Distribution of etiologies of SIADH in hospitalized patients

From a recent study:

A single-center retrospective study including all patients diagnosed with SIADH in a large community hospital and tertiary center between 1.1.2007 and 1.1.2013...

Results

The study cohort included 555 patients. The most common etiologies were malignancies and medication-induced SIADH, followed by idiopathic SIADH, pulmonary infections, pain and nausea, and central nervous system (CNS) disorders. Subgroup analysis according to etiology showed that CNS disorders were associated with more severe episodes of SIADH. Patients with idiopathic SIADH were older than patients with a specific diagnosis, had a lower urine osmolality, and required less treatment with hypertonic saline. Long-term survival was determined primarily by SIADH etiology rather than hyponatremia severity, with hazard ratios for death of up to 7.31 (95% CI 4.93–10.82, p less than 0.001) for patients with malignancy-associated SIADH as compared to patients with idiopathic SIADH. Hyponatremia grade at short-term follow-up was also predictive for long-term survival (HR 1.42 per grade, 95% CI 1.21–1.66, p less than 0.001).

Short episodes of a fib and a tach: are they clinically significant?

Investigators recently addressed this question by capturing telemetry recordings from pacemakers and AICDs. From their paper:

Background: The RATE Registry (Registry of Atrial Tachycardia and Atrial Fibrillation Episodes) is a prospective, outcomes-oriented registry designed to document the prevalence of atrial tachycardia and/or fibrillation (AT/AF) of any duration in patients with pacemakers and implantable cardioverter defibrillators (ICDs) and evaluate associations between rigorously adjudicated AT/AF and predefined clinical events, including stroke. The appropriate clinical response to brief episodes of AT/AF remains unclear.

Methods: Rigorously adjudicated electrogram (EGM) data were correlated with adjudicated clinical events with logistic regression and Cox models. Long episodes of AT/AF were defined as episodes in which the onset and/or offset of AT/AF was not present within a single EGM recording. Short episodes of AT/AF were defined as episodes in which both the onset and offset of AT/AF were present within a single EGM recording.

Results: We enrolled 5379 patients with pacemakers (N=3141) or ICDs (N=2238) at 225 US sites (median follow-up 22.9 months). There were 359 deaths. There were 478 hospitalizations among 342 patients for clinical events. We adjudicated 37 531 EGMs; 50% of patients had at least one episode of AT/AF. Patients with clinical events were more likely than those without to have long AT/AF (31.9% vs. 22.1% for pacemaker patients and 28.7% vs. 20.2% for ICD patients; P less than 0.05 for both groups). Only short episodes of AT/AF were documented in 9% of pacemaker patients and 16% of ICD patients. Patients with clinical events were no more likely than those without to have short AT/AF (5.1% vs. 7.9% for pacemaker patients and 11.5% vs. 10.4% for ICD patients; P=0.21 and 0.66, respectively).

Conclusions: In the RATE Registry, rigorously adjudicated short episodes of AT/AF, as defined, were not associated with increased risk of clinical events compared with patients without documented AT/AF.

“Short” episodes lasted 10-12 seconds on average.

More from Clinical Correlations on this study.

Treatment of severely elevated BP without target organ damage

Findings from a recent study:

Methods

This is a retrospective cohort study of ED patients age 18 years and older with an initial BP greater than or equal to 180/100 mm Hg and no acute TOD, who were discharged with a primary diagnosis of hypertension. Patients were divided based on receipt of antihypertensive therapy and outcomes (ED revisits and mortality) and were compared.

Results

Of 1016 patients, 435 (42.8%) received antihypertensive therapy, primarily (88.5%) oral clonidine. Average age was 49.2 years, and 94.5% were African American. Treated patients more often had a history of hypertension (93.1% vs 84.3%; difference = −8.8; 95% confidence interval [CI], −12.5 to −4.9) and had higher mean initial systolic (202 vs 185 mm Hg; difference = 16.9; 95% CI, −19.7 to −14.1) and diastolic (115 vs 106 mm Hg; difference = −8.6; 95% CI, −10.3 to −6.9) BP. Emergency department revisits at 24 hours (4.4% vs 2.4%; difference = −2.0; 95% CI, −4.5 to 0.3) and 30 days (18.9% vs 15.2%; difference = −3.7; 95% CI, −8.5 to 0.9) and mortality at 30 days (0.2% vs 0.2%; difference = 0; 95% CI, −1.1 to 0.8) and 1 year (2.1% vs 1.6%; difference = −0.5; 95% CI, −2.5 to 1.2) were similar.

Conclusions

Revisits and mortality were similar for ED patients with markedly elevated BP but no acute TOD, whether they were treated with antihypertensive therapy, suggesting relative safety with either approach.

