Colchicine and high-intensity rosuvastatin in the treatment of non-critically ill patients hospitalised with COVID-19: a randomised clinical trial.

OBJECTIVE: To evaluate the effect of colchicine and high-intensity rosuvastatin in addition to standard of care on the progression of COVID-19 disease in hospitalised patients. DESIGN: A pragmatic, open-label, multicentre, randomised controlled trial conducted from October 2020 to September 2021. Follow-up was conducted at 30 and 60 days. The electronic medical record was used at all stages of the trial including screening, enrolment, randomisation, event ascertainment and follow-up. SETTING: Four centres in the Yale New Haven Health System. PARTICIPANTS: Non-critically ill hospitalised patients with COVID-19. INTERVENTIONS: Patients were randomised 1:1 to either colchicine plus high-intensity rosuvastatin in addition to standard of care versus standard of care alone. Assigned treatment was continued for the duration of index hospitalisation or 30 days, whichever was shorter. PRIMARY AND SECONDARY OUTCOME MEASURES: The prespecified primary endpoint was progression to severe COVID-19 disease (new high-flow or non-invasive ventilation, mechanical ventilation, need for vasopressors, renal replacement therapy or extracorporeal membrane oxygenation, or death) or arterial/venous thromboembolic events (ischaemic stroke, myocardial infarction, deep venous thrombosis or pulmonary embolism) evaluated at 30 days. RESULTS: Among the 250 patients randomised in this trial (125 to each arm), the median age was 61 years, 44% were women, 15% were Black and 26% were Hispanic/Latino. As part of the standard of care, patients received remdesivir (87%), dexamethasone (92%), tocilizumab (18%), baricitinib (2%), prophylactic/therapeutic anticoagulation (98%) and aspirin (91%). The trial was terminated early by the data and safety monitoring board for futility. No patients were lost to follow-up due to electronic medical record follow-up. There was no significant difference in the primary endpoint at 30 days between the active arm and standard of care arm (15.2% vs 8.8%, respectively, p=0.17). CONCLUSIONS: In this small, open-label, randomised trial of non-critically ill hospitalised patients with COVID-19, the combination of colchicine and rosuvastatin in addition to standard of care did not appear to reduce the risk of progression of COVID-19 disease or thromboembolic events, although the trial was underpowered due to a lower-than-expected event rate. The trial leveraged the power of electronic medical records for efficiency and improved follow-up and demonstrates the utility of incorporating electronic medical records into future trials. TRIAL REGISTRATION: NCT04472611.

Design and rationale of the colchicine/statin for the prevention of COVID-19 complications (COLSTAT) trial.

BACKGROUND: Despite improvement in the standard of care (SOC) for hospitalized COVID-19 patients, rates of morbidity and mortality remain high. There continues to be a need for easily available and cost-effective treatments. Colchicine and rosuvastatin are both safe and well-studied medications with anti-inflammatory and other pleiotropic effects that may provide additional benefits to hospitalized COVID-19 patients. METHODS AND RESULTS: The Colchicine/Statin for the Prevention of COVID-19 Complications (COLSTAT) trial is a pragmatic, open-label, multicenter, randomized trial comparing the combination of colchicine and rosuvastatin in addition to SOC to SOC alone in hospitalized COVID-19 patients. Four centers in the Yale New Haven Health network will enroll a total of 466 patients with 1:1 randomization. The trial will utilize the electronic health record (Epic® Systems, Verona, Wisconsin, USA) at all stages including screening, randomization, intervention, event ascertainment, and follow-up. The primary endpoint is the 30-day composite of progression to severe COVID-19 disease as defined by the World Health Organization ordinal scale of clinical improvement and arterial/venous thromboembolic events. The secondary powered endpoint is the 30-day composite of death, respiratory failure requiring intubation, and myocardial injury. CONCLUSIONS: The COLSTAT trial will provide evidence on the efficacy of repurposing colchicine and rosuvastatin for the treatment of hospitalized COVID-19 patients. Moreover, it is designed to be a pragmatic trial that will demonstrate the power of using electronic health records to improve efficiency and enrollment in clinical trials in an adapting landscape. CLINICAL TRIAL REGISTRATION: NCT04472611 (https://clinicaltrials.gov/ct2/show/NCT04472611).

Demonstrating synchronization of isorhythmic dissociation with stress testing.

