Tuesday, October 21, 2014

George Lundberg: the EMR is a mess

Still, after all these years.

Statins and diabetes

As Larry Husten at Cardiobrief points out, statin use has been associated with slight elevations in blood sugar leading to a diagnosis of diabetes in small numbers of patients. (This phenomenon, by the way, has been observed in other classes of drugs such as thiazides). The clinical importance has been unclear.

Here is a study that sheds more light on the controversy. The study focused on microvascular disease. This is appropriate since it is well known that statins protect against macrovascular disease in a wide apectrum of patients with and without diabetes. From the paper:

We identified all patients living in Denmark who were aged 40 years or older and were diagnosed with incident diabetes between Jan 1, 1996, and Dec 31, 2009. We obtained patients' data from the Danish Patient Registry and information on drug use from the Danish Registry of Medicinal Product Statistics. We randomly selected 15 679 individuals from the database who had used statins regularly until their diagnosis of diabetes (statin users) and matched them in a 1:3 ratio with 47 037 individuals who had never used statins before diagnosis (non-statin users). Our primary outcome was to compare the cumulative incidence of diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, or gangrene of the foot in statin users versus non-statin users. We analysed data with Cox regression models, adjusted for covariates including sex, age at diabetes diagnosis, and method of diabetes diagnosis. To address potential biases between statin users and non-statin users, we made adjustments to our analysis with a propensity score and with other factors. Median follow-up was 2·7 years (range 0—13).

During 215 725 person-years of follow-up, 2866 patients developed diabetic retinopathy, 1406 developed diabetic neuropathy, 1248 developed diabetic nephropathy, and 2392 developed gangrene of the foot. Compared with non-statin users, statin users had a lower cumulative incidence of diabetic retinopathy (hazard ratio 0·60, 95% CI 0·54—0·66; p less than 0·0001), diabetic neuropathy (0·66, 0·57—0·75; p less than 0·0001), and gangrene of the foot (0·88, 0·80—0·97; p=0·010), but not diabetic nephropathy (0·97, 0·85—1·10; p=0·62). These results were similar after adjusting for the competing risk of death, after matching for a propensity score, after adjusting for visits to a family doctor, and by stratification on covariates. The corresponding multivariable adjusted hazard ratio for risk of diabetes in the total population was 1·17 (95% CI 1·14—1·21; p less than 0·0001).

Use of statins before diagnosis of incident diabetes was not associated with an increased risk of microvascular disease. Whether statins are protective against some forms of microvascular disease—a possibility raised by these data—will need to be addressed in other studies similar to ours, in mendelian randomisation studies, and preferably in randomised controlled trials.

Monday, October 20, 2014

Delirium in the elderly: pharmacologic management is a last resort

From a paper in American Family Physician via Hospital Medicine Virtual Journal Club:

Treatment of delirium should focus on identifying and managing the causative medical conditions, providing supportive care, preventing complications, and reinforcing preventive interventions. Pharmacologic interventions should be reserved for patients who are a threat to their own safety or the safety of others and those patients nearing death.

Sunday, October 19, 2014

Comparison of anticoagulation strategies for acute VTE

There are now multiple strategies available. They were compared in a recent systematic review and meta-analysis:

Objective To summarize and compare the efficacy and safety outcomes associated with 8 anticoagulation options (unfractionated heparin [UFH], low-molecular-weight heparin [LMWH], or fondaparinux in combination with vitamin K antagonists); LMWH with dabigatran or edoxaban; rivaroxaban; apixaban; and LMWH alone) for treatment of venous thromboembolism.
Data Sources A systematic literature search was conducted using MEDLINE, EMBASE, and the evidence-based medicine reviews from inception through February 28, 2014.
Study Selection Eligible studies were randomized trials reporting rates of recurrent venous thromboembolism and major bleeding in patients with acute venous thromboembolism. Of the 1197 studies identified, 45 trials including 44 989 patients were included in the analyses.
Data Extraction and Synthesis Two reviewers independently extracted trial-level data including number of patients, duration of follow-up, and outcomes. The data were pooled using network meta-analysis.
Main Outcomes and Measures The primary clinical and safety outcomes were recurrent venous thromboembolism and major bleeding, respectively.
Results Compared with the LMWH–vitamin K antagonist combination, a treatment strategy using the UFH–vitamin K antagonist combination was associated with an increased risk of recurrent venous thromboembolism (hazard ratio [HR], 1.42; 95% credible interval [CrI], 1.15-1.79). The proportion of patients experiencing recurrent venous thromboembolism during 3 months of treatment were 1.84% (95% CrI, 1.33%-2.51%) for the UFH–vitamin K antagonist combination and 1.30% (95% CrI, 1.02%-1.62%) for the LMWH–vitamin K antagonist combination. Rivaroxaban (HR, 0.55; 95% CrI, 0.35-0.89) and apixaban (HR, 0.31; 95% CrI, 0.15-0.62) were associated with a lower risk of bleeding than was the LMWH–vitamin K antagonist combination, with a lower proportion of patients experiencing a major bleeding event during 3 months of anticoagulation: 0.49% (95% CrI, 0.29%-0.85%) for rivaroxaban, 0.28% (95% CrI, 0.14%-0.50%) for apixaban, and 0.89% (95% CrI, 0.66%-1.16%) for the LMWH–vitamin K antagonist combination.
Conclusions and Relevance Using meta-analytic pooling, there were no statistically significant differences for efficacy and safety associated with most treatment strategies used to treat acute venous thromboembolism compared with the LMWH–vitamin K antagonist combination. However, findings suggest that the UFH–vitamin K antagonist combination is associated with the least effective strategy and that rivaroxaban and apixaban may be associated with the lowest risk for bleeding.

