Antimicrobial stewardship: Prescribing across the primary care health professions.

We examined the patterns of antibiotic prescribing by medical and non-medical prescribers (dentists, nurse practitioners, and midwives) in Australia. We explored trends in the dispensed use of antibiotics (scripts and defined daily dose [DDD] per 1000 population/day) by Australian prescribers over the 12-year period, 2005-2016. We obtained data on dispensed prescriptions of antibiotics from registered health professionals subsidized on the Pharmaceutical Benefits Scheme (PBS). There were 216.2 million medical and 7.1 million non-medical dispensed prescriptions for antibiotics over 12 years. The top four antibiotics for medical prescribers were doxycycline; amoxicillin, amoxicillin plus clavulanic acid, and cefalexin, constituting 80% of top 10 use in 2005 and 2016; the top three for non-medical were amoxicillin, amoxicillin plus clavulanic acid and metronidazole (84% of top 10 use in 2016). The proportional increase in antibiotic use was higher for non-medical than medical prescribers. While medical prescribers preferentially prescribed broad-spectrum and non-medical prescribers moderate-spectrum antibiotics, there was a large increase in the use of broad-spectrum antibiotics over time by all prescribers. One in four medical prescriptions were repeats. Overprescribing of broad-spectrum antibiotics conflicts with national antimicrobial stewardship initiatives and guidelines. The proportional higher increase in antibiotic use by non-medical prescribers is a concern. To reduce inappropriate use of antibiotics and antimicrobial resistance, educational strategies targeted at all medical and non-medical prescribers are needed to align prescribing with current best practice within the scope of practice of respective prescribers.

Evaluation of the Prescribing Skills Assessment implementation, performance and medical student experience in Australia and New Zealand.

AIMS: The UK Prescribing Safety Assessment was modified for use in Australia and New Zealand (ANZ) as the Prescribing Skills Assessment (PSA). We investigated the implementation, student performance and acceptability of the ANZ PSA for final-year medical students. METHODS: This study used a mixed-method approach involving student data (n = 6440) for 2017-2019 (PSA overall score and 8 domain subscores). Data were also aggregated by medical school and included student evaluation survey results. Quantitative data were analysed using descriptive and multivariate analyses. The pass rate was established by a modified Angoff method. Thematic analyses of open-ended survey comments were conducted. RESULTS: The average pass rate was slightly higher in 2017 (89%) which used a different examination to 2018 (85%) and 2019 (86%). Little difference was identified between schools for the PSA overall performance or domain subscores. There was low intercorrelation between subscores. Most students provided positive feedback about the PSA regarding the interface and clarity of questions, but an average of 35% reported insufficient time for completion. Further, 70% on average felt unprepared by their school curricula for the PSA, which is in part explained by the low prescribing experience; 69% reported completing ≤10 prescriptions during training. CONCLUSION: The ANZ PSA was associated with high pass rates and acceptability, although student preparedness was highlighted as a concern for further investigation. We demonstrate how a collaboration of medical schools can adapt a medical education assessment resource (UK PSA) as a means for fulfilling an unmet need.

Nurse practitioner and midwife antibiotic prescribing in Australia.

INTRODUCTION: Antimicrobial resistance is of global significance. To reduce the risk of harm associated with antibiotic prescribing in Australia, a recent strategy to tackle antimicrobial resistance has included non-medical prescribers. Traditionally, antibiotic prescribing has been the domain of the medical profession but, more recently, nurse practitioners and endorsed midwives have been authorized to prescribe antibiotics. This study describes the antibiotic prescribing practices by nurse practitioners and endorsed midwives in Australia, with clinical implications for international settings. METHODS: This was a retrospective analysis of routinely collected aggregated data of anonymous individuals. Data on dispensed prescriptions of antibiotics were obtained from the Australian Department of Human Services, for the period 2005-2016. All antibiotics were allocated to a spectrum class (narrow, moderate, broad). Analysis using descriptive statistics was undertaken to determine the antibiotic prescribing patterns of nurse practitioners and endorsed midwives. RESULTS: Nurse practitioners have been prescribing within Australia since 2000, and midwives since 2012. Nurse practitioner antibiotic written scripts increased from 3143 during 2005-2011 to 34615 in 2012-2016, while antibiotic written scripts by midwives increased from 2012 (n=2) to 2016 (n=469). Nurse practitioners and midwives prescribed similar classes of antibiotics. These professionals are important non-medical prescribers and are increasingly writing antibiotic prescriptions.Both nursing and midwifery cohorts complete accredited education programs, albeit with some differences in structure. CONCLUSIONS: When prescribing antibiotics, nurse practitioners and midwives are following evidenced-based therapeutic guidelines. They are increasingly relevant clinicians prescribing antibiotics, particularly in acute and primary care settings, which has relevance in global antimicrobial strategies.

