were 3.38% and 2.6% respectively. The relative bias was calculated as 8.68% for repeated performances by different analysts and found in accordance with parameter of accuracy as per various pharmacopoeial guidelines. The developed method is established as robust, effective, and less expensive than high maintenance setup like flow cytometry based assay.

Deciding Whether to Take Sacubitril/Valsartan: How Cardiologists and Patients Discuss Out-of-Pocket Costs.

Background Out-of-pocket costs have significant implications for patients with heart failure and should ideally be incorporated into shared decision-making for clinical care. High out-of-pocket cost is one potential reason for the slow uptake of newer guideline-directed medical therapies for heart failure with reduced ejection fraction. This study aims to characterize patient-cardiologist discussions involving out-of-pocket costs associated with sacubitril/valsartan during the early postapproval period. Methods and Results We conducted content analysis on 222 deidentified transcripts of audio-recorded outpatient encounters taking place between 2015 and 2018 in which cardiologists (n=16) and their patients discussed whether to initiate, continue, or discontinue sacubitril/valsartan. In the 222 included encounters, 100 (45%) contained discussions about cost. Cost was discussed in a variety of contexts: when sacubitril/valsartan was initiated, not initiated, continued, and discontinued. Of the 97 cost conversations analyzed, the majority involved isolated discussions about insurance coverage (64/97 encounters; 66%) and few addressed specific out-of-pocket costs or affordability (28/97 encounters; 29%). Discussion of free samples of sacubitril/valsartan was common (52/97 encounters; 54%), often with no discussion of a longer-term plan for addressing cost. Conclusions Although cost conversations were somewhat common in patient-cardiologist encounters in which sacubitril/valsartan was discussed, these conversations were generally superficial, rarely addressing affordability or cost-value judgments. Cardiologists frequently provided patients with a course of free sacubitril/valsartan samples without a plan to address the cost after the samples ran out.

National Control Laboratory Assessment of Quality of Rituximab Biosimilars in India.

In past few years many rituximab (RTX) biosimilars have been launched in India. Biosimilars are products that are similar in terms of quality, safety, and efficacy to its innovator product and are expected to offer improved affordability. The less clinical examination is a significant source of reduction in the cost of development of a biosimilar. However, this clinical relief is predicated on the assumption that there is analytical similarity between the biosimilar and the innovator product. Therefore, the role of National Control Laboratory become very important to ensure the quality of these drugs by carrying out analytical characterization at the point of drug product release level as when referred by National Regulatory Authority for quality evaluation. To assess the similarity between innovator and biosimilars, different physicochemical and biological quality attributes were assessed. A multitude of state-of-the-art analysis of N = 3 RTX biosimilars marketed in India revealed that the impurity profiles of these biosimilars measured by charge variant analysis (cation exchange chromatography-high performance liquid chromatography [HPLC], capillary zone electrophoresis, and capillary isoelectric focusing), aggregates profiling (size exclusion chromatography-HPLC), fragments analysis (capillary electrophoresis-sodium dodecyl sulfate) were found to be significantly varying as compared with the innovator product. There were significant variations in acidic variants (p = 0.023) and basic variants (p = 0.0005), isoelectric point value (p < 0.0001), aggregates (p = 0.0231), and fragments (p < 0.0001) of biosimilars were found as that of innovator product. However, these differences were not affecting the biological activity in the cell-based potency analysis by complement-dependent cytotoxicity (CDC) assay (p = 0.1026), antibody-dependent cell-mediated cytotoxicity (ADCC) (p = 0.3736), and binding assay by flow cytometer fluorescence-activated cell sorting (p = 0.4005) of these biosimilars as compared with the innovator product.

Integrated Health and Social Care in the United States: A Decade of Policy Progress.

