Saturday, January 19, 2019

Report of a large experience with severe systemic capillary leak syndrome

Objective: Systemic capillary-leak syndrome is a very rare cause of recurrent hypovolemic shock. Few data are available on its clinical manifestations, laboratory findings, and outcomes of those patients requiring ICU admission. This study was undertaken to describe the clinical pictures and ICU management of severe systemic capillary-leak syndrome episodes.

Design, Setting, Patients: This multicenter retrospective analysis concerned patients entered in the European Clarkson’s disease (Eur├¬Clark) Registry and admitted to ICUs between May 1992 and February 2016.

Measurements and Main Results: Fifty-nine attacks occurring in 37 patients (male-to-female sex ratio, 1.05; mean ± SD age, 51 ± 11.4 yr) were included. Among 34 patients (91.9%) with monoclonal immunoglobulin G gammopathy, 20 (58.8%) had kappa light chains. ICU-admission hemoglobin and proteinemia were respectively median (interquartile range) 20.2 g/dL (17.9–22 g/dL) and 50 g/L (36.5–58.5 g/L). IV immunoglobulins were infused (IV immunoglobulin) during 15 episodes (25.4%). A compartment syndrome developed during 12 episodes (20.3%). Eleven (18.6%) in-ICU deaths occurred. Bivariable analyses (the 37 patients’ last episodes) retained Sequential Organ-Failure Assessment score greater than 10 (odds ratio, 12.9 [95% CI, 1.2–140]; p = 0.04) and cumulated fluid-therapy volume greater than 10.7 L (odds ratio, 16.8 [1.6–180]; p = 0.02) as independent predictors of hospital mortality.

Conclusions: We described the largest cohort of severe systemic capillary-leak syndrome flares requiring ICU admission. High-volume fluid therapy was independently associated with poorer outcomes. IV immunoglobulin use was not associated with improved survival; hence, their use should be considered prudently and needs further evaluation in future studies.

Pre admission oral corticosteroids and the risk of ARDS in septic patients

Objectives: To determine the association between preadmission oral corticosteroid receipt and the development of acute respiratory distress syndrome in critically ill patients with sepsis.

Design: Retrospective observational study.

Setting: Medical, surgical, trauma, and cardiovascular ICUs of an academic medical center.

Patients: A total of 1,080 critically ill patients with sepsis.

Interventions: None.

Measurements and Main Results: The unadjusted occurrence rate of acute respiratory distress syndrome within 96 hours of ICU admission was 35% among patients who had received oral corticosteroids compared with 42% among those who had not (p = 0.107). In a multivariable analysis controlling for prespecified confounders, preadmission oral corticosteroids were associated with a lower incidence of acute respiratory distress syndrome in the 96 hours after ICU admission (odds ratio, 0.53; 95% CI, 0.33–0.84; p = 0.008), a finding that persisted in multiple sensitivity analyses. The median daily dose of oral corticosteroids among the 165 patients receiving oral corticosteroids, in prednisone equivalents, was 10 mg (interquartile range, 5–30 mg). Higher doses of preadmission oral corticosteroids were associated with a lower incidence of acute respiratory distress syndrome (odds ratio for 30 mg of prednisone compared with 5 mg 0.53; 95% CI, 0.32–0.86). In multivariable analyses, preadmission oral corticosteroids were not associated with in-hospital mortality (odds ratio, 1.41; 95% CI, 0.87–2.28; p = 0.164), ICU length of stay (odds ratio, 0.90; 95% CI, 0.63–1.30; p = 0.585), or ventilator-free days (odds ratio, 1.06; 95% CI, 0.71–1.57; p = 0.783).

Conclusions: Among ICU patients with sepsis, preadmission oral corticosteroids were independently associated with a lower incidence of early acute respiratory distress syndrome.

Should subclinical hyperthyroidism be treated? If so, when?

Here are some key points from the ATA guidelines:

When TSH is persistently less than 0.1 mU/L, treatment of SH is recommended in all individuals greater than or equal to 65 years of age; in patients with cardiac risk factors, heart disease or osteoporosis; in postmenopausal women who are not on estrogens or bisphosphonates; and in individuals with hyperthyroid symptoms…

When TSH is persistently less than 0.1 mU/L, treatment of SH should be considered in asymptomatic individuals less than 65 years of age without the risk factors listed in Recommendation 73...

