Patterns, outcomes, and preventability of clinically manifest drug-drug interactions in older outpatients: a subgroup analysis from a 6-year-long observational study in North India.

Older adults are vulnerable to adverse drug reactions (ADRs) and drug-drug interactions (DDIs). Evidence on clinically manifest DDIs in older outpatients is scanty. The present study aims to report clinically manifest DDIs, their risk factors, and preventive measures. A subgroup analysis of a 6-year (2015-2021) long prospective study was conducted in a tertiary hospital in North India. Older outpatients with ADRs constituted the study participants. Among 933 ADRs reported in 10,400 patient registrations, clinically manifest DDIs were involved in 199 (21.3%). DDIs accounted for 29.9%, 26.5%, and 21.3% of drug-related metabolic, vascular, and nervous system disorders, respectively. Movement disorders (n = 18), hypotension (n = 16), and hypoglycemia (n = 15) were the most common manifestations. Eighty-six percent of DDIs were of the pharmacodynamic type, and 13.1% were immune-mediated. Around 35% of DDIs resulted in hospitalization, with hyponatremia, movement disorder, and renal impairment as the common reasons. Older adults with Parkinsonism, infection, coronary artery disease, neuropsychiatric disease, and diabetes mellitus, respectively, had 3.28, 2.85, 1.97, 1.76, and 1.80 times higher odds of DDIs. Those receiving ≥ 10 drugs had 5.31 times higher odds of DDIs compared to individuals receiving 1-4 drugs. "Avoiding the causative drug," "optimal monitoring of the patient," and "start-low and go-slow" policy together could prevent 85% of DDIs. In conclusion, every fifth case of ADRs and nearly one third of ADR-related hospitalizations in older adults are related to DDIs. Movement disorder, hypotension, and hypoglycemia are the common manifestations. A holistic approach with drug omission, optimal patient monitoring, and slow titration of therapy can prevent significant DDIs in older adults.

Drug-related problems in older adults in outpatient settings: Results from a 6-year long prospective study in a tertiary hospital of north India.

AIM: Drug-related problems (DRPs) are a common cause of hospitalization in older patients. So far, these issues have been studied in hospitalized settings, and evidence on patterns and outcomes of DRPs, such as adverse drug reactions, is relatively scarce in older outpatients. The main aim of this study was to provide a comprehensive description and possible solutions for DRPs in older adults in outpatient settings. METHODS: The study was carried out from January 2015 to September 2021 in a tertiary hospital in north India. Patients aged ≥50 years with DRPs were enrolled. DRPs causing hospitalization, drug interactions and drug-disease interactions were identified, along with preventive measures. RESULTS: Of 10 400 patients registered, 1031 DRPs occurred in 666 patients (9.9%). Adverse drug reactions were the major DRPs (n = 933, 8.9%). Metabolic disorders were the commonest DRP in individuals aged ≥65 years compared with gastrointestinal disorders in the 50-64 years group. Drug interactions and drug-disease interactions contributed to 20.1% and 7.9% of patients, respectively. Nearly 15.8% of DRPs directly led to hospitalization, with drug-induced metabolic disturbances and movement disorders as the common causes. The Naranjo scale was not applicable in 35.3% of patients, and drug interactions were the commonest cause. Frequent monitoring, omission of unnecessary drugs, slow titration and proper instructions on therapy, together, could avoid one-third of DRPs. CONCLUSION: One out of 10 prescriptions of older outpatients carries a DRP. New-onset metabolic and neurological disturbances should prompt a thorough drug history. A multifaceted holistic approach can prevent significant drug-related morbidity and requires future evaluation. Geriatr Gerontol Int 2024; 24: 285-291.

Prevalence of dementia in India: National and state estimates from a nationwide study.

