A comparative study of the efficacy and outcome of methylprednisolone and dexamethasone in moderate to severe COVID-19 disease

Background: COVID-19 disease is caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). In the first half of 2020 COVID-19 disease has already converted into a global pandemic. Many treatment options were explored through the world. Aims and Objectives: To compare the efficacy and outcome of methylprednisolone (MTP) and dexamethasone (DEXA) in moderate-to-severe COVID-19 disease. Materials and Methods: In this prospective study, a total of 140 moderate to severe COVID-19 patients were enrolled from 15 April to June 15, 2021. These patients were randomly allocated into two groups, 70 patients were received MTP 2 mg/kg/day for 3 days followed by 1.0 mg/kg/day for 3 days in divided doses while 70 patients received DEXA 8 mg/day in divided dose up to 10 days. Results: The mean age was 45.5 years in MTP group whereas 45.34 years in DEXA group. The clinical outcome in MTP group and DEXA group was assessed in terms of clinical improvement (92.85% vs. 81.42%), radiological improvement (82.85% vs. 68.57%), transfer to ICU (5.71 vs. 14.57%), needs of ventilatory support (2.85% vs. 8.57%) and mortality (7.14% vs. 18.57%) respectively. Conclusion: In this study, MTP demonstrated better outcome as compared to DEXA in COVID-19 patients.

Realgar Indigo Formula Plus ATRA As Postremission Treatment in an Rral and Chemo-Free Model for High-Risk Acute Promyelocytic Leukemia Patients: A Prospective, Multicenter, Phase II Study

Background: Low-risk patients with acute promyelocytic leukemia (APL) can be cured using only ATRA and arsenic trioxide (ATO), without chemotherapy(Lo-Coco F, et al. NEJM 2013) .Our group simplified the protocol by replacing iv ATO with oral arsenic, referred to as RIF, allowing for outpatient, oral and chemotherapy-free treatment for an increasing number of APL patients (Zhu HH, et al. NEJM 2014; 371:2239-41;Zhu HH, et al. Lancet Oncol 2018;19:871-879; Zhu HH, et al. Blood 2019;134:597-605). We also reported a promising single-center results using chemo-free postremission treatment for high-risk APL patients (Zhu HH, Blood 2018;131:2987-2989), which need to be confirmed in a well designed multi-center trial. Objective: To evaluate the efficacy of safety Realgar indigo formula plus retinoic acid as postremission treatment in an oral and chemo-free model for high-risk APL patients . Design, setting and participants: a prospective, multicenter, single-arm, phase II clinical trial conducted in the First Affiliated Hospital, Zhejiang University College of Medicine, China. Eligible patients (>18 years old) with newly diagnosed APL and achieved complete remission(CR) were enrolled since May 2019, with final follow-up in July 31,2021. Interventions: The consolidation therapy included realgar-Indigo naturalis formula (60 mg/kg daily in an oral divided dose) in a 4-week-on and4-week-off regimen for 4 cycles and ATRA (25 mg/m 2 daily in anoral divided dose) in a 2-week-on and 2-week-off regimen for 7 cycles. The primary endpoint was the 2-year DFS. Secondary endpoints included complete molecular remission (CMR) defined as the absence of detectable PML-RARA transcripts., event-free survival (EFS), OS, and safety. Main outcomes and measures: 38 eligible patients were enrolled including 18 males and 20 females and the median age was 41 years old (18-77 years). The median of WBC count is 25.39（10.2-113.9）×109/L[ >50×10 9/L n=10; (20-50)×10 9/L n=14，(10-20)×10 9/L n=14].All the patients achieved CMR during post-remission treatment phase (7 months). Until now, no molecular, hematologic recurrence,and central nervous system leukemia has happened with median follow-up of 13 months. What's more, this chemotherapy-free, completely oral regimen was well tolerated. C onclusions: These exciting results proved that RIF plus retinoic acid as postremission treatment of high-risk APL was effective, safe and convenient. The study is ongoing, and the effective of this regimen need to be evaluated by more patients and longer time. Figure 1. The overall survival(OS) and disease-free survival (DFS) of high-risk APL patients. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Effect of follicular ablation and gonadotropin priming on the recovery and quality of oocytes in Boran cows

