Comparison of efficacy of topical alcaftadine (0.25%) versus olopatadine (0.1%) in allergic conjunctivitis

The most common atopic ocular condition in clinical practice is allergic conjunctivitis. One of the preferred treatment options for allergic Conjunctivitis is anti histamines eye drops. The study purpose is to compare the clinical efficacy between topical alcaftadine 0.25% and olopatadine hydrochloride 0.1% in allergic conjunctivitis patients.A prospective, randomized, open label, parallel group, comparative study was conducted on 60 Patients with bilateral allergic conjunctivitis (30 in each group) after taking an informed written consentand was evaluated from May 2018 to November 2018. Patients were randomized into 2 groups of 30 each, group A received topical Alcaftadine 0.25% twice daily and patients in Group B received topical olopatadine hydrochloride 0.1% twice daily for 2 weeks. The patients were evaluated on first visit (baseline) followed by 7 and 14 day after starting the treatment. At each visit signs and symptoms were evaluated and rated using a scale from 0-3(0-Absent, 1- mild, 2 moderate and 3- severe). The change from baseline in the mean scores of itching, hyperemia, photophobia and tearing on day 14 is the primary outcome variable.: The signs and symptoms of allergic conjunctivitis were reduced by 2 weeks from baseline after using both the drugs. Relative significant efficacy was achieved in alcaftadine group for Itching, hyperemia and photophobia, but not for tearing (p=0.3). When compared to 0.1% olopatadine hydrochloride, 0.25% alcaftadine is more effective in reducing the symptoms of all types of allergic conjunctivitis except those mentioned in exclusion criteria.

Effect of dexamethasone in patients with ARDS and COVID-19 (REMED trial)—study protocol for a prospective, multi-centre, open-label, parallel-group, randomized controlled trial

Background Since December 2019, SARS-CoV-2 virus has infected millions of people worldwide. In patients with COVID-19 pneumonia in need of oxygen therapy or mechanical ventilation, dexamethasone 6 mg per day is currently recommended. However, the dose of 6 mg of dexamethasone is currently being reappraised and may miss important therapeutic potential or may prevent potential deleterious effects of higher doses of corticosteroids. Methods REMED is a prospective, open-label, randomised controlled trial testing the superiority of dexamethasone 20 mg (dexamethasone 20 mg on days 1–5, followed by dexamethasone 10 mg on days 6–10) vs 6 mg administered once daily intravenously for 10 days in adult patients with moderate or severe ARDS due to confirmed COVID-19. Three hundred participants will be enrolled and followed up for 360 days after randomization. Patients will be randomised in a 1:1 ratio into one of the two treatment arms. The following stratification factors will be applied: age, Charlson Comorbidity Index, CRP levels and trial centre. The primary endpoint is the number of ventilator-free days (VFDs) at 28 days after randomisation. The secondary endpoints are mortality from any cause at 60 days after randomisation; dynamics of the inflammatory marker, change in WHO Clinical Progression Scale at day 14; and adverse events related to corticosteroids and independence at 90 days after randomisation assessed by the Barthel Index. The long-term outcomes of this study are to assess long-term consequences on mortality and quality of life at 180 and 360 days. The study will be conducted in the intensive care units (ICUs) of ten university hospitals in the Czech Republic. Discussion We aim to compare two different doses of dexamethasone in patients with moderate to severe ARDS undergoing mechanical ventilation regarding efficacy and safety. Trial registration EudraCT No. 2020-005887-70. ClinicalTrials.gov NCT04663555. Registered on December 11, 2020

Strategies for discontinuation of proton pump inhibitors (PPIs) in patients with long-term PPI administration: a randomized controlled trial

