Opioid analgesics for nociceptive cancer pain: A comprehensive review.

Pain is one of the most burdensome symptoms in people with cancer, and opioid analgesics are considered the mainstay of cancer pain management. For this review, the authors evaluated the efficacy and toxicities of opioid analgesics compared with placebo, other opioids, nonopioid analgesics, and nonpharmacologic treatments for background cancer pain (continuous and relatively constant pain present at rest), and breakthrough cancer pain (transient exacerbation of pain despite stable and adequately controlled background pain). They found a paucity of placebo-controlled trials for background cancer pain, although tapentadol or codeine may be more efficacious than placebo (moderate-certainty to low-certainty evidence). Nonsteroidal anti-inflammatory drugs including aspirin, piroxicam, diclofenac, ketorolac, and the antidepressant medicine imipramine, may be at least as efficacious as opioids for moderate-to-severe background cancer pain. For breakthrough cancer pain, oral transmucosal, buccal, sublingual, or intranasal fentanyl preparations were identified as more efficacious than placebo but were more commonly associated with toxicities, including constipation and nausea. Despite being recommended worldwide for the treatment of cancer pain, morphine was generally not superior to other opioids, nor did it have a more favorable toxicity profile. The interpretation of study results, however, was complicated by the heterogeneity in the study populations evaluated. Given the limited quality and quantity of research, there is a need to reappraise the clinical utility of opioids in people with cancer pain, particularly those who are not at the end of life, and to further explore the effects of opioids on immune system function and quality of life in these individuals.

Efficacy and safety of antidepressants for pain in older adults: A systematic review and meta-analysis.

AIMS: In many countries, pain is the most common indication for use of antidepressants in older adults. We reviewed the evidence from randomized controlled trials on the efficacy and safety of antidepressants, compared to all alternatives for pain in older adults (aged ≥65 years). METHODS: Trials published from inception to 1 February 2024, were retrieved from 13 databases. Two independent reviewers extracted data on study and participant characteristics, primary efficacy (pain scores, converted to 0-100 scale) and harms. Estimates for efficacy were pooled using a random effects model and reported as difference in means and 95% CI. Quality of included trials was assessed using the Cochrane risk of bias tool. RESULTS: Fifteen studies (n = 1369 participants) met the inclusion criteria. The most frequently studied antidepressants were duloxetine and amitriptyline (6/15 studies each). Pain related to knee osteoarthritis was the most studied (6/15 studies). For knee osteoarthritis, antidepressants did not provide a statistically significant effect for the immediate term (0-2 weeks), (-5.6, 95% confidence interval [CI]: -11.5 to 0.3), but duloxetine provided a statistically significant, albeit a very small effect in the intermediate term, (≥6 weeks and <12 months), (-9.1, 95% CI: -11.8 to -6.4). Almost half (7/15) of the studies reported increased withdrawal of participants in the antidepressant treatment group vs. the comparator group due to adverse events. CONCLUSIONS: For most chronic painful conditions, the benefits and harms of antidepressant medicines are unclear. This evidence is predominantly from trials with sample sizes of <100, have disclosed industry ties and classified as having unclear or high risk of bias.

Preventability of venous thromboembolism in hospitalised patients.

BACKGROUND: Hospital-acquired venous thromboembolism (VTE) is a major cause of morbidity and mortality. AIMS: To determine the proportion of patients with hospital-acquired VTE that are preventable. METHODS: This was a retrospective study of patients in two tertiary care hospitals in Sydney, Australia. Data were collected for patients with hospital-acquired VTE based on International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Australian Modification (ICD-10-AM) coding from January 2018 to May 2020. Patients were classified as low, moderate or high risk of developing a VTE during hospitalisation based on demographic and clinical factors. A hospital-acquired VTE was considered to be potentially preventable if there was suboptimal prophylaxis in the absence of contraindications. Suboptimal therapy included at least one of the following related to VTE prophylaxis: low dose, missed dose (prior to developing a VTE), suboptimal drug and delayed start (>24 h from admission). RESULTS: There were 229 patients identified with VTE based on ICD-10-AM coding. A subset of 135 patients were determined to have actual hospital-acquired VTE. Of these, there were no patients at low risk, 64% (87/135) at moderate risk and 44% (48/135) at high risk of developing a VTE. Most (65%; n = 88/135) patients had one or more contraindications to receive recommended prophylaxis. Overall, the proportion of patients who received suboptimal prophylaxis was 11% (15/135). CONCLUSION: Approximately one out of 10 hospital-acquired VTE are preventable. Hospitals should focus on measuring and reporting VTE that are preventable to provide a more accurate measure of the burden of VTE that can be reduced by improving care.

