Targeting dendritic cell-specific TNFR2 improves skin and joint inflammation by inhibiting IL-12/ IFN-γ pathways in a mouse model of psoriatic arthritis.

Psoriasis (PsO) and Psoriatic arthritis (PsA) are immune-mediated inflammatory diseases affecting the skin and joints. Approximately, 30% of patients with PsO develop PsA over time with both conditions being associated with elevated tumor necrosis factor-alpha (TNF-α) expression. TNF-α mediates its effect through two membrane receptors, TNFR1 and TNFR2. While current TNF-α-neutralizing agents, targeting both TNFR1 and TNFR2 receptors, constitute the primary treatment for psoriatic diseases, their long-term use is limited due to an increase in opportunistic infections, tuberculosis reactivation and malignancies likely attributed to TNFR1 inactivation. Recent findings suggest a pivotal role of TNFR2 in psoriatic disease, as evidenced by its amelioration in global TNFR2-knockout (TNFR2KO) mice, but not in TNFR1KO mice. The diminished disease phenotype in TNFR2KO mice is accompanied by a decrease in DC populations. However, the specific contribution of TNFR2 in dendritic cells (DCs) remains unclear. Here, utilizing a mannan-oligosaccharide (MOS)-induced PsA model, we demonstrate a significant reduction in PsA-like skin scaling and joint inflammation in dendritic cell-specific TNFR2 knockout mice (DC-TNFR2KO). Notably, MOS treatment in control mice (TNFR2 fl/fl) led to an increase in conventional type 1 dendritic cells (cDC1) population in the spleen, a response inhibited in DC-TNFR2KO mice. Furthermore, DC-TNFR2KO mice exhibited reduced levels of interleukin-12 (IL-12), a Th1 cell activator, as well as diminished Th1 cells, and interferon-gamma (IFN-γ) levels in the serum compared to controls following MOS stimulation. In summary, our study provides compelling evidence supporting the role of TNFR2 in promoting PsA-like inflammation through cDC1/Th1 activation pathways.

Advancing Basic and Translational Science: Highlights From the Basic Science Workshop at the GRAPPA 2023 Annual Meeting.

Contemporary translational and clinical research advances in psoriatic disease (PsD) were highlighted at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 annual meeting basic science workshop. This year's workshop focused on key topics, including the significance of the annual GRAPPA meetings as a platform for collaboration and knowledge exchange. Discussions centered around expanding our understanding of tumor necrosis factor inhibitor (TNFi) treatment in PsD and enhancing early detection strategies for PsD comorbidities, specifically for the timely intervention and management of cardiovascular (CV) comorbidities. Insights on the role of the C-C chemokine receptor type 6 (CCR6) in PsD and psoriatic arthritis were provided, suggesting that blockade of CCR6 can reduce psoriasis-like dermatitis and joint inflammation in mouse models.

TNFR2 Depletion Reduces Psoriatic Inflammation in Mice by Downregulating Specific Dendritic Cell Populations in Lymph Nodes and Inhibiting IL-23/IL-17 Pathways.

TNF-α, a proinflammatory cytokine, is a crucial mediator of psoriasis pathogenesis. TNF-α functions by activating TNFR1 and TNFR2. Anti-TNF drugs that neutralize TNF-α, thus blocking the activation of TNFR1 and TNFR2, have been proven highly therapeutic in psoriatic diseases. TNF-α also plays an important role in host defense; thus, anti-TNF therapy can cause potentially serious adverse effects, including opportunistic infections and latent tuberculosis reactivation. These adverse effects are attributed to TNFR1 inactivation. Therefore, understanding the relative contributions of TNFR1 and TNFR2 has clinical implications in mitigating psoriasis versus global TNF-α blockade. We found a significant reduction in psoriasis lesions as measured by epidermal hyperplasia, characteristic gross skin lesion, and IL-23 or IL-17A levels in Tnfr2-knockout but not in Tnfr1-knockout mice in the imiquimod psoriasis model. Furthermore, imiquimod-mediated increase in the myeloid dendritic cells, TNF/inducible nitric oxide synthase‒producing dendritic cells, and IL-23 expression in the draining lymph nodes were dependent on TNFR2 but not on TNFR1. Together, our results support that psoriatic inflammation is not dependent on TNFR1 activity but is driven by a TNFR2-dependent IL-23/IL-17 pathway activation. Thus, targeting the TNFR2 pathway may emerge as a potential next-generation therapeutic approach for psoriatic diseases.

