Retrospective, Observational Study to Determine the Choice of Antihypertensive agent According to Stage of Hypertension, Risk factors and Co-morbidities in Real World Setting in India: A Report of Baseline Data.

BACKGROUND: The present study intended to estimate the comorbidities and risk factors among patients with hypertension in India. Further, the current practice of hypertension management was evaluated and the choice of therapy was assessed based on hypertension grade, risk factors, and comorbidities. METHODS: Electronic medical record data (June 2017-June 2019) of Indian adult hypertensive patients (≥140/90 mmHg) who had two blood pressure (BP) readings were retrospectively analyzed. Demographic characteristics, BP readings, comorbidities, medications and co-medications, and laboratory data were collected at baseline. Grids based on hypertension grade (I, II, and III), demographic factors, risk factors, and comorbidities were created and prescribed antihypertensive drugs (AHDs) in each grid were evaluated. RESULTS: Among 100,075 patients, the proportion of patients in 18-40 year, 40-65 year, and >65 year age groups were 11.4%, 65.1%, and 23.4%, respectively. Proportion of men and women was similar (52.0% vs 47.9%). Proportion of patients with BMI <25 Kg/m2 was 8.1%, 25-29.9 Kg/m2 was 11.9%, and >30 Kg/m2 was 8.8%. Mean BP of patients with hypertension was: grade I (145.05/90.73 mmHg), grade II (160.07/95.64 mmHg), and grade III (180.82/102.76 mmHg). Mean low density lipoprotein (113.26 mg/dL), serum creatinine (2.28 mg/dL), mean HbA1c (8.7%) levels were highest among patients with grade III hypertension. Commonly observed comorbidities were type 2 diabetes mellitus (T2DM: 51.5%), dyslipidemia (36.4%), and chronic kidney disease (CKD: 4.4%). Top concomitant medications included anti-diabetic therapies (34.6%), drugs for dyslipidemia (30.0%), and anti-platelet therapies (6.9%). CONCLUSION: Most prescribed AHD monotherapies were angiotensin receptor II blockers (ARBs) and calcium channel blockers (CCBs) and most prescribed combination therapies were ARBs + diuretics and ARBs + CCBs. Telmisartan and amlodipine+telmisartan for patients with comorbid T2DM or dyslipidemia and metoprolol for those with coronary artery disease were the commonly prescribed AHDs.

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.

Effectiveness of Olmesartan on Blood Pressure Control in Hypertensive Patients in India: A Real World, Retrospective, Observational Study from Electronic Medical Records.

BACKGROUND: Real-world data on the effectiveness of antihypertensive drugs (AHDs) in India is limited. The present study aims to provide updated evidence regarding the effectiveness of olmesartan as monotherapy or in combination with other AHDs in Indian patients with essential hypertension. METHODS: Electronic medical record data of adult patients who were diagnosed with essential hypertension (≥140/90 mmHg) and were prescribed olmesartan as mono- or add-on therapy were retrospectively analyzed. Patients were classified based on the number of AHD classes prescribed on initiation of olmesartan. Change in systolic and diastolic blood pressure (SBP and DBP) from baseline was the primary endpoint. Secondary endpoint was evaluation of proportion of patients who achieved treatment goals as per 2018 European Society of Cardiology/European Society of Hypertension guidelines. Readings were obtained before initiating olmesartan and after at least a month of therapy with olmesartan. RESULTS: Among the 459 included patients, majority were on olmesartan monotherapy or olmesartan+1AHD (91.7%). Mean (95% confidence interval [CI]) change in olmesartan monotherapy group was: SBP (-13.4 [-15.7, -11.1] mmHg) and DBP (-8.3 [-9.5, -7.1] mmHg) and mean (95% CI) change in olmesartan+1AHD group was: SBP (-11.7 [-15.1, -8.3] mmHg) and DBP (-6.6 [-8.3, -4.9] mmHg) (P<0.001 for all). SBP and DBP goals were achieved by 40.4% and 50.3% of patients on olmesartan monotherapy and by 36.1% and 46.2% of patients on olmesartan+1AHD. Among patients with comorbid diabetes, mean (95% CI) change in olmesartan monotherapy group was: SBP (-15.5 [-18.6, -12.4] mmHg) and DBP (-8.7 [-10.2, -7.2] mmHg) and mean (95% CI) change in olmesartan+1AHD group was: SBP (-13.5 [-18.3, -8.7] mmHg) and DBP (-7.6 [-9.8, -5.4] mmHg) (P<0.001 for all). SBP and DBP goals were achieved by 38.5% and 49.4% of patients on olmesartan monotherapy and by 31.7% and 42.9% of patients on olmesartan+1AHD. CONCLUSION: Olmesartan prescribed as mono- or add-on therapy during routine clinical practice significantly reduced blood pressure in Indian patients with essential hypertension as well as in patients with comorbid diabetes.

Emerging Landscape of Antibiotic Resistance and Use of Endoscopic Injection in Vesicoureteral Reflux.

