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.

3-[(E)-2-(2-Meth-oxy-phen-yl)vin-yl]-5,5-di-methyl-cyclo-hex-2-enone.

The title compound, C17H20O2, has an E conformation about the bridging C=C bond. The cyclo-hexene ring adopts an envelope conformation with the dimethyl-substituted C atom as the flap. Its mean plane makes a dihedral angle of 7.20 (12)° with the benzene ring. In the crystal, neighbouring mol-ecules are connected via C-H⋯O hydrogen bonds, forming chains running along the a-axis direction.

1-[2-(3-Meth-oxy-phen-yl)eth-yl]pyrroli-dine-2,5-dione.

In the title compound, C13H15NO3, the pyrrolidine ring makes a dihedral angle of 4.69 (9)° with the 3-meth-oxy-phenyl ring. In the crystal, hydrogen-bonded chains running along [101] are generated by connecting neighbouring mol-ecules via C-H⋯O hydrogen bonds. Parallel chains are linked by further C-H⋯O hydrogen bonds, forming a three-dimensional structure.

N-tert-Butyl-2-(2,6-di-chloro-phen-yl)imidazo[1,2-a]pyrazin-3-amine.

In the title compound, C16H16Cl2N4, the imidazole ring mean plane makes a dihedral angle of 70.01 (1)° with the phenyl ring. The Cl atoms deviate by -0.0472 (6) and 0.0245 (8) Šfrom the plane of their attached benzene ring. In the crystal, mol-ecules are linked via pairs of C-H⋯N hydrogen bonds, forming inversion dimers.

3-[(E)-2-(4-Chloro-phen-yl)ethen-yl]-5,5-di-methyl-cyclo-hex-2-en-1-one.

In the title compound, C16H17ClO, the cyclo-hexene ring adopts a half-chair conformation and the best plane through the six ring atoms makes a dihedral angle of 6.69 (7)° with the chlorophenyl ring. In the crystal, pairs of C-H⋯O hydrogen bonds link the mol-ecules into centrosymmetric R 2 (2)(20) dimers. The dimers are linked into an infinite chains along the b-axis direction by further C-H⋯O hydrogen bonds.

N-(4-Meth-oxy-phen-yl)-2,6-dimethyl-1,3-dioxan-4-amine.

In the title compound, C13H19NO3, the dioxane ring adopts a chair conformation. Its mean plane is inclined to the 4-meth-oxy-phenyl ring by 70.34 (9)°. In the crystal, mol-ecules are linked by pairs of C-H⋯O hydrogen bonds, forming inversion dimers with an R (2) 2(16) ring motif. The dimers are linked via C-H⋯π inter-actions, forming two-dimensional networks lying parallel to the ac plane.

N-(4-Fluoro-phen-yl)-2,6-dimethyl-1,3-dioxan-4-amine.

In the title compound, C12H16FNO2, the dioxane ring adopts a chair conformation with the methyl substituents and the C-N bond in equatorial orientations. Its mean plane subtends a dihedral angle of 40.17 (6)° with the benzene ring. In the crystal, weak N-H⋯F hydrogen bonds link the mol-ecules into C(7) chains propagating in [100].

N-tert-Butyl-2-[4-(dimethyl-amino)-phen-yl]imidazo[1,2-a]pyrazin-3-amine.

In the title compound, C18H23N5, the imidazole ring makes a dihedral angles of 3.96 (8) and 19.02 (8)°, respectively, with the pyrazine and benzene rings while the dihedral angle between the pyrazine and benzene rings is 16.96 (7)°. In the crystal, mol-ecules are linked via N-H⋯N hydrogen bonds, forming chains along [010]. These chains are linked by C-H⋯N hydrogen bonds, forming two-dimensional networks lying parallel to (001).

Allyl 2-(2,2-dimethyl-3a,6a-di-hydro-furo[3,2-d][1,3]dioxol-5-yl)-4-oxo-4H-chromene-3-carboxyl-ate.

