Tuning the rheology and microstructure of particle-laden fluid interfaces with Janus particles.

HYPOTHESIS: Particle-laden fluid interfaces are the central component of many natural and engineering systems. Understanding the mechanical properties and improving the stability of such interfaces are of great practical importance. Janus particles, a special class of heterogeneous colloids, might be used as an effective surface-active agent to control the assembly and interfacial rheology of particle-laden fluid interfaces. EXPERIMENTS: Using a custom-built interfacial stress rheometer, we explore the effect of Janus particle additives on the interfacial rheology and microscopic structure of particle-laden fluid interfaces. FINDINGS: We find that the addition of a small amount of platinum-polystyrene (Pt-PS) Janus particles within a monolayer of PS colloids (1:40 number ratio) can lead to more than an order-of-magnitude increase in surface moduli with enhanced elasticity, which improves the stability of the interface. This drastic change in interfacial rheology is associated with the formation of local particle clusters surrounding each Janus particle. We further explain the origin of local particle clusters by considering the interparticle interactions at the interface. Our experiments reveal the effect of local particle structures on the macroscopic rheological behaviors of particle monolayers and demonstrate a new way to tune the microstructure and mechanical properties of particle-laden fluid interfaces.

Transport Evidence for Sulfur Vacancies as the Origin of Unintentional n-Type Doping in Pyrite FeS2.

Pyrite FeS2 has long been considered a potential earth-abundant low-cost photovoltaic material for thin-film solar cells but has been plagued by low power conversion efficiencies and open-circuit voltages. Recent efforts have identified a lack of understanding and control of doping, as well as uncontrolled surface conduction, as key roadblocks to the development of pyrite photovoltaics. In particular, while n-type bulk behavior in unintentionally doped single crystals and thin films is speculated to arise from sulfur vacancies (VS), proof remains elusive. Here, we provide strong evidence, from extensive electronic transport measurements on high-quality crystals, that VS are deep donors in bulk pyrite. Otherwise identical crystals grown via chemical vapor transport under varied S vapor pressures are thoroughly characterized structurally and chemically, and shown to exhibit systematically different electronic transport. Decreased S vapor pressure during growth leads to reduced bulk resistivity, increased bulk Hall electron density, reduced transport activation energy, onset of positive temperature coefficient of resistivity, and approach to an insulator-metal transition, all as would be expected from increased VS donor density. Impurity analyses show that these trends are uncorrelated with metal impurity concentration and that extracted donor densities significantly exceed total impurity concentrations, directly evidencing a native defect. Well-controlled, wide-range n-doping of pyrite is thus achieved via the control of VS concentration, with substantial implications for photovoltaic and other applications. The location of the VS state within the gap, the influence of specific impurities, unusual aspects to the insulator-metal transition, and the influence of doping on surface conduction are also discussed.

Superlattice-based thin-film thermoelectric modules with high cooling fluxes.

In present-day high-performance electronic components, the generated heat loads result in unacceptably high junction temperatures and reduced component lifetimes. Thermoelectric modules can, in principle, enhance heat removal and reduce the temperatures of such electronic devices. However, state-of-the-art bulk thermoelectric modules have a maximum cooling flux qmax of only about 10 W cm(-2), while state-of-the art commercial thin-film modules have a qmax <100 W cm(-2). Such flux values are insufficient for thermal management of modern high-power devices. Here we show that cooling fluxes of 258 W cm(-2) can be achieved in thin-film Bi2Te3-based superlattice thermoelectric modules. These devices utilize a p-type Sb2Te3/Bi2Te3 superlattice and n-type δ-doped Bi2Te3-xSex, both of which are grown heteroepitaxially using metalorganic chemical vapour deposition. We anticipate that the demonstration of these high-cooling-flux modules will have far-reaching impacts in diverse applications, such as advanced computer processors, radio-frequency power devices, quantum cascade lasers and DNA micro-arrays.

Non-contact method for characterization of small size thermoelectric modules.

