Saturday, October 13, 2018

The cost of an outbreak of carbapenemase-producing Enterobacteriaceae

Report here.

Friday, October 12, 2018

Fludrocortisone versus midodrine for orthostatic hypotension


Background Orthostatic hypotension causes ≈80 000 hospitalizations per year in the United States. Treatments for orthostatic hypotension include fludrocortisone, a mineralocorticoid analog that promotes sodium reabsorption; and midodrine, an α‐1 adrenergic agonist that is a direct vasoconstrictor. Although both medications are used to treat orthostatic hypotension, few studies have compared their relative safety.

Methods and Results We compared incidence rates of hospitalizations for all causes, and for congestive heart failure between users of fludrocortisone and users of midodrine in a retrospective cohort study of Tennessee Medicaid adult enrollees (1995–2009). Adjusted incidence rate ratios were calculated using negative binomial regression models. Subgroup analyses based on history of congestive heart failure were conducted. We studied 1324 patients initiating fludrocortisone and 797 patients initiating midodrine. Compared with fludrocortisone users, midodrine users had higher prevalence of cardiovascular conditions. Incidence rates of all‐cause hospitalizations for fludrocortisone and midodrine users were 1489 and 1330 per 1000 person‐years, respectively (adjusted incidence‐rate ratio 1.20, 95% confidence interval, 1.02–1.40). The respective rates of heart failure–related hospitalization were 76 and 84 per 1000 person‐years (adjusted incidence‐rate ratio: 1.33, 95% confidence interval, 0.79–2.56). Among patients with a history of congestive heart failure, the rates of all‐cause hospitalization for fludrocortisone and midodrine were 2448 and 1820 per 1000 person‐years (adjusted incidence‐rate ratio: 1.42, 95% confidence interval, 1.07–1.90), and the respective rates of heart failure exacerbation–related hospitalizations were 297 and 263 per 1000 person‐years (adjusted incidence‐rate ratio: 1.48, 95% confidence interval, 0.69–3.16).

Conclusions Compared with users of midodrine, users of fludrocortisone had higher rates of all‐cause hospitalizations, especially among patients with congestive heart failure.

Clinical Perspective

What Is New?

This is the first study to evaluate the comparative safety of fludrocortisone and midodrine, 2 drugs commonly used for the treatment of orthostatic hypotension.

Fludrocortisone use was associated with increased risk of all‐cause hospitalizations, particularly among patients with prevalent history of heart failure and orthostatic hypotension.

What Are the Clinical Implications?

Our findings should help inform healthcare providers about safety of fludrocortisone use in patients with orthostatic hypotension.

Our findings could be used to aid healthcare providers to make treatment decisions for patients with orthostatic hypotension.

In patients with heart failure and orthostatic hypotension, fludrocortisone should not be used.

Thursday, October 11, 2018

Oral agents for type 2 diabetes: ACP guidelines

Recommendation 1:

ACP recommends that clinicians prescribe metformin to patients with type 2 diabetes when pharmacologic therapy is needed to improve glycemic control. (Grade: strong recommendation; moderate-quality evidence)
Recommendation 2:

ACP recommends that clinicians consider adding either a sulfonylurea, a thiazolidinedione, an SGLT-2 inhibitor, or a DPP-4 inhibitor to metformin to improve glycemic control when a second oral therapy is considered. (Grade: weak recommendation; moderate-quality evidence.) ACP recommends that clinicians and patients select among medications after discussing benefits, adverse effects, and costs.

Appendix table 1 has a nice summary on outcomes.

Wednesday, October 10, 2018

Adrenal insufficiency due to chronic opiate use

Available data from small heterogeneous studies suggest that 9% to 29% of patients receiving long-term treatment with opiates have development of adrenal insufficiency. However, predictors and the timing of the OIAI onset are unclear. Given the widespread use of narcotics in every field of medicine, physicians should be aware of the potential for endocrine-related adverse effects, in particular OIAI. We suggest careful consideration of OIAI in any patient receiving long-term opiate therapy who manifests symptoms and signs suggestive of adrenal insufficiency. Prospective large studies need to be designed with the goals of elucidating factors associated with OIAI, developing the best approach to case detection of OIAI, and establishing an appropriate management and monitoring plan.