Genetic differences have been suggested as a possible cause for variation in responses to exogenous hormones. Here we evaluated the effect of follicle ablation, exogenous FSH and coasting time prior to ovum pick-up (OPU) on the number of follicles suitable for aspiration, oocyte quality, and cleavage rate in Ethiopian Boran cows. The experiment was carried out in three parts, I) Cows were synchronized using 500µg PGF2α given 11 days apart. Cows were then subjected to a biweekly ovum pickup session before ovulation (n=5) or starting Day 7 after ovulation (n=4) for three weeks. II) Cows were similarly synchronized and all visible follicles were ablated on the first days of overt estrus which were then further grouped into cows that received a divided dose of 350IU FSH (n=5) or 175IU FSH (n=5) over three days. In both groups OPU was carried out weekly starting 48h after the last FSH for six weeks. III) A similar protocol as in part II was carried out but coasting period was increased to 72hrs for cows that received 350IU FSH as divided dose (n=5) and 48hrs coasting period for single 350IU FSH dose (n=5). The covariates of follicles and oocyte were not affected (P>0.05) by corpus luteum presence at OPU. The mean number of medium (7.36±0.57) and large (8.28±0.96) follicles were significantly higher (P<0.05) in group that received divided 350IU FSH. Similarly, the mean number of Grade-1 (4.19±0.24) and Grade-2 (4.32±.27) COC, maturation rate (70.41%) and cleavage rate (47.5%) were significantly higher (P<0.05) in group that received 350IU FSH. COC quality was significantly (P<0.05) influenced by costing period. However, both maturation and cleavage rates were not affected by the coasting period. This study demonstrated that follicular ablation and treatment with FSH improves follicular population and oocyte recovery rate in Boran cows.

Single Dose or Divided Dose of Polyethylene Glycol in Treatment of Pediatric Functional Constipation: A Randomized Clinical Trial

BackgroundThis study aimed to compare different regimens of Polyethylene Glycol (PEG, single dose vs. divided dose) in the treatment of functional constipation among children aged 4-15 years.Materials and MethodsThis double-blind randomized clinical trial was conducted on the children (4-15 years old) with functional constipation who were visited in an outpatient pediatric clinic affiliated to Shiraz University of Medical Sciences between February and July 2021. Among the120 eligible patients, 80 ones who met the inclusion criteria were recruited. The patients were divided into two parallel groups; the children who received single-dose PEG (group A) and those who received PEG in divided doses (group B). The study was performed during 12 weeks and follow-up visits were scheduled at 1, 3, 6, and 12 weeks after enrollment. The outcomes were measured using the Bristol Stool Form Scale (BSFS).ResultsThe study was performed on 78 cases including 45 boys (57.7%) and 33 girls (42.3%) with the mean age of 5.52±1.79 years. After 12 weeks, a significant difference was observed between groups A and B regarding the mean of BSFS (4.94±0.52 vs. 4.50±0.88, p=0.008). However, no significant difference was observed between the two groups regarding the number of defecation times during the study. The detected complications included mild abdominal pain in eight children in group A (5.3%), fecal incontinency in six children in group B (3.8%), and painful defecation in six children in group B (3.8%).ConclusionThis study confirmed that the administration of the single dose (0.4 g/kg) of PEG early in the morning was more effective, well tolerated, and accompanied by fewer complications compared to the divided dose.

The divided dose approach to perioperative buprenorphine management in patients with opioid use disorder

There is limited evidence and no clear consensus suggesting best practices for perioperative buprenorphine management in patients with opioid use disorder. As such, we aimed to develop a standardized perioperative management approach with the goals of (1) optimizing perioperative analgesia, (2) minimizing relapse risk, (3) setting expectations for patients and clinicians, (4) achieving prescribing consistency and mitigating risk among clinicians not familiar with perioperative buprenorphine management, and (5) maintaining continuity throughout care transitions. An interprofessional expert focus group convened to develop a consensus algorithm based upon buprenorphine's unique pharmacologic features and published perioperative management recommendations. The resulting consensus algorithm continues the patient's home buprenorphine dose in order to minimize relapse risk, but utilizes a divided dose approach starting the day of surgery if moderate to severe post-operative pain is expected. This strategy leverages the analgesic effects of buprenorphine while allowing for additional opioid binding to optimize analgesia. A patient-centered multimodal perioperative approach including local and/or regional anesthetics and nonopioid adjuncts is employed. Post-operative care is optimized by preoperative planning, including standardized patient assessment, perioperative communication with the buprenorphine prescriber, and education for patients and clinicians. Overall, integrating an understanding of pharmacology and clinical impact through the use of a readily adaptable algorithm such as the divided dose approach is key to optimizing patient care in this high-risk population.