Conventional techniques for characterization of thermoelectric performance require bringing measurement equipment into direct contact with the thermoelectric device, which is increasingly error prone as device size decreases. Therefore, the novel work presented here describes a non-contact technique, capable of accurately measuring the maximum ΔT and maximum heat pumping of mini to micro sized thin film thermoelectric coolers. The non-contact characterization method eliminates the measurement errors associated with using thermocouples and traditional heat flux sensors to test small samples and large heat fluxes. Using the non-contact approach, an infrared camera, rather than thermocouples, measures the temperature of the hot and cold sides of the device to determine the device ΔT and a laser is used to heat to the cold side of the thermoelectric module to characterize its heat pumping capacity. As a demonstration of the general applicability of the non-contact characterization technique, testing of a thin film thermoelectric module is presented and the results agree well with those published in the literature.

A Thermally Conductive Separator for Stable Li Metal Anodes.

Li metal anodes have attracted considerable research interest due to their low redox potential (-3.04 V vs standard hydrogen electrode) and high theoretical gravimetric capacity of 3861 mAh/g. Battery technologies using Li metal anodes have shown much higher energy density than current Li-ion batteries (LIBs) such as Li-O2 and Li-S systems. However, issues related to dendritic Li formation and low Coulombic efficiency have prevented the use of Li metal anode technology in many practical applications. In this paper, a thermally conductive separator coated with boron-nitride (BN) nanosheets has been developed to improve the stability of the Li metal anodes. It is found that using the BN-coated separator in a conventional organic carbonate-based electrolyte results in the Coulombic efficiency stabilizing at 92% over 100 cycles at a current rate of 0.5 mA/cm(2) and 88% at 1.0 mA/cm(2). The improved Coulombic efficiency and reliability of the Li metal anodes is due to the more homogeneous thermal distribution resulting from the thermally conductive BN coating and to the smaller surface area of initial Li deposition.

Phase Stability and Stoichiometry in Thin Film Iron Pyrite: Impact on Electronic Transport Properties.

The use of pyrite FeS2 as an earth-abundant, low-cost, nontoxic thin film photovoltaic hinges on improved understanding and control of certain physical and chemical properties. Phase stability, phase purity, stoichiometry, and defects, are central in this respect, as they are frequently implicated in poor solar cell performance. Here, phase-pure polycrystalline pyrite FeS2 films, synthesized by ex situ sulfidation, are subject to systematic reduction by vacuum annealing (to 550 °C) to assess phase stability, stoichiometry evolution, and their impact on transport. Bulk probes reveal the onset of pyrrhotite (Fe(1-δ)S) around 400 °C, rapidly evolving into the majority phase by 425 °C. This is supported by X-ray photoelectron spectroscopy on (001) crystals, revealing surface Fe(1-δ)S formation as low as 160 °C, with rapid growth near 400 °C. The impact on transport is dramatic, with Fe(1-δ)S minority phases leading to a crossover from diffusive transport to hopping (due to conductive Fe(1-δ)S nanoregions in an FeS2 matrix), followed by metallicity when Fe(1-δ)S dominates. Notably, the crossover to hopping leads to an inversion of the sign, and a large decrease in magnitude of the Hall coefficient. By tracking resistivity, magnetotransport, magnetization, and structural/chemical parameters vs annealing, we provide a detailed picture of the evolution in properties with stoichiometry. A strong propensity for S-deficient minority phase formation is found, with no wide window where S vacancies control the FeS2 carrier density. These findings have important implications for FeS2 solar cell development, emphasizing the need for (a) nanoscale chemical homogeneity, and (b) caution in interpreting carrier types and densities.

Hepatitis C virus seroconversion among HIV-positive men who have sex with men with no history of injection drug use: Results from a clinical HIV cohort.