Rethinking the sepsis definition: should we go back to SIRS?

That's what the authors of this paper suggest:

Objective   A proposed revision of sepsis definitions has abandoned SIRS, defined organ dysfunction as an increase in total SOFA score of greater than or equal to 2, and conceived “qSOFA” as a bedside indicator of organ dysfunction. We aimed to (1) determine the prognostic impact of SIRS, (2) compare diagnostic accuracy of SIRS and qSOFA for organ dysfunction, and (3) compare standard (Sepsis-2) and revised (Sepsis-3) definitions for organ dysfunction in emergency department patients with infection.

Methods   Consecutive ED patients admitted with presumed infection were prospectively enrolled over three years. Observational data were collected sufficient to calculate SIRS, qSOFA, SOFA, comorbidity and mortality.

Results  8871 patients were enrolled, 4176 (47.1%) with SIRS. SIRS was associated with increased risk of organ dysfunction (RR 3.5), and mortality in patients without organ dysfunction (OR 3.2). SIRS and qSOFA showed similar discrimination for organ dysfunction (AUROC 0.72 vs 0.73). qSOFA was specific but poorly sensitive for organ dysfunction (96.1%, 29.7% respectively). Mortality for patients with organ dysfunction was similar for Sepsis-2 and Sepsis-3 (12.5%, 11.4%) although 29% of patients with Sepsis-3 organ dysfunction did not meet Sepsis-2 criteria. Increasing number of Sepsis-2 organ dysfunctions was associated with greater mortality.

Conclusions   SIRS was associated with organ dysfunction and mortality, and abandoning the concept appears premature. Although qSOFA greater than or equal to 2 showed high specificity, poor sensitivity may limit utility as a bedside screen. Although mortality for organ dysfunction was comparable between Sepsis-2 and Sepsis-3, more prognostic and clinical information is conveyed using Sepsis-2 regarding number of organ dysfunctions. ​The SOFA score may require recalibration.

I believe clinicians talking to one another and communicating in the chart should use the most current and agreed upon clinical terminology, which is Sepsis-3. Unfortunately the coding and regulatory world still operates in Sepsis-2. These competing influences pull providers all over the map when they document, such that these days, when I see the word sepsis at the top of the problem list I have no idea what the patient actually has. I always have to go back and examine the raw data.

There were good reasons for transitioning to Sepsis-3 and abandoning SIRS which failed to capture many patients who were infected and had a high risk of death. Moreover, many infected patients with SIRS are not at risk of death.

But, as the article points out, neither definition is perfect. Clinical judgment dictates that patients must be assessed for their risk of mortality and organ failure regardless of what label is applied. Unfortunately the word sepsis has become as much an administrative term as a clinical one.

Adherence to the Surviving Sepsis Campaign bundles and outcome in severe sepsis and septic shock

From a recent study:

Methods

This was a global, prospective, observational, quality improvement study of compliance with the SSC bundles in patients with either severe sepsis or septic shock.

Results

A total of 1794 patients from 62 countries were enrolled in the study with either severe sepsis or septic shock. Overall compliance with all the 3-h bundle metrics was 19 %. This was associated with lower hospital mortality than non-compliance (20 vs. 31 %, p less than 0.001). Overall compliance with all the 6-h bundle metrics was 36 %. This was associated with lower hospital mortality than non-compliance (22 vs. 32 %, p less than 0.001). After adjusting the crude mortality differences for ICU admission, sepsis status (severe sepsis or septic shock), location of diagnosis, APACHE II score and country, compliance remained independently associated with improvements in hospital mortality for both the 3-h bundle (OR = 0.64 (95 % CI 0.47−0.87), p = 0.004)) and 6-h bundle (OR = 0.71 (95 % CI 0.56−0.90), p = 0.005)).

Discussion

Compliance with all of the evidence-based bundle metrics was not high. Patients whose care included compliance with all of these metrics had a 40 % reduction in the odds of dying in hospital with the 3-h bundle and 36 % for the 6-h bundle.

Should we screen first degree relatives of victims of unexplained cardiac arrest?

From a recent paper:

Conclusions—Cardiac screening revealed abnormalities in 30% of first-degree relatives of UCA or sudden unexplained death victims, with a clear working diagnosis in 17%. Long-QT, arrhythmogenic right ventricular cardiomyopathy, and catecholaminergic polymorphic ventricular tachycardia were the most common diagnoses. Systematic cascade screening and genetic testing in asymptomatic individuals will lead to preventive lifestyle and medical interventions with potential to prevent sudden cardiac death.

Indications for hemodialysis in salicylate poisoning

A systematic review with recommendations.

