Development of evidence-based indicators for the detection of drug-related problems among ovarian cancer patients.

Background: Antineoplastic drugs produce serious drug-related problems and their management is challenging. DRPs are critical, for saving on therapeutic costs, particularly in resource poor settings within low-middle-income countries such as India. Indicators are clues that helps to detect DRPs within the healthcare organization and minimize overall harm from medications. Indicators enable healthcare professionals to determine the future therapeutic course. And enable healthcare professionals to take a proactive stand, and stay informed and empowered to both prevent and manage DRPs. This study aims to develop evidence-based indicators for detecting potential drug-related problems in ovarian cancer patients. Patients and Methods: A retrospective study was conducted in the Department of Oncology of a tertiary care teaching hospital in South India. Based on literature search, we developed a list of indicators, which were validated by a Delphi panel of multidisciplinary healthcare professionals (16 members). Based on 2 years of ovarian cancer data, we performed a feasibility test retrospectively and classified the DRPs according to the Pharmaceutical Care Network Europe classification of DRPs version-9.1. Results: The feasibility test identified 130 out of 200 indicators. A total of 803 pDRPs were identified under four main categories: drug selection problem, drug use problem, adverse drug reaction and drug-drug interaction The most frequently observed were ADR 381 (47.45%), DDIs 354 (44.08%), and drug selection problems 62 (7.72%). Conclusion: Indicators developed by us effectively identified pDRPs in ovarian cancer patients, which can potentially help healthcare professionals in the early detection, timely management, and attenuating severity of DRPs. Identifying the pDDIs can potentially improve interdisciplinary involvement and task sharing, including enhanced pharmacists' participation within the healthcare team.

A Systematic Review on Sociodemographic, Financial and Psychological Factors Associated with COVID-19 Vaccine Booster Hesitancy among Adult Population.

BACKGROUND: While considerable evidence supports the safety and efficacy of COVID-19 vaccines, a sizable population expresses vaccine hesitancy. As per the World Health Organization, vaccine hesitancy is one of the top 10 hazards to global health. Vaccine hesitancy varies across countries, with India reporting the least vaccine hesitancy. Vaccine hesitancy was higher toward COVID-19 booster doses than previous shots. Therefore, identifying factors determining COVID-19 vaccine booster hesitance (VBH) is the sine qua non of a successful vaccination campaign. METHODOLOGY: This systematic review followed Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) 2020 standards. A total of 982 articles were pooled from Scopus, PubMed and Embase, while 42 articles that addressed the factors of COVID-19 VBH were finally included for further analysis. RESULT: We identified factors responsible for VBH and divided them into three major groups: sociodemographic, financial, and psychological. Hence, 17 articles stated age to be a major factor for vaccine hesitancy, with most reports suggesting a negative correlation between age and fear of poor vaccination outcomes. Nine studies found females expressing greater vaccine hesitancy than males. Trust deficit in science (n = 14), concerns about safety and efficacy (n = 12), lower levels of fear regarding infection (n = 11), and worry about side effects (n = 8) were also reasons for vaccine hesitancy. Blacks, Democrats, and pregnant women showed high vaccine hesitancy. Few studies have stated income, obesity, social media, and the population living with vulnerable members as factors influencing vaccine hesitancy. A study in India showed that 44.1% of vaccine hesitancy towards booster doses could be attributed dominantly to low income, rural origin, previously unvaccinated status, or living with vulnerable individuals. However, two other Indian studies reported a lack of availability of vaccination slots, a lack of trust in the government, and concerns regarding safety as factors for vaccine hesitancy toward booster doses. CONCLUSION: Many studies have confirmed the multifactorial nature of VBH, which necessitates multifaceted, individually tailored interventions that address all potentially modifiable factors. This systematic review chiefly recommends strategizing the campaign for booster doses by identifying and evaluating the reasons for vaccine hesitancy, followed by appropriate communication (at both individual and community levels) about the benefits of booster doses and the risk of losing immunity without them.

Vitamin D attenuates biofilm-associated infections via immunomodulation and cathelicidin expression: a narrative review.