Background Proton pump inhibitors (PPIs), including potassium ion-competitive acid blocker, are widely used worldwide and are often used for long periods of time. However, in recent years, potential side effects associated with long-term PPI use have been reported. Many patients take PPI for a long period of time, even though it is unnecessary, and it is necessary to discontinue PPI administration in such patients. However, sudden discontinuation may cause symptoms to recur and discontinuation may be unsuccessful. A strategy for safe and secure PPI discontinuation has not yet been established. The purpose of this study is to determine whether PPI can be safely discontinued by tapering the PPI dose or by abrupt discontinuation of PPI, and to establish a strategy for safe and secure PPI discontinuation. Methods The evaluation will be conducted as a multicenter, randomized, parallel-group clinical trial with five assessment points at the start of the study and 2 weeks, 4 weeks, 6 months, and 12 months after the start of the study. One intervention group is the group in which PPI administration is abruptly discontinued (Group A), and the second group is the group in which the PPI dose is gradually tapered and then PPI administration is discontinued (Group B). The primary outcome and secondary outcome are the proportion of patients who successfully discontinued the PPI at 6 months and at 12 months after the start of the study in groups A and B, respectively. Discussion We predict that the proportion of patients who successfully discontinue PPI will be higher in the group in which PPI administration was gradually tapered than in the group in which PPI administration was abruptly discontinued. On the other hand, we expect that many participants will succeed in discontinuing PPI regardless of the discontinuation strategy due to the explanation that discontinuation is necessary. Trial registration Japan Registry of Clinical Trials, jRCT1031180383. Registered 20 March 2019, https://jrct.niph.go.jp/latest-detail/jRCT1031180383.

Insecticidal efficacy against Phlebotomus perniciosus in dogs treated orally with fluralaner in two different parallel-group, negative-control, random and masked trials

Background Dogs are the reservoir host of Leishmania infantum, the agent of zoonotic visceral leishmaniasis (VL), which is transmitted by the bite of phlebotomine sand flies. The sand fly Phlebotomus perniciosus is the main vector of zoonotic VL in the western Mediterranean region. Fluralaner has been shown to effectively kill this vector. The aim of this study was to evaluate the insecticidal efficacy of oral fluralaner in dogs bitten by P. perniciosus. Methods Two parallel-group, negative-controlled, randomized, masked laboratory trials with equivalent designs were performed in two different locations using two different pathogen-free laboratory-bred P. perniciosus strains for the challenge. In each trial, 12 purpose-bred beagles, initially ranked on natural attractiveness to sand flies, were randomly allocated to two groups (6 animals/group). Dogs in one group received fluralaner orally at the approved dose on day 0, and dogs in the control group were not treated. Each dog was subsequently exposed to an average of 70 unfed live sand fly females on days 1, 28, 56 and 84. Viability of blood-fed females was then evaluated for up to 96 h after exposure, and insecticidal efficacy was measured as the survival rate of flies fed on the fluralaner-treated dogs versus that of dogs in the control group. Significance was calculated for the proportion of live fed sand fly counts from treated versus control group dogs. Results Comparison of the survival proportions between treated and control groups showed that fluralaner insecticidal efficacy was highly significant in both trials (P < 0.001 or P < 0.01 in different assessments) through to day 56. In the first trial, efficacy reached 100% on days 1 and 28, and 99.1% on day 56; in the second trial, the insecticidal efficacy was 98.5, 100 and 85.9%, respectively on the same days. On day 84, efficacy was in the range of 53–57% (P < 0.05) in the first trial and 0% in the second trial. Conclusion A single oral fluralaner administration to dogs under laboratory conditions results in strong and reproducible insecticidal efficacy against P. perniciosus for at least 8 weeks. Graphical Abstract

A comparative clinical study of Khanda Shunthi and Prasarni Avaleha in the Management of Ama Vata w.s.r. to Rheumatoid Arthritis

Rheumatoid Arthritis is a chronic inflammatory joint disease characterized by swollen, painful and stiff joints. Amavata is a disease of Madhyama Roga Marga as it affects Sandhis and Haridaya Marma. Though Ama and Vata are the predominant pathogenic factors but the disease represents Tridoshic vitiation. The affliction of Sandhis by Vata dosha in association with Ama reflects the equal role of both Dosha and Dushya in the causation of disease. Moreover, the chief pathogenic factors, being contradictory in nature possess difficulty in planning the line of treatment. The objectives of this randomized parallel group comparative study were to evaluate the effect of Khanda Shunthi and Prasarni Avaleha in the management of Amavata. This Study was conducted on 40 patients selected randomly from OPD and IPD of Desh Bhagat Ayurvedic Hospital and divided into 2 trial groups A and B having 20 patients in each group. Group A received Khanda Shunthi 10 gms BD and Group B received Prasarni Avaleha 10 gms BD with lukewarm water for 60 days. Results showed statistically significant difference in effect of Group A and Group B on, Pain, Swelling, Stiffness, ESR, Walking time and Grip Strength except on Fever and HB. Percent wise Khanda Shunthi is found to be more effective than Prasarni Avaleha for all assessment criteria in the management of Amavata.

