Influence Of Medicare Formulary Restrictions On Evidence-Based Prescribing Practices

Controlling the cost of prescription drugs is integral to improving health outcomes, and patient access and adherence to treatment. While prescription drugs can often provide essential therapeutic benefit, previous studies have suggested that inappropriate prescription drug use is a principal cause of adverse drug events as well as abuse and diversion of drugs. Thus, balancing the benefits and harms to promote appropriate prescription drug use is an essential component of healthcare delivery in the United States. There are multiple ways appropriate prescription drug use is promoted. Black-box warnings and drug labeling controlled by the FDA as well as guidelines released by the CDC, such as the 2013 guidelines released during the opioid epidemic, aim to promote appropriate prescription at a population level. At a patient-level, drug formularies have multiple strategies in place to promote safe and cost-effective prescribing of individual medications. The Center for Medicare & Medicaid Services (CMS) makes use of prescription drug formularies that are used for the coverage of around 17% of the US population. These formularies have uniformly adopted utilization management strategies, such as quantity limits, prior authorization, and step therapy, in order to promote safe, evidence-based and cost-effective prescribing. These strategies are in place to impact drug prescription rates as well as to incentivize use of biological or therapeutically interchangeable generics over brand-name drugs. Thus far, the implementation of utilization management strategies for commonly prescribed drugs has not been thoroughly studied. This study presents three main analyses conducted and published in the peer reviewed literature during my time in medical school. The first characterized the change in opioid prescription versus non-opioid analgesics in both the outpatient and emergency room setting in the context of the 2013 CDC guidelines encouraging prescription on non-opioid analgesic alternatives. We found that overall rates of pain medication prescribing were high and that opioid pain medication prescription increased in the outpatient setting only, whereas non-opioid pain medication prescribing increased in both the outpatient and ED settings, an area that has not been previously reported or well-investigated. The second study characterized how Medicare formulary restrictions were applied to opioid “potentiators”, which are commonly used in conjunction with opioids and increase patients’ risk of adverse events. We found that from 2013-2017, Medicare prescription drug plan formularies had relatively unchanged rates of benzodiazepine, non-benzodiazepine sedative-hypnotic, and gabapentinoid coverage with small increases in use of quantity limits, and that more than a quarter of formularies provided unrestrictive coverage of these potentially unsafe opioid potentiators in 2017. The third and final study herein presents a more global analysis of whether Medicare used formulary restrictions to promote prescription of therapeutically interchangeable generics over the top 100-grossing brand-name drugs in light of the 2020 CMS plans for an indication-based formulary design. We showed that a substantial portion of CMS formularies provided similarly restrictive coverage of brand-name drugs and their therapeutically interchangeable generics, including the same tier placement or utilization management, thereby missing opportunities to incentivize prescribing of less costly generics. Overall, the results of this comprehensive study on safe and cost-effective drug prescription showed that while current formulary design includes opportunities to reduce costly and potentially unsafe prescribing, the impact of these tools is sub-optimal. These results highlight the need for both physician and patient education on the utility of the formulary restriction strategies. On a larger scale, it suggests that these strategies alone may not be sufficient to reduce over-prescription of potentially unsafe drugs like opioid potentiators, or to incentivize prescription of cost-saving generics over brand-name drugs. The Center for Medicare & Medicaid Services (CMS) has proposed an indication-based formulary design starting in 2020, allowing Medicare Advantage and Part D prescription drug plans to cover drugs only for select indications, which could increase formulary negotiating power and secure more competitive pricing. This might be the change needed in order to ensure continued patient access to affordable and safe prescription drugs

