Susceptibility Pattern of Doxycycline in Comparison to Azithromycin, Cefuroxime and Amoxicillin against Common Isolates: A Retrospective Study Based on Diagnostic Laboratory Data.

INTRODUCTION: Doxycycline acts against a broad range of gram-positive, gramnegative and 'atypical' bacteria as well as some protozoan pathogens such as malaria. In this era of increasing multidrug-resistance, recycling of old antimicrobials should be considered and need more focus in this domain of research. We, therefore, aimed to assess the antimicrobial susceptibility patterns of commonly isolated pathogens against doxycycline, azithromycin, cefuroxime, and amoxicillin from common clinical specimens by using laboratory-based diagnostic data from western India. MATERIALS AND METHODS: The non-interventional retrospective study was conducted on secondary data extracted from multi-center diagnostic laboratory based in Mumbai, India. Susceptibility data of bacteria isolated from blood, urine, pus, and sputum were used in the study and culture positive samples were segregated. Antimicrobial susceptibility status of doxycycline was checked and compared with azithromycin, cefuroxime, and amoxicillin. Chi-square tests of significance were carried out to assess significant differences in susceptibility patterns. Association between variables was considered statistically significant if the p-value was <0.05. RESULTS: Percentage susceptibility of collective bacterial isolates was found to be highest for doxycycline in all four specimens (93.1%). Individual percentage susceptibility was observed to be highest for sputum isolates (97.5%) followed by blood (93.8%), pus (92.7%) and urine (70.0%). The activity of doxycycline was found to be 93.5% for the samples resistant to azithromycin. Doxycycline also showed good susceptibility for the isolates resistant to amoxicillin and cefuroxime which was 75.9% and 64.8%, respectively. CONCLUSION: Several bacterial isolates from all four sources were found to be susceptible to Doxycycline. It has an important role in the form of a better alternative of major antimicrobial agents like azithromycin, cefuroxime, and amoxicillin against gram-positive cocci. Doxycycline appeared to show better activity against isolates which were resistant to other three antimicrobials.

Approaches in Managing Resistant Hypertension: A Review.

In India, around 234 million adults (one in three) suffer from hypertension (HTN). An average of 10% of these cases are likely to be resistant hypertension (RH). This load of 23 million patients is expected to expand further with revisions in diagnostic criteria. The treatment and control rates of hypertension in India average around 30% and 15%, respectively. Pharmacological management involves a stepwise approach starting with optimizing the A-C-D (angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), and thiazide-like diuretics) triple-drug combination, followed by substitution with a thiazide-like diuretic and use of spironolactone as a next step (fourth drug). The subsequent steps are suggestions based on expert input and must be individualized. These include using a ß-blocker as the fifth drug and an α1-blocker or a peripheral vasodilator as a final option when target blood pressure (BP) values are not achieved. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are likely to be helpful in managing RH due to their renal and cardiovascular protection as well as mortality benefits. SGLT2i lowers BP independent of the dosage and concomitant anti-hypertensive medications. Patient education and tools to monitor BP and treatment compliance will improve outcomes with these medications. In addition to therapeutic intervention, a preventive approach for RH mandates a need to identify patients at risk and use appropriate preventive and optimal therapy to prevent uncontrolled hypertension in patients with cardiovascular disorders.

Management of Heart Failure in a Resource-Limited Setting: Expert Opinion from India.

Heart failure poses a global health challenge affecting millions of individuals, and access to guideline-directed medical therapy is often limited. This limitation is frequently attributed to factors such as drug availability, slow adoption, clinical inertia, and delayed diagnosis. Despite international recommendations promoting the use of guideline-directed medical therapy for heart failure management, personalized approaches are essential in settings with resource constraints. In India, crucial treatments like angiotensin II receptor blocker neprilysin inhibitors and sodium-glucose co-transporter 2 inhibitors are not fully utilized despite their established safety and efficacy. To address this issue, an expert consensus involving 150 specialists, including cardiologists, nephrologists, and endocrinologists, was convened. They deliberated on patient profiles, monitoring, and adverse side effects and provided tailored recommendations for guideline-directed medical therapy in heart failure management. Stressing the significance of early initiation of guideline-directed medical therapy in patients with heart failure, especially with sodium-glucose co-transporter 2 inhibitors, the consensus also explored innovative therapies like vericiguat. To improve heart failure outcomes in resource-limited settings, the experts proposed several measures, including enhanced patient education, cardiac rehabilitation, improved drug access, and reforms in healthcare policies.

