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Since 2020, there have been changes in Food and Drug Administration guidance and in recommendations by national organizations with a focus on kidney diseases pertaining to the choice of equations used to estimate creatinine clearance and glomerular filtration rate in patients with renal impairment. This includes a recommendation by the National Kidney Foundation to avoid the use of the Cockcroft-Gault equation for drug dosing in patients with renal impairment. This commentary provides an overview of recent recommendations concerning kidney function assessment that have important implications for drug dosing in patients with renal impairment and provides suggestions for implementing these recommendations. [ABSTRACT FROM AUTHOR]

Critical care clinicians are likely to see an increasing number of patients admitted to the ICU who are receiving US Food and Drug Administration-approved medications for opioid use disorder (MOUDs) given the well-documented benefits of these agents. Oral methadone, multiple formulations of buprenorphine, and extended-release naltrexone are the three types of MOUD most likely to be encountered by ICU clinicians; however, these drugs vary with respect to formulations, pharmacokinetics, and adverse effects. No published clinical practice guidelines or consensus statements are available to guide decision-making in patients admitted to the ICU setting who are receiving MOUDs before admission. Additionally, no randomized trials and limited observational studies have evaluated issues related to MOUD use in the ICU. Therefore, ICU clinicians caring for patients admitted who are taking MOUDs must base their decision-making on data extrapolation from pharmacokinetic, pharmacologic, and clinical studies performed in non-ICU settings. Despite the challenges in administering MOUDs in critically ill patients, extrapolation of data from other hospital settings suggests that the benefits of continuing MOUD therapy outweigh the risks in patients able to continue therapy. This article provides guidance for critical care clinicians caring for patients admitted to the ICU already receiving methadone, buprenorphine, or extended-release naltrexone. The guidance includes algorithms to aid clinicians in the clinical decision-making process, recognizing the inherent limitations of the existing evidence on which the algorithms are based and the need to account for patient-specific considerations. [ABSTRACT FROM AUTHOR]

Objectives: To review the current definitions and diagnostic criteria for acute kidney injury (AKI) and type 1 hepatorenal syndrome (HRS) now termed HRS-AKI and discuss the challenges in deciding the most appropriate medication regimens to treat patients with HRS-AKI. Data sources: PubMed (inception to April 2023) with bibliographies of retrieved articles searched for additional articles; organizational websites for clinical practice guidelines (CPGs). Study selection and data extraction: Randomized controlled trials (RCTs) evaluating albumin and vasoconstrictors for HRS-AKI. Data synthesis: A major change in the most recent revision of definitions and diagnostic criteria for HRS-AKI is the elimination of the set cutoff serum creatinine values for AKI. This change should be considered when comparing studies of HRS-AKI over time. Albumin has been administered to both vasoconstrictor treatment and placebo groups in all recent RCTs; however, there has never been a large RCT evaluating a no-albumin group. Most prospective trials comparing a midodrine/octreotide combination or norepinephrine to placebo or terlipressin have enrolled less than 100 patients limiting any conclusions regarding clinically important outcomes. Terlipressin with albumin has shown mixed results for complete HRS-AKI reversal with no reductions in crude mortality but adverse effect concerns involving ischemic and pulmonary events. Relevance to patient care and clinical practice: Type 1 hepatorenal syndrome with acute kidney injury is a potentially life-threatening syndrome with diagnostic and treatment challenges. Albumin plus a vasoconstrictor has become the routine HRS-AKI treatment even though there has not been a large RCT evaluating a no-albumin group. Terlipressin is the vasoconstrictor of choice for HRS-AKI in current CPGs, but it has adverse effect concerns and, until recently, was not available in the United States. Conclusions: In conjunction with changes in the definitions and diagnostic criteria for HRS-AKI, debate continues regarding the optimal therapy for HRS-AKI, particularly considering recent trials demonstrating ischemic and pulmonary adverse events with terlipressin used in combination with albumin. [ABSTRACT FROM AUTHOR]

Monoclonal antibody products are an increasing portion of novel drug approvals. The labeling of initial drug approvals frequently involves body-size-based rather than fixed-dose administration regimens for adults without clear rationale for doing so. This presents challenges when prescribing these products for patients with extremes of body habitus who constitute a small portion of enrollment in pre-approval investigations. Fixed-dose regimens allow for standardized preparation with the potential to reduce the risk of calculation errors, drug waste, and make home administration more practical. Fixed-dose rather than body-size-based monoclonal antibody regimens should serve as the initial approach in early phase 1 clinical trials. [ABSTRACT FROM AUTHOR]

The article discusses the evolution of critical care pharmacy practice and the acceptance of critical care pharmacists by their colleagues. It highlights the importance of a landmark study by Leape et al. published in 1999, which demonstrated the value of pharmacists in preventing adverse drug events (ADEs) in the ICU setting. The study found that involving a pharmacist in ICU rounding significantly reduced preventable ADEs. This study, along with other publications and consensus recommendations, has helped establish the role and value of critical care pharmacists in medication optimization and patient safety. [Extracted from the article]

There are several clinical practice guidelines concerning the use of fluid and vasoactive drug therapies in critically ill adult patients, but the recommendations in these guidelines are often based on low‐quality evidence. Further, some were compiled prior to the publication of landmark clinical trials, particularly in the comparison of balanced crystalloid and normal saline. An important consideration in the treatment of critically ill patients is the application of precision medicine to provide the most effective care to groups of patients most likely to benefit from the therapy. Although not currently widely integrated into these practice guidelines, the utility of precision medicine in critical illness is a recognized research priority for fluid and vasoactive therapy management. The purpose of this narrative review was to illustrate the evaluation and challenges of providing precision fluid and vasoactive therapies to adult critically ill patients. The review includes a discussion of important investigations published after the release of currently available clinical practice guidelines to provide insight into how recommendations and research priorities may change future guidelines and bedside care for critically ill patients. [ABSTRACT FROM AUTHOR]

