An open-hardware community ice nucleation cold stage for research and teaching.

Aerosol particles with rare specific properties act as nuclei for ice formation. The presence of ice nucleating particles in the atmosphere leads to heterogeneous freezing at warm temperatures and thus these particles play an important role in modulating microphysical properties of clouds. This work presents an ice nucleation cold stage instrument for measuring the concentration of ice nucleating particles in liquids. The cost is âˆ¼ $10 k including an external chiller. Using a lower cost heat sink reduces the cost to âˆ¼ $6 k. The instrument is suitable for studying ambient ice nucleating particle concentrations and laboratory-based process-level studies of ice nucleation. The design plans allow individuals to self-manufacture the cold-stage using 3D printing, off-the-shelf parts, and a handful of standard tools. Software to operate the instrument and analyze the data is also provided. The design is intended to be simple enough that a graduate student can build it as part of a course or thesis project. Costs are kept to a minimum to facilitate use in classroom demonstrations and laboratory classes.

Rhythm and rate control of atrial fibrillation in the emergency department - A large community-based observational study.

OBJECTIVE: Atrial fibrillation (AF) is the most common arrhythmia presentation to the emergency department (ED) and frequently results in admission to the hospital. Although rarely life-threatening and not usually an emergent condition, AF places a large burden on our health-care system. The objective of this study was to describe the practices of ED physicians in the management of AF in a large urban Canadian city. METHODS: From January 1, 2010 to December 31, 2010, patients with a primary diagnosis of AF were identified across 10 EDs in Toronto, Canada (N=2,609). Fifty patients were selected at random from each hospital for a detailed chart review (n=500). RESULTS: Two hundred thirty-two patients (46%) received rate control, and 129 (26%) received rhythm control with the remainder (28%) receiving neither therapy. Sixty-seven percent of patients were discharged home. Most patients (79%) were symptomatic on arrival; however, only a minority of these (31%) received rhythm control. Factors that were associated with rhythm control included younger age, duration of palpitations ≤ 48 hours, a lower CHADS2 score, and the absence of left ventricular dysfunction. CONCLUSION: Our data suggest a wide range of practice amongst ED physicians treating patients presenting to the ED with a primary diagnosis of AF. A randomized trial is needed to better understand the optimal management strategy in this patient population and setting.

Incidence, Diagnosis, and Management of QT Prolongation Induced by Cancer Therapies: A Systematic Review.

BACKGROUND: The cardiovascular complications of cancer therapeutics are the focus of the burgeoning field of cardio-oncology. A common challenge in this field is the impact of cancer drugs on cardiac repolarization (ie, QT prolongation) and the potential risk for the life-threatening arrhythmia torsades de pointes. Although QT prolongation is not a perfect marker of arrhythmia risk, this has become a primary safety metric among oncologists. Cardiologists caring for patients receiving cancer treatment should become familiar with the drugs associated with QT prolongation, its incidence, and appropriate management strategies to provide meaningful consultation in this complex clinical scenario. METHODS AND RESULTS: In this article, we performed a systematic review (using Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) guidelines) of commonly used cancer drugs to determine the incidence of QT prolongation and clinically relevant arrhythmias. We calculated summary estimates of the incidence of all and clinically relevant QT prolongation as well as arrhythmias and sudden cardiac death. We then describe strategies to prevent, identify, and manage QT prolongation in patients receiving cancer therapy. We identified a total of 173 relevant publications. The weighted incidence of any corrected QT (QTc) prolongation in our systematic review in patients treated with conventional therapies (eg, anthracyclines) ranged from 0% to 22%, although QTc >500 ms, arrhythmias, or sudden cardiac death was extremely rare. The risk of QTc prolongation with targeted therapies (eg, small molecular tyrosine kinase inhibitors) ranged between 0% and 22.7% with severe prolongation (QTc >500 ms) reported in 0% to 5.2% of the patients. Arrhythmias and sudden cardiac death were rare. CONCLUSIONS: Our systematic review demonstrates that there is variability in the incidence of QTc prolongation of various cancer drugs; however, the clinical consequence, as defined by arrhythmias or sudden cardiac death, remains rare.

Hemodynamic and neurochemical determinates of renal function in chronic heart failure.