Choice of resuscitation fluid

The latest from a review:

Recent findings: Administration of intravenous fluids may contribute to the development and sustention of acute kidney injury. In excess, fluids cause kidney interstitial edema and venous congestion, which prevents renal blood flow and glomerular filtration rate. In contrast to balanced crystalloids, chloride-rich solutions impair renal blood flow via autoregulatory mechanisms. Synthetic colloids, such as hydroxyethyl starches, gelatins, and dextrans are potentially nephrotoxic because they can cause osmotic nephrosis, which, in susceptible patients, might precede permanent kidney damage. Albumin solutions appear well tolerated to use in septic patients, although their renal efficacy over balanced crystalloids is not established. In contrast, administration of albumin solutions to patients with decompensated liver failure effectively prevents and ameliorates hepatorenal syndrome.

Summary: Being nephrotoxic, synthetic colloids should be avoided in patients with reduced renal reserve, such as in critically ill patients and in patients with preexisting renal dysfunction. Suggested adverse effects with chloride-rich solutions need confirmation from ongoing trials. Albumin solutions are well tolerated in patients with sepsis and/or liver failure and improve outcomes in the latter.

P wave duration and a fib risk: not too short, not too long

From a recent paper:

Methods

Using computerized analysis of electrocardiograms from a large primary care population, we evaluated the association between P-wave duration and the risk of AF. Secondary end-points were death from cardiovascular causes and putative ischemic stroke. Data on drug use, comorbidity, and outcomes were collected from administrative registries.

Results

A total of 285,933 individuals were included. During median follow-up period of 6.7 years, 9550 developed AF, 9371 died of a cardiovascular cause, and 8980 had a stroke. Compared with the reference group (100–105 ms), individuals with very short (less than or equal to 89 ms; hazard ratio [HR] 1.60, 95% confidence interval [CI] 1.41–1.81), intermediate (112–119 ms; HR 1.22, 95% CI 1.13–1.31), long (120–129 ms; HR 1.50, 95% CI 1.39–1.62), and very long P-wave duration (greater than or equal to 130 ms; HR 2.06, 95% CI 1.89–2.23) had an increased risk of incident AF. With respect to death from cardiovascular causes, we found an increased risk for very short (less than or equal to 89 ms; HR 1.20, 95% CI 1.06–1.34), long (120–129 ms; HR 1.11, 95% CI 1.04–1.19), and very long P-wave duration (greater than or equal to 130 ms; HR 1.30, 95% CI 1.21–1.40) compared with the reference group (106–111 ms). Similar but weaker associations were found between P-wave duration and the risk of putative ischemic stroke.

Conclusion

In a large primary care population we found both short and long P-wave duration to be robustly associated with an increased risk of AF.

Determinants of PVC induced cardiomyopathy

From a recent study:

Objective

The purpose of this study was to test the correlation of various factors to the presence PVCi-CMP in a large multicenter population.

Methods

One hundred sixty-eight consecutive patients referred for ablation of frequent premature ventricular contractions (PVCs) were included. Patients were divided into 2 groups: group 1 with suspected PVCi-CMP (96 patients, ejection fraction 38% ± 10%, left ventricular end-diastolic diameter 62 ± 8 mm, with or without additional structural heart disease); and group 2 (control group, 72 patients with normal ejection fraction and left ventricular dimensions). Various clinical and electrophysiologic parameters were compared between groups.

Results

In univariate analysis, left ventricular origin of PVC, lack of palpitations, long PVC coupling interval, epicardial origin of the focus, long sinus beat QRS duration, male gender, high PVC burden, presence of polymorphic PVCs, high PVC QRS duration, and older age were significantly related to the presence of PVCi-CMP. In multivariate analysis, only lack of palpitations, PVC burden, and epicardial origin remained significantly and independently correlated with the presence of cardiomyopathy.

Pulmonary vein stenosis as a complication of ablation for atrial fibrillation

From a recent series in Circulation:

Background: The frequency of pulmonary vein stenosis (PVS) after ablation for atrial fibrillation has decreased, but it remains a highly morbid condition. Although treatment strategies including pulmonary vein dilation and stenting have been described, the long-term impacts of these interventions are unknown. We evaluated the presentation of severe PVS, and examined the risk for restenosis after intervention using either balloon angioplasty (BA) alone or BA with stenting.

Methods: This was a prospective, observational study of 124 patients with severe PVS evaluated between 2000 and 2014.

Results: All 124 patients were identified as having severe PVS by computed tomography in 219 veins. One hundred two patients (82%) were symptomatic at diagnosis. The most common symptoms were dyspnea (67%), cough (45%), fatigue (45%), and decreased exercise tolerance (45%). Twenty-seven percent of patients experienced hemoptysis…

Conclusions: The diagnosis of PVS is challenging because of nonspecific symptoms and the need for dedicated pulmonary vein imaging. There is no difference in acute success by type of initial intervention; however, stenting significantly reduces the risk of subsequent pulmonary vein restenosis in comparison with BA.