PHYTOCHEMISTRY AND PHARMACOLOGY OF PTEROCARPUS SANTALINUS AND ITS ROLE IN DERMATOLOGY

The review provides an updated overview of the phytochemical and pharmacological studies on Pterocarpus santalinus. It briefs on the synergistic interactions of P. santalinus with other medicinal plants and its use in Ayurvedic formulations. Phytochemical analysis suggests the presence of triterpenoids, steroids, flavonoids, and phenolic acids. The phytoconstituents and related pharmacological activities of various parts of P. santalinus include antifungal, anticholinesterase, antidiabetic, antibacterial, antipyretic, anti-inflammatory, anticancer, and antiulcer. Literature survey highlights the dermatological applications of the phytoconstituents such as pterostilbene, savinin, and betulin as potential leads for anti-aging, ultraviolet rays (UV-B) protective, and wound healing effects. Undoubtedly, P. santalinus has wide therapeutic value. The dermatologically significant phytoconstituents, namely, pterostilbene, cedrol, savinin, lupeol, betulin, β-eudesmol, and α-bisabolol, if isolated and used in dermatological formulations, can show promising skin protective effect. The data were compiled using scientific databases, namely, Google Scholar and PubMed, the data made available specifically from 2010 to 2021

ELECTROPHYSIOLOGICAL CHANGES IN LATENCY IN DIABETIC RETINOPATHY: AN OBSERVATIONAL STUDY

Purpose: Multifocal ERG is a useful indicator of diabetic retinopathy. The significant delay in local responses provides a chance for the detection and understanding of the various stages of diabetic retinopathy. Materials and Methods: This is a cross sectional study conducted in ERG clinic at M & J Western regional institute of ophthalmology, Ahmedabad from January 2013 to September 2015 who were more than 35yrs of age. Results: In our study, we studied 45 eyes of diabetic patients and 20 eyes of normal subjects. In our study the mean values of the various parameters was calculated in the control group with N1, P1 and N2 latency being 14.09ms. 29,76ms and 45.55ms respectively. The N1, P1 and N2 amplitude was found to be 31.52nV, 73.61nV and 90.38nV respectively. The maximum delay in N1, P1 and N2 latency was seen to be 3.24ms, 7.11ms and 8.40ms respectively from the normal value. We also found a decrease in amplitude of the ERG waveform with N1, P1 and N2 amplitude being 20.98nV, 61.48nV and 76.4nV respectively from the normal value. Also it is helpful in cases with clinically significant macular edema where responses are remarkably delayed suggesting local retinal dysfunction and macular pathology. It provides us information regarding the condition of the macula and some ideas about the extent of ischemia affecting this area. Conclusion: In conclusion, we can say that the delayed responses obtained indicate abnormal retinal function corresponding to local discrete retinal lesions. It provides a very sensitive and objective assessment of the local retinal condition in various stages of diabetic retinopathy. KEYWORDS: Diabetes mellitus; Diabetic retinopathy; Multifocal electroretinogram

ELECTROPHYSIOLOGICAL CHANGES IN LATENCY IN DIABETIC RETINOPATHY: AN OBSERVATIONAL STUDY

Purpose: Multifocal ERG is a useful indicator of diabetic retinopathy. The significant delay in local responses provides a chance for the detection and understanding of the various stages of diabetic retinopathy. Materials and Methods: This is a cross sectional study conducted in ERG clinic at M & J Western regional institute of ophthalmology, Ahmedabad from January 2013 to September 2015 who were more than 35yrs of age. Results: In our study, we studied 45 eyes of diabetic patients and 20 eyes of normal subjects. In our study the mean values of the various parameters was calculated in the control group with N1, P1 and N2 latency being 14.09ms. 29,76ms and 45.55ms respectively. The N1, P1 and N2 amplitude was found to be 31.52nV, 73.61nV and 90.38nV respectively. The maximum delay in N1, P1 and N2 latency was seen to be 3.24ms, 7.11ms and 8.40ms respectively from the normal value. We also found a decrease in amplitude of the ERG waveform with N1, P1 and N2 amplitude being 20.98nV, 61.48nV and 76.4nV respectively from the normal value. Also it is helpful in cases with clinically significant macular edema where responses are remarkably delayed suggesting local retinal dysfunction and macular pathology. It provides us information regarding the condition of the macula and some ideas about the extent of ischemia affecting this area. Conclusion: In conclusion, we can say that the delayed responses obtained indicate abnormal retinal function corresponding to local discrete retinal lesions. It provides a very sensitive and objective assessment of the local retinal condition in various stages of diabetic retinopathy. KEYWORDS: Diabetes mellitus; Diabetic retinopathy; Multifocal electroretinogram

