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One player is trapped in a virtual room with a ticking time bomb they must defuse. In The Talos Principle, players assume the role of a sentient artificial intelligence placed within a simulation of humanity?
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Consult ICU early for deteriorating patients, as this can escalate rapidly. Provide dexamethasone 6 mg daily for patients requiring oxygen or an equivalent dose of steroid — 40 mg prednisone daily or 32 mg IV methylprednisolone.
Avoid nebulized bronchodilators Only use bronchodilators if truly indicated. Instead of nebulizers, use a metered dose in haler puffs may be roughly equivalent to one nebulizer treatment.
Follow microbiologic studies. For patients with marked D-dimer elevation, consider higher doses of enoxaparin such as 0. Melatonin 5 mg QHS for sleep.
Zhang et al , Zhou et al. Confirm ETT depth at the upper teeth ensure no migration of the tube. Tighten connections between ETT, connecting tubing, and ventilator to prevent accidental disconnection.
Neurologic status. Cardiac and lung ultrasonography if clinical question. Do not use a stethescope this is a fomite that poses risk of disease transmission.
Liver function tests every other day. Titrated fluid resuscitation may be helpful initially, based on physical examination and history. It may be reasonable to allow patients to have a net positive fluid status over the first couple days in ICU.
Follow fluid balance and generally target an even fluid status. Consider using low-dose vasopressor as necessary to support MAP rather than fluid.
Sedation and positive-pressure ventilation will tend to reduce the blood pressure, so antihypertensive agents may be unnecessary. Conventional low-tidal volume ventilation is also effective.
Steroid Start dexamethasone 6 mg daily or equivalent steroid dose. Oxygen saturation generally does appear to track with pO2 in these patients and can be used to titrate oxygen administration.
Stress ulcer prophylaxis. If MRSA coverage is truly necessary, consider linezolid or ceftaroline. For patients marked elevation of D-dimer, consider higher doses of enoxaparin e.
This is discussed further below. Insulin as needed to avoid severe hyperglycemia consider allowing some permissive hyperglycemia, to reduce the need for frequent glucose checks.
Opioid bolus PRN pain e. Low-dose propofol as a titratable sedative e. COVID patients appear prone to developing hypertriglyceridemia possibly due to systemic inflammation.
Ideally keep propofol doses low, to avoid hypertriglyceridemia which may necessitate stopping propofol entirely. Adjunctive atypical antipsychotic e.
For ongoing pain, consider adding a pain-dose ketamine infusion 0. Melatonin 10 mg QHS for sleep. More on ICU analgesia and ICU sedation.
Best site may be left internal jugular vein save the right internal jugular for dialysis or ECMO.
Consider early transition to a PICC catheter for patients with an ongoing ICU stay. For non-shocked patients, utility of an arterial line is dubious.
This phase may last for several days, with fairly mild symptoms. Patients often don't require hospital admission. An innate immune response follows, but this fails to contain the virus.
Symptoms reflect a combination of direct viral cytopathic effect and innate immune responses e. Type-I interferon release.
Treatment : Anti-viral therapies could be beneficial, especially in patients predicted to be at higher risk for poor outcome.
Anti-viral therapies probably have maximal efficacy when given early, during this phase. Interferon I-beta could theoretically be useful to augment the innate immune system response to the virus.
This involves rendering cells resistant to viral infection, an intervention which would probably be most effective if deployed as early as possible however this is a theoretical consideration, which currently is not recommended.
Immunosuppression could theoretically be dangerous at this point, as it could delay the development of an adequate adaptive immune response.
For example, early initiation of steroid has been shown to prolong virus shedding in SARS Lee et al Patients will often present to the hospital at this point.
They may progress rapidly to ARDS, requiring intubation. Markers of systemic inflammation are often moderately elevated e. C-reactive protein, ferritin.