Dose equivalence between metaraminol and norepinephrine in critical care.

AIMS: The aim of this study was to determine the conversion dose ratio between continuous infusion metaraminol and norepinephrine in critically ill patients with shock. METHODS: A retrospective cohort study was conducted in adult patients with shock admitted to an intensive care unit from 29 October 2018 to 30 October 2019 and who transitioned from metaraminol monotherapy to norepinephrine monotherapy. Mean arterial pressure (MAP) and infusion doses for both drugs were collected at hourly intervals; 2 hours before to 5 hours after switching from metaraminol monotherapy to norepinephrine monotherapy. The conversion dose ratio was defined as the ratio of metaraminol (µg.kg-1 .min-1) : norepinephrine (µg.kg-1 .min-1 ) required to achieve a similar MAP. RESULTS: A total of 43 out of 144 eligible patients were included. The median age was 68 years (IQR 56-76) and 22 (51%) were male. There was no significant difference between the baseline MAP during metaraminol monotherapy (median 71 mm Hg, IQR 66-76) and the post-transition MAP during norepinephrine monotherapy (median 70 mm Hg, IQR 66-73) (P = .09). The median conversion dose ratio between metaraminol and norepinephrine was 13 (IQR 7-24). In the sensitivity analyses, the median conversion dose ratio using the maximum and the mean norepinephrine infusion dose was 8 (IQR 5-16) and 12 (IQR 8-23), respectively. CONCLUSION: A conversion dose ratio of 10:1 (metaraminol µg.kg-1 .min-1 :norepinephrine µg.kg-1 .min-1 ) may be used in critically ill patients with shock to account for ease of calculations and variability of the conversion ratio in the primary and sensitivity analyses.

Predictive Performance of Bayesian Vancomycin Monitoring in the Critically Ill.

OBJECTIVES: It is recommended that therapeutic monitoring of vancomycin should be guided by 24-hour area under the curve concentration. This can be done via Bayesian models in dose-optimization software. However, before these models can be incorporated into clinical practice in the critically ill, their predictive performance needs to be evaluated. This study assesses the predictive performance of Bayesian models for vancomycin in the critically ill. DESIGN: Retrospective cohort study. SETTING: Single-center ICU. PATIENTS: Data were obtained for all patients in the ICU between 1 January, and 31 May 2020, who received IV vancomycin. The predictive performance of three Bayesian models were evaluated based on their availability in commercially available software. Predictive performance was assessed via bias and precision. Bias was measured as the mean difference between observed and predicted vancomycin concentrations. Precision was measured as the sd of bias, root mean square error, and 95% limits of agreement based on Bland-Altman plots. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 466 concentrations from 188 patients were used to evaluate the three models. All models showed low bias (-1.7 to 1.8 mg/L), which was lower with a posteriori estimate (-0.7 to 1.8 mg/L). However, all three models showed low precision in terms of sd (4.7-8.8 mg/L) and root mean square error (4.8-8.9 mg/L). The models underpredicted at higher observed vancomycin concentrations (bias 0.7-3.2 mg/L for < 20 mg/L; -5.1 to -2.3 for ≥ 20 mg/L) and the Bland-Altman plots showed a great deviation between observed and predicted concentrations. CONCLUSIONS: Bayesian models of vancomycin show not only low bias, but also low precision in the critically ill. Thus, Bayesian-guided dosing of vancomycin in this population should be used cautiously.

Cannabinoids for drug-resistant seizures in a critically ill patient-Case report and literature review.