Effectiveness of blended learning in pharmacy education: An experimental study using clinical research modules.

BACKGROUND &OBJECTIVES: Though there are studies to evaluate the effectiveness of blended learning in pharmacy education, most of them originate from USA and have used previous year students' scores as control. Also there is less research in comparing use of self -regulated learning strategies between blended and other learning strategies. Primary aim was to evaluate the effectiveness of blended learning on knowledge score using clinical research modules. Secondary objective was designed to compare the use of self-regulated learning strategies between blended learning, web-based e-learning and didactic teaching. MATERIALS AND METHODS: A prospective cluster randomized trial was conducted with didactic teaching as control and web-based e-learning and blended learning as interventions. The target population was final year Pharm D students. Outcome was assessed using a validated knowledge questionnaire, a motivated strategies for learning questionnaire and a feedback form. All statistical analyses were carried out using Statistical Package for Social Science (SPSS) Version 20. RESULTS: A total of 241 students from 12 colleges completed the study. Mean knowledge score of students in blended learning group was higher than those in the didactic teaching and web- based e- learning program (64.26±18.19 Vs 56.65±8.73 Vs 52.11±22.06,p<0.001).Frequency of use of learning strategies namely rehearsal, elaboration, organization and critical thinking was statistically significantly higher in the blended learning group compared to those of didactic and web-based e-learning group (p<0.05) But there were no statistically significant difference of motivational orientations between didactic and blended learning group except strategies of extrinsic goal orientation and self-efficacy. Students preferred blended learning (86.5%) over didactic and web-based e-learning. CONCLUSION: Blended learning approach is an effective way to teach clinical research module. Students of blended learning group employed all motivational and learning strategies more often than students of the didactic and web- based e-learning groups except strategies of intrinsic goal orientation, task value, control of learning belief and help seeking.

Availability, price and affordability of essential medicines for managing cardiovascular diseases and diabetes: a statewide survey in Kerala, India.

OBJECTIVE: Limited access to essential medicines (EMs) for cardiovascular disease (CVD) and diabetes is a major concern in low- and middle-income countries. We aimed to generate data on availability, price and affordability of EMs for CVD and diabetes in India. METHODS: Using WHO/HAI survey methodology, we evaluated availability and prices of 23 EMs in 30 public sector facilities (government hospitals and semi-public/government-subsidised-discount-pharmacies (GSDPs)) and 60 private retail pharmacies across six districts in Kerala state, India (November 2018 - May 2019). Median Price Ratios (MPRs) were calculated by comparing consumer prices with international reference prices. We also analysed data (collected in July 2020) on six anti-hypertensive fixed-dose-combinations (FDCs) that were designated as 'essential' by the WHO in 2019. RESULTS: Mean availability of surveyed generic EMs was 45.7% in government hospitals, 64.7% in GSDPs and 72.0% in private retail pharmacies. On average, the most-sold and highest-priced generics, respectively, were 6.6% and 8.9% costlier than the lowest-priced generics (LPG). Median MPR for LPG was 2.71 in private retail and 2.25 in GSDPs. Monthly supply of LPG would cost the lowest-paid worker 1.11 and 0.79 days' wages in private retail and GSDPs, respectively. Mean availability of the surveyed FDCs was poor (private retail: 15-85%; GSDPs: 8.3-66.7%), and the private retail prices of FDCs were comparable to the sum of corresponding constituent monotherapies. CONCLUSION: Availability of CVD and diabetes EMs fall short of WHO's 80% target in both sectors. Although availability in the private retail pharmacies was near-optimal, prices appear unaffordable compared to GSDPs. Initiatives such as mandating generic prescribing, adding the WHO-approved FDCs in local EM lists, improving price transparency, and streamlining medicine supply to ensure equitable access to EMs, especially in the public sector, are crucial in tackling Kerala's ever-increasing CVD burden.