In the title compound, C20H18O7, the dioxolane ring adopts an envelope conformation with the dimethyl-substituted C atom as the flap, and its mean plane makes a dihedral angle of 73.25 (2)° with the pyran ring mean plane. The furan ring makes dihedral angles of 67.43 (12) and 6.20 (11)° with the mean plane of the dioxolane and pyran rings, respectively. The O atom attached to the pyran ring deviates by 0.0219 (2) Šfrom its mean plane. In the crystal, mol-ecules are linked via C-H⋯O hydrogen bonds, forming chains along [010] and enclosing R 2 (2)(9) loops. They stack along the a axis with π-π inter-actions involving the 4H-chromene units [centroid-centroid distances of 3.6389 (13) and 3.6555 (13) Å]. The terminal CH2=CH- atoms of the allyl acetate group are disordered over two sets of sites with a refined occupancy ratio of 0.717 (6):0.283 (6).

Methyl 2-(2,2-dimethyl-3a,6a-di-hydro-furo[3,2-d][1,3]dioxol-5-yl)-4-oxo-4H-chromene-3-carboxyl-ate.

In the title mol-ecule, C18H16O7, the dioxolane ring adopts an envelope conformation with the dimethyl-substituted C atom as the flap. The furan ring is almost coplanar with the pyran ring, with a dihedral angle of 1.04 (10)° between the planes, and it makes a dihedral angle of 67.97 (11)° with the mean plane of the dioxolane ring. The latter makes a dihedral angle of 67.15 (10)° with the pyran ring. The O atom attached to the pyran ring deviates by -0.009 (1) Å. The crystal packing features C-H⋯O hydrogen bonds, forming a three-dimensional structure. The meth-oxy-carbonyl atoms are disordered over two positions, with a refined occupancy ratio of 0.508 (18):0.492 (18).

N-(2-Fluoro-phen-yl)-2,6-dimethyl-1,3-dioxan-4-amine.

In the title compound, C12H16FNO3, the dioxane ring adopts a chair conformation with the methyl groups and amine N atom in equatorial positions. The best plane through the dioxane ring makes a dihedral angle of 43.16 (8)° with the phenyl ring. In the crystal, pairs of C-H⋯O hydrogen bonds link the mol-ecules into centrosymmetric R 2 (2)(8) dimers, which are linked into [100] chains by further C-H⋯O hydrogen bonds. The N-H group does not participate in hydrogen bonding.

2,6-Dimethyl-N-(2-methyl-phen-yl)-1,3-dioxan-4-amine.

In the title compound, C13H19NO2, the dioxane ring adopts a chair conformation and its mean plane makes a dihedral angle of 45.36 (8)° with the phenyl ring. In the crystal, mol-ecules are linked by pairs of N-H⋯O hydrogen bonds, forming inversion dimers with R (2) 2(12) ring motifs. These dimers are consolidated by pairs of C-H⋯O hydrogen bonds with R (2) 2(8) ring motifs.

N-(4-Bromo-phen-yl)-2,6-dimethyl-1,3-dioxan-4-amine.

In the title compound, C12H16BrNO2, the dioxane ring adopts a chair conformation and its mean plane makes a dihedral angle of 60.63 (12)° with the 4-bromo-phenyl ring. In the crystal, mol-ecules are linked by pairs of N-H⋯O hydrogen bonds, forming inversion dimers with an R 2 (2)(8) ring motif. These dimers are consolidated by pairs of C-H⋯O hydrogen bonds with an R 2 (2)(16) ring motif. Adjacent dimers are connected via C-H⋯O hydrogen bonds, forming infinite chains propagating along the c-axis direction.

Implications and Economic Impact of Applying International Guidelines and Recommendations to the Management of High-Risk Group of Type 2 Diabetes Mellitus Patients in India.

