Wednesday, July 30, 2014

Physical activity and the metabolic syndrome

Another reminder, from a review:

Physical activity has favorable effects on all components of the metabolic syndrome and on the resulting cardiovascular risk, the cornerstone in the development of cardiometabolic diseases. The quantity and the frequency of physical activity necessary to produce beneficial effects has not been defined as yet, but brisk walking is considered particularly appropriate, as it can be practiced by a large number of individuals, without any additional cost, and has a low rate of injury. The effects of exercise and leisure time physical activity extend from prevention to treatment of the various components of the metabolic syndrome, as well as to mood and quality of life.

Tuesday, July 29, 2014

Meta-analysis of prone ventilation for severe ARDS

From the paper:

Data Synthesis:This analysis included 11 randomized controlled trial, 2,246 total adult patients, and 1,142 patients ventilated in the prone position. Prone positioning during ventilation significantly reduced overall mortality in the random-effect model (odds ratio, 0.77; 95% CI, 0.59–0.99; p = 0.039; I2 = 33.7%), and the effects were marked in the subgroup in which the duration of prone positioning was more than 10 hr/session, compared with the subgroup with a short-term duration of prone positioning (odds ratio, 0.62; 9% CI, 0.48–0.79; p = 0.039; pinteraction = 0.015). Prone positioning was significantly associated with pressure ulcers (odds ratio, 1.49; 95% CI, 1.18–1.89; p = 0.001; I2 = 0.0%) and major airway problems (odds ratio, 1.55; 95% CI, 1.10–2.17; p = 0.012; I2 = 32.7%).
Conclusions:Ventilation in the prone position significantly reduced overall mortality in patients with severe acute respiratory distress syndrome. Sufficient duration of prone positioning was significantly associated with a reduction in overall mortality. Prone ventilation was also significantly associated with pressure ulcers and major airway problems.

Monday, July 28, 2014

How low can you go? Evaluating the trigger for a restrictive transfusion strategy

From a recent systematic review and meta-analysis:

In the primary analysis, pooled results from 3 trials with 2364 participants showed that a restrictive hemoglobin transfusion trigger of less than 7 g/dL resulted in reduced in-hospital mortality (risk ratio [RR], 0.74; confidence interval [CI], 0.60-0.92), total mortality (RR, 0.80; CI, 0.65-0.98), rebleeding (RR, 0.64; CI, 0.45-0.90), acute coronary syndrome (RR, 0.44; CI, 0.22-0.89), pulmonary edema (RR, 0.48; CI, 0.33-0.72), and bacterial infections (RR, 0.86; CI, 0.73-1.00), compared with a more liberal strategy. The number needed to treat with a restrictive strategy to prevent 1 death was 33. Pooled data from randomized trials with less restrictive transfusion strategies showed no significant effect on outcomes.
In patients with critical illness or bleed, restricting blood transfusions by using a hemoglobin trigger of less than 7 g/dL significantly reduces cardiac events, rebleeding, bacterial infections, and total mortality. A less restrictive transfusion strategy was not effective.

Observational studies on patients with very low hemoglobin concentrations (5 or 6) who are normovolemic show that they tolerate it well. Compensatory mechanisms for the anemia are cited:

A systematic review found consistent evidence that normovolemic anemia is associated with a reduction in systemic vascular resistance and an increase in cardiac output, coronary and cerebral blood flow, and synthesis of 2,3-diphosphoglycerate in red blood cells, resulting in maintenance of oxygen delivery and extraction.

Increased red cell 2,3 DPG levels shifts the oxy-hemoglobin dissociation curve to the right, making hemoglobin less stingy. Transfused red cells on the other hand may have decreased 2,3 DPG levels as a result of storage.

Improved outcomes with a restrictive strategy were seen across the board, including two groups of particular interest: acute bleeding and coronary artery disease.

Here is a recent study showing improved outcomes with a restrictive strategy in patients with GI bleeding.

Related editorial here.

My institution has adopted a restrictive transfusion strategy, leveraged by the EMR. It has worked, as evidenced by the number of frantic calls I get from nursing personnel, triggered by very low H&H levels on morning labs.

