Case Series: Limited Opioid Withdrawal With Use of Transdermal Buprenorphine to Bridge to Sublingual Buprenorphine in Hospitalized Patients.

BACKGROUND: Prerequisite opioid withdrawal symptoms prior to buprenorphine induction are unacceptable to many patients. We assessed whether transdermal buprenorphine minimized withdrawal while bridging to sublingual therapy among hospital inpatients. METHODS: Retrospective chart review of (n = 23) inpatients with opioid use disorder or opioid dependence due to chronic pain. RESULTS: Of 23 inpatients, 65% transitioned without symptoms, while 35% experienced mild withdrawal. Ninety-six percent completed planned hospitalizations, with 83% engaged in treatment 4 weeks post-discharge. DISCUSSION AND CONCLUSIONS: Bridging to sublingual therapy with transdermal buprenorphine patches was feasible without withdrawal symptoms. SCIENTIFIC SIGNIFICANCE: This strategy may facilitate buprenorphine therapy in hospital inpatients. (Am J Addict 2019;00:1-4).

Correction to: Carfentanil: a narrative review of its pharmacology and public health concerns.

In the article entitled: "Carfentanil: a narrative review of its pharmacology and public health concerns" published online and in the April 2019 issue of the Journal, Can J Anesth 2019; DOI: https://doi.org/10.1007/s12630-019-01294-y , the Figure showed the wrong structures for remifentanil and carfentanil. This is now corrected in the accompanying revised figure and legend.

Carfentanil: a narrative review of its pharmacology and public health concerns.

Carfentanil is a synthetic fentanyl analogue approved for veterinary use. It is a mu-opioid receptor agonist with an estimated analgesic potency approximately 10,000 times that of morphine and 20-30 times that of fentanyl, based on animal studies. Since 2016, an increasing number of reports describe detection of carfentanil in the illicit drug supply. Little is known about the pharmacology of carfentanil in humans. Its high potency and presumed high lipophilicity, large volume of distribution, and potential active metabolites have raised concerns about the management of people exposed to carfentanil as well as the safety of first responders. Exposed individuals exhibit features of an opioid toxidrome and respond to opioid antagonists such as naloxone, although empiric dose requirements are unknown and very high doses may be required. Rare reports of suspected accidental poisoning of first responders have not been analytically confirmed and are unlikely to represent true poisoning. General occupational hygiene measures, including regular decontamination with soap and water, basic personal protective equipment (nitrile gloves, N95 mask, and eye goggles), and ready access to naloxone are generally sufficient in most circumstances.

RéSUMé: Le carfentanil est un analogue synthétique du fentanyl approuvé pour usage vétérinaire. C'est un agoniste du récepteur mû des opioïdes ayant une puissance analgésique estimée, à partir d'études chez l'animal, à environ 10 000 fois celle de la morphine et 20 à 30 fois celle du fentanyl. Depuis 2016, un nombre croissant de rapports font état de la présence de carfentanil dans les drogues illicites. On ne sait que peu de choses sur la pharmacologie du carfentanil chez l'homme. Sa puissance pharmacologique et sa forte lipophilie supposée, un grand volume de distribution et de possibles métabolites actifs ont soulevé des préoccupations pour le traitement des personnes exposées au carfentanyl et pour la sécurité des premiers intervenants. Les sujets exposés présentent les caractéristiques d'un syndrome toxique aux opioïdes et répondent à leurs antagonistes, comme la naloxone, bien que les doses empiriques nécessaires soient inconnues et qu'il faille possiblement administrer de très fortes doses. Les rares descriptions d'intoxications accidentelles suspectées chez des premiers intervenants n'ont pas été confirmées par des analyses et il est peu probable qu'elles représentent de véritables empoisonnements. Des mesures générales d'hygiène professionnelles, incluant une décontamination régulière à l'eau et au savon, un équipement de protection individuelle élémentaire (gants en nitrile, masque N95, et lunettes de protection), ainsi qu'un accès rapide à la naloxone sont généralement suffisants dans la majorité des cas.

Impact of Reported Beta-Lactam Allergy on Inpatient Outcomes: A Multicenter Prospective Cohort Study.