Saturday, October 18, 2014

Cocaine related Aortic Dissection

From the International Registry of Acute Aortic Dissection:

Our study analyzed 3584 patients enrolled in the International Registry of Acute Aortic Dissection from 1996 to 2012. We divided the population on the basis of documented cocaine use (C+) versus noncocaine use (C-) and further stratified the cohorts into type A (33 C+/2332, 1.4%) and type B (30 C+/1252, 2.4%) dissection.

C+ patients presented at a younger age and were more likely to be male and black. Type B dissections were more common among C+ patients than in C- patients. Cocaine-related acute aortic dissection was reported more often at US sites than at European sites (86.4%, 51/63 vs 13.6%, 8/63; P less than .001). Tobacco use was more prevalent in the C+ cohort. No differences were seen in history of hypertension, known atherosclerosis, or time from symptom onset to presentation. Type B C+ patients were more likely to be hypertensive at presentation. C+ patients had significantly smaller ascending aortic diameters at presentation. Acute renal failure was more common in type A C+ patients; however, mortality was significantly lower in type A C+ patients.

Cocaine use is implicated in 1.8% of patients with acute aortic dissection. The typical patient is relatively young and has the additional risk factors of hypertension and tobacco use. In-hospital mortality for those with cocaine-related type A dissection is lower than for those with noncocaine-related dissection, likely due to the younger age at presentation.

Friday, October 17, 2014

The cardiometabolic risks attributable to chronic inflammtory diseases

From Circulation:

Background—This study sought to evaluate whether risks of diabetes mellitus and cardiovascular disease are elevated across a range of organ-specific and multisystem chronic inflammatory disorders.
Methods and Results—A matched cohort study was implemented in the UK Clinical Practice Research Datalink including participants with severe psoriasis (5648), mild psoriasis (85 232), bullous skin diseases (4284), ulcerative colitis (12 203), Crohn’s disease (7628), inflammatory arthritis (27 358), systemic autoimmune disorders (7472), and systemic vasculitis (6283) and in 373 851 matched controls. The main outcome measures were new diagnoses of type 2 diabetes mellitus, stroke, or coronary heart disease... The hazard ratio for pooled multiple failure estimate was 1.20 (95% confidence interval [CI], 1.15–1.26). The highest relative hazards were observed in systemic autoimmune disorders (1.32; 95% CI, 1.16–1.50) and systemic vasculitis (1.29; 95% CI, 1.16–1.44). Hazards were increased in organ-specific disorders, including severe psoriasis (1.29; 95% CI, 1.12–1.47) and ulcerative colitis (1.26; 95% CI, 1.14–1.40). Participants in the highest tertile of C-reactive protein had greater risk of multiple outcomes (1.52; 95% CI, 1.37–1.68).
Conclusions—The risk of cardiovascular diseases and type 2 diabetes mellitus is increased across a range of organ-specific and multisystem chronic inflammatory disorders with evidence that risk is associated with severity of inflammation. Clinical management of patients with chronic inflammatory disorders should seek to reduce cardiovascular risk.

Thursday, October 16, 2014

Brand name versus generic statins

Generic statins had a slight edge in this study, likely due to better adherence:

Measurements: Adherence to statin therapy (measured as the proportion of days covered [PDC] up to 1 year) and a composite outcome comprising hospitalization for an acute coronary syndrome or stroke and all-cause mortality. Hazard ratios (HRs) and absolute rate differences were estimated.
Results: A total of 90 111 patients who initiated a statin during the study was identified; 83 731 (93%) initiated a generic drug, and 6380 (7%) initiated a brand-name drug. The mean age of patients was 75.6 years, and most (61%) were female. The average PDC was 77% for patients in the generic group and 71% for those in the brand-name group (P less than 0.001). An 8% reduction in the rate of the clinical outcome was observed among patients in the generic group versus those in the brand-name group (HR, 0.92 [95% CI, 0.86 to 0.99]). The absolute difference was −1.53 events per 100 person-years (CI, −2.69 to −0.19 events per 100 person-years).
Limitation: Results may not be generalizable to other populations with different incomes or drug benefit structures.
Conclusion: Compared with those initiating brand-name statins, patients initiating generic statins were more likely to adhere and had a lower rate of a composite clinical outcome.

Wednesday, October 15, 2014

What works in ARDS?

Here are results from an umbrella review---a review of all RCTs and meta-analyses:

We searched PubMed, the Cochrane Library, and Web of Knowledge until July 2013. We included RCTs in ARDS published in English. We excluded trials of newborns and children; and those on short-term interventions, ARDS prevention, or post-traumatic lung injury. We also reviewed all meta-analyses of RCTs in this field that addressed mortality. Treatment modalities were grouped in five categories: mechanical ventilation strategies and respiratory care, enteral or parenteral therapies, inhaled/intratracheal medications, nutritional support, and hemodynamic monitoring.

We identified 159 published RCTs of which 93 had overall mortality reported (n = 20,671 patients)--44 trials (14,426 patients) reported mortality as a primary outcome. A statistically significant survival benefit was observed in eight trials (seven interventions) and two trials reported an adverse effect on survival. Among RCTs with more than 50 deaths in at least one treatment arm (n = 21), two showed a statistically significant mortality benefit of the intervention (lower tidal volumes and prone positioning), one showed a statistically significant mortality benefit only in adjusted analyses (cisatracurium), and one (high-frequency oscillatory ventilation) showed a significant detrimental effect. Across 29 meta-analyses, the most consistent evidence was seen for low tidal volumes and prone positioning in severe ARDS.

Via Intensive care medicine worth knowing.