Homeopathic medicinal products for preventing and treating acute respiratory tract infections in children.

BACKGROUND: Acute respiratory tract infections (ARTIs) are common and may lead to complications. Most children experience between three and six ARTIs annually. Although most infections are self-limiting, symptoms can be distressing. Many treatments are used to control symptoms and shorten illness duration. Most treatments have minimal benefit and may lead to adverse events. Oral homeopathic medicinal products could play a role in childhood ARTI management if evidence for their effectiveness is established. This is an update of a review first published in 2018. OBJECTIVES: To assess the effectiveness and safety of oral homeopathic medicinal products compared with placebo or conventional therapy to prevent and treat ARTIs in children. SEARCH METHODS: We searched CENTRAL (2022, Issue 3), including the Cochrane Acute Respiratory Infections Specialised Register, MEDLINE (1946 to 16 March 2022), Embase (2010 to 16 March 2022), CINAHL (1981 to 16 March 2022), AMED (1985 to 16 March 2022), CAMbase (searched 16 March 2022), and British Homeopathic Library (searched 26 June 2013 - no longer operating). We also searched the WHO ICTRP and ClinicalTrials.gov (16 March 2022), checked references, and contacted study authors to identify additional studies. SELECTION CRITERIA: We included double-blind randomised controlled trials (RCTs) or double-blind cluster-RCTs comparing oral homeopathy medicinal products with identical placebo or self-selected conventional treatments to prevent or treat ARTIs in children aged 0 to 16 years. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: In this 2022 update, we identified three new RCTs involving 251 children, for a total of 11 included RCTs with 1813 children receiving oral homeopathic medicinal products or a control treatment (placebo or conventional treatment) for ARTIs. All studies focused on upper respiratory tract infections (URTIs), with only one study including some lower respiratory tract infections (LRTIs). Six treatment studies examined the effect on URTI recovery, and five studies investigated the effect on preventing URTIs after one to four months of treatment. Two treatment and three prevention studies involved homeopaths individualising treatment. The other studies used predetermined, non-individualised treatments. All studies involved highly diluted homeopathic medicinal products, with dilutions ranging from 1 x 10-4 to 1 x 10-200. We identified several limitations to the included studies, in particular methodological inconsistencies and high attrition rates, failure to conduct intention-to-treat analysis, selective reporting, and apparent protocol deviations. We assessed three studies as at high risk of bias in at least one domain, and many studies had additional domains with unclear risk of bias. Four studies received funding from homeopathy manufacturers; one study support from a non-government organisation; two studies government support; one study was co-sponsored by a university; and three studies did not report funding support. Methodological inconsistencies and significant clinical and statistical heterogeneity precluded robust quantitative meta-analysis. Only four outcomes were common to more than one study and could be combined for analysis. Odds ratios (OR) were generally small with wide confidence intervals (CI), and the contributing studies found conflicting effects, so there was little certainty that the efficacy of the intervention could be ascertained. All studies assessed as at low risk of bias showed no benefit from oral homeopathic medicinal products, whilst trials at unclear or high risk of bias reported beneficial effects. For the comparison of individualised homeopathy versus placebo or usual care for the prevention of ARTIs, two trials reported on disease severity; due to heterogeneity the data were not combined, but neither study demonstrated a clinically significant difference. We combined data from two trials for the outcome need for antibiotics (OR 0.79, 95% CI 0.35 to 1.76; low-certainty evidence). For the comparison of non-individualised homeopathy versus placebo or usual care for the prevention of ARTIs, only the outcome recurrence of ARTI was reported by more than one trial; data from three studies were combined for this outcome (OR 0.60, 95% CI 0.21 to 1.72; low-certainty evidence). For the comparison of both individualised and non-individualised homeopathy versus placebo or usual care for the treatment of ARTIs, two studies provided data on short-term cure (OR 1.31, 95% CI 0.09 to 19.54) and long-term cure (OR 1.01, 95% CI 0.10 to 9.96; very low-certainty evidence). The studies demonstrated an opposite direction of effect for both outcomes. Six studies reported on disease severity but were not combined as they used different scoring systems and scales. Three studies reported adverse events (OR 0.79, 95% CI 0.16 to 4.03; low-certainty evidence). AUTHORS' CONCLUSIONS: Pooling of five prevention and six treatment studies did not show any consistent benefit of homeopathic medicinal products compared to placebo on ARTI recurrence or cure rates in children. We assessed the certainty of the evidence as low to very low for the majority of outcomes. We found no evidence to support the efficacy of homeopathic medicinal products for ARTIs in children. Adverse events were poorly reported, and we could not draw conclusions regarding safety.