When TSH is persistently below the lower limit of normal but greater than or equal to 0.1 mU/L, treatment of SH should be considered in individuals greater than or equal to 65 years of age and in patients with cardiac disease, osteoporosis, or symptoms of hyperthyroidism…

When TSH is persistently below the lower limit of normal but greater than or equal to 0.1 mU/L, asymptomatic patients under age 65 without cardiac disease or osteoporosis can be observed without further investigation of the etiology of the subnormal TSH or treatment.

Friday, January 18, 2019

Spontaneous coronary artery dissection (SCAD): recent findings

From the review:

Previously considered rare, SCAD is now recognised to be the cause of 2–4% of all cases of ACS, 24–36% of myocardial infarcts (MI) in women less than 50 years, and the commonest cause of an MI associated with pregnancy. SCAD predominantly affects women (92–98% of cases), who are relatively young (42–52 yrs) and have a low incidence of traditional risk factors.

In addition to primary or isolated SCAD, spontaneous dissection of coronary arteries can occur in association with connective tissue disorders [10] [e.g., Marfan's syndrome (fibrillin, FBN1, gene defect), Ehlers Danlos, type 4 (collagen, COL3A1, gene), cystic medial necrosis, Loeys-Dietz syndrome (LDS), type II (transforming growth factor B receptor, TGFBR2, or SMAD3 genes); atherosclerotic coronary artery disease; aortic dissection with coronary artery extension, or inflammatory disorders (e.g., systemic lupus erythematosus (SLE), Crohn's disease, ulcerative colitis).

These cases might be termed syndromic (as opposed to primary) SCAD.

More from the review:

There is no single unifying disease process leading to SCAD, although, based on the finding of familial clustering of SCAD cases with involvement of mother-daughter, identical twin sisters, sister-sister, aunt-niece, and first-cousin pairs [14] , and strong association of SCAD with fibromuscular dysplasia (FMD)…

Risk factors for SCAD include intense physical exercise (isometric or aerobic), Valsalva manoeuvre (e.g., retching, vomiting, bowel movement, coughing), pregnancy (most commonly in the peripartum period)…

Conservative medical management is recommended in patients without ongoing chest pain or ECG changes and usually is associated with spontaneous healing of the affected segment on subsequent angiography [18] . Long-term aspirin and ╬▓-blockers are commonly prescribed, although the rationale for using anti-platelet or anti-coagulant therapy, including aspirin, in patients with an IMH without an intimal tear, is tenuous, given that such therapy may increase bleeding within the vessel wall. Intravenous heparin should not be given or should be stopped in such patients once the diagnosis has been made. Thrombolytic therapy, dual antiplatelet therapy and glycoprotein IIb/IIIa inhibitors should be typically avoided. There is also little rationale for the use of statins unless the patient is dyslipidaemic. Angiotensin converting enzyme inhibitors or angiotensin receptor blockers may be administered to patients with a large MI providing they are not hypotensive.

Percutaneous coronary interventions (PCI) ± stenting should be avoided as outcomes are poor. Moreover, the affected vessel is prone to iatrogenic dissection and extension...

Sarcopenia in heart failure

Concealed conduction of PVCs prolonging the following PR interval

Thursday, January 17, 2019

Sepsis alerts by the EMR failed to improve outcomes

Yet another “systems improvement” that has failed to live up to the hype. Sepsis harassment.

Understanding premature cardiovascular disease in SLE

Purpose of review

The mechanisms leading to the development of premature atherosclerosis and vascular injury in systemic lupus erythematosus (SLE) remain to be fully elucidated. This is a comprehensive review of recent research developments related to the understanding of cardiovascular disease (CVD) in lupus.