Electronic medical records-based retrospective, longitudinal, observational study to understand the patient management of benign prostatic hyperplasia with alpha-blockers monotherapy in Indian population.

Objective: The present retrospective study evaluates the effectiveness and tolerability of alpha-blockers as monotherapy in patients with benign prostatic hyperplasia associated with lower urinary tract symptoms (LUTS). Materials and Methods: A total of 335 male patients >50 years were categorized into four groups (Alfuzosin: 166, Silodosin: 67, Tamsulosin: 70, Prazosin: 32). The efficacy evaluated as a change in International Prostate Symptom Score (IPSS), peak flow rate (Qmax), residual urine volume, and relief from LUTS, and tolerability of the various alpha-blockers was assessed across the study group. Results: At baseline, most of the patients in alfuzosin (60%), silodosin (77%), and tamsulosin (90%) groups presented with severe IPSS (20-35), whereas patients in the prazosin group (69%) presented with a moderate score. At the end of the study, the mean IPSS gradually improved to moderate (41%, 62%, 66%, and 28%) and mild (59%, 38%, 28%, and 72%) in the alfuzosin, silodosin, tamsulosin, and prazosin groups, respectively (P = 0.004), with improvement in mean change in residual urine volume and complete relief from LUTS symptoms with no surgical or radiological interventions. Overall, 194 adverse events (AEs) were observed in 38.8% of patients. Of the total AEs, patients in the alfuzosin, silodosin, tamsulosin, and prazosin groups experienced 21%, 22%, 39%, and 18% of AEs, respectively. Conclusion: The nonselective alpha-adrenergic receptor antagonist, alfuzosin, emerged as noninferior in effectiveness and superior in tolerability than other selective alpha-blockers, silodosin, tamsulosin, and prazosin.

Efficacy and Safety of Novel Formulation of Clobetasol Propionate 0.025% Cream in Indian Moderate-to-Severe Psoriasis Patients: Phase-2a, Randomized 3-Arm Study.

INTRODUCTION: Clobetasol propionate (0.05% standard dose formulation), a topical corticosteroid, leads to systemic side-effects like hypothalamic-pituitary-adrenal (HPA) axis suppression at doses as low as 2 g/day. The aim of this study was to evaluate HPA axis suppression, efficacy, and safety of clobetasol propionate (0.025%, formulation 5 and 13) versus currently marketed 0.05% cream in Indian patients with moderate-to-severe psoriasis. METHODS: In this phase 2a investigator-blinded study, patients aged ≥ 18 years with moderate-to-severe psoriasis were randomized 1:1:1 to receive clobetasol propionate 0.025% formulation 5, or 13, or 0.05% cream; twice daily for 28 days. Safety endpoints included adrenocorticotropic hormone (ACTH) test results at day 28 (primary), and local tolerability at each visit (burning/stinging/pruritus, secondary). Efficacy endpoints included Psoriasis Global Assessment (PGA) score. RESULTS: Overall, 88 patients received clobetasol propionate 0.025% formulation 5 and 13 (n = 29 for both) and 0.05% cream (n = 30). At day 28, the proportion of patients with an abnormal ACTH stimulation test (cortisol levels ≤ 18 µg/dl) was numerically lower in 0.025% formulations: 5 (20.7%) and 13 (17.2%) compared with 0.05% cream (30.0%), (p = 0.320). Decrease in burning/stinging /pruritus scores were comparable in all treatment groups and PGA success rates were higher with 0.025% formulations: 5 (38.9%) and 13 (36.8%) compared with 0.05% cream (30.8%). CONCLUSION: Clobetasol propionate 0.025% could be an effective treatment for moderate-to-severe psoriasis compared with 0.05% cream, demonstrating comparable efficacy with a better systemic safety profile. TRIAL REGISTRATION NUMBER: REF/2018/01/016779.