Objectives Sodium-glucose cotransporter-2 (SGLT-2) inhibitors and dipeptidyl peptidase IV (DPP-IV) inhibitors are recommended as preferred add-on oral antidiabetic drugs (OADs) after metformin among type 2 diabetes mellitus (T2DM) patients with atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and chronic kidney disease (CKD). They are generally many folds costlier than other OADs. This is a simulatory analysis to assess the incremental cost escalation and risk reduction with their hypothetical substitution/addition in prescriptions of high-risk patients. Methods A simple simulation of cost-effectiveness analysis was performed using prescriptions of T2DM patients with established cardiovascular (CV) or renal disease or high-risk factors. SGLT-2 and DPP-IV inhibitors with proven benefits/safety were substituted or added in place of other OADs. Increments in treatment costs were calculated, and the anticipated decrease in hazards was extrapolated from cardiovascular outcome trials (CVOTs) and real-world studies. The incremental cost-effectiveness ratios (ICERs) were calculated. Results Prescriptions of 351 patients with a mean age of 58.04 ± 8.67 years were analyzed. The median annual acquisition cost of drug therapy for diabetes per patient was found to be Indian national rupee (INR) 8,964.4 for the original prescriptions when calculated using median retail prices of drugs prescribed for diabetes. Upon substituting one of the SGLT-2 inhibitors for the other OADs in the regimen, the cost increased to INR 12,265 (increase by 36.8%) for dapagliflozin, and INR 26,718 and INR 29,419 (increase by ~200%), respectively, for canagliflozin and empagliflozin. Upon calculating the ICERs, additional cost to prevent one all-cause death with dapagliflozin substitution is INR 660,020-25,384,369; INR 2,223,326 with empagliflozin substitution and INR 8,069,818 with canagliflozin substitution. The ICER for prevention of hospitalization with HF with dapagliflozin substitution is INR 1,320,040-1,435,543; INR 4,010,706 with empagliflozin and INR 5,548,000 with canagliflozin. To prevent a three-point major adverse cardiac event (3P-MACE), INR 2,062,562 would be needed with dapagliflozin substitution, and INR 3,146,861 and INR 3,859,478 with empagliflozin and canagliflozin, respectively. Incremental costs for various outcomes were higher with the addition of SGLT-2 inhibitors and significantly more if substitution with sitagliptin/linagliptin was also done. The numbers needed to treat were calculated too and ranged from 35 to 1,831 for various outcomes and drugs. Conclusion While the recommendations for use of SGLT-2 and DPP-IV inhibitors are adequately backed by evidence from CVOTs and real-world data, the incremental costs per event reduction are quite high for most outcomes in the Indian context. Dapagliflozin, being available as cheaper generic versions, appears to be most effective for most outcomes. Interpretations are subjective in terms of value assigned for preventing a major event.

Patterns of drug therapy, glycemic control, and predictors of escalation - non-escalation of treatment among diabetes outpatients at a tertiary care center.

OBJECTIVES: The study was conducted to assess patterns of prescribed drug therapy and clinical predictors of need for therapy escalation in outpatients with diabetes mellitus (DM). METHODS: This was a prospective cohort study, conducted at an apex tertiary care teaching hospital in central India for a period of 18 months. The demographic, clinical, and treatment details on the baseline and follow up visits were collected from the patients' prescription charts. Glycemic control, adherence, pill burdens along with pattern of antidiabetic therapy escalation, and deescalations were analyzed. RESULTS: A total of 1,711 prescriptions of 925 patients of diabetes with a mean age of 53.81 ± 10.42 years and duration of disease of 9.15 ± 6.3 years were analyzed. Approximately half of the patients (n=450) came for ≥1 follow up visits. Hypertension (59.35%) was the most common comorbidity followed by dyslipidemia and hypothyroidism. The mean total daily drugs and pills per prescription were 4.03 ± 1.71 and 4.17 ± 1.38, respectively. Metformin (30.42%) followed by sulphonylureas (SUs) (21.39%) constituted majority of the AHA's and dual and triple drug therapy regimens were most commonly prescribed. There were improvements in HbA1c, fasting/postprandial/random blood sugar (FBS/PPBS/RBS) as well as adherence to medication, diet, and exercise in the follow up visits. Among patients with follow ups, therapy escalations were found in 31.11% patients, among whom dose was increased in 12.44% and drug was added in 17.28%. Apart from Hb1Ac, FBS, and PPBS levels (p<0.001), characteristics such as age, BMI, duration of diagnosed diabetes, presence of hypertension and dyslipidemia, and daily pill burdens were found to be significantly higher in the therapy escalation group (p<0.05). Inadequate medication adherence increased the relative risk (RR) of therapy escalation by almost two times. CONCLUSIONS: Disease and therapy patterns are reflective of diabetes care as expected at a tertiary care center. Higher BMI, age, pill burden, duration of diabetes, presence of comorbidities, and poor medication adherence may be the predictors of therapy escalation independent of glycemic control and such patients should be more closely monitored.

