Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19.

BACKGROUND: After COVID-19 emerged on U.S shores, providers began reviewing the emerging basic science, translational, and clinical data to identify potentially effective treatment options. In addition, a multitude of both novel and repurposed therapeutic agents were used empirically and studied within clinical trials. AREAS OF UNCERTAINTY: The majority of trialed agents have failed to provide reproducible, definitive proof of efficacy in reducing the mortality of COVID-19 with the exception of corticosteroids in moderate to severe disease. Recently, evidence has emerged that the oral antiparasitic agent ivermectin exhibits numerous antiviral and anti-inflammatory mechanisms with trial results reporting significant outcome benefits. Given some have not passed peer review, several expert groups including Unitaid/World Health Organization have undertaken a systematic global effort to contact all active trial investigators to rapidly gather the data needed to grade and perform meta-analyses. DATA SOURCES: Data were sourced from published peer-reviewed studies, manuscripts posted to preprint servers, expert meta-analyses, and numerous epidemiological analyses of regions with ivermectin distribution campaigns. THERAPEUTIC ADVANCES: A large majority of randomized and observational controlled trials of ivermectin are reporting repeated, large magnitude improvements in clinical outcomes. Numerous prophylaxis trials demonstrate that regular ivermectin use leads to large reductions in transmission. Multiple, large "natural experiments" occurred in regions that initiated "ivermectin distribution" campaigns followed by tight, reproducible, temporally associated decreases in case counts and case fatality rates compared with nearby regions without such campaigns. CONCLUSIONS: Meta-analyses based on 18 randomized controlled treatment trials of ivermectin in COVID-19 have found large, statistically significant reductions in mortality, time to clinical recovery, and time to viral clearance. Furthermore, results from numerous controlled prophylaxis trials report significantly reduced risks of contracting COVID-19 with the regular use of ivermectin. Finally, the many examples of ivermectin distribution campaigns leading to rapid population-wide decreases in morbidity and mortality indicate that an oral agent effective in all phases of COVID-19 has been identified.

Clinical and Scientific Rationale for the "MATH+" Hospital Treatment Protocol for COVID-19.

In December 2019, COVID-19, a severe respiratory illness caused by the new coronavirus SARS-CoV-2 (COVID-19) emerged in Wuhan, China. The greatest impact that COVID-19 had was on intensive care units (ICUs), given that approximately 20% of hospitalized cases developed acute respiratory failure (ARF) requiring ICU admission. Based on the assumption that COVID-19 represented a viral pneumonia and no anti-coronaviral therapy existed, nearly all national and international health care societies' recommended "supportive care only" avoiding other therapies outside of randomized controlled trials, with a specific prohibition against the use of corticosteroids in treatment. However, early studies of COVID-19-associated ARF reported inexplicably high mortality rates, with frequent prolonged durations of mechanical ventilation (MV), even from centers expert in such supportive care strategies. These reports led the authors to form a clinical expert panel called the Front-Line COVID-19 Critical Care Alliance (www.flccc.net). The panel collaboratively reviewed the emerging clinical, radiographic, and pathological reports of COVID-19 while initiating multiple discussions among a wide clinical network of front-line clinical ICU experts from initial outbreak areas in China, Italy, and New York. Based on the shared early impressions of "what was working and what wasn't working," the increasing medical journal publications and the rapidly accumulating personal clinical experiences with COVID-19 patients, a treatment protocol was created for the hospitalized patients based on the core therapies of methylprednisolone, ascorbic acid, thiamine, heparin and co-interventions (MATH+). This manuscript reviews the scientific and clinical rationale behind MATH+ based on published in-vitro, pre-clinical, and clinical data in support of each medicine, with a special emphasis of studies supporting their use in the treatment of patients with viral syndromes and COVID-19 specifically. The review concludes with a comparison of published multi-national mortality data with MATH+ center outcomes.

Aeromedical helicopter transport of prisoners: The Mexico City experience.

