Medication adherence, recall periods and factors affecting it: A community-based assessment on patients with chronic diseases in urban slums.

OBJECTIVE: To evaluate medication adherence, the effect of recall periods on self-reported adherence and factors influencing medication adherence among patients of chronic diseases, such as hypertension and diabetes, particularly in the community. METHODS: A cross-sectional cohort study was conducted among individuals with hypertension and/or diabetes coming as outpatients in community camps organised in a cluster of urban slums. Responses towards questions regarding self-reported quantitative and qualitative adherence for one week and one month along with information on pill burden, socio-demographic and other factors were recorded using a mobile application. RESULTS: Among 379 participants living in urban slum communities, who were prescribed anti-hypertensive or oral anti-diabetic medications previously, mean medication adherence over previous one week was 67.99% (standard deviation (SD) ± 38.32) and 6.87 (SD ± 3.62) on a ten-point numeric scale. The medication adherence for one month showed a strong significantly positive correlation with that of 1 week for both percentage-based (r = +0.910, 95% CI = 0.864 to 0.950, P < .0001) and Likert (ρ = +0.836, 95% CI = 0.803 to 0.863, P < .0001) scales. Age (r = 0.219, 95% CI = 0.120 to 0.313, P = .043) and pill burden (r = -0.231, 95% CI = -0.145 to -0.322, P < .0001) were found to significantly affect medication adherence. The odds of random blood sugar reduction were found to be significant (OR 1.98, 95% CI = 1.30 to 3.00, P = .001) with adequate adherence. A linear regression equation was developed to predict medication adherence percentage for a patient which was found to have 61.8% predictive power using multilayer perceptron modelling. CONCLUSION: Overall, medication adherence was sub-optimal. Adherence assessments can be reliably performed using either one week or one month recall periods. With further refinement and validation, the regression equation could prove to be a useful tool for physicians.

Reversal of hypertensive heart disease: a multiple linear regression model.

BACKGROUND: The development of left ventricular hypertrophy in primary hypertension increases cardiovascular mortality and morbidity. Reversal of left ventricular hypertrophy through therapeutic control of blood pressure reduces the risk of adverse cardiovascular incidents.   Objective:  In our study, we explored for the determinants of left ventricular hypertrophy regression.  Methods: A cohort (n=217) of patients with hypertensive left ventricular hypertrophy was identified by screening consecutive patients in medical outpatient unit. The primary inclusion criteria were (i) Blood pressure more than140/90 mm of Hg (ii) Left Ventricular Mass Index more than 115 and 95 gm/m2 for males and females respectively. Left Ventricular Mass Index was determined by echocardiography at the time of recruitment and after 24 weeks of standard pharmacotherapy. The change in Left Ventricular Mass Index was modelled using multiple linear regression with both categorical and continuous explanatory variables. The effect of drug therapy on change in Left Ventricular Mass Index was tested in the model with dummy coded variables for the treatment categories.  Results: In simple linear regression, the variables significantly correlating with change in Left Ventricular Mass Index were baseline Left Ventricular Mass Index (r=0.62, p<0.001), change in systolic blood pressure (r=0.22, p=0.001), change in mean blood pressure (r=0.16, p=0.02), baseline systolic blood pressure (r=0.15, p=0.02), age (r=0.12, p=0.09) and diabetes (r=0.12, p=0.09). The best fit model (r2=0.408) retained baseline Left Ventricular Mass Index (ß=0.59, p<0.001), change in systolic blood pressure (ß=0.14, p=0.01) and diabetes (ß=-0.104, p=0.05) as the significant predictors. Introduction of treatment effect into the model non-significantly increased the fit of the model (r2=0.414, p=0.27-0.98).   Conclusions: Pre-treatment Left Ventricular Mass Index and reduction in systolic blood pressure were the major determinants of left ventricular hypertrophy regression. We also observed that there is lesser left ventricular hypertrophy regression in diabetic patients, warranting future research to explore glycaemic control as a modifiable factor in left ventricular hypertrophy reversal.

A Novel Metric System to Quantify Antibiotic Consumption in Paediatric Population: A Hospital Based, Biphasic Pilot Study.