However, this also leads to increased levels of inflammation and tissue damage. Treatment : Antiviral-therapy could be beneficial although the later on that antiviral treatment is initiated, the less effective it is likely to be.
Some immunosuppression could be beneficial for patients with more severe manifestations e. Laboratory abnormalities include marked elevation of D-dimer, C-reactive protein, and ferritin.
Patients may initially respond well to intubation and ventilation during stage II, but subsequently develop increasing levels of inflammation, which leads to clinical deterioration.
Mehta et al. Treatment : All the treatments from Stage II may be continued e. Depending on the level of inflammation, a higher dose of steroid could be considered.
Steroid should not be used in patients with normal oxygenation. Indications for steroid include the following: 1 Acute hypoxemic respiratory failure true increase in oxygen requirement compared to baseline 2 Requirement for mechanical ventilation 3 Another accepted indication for steroid e.
COVID plus asthma or COPD exacerbation dose and duration of steroid Dose Dexamethasone 6 mg daily for up to 10 days was studied in the RECOVERY trial, so this is the most evidence-based dose.
If dexamethasone isn't available, other equivalent doses of steroid may be utilized: Oral betamethasone 6 mg overall most similar to dexamethasone IV or oral methylprednisolone 32 mg Oral prednisone 40 mg or prednisolone 40 mg Higher doses of steroid e.
However, the median duration of steroid utilization in that study was only 7 days. Therefore, if patients are making solid clinical improvement then it may be safe to discontinue dexamethasone prior to 10 days.
Dexamethasone has a long biological half-life, so it will auto-taper and thereby prevent rebound inflammation.
If using a shorter-acting steroid e. Unfortunately, most patients present to the hospital with severe illness after about a week of clinical illness.
To date, evidence with numerous anti-viral therapies has proven to be disappointing. Overall, the use of antiviral therapy for critically ill patients with COVID may be limited.
It didn't really work for Ebola, so further approval or testing wasn't pursued at that time. Remdesivir is an investigational drug which is not currently FDA approved for any indication , including COVID However, remdesivir has received an emergency use authorization EUA for COVID a lower bar than FDA approval.
As such, this is a very new drug which we don't fully understand. Little is known regarding side-effects. Over time, it's likely that additional side-effects will emerge.
Elevated liver enzymes AST, ALT, hyperbilirubinemia. Volunteers given remdesivir have reported phlebitis, constipation, headache, ecchymosis, nausea, and extremity pain.
Jorgensen CJ et al Renal failure Remdesivir may be contraindicated in renal insufficiency. To date, studies involving remdesivir in COVID have excluded these patients due to concern that the intravenous vehicle sulfobutylether beta-cyclodextrin could accumulate — so the safety of remdesivir in this context is unknown.
Given that remdesivir is a nucleoside analogue it might be teratogenic. In the ACTT-1 trial, women of child-bearing age were required to use contraception for a month after exposure to remdesivir.
AST or ALT above five times normal. Pregnancy Many studies have aggressively excluded women who might become pregnant. Teratogeinicity remains unclear.
As a nucleoside analogue, this is possible. Remdesivir does not have a robust or reproducible effect on hospital length of stay. This generated the popular misconception that ACTT-1 decreases hospital length of stay.
However, it's actually unclear whether remdesivir caused a statistically significant reduction in length of stay within the ACTT-1 trial extraneous factors often affect the length of stay, making it a difficult variable to reduce.
WHO et al. Open-label use of remdesivir likely prolonged length of stay because patients were kept in the hospital longer to receive remdesivir.
Further discussion of this trial here. Stop therapy after five days. Goldman et al. However, patients treated for ten days had increased rates of renal failure more on this study here.
Follow liver function tests. The World Health Organization currently does not recommend the use of Remdesivir. Rochwerg et al. Remdesivir has some known harms and probably additional unknown side-effects it has never been broadly utilized, so rare side-effects may remain unknown.
Practitioners will continue to be pressured to administer remdesivir, especially in the United States. A five-day course may be reasonable in patients with no contraindications.