Vesicoureteral reflux (VUR) in children is often treated with antimicrobials for prolonged durations, which often leads to antimicrobial resistance. In this context, this review article discusses the use of endoscopic injection in VUR as a safe and efficacious option for these children. The literature pertaining to VUR- its clinical manifestation and management, antibiotic resistance- with special reference to management of VUR, and endoscopic dextranomer/hyaluronic acid gel injection for management of VUR was reviewed by identifying key words in a PubMed search. Vesicoureteral reflux is managed using antibiotic prophylaxis, urotherapy, or surgical correction (open, endoscopic injection therapy, or laparoscopic). Continuous antibiotic prophylaxis for urinary tract infections in VUR can lead to antibiotic resistance. Urotherapy cures about 75% of cases with dysfunctional voiding and the rest have to be managed at specialized centers. While open surgery provides relief of VUR and related complications in majority, it requires hospitalization. Endoscopic injection of dextranomer/hyaluronic acid gel into the submucosa of bladder or ureter near ureteral orifice increases the tissue bulk and creates a valve function. Various studies show the efficacy and safety of endoscopic injection of dextranomer/hyaluronic acid gel in VUR. The use of endoscopic injection being a non-invasive modality, can be performed in children with VUR in the outpatient department, precluding hospitalization. In view of the threat of developing antimicrobial resistance and also realising the need for definitive treatment of VUR, endoscopic injection is an efficacious and safe option in primary VUR.

A review on the pharmacology of cariprazine and its role in the treatment of negative symptoms of schizophrenia.

Management of negative symptoms is one of the most challenging and important unmet needs of schizophrenia treatment. Negative symptoms together with positive symptoms result in significant psychosocial impairment and poor quality of life. Existing studies on atypical antipsychotics reported limited treatment adherence due to higher prevalence of treatment-emergent adverse events, such as diabetes, weight gain, hyperlipidemia, hyperprolactinemia and hypertension. A compound with greater affinity for dopamine D2/D3 receptors may improve negative symptoms, mood, and cognitive impairment associated with schizophrenia. In 2015, the US FDA has approved cariprazine, a partial D2/D3 agonist for treatment of schizophrenia, mania or mixed episodes. Midlands and Lancashire Commissioning Support Unit, UK (2019) has particularly suggested cariprazine for the treatment of predominant negative symptoms of schizophrenia. India's Central Drugs Standard Control Organization (CDSCO) has approved cariprazine in 2021 for the treatment of schizophrenia, manic or mixed episodes associated with bipolar I disorder. A ten-fold greater affinity for D3 receptors and partial agonism to serotonin receptors, along with longer half-life make cariprazine distinct when compared with other atypical antipsychotics. Cariprazine is also reported to have fewer incidents of metabolic and hormonal adverse events, and has been shown to provide better relapse prevention. Recent evidence indicates promising effect of cariprazine in ameliorating negative symptoms as well as psychotic symptoms in patients with schizophrenia. In addition, improved adherence to treatment (adjunctive/monotherapy) with cariprazine in patients having inadequate response to an ongoing antipsychotic treatment has also been clinically established. This review presents the evidence-based safety and efficacy of cariprazine for treatment of predominant negative symptoms of schizophrenia.

Effectiveness of Oral Cephalexin-Clavulanic Acid, Cefuroxime, and Amoxicillin-Clavulanic Acid in the Management of Dental Infections: A Real-World, Retrospective, Electronic Medical Record-Based Study in India.

BACKGROUND: Despite multiple antibiotics being available to manage dental infections (DI), there is lack of data comparing commonly prescribed antibiotics in India. OBJECTIVES: The aim of this study was to evaluate the real-world effectiveness and tolerability of cephalexin-clavulanic acid fixed-dose combination (cephalexin CV FDC) in contrast with amoxicillin-clavulanic acid (co-amoxiclav FDC) and cefuroxime among patients with dental infections (odontogenic) in India. METHODS: This retrospective, multi-centric, observational, real-world electronic medical record (EMR)-based study was conducted between January 2022 and December 2022. The EMRs of 355 adults with DI receiving oral cephalexin CV, co-amoxiclav, or cefuroxime were categorized into two distinct groups: Group I (Test Group) with patients prescribed cephalexin extended release 375/750 mg along with clavulanic acid 125 mg; and Group II (Comparator Group) with patients prescribed co-amoxiclav 625 mg (500 mg amoxicillin + 125 mg clavulanic acid) or cefuroxime (250 mg/500 mg). RESULTS: Toothache was the most common complaint, reported by 95.5% of patients, followed by swelling (46.8%), tooth sensitivity (35.5%), pus discharge (33.0%), redness and halitosis (30.4% each). Dental caries was observed in 81.1% of patients. Clinical improvement, defined as improvement/partial resolution of infection-related clinical signs and symptoms (composite measure of pain, swelling, fever, requirement of additional antimicrobial therapy) as per dentists' judgment, was recorded in 98.3% of patients with cephalexin CV, 96.8% of patients with co-amoxiclav, and 98.9% of patients treated with cefuroxime within 10 days. Time (days) to clinical improvement was numerically lesser among patients receiving cephalexin CV (4.6 ± 2.0) compared with cefuroxime (4.9 ± 2.1) and co-amoxiclav (5.0 ± 2.6). All treatments were well tolerated. CONCLUSION: Cephalexin CV was as effective as co-amoxiclav and cefuroxime, with faster clinical improvement and better resolution of certain symptoms.