Tuesday, October 09, 2018

Monday, October 08, 2018

Obfuscation of the language: assisted suicide and euthanasia are now medical assistance in dying (MAID)

Sunday, October 07, 2018

TAVR reverses the acquired Von Willebrand syndrome in severe aortic stenosis



In this study, we sought to analyze the incidence and relevance of von Willebrand factor (VWF) abnormalities in patients undergoing transcatheter aortic valve implantation (TAVI), especially on perioperative bleeding. Furthermore, we hypothesized that, similar to aortic valve surgery, TAVI results in a restoration of VWF abnormalities.

Methods and results

We performed a prospective analysis of periinterventional VWF parameters in 74 patients (80 ± 7 years, female in 37.5%) undergoing transfemoral TAVI for severe symptomatic aortic valve stenosis. At baseline, VWF:Ag was 210 ± 90 IU/dl with a mean VWF activity of 166 ± 106 IU/dl; activity-to-antigen ratio was 0.85 ± 0.45. Heyde's syndrome (severe aortic stenosis plus GI bleeding from angiodyplasia) was observed in 2/74 (2.7%). Whereas preprocedural loss of high-molecular-weight (HMW) VWF multimers was found in thirty-six patients (48.6%), none of the patients fulfilled criteria for possible acquired VW syndrome. After TAVI, an increase of both VWF:Ag and activity compared to baseline was observed (p less than 0.01). In patients with HMW multimer loss, post-interventional recovery of multimers occurred in all cases. In the two patients with Heyde's syndrome, a trend towards reduced VWF:Ag was seen, with loss of HMW multimers in one patient. Of interest, all patients suffering from periprocedural major bleeding (5/74; 6.8%) exhibited activity-to-antigen ratios less than 0.7, indicating subclinical VWF dysfunction.


Whereas clinically relevant VWF dysfunction is rare, loss of HMW VWF multimers is common in TAVI patients. Similar to surgery, TAVI leads to a restoration of this loss. Furthermore, VWF parameters may be useful parameter to evaluate risk of periprocedural bleeding.

PE related cardiac arrest



Pulmonary Embolism (PE) is a relatively common cardiovascular condition, occasionally and tragically manifesting as Sudden Cardiac Arrest (SCA). The natural history of SCA complicating PE has been poorly evaluated.In this study, we described the management and outcome of PE-related SCA.


In this prospective population-­based study, we included all patients admitted at hospital alive after out­ of­ hospital SCA, in Paris and suburbs, France (6.6 million inhabits), from May 2011 to September 2015.


Of 2926 patients hospitalized after SCA, 82 cases were diagnosed as PE-related SCA (2.8%, 95%CI = 2.2–3.4). Systemic thrombolysis was performed in 47 patients (57%), without significant increased risk of major bleeding among patients treated with thrombolysis. 12 patients (15%) were treated with ECLS, 29 patients (36%) had targeted temperature management, and 20 patients (24%) underwent coronary angiography. 94% of PE-related SCA had initial non-shockable rhythm, and were associated with better survival compared with other non-shockable SCA (crude OR = 3.0, 95%CI = 1.7–5.4, P less than 0.001; adjusted OR = 4.1, 95%CI 2.0–8.3, P less than  0.001). Among PE-related SCA, thrombolysis was independently associated with survival (OR = 12.5, 95%CI = 1.8–89.1, P = 0.01). Multiple sensitivity analysis was performed, with consistent results.


PE is responsible of approximately 3% of hospitalizations for SCA. Thrombolysis was associated with an increased survival in this population, reinforcing current guidelines advocating for such treatment in PE-related SCA.

