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Aims Methods Results Conclusions Using pharmacokinetics (PK)‐guided 5‐fluorouracil (5‐FU) for metastatic colorectal cancer (mCRC) improves overall survival (OS) and decreases toxicity, yet its value for money in the Australian setting is unknown. Our study assesses the cost‐effectiveness of PK vs. body surface area (BSA) dosing of 5‐FU for patients with mCRC.We developed a semi‐Markov model with four health states to compare PK‐guided dosing within a FOLFOX regimen vs. BSA‐guided dosing for mCRC patients from an Australian healthcare system perspective. Transition probabilities were derived from fitted survival models, with utility values obtained directly from published studies. We calculated direct healthcare costs, quality‐adjusted life years (QALYs) and incremental cost‐effectiveness ratios (ICERs), and included both one‐way and probabilistic sensitivity analyses.BSA‐guided FOLFOX provided 1.291 QALYs at a cost of $36 379, compared with PK‐guided FOLFOX which delivered 1.751 QALYs at a cost of $32 564. Therefore, PK‐guided dosing emerges as the dominant strategy offering both better health outcomes and lower costs. The variables that had the greatest impact on the overall ICER were the adverse event rates in the BSA and PK groups, model time horizon, utility of progression‐free survival and PREDICT assay cost. Our univariate and multivariate sensitivity analysis confirmed that the ICER for PK FOLFOX consistently remained below $50 000 per QALY across all tested variables.PK dose management of 5‐FU‐based chemotherapy in mCRC patients appears to be a cost‐saving strategy in Australia. However, our model estimates are drawn from limited, low‐quality evidence. Further evidence from randomized controlled trials (RCTs), directly comparing PK‐based to BSA‐based dosing across a variety of current regimens, is needed to address our model's uncertainties. [ABSTRACT FROM AUTHOR]

Objective: In this Mendelian randomization (MR) study, the objective was to investigate the causal effect of metabolically different adiposity subtypes on osteoarthritis. Methods: We performed 2‐sample MR using summary‐level data for osteoarthritis (10,083 cases and 40,425 controls) from a genome‐wide association using the UK Biobank, and for site‐specific osteoarthritis from the Arthritis Research UK Osteoarthritis Genetics consortium. We used 3 classes of genetic instruments, which all increase body mass index but are associated with different metabolic profiles (unfavorable, neutral, and favorable). Primary analysis was performed using inverse variance weight (IVW), with additional sensitivity analysis from different MR methods. We further applied a nonlinear MR using UK Biobank data to understand the nature of the adiposity–osteoarthritis relationship. Results: Greater metabolically unfavorable and metabolically neutral adiposity were associated with higher odds of osteoarthritis (IVW odds ratio [OR] 1.56 [95% confidence interval (95% CI) 1.31, 1.85] and OR 1.60 [95% CI 1.15, 2.23], respectively). The estimate for the association between metabolically favorable adiposity and osteoarthritis was similar, although with notable imprecision (OR 1.55 [95% CI 0.70, 3.41]). Using site‐specific osteoarthritis, metabolically unfavorable, neutral, and favorable adiposity were all associated with higher odds of knee osteoarthritis (OR 1.44 [95% CI 1.04, 1.98], OR 2.28 [95% CI 1.04, 4.99], and OR 6.80 [95% CI 2.08, 22.19], respectively). We found generally consistent estimates with a wider confidence interval crossing the null from other MR methods. The nonlinear MR analyses suggested a nonlinear relationship between metabolically unfavorable adiposity and osteoarthritis (Pnonlinear = 0.003). Conclusion: Metabolic abnormalities did not explain the association between greater adiposity and the risk of osteoarthritis, which might suggest that the association is largely due to a mechanical effect on the joints. [ABSTRACT FROM AUTHOR]