The Efficacy and Safety of High Dose (10 mg) of Desloratadine (Dazit® 10) in the Treatment of Chronic Spontaneous Urticaria in India: A Phase III, Multicentric, Open-Label, Single-Arm Study.

BACKGROUND: Chronic spontaneous urticaria (CSU) is a debilitating affliction that affects diverse quality of life (QoL) parameters such as sleep, self-esteem, and daily activities. Second-generation antihistamines, such as desloratadine, are more effective and safer in managing CSU. Desloratadine is a nonsedating, potent, and highly selective H1 receptor antagonist. At its daily dose of 5 mg, almost half of CSU patients do not show symptomatic improvement. European Academy of Allergy and Clinical Immunology (EAACI)/Global Allergy and Asthma European Network (GA2LEN)/European Dermatology Forum (EDF) (EuroGuiDerm)/Asia Pacific Association of Allergy, Asthma and Clinical Immunology (APAAACI) guidelines recommend increasing the dosage to up to four times in such nonresponsive patients. However, there is insufficient clinical evidence in Indian settings. METHOD: We evaluated the efficacy and safety of 10 mg desloratadine (OD) in 256 nonresponsive patients with moderate to severe CSU. The primary outcome was the change in Urticaria Activity Score (UAS7) from baseline to four weeks. Additionally, change in Chronic Urticaria Quality of Life (CU-Q2oL) scores during the course of treatment was also evaluated. RESULT: The mean UAS7 scores showed a significant reduction from 31.9 ± 4.8 at baseline to 18.2 ± 8.1 at the end of the study (p < 0.0001). The use of a higher dose of desloratadine also decreased the CU-Q2oL scores significantly from 59.8 ± 14.7 at baseline to 35.4 ± 10 at four weeks (p < 0.0001). The incidence of adverse events (AEs) possibly linked to the drug was low (1.6%), and no serious adverse events were reported. CONCLUSION: Results indicated improvements in the disease severity as well as its positive impact on participants' QoL. This study confirms the efficacy and safety of daily use of a twofold dose of desloratadine in nonresponsive moderate to severe CSU patients.

Fixed-Dose Combination of Dapagliflozin + Sitagliptin + Metformin in Patients with Type 2 Diabetes Poorly Controlled with Metformin: Phase 3, Randomized Comparison with Dual Combinations.

INTRODUCTION: This study compared efficacy and safety of triple drug fixed-dose combination (FDC) of dapagliflozin (DAPA) + sitagliptin (SITA) + metformin (MET) extended release (ER) with SITA + MET sustained release (SR) and DAPA + MET ER in patients with type 2 diabetes poorly controlled with metformin. METHODS: This phase 3, randomized, open-label, active-controlled study included adult patients with glycated hemoglobin (HbA1c) ≥ 8% (64 mmol/mol) and ≤ 11% (97 mmol/mol), randomized in 1:1:1 ratio to receive either FDC of DAPA + SITA + MET ER (10 mg + 100 mg + 1000 mg) tablets once daily (n = 137) or co-administration of SITA + MET SR (100 mg + 1000 mg) tablets once daily (n = 139) or FDC of DAPA + MET ER (10 mg + 1000 mg) tablets once daily (n = 139). Primary endpoint was mean change in HbA1c from baseline to week 16. RESULTS: Mean baseline HbA1c was approximately 9% (75 mmol/mol) in each treatment group. At week 16, adjusted mean reduction in HbA1c from baseline was significantly greater with DAPA + SITA + MET ER (- 1.73% [- 19.0 mmol/mol]) compared to SITA + MET SR (- 1.28% [- 14.1 mmol/mol]; difference of - 0.46% [- 5.1 mmol/mol], p < 0.001) and DAPA + MET ER (- 1.33% [- 14.6 mmol/mol]; difference - 0.4% [4.4 mmol/mol], p < 0.001). Similarly, at week 12, reduction in HbA1c from baseline was significantly greater with DAPA + SITA + MET ER compared to SITA + MET SR (p = 0.0006) and DAPA + MET ER (p = 0.0276). At week 16, DAPA + SITA + MET ER showed significant reduction in postprandial blood glucose compared to DAPA + MET ER (p = 0.0394) and significant reduction in fasting blood glucose with DAPA + SITA + MET ER compared to SITA + MET SR (p = 0.0226). The proportion of patients achieving HbA1c < 7.0% (53 mmol/mol) at week 16 was significantly higher with DAPA + SITA + MET ER (38.5%) versus SITA + MET SR (12.8%) (p < 0.001) and DAPA + MET ER (21.3%) (p = 0.0023). All study medications were well tolerated. CONCLUSION: Triple FDC of DAPA + SITA + MET ER tablets once daily was significantly better in achieving glycemic control versus dual combination once daily in patients with type 2 diabetes poorly controlled with metformin without any significant safety concerns. TRIAL REGISTRATION: CTRI/2021/11/038176, registered on 22 November 2021.