Dynamics of Patient-Based Benefit-Risk Assessment of Medicines in Chronic Diseases: A Systematic Review.

Background: A critical gap exits in understanding the dynamics of patient-based benefit-risk assessment (BRA) of medicines in chronic diseases during the disease journey. Purpose: To systematically review and synthesize current evidence on the changes of patients' preferences about the benefits and risks of medicines during their disease journey including the influence of disease duration and severity, and previous treatment experience. Methods: A systematic review of studies identified in PubMed and Embase, from inception to November 2020, was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Articles were eligible if they analyzed adult patient-based BRA of medicines with a chronic disease, based on at least one of the pre-specified dimensions: disease severity, disease duration, or previous treatment experience. Results: A total of 26,228 articles were identified and 105 were eligible for inclusion. Of these, 85 detected a variation in patient-based BRA of medicines with at least one of the pre-specified criteria. Patients with higher disease severity and more treatment experience have increased risk tolerance. It remains inconclusive whether disease duration directly affects the relative importance of a patient's preference. Conclusion: Factors important for patients' BRA of their medicines during a chronic disease journey vary more with their clinical situation and previous treatment experience than with time since diagnosis. Due to the importance of these factors on patients' perspectives and potential impact on their decision-making and eventually their clinical outcomes, there is a need for more studies to assess the dynamics of patients' BRA in every disease.

Patient concerns regarding antidepressant drug–drug interactions: a retrospective analysis using data from a medicines call centre.

Introduction Antidepressant use has increased over the last two decades, with Australia and New Zealand among the highest antidepressant users in Organisation for Economic Co-operation and Development (OECD) countries. Comorbidity and polypharmacy are common in antidepressant users, increasing the likelihood of interaction-related adverse drug events, which are frequently preventable. Aim We aimed to identify, profile, and analyse potential antidepressant drug-drug interactions in information-seeking antidepressant users. Methods We retrospectively analysed antidepressant-related drug-drug interaction enquiries from patients or carers who contacted a pharmacist-led Australian national medicines call centre over an 8-year period to determine patient characteristics, concomitant drugs involved, prevalence and type of antidepressant-related drug-drug interaction across life stages, and associated risks. Results Of 3899 antidepressant drug-drug interaction calls, the most frequent concomitant drugs were antipsychotics, opioids, benzodiazepines, and complementary medicines. Narrative analyses of 2011 calls identified 81.0% of patients with potential drug-drug interactions and 10.4% categorised with worrying symptoms. The most frequent drug-drug interaction risks were excessive sedation, increased anticholinergic effects, serotonin syndrome, and suicidal thoughts. Carers of children aged Discussion Antidepressant users often have information gaps and safety concerns regarding drug-drug interactions that motivate help-seeking behaviour. Symptoms and drug-drug interaction consequences may be underestimated in these patients. Primary care health professionals have a role in proactively addressing the risk of drug-drug interactions to support benefit-risk assessment and shared decision-making.

