Effective Treatment For High-risk Patients Research Articles

Effect of spirulina on risk of hospitalization among patients with COVID-19: the TOGETHER randomized trial

BackgroundAlgae-derived nutraceuticals, such as spirulina, have been reported to have biological activities that may minimize clinical consequences to COVID-19 infections. ObjectivesThis study aimed to determine whether spirulina is an effective treatment for high-risk patients with early COVID-19 in an outpatient setting. MethodsThe TOGETHER trial is a placebo-controlled, randomized, platform trial conducted in Brazil. Eligible participants were symptomatic adults with a positive rapid test for SARS-CoV-2 older than 50 y or with a known risk factor for disease severity. Patients were randomly assigned to receive placebo or spirulina (1 g twice daily for 14 d). The primary end point was hospitalization defined as either retention in a COVID-19 emergency setting for >6 h or transfer to tertiary hospital owing to COVID-19 at 28 d. Secondary outcomes included time-to-hospitalization, mortality, and adverse drug reactions. We used a Bayesian framework to compare spirulina with placebo. ResultsWe recruited 1126 participants, 569 randomly assigned to spirulina and 557 to placebo. The median age was 49.0 y, and 65.3% were female. The primary outcome occurred in 11.2% in the spirulina group and 8.1% in the placebo group (odds ratio [OR]: 1.24; 95% credible interval: 0.84, 1.86). There were no differences in emergency department visit (OR: 1.21; 95% credible interval: 0.81, 1.83), nor time to symptom relief (hazard ratio: 0.90; 95% credible interval: 0.79, 1.03). Spirulina also not demonstrate important treatment effects in the prespecified subgroups defined by age, sex, BMI, days since symptom onset, or vaccination status. ConclusionsSpirulina has no any clinical benefits as an outpatient therapy for COVID-19 compared with placebo with respect to reducing the retention in an emergency setting or COVID-19–related hospitalization. There are no differences between spirulina and placebo for other secondary outcomes.This trial was registered at clinicaltrials.gov as NCT04727424.

Effect of early treatment with metformin on risk of emergency care and hospitalization among patients with COVID-19: The TOGETHER randomized platform clinical trial

BackgroundObservational studies have postulated a therapeutic role of metformin in treating COVID-19. We conducted an adaptive platform clinical trial to determine whether metformin is an effective treatment for high-risk patients with early COVID-19 in an outpatient setting.MethodsThe TOGETHER Trial is a placebo-controled, randomized, platform clinical trial conducted in Brazil. Eligible participants were symptomatic adults with a positive antigen test for SARS-CoV-2. We enroled eligible patients over the age of 50 years or with a known risk factor for disease severity. Patients were randomly assigned to receive either placebo or metformin (750 mg twice daily for 10 days or placebo, twice daily for 10 days). The primary outcome was hospitalization defined as either retention in a COVID-19 emergency setting for > 6 h or transfer to tertiary hospital due to COVID-19 at 28 days post randomization. Secondary outcomes included viral clearance at day 7, time to hospitalization, mortality, and adverse drug reactions. We used a Bayesian framework to determine probability of success of the intervention compared to placebo.FindingsThe TOGETHER Trial was initiated June 2, 2020. We randomized patients to metformin starting January 15, 2021. On April 3, 2021, the Data and Safety Monitoring Committee recommended stopping enrollment into the metformin arm due to futility. We recruited 418 participants, 215 were randomized to the metformin arm and 203 to the placebo arm. More than half of participants (56.0%) were over the age of 50 years and 57.2% were female. Median age was 52 years. The proportion of patients with the primary outcome at 28 days was not different between the metformin and placebo group (relative risk [RR] 1.14[95% Credible Interval 0.73; 1.81]), probability of superiority 0.28. We found no significant differences between the metformin and placebo group on viral clearance through to day 7 (Odds ratio [OR], 0.99, 95% Confidence Intervals 0.88–1.11) or other secondary outcomes.InterpretationIn this randomized trial, metformin did not provide any clinical benefit to ambulatory patients with COVID-19 compared to placebo, with respect to reducing the need for retention in an emergency setting or hospitalization due to worsening COVID-19. There were also no differences between metformin and placebo observed for other secondary clinical outcomes.FundingThe trial was supported by FastGrants and The Rainwater Foundation.