INTRODUCTION: Prior estimates of dementia prevalence in India were based on samples from selected communities, inadequately representing the national and state populations. METHODS: From the Longitudinal Aging Study in India (LASI) we recruited a sample of adults ages 60+ and administered a rich battery of neuropsychological tests and an informant interview in 2018 through 2020. We obtained a clinical consensus rating of dementia status for a subsample (N = 2528), fitted a logistic model for dementia status on this subsample, and then imputed dementia status for all other LASI respondents aged 60+ (N = 28,949). RESULTS: The estimated dementia prevalence for adults ages 60+ in India is 7.4%, with significant age and education gradients, sex and urban/rural differences, and cross-state variation. DISCUSSION: An estimated 8.8 million Indians older than 60 years have dementia. The burden of dementia cases is unevenly distributed across states and subpopulations and may therefore require different levels of local planning and support. HIGHLIGHTS: The estimated dementia prevalence for adults ages 60+ in India is 7.4%. About 8.8 million Indians older than 60 years live with dementia. Dementia is more prevalent among females than males and in rural than urban areas. Significant cross-state variation exists in dementia prevalence.

Deep phenotyping and genomic data from a nationally representative study on dementia in India.

The Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD) is a nationally representative in-depth study of cognitive aging and dementia. We present a publicly available dataset of harmonized cognitive measures of 4,096 adults 60 years of age and older in India, collected across 18 states and union territories. Blood samples were obtained to carry out whole blood and serum-based assays. Results are included in a venous blood specimen datafile that can be linked to the Harmonized LASI-DAD dataset. A global screening array of 960 LASI-DAD respondents is also publicly available for download, in addition to neuroimaging data on 137 LASI-DAD participants. Altogether, these datasets provide comprehensive information on older adults in India that allow researchers to further understand risk factors associated with cognitive impairment and dementia.

Of Cross-immunity, Herd Immunity and Country-specific Plans: Experiences from COVID-19 in India.

India has witnessed a high number of COVID-19 cases, but mortality has been quite low, and most cases have been asymptomatic or mild. In early April, we had hypothesized a low COVID-19 mortality in India, based on the concept of cross-immunity. The presence of cross-immunity is presumed to lead to a milder course of disease and allow the time necessary for the development of adaptive immunity by the body to eliminate the virus. Evidence supporting our hypothesis has started showing up. Multiple studies have shown the generation of different T cell subsets and B cells responding to epitopes of viral proteins, especially of the spike protein, as a part of adaptive immunity against SARS-CoV-2. Cross-reactive T-cells have been demonstrated in patients who have been previously exposed to endemic coronaviruses. The interplay of cross-immunity and herd immunity is apparent in the COVID-19 scenario in India from the presence of a large number of asymptomatic or mild cases, a low infection-fatality ratio and a generally flat curve of percentage positivity of cases with respect to total testing, both in periods of strict lock-down and step-wise unlocking. It seems that cross-immunity resulted in faster generation of herd immunity. Although the initial restrictive measures such as lockdown prevented the rapid spread of the outbreak, further extension of such measures and overly expensive ones such as enhanced testing in India will result in a huge burden on the health economics as well as the society. Hence, we propose a restructuring of the health services and approach to COVID-19. The restructured health services should move away from indiscriminate testing, isolation and quarantine, and instead, the emphasis should be on improving facilities for testing and management of only critical COVID cases and the replacement of complete lockdowns by the selective isolation and quarantine of susceptible persons such as the aged and those with co-morbidities. In the process of describing India-specific plans, we emphasize why the development of country-specific plans for tackling epidemics is important, instead of adopting a "one policy fits all" approach.

Methodological considerations in designing and implementing the harmonized diagnostic assessment of dementia for longitudinal aging study in India (LASI-DAD).