A drug utilization study to provide background data for bringing amendments in the drug dispensing policy of a pediatric referral center.

OBJECTIVES: The purpose of this study was to generate data regarding the drug utilization pattern in pediatric population of our tertiary care hospital so that we could generate an essential medicine list (EML). BACKGROUND: Drug therapy accounts for a major portion of expenditure toward health care. Reduction in health care cost for an individual can be achieved by lowering the cost of drug treatment. METHODS: This was an observational study conducted in the Advanced Pediatric Centre of our hospital, during which prescriptions and case records were reviewed. RESULTS: During the study a total of 891 prescriptions were reviewed. Antibiotics and nutritional supplements were the major drugs prescribed. A large percentage of drugs were prescribed as trade names. Eighty three per cent of the drugs were prescribed from the National List Of Essential Medicine 2003 (India). Antibiotics accounted for the major bulk of cost of drugs, most of which were purchased by the patients. CONCLUSIONS: Restricted use of newer antibiotics, branded drugs and prescribing from the EML could be considered as targets for reduction of cost of therapy.

Dose-dependent actions of curcumin in experimentally induced myocardial necrosis: a biochemical, histopathological, and electron microscopic evidence.

Curcumin, an active component of turmeric, is a well-known antioxidant due to its reactive oxygen species (ROS) scavenging property. However, some in vitro studies have suggested that curcumin induces generation of ROS at higher doses and thus exerts pro-oxidant effect. We demonstrate, for the first time, the dose-dependent effects of curcumin in isoprenaline-induced model of myocardial necrosis in rats. The animals were assigned to control, isoprenaline and three curcumin treatment groups. Curcumin (100, 200, and 400 mg/kg) and vehicle (dimethyl sulfoxide) were administrated orally for 15 days and isoprenaline (85 mg/kg, s.c.) was given to curcumin treated and isoprenaline group on 13th and 14th day, respectively. Thereafter, on 15th day, the animals were sacrificed for biochemical analysis along with histopathological and ultrastructural examination. There was an increase in glutathione, superoxide dismutase (SOD), creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) levels, decrease in thiobarbituric acid reactive substances (TBARS), and preservation of myocardial architecture in the curcumin (100 and 200 mg/kg) treated groups. However, at 400 mg/kg dose there was ineffectual protection against isoprenaline-induced myocardial damage. Instead, there was significant lipid peroxidation as evident by increased levels of TBARS (93.87 +/- 9.93, p < 0.0001) and decrease in CK-MB (206.32 +/- 13.54, p < 0.0001) and LDH (134.26 +/- 9.13, p < 0.01) as compared to the two lower doses. Hence, it can be concluded that curcumin augments endogenous antioxidant system at lower doses but mediates ROS induction at higher concentration leading to myocardial damage.

A Real-World, Non-interventional Indian Study Evaluating Intensive Plant-Based Butter Moisturizing Cream in Psoriasis.

INTRODUCTION: Psoriasis is estimated to affect 0.44-2.8% of the Indian population. Moisturizers are a key adjuvant psoriasis treatment strategy, but data regarding their effectiveness, safety and compliance pattern in an Indian context are lacking. Hence, this real-world study on an intensive plant-based butter moisturizing cream (Venusia ® Max) was conducted among Indian patients with psoriasis. METHODS: This was an observational, patient-reported outcomes (PRO) study in patients with psoriasis aged 18-75 years who were prescribed the cream in routine clinical practice, as per clinician's discretion, over 4 weeks. The primary outcome measure was improvement from baseline in quality of life assessed using the Dermatology Quality of Life Index (DLQI) at 4 weeks of the study period. The secondary outcome measures were improvement in dryness using the Dry Skin/Ichthyosis Area and Severity Index (DASI) score at 4 weeks, safety and compliance. The DLQI and DASI scores were recorded by the clinicians at baseline and after 2 (optional) and 4 weeks of starting the cream. Safety was assessed throughout the study. RESULTS: The study included 400 patients from 9 outpatient dermatology centers across India. Of 400 patients, 384 completed the study. A significant reduction in both the mean DLQI score (66.7%; p < 0.001) and mean DASI score (84.6%; p < 0.001) was observed at week 4 after starting the cream vs. baseline in the overall population. Overall, the cream showed a good safety and compliance profile during the study period. There were no serious adverse events or deaths. CONCLUSIONS: The evidence from the PRO study suggests that use of the intensive plant-based butter moisturizing cream in a real-world scenario has a noticeable impact on improving the quality of life and reducing the skin dryness associated with psoriasis over 4 weeks. The moisturizing cream may serve as a valuable adjuvant treatment option for the management of psoriasis. TRIAL REGISTRATION NUMBER: CTRI/2017/03/008023. FUNDING: Dr. Reddy's Laboratories Ltd.