Sunday, July 27, 2014

SARS versus MERS

From a recent review:

Recent findingsBats are the natural reservoirs of SARS-like coronaviruses (CoVs) and are likely the reservoir of MERS coronavirus (MERS-CoV). Although a small number of camels have been found to have positive nasal swabs by real-time polymerase chain reaction and to carry antibody against MERS-CoV, the transmission route and the intermediary animal source remain uncertain amongst the sporadic primary cases. Both SARS-CoV and MERS-CoV may cause severe respiratory failure and extrapulmonary features such as diarrhoea, whereas mild or asymptomatic cases also occur in both conditions. In comparison with SARS, patients with MERS are older with male predominance, more comorbid illness and relatively lower human-to-human transmission potential. Although the viral kinetics of MERS-CoV remain unknown, nosocomial infections of MERS occur early within the first week of illness of the index case, whereas those of SARS occurred mainly in the second week of illness when the patient's upper airway viral load peaks on day 10 of illness. In-vitro data suggest that interferon (IFN) with or without ribavirin and mycophenolic acid may inhibit MERS-CoV, whereas protease inhibitors and IFN have inhibitory activity against SARS-CoV.

SummaryAlthough there are some similarities in the clinical features, MERS progresses to respiratory failure much more rapidly than SARS. The higher case fatality rate of MERS is likely related to older age and comorbid illness. More studies are needed to understand MERS-CoV in order to guide public health infection control measures and treatment.

Saturday, July 26, 2014

Effect of a transitions program on readmission


Results Over the 2-year study period, 19,659 unique patients had 26,781 qualifying index admissions, 2,523 of which resulted in a readmission within 30 days of discharge. After adjusting for various demographic and clinical characteristics, the usual care group (i.e., patients who did not participate in the program) had nearly twice the odds of readmission within 30 days (odds ratio [OR], 1.90; 95% confidence interval [CI], 1.35–2.67), compared with the intervention group (i.e., program participants). For patients age 65 years or older, those in the usual care group had a sixfold increase in the odds of a 30-day readmission (OR, 6.05; 95% CI, 1.92–19.00) relative to those in the intervention group.

Via Hospital Medicine Virtual Journal Club.

Uric acid as a risk factor for erectile dysfunction

In this study there was a two fold increase in risk of ED for every 1 mg/dL increase in uric acid.

HT to Clinical Cases and Images.

Thursday, July 24, 2014

IVC filters for patients with unstable pulmonary embolism

PE of such severity that another one is likely to be fatal has been a popular, though not strictly evidence based, indication for IVC filter insertion. However accumulating lower level evidence and opinion increasingly favor such use. Here's such an opinion recently published in the American Journal of Medicine.

Wednesday, July 23, 2014

Sedation in mechanically ventilated patients

Here's a trial comparing daily interruption of continuous infusion sedation with prn sedation. From the study:

Adult patients expected to need mechanical ventilation for more than 24 hours were randomly assigned, in a single center, either to daily interruption of continuous sedative and opioid infusion or to intermittent sedation. In both cases, our goal was to maintain a Sedation Agitation Scale (SAS) level of 3 or 4; that is patients should be calm, easily arousable or awakened with verbal stimuli or gentle shaking. Primary outcome was ventilator-free days in 28 days. Secondary outcomes were ICU and hospital mortality, incidence of delirium, nurse workload, self-extubation and psychological distress six months after ICU discharge.

A total of 60 patients were included. There were no differences in the ventilator-free days in 28 days between daily interruption and intermittent sedation (median: 24 versus 25 days, P = 0.160). There were also no differences in ICU mortality (40 versus 23.3%, P = 0.165), hospital mortality (43.3 versus 30%, P = 0.284), incidence of delirium (30 versus 40%, P = 0.472), self-extubation (3.3 versus 6.7%, P = 0.514), and psychological stress six months after ICU discharge. Also, the nurse workload was not diPatients in the intermittent sedation group would be kept without continuous infusion of sedatives if the intubation had been performed in the ICU, or would have their infusion interrupted after randomization if they had been admitted already intubated from emergency department, surgical room, wards or another ICU. Patients would be kept without sedatives infusion until they awoke. After patients were awake, if they were calm and collaborative (SAS of 4), they would be kept without infusion of sedatives. If the patient was uncomfortable or agitated (SAS greater then or equal to 5), the physician (attending or resident) would be consulted, and possible causes of discomfort would be investigated in a standardized method (pain, patient-ventilator asynchrony, thirst, hunger, and position on the bed, all of them using a poster which included figures expressing these uncomfortable sensations) and treated. Pain was treated with boluses of fentanyl (50 to 150 μg). If the pain recrudesced in less than two hours or there was a persistent pain stimulus (for example, surgical scar, drains) a continuous infusion of fentanyl would be initiated and titrated by the attending nurse using numeric pain scale (which measures pain from 0 = no pain, to 10 = the worst pain ever experienced) aiming a value less than or equal to 4. If agitation had no visible cause and pain was already empirically treated with a bolus of fentanyl, then delirium would be suspected and haloperidol administrated (bolus of 2.5 or 5 mg). After 15 minutes, if the patient was still uncomfortable or agitated, a continuous infusion of midazolam or propofol would be initiated to achieve a SAS of 3 to 4. The choice between midazolam and propofol was at the discretion of the attending physician. Sedative dosing would be titrated every two hours thereafter or sooner if the patient was agitated (that is, SAS greater than or equal to 5). Interruption of sedatives infusions would then be performed during the next shift (morning, afternoon or night) in order to try to keep the patient without sedation again.fferent between groups, but it was reduced on day 5 compared to day 1 in both groups (Nurse Activity Score (NAS) in the intermittent sedation group was 54 on day 1 versus 39 on day 5, P less than 0.001; NAS in daily interruption group was 53 on day 1 versus 38 on day 5, P less than 0.001). Fentanyl and midazolam total dosages per patient were higher in the daily interruption group. The tidal volume was higher in the intermittent sedation group during the first five days of ICU stay. 

