COST VARIATION STUDY OF ANTIEPILEPTIC DRUGS AVAILABLE IN INDIA

ABSTRACTObjective: To list the available dosage forms in different strengths of various antiepileptic drugs marketed in India. To calculate percentage costvariation of individual formulation of drug manufactured by different companies. To evaluate percentage cost variation of drug due to different dosageforms and formulation of the same drug by cost/defined daily dose (DDD) method and to identify less costlier antiepileptic.Methods: Cost of a particular drug being manufactured by different companies, in the same strength and dosage forms was obtained from CurrentIndex of Medical Specialties†2015 and Indian Drug Review†September 2015. The difference in the maximum and minimum price of the same drugmanufactured by different pharmaceutical companies and the percentage cost variation was calculated. The price was measured in Indian rupess(cost/DDD units). The percentage cost variation of drug due to different formulations was also calculated using minimum and maximum cost/DDDThe cost of each drug were also estimated as mean cost per DDD considering different formulation cost.Results: The prices of total 11 drugs available in 12 different dosage forms and 65 formulations were reviewed. Except Zonisamide, all drugs(for 31 different formulations) showed more than 100% cost variation. Levetiracetam (conventional 250 mg tablet) showed a maximum of 1034.09%and carbamazepine (dispersible 100 mg tablet) showed minimum cost variation of 2.09%. Levetiracetam formulations showed high (3125.74%), andTopiramate formulations showed less (11.7%) variation in cost to achieve same DDD. The topiramate was expensive, and phenobarbital was cheaperbased on cost/DDD only.Conclusion: There was a high-cost variation of antiepileptic drugs. It shows need for conducting pharmacoeconomic analysis. The prescribers andpatient should be educated about drug prices. The government has to change the pricing policy of medicine.Keywords: Antiepileptics, Cost/defined daily dose, Cost variation

Working practices and incomes of health workers : evidence from an evaluation of a delivery fee exemption scheme in Ghana

Background: This article describes a survey of health workers and traditional birth attendants (TBAs) which was carried out in 2005 in two regions of Ghana. The objective of the survey was to ascertain the impact of the introduction of a delivery fee exemption scheme on both health workers and those providers who were excluded from the scheme (TBAs). This formed part of an overall evaluation of the delivery fee exemption scheme. The results shed light not only on the scheme itself but also on the general productivity of a range of health workers in Ghana. Methods: A structured questionnaire was developed, covering individual and household characteristics, working hours and practices, sources of income, and views of the exemptions scheme and general motivation. After field testing, this was administered to 374 respondents in 12 districts of Central and Volta regions. The respondents included doctors, medical assistants (MAs), public and private midwives, nurses, community health nurses (CHNs), and traditional birth attendants, both trained and untrained. Results: Health workers were well informed about the delivery fee exemptions scheme and their responses on its impact suggest a realistic view that it was a good scheme, but one that faces serious challenges regarding financial sustainability. Concerning its impact on their morale and working conditions, the responses were broadly neutral. Most public sector workers have seen an increased workload, but counterbalanced by increased pay. TBAs have suffered, in terms of client numbers and income, while the picture for private midwives is mixed. The survey also sheds light on pay and productivity. The respondents report long working hours, with a mean of 54 hours per week for community nurses and up to 129 hours per week for MAs. Weekly reported client loads in the public sector range from a mean of 86 for nurses to 269 for doctors. Over the past two years, reported working hours have been increasing, but so have pay and allowances (for doctors, allowances now make up 66% of their total pay). The lowest paid public health worker now earns almost ten times the average gross national income (GNI) per capita, while the doctors earn 38.5 times GNI per capita. This compares well with average government pay of four times GNI per capita. Comparing pay with outputs, the relatively high number of clients reported by doctors reduces their pay differential, so that the cost per client – $1.09 – is similar to a nurse's (and lower than a private midwife's). Conclusion: These findings show that a scheme which increases demand for public health services while also sustaining health worker income and morale, is workable, if well managed, even within the relatively constrained human resources environment of countries like Ghana. This may be linked to the fact that internal comparisons reveal Ghana's health workers to be well paid from public sector sources.This work was undertaken as part of an international research programme – IMMPACT (Initiative for Maternal Mortality Programme Assessment) – funded by the Bill & Melinda Gates Foundation, the Department for International Development, the European Commission and USAID