Type 2 diabetes is a progressive disease in which the risks of microvascular and macrovascular complications and mortality are strongly associated with hyperglycemia. Achieving glycemic control remains the main goal of treatment to prevent these complications. Estimates in 2019 showed that 77 million individuals had diabetes in India, which is expected to rise over 134 million by 2045. Considering the progressive nature of the disease, many guidelines recommend use of dual or triple drug therapy based on glycated hemoglobin (HbA1c) level. Use of fixed-dose combination (FDC) helps to improve therapy compliance and can provide optimum therapeutic benefits. Mechanisms of action of dipeptidyl peptidase 4 (DPP4) and sodium­glucose cotransporter 2 (SGLT2) inhibitors are complementary to that of metformin with low risk of hypoglycemia. Studies have shown beneficial effects of adding both DPP4 inhibitors and SGLT2 inhibitors after metformin monotherapy. This phase 3 study was designed to assess efficacy and safety of triple FDC of dapagliflozin + sitagliptin + metformin extended release in comparison with combipack of sitagliptin + metformin sustained release and FDC of dapagliflozin + metformin ER in patients with type 2 diabetes inadequately controlled with metformin monotherapy. The study demonstrated superiority of triple FDC of dapagliflozin + sitagliptin + metformin ER over dual combinations in terms of reduction in HbA1c and percentage of patients achieving target HbA1c at the end of week 16. The current study provides evidence for considering triple FDC of dapagliflozin + sitagliptin + metformin ER as an alternative option with minimal risk of hypoglycemia and weight gain, while considering oral triple-combination therapy for patients to achieve their glycemic target.

Exploring the common pathophysiological links between IPF, SSc-ILD and post-COVID fibrosis.

In coronavirus disease 2019 (COVID-19) patients, dysregulated release of matrix metalloproteinases occurs during the inflammatory phase of acute respiratory distress syndrome (ARDS), resulting in epithelial and endothelial injury with excessive fibroproliferation. COVID-19 resembles idiopathic pulmonary fibrosis (IPF) in several aspects. The fibrotic response in IPF is driven primarily by an abnormally activated alveolar epithelial cells (AECs) which release cytokines to activate fibroblasts. Endoplasmic reticulum (ER) stress is postulated to be one of the early triggers in both diseases. Systemic sclerosis (SSc) is a heterogeneous autoimmune rare connective tissue characterised by fibrosis of the skin and internal organs. Interstitial lung disease (ILD) is a common complication and the leading cause of SSc-related death. Several corollaries have been discussed in this paper for new drug development based on the pathogenic events in these three disorders associated with pulmonary fibrosis. A careful consideration of the similarities and differences in the pathogenic events associated with the development of lung fibrosis in post-COVID patients, IPF patients and patients with SSc-ILD may pave the way for precision medicine. Several questions need to be answered through research, which include the potential role of antifibrotics in managing IPF, SSc-ILD and post-COVID fibrosis. Many trials that are underway will ultimately shed light on their potency and place in therapy.

Impact of Partial Meal Replacement on Glycemic Levels and Body Weight in Indian Patients with Type 2 Diabetes (PRIDE): A Randomized Controlled Study.

INTRODUCTION: Partial meal replacement (PMR) offers potential glycemic and weight control benefits in type 2 diabetes mellitus (T2DM) patients. We evaluated the clinical impact of PMR (diabetes-specific nutritional supplement [DSNS]) in overweight/obese Indian patients with T2DM. METHODS: PRIDE, a 12-week, phase IV, open-label, multicenter study randomized (1:1) newly diagnosed T2DM patients (≤ 1 year) to either DSNS plus standard of care (SOC; diabetes treatment with dietary counseling) group (PMR) or SOC alone group (SOC). The primary endpoint was mean change in glycated hemoglobin (HbA1c) from baseline to week 12. Secondary endpoints were changes in glucose profiles, body weight, waist circumference, lipid profile, and factors impacting quality-of-life (QoL) at week 6 and 12 from baseline. Safety was assessed throughout the study. RESULTS: Of the 176 patients enrolled, 171 (n = 85 in PMR group; n = 86 in SOC group) were included in the modified intent-to-treat population. The mean reduction in HbA1c at week 12 from baseline in PMR group was significant compared to the SOC group (- 0.59 vs. - 0.21%, p = 0.002). At week 12, the PMR group showed significant reduction in mean body weight (- 2.19 vs. - 0.22 kg; p = 0.001) and waist circumference (- 2.34 vs. - 0.48 cm; p = 0.001) compared to SOC group. Mean fasting plasma glucose and post-prandial glucose significantly reduced from baseline at week 6 and 12 in each group (p < 0.05). No significant change was observed in lipid profile. QoL parameters (treatment adherence, general well-being, and energy fulfilment) in the PMR were significantly better than SOC group (p < 0.05). Patients were satisfied with the taste of DSNS. No serious adverse events were reported. CONCLUSIONS: DSNS is an encouraging option for PMR strategy, as it significantly improved HbA1c, body weight, waist circumference, and overall well-being among overweight/obese Indian T2DM patients. TRIAL IDENTIFICATION NO: CTRI/2019/10/021595.

Efficacy and Safety of a Phytopharmaceutical Drug Derived from Cocculus hirsutus in Adults with Moderate COVID-19: a Phase 2, Open-label, Multicenter, Randomized Controlled Trial.