There was no difference in the number of ventilator-free days in 28 days between both groups. Intermittent sedation was associated with lower sedative and opioid doses.

Prior research cited in the paper yielded similar results. In looking at the accumulating experience it appears that the less sedation given the better. No sedation at all may be best for those patients who can tolerate it.

The protocol for the prn sedative group is noteworthy. Again, from the paper:

Patients in the intermittent sedation group would be kept without continuous infusion of sedatives if the intubation had been performed in the ICU, or would have their infusion interrupted after randomization if they had been admitted already intubated from emergency department, surgical room, wards or another ICU. Patients would be kept without sedatives infusion until they awoke. After patients were awake, if they were calm and collaborative (SAS of 4), they would be kept without infusion of sedatives. If the patient was uncomfortable or agitated (SAS greater then or equal to 5), the physician (attending or resident) would be consulted, and possible causes of discomfort would be investigated in a standardized method (pain, patient-ventilator asynchrony, thirst, hunger, and position on the bed, all of them using a poster which included figures expressing these uncomfortable sensations) and treated. Pain was treated with boluses of fentanyl (50 to 150 μg). If the pain recrudesced in less than two hours or there was a persistent pain stimulus (for example, surgical scar, drains) a continuous infusion of fentanyl would be initiated and titrated by the attending nurse using numeric pain scale (which measures pain from 0 = no pain, to 10 = the worst pain ever experienced) aiming a value less than or equal to 4. If agitation had no visible cause and pain was already empirically treated with a bolus of fentanyl, then delirium would be suspected and haloperidol administrated (bolus of 2.5 or 5 mg). After 15 minutes, if the patient was still uncomfortable or agitated, a continuous infusion of midazolam or propofol would be initiated to achieve a SAS of 3 to 4. The choice between midazolam and propofol was at the discretion of the attending physician. Sedative dosing would be titrated every two hours thereafter or sooner if the patient was agitated (that is, SAS greater than or equal to 5). Interruption of sedatives infusions would then be performed during the next shift (morning, afternoon or night) in order to try to keep the patient without sedation again.

As illustrated above prn sedation requires a systematic, not a knee-jerk, approach to the patient involving pain control and a series of assessments for the causes of agitation, followed by bolus haloperidol before resorting to benzodiazepines or propofol.

The caveat is that this approach is not likely suitable for patients with ARDS who require low tidal volume ventilation and sometimes prone positioning and neuromuscular blockade, modalities which require continuous sedation.

Sunday, July 20, 2014

Disappointing results for ICU telemedicine

From a recent study:

Design, Setting, and Participants  Observational pre-post study of patients treated in 8 “intervention” ICUs (7 hospitals within the US Department of Veterans Affairs health care system) during 2011-2012 that implemented TM monitoring during the post-TM period as well as patients treated in concurrent control ICUs that did not implement an ICU TM program.
Intervention  Implementation of ICU TM monitoring.
Main Outcomes and Measures  Unadjusted and risk-adjusted ICU, in-hospital, and 30-day mortality rates and ICU and hospital LOS for patients who did or did not receive treatment in ICUs equipped with TM monitoring.
Results Our study included 3355 patients treated in our intervention ICUs (1708 in the pre-TM period and 1647 in the post-TM period) and 3584 treated in the control ICUs during the same period. Patient demographics and comorbid illnesses were similar in the intervention and control ICUs during the pre-TM and post-TM periods...Implementation of ICU TM was not associated with a significant decline in ICU, in-hospital, or 30-day mortality rates or LOS in unadjusted or adjusted analyses. For example, unadjusted ICU mortality in the pre-TM vs post-TM periods were 2.9% vs 2.8% (P = .89) for the intervention ICUs and 4.0% vs 3.4% (P = .31) for the control ICUs. Unadjusted 30-day mortality during the pre-TM vs post-TM periods were 7.7% vs 7.8% (P = .91) for the intervention ICUs and 12.0% vs 10.2% (P = .08) for the control ICUs. Evaluation of interaction terms comparing the magnitude of mortality rate change during the pre-TM and post-TM periods in the intervention and control ICUs failed to demonstrate a significant reduction in mortality rates or LOS.

Saturday, July 19, 2014

Transfusion thresholds and the risk of hospital associated infections

Interesting findings from a recent meta-analysis:

Data Extraction and Synthesis Twenty-one randomized trials with 8735 patients met eligibility criteria, of which 18 trials (n = 7593 patients) contained sufficient information for meta-analyses…
Results The pooled risk of all serious infections was 11.8% (95% CI, 7.0%-16.7%) in the restrictive group and 16.9% (95% CI, 8.9%-25.4%) in the liberal group. The risk ratio (RR) for the association between transfusion strategies and serious infection was 0.82 (95% CI, 0.72-0.95) with little heterogeneity (I2 = 0%; τ2 less than .0001). The number needed to treat (NNT) with restrictive strategies to prevent serious infection was 38 (95% CI, 24-122). The risk of infection remained reduced with a restrictive strategy, even with leukocyte reduction (RR, 0.80 [95% CI, 0.67-0.95]). For trials with a restrictive hemoglobin threshold of less than 7.0 g/dL, the RR was 0.82 (95% CI, 0.70-0.97) with NNT of 20 (95% CI, 12-133). With stratification by patient type, the RR was 0.70 (95% CI, 0.54-0.91) in patients undergoing orthopedic surgery and 0.51 (95% CI, 0.28-0.95) in patients presenting with sepsis. There were no significant differences in the incidence of infection by RBC threshold for patients with cardiac disease, the critically ill, those with acute upper gastrointestinal bleeding, or for infants with low birth weight.
Conclusions and Relevance Among hospitalized patients, a restrictive RBC transfusion strategy was associated with a reduced risk of health care–associated infection compared with a liberal transfusion strategy.

Friday, July 18, 2014

Update on vena caval filters

Here's a recent review.

The review covers both SVC and IVC filters.

SVC filters

Upper extremity DVT has a relatively low risk of causing PE. Moreover a significant complication rate associated with SVC filters raises the question of whether the benefits exceed the risks. From the review:

The low rate of PE and fatal PE associated with upper extremity thrombosis and the morbidity and mortality associated with SVC filters indicate that filters should not be used for upper extremity thrombosis except in the most extreme of circumstances.

IVC filters

Clinical judgment may occasionally dictate the use of an IVC filter in patients with high risk, large clot burden PEs who also have acute DVT. Low level evidence suggests that this approach may be beneficial. However, support for IVC filters based on high quality evidence is limited and at present the only well established indication is for acute proximal DVT and a contraindication to anticoagulant therapy. Here is a summary from the review:

Practice points
Vena cava filters prevent pulmonary embolism.

Vena cava filters increase the risk for deep venous thrombosis and vena cava thrombosis.

The only guideline approved indication for vena cava filter placement is prevention of pulmonary embolism in patients with known DVT and contraindication to anticoagulation.

Optional vena cava filters are preferred for most patients unless they have a permanent contraindication to anticoagulation and their risk for thromboembolism is persistent.

Optional vena cava filters should be removed whenever they are no longer indicated. Physicians and hospitals need to implement programs to follow patients with optional filters in order to optimize filter retrieval rates.

Wednesday, July 16, 2014

Work up and secondary prevention after ischemic stroke

Here is an excellent free full text review in Circulation.

A few important points from the review:

Initial imaging localizes the ischemic lesion and may identify the culprit artery.
Such imaging consists of MRI, MRA, CTA, carotid ultrasound, some combination thereof.

This initial evaluation allows placement of the ischemic stroke into one of several categories:

Based on the results of the initial neuroimaging studies, the stroke can be classified into preliminary diagnostic categories: large vessel occlusion, small vessel occlusion, potential cardioembolic, or unknown/other.