Comparison between Epidural Bupivacaine with and without Magnesium Sulphate in Patients undergoing Elective Total Abdominal Hysterectomy: A Double-blinded Randomised Clinical Trial

Introduction: The effectiveness of a local anaesthetics increased by the addition of an adjuvant. Magnesium sulphate along with bupivacaine is effective in reducing the pain and extending the analgesia period. Aim: To compare the duration of analgesia among subjects receiving plain bupivacaine and bupivacaine with magnesium sulphate among patients undergoing total abdominal hysterectomy. Materials and Methods: This double-blinded randomised clinical trial was conducted in Department of Anaesthesiology at Shri Sathya Sai Medical College and Research Institute, Ammapettai, Tamil Nadu, India, (tertiary care center) between November 2019 to October 2021. The study was done among 50 subjects undergoing elective total abdominal hysterectomy. The subjects were divided into two groups: one group received only bupivacaine while the other group received bupivacaine with 500 mg magnesium sulphate. Onset and duration of blocks were observed. Haemodynamic parameters were monitored intraoperatively and postoperatively. Data was analysed using Chi-square test and Fischer’s-exact test. Results: Demographic variables like age (p-value=0.17), height (p-value=0.62), weight (p-value=0.14) and Body Mass Index (BMI) (p-value=0.24) were comparable between the two groups. The mean duration of analgesia was significantly more among the bupivacaine with magnesium sulphate group (416.72±93.6) in comparison to the bupivacaine alone group (204.96±71.25). The bupivacaine with magnesium sulphate group required two doses of rescue analgesia in 24 hours, while the other group required four doses of analgesia. Significantly more side-effects were noted among the bupivacaine alone group (12 vs 6) (p-value=0.04). Conclusion: The study showed that bupivacaine with magnesium sulphate group showed less intraoperative side effects, reduced postoperative Visual Analogue Scale (VAS) score, increased duration of analgesia, decreased requirement of analgesia required in 24 hours and reduced postoperative side-effect

Toxicity screening of two prevalent metal organic frameworks for therapeutic use in human lung epithelial cells

Introduction: The flexibility and tunability of metal organic frameworks (MOFs), crystal- line porous materials composed of a network of metal ions coordinated by organic ligands, confer their variety of applications as drug delivery systems or as sensing and imaging agents. However, such properties also add to the difficulty in ensuring their safe implementa- tion when interaction with biological systems is considered. Methods: In the current study, we used real-time sensorial strategies and cellular-based approaches to allow for fast and effective screening of two MOFs of prevalent use, namely, MIL-160 representative of a hydrophilic and ZIF-8 representative of a hydrophobic frame- work. The two MOFs were synthesized “in house” and exposed to human bronchial epithelial (BEAS-2B) cells, a pertinent toxicological screening model. Results: Analysis allowed evaluation and differentiation of particle-induced cellular effects as well identification of different degrees and routes of toxicity, all in a high-throughput manner. Our results show the importance of performing screening toxicity assessments before introducing MOFs to biomedical applications. Discussion: Our proposed screening assays could be extended to a wider variety of cell lines to allow for identification of any deleterious effects of MOFs, with the range of toxic mechanisms to be differentiated based on cell viability, morphology and cell–substrate interactions, respectively. Conclusion: Our analysis highlights the importance of considering the physicochemical properties of MOFs when recommending a MOF-based therapeutic option or MOFs imple- mentation in biomedical applications

Polyherbal formulation PL02 alleviates pain, inflammation, and subchondral bone deterioration in an osteoarthritis rodent model