Pulmonary hypertension and right ventricular failure in critical illness

A review.

Pulmonary hypertension in left heart disease

Free full text here.

Animal versus plant protein intake and mortality

From a recent study in JAMA Internal Medicine:

Design, Setting, and Participants This prospective cohort study of US health care professionals included 131 342 participants from the Nurses’ Health Study (1980 to end of follow-up on June 1, 2012) and Health Professionals Follow-up Study (1986 to end of follow-up on January 31, 2012). Animal and plant protein intake was assessed by regularly updated validated food frequency questionnaires. Data were analyzed from June 20, 2014, to January 18, 2016.

Main Outcomes and Measures Hazard ratios (HRs) for all-cause and cause-specific mortality.

Results Of the 131 342 participants, 85 013 were women (64.7%) and 46 329 were men (35.3%) (mean [SD] age, 49 [9] years). The median protein intake, as assessed by percentage of energy, was 14% for animal protein (5th-95th percentile, 9%-22%) and 4% for plant protein (5th-95th percentile, 2%-6%). After adjusting for major lifestyle and dietary risk factors, animal protein intake was not associated with all-cause mortality (HR, 1.02 per 10% energy increment; 95% CI, 0.98-1.05; P for trend = .33) but was associated with higher cardiovascular mortality (HR, 1.08 per 10% energy increment; 95% CI, 1.01-1.16; P for trend = .04). Plant protein was associated with lower all-cause mortality (HR, 0.90 per 3% energy increment; 95% CI, 0.86-0.95; P for trend less than  .001) and cardiovascular mortality (HR, 0.88 per 3% energy increment; 95% CI, 0.80-0.97; P for trend = .007). These associations were confined to participants with at least 1 unhealthy lifestyle factor based on smoking, heavy alcohol intake, overweight or obesity, and physical inactivity, but not evident among those without any of these risk factors. Replacing animal protein of various origins with plant protein was associated with lower mortality. In particular, the HRs for all-cause mortality were 0.66 (95% CI, 0.59-0.75) when 3% of energy from plant protein was substituted for an equivalent amount of protein from processed red meat, 0.88 (95% CI, 0.84-0.92) from unprocessed red meat, and 0.81 (95% CI, 0.75-0.88) from egg.

Conclusions and Relevance High animal protein intake was positively associated with cardiovascular mortality and high plant protein intake was inversely associated with all-cause and cardiovascular mortality, especially among individuals with at least 1 lifestyle risk factor. Substitution of plant protein for animal protein, especially that from processed red meat, was associated with lower mortality, suggesting the importance of protein source.

Predictors of non invasive ventilation failure in patients with ARDS

From a recent study:

Methods

In this prospective observational study, we included all consecutive adults, over a 3-year period, who fulfilled criteria for ARDS by the Berlin definition. Basic demographics, ventilatory support, intensive care unit course, and outcome were recorded.

Results

Of 170 patients, 96 (56.47%) were initially managed with NIV. Noninvasive ventilation failure was seen in 42 (43.75%) of 96, and low baseline Pao2/Fio2, shock, and ARDS severity were associated with NIV failure. Overall intensive care unit mortality was 63 (37.1%) of 170, and high Acute Physiology and Chronic Health Evaluation II score, low Pao2/Fio2, shock, and ARDS severity were associated with increased mortality. Noninvasive ventilation failure and mortality were significantly higher in moderate and severe ARDS.

Conclusions

Noninvasive ventilation maybe useful in selected patients with mild ARDS but should be used with great caution in moderate and severe ARDS, as failure risk is high. In addition, low Pao2/Fio2 and shock are associated with NIV failure. Acute Physiology and Chronic Health Evaluation II score, shock, low Pao2/Fio2, and ARDS severity are associated with increased mortality.

Dexmedetomidine for agitated patients on mechanical ventilation

From a recent study:

Importance Effective therapy has not been established for patients with agitated delirium receiving mechanical ventilation.

Objective To determine the effectiveness of dexmedetomidine when added to standard care in patients with agitated delirium receiving mechanical ventilation.

Design, Setting, and Participants The Dexmedetomidine to Lessen ICU Agitation (DahLIA) study was a double-blind, placebo-controlled, parallel-group randomized clinical trial involving 74 adult patients in whom extubation was considered inappropriate because of the severity of agitation and delirium. The study was conducted at 15 intensive care units in Australia and New Zealand from May 2011 until December 2013. Patients with advanced dementia or traumatic brain injury were excluded.