Background: Current critical care pharmacist (CCP) practices and perceptions related to neuromuscular infusion (NMBI) use for acute respiratory distress syndrome (ARDS) maybe different with the COVID-19 pandemic and the publication of 2020 NMBI practice guidelines. Objective: To evaluate CCP practices and perceptions regarding NMBI use for patients with moderate-severe ARDS. Methods: We developed, tested, and electronically administered a questionnaire (7 parent-, 42 sub-questions) to 409 American College of Clinical Pharmacy (ACCP) Critical Care Practice and Research Network members in 12 geographically diverse states. The questionnaire focused on adults with moderate-severe ARDS (PaO2:FiO2<150) whose causes of dyssynchrony were addressed. Two reminders were sent at 10-day intervals. Results: Respondents [131/409 (32%)] primarily worked in a medical intensive care unit (ICU) 102 (78%). Compared to COVID-negative(-) ARDS patients, COVID positive(+) ARDS patients were twice as likely to receive a NMBI (34 ± 18 vs.16 ± 17%; P < 0.01). Respondents somewhat/strongly agreed a NMBI should be reserved until after trials of deep sedation (112, 86%) or proning (92, 81%) and that NMBI reduced barotrauma (88, 67%), dyssynchrony (87, 66%), and plateau pressure (79, 60%). Few respondents somewhat/strongly agreed that a NMBI should be initiated at ARDS onset (23, 18%) or that NMBI reduced 90-day mortality (12, 10%). Only 2/14 potential NMBI risks [paralysis awareness (101, 82%) and prolonged muscle weakness (84, 68%)] were frequently reported to be of high/very high concern. Multiple NMBI titration targets were assessed as very/extremely important including arterial pH (109, 88%), dyssynchrony (107, 86%), and PaO2: FiO2 ratio (82, 66%). Train-of-four (55, 44%) and BIS monitoring (36, 29%) were deemed less important. Preferred NMBI discontinuation criteria included absence of dysschrony (84, 69%) and use ≥48 hour (72, 59%). Conclusions and Relevance: Current critical care pharmacists believe NMBI for ARDS patients are best reserved until after trials of deep sedation or proning; unique considerations exist in COVID+ patients. Our results should be considered when ICU NMBI protocols are being developed and bedside decisions regarding NMBI use in ARDS are being formulated. [ABSTRACT FROM AUTHOR]

Objective: The objective of the study was to discuss the controversies surrounding the use and dosing of direct-acting oral anticoagulants (DOACs) in obese patients recognizing the limitations of the existing evidence base that preclude strong recommendations. Data Sources: A literature search of MEDLINE was performed (2020 to end August 2022) subsequent to recent guidelines using the following search terms: direct acting anticoagulants, obesity, rivaroxaban, apixaban, edoxaban, dabigatran, dabigatran etexilate, and clinical practice guidelines. English-language studies and those conducted in adults were selected. Data Synthesis: The available randomized studies evaluating DOACs had relatively small numbers of patients with more extreme forms of obesity (body mass index [BMI] > 40 kg/m2) and none of the larger studies had a specific focus on dosing DOACs in obese patients. Recent guidelines by the International Society on Thrombosis and Haemostasis (ISTH) have specific recommendations for dosing DOACs in obesity. There are pharmacokinetic/pharmacodynamic and observational studies published before and after the ISTH guidelines with a focus on DOAC dosing in obese patients that generally support the recommendations in the guidelines, but most involved small numbers of patients usually with BMIs <45 kg/m2. Relevance to Patient Care and Clinical Practice: This review discusses DOAC dosing in obesity with important considerations for clinicians related to DOAC choice and dosing. Conclusions: Dosing alterations of DOACs do not appear to be necessary when used for either prophylaxis or treatment in patients with BMIs up to approximately 45 to 50 kg/m2, but research is needed for BMIs >50 kg/m2. [ABSTRACT FROM AUTHOR]

Albumin has only reduced crude mortality in one randomized controlled trial conducted to date. This raises the question as to why potentially beneficial oncotic and pleiotropic properties of albumin do not consistently translate into clinically important outcomes. Four postulated explanations are provided as to why the theoretical advantages of albumin are not apparent in clinical trials: diminished oncotic action due to leakage of albumin from the intravascular compartment, modification of the pleiotropic properties of albumin both in vitro and in vivo, the ability of other plasma proteins to take over the major functions of albumin, and possible adverse effects. [ABSTRACT FROM AUTHOR]

At least 30 mL/kg of crystalloid fluid administration within the first 3 hours of resuscitation is suggested by the current Surviving Sepsis Campaign guidelines for management of sepsis and septic shock. This commentary discusses the challenges with using a weight-based approach to bolus fluid dosing during the early phase of resuscitation of adult, obese patients. Based on the available literature, arguments can be made for the use of either ideal or adjusted body weight for weight-based fluid dosing, but there are concerns with fluid overload if using actual body weight to dose patients with more severe forms of obesity. [ABSTRACT FROM AUTHOR]