Bioprosthetic Valve Remodeling of Trifecta Surgical Valves to Facilitate Valve-in-Valve TAVR

ABSTRACT Background: Valve-in-valve transcatheter aortic valve replacement (VIV TAVR) is an effective treatment for high-risk patients with failed surgical bioprosthetic valves, but may be complicated by patient-prosthesis mismatch (PPM). We describe a novel technique – bioprosthetic valve remodeling (BVR) – to distort the frame of Trifecta surgical valves with a high-pressure balloon inflation, allowing for improved expansion and hemodynamics of the transcatheter heart valve (THV). Methods: We performed bench testing of BVR by deploying Portico THVs (Abbott, Minneapolis, MN, USA) inside Trifecta GT valves both at baseline and following BVR. Fluoroscopic and video imaging was performed to assess Trifecta frame distortion, THV expansion, and leaflet motion. Hydrodynamic testing was performed to determine transvalvular gradient under baseline conditions and following BVR. We performed 6 clinical cases of VIV TAVR with Evolut R THVs (Medtronic, Minneapolis, MN), followed by BVR. Hemodynamic measurements and calculation of the effective orifice area (EOA) were performed at baseline, immediately after implantation of the THV, and after BVR. Results: BVR resulted in an increase in the post-to-post diameter in Trifecta valves, and a lower transvalvular gradient after THV implantation. VIV TAVR and BVR was successful in all cases, with no major short-term complications. The mean baseline transvalvular gradient was 47.5 ± 14.4 mmHg, which was reduced to 21.0 ± 6.2 mmHg after THV implantation, and further reduced to 11.7 ± 4.1 mmHg following BVR. Gradients were stable at 1 month follow up. Conclusion: BVR distorts the frame of Trifecta valves, improving THV expansion and procedural hemodynamics of VIV TAVR.

Modelling the burden of cardiovascular disease in Saudi Arabia and the impact of reducing modifiable risk factors

This study aims to estimate the current and future burden of cardiovascular diseases (CVD) in Saudi Arabia, and quantify the impact of reducing modifiable risk factors. A burden of disease model was used to forecast the burden of CVD in Saudi Arabia, and estimate the impact of reducing modifiable risk factors (tobacco use, hypertension, type 2 diabetes, obesity and physical inactivity) in the Saudi Nationals population, in accordance with World Health Organization (WHO) targets. Another model estimated the impact of reducing LDL-cholesterol through increased access to effective treatment for two high risk populations: heterozygous familial hypercholesterolemia (HeFH) and secondary prevention (SP), with a focus on patients with LDL-cholesterol >100 mg/dL. Inputs for the models included disease and risk factor prevalence, population forecast, CVD event rates, and treatment effectiveness, primarily derived from published literature. Direct costs to the public health care system and indirect costs from lost productivity due to premature mortality, hospitalizations, and early retirement were included, although the cost of programs and pharmacological interventions to reduce risk factors was not considered. The prevalence of CVD is projected to increase to 479,500 Nationals by 2035, while the economic burden, including both direct and indirect costs, would increase threefold to US$9.8 billion. The value of reducing modifiable risk factors (except LDL-cholesterol) is estimated at US$3.7 billion over the forecast period. Reducing the prevalence of uncontrolled LDL-cholesterol through increased access to evolocumab could lead to savings of up to US$532 million for HeFH patients and up to US$9 billion for high-risk SP patients over the forecast period. The burden of CVD is significant and growing. Efforts to achieve WHO risk factor targets and further lower LDL-cholesterol through increased access to effective treatment for high-risk patients are projected to greatly reduce the clinical, economic, and humanistic burden of cardiovascular disease in Saudi Arabia.