Obesity related digestive diseases

From a free full text review:

Obesity is a growing medical and public health problem worldwide. Many digestive diseases are related to obesity. In this article, the current state of our knowledge of obesity-related digestive diseases, their pathogenesis, and the medical and metabolic consequences of weight reduction are discussed. Obesity-related digestive diseases include gastroesophageal reflux disease, Barrett’s esophagus, esophageal cancer, colon polyp and cancer, nonalcoholic fatty liver disease, hepatitis C-related disease, hepatocellular carcinoma, gallstone, cholangiocarcinoma, and pancreatic cancer. Although obesity-related esophageal diseases are associated with altered mechanical and humoral factors, other obesity-related digestive diseases seem to be associated with obesity-induced altered circulating levels of adipocytokines and insulin resistance. The relationship between functional gastrointestinal disease and obesity has been debated. This review provides a comprehensive evaluation of the obesity-related digestive diseases, including pathophysiology, obesity-related risk, and medical and metabolic effects of weight reduction in obese subjects.

Saturday, October 06, 2018

Practical aspects of outpatient management of PE


•Selected patients with acute pulmonary embolism can be safely treated at home.
•Eligibility criteria are firstly pragmatic as those regrouped in the HESTIA rule.
•Severity criteria as a low PESI score are sometimes used in addition.
•A specific procedure for outpatient care of PE patients must be provided.


Despite clear potential benefits of outpatient care, most patients suffering from pulmonary embolism (PE) are currently hospitalized due to the fear of possible adverse events. Nevertheless, some teams have increased or envisage to increase outpatient treatment or early discharge.

We performed a narrative systematic review of studies published on this topic. We identified three meta-analyses and 23 studies, which involved 3671 patients managed at home (n = 3036) or discharged early (n = 535). Two main different approaches were applied to select patients eligible for outpatient in recent prospective studies, one based on a list of pragmatic criteria as the HESTIA rule, the other adding severity criteria (i.e. risk of death) as the Pulmonary Embolism Severity Criteria (PESI) or simplified PESI. In all these studies, a specific follow-up was performed for patients managed at home involving a dedicated team. The overall early (i.e. between 1 to 3 months) complication rate was low, less than 2% for thromboembolic recurrences or major bleedings and less than 3% for deaths with no evidence in favour of one selection strategy or another.

Outpatient management appears to be feasible and safe for many patients with PE.

In the coming years, outpatient treatment may be considered as the first line management for hemodynamically stable PE patients, subject to the respect of simple eligibility criteria and on the condition that a specific procedure for outpatient care is developed in advance.

We could be treating more PE patients at home

Careful clinical assessment to determine which patients are at low risk is important but maybe that’s too much trouble for some.

Enoxaparin dose for VTE prophylaxis in obese patients

The higher dose in obese patients was associated with better anti-Xa levels and no increase in bleeding. This was a small study.

Friday, October 05, 2018

PE hiding out in COPD exacerbation

Background Patients with COPD experience episodes of increased inflammation, so-called acute exacerbations of COPD (AE-COPD). In 30% of AE-COPD cases, no clear cause is found. Since there is well-known cross talk between inflammation and thrombosis, the objectives of this study were to determine the prevalence, embolus localization, clinical relevance, and clinical markers of pulmonary embolism (PE) in unexplained AE-COPD.

Methods A systematic search was performed using MEDLINE and EMBASE platforms from 1974 to October 2015. Prospective and cross-sectional studies that included patients with AE-COPD and used pulmonary CT-angiography for diagnosis of PE were included.

Results The systematic search resulted in 1,650 records. The main reports of 22 articles were reviewed, and 7 studies were included. The pooled prevalence of PE in unexplained AE-COPD was 16.1% (95% CI, 8.3%-25.8%) in a total of 880 patients. Sixty-eight percent of the emboli found were located in the main pulmonary arteries, lobar arteries, or interlobar arteries. Mortality and length of hospital admission seemed to be increased in patients with unexplained AE-COPD and PE. Pleuritic chest pain and cardiac failure were more frequently reported in patients with unexplained AE-COPD and PE. In contrast, signs of respiratory tract infection was less frequently related to PE.