OBJECTIF: L'accès limité aux médicaments essentiels (ME) pour les maladies cardiovasculaires (MCV) et le diabète est une préoccupation majeure dans les pays à revenu faible et intermédiaire. Nous visions à générer des données sur la disponibilité, le prix et l'aspect abordable des ME pour les MCV et le diabète en Inde. MÉTHODES: En utilisant la méthodologie OMS/HAI, nous avons évalué la disponibilité et les prix de 23 ME dans 30 établissements du secteur public (hôpitaux publics et pharmacies semi-publiques/à discompte subventionnées par le gouvernement (GSDP)) et 60 pharmacies de détail privées dans 6 districts de l'Etat du Kerala, en Inde. Les ratios de prix médians (RPM) ont été calculés en comparant les prix des consommateurs aux prix de référence internationaux. Nous avons également analysé les données de six combinaisons à dose fixe (CDF) d'antihypertensives désignées ''essentielles'' par l'OMS en 2019. RÉSULTATS: La disponibilité moyenne des ME génériques étudiés était de 45,7% dans les hôpitaux publics, de 64,7% dans les GSDP et de 72,0% dans le commerce de détail privé. En moyenne, les génériques les plus vendus et les plus chers, respectivement, étaient de 6,6% et 8,9% plus chers que les génériques les moins chers (GMC). Le RPM pour les (GMC) était de 2,71 dans le secteur privé et de 2,25 dans les GSDP. L'approvisionnement mensuel en GMC coûterait au travailleur le moins payé le salaire de 1,11 et 0,79 jour de travail dans le secteur de la vente au détail privé et dans les GSDP, respectivement. La disponibilité moyenne des CDF était faible (vente au détail privée: 15% - 85%; GSDP: 8,3%-66,7%), avec des prix de détail privés comparables à la somme des monothérapies constituantes correspondantes. CONCLUSION: La disponibilité des ME pour les MCV et le diabète est inférieure à l'objectif de 80% de l'OMS dans les deux secteurs. Bien que la disponibilité dans les pharmacies de détail privées soit presque optimale, les prix semblent inabordables par rapport aux GSDP. Des initiatives telles que la prescription de médicaments génériques, l'inscription des CDF sous ME, l'amélioration de la transparence des prix, la rationalisation de l'approvisionnement en médicaments pour assurer un accès équitable aux ME, en particulier dans le secteur public, sont essentielles pour faire face à la charge toujours croissante des MCV dans le Kerala.

Effects of sedative-hypnotics on sleep quality among patients with insomnia: evidence from an observational, pre-post study in India.

BACKGROUND: Insomnia continues to be neglected globally, despite its high prevalence. Guidelines by the health regulatory agencies call for studies to evaluate the effect of sedative-hypnotics on sleep quality. METHODS: We conducted a pre-post observational study to evaluate sleep quality among 186 inpatients receiving short-term oral sedative-hypnotic therapy in a tertiary care teaching hospital in Kozhikode (Kerala), India. Using Pittsburgh Sleep Quality Index_Past-Week (PSQI_PW) questionnaire, patients were interviewed upon hospital admission and at follow up after ≥1-week of sedative-hypnotic therapy. Additionally, we interviewed 36 physicians to understand the current clinical perception about sedative-hypnotics. RESULTS: Mean (SD) age of the study patients was 59 (7.5) years. Majority (63.4%) of the patients were men. Of the various primary diagnoses for hospitalization, cardiovascular disease was the most common (22.6%, n = 49). Sedative-hypnotic therapy improved the mean (SD) PSQI_PW overall score by 6.79 points (pre: 12.70 (3.5) vs. post: 5.91 (2.8); p < 0.0001). Statistically significant improvements in sleep duration, latency, efficacy, and day dysfunction were observed. Higher proportion of study patients were prescribed benzodiazepines (73.7%) compared to zolpidem (26.3%). Patients treated with zolpidem reported higher improvements in mean overall PSQI_PW scores compared to those treated with benzodiazepines, however these differences were not statistically significant upon adjusting for age, gender and primary diagnosis for hospitalization. Qualitative interviews indicate that that physicians consider zolpidem to be safer and more efficacious. CONCLUSIONS: In our study, sedative-hypnotic therapy helped improve sleep quality among the hospitalized patients. More studies evaluating the comparative efficacy and safety of zolpidem vs. benzodiazepines - including among patient groups with varying demographic and clinical characteristics - are needed. India must develop evidence-based treatment guidelines to inform the clinical practice around the use of sedative-hypnotics.

Challenges constraining availability and affordability of insulin in Bengaluru region (Karnataka, India): evidence from a mixed-methods study.