Small vessel strokes, aka lacunar strokes are defined by size (under 15 mm diameter) and subcortical location.

Secondary prevention in these cases involves antiplatelet therapy and management of vascular risk factors.

If no large artery culprit is identified, the stroke is not lacunar and the patient is not in atrial fibrillation then further investigation for a cardioembolic source is indicated.

This will consist of further monitoring for atrial fibrillation as well as TTE and/or TEE.

Intracranial large vessel stenosis is managed with antiplatelet therapy and standard risk factor modification.

Systemic anticoagulation and mechanical revascularization have not proven favorable in clinical trials.

Many patients with so called cryptogenic strokes are later found to have paroxysmal atrial fibrillation.

Outpatient event monitoring is recommended for patients whose strokes are considered cryptogenic at discharge.

Recommendations for duration of monitoring vary. The review author says at least two weeks.

Extensive thrombophilia testing is not recommended.

Mitral valve prolapse is no longer considered an important cause of cryptogenic stroke.

PFO management for secondary stroke prevention remains controversial.

High level studies do not support any special approach (systemic anticoagulation, closure) for most patients.

Monday, July 14, 2014

Effects of target specific (novel) oral anticoagulants on the coag assays

Quantitative monitoring or TSOACs is not available in most community hospitals nor is it necessary. Nevertheless some knowledge of the qualitative effects of these agents on commonly used assays may come in handy to assess for “drug on board” or to get some idea of excessive effect and bleeding risk. The information below was taken from this resource.

For dabigatran, the aPTT may provide a qualitative assessment of dabigatran level and activity. The relation between dabigatran and the aPTT is curvilinear (Figure 3).12 Nevertheless, the sensitivity of the different aPTT reagents varies greatly. In patients receiving chronic therapy with dabigatran 150 mg twice daily (bid), the median peak aPTT was approximately two-fold that of control. Twelve hours after the last dose, the median aPTT was 1.5-fold that of control, with less than 10% of patients exhibiting two-fold increases. Therefore, if the aPTT level at trough (i.e. 12–24 h after ingestion) still exceeds two times the upper limit of normal, this may be associated with a higher risk of bleeding, and may warrant caution especially in patients with bleeding risk factors.12
Dabigatran has little effect on the PT and INR at clinically relevant plasma concentrations, resulting in a very flat response curve...
Factor Xa-inhibitors demonstrate a concentration-dependent prolongation of the PT. Nevertheless the effect on the PT depends both on the assay and on the FXa inhibitor. For rivaroxaban, the PT may provide some quantitative information, even though the sensitivity of the different PT reagents varies greatly (Figure 4). If Neoplastin Plus or Neoplastin is used as thromboplastin reagent, the PT is influenced in a dose-dependent manner with a close correlation to plasma concentrations.16 Neoplastin Plus is also more sensitive than Neoplastin.14 Assay-specific calibrators and calibration curves can be made (Figure 4). There are currently no such data available for edoxaban and apixaban. Importantly, the INR (and certainly a point-of-care determined INR) is completely unreliable for the evaluation of FXa inhibitory activity.

Finally it should be noted that the TSOACs can interfere with thrombophilia tests.

Sunday, July 13, 2014

Type B lactic acidosis

A nice discussion over at Renal Fellow Network.

Classically, Type A lactic acidosis is related to tissue hypoperfusion resulting in an increase in anaerobic glycolysis. Type B lactic acidosis occurs despite the presence of sufficient oxygen for aerobic glycolysis. There are a number of important causes..

Friday, July 11, 2014

New oral anticoagulants in the treatment of DVT and PE

This editorial contains a rundown of the phase III trials for all four agents that have been studied. It is available as free full text. Key points:

...First, all DOACs were shown consistently to be non-inferior compared with well-managed warfarin. The high quality of warfarin management, with a superior time in international normalized ratio target range compared with daily clinical practice, strengthens both the internal and external validity of these studies but also underscores that well-managed warfarin is an effective therapy for preventing recurrent VTE...

To me the time in therapeutic range for warfarin was not that great in those trials. However, you can be sure it was better than it is in the community.