Aims: To systematically review the literature on (i) whether and how various risk messages about nicotine vaping products (NVPs) alter harm perception and behavioural intentions of smokers and non‐smokers and (ii) how trust in sources of NVP risk communication affects message reception and behavioural intentions. Methods: Seven electronic databases and reference lists of relevant articles were searched for articles published up to April 2020. Experimental and quasi‐experimental studies on message effects and cross‐sectional studies on source credibility were included. The Newcastle–Ottawa Scale and the Evidence Project Risk of Bias Tool were used to assess the quality of observational and intervention studies, respectively. For each outcome variable, we indicated whether there was an effect (as a 'yes' or 'no') and used effect direction plots to display information on the direction of effects. Results: Nicotine addiction messages resulted in greater health and addiction risk perceptions, relative risk messages comparing the health risks of NVPs to cigarette smoking increased the perception that NVPs are less harmful than combustible cigarettes, and a nicotine fact sheet corrected misperceptions of nicotine and NVPs. Smokers' intention to purchase, try or switch to NVPs was higher when exposed to a relative risk message and lower when exposed to nicotine addiction warnings. Trust in NVP risk information from public health agencies was associated with lower odds of; (i) NVP use and (ii) perceiving NVPs as less harmful, whereas those who trusted information from NVP companies were more likely to perceive NVPs as less harmful than combustible cigarettes. Conclusions: Relative risk messages may help improve the accuracy of harm perceptions of nicotine vaping products and increase smokers' intentions to quit smoking and/or to switch to vaping, although the literature is nascent. [ABSTRACT FROM AUTHOR]

COVID‐19 is one of the worst pandemics in recent human history, causing huge health, economic, and psychosocial damage. Since the pandemic hit, several unsubstantiated claims regarding exposure, transmission and management have been disseminated. Misinformation and associated public confusion now extend to the COVID‐19 vaccines, spanning from claims based on possible links between some vaccine types and rare blood clots, to baseless claims. As a result, the public's trust in COVID‐19 vaccines has been eroded, fuelling an already troubling trend of vaccine hesitancy. As medication experts and the most accessible healthcare providers, pharmacists are well equipped with the required skills and knowledge to improve COVID‐19 vaccine uptake by taking roles that range from dispelling myths, to providing reliable evidence‐based information, through to vaccine administration. This paper discusses public hesitancy to COVID‐19 vaccines, major contributing factors, and the role pharmacists can play in reducing hesitancy and increasing vaccine uptake. [ABSTRACT FROM AUTHOR]

Issues With the advancement and rapid increase in the public's interest in utilisation of Internet and mobile phones, technology‐based interventions are being implemented across a range of health conditions to improve patient outcomes. The aim of this review was to summarise findings from systematic reviews that evaluated the effectiveness of technology‐based smoking cessation interventions and to critically appraise their methodological qualities. Approach: An umbrella review was conducted using studies identified from a comprehensive literature search of six databases and grey literature. All included systematic reviews were checked for eligibility criteria and quality using the Assessment of Multiple Systematic Reviews tool. The level of evidence for each intervention category was assessed, citation matrices were generated and corrected covered area was calculated. Key Findings: Five systematic reviews with a total of 212 randomised controlled trials and 237 760 participants were included. Fourteen intervention approaches were identified and classified into three categories: stand‐alone web‐based; stand‐alone mobile phone‐based and multicomponent interventions. Incorporating web and/or mobile‐based interventions with face‐to‐face approach improved the rate of smoking cessation. However, there was no consistent evidence regarding the effectiveness of stand‐alone Internet or mobile‐based interventions. Implications: Policymakers are recommended to develop strategies that enable health professionals to integrate these approaches with face‐to‐face smoking cessation support. Health professionals are recommended to be trained and equipped for online and mobile‐based interventions. Conclusion: Adding technology‐based intervention to face‐to‐face smoking cessation support improves smoking cessation. Further research is needed to evaluate stand‐alone web‐based and mobile phone‐based interventions. [ABSTRACT FROM AUTHOR]