Each survey allowed for the assessment of two specialty practice organizations, so there could have been up to four organizations assessed if both the chair and vice chair/chair elect provided an assessment of two organizations, but this did not happen. SCCM was cited as a major interprofessional organization by Emergency Medicine PRN leadership but had one "no" response in contrast to all "yes" responses from the Critical Care PRN, but it is unclear how much to read into this single difference. In a previous publication of JACCP, I wrote an editorial providing criteria that might prove useful by health care professionals for determining their perceptions of interprofessional involvement in their specialty interprofessional health care organizations.[1] The criteria had three levels with a series of questions allowing for yes or no responses and a column for comments. [Extracted from the article]

Objectives: The purpose of this article is to summarize the results of major randomized controlled trials (RCTs) comparing clinical outcomes of critically ill patients treated with normal saline (NS) or balanced salt solutions (BSSs), address discordant results of these studies, and provide direction for future investigations. Data Sources: PubMed (2011 to January 2022) with bibliographies of retrieved articles searched for additional articles. Study Selection and Data Extraction: RCTs comparing NS and BSSs in critically ill adult patients. Data Synthesis: Recently published large RCTs comparing NS with BSSs in heterogeneous populations of intensive care unit patients did not find significant differences in mortality, despite positive findings in some end points in prior RCTs. However, there were a number of methodologic issues common to the RCTs including: varying study designs and end points, clinician discretion for the majority or all treatments other than the primary intervention fluid, heterogeneous patients with varying levels of acuity, and lack of power to investigate potential subgroup differences. In addition, there were problematic issues related to blinding and use of nonstudy fluids. Relevance to Patient Care and Clinical Practice: Intravenous fluids are a mainstay of supportive care for critically ill patients. Similar to the so-called crystalloid-colloid debate, there has been a long-standing debate among critical care clinicians and researchers concerning the preferred crystalloid solution, NS versus one of the available BSSs. Conclusions: Despite the recent publication of large multicenter RCTs, the preferred resuscitation fluid, NS or a BSS, for critically ill patients is still open for debate, although the available investigations do provide some direction for clinicians and for future investigations. [ABSTRACT FROM AUTHOR]

Introduction: Despite its widespread use, there is a paucity of data to guide the optimal use of arginine vasopressin (AVP) in critically ill patients with septic shock. Methods: This multicenter retrospective cohort study conducted in critically ill adults sought to evaluate the role of catecholamine requirements and timing on responsiveness to AVP. Responsiveness was defined as both a decrease in = 50% of catecholamine requirements and no decrease in mean arterial pressure (MAP) at 4 hours post-AVP initiation. Primary outcomes of interest included the proportion of patients who started AVP within 4 hours after starting catecholamine therapy, as well as baseline norepinephrine (NE) equivalents (< 15, 15-39, or = 40 mcg/min). Multivariate analyses and logistic regression were performed to identify other factors associated with AVP responsiveness. Results: There were 300 patients included in this study, with 74 patients being responders and 226 being non-responders. There was no significant difference in the number of patients who received AVP within 4 hours from catecholamine initiation between responders and non-responders (35% vs. 42%, P=0.29). There were more patients in the non-responder group requiring = 40 mcg/min of NE equivalents at AVP initiation (30% vs. 16%, P=0.023). Stress dose steroid use was less common in responders (35% vs. 52%, P=0.011), which was consistent with logistic regression analysis (OR 0.56, 95% 0.32-0.98, P=0.044). Clinical outcomes between responders and non-responders were similar, apart from ICU (5.4% vs. 19.5%) and hospital (5.4% vs. 20.4%) mortality being lower in responders (P =0.0032 and P=0.0002, respectively). Conclusion: Shorter times to AVP initiation was not associated with responsiveness at 4 hours post-catecholamine initiation, although non-responders tended to require higher doses of NE equivalents at time of AVP initiation. Concomitant corticosteroids were associated with a lower likelihood of AVP responsiveness. [ABSTRACT FROM AUTHOR]

Take the example of a weight-based drug dosing study in which there are two groups of patients, those with a BMI < 30 kg/m SP 2 sp and those with a BMI U > u 30 kg/m SP 2 sp . The ability to group patients by BMI does not mean some form of categorization of BMI as an independent variable is the best method for evaluating its association with the dependent (outcome) variable of dosing. Keywords: obesity BMI; drug dosing; body composition; body mass; body weight; sample size EN obesity BMI drug dosing body composition body mass body weight sample size 107 109 3 11/01/22 20230101 NES 230101 In 1832, Adolphe Quetelet developed a calculation for relating height to weight that subsequently became known as Quetelet's Index, until 1972 when Ancel Keys coined the term body mass index (BMI).[1] Even prior to the use of the term BMI, the first half of the 20th century saw life insurance companies taking an interest in indices such as height, weight, age, and sex relative to their relationship with mortality for the purpose of developing actuarial tables. [Extracted from the article]

Obesity is highly prevalent in hospitalized patients admitted with COVID-19. Evidence based guidelines are available for COVID-19-related therapies but dosing information specific to patients with obesity is lacking. Failure to account for the pharmacokinetic alterations that exist in this population can lead to underdosing, and treatment failure, or overdosing, resulting in an adverse effect. The objective of this manuscript is to provide clinicians with guidance for making dosing decisions for medications used in the treatment of patients with COVID-19. A detailed literature search was conducted for medications listed in evidence-based guidelines from the National Institutes of Health with an emphasis on pharmacokinetics, dosing and obesity. Retrieved manuscripts were evaluated and the following prioritization strategy was used to form the decision framework for recommendations: clinical outcome data > pharmacokinetic studies > adverse effects > physicochemical properties. Most randomized controlled studies included a substantial number of patients who were obese but few had large numbers of patients more extreme forms of obesity. Pharmacokinetic data have described alterations with volume of distribution and clearance but this variability does not appear to warrant dosing modifications. Future studies should provide more information on size descriptors and stratification of data according to obesity and body habitus. [ABSTRACT FROM AUTHOR]