There are a variety of causes of atrial and ventricular dyssynchrony. The mechanism underlying the arrhythmia is usually a guide to further management. This case highlights the key distinguishing features of more benign etiologies.

Percutaneous Cecostomy in Adult Patients: Safety and Quality-of-Life Results.

PURPOSE: To assess the safety and quality of life in adult patients undergoing cecostomy tube placement. MATERIALS AND METHODS: Percutaneous cecostomy was performed in 23 adults (10 men and 13 women) with neurogenic bowel for whom noninvasive therapeutic approaches for chronic refractory constipation or fecal incontinence had failed. Mean patient age was 41 years (range, 19-74 y). A retrospective, standardized questionnaire evaluated satisfaction and quality of life before and after cecostomy. RESULTS: All 23 cecostomy procedures were technically successful with no intraprocedural complications. At a mean follow-up of 42 months (range, 1-160 mo), there was one (5%) major complication, a pericecal abscess. One or more minor complications in 11 of 23 (48%) patients included leaking around the tube (5 of 23; 22%) and partial or complete dislodgment of the tube (3 of 23; 13%). In all cases, the cecostomy tube was exchanged successfully. Satisfaction scores improved from a mean of 2.2 points (range, 0-6 points; median, 1.5) to 7.6 points (range, 4-10 points; median, 8). The percentage of patients using laxative softeners decreased from 74% to 40%, and patients requiring assistance decreased from 52% to 35% after cecostomy placement. CONCLUSIONS: Percutaneous cecostomy is a safe procedure for the management of adult patients. Patients are able to achieve greater independence in their activities of daily living and are highly satisfied with the outcomes.

Bleomycin Foam Treatment of Venous Malformations: A Promising Agent for Effective Treatment with Minimal Swelling.

PURPOSE: To report clinical and radiographic outcomes of patients with venous malformations (VMs) treated with bleomycin foam. MATERIALS AND METHODS: Twenty patients (age, 2-68 y) presented with symptoms of swelling (n = 19; 95%), pain (n = 14; 70%), and bleeding (n = 4; 20%). Lesions were located in the head and neck in 17 patients (85%), extremities in two (10%), and mediastinum in one (5%). Twenty-seven embolizations were performed, with a mean of 1.7 ± 1.0 treatments per patient (range, 1-4). An average of 0.45 ± 0.4 U/kg of bleomycin foam was used per procedure, with a range of 0.1-2.3 U/kg. RESULTS: All procedures were technically successful with no intraprocedural complications. Mean follow-up was 66 days ± 80, with a range of 4-403 days. Postprocedure complications were minor in 6 of 27 procedures (22%) and major in 2 of 27 procedures (7%). All 20 patients (100%) reported improvement in their symptoms after a single treatment session. Postprocedural magnetic resonance (MR) imaging demonstrated volume reduction of treated lesions in 13 of 14 patients (93%), with a mean lesion volume reduction of 66% ± 21. Enhancement on MR imaging after treatment was decreased in 11 of 14 patients (79%), increased in two (14%), and stable in one (7%). T2 signal intensity on MR imaging after treatment was decreased in 12 of 14 patients (86%) and stable in two (14%). CONCLUSIONS: The use of bleomycin foam for the percutaneous treatment of VMs is safe and effective. Foaming bleomycin may be used to address the dose limitations of the liquid.

Risk factors predisposing to congenital heart defects.

INTRODUCTION: Congenital heart disease (CHD) is associated with multiple risk factors, consanguinity may be one such significant factor. The role of consanguinity in the etiology of CHD is supported by inbreeding studies, which demonstrate an autosomal recessive pattern of inheritance of some congenital heart defects. This study was done to find out the risk factors for CHD. METHODS: A case-control study was done on pediatric patients at a tertiary care hospital, Aga Khan University Hospital, located in Karachi, Pakistan. A total of 500 patients, 250 cases and 250 controls were included in the study. RESULTS: Amongst the 250 cases (i.e. those diagnosed with CHD), 122 patients (48.8%) were born of consanguineous marriages while in the controls (i.e. non-CHD) only 72 patients (28.9%) showed a consanguinity amongst parents. On multivariate analysis, consanguinity emerged as an independent risk factor for CHD; adjusted odds ratio 2.59 (95% C. I. 1.73 - 3.87). Other risk factors included low birth weight, maternal co-morbidities, family history of CHD and first born child. On the other hand, medications used by the mother during the index pregnancy, maternal age and gender of the child did not significantly increase the risk of developing CHD. CONCLUSIONS: Analyses of our results show that parental consanguinity, family history of CHD, maternal co-morbidities, first born child and low birth weight are independent risk factors for CHD.