Second, all DOACs caused less bleeding. Importantly, the shift in the bleeding pattern that is observed in patients with atrial fibrillation, with less intracranial, less life-threatening, and less critical site bleedings, is also seen in patients with VTE. DOACs cause less major (Table) and less intracranial bleedings in patients with VTE, but caution remains, in particular for patients at risk for gastrointestinal bleeding.
Third, the new regimens differ in their initial treatment approach. The first couple of weeks are of particular interest because of the high risk for recurrence and bleeding. The dual-drug bridging period with overlapping heparin and vitamin K antagonists constitutes a risk for overtreatment and undertreatment and requires intensive international normalized ratio monitoring that is labor- and time-consuming and costly. Furthermore, lessons have been drawn from the observation that ximelagatran9 and idraparinux,10 administered without heparin lead-in and without initial intensified dosing, caused more early recurrence compared with heparin/vitamin K antagonists. This helps to explain the 2 different strategies of DOACs for acute VTE (ie, including a heparin lead-in or starting with an intensified dose)...
Parenteral heparin will remain a preferred treatment option for many patients, especially those with more severe clinical presentations and patients with high thrombus burden who are admitted to the hospital. When parenteral heparin has been administered for 5 to 10 days, peroral anticoagulation with dabigatran or edoxaban can be continued.
For most cancer patients, the continued treatment with LMWH is currently the recommended and preferred therapy. Patients with active cancer for whom long-term treatment with LMWH was anticipated were not eligible for the phase III trials. Hence, additional studies are needed in cancer patients with continued LMWH and not warfarin as the comparator before DOACs can be considered an alternative standard to continued LMWH in these patients...
Besides particular patient characteristics, also less common clinical manifestations of VTE require our attention. DOACs have only been studied in patients with proximal DVT of the lower limb or hemodynamically stable pulmonary embolism. Patients with distal DVT, DVT of the upper limb, superficial thrombophletitis, or catheter-related thrombosis, patients who underwent thrombolysis, and patients with cerebral vein or mesenteric vein thrombosis have not been studied yet.

Thursday, July 10, 2014

Remember thrombotic storm?

A while back I blogged about this condition.

It's essentially what the name implies. There is no known single substrate nor is there a known single trigger (a number of patients seem to have had infection). Very few patients had known hereditary thrombophilia. Some had antipholpholipid syndrome and catastrophic APLS may be a subset of TS. It is defined clinically and likely represents a variety of (as yet undiscovered?) underlying disorders.

Despite a probable diversity of underlying hypercoagulable disorders TS is emerging as a clinically distinct entity. Since the above posting investigators have gotten more organized, and there are now more resources available regarding the condition which can be accessed here and here.

Wednesday, July 09, 2014

New definitions for ventilator associated adverse events

Summarized here in Chest, the new definitions apply more caution in labeling patients with ventilator associated pneumonia.

Tuesday, July 08, 2014

The principal barrier to implementation of palliative care: misunderstanding of what it is

That point was brought out again in this study, which focused on heart failure patients:
We interviewed 18 physician, nurse practitioner, and physician assistant providers from 3 specialties: cardiology, primary care, and palliative care. Providers had limited knowledge regarding what palliative care is, and how it can complement traditional HF therapy to decrease HF‐related suffering. Interviews identified several potential barriers: the unpredictable course of HF; lack of clear referral triggers across the HF trajectory; and ambiguity regarding what differentiates standard HF therapy from palliative care...
Conclusions Palliative care referral for HF patients may be suboptimal due to limited provider knowledge and misperceptions of palliative care as a service reserved for those near death.

Why is there such widespread misperception? Because no one has done an adequate job of defining what palliative care really is. A while back I went on a search for clarity on this subject. After identifying what I thought was the best article available on the topic I realized that even it failed. In a post in which I linked to that article I pondered why no one has defined palliative care and concluded, shockingly, that the true definition of the role of palliative care is an embarrassment to our profession. That's right. As I said in the post (emphasis added):

So lots of helpful information there. But the authors fail in one aspect. They fail to define palliative care. They talk around it but don't define it. As I've become comfortable with the idea of palliative care in recent years I've come to know what it is. Despite that, no one has precisely articulated a definition that I know of.
If palliative care is a specialty as the authors claim, what are the distinctives? Again, we need a definition. A definition has two steps. First it places the thing under discussion in a general category. Then it lists attributes that distinguish that particular thing from other members of the same category. For example, step 1: Palliative care is a medical discipline.. Step 2: characterized by ?????. There's the hard part. What are the distinguishing characteristics of palliative care? The authors list quite a few characteristics. The problem is those characteristics don't distinguish palliative care from other disciplines of medicine: Palliative care focuses on severe illness in patients with multiple and complex problems. It applies expertise to the management of a variety of symptoms. It educates patients and their families on diagnosis, prognosis and the goals of treatment. It coordinates complex care across multiple disciplines and settings.
Do you begin to see the problem here? Palliative care is nothing more than good primary care. Or what an excellent internist or hospitalist should be doing. So yes, there is a definition for palliative care but it goes unspoken because the profession is, or should be, embarrassed by the fact that we need a “specialty” whose focus is to offload the rest of us from doing all those things that make for excellence in comprehensive care because we don't have the time.