What is known and objective: The purpose of this paper is to discuss the limitations of the evidence supporting the SIS recommendations for antibiotic prescribing in patients with traumatic facial fractures and to provide suggestions for clinical decision‐making and further research in this area given the wide variation in prescribing practices. Comment: The Surgical Infection Society (SIS) recently published guidelines on antibiotic use in patients with traumatic facial fractures. The guidelines recommend against the use of prophylactic antibiotics for all adult patients with mandibular or non‐mandibular facial fractures undergoing non‐operative or operative procedures. Despite the available evidence, surveys conducted in the United States and the United Kingdom prior to the publication of the SIS guidelines demonstrate substantial preoperative, intraoperative and postoperative prophylactic prescribing of antibiotics for patients with facial fractures undergoing surgery. What is new and conclusion: With the exception of strong recommendations based on moderate‐quality evidence to avoid prolonged postoperative antibiotic prophylaxis, the weak recommendations in the guidelines are a function of low‐quality evidence. A logical choice for a narrow‐spectrum antibiotic is cefazolin administered within 1 h of surgery and no longer than 24 h after surgery, since it is the gold standard of comparison based on clinical practice guidelines concerning antibiotic prophylaxis. [ABSTRACT FROM AUTHOR]

The decision to develop and implement an organizational Code of Conduct required the collective effort and input of the American College of Clinical Pharmacy (ACCP) Board of Regents and staff. The process was systematic, deliberate, and reflective of the College's core values. Building an inclusive organization and embracing diversity require transparent communication of expected standards of conduct. A culture of belonging and equity for all members is necessary to ensure representation and opportunities for engagement throughout the organization. [ABSTRACT FROM AUTHOR]

Objectives: To review the clinical usefulness of the biomarker TIMP-2•IGFBP7 in adult, general medical-surgical intensive care unit (ICU) settings. Data Sources: PubMed (1946 to mid-February 2021) and EMBASE (1947 to mid-February 2021) with bibliographies of retrieved articles reviewed for additional articles. Study Selection and Data Extraction: Studies evaluating use of the urinary TIMP-2•IGFBP7 assay in adult patients in ICU settings. Data Synthesis: Studies published after investigations leading to TIMP-2•IGFBP7 assay approval confirm the appropriateness of considerations discussed in product labeling, such as use of the test within 12 hours of assessment, use of a dichotomous 0.3 (ng/mL)2/1000 cutoff, and use only in combination with other assessments of acute kidney injury (AKI). However, as a biomarker routinely used for early identification of patients at risk for AKI in mixed ICU populations, the additional resources required for TIMP-2•IGFBP monitoring are difficult to justify because of limited data demonstrating usefulness in preventing or ameliorating AKI and its attendant complications. Relevance to Patient Care and Clinical Practice: Biomarkers are potentially useful not only for assessment and diagnosis of AKI, but also for practitioners involved in the management of nephrotoxic medications and medications needing adjustment for decreased kidney function. Conclusions: Although there is evidence to suggest that the urinary TIMP-2•IGFBP7 biomarker is helpful in predicting AKI progression in general medical-surgical ICU patients when used within 12 hours of patient assessment in combination with routine testing, including serum creatinine and urine output, there is little evidence that its use leads to improvements in clinically important patient outcomes. [ABSTRACT FROM AUTHOR]

Objectives: To discuss methods for the assessment of creatinine clearance (Clcr) when serum creatinine (SCr) is not at steady state in order to estimate kidney function and apply the estimate to kidney function staging for clinical assessment or drug dosing. Data Sources: A PubMed search was conducted from 1976 to mid-January 2021 with other articles identified through review of bibliographies of retrieved articles and citations in Scopus. Study Selection and Data Extraction: Articles assessing Clcr under non–steady-state conditions and studies evaluating predictive equations were selected. Data Synthesis: When SCr is systematically changing (ie, trending up or down), kinetic methods to estimate Clcr are appropriate. Estimates from kinetic methods should be individual based and not indexed to body surface area, and careful monitoring is required to confirm predictions as the situation evolves. Standard methods intended for steady-state conditions should not be used to estimate Clcr in patients with unstable SCr. Relevance to Patient Care and Clinical Practice: Creatinine continues to be a monitoring parameter of choice and is an important variable in all the commonly used equations for estimating Clcr and most important for estimating glomerular filtration rate. However, standard methods of estimating Clcr for medication dosing are not accurate under non–steady-state conditions. Conclusion: The methods for kinetic clearance estimation and standards methods for clearance estimation, such as the Cockcroft-Gault equation, are mutually exclusive. There are no benefits of using the kinetic method in patients with stable SCr concentrations, and standard equations are not appropriate with unstable SCr concentrations. [ABSTRACT FROM AUTHOR]