Recent findings

SLE patients with lupus nephritis display significantly increased risk of myocardial infarction and CVD mortality than SLE patients without lupus nephritis. SLE disease-related parameters could be taken into consideration when calculating CVD risks. The type I interferon pathway is detrimental to the vasculature and may contribute to the development of insulin resistance. The level of low-density granulocytes, a distinct subset of proinflammatory neutrophils present in SLE, was independently associated with coronary plaque burden and endothelial dysfunction. Invariant natural killer T cells may promote an atheroprotective effect in SLE patients with asymptomatic atherosclerotic plaques. Oxidized lupus high-density lipoprotein promotes proinflammatory responses in macrophages.


Recent discoveries have further strengthened the critical role of SLE-related immune dysregulation and metabolic disturbances in promoting accelerated CVD. Understanding how these pathogenic factors promote vascular injury may provide better molecular candidates for therapeutic targeting, and ultimately to improve CVD outcomes.

Hospitalists feel rushed and maneuvered to get elderly patients discharged

Wednesday, January 16, 2019

Retinal vein occlusion: what the internist needs to know


•Retinal vein occlusion is a common cause of vision loss.
•Risk factors include hypertension, dyslipidemia, diabetes and obstructive sleep apnea.
•Thrombophilia screening is usually not required.
•No high-quality evidence exists to support routine use of antithrombotic drugs.
•Anticoagulation may be considered in select patients.


Retinal vein occlusion is a common and important cause of vision loss. In general, knowledge about this condition is scant within an internist's practice but the condition is relevant because of its association with other chronic ailments. A diagnosis of RVO should prompt the investigation of conditions needing chronic management in these patients. In this review we summarize the clinical presentation of RVO, its classification, associated risk factors, and treatment focused in the internist's scope of practice.

Rapid response calls are fewer in the middle of the night, mortality spikes at 7 AM

No, not in my reading of the study. Here’s a summary of the findings:

Objectives: Decreased staffing at nighttime is associated with worse outcomes in hospitalized patients. Rapid response teams were developed to decrease preventable harm by providing additional critical care resources to patients with clinical deterioration. We sought to determine whether rapid response team call frequency suffers from decreased utilization at night and how this is associated with patient outcomes.

Design: Retrospective analysis of a prospectively collected registry database.

Setting: National registry database of inpatient rapid response team calls.

Patients: Index rapid response team calls occurring on the general wards in the American Heart Association Get With The Guidelines-Medical Emergency Team database between 2005 and 2015 were analyzed.

Interventions: None.

Measurements and Main Results: The primary outcome was inhospital mortality. Patient and event characteristics between the hours with the highest and lowest mortality were compared, and multivariable models adjusting for patient characteristics were fit. A total of 282,710 rapid response team calls from 274 hospitals were included. The lowest frequency of calls occurred in the consecutive 1 AM to 6:59 AM period, with 266 of 274 (97%) hospitals having lower than expected call volumes during those hours. Mortality was highest during the 7 AM hour and lowest during the noon hour (18.8% vs 13.8%; adjusted odds ratio, 1.41 [1.31-1.52]; p less than 0.001). Compared with calls at the noon hour, those during the 7 AM hour had more deranged vital signs, were more likely to have a respiratory trigger, and were more likely to have greater than two simultaneous triggers.

Conclusions: Rapid response team activation is less frequent during the early morning and is followed by a spike in mortality in the 7 AM hour. These findings suggest that failure to rescue deteriorating patients is more common overnight. Strategies aimed at improving rapid response team utilization during these vulnerable hours may improve patient outcomes.

I have no data but my strong subjective impression is that this diurnal pattern existed long before anybody thought up the idea of rapid response teams. Hospital resources are slim at night and are most readily available mid day. 7 AM is shift change in most hospitals. There are a lot of confounders here.

Insulin pump versus multiple injections for DM 1

Conclusions and Relevance Among young patients with type 1 diabetes, insulin pump therapy, compared with insulin injection therapy, was associated with lower risks of severe hypoglycemia and diabetic ketoacidosis and with better glycemic control during the most recent year of therapy. These findings provide evidence for improved clinical outcomes associated with insulin pump therapy compared with injection therapy in children, adolescents, and young adults with type 1 diabetes.

Tuesday, January 15, 2019

Second dose antibiotic delay: responsible factors, outcomes

Objective: 1) Determine frequency and magnitude of delays in second antibiotic administration among patients admitted with sepsis; 2) Identify risk factors for these delays; and 3) Exploratory: determine association between delays and patient-centered outcomes (mortality and mechanical ventilation after second dose).