INTRODUCTION: Infections are becoming more difficult to treat, at least partly on account of microbes that produce biofilms. Reports suggest that decreased levels of antimicrobial peptides like cathelicidin, elevated levels of inflammatory cytokines, and biofilm formation are all associated with vitamin D deficiency, making vitamin D - deficient individuals more susceptible to infection. Infections attributable to biofilm-producing microbes can be managed by adjuvant therapy with vitamin D because of its immunomodulatory role, particularly because of the ability of vitamin D-pathway to induce the antimicrobial peptides like cathelicidin and decrease proinflammatory cytokines. AREAS COVERED: This narrative review covers biofilm formation, infections associated with biofilm due to vitamin D deficiency, putative role of vitamin D in host protection and the effect of vitamin D supplementation in biofilm-associated infections. A comprehensive literature search in PubMed and Google Scholar utilizing suitable keywords at multiple time points extracted relevant articles. EXPERT OPINION: Although vitamin D deficiency has been associated with infections by biofilm producing microbes, comprehensive clinical trials in various ethnicities are required to understand the likely relationships between vitamin D receptor gene expression, cathelicidin levels, and infection outcome. Current evidence hypothesizes that maintaining normal vitamin D level can help prevent and treat these infections.

Computational investigations of indanedione and indanone derivatives in drug discovery: Indanone derivatives inhibits cereblon, an E3 ubiquitin ligase component.

BACKGROUND: Cereblon, an extensively studied multifunctional protein, is a Cullin 4-RING E3 ubiquitin ligase complex component. Cereblon is a well-known target of thalidomide and its derivatives. Cereblon is involved in multiple myeloma cell apoptosis. When ligands such as thalidomide and lenalidomide bind to cereblon, it recognizes various neosubstrates based on the ligand shape and properties. We have identified novel CRBN inhibitors, namely DHFO and its analogs, with structural features that are slightly different from thalidomide but stronger cereblon-binding affinity. We selected indanedione and indanone derivatives from the literature to understand and compare their cereblon-mediated substrate recognition potential. METHODS: Computational investigations of possible CRBN inhibitors were investigated by molecular docking with Autodock Vina and DockThor programs. The properties of the compounds' ADME/T and drug-likeness were investigated. A molecular dynamics study was carried out for four selected molecules, and the molecular interactions were analyzed using PCA-based FEL methods. The binding affinity was calculated using the MM/PBSA method. RESULTS: We conducted computational investigations on 68 indanedione and indanone derivatives binding with cereblon. Ten molecules showed better CRBN binding affinity than thalidomide. We studied the drug-likeness properties of the selected ten molecules, and four of the most promising molecules (DHFO, THOH, DIMS, and DTIN) were chosen for molecular dynamics studies. The MM/PBSA calculations showed that the DHFO, already shown to be a 5-LOX/COX2 inhibitor, has the highest binding affinity of - 163.16 kJ/mol with cereblon. CONCLUSION: The selected CRBN inhibitor DHFO has demonstrated the highest binding affinity with cereblon protein compared to other molecules. Thalidomide and its derivatives have a new substitute in the form of DHFO, which produces an interaction hotspot on the surface of the cereblon. Ease of chemical synthesis, low toxicity, versatile therapeutic options, and pleiotropism of DHFO analogs provide an opportunity for exploring clinical alternatives with versatile therapeutic potential for a new category of indanedione molecules as novel modulators of E3 ubiquitin ligases.

Critical role of nitric oxide in impeding COVID-19 transmission and prevention: a promising possibility.

COVID-19 is a serious respiratory infection caused by a beta-coronavirus that is closely linked to SARS. Hypoxemia is a symptom of infection, which is accompanied by acute respiratory distress syndrome (ARDS). Augmenting supplementary oxygen may not always improve oxygen saturation; reversing hypoxemia in COVID-19 necessitates sophisticated means to promote oxygen transfer from alveoli to blood. Inhaled nitric oxide (iNO) has been shown to inhibit the multiplication of the respiratory coronavirus, a property that distinguishes it from other vasodilators. These findings imply that NO may have a crucial role in the therapy of COVID-19, indicating research into optimal methods to restore pulmonary physiology. According to clinical and experimental data, NO is a selective vasodilator proven to restore oxygenation by helping to normalize shunts and ventilation/perfusion mismatches. This study examines the role of NO in COVID-19 in terms of its specific physiological and biochemical properties, as well as the possibility of using inhaled NO as a standard therapy. We have also discussed how NO could be used to prevent and cure COVID-19, in addition to the limitations of NO.