INTRODUCTION: There is an urgent need for an effective, oral therapy for COVID-19. Purified aqueous extract of Cocculus hirsutus (AQCH) has shown robust antiviral activity in in vitro studies. We aimed to evaluate the efficacy and safety of AQCH plus standard of care in hospitalized patients with moderate COVID-19. METHODS: In an open-label, multicenter, randomized controlled trial conducted in India, eligible patients (aged 18-75 years) were randomized (1:1) to receive AQCH 400 mg orally three times a day plus standard of care (AQCH group) or standard of care alone (control group) for 10 days. Primary endpoint was the proportion of patients showing clinical improvement by day 14. Time to clinical improvement, time to viral clearance, and duration of hospitalization were secondary endpoints. RESULTS: A total of 210 patients were randomized. By day 14 most patients in both groups showed clinical improvement [difference - 0.01 (95% CI - 0.07 to 0.05); p = 1.0]. Median time to clinical improvement was 8 days (IQR 8-11) in the AQCH group versus 11 days (IQR 8-11) in the control group [HR 1.27 (95% CI 0.95-1.71); p = 0.032]. Time to viral clearance and duration of hospitalization were also significantly shorter in the AQCH group (p = 0.0002 and p = 0.016, respectively). AQCH was well tolerated, with no safety concerns identified. CONCLUSIONS: AQCH significantly reduced time to clinical improvement, time to viral clearance, and duration of hospitalization. In a pandemic, this has significant potential to decrease healthcare resource utilization and increase hospital bed availability. Further investigation of the therapeutic potential of AQCH in patients with COVID-19 is warranted. TRIAL REGISTRATION: Clinical Trials Registry - India (CTRI/2020/05/025397).

Fixed-dose Combination of Metoprolol, Telmisartan, and Chlorthalidone for Essential Hypertension in Adults with Stable Coronary Artery Disease: Phase III Study.

INTRODUCTION: The aim of the study was to evaluate the efficacy and safety of fixed-dose combination (FDC) of metoprolol, telmisartan, and chlorthalidone in patients with essential hypertension and stable coronary artery disease (CAD) who showed inadequate response to dual therapy. METHODS: In this phase III, open-label, multicenter study, 254 adults with stable CAD having uncontrolled hypertension despite being treated with FDC of metoprolol (25/50 mg) and telmisartan (40 mg) were included. Patients received either of the following FDC for 24 weeks: metoprolol (25 mg), telmisartan (40 mg), and chlorthalidone (12.5 mg) (FDC1; n = 139) or metoprolol (50 mg), telmisartan (40 mg), and chlorthalidone (12.5 mg) (FDC2; n = 115) tablets once daily. The FDCs were developed using the novel Wrap Matrix™ platform technology. Primary endpoint assessed the mean change in seated diastolic blood pressure (SeDBP) and seated systolic blood pressure (SeSBP) from baseline to 24 weeks. Secondary efficacy endpoints included proportion of patients achieving < 90 mmHg SeDBP (SeDBP responder) and < 140 mmHg SeSBP (SeSBP responder) at weeks 12, 16, 20, and 24. Safety was assessed throughout the study. RESULTS: A total of 243 (95.70%) patients completed study. The mean change in BP from baseline (FDC1, 155/96 mmHg; FDC2, 165/98 mmHg) to week 24 (FDC1, 128/82 mmHg; FDC2, 131/83 mmHg) was statistically significant (both groups p < 0.0001). Within FDC1 and FDC2, the mean change from baseline to week 24 in SeDBP (82.60 mmHg and 83.09 mmHg) and SeSBP (128.07 mmHg and 131.29 mmHg) was statistically significant (both groups p < 0.0001). At week 24, in FDC1, 80.15% and 84.73% were SeDBP and SeSBP responders, respectively; in FDC2, 79.46% and 74.11% were SeDBP and SeSBP responders, respectively. No serious adverse events or deaths were reported. CONCLUSION: Triple FDCs of metoprolol, telmisartan, and chlorthalidone were considered effective and well tolerated in patients with hypertension who respond inadequately to dual therapy. CLINICAL TRIAL REGISTRATION: CTRI/2016/11/007491.

The increasing prevalence of hypertension in India requires immediate attention. To adequately manage blood pressure and ensure compliance to medications, innovative treatment options involving combination therapy with three or more drugs to treat hypertension need to be explored. Fixed-dose combination (FDC) of three antihypertension drugs, viz., metoprolol, telmisartan, and chlorthalidone, were tested in Indian patients who could not respond adequately to dual treatment. The rationale behind using a combination of three drug types was to take advantage of the complementary actions of each drug class for an enhanced treatment effect. The two variants of FDCs were tested in 254 adults with the most common form of heart disease, i.e., stable coronary artery disease. Changes in seated diastolic and systolic blood pressure (SeDBP and SeSBP) were measured to assess the effectiveness of the FDC. The mean changes in SeDBP and SeSBP were statistically significant by the end of the study, i.e., it determined that results are not explainable by chance alone. A greater proportion of patients (range 74­84%) achieved their target BPs with the FDC used in the study. The FDC variants were well tolerated without any reports of serious adverse events or deaths. Overall, this triple combination therapy option was effective and considered safe to be administered to hypertensive Indian adults with stable coronary artery disease who did not respond adequately to dual antihypertension therapy.