BACKGROUND: The Anatomical Therapeutic Chemical Classification / Defined Daily Dose (ATC/DDD) system recommended by World Health Organization is accepted worldwide as the standard method of quantification of drug consumption. However, owing to individual variation in body weight, the ATC/DDD system cannot be used for comparison across paediatric population. OBJECTIVE: This study aimed to develop a novel metric system for standard quantification of antibiotic consumption in paediatric population. METHOD: The standard unit of drug quantification in adult population is DDD/100 patient days (PD). We conceived a new unit of DDD/1000 kg-days (KD) where KD is the product of the body weight and length of hospital stay of an individual patient. We simulated the quantification and comparison of drugs in a computer model of five virtual paediatric hospitals (H1 to H5, n=100, 200, 100, 100, 100 respectively). We re-applied the metric system on two, real world, hospital-based, time cohorts (TC) (TC18, n=38 and TC19, n=47) of 2 weeks each, in two consecutive years. RESULTS: The body weights (mean±SD) in H1-H5 were 5.7±3.0, 5.7±2.8, 25.3±8.5, 20.6±11.7 and 19.8±11.4 kg, respectively. The antibiotic consumption in terms of DDD/100 PD and DDD/1000 KD in the five hospitals was 1.26, 1.20, 5.52, 4.41 and 2.00, and 2.24, 2.14, 2.22, 2.17 and 1.06 respectively. In TC18 and TC19, the mean body weight, DDD/100 PD and DDD/1000 KD were 12.24±13.17, 30.93, 20.34 and 19.51±12.28, 11.99, 6.23, respectively. CONCLUSION: DDD/1000 kg-days is a potential standard unit for drug quantification in paediatric population independent of weight distribution and size of the study sample. The universal application and comparison across diverse samples can generate useful information for resource allocation, anti-microbial stewardship, disease burden and drug use, and can help in taking policy decisions to improve healthcare delivery in the paediatric population.

Regression of the Left Ventricular Hypertrophy in Patients with Essential Hypertension on Standard Drug Therapy.

 PURPOSE: The American College of Cardiology/ American Heart Association 2017 and European Society of Cardiology/European Society of Hypertension 2018 guidelines were a paradigm shift in hypertension management in contemporary medicine. Lowering of blood pressure to less than 130 (systolic) and 80 (diastolic) mm of Hg irrespective of cardiovascular risk is recommended. While intensive blood pressure control is commonly achievable with rational pharmacotherapy, the magnitude of left ventricular hypertrophy regression is an independent factor in improvement in cardiovascular health. The regression of left ventricular hypertrophy has been adjudged as a clinically useful surrogate marker that reflects the efficacy of hypertension treatment. Though angiotensin converting enzyme inhibitors/ angiotensin receptor blockers (ACEI/ARB) are the preferred initial drug for greater regression of left ventricular mass, the choice of add-on therapy, if required, is still debatable. Therefore, in our observational study, we sought to compare the reduction in left ventricular mass index in hypertensives with left ventricular hypertrophy on standard ACEI/ARB based drug therapy.  MATERIALS AND METHODS: The cohort (n=217) comprised of patients with uncontrolled hypertension (blood pressure>140/90 mm of Hg) and left ventricular hypertrophy (left ventricular mass index>115 and 95 gram/square meter in males and females respectively). The add-on drug in ACEI/ARB therapy was either thiazide diuretics (TD) or calcium channel blockers (CCB). Four sub-cohorts were constituted: mono-therapy - group A (n=70, ACEI/ARB), dual-therapy - group B (n=48, ACEI/ARB+TD) and  group C (n=51, ACEI/ ARB+CCB), triple therapy - group D (n=48, ACEI/ ARB+TD+CCB). Left ventricular mass index was determined using echocardiography at baseline and after 24 weeks of therapy.  RESULTS: There was no significant difference in baseline clinical or demographic variables between group B and group C. Baseline blood pressure and duration of hypertension was greater in group D compared to group A (P<0.001). The reduction in left ventricular mass index (mean ±SD) in the four groups (A to D) was 16.7±18.7, 21.0±20.8, 20.5±15.5  and 29.1±21.5 g/m2  respectively (D>A, P=0.011, B versus C, P=1.00). The corresponding change in blood pressure (systolic/diastolic) was 18.5±13.6/8.9±11.2, 27.5±19.2/12.2±9.3, 23.4±16.7/ 5.4±10.1, 26.6±19.5/10.7±12.8 mm of Hg respectively (systolic, B>A, P=0.027, D>A, P=0.048) (diastolic, B>C, P=0.013).  CONCLUSION: Anti-hypertensive treatment with angiotensin converting enzyme inhibitors/angiotensin receptor blockers-based therapy produced graded regression of left ventricular hypertrophy with monotherapy, dual therapy and triple therapy.  In dual therapy, add-on of either thiazide diuretics or calcium channel blockers to angiotensin converting enzyme inhibitors/angiotensin receptor blockers showed equal efficacy in regression of left ventricular hypertrophy independent of blood pressure reduction.

