Background Lateral elbow tendinopathy is one of the most common chronic and degenerative diseases which significantly affects quality of life and the activities of daily living of a person. The following is a systematic review reporting a comparison between physical therapy intervention and corticosteroid injection for the treatment of lateral elbow tendinopathy. Method PubMed, Web of Science, and Embase were searched using headings related to treatment options for Lateral elbow tendinopathy. The following keywords were used: lateral epicondylitis, physical therapy, and corticosteroid injection. Result We descriptively analyzed and reviewed a total of 12 studies including a total of 1253 patients for lateral elbow tendinopathy. The physical therapy intervention included interventions like electrotherapy, manual therapy, and exercise. The studies included had an overall low to unknown risk of bias. Conclusion Our review suggests corticosteroid injection provides beneficial short-term effects and physical therapy interventions provide intermediate to long-term effects, less additional treatment and low recurrence rate in patients with lateral elbow tendinopathy. Although high-quality randomized control trials are required in order to have a better understanding of both intervention types.

To compare the relative effects of different dosages of sodium-glucose cotransport inhibitors (SGLT2i) for renoprotection in Type 2 diabetes mellitus. The study searched different databases (PubMed, Embase, Scopus, and Web of Science) for studies comparing dose-dependent renoprotective efficacy defined as a decline in eGFR with the different “-flozins namely Empagliflozin, Canagliflozin, Dapagliflozin, Ertugliflozin, Ipragliflozin, Luseogliflozin, Remogliflozin and Sotagliflozin. The studies were compared with the Bayesian approach of network meta-analysis coupled with the random-effect model using the Cochrane risk of bias tool (RoB 2.0), and the surface under the cumulative ranking curve (SUCRA) score was allotted to each dosage of different SGLT-2i. A total of 43,434 citations were identified, out of which forty-five randomized trials with 48,067 patients, mentioning the flozin dose and eGFR as an endpoint, were found to be eligible for further analysis. The median duration of the follow-up in the trials was 12 months (IQR 5.5–16 months). Canagliflozin 100 mg demonstrated distinct eGFR benefit with an odds ratio of 2.3 (CI 0.72–3.9) compared to placebo. A statistically non-significant eGFR benefit was observed with all other “-flozins.” Canagliflozin 100 mg drug dose category showed the highest sucra rank probability score of 93

Background and Aim: There has been a lack of uniformity on how to triage coronavirus disease 2019 (COVID-19) patients visiting the emergency units of hospitals. Triage tools are themselves spreading the pandemic in hospital areas. The present study compared a master two-step (M2ST) exercise stress test versus a 6-min walk test (6MWT) in COVID-19-positive patients visiting the emergency unit of a hospital. Materials and Methods: Thirty-nine patients underwent 6MWT followed by M2ST, while another set of 38 patients underwent M2ST followed by 6MWT in this randomized, crossover, open-label, and noninferiority study. The exercise tests assessed the change from baseline in SpO(2), heart rate (HR), respiratory rate, blood pressure, exertion, and dyspnea on the modified-Borg scale. Results: Noninferiority was established for SpO(2) (P < 0.05), systolic blood pressure (SBP; P < 0.001), and diastolic blood pressure (DBP; P < 0.05), but not for HR (P = 0.3) and respiratory rate (P = 0.6). The difference between the pretest and posttest (delta change) values for the parameters SpO(2), respiratory rate, HR, SBP, and DBP correlated significantly (P < 0.001) with Pearson correlation coefficient (r = 0.764, 0.783, 0.473, 0.838, and 0.783, respectively). The delta change values of modified-Borg scale for dyspnea (P = 0.291) and exertion (P = 0.208) were statistically insignificant between the two exercise tests. However, the correlation between the tests was statistically significant (P < 0.001). Conclusion: M2ST, a timesaving, cost-effective, and easy to perform exercise stress test, has been identified as a reliable alternative for 6MWT.