Role of Lactobacillus reuteri DSM 17938 on Crying Time Reduction in Infantile Colic and Its Impact on Maternal Depression: A Real-Life Clinic-Based Study.

BACKGROUND: Infantile colic is characterized by prolonged periods of inconsolable, incessant crying and persistent fussing in an otherwise healthy infant. It is a self-limiting condition, but causes significant stress to mothers. AIM: To observe the role of Lactobacillus reuteriDSM 17938 in reducing crying time in colicky infants in routine clinical practice. METHODS: This was a prospective observational multicentric clinic-based study. Each practitioner included approximately 30 infants < 5 months of age with infantile colic who were prescribed L. reuteri DSM 17938 for a period of 21 days. There were four physical consultations and two telephonic consultations. The parents were given a daily diary to record the duration of crying and fussing episodes and a questionnaire was administered during the consultations. RESULTS: A total of 120 infants with a mean age of 56.9 ± 34.2 days were included in this 28-day study. The mean crying time as reported by the parents in the subject diary reduced from 248.2 ± 101.2 min, 95% CI: 229.45, 266.94 at baseline to 45.6 ± 79.1 min 95% CI: 31.02, 60.31 at study end (P < 0.01). The clinical response (defined as reduction of 50% in crying time) was observed in 85% of subjects at study end. The fussiness and parental perception of colic recorded during the consultations were reduced by 66% and 72%, respectively, at study end. The maternal depression scores were reduced to 63% at study end. CONCLUSION: L. reuteri DSM 17938 was associated with a significant reduction in crying time in colicky infants, and showed improvement in maternal depression.

Efficacy and Safety of Pregabalin Prolonged Release-Etoricoxib Combination Compared to Etoricoxib for Chronic Low Back Pain: Phase 3, Randomized Study.

INTRODUCTION: Currently available treatments for chronic lower back pain (CLBP) do not adequately address both nociceptive and neuropathic components of pain. We evaluated efficacy and safety of fixed-dose combination (FDC) of low-dose pregabalin prolonged release 75 mg-etoricoxib 60 mg to address both pain components. METHODS: This randomized phase 3 trial conducted at 12 centres across India evaluated efficacy (based on mean change in numeric rating scale [NRS], Roland-Morris disability questionnaire [RDQ], visual analogue scale [VAS], patient global impression of improvement [PGI-I], clinical global impression of improvement [CGI-I] and rescue medication consumption) and safety of FDC in comparison to etoricoxib alone in adult patients with CLBP. Treatment duration was 8 weeks. RESULTS: Of the 371 patients screened, 319 were randomized and considered for efficacy and safety analysis. Both treatment groups had no significant difference in terms of demography and baseline disease characteristics. Significantly better outcomes with FDC compared to etoricoxib were observed at week 4 onwards. At week 8, both groups showed significant reduction in mean NRS score from baseline (- 4.00 ± 1.65 in FDC; - 2.92 ± 1.59 in etoricoxib) with mean NRS score being significantly less in the FDC group compared to etoricoxib group (3.26 ± 1.56 vs 4.31 ± 1.56; p < 0.0001). The FDC was more effective than etoricoxib in terms of significantly greater reduction in RDQ score (- 9.28 ± 4.48 vs - 6.78 ± 4.34; p < 0.0001) and VAS score (- 37.66 ± 18.7 vs - 28.50 ± 16.31; p < 0.0001) at week 8. The FDC was also better in terms of significantly more patients reporting their condition as 'very much better' (36.9% vs 5.0%; p < 0.0001) and clinicians reporting patient's condition as 'very much improved' (36.3% vs 5.7%; p < 0.0001). Overall, study medications were well tolerated. CONCLUSION: FDC of pregabalin and etoricoxib provided significant benefits in reducing pain and improving functional status compared with etoricoxib alone in patients with CLBP. Pregabalin prolonged release-etoricoxib FDC could be one of the treatment options for early and sustained pain relief and improvement in quality-of-life in treating CLBP as it addresses both neuropathic and nociceptive components of pain. TRIAL REGISTRATION: CTRI/2018/10/015886.

Low back pain is one of the most common causes of loss of productivity worldwide. About 60% of Indians suffer from low back pain at some point. Low back pain that persists for more than 3 months is classified as chronic low back pain which mostly includes both nociceptive and neuropathic components. Monotherapies, if prescribed, are not completely effective, as they generally only target either nociceptive or neuropathic components of pain. Multiple drugs are usually needed at multiple times a day, at higher doses for optimal effectiveness, and in most cases they have significant side effects if taken over prolonged periods and also add to the pill burden. To minimize treatment-associated adverse effects, and to increase treatment compliance, while addressing both the components of pain, we developed a fixed-dose combination of low-dose pregabalin prolonged release and etoricoxib. A phase 3 trial was designed to assess the efficacy and safety of the fixed-dose combination in comparison with etoricoxib alone in treating chronic low back pain. The combination demonstrated statistically and clinically significant improvement in patient-reported outcomes­pain, functionality and quality of life­as early as 4 weeks after starting the medication. No severe or serious adverse effects were reported. Thus, the combination of low-dose pregabalin prolonged release and etoricoxib could provide an option for optimal management of chronic low back pain. This would provide multiple benefits, such as addressing both nociceptive and neuropathic components of chronic low back pain, reducing drug-related adverse effects because of low dose, reducing pill burden and thereby increasing drug compliance.