BACKGROUND: Internationally, there is a growing recognition that hepatitis C virus (HCV) may be sexually transmitted among HIV-positive men who have sex with men (MSM). OBJECTIVE: To report the first Canadian estimate of HCV seroincidence in 2000 to 2010 and its risk factors among HIV-positive MSM with no known history of injection drug use. METHODS: Data from the Ontario HIV Treatment Network Cohort Study, an ongoing cohort of individuals in HIV care in Ontario, were analyzed. Data were obtained from medical charts, interviews and record linkage with the provincial public health laboratories. The analysis was restricted to 1534 MSM who did not report injection drug use and had undergone ≥2 HCV antibody tests, of which the first was negative (median 6.1 person-years [PY] of follow-up; sum 9987 PY). RESULTS: In 2000 to 2010, 51 HCV seroconversions were observed, an overall incidence of 5.1 per 1000 PY (95% CI 3.9 to 6.7). Annual incidence varied from 1.6 to 8.9 per 1000 PY, with no statistical evidence of a temporal trend. Risk for seroconversion was elevated among men who had ever had syphilis (adjusted HR 2.5 [95% CI 1.1 to 5.5) and men who had acute syphilis infection in the previous 18 months (adjusted HR 2.8 [95% CI 1.0 to 7.9]). Risk was lower for men who had initiated antiretroviral treatment (adjusted HR 0.49 [95% CI 0.25 to 0.95]). There were no statistically significant effects of age, ethnicity, region, CD4 cell count or HIV viral load. CONCLUSIONS: These findings suggest that periodic HCV rescreening may be appropriate in Ontario among HIV-positive MSM. Future research should seek evidence whether syphilis is simply a marker for high-risk sexual behaviour or networks, or whether it potentiates sexual HCV transmission among individuals with HIV.

HISTORIQUE: Sur la scène internationale, il apparaît de plus en plus clairement que le virus de l'hépatite C (VHC) peut être transmis sexuellement entre hommes positifs au VIH ayant des relations sexuelles avec des hommes (HARSAH). OBJECTIF: Rendre compte de la première estimation canadienne de la séro-incidence de VHC entre 2000 et 2010 et de ses facteurs de risque chez les HARSAH positifs au VIH sans antécédents connus de consommation de drogues injectables. MÉTHODOLOGIE: Les chercheurs ont analysé les données de l'Ontario HIV Treatment Network Cohort Study, une cohorte continue de personnes soignées pour le VIH en Ontario. Ils ont tiré les données de dossiers médicaux, d'entrevues et de liens entre les dossiers et les laboratoires provinciaux de santé publique. Ils ont restreint l'analyse à 1 534 HARSAH qui ne déclaraient pas consommer de drogues injectables et qui avaient subi au moins deux tests d'anticorps du VHC, dont le premier était négatif (suivi médian de 6,1 années-personne [AP]; somme de 9 987 AP). RÉSULTATS: De 2000 à 2010, les chercheurs ont observé 51 cas de séroconversion au VHC, pour une incidence globale de 5,1 cas sur 1 000 AP (95 % IC 3,9 à 6,7). L'incidence annuelle variait entre 1,6 et 8,9 cas sur 1 000 AP, sans preuve statistique de tendance temporelle. Le risque de séroconversion était élevé chez les hommes qui n'avaient jamais eu la syphilis (RR rajusté 2,5 [95 % IC 1,1 à 5,5) et chez les hommes qui avaient eu une infection aiguë par la syphilis dans les 18 mois précédents (RR rajusté 2,8 [95 % IC 1,0 à 7,9]). Le risque était plus faible chez les hommes qui avaient entrepris un traitement anti-rétroviral (RR rajusté 0,49 [95 % IC 0,25 à 0,95]). L'âge, l'ethnie, la région, la numération des cellules CD4 et la charge virale du VIH n'avaient pas d'effet statistiquement significatif. CONCLUSIONS: D'après ces observations, il serait judicieux de procéder au dépistage périodique du VHC chez les HARSAH positifs au VIH de l'Ontario. De prochaines recherches devraient viser à établir si la syphilis est un simple marqueur de comportements ou de réseaux sexuels à haut risque ou si elle potentialise la transmission sexuelle du VHC chez les personnes atteintes du VIH.