INTRODUCTION: Helicopter medical transport of prisoner patients has unique logistical and medical challenges, as well as potential risks to healthcare providers. Prisoners have specific requirements for safe transport, and it is of paramount importance to know the variables related to transport related mortality since most prisoners that need air evacuation are critically ill. Because we understand that there is a potentially dangerous nature of transport of this population, and because of the unique nature of them, we aimed to provide a detailed insight on predictors of outcome in prisoners who were injured as a result of trauma and that needed to be transported via air medical transport in Mexico City. METHODS: A retrospective chart analysis was conducted using data from the Mexico City Police Helicopter Emergency Medical Service (HEMS) for air medical transport of felons that occurred between January 1, 2000 and December 31, 2013. Subject demographics, injury, procedures performed, transport time, Glasgow Coma Scale (GCS), and mortality were collected. Exploratory data analysis, Chi-square, and T-test were performed. Statistical significance was assumed to be p ≤ 0.05 for two-sided hypothesis. RESULTS: Fifty-three patients were included in this study. Forty-two were men and 11 were women. Median age of the patients was 30 ± 8 years. Total transport time was 23 ± 5 min. Gunshot wounds accounted for 39.6% of patients, stabbing wounds 28.3%, head trauma 7.5%, motor vehicle accidents 5.7%, blunt trauma (i.e., fist assaults) 5.6%, falls 5.7%, motorcycle accidents 3.8%, and prisoner-motor vehicle collisions 3.8%. Median heart rate was 114 ± 41 beats per minute (BPM), median systolic blood pressure (SBP) was 103 ± 14 mmHg, median diastolic blood pressure (DBP) was 70 ± 12 mmHg, and median GCS was 10 ± 5. Mortality rate was 16.9% (n = 9). The variables that were statistically significant, and therefore related to mortality were: heart rate > 130 bpm (p < 0.001), SBP <95 mmHg (p = 0.039), GCS <7 (p = 0.040), age > 42 years (range, 17-47 years) p < 0.001, and need for cardiopulmonary resuscitation (CPR) (p < 0.001). CONCLUSIONS: As dangerous and challenging as it may seem, air medical transport of prisoners by a police crew physician, may be safe and reliable, since no complications or safety events were observed.

Cardiopulmonary resuscitation in television medical dramas: Results of the TVMD2 study.

INTRODUCTION: Television medical dramas (TVMDs) use cardiopulmonary resuscitation (CPR) as a mean of achieving higher viewing rates. TVMDs portrayal of CPR can be used to teach laypersons attempting to perform CPR and to form a shared professional and layperson mental model for CPR decisions. We studied the portrayal of CPR across a wide range of TVMDs to see whether newer series fulfill this promise. MATERIALS AND METHODS: Advanced cardiac life support (ACLS) certified healthcare providers underwent training in the use of a unique instrument based on the AHA (American Heart Association) guidelines to assess TVMD CPR scenarios. Components of the assessment included the adequacy of CPR techniques, gender distribution in CPR scenes, performance quality by different healthcare providers, and CPR outcomes. Thirty-one TVMDs created between 2010 and 2018 underwent review. RESULTS: Among 836 TVMD episodes reviewed, we identified 216 CPR attempts. CPR techniques were mostly portrayed inaccurately. The recommended compressions depth was shown in only 32.0% of the attempts (n = 62). The recommended rate was shown in only 44.3% of the attempts (n = 86). Survival to hospital discharge was portrayed as twice higher in male patients (67.6%, n = 71) than in female patients (32.4%, n = 29) (p < 0.05). Paramedics were portrayed as having better performance than physicians or nurses; compression rates were shown to be within the recommendations in only 42% (n = 73) of the CPR attempts performed by physicians, 44% (n = 8) of those performed by nurses, and 64% (n = 9) of those performed by paramedics. Complete chest recoil after compression was shown in only 34% (n = 58) of the CPR attempts performed by physicians, 38% (n = 7) of those performed by nurses, and 64% (n = 9) of those performed by paramedics. Outcomes were better on the screen than in real life; among the episodes showing outcome (n = 202), the overall rate of survival from CPR was 61.9% (n = 125). CONCLUSION: Portrayal of CPR in TVMDs remains a missed opportunity for improving performance and communication on CPR.

Administration of inhaled noble and other gases after cardiopulmonary resuscitation: A systematic review.

OBJECTIVE: Inhalation of noble and other gases after cardiac arrest (CA) might improve neurological and cardiac outcomes. This article discusses up-to-date information on this novel therapeutic intervention. DATA SOURCES: CENTRAL, MEDLINE, online published abstracts from conference proceedings, clinical trial registry clinicaltrials.gov, and reference lists of relevant papers were systematically searched from January 1960 till March 2019. STUDY SELECTION: Preclinical and clinical studies, irrespective of their types or described outcomes, were included. DATA EXTRACTION: Abstract screening, study selection, and data extraction were performed by two independent authors. Due to the paucity of human trials, risk of bias assessment was not performed DATA SYNTHESIS: After screening 281 interventional studies, we included an overall of 27. Only, xenon, helium, hydrogen, and nitric oxide have been or are being studied on humans. Xenon, nitric oxide, and hydrogen show both neuroprotective and cardiotonic features, while argon and hydrogen sulfide seem neuroprotective, but not cardiotonic. Most gases have elicited neurohistological protection in preclinical studies; however, only hydrogen and hydrogen sulfide appeared to preserve CA1 sector of hippocampus, the most vulnerable area in the brain for hypoxia. CONCLUSION: Inhalation of certain gases after CPR appears promising in mitigating neurological and cardiac damage and may become the next successful neuroprotective and cardiotonic interventions.