Background:Medications studied for therapeutic benefits in coronavirus disease 2019 (COVID-19) have produced inconclusive efficacy results except for steroids.Objective:A prospective randomized open-label, parallel-arm Phase I/II clinical trial was planned to compare essential oil (EO) blend versus placebo nebulization in mild COVID-19.Methods:A Phase I safety evaluation was carried out in a single ascending and multiple ascending dose study designs. We assessed Phase II therapeutic efficacy on COVID-19 and general respiratory symptoms on days 0, 3, 5, 7, 10, and 14 on the predesigned case record form. Viremia was evaluated on day 0, day 5, and day 10.Results:Dose-limiting toxicities were not reached with the doses, frequencies, and duration studied, thus confirming the formulation's preliminary safety. General respiratory symptoms (p < 0.001), anosmia (p < 0.05), and dysgeusia (p < 0.001) benefited significantly with the use of EO blend nebulization compared to placebo. Symptomatic COVID-19 participants with mild disease did not show treatment benefits in terms of symptomatic relief (p = 1.0) and viremia clearance (p = 0.74) compared to the placebo. EO blend was found to be associated with the reduced evolution of symptoms in previously asymptomatic reverse transcription polymerase chain reaction (RT-PCR)-positive study participants (p = 0.034).Conclusion:EO nebulization appears to be a safer add-on symptomatic relief approach for mild COVID-19. However, the direct antiviral action of the EO blend needs to be assessed with different concentrations of combinations of individual phytochemicals in the EO blend.

Introduction Econazole has been found efficacious as antitubercular in in vitro and in vivo animal studies. However, limited information is available for its safety and pharmacokinetics in humans. In our present study we have conducted single ascending dose, safety, and pharmacokinetic evaluation in healthy human volunteers with the purpose of enabling translation for tuberculosis. Methods This study was conducted as a single-center, ascending-dose, placebo-controlled, double blind design. Three ascending dose were chosen (250 , 500 , and 1000 mg) to be administered as a single oral dose. The volunteers were screened for potential eligibility. Participants were randomized to receive either Econazole or Placebo in a 6:2 design. Safety assessments and pharmacokinetic evaluations were carried out for each cohort. Results Econazole was found to be safe at all dose levels. No serious or severe adverse events occurred during the study. The AUC (0-infinity) showed a response relationship with a value of 49 +/- 3.47 h* mu g/ml, 17. 86 +/- 8.40 hr* mu g/ml, 35.54 +/- 13.94 hr* mu g/ml for 250 mg, 500 mg, and 1000 mg, respectively. Conclusion Based on the findings of our study, a dose of 500 mg Econazole, once a day orally was considered as appropriate for further evaluation.

Aim: To review the status of various approaches for prophylaxis of coronavirus disease 2019 (COVID-19) Background: The extensive spread of the novel COVID-19 has seen tremendous success over the span of few months In comparison, our progress in developing an adequate treatment or preventive modality has been sluggish, at most Review results: Many observational studies and clinical trials are published evaluating chloroquine and hydroxychloroquine as prophylactic measures for COVID-19 Some question its safety, some refute its use while some uphold its beneficial effect Although some scientific bodies advocated its routine use in some population without adequate evidence, current consensus proposes its prophylactic use in the context of clinical research only Apart from chemotherapeutic drugs, several vaccines are under various phases of clinical development Innovative vaccine development faces many hurdles as do the new drugs - from the inception of concept and establishing manufacturing process to time-consuming preclinical and clinical development, regulatory processes, large scale production, and then marketing There is a lot of hope and expectation from AstraZeneca's candidate vaccine, ChAdOx1-S, and Serum Institute of India's recombinant bacille Calmette-Guerin that are currently in phase III clinical trial In order to expedite vaccine development, controlled human infection models are also being explored Some research bodies also suggest using complementary and alternative medicine to supplement the existing and novel prophylactic therapies in preventing the infection Conclusion and clinical significance: The increase in literature on the management of COVID-19 reflects the demand to address the current pandemic At the same time, it becomes critical that research community works toward providing best evidence for guiding the clinicians' practice and that clinicians and regulators emphasize on appraising the existing evidence before prescribing and making policies, respectively