Modelling The Burden Of Cardiovascular Disease In Turkey And The Impact Of Reducing Modifiable Risk Factors

This study aims to estimate the current and future burden of cardiovascular diseases (CVD) in Turkey, and quantify the impact of reducing modifiable risk factors. A burden of disease model was used to forecast the burden of CVD in Turkey, and estimate the impact of reducing modifiable risk factors (tobacco use, hypertension, type 2 diabetes, obesity and physical inactivity) in the general Turkish population, in accordance with World Health Organization (WHO) targets. Another model estimated the impact of reducing LDL-cholesterol through increased access to effective treatment for two high risk populations: heterozygous familial hypercholesterolemia (HeFH) and secondary prevention (SP), with a focus on patients with LDL-cholesterol >100 mg/dL. Inputs for the models included disease and risk factor prevalence, population forecast, CVD event rates, and treatment effectiveness, primarily derived from published literature. Direct costs to the public health care system and indirect costs from lost productivity due to premature mortality, hospitalizations, and early retirement were included, although the cost of programs and pharmacological interventions to reduce risk factors was not considered. The prevalence of CVD is projected to increase to 5.4 million adults by 2035, while the economic burden, including both direct and indirect costs, would increase to US$5.7 billion. The value of reducing modifiable risk factors (except LDL-cholesterol) is estimated at US$9.2 billion over the forecast period. Reducing the prevalence of uncontrolled LDL-cholesterol through increased access to evolocumab could lead to savings of up to US$691.3 million for HeFH patients and up to US$8.1 billion for high-risk SP patients over the forecast period. The burden of CVD is significant and growing. Efforts to achieve WHO risk factor targets and further lower LDL-cholesterol through increased access to effective treatment for high-risk patients are projected to greatly reduce the clinical, economic, and humanistic burden of cardiovascular disease in Turkey.

PET response-adapted clinical trials in Hodgkin lymphoma: a comprehensive review

Hodgkin lymphoma (HL) is a highly curable disease, as most HL patients become long-term survivors, with 10-years cure and survival rates after first-line treatment exceeding 80 and 90 %, respectively. Despite these rewarding results, 10–15 % of early stage and 20–25 % of advanced stage patients became chemo-refractory to first-line treatment, and nearly half of them ultimately succumb to their disease. On the other hand, a small but significant fraction of long-term survivors, especially those treated with combined chemoradiation, experience treatment related morbidity and mortality with cardiovascular events and secondary neoplasms arising 5–20 years after the end of therapy. Therefore, an unfulfilled need still exists for a risk-adapted strategy, with a very effective treatment in high-risk patients and a low toxicity regimen in the vast majority of patients who are indeed chemo sensitive. Interim PET scan, performed after few cycles of chemotherapy proved the main predictor of treatment outcome in ABVD-treated patients and superseded the predictive role of traditional prognostic markers. Moreover, simple and reproducible rules for interim PET interpretation agreed among experts have been validated in HL, and are now available for the clinical practice. A number of phase II trials yielded the prof of concept that adapting treatment to interim PET result could ultimately increase long-term disease control in the entire patient population, compared to that obtained with the standard chemotherapy approach. In the present article the results of these pioneer single-centre small trials, as well as the preliminary results of large international prospective trials will be reviewed.

Prevalence, clinical characteristics and outcomes of high-risk patients treated for severe aortic stenosis prior to and after transcatheter aortic valve implantation availability.