INTRODUCTION: Over the last decade in the United States (US), the burden of chronic disease, health care costs, and fragmented care delivery have increased at alarming rates. To address these challenges, policymakers have prioritized new payment and delivery models to incentivize better integrated health and social services. POLICY PRACTICE: This paper outlines three major national and state policy initiatives to improve integrated health and social care over the last ten years in the US, with a focus on the Medicaid public insurance program for Americans with low incomes. Activities supported by these initiatives include screening patients for social risks in primary care clinics; building new cross-sector collaborations; financing social care with healthcare dollars; and sharing data across health, social and community services. Stakeholders from the private sector, including health systems and insurers, have partnered to advance and scale these initiatives. This paper describes the implementation and effectiveness of such efforts, and lessons learned from translating policy to practice. DISCUSSION AND CONCLUSION: National policies have catalyzed initiatives to test new integrated health and social care models, with the ultimate goal of improving population health and decreasing costs. Preliminary findings demonstrated the need for validated measures of social risk, engagement across levels of organizational leadership and frontline staff, and greater flexibility from national policymakers in order to align incentives across sectors.

Assessment of The Bethesda System for Reporting Thyroid Cytopathology.

OBJECTIVES: Long-term follow-up is important for determining performance characteristics of thyroid fine-needle aspiration (FNA). METHODS: Histologic or 3 or more years of clinical follow-up was used to calculate performance characteristics of thyroid FNA before and after implementation of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). The impact of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) classification was also investigated. RESULTS: Follow-up was obtained for 1,277/1,134 and 1,616/1,393 aspirates/patients (median clinical follow-up, 9.9 and 4.4 years, pre- and post-TBSRTC, respectively). Nondiagnostic, suspicious for follicular neoplasm, and suspicious for malignancy (SFM) diagnoses decreased and benign diagnoses increased post-TBSRTC, while atypical rate remained less than 1%. Negative predictive value for benign nodules and positive predictive value (PPV) for SFM increased significantly. Eleven nodules were reclassified as NIFTP, slightly decreasing PPV/risk of malignancy (ROM). CONCLUSIONS: Appropriate ROM for thyroid FNA can be achieved through application of TBSRTC terminology with minimal use of atypical category.

Assessment of pulsatile insulin secretion derived from peripheral plasma C-peptide concentrations by nonparametric stochastic deconvolution.

The characteristics of pulsatile insulin secretion are important determinants of type 2 diabetes pathophysiology, but they are understudied due to the difficulties in measuring pulsatile insulin secretion noninvasively. Deconvolution of either peripheral C-peptide or insulin concentrations offers an appealing alternative to hepatic vein catheterization. However, to do so, there are a series of methodological challenges to overcome. C-peptide has a relatively long half-life and accumulates in the circulation. On the other hand, peripheral insulin concentrations reflect relatively fast clearance and hepatic extraction as it leaves the portal circulation to enter the systemic circulation. We propose a method based on nonparametric stochastic deconvolution of C-peptide concentrations, using individually determined C-peptide kinetics, to overcome these limitations. The use of C-peptide (instead of insulin) concentrations allows estimation of portal (and not post-hepatic) insulin pulses, whereas nonparametric stochastic deconvolution allows evaluation of pulsatile signals without any a priori assumptions of pulse shape and occurrence. The only assumption required is the degree of smoothness of the (unknown) secretion rate. We tested this method first on simulated data and then on 29 nondiabetic subjects studied during euglycemia and hyperglycemia and compared our estimates with the profiles obtained from hepatic vein insulin concentrations. This method produced satisfactory results both in the ability to fit the data and in providing reliable estimates of pulsatile secretion, in agreement with hepatic vein measurements. In conclusion, the proposed method enables reliable and noninvasive measurement of pulsatile insulin secretion. Future studies will be needed to validate this method in people with type 2 diabetes.

Health risk assessment due to biomass smoke exposure in Indian indoor environment: An empirical approach using lung deposition model.