With the increasing occurrence of infectious diseases in lower-and-middle-income countries (LMICs), emergency preparedness is essential for rapid response and mitigation. Economic evaluations of mitigation technologies and strategies have been recommended for inclusion in emergency preparedness plans. We aimed to perform an economic evaluation using dynamic transition modeling of ebola virus disease (EVD) vaccination in a hypothetical community of 1,000 persons in the Democratic Republic of Congo (DRC). Using a modified SEIR (Susceptible, Exposed, Infectious, Recovered, with Death added [SEIR-D]) model that accounted for death and epidemiological data from an EVD outbreak in the DRC, we modeled the transmission of EVD in a hypothetical population of 1,000. With our model, we estimated the cost-effectiveness of an EVD vaccine and an EVD vaccination intervention. The results showed vaccinating 50% of the population at risk prevented 670 cases, 538 deaths, and 22,022 disability-adjusted life years (DALYs). The vaccine was found to be cost-effective with an incremental cost-effectiveness ratio (ICER) of $95.63 per DALY averted. We also determined the minimum required vaccination coverage for cost-effectiveness to be 40%. Sensitivity analysis showed our model to be fairly robust, assuring relatively consistent results even with variations in such input parameters as cost of screening, as well as transmission, infection, incubation, and case fatality rates. EVD vaccination in our hypothetical population was found to be cost-effective from the payer perspective. Our model presents an efficient and reliable approach for conducting economic evaluations of infectious disease interventions as part of an emergency preparedness plan. Infectious diseases affect lower-and-middle-income (LMIC) countries, with their limited resources, disproportionately more. This is certainly the case for ebola virus disease (EVD), a rare, severe, and mostly fatal disease. Vaccination is now available, but whether it is cost-effective remains an open question. We evaluated its cost-effectiveness by modeling the spread of EVD in a hypothetical population of 1000 persons. Using data from an EVD outbreak in the Democratic Republic of Congo (DRC), we estimated how many of persons susceptible to infection were exposed to the virus, became infected, recovered, or died. We did so for two scenarios: vaccinating versus not vaccinating enough people to achieve herd immunity. We assumed vaccinating 50% of the people and estimated how many infections, deaths, and disability-adjusted life years (DALY; the loss of the equivalent of a year of full health) would be prevented by vaccination. Our cost-effectiveness metric was the incremental cost of preventing one DALY. The outcomes of vaccination offset the additional costs. Vaccinating 50% of the population of 1000 cost an additional $2,081,358 but prevented 670 infections, 538 deaths, and 22022 DALYs. Preventing one DALY cost $95.63. This is very cost-effective as it is less than the gross domestic product (GDP) per capita for the DRC of $556.81. Vaccination below 40% of the population was less cost-effective, was most cost-effective at the herd immunity threshold of 45.3%, beyond which there were diminishing returns. Summarized, vaccination against EVD is clinically very effective and certainly worth the additional cost. [ABSTRACT FROM AUTHOR]

In this population-based study, we used the SEER database (1985–2015) to examine survival outcomes in chronic lymphocytic leukemia (CLL) patients followed up to the era of advanced treatments including targeted therapies. Data were extracted for patients 15 years or older with a primary diagnosis of CLL. A period analysis was performed to estimate 5- and 10-year relative survival rates for patients diagnosed during different calendar periods from 1985 to 2015. A mixture cure model was used to examine long-term survivors' proportions among patients diagnosed in 1985–2015 and for two cohorts diagnosed in 2000–2003, followed up to 2012 and 2004–2007, and followed up to 2015. Cox proportional hazard modeling was used for the two cohorts to estimate hazard ratios (HRs) of death adjusted for gender and age. The 5-year and 10-year age-adjusted relative survival rate ranged between 73.7 and 89.4% and from 51.6% to "not reached," respectively, for calendar periods of 1985–1989 to 2010–2014. The long-term survivor proportions varied by age and gender from 0 to 59%. The HRs (95%CI) for the 2004–2007 cohort in comparison to the 2000–2003 cohort were 0.58 (0.43–0.78), 0.58 (0.48–0.70), 0.57 (0.49–0.0.67), 0.68 (0.54–0.85), and 0.83 (0.68–1.02) for the age categories of 45–54, 55–64, 65–74, 75–84, and ≥ 85 years, respectively. Overall, relative survival improved significantly for CLL patients diagnosed between 1985 and 2015. These improvements were markedly better following the introduction of targeted therapies. [ABSTRACT FROM AUTHOR]

What is known and objective: The purpose of this paper was to discuss the limitations of the studies serving as the evidence for recommendations in clinical practice guidelines concerning albumin use for cirrhosis‐related complications, review relevant studies published since the guidelines and suggest directions for future investigations. Comment: There are no recent comprehensive clinical practice guidelines concerning albumin. Instead, more recent albumin guidelines reflect areas of specialty practice such as those by American and European associations for the study of the liver and liver disease. Studies published since the guidelines are useful for helping to define the most appropriate indications for albumin with respect to cirrhosis‐related complications, as well as directions for future research. What is new and conclusion: Albumin has a long history of attempts to define appropriate uses by meta‐analysis, but given the high cost and episodic shortages of albumin, there is a need for adequately powered randomized controlled trials using current state‐of‐the‐art care evaluating the use of albumin to prevent or treat cirrhosis‐related complications. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this critical narrative review is to discuss common indications for ordering serum albumin levels in adult critically ill patients, evaluate the literature supporting these indications, and provide recommendations for the appropriate ordering of serum albumin levels.Data Sources: PubMed (1966 to August 2020), Cochrane Library, and current clinical practice guidelines were used, and bibliographies of retrieved articles were searched for additional articles.Study Selection and Data Extraction: Current clinical practice guidelines were the preferred source of recommendations regarding serum albumin levels for guiding albumin administration and for nutritional monitoring. When current comprehensive reviews were available, they served as a baseline information with supplementation by subsequent studies.Data Synthesis: Serum albumin is a general marker of severity of illness, and hypoalbuminemia is associated with poor patient outcome, but albumin is an acute phase protein, so levels vacillate in critically ill patients in conjunction with illness fluctuations. The most common reasons for ordering serum albumin levels in intensive care unit (ICU) settings are to guide albumin administration, to estimate free phenytoin or calcium levels, for nutritional monitoring, and for severity-of-illness assessment.Relevance To Patient Care and Clinical Practice: Because hypoalbuminemia is common in the ICU setting, inappropriate ordering of serum albumin levels may lead to unnecessary albumin administration or excessive macronutrient administration in nutritional regimens, leading to possible adverse effects and added costs.Conclusions: With the exception of the need to order serum albumin levels as a component of selected severity-of-illness scoring systems, there is little evidence or justification for routinely ordering levels in critically ill patients. [ABSTRACT FROM AUTHOR]