Development and validation of a mathematical model to quantify antibiotic consumption in paediatric population: A hospital-based pilot study.

WHAT IS KNOWN AND OBJECTIVES: A standard drug classification system and a fundamental measurement unit of drug consumption are prerequisites in a healthcare information system for generating quality data on drug use. Globally, the ATC/DDD (Anatomical Therapeutic Chemical Classification/Defined Daily Dose) system recommended by WHO is accepted as the international standard. However, owing to variability in body weight, it cannot be used directly in paediatric population. In our work, we aimed to develop a standard method of quantification of antibiotic consumption in paediatric population using a modified approach of the ATC/DDD system. METHOD: We developed a mathematical model in a simulated paediatric cohort (n = 1000) and calculated antibiotic consumption in units of days of therapy (DOT) and DDD/100 patient days (PD). We validated the model in an observational cohort (n = 38) of inpatients admitted in Paediatric Department of a tertiary care centre. RESULTS: Model simulation showed near perfect positive correlation (R = .99-1.00) between DOT and DDD/100 PD in discrete weight based sub-cohorts (weight 1-10 kg). In the validation cohort, consumption of antibiotics was 121.76 and 33.16 in terms of DOT and DDD/100 PD respectively. Strong positive correlation between the two units (R = .73) was obtained. The correlation was better in predefined age and weight categories as compared to the uncategorised consumption (R = .78-.97). The model was proved validated when weight specific (in sub-cohorts of patients weighing 4, 5, 7 kg) DDD/100 PD and DOT also showed near perfect positive correlation (R = .96-.99). WHAT IS NEW AND CONCLUSION: Weight specific DDD/100 PD can be explored further as a tool to standardise the quantification and comparison of consumption of drugs in paediatric population.

Prediction of Left Ventricular Mass Index Using Electrocardiography in Essential Hypertension - A Multiple Linear Regression Model.

BACKGROUND: Current electrocardiography (ECG) criteria indicate only the presence or absence of left ventricular hypertrophy (LVH). LVH is a continuum and a direct relationship exists between left ventricular mass (LVM) and cardiovascular event rate. We developed a mathematical model predictive of LVM index (LVMI) using ECG and non-ECG variables by correlating them with echocardiography determined LVMI. PATIENTS AND METHODS: The model was developed in a cohort of patients on treatment for essential hypertension (BP>140/90 mm of Hg) who underwent concurrent ECG and echocardiography. One hundred and forty-seven subjects were included in the study (56.38±11.84 years, 66% males). LVMI was determined by echocardiography (113.76±33.06 gm/m2). A set of ECG and non-ECG variables were correlated with LVMI for inclusion in the multiple linear regression model. The model was checked for multicollinearity, normality and homogeneity of variances. RESULTS: The final regression equation formulated with the help of unstandardized coefficients and constant was LVMI=18.494+ 1.704 (aLL) + 0.969 (RaVL+SV3) + 0.295 (MBP) + 15.406 (IHD) (aLL - sum of deflections in augmented limb leads; RaVL+SV3 - sum of deflection of (R wave in aVL + S wave in V3); MBP - mean blood pressure; IHD=1 for the presence of the disease, IHD=0 for the absence of the disease). CONCLUSION: In the model, 50.4% of the variability in LV mass is explained by the variables used. The findings warrant further studies for the development of better and validated models that can be incorporated in microprocessor-based ECG devices. The determination of LVMI with ECG only will be a cost-effective and readily accessible tool in patient care.

The Battle against COVID 19 Pandemic: What we Need to Know Before we "Test Fire" Ivermectin.

