Comparative Safety and Effectiveness of Urea and Tolvaptan for the Management of Hyponatremia.

Background: The optimal management of euvolemic and hypervolemic hyponatremia remains controversial. The effectiveness of the vasopressin receptor antagonist tolvaptan on serum sodium normalization has been well described in the literature, although the associated risk of serum sodium overcorrection limits its use. Urea has been proposed as an alternative treatment option due to its milder serum sodium raising effects and adverse event profile. Objective: This study aimed to compare urea and tolvaptan for their serum sodium raising effects and potential for overcorrection. Methods: In a multicenter retrospective review, 46 hospitalized patients who received either urea or tolvaptan for the management of hyponatremia were evaluated for the rate of serum sodium normalization and overcorrection. Results: Mean serum sodium concentrations at baseline were 125.91 mEq/L and 123.83 mEq/L for patients treated with urea and tolvaptan, respectively. After 12 hours, tolvaptan was associated with a significantly higher rate of serum sodium increase compared with urea (5.05 mEq/L vs 1.10 mEq/L; P = .001). However, no statistically significant differences were observed in the mean change in serum sodium concentrations at 24 hours, 48 hours, or with the proportion of patients who reached a serum sodium concentration of 135 mEq/L. Overcorrection rates were significantly higher with tolvaptan compared with urea at 43% and 9%, respectively. Conclusion: The results of this study suggest that urea has a comparable effectiveness profile to tolvaptan for the management of hyponatremia with a significantly reduced risk of overcorrection.

Use of Low-Molecular-Weight Heparin and Peak anti-Xa Monitoring In Severe SARS-CoV-2 Disease: A Brief Report.

In 2019, a novel coronavirus was identified in Wuhan, China. This strain was classified as a pandemic in early 2020 by the World Health Organization (WHO), rapidly reaching millions of cases worldwide and overwhelming intensive care units. One distinct feature identified in severe SARS-CoV-2 is abnormal and complex coagulation and hematologic abnormalities, including significantly elevated D-dimer and fibrin/fibrinogen values possibly increasing morbidity and mortality in this patient population. Aggressive anticoagulation therapy with appropriate peak anti-Xa level monitoring has produce satisfactory results at our institution. Our intent is to present a case series of our strategy to highlight the benefits of this approach.

Evaluation of the Efficacy of Liposomal Bupivacaine in Total Joint Arthroplasty.

BACKGROUND: Appropriate pain control is one of the cornerstones necessary to promote positive clinical outcomes. A new bupivacaine liposomal formulation was designed to extend its analgesic effect for up to 72-hours post-surgery, reportedly leading to significant opioid-sparing. METHOD: Retrospective and prospective chart review conducted in a 178-bed academic institution between January 2013 to December 2013 and August 2014 to November 2014, in 115 patients that receive hip and knee arthroplasty. The primary outcome was the measurement of average daily pain score on post-operative days 1 and 2. Secondary outcomes included length of stay, overall opioid use post-surgery and pain control satisfaction using Press-Ganey® scores. RESULTS: The average pain scores in the HCl group were 4.64 and 4.38 (Likert score: 0-10) for POD 1 and POD 2, compared to 4.72 POD 1 and 4.2 POD 2 in the liposome group (POD 1: p = 0.413; POD 2: p = 0.303). The difference in LOS for knee arthroplasty was statistically significant [HCl group: 1.94 days (± 0.66) versus liposome group: 2.27 days (±0.77) p-value = 0.038)] favoring the standard of care. For hip arthroplasty or bilateral knee arthroplasty the differences in LOS were not statistically significant (p = 0.052 and p = 0.484 respectively). 93% of the patients in the HCl group, pain was well controlled, versus 88.5% in the liposome group with similar oxycodone IR use among groups. CONCLUSION: Liposome bupivacaine did not offer a notable benefit compared to the HCl formulation in our study.

Dolutegravir And Lamivudine Combination For The Treatment Of HIV-1 Infection.

There have been remarkable advances in drug development for the treatment of HIV-1 infection. From the co-formulation of combination antiretroviral therapy (cART) into single-tablet regimens to the development of long-acting antiretroviral (ARV) drug formulations, the treatment of HIV has and will become much more tolerable and less complicated for patients. In addition, and appropriately, there is a focus on reducing short- and long-term toxicities of treatment while maintaining robust efficacy. One of such approaches includes 2-drug regimen constructs that contain and retain effective ARV compounds while excluding components that have relatively unfavorable toxicity profiles. The first-ever 2-drug regimen approved for the treatment of HIV-1 infection for treatment-naive people living with HIV (PLWH), consisting of the integrase inhibitor dolutegravir (DTG) and the nucleoside reverse transcriptase inhibitor (NRTI) lamivudine (3TC), is reviewed in this paper. The chemical composition and properties, pharmacokinetic and pharmacodynamics profile, and clinical trial data on efficacy and safety of DTG/3TC are presented. An expert opinion aims to highlight important considerations for the use of DTG/3TC in the context of existing and emerging ARV options.

Inpatient pain management in sickle cell disease.