Real-World, Non-Interventional, Observational Study of Hydroxyzine Hydrochloride in Chronic Pruritus: a Prospective, Non-Comparative Study.

INTRODUCTION: Although hydroxyzine is widely used for symptom relief in pruritus, its clinical safety and efficacy data in the Indian setting are scarce. We conducted a study to assess the effectiveness and tolerability of hydroxyzine in the management of Indian patients with chronic pruritus in a real-world setting. METHODS: This was a prospective, observational, patient-reported outcomes (PRO) study in patients with chronic pruritus due to dermatological causes treated with hydroxyzine as per the clinician's discretion for a period of up to 12 weeks. The primary outcome was improvement in quality of life from baseline, assessed using the 10-point Dermatology Quality of Life Index (DLQI) at week 12 of the study period. Secondary outcomes were improvement in the pruritus scores (5-D itch scale) at 12 weeks, improvements in the DLQI and 5-D itch scores at 2, 4 and 8 weeks and safety. RESULTS: The study included 400 patients (179 males, 221 females) from 7 dermatology centres across India. Of the 400 patients recruited, 391 patients completed at least 2 weeks of treatment. There was significant (p < 0.0001) improvement from baseline in the DLQI scores and 5-D itch scores at 2, 4, 8 and 12 weeks; 189/391 (48.34%) patients had symptom relief leading to early termination. Overall, the treatment was well tolerated with a total of 11 mild-to-moderate adverse events reported during the study, which included dizziness, constipation, drowsiness, dry mouth and sedation. All events resolved without any intervention. There were no serious adverse events. CONCLUSION: This real-world, observational, PRO study demonstrates that hydroxyzine significantly improves symptoms of pruritus and quality of life in patients with chronic pruritus due to dermatological causes over 12 weeks. Despite the sedating potential of the drug, hydroxyzine is well tolerated in real-world settings. TRIAL REGISTRATION: CTRI/2017/06/008847. FUNDING: Dr. Reddy's Laboratories.

Cardioprotective response to chronic administration of vitamin E in isoproterenol induced myocardial necrosis: Hemodynamic, biochemical and ultrastructural studies.

The present study evaluated the cardioprotective potential of vitamin-E by studying its effect on hemodynamic parameters, lipid peroxidation, myocyte injury marker and ultrastructural changes in model of isoproterenol-induced myocardial necrosis in rats. Wistar albino male rats (150-200 g) were randomly divided into saline, ISP control, and vit E groups. Vitamin E group was administered vitamin E at a dose of 100mg/kg/day while saline and ISP control groups received saline orally for one month. On 29(th) and 30(th) day, ISP (85 mg/kg, sc) was administered at an interval of 24 h to vit E and ISP control rats. On 31(st) day, rats of all groups were anesthetized and hemodynamic parameters were recorded. At the end of experimentation, animals were sacrificed; hearts were excised and processed for biochemical and ultrastructural studies. ISP administration produced marked cardiac necrosis as evidenced by significant decrease in my ocardial creatine kinase-MB as well as increase in malonaldialdehyde levels. ISP-induced myocardial necrosis resulted in myocardial dysfunction as evidenced by significant depression in heart rate and mean arterial pressure in the ISP control group as compared to saline control. Salient ultrastructural changes including extensive loss of myofibrils, muscle necrosis, loss of mitochondria, and formation of several intracytoplasmic vacuoles and lipid droplets further confirmed the ISP-induced myocardial damage. However, subsequent to ISP challenge, vit E treatment significantly preserved the myocardium by restoring myocardial CK-MB activity, inhibiting the ISP-induced lipid peroxidation and ultrastructural changes. Additionally, pre-and co-treatment of vit E prevented the deleterious ultrastructural changes caused by ISP. These beneficial effects of chronic vit E treatment also translated into significant restoration of the altered hemodynamic parameters. The present study clearly demonstrated the cardioprotective potential of vit E at dose of 100 mg/kg in ISP-induced model of myocardial necrosis in rats. The significant restoration of altered hemodynamic parameters, myocardial CK-MB activity, prevention of ISP-induced rise in lipid peroxidation and ultrastructural changes may confirm its cardioprotective effect.