Is the antiseizure effect of ketogenic diet in children with drug-resistant epilepsy mediated through proinflammatory cytokines?

In order to understand whether the antiseizure mechanism of ketogenic diet (KD) is mediated through its anti-inflammatory effect, we measured the serum concentrations of cytokines IL- 1ß and IL-6 in 21 children with drug-resistant epilepsy. We found a significant reduction in the levels of serum IL- 1ß and IL-6 levels at one-year of KD therapy compared to baseline. However, we did not find any correlation between decrease in the serum concentrations of these interleukins with the reduction in seizure frequency at one-year of KD therapy, which may be due to the small sample size and heterogeneous patient population we studied. Future studies should try to overcome these limitations.

Probiotics in Prevention and Treatment of COVID-19: Current Perspective and Future Prospects.

Saving lives and flattening the curve are the foremost priorities during the ongoing pandemic spread of SARS-CoV-2. Developing cutting-edge technology and collating available evidence would support frontline health teams. Nutritional adequacy improves general health and immunity to prevent and assuage infections. This review aims to outline the potential role of probiotics in fighting the COVID-19 by covering recent evidence on the association between microbiota, probiotics, and COVID-19, the role of probiotics as an immune-modulator and antiviral agent. The high basic reproduction number (R0) of SARS-CoV-2, absence of conclusive remedies, and the pleiotropic effect of probiotics in fighting influenza and other coronaviruses together favour probiotics supplements. However, further support from preclinical and clinical studies and reviews outlining the role of probiotics in COVID-19 are critical. Results are awaited from many ongoing clinical trials investigating the benefits of probiotics in COVID-19.

Vitamin D in Prevention and Treatment of COVID-19: Current Perspective and Future Prospects.

Vitamin D deficiency (VDD) partly explains geographical differences in COVID-19 susceptibility, severity, and mortality. VDD among African-Americans, diabetics, hypertensive, and aged populations possibly explain the higher death rate, aggravated by cocooning. Vitamin D is pleiotropic, mediating bone metabolism, calcium homeostasis, and immune functions, whereas VDD is associated with inflammatory reactions and immune dysfunction, predisposing individuals to severe infections. Vitamin D modulates innate and adaptive immunity via the expression of genes that code antimicrobial peptides (AMPs). And the expression of cluster of differentiation (CD)14, the co-receptor for epidermal toll-like receptor (TLR)4. AMPs stimulate TLR2 in macrophages, increasing the conversion of vitamin D into its active form by cytochrome P450 27B1. Antiviral properties of vitamin D-induced AMPs can shift the polarization of the adaptive immune response from helper T cells (Th)1 to the more regulatory Th2 responses that suppress immune over-reactivity by preventing cytokine storm, which is already demonstrated during the Spanish flu episode. Vitamin D induces antiviral effects by both direct and indirect mechanisms via AMPs, immunomodulation, the interplay between major cellular and viral elements, induction of autophagy and apoptosis, variation of genetic and epigenetic factors. The crosstalk between vitamin D and intracellular signaling pathways may operate as a primary regulatory action on viral gene transcription. VDD may increase the likelihood of infection with enveloped viruses, including retrovirus, hepatitis, and dengue. Global data correlates severe VDD with COVID-19 associated coagulopathy, disrupted immune response and mortality, reduced platelet count, and prolonged prothrombin time, suggesting benefits from supplementation.Key teaching pointsVitamin D induces antiviral effects by direct and indirect mechanisms via AMPs, immunomodulation, induction of autophagy, etc.Epidemiology of VDD partly explains geographical differences in COVID-19 susceptibility, severity, and mortality.Global data correlates severe VDD with COVID-19 associated coagulopathy, disrupted immune response and mortality, reduced platelet count, and prolonged prothrombin time, together suggesting benefits from supplementation.Many clinical trials are underway globally to delineate the role of vitamin D in both prevention and treatment of COVID-19.