There is no consensus on which weight clinicians should use for weight-based dosing of neuromuscular blocking agents (NMBAs), as exemplified by differing or absent recommendations in clinical practice guidelines. The purpose of this paper is to review studies that evaluated various size descriptors for weight-based dosing of succinylcholine and non-depolarising NMBAs, and to provide recommendations for the descriptors of choice for the weight-based dosing of these agents in patients with obesity. All of the studies conducted to date involving depolarising and non-depolarising NMBAs in patients with obesity have assessed single doses or short-term infusions conducted in perioperative settings. Recognising that any final dosing regimen must take into account patient-specific considerations, the available evidence suggests that actual body weight is the size descriptor of choice for weight-based dosing of succinylcholine and that ideal body weight, or an adjusted (or lean) body weight, is the size descriptor of choice for weight-based dosing of non-depolarising NMBAs. [ABSTRACT FROM AUTHOR]

Objective: The Beta-Blocker Evaluation Survival Trial showed no survival benefit for bucindolol in New York Heart Association (NYHA) class III/IV heart failure (HF) with reduced ejection fraction, but subanalyses suggested survival benefits for non-Black subjects and Arg389 homozygotes. We conducted an ex ante economic evaluation of Arg389 targeted treatment with bucindolol versus carvidolol, complementing a previous ex ante economic evaluation of bucindolol preceded by genetic testing for the Arg389 polymorphism, in which genetic testing prevailed economically over no testing. Methods: A decision tree analysis with an 18-month time horizon was performed to estimate the cost effectiveness/cost utility of trajectories of 100%, 50%, and 0% of patients genetically tested for Arg389 and comparing bucindolol with empirical carvedilol treatment as per prior BEST subanalyses. Incremental cost-effectiveness/cost-utility ratios (ICERs/ICURs) were estimated. Results: Race-based analyses for non-White subjects at 100% testing showed a loss of (0.04) life-years and (0.03) quality-adjusted life-years (QALYs) at an incremental cost of $2185, yielding a negative ICER of ($54,625)/life-year and ICUR of ($72,833)/QALY lost; at 50%, the analyses showed a loss of (0.27) life-years and (0.16) QALYs at an incremental cost of $1843, yielding a negative ICER of ($6826)/life-year and ICUR of ($11,519)/QALY lost; at 0%, the analyses showed a loss of (0.33) life-years and (0.30) QALYs at an incremental cost of $1459, yielding a negative ICER of ($4421)/life-year and ICUR of ($4863)/QALY lost. Arg389 homozygote analyses at 100% testing showed incremental gains of 0.02 life-years and 0.02 QALYs at an incremental cost of $378, yielding an ICER of 18,900/life-year and ICUR of $18,900/QALY gained; at 50%, the analyses showed a loss of (0.24) life-years and (0.09) QALYs at an incremental cost of $1039, yielding a negative ICER of ($4329)/life-year and ICUR of ($9336)/QALY lost; at 0%, the analyses showed a loss of (0.33) life-years and (0.30) QALYs at an incremental cost of $1459, yielding a negative ICER of ($4421)/life-year and ICUR of ($4863)/QALY lost. Conclusion: This independent ex ante economic evaluation suggests that genetically targeted treatment with bucindolol is unlikely to yield clinicoeconomic benefits over empirical treatment with carvedilol in NYHA III/IV HF. [ABSTRACT FROM AUTHOR]

Medications used for supportive care or prophylaxis constitute a significant portion of drug utilization in the intensive care unit. Evidence-based guidelines are available for many aspects of supportive care but drug doses listed are typically for patients with normal body habitus and not morbid obesity. Failure to account for the pharmacokinetic changes that occur with obesity can lead to an incorrect dose and treatment failure or toxicity. This paper is intended to help clinicians design initial dosing regimens in critically ill obese patients for medications commonly used for hemodynamic support or prophylaxis. A detailed literature search of medications used for supportive care or prophylaxis listed in practice guidelines was conducted with an emphasis on obesity, pharmacokinetics and dosing. Relevant manuscripts were reviewed and strategies for dosing are provided. For medications used for hemodynamic support, a similar strategy can be used as in non-obese patients. Similarly, medications for stress ulcer prophylaxis do not need to be adjusted. Anticoagulants for venous thromboembolism prophylaxis, on the other hand, require an individualized approach where higher doses are necessary. [ABSTRACT FROM AUTHOR]