Interventions Bedside nursing staff administered dexmedetomidine (or placebo) initially at a rate of 0.5 µg/kg/h and then titrated to rates between 0 and 1.5 µg/kg/h to achieve physician-prescribed sedation goals. The study drug or placebo was continued until no longer required or up to 7 days. All other care was at the discretion of the treating physician.

Main Outcomes and Measures Ventilator-free hours in the 7 days following randomization. There were 21 reported secondary outcomes that were defined a priori.

Results Of the 74 randomized patients (median age, 57 years; 18 [24%] women), 2 withdrew consent later and 1 was found to have been randomized incorrectly, leaving 39 patients in the dexmedetomidine group and 32 patients in the placebo group for analysis. Dexmedetomidine increased ventilator-free hours at 7 days compared with placebo (median, 144.8 hours vs 127.5 hours, respectively; median difference between groups, 17.0 hours [95% CI, 4.0 to 33.2 hours]; P = .01). Among the 21 a priori secondary outcomes, none were significantly worse with dexmedetomidine, and several showed statistically significant benefit, including reduced time to extubation (median, 21.9 hours vs 44.3 hours with placebo; median difference between groups, 19.5 hours [95% CI, 5.3 to 31.1 hours]; P less than .001) and accelerated resolution of delirium (median, 23.3 hours vs 40.0 hours; median difference between groups, 16.0 hours [95% CI, 3.0 to 28.0 hours]; P = .01). Using hierarchical Cox modeling to adjust for imbalanced baseline characteristics, allocation to dexmedetomidine was significantly associated with earlier extubation (hazard ratio, 0.47 [95% CI, 0.27-0.82]; P = .007).

Conclusions and Relevance Among patients with agitated delirium receiving mechanical ventilation in the intensive care unit, the addition of dexmedetomidine to standard care compared with standard care alone (placebo) resulted in more ventilator-free hours at 7 days. The findings support the use of dexmedetomidine in patients such as these.

Impact of a post-arrest consult team

From a recent study:

Objective: To evaluate whether a Post-Arrest Consult Team improved care and outcomes for patients with out-of-hospital cardiac arrest.

Design: Prospective cohort study of Post-Arrest Consult Team implementation at two hospitals, with concurrent controls from 27 others.

Setting: Twenty-nine hospitals within the Strategies for Post-Arrest Care Network of Southern Ontario, Canada.

Patients: We included comatose adult nontraumatic out-of-hospital cardiac arrest patients surviving more than or equal to 6 hours after emergency department arrival who had no contraindications to targeted temperature management.

Intervention: The Post-Arrest Consult Team was an advisory consult service to improve 1) targeted temperature management, 2) assessment for percutaneous coronary intervention, 3) electrophysiology assessment, and 4) appropriately delayed neuroprognostication.

Measurements and Main Results: We used generalized linear mixed models to explore the association between Post-Arrest Consult Team implementation and performance of targeted processes. We included 1,006 patients. The Post-Arrest Consult Team was associated with a significant reduction over time in rates of withdrawal of life-sustaining therapy within 72 hours of emergency department arrival on the basis of predictions of poor neurologic prognosis (ratio of odds ratios, 0.13; 95% CI, 0.02–0.98). Post-Arrest Consult Team was not associated with improved successful targeted temperature management (ratio of odds ratios, 0.91; 95% CI, 0.31–2.65), undergoing angiography (ratio of odds ratios, 1.91; 95% CI, 0.17–21.04), receiving electrophysiology consultation (ratio of odds ratios, 0.93; 95% CI, 0.11–8.16), or functional survival (ratio of odds ratios, 0.75; 95% CI, 0.19–2.94).

Conclusions: Implementation of a Post-Arrest Consult Team reduced premature withdrawal of life-sustaining therapy but did not improve rates of successful targeted temperature management, coronary angiography, formal electrophysiology assessments, or functional survival for comatose patients after out-of-hospital cardiac arrest.

This is an appealing idea to me. Although the consult team did not have much impact in this study I believe it is an idea worth considering which may be of value in some institutions when used for all it is worth.

Point of care echo and diastolic dysfunction

In this study emergency physicians were competent in the identification of diastolic dysfunction after limited training but not in the classification of DD.

Point of care chest ultrasound

Here is a review of its usefulness as a clinical tool, excluding cardiac applications.

Pnuemonia in comatose patients post cardiac arrest

75% of patients developed pneumonia!

From a presentation at AHA 2016:

Methods: We identified consecutive patients undergoing targeted temperature management following OHCA secondary to a shockable rhythm (ventricular tachycardia or fibrillation). To address survival bias we excluded patients who died within 48 hours of hospital admission. We then compared clinical outcomes between patients with and without pneumonia. The primary outcome was severe neurologic dysfunction as defined by a cerebral performance category (CPC) ≥3; secondary outcomes included duration of mechanical ventilation and length of stay in hospital and in the cardiac intensive care unit (CICU).