An Agathokakological Tale of Δ9-THC: Exploration of Possible Biological Targets.

Δ9-Tetrahydrocannabinol (Δ9-THC), the active phytocannabinoid in cannabis, is virtually an adjunct to the endogenous endocannabinoid signaling system. By interacting with G-proteincoupled receptors CB1 and CB2, Δ9-THC affects peripheral and central circulation by lowering sympathetic activity, altering gene expression, cell proliferation, and differentiation, decreasing leukocyte migration, modulating neurotransmitter release, thereby modulating cardiovascular functioning, tumorigenesis, immune responses, behavioral and locomotory activities. Δ9-THC effectively suppresses chemotherapy-induced vomiting, retards malignant tumor growth, inhibits metastasis, and promotes apoptosis. Other mechanisms involved are targeting cell cycle at the G2-M phase in human breast cancer, downregulation of E2F transcription factor 1 (E2F1) in human glioblastoma multiforme, and stimulation of ER stress-induced autophagy. Δ9-THC also plays a role in ameliorating neuroinflammation, excitotoxicity, neuroplasticity, trauma, and stroke and is associated with reliving childhood epilepsy, brain trauma, and neurodegenerative diseases. Δ9-THC via CB1 receptors affects nociception, emotion, memory, and reduces neuronal excitability and excitotoxicity in epilepsy. It also increases renal blood flow, reduces intraocular pressure via a sympathetic pathway, and modulates hormonal release, thereby decreasing the reproductive function and increasing glucose metabolism. Versatile medical marijuana has stimulated abundant research demonstrating substantial therapeutic promise, suggesting the possibilities of first-in-class drugs in diverse therapeutic segments. This review represents the current pharmacological status of the phytocannabinoid, Δ9-THC, and synthetic analogs in cancer, cardiovascular, and neurodegenerative disorders.

Revisiting the blood-brain barrier: A hard nut to crack in the transportation of drug molecules.

Barriers are the hallmark of a healthy physiology, blood-brain barrier (BBB) being a tough nut to crack for most of the antigens and chemical substances. The presence of tight junctions plays a remarkable role in defending the brain from antigenic and pathogenic attacks. BBB constitutes a diverse assemblage of multiple physical and chemical barriers that judiciously restrict the flux of blood solutes into and out of the brain. Restrictions through the paracellular pathway and the tight junctions between intercellular clefts, together create well regulated metabolic and transport barricades, critical to brain pathophysiology. The brain being impermeable to many essential metabolites and nutrients regulates transportation via specialized transport systems across the endothelial abluminal and luminal membranes. The epithelial cells enveloping capillaries of the choroid plexus regulates the transport of complement, growth factors, hormones, microelements, peptides and trace elements into ventricles. Nerve terminals, microglia, and pericytes associated with the endothelium support barrier induction and function, ensuring an optimally stable ionic microenvironment that facilitates neurotransmission, orchestrated by multiple ion channels (Na+, K+ Mg2+, Ca2+) and transporters. Brain pathology which can develop due to genetic mutations or secondary to other cerebrovascular, neurodegenerative diseases can cause aberration in the microvasculature of CNS which is the uniqueness of BBB. This can also alter BBB permeation and result in BBB breakdown and other neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. The concluding section outlines contemporary trends in drug discovery, focusing on molecular determinants of BBB permeation and novel drug-delivery systems, such as dendrimers, liposomes, nanoparticles, nanogels, etc.