INTRODUCTION: Considering limited global access to affordable insulin, we evaluated insulin access in public and private health sectors in Bengaluru, India. METHODS: Employing modified WHO/HAI methodology, we used mixed-methods analysis to study insulin access and factors influencing insulin supply and demand in Bengaluru in December 2017. We assessed insulin availability, price and affordability in a representative sample of 5 public-sector hospitals, 5 private-sector hospitals and 30 retail pharmacies. We obtained insulin price data from websites of government Jan Aushadhi scheme (JAS) and four online private-sector retail pharmacies. We interviewed wholesalers in April 2018 to understand insulin market dynamics. RESULTS: Mean availability of insulins on India's 2015 Essential Medicine List was 66.7% in the public sector, lower than private-sector retail (76.1%) and hospital pharmacies (93.3%). Among private retailers, mean availability was higher among chain (96.7%) than independent pharmacies (68.3%). Non-Indian companies supplied 67.3% products in both sectors. 79.1% products were manufactured in India, of which 60% were marketed by non-Indian companies.In private retail pharmacies, median consumer prices of human insulin cartridges and pens were 2.5 and 3.6 times, respectively, that of human insulin vials. Analogues depending on delivery device were twice as expensive as human insulin. Human insulin vials were 18.3% less expensive in JAS pharmacies than private retail pharmacies. The lowest paid unskilled worker would pay 1.4 to 9.3 days' wages for a month's supply, depending on insulin type and health sector. Wholesaler interviews suggest that challenges constraining patient insulin access include limited market competition, physicians' preference for non-Indian insulins, and the ongoing transition from human to analogue insulin. Rising popularity of online and chain pharmacies may influence insulin access. CONCLUSION: Insulin availability in Bengaluru's public sector falls short of WHO's 80% target. Insulin remains unaffordable in both private and public sectors. To improve insulin availability and affordability, government should streamline insulin procurement and supply chains at different levels, mandate biosimilar prescribing, educate physicians to pursue evidence-based prescribing, and empower pharmacists with brand substitution. Patients must be encouraged to shop around for lower prices from subsidized schemes like JAS. While non-Indian companies dominate Bengaluru's insulin market, rising market competition from Indian companies may improve access.

Elevated levels of plasma symmetric dimethylarginine and increased arginase activity as potential indicators of cardiovascular comorbidity in rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) patients are at high risk of developing cardiovascular disease (CVD). In RA, chronic inflammation may lead to endothelial dysfunction, an early indicator of CVD, owing to diminished nitric oxide (NO) production. Because L-arginine is the sole precursor of NO, we hypothesized that levels of L-arginine metabolic products reflecting NO metabolism are altered in patients with RA. METHODS: Plasma samples from patients with RA (n = 119) and age- and sex-matched control subjects (n = 238) were used for this study. Using LC-MS/MS, we measured plasma levels of free L-arginine, L-ornithine, L-citrulline, L-NG-monomethyl arginine (MMA), asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA). We compared global arginine bioavailability ratio (GABR) (i.e., ratio of L-arginine to L-ornithine + L-citrulline) and arginine methylation index (ArgMI) (i.e., ADMA + SDMA/MMA) in patients with RA vs. control subjects. Plasma arginase activity was measured using a sensitive arginase assay kit. The relationship of L-arginine metabolites and arginase activity to CVD risk factors was evaluated using Pearson's chi-square test. RESULTS: Compared with healthy control subjects, the RA cohort showed significantly lower levels of plasma L-arginine (46.11 ± 17.29 vs. 74.2 ± 22.53 µmol/L, p < 0.001) and GABR (0.36 ± 0.16 vs. 0.73 ± 0.24, p < 0.001), elevated levels of ADMA (0.76 ± 0.12 vs. 0.62 ± 0.12 µmol/L, p < 0.001), SDMA (0.54 ± 0.14 vs. 0.47 ± 0.13 µmol/L, p < 0.001), and ArgMI (6.51 ± 1.86 vs. 5.54 ± 1.51, p < 0.001). We found an approximately fourfold increase in arginase activity (33.8 ± 1.1 vs. 8.4 ± 0.8 U/L, p < 0.001), as well as elevated levels of arginase-mediated L-arginine catalytic product L-ornithine (108.64 ± 30.26 vs. 69.3 ± 20.71 µmol/L, p < 0.001), whereas a nitric oxide synthase (NOS) catalytic product, the L-citrulline level, was diminished in RA (30.32 ± 9.93 vs. 36.17 ± 11.64 µmol/L, p < 0.001). Patients with RA with existing CVD had higher arginase activity than patients with RA without CVD (p = 0.048). CONCLUSIONS: Global L-arginine bioavailability was diminished, whereas plasma arginase activity, ADMA, and SDMA levels were elevated, in patients with RA compared with healthy control subjects. Plasma SDMA was associated with hypertension and hyperlipidemia in patients with RA. This dysregulated L-arginine metabolism may function as a potential indicator of CVD risk in patients with RA.

