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Background: Current risk scores to estimate atherosclerotic cardiovascular disease (ASCVD) risk and allocate statins in at-risk persons have largely been developed in Western populations; their applicability in India is uncertain., Objective: To assess eligibility for primary prevention statin therapy using the 2018 U.S Multisociety Guideline and other contemporary cholesterol guidelines in patients presenting with ST-elevation myocardial infarction (STEMI) in the North India STEMI (NORIN-STEMI) registry., Methods: NORIN-STEMI registry prospectively enrolled 3,635 patients at 2 tertiary care centers in Delhi, India from January 2019 to February 2020. Pooled cohort risk equations were used to estimate ASCVD risk at presentation. Patients were evaluated for statin eligibility using the 2018 U.S Multisociety Guideline, United States Preventive Services Task Force (USPSTF), and National Cholesterol Education Program (NCEP) III cholesterol guidelines., Results: A total of 2,551 met the inclusion criteria. The median age was 54 years; 17% were women. The median ASCVD risk was 7.0%. At the time of MI, 54% of patients were eligible for primary prevention statin therapy by Multisociety Guideline, 46% by USPSTF, and 30% by NCEP III guidelines. These findings were applicable in both women and men. Compared with patients aged ≥50 years, those <50 years were less likely to be recommended statin therapy by all the three guidelines., Conclusion: A significant proportion of patients with STEMI in India did not meet the current guideline-based threshold for statin therapy for primary prevention. Novel risk stratification tools are needed to identify patients for primary prevention statin therapy in this population., (Copyright © 2021. Published by Elsevier Inc.)

While heart disease remains a common cause of mortality, cerebrovascular disease also increases with age, and has been implicated in Alzheimer's disease and related dementias (ADRD). We have described hydrogen sulfide (H 2 S), a signaling molecule important in vascular homeostasis, as a biomarker of cardiovascular disease. We hypothesize that plasma H 2 S and its metabolites also relate to vascular and cognitive dysfunction in ADRD. We used analytical biochemical methods to measure plasma H 2 S metabolites and MRI to evaluate indicators of microvascular disease in ADRD. Levels of total H 2 S and specific metabolites were increased in ADRD versus controls. Cognition and microvascular disease indices were correlated with H 2 S levels. Total plasma sulfide was the strongest indicator of ADRD, and partially drove the relationship between cognitive dysfunction and white matter lesion volume, an indicator of microvascular disease. Our findings show that H 2 S is dysregulated in dementia, providing a potential biomarker for diagnosis and intervention., (© 2021 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Tobacco smoking is the most important preventable cause of death and disease. Despite an increased awareness of the addictive nature of smoking and availability of effective treatments, smoking continues to be widespread among individuals with psychiatric disorders. Moreover, mental health professionals remain reluctant to address smoking among their patients for a variety of reasons. Recent research has provided a wealth of data that have shaped the concept of tobacco smoking as a chronic addictive disorder and also demonstrated the efficacy of smoking cessation interventions. This paper reviews the important factors that contribute to smoking and the various pharmacological and psychosocial interventions for smoking cessation from a biopsychosocial perspective. It also makes recommendations for the rational use of these interventions to treat nicotine dependence in individuals with psychiatric disorders.

The Food and Drug Administration (FDA) issued a second-draft guidance in August 1999 on the subject of in vivo bioequivalence, which is based on the concepts of individual and population bioequivalence (IBE and PBE, respectively). The intention of this guidance is to replace the 1992 guidance that requires that in vivo bioequivalence be demonstrated by average bioequivalence (ABE). Although the concepts of population and individual bioequivalence are intuitively reasonable, a detailed review of the literature has not uncovered clinical evidence to justify the additional burden to the innovator and generic companies as well as the consumer that the new guidelines would impose. The criteria for bioequivalence described in the draft guidance employ aggregate statistics that combine information about differences in bioavailability between formulation means and differences in bioavailability variation of formulations between and within subjects. The purely technical aspects of the statistical approach are reasonably sound. However, PhRMA believes that important operational issues remain that need to be resolved before any changes to current practice are implemented. PhRMA believes that the ideals of prescribability and switchability are intuitively reasonable, but it is uncertain of the extent to which the proposed guidance can achieve these goals. It is not clear whether the attainment of such goals is necessary in the evaluation of bioequivalence given the role this plays in drug development, and the lack of clinical evidence argues against a pressing need to change current practice. PhRMA is concerned that the trade-off offered by the aggregate criteria may ultimately represent more harm than good to the public interest. PhRMA recommends more rigorous evaluation of methods based on two-way crossover designs before moving to methods that require more complex designs. One such method is identified herein and contains procedures for estimating prescribability and switchability. The possibility of a phase-in or trial period to collect replicate crossover data to further evaluate IBE and PBE and possibly allow market access based on these criteria as they are being evaluated has been proposed. PhRMA believes this is unprecedented and will offer little additional information beyond that which can be obtained by simulation or has already been collected by the FDA. Simulation studies have the advantage of allowing evaluation of the sensitivity of various procedures to represent the data patterns as created within the simulation. Operating characteristics by which proposed criteria can be adequately judged have not yet been defined. The limitations of ABE for highly variable drugs and narrow therapeutic drugs are well appreciated and may be addressed by means other than a wholesale change in the current criteria.