Impact of a Clinical Pharmacist Intervention on Medicine Costs in Patients with Chronic Obstructive Pulmonary Disease in India.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality, especially in low- and middle-income countries (LMICs) such as India. Medicine costs are a key issue in LMICs, with typically high patient co-payments. In addition, pharmacists are underutilised in LMICs, including India. However, pharmacist-led educational interventions may improve the care of patients with COPD, as well as reduce medicine costs. Consequently, the objective of this study was to assess the effectiveness of a pharmacist-led intervention in reducing medicine costs. METHODOLOGY: We assessed the impact of a pharmacist intervention on direct medicine costs in COPD patients (medicine costs and pharmacist time) in a randomised controlled study involving an intervention and control group, conducted at a tertiary care teaching hospital in India. RESULTS: The 6-monthly cost of medicines at baseline increased with disease severity, from a maximum of US$29.46 for those with mild COPD to US$63.28 for those with very severe COPD. Substantial savings in medical costs were achieved with the pharmacist-led programme, to a maximum of US$20.49 over 6 months for very severe patients. This equates to a reduction of 30.6% in medicine costs (p < 0.001), reduced to 26.1% when pharmacists' time (US$3.00/patient) was included. CONCLUSION: There could be a key role for pharmacists as educators for COPD patients in LMICs, to improve care and reduce costs, including patient co-payments.

Pharmacotherapeutic interventions for bipolar disorder type II: addressing multiple symptoms and approaches with a particular emphasis on strategies in lower and middle-income countries.

Introduction: Appropriately managing mental disorders is a growing priority across countries in view of the impact on morbidity and mortality. This includes patients with bipolar disorders (BD). Management of BD is a concern as this is a complex disease with often misdiagnosis, which is a major issue in lower and middle-income countries (LMICs) with typically a limited number of trained personnel and resources. This needs to be addressed.Areas covered: Medicines are the cornerstone of managing patients with Bipolar II across countries including LMICs. The choice of medicines, especially antipsychotics, is important in LMICs with high rates of diabetes and HIV. However, care is currently compromised in LMICs by issues such as the stigma, cultural beliefs, a limited number of trained professionals and high patient co-payments.Expert opinion: Encouragingly, some LMICs have introduced guidelines for patients with BD; however, this is very variable. Strategies for the future include addressing the lack of national guidelines for patients with BD, improving resources for mental disorders including personnel, improving medicine availability and patients' rights, and monitoring prescribing against agreed guidelines. A number of strategies have been identified to improve the treatment of patients with Bipolar II in LMICs, and will be followed up.

Emerging therapeutic potentials of dual-acting MAO and AChE inhibitors in Alzheimer's and Parkinson's diseases.

No drug has been approved to prevent neuronal cell loss in patients suffering from Parkinson's disease (PD) or Alzheimer's disease (AD); despite increased comprehension of the underlying molecular causes, therapies target cognitive functional improvement and motor fluctuation control. Drug design strategies that adopt the "one protein, one target" philosophy fail to address the multifactorial aetiologies of neurodegenerative disorders such as AD and PD optimally. On the contrary, restoring neurotransmitter levels by combined combinatorial inhibition of cholinesterases, monoamine oxidases, and adenosine A2A A receptors, in conjunction with strategies to counter oxidative stress and beta-amyloid plaque accumulation, would constitute a therapeutically robust, multitarget approach. This extensive review delineates the therapeutic advantages of combining dual-acting molecules that inhibit monoamine oxidases and cholinesterases and/or adenosine A2A A receptors, and describes the structure-activity relationships of compound classes that include, but are not limited to, alkaloids, coumarins, chalcones, donepezil-propargylamine conjugates, homoisoflavonoids, resveratrol analogs, hydrazones, and pyrazolines. In the wake of recent advances in network biology, in silico approaches, and omics, this review emphasizes the need to consider conceptually informed research strategies for drug discovery, in the context of the mounting burden posed by chronic neurodegenerative diseases with complex aetiologies and pathophysiologies involving multiple signalling pathways and numerous drug targets.

Evolution of dietary preferences and the innate urge to heal: Drug discovery lessons from Ayurveda.