Synthesis of Biomass-Derived Activated Carbons and Their Immobilization on Alginate Gels for the Simultaneous Removal of Cr(VI), Cd(II), Pb(II), As(III), and Hg(II) from Water.

Low-cost alginate gels of activated carbons were prepared, which were derived from the peels of banana and sweet lime. The synthesized carbon was activated and immobilized on alginate, producing its gel. These gels were categorized according to their methods of drying, in which air drying, freeze drying, and supercritical drying led to the formation of xerogels, cryogels, and aerogels, respectively. The gels were used for adsorption of heavy metals from their aqueous solution. The heavy metals that were targeted for removal were Pb(II), Cd(II), Cr(VI), As(III), and Hg(II). Among all the adsorbents, the alginate cryogel of sweet lime-derived activated carbon (SLACC) showed the highest removal percentage of heavy metals, and thus, it was used for batch study. The adsorption of heavy metals by SLACC was checked at different times, pH values, adsorbent doses, temperatures, and adsorbate concentrations. The study revealed that the pseudo-second-order model best described the kinetic study, while the adsorption followed the Freundlich isotherm. SLACC showed maximum adsorption capacities (q cal) of 3.71, 4.22, 20.04, 7.31, and 4.37 mg/g for Cr, Cd, Pb, As, and Hg, respectively, when 20 mg of SLACC was used for the removal of 4 ppm concentration of the targeted heavy metals from their 20 mL solution. Based on the thermodynamic study, it was found that the adsorption was spontaneous and exothermic. Furthermore, the adsorbent was also used on real water samples and showed up to 90% removal efficiency for these targeted heavy metals. SLACC was regenerated with 0.1 M ethylenediaminetetraacetic acid (EDTA) solution and reused for five cycles, in which the percentage removal of heavy metals was more than 50% till the fourth cycle. Furthermore, the leaching study showed that no toxic elements had leached from SLACC into water, making it a safe adsorbent.

Remogliflozin: the new low cost SGLT-2 inhibitor for type 2 diabetes mellitus.

SGLT-2 inhibitors have recently emerged as an important class of oral drugs for treatment of type 2 diabetes mellitus, especially in patients with cardiovascular or renal impairment, recommended in all recent treatment guidelines. They have additional advantages of weight and blood pressure reduction but also pose problems like genitourinary infections. These drugs generally have a high cost making affordability a major consideration in their prescription in developing countries like India. A new molecule remogliflozin has been approved in India in 2019 after a phase 3 trial proved its efficacy and safety in comparison to dapagliflozin. This drug has been priced substantially lower than other SGLT-2 inhibitors, and despite the disadvantage of twice daily administration, it potentially reduces treatment cost to less than half compared to other molecules of this class. With a good tolerability profile on the basis of available safety data till date, remogliflozin could be a useful alternative for providing SGLT-2 inhibitor therapy in a country like India where out of pocket expenses for drug acquisition matter significantly for the general population. However, long term safety and efficacy data especially on cardiovascular and renal outcomes are currently lacking for the drug.

Pattern of Disease and Therapy for Diabetes along with Impact of Generic Prescribing on Cost of Treatment among Outpatients at a Tertiary Care Facility.