There's an emerging data set which informs us that palliative care is very high value care because it saves money while increasing quality of life and maybe even survival. But that's nothing more than saying that time spent with patients, excellence in care and coordination across transitions improves lives and saves money. Palliative care can rightly claim “We specialize in excellence.” What that, the fact that we need a special “service” to deliver excellence, says about the rest of us who are increasingly pushed toward mediocrity by performance metrics and time pressures, goes largely unspoken.

Physical activity and cardiovascular disease: the latest evidence

According to a recent review:

Recent findings: Drawing on recommended and established guidelines for study selection, we identified and included 23 prospective epidemiological studies published during the last 2 years. These studies included a total of more than 790 000 adults at baseline with some 22 000 incident cases occurring during follow-up. Our findings suggest that moderate and high levels of leisure time physical activity are associated with a moderately reduced risk of CVD. In contrast, moderate and high levels of occupational physical activity showed weak positive associations, that is, a slightly increased risk of CVD.
Summary: This updated meta-analysis supports the notion of primary prevention of CVD through engagement in leisure time physical activity. The role of occupational physical activity in CVD prevention is questionable.

Saturday, July 05, 2014

Bleeding associated with target specific oral anticoagulants (TSOACs): what the hospitalist needs to know

Treating the patient with bleeding related to TSOACs is problematic. There is little in terms of pathophysiologic rationale for antidotes, many of whose components work “upstream” from the site of action of the TSOAC. Moreover, no approach to TSOAC associated bleeding has been subjected to high level research. A systematic review would conclude that there is insufficient evidence to guide clinicians. Nevertheless when confronted with a patient on a TSOAC who is bleeding clinicians need a management approach.

In the recent past I've linked to a number of articles that touch on this topic but they only talk around it. This review from the journal Blood, an expert based review from the How I Treat series, does the best job of any paper I've seen in summarizing the relevant information and outlining a specific (suggested) approach. It is a reference every hospitalist should have quick access to. Key points are listed below but the paper is worth reading in the original and is available at the link above as free full text.

Laboratory measurement of anticoagulant effect is difficult.

Readily available tests in community hospitals are not optimal. At best they provide only a “guestimate” of drug on board and are not very reliable. By way of a rundown form the article: dabigatran prolongs the aPTT and may prolong or have no effect on the PT. Rivaroxaban and apixaban may prolong or have no effect on both tests.

Minor bleeding is managed primarily by local measures.

Brief drug discontinuation may or may not be necessary.

Moderate bleeding is managed by standard supportive measures and temporary drug discontinuation.

If normal pharmacokinetics prevail anticoagulant effects diminish fairly rapidly.

Severe or life threatening bleeding implies the need for an attempt at anticoagulant reversal.

Acknowledging the lack of high level evidence, the review authors drilled down (way down) to formulate a summary of the best we now know and came up with some specific suggestions for reversal:

In addition to the maximum supportive measures described above, nonspecific reversal therapies may be considered based on available, but limited, evidence. aPCC (80 U/kg) is weakly preferred over PCC for dabigatran-associated bleeding, whereas 4-factor PCC (50 U/kg) is weakly preferred over aPCC for rivaroxaban- or apixaban-associated bleeding; however, use of either agent is based on poor-quality data and as such should not be considered a requirement in the setting of severe or life-threatening bleeding. Hemodialysis may be a useful adjunctive therapy for dabigatran removal, when feasible.

aPCC is also known as factor 8 inhibitor bypassing activity. Although hemodialysis accelerates the removal of dabigatran and may be an important part of the management of the bleeding patient it is not very useful for the other two TSOACs due to their degree of protein binding.

Kevin Ahern lectures

---in biochemistry.

Thursday, July 03, 2014

Hospitalist driven process to improve antibiotic utilization

These include a periodic antibiotic timeout (scheduled conversations with a clinical pharmacist) and certain documentation requirements concerning the antibiotic order in the medical record. The result was improvement in processes of care:


During a 2 week pilot period, 46% (251/545) of sampled patients were on antibiotics. Documentation of all antibiotic components (indication, day of treatment, and expected duration) significantly improved from baseline after the intervention; 4% (2/48) vs. 51% (36/70) for progress notes, 10% (2/20) vs. 84% (62/74) for discharge summaries, and 18% (8/44) vs. 50% (68/135)for service sign-outs (P less than 0.001 for all comparisons). In total, 582 antibiotic time-outs were evaluated, a quarter of which resulted in changes to antibiotic regimens, and of all changes made, 27% resulted in discontinuation of antibiotics during the time-out (See Figure).