The world is faced with the dire challenge of finding an effective treatment against the rampaging COVID 19 pandemic. Amidst the crisis, reports of in vitro inhibitory activity of ivermectin, an approved anthelmintic, against the causative SARSCoV2 virus, have generated lot of optimism. In this article, we have fished and compiled the needed information on the drug, that will help readers and prospective investigators in having a quick overview. Though the primordial biological action of the drug is allosteric modulation of helminthic ion channel receptor, its in vitro activity against both RNA and DNA viruses is known for almost a decade. In the past two years, efficacy study in animal models of pseudorabies and zika virus was found to be favourable and unfavourable respectively. Only one clinical study evaluated the drug in dengue virus infection without any clinical efficacy. However, the proposed mechanism of drug action, by inhibiting the importin family of nucleus-cytoplasmic transporters along with favourable pharmacokinetics, warrants exploration of its role in COVID 19 through safely conducted clinical trials. Being an available and affordable drug, enlisted in WHO List of Essential Medicine, and a long track record of clinical safety, the drug is already in clinical trials the world over. As the pandemic continues to ravage human civilisation with unabated intensity, the world eagerly waits for a ray of hope emanating from the outcome of the ongoing trials with ivermectin as well as other drugs.

A comparative experimental study of analgesic activity of a novel non-steroidal anti-inflammatory molecule - zaltoprofen, and a standard drug - piroxicam, using murine models.

PURPOSE: Pain is an unpleasant sensation, but a protective mechanism of our body. It is the most common medical complaint requiring a visit to a physician. The new non-steroidal anti-inflammatory drug (NSAID) - zaltoprofen, is a preferential COX-2 inhibitor. It also inhibits bradykinin-induced nociceptive responses by blocking the B2 receptor-mediated pathway in the primary sensory neurons. The present study was conducted to evaluate and compare the anti-nociceptive activity of zaltoprofen with a conventional NSAID - piroxicam, in a mouse model of acute pain using hot plate and tail flick tests. MATERIALS AND METHODS: Twenty-four adult Swiss albino mice (20-25 g) of either sex were used in this study. Oral zaltoprofen and piroxicam were used as test and standard drugs respectively. Anti-nociceptive activity was evaluated and compared using hot plate and tail flick tests. RESULTS: In comparison to the control group (vehicle), zaltoprofen showed a significant increase in reaction time at various time periods in the hot plate and tail flick tests. In the hot plate method, zaltoprofen groups (15 and 20 mg/kg) showed a significant elevation in pain threshold in comparison to control group (vehicle) (p<0.001). In the tail flick model also, zaltoprofen groups (15 and 20 mg/kg) showed a significant increase in the reaction time in comparison to control group (vehicle). In both the analgesiometer assays, zaltoprofen was found to be non-inferior compared to a standard drug - piroxicam (positive control). CONCLUSION: Our study concludes that zaltoprofen is an effective analgesic agent in various pain models. Our results support that zaltoprofen has therapeutic potential for treating pain disorders and is non-inferior to a standard drug - piroxicam.

Medication concordance in modern medicine - A critical appraisal from an Indian perspective.

Modern medicine encompasses a holistic approach toward patient care that seeks to integrate the social, psychological, and pathological aspects of a disease. In line with this, the traditional model of improving treatment outcomes through improved compliance or adherence has given way to the concept of "concordance" that respects the integrity of the patient, autonomy, and self-determination. A self-conscious patient actively and equally participating in her or his comprehensive healthcare can bring a paradigm shift in the perceptions and functioning of the healthcare sector. Medication concordance can be expected to play a key role in improving patient well-being, clinical outcomes, and healthcare delivery. However, it is fraught with numerous questions to be addressed ranging from lack of clarity or standard protocol, medicolegal intricacies, cultural-linguistic barriers, illiteracy, shortage of time, infrastructure, and manpower. There are major challenges in the effective implementation of this initiative which has definite potential to prove beneficial in Indian healthcare settings. The success of this novel approach can only be accomplished by coordinated, inclusive, and persistent efforts from all participants of healthcare with fostering of a milieu of trust, belief, and communication. A systematic literature search was conducted using key words from relevant articles and MeSh terms on Google Scholar and PubMed. Data were abstracted according to their relevance to subheadings of the review and synthesis of concepts was done through multiple reviews by atleast two reviewers for any subsection.