Role of clean intermittent self catheterisation (CISC) in the prevention of recurrent urethral strictures after internal optical urethrotomy.

BACKGROUND: Urethral stricture is one of the oldest diseases Urethral dilatation Internal optical urethrotomy,were the only treatment. Clean Intermittent Self Catheterisation was introduced by Lapides has greatly decreased the recurrence of stricture. Objectives were to determine the role of Clean Intermittent Self Catheterisation (CISC) in the prevention of recurrence of urethral strictures after Internal Optical Urethrotomy and to study the frequency of any postoperative complications and tolerability for the patients associated with this procedure. METHODS: A randomised controlled study conducted in the department of urology and renal transplantation, Institute of Kidney Diseases Hayatabad Medical Complex, Peshawar from June 2007 to June 2010. Total of 60 patients with mean age 48 years (range 20-73) were selected and randomly divided into Treatment Group (30 patients) and Control Group (30 Patients). Eight "drop out" occurred in the treatment group and four "drop out" occurred in the controlled group. All the patients were treated with Internal Optical Urethrotomy using Sachse method followed by indwelling catheter for 5 days. The treatment group was then taught to perform Clean Intermittent Self Catheterisation by inserting a Classic Neleton Catheter (No. 16 or 18) twice a day for 1 week, then once a day for another 4 weeks and then once weekly continued for one year. All the patients were followed up regularly at 1 month intervals during the first 6 months and then every 2 months for the next 6 months. RESULTS: Total of 48 patients completed the study, 22 in the treatment group and 26 in the control group. Within the first year, 4 patients (22%) in the treatment group developed urethral stricture. In the control group, 12 patients (46%) developed urethral stricture within the first year, showing a significant difference (p < 0.01). In the treatment group four patients developed simple UTIs while in the control group three patients developed UTIs, one with concomitant epididymitis. No other complications were noted up to one year follow up. CONCLUSION: Clean Intermittent Self Catheterisation is a simple and effective way of reducing stricture recurrence after Internal Optical Urethrotomy and is associated with less morbidity and is cost effective. CISC is an important modality for maintaining the normal urethral calibre.

Role of simplified admission criteria for predicting severe complications of gall stone pancreatitis.

BACKGROUND: Gallstone Pancreatitis (GP) is not an uncommon disease in our country and is associated with large number of morbidity and mortality especially if severe complications develop. Different criteria have been developed to predict the complications of GP. Simple admission criteria are better predictors of severe complications of GP than an APACHE II score of 5 or greater, a modified Imrie (Glasgow) score of 3 or greater, and a Biliary Ranson score of 3 or greater. The purpose of this study was to determine the role of simplified admission criteria in predicting severe complications of Gallstone Pancreatitis. METHODS: This was a descriptive study conducted in Surgical 'A' Unit, Khyber Teaching Hospital Peshawar between July 16th 2007 to November 30th 2008. Total 52 patients (42 women and 10 men, aged range from 18 to 76 years, with mean age, 39 years) who presented to our unit with gallstone pancreatitis were included in the study through technique of non-probability convenient sampling. The main outcome measures were major local and systemic complications requiring intensive care unit care, and death. Physiological factors and laboratory data were collected on admission and recorded daily. RESULTS: Seven patients (14%) had severe complications with mortality of 2%. On univariate analysis, a white blood cell count of 14500/dL or more (p = 0.03), a serum glucose level of or more > or = 150 mg/dL (8.3 mmol/L) (p < 0.001), an APACHE II score of 5 or greater (p = 0.008), a modified Imrie score of 3 or greater (p < 0.001), and a biliary Ranson score of 3 or greater (p = 0.03) were statistically associated with the development of severe complications. On multivariate analysis, only a serum glucose level of > or = 150 mg/dL or more (8.3 mmol/L) was predictive of adverse events (p < 0.001). CONCLUSIONS: Glucose level (> or = 150 mg/dL) is the best single admission predictor of severe complications of Gallstone Pancreatitis and is superior to an APACHE II score of 5 or greater, a modified Imrie score of 3 or greater, and a biliary Ranson score of 3 or greater.