Evaluation of Supportive Care Management Outcomes in Cancer Chemotherapy: A Prospective Observational Study in a Tertiary Care Teaching Hospital in South India.

AIMS: Evaluation of supportive care management of cancer patients experiencing drug-related problems (DRPs) is a challenge because it might increase the cost due to additional therapy. The main objectives of this study were to estimate chemotherapy-associated drug-related hospital admissions in the department of medical oncology and to estimate the cost of managing chemotherapy-associated DRPs. SETTINGS AND DESIGN: This study is a prospective observational study. SUBJECTS AND METHODS: Patients with chemotherapy-related DRPs were prospectively identified from the patient's medical records. The contribution of DRPs and cost incurred due to each hospitalization was assessed. STATISTICAL ANALYSIS USED: Data were analyzed using SPSS® 20.0 version. RESULTS: Out of 55 patients analyzed for DRPs, 25 (45.5%) patients in the age group of 51-60 years experienced DRPs most frequently. Most commonly occurring DRP was adverse drug reactions 42 (76.4%), which were more frequent in females. DRPs were maximum with alkylating agents 15 (27.3%) and the least with hormonal agents 1 (1.8%). The mean length of hospitalization was 9.6 ± 6.5 days. The total direct medical cost was Rs. 31,540 ± 42,476, of which medicine cost accounted for Rs. 16,550 ± 25,404, constituting a major share of the total medical costs. CONCLUSIONS: Pharmacists can provide better patient care by identifying and preventing DRPs and reducing drug-related morbidity and mortality.

Topical heat shock protein 70 prevents imiquimod-induced psoriasis-like inflammation in mice.

Psoriasis is a chronic inflammatory skin disease with systemic manifestations and potential genetic etiology. The newest treatments utilize antibodies against one of several cytokines known to underlie the inflammatory signaling molecules that produce the skin and systemic symptoms. However, these agents must be regularly injected, and they may compromise the normal responses of the immune system. Furthermore, they do not address the causes of the abnormal immunoregulatory responses of the disease because the etiology is not yet completely understood. In this short-term treatment study, the potential anti-inflammatory activity of an alfalfa-derived Hsp70-containing skin cream (aHsp70) was tested on imiquimod (IMQ)-induced psoriasis-like lesions in wild-type mice. Treatment of the mice with the aHsp70 skin cream simultaneously with the imiquimod application mitigated the induction of psoriatic-like lesions and correlated with altered expression of various skin cytokines.

Atherosclerotic Carotid Plaques: Multimodality Imaging with Contrast-enhanced Ultrasound, Computed Tomography, and Magnetic Resonance Imaging.

INTRODUCTION: The imaging of carotid plaques has undergone a paradigm shift increasing importance being given to plaque characterization. Patients with "vulnerable" plaques are more prone to develop future neurovascular events. PURPOSE: The purpose of this study is to analyze the role of multimodality imaging techniques in the assessment of carotid atherosclerotic plaques. MATERIALS AND METHODS: Twenty-six patients were prospectively enrolled in the study. Patients underwent multidetector computed tomography (CT) angiography, ultrasound, contrast-enhanced ultrasound, and high-resolution magnetic resonance imaging (MRI) of the carotid arteries with special emphasis on the carotid bifurcation. RESULTS: The mean age of patients was 65.41 years. Twenty-one were males. Plaque neovascularization was seen in 10 of the 18 plaques studied (55.56%). Based on the predominant components of the plaque, plaques were characterized as lipid (3), lipid with recent hemorrhage (1), fibrous (7), fibrofatty (4), fibrofatty with some hemorrhagic components (3), and recent hemorrhage (2). CONCLUSIONS: Together, contrast-enhanced ultrasound, CT, and MRI provide complete information about the plaque characteristics.