Impact of a chronic disease self-management program on health care utilization in rural communities: a retrospective cohort study using linked administrative data.

BACKGROUND: Internationally, chronic disease self-management programs (CDSMPs) have been widely promoted with the assumption that confident, knowledgeable patients practicing self-management behavior will experience improved health and utilize fewer healthcare resources. However, there is a paucity of published data supporting this claim and the majority of the evidence is based on self-report. METHODS: We used a retrospective cohort study using linked administrative health data. Data from 104 tele-CDSMP participants from 13 rural and remote communities in the province of Ontario, Canada were linked to administrative databases containing emergency department (ED) and physician visits and hospitalizations. Patterns of health care utilization prior to and after participation in the tele-CDSMP were compared. Poisson Generalized Estimating Equations regression was used to examine the impact of the tele-CDSMP on health care utilization after adjusting for covariates. RESULTS: There were no differences in patterns of health care utilization before and after participating in the tele-CDSMP. Among participants ≤ 66 years, however, there was a 34% increase in physician visits in the 12 months following the program (OR = 1.34, 95% CI 1.11-1.61) and a trend for decreased ED visits in those >66 years (OR = 0.59, 95% CI 0.33-1.06). CONCLUSIONS: This is the first study to examine health care use following participation in the CDSMP in a Canadian population and to use administrative data to measure health care utilization. Similar to other studies that used self-report measures to evaluate health care use we found no differences in health care utilization before and after participation in the CDSMP. Future research needs to confirm our findings and examine the impact of the CDSMP on health care utilization in different age groups to help to determine whether these interventions are more effective with select population groups.

Effect of a course-based intervention and effect of medical regulation on physicians' opioid prescribing.

OBJECTIVE: To examine the effects of an intensive 2-day course on physicians' prescribing of opioids. DESIGN: Population-based retrospective observational study. SETTING: College of Physicians and Surgeons of Ontario (CPSO) in Toronto. PARTICIPANTS: Ontario physicians who took the course between April 1, 2000, and May 30, 2008. INTERVENTION: A 2-day opioid-prescribing course with a maximum of 12 physician participants. Educational methods included didactic presentations, case discussions, and standardized patients. A detailed syllabus and office materials were provided. MAIN OUTCOME MEASURES: Participants were matched with control physicians using specific variables. The primary outcome was the rate of opioid prescribing, expressed as milligrams of morphine equivalent per quarter. RESULTS: One hundred thirty-eight course participants (120 family physicians, 15 specialists, and 3 physicians whose status was uncertain) were eligible for analysis. Of these, 68.1% were self-referred and 31.9% were referred by the CPSO. Overall, among physicians referred by the CPSO, the rate of opioid prescribing decreased dramatically in the year before course participation compared with matched control physicians. The course had no added effect on the rate of physicians' opioid prescribing in the subsequent 2 years. There was no statistically significant effect on the rate of opioid prescribing observed among the self-referred physicians. Among 15 of the self-referred physicians who, owing to the high quantities of opioids they prescribed, were not matched with control physicians, the rate of opioid prescribing decreased by 43.9% in the year following course completion. CONCLUSION: Physicians markedly reduced the quantities of opioids they prescribed after medical regulators referred them to an opioid-prescribing course. The course itself did not lead to significant additional reductions; however, a subgroup of physicians who prescribed high quantities of opioids might have responded to what was taught in the course.

Crossover from nanoscopic intergranular hopping to conventional charge transport in pyrite thin films.