When possible, shared decision-making may be beneficial. When administered to rhesus macaques prior to infection with COVID, bamlanivimab reduced the viral load.
Publication of this trial is pending currently only a press release is available. The BLAZE-1 trial evaluated the use of bamlanivimab among outpatients.
Chen et al. Bamlanivimab had no consistent effect on viral load the intermediate dosage of bamlanivimab did seem to reduce viral load, but when considering the multiplicity of statistical tests involved, this may have been due to chance.
A secondary endpoint was hospitalization, which was re-defined in a post-hoc fashion as either admission to the hospital or the emergency department.
Bamlanivimab can cause anaphylaxis. The precise incidence of this adverse event remains unclear, but it seems to be rare. The NIH and CDC guidelines currently recommend against the use of bamlanivimab.
Studies are ongoing, including the use of bamlanivimab combined with another monoclonal antibody into a cocktail. Bamlanivimab has received an Emergency Use Authorization EUA in the United States, with some centers administering it.
This is likely an unwise use of healthcare resources. More on bamlanivimab here. Aggressive fluid resuscitation e. The virus doesn't seem to generally cause a septic shock picture but of course, patients may always suffer from superimposed bacterial septic shock.
More discussion on fluid therapy for COVID is here. This is a strong predictor of mortality. Among non-survivors, troponin tends to increase steadily from day 4 of illness through day 22 Zhou et al.
Type-II MI stress MI Stress cardiomyopathy a. Takotsubo cardiomyopathy Viral cardiomyopathy Investigation should focus on integration of EKG and echocardiographic findings as well as clinical context.
In most cases, specific therapies for acute coronary syndrome will not be indicated. This may be a late feature, which can occur even after patients are recovering from respiratory failure.
These studies lack control groups, so it's unclear to what extent COVID may be causing arrhythmias or whether arrhythmias simply occur in sick patients.
Potential causes: Cardiogenic shock i. PEEP or APRV Anaphylactic reaction to medication Evaluation Complete septic workup e. Treatment Vasopressor support as guided by echocardiography and physical examination.
Empiric antibiotic therapy if concern for septic shock. Corticosteroid therapy may be considered although most patients will be on this allready.
Inhaled pulmonary vasodilator could be considered for intubated patients with acute cor pulmonale. This doesn't appear to be evidence-based.
Guidelines say HFNC is safe. Negative pressure rooms are preferable for patients receiving HFNO therapy. Therefore, it's doubtful that a patient on HFNC is more contagious than a patient on standard nasal cannula who is coughing.
HFNC typically requires less maintenance than invasive mechanical ventilation. For example, a patient who is on HFNC watching television may be less likely to spread the virus compared to an intubated patient whose ventilator is alarming every 15 minutes, requiring active suctioning and multiple providers in the room.
The Premier League distributes a portion of its television revenue to clubs that are relegated from the league in the form of "parachute payments".
For some clubs who have failed to win immediate promotion back to the Premier League, financial problems, including in some cases administration or even liquidation have followed.
Further relegations down the footballing ladder have ensued for several clubs unable to cope with the gap. As of the —18 season, Premier League football has been played in 58 stadiums since the formation of the division.
As a result, all stadiums in the Premier League are all-seater. The stadiums for the —18 season show a large disparity in capacity.
For example, Wembley Stadium , the temporary home of Tottenham Hotspur, has a capacity of 90, while Dean Court , the home of Bournemouth , has a capacity of 11, Stadium attendances are a significant source of regular income for Premier League clubs.
Managers in the Premier League are involved in the day-to-day running of the team, including the training, team selection and player acquisition.
Their influence varies from club-to-club and is related to the ownership of the club and the relationship of the manager with fans.
Several caretaker managers have gone on to secure a permanent managerial post after performing well as a caretaker, including Paul Hart at Portsmouth and David Pleat at Tottenham Hotspur.