Abnormal renal function is common in acute and chronic congestive heart failure (CHF) and is related to the severity of congestion. However, treatment of congestion often leads to worsening renal function. Our objective was to explore basal determinants of renal function and their response to hemodynamic interventions. Thirty-seven patients without CHF and 59 patients with chronic CHF (ejection fraction; 23 ± 8%) underwent right heart catheterization, measurements of glomerular filtration rate (GFR; inulin) and renal plasma flow (RPF; para-aminohippurate), and radiotracer estimates of renal sympathetic activity. A subset (26 without, 36 with CHF) underwent acute pharmacological intervention with dobutamine or nitroprusside. We explored the relationship between baseline and drug-induced hemodynamic changes and changes in renal function. In CHF, there was an inverse relationship among right atrial mean pressure (RAM) pressure, RPF, and GFR. By contrast, mean arterial pressure (MAP), cardiac index (CI), and measures of renal sympathetic activity were not significant predictors. In those with CHF there was also an inverse relationship among the drug-induced changes in RAM as well as pulmonary artery mean pressure and the change in GFR. Changes in MAP and CI did not predict the change in GFR in those with CHF. Baseline values and changes in RAM pressure did not correlate with GFR in those without CHF. In the CHF group there was a positive correlation between RAM pressure and renal sympathetic activity. There was also an inverse relationship among RAM pressure, GFR, and RPF in patients with chronic CHF. The observation that acute reductions in RAM pressure is associated with an increase in GFR in patients with CHF has important clinical implications.

No increase in adverse events during aliskiren use among ontario patients receiving angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers.

BACKGROUND: Some evidence suggests that the direct renin inhibitor aliskiren may increase the risk of severe hyperkalemia, stroke, or acute kidney injury (AKI) when prescribed with angiotensin-converting enzyme inhibitors (ACEi's) or angiotensin-receptor blockers (ARBs). The extent to which concomitant treatment increases the risk of these outcomes in routine clinical practice is unknown. We addressed this issue with the use of administrative databases. METHODS: We established a cohort of Ontarians treated with an ACEi or an ARB. Within this cohort, we conducted 3 case-control studies. Cases were patients hospitalized with 1 of 3 outcomes (hyperkalemia, AKI, or stroke). In each analysis, we identified up to 5 matched control subjects for each case. Conditional logistic regression was used to examine the association between hospitalization for each outcome and the use of aliskiren in the preceding 60 days. RESULTS: Among 903,346 patients aged 66 years and older treated with an ACEi or ARB during the 28-month study period, we identified 4235 hospitalized with hyperkalemia, 18,231 hospitalized with AKI, and 8283 hospitalized with stroke. After extensive multivariable adjustment, aliskiren therapy was not associated with a significant increase in the risk of hospitalization for hyperkalemia, AKI, or stroke. We found similar results in stratified analyses of patients with and without a history of chronic kidney disease, diabetes, or heart failure. CONCLUSIONS: Among community-dwelling patients aged 66 years and older receiving therapy with an ACEi or an ARB, aliskiren use was not associated with hospitalization for hyperkalemia, AKI, or stroke.

Hip pain and heart failure: the missing link.

A man presented with hypothyroidism, dilated cardiomyopathy, a pericardial effusion, liver failure, and polycythaemia. He had a history of bilateral hip replacements and new-onset hip pain. The patient progressed to develop shock. Given his acutely profound illness and constellation of symptoms, as well as the history of hip replacement, a diagnosis of cobalt toxicity was made.

The effect of combination treatment with aliskiren and blockers of the renin-angiotensin system on hyperkalaemia and acute kidney injury: systematic review and meta-analysis.

OBJECTIVE: To examine the safety of using aliskiren combined with agents used to block the renin-angiotensin system. DESIGN: Systematic review and meta-analysis of randomised controlled trials. DATA SOURCES: Medline, Embase, the Cochrane Library, and two trial registries, published up to 7 May 2011. STUDY SELECTION: Published and unpublished randomised controlled trials that compared combined treatment using aliskiren and angiotensin converting enzyme inhibitors or angiotensin receptor blockers with monotherapy using these agents for at least four weeks and that provided numerical data on the adverse event outcomes of hyperkalaemia and acute kidney injury. A random effects model was used to calculate pooled risk ratios and 95% confidence intervals for these outcomes. RESULTS: 10 randomised controlled studies (4814 participants) were included in the analysis. Combination therapy with aliskiren and angiotensin converting enzyme inhibitors or angiotensin receptor blockers significantly increased the risk of hyperkalaemia compared with monotherapy using angiotensin converting enzymes or angiotensin receptor blockers (relative risk 1.58, 95% confidence interval 1.24 to 2.02) or aliskiren alone (1.67, 1.01 to 2.79). The risk of acute kidney injury did not differ significantly between the combined therapy and monotherapy groups (1.14, 0.68 to 1.89). CONCLUSION: Use of aliskerin in combination with angiotensin converting enzyme inhibitors or angiotensin receptor blockers is associated with an increased risk for hyperkalaemia. The combined use of these agents warrants careful monitoring of serum potassium levels.