Patient-based benefit-risk assessment of medicines: development, refinement, and validation of a content search strategy to retrieve relevant studies.

Introduction: Poor indexing and inconsistent use of terms and keywords may prevent efficient retrieval of studies on the patient-based benefit-risk assessment (BRA) of medicines. We aimed to develop and validate an objectively derived content search strategy containing generic search terms that can be adapted for any search for evidence on patient-based BRA of medicines for any therapeutic area. Methods: We used a robust multistep process to develop and validate the content search strategy: (1) we developed a bank of search terms derived from screening studies on patient-based BRA of medicines in various therapeutic areas, (2) we refined the proposed content search strategy through an iterative process of testing sensitivity and precision of search terms, and (3) we validated the final search strategy in PubMed by firstly using multiple sclerosis as a case condition and secondly computing its relative performance versus a published systematic review on patient-based BRA of medicines in rheumatoid arthritis. Results: We conceptualized a final search strategy to retrieve studies on patient-based BRA containing generic search terms grouped into two domains, namely the patient and the BRA of medicines (sensitivity 84%, specificity 99.4%, precision 20.7%). The relative performance of the content search strategy was 85.7% compared with a search from a published systematic review of patient preferences in the treatment of rheumatoid arthritis. We also developed a more extended filter, with a relative performance of 93.3% when compared with a search from a published systematic review of patient preferences in lung cancer.

Trends in Systemic Antifungal Use in Australia, 2005-2016: a Time-Series Analysis.

Data on antifungal utilization trends are important for encouraging antifungal stewardship. This study explored the use of antifungal agents for systemic application and the impact of reimbursement policy changes in Australia. We analyzed national data from the Australian Pharmaceutical Benefits Scheme (PBS) (2005-2016) and determined patterns of use over time and the impact of reimbursement decisions using an interrupted time-series model. From 2005-2016, there was an increase in the use of most antifungals, especially fluconazole, itraconazole, and posaconazole. Ketoconazole was the most commonly dispensed systemic antifungal agent (46.0%) prior to being removed from the PBS list and being replaced by fluconazole (69.8%). The PBS event "Fluconazole and itraconazole restrictions eased" led to the immediate increased use of fluconazole (0.025/1,000 per day), with both the highest rates and numerical increases attributed to obstetricians and gynecologists (1,969%; 1,851 dispensed prescriptions), as well as dermatologists (1,723%; 1,689 dispensed prescriptions) in 2010 and 2016. This is the first Australian national longitudinal estimate of systemic antifungal use. Our findings show an overall increase in the prescription of most antifungals during the investigated period, with reimbursement decisions impacting utilization. These data provide a baseline to inform the development of national antifungal guidelines and policies to encourage more targeted antifungal stewardship.

Long term impact of the WHI studies on information-seeking and decision-making in menopause symptoms management: a longitudinal analysis of questions to a medicines call centre.