Cardioprotective effect of 'Khamira Abresham Hakim Arshad Wala' a unani formulation in isoproterenol-induced myocardial necrosis in rats.

The present study was designed to investigate whether Khamira Abresham Hakim Arshad Wala (KAHAW), a preparation of Unani System of Medicine, is able to attenuate the isoproterenol (ISO)-induced myocardial necrosis on the basis of its effects on hemodynamic, antioxidant, histopathological and ultrastructural parameters. Male Wistar albino rats were administered KAHAW (200, 400 and 800mg/kg/day, orally) or vehicle for 14 days with concurrent ISO administration (85mg/kg, subcutaneously, 2 doses at 24h interval) on 13th and 14th day. On the 15th day, vehicle+ISO-treated rats exhibit cardiac dysfunctions as indicated by decrease in systolic, diastolic, and mean arterial pressures, reduction in both maximum positive and maximum negative rates of developed left ventricular pressure (+/-LVdp/dt) and an increase in left ventricular end-diastolic pressure (LVEDP). Biochemical analysis of their heart homogenate presented reduced levels of enzymes viz., superoxide dismutase (SOD), catalase (CAT), lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB) isoenzyme. A marked reduction in reduced glutathione (GSH) levels along with increase in levels of thiobarbituric acid reactive substances (TBARS) was also observed in rat myocardium. Myocardial necrosis, edema and inflammation were evident from the light microscopic and ultrastructural changes. KAHAW at dose of 800mg/kg/day significantly reversed majority of hemodynamic and antioxidant derangements. The protective role of KAHAW on ISO-induced myocardial necrosis was further confirmed by histopathological and ultrastructural examination. There was no significant change in heart rate in all experimental groups. KAHAW per se groups showed no significant change when compared with vehicle control group. The study results thus demonstrated the cardioprotective potential of KAHAW against ISO-induced myocardial necrosis and associated oxidative stress.

Efficacy and safety of combination Acitretin and Pioglitazone therapy in patients with moderate to severe chronic plaque-type psoriasis: a randomized, double-blind, placebo-controlled clinical trial.

OBJECTIVE: To evaluate the efficacy and safety of combination therapy with acitretin and pioglitazone hydrochloride in patients with moderate to severe chronic plaque-type psoriasis. DESIGN: Randomized, double-blind, placebo-controlled clinical trial. SETTING: A tertiary care referral hospital. Patients The study included patients of either sex (age range, 18-65 years) with moderate to severe chronic plaque-type psoriasis. Patients were excluded if they were of child-bearing potential or if they had impaired liver or renal function, hyperlipidemia, diabetes mellitus, coronary artery disease, or a body mass index greater than 30 (calculated as weight in kilograms divided by height in meters squared). Of the 62 patients screened, 41 were randomly assigned to 2 groups: 22 to an acitretin (25 mg) plus placebo group and 19 to an acitretin (25 mg) plus pioglitazone hydrochloride (15 mg) group. Main Outcome Measure Change in Psoriasis Area and Severity Index score between the 2 groups from baseline to 12 weeks. RESULTS: After 12 weeks of therapy, the percentage of reduction in the Psoriasis Area and Severity Index score was 64.2% in the acitretin plus pioglitazone group and 51.7% in the acitretin plus placebo group. The majority of the adverse events were mild to moderate except for 1 possibly unrelated episode of acute myocardial infarction in a 49-year-old woman in the acitretin plus placebo group. CONCLUSIONS: Pioglitazone has a potential beneficial antipsoriatic effect and may provide a convenient, efficacious, and relatively safe option to combine with acitretin, although further studies are needed. Trial Registration clinicaltrials.gov Identifier: NCT00395941.