Transcatheter aortic valve implantation (TAVI) has emerged as an effective treatment for high-risk patients with severe aortic stenosis (AS). The aim of our study was to compare the prevalence, characteristics and outcomes of high-risk patients treated prior to and after the availability of TAVI in our high-volume surgical institution. Among 879 consecutive patients treated 2 years before ('pre-TAVI era') and after ('modern era') the availability of TAVI in our institution, 83 patients were at high risk [defined by logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) >20%]. Among all patients treated for severe AS, the prevalence of high-risk patients was higher in the modern era (12.7 vs 4.9%, P < 0.0001). In the modern era, high-risk patients were treated by TAVI in 89% of cases. Despite similar logistic EuroSCORE (34.9 vs 34%, P = 0.96), the clinical characteristics of these patients have evolved: high-risk patients in the modern era were older (85.3 ± 5.9 vs 78.5 ± 6.5 years, P = 0.0005) and presented more frequently with New York Heart Association class III-IV (92.3 vs 61.1%, P = 0.003), while high-risk patients treated by surgical aortic valve replacement in the pre-TAVI era presented more frequently with a critical preoperative status (33.3 vs 7.7%, P = 0.01), lower left ventricular ejection fraction (41 ± 14 vs 49 ± 15%, P = 0.05) and a history of recent myocardial infarction (27.8 vs 6.1%, P = 0.02). The overall 1-year survival was not different for high-risk patients treated in the pre-TAVI era or in the modern era (61 ± 11 vs 68 ± 6%, P = 0.52). The availability of TAVI has increased the prevalence of high-risk patients treated for severe AS and changed the clinical features of this kind of patients who were rarely surgically treated before. The 1-year survival was similar between pre-TAVI and modern eras.

Device-dependent association between paravalvar aortic regurgitation and outcome after TAVI

ObjectiveThe aim of the current study was to identify predictors of paraprosthetic aortic regurgitation (AR) after transcatheter aortic valve implantation (TAVI) and examine its influence on short/medium-term mortality using the...

Carotid artery stenting with routine cerebral protection in high-risk patients

Background Carotid artery stenting has emerged as an alternative treatment modality in carotid occlusive disease. This study examined our experience of carotid stenting with routine cerebral embolization protection in high-risk patients. Methods Clinical variables and treatment outcome of high-risk patients who underwent carotid stenting with neuroprotection were analyzed during a 26-month period. Results Sixty-eight high-risk patients with 72 carotid artery stenoses were treated. Procedural success was achieved in 70 cases (97%), and symptomatic lesions existed in 17 (24%) patients. Monorail Wallstents stents were used in all cases. Neuroprotective devices used were PercuSurge (28%) and Filterwire (72%). There was no periprocedural mortality or neuroprotective device-related complications. The 30-day stroke and death rate was 2.7%, and the overall complication rate was 6.9%. All stented vessels remained patent during the follow-up period (mean 15.3 ± 4.2, range 1 to 23 months). Two asymptomatic in-stent restenosis (3%) occurred at 6 and 8 months, which were both successfully treated with balloon angioplasty. Conclusions Our study showed that percutaneous carotid stenting with routine use of a cerebral protection device is a feasible and effective treatment in high-risk patients with carotid occlusive disease.

Aspergilloma: a series of 89 surgical cases

Background. Surgery for pleuropulmonary aspergilloma is reputed to be risky. We reviewed our results, focusing attention on the postoperative complications.Methods. During a 20-year period, 87 patients were operated on for pulmonary (86) or pleural (3) aspergillomas. Seventy-two percent of patients were complaining of hemoptysis. Eighty-nine resections were performed because there were two bilateral cases. Seventy percent of aspergillomas had developed in cavitation sequelaes from tuberculosis disease. Thirty-four patients had severe respiratory insufficiency that allowed us to perform only lobectomy (18), segmentectomy (2), or cavernostomy (14).Results. Thirty-seven lobectomies (five with associated segmentectomies), two bilobectomies, 21 segmentectomies, 10 pneumonectomies, and 17 cavernostomies were performed. Total blood loss exceeded 1,500 mL in 14 cases, and 71% of patients required blood transfusion. There were five postoperative deaths (5.7%), related to respiratory failure (2), infectious complication (1), pulmonary embolus (1), and cardiorythmic disorder (1). Incomplete reexpansions were frequently seen in patients undergoing lobectomies or segmentectomies. No death or major complications occurred in asymptomatic patients. During follow-up, none of the patients had recurrent hemoptysis.Conclusions. Surgical resection of aspergilloma is effective in preventing recurrence of hemoptysis. It has low risk in asymptomatic patients and in the absence of underlying pulmonary disease. Incomplete reexpansion is frequent after lobectomy and segmentectomy, especially when there is underlying lung disease. Cavernostomy is an effective treatment in high-risk patients. Long-term prognosis is mainly dependent on the general condition of patients.