Results: Of 116 patients included (mean age 57 years, mean downtime 24 min, 22% female, 47% STEMI), 87 (75%) developed pneumonia. Patients who developed pneumonia were older; baseline patient and index event characteristics were otherwise comparable between the two cohorts. The most common pathogens isolated included Staphylococcus aureus, Haemophilus influenza, Streptococcal species and Klebsiella species. Piperacillin/tazobactam and cephalosporins were used to treat the majority of patients. The incidence of the primary outcome (28%) was comparable in patients with versus without pneumonia. However, compared to patients without pneumonia, OHCA patients with pneumonia required longer periods of mechanical ventilation and longer lengths of stay in hospital and in the CICU.

Your GI bleeding patient is on antiplatelet therapy. Should you transfuse platelets?

From a recent retrospective cohort study:

Background & Aims

Antiplatelet agents decrease cardiovascular events but increase gastrointestinal bleeding (GIB). Guidelines propose platelet transfusion for patients who take antiplatelet agents and have serious GIB. We investigated whether such patients are at decreased risk for rebleeding or increased risk for cardiovascular events after platelet transfusion.

Methods

We performed a retrospective cohort study of patients with GIB admitted to Yale-New Haven Hospital from 2008 to 2013 who were taking antiplatelet agents and had platelet counts higher than 100 × 109/L. Cases (patients who received platelet transfusion, n = 204) were matched with controls (no platelet transfusions, n = 204) for sex, age, and GIB location. The primary outcome was recurrent GIB. Multivariable regression analyses were performed to adjust for differences in baseline characteristics.

Results

Cases and controls had similar proportions of GIB due to non-variceal upper GIB (117 of 204, 57% vs 115 of 204, 56%) and colonic GIB (80 of 204, 39% vs 81 of 204, 40%). Cases had more severe GIB than controls, which was based on lower blood pressure and hemoglobin levels and higher heart rates and the proportion admitted to intensive care. Univariate analyses showed that higher proportions of cases had major cardiovascular events (23% vs 13% for controls), died (7% vs 1% for controls), or had hospital stay longer than 4 days (47% vs 33% for controls). However, multivariable analyses showed a significant difference between cases and controls in only risk of death (odds ratio, 5.57; 95% confidence interval, 1.52–27.1). The adjusted odds ratio for recurrent bleeding was 1.47 (95% confidence interval, 0.73–3.05) for cases vs controls.

Conclusions

The use of platelet transfusions in patients with GIB who are taking antiplatelet agents without thrombocytopenia did not reduce rebleeding but was associated with higher mortality. At least some of the increase in mortality could be due to the residual bias of an observational study, but because of the lack of benefit, we do not support the use of platelet transfusions in patients with GIB who are taking antiplatelet agents.

Link from journal site.

Link via Science Direct.

Pulmonary hypertension in myeloproliferative disorders

Free full text review.

Genetic variants and the efficacy of clopidogrel in stroke and TIA

From a recent study in Circulation:

Background: The association of genetic polymorphisms and clopidogrel efficacy in patients with ischemic stroke or transient ischemic attack (TIA) remains controversial. We performed a systematic review and meta-analysis to assess the association between genetic polymorphisms, especially CYP2C19 genotype, and clopidogrel efficacy for ischemic stroke or TIA.

Methods: We conducted a comprehensive search of PubMed and EMBASE from their inceptions to June 24, 2016. Studies that reported clopidogrel-treated patients with stroke or TIA and with information on genetic polymorphisms were included. The end points were stroke, composite vascular events, and any bleeding.

Results: Among 15 studies of 4762 patients with stroke or TIA treated with clopidogrel, carriers of CYP2C19 loss-of-function alleles (*2, *3, and *8) were at increased risk of stroke in comparison with noncarriers (12.0% versus 5.8%; risk ratio, 1.92, 95% confidence interval, 1.57–2.35; P less than 0.001). Composite vascular events were also more frequent in carriers of CYP2C19 loss-of-function alleles than in noncarriers (13.7% versus 9.4%; risk ratio, 1.51, 95% confidence interval, 1.10–2.06; P=0.01), whereas bleeding rates were similar (2.4% versus 3.1%; risk ratio, 0.89, 95% confidence interval, 0.58–1.35; P=0.59). There was no evidence of statistical heterogeneity among the included studies for stroke, but there was for composite vascular events. Genetic variants other than CYP2C19 were not associated with clinical outcomes, with the exception that significant associations of PON1, P2Y12, and COX-1 with outcomes were observed in 1 study.

Conclusions: Carriers of CYP2C19 loss-of-function alleles are at greater risk of stroke and composite vascular events than noncarriers among patients with ischemic stroke or TIA treated with clopidogrel.