Culture and personal influences on cardiopulmonary resuscitation- results of international survey.

BACKGROUND: The ethical principle of justice demands that resources be distributed equally and based on evidence. Guidelines regarding forgoing of CPR are unavailable and there is large variance in the reported rates of attempted CPR in in-hospital cardiac arrest. The main objective of this work was to study whether local culture and physician preferences may affect spur-of-the-moment decisions in unexpected in-hospital cardiac arrest. METHODS: Cross sectional questionnaire survey conducted among a convenience sample of physicians that likely comprise code team members in their country (Indonesia, Israel and Mexico). The questionnaire included details regarding respondent demographics and training, personal value judgments and preferences as well as professional experience regarding CPR and forgoing of resuscitation. RESULTS: Of the 675 questionnaires distributed, 617 (91.4%) were completed and returned. Country of practice and level of knowledge about resuscitation were strongly associated with avoiding CPR performance. Mexican physicians were almost twicemore likely to forgo CPR than their Israeli and Indonesian/Malaysian counterparts [OR1.84 (95% CI 1.03, 3.26), p = 0.038]. Mexican responders also placed greater emphasison personal and patient quality of life (p <  0.001). In multivariate analysis, degree of religiosity was most strongly associated with willingness to forgo CPR; orthodox respondents were more than twice more likely to report having forgone CPR for apatient they do not know than secular and observant respondents, regardless of the country of practice [OR 2.12 (95%CI 1.30, 3.46), p = 0.003]. CONCLUSIONS: In unexpected in-hospital cardiac arrest the decision to perform or withhold CPR may be affected by physician knowledge and local culture as well as personal preferences. Physician CPR training should include information regarding predictors of patient outcome at as well as emphasis on differentiating between patient and personal preferences in an emergency.

Echocardiographic assessment with right ventricular function improvement following ultrasound-accelerated catheter-directed thrombolytic therapy in submassive pulmonary embolism.

Introduction The objective of this study was to evaluate the efficacy of ultrasound-accelerated catheter-directed thrombolytic therapy in patients with submassive pulmonary embolism. Methods Clinical records of 46 patients with submassive pulmonary embolism who underwent ultrasound-accelerated catheter-directed pulmonary thrombolysis using tissue plasminogen activator, from 2007 to 2017, were analyzed. All patients experienced clinical symptoms with computed tomography evidence of pulmonary thrombus burden. Right ventricular dysfunction was present in all patients by echocardiographic finding of right ventricle-to-left ventricle ratio > 0.9. Treatment outcome, procedural complications, right ventricular pressures, and thrombus clearance were evaluated. Follow-up evaluation included echocardiographic assessment of right ventricle-to-left ventricle ratio at one month, six months, and one year. Results Technical success was achieved in all patients ( n = 46, 100%). Our patients received an average of 18.4 ± 4.7 mg of tissue plasminogen activator using ultrasound-accelerated thrombolytic catheter with an average infusion time of 16.5± 5.4 h. Clinical success was achieved in all patients (100%). Significant reduction of mean pulmonary artery pressure occurred following the treatment, which decreased from 36 ± 8 to 21 ± 5 mmHg ( p < 0.001). There were no major bleeding complications. All-cause mortality at 30 days was 0%. No patient developed recurrent pulmonary embolism during follow-up. During the follow-up period, 43 patients (93%) showed improvement of right ventricular dysfunction based on echocardiographic assessment. The right ventricle-to-left ventricle ratio decreased from 1.32 ± 0.18 to 0.91 ± 0.13 at the time of hospital discharge ( p < 0.01). The right ventricular function remained improved at 6 months and 12 months of follow-up, as right ventricle-to-left ventricle ratio were 0.92 ± 0.14 ( p < 0.01) and 0.91 ± 0.15 ( p < 0.01), respectively. Conclusion Ultrasound-accelerated catheter-directed thrombolysis is a safe and efficacious treatment for submassive pulmonary embolism. It reduces pulmonary hypertension and improves right ventricular function in patients with submassive pulmonary embolism.