Objective Macrolide antibiotics are among the most commonly used antibiotics; the association of macrolide antibiotics exposure with sensorineural hearing loss (SNHL) has been hypothesized. A systematic search was conducted in PubMed, EMBASE and Cochrane Library from inception to 15 July 2019 to identify studies used macrolide antibiotics for any indication. The results were reported as odds ratio (OR) with 95% confidence interval (CI) using random-effects model to derive the association of macrolide antibiotics exposure with SNHL. The objective of this meta-analysis was to estimate the association of macrolide antibiotics exposure and SNHL from up-to-date evidence. Key findings: Nine studies met the inclusion criteria. There was no statistically significant association between macrolide antibiotics exposure and SNHL; the OR was 1.20 (95% CI: 0.96 to 1.49). No significant association was found with any of the subgroup meta-analyses. Summary Whilst the frequency of SNHL was higher with macrolide antibiotics exposure compared with controls, overall, no association was found between macrolide antibiotics and SNHL. [ABSTRACT FROM AUTHOR]

Objectives: To discuss the evidence and caveats associated with estimated and measured creatinine clearance (eClCr and mClCr) and glomerular filtration rate (eGFR and mGFR) assessments of kidney function in patients with more extreme forms of obesity. Data Sources: PubMed (1976 to mid-May 2020) was used, with bibliographies of retrieved articles searched for additional articles. Study Selection and Data Extraction: Articles using gold standard mGFR to evaluate eClCr, mClCr, and eGFR assessments of kidney function in patients with more extreme forms of obesity were included. Data Synthesis: The overestimation of GFR by mClCr is well established, but mClCr is an alternative to mGFR assessments for determining medication dosing in patients with extremes of body size or muscle mass, or in patients receiving narrow therapeutic index medications when eGFR is likely to be inaccurate. The vast majority of studies comparing eGFR assessments with gold standard indicators of kidney function were attempts to validate eGFR equations for diagnosing and staging chronic kidney disease (CKD). Relevance to Patient Care and Clinical Practice: For dosing medications in patients with stable kidney function and extreme obesity, a deindexed 4-variable Modification of Diet in Renal Disease or CKD Epidemiology Collaboration equation is an alternative to Cockcroft-Gault. Consistent use of the same equation by provider and between providers within any given setting is of paramount importance. Conclusions: In patients with extreme obesity and stable kidney function, eClCr or eGFR using deindexed values provides estimates of function for dosing adjustments of medications with elimination by the kidneys, but more research is needed with respect to the best size descriptor to use with estimating equations. [ABSTRACT FROM AUTHOR]

Background: Inappropriate albumin use in clinical practice remains problematic. Health-systems face continued challenges in promoting cost-appropriate use. Objective: To evaluate the clinical and economic impact of a clinical pharmacist–led intervention strategy targeting inappropriate albumin use in general ward patients. Methods: A retrospective cohort study evaluated all adult (≥18 years) general ward patients administered ≥1 dose of albumin at a university medical center over a 2-year period. The intervention consisted of a clinical pharmacist–led strategy intervening on all albumin orders not in accordance with institutional guidelines. The primary end point was to compare inappropriate albumin utilization before and after implementation. Secondary end points compared the rates of inappropriate albumin use adjusted for hospital admission and patient-days as well as associated costs by appropriateness between study periods. Results: A total of 4420 patients were screened, with 1971 (44.6%) patients meeting inclusion criteria. The clinical pharmacist strategy significantly reduced inappropriate albumin (grams) utilization by 86.0% (P < 0.001). A 7-fold reduction of inappropriate albumin administered adjusted for the number of patient admissions was found from the preimplementation period following clinical pharmacist intervention strategy implementation (415.3 ± 83.2 vs 57.5 ± 34.2 g per 100 general ward hospital admissions, respectively; P < 0.001). Also, the adjusted inappropriate albumin rate was reduced from 62.2 ± 12.3 to 8.6 ± 5.2 g per 100 patient-days in the preimplementation and postimplementation periods, respectively (P < 0.001). Annual cost savings were $421 455 overall, with $341 930 resulting from mitigation of inappropriate use. Conclusion and Relevance: Clinical pharmacist–led interventions significantly reduced inappropriate albumin use and costs in hospitalized patients. [ABSTRACT FROM AUTHOR]

Critical drug shortages have been widely documented during the coronavirus disease 2019 (COVID-19) pandemic, particularly for IV sedatives used to facilitate mechanical ventilation. Surges in volume of patients requiring mechanical ventilation coupled with prolonged ventilator days and the high sedative dosing requirements observed quickly led to the depletion of "just-in-time" inventories typically maintained by institutions. This manuscript describes drug shortages in the context of global, manufacturing, regional and institutional perspectives in times of a worldwide crisis such as a pandemic. We describe etiologic factors that lead to drug shortages including issues related to supply (eg, manufacturing difficulties, supply chain breakdowns) and variables that influence demand (eg, volatile prescribing practices, anecdotal or low-level data, hoarding). In addition, we describe methods to mitigate drug shortages as well as conservation strategies for sedatives, analgesics and neuromuscular blockers that could readily be applied at the bedside. The COVID-19 pandemic has accentuated the need for a coordinated, multi-pronged approach to optimize medication availability as individual or unilateral efforts are unlikely to be successful. [ABSTRACT FROM AUTHOR]