Percutaneous Cholecystostomy is an Effective Treatment for High-Risk Patients with Acute Cholecystitis

We sought to determine the safety, efficacy, and outcome of percutaneous cholecystostomy (PC) in all patients undergoing the procedure at our institutions. We reviewed 53 consecutive cases of acute cholecystitis seen at our hospitals over 5.5 years in which PC was performed at the initial treatment. Follow-up was obtained by chart review and telephone questionnaire. Acute cholecystitis was the primary admitting diagnosis in 18 cases. In the remaining 35, cholecystitis developed during hospitalization. All patients were considered high surgical risks on the basis of the presence of comorbid conditions. The gallbladder was successfully catheterized under radiologic guidance in all patients and with no immediate procedure-related morbidity. Acute cholecystitis resolved in 44 of 53 patients (83%), whereas nine patients (17%) did not improve clinically after PC and died during the same hospitalization. A total of 33 (62%) eventually survived hospitalization. Elective cholecystectomy was done in 25 patients with no mortality. After cholecystectomy, three of these patients subsequently died of other causes, whereas 22 are alive. Eight patients did not undergo cholecystectomy because of underlying medical conditions or because they had acalculous cholecystitis. These patients remained free of biliary problems after removal of their cholecystostomy tube, but two have subsequently died of nonbiliary conditions. Percutaneous cholecystostomy is a safe, effective treatment for high-risk patients with acute cholecystitis. Cholecystostomy can be followed by elective cholecystectomy at a later time if the patient's condition permits or by expectant conservative management in patients who have had acalculous cholecystitis or have a very high mortality risk with surgery.

Systematic review of randomized controlled trials of aspirin and oral anticoagulants in the prevention of graft occlusion and ischemic events after infrainguinal bypass surgery

Purpose: We sought to determine the efficacy of antiplatelet therapy and oral anticoagulants in maintaining graft patency and preventing ischemic complications in patients after infrainguinal bypass surgery. Methods: We performed a meta-analysis of randomized controlled trials of aspirin with or without other antiplatelet therapy and oral anticoagulants after infrainguinal bypass surgery. Outcome measures studied were graft occlusion, stroke, myocardial infarction, vascular and total mortality, and the composite outcome of stroke, myocardial infarction, and vascular mortality. Results: Five trials of antiplatelet therapy versus placebo were included. The relative risk (RR) for occlusion was 0.78 (95% CI, 0.64-0.95). For prevention of stroke, myocardial infarction, and death, and for the composite outcome, no significant effect was measured. Only one trial of oral anticoagulants versus control treatment was included. The RR for occlusion was 0.55 (95% CI, 0.30-0.99), and that for amputation was 0.30 (95% CI, 0.10-0.87). The mortality rate did not differ significantly between the groups. One trial of oral anticoagulant therapy plus aspirin versus aspirin alone in high-risk patients was included. The RR for occlusion was 0.38 (95% CI, 0.15-0.95). There were no significant differences for prevention of amputation, myocardial infarction, and death between the groups. Conclusion: Antiplatelet therapy and oral anticoagulants reduce the risk of graft occlusion. Oral anticoagulant therapy appears to be the more effective treatment in high-risk patients. Data on the reduction of the risk of stroke, myocardial infarction, and death are inconclusive. Evidence for the beneficial effects of antiplatelet and oral anticoagulant therapy after infrainguinal bypass surgery is based on a small number of trials only. There is no proof as to which modality is the most effective in the prevention of graft occlusion and ischemic events in patients after infrainguinal bypass surgery, which is reason for a randomized comparison of aspirin with oral anticoagulants. (J Vasc Surg 1999;30:701-9.)