Design: Retrospective, consecutive sample sepsis cohort over 10 months.

Setting: Single, tertiary, academic medical center.

Patients: All patients admitted from the emergency department with sepsis or septic shock (defined: infection, greater than or equal to 2 systemic inflammatory response syndrome criteria, hypoperfusion/organ dysfunction) identified by a prospective quality initiative. Exclusions: less than 18 years old, not receiving initial antibiotics in the emergency department, death before antibiotic redosing, and patient refusing antibiotics.

Interventions: We determined first-to-second antibiotic time and delay frequency. We considered delay major for first-to-second dose time greater than or equal to 25% of the recommended interval. Factors of interest were demographics, recommended interval length, comorbidities, clinical presentation, location at second dose, initial resuscitative care, and antimicrobial activity mechanism.

Measurements and Main Results: Of 828 sepsis cases, 272 (33%) had delay greater than or equal to 25%. Delay frequency increased dose dependently with shorter recommended interval: 11 (4%) delays for 24-hour intervals (median time, 18.52 hr); 31 (26%) for 12-hour intervals (median, 10.58 hr); 117 (47%) for 8-hour intervals (median, 9.60 hr); and 113 (72%) for 6-hour intervals (median, 9.55 hr). In multivariable regression, interval length significantly predicted major delay (12 hr: odds ratio, 6.98; CI, 2.33–20.89; 8 hr: odds ratio, 23.70; CI, 8.13–69.11; 6 hr: odds ratio, 71.95; CI, 25.13–206.0). Additional independent risk factors were inpatient boarding in the emergency department (odds ratio, 2.67; CI, 1.74–4.09), initial 3-hour sepsis bundle compliance (odds ratio, 1.57; CI, 1.07–2.30), and older age (odds ratio, 1.16 per 10 yr, CI, 1.01–1.34). In the exploratory multivariable analysis, major delay was associated with increased hospital mortality (odds ratio, 1.61; CI, 1.01–2.57) and mechanical ventilation (odds ratio, 2.44; CI, 1.27–4.69).

Conclusions: Major second dose delays were common, especially for patients given shorter half-life pharmacotherapies and who boarded in the emergency department. They were paradoxically more frequent for patients receiving compliant initial care. We observed association between major second dose delay and increased mortality, length of stay, and mechanical ventilation requirement.

Solutions? Better integration of the emergency department with the rest of the hospital might help.


Don’t miss it on the wards. The presentation may be atypical.

Rhythm control of atrial fibrillation

Monday, January 14, 2019

NOACs versus warfarin for secondary stroke prevention in atrial fibrillation

Conclusions—Results from our study of the 3 NOACs versus warfarin in nonvalvular atrial fibrillation patients with a previous history of stroke/transient ischemic attack are relatively consistent with their respective phase III trials and previous stroke/transient ischemic attack subgroup analyses. All NOACs seemed no worse than warfarin in respect to ischemic stroke, ICH, or major bleeding risk.

SGLT-2 inhibitors: no increased risk of ketoacidosis in clinical trials in meta-analysis

This is in contrast to what is seen in the real world.

Status epilepticus and stress cardiomyopathy

From a paper in Critical Care Medicine:


Although stress cardiomyopathy has been described in association with epilepsy, its frequency in patients with convulsive status epilepticus remains unknown. Accordingly, we sought to determine the prevalence and risk factors of stress cardiomyopathy in patients admitted to the ICU for convulsive status epilepticus.


Prospective, descriptive, single-center study.


Medical-surgical ICU of a teaching hospital.


Thirty-two consecutive ventilated patients (21 men; age, 50 ± 18 yr; Simplified Acute Physiology Score II, 53 ± 15; Sequential Organ Failure Assessment, 6 ± 2) hospitalized in the ICU for convulsive status epilepticus.