Highly specialized and functionally integrated cognitive systems facilitate hedonistic and healthy food preferences. Guided by survival needs, flavor preferences not only select safe, nutritious dietary components, but also those with negligible calorific value but significant health benefits, for example, spices. Feeding behavior, both innate and acquired, is guided not only by taste receptors on the tongue but also visceral organs. The gustatory cortex receives information from all senses, not just taste, suggesting multiple checkpoints in predicting and evaluating healthy foods. Ayurvedic interpretation of 'rasa' as chemistry is compatible with medicinal value of diets because, taste and odor are chemosensory perceptions. As flavor and taste are linked to the chemical structure of compounds, taste might offer clues about pharmacological activity. Ayurvedic idea of vipaka, or post digestive perception of taste, recognizes the extended role of taste receptors beyond the tongue and stretching into the viscera. Ayurvedic wisdom is consistent with evolutionary guideposts that suggest three successive stages of nutritional appraisal: before, during, and after ingesting food. While olfaction induces affinity or revulsion even before ingestion, gustatory receptors on the tongue evaluates nutritional value upon contact, and the chemoreceptors in the deeper metabolic systems probably pronounce the final verdict on the nutritive and health benefits of ingested substances. Alliesthesia, neophobia, and the extreme variation in human T2R genes (coding for bitterness receptors) illustrate the importance of adaptive learning of dietary preferences. These evolutionary clues are compatible with the Ayurvedic principle of 'rasa', in facilitating the process of drug discovery.

Structured pharmacist-led intervention programme to improve medication adherence in COPD patients: A randomized controlled study.

BACKGROUND: COPD is characterised by a progressive airflow limitation in the lungs. However, adherence to therapy improves management of symptoms and delays disease progression. Therefore, patients' knowledge and awareness about the disease are important. Hence, pharmacist-led educational interventions could achieve this and improve medication adherence. OBJECTIVE: This study evaluated the effectiveness of a clinical pharmacist-led intervention on medication adherence in COPD patients in a teaching hospital. METHODS: In an open-labelled randomized controlled study at Kasturba Medical College Hospital, Manipal, India, patients were randomly assigned to two groups (Intervention group [IG] and Control group [CG]), and were matched for socio-demographics and clinical characteristics. Medication adherence was assessed by the Morisky, Green and Levine Medication Adherence Questionnaire (MAQ). In IG, pharmacist intervention placed emphasis on (1) compliance, (2) smoking cessation, (3) exercise, (4) inhaler use and (5) need for timely follow up. The MAQ assessment was repeated at 6, 12, 18 and 24 months. Data were analysed statistically by SPSS version 20.0. RESULTS: Out of 328 patients screened during March 2012 to June 2013, 260 were recruited. Of these, 206 completed the follow-up (98 in CG and 104 in IG). Medication adherence improved significantly after pharmacist intervention in IG at all follow-up time points (P < 0.001). It increased from 49% at the baseline to 80% after 24 months (P < 0.001). Carelessness about taking medicines was one of the main reasons for non-adherence in COPD patients, but was effectively reduced by the intervention. CONCLUSIONS: This is the first randomized controlled trial in India that demonstrates the pivotal role of pharmacist-led educational intervention in improving medication adherence in COPD. Involving non-physician health professionals could be the best strategy, for resource-poor nations like India, because the current physician-centric healthcare has no emphasis on patient education and counselling.

Protective effect of metformin against tuberculosis infections in diabetic patients: an observational study of south Indian tertiary healthcare facility

ABSTRACT Background: World Health Organization estimated that people with diabetes (DM) are at 2-3 times higher risk for tuberculosis (TB). Studies have shown that DM not only increases the risk of active TB, but also puts co-affected persons at increased risk of poor outcomes. Objectives: To determine the protective effect of metformin against TB in DM patients and also, to investigate the relationship between poor glycemic control and TB. Methods: A case-control study was conducted over 8 months, where cases and controls were selected based on the inclusion and exclusion criteria of the study. The diabetics diagnosed with TB were selected as study group (SG = 152) and without TB were as control group (CG = 299). Exposure status of metformin in both groups were analyzed. Results: The mean (SD) age of both CG and SG were 55.54 ± 11.82 and 52.80 ± 11.75, respectively. Majority of the subjects in the study were males. The mean hospital stay of SG and CG were 7 days and 6 days, respectively. Poor glycemic control (HbA1c > 8) observed in SG (51.7%) vs CG (31.4%). HbA1c value <7 is associated protective factor for TB occurrence [OR = 0.52 (95% CI 0.29-0.93)]. The protective effect of metformin against TB was 3.9-fold in diabetics (OR = 0.256, 0.16-0.40). Conclusion: Poor glycemic control among diabetics is a risk factor for TB occurrence. The result shows metformin use is a protective agent against TB infection in diabetics. Hence, incorporation of metformin into standard clinical care would offer a therapeutic option for the prevention of TB.