BACKGROUND: While women are taking a greater role in decisions about menopause symptom management, the legacy of the Women's Health Initiative (WHI) studies persist. Despite hormone therapy (HT) being effective in reducing all-cause mortality, many women seeking relief of menopausal symptoms exaggerate HT harms and overstate the perceived benefits or ignore the risks of alternative therapies. We aimed to explore the longitudinal impact of the widely-publicised WHI 2002 study on women's information-seeking and describe determinants of decision-making about managing menopausal symptoms. METHODS: In a longitudinal analysis of both quantitative and qualitative data, we explored consumer questions about menopause-related medicines received by two Australian medicines call centres (1996-2010) before, during, and after WHI 2002. We analysed calls by age and gender of caller and patient, their relationship, postcode, enquiry type, and motivation to help-seek. We compared calls regarding HT and herbal medicines (HM) with the rest of calls, and thematically analysed question narratives across the three time-periods. RESULTS: There were 1,829 menopause-related calls received of over this time-period, with a call surge, primarily from women in their mid-fifties, in the two months after the WHI 2002 publication. Two in three calls were motivated by negative media reports as women sought support for decision-making, primarily reassurance to cease HT. While HT safety concerns persisted for eight years post-publication, the nature of information-seeking changed over time. Callers subsequently sought reassurance to use menopause treatments together with their other medicines; and pursued HT substitutes, including HM, in response to HT product discontinuation. CONCLUSIONS: Women sought information or reassurance to support a decision, based on dynamic changes in internal (symptom or risk intolerance, attitude towards menopause and treatment preferences) and external factors (perceived source trust and changes in treatment availability). In assessing HT benefit versus risk, women tend to overestimate risk with HT safety concerns persisting over time. Decision-making in managing menopause symptoms is complex and dynamic. Reassurance to reach or justify decisions from a perceived trusted source can support informed decision-making.

Heliox for croup in children.

BACKGROUND: Croup is an acute viral respiratory infection with upper airway mucosal inflammation that may cause respiratory distress. Most cases are mild. Moderate to severe croup may require treatment with corticosteroids (the benefits of which are often delayed) and nebulised epinephrine (adrenaline) (the benefits of which may be short-lived and which can cause dose-related adverse effects including tachycardia, arrhythmias, and hypertension). Rarely, croup results in respiratory failure necessitating emergency intubation and ventilation. A mixture of helium and oxygen (heliox) may prevent morbidity and mortality in ventilated neonates by reducing the viscosity of the inhaled air. It is currently used during emergency transport of children with severe croup. Anecdotal evidence suggests that it relieves respiratory distress. This review updates versions published in 2010, 2013, and 2018. OBJECTIVES: To examine the effect of heliox compared to oxygen or other active interventions, placebo, or no treatment on relieving signs and symptoms in children with croup as determined by a croup score and rates of admission and intubation. SEARCH METHODS: We searched CENTRAL, which includes the Cochrane Acute Respiratory Infections Group Specialised Register, MEDLINE, Embase, CINAHL, Web of Science, and LILACS, on 15 April 2021. We also searched the World Health Organization International Clinical Trials Registry Platform (apps.who.int/trialsearch/) and ClinicalTrials.gov (clinicaltrials.gov) on 15 April 2021. We contacted the British Oxygen Company, a leading supplier of heliox. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing the effect of heliox in comparison with placebo, no treatment, or any active intervention(s) in children with croup. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Data that could not be pooled for statistical analysis were reported descriptively. MAIN RESULTS: We included 3 RCTs involving a total of 91 children aged between 6 months and 4 years. Study duration was from 7 to 16 months, and all studies were conducted in emergency departments. Two studies were conducted in the USA and one in Spain. Heliox was administered as a mixture of 70% heliox and 30% oxygen. Risk of bias was low in two studies and high in one study because of its open-label design. We did not identify any new trials for this 2021 update. One study of 15 children with mild croup compared heliox with 30% humidified oxygen administered for 20 minutes. There may be no difference in croup score changes between groups at 20 minutes (mean difference (MD) -0.83, 95% confidence interval (CI) -2.36 to 0.70) (Westley croup score, scale range 0 to 16). The mean croup score at 20 minutes postintervention may not differ between groups (MD -0.57, 95% CI -1.46 to 0.32). There may be no difference between groups in mean respiratory rate (MD 6.40, 95% CI -1.38 to 14.18) and mean heart rate (MD 14.50, 95% CI -8.49 to 37.49) at 20 minutes. The evidence for all outcomes in this comparison was of low certainty, downgraded for serious imprecision. All children were discharged, but information on hospitalisation, intubation, or re-presenting to emergency departments was not reported. In another study, 47 children with moderate croup received one dose of oral dexamethasone (0.3 mg/kg) with either heliox for 60 minutes or no treatment. Heliox may slightly improve Taussig croup scores (scale range 0 to 15) at 60 minutes postintervention (MD -1.10, 95% CI -1.96 to -0.24), but there may be no difference between groups at 120 minutes (MD -0.70, 95% CI -1.56 to 0.16). Children treated with heliox may have lower mean Taussig croup scores at 60 minutes (MD -1.11, 95% CI -2.05 to -0.17) but not at 120 minutes (MD -0.71, 95% CI -1.72 to 0.30). Children treated with heliox may have lower mean respiratory rates at 60 minutes (MD -4.94, 95% CI -9.66 to -0.22), but there may be no difference at 120 minutes (MD -3.17, 95% CI -7.83 to 1.49). There may be a difference in hospitalisation rates between groups (odds ratio 0.46, 95% CI 0.04 to 5.41). We assessed the evidence for all outcomes in this comparison as of low certainty, downgraded due to imprecision and high risk of bias related to an open-label design. Information on heart rate and intubation was not reported. In the third study, 29 children with moderate to severe croup all received continuous cool mist and intramuscular dexamethasone (0.6 mg/kg). They were then randomised to receive either heliox (given as a mixture of 70% helium and 30% oxygen) plus one to two doses of nebulised saline or 100% oxygen plus nebulised epinephrine (adrenaline), with gas therapy administered continuously for three hours. Heliox may slightly improve croup scores at 90 minutes postintervention, but may result in little or no difference overall using repeated-measures analysis. We assessed the evidence for all outcomes in this comparison as of low certainty, downgraded due to high risk of bias related to inadequate reporting. Information on hospitalisation or re-presenting to the emergency department was not reported. The included studies did not report on adverse events, intensive care admissions, or parental anxiety. We could not pool the available data because each comparison included data from only one study. AUTHORS' CONCLUSIONS: Given the very limited available evidence, uncertainty remains regarding the effectiveness and safety of heliox. Heliox may not be more effective than 30% humidified oxygen for children with mild croup, but may be beneficial in the short term for children with moderate croup treated with dexamethasone. The effect of heliox may be similar to 100% oxygen given with one or two doses of adrenaline. Adverse events were not reported, and it is unclear if these were monitored in the included studies. Adequately powered RCTs comparing heliox with standard treatments are needed to further assess the role of heliox in the treatment of children with moderate to severe croup.