Context: Pharmaceuticals are released into the environment through human and industrial waste and waste due to handling. They significantly contaminate aquatic systems and through food chain, enter the body of human beings. The development of new techniques such as liquid chromatography and mass spectrometry has helped to detect and measure even the trace amounts of pharmaceutical compounds in the environment. At present, cardiovascular and antidiabetic agents are one of the most commonly prescribed drugs worldwide owing to chronicity of the diseases. However, there is a lack of knowledge regarding their effects on aquatic organisms and human beings once they are released into the environment. Aim: The aim of the study is to identify the extent and characteristics of the toxicity caused by environmental cardiovascular and antidiabetic agents on aquatic organisms and humans. Settings and Design: It will be systematic review of all original research articles which assess the environmental toxicity of one or more cardiovascular and antidiabetic drugs. Methodology: This systematic review will be conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data regarding acute and chronic toxicities caused by cardiovascular and antidiabetic drugs to fish, daphnia, algae, and humans will be collected. In addition, we will report sampling strategies and methodologies adopted to quantify drugs from the samples.

Inappropriate antimicrobial prescribing is considered to be the leading cause of high burden of antimicrobial resistance (AMR) in resource-constrained lower- and middle-income countries. Under its global action plan, the World Health Organization has envisaged tackling the AMR threat through promotion of rational antibiotic use among prescribers. Given the lack of consensus definitions and other associated challenges, we sought to devise and validate an Antimicrobial Rationality Assessment Tool—AmRAT—for standardizing the assessment of appropriateness of antimicrobial prescribing. A consensus algorithm was developed by a multidisciplinary team consisting of intensivists, internal medicine practitioners, clinical pharmacologists, and infectious disease experts. The tool was piloted by 10 raters belonging to three groups of antimicrobial stewardship (AMS) personnel: Master of Pharmacology (M.Sc.) (n = 3, group A), Doctor of Medicine (MD) residents (n = 3, group B), and DM residents in clinical pharmacology (n = 4, group C) using retrospective patient data from 30 audit and feedback forms collected as part of an existing AMS program. Percentage agreement and the kappa (κ) coefficients were used to measure inter-rater agreements amongst themselves and with expert opinion. Sensitivity and specificity estimates were analyzed comparing their assessments against the gold standard. For the overall assessment of rationality, the mean percent agreement with experts was 76.7% for group A, 68.9% for group B, and 77.5% for group C. The kappa values indicated moderate agreement for all raters in group A (κ 0.47–0.57), and fair to moderate in group B (κ 0.22–0.46) as well as group C (κ 0.37–0.60). Sensitivity and specificity for the same were 80% and 68.6%, respectively. Though evaluated by raters with diverse educational background and variable AMS experience in this pilot study, our tool demonstrated high percent agreement and good sensitivity and specificity, assuring confidence in its utility for assessing appropriateness of antimicrobial prescriptions in resource-constrained healthcare environments.

Objective To evaluate the efficacy, tolerability, and cost of four commonly prescribed oral iron preparations: ferrous sulfate (FS), ferrous fumarate (FF), ferrous ascorbate (FA), and carbonyl iron (CI) in the treatment of iron-deficiency anemia (IDA) in pregnant women. Methods It was a prospective, randomized, open-label, blinded endpoint (PROBE) design with four parallel active control groups: FS, FF, FA, CI. The primary outcome was the proportion of participants becoming non-anemic (Hb >= 11 g%) at the end of the study period. The secondary outcomes were the proportion of participants achieving normal red blood corpuscular indices such as mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration; the proportion of participants achieving normal iron indices such as serum iron, serum ferritin, total iron-binding capacity, and transferrin saturation; and comparison of incidence of any adverse events between treatment groups and comparison of costs of individual drug therapy between treatment groups. Results One hundred and twenty patients were randomized to four different groups (n = 30). The results of the present study show that all the four iron salts at the dose of 200 mg elemental iron per day were equally effective in improving hemoglobin concentration and other hematological parameters. The adverse effects were more common in the FF group (56.7%). The pharmacoeconomic analysis showed that all the drugs are equally cost-effective. Conclusion To conclude from the results of the present study, it can be said that FS, FF, FA, and CI are equally effective in treating IDA and they can be prescribed interchangeably.