WHAT IS KNOWN AND OBJECTIVE: Drug-resistant seizures are life-threatening and contribute to sustained hospitalization. We present the case of a critically ill 28-year-old male with Lennox-Gastaut syndrome who had approximately 30 seizures/day in the intensive care unit. CASE DESCRIPTION: Patient required mechanical ventilation and pharmacologically induced thiopentone coma. He was commenced on cannabidiol and subsequently extubated. He remained seizure-free thereafter on a combination of cannabidiol and anti-epileptic medication that predated his critical illness. WHAT IS NEW AND CONCLUSION: Our case report provides a unique perspective on the role of cannabidiol in achieving remission from drug-resistant seizures in critically ill patients.

Anticholinergic medicines use among older adults before and after initiating dementia medicines.

AIMS: We investigated anticholinergic medicines use among older adults initiating dementia medicines. METHODS: We used Pharmaceutical Benefits Scheme dispensing claims to identify patients who initiated donepezil, rivastigmine, galantamine or memantine between 1 January 2013 and 30 June 2017 (after a period of ≥180 days with no dispensing of these medicines) and remained on therapy for ≥180 days (n = 4393), and dispensed anticholinergic medicines in the 180 days before and after initiating dementia medicines. We further examined anticholinergic medicines prescribed by a prescriber other than the one initiating dementia medicines. RESULTS: One-third of the study cohort (1439/4393) was exposed to anticholinergic medicines up to 180 days before or after initiating dementia medicines. Among patients exposed to anticholinergic medicines, 46% (659/1439) had the same medicine dispensed before and after initiating dementia medicines. The proportion of patients dispensed anticholinergic medicines increased by 2.5% (95% confidence interval [CI]: 1.3-3.7) after initiating dementia medicines. Antipsychotics use increased by 10.1% (95% CI: 7.6-12.7) after initiating dementia medicines; driven by increased risperidone use (7.3%, 95% CI: 5.3-9.3). Nearly half of patients dispensed anticholinergic medicines in the 180 days after (537/1133), were prescribed anticholinergic medicines by a prescriber other than the one initiating dementia medicines. CONCLUSION: Use of anticholinergic medicines is common among patients initiating dementia medicines and this occurs against a backdrop of widespread campaigns to reduce irrational medicine combinations in this vulnerable population. Decisions about deprescribing medicines with questionable benefit among patients with dementia may be complicated by conflicting recommendations in prescribing guidelines.

Anticipating the effects of restricting high-dose preparations of strong opioids in Australia: A population-based analysis to inform the current policy debate.

PURPOSE: Countries worldwide are developing a variety of strategies to combat the opioid epidemic, such as restricting access to high-strength opioid formulations. We aimed to examine the dispensing patterns of strong opioids by dose units (DUs), age, and sex. METHODS: We used Australian population-level dispensing data from January 2003 to December 2015 and categorised strong opioids by DU: very low, low, moderate, and high, corresponding to total daily doses of less than or equal to 25, 26 to 50, 51 to 100, and greater than 100 morphine milligramme equivalents, respectively. We measured trends in strong opioid use as dispensings/1000 population/year and stratified dispensing in 2015 by patient age and sex. RESULTS: From 2003 to 2015, strong opioid dispensing of very low, low, moderate, and high DU increased 6.7-, 6.2-, 2.2-, and 1.8-fold, respectively. The increase in very low and low DU dispensing was driven primarily by oxycodone (5, 10, and 15 mg tablets and capsules) and buprenorphine transdermal patches. In 2015, the number of dispensings/1000 population for very low, low, moderate, and high DU were 180.3, 77.0, 52.7, and 34.8, respectively. Females aged greater than or equal to 85 years had the highest opioid use, ranging from 157.1 dispensings/1000 population for high DU to 2104.5 dispensings/1000 population for very low DU. In contrast, the high DU dispensings in males aged 25 to 64 years exceeded their female counterparts by approximately 1.3-fold. CONCLUSION: Relative to moderate and high DU strong opioids, dispensing of very low and low DU strong opioids increased dramatically during the study period in Australia. Future studies investigating opioids use and harms in elderly females and males between 25 to 64 years are warranted.

Potentially inappropriate medications in community-dwelling older adults undertaken as a comprehensive geriatric risk assessment.