Conclusions PE is frequently seen in unexplained AE-COPD. Two-thirds of emboli are found at locations that have a clear indication for anticoagulant treatment. These findings merit clinical attention. PE should receive increased awareness in patients with unexplained AE-COPD, especially when pleuritic chest pain and signs of cardiac failure are present, and no clear infectious origin can be identified.

Update on procalcitonin use to facilitate antibiotic stewardship

Obesity, body fat distribution and cancer risk


We evaluated the associations of anthropometric indicators of general obesity (body mass index, BMI), an established risk factor of various cancer, and body fat distribution (waist circumference, WC; hip circumference, HC; and waist-to-hip ratio, WHR), which may better reflect metabolic complications of obesity, with total obesity-related and site-specific (colorectal and postmenopausal breast) cancer incidence.


This is a meta-analysis of seven prospective cohort studies participating in the CHANCES consortium including 18 668 men and 24 751 women with a mean age of 62 and 63 years, respectively. Harmonised individual participant data from all seven cohorts were analysed separately and alternatively for each anthropometric indicator using multivariable Cox proportional hazards models.


After a median follow-up period of 12 years, 1656 first-incident obesity-related cancers (defined as postmenopausal female breast, colorectum, lower oesophagus, cardia stomach, liver, gallbladder, pancreas, endometrium, ovary, and kidney) had occurred in men and women. In the meta-analysis of all studies, associations between indicators of adiposity, per s.d. increment, and risk for all obesity-related cancers combined yielded the following summary hazard ratios: 1.11 (95% CI 1.02–1.21) for BMI, 1.13 (95% CI 1.04–1.23) for WC, 1.09 (95% CI 0.98–1.21) for HC, and 1.15 (95% CI 1.00–1.32) for WHR. Increases in risk for colorectal cancer were 16%, 21%, 15%, and 20%, respectively per s.d. of BMI, WC, HC, and WHR…


BMI, WC, HC, and WHR show comparable positive associations with obesity-related cancers combined and with colorectal cancer in older adults.

Thursday, October 04, 2018

PCSK 9 inhibitors

Reported penicillin allergy was a driver of carbapanem use

Review article on obesity

Here’s a nice review in JACC. The accompanying audio file is free.

Wednesday, October 03, 2018

Dealing with penicillin allergy

Pathways, protocols, core measures, bundles and check lists

The latest on oral anticoagulant reversal


•The use of PCC for VKA-associated INR elevation is effective and well-studied.
•Use of Four factor-PCC is superior to FFP for reversal of VKA-associated INR elevation.
•There are no studies on clinical efficacy of non-specific agents for DOAC reversal.



Approximately 4–6% of patients treated with oral anticoagulants (OAC) will suffer from major hemorrhage or be in need of urgent surgery necessitating anticoagulant reversal therapy. Several new oral anticoagulants and reversal agents have been introduced that make it difficult for physicians to stay updated on the current evidence of reversal management. This study aims to review the recent literature on oral anticoagulation reversal therapy and to present the current evidence in an easily approachable manner.

Materials and methods

A systematic literature search was conducted using PubMed and EMBASE to identify the latest publications on both vitamin K antagonist (VKA) and direct oral anticoagulant (DOAC) reversal strategies. All studies on humans who received any acute reversal management of VKA treatment were included, except case studies. Since only two studies on acute reversal of DOAC treatment have been published, clinical trials on healthy volunteers were also included.