As of 15 December 2020, 52 candidate vaccines are under clinical evaluation for novel COVID-19 and one vaccine has received emergency use authorisation.1 2 However, vaccine research ethics is evolving and finding urgent solutions becomes paramount. In this article, we highlight such ethical issues in the vaccine trials especially those being faced by low-middle-income countries (LMIC). 1. Review by institutional ethics committees (IECs) Even after months of pandemic, IECs in LMIC are finding it difficult to balance increasing number of clinical trials with timely review. Political pressure and unusual circumstances are compelling expedited reviews and approvals of seamless phase 1/2 and 2/3 trials. Although these processes provide early access to market, cutting short on vaccine development from 10 to 15 years to 10 to 18 months might compromise safety. Besides, assessment of ethical standards of new trial designs and ways adopted for data capture, recruitment and follow-up during pandemic requires time and vigilance and should not be hurried through. For instance, some sponsors are omitting the clause, ‘the participant should not have participated in any clinical trials within the last 3 or 6 months’, from the exclusion criteria,3 4 that is leading to co-enrolment of participants in multiple trials and acceptance of multiple payments for participation, which violate ethics in research. 2. Research conduct Smart devices are increasingly being used to address subject recruitment and follow-up during lockdowns. …

ObjectiveTo show that overpowered trials claim statistical significance detouring clinical relevance and warrant the need of superiority margin to avoid such misinterpretation.DesignSelective review of articles published in the New England Journal of Medicine between 1 January 2015 and 31 December 2018 and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist.Eligibility criteria for selecting studies and methodsPublished superiority trials evaluating cardiovascular diseases and diabetes mellitus with positive efficacy outcome were eligible. Fixed effects meta-analysis was performed using RevMan V.5.3 to calculate overall effect estimate, pooled HR and it was compared with mean clinically significant difference.ResultsThirteen eligible trials with 164 721 participants provided the quantitative data for this review. Largely, the primary efficacy endpoint in these trials was the composite of cardiovascular death, non-fatal myocardial infarction, unstable angina requiring rehospitalisation, coronary revascularisation and fatal or non-fatal stroke. The pooled HR was 0.86 (95% CI 0.84 to 0.89, I2=45%) which was lower than the mean clinically significant difference of 0.196 (19.6%, range: 0.09375–0.35) of these studies. There was a wide 95% CI in these studies from 0.56 to 0.99. The upper margin of CI in most of the studies was close to the line of no difference. Absolute risk reduction was small (1.19% to 2.3%) translating to a high median number needed to treat of 63 (range: 43 to 84) over a follow-up duration of 2.95 years.ConclusionsThe results of this meta-analysis indicate that overpowered trials give statistically significant results undermining clinical relevance. To avoid such misuse of current statistical tools, there is a need to derive superiority margin. We hope to generate debate on considering clinically significant difference, used to calculate sample size, as superiority margin.