Effectiveness of Telmisartan on Blood Pressure Control in Hypertensive Patients in India: A Real-World Retrospective Study from Electronic Medical Records.

INTRODUCTION: The effectiveness of telmisartan has been reported in Indian clinical trials; however, real-world data are limited. We aimed to provide real-world evidence regarding the effectiveness of telmisartan as monotherapy or in combination with other antihypertensive drugs (AHDs) in Indian patients with essential hypertension. METHODS: Electronic medical record data of adult patients diagnosed with essential hypertension (≥ 140/90 mmHg) and who were prescribed telmisartan as mono- or add-on therapy were retrospectively analyzed. Patients were classified according to the number of AHD classes prescribed on initiating telmisartan. Change in systolic and diastolic blood pressure (SBP and DBP) after a month of treatment and the proportion of patients who achieved treatment goals according to the 2018 European Society of Cardiology/European Society of Hypertension guidelines were evaluated. RESULTS: A majority (90.6%) of the 1304 patients included in the study were on telmisartan monotherapy or telmisartan + 1 AHD. The mean (95% confidence interval [CI]) change in the telmisartan monotherapy group was SBP (-13.3 [-14.6, -12.0] mmHg) and DBP (-7.2 [-7.9, -6.5] mmHg), and the mean (95% CI) change in the telmisartan + 1 AHD group was SBP (-10.8 [-13.1, -8.5] mmHg) and DBP (-6.5 [-7.7, -5.3] mmHg) (P < 0.001 for all). SBP and DBP goals were achieved by 35.9% and 47.3% of patients on telmisartan monotherapy and by 35.9% and 46.8% of patients on telmisartan + 1 AHD. Among patients with comorbid diabetes, the mean (95% CI) change in the telmisartan monotherapy group was SBP (-13.3 [-15.0, -11.6] mmHg) and DBP (-7.3 [-8.2, -6.5] mmHg), and the mean (95% CI) change in the telmisartan + 1 AHD group was SBP (-13.0 [-16.5, -9.5] mmHg) and DBP (-6.9 [-8.7, -5.1] mmHg) (P < 0.001 for all). SBP and DBP goals were achieved by 31.7% and 39.7% of patients on telmisartan monotherapy and by 31.9% and 41.8% of patients on telmisartan + 1 AHD. CONCLUSION: Telmisartan may be a good candidate for blood pressure control in Indian patients with essential hypertension and comorbidities.

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.

Effect of a High-Protein High-Fibre Nutritional Supplement on Lipid Profile in Overweight/Obese Adults with Type 2 Diabetes Mellitus: A 24-Week Randomized Controlled Trial.

BACKGROUND: Foods rich in protein and dietary fibre could potentially improve lipid profile in overweight or obese diabetic patients with dyslipidemia and, thereby, mitigate their risk of cardiovascular disease (CVD). In this study, the effect of providing high-protein high-fibre (HPHF) nutritional supplement in addition to standard care of type 2 diabetes mellitus (T2DM) on lipid profile was evaluated. METHODS: In this open-label, parallel-arm, prospective, randomized study, a total of 100 overweight/obese participants with T2DM were randomized to either an intervention group (25 g HPHF nutritional supplement given twice daily along with a standard care of T2DM) or a control group (standard care of T2DM) for 24 weeks. Change from baseline in lipid parameters such as total cholesterol (TChol), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) was assessed between the intervention and control group at week 12 and week 24. Participant compliance was assessed using the dietary 24-hour recall. Statistical analysis was performed to assess the main effects on within- and between-group changes from baseline to end of 24 weeks. RESULTS: Participants in the HPHF nutritional supplement group showed a statistically significant improvement in HDL-C levels by the end of 24 weeks (p=0.04) and a significant increase in protein and total dietary fibre intake (p=0.002 and p=0.00, respectively) compared to the control group. The TChol/HDL-C ratio was significantly lower (p=0.03) in the HPHF group from baseline to 24 weeks. CONCLUSION: Twice-daily consumption of a HPHF nutritional supplement significantly improved HDL-C levels. Inclusion of the HPHF supplement would be a useful effective aid for managing dyslipidemia in overweight/obese individuals with T2DM.

Effectiveness of Amlodipine on Blood Pressure Control in Hypertensive Patients in India: A Real-World, Retrospective Study from Electronic Medical Records.