PURPOSE: The prescription of potentially inappropriate medications (PIMs) is associated with an increase in adverse events, prescribing cascades, high health-care costs, morbidity, and mortality in the elderly. The overarching objective of this study is to examine the prevalence of PIMs in the elderly, applying the 2012 American Geriatrics Society Beers criteria for the study period 2012-2014, and the updated 2015 Beers criteria for 2015. METHODS: The study population (N = 70,479) included a continuously recruited national cohort of community-dwelling older (aged ≥ 65 years) New Zealanders who had undertaken the International Resident Assessment Instrument-Home Care (interRAI-HC) assessments between September 2012 and October 2015. Exposure of PIMs 90 days before and after assessment, and 90-180 days after assessment are reported. RESULTS: Exposure to PIMs was highest in individuals aged over 95 years and in males. The average number of PIMs prescribed 90 days before assessment during the period 2015 was marginally higher compared to 2012-2014 (0.19 versus 0.04), and a greater number of individuals were exposed to one or more PIMs in 2015 compared to 2012-2014 (7.13 versus 2.17%). The prevalence of PIMs 90 days before and after assessment was 2.17 and 6.92% for 2012-2014, and 7.13 and 24.7% for 2015, respectively. The percent change in PIMs in 2012-2014 and 2015 after 90 days of assessment were 4.70% (confidence interval (CI) 4.50%, 5.00%, p < 0.001) and 17.60% (95% CI 16.80%, 18.30%, p < 0.001), respectively. The majority of PIMs prescribed belonged to the therapeutic class of medications acting on the central nervous system and the gastrointestinal system. CONCLUSION: Geriatric risk assessments may provide a vital opportunity to review medication lists by multidisciplinary teams with a view to reducing PIMs and unnecessary polypharmacy in older adults. Comprehensive geriatric risk assessment has the potential to reduce adverse medication outcomes and costs associated with inappropriate prescribing in a vulnerable population of older adults.

Evaluation of the National Minimum Data Set for Neurological Conditions in Older Adults.

AIM: To evaluate the National Minimum Data Set (NMDS) against the International Resident Assessment Instrument-Home Care (interRAI-HC) in diagnosing dementia or Parkinson disease (PD). METHOD: The NMDS data were matched with interRAI-HC for all older individuals in New Zealand. Dementia or PD was compared within 90 and 180 days and 1 to 4 years preceding and subsequent to the date of diagnosis in interRAI-HC. Consistency was measured through sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), weighted kappa (κ), and McNemar test. RESULTS: For a diagnosis within 90 days, dementia showed 60.77% sensitivity, 95.33% specificity, 68.46% PPV, and 93.58% NPV. The PD showed 65.74% sensitivity, 99.52% specificity, 80.43% PPV, and 98.98% NPV. κ for dementia (κ = 0.59), PD (κ = 0.720), and McNemar test was significant ( P < .001) for all lengths of follow-up. CONCLUSION: Substantial agreement between multiple sources of health data can be a valuable resource for decision-making in older people with neurological conditions.

Development and validation of a Medicines Comorbidity Index for older people.

PURPOSE: An index for estimating multimorbidity based on prescription claims data is important for predicting health outcomes for older people in pharmacoepidemiological studies. We aimed to develop a Medicines Comorbidity Index (MCI) based on nationwide prescription claims data and evaluate its performance in predicting adverse outcomes in older individuals. METHODS: The index was developed on a retrospective cohort comprising of all individuals aged ≥ 65 years old, captured in the claims dataset from 1st January to 31st December 2012. The cohort was followed for 1 year to identify an event of hospitalisation or mortality. A list of medications for 20 comorbidities based on the Chronic Disease Score framework was collated. Predictive performance of the MCI was evaluated against the Charlson Comorbidity Index (CCI) using measures of discrimination (Receiver Operating Characteristic curves), sensitivity and specificity (c-statistic) and calibration (Brier scores) for regression models. RESULTS: The MCI was validated for an outcome of mortality (n = 161,461) and hospitalisation (n = 149,729). For mortality, MCI had a marginally lower c-statistic in comparison to CCI (0.70, 95% CI 0.70-0.71 vs 0.72, 95% CI 0.71-0.72 at p < 0.05) with Brier scores of 0.07 at p < 0.05. For hospitalisation, the Hazard Ratio was higher with MCI (1.08, 95% CI 1.08-1.08, p < 0.001) compared to CCI (0.92, 95% CI 0.91-0.92, p < 0.001). CONCLUSION: Initial testing indicates that the MCI is a valid and appropriate tool for measuring multimorbidity and predicting health outcomes for older individuals, and can be an important index for adjusting comorbidity in pharmacoepidemiological studies.