PURPOSE: A novel strategy for management of acute pain associated with sickle cell disease (SCD), referred to as the oral tier approach, is described. SUMMARY: SCD is an inherited blood disorder characterized by episodic acute pain known as vaso-occlusive crisis (VOC), which is the most common reason for emergency department visits and hospital admissions in patients with SCD; these patients are often treated with parenteral opioids on admission and then transitioned to oral opioids prior to discharge. In this report, experience with use of the oral tier approach in 3 patients with SCD hospitalized for management of VOC is reported. As per usual practice, acute pain was initially managed with parenteral opioids via patient-controlled analgesia (PCA). Once pain control was established, an oral tier was added. The oral tier consisted of 3 orders. The first order was for an oral opioid, to be administered every 3 hours on a scheduled basis; however, the patient could refuse 1 or more of these scheduled doses. Two additional orders specified that the patients could receive additional oral opioids in incremental doses for moderate (grade 4-7) or severe (grade 8-10) pain if appropriate. To facilitate transition to an oral regimen with which the patients might be discharged, they were encouraged to use oral opioids in preference to parenteral opioids. Opioid usage and average daily pain scores for the 3 patients are reported. CONCLUSION: Healthcare providers can use the oral tier approach to facilitate rapid inpatient conversion from i.v. PCA to oral opioids while providing adequate pain control in patients with SCD who develop VOC.

Posttranscriptional regulation of T-type Ca(2+) channel expression by interleukin-6 in prostate cancer cells.

BACKGROUND: At early stages, the growth of prostate cancers is androgen dependent. At later stages, however, the growth of prostate cancers becomes androgen independent, which leads to an increase in mortality. The switch to an androgen-refractory state is associated with neuroendocrine differentiation (NED) of prostate cancer cells. Several factors including interleukin-6 (IL-6) and increased cAMP production promote NED of prostate cancer cells. In this work we investigated whether IL-6 evoked NED of LNCaP cells results in a significant change in T-type Ca(2+) channel expression in comparison to non-stimulated LNCaP cells. METHODS: T-type Ca(2+) channel subunit Cav3.2 expression was studied using PCR analysis, western blot and whole cell recordings. Tubulin IIIß expression and neurite-like morphology was assessed to investigate the role of T-type Ca(2+) channels in the differentiation of prostate cancer cells. RESULTS: Treatment of LNCaP cells with IL-6 for 4days evokes considerable morphological and biochemical changes consistent with NED. Transcripts of the T-type Ca(2+) channel subunit Cav3.2 but not Cav3.1 or Cav3.3 are detected in IL-6 stimulated cells. Real time PCR analysis of IL-6 stimulated cells indicates no significant change in Cav3.2 mRNA expression in comparison to non-stimulated cells. LNCaP cells stimulated with IL-6 show a threefold increase in T-type Ca(2+) channel subunit Cav3.2 protein expression, suggesting that channel expression is upregulated by a posttranscriptional mechanism. Electrophysiological recordings reveal that increased Cav3.2 protein expression following IL-6 stimulation of LNCaP cells does not result in increased expression of functional channels in the membrane. Functional expression of Cav3.2 channels in LNCaP cells is facilitated by co-stimulation with IL-6 and the cAMP-stimulating agent, forskolin (FSK). Inhibition of T-type Ca(2+) channel activity in IL-6 stimulated LNCaP cells prevents the development of morphological characteristics consistent with NED. CONCLUSIONS: These results indicate that the functional expression of T-type Ca(2+) channels is regulated by the interplay of multiple factors in LNCaP cells.

Regulation of T-type calcium channel expression by sodium butyrate in prostate cancer cells.

Several cellular mechanisms contribute to the neuroendocrine differentiation of prostate cancer cells, including exposure to sodium butyrate (NaBu), a naturally occurring salt of the short chain fatty acid n-butyric acid. NaBu belongs to a class of histone deacetylase inhibitors with potential anticancer function. T-type calcium channel expression constitutes an important route for calcium influx in tumor cells that may trigger changes in cell proliferation and differentiation. In this work we investigated the role NaBu on the differentiation of lymph node carcinoma of the prostate (LNCaP) cells and its effect on T-type Ca(2+) channel expression. NaBu stimulates the morphological and molecular differentiation of LNCaP cells. Stimulation of LNCaP cells with NaBu evokes a significant increase in the expression of the Cav3.2 T-type channel subunits. Furthermore, the increased Cav3.2 expression promotes membrane insertion of T-type Ca(2+) channels capable of generating fast inactivating Ca(2+) currents, sensitive to 100µM Ni(2+) ions. Inhibition of T-type Ca(2+) channel function reduces the outgrowth of neurite-like processes in LNCaP cells. NaBu-evoked expression of T-type Ca(2+) channels is also involved in the regulation of cell viability. Inhibition of T-type Ca(2+) channels causes a significant reduction in the viability of LNCaP cells treated with 1mM NaBu, suggesting that Ca(2+) influx via T-type channels can promote cell proliferation. However, increased expression of T-type Ca(2+) channels enhanced the cytotoxic effect of thapsigargin and paclitaxel on cell proliferation. These findings demonstrate that NaBu stimulates T-type Ca(2+) channel expression, thereby regulating both the morphological differentiation and growth of prostate cancer cells.