A Comparative Study of High-Dose Colistin Administration for the Management of Multidrug-Resistant Gram-Negative Infections in the ICU

The aim of this study was to assess the clinical and microbiological efficacy and toxicity of different high-dose regimens of colistin in the ICU patients with colistin-sensitive MDR Gram-negative infections. In this prospective, open label, randomized clinical trial, patients with clinical features of infection and positive culture for MDR colistin-sensitive Gram-negative bacteria were randomly allocated to receive colistin, 3 or 9 million units every 8 and 24 hours, (groups A and B), respectively. For each dose regimen, clinical and microbiological response, the rates of nephrotoxicity, and its risk factors were analyzed. Forty-three patients were enrolled, and 35 completed the study protocol, of whom 30 (88.2%) had ventilator-associated pneumonia (VAP) and 5 (14%) had bacteremia. Although there were no statistically significant differences in the clinical or microbiological response between the study groups, the microbiological response favored the divided dose group numerically ( p = 0.40 ). Clinical response was achieved in 27 of 35 (77.1%) patients ( p = 0.999 ). Twelve (34.28%) patients developed AKI during colistin treatment, 4 and 8 in groups A and B, respectively ( p value =0.193). Significant risk factors for nephrotoxicity related to colistin were age, hyperbilirubinemia, and coadministration of other nephrotoxic agents. In multivariate regression analysis, the only independent risk factor for CMS-associated AKI was hyperbilirubinemia ( p value =0.008). Although the clinical and microbiological responses to colistin administration were not statistically different in two groups, the microbiological response favored the divided dose regimen group numerically. We did not observe any significant safety concerns with high-dose colistin administration in this population.

STUDY ON OUTCOME OF SINGLE MORNING TOTAL DOSE OF ORAL PREDNISOLONE VERSUS DIVIDED DOSE OF ORAL PREDNISOLONE IN TREATMENT OF STEROID SENSITIVE NEPHROTIC SYNDROME

Nephrotic syndrome is a common renal disorder characterised by Massive proteinuria (>40 mg/m2/day); hypoalbuminemia and edema. Relapses of nephrotic syndrome are usually treated with prednisolone. Study was aimed to compare the efficacy, complication and compliance of single morning daily total dose versus divide daily dose of oral prednisolone in treating steroid sensitive nephrotic syndrome(SSNS). The study was conducted on patients diagnosed as 1st attack Nephrotic Syndrome or relapse case with SSNS visiting nephrology clinic and admitted in pediatric ward in S.S.G Hospital Vadodara. Total 60 patients were taken in prospective randomised observational study.Patients with 1st attack or relapse were randomized to receive prednisolone 2 mg/ kg per day, either as a single dose (Group A) or in divided doses (Group B) until remission, followed by 1.5 mg/kg on every alternate day. Complication parameters Blood Pressure, Random Blood Sugar, urine output and GI upset were noted. Data was analysed by applying standard statistical test and Med CalC. We observed that average time take for remission after starting the treatment in group A and group B was 14.13 and 17.13 days. Compliance was observed better with single dose then divided dose and fluctuation in blood pressure, random blood sugar, GI upset were observed more with divided dose. Study concluded that single dose did not suppress HPA axis.

Micronutrient supplementation of lactating Guatemalan women acutely increases infants’ intake of riboflavin, thiamin, pyridoxal, and cobalamin, but not niacin, in a randomized crossover trial