The Harmonized Diagnostic Assessment of Dementia for Longitudinal Aging Study in India (LASI-DAD) is a population-representative, prospective cohort study of late-life cognition and dementia. It is part of an ongoing international research collaboration that aims to measure and understand cognitive impairment and dementia risk by collecting a set of cognitive and neuropsychological assessments and informant reports, referred to as the Harmonized Cognitive Assessment Protocol (HCAP). LASI-DAD provides nationally representative data drawn from a subsample of the ongoing Longitudinal Aging Study in India (LASI). One of LASI-DAD's distinctive features is its rich geriatric assessment, including the collection of venous blood samples and brain imaging data for a subsample of respondents. In this paper, we discuss the methodological considerations of developing and implementing the HCAP protocol in India. The lessons we learned from translating and applying the HCAP protocol in an environment where illiteracy and innumeracy are high will provide important insights to researchers interested in measuring and collecting data on late-life cognition and dementia in developing countries. We further developed an innovative blood management system that enables us to follow the collection, transportation, assay, and storage of samples. Such innovation can benefit other population surveys collecting biomarker data.

COVID-19 in India: Are Biological and Environmental Factors Helping to Stem the Incidence and Severity?

The ongoing Corona virus (COVID-19) pandemic has witnessed global political responses of unimaginable proportions. Many nations have implemented lockdowns that involve mandating citizens not to leave their residences for non-essential work. The Indian government has taken appropriate and commendable steps to curtail the community spread of COVID-19. While this may be extremely beneficial, this perspective discusses the other reasons why COVID-19 may have a lesser impact on India. We analyze the current pattern of SARS-CoV-2 transmission, testing, and mortality in India with an emphasis on the importance of mortality as a marker of the clinical relevance of COVID-19 disease. We also analyze the environmental and biological factors which may lessen the impact of COVID-19 in India. The importance of cross-immunity, innate immune responses, ACE polymorphism, and viral genetic mutations are discussed.

Association of oxidative stress and endothelial dysfunction in hypertension.

BACKGROUND: Biomarkers of oxidative stress (OS) are involved in the pathophysiology of hypertension (HTN) and endothelial dysfunction is also related to HTN. Still, a significant association of OS, as well as endothelial function, remains unclear in HTN. METHODS: Totalling 222 North Indian peoples aged 18-80 participated in the study. Of these participants, 74 were elderly hypertensive subjects (age ≥60 years), and 128 were normotensive subjects (age ≥60 years-control I; n = 74, and <60 years-control II; n = 74). OS was assessed by measurement of total oxidant status (TOS) and total antioxidant status (TAS) using a colorimetric and automated method developed by Erel O. Endothelial dysfunction was assessed by measurement of flow-mediated dilation (FMD) using doppler ultrasound system. RESULTS: TOS and OSI were significantly increased and TAS and FMD significantly decreased in patients with HTN as compared to control I and control II. The increase in the level of TOS and a decrease in the level of TAS and FMD were also evident with advancing age. FMD was negatively correlated with TOS and positively correlated with TAS. CONCLUSION: Decreased TAS level, increased TOS level reflect OS that may be the reason for reduced FMD in elderly hypertensive patients.

Case Report: Histoplasmosis Accompanying Disseminated Tuberculosis in an Immunocompetent Adolescent Boy.

The incidence of tuberculosis in India is quite high. In such a situation, empirical antitubercular therapy (ATT) is often resorted to, when some of the investigation findings are clearly diagnostic of tuberculosis. This may mean missing out on coinfections. Whereas this is particularly true for immunosuppressed patients, rarely even immunocompetent patients may present with such diagnostic dilemmas. We present the case of an adolescent boy who had been previously asymptomatic and who presented with fever with lymphadenopathy, splenomegaly, and pancytopenia. Initially, ATT was administered based on the detection of acid-fast bacteria in lymph node, caseating granulomas with Langhans giant cells, and a positive cartridge-based nucleic acid amplification test specific for Mycobacterium tuberculosis. However, when the patient failed to respond fully to the treatment, additional investigation in the form of bone marrow fungal culture led to the diagnosis of histoplasmosis.

Sheehan syndrome with Gitelman syndrome, Tackling Additive Morbidity.