Associations of drug burden index with falls, general practitioner visits, and mortality in older people.

AIM: On a population level in people aged ≥65 years old living in New Zealand, the aim of this study is to quantify each individual's cumulative exposure to anticholinergic and sedative medicines using the Drug Burden Index (DBI) and examine the impact of DBI on fall-related hospitalisations, general practitioner (GP) visits, and all-cause mortality. METHOD: The study used data extracted from Pharmaceutical Claims Data Mart (2011), National Minimum Data set (2012), Births, Death and Marriages (2012) and GP Visits (2012) for patient demographics, hospitalisations and mortality. Cumulative anticholinergic and sedative exposure was measured using the DBI. Polypharmacy was defined as greater than or equal to five medicines dispensed concurrently at any time during the study period. RESULTS: Amongst the study population (n = 537,387; 45% male), 43.22% were exposed to DBI drugs (95% confidence intervals (CIs) = 43.09-43.35). The odds of DBI exposure for individuals with polypharmacy are 4.92 (95%CI = 4.86-4.98) times greater than that for individuals without polypharmacy. DBI drugs were associated with fall-related hospitalisations (incidence rate ratio (IRR) 1.56, 95%CI = 1.47-1.65) and greater number of GP visits (IRR 1.13, 95%CI = 1.12-1.13). Individuals with DBI > 0 had a 1.29 times higher mortality risk (95%CI = 1.25-1.33). Polypharmacy is also associated with a higher mortality risk with a hazard ratio (HR) of 1.66 (95%CI = 1.59-1.73). CONCLUSION: Polypharmacy and exposure to DBI drugs were independently associated with fall-related hospitalisations, frequency of GP visits, and risk of mortality. On a population level, DBI may be useful as a quality indicator to guide policy to improve prescribing and optimize clinical outcomes in older people.

Persistent postoperative opioid use after total hip or knee arthroplasty: A systematic review and meta-analysis.

PURPOSE: To identify the proportion of patients with continued opioid use after total hip or knee arthroplasty. METHODS: This systematic review and meta-analysis searched Embase, MEDLINE, the Cochrane Central Register of Controlled Trials, and International Pharmaceutical Abstracts for articles published from January 1, 2009, to May 26, 2021. The search terms (opioid, postoperative, hospital discharge, total hip or knee arthroplasty, and treatment duration) were based on 5 key concepts. We included studies of adults who underwent total hip or knee arthroplasty, with at least 3 months postoperative follow-up. RESULTS: There were 30 studies included. Of these, 17 reported on outcomes of total hip arthroplasty and 19 reported on outcomes of total knee arthroplasty, with some reporting on outcomes of both procedures. In patients having total hip arthroplasty, rates of postoperative opioid use at various time points were as follows: at 3 months, 20% (95% CI, 13%-26%); at 6 months, 17% (95% CI, 12%-21%); at 9 months, 19% (95% CI, 13%-24%); and at 12 months, 16% (95% CI, 15%-16%). In patients who underwent total knee arthroplasty, rates of postoperative opioid use were as follows: at 3 months, 26% (95% CI, 19%-33%); at 6 months, 20% (95% CI, 17%-24%); at 9 months, 23% (95% CI, 17%-28%); and at 12 months, 21% (95% CI, 12%-29%). Opioid naïve patients were less likely to have continued postoperative opioid use than those who were opioid tolerant preoperatively. CONCLUSION: Over 1 in 5 patients continued opioid use for longer than 3 months after total hip or knee arthroplasty. Clinicians should be aware of this trajectory of opioid consumption after surgery.

Gastrointestinal Adverse Events in Hospitalized Patients Following Orthopedic Surgery: Tapentadol Immediate Release Versus Oxycodone Immediate Release.