More evidence for obesity as a risk factor for atrial fibrillation

From a recently published study:

Methods

We analyzed data from 2,717 participants of the Health, Aging, and Body Composition Study. Adiposity measures were BMI, abdominal circumference, subcutaneous and visceral fat area, and total and percent fat mass. We determined the associations between the adiposity measures and 10-year incidence of AF using Cox proportional hazards models and assessed for their racial differences in these estimates.

Results

In multivariable-adjusted models, 1-SD increases in BMI, abdominal circumference, and total fat mass were associated with a 13% to 16% increased AF risk (hazard ratio [HR] 1.14, 95% CI 1.02-1.28; HR 1.16, 95% CI 1.04-1.28; and HR 1.13, 95% CI 1.002-1.27). Subcutaneous and visceral fat areas were not significantly associated with incident AF. We did not identify racial differences in the associations between the adiposity measures and AF.

Conclusion

Body mass index, abdominal circumference, and total fat mass are associated with risk of AF for 10 years among white and black older adults. Obesity is one of a limited number of modifiable risk factors for AF; future studies are essential to evaluate how obesity reduction can modify the incidence of AF.

The evidence is mounting that obesity is a risk factor for atrial fibrillation. The extent to which weight loss intervention will impact atrial fibrillation is less clear.

Performance linked to MI survival???

The title to a recent NEJM paper, Life Expectancy after Myocardial Infarction, According to Hospital Performance, (and there was a positive correlation) is deceptive. From the paper:

Methods

We analyzed data from the Cooperative Cardiovascular Project, a study of Medicare beneficiaries who were hospitalized for acute myocardial infarction between 1994 and 1996 and who had 17 years of follow-up. We grouped hospitals into five strata that were based on case-mix severity. Within each case-mix stratum, we compared life expectancy among patients admitted to high-performing hospitals with life expectancy among patients admitted to low-performing hospitals. Hospital performance was defined by quintiles of 30-day risk-standardized mortality rates. Cox proportional-hazards models were used to calculate life expectancy.

Results

The study sample included 119,735 patients with acute myocardial infarction who were admitted to 1824 hospitals. Within each case-mix stratum, survival curves of the patients admitted to hospitals in each risk-standardized mortality rate quintile separated within the first 30 days and then remained parallel over 17 years of follow-up. Estimated life expectancy declined as hospital risk-standardized mortality rate quintile increased. On average, patients treated at high-performing hospitals lived between 0.74 and 1.14 years longer, depending on hospital case mix, than patients treated at low-performing hospitals. When 30-day survivors were examined separately, there was no significant difference in unadjusted or adjusted life expectancy across hospital risk-standardized mortality rate quintiles.

Conclusions

In this study, patients admitted to high-performing hospitals after acute myocardial infarction had longer life expectancies than patients treated in low-performing hospitals. This survival benefit occurred in the first 30 days and persisted over the long term.

The time in question for this study, 1994-1996, was quite a bit before what we know today as the performance movement, in the forms of public reporting and pay incentives, was underway. So what is termed performance in this paper has little to do with performance as the phony surrogate for quality as we know it today. What this study really shows is that hospitals with good overall outcomes also have better outcomes in the more narrowly focused category of myocardial infarction.

PCSK9 inhibitors: what you need to know

This Medscape review is a little dated but still relevant.

Outcome comparisons for type 2 diabetes drugs

From a recent JAMA meta-analysis:

Importance Numerous glucose-lowering drugs are used to treat type 2 diabetes.

Objective To estimate the relative efficacy and safety associated with glucose-lowering drugs including insulin.

Data Sources Cochrane Library Central Register of Controlled Trials, MEDLINE, and EMBASE databases through March 21, 2016.

Study Selection Randomized clinical trials of 24 weeks’ or longer duration.

Data Extraction and Synthesis Random-effects network meta-analysis.

Main Outcomes and Measures The primary outcome was cardiovascular mortality. Secondary outcomes included all-cause mortality, serious adverse events, myocardial infarction, stroke, hemoglobin A1c (HbA1C) level, treatment failure (rescue treatment or lack of efficacy), hypoglycemia, and body weight.