Hemodynamic parameters, transthoracic echocardiography, biological data, and electrocardiogram were obtained serially on ICU admission (H0), and after 6, 12, 24, and 48 hours of hospitalization (H6, H12, H24, and H48). Stress cardiomyopathy was defined as a 20% decrease in left ventricular ejection fraction between H0 or H6 and H48. Stress cardiomyopathy was diagnosed in 18 patients (56%; 95% CI, 38-74%). Mean left ventricular ejection fraction, left ventricular stroke index and cardiac index were initially (at H0 or H6 according to lowest individual values) significantly reduced in stress cardiomyopathy patients (45 ± 14% vs 61 ± 6%, p less than 0.001; 24 ± 8 vs 28 ± 8 mL/m(2), p less than 0.05; 2.3 ± 0.7 vs 3.0 ± 0.8 L/min/m(2), p less than 0.05, respectively) and increased secondarily to reach similar mean values than those observed in patients without transient left ventricular dysfunction at H24. Dobutamine was more frequently used in patients with stress cardiomyopathy. Mean lactate level was increased and significantly higher in stress cardiomyopathy patients at H0 and H6, whereas mean central venous oxygen saturation was preserved but significantly lower in this group. Only three patients with stress cardiomyopathy had left ventricular regional wall motion abnormalities but normal coronary angiography. Risk factors of stress cardiomyopathy were age and Simplified Acute Physiology Score II.


These results suggest that stress cardiomyopathy is common in patients admitted to the ICU for convulsive status epilepticus. Accordingly, these patients should be screened for stress cardiomyopathy and monitored if they present with hemodynamic compromise.

Sunday, January 13, 2019

Crusted scabies

Patients’ perceptions of doctors’ relations with industry


The Physician Payments Sunshine Act, part of the Affordable Care Act, requires pharmaceutical and medical device firms to report payments they make to physicians and, through its Open Payments program, makes this information publicly available.


To establish estimates of the exposure of the American patient population to physicians who accept industry payments, to compare these population-based estimates to physician-based estimates of industry contact, and to investigate Americans’ awareness of industry payments.


Cross-sectional survey conducted in late September and early October 2014, with data linkage of respondents’ physicians to Open Payments data.


A total of 3542 adults drawn from a large, nationally representative household panel.

Main Measures

Respondents’ contact with physicians reported in Open Payments to have received industry payments; respondents’ awareness that physicians receive payments from industry and that payment information is publicly available; respondents’ knowledge of whether their own physician received industry payments.

Key Results

Among the 1987 respondents who could be matched to a specific physician, 65% saw a physician who had received an industry payment during the previous 12 months. This population-based estimate of exposure to industry contact is much higher than physician-based estimates from the same period, which indicate that 41% of physicians received an industry payment. Across the six most frequently visited specialties, patient contact with physicians who had received an industry payment ranged from 60 to 85%; the percentage of physicians with industry contact in these specialties was much lower (35–56%). Only 12% of survey respondents knew that payment information was publicly available, and only 5% knew whether their own doctor had received payments.

Patients’ contact with physicians who receive industry payments is more prevalent than physician-based measures of industry contact would suggest. Very few Americans know whether their own doctor has received industry payments or are aware that payment information is publicly available.

Nor do they seem to care.

Post-thrombotic syndrome: prevention and treatment

From a recent review:


•PTS can be more easily prevented by preventing first or recurrent DVT, than treated.
•Optimal anticoagulation is essential to reduce the risk and severity of PTS.
•Patients with iliofemoral DVT may require a more aggressive treatment approach over anticoagulation alone.
•Treatment of PTS is primarily based on compression therapy.
•Selected patients with severe PTS can be referred for consideration of interventional procedures in expert centers.


Post-thrombotic syndrome (PTS) is a complication that develops in up to 50% of patients with deep vein thrombosis (DVT) and manifests as symptoms and signs of chronic venous insufficiency of varying severity. PTS negatively affects patient's quality of life and causes significant burden to the healthcare system. The risk for PTS development can be markedly reduced by preventing DVT and providing appropriate anticoagulation once it develops. Patients with extensive proximal (iliofemoral) DVT may benefit from invasive interventions, such as catheter-directed thrombolysis. The effectiveness of elastic compression stockings (ECS) for PTS prevention has not been conclusively demonstrated in randomized trials.