BACKGROUND: Reported allergy to beta-lactam antibiotics is common and often leads to unnecessary avoidance in patients who could tolerate these antibiotics. We prospectively evaluated the impact of these reported allergies on clinical outcomes. METHODS: We conducted a trainee-led prospective cohort study to determine the burden and clinical impact of reported beta-lactam allergy on patients seen by infectious diseases consultation services at 3 academic hospitals. The primary outcome was a composite measure of readmission for the same infection, acute kidney injury, Clostridium difficile infection, or drug-related adverse reactions requiring discontinuation. Predictors of interest were history of beta-lactam allergy and receipt of preferred beta-lactam therapy. RESULTS: Among 507 patients, 95 (19%) reported beta-lactam allergy; preferred therapy was a beta-lactam in 72 (76%). When beta-lactam therapy was preferred, 25 (35%) did not receive preferred therapy due to their report of allergy even though 13 (52%) reported non-severe prior reactions. After adjustment for confounders, patients who did not receive preferred beta-lactam therapy were at greater risk of adverse events (adjusted odds ratio [aOR], 3.1; 95% confidence interval [CI], 1.28-7.89) compared with those without reported allergy. In contrast, patients who received preferred beta-lactam therapy had a similar risk of adverse events compared with patients not reporting allergy (aOR, 1.33; 95% CI, .62-2.87). CONCLUSIONS: Avoidance of preferred beta-lactam therapy in patients who report allergy is associated with an increased risk of adverse events. Development of inpatient programs aimed at accurately identifying beta-lactam allergies to safely promote beta-lactam administration among these patients is warranted.

The effect of personality dimensions on functional outcomes in mood disorders.

INTRODUCTION: Functional impairment associated with mood disorders may be related to a characteristic "profile" of normative personality dimensions. METHODS: Individuals (age ≥ 18 years) with MDD (n = 400) or BD (n = 317), as defined by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM-IV-TR), were enrolled in the IMDCP. Personality was evaluated with the Neuroticism-Extraversion-Openness Five-Factor Inventory (NEO-FFI), and functionality with the Sheehan Disability Scale and Endicott Work Productivity Scale. Path analysis using linear multiple regressions was performed to identify direct and indirect effects of personality on functional impairment. RESULTS: Lower conscientiousness exerted a significant direct effect on global (p = 0.017) and family life dysfunction in individuals with MDD (p = 0.002), as well as lower work productivity in both MDD (p = 0.020) and BD (p = 0.018). Lower extraversion exerted a significant direct effect on social impairment in individuals with BD (p = 0.017). Higher neuroticism and agreeableness as well as lower extraversion exerted indirect effects on global and social dysfunction in individuals with MDD via their effects on depression severity. In BD, higher neuroticism and openness indirectly affected global dysfunction. Family dysfunction was indirectly affected by higher neuroticism and openness as well as lower extraversion in MDD and BD. CONCLUSION: The results suggest that discrete personality dimensions may exert direct and indirect effects on functional outcomes in individuals with mood disorders. Personalizing disease management approaches in mood disorders with emphasis on vocational rehabilitation may benefit from measurement and intervention targeting personality.

Multimodality imaging in the evaluation of cardiovascular manifestations of malignancy.

Up to one third of the population will die as a direct result of cancer. Accurate and timely diagnosis of disease often requires multiple different approaches including the use of modern imaging techniques. Prompt recognition of adverse consequences of some anti-cancer therapies also requires a knowledge of the optimum imaging strategy for the problem at hand. The purpose of this article is to review not only some of the commoner cardiovascular manifestations of malignancy but also to discuss the strengths, weaknesses and appropriate use of cardiovascular imaging modalities.

Differential sensitivities of CaV1.2 IIS5-S6 mutants to 1,4-dihydropyridine analogs.

1,4-Dihydropyridines (DHPs), L-type calcium channel (Ca(V)1) blockers, are known to interact with Ca(V)1.2 subunits through their binding site located at IIIS5-S6 and IVS6 regions. We recently identified two domain II residues (S666 and A752) critical for nifedipine blockade (Kwok et al., 2008). In this study, we examined the blockade effects of two DHP analogues, nemadipine and nicardipine, on wildtype, M1161A (in IIIS6), S666V (in IIS5) and A752T (in IIS6) mutants of the rat alpha(1C) subunit transiently expressed with beta(2a) and alpha(2)delta in cultured tsA201 cells. We found that the IC(50) ratio of the mutants to the wildtype channel was similar in S666V and M1161A mutants for both drugs, but in A752T it was lower for nemadipine than nicardipine (P<0.05). At saturating drug concentrations, not all the current was completely blocked in the mutants. The residual current recorded in 100 microM nemadipine was approximately 10% of the total current for the A752T channel, which was significantly higher than that in 100 microM nicardipine (approximately 2%). In wildtype, S666V and M1161A, there was no significant difference in residual current between nemadipine and nicardipine, although it was greater in S666V (approximately 15%) and M1161A approximately 30%) as compared to the wildtype channel (<5%). Taken together, our findings suggest that the domain II residues alter the DHP effect in a structure-specific manner and may be involved in a pathway downstream of DHP binding.