Pyrite FeS2 is receiving a resurgence of interest as a uniquely attractive thin film solar absorber based on abundant, low-cost, nontoxic elements. Here we address, via ex situ sulfidation synthesis, the long-standing problem of understanding conduction and doping in FeS2 films, an elusive prerequisite to successful solar cells. We find that an abrupt improvement in crystallinity at intermediate sulfidation temperatures is accompanied by unanticipated crossovers from intergranular hopping to conventional transport, and, remarkably, from hole-like to electron-like Hall coefficients. The hopping is found to occur between a small volume fraction of conductive nanoscopic sulfur-deficient grain cores (beneath our X-ray diffraction detection limits), embedded in nominally stoichiometric FeS2. In addition to placing constraints on the conditions under which useful properties can be obtained from FeS2 synthesized in diffusion-limited situations, these results also emphasize that FeS2 films are not universally p-type. Indeed, with no knowledge of the active transport mechanism we demonstrate that the Hall coefficient alone is insufficient to determine the sign of the carriers. These results elucidate the possible transport mechanisms in thin film FeS2 in addition to their influence on the deduced carrier type, an enabling advancement with respect to understanding and controlling doping in pyrite films.

Resonant photoemission and spin polarization of Co(1-x)Fe(x)S(2).

The valence band occupied state electronic structure of Co(1-x)Fe(x)S(2) in the region of the Fe/Co 3d bands has been investigated using photoemission and spin-polarized photoemission. As measured by using spin-polarized ultraviolet photoemission, the surface Fermi level spin polarization of Co(1-x)Fe(x)S(2) thin films at 50 K, specifically at x = 0, 0.05, 0.10 and 0.15, was found to be much reduced compared to that of the bulk. The spin polarization nonetheless increases with Fe concentration. The resonant photoemission spectroscopy provides evidence that S bands have a strong resonance at the photon energy corresponding to the Co 2p core level, indicating strong hybridization between Co and S bands in Co(1-x)Fe(x)S(2) (at small x). Similar evidence exists for Fe hybridization with the S bands.

Multiple sclerosis disease-modifying therapy prescribing patterns in Ontario.

BACKGROUND: Differences in Multiple sclerosis (MS) disease-modifying therapy (DMT) prescribing patterns between different groups of neurologists have not been explored. OBJECTIVE: To examine concentrations of prescribing patterns and to assess if MS-specialists use a broader range of DMTs relative to general neurologists. METHODS: We conducted a cross-sectional study using administrative claims databases in Ontario, Canada to link neurologists to 2009 DMT prescription data. MS specialization was defined using both practice location and prescription patterns. Lorenz curves and Gini coefficients were constructed to examine prescribing patterns, separating neurologist characteristics dichotomously and separating Avonex from the other standard DMTs (Betaseron, Rebif and Copaxone). Gini coefficient 95% confidence intervals (CIs) were derived using jack-knife statistical techniques. RESULTS: Prescriptions were highly concentrated with 12% of Ontario neurologists prescribing 80% of DMTs. There was a trend towards Avonex being more commonly prescribed relative to the other DMTs. When MS specialization was defined by DMT prescribing, high-volume prescribing neurologists showed a broader range of DMT prescribing (Gini 0.38-0.44) in comparison to low-volume prescribers (Gini 0.57-0.66). CONCLUSIONS: The majority of DMTs are prescribed by a small subset of neurologists. High-volume prescribing MS-specialists show more variability in DMT use while low-volume prescribers tend to individually focus on a narrower range of DMTs.

Hopping transport and the Hall effect near the insulator-metal transition in electrochemically gated poly(3-hexylthiophene) transistors.

Despite 35 years of investigation, much remains to be understood regarding charge transport in semiconducting polymers, including the ultimate limits on their conductivity. Recently developed ion gel gating techniques provide a unique opportunity to study such issues at very high charge carrier density. Here we have probed the benchmark polymer semiconductor poly(3-hexylthiophene) at electrochemically induced three-dimensional hole densities approaching 10(21) cm(-3) (up to 0.2 holes per monomer). Analysis of the hopping conduction reveals a remarkable phenomenon where wavefunction delocalization and Coulomb gap collapse are disrupted by doping-induced disorder, suppressing the insulator-metal transition, even at these extreme charge densities. Nevertheless, at the highest dopings, we observe, for the first time in a polymer transistor, a clear Hall effect with the expected field, temperature and gate voltage dependencies. The data indicate that at such mobilities (~0.8 cm(2)V(-1) s(-1)), despite the extensive disorder, these polymers lie close to a regime of truly diffusive band-like transport.