IntroductionOsteoarthritis (OA) is a debilitating disease with significant personal and socioeconomic burdens worldwide.MethodsTo address this, we developed a multitargeted formulation called PL02, which includes standardized extracts of Rosa canina L, Hippophae rhamnoides, and collagen peptide. We tested the pharmacological efficacy of PL02 in a rodent model of OA induced by Monosodium iodoacetate (MIA).ResultsOur results demonstrate that oral administration of PL02 has antioxidant effects by down-regulating NOS, reduces pain-related behavior, and mitigates inflammation by inhibiting IL-1b and TNF-α production, as well as downregulating CGRP1 and COX-II. PL02 also exhibits anti-catabolic and chondroprotective activity by significantly downregulating MMP13 and upregulating BCL2. Additionally, PL02 demonstrates chondrogenic activity by significantly upregulating SOX-9 (a master regulator of chondrogenesis), Coll-I, and aggrecan, which are major components of articular cartilage. Furthermore, PL02 prevents microarchitectural deterioration of subchondral bone.ConclusionOverall, PL02 is an orally active, multi-targeted therapy that not only alleviates pain and inflammation but also effectively halts cartilage and subchondral bone deterioration. It represents a safe and promising candidate for the treatment and management of OA

Stakeholder perspectives on the demand and supply factors driving substandard and falsified blood pressure lowering medications in Nigeria: A qualitative study

OBJECTIVES: Although substandard and falsified (SF) blood pressure (BP) lowering medications are a global problem, qualitative research exploring factors driving this in Nigeria has not been reported. This study provides information on factors driving demand for and supply of low-quality BP lowering medications in Nigeria and potential strategies to address these factors. METHODS: This was a cross-sectional qualitative study. Between August 2020 and September 2020, we conducted 11 in-depth interviews and 7 focus group discussions with administrators of health facilities, major manufacturers and distributors of BP lowering medications, pharmacists, drug regulators, patients and primary care physicians purposively sampled from the Federal Capital Territory, Nigeria. Data were analysed using directed content analysis, with the aid of Dedoose. RESULTS: We found that demand for SF BP lowering medications in Nigeria was driven by high out-of-pocket expenditure and stockouts of quality-assured BP lowering medications. Supply of low-quality BP lowering medications was driven by limited in-country manufacturing capacity, non-adherence to good manufacturing and distribution practices, under-resourced drug regulatory systems, ineffective healthcare facility operations, poor distribution practices, limited number of trained pharmacists and the COVID-19 pandemic which led to stockouts. Central medicine store procurement procedures, active pharmaceutical ingredient quality check and availability of trained pharmacists were existing strategies perceived to lower the risk of supply and demand of SF BP lowering medications. CONCLUSION: Our findings suggest that demand for and supply of SF BP lowering medications in Nigeria are driven by multi-level, interrelated factors. Multi-pronged strategies need to target stakeholders and systems involved in drug production, distribution, prescription, consumption, regulation and pricing

Rapid growth and high cloud-forming potential of anthropogenic sulfate aerosol in a thermal power plant plume during COVID lockdown in India

The COVID lockdown presented an interesting opportunity to study the anthropogenic emissions from different sectors under relatively cleaner conditions in India. The complex interplays of power production, industry, and transport could be dissected due to the significantly reduced influence of the latter two emission sources. Here, based on measurements of cloud condensation nuclei (CCN) activity and chemical composition of atmospheric aerosols during the lockdown, we report an episodic event resulting from distinct meteorological conditions. This event was marked by rapid growth and high hygroscopicity of new aerosol particles formed in the SO2 plume from a large coal-fired power plant in Southern India. These sulfate-rich particles had high CCN activity and number concentration, indicating high cloud-forming potential. Examining the sensitivity of CCN properties under relatively clean conditions provides important new clues to delineate the contributions of different anthropogenic emission sectors and further to understand their perturbations of past and future climate forcing

Polypill Eligibility for Patients with Heart Failure With Reduced Ejection Fraction in South India: A Secondary Analysis of a Prospective, Interrupted Time Series Study.

RESEARCH LETTER - No abstract available