The Ubiquitin Ligase Adaptor NDFIP1 Selectively Enforces a CD8⁺ T Cell Tolerance Checkpoint to High-Dose Antigen

Escape from peripheral tolerance checkpoints that control cytotoxic CD8+ T cells is important for cancer immunotherapy and autoimmunity, but pathways enforcing these checkpoints are mostly uncharted. We reveal that the HECT-type ubiquitin ligase activator, NDFIP1, enforces a cell-intrinsic CD8+ T cell checkpoint that desensitizes TCR signaling during in vivo exposure to high antigen levels. Ndfip1-deficient OT-I CD8+ T cells responding to high exogenous tolerogenic antigen doses that normally induce anergy aberrantly expanded and differentiated into effector cells that could precipitate autoimmune diabetes in RIP-OVAhi mice. In contrast, NDFIP1 was dispensable for peripheral deletion to low-dose exogenous or pancreatic islet-derived antigen and had little impact upon effector responses to Listeria or acute LCMV infection. These data provide evidence that NDFIP1 mediates a CD8+ T cell tolerance checkpoint, with a different mechanism to CD4+ T cells, and indicates that CD8+ T cell deletion and anergy are molecularly separable checkpoints.This work was funded by NIH grant U19-AI100627, by an Australian Government Research Training Program Domestic Scholarship (to M.V.W.), by a Sydney Parker Smith Postdoctoral Research Fellowship from the Cancer Council of Victoria (to J.M.M.), and by the National Health and Medical Research Council (NHMRC) through Program Grants 1016953, 1113904, and 1054925, Australia Fellowship 585490 (to C.C.G.), Senior Principal Research Fellowship 1081858 (to C.C.G.), CJ Martin Early Career Fellowship 585518 (to I.A.P.), and Independent Research Institutes Infrastructure Support Scheme Grant 361646. Florey Institute of Neuroscience and Mental Health and WEHI acknowledge the strong support from the Victorian Government and in particular funding from the Operational Infrastructure Support Grant

cDNA-detector: detection and removal of cDNA contamination in DNA sequencing libraries

BACKGROUND: Exogenous cDNA introduced into an experimental system, either intentionally or accidentally, can appear as added read coverage over that gene in next-generation sequencing libraries derived from this system. If not properly recognized and managed, this cross-contamination with exogenous signal can lead to incorrect interpretation of research results. Yet, this problem is not routinely addressed in current sequence processing pipelines. RESULTS: We present cDNA-detector, a computational tool to identify and remove exogenous cDNA contamination in DNA sequencing experiments. We demonstrate that cDNA-detector can identify cDNAs quickly and accurately from alignment files. A source inference step attempts to separate endogenous cDNAs (retrocopied genes) from potential cloned, exogenous cDNAs. cDNA-detector provides a mechanism to decontaminate the alignment from detected cDNAs. Simulation studies show that cDNA-detector is highly sensitive and specific, outperforming existing tools. We apply cDNA-detector to several highly-cited public databases (TCGA, ENCODE, NCBI SRA) and show that contaminant genes appear in sequencing experiments where they lead to incorrect coverage peak calls. CONCLUSIONS: cDNA-detector is a user-friendly and accurate tool to detect and remove cDNA detection in NGS libraries. This two-step design reduces the risk of true variant removal since it allows for manual review of candidates. We find that contamination with intentionally and accidentally introduced cDNAs is an underappreciated problem even in widely-used consortium datasets, where it can lead to spurious results. Our findings highlight the importance of sensitive detection and removal of contaminant cDNA from NGS libraries before downstream analysis