Treatment of PTS is primarily based on ECS, exercise and lifestyle modifications. The effectiveness of various pharmacologic agents for PTS treatment remains controversial. Surgical or radiological interventions for vein reconstruction or revascularization may be considered in refractory cases.

This review summarizes current evidence regarding prevention and treatment of PTS of the lower limbs in adults.

Note that regarding regional thrombolysis, the ACCP guidelines do not generally recommend it. They do acknowledge that the therapeutic decision may be driven by patient preferences and values.

Saturday, January 12, 2019

In case you didn’t know, over a third of ER docs are industry puppets

I am a close follower of the Emergency Medicine Literature of Note blog. The author, Ryan Radecki, takes a skeptical approach to surrogate endpoints and is generally careful to avoid conclusions that over reach the data.

He seems to have violated his own rules, however, in his approach to this report on industry gifts to physicians. From the paper:


Characterize the frequency and magnitude of all categories of publicly reported financial payments made to emergency physicians (EPs) in the United States (U.S.) in 2017.


This cross-sectional study of the 2017 Centers for Medicare and Medicaid Services Open Payments Database was exempt from Institutional Review Board Review. We calculated descriptive statistics of the frequency, type, and amount (medians) of general, research, and ownerships transactions made to EPs from industry, described regional differences of median payments to EPs, and characterized the drugs or devices most commonly associated with transactions.


In 2017, among 40,899 practicing U.S. EPs, 14,447 (35.4%) received 51,870 general payments from industry totaling $12,870,832. The median per-physician payment was $18.30 (interquartile range [IQR], $13.63–$60.90). The most frequent transaction was food and beverage (89.6%), though most payments by dollar amount were related to speaker and consulting fees (74.5%). Antithrombotics were the most frequently drug or device associated with transactions. Only 35 (0.08%) and 20 (0.05%) EPs had research and ownership relationships with industry, respectively. A significant difference was observed in median payments per physician across all U.S. Census regions (p  less than 0.01) except when comparing Northeast and West (p = 1.00).


Over one-third of U.S. EPs had general payments from industry in 2017, while less than 1% of EPs had either research and ownership payments during this time period. Consistent with previous research, most payments to EPs are of low monetary value. Antithrombotics remain the most frequent drug associated with payments to EPs.

The vast majority of the gifts were small: lunches and dinners. There’s been quite a bit of research showing that even small gifts such as these influence physicians, largely out of their awareness. The problem with this research, extensive as it is, is that it is based on soft surrogate endpoints. Virtually nothing is known about the extent of the influence, let alone any downstream effects that might impact patient outcomes, for good or harm.

But Radecki’s post says this:

It’s CMS Open Payments Database time again, updated for 2017. Sadly, it turns out you or at least one of your closest colleagues is a witting or unwitting puppet of the pharmaceutical industry: a full 35.4% of practicing U.S. emergency physicians received payments from industry last year.

Clearly out of keeping with his usually cautions approach. Doesn’t the issue deserve more nuance?

EMR generated sepsis alerts: do they help patients at all?

Sepsis 3 versus Sepsis 2: practical impact on clinicians, systems improvement initiatives and coding

Don’t forget spontaneous coronary artery dissection (SCAD)

Refeeding syndrome in critical illness

From a review:

RFS is a potentially life-threatening condition induced by initiation of feeding after a period of starvation. Although a uniform definition is lacking, most definitions comprise a complex constellation of laboratory markers (i.e. hypophosphatemia, hypokalemia, hypomagnesemia) or clinical symptoms, including cardiac and pulmonary failure. Recent studies show that low caloric intake results in lower mortality rates in critically ill RFS patients compared with RFS patients on full nutritional support. Therefore, standard monitoring of RFS-markers (especially serum phosphate) and caloric restriction when RFS is diagnosed should be considered. Furthermore, standard therapy with thiamin and electrolyte supplementation is essential.

Friday, January 11, 2019

Review of mechanical ventilation

This free full text review from Mayo Clinic Proceedings extends beyond invasive mechanical ventilation to a general overview of respiratory failure.

Wednesday, January 09, 2019

The use of steroids and antimalarials in SLE

From a review:


Purpose of review

The purpose of this review is highlighting the most recent evidence on the clinical efficacy and toxicity of glucocorticoids and antimalarials in systemic lupus erythematosus (SLE) and provide recommendations on their current use.