BACKGROUND: India has become the diabetes capital of the world. Analyzing trends in drug prescribing helps in judging rationality of prescriptions in different settings. This study aimed to assess disease and prescribing trends with a special emphasis on evaluating use of metformin, insulin, fixed dose combinations (FDCs), concomitant medications, pill burden, and costs of drug therapy in diabetes. MATERIALS AND METHODS: This was a cross-sectional study in which patients of either sex who attended the diabetes clinic at a tertiary care center over 9 months were included consecutively. Basic demographic profile, clinical, and treatment details on the day of visit were collected from the prescription charts. Drug costs for prescriptions were calculated using generic and median brand prices of formulations using a recognized commercial drug directory and generic price list of the government, respectively. Data were analyzed by using Microsoft Excel and Open Epi online software to compare results with published studies. RESULTS: Average age of diabetics was 53.9 ± 11.8 years and disease duration was 8.13 ± 7.78 years in 336 prescriptions analyzed. Dual drug regimens were seen in 32.7% prescriptions, most commonly metformin and sulfonylureas, followed by triple drug regimens (25%) with inhibition of dipeptidyl peptidase IV (DPP IV) inhibitor. Metformin was prescribed in 95% prescriptions (mean dose 1511 ± 559.87 mg) and insulin in 22.6% prescriptions. Angiotensin receptor blocker (ARBs) and statins were the most commonly prescribed concomitant drugs. One FDC per prescription (median) each for diabetes and comorbidities were prescribed. Daily pill burden was 4.59 ± 2.65 pills. The median monthly cost of drug therapy with branded prescribing was INR 870.43 and INR 393.72 with the use of generics. Inferences drawn by comparison with published data showed variable results for different parameters analyzed. CONCLUSION: Disease pattern was as expected for the region and trends of therapy showed concurrence with rational prescribing. Pill burden and cost of therapy remain high with a significant contribution of comorbidities.

IL-6 Inhibitors in the Treatment of Serious COVID-19: A Promising Therapy?

At present, there are no proven agents for treatment of coronavirus disease (COVID-19). The available evidence has not allowed guidelines to clearly recommend any drugs outside the context of clinical trials. The novel coronavirus SARS-CoV-2 that causes COVID-19 invokes a hyperinflammatory state driven by multiple cells and mediators like interleukin (IL)-1, IL-6, IL-12, and IL-18, tumor necrosis factor alpha (TNFα), etc. Considering the proven role of cytokine dysregulation in causing this hyperinflammation in the lungs with IL-6 being a key driver, particularly in seriously ill COVID-19 patients, it is crucial to further explore selective cytokine blockade with drugs like the IL-6 inhibitors tocilizumab, sarilumab, and siltuximab. These targeted monoclonal antibodies can dampen the downstream IL-6 signaling pathways, which can lead to decreased cell proliferation, differentiation, oxidative stress, exudation, and improve clinical outcomes in patients with evident features of cytokine-driven inflammation like persistent fever, dyspnea and elevated markers. Preliminary evidence has come for tocilizumab from some small studies, and interim analysis of a randomized controlled trial; the latter also being available for sarilumab. International guidelines do include IL-6 inhibitors as one of the options available for severe or critically ill patients. There has been increased interest in evaluating these drugs with a series of clinical trials being registered and conducted in different countries. The level of investigation though perhaps needs to be further intensified as there is a need to focus on therapeutic options that can prove to be 'life-saving' as the number of COVID-19 fatalities worldwide keeps increasing alarmingly. IL-6 inhibitors could be one such treatment option, with generation of more evidence and completion of a larger number of systematic studies.

Approval of Itolizumab for COVID-19: A Premature Decision or Need of The Hour?

Itolizumab is a first-in-class anti-CD6 monoclonal antibody that was initially developed for various cancers and was later developed and approved in India for treatment of moderate to severe chronic plaque psoriasis in 2013. This drug is now being re-purposed for COVID-19. The potential utility of itolizumab in COVID-19, based on its unique mechanism of action in ameliorating cytokine release syndrome (CRS), was proposed first in Cuba with approval of a single-arm clinical trial and expanded access use. Subsequently, a phase II, open-label, randomized, placebo-controlled trial has been conducted in 30 COVID-19 patients in India after receiving regulatory permission. Based on the results, the Indian drug regulatory agency recently approved itolizumab in July 2020 for 'restricted emergency use' for the treatment of CRS in moderate to severe acute respiratory distress syndrome (ARDS) due to COVID-19. This has drawn sharp criticism within the scientific community, with the approval being granted on the basis of a relatively small phase II trial, without conduct of a conventional phase III trial, and lacking availability of the claimed supportive real-world evidence in the public domain to date. In a global scenario where finding a successful treatment for COVID-19 is of utmost priority, a biologic agent has been re-purposed and approved with a successfully completed RCT, in a country where cases and mortality due to COVID-19 are growing exponentially. However, instead of welcoming the approval with open arms, many doubts are being raised. This is an issue that needs to be considered and dealt with sensitively, as well as scientifically.