Myocardial salvaging effect of telmisartan in experimental model of myocardial infarction.

Telmisartan is a unique angiotensin II receptor blocker with an additional peroxisome proliferator-activated receptor-gamma (PPAR-gamma) activity. The present study has been designed to investigate whether telmisartan treatment attenuates the development of acute myocardial infarction in isoproterenol-treated rats by restoring hemodynamic, biochemical, histopathological and ultrastructural changes. Isoproterenol-induced cardiotoxicity was evidenced by marked decrease in systolic, diastolic, mean arterial pressures, maximal positive rate of developed left ventricular pressure (+LVdP/dt(max), a marker of myocardial contraction), maximal negative rate of developed left ventricular pressure (-LVdP/dt(max), a marker of myocardial relaxation) and an increase in left ventricular end-diastolic pressure (LVEDP, a marker of pre-load). In addition, a significant reduction in activities of myocardial creatine kinase-MB (CK-MB) isoenzyme, lactate dehydrogenase (LDH), superoxide dismutase (SOD), catalase, and reduced glutathione (GSH) level along with increase in malondialdehyde (MDA) content were observed. Oral pretreatment with telmisartan (1, 5 and 10mg/kg body weight) daily for a period of 14 days, favourably modulated the studied parameters in isoproterenol-induced myocardial injury. In addition, the protective role of telmisartan on isoproterenol-induced myocardial damage was further confirmed by histopathological and ultrastructural examinations. Telmisartan at a dose of 10mg/kg produced more pronounced protective effects than the other two doses (1 and 5mg/kg body weight). Present study thus provides evidence for protective effects of telmisartan on myocardium in experimentally induced myocardial infarction.

A study of anti-inflammatory activity of some novel alpha-amino naphthalene and beta-amino naphthalene derivatives.

In the present study, some naphthalene derivatives have been synthesized by incorporating azetidinyl and thiazolidinyl moieties at its alpha- or beta-positions such as alpha-(3-chloro-2-oxo-4-substituted)aryl-1-azetidinyl)naphthalenes 6-10, alpha-((substituted)aryl-4-oxo-1,3-thiazolidin-3-yl)naphthalenes 11-15, beta-(3-chloro-2-oxo-4-substituted aryl-1-azetidinyl)naphthalenes 21-25, and beta-(substituted aryl-4-oxo-1,3-thiazolidin-3-yl)naphthalenes 26-30. These compounds have also been screened for acute toxicity and anti-inflammatory and analgesic activities. Compounds which showed better anti-inflammatory and analgesic activities were also examined for their ulcerogenic liability and underwent a cyclooxygenase assay. Two compounds, 12 and 28, were found to exhibit potent anti-inflammatory activity as compared to the standard drugs phenylbutazone and naproxen.

Cardioprotective effect of lycopene in the experimental model of myocardial ischemia-reperfusion injury.

The efficacy of lycopene to limit myocardial injury after ischemia and reperfusion was explored in the present study. Adult male albino Wistar rats were divided into three experimental groups and orally received olive oil as vehicle (sham and control I-R) or lycopene 1 mg/kg dissolved in olive oil (lycopene treated group) respectively for 31 days. On the 31st day, animals of the control I-R and lycopene treated groups were subjected to 45 min of occlusion of the LAD coronary artery and were thereafter reperfused for 1 h. The ischemia-reperfusion injury resulted in significant cardiac necrosis, depression in hemodynamics, decline in antioxidant status and rise in lipid peroxidation product levels in the control I-R group as compared to sham control. In histopathological examinations myocardial damage produced after I-R was significantly prevented in the lycopene treated group. Lycopene treatment resulted in preservation of the myocardial antioxidant status and altered hemodynamic parameters as compared to control I-R group. Furthermore, I-R-induced lipid peroxidation was significantly inhibited in the lycopene treated group. These beneficial cardioprotective effects also translated into the functional recovery of the heart. The beneficial effect of lycopene likely results from the suppression of oxidative stress, which results in the reduction of myocardial injury.