The origins of pharmacy specialization has its beginning in the efforts of Harvey A. K. Whitney, Sr. through his leadership in establishing progressive hospital pharmacy services and hospital‐focused programs and policies within the nation's professional pharmacy organizations. Later, Donald Francke spoke of specialization in the hospital pharmacy setting as a natural outgrowth of practice activities that required more time and specialized expertise. A broader national discussion and eventual codification of specialty recognition and attendant certification within pharmacy began in 1971 with a policy statement approved by the APhA House of Delegates that led to the creation of a Task Force on Specialties in Pharmacy followed by the creation of the Board of Pharmaceutical Specialties (BPS). Given that specialization in any health profession is primarily a function of the reality of ever‐increasing scientific and technological developments, debate regarding the need, types, and value of specialization in pharmacy seem destined to be driven not by intra‐ or inter‐professional debates within pharmacy, but by the needs, expectations, and values of patients and health care systems. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this critical narrative review is to discuss the revised Starling equation for microvascular fluid exchange and the associated implications for intravenous fluid administration. Data Sources: PubMed (1946 to December 2019) and EMBASE (1947 to December 2019) were used, and bibliographies of retrieved articles were searched for additional articles. Study Selection and Data Extraction: Articles pertaining to the revised Starling equation and microvascular fluid exchange. Additionally, prospective human studies involving the disposition and oncotic action of radiolabeled albumin and large randomized trials comparing fluid requirements associated with isotonic crystalloid and albumin administration were included. Data Synthesis: In the revised Starling equation, oncotic forces act across the endothelial cell layer, more specifically between the fluid in the vessel lumen and the protein-sparse subglycocalyx space. The revised Starling equation and radiolabeled investigations of albumin necessitate a reconsideration of conventional views of the plasma-expanding properties of exogenous albumin. Large clinical trials demonstrate that the administration of iso-oncotic or hyper-oncotic albumin solutions in patients undergoing resuscitation does not have the reductions in fluid requirements anticipated from a traditional understanding of the oncotic actions of albumin. Relevance to Patient Care and Clinical Practice: When used as a resuscitation fluid, albumin does not have the degree of plasma expansion or intravascular retention commonly used to justify its use. Conclusions: The principles underlying the revised Starling equation in conjunction with data from radiolabeled studies of albumin and large clinical trials demonstrate that albumin does not have the perceived degree of plasma expansion or duration of intravascular retention beyond crystalloid solutions predicted by the classic Starling equation. [ABSTRACT FROM AUTHOR]

Practice guidelines provide clear evidence-based recommendations for the use of drug therapy to manage pain, agitation, and delirium associated with critical illness. Dosing recommendations however are often based on strategies used in patients with normal body habitus. Recommendations specific to critically ill patients with extreme obesity are lacking. Nonetheless, clinicians must craft dosing regimens for this population. This paper is intended to help clinicians design initial dosing regimens for medications commonly used in the management of pain, agitation, and delirium in critically ill patients with extreme obesity. A detailed literature search was conducted with an emphasis on obesity, pharmacokinetics, and dosing. Relevant manuscripts were reviewed and strategies for dosing are provided. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to compare the volume of fluid removal associated with and without 25% albumin administration in conjunction with hemodialysis. Methods: This retrospective, cohort study was conducted at a large academic medical center over a 6-month period to compare the net fluid amount removed (mL) during hemodialysis between patients administered 25% albumin and those without albumin. Results: A total of 238 patients consisting of 973 unique hemodialysis sessions were evaluated. The mean overall net fluid removed by hemodialysis in the 25% albumin and no albumin groups were 1242 mL and 1899 mL, P <.001, respectively. No albumin group had significantly higher mean fluid losses compared with 25% albumin for a total dose of either 25 g (P =.001) or 50 g (P =.001). There were no significant differences in mean fluid loss between the no albumin group and patients receiving 75 g or 100 g of albumin. Post hoc analysis failed to demonstrate a dose-dependent response in those patients receiving 25% albumin and no albumin. Conclusion: Hyperoncotic albumin administered during hemodialysis sessions reduced net fluid loss associated with hemodialysis. The findings of this study do not support the routine use of 25% albumin to improve fluid removal during dialysis. [ABSTRACT FROM AUTHOR]

Introduction: Nearly 2.5 million Americans have an opioid use disorder (OUD) related to prescription and/or illicit opioids. Pharmacists, as one of the most accessible care providers, are essential in mitigating the mortality and morbidity of the opioid overdose crisis. Pharmacists are involved in numerous care activities related to this crisis and to caring for patients with an OUD. Objective: The objective of this paper was to conduct a literature review to highlight several pharmacist‐driven practices that provide a broad range of prevention, harm reduction, treatment, and recovery services to patients affected or potentially affected by the opioid crisis. Methods: Articles had to meet the criteria of describing pharmacist‐led practice related to providing care to patients at risk of an opioid overdose, with an OUD, or related to opioid safety. The literature search was conducted in 2018 and utilized numerous sources including: OneSearch (EBSCOhost), PubMed, ScienceDirect, and the Journal of the American Pharmacists Association Opioid Topic Collection. Results: Seven articles were chosen for inclusion in this review. These studies report on innovative programs and practices that describe the role of pharmacists in the opioid crisis. Studies demonstrate the types of involvement pharmacists have in caring for patients throughout the care continuum: actively engaged in upstream interventions aimed at preventing misuse and improve safety; screening and monitoring opioid prescribing and usage; providing access to naloxone; and, assisting in the recovery and rehabilitation process of patients with OUD, including collaboratively managing OUD with evidence‐based pharmacotherapy. Conclusion: The studies included in our narrative review demonstrate how innovative programs and practices can expand the role of pharmacists throughout the entire spectrum of interventions applied to the opioid crisis by capitalizing on their existing skill sets and knowledge. [ABSTRACT FROM AUTHOR]