Sheehan syndrome (SS) is postpartum hypopituitarism resulting from pituitary gland necrosis caused by severe hypotension due to massive intra or post-partum hemorrhage. Defective NaCl transport in the distal convoluted tubule, due to mutations affecting the thiazide sensitive Na-Cl-cotransporter results in the autosomal recessive salt-losing renal tubulopathy, Gitelman syndrome (GS). These two have been rarely described together. We report the case of a middle-aged woman with both these conditions, resulting in management issues. Physicians encountering unexplained hypokalemia refractory to standard management must consider the possibility of renal tubular disorders.

Antiepileptic drug therapy in the elderly: a clinical pharmacological review.

Seizure disorder is the third most common neurological disorder in the elderly after stroke and dementia. With the increasing geriatric population, the situation of clinicians seeing more and more elderly epilepsy patients is very likely. Not only is the diagnosis of epilepsy tedious in the elderly, its management raises many challenging issues for the treating physicians. Altered physiology, age-related decline in organ function, and plasma protein binding and altered pharmacodynamics make the elderly patients with seizure disorder a difficult group to treat. This is further complicated by the presence of comorbidities and polypharmacy which increase the chances of drug interactions. The adverse effects that might be tolerated well in younger populations may be disastrous for the aged. Although the newer antiepileptic drugs are found to have a favorable safety profile, there is relative scarcity of randomized-controlled trials involving older and newer antiepileptics in the geriatric population. This review tries to compile the available literature on management of epilepsy in the elderly population including evidence of safety and efficacy of newer and older antiepileptics with special reference to the 'geriatric giants'. It also deals with the interactions between antiepileptic medications and other commonly prescribed drugs in the elderly such as anti-hypertensives and antiischemic agents. The recommended guidelines of various international bodies are also analyzed from the perspective of elderly with seizure disorder.

APOE4 allele in north Indian elderly patients with dementia or late onset depression-a multiple-disease case control study.

The objective of the study was to analyze the frequency of APOE4 allele in elderly patients with Alzheimer's or vascular dementia or depression; compare these to age/sex matched controls; compare the results with established literature and highlight new findings. A single center, multiple disease, case-control study was performed with three case groups- probable AD patients (n=36), vascular dementia patients (n=29) and depression patients (n=20) and with a control group (n=32). APOE genotyping was performed in whole blood samples collected from patients and controls by restriction isotyping using the enzymes AflIII and HaeII. There was significant difference in frequency distribution of E4 allele between the AD (12/72; 16.7%) and control groups (3/64; 4.7%) (P=0.03). However, no significant difference was found in any of the other comparisons. The current study demonstrates absence of a significant association between APOE4 positivity and presence of late-onset depression in the north Indian elderly and reinforces the higher APOE4 prevalence in LOAD patients but not in VD patients. It is the first study of its kind from the northern part of India involving multiple disease groups and lays the framework for larger cohort studies.

New genetic players in late-onset Alzheimer's disease: Findings of genome-wide association studies.

Late-onset Alzheimer's disease (LOAD) or sporadic AD is the most common form of AD. The precise pathogenetic changes that trigger the development of AD remain largely unknown. Large-scale genome-wide association studies (GWASs) have identified single-nucleotide polymorphisms in multiple genes which are associated with AD; most notably, these are ABCA7, bridging integrator 1 (B1N1), triggering receptor expressed on myeloid cells 2 (TREM2), CD33, clusterin (CLU), complement receptor 1 (CRI), ephrin type-A receptor 1 (EPHA1), membrane-spanning 4-domains, subfamily A (MS4A) and phosphatidylinositol binding clathrin assembly protein (PICALM) genes. The proteins coded by the candidate genes participate in a variety of cellular processes such as oxidative balance, protein metabolism, cholesterol metabolism and synaptic function. This review summarizes the major gene loci affecting LOAD identified by large GWASs. Tentative mechanisms have also been elaborated in various studies by which the proteins coded by these genes may exert a role in AD pathogenesis have also been elaborated. The review suggests that these may together affect LOAD pathogenesis in a complementary fashion.