Protective effect of metformin against tuberculosis infections in diabetic patients: an observational study of south Indian tertiary healthcare facility.

BACKGROUND: World Health Organization estimated that people with diabetes (DM) are at 2-3 times higher risk for tuberculosis (TB). Studies have shown that DM not only increases the risk of active TB, but also puts co-affected persons at increased risk of poor outcomes. OBJECTIVES: To determine the protective effect of metformin against TB in DM patients and also, to investigate the relationship between poor glycemic control and TB. METHODS: A case-control study was conducted over 8 months, where cases and controls were selected based on the inclusion and exclusion criteria of the study. The diabetics diagnosed with TB were selected as study group (SG=152) and without TB were as control group (CG=299). Exposure status of metformin in both groups were analyzed. RESULTS: The mean (SD) age of both CG and SG were 55.54±11.82 and 52.80±11.75, respectively. Majority of the subjects in the study were males. The mean hospital stay of SG and CG were 7 days and 6 days, respectively. Poor glycemic control (HbA1c>8) observed in SG (51.7%) vs CG (31.4%). HbA1c value <7 is associated protective factor for TB occurrence [OR=0.52 (95% CI 0.29-0.93)]. The protective effect of metformin against TB was 3.9-fold in diabetics (OR=0.256, 0.16-0.40). CONCLUSION: Poor glycemic control among diabetics is a risk factor for TB occurrence. The result shows metformin use is a protective agent against TB infection in diabetics. Hence, incorporation of metformin into standard clinical care would offer a therapeutic option for the prevention of TB.

Efficacy and safety of empagliflozin in type 2 diabetes mellitus: a meta-analysis of randomized controlled trials.

OBJECTIVES: The prevalence of diabetes has increased in the recent decades and optimum glycemic control is required to reduce morbidity and mortality. We meta-analyzed randomized controlled trials in order to assess the efficacy and safety of empagliflozin compared to placebo in type 2 diabetes mellitus patients. METHODS: We included double-blind, placebo controlled trials of empagliflozin that evaluated glycemic efficacy and safety (10 mg or 25 mg) either as monotherapy or as add-on to existing diabetes pharmacotherapy. RESULTS: The results demonstrated significant improvements in HbA1c (SMD -0.929%, 95 % CI -1.064 to -0.793, for 10 mg and -1.064%, 95 % CI -1.184 to -0.944, for 25 mg) and FPG (SMD -0.929%, 95 % CI -1.064 to -0.793, for 10 mg and -1.064%, 95 % CI -1.184 to -0.944, for 25 mg) with empagliflozin monotherapy (n = 609) compared to placebo. Significant improvements in HbA1c [SMD -1.582%, 95% CI -2.164 to -1.000, for 10 mg (n = 1079) and -1.668%, 95% CI -2.260 to -1.077, for 25 mg (n = 1070)] and FPG [SMD -0.865 mmol/L, 95 % CI -1.309 to -0.420, for 10 mg (n = 854) and -0.996 mmol/L, 95% CI -1.456 to -0.536, for 25 mg (n = 854)] were also observed in empagliflozin add-on therapy trials. Reductions in blood pressure and body weight were also seen in both monotherapy and add-on therapy. Empagliflozin was associated with increased risk of hypoglycemia, genital and urinary tract infections (OR 1.043, 2.814, 1.119 respectively). CONCLUSION: This meta-analysis shows empagliflozin is safe and effective for the treatment of T2DM along with existing diabetes pharmacotherapy.