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

Free full text review.

New (direct) oral anticoagulants in VTE

Here is a recent review.

From the conclusion:

Selective thrombin and FXa inhibitors are a new class of anticoagulant drugs, designed to overcome the unmet needs of current therapy. They are orally active, reach full anticoagulant effects shortly after intake, have a relatively short half-life after discontinuation and, in most clinical circumstances, no regular laboratory monitoring or dose adjustment is required. These characteristics render these agents more manageable and appealing for both patients and physicians than heparins or VKAs, but apart these practical advantages of direct oral anticoagulants, what have we learnt from published phase III trials regarding their efficacy and safety in the clinical setting of VTE? A number of recently published systematic reviews and meta-analyses did pool data from randomised trials and performed indirect comparisons. Collectively, they showed that the four direct anticoagulants currently available have at least a similar efficacy for primary prevention and secondary prevention of VTE recurrence and all-cause mortality compared with standard treatments [50–54]. Pertaining to safety, the main issue is whether or not direct anticoagulants are associated with less bleeding complications that the traditional anticoagulants, particularly VKA antagonists. All in all, it was clearly and consistently shown that direct anticoagulants are associated with less intracranial bleeding than traditional agents, whereas the evidence of their superiority pertaining to other sites of bleeding is more uncertain [51].

Note that in the new ACCP guidelines DOACs are given preference over other oral anticoagulants in all non cancer related VTE.

Non invasive ventilation: ward or ICU?

Recently published:

Design: Prospective, observational, pragmatic study.

Setting: Ordinary wards of a teaching hospital.

Patients: Consecutive patients treated with noninvasive ventilation for acute respiratory failure.

Interventions: None.

Measurements and Main Results: Two-hundred and twenty-patients were enrolled. Mortality rates at 30-day, 90-days, and 1-year follow-up were 20%, 26%, and 34%. When excluding patients with “do-not-resuscitate” status, mortality rates were 13%, 19%, and 28%. The multivariate analyses identified solid cancer, pneumonia in hematologic patients, and do-not-resuscitate status as independent predictors of mortality with postoperative acute respiratory failure associated with improved survival. The same predictors were confirmed when excluding do-not-resuscitate patients from the analyses.

Conclusions: Noninvasive ventilation applied in ordinary wards was effective, with long-term outcomes not different from those reported for ICU settings. Solid cancer, pneumonia in hematologic malignancies, and do-not-resuscitate status predicted mortality, whereas patients with postoperative acute respiratory failure had the best survival rate. Additional studies are required to evaluate noninvasive ventilation efficacy in the wards compared with ICU.

Membrane active non cardiac drugs and the risk of cardiac arrest

From a poster presentation at AHA 2016:

Introduction: Drugs may increase risk of ventricular tachycardia/fibrillation (VT/VF) and sudden cardiac arrest (SCA) in susceptible individuals by blocking cardiac ion channels. This also applies to drugs prescribed for non-cardiac conditions (non-cardiac drugs) if these drugs possess such properties. A well-known example is non-cardiac drugs that block cardiac potassium channels and cardiac repolarization. These drugs may cause excessive QT-interval prolongation and VT/VF in individuals with reduced repolarization reserve (e.g., Long QT syndrome). Similarly, non-cardiac drugs that block cardiac sodium channels and cardiac depolarization increase VT/VF risk in individuals with reduced depolarization reserve (e.g., Brugada syndrome). We hypothesized that non-cardiac depolarization blocking drugs (DB-drugs) are associated with increased VT/VF risk in the general population.

Methods and results: A community based case-control study was performed. Cases were out-of-hospital SCA victims with documented VT/VF included in the ARREST study in June 2005 - December 2009…

We included 1787 SCA cases (mean age 66 years, 77% male) and matched them to 7666 non-SCA controls. Non-cardiac DB-drugs were used by 81 cases (4.5%) and 249 controls (3.2%), and were associated with a 41% increased SCA risk (ORadj: 1.41 [95% CI: 1.10-1.83] P less than 0.05). Use of two or more DB-drugs was associated with a 5.6-fold risk (OR: 5.63 [1.95-16.23] P less than 0.05)…

Conclusion: Current use of non-cardiac DB-drugs is associated with increased risk of SCA, especially when two or more DB-drugs are used simultaneously.

Magnesium levels, magnesium supplementation and neurological outcome following cardiac arrest

From a poster presentation at AHA 2016:

Introduction: Therapeutic hypothermia (TH) improves neurological outcomes after cardiac arrest by mitigating cerebral reperfusion injury. Plasma magnesium (Mg) inhibits glutamate release, restores blood brain barrier integrity and decreases brain edema. The neuroprotective role of Mg in cardiac arrest patients undergoing TH is not well established. We sought to determine the relationship of plasma Mg and neurologic outcomes in these patients.

Methods: A cohort of 384 consecutive patients who completed TH (33°C) from 2007 to 2016 was retrospectively studied. We evaluated favorable neurologic outcomes as a function of Mg levels before, during, and after TH as well as the relationship between neurologic outcomes and Mg supplementation during TH…

Patients with favorable neurologic outcomes had lower Mg levels at presentation (2.1 mEq/L vs. 2.2 mEq/L, p=0.031). Mg levels on presentation inversely correlated with favorable neurologic outcomes (r=-0.107). A larger percentage of patients who received magnesium supplementation had favorable neurologic outcomes (33% vs. 22%, p=0.033). We also stratified patients based on Mg levels in increments of 0.2 mEq/L to evaluate neurologic outcomes. A non-statistically significant trend towards worse neurologic outcomes was noted in patients with Mg less than 1.6 mEq/L at 24 hours and greater than 2.7 mEq/L at 24 and 48 hours…

Discussion: Lower Mg levels at presentation and magnesium supplementation during TH were associated with favorable outcomes. Intracellular shift and increased renal excretion of Mg have been associated with TH and could worsen hypomagnesemia on presentation after a cardiac arrest. Mg supplementation may potentiate the beneficial effects of TH.

Early repolarization pattern in families of victims of sudden arrhythmic death

From a recent study:

Background—The early repolarization (ER) pattern is associated with sudden death and has been shown to be heritable. Its significance when identified in families affected by sudden arrhythmic death syndrome (SADS) remains unclear…

Conclusions—The ER pattern is more common in SADS family members than controls adjusted in particular for relatedness. The increased prevalence is irrespective of ER subtype and the presence of other inherited arrhythmia syndromes. ER may therefore represent an underlying heritable arrhythmia syndrome or risk factor for sudden death in the context of other cardiac pathology.

Cobalt cardiomyopathy: it may be coming back

Report here.