ABSTRACT Background Maternal supplementation during lactation could increase milk B-vitamin concentrations, but little is known about the kinetics of milk vitamin responses. Objectives We compared acute effects of maternal lipid-based nutrient supplement (LNS) consumption (n = 22 nutrients, 175%–212% of the RDA intake for the nutrients examined), as a single dose or at spaced intervals during 8 h, on milk concentrations and infant intake from milk of B-vitamins. Methods This randomized crossover trial in Quetzaltenango, Guatemala included 26 mother–infant dyads 4–6 mo postpartum who were randomly assigned to receive 3 treatments in a random order: bolus 30-g dose of LNS (Bolus); 3 × 10-g doses of LNS (Divided); and no LNS (Control), with control meals. Mothers attended three 8-h visits during which infant milk consumption was measured and milk samples were collected at every feed. Infant intake was assessed as $\mathop \sum \nolimits_{i\ = \ 1}^n ( {{\rm{milk\ volum}}{{\rm{e}}_{{\rm{feed\ }}n}} \times \ {\rm{nutrient\ concentratio}}{{\rm{n}}_{{\rm{feed}}\ n}}} )$ over 8 h. Results Maternal supplementation with the Bolus or Divided dose increased least-squares mean (95% CI) milk and infant intakes of riboflavin [milk: Bolus: 154.4 (138.2, 172.5) μg · min−1 · mL−1; Control: 84.5 (75.8, 94.3) μg · min−1 · mL−1; infant: Bolus: 64.5 (56.1, 74.3) μg; Control: 34.5 (30.0, 39.6) μg], thiamin [milk: Bolus: 10.9 (10.1, 11.7) μg · min−1 · mL−1; Control: 7.7 (7.2, 8.3) μg · min−1 · mL−1; infant: Bolus: 5.1 (4.4, 6.0) μg; Control: 3.4 (2.9, 4.0) μg], and pyridoxal [milk: Bolus: 90.5 (82.8, 98.9) μg · min−1 · mL−1; Control: 60.8 (55.8, 66.3) μg · min−1 · mL−1; infant: Bolus: 39.4 (33.5, 46.4) μg; Control: 25.0 (21.4, 29.2) μg] (all P &lt; 0.001). Only the Bolus dose increased cobalamin in milk [Bolus: 0.054 (0.047, 0.061) μg · min−1 · mL−1; Control: 0.041 (0.035, 0.048) μg · min−1 · mL−1, P = 0.039] and infant cobalamin intake [Bolus: 0.023 (0.020, 0.027) μg; Control: 0.015 (0.013, 0.018) μg, P = 0.001] compared with Control. Niacin was unaffected. Conclusions Maternal supplementation with LNS as a Bolus or Divided dose was similarly effective at increasing milk riboflavin, thiamin, and pyridoxal and infant intakes, whereas only the Bolus dose increased cobalamin. Niacin was unaffected in 8 h. This trial was registered at clinicaltrials.gov as NCT02464111.

Topiramate Versus Propranolol in the Prophylaxis of Migraine in Bangladeshi Population

Background : Migraine is primary headache disorder characterized by recurring attacks of pain and associated symptoms. The management modality is still unsatisfactory due to poor understanding of its cause and pathogenesis. To assess the efficacy and safety of low dose Topiramate vs Propranolol in migraine prophylaxis. Materials and methods : A randomized clinical trial including 130 patients with frequent migraine headache >5 attacks per month was performed in the out patients Department of Medicine and Neurology, CMCH for a period of 12 weeks. The patients were randomly divided into two treatment groups – treated by Topiramate 50mg/day and Propranolol 80mg/day respectively. Topiramate started with 25mg/day for 7 days then increased up to 50mg/day in two divided dose. Propranolol started with 40mg/day for 7 days then increased up to 80mg/day in two divided dose. The patients were assessed at 0, 8 and 12 weeks of the study. Results: The Topiramate group showed a reduction in the mean (±SD) of frequency of migraine attack from 6.95(±2.88) to 1.75(±1.08) episode per month, headache days per month from 7.62(±4.14) to 1.83(±1.10), intensity of headache per attack from 8.98(±1.05) to 6.10(±2.50) based on VAS scale, duration of headache per episode from 11.56(±9.16) to 5.40(±2.97) per hour and MIDAS score from 16.19(±3.91) to 8.14(±3.93). In patient treated with Propranolol, the mean (±SD) of monthly frequency of migraine attack declined from 7.09(±2.87) to 1.92(±0.98) episode per month, headache days per month from 8.17(±4.52) to 1.86(±o.83), intensity of headache per attack from 8.47(±1.10) to 6.03(±2.05) based on VAS scale, duration of headache per episode from 11.16(±8.08) to 5.97(±3.45), MIDAS score from 15.48(±3.55) to7.77(±3.49). Pre- and post-treatment values were significantly different for individual groups but no significant difference observed between groups. Conclusion: This study demonstrated that both low dose Topiramate and propranolol could significantly reduce migraine frequency, intensity and duration. Chatt Maa Shi Hosp Med Coll J; Vol.18 (2); July 2019; Page 12-17