PRMT5-Mediated Methylation of NF-κB p65 at Arg174 Is Required for Endothelial CXCL11 Gene Induction in Response to TNF-α and IFN-γ Costimulation.

Inflammatory agonists differentially activate gene expression of the chemokine family of proteins in endothelial cells (EC). TNF is a weak inducer of the chemokine CXCL11, while TNF and IFN-γ costimulation results in potent CXCL11 induction. The molecular mechanisms underlying TNF plus IFN-γ-mediated CXCL11 induction are not fully understood. We have previously reported that the protein arginine methyltransferase PRMT5 catalyzes symmetrical dimethylation of the NF-κB subunit p65 in EC at multiple arginine residues. Methylation of Arg30 and Arg35 on p65 is critical for TNF induction of CXCL10 in EC. Here we show that PRMT5-mediated methylation of p65 at Arg174 is required for induction of CXCL11 when EC are costimulated with TNF and IFN-γ. Knockdown of PRMT5 by RNAi reduced CXCL11 mRNA and protein levels in costimulated cells. Reconstitution of p65 Arg174Ala or Arg174Lys mutants into EC that were depleted of endogenous p65 blunted TNF plus IFN-γ-mediated CXCL11 induction. Mass spectrometric analyses showed that p65 Arg174 arginine methylation is enhanced by TNF plus IFN-γ costimulation, and is catalyzed by PRMT5. Chromatin immunoprecipitation assays (ChIP) demonstrated that PRMT5 is necessary for p65 association with the CXCL11 promoter in response to TNF plus IFN-γ. Further, reconstitution of p65 Arg174Lys mutant in EC abrogated this p65 association with the CXCL11 promoter. Finally, ChIP and Re-ChIP assays revealed that symmetrical dimethylarginine-containing proteins complexed with the CXCL11 promoter were diminished in p65 Arg174Lys-reconstituted EC stimulated with TNF and IFN-γ. In total, these results indicate that PRMT5-mediated p65 methylation at Arg174 is essential for TNF plus IFN-γ-mediated CXCL11 gene induction. We therefore suggest that the use of recently developed small molecule inhibitors of PRMT5 may present a therapeutic approach to moderating chronic inflammatory pathologies.

Effectiveness of clinical pharmacist intervention on health-related quality of life in chronic obstructive pulmonary disorder patients - a randomized controlled study.

WHAT IS KNOWN AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD), a preventable and treatable disease, has been described as '10% medication and 90% education'. Extreme physician scarcity limits the implementation of quality healthcare delivery in India. We conducted this study to evaluate the effectiveness of clinical pharmacist intervention on health-related quality of life (HRQoL) in patients with COPD in an Indian tertiary care hospital. METHODS: An open-labelled randomized controlled study was conducted over a 3-year period, at Kasturba Medical College Hospital, Manipal, India, after obtaining institutional ethics clearance (IEC 88/2012). The study was registered with the Indian clinical trial registry (CTRI/2014/08/004848). Patients were randomly assigned to two groups (intervention group [IG] and control group [CG]) by envelope method. St. George's Respiratory Questionnaire (SGRQ) was used to assess the HRQoL. The pharmacist intervention laid emphasis on (i) importance of medication compliance, (ii) need for smoking cessation, (iii) simple exercise, (iv) proper use of inhaler devices and (v) need for timely follow-up by pulmonary medicine department. SGRQ assessment was repeated at 6, 12, 18 and 24 months. RESULTS: Of 328 patients with COPD screened during the study period (March 2012 to June 2013), 260 (79%) were recruited. Of these, 202 (78%) patients completed follow-up (98 in CG and 104 in IG). Both groups were matched for baseline, sociodemographics and clinical characteristics. SGRQ scores and its subscales (symptoms, activity and impact) improved significantly after the pharmacist intervention in IG at follow-up (P < 0·001). WHAT IS NEW AND CONCLUSION: Our randomized controlled study shows that pharmacist intervention improved the HRQoL of patients with COPD in India. The generalizability of our results requires exploration even within other settings in India. Nonetheless, our results provide support for a greater involvement of pharmacists in the care of patients with COPD.