Protocol of a parallel group Randomized Control Trial (RCT) for Mobile-assisted Medication Adherence Support (Ma-MAS) intervention among Tuberculosis patients

Background Non-adherence to Tuberculosis (TB) medication is a serious threat to TB prevention and control programs, especially in resource-limited settings. The growth of the popularity of mobile phones provides opportunities to address non-adherence, by facilitating direct communication more frequently between healthcare providers and patients through SMS texts and voice phone calls. However, the existing evidence is inconsistent about the effect of SMS interventions on TB treatment adherence. Such interventions are also seldom developed based on appropriate theoretical foundations. Therefore, there is a reason to approach this problem more rigorously, by developing the intervention systematically with evidence-based theory and conducting the trial with strong measurement methods. Methods This study is a single-blind parallel-group design individual randomized control trial. A total of 186 participants (93 per group) will be individually randomized into one of the two groups with a 1:1 allocation ratio by a computer-generated algorithm. Group one (intervention) participants will receive daily SMS texts and weekly phone calls concerning their daily medication intake and medication refill clinic visit reminder and group two (control) participants will receive the same routine standard treatment care as the intervention group, but no SMS text and phone calls. All participants will be followed for two months of home-based self-administered medication during the continuation phases of the standard treatment period. Urine test for the presence of isoniazid (INH) drug metabolites in urine will be undertaken at the random point at the fourth and eighth weeks of intervention to measure medication adherence. Medication adherence will also be assessed by self-report measurements using the AIDS Clinical Trial Group adherence (ACTG) and Visual Analogue Scales (VAS) questionnaires, and clinic appointment attendance registration. Multivariable regression model analysis will be employed to assess the effect of the Ma-MAS intervention at a significance level of P-value < 0.05 with a 95% confidence interval. Discussion For this trial, a mobile-assisted medication adherence intervention will first be developed systematically based on the Medical Research Council framework using appropriate behavioural theory and evidence. The trial will then evaluate the effect of SMS texts and phone calls on TB medication adherence. Evidence generated from this trial will be highly valuable for policymakers, program managers, and healthcare providers working in Ethiopia and beyond. Trial registration The trial is registered in the Pan-Africa Clinical Trials Registry with trial number PACTR202002831201865.

Daily intake of Citrus jabara fruit peel powder (Japanese Patent No. 5,323,127) improves allergy-like symptoms: A randomized double-blind parallel-group comparative study

Citrus jabara (CJ) is a rare citrus fruit that used to grow naturally only in the southern part of the Kii Peninsula in Japan. Human intervention studies with oral intake of CJ fruit have shown its anti-allergic effects, but the testing method was a pre-post comparison study. In this study, we conducted a randomized, double-blind, parallel-group interventional study to evaluate the volume-dependent effects of oral intake of CJ fruit peel powder (Japanese Patent No. 5,323,127) on nasal and eye allergy-like symptoms. Ninety healthy adults were allocated to three groups and given test foods containing 1,000, 500, and 0 mg of CJ peel powder, with one packet per day for 4 weeks. After excluding those who dropped out or deviated from the study protocol, 73 were included in the efficacy analysis and 86 in the safety analysis. The high-dose group (1,000 mg/day) was significantly lower than the placebo group in the scores of “nasal and eye symptoms” at week 4, and “blocked nose” at weeks 2 and 4 in the evaluation of question I of Japanese Rhino-conjunctivitis Quality of Life Questionnaire (JRQLQ No. 1). The changes in scores (difference from the pre-observation period) on the Nasal and Eye Symptom Questionnaire showed a dose-dependent reduction in rhinorrhea. In the safety evaluation, there were no significant differences in examinations of physiology, hematology, and blood biochemistry between the groups, and no adverse events attributable to the test foods were observed. These results suggest that intake of CJ peel powder can alleviate allergy-like symptoms.