Pregnancy outcome after first-trimester exposure to metformin: a meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis of pregnancy outcome after metformin use for polycystic ovary syndrome (PCOS), because the efficacy of metformin has been demonstrated in the treatment of infertility caused by PCOS, whereas the fetal safety of metformin has received very little attention, and the few studies addressing this issue are limited by small sample sizes. DESIGN: Meta-analytic review. SETTING: All pertinent studies in MEDLINE and EMBASE from 1966 to September 2004. PATIENT(S): Women with PCOS or diabetes. INTERVENTION(S): Exposure to metformin in the first trimester of pregnancy. MAIN OUTCOME MEASURE(S): Major malformations. RESULT(S): Eight studies were included in the meta-analysis, with an odds ratio of 0.50 (95% confidence interval, 0.15, 1.60). After adjustment for publication bias, metformin treatment in the first trimester was associated with a statistically significant 57% protective effect. After pooling the studies, the malformation rate in the disease-matched control group was approximately 7.2%, statistically significantly higher than the rate found in the metformin group (1.7%). CONCLUSION(S): On the basis of the limited data available today, there is no evidence of an increased risk for major malformations when metformin is taken during the first trimester of pregnancy. Large studies are needed to corroborate these preliminary results.

Metformin use during the first trimester of pregnancy. Is it safe?

QUESTION: A pregnant patient with polycystic ovary syndrome asked me whether continuing metformin, which she was taking to treat infertility before her pregnancy, is safe for her fetus. She has heard that metformin is a "drug for diabetes." How safe is it to take metformin during the first trimester of pregnancy and beyond? ANSWER: Despite the traditional response that all oral hypoglycemic agents are absolutely contraindicated during pregnancy, evidence that metformin is probably safe during the first trimester of pregnancy and beyond is accumulating. Results of a recent meta-analysis by the Motherisk Program showed no increase in incidence of major malformations and a potential protective effect in this patient population.

Fetal safety of drugs used in the treatment of allergic rhinitis: a critical review.

Allergic rhinitis is the most common allergic disease. Pharmacological interventions are often not used in pregnancy because of alarming information in drug labels and patient information, even when evidence for safety exists.Low-risk therapies could include immunotherapy, intranasal sodium cromoglycate (cromolyn sodium), beclometasone, budesonide and first-generation antihistamines. In a meta-analysis examining the safety of first-generation antihistamines in pregnancy, 200 000 first trimester exposures failed to show increased teratogenic risk. Loratadine is the most studied second-generation antihistamine (with a total patient cohort of 2147 women who were exposed) and does not appear to increase the risk of major congenital malformations; however, it has not been as well studied as the earlier antihistamines. Since desloratadine is the principal metabolite of loratadine, it can be assumed that a similar safety profile would fit for desloratadine as was described for loratadine although no direct human studies have been done. Decongestants have not been conclusively proven to affect the fetal outcome and may be used for short-term relief when no other safer alternatives are available. Intranasal corticosteroids have not been associated with an increase in congenital malformations in humans. Based on efficacy and the fact that there would be little systemic absorption, they can be considered a first-line treatment over oral antihistamines, decongestants and mast cell stabilisers; however, the number of controlled trials in pregnancy is limited. Intranasal corticosteroids are associated with minimal systemic effects in adults and are the most effective therapy for allergic rhinitis. Benefit-risk considerations must, therefore, be done but favour their first-line use during pregnancy. Because fetal safety is paramount, recommendations should be based both on the safety of the drugs during pregnancy and the comparative efficacy of the agent in the treatment of the underlying condition. This review exemplifies the fact that there are many safe treatment options for the clinician when dealing with allergic rhinitis during pregnancy.