BACKGROUND: Tapentadol has relatively less effect on mu-opioid receptors compared with other opioids. This has the potential to reduce the occurrence of gastrointestinal (GI) adverse drug events (ADEs). OBJECTIVES: To compare the GI ADEs during hospitalization between tapentadol immediate release (IR) and oxycodone IR following orthopedic surgeries. STUDY DESIGN: Retrospective cohort study. SETTING: A major metropolitan tertiary referral hospital in Australia. METHODS: Data for adult orthopedic surgery patients receiving postoperative tapentadol IR or oxycodone IR during hospitalization between January 1, 2018 and June 30, 2019, were collected from electronic medical records. The primary outcome was the occurrence of postoperative GI ADEs occurring during hospitalization. This was defined as a composite of nausea, vomiting, or constipation. RESULTS: The study cohort included 199 patients. Of these, 99 patients received tapentadol IR and 100 patients received oxycodone IR for postoperative pain during hospitalization. The mean age was 66 ± 12 years, and 111 patients (56%) were women. There was no significant difference between groups on the occurrence of GI ADEs (53% in oxycodone group and 51% in tapentadol group, difference 2%, 95% confidence interval [CI], -11% to 16%; P = 0.777). After adjusting for potential confounders, the use of tapentadol IR was not associated with a significant reduction of GI ADEs (odds ratio, 0.62; 95% CI, 0.32-1.20; P = 0.154). LIMITATIONS: This was a single-center study and should be extrapolated with caution. As this was a retrospective study, the accuracy and availability of data were dependent on documentation in electronic medical records. CONCLUSIONS: Tapentadol IR is associated with similar GI ADE occurrence compared with oxycodone IR in patients with orthopedic postoperative pain during hospitalization.

Comparison of opioid prescribing upon hospital discharge in patients receiving tapentadol versus oxycodone following orthopaedic surgery.

Background The changing of opioids during the transition of care from hospital to home may be associated with harm. Objective To compare patients receiving tapentadol IR versus oxycodone IR following orthopaedic surgery during hospitalisation with regard to the changing of opioids at hospital discharge. Setting A major metropolitan tertiary referral hospital in Australia. Methods This is a retrospective cohort study. Participants included adult orthopaedic surgery patients receiving postoperative tapentadol IR or oxycodone IR during hospitalisation between 1 January 2018 and 30 June 2019. Main outcome measure The proportion of patients for whom the opioid prescribed was changed at hospital discharge. Results The study cohort included 199 patients. Of these, 100 patients received oxycodone and 99 patients received tapentadol post-operatively during hospitalisation. The mean age was 66 years (SD, 12 years) and 111 (56%) were female. The most common surgeries were total knee arthroplasty (91, 46%), total hip arthroplasty (63, 32%) and shoulder surgery (26, 13%). Patients in the tapentadol group were more likely to be changed to a different opioid upon hospital discharge than the oxycodone group (57% versus 9%, difference 48% [95% CI 36-59%, p < 0.01). After adjusting for confounders, post-operative tapentadol use was more likely to be associated with opioid changing upon discharge (OR 16.5, 95% CI 6.7 to 40.8, p < 0.01). Conclusions The post-operative use of tapentadol IR during hospitalisation was associated with an increased likelihood of opioid changing at hospital discharge. This practice could have patient safety implications.

Vasopressor dose equivalence: A scoping review and suggested formula.

PURPOSE: Calculating equipotent doses between vasopressor agents is necessary in clinical practice and research pertaining to the management of shock. This scoping review summarizes conversion ratios between vasopressors and provides a formula to incorporate into study designs. MATERIALS AND METHODS: Medline, Embase and Web of Science databases were searched from inception to 21st October 2020. Additional papers were obtained through bibliography searches of retrieved articles. Two investigators assessed articles for eligibility. Clinical trials comparing the potency of at least two intravenous vasopressors (norepinephrine, epinephrine, dopamine, phenylephrine, vasopressin, metaraminol or angiotensin II), with regard to an outcome of blood pressure, were selected. RESULTS: Of 16,315 articles, 21 were included for synthesis. The range of conversion ratios equivalent to one unit of norepinephrine were: epinephrine (0.7-1.4), dopamine (75.2-144.4), metaraminol (8.3), phenylephrine (1.1-16.3), vasopressin (0.3-0.4) and angiotensin II (0.07-0.13). The following formula may be considered for the calculation of norepinephrine equivalents (NE) (all in mcg/kg/min, except vasopressin in units/min): NE = norepinephrine + epinephrine + phenylephrine/10 + dopamine/100 + metaraminol/8 + vasopressin*2.5 + angiotensin II*10. CONCLUSION: A summary of equipotent ratios for common vasopressors used in clinical practice has been provided. Our formula may be considered to calculate NE for studies in the intensive care unit.