The paper subsumes a framework that assesses health risk due to exposure to different fuel combustion through articulation of modern microscopic techniques, empirical equations, lung diagnostic tools and a pre-existing model that has been extrapolated to futuristic aspects (within controlled conditions). The framework was tested on 132 household cooks belonging to different age groups and using different types of fuel. The inhalable fraction released during fuel combustion varied in morphological characteristics and deposition site. Micrographs obtained using Scanning Electron Microscope (SEM) analysis of (biomass smoke) soot indicates aggregate formation attributing to a higher level of health risk. Further, abnormal ventilatory function along with higher risk (RR > 1) was more evident within biomass fuel users. The condition further exacerbates while using dung cakes due to high levels of emissions (294.3 particles/liter) that deposit in the upper respiratory tract (0.0899). Further, the population attributable risk percent (79%) calculated on the basis of cooking behavior suggests a 'rural culture' health determinant as clean fuel usage is not practiced as an outcome of low literacy and poor income in the region. These preliminary findings highlight the drudgery of impuissant women who are exposed to high particulate emissions on a regular basis which results in reduced lung function. Nevertheless, further cogitation is required to eliminate the limitations in this study and explore further linkages between exposure and vulnerable group to generate meaningful policy recommendations.

Phenotypic and molecular assessment of chickpea rhizobia from different chickpea cultivars of India.

In the present study, heterogeneity in natural chickpea rhizobia populations associated with 18 different chickpea (Cicer arientinum) cultivars of India was investigated. Physiological diversity of 20 chickpea rhizobia was characterized based on phenotypic parameters such as Bromothymol blue (BTB) test, pH, temperature and salinity tolerance. Based on response to BTB test and pH tolerance, all chickpea rhizobia were further divided into slow growers/alkali producers (14 isolates) and fast growers/acid producers (6 isolates). The temperature (upto 40 °C) and salinity (NaCl) tolerance (upto 6%) tests provided a wide description of physiological diversity among the rhizobial isolates. The intrinsic antibiotic resistance of each isolate against 14 different antibiotics distinguished all chickpea rhizobia into five clades at the level of 80% similarity coefficient. Further, based on UPGMA phylogeny of carbon utilization profile, all isolates were dispersed into six clusters at the level of 85% similarity coefficient, which indicated a remarkable variability among the rhizobia. The evaluation of nodule-forming efficiency of all isolates revealed that the isolate ACR15 was more competent for nodule formation than all other isolates. The representative strain from each carbon metabolic cluster was further subjected for molecular identification through 16S rRNA gene characterization. Neighbour-joining method-based phylogeny of 16S rRNA gene sequence revealed a high degree of species diversity among the isolates. Further, the prominent nodule-forming isolate such as ACR15 was identified as Mesorhizobium ciceri, while other isolates showed similarity with other species of Mesorhizobium genus. The present study contributed to the knowledge that besides M. ciceri and M. mediterraneum, chickpea can also be nodulated by many other native chickpea rhizobia which indicates the impact of exploration of promising native populations. These findings may support the further investigation of symbiotic as well as stress responsive genes of chickpea rhizobia leading to develop more effective inoculant strains for wide agricultural applications.

Assessment of regional climatic changes in the Eastern Himalayan region: a study using multi-satellite remote sensing data sets.

In this study, an attempt has been made to capture the sensitivity of a mountainous region to elevation-dependent warming and the response of a glacier-laden surface to increasing greenhouse gases (GHGs) and aerosol concentration. Some of the changes Sikkim has undergone due to urban sprawl are as follows: an increase of ~0.7 ± 0.46 °C temperature in the past 40 years at an altitude of 5.5 km; a 2.21 km(2)/year rate of loss of glacierised area in the past 33 years; an increase in absorbed longwave radiation (6 ± 2.41 W/m(2)); an increase in heat fluxes (2 ± 0.97 W/m(2)); a decrease in albedo during the last 30 years; an increase in the concentrations of carbon dioxide (4.42%), methane (0.61%), ozone (0.67%) and black carbon column optical depth (7.19%); a decrease in carbon monoxide (2.61%) and an increase in aerosol optical depth (19.16%) during the last decade; a decrease in precipitation, water yield, discharge and groundwater; and an increase in evapotranspiration during 1971-2005. Detection of three climate signals (1976, 1997 and 2005) in the entire analysis is the quantification of the fact that the climate of Sikkim is moving away from its inter-annual variability. An increase in temperature (0.23 °C/decade) at higher altitude (~5.5 km), suppression of precipitation, decreasing water availability and rapid loss of glacierised area are the evidences of the fact that air pollution is playing a significant role in bringing about regional climatic changes in Sikkim. In this study, change detection method has been used for the first time for the estimation of change in a glacierised area of the region.