The standard approach for dose individualization of chemotherapy in the oncology setting has long been based on body surface area (BSA) as a measure of body size. However, for many anticancer drugs, administration of dosages based on BSA may result in some patients receiving supratherapeutic or subtherapeutic concentrations due to substantial interindividual pharmacokinetic variability. Therapeutic drug monitoring (TDM)–guided dosing aims to ensure that the patient's serum drug concentration is in a target range which has been shown to produce optimal clinical outcomes. The management of several malignancies is now moving away from using traditional intravenous chemotherapy to longer‐term treatment with targeted molecular therapies. These targeted anticancer drugs are currently dosed based on a fixed dose for all patients. The pharmacokinetic characteristics of most of these drugs (e.g., tyrosine‐kinase inhibitors) support implementation of individualized dosing via TDM. However, prior to adopting TDM–guided dosing in oncology settings, the economic efficiency and value for money of introducing TDM interventions should be critically and systematically examined along with the impacts on patient care and outcomes. Yet, current evidence in this area is limited, and more generally, there is lack of methodological guidance on how to identify, estimate and value clinical and cost information necessary to conduct economic evaluations of TDM interventions. In this paper, we propose a coherent framework for conducting economic evaluation of TDM interventions in oncology settings and discuss some practical challenges of conducting economic evaluations of TDM. [ABSTRACT FROM AUTHOR]

Introduction and Aims: Despite regulatory barriers for accessing nicotine liquid, use of nicotine vaping products (NVPs) has increased rapidly in Australia. Legal use of NVPs to aid smoking cessation requires a prescription, and pharmacies report receiving enquiries about the use of and access to NVPs. In this study, we assessed vaping product use, harm perception and policy support among community pharmacy customers.Design and Methods: A cross-sectional survey was conducted among customers (n = 470) from a large community pharmacy chain in Brisbane, Australia. Multivariable logistic regression was used to examine perception of NVPs as less harmful than combustible cigarettes and regulatory recommendations in relation to demographics, smoking status and NVP use.Results: Almost one-third of the sample (31%) had either tried NVPs in the past (16%) or were current vapers (15%), the majority of them being current smokers (67%) who are trying to quit (31%) or substitute smoking (41%). Vapers primarily depended on family/friends as a source of information (76%). Current smokers and vapers were more likely to perceive NVPs as less harmful than cigarettes than non-smokers and non-vapers. Perceiving NVPs as safer than cigarettes was correlated with a recommendation to regulate as a tobacco product.Discussion and Conclusions: There was widespread misperception about relative risk of nicotine-containing products, with 37% of respondents perceiving nicotine-containing NVPs to be as harmful as combustible cigarettes. Community pharmacies represent an ideal setting for educating smokers about smoking and vaping. Thus, pharmacy staff needs educational support to ensure that they are equipped to provide current evidence-based information to customers. [ABSTRACT FROM AUTHOR]

Most of the medications which are currently used for the treatment of childhood diseases are either not licensed or being prescribed outside the terms of the product license (off-label prescribing). This study aimed at determining the extent of unlicensed and off-label drug uses and associated factors in children hospitalized in Gondar University Referral Hospital, Northwest Ethiopia . An institution-based prospective cross-sectional study was employed from April 15 to July 15, 2016. A total of 243 pediatric patients admitted to Gondar university referral hospital were included in the study using simple random sampling method. Data were collected using structured questionnaire, and the data collected were entered and analyzed using Statistical Packages for Social Sciences ( SPSS) version 20. From the total of 800 drugs prescribed, 607 (75.8%) were off-label. Off-label medicine use was frequently observed in antimicrobials (60.6%) followed by central nervous system drugs (14.3%). The extent off-label prescribing was highest in age group of 6-13 years (30%). Inappropriate dosing and frequency (42.3%) were the most common reason for off-label medicine use. Having other variables controlled, age group and undergoing surgical procedure remained to be significant predictors of off-label prescribing in the multivariate regression analysis. Implementing evidence-based approach in prescribing by generating more quality literatures on the safety profile and effectiveness of off-label would improve the injudicious use of drugs in pediatric population. [ABSTRACT FROM AUTHOR]