Results A total of 301 clinical trials (1 417 367 patient-months) were included; 177 trials (56 598 patients) of drugs given as monotherapy; 109 trials (53 030 patients) of drugs added to metformin (dual therapy); and 29 trials (10 598 patients) of drugs added to metformin and sulfonylurea (triple therapy). There were no significant differences in associations between any drug class as monotherapy, dual therapy, or triple therapy with odds of cardiovascular or all-cause mortality. Compared with metformin, sulfonylurea (standardized mean difference [SMD], 0.18 [95% CI, 0.01 to 0.34]), thiazolidinedione (SMD, 0.16 [95% CI, 0.00 to 0.31]), DPP-4 inhibitor (SMD, 0.33 [95% CI, 0.13 to 0.52]), and α-glucosidase inhibitor (SMD, 0.35 [95% CI, 0.12 to 0.58]) monotherapy were associated with higher HbA1C levels. Sulfonylurea (odds ratio [OR], 3.13 [95% CI, 2.39 to 4.12]; risk difference [RD], 10% [95% CI, 7% to 13%]) and basal insulin (OR, 17.9 [95% CI, 1.97 to 162]; RD, 10% [95% CI, 0.08% to 20%]) were associated with greatest odds of hypoglycemia. When added to metformin, drugs were associated with similar HbA1C levels, while SGLT-2 inhibitors offered the lowest odds of hypoglycemia (OR, 0.12 [95% CI, 0.08 to 0.18]; RD, −22% [−27% to −18%]). When added to metformin and sulfonylurea, GLP-1 receptor agonists were associated with the lowest odds of hypoglycemia (OR, 0.60 [95% CI, 0.39 to 0.94]; RD, −10% [95% CI, −18% to −2%]).

Conclusions and Relevance Among adults with type 2 diabetes, there were no significant differences in the associations between any of 9 available classes of glucose-lowering drugs (alone or in combination) and the risk of cardiovascular or all-cause mortality. Metformin was associated with lower or no significant difference in HbA1C levels compared with any other drug classes. All drugs were estimated to be effective when added to metformin. These findings are consistent with American Diabetes Association recommendations for using metformin monotherapy as initial treatment for patients with type 2 diabetes and selection of additional therapies based on patient-specific considerations.

It is important to note that this analysis did not distinguish between microvascular and macrovascular causes of all cause and cardiovascular mortality.

All forms of obesity correlate with atrial fibrillation risk but some are worse than others

From a recent study:

Methods and Results—We conducted a meta-analysis of 63 observational studies including 352 275 individuals, comparing AF risk for 1-SD increases in epicardial fat, waist circumference, waist/hip ratio, and body mass index. A 1-SD higher epicardial fat volume was associated with a 2.6-fold higher odds of AF (odds ratio, 2.61; 95% confidence interval [CI], 1.89–3.60), 2.1-fold higher odds of paroxysmal AF (odds ratio, 2.14; 95% CI, 1.45–3.16) and, 5.4-fold higher odds of persistent AF (odds ratio, 5.43; 95% CI, 3.24–9.12) compared with sinus rhythm. Likewise, a 1-SD higher epicardial fat volume was associated with 2.2-fold higher odds of persistent compared with paroxysmal AF (odds ratio, 2.19; 95% CI, 1.66–2.88). Similar associations existed for postablation, postoperative, and postcardioversion AF. In contrast, associations of abdominal and overall adiposity with AF were less extreme, with relative risks per 1-SD higher values of 1.32 (95% CI, 1.25–1.41) for waist circumference, 1.11 (95% CI, 1.08–1.14) for waist/hip ratio, and 1.22 (95% CI, 1.17–1.27) for body mass index.

Conclusions—Strong and graded associations were observed between increasing epicardial fat and AF. Moreover, the strength of associations of AF with epicardial fat is greater than for measures of abdominal or overall adiposity.

NSAID use and heart failure exacerbation

More evidence of the cardiorenal risks of NSAIDS in this meta-analysis:

Background

The association between exacerbation of heart failure (HF) and use of non-steroidal anti-inflammatory drugs (NSAIDs) has long been recognized but the data on this adverse effect are limited.

Methods

To further characterize this possible association, we conducted a systematic review and meta-analysis of observation studies that reported odds ratio, relative risk, hazard ratio or standardized incidence ratio comparing risk of exacerbation of HF in patients with pre-existing HF who took NSAIDs versus non-users. Pooled risk ratios (RR) and 95% confidence intervals for conventional NSAIDs, celecoxib and rofecoxib were calculated using random-effect, generic inverse variance method.

Results

Six studies were identified and included in our data analysis. Use of conventional NSAIDs was associated with a significantly higher risk of development of exacerbation of HF with the pooled RR of 1.39 (95% CI 1.20–1.62). Elevated risk was also observed among celecoxib and rofecoxib users (RR 1.34, 95% CI 0.98–1.85 and RR 2.04, 95% CI 1.68–2.48). The pooled RR of rofecoxib was significantly higher than conventional NSAIDs (p = 0.02).

Conclusion

Use of NSAIDs is associated with an increased risk of HF exacerbation among patients with pre-existing HF. The excess risk was approximately 40% for conventional NSAIDs and celecoxib. The highest risk was observed among rofecoxib users.

Evaluation and management of non-malignant pleural effusions

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