Thrombolytic Therapy of Acute Massive Pulmonary Embolism Using Swan-Ganz Pulmonary Artery Catheter.

Acute massive pulmonary embolism (PE) is associated with high fatality, and catheter-directed thrombolytic therapy has been shown to be an efficacious treatment for this condition. We herein report a patient who developed acute massive PE but could not undergo the conventional catheter-directed thrombolytic therapy. A Swan-Ganz pulmonary artery catheter was placed at bedside to initiate immediate thrombolytic infusion, which resulted in dramatic clinical improvement. This report underscores a potential role of thrombolytic therapy via a transjugular pulmonary artery catheter in patients with acute massive PE who could not undergo the conventional catheter-based thrombolytic intervention.

Hospital Workers' Confidence for End-of-Life Decisions in their Family: A Multicenter Study.

AIMS: To study whether health-care workers feel capable of making resuscitation decisions for their own families, the confidence in their family to represent their own preferences, and if some health-care workers feel greater confidence in their ability to undertake such decisions for their family than others. METHODS: An anonymous survey conducted among health-care workers of nine institutions in North and Central America. The self-administered questionnaire included demographic and professional characteristics, attitudes, personal preferences, and value judgments on the topic of resuscitation. RESULTS: Eight hundred and fifty-eight surveys were completed; 21.1% by physicians, 37.2% by nurses, and 41.7% by other health-care. Most of the health-care workers (83.5%) stated that they should be unable to determine their own code status and they would allow their family or spouse/significant other to make this decision for themselves. Physicians felt significantly more capable of making a decision regarding the code status of a close family member than other hospital workers (P = 0.019). Professionals who chose to not undergo cardiopulmonary resuscitation were less likely to feel capable of determining the code status of their family. CONCLUSIONS: Most of the health-care workers feel capable of making code status decisions for a close family member and most feel equally comfortable having their family or spouse/significant other represent their code status preference should they be incapacitated. There is considerable reciprocity between the two situations. Physicians feel more confident in their ability to make code status decisions for their loved ones than other health-care workers. Regardless of profession, a personal preference for do not attempt resuscitation status is related to less confidence.

Beyond muscle destruction: a systematic review of rhabdomyolysis for clinical practice.

BACKGROUND: Rhabdomyolysis is a clinical syndrome that comprises destruction of skeletal muscle with outflow of intracellular muscle content into the bloodstream. There is a great heterogeneity in the literature regarding definition, epidemiology, and treatment. The aim of this systematic literature review was to summarize the current state of knowledge regarding the epidemiologic data, definition, and management of rhabdomyolysis. METHODS: A systematic search was conducted using the keywords "rhabdomyolysis" and "crush syndrome" covering all articles from January 2006 to December 2015 in three databases (MEDLINE, SCOPUS, and ScienceDirect). The search was divided into two steps: first, all articles that included data regarding definition, pathophysiology, and diagnosis were identified, excluding only case reports; then articles of original research with humans that reported epidemiological data (e.g., risk factors, common etiologies, and mortality) or treatment of rhabdomyolysis were identified. Information was summarized and organized based on these topics. RESULTS: The search generated 5632 articles. After screening titles and abstracts, 164 articles were retrieved and read: 56 articles met the final inclusion criteria; 23 were reviews (narrative or systematic); 16 were original articles containing epidemiological data; and six contained treatment specifications for patients with rhabdomyolysis. CONCLUSION: Most studies defined rhabdomyolysis based on creatine kinase values five times above the upper limit of normal. Etiologies differ among the adult and pediatric populations and no randomized controlled trials have been done to compare intravenous fluid therapy alone versus intravenous fluid therapy with bicarbonate and/or mannitol.

Exogenous Vasopressin-Induced Hyponatremia in Patients With Vasodilatory Shock: Two Case Reports and Literature Review.

Vasopressin has gained wide support as an adjunct vasopressor in patients with septic shock. This agent exerts its vasoconstriction effects through smooth muscle V1 receptors and also has antidiuretic activity via renal V2 receptors. This interaction with the renal V2 receptors results in the integration of aquaporin 2 channels in the apical membrane of the renal collecting duct leading to free water reabsorption. Thus, water intoxication with subsequent hyponatremia, although rare, is a potentially serious side effect of exogenous vasopressin administration. We present 2 patients who developed hyponatremia within hours of initiation of vasopressin infusion. Extensive diuresis followed its discontinuation with subsequent normalization of serum sodium. One of the patients required the use of hypertonic saline for more rapid normalization of serum sodium due to concerns for potential seizure activity. A review of the literature relevant to the incidence of vasopressin-induced hyponatremia is provided as well as discussion on additional factors relevant to septic shock that should be considered when determining the relative risk of hyponatremia in patients receiving vasopressin.