Recent findings

Glucocorticoid toxicity is well known. Recent data confirm the increased risk of infection and damage accrual. An observational study form Hong Kong has seen increased mortality among users of high-dose prednisone regimes. Several studies support the efficacy of medium-low doses and methyl-prednisolone pulses in lupus patients, both with and without nephritis.

New data confirm the effects of antimalarials in preventing SLE activity, damage and infections, and in decreasing mortality. New screening recommendations for hydroxychloroquine maculopathy have been recently published. Combining mepacrine and hydroxychloroquine in patients with refractory cutaneous and/or articular lupus activity has proved highly effective.


Universal therapy with hydroxychloroquine should be aimed to patients with SLE without contraindications. Doses greater than 4 mg/kg/day should be avoided and regular eye screening warranted to minimize the risk of macular toxicity. Every effort should be made to reduce the dose of oral glucocorticoids. In moderate-severe flares, pulse methyl-prednisolone are more effective and much less toxic than increasing the oral doses of prednisone.

Reinitiation of systemic anticoagulation after a head bleed

Methods—We searched published medical literature to identify cohort studies involving adults with anticoagulation-associated ICH. Our predictor variable was resumption of anticoagulation. Outcome measures were thromboembolic events (stroke and myocardial infarction) and recurrence of ICH. After assessing study heterogeneity and publication bias, we performed a meta-analysis using random-effects models to assess the strength of association between anticoagulation resumption and our outcomes.

Results—Eight studies were eligible for inclusion in the meta-analysis, with 5306 ICH patients. Almost all studies evaluated anticoagulation with vitamin K antagonists. Reinitiation of anticoagulation was associated with a significantly lower risk of thromboembolic complications (pooled relative risk, 0.34; 95% confidence interval, 0.25–0.45; Q=5.12, P for heterogeneity=0.28). There was no evidence of increased risk of recurrent ICH after reinstatement of anticoagulation therapy, although there was significant heterogeneity among included studies (pooled relative risk, 1.01; 95% confidence interval, 0.58–1.77; Q=24.68, P for heterogeneity less than 0.001). No significant publication bias was detected in our analyses.

Conclusions—In observational studies, reinstitution of anticoagulation after ICH was associated with a lower risk of thromboembolic complications and a similar risk of ICH recurrence. Randomized clinical trials are needed to determine the true risk–benefit profile of anticoagulation resumption after ICH.

But the big question: how soon can you restart?

Reinitiation of anticoagulation occurred at a median of 10 to 39 days (Table 2). Four studies did not report the exact timing of resumption of anticoagulation, 12,15,16,19 but the majority of patients were prescribed anticoagulation within the first 3 months after ICH.

Epidemiology of post-thrombotic syndrome

Here is a recent review. From the paper:


•Post-thrombotic syndrome is the most frequent complication of DVT.
•After a proximal DVT, 20–50% of patients will develop PTS.
•Most important PTS predictors are extensive proximal DVT and ipsilateral recurrence.


The post thrombotic syndrome (PTS) refers to clinical manifestations of chronic venous insufficiency (CVI) following a deep-vein thrombosis (DVT). PTS is the most frequent complication of DVT, which develops in 20 to 50% of cases after proximal DVT and is severe in 5–10% of cases. The reported prevalence of PTS differs widely among studies because of differences in study populations, tools used to assess PTS, and time interval between acute DVT and PTS assessment. The two most important predictors of PTS are extensive proximal character of DVT and previous ipsilateral DVT. Other reported risk factors include pre-existing CVI, obesity, quality of anticoagulant treatment, older age and residual venous obstruction. Standardization of PTS assessment tools combined with the development of patient self-reported PTS scales are likely to constitute a breakthrough in research of the epidemiology of PTS, by allowing comparison between studies, meta-analyses and increasing the feasibility of longer follow-up of DVT patients. This should enable identification of patient populations at high risk of severe PTS, new predictors of PTS and targets for potential new treatments. In this perspective, identification of biomarkers that are predictive of PTS such as markers of inflammation is crucial in ongoing research.