Twenty-one studies with a total of 4783 VKA treated patients, and 12 studies with a total of 529 DOAC treated patients were included. Elevated INR values due to VKA treatment could be reversed (INR less than or equal to 1.5) in 63.1% (95% CI: 61.0–65.2) of study subjects after treatment with 4F-PCC, as compared with 12.2% (95% CI: 8.2–16.2) after treatment with fresh frozen plasma (FFP), (p less than  0.001). Thromboembolism occurred in 1.6% (95% CI: 1.2–2.1) of VKA-patients treated with 4F-PCC, and in 4.5% (95% CI: 2.3–6.7) of FFP-treated patients. To date, reversal of laboratory parameters has been demonstrated for two reversal agents specific to DOACs: idarucizumab for dabigatran reversal and andexanet-alfa for factor Xa-inhibitor reversal.


This review supports the use of PCC for VKA reversal, specifically for 4F-PCC over FFP for laboratory reversal. There are no studies on clinical efficacy of non-specific agents for DOAC reversal and the evidence for laboratory reversal is not consistent.

Tuesday, October 02, 2018

Pan CT scanning to look for occult malignancy after a diagnosis of unprovoked VTE

Periprocedural management of anticoagulation in non-valvular a fib: what the hospitalist needs to know

This expert consensus decision pathway is available as free full text here. It is in line with published guidelines and other posts I have written on this topic. This applies only to non-valvular a fib as the anticoagulation indication.

Monday, October 01, 2018

The pancreatitis activity scoring system (PASS)

Pancreatitis is both vexing and fascinating. The spectrum of severity and complications is wide. Unfortunately, all too often it is not apparent on day one. Complications typically unfold, one organ system at a time, over several days. When admitting a patient with pancreatitis from the ER it is all but impossible to answer the question “Where will this patient be in four days?” Home? Or in the ICU on mechanical ventilation? The Ranson score, for example, requires assessment out to 48 hours in order to predict mortality. Since Ranson there have been many attempts to develop easier to use tools to assess severity and predict complications. One of the latest is the PASS. The PASS can predict severity on day one according to this report. This free full text article explains the score in more detail. My concern is that it is difficult to use and incorporates subjective components (numeric pain scale).

Nut consumption and health


Although nut consumption has been associated with a reduced risk of cardiovascular disease and all-cause mortality, data on less common causes of death has not been systematically assessed. Previous reviews missed several studies and additional studies have since been published. We therefore conducted a systematic review and meta-analysis of nut consumption and risk of cardiovascular disease, total cancer, and all-cause and cause-specific mortality.

PubMed and Embase were searched for prospective studies of nut consumption and risk of cardiovascular disease, total cancer, and all-cause and cause-specific mortality in adult populations published up to July 19, 2016. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random-effects models. The burden of mortality attributable to low nut consumption was calculated for selected regions.


Twenty studies (29 publications) were included in the meta-analysis. The summary RRs per 28 grams/day increase in nut intake was for coronary heart disease, 0.71 (95% CI: 0.63–0.80, I2 = 47%, n = 11), stroke, 0.93 (95% CI: 0.83–1.05, I2 = 14%, n = 11), cardiovascular disease, 0.79 (95% CI: 0.70–0.88, I2 = 60%, n = 12), total cancer, 0.85 (95% CI: 0.76–0.94, I2 = 42%, n = 8), all-cause mortality, 0.78 (95% CI: 0.72–0.84, I2 = 66%, n = 15), and for mortality from respiratory disease, 0.48 (95% CI: 0.26–0.89, I2 = 61%, n = 3), diabetes, 0.61 (95% CI: 0.43–0.88, I2 = 0%, n = 4), neurodegenerative disease, 0.65 (95% CI: 0.40–1.08, I2 = 5.9%, n = 3), infectious disease, 0.25 (95% CI: 0.07–0.85, I2 = 54%, n = 2), and kidney disease, 0.27 (95% CI: 0.04–1.91, I2 = 61%, n = 2). The results were similar for tree nuts and peanuts. If the associations are causal, an estimated 4.4 million premature deaths in the America, Europe, Southeast Asia, and Western Pacific would be attributable to a nut intake below 20 grams per day in 2013.


Higher nut intake is associated with reduced risk of cardiovascular disease, total cancer and all-cause mortality, and mortality from respiratory disease, diabetes, and infections.