The impact on patient outcomes is unknown and further study on that question is needed.

From the abstract presentations at SHM 14.

Wednesday, July 02, 2014

Age adjusted D dimer cutoff in the exclusion of pulmonary embolism: the ADJUST-PE study

Recently published in JAMA:

Objective To prospectively validate whether an age-adjusted D-dimer cutoff, defined as age × 10 in patients 50 years or older, is associated with an increased diagnostic yield of D-dimer in elderly patients with suspected PE…
Main Outcomes and Measures The primary outcome was the failure rate of the diagnostic strategy, defined as adjudicated thromboembolic events during the 3-month follow-up period among patients not treated with anticoagulants on the basis of a negative age-adjusted D-dimer cutoff result.
Results Of the 3346 patients with suspected PE included, the prevalence of PE was 19%. Among the 2898 patients with a nonhigh or an unlikely clinical probability, 817 patients (28.2%) had a D-dimer level lower than 500 µg/L (95% CI, 26.6%-29.9%) and 337 patients (11.6%) had a D-dimer between 500 µg/L and their age-adjusted cutoff (95% CI, 10.5%-12.9%). The 3-month failure rate in patients with a D-dimer level higher than 500 µg/L but below the age-adjusted cutoff was 1 of 331 patients (0.3% [95% CI, 0.1%-1.7%]). Among the 766 patients 75 years or older, of whom 673 had a nonhigh clinical probability, using the age-adjusted cutoff instead of the 500 µg/L cutoff increased the proportion of patients in whom PE could be excluded on the basis of D-dimer from 43 of 673 patients (6.4% [95% CI, 4.8%-8.5%) to 200 of 673 patients (29.7% [95% CI, 26.4%-33.3%), without any additional false-negative findings.
Conclusions and Relevance Compared with a fixed D-dimer cutoff of 500 µg/L, the combination of pretest clinical probability assessment with age-adjusted D-dimer cutoff was associated with a larger number of patients in whom PE could be considered ruled out with a low likelihood of subsequent clinical venous thromboembolism.

Tuesday, July 01, 2014

Glucose-insulin-potassium (GIK) for ACS

GIK therapy has been studied and shown promise for decades but never made prime time. Here is the latest:

The Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency care Trial of very early intravenous glucose-insulin-potassium (GIK) for acute coronary syndromes (ACS) in out-of-hospital emergency medical service (EMS) settings showed 80% reduction in infarct size at 30 days, suggesting potential longer-term benefits. Here we report 1-year outcomes. Prespecified 1-year end points of this randomized, placebo-controlled, double-blind, effectiveness trial included all-cause mortality and composites including cardiac arrest, mortality, or hospitalization for heart failure (HF). Of 871 participants randomized to GIK versus placebo, death occurred within 1 year in 11.6% versus 13.5%, respectively (unadjusted hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.57 to 1.23, p = 0.36). The composite of cardiac arrest or 1-year mortality was 12.8% versus 17.0% (HR 0.71, 95% CI 0.50 to 1.02, p = 0.06). The composite of hospitalization for HF or mortality within 1 year was 17.2% versus 17.2% (HR 0.98, 95% CI 0.70 to 1.37, p = 0.92). The composite of mortality, cardiac arrest, or HF hospitalization within 1 year was 18.1% versus 20.4% (HR 0.85, 95% CI 0.62 to 1.16, p = 0.30). In patients presenting with suspected ST elevation myocardial infarction, HRs for 1-year mortality and the 3 composites were, respectively, 0.65 (95% CI 0.33 to 1.27, p = 0.21), 0.52 (95% CI 0.30 to 0.92, p = 0.03), 0.63 (95% CI 0.35 to 1.16, p = 0.14), and 0.51 (95% CI 0.30 to 0.87, p = 0.01). In patients with suspected acute coronary syndromes, serious end points generally were lower with GIK than placebo, but the differences were not statistically significant. However, in those with ST elevation myocardial infarction, the composites of cardiac arrest or 1-year mortality, and of cardiac arrest, mortality, or HF hospitalization within 1 year, were significantly reduced.