Fluoroquinolone therapy and idiosyncratic acute liver injury: a population-based study.

BACKGROUND: Although fluoroquinolones are sometimes associated with mild, transient elevations in aminotransferase levels, serious acute liver injury is uncommon. Regulatory warnings have identified moxifloxacin as presenting a particular risk of hepatotoxicity. Thus, we examined the risk of idiosyncratic acute liver injury associated with the use of moxifloxacin relative to other selected antibiotic agents. METHODS: We conducted a population-based, nested, case-control study using health care data from Ontario for the period April 2002 to March 2011. We identified cases as outpatients aged 66 years or older with no history of liver disease, and who were admitted to hospital for acute liver injury within 30 days of receiving a prescription for 1 of 5 broad-spectrum antibiotic agents: moxifloxacin, levofloxacin, ciprofloxacin, cefuroxime axetil or clarithromycin. For each case, we selected up to 10 age- and sex-matched controls from among patients who had received a study antibiotic, but who were not admitted to hospital for acute liver injury. We calculated odds ratios (ORs) to determine the association between admission to hospital and previous exposure to an antibiotic agent, using clarithromycin as the reference. RESULTS: A total of 144 patients were admitted to hospital for acute liver injury within 30 days of receiving a prescription for one of the identified drugs. Of these patients, 88 (61.1%) died while in hospital. After multivariable adjustment, use of either moxifloxacin (adjusted OR 2.20, 95% confidence interval [CI] 1.21-3.98) or levofloxacin (adjusted OR 1.85, 95% CI 1.01-3.39) was associated with an increase in risk of acute liver injury relative to the use of clarithromycin. We saw no such risk associated with the use of either ciprofloxacin or cefuroxime axetil. INTERPRETATION: Among older outpatients with no evidence of liver disease, moxifloxacin and levofloxacin were associated with an increased risk of acute liver injury relative to clarithromycin.

Single-crystalline silver films for plasmonics.

A simple route to flat, large-area, single-crystalline films for plasmonics is demonstrated by sputter deposition of silver onto mica substrates at elevated temperatures. The films exhibit improved dielectric properties and allow more precise patterning of high-quality nanostructures for plasmonic applications.

New fibrate use and acute renal outcomes in elderly adults: a population-based study.

BACKGROUND: Fibric acid derivatives (fibrates) have been shown to increase serum creatinine level in randomized trials. OBJECTIVE: To assess renal outcomes in elderly adults within 90 days of a new fibrate prescription. DESIGN: Population-based cohort study. SETTING: Ontario, Canada. PATIENTS: Patients aged 66 years or older with a new outpatient prescription for a fibrate or ezetimibe (comparator drug) between January 2004 and December 2008. MEASUREMENTS: Hospitalization for an increase in serum creatinine level (primary outcome) and consultation with a nephrologist, receipt of dialysis for severe acute kidney injury, all-cause mortality, and increases in serum creatinine level (secondary outcomes). All outcomes were assessed within 90 days of a new prescription for ezetimibe or a fibrate. RESULTS: Compared with ezetimibe users (n = 61,831), fibrate users (n = 19,072) were more likely to be hospitalized for an increase in serum creatinine level (adjusted odds ratio, 2.4 [95% CI, 1.7 to 3.3]) and were more likely to consult a nephrologist (absolute risk difference, 0.15% [CI, 0.01% to 0.29%]; adjusted odds ratio, 1.3 [CI, 1.0 to 1.6]). There were no differences between groups in the risk for all-cause mortality or receiving dialysis for severe acute kidney injury. In a subpopulation of 1110 patients (fibrates, n = 220; ezetimibe, n = 890), 9.1% of fibrate users and 0.3% of ezetimibe users had an increase in serum creatinine level of 50% or more (absolute difference, 8.8% [CI, 4.5% to 13.1%]; odds ratio, 29.6 [CI, 8.7 to 100.5]). Risks were greater among fibrate users with chronic kidney disease. LIMITATIONS: Because hospitalizations for an increase in serum creatinine level were underestimated, absolute differences may be misleading. Most patients (91%) were prescribed fenofibrate. Serum creatinine levels were measured as part of routine care and were not available for everyone or at predefined times. CONCLUSION: New fibrate use in elderly adults was associated with an increase in serum creatinine level and a small 90-day absolute increase in hospitalizations and nephrologist consultations. There was no detectable effect on dialysis for severe acute kidney injury or on mortality. The mechanism and clinical significance of the increase in serum creatinine level with fibrates is unclear. PRIMARY FUNDING SOURCE: Ontario Ministry of Health and Long-Term Care Drug Innovation Fund.