BACKGROUND: The effectiveness of amlodipine has been reported in clinical trials in India. However, real-world data on the effectiveness of amlodipine in India is limited. OBJECTIVE: To provide real-world evidence regarding the effectiveness of amlodipine as monotherapy or in combination with other antihypertensive drugs (AHDs) in Indian patients with essential hypertension. METHODS: Electronic medical record data of adult patients who were diagnosed with essential hypertension (≥ 140/90 mmHg) and were prescribed amlodipine as monotherapy or add-on therapy were retrospectively analyzed. Patients were classified based on the number of AHD classes prescribed on initiation of amlodipine. Change in systolic (SBP) and diastolic (DBP) blood pressure from baseline was the primary endpoint. Evaluation of proportion of patients who achieved treatment goals as per 2018 European Society of Cardiology/European Society of Hypertension guidelines was the secondary endpoint. Readings were obtained before initiating amlodipine and after at least a month of therapy with amlodipine. RESULTS: Among the 462 included patients, the majority (90.7%) were on amlodipine monotherapy or amlodipine + 1AHD. Mean (95% confidence interval [CI]) change in the amlodipine monotherapy group was: SBP (- 12.1 [- 14.9, - 9.3] mmHg) and DBP (- 7.5 [- 8.9, - 6.1] mmHg) and mean (95% CI) change in the amlodipine + 1AHD group was: SBP (- 17.8 [- 21.0, - 14.6] mmHg) and DBP (- 9.5 [- 11.0, - 8.0] mmHg) (P < 0.001 for all). SBP and DBP goals were achieved by 31.4% and 42.9% of patients on amlodipine monotherapy and by 38.9% and 51.8% of patients on amlodipine + 1AHD, respectively. Among patients aged ≤ 45 years, mean (95% CI) change in the amlodipine monotherapy group was: SBP (- 11.7 [- 16.0, - 7.4] mmHg; P < 0.001) and DBP (- 7.2 [- 9.7, - 4.7] mmHg; P < 0.001) and mean (95% CI) change in the amlodipine + 1AHD group was: SBP (- 14.6 [- 21.9, - 7.3] mmHg; P < 0.05) and DBP (- 10.6 [- 14.8, - 6.4] mmHg; P < 0.01). SBP and DBP goals were achieved by 35.4% and 33.8% of patients on amlodipine monotherapy and by 48.0% and 56.0% of patients on amlodipine + 1AHD, respectively. Among patients aged ≥ 65 years, mean (95% CI) change in the amlodipine monotherapy group was: SBP (- 13.9 [- 20.2, - 7.6] mmHg; P < 0.01) and DBP (- 8.5 [- 11.4, - 5.7] mmHg; P < 0.001) and mean (95% CI) change in the amlodipine + 1AHD group was: SBP (- 22.4 [- - 28.8, - 16.0] mmHg; P < 0.001) and DBP (- 10.8 [- 14.0, - 7.6] mmHg; P < 0.001). SBP and DBP goals were achieved by 25.5% and 13.7% of patients on amlodipine monotherapy and by 29.8% and 14.0% of patients on amlodipine + 1AHD. CONCLUSION: Amlodipine prescribed as monotherapy or add-on therapy during routine clinical practice significantly reduced BP in ≤ 45- and ≥ 65-year-old Indian patients with mild to moderate hypertension, emphasizing that amlodipine may be a good candidate for BP control in Indian patients with essential hypertension in these age groups.

Correction to: Comparative Study to Evaluate Tolerability of Topical 5% Minoxidil Novel Formulation and Alcohol-Based Conventional Solutions in Treatment of Androgenetic Alopecia in Indian Men: Randomized Double-Blind Study.

In Methods section under Study Design and Patients.

Comparative Study to Evaluate Tolerability of Topical 5% Minoxidil Novel Formulation and Alcohol-Based Conventional Solutions in Treatment of Androgenetic Alopecia in Indian Men: Randomized Double-Blind Study.

INTRODUCTION: Patients with androgenetic alopecia treated with alcohol-based minoxidil topical solutions often report local irritation, dryness, and redness of the scalp. We evaluate the in-use tolerance of 5% minoxidil novel formulation topical solution-test product (TP)-compared with 5% minoxidil alcohol-based topical solutions-reference product 1 (RP1) and reference product 2 (RP2)-in Indian men with androgenetic alopecia. METHODS: In this randomized double-blind study, patients aged ≥ 18 years with androgenetic alopecia were randomized 1:1:1 to apply TP, RP1, and RP2 twice daily for 30 days. The safety endpoints included mean hydration, mean redness, and mean scaling on scalp. RESULTS: All screened patients (N = 100) were enrolled and randomized to TP (n = 33), RP1 (n = 33), or RP2 (n = 34). At day 30, the mean (SD) hydration was significantly increased in patients treated with TP [9.74 (4.98)] but significantly reduced in patients treated with RP1 [3.28 (2.67)] or RP2 [3.03 (1.57)] (p-value 0.001). The mean (SD) score for redness was significantly decreased in the TP group [0.01 (0.04)], (p-value, 0.009) at day 30 compared with baseline, while no change was observed in the RP1 [0.08 (0.13)] or RP2 [0.11 (0.17)] group. After 30 days of treatment, no significant difference was observed in the mean score of scaling in any of the three groups. CONCLUSIONS: Twice daily application of 5% minoxidil novel formulation for 30 days significantly improved hydration and reduced redness of the scalp. Hence, 5% minoxidil novel formulation could be a safer alternative in treating men with androgenetic alopecia who are sensitive to alcoholic formulations. TRIAL REGISTRATION: Clinical Trial Registry of India; CTRI/2018/11/016431.