Objective To show that overpowered trials claim statistical significance detouring clinical relevance and warrant the need of superiority margin to avoid such misinterpretation. Design Selective review of articles published in the New England Journal of Medicine between 1 January 2015 and 31 December 2018 and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Eligibility criteria for selecting studies and methods Published superiority trials evaluating cardiovascular diseases and diabetes mellitus with positive efficacy outcome were eligible. Fixed effects meta-analysis was performed using RevMan V.5.3 to calculate overall effect estimate, pooled HR and it was compared with mean clinically significant difference. Results Thirteen eligible trials with 164 721 participants provided the quantitative data for this review. Largely, the primary efficacy endpoint in these trials was the composite of cardiovascular death, non-fatal myocardial infarction, unstable angina requiring rehospitalisation, coronary revascularisation and fatal or non-fatal stroke. The pooled HR was 0.86 (95% CI 0.84 to 0.89, I-2=45%) which was lower than the mean clinically significant difference of 0.196 (19.6%, range: 0.09375-0.35) of these studies. There was a wide 95% CI in these studies from 0.56 to 0.99. The upper margin of CI in most of the studies was close to the line of no difference. Absolute risk reduction was small (1.19% to 2.3%) translating to a high median number needed to treat of 63 (range: 43 to 84) over a follow-up duration of 2.95 years. Conclusions The results of this meta-analysis indicate that overpowered trials give statistically significant results undermining clinical relevance. To avoid such misuse of current statistical tools, there is a need to derive superiority margin. We hope to generate debate on considering clinically significant difference, used to calculate sample size, as superiority margin.

Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India The authors have no conflicts of interest to declare.

Objective: Progress towards superiority trial design and analysis has been slow. A statistically significant result may not be clinically relevant. In this study, we aimed to show that overpowered trials show statistical significance sans clinical relevance. Design and method: We did a systematic review of all the superiority trials published in The New England Journal of Medicine, NEJM between January 1st, 2015 to December 31st, 2018. Search was restricted to trial populations with specific diseases such as cardiovascular diseases and diabetes mellitus. We evaluated clinically significant difference used to calculate sample size and compared with the findings. Results: Overall, 218,664 participants were included in the 16 trials that provided the quantitative data for this review. Largely, the primary efficacy endpoint in these trials was composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization, fatal or nonfatal stroke. Overall effect estimate was 0.85 (95% CI 0.83–0.88) which was lower than the mean clinically significant difference of 19.3 (range: 9.375 to 35) of these studies. There was a wide 95% CI in these studies from 0.56 to 0.99. CI in most of the studies was close to line of no difference. Absolute risk reduction was very low (0.08 to 2.3%) translating to high number needed to treat (mean: 70). Conclusions: The result of this systematic review suggests that overpowered trials give statistically significant results undermining clinical relevance. To avoid such misuse of current statistical tools, there is a need to derive superiority margin. We hope to generate debate on considering clinically significant difference, used to calculate sample size, as superiority margin.

Objective: Reporting and handling of missing data have recently received considerable attention. This systematic review has been planned to evaluate the patterns of reporting and handling missing data in cardiovascular clinical trials. In addition, the objective is to compare the current data management practices with the decade earlier Design and method: We conducted a systematic search of randomized controlled trials with pharmacological intervention on cardiovascular diseases published in 2018 in major clinical journals. Articles were tested for eligibility and assessed for documentation of handling missing data and the methodology used in the main article. Similar search for trials published in 2008 was also done Results: For the year 2018, a total of 29 cardiovascular trials were eligible. Trials which reported the findings of subgroup or post hoc analysis of other major trials were excluded. Out of 29, only six (20.7%) trials reported handling of missing data clearly. The approaches chosen in these trials were maximum likelihood (n = 2), Bayesian hierarchal logistic dose-response model (n = 1), multiple imputation (n = 2) and last observation carry forward (n = 1). Two trials clearly mentioned not using missing data for their final analysis. The remaining 21 (72.4%) trials did not mention anything about missing data and methods to handle it in their main manuscript. A comparison with the year 2008 is planned Conclusions: This review highlights the need for improvement in handling and reporting of missing outcome data in cardiovascular clinical trials since inadequate handling can lead to bias

[This corrects the article DOI: 10.3389/fphar.2016.00155.].