Antidepressants, metoprolol and the risk of bradycardia.

Case reports and pharmacologic theory suggest that some antidepressants can interfere with the hepatic metabolism of metoprolol by cytochrome P450 2D6 (CYP2D6), potentially increasing the risk of bradycardia. The objective of this study was to characterize the clinical consequences of this potential drug interaction at the population level. We conducted a population-based, nested case-control study of Ontario residents 66 years of age or older receiving metoprolol. Cases hospitalized for bradycardia were compared with matched controls (4:1) to explore the odds ratio for initiation of antidepressants that inhibit CYP2D6 (fluoxetine and paroxetine) and those that do not inhibit CYP2D6 (fluvoxamine, citalopram, venlafaxine, and sertraline) 30 days before hospitalization. From April 1997 to March 2009, we identified 332,254 older patients continuously receiving metoprolol, of whom 8232 (2.5%) were treated in hospital for bradycardia. The adjusted odds ratio for exposure to fluoxetine or paroxetine compared with other antidepressants 30 days prior to hospitalization for bradycardia was 0.76 (95% confidence interval 0.42-1.37). Among older patients receiving metoprolol, the initiation of antidepressants that inhibit CYP2D6 was not associated with a significant increase in the risk of bradycardia compared with antidepressants that do not inhibit CYP2D6.

Beta-blockers and cardiovascular outcomes in dialysis patients: a cohort study in Ontario, Canada.

BACKGROUND: Beta-blockers may be cardioprotective in patients receiving chronic dialysis. We examined cardiovascular outcomes among incident dialysis patients receiving beta-blocker therapy. METHODS: We conducted a retrospective cohort study employing linked healthcare databases in Ontario, Canada. We studied all consecutive chronic dialysis patients aged≥66 years who initiated dialysis between 1 July 1991 and 31 July 2007. Patients were divided into three groups according to new medication use after the initiation of chronic dialysis. The three groups were patients initiated on beta-blockers, calcium channel blockers and statins only. Patients in the beta-blocker and calcium channel blocker groups could also be concurrently receiving a statin. The primary outcome was time to a composite endpoint of death, myocardial infarction, stroke or coronary revascularization. RESULTS: There were a total of 1836 patients (504 beta-blocker, 570 calcium channel blocker and 762 statin-only users). Compared to statin-only use, beta-blocker use was not associated with improved cardiovascular outcomes [adjusted hazard ratio (aHR) 1.07, 95% confidence interval (CI) 0.92-1.23]. As expected, calcium channel blocker use was also not associated with improved cardiovascular outcomes (aHR 0.91, 95% CI 0.79-1.06). Among all subgroup analyses by beta-blocker attributes, only high-dose beta-blocker therapy was associated with better cardiovascular outcomes as compared to low-dose beta-blockers (aHR 0.50, 95% CI 0.29-0.88). CONCLUSIONS: We observed no beneficial effect of beta-blocker use among patients receiving chronic dialysis relative to our comparator groups. Given current uncertainty around the cardioprotective benefits of beta-blockers in patients receiving dialysis, a large randomized clinical trial is warranted.