The impact assessment of Diwali fireworks emissions on the air quality of a tropical urban site, Hyderabad, India, during three consecutive years.

Diwali is one of the largest festivals for Hindu religion which falls in the period October-November every year. During the festival days, extensive burning of firecrackers takes place, especially in the evening hours, constituting a significant source of aerosols, black carbon (BC), organics, and trace gases. The widespread use of sparklers was found to be associated with short-term air quality degradation events. The present study focuses on the influence of Diwali fireworks emissions on surface ozone (O3), nitrogen oxides (NO x ), and BC aerosol concentration over the tropical urban region of Hyderabad, India during three consecutive years (2009-2011). The trace gases are analyzed for pre-Diwali, Diwali, and post-Diwali days in order to reveal the festivity's contribution to the ambient air quality over the city. A twofold to threefold increase is observed in O3, NO x , and BC concentrations during the festival period compared to control days for 2009-2011, which is mainly attributed to firecrackers burning. The high correlation coefficient (~0.74) between NO x and SO2 concentrations and higher SO2/NO x (S/N) index suggested air quality degradation due to firecrackers burning. Furthermore, the Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation-derived aerosol subtyping map also confirmed the presence of smoke aerosols emitted from firecrackers burning over the region. Nevertheless, the concentration level of pollutants exhibited substantial decline over the region during the years 2010 and 2011 compared to 2009 ascribed to various awareness campaigns and increased cost of firecrackers.

Assessment of cochlear implant candidacy in patients with cochlear nerve deficiency using the P1 CAEP biomarker.

OBJECTIVE: The goal of this report was to ascertain the efficacy of the P1 cortical auditory evoked potential (CAEP) biomarker as an objective tool to assist in the evaluation of cochlear implant (CI) candidacy in children with a radiological diagnosis of cochlear nerve deficiency (CND). METHODS: Retrospective case study review of audiological and radiological findings was performed in four pediatric patients identified with CND and severe-to-profound sensorineural hearing loss. Cortical auditory evoked potential testing was conducted, and the presence and latency of the P1 component were analyzed. RESULTS: Three out of four children demonstrated robust P1 CAEP responses, indicating activation of the central auditory pathways by auditory stimulation, despite the diagnosis of CND. These children were considered good candidates for cochlear implantation. DISCUSSION: Although cochlear implantation in children is a fairly routine procedure, cases exist for which implant candidacy is questionable. Among these cases are children with CND. In these children, cochlear implantation may be contraindicated due to the likelihood that the implant electrodes may not stimulate the VIII nerve adequately. Magnetic resonance imaging (MRI) is considered the gold standard in the assessment of CND, but this measure is not always sufficient to determine CI candidacy in cases of CND. The addition of the P1 CAEP measurement to the usual electrophysiological, audiometric, and radiological test battery may prove to be useful in determining CI options for children with CND.

The environments of adopted and non-adopted youth: evidence on range restriction from the Sibling Interaction and Behavior Study (SIBS).

Previous reviews of the literature have suggested that shared environmental effects may be underestimated in adoption studies because adopted individuals are exposed to a restricted range of family environments. A sample of 409 adoptive and 208 non-adoptive families from the Sibling Interaction and Behavior Study (SIBS) was used to identify the environmental dimensions on which adoptive families show greatest restriction and to determine the effect of this restriction on estimates of the adoptive sibling correlation. Relative to non-adoptive families, adoptive families experienced a 41% reduction of variance in parent disinhibitory psychopathology and an 18% reduction of variance in socioeconomic status (SES). There was limited evidence for range restriction in exposure to bad peer models, parent depression, or family climate. However, restriction in range in parent disinhibitory psychopathology and family SES had no effect on adoptive-sibling correlations for delinquency, drug use, and IQ. These data support the use of adoption studies to obtain direct estimates of the importance of shared environmental effects on psychological development.