He broke the record set by Alex Ferguson , who had managed matches with Manchester United from the Premier League's inception to his retirement at the end of the —13 season.
Ferguson was in charge of Manchester United from November until his retirement at the end of the —13 season, meaning he was manager for the last five years of the old Football League First Division and all of the first 21 seasons of the Premier League.
There have been several studies into the reasoning behind, and effects of, managerial sackings. Bas ter Weel of the University of Amsterdam , performed two separate studies which helped to explain the statistics behind managerial sackings.
Bridgewater's study found clubs generally sack their managers upon dropping below an average of one point per match. At the inception of the Premier League in —93 , just 11 players named in the starting line-ups for the first round of matches hailed from outside of the United Kingdom or Ireland.
On 26 December , Chelsea became the first Premier League side to field an entirely foreign starting line-up,  and on 14 February , Arsenal were the first to name a completely foreign man squad for a match.
In response to concerns that clubs were increasingly passing over young English players in favour of foreign players, in , the Home Office tightened its rules for granting work permits to players from countries outside of the European Union.
If a player does not meet those criteria, the club wishing to sign him may appeal. Players may only be transferred during transfer windows that are set by the Football Association.
The two transfer windows run from the last day of the season to 31 August and from 31 December to 31 January. Player registrations cannot be exchanged outside these windows except under specific licence from the FA, usually on an emergency basis.
There is no team or individual salary cap in the Premier League. The ratio of the wages of the highest paid team to lowest paid in the Premier League is 6.
This is much lower than in La Liga Because of the lower differential between team wage bills in the Premier League, it is often regarded as being more competitive than other top European leagues.
The record transfer fee for a Premier League player has risen steadily over the lifetime of the competition.
Italics denotes players still playing professional football, Bold denotes players still playing in the Premier League. The Premier League Golden Boot is awarded each season to the top scorer in the division.
Andrew Cole and Alan Shearer hold the record for most goals in a season 34 — for Newcastle and Blackburn respectively.
The Premier League maintains two trophies — the genuine trophy held by the reigning champions and a spare replica. Two trophies are held in the event that two clubs could win the League on the final day of the season.
It consists of a trophy with a golden crown and a malachite plinth base. Its main body is solid sterling silver and silver gilt , while its plinth is made of malachite, a semi-precious stone.
The plinth has a silver band around its circumference, upon which the names of the title-winning clubs are listed.
Malachite's green colour is also representative of the green field of play. Two of the lions are found above the handles on either side of the trophy — the third is symbolised by the captain of the title-winning team as he raises the trophy, and its gold crown, above his head at the end of the season.
In , a special gold version of the trophy was commissioned to commemorate Arsenal winning the title without a single defeat.
In addition to the winner's trophy and the individual winner's medals awarded to players who win the title, the Premier League also issues other awards throughout the season.
A man of the match award is awarded to the player who has the greatest impact in an individual match. The Golden Boot award is given to the top goalscorer of every season, The Playmaker of the Season award is given to the player who make the most assists of every season  and the Golden Glove award is given to the goalkeeper with the most clean sheets at the end of the season.
From the —18 season , players also receive a milestone award for appearances and every century there after and also players who score 50 goals and multiples thereof.
Each player to reach these milestones will receive a presentation box from the Premier League containing a special medallion and a plaque commemorating their achievement.
In , the Premier League celebrated its second decade by holding the 20 Seasons Awards: . From Wikipedia, the free encyclopedia. Redirected from English Premier League.
This article is about the English association football league. For other uses, see Premier League disambiguation.
Association football league in England. See also: Foundation of the Premier League. See also: List of Premier League seasons.
Main article: List of Premier League clubs. See also: List of English football champions. Aston Villa.
Leicester City. Manchester City. Man- chester United. Norwich City. Sheffield United. Crystal Palace. West Ham United. See also: List of association football clubs playing in the league of another country.