Movement Interventions for Children with Autism and Developmental Disabilities: An Evidence-Based Practice Project

This review explored the following question: Are the comprehensive treatment models Makoto Therapy, Brain Gym, and Interactive Metronome effective interventions for improving occupational performance including improving executive function, academic performance, and physical coordination in children and adolescents with Autism Spectrum Disorder (ASD)? Because current research on Interactive Metronome, Brain Gym®, and Makoto Therapy fails to address children and adolescents with autism spectrum disorder, presents multiple flaws in research design, and does not measure occupational outcomes such as occupational performance, we recommend that these interventions should not be used as comprehensive treatment models in occupational therapy. We recommend that more occupational-based, methodologically-sound research involving youth with ASD be conducted before implementing these interventions in occupational therapy practice

Comparison of the Relationship between Lying and Standing Ultrasonography Measures of Muscle Morphology with Isometric and Dynamic Force Production Capabilities

The purpose of the current study was (1) to examine the differences between standing and lying measures of vastus lateralis (VL), muscle thickness (MT), pennation angle (PA), and cross-sectional area (CSA) using ultrasonography; and (2) to explore the relationships between lying and standing measures with isometric and dynamic assessments of force production—specifically peak force, rate of force development (RFD), impulse, and one-repetition maximum back squat. Fourteen resistance-trained subjects (age = 26.8 ± 4.0 years, height = 181.4 ± 6.0 cm, body mass = 89.8 ± 10.7 kg, back squat to body mass ratio = 1.84 ± 0.34) agreed to participate. Lying and standing ultrasonography images of the right VL were collected following 48 hours of rest. Isometric squat assessments followed ultrasonography, and were performed on force platforms with data used to determine isometric peak force (IPF), as well as RFD and impulse at various time points. Forty-eight hours later, one-repetition maximum back squats were performed by each subject. Paired-samples t-tests revealed statistically significant differences between standing and lying measurements of MT (p \u3c 0.001), PA (p \u3c 0.001), and CSA (p ≤ 0.05), with standing values larger in all cases. Further, standing measures were correlated more strongly and abundantly to isometric and dynamic performance. These results suggest that if practitioners intend to gain insight into strength-power potential based on ultrasonography measurements, performing the measurement collection with the athlete in a standing posture may be preferred

Comparison of the Relationship between Lying and Standing Ultrasonography Measures of Muscle Morphology with Isometric and Dynamic Force Production Capabilities

The purpose of the current study was (1) to examine the differences between standing and lying measures of vastus lateralis (VL), muscle thickness (MT), pennation angle (PA), and cross-sectional area (CSA) using ultrasonography; and (2) to explore the relationships between lying and standing measures with isometric and dynamic assessments of force production—specifically peak force, rate of force development (RFD), impulse, and one-repetition maximum back squat. Fourteen resistance-trained subjects (age = 26.8 ± 4.0 years, height = 181.4 ± 6.0 cm, body mass = 89.8 ± 10.7 kg, back squat to body mass ratio = 1.84 ± 0.34) agreed to participate. Lying and standing ultrasonography images of the right VL were collected following 48 hours of rest. Isometric squat assessments followed ultrasonography, and were performed on force platforms with data used to determine isometric peak force (IPF), as well as RFD and impulse at various time points. Forty-eight hours later, one-repetition maximum back squats were performed by each subject. Paired-samples t-tests revealed statistically significant differences between standing and lying measurements of MT (p \u3c 0.001), PA (p \u3c 0.001), and CSA (p ≤ 0.05), with standing values larger in all cases. Further, standing measures were correlated more strongly and abundantly to isometric and dynamic performance. These results suggest that if practitioners intend to gain insight into strength-power potential based on ultrasonography measurements, performing the measurement collection with the athlete in a standing posture may be preferred