Proposed guidance on cost-avoidance studies in pharmacy practice.

PURPOSE: Cost-avoidance studies of pharmacist interventions are common and often the first type of study conducted by investigators to quantify the economic impact of clinical pharmacy services. The purpose of this primer is to provide guidance for conducting cost-avoidance studies pertaining to clinical pharmacy practice. SUMMARY: Cost-avoidance studies represent a paradigm conceptually different from traditional pharmacoeconomic analysis. A cost-avoidance study reports on cost savings from a given intervention, where the savings is estimated based on a counterfactual scenario. Investigators need to determine what specifically would have happened to the patient if the intervention did not occur. This assessment can be fundamentally flawed, depending on underlying assumptions regarding the pharmacists' action and the patient trajectory. It requires careful identification of the potential consequence of nonaction, as well as probability and cost assessment. Given the uncertainty of assumptions, sensitivity analyses should be performed. A step-by-step methodology, formula for calculations, and best practice guidance is provided. CONCLUSIONS: Cost-avoidance studies focused on pharmacist interventions should be considered low-level evidence. These studies are acceptable to provide pilot data for the planning of future clinical trials. The guidance provided in this article should be followed to improve the quality and validity of such investigations.

Methods used to attribute costs avoided from pharmacist interventions in acute care: A scoping review.

PURPOSE: Cost-avoidance studies are common in pharmacy practice literature. This scoping review summarizes, critiques, and identifies current limitations of the methods that have been used to determine cost avoidance associated with pharmacists' interventions in acute care settings. METHODS: An Embase and MEDLINE search was conducted to identify studies that estimated cost avoidance from pharmacist interventions in acute care settings. We included studies with human participants and articles published in English from July 2010 to January 2021, with the intent of summarizing the evidence most relevant to contemporary practice. RESULTS: The database search retrieved 129 articles, of which 39 were included. Among these publications, less than half (18 of 39) mentioned whether the researchers assigned a probability for the occurrence of a harmful consequence in the absence of an intervention; thus, a 100% probability of a harmful consequence was assumed. Eleven of the 39 articles identified the specific harm that would occur in the absence of intervention. No clear methods of estimating cost avoidance could be identified for 7 studies. Among all 39 included articles, only 1 attributed both a probability to the potential harm and identified the cost specific to that harm. CONCLUSION: Cost-avoidance studies of pharmacists' interventions in acute care settings over the last decade have common flaws and provide estimates that are likely to be inflated. There is a need for guidance on consistent methodology for such investigations for reporting of results and to confirm the validity of their economic implications.

Effect of mannitol plus hypertonic saline combination versus hypertonic saline monotherapy on acute kidney injury after traumatic brain injury.

PURPOSE: To compare the effect of mannitol plus hypertonic saline combination (MHS) versus hypertonic saline monotherapy (HS) on renal function in patients with traumatic brain injury (TBI). MATERIALS AND METHODS: This was a secondary analysis of data from the Resuscitation Outcomes Consortium Hypertonic Saline Trial Shock Study and Traumatic Brain Injury Study. The study cohort included a propensity matched subset of patients with TBI who received MHS or HS. The primary outcome measure was the maximum serum creatinine value during critical illness. RESULTS: The cohort consisted of 163 patients in the MHS group and 163 patients in the HS group (n = 326). The maximum serum creatinine value during hospitalization was 82 ± 47 µmol/L (0.86 ± 0.26 mg/dL) in the MHS group and 76 ± 23 µmol/L (0.92 ± 0.53 mg/dL) in the HS group (difference -6 µmol/L, 95% CI -14 to 2 µmol/L, p = .151). The lowest eGFR during hospitalization was 108 ± 25 mL/min in the MHS group and 112 ± 24 mL/min in the HS group (difference -4 mL/min, 95% CI -1 to 9 mLmin, p = .150). CONCLUSIONS: The addition of mannitol to HS did not increase the risk of renal dysfunction compared to HS alone in patients with TBI.