Hypertonic saline in elevated intracranial pressure: past, present, and future.

Hypertonic Saline (HS) has been a proven and effective therapy and a safe alternative to mannitol in patients with increase intracranial pressure (ICP). We hereby present a case of 25-year-old women with intracranial bleed secondary to right parietal arteriovenous malformation. Patient underwent surgery for evacuation of hematoma and resection of arteriovenous malformation. Post- operative course was complicated by recurrent episodes of elevated ICP. She received total of 17 doses of 23.4% HS and 30 doses of mannitol with good outcome. Despite reluctance from some clinicians to use HS, hypertonic saline seems to be a safe and effective therapy.

Do not drown the patient: appropriate fluid management in critical illness.

Administering intravenous fluids to support the circulation in critically ill patients has been a mainstay of emergency medicine and critical care for decades, especially (but not exclusively) in patients with distributive or hypovolemic shock. However, in recent years, this automatic use of large fluid volumes is beginning to be questioned. Analysis from several large trials in severe sepsis and/or acute respiratory distress syndrome have shown independent links between volumes of fluid administered and outcome; conservative fluid strategies have also been associated with lower mortality in trauma patients. In addition, it is becoming ever more clear that central venous pressure, which is often used to guide fluid administration, is a completely unreliable parameter of volume status or fluid responsiveness. Furthermore, 2 recently published large multicenter trials (ARISE and ProCESS) have discredited the "early goal-directed therapy" approach, which used prespecified targets of central venous pressure and venous saturation to guide fluid and vasopressor administration. This article discusses the risks of "iatrogenic submersion" and strategies to avoid this risk while still giving our patients the fluids they need. The key lies in combining good clinical judgement, awareness of the potential harm from excessive fluid use, restraint in reflexive administration of fluids, and use of data from sophisticated monitoring tools such as echocardiography and transpulmonary thermodilution. Use of smaller volumes to perform fluid challenges, monitoring of extravascular lung water, earlier use of norepinephrine, and other strategies can help further reduce morbidity and mortality from severe sepsis.

Pattern of external injuries sustained during bomb blast attacks in Karachi, Pakistan from 2000 to 2007.

OBJECTIVE: To evaluate patterns of external injury resulting from bomb blasts in Karachi, and compare the injury profile resulting from explosions in open versus semi-confined blast environments. METHODS: The retrospective, cross-sectional study was conducted in Karachi and comprised relevant data from January 2000 to October 2007. Casualty medical records and medico-legal certificates of the victims presented to three large public-sector hospitals were evaluated using a self-designed proforma. SPSS 17 was used for statistical analysis. RESULTS: Of the 1146 victims, data of 481(42%) represented the final study sample. Of these, 306(63.6%) were injured in open spaces and 175(36.4%) in semi-confined spaces. Of the 896 recorded injuries, lacerations were encountered as external injury in 427(47.7%) cases, followed by penetrating wounds in 137(15.3%). Lower and upper extremities were injured in 348(38.8%) and 170(19%) victims respectively. Open and semi-confined blast environments produced specific injury pattern and profile (p<0.001). CONCLUSIONS: External injuries sustained during bomb blast attacks in Karachi demonstrated specific injury patterns and profiles. Further studies are required to account for internal injuries and classification of injuries based on standardised scoring systems.

Current and newer agents for hypertensive emergencies.

Hypertension is an increasingly prevalent chronic illness. The condition may present as a hypertensive crisis, and this entity may be further categorized as either hypertensive emergency or urgency. As the presentation is quite variable and is dependent upon the specific end-organ injury, a thorough history and examination are necessary. Once the underlying pathology is known, a target blood pressure can be determined and a specific therapeutic agent selected. The choice of most appropriate agent must take into consideration coexisting morbidities, desired rate of blood pressure decline, monitoring capabilities of the environment, and experience of the clinician. In hypertensive emergencies, the therapeutic goal is to protect remaining end-organ function, reduce the risk of complications, and thereby improve patient outcomes. This article reviews commonly used antihypertensive medications as well as evidence-based recommendations for state-of-the-art treatment for hypertensive emergencies.