Multi-target drugs to address multiple checkpoints in complex inflammatory pathologies: evolutionary cues for novel "first-in-class" anti-inflammatory drug candidates: a reviewer's perspective.

Inflammation is a complex, metabolically expensive process involving multiple signaling pathways and regulatory mechanisms which have evolved over evolutionary timescale. Addressing multiple targets of inflammation holistically, in moderation, is probably a more evolutionarily viable strategy, as compared to current therapy which addresses drug targets in isolation. Polypharmacology, addressing multiple targets, is commonly used in complex ailments, suggesting the superior safety and efficacy profile of multi-target (MT) drugs. Phenotypic drug discovery, which generated successful MT and first-in-class drugs in the past, is now re-emerging. A multi-pronged approach, which modulates the evolutionarily conserved, robust and pervasive cellular mechanisms of tissue repair, with AMPK at the helm, regulating the complex metabolic/immune/redox pathways underlying inflammation, is perhaps a more viable strategy than addressing single targets in isolation. Molecules that modulate multiple molecular mechanisms of inflammation in moderation (modulating TH cells toward the anti-inflammatory phenotype, activating AMPK, stimulating Nrf2 and inhibiting NFκB) might serve as a model for a novel Darwinian "first-in-class" therapeutic category that holistically addresses immune, redox and metabolic processes associated with inflammatory repair. Such a multimodal biological activity is supported by the fact that several non-calorific pleiotropic natural products with anti-inflammatory action have been incorporated into diet (chiefly guided by the adaptive development of olfacto-gustatory preferences over evolutionary timescales) rendering such molecules, endowed with evolutionarily privileged molecular scaffolds, naturally oriented toward multiple targets.

South-Asian population has a higher likelihood for diabetes risk for statins regardless of potency.

Higher potency statins are associated with increased risk of new-onset diabetes (NOD) in Western populations. South-Asians phenotype, with certain unique features such as young onset of diabetes and lower threshold for diabetes risk factors, present a higher likelihood for NOD risk for statins regardless of potency.

Impact of diabetic foot ulcer on health-related quality of life: A cross-sectional study.

Studies have reported that health-related quality of life (HRQoL) is adversely affected by diabetic foot ulcer (DFU). There is a paucity of data on the effects of foot ulcers on HRQoL of diabetes patients in our population. Because South-Asians, especially Indians, have unique features related to diabetes and its complications, generalizing the data about their effect on HRQoL from any other part of the world is not a pragmatic approach. This study evaluated the impact of foot ulcers on HRQoL of diabetes patients. This cross-sectional study, conducted in Kasturba Hospital, Manipal (coastal South India), included 200 DFU patients in a study group (SG) and 200 diabetes patients in a control group (CG). The RAND-36 questionnaire was employed for evaluating HRQoL scores for the patients in both groups. DFU patients also completed the Diabetic Foot Ulcer Scale-Short Form questionnaire. Independent t-test was used to test the differences in mean scores. Results found that both CG and SG have "poor" HRQoL (mean score <50) on all the subscales except for two in CG. There is a statistically significant difference between groups (P < 0.05) on all eight of the subscales of HRQoL. For both CG and SG, the Physical Component Summary domain score (44.9 ± 6.3 v 28.4 ± 3.4) and Mental Component Summary domain score (42.5 ± 3.8 v 29.5 ± 7.1) were poor. There were significant differences between CG and SG for both mean Physical Component Summary score and Mental Component Summary score of HRQoL (p < 0.05). The Diabetic Foot Ulcer Scale-Short Form found that HRQoL is very poor for DFU patients on all six domains. The study concludes that DFU patients have very poor HRQoL compared with diabetic patients. Likewise, the diabetic foot is associated with severely impaired HRQoL in both physical and mental health aspects. This study will help to develop a patient education model for DFU patients by looking at the various HRQoL domains that are adversely affected by the presence of foot ulcer.

Sexual violence in India: addressing gaps between policy and implementation.

The savage Delhi rape of 16 December 2012 was instrumental in generating the Verma Report that framed policies for amending the Criminal Laws related to sexual violence, professionalizing forensic/medical examination of victims, and sensitizing the police, electorate and the educational sectors. Unfortunately, even after a year, the Indian Home Ministry has abysmally failed to implement most recommendations, even underutilizing budgetary allocations. This article addresses gaps in governance systems and offers solutions to the problem of sexual violence in India.