ICU Patients' Antibiotic Exposure and Triazole-Resistance in Invasive Candidiasis: Parallel Analysis of Aggregated and Individual Data.

Background: The relationship between antibiotic use and the incidence of triazole-resistant phenotypes of invasive candidiasis (IC) in critically ill patients is unclear. Different methodologies on determining this relationship may yield different results. Methods: A retrospective multicenter observational analysis was conducted to investigate exposure to antibiotics and the incidence of non-duplicate clinical isolates of Candida spp. resistant to fluconazole, voriconazole, or both during November 2013 to April 2018, using two different methodologies: group-level (time-series analysis) and individual-patient-level (regression analysis and propensity-score adjusting). Results: Of 393 identified Candida spp. from 388 critically ill patients, there were three phenotypes of IC identified: fluconazole-resistance (FR, 63, 16.0%); voriconazole-resistance (VR, 46, 11.7%); and cross-resistance between fluconazole and voriconazole (CR, 32, 8.1%). Exposure to several antibacterial agents with activity against the anaerobic gastrointestinal flora, especially third-generation cefalosporins (mainly cefoperazone/sulbactam and ceftriaxone), but not triazoles, have an immediate effect (time lag = 0) on subsequent ICU-acquired triazole-resistant IC in the group-level (p < 0.05). When the same patient database was analyzed at the individual-patient-level, we found that exposure to many antifungal agents was significantly associated with triazole-resistance (fluconazole [adjusted odds ratio (aOR) = 2.73] or caspofungin [aOR = 11.32] on FR, voriconazole [aOR = 2.87] on CR). Compared to the mono-triazole-resistant phenotype, CR IC has worse clinical outcomes (14-days mortality) and a higher level of resistance. Conclusion: Group-level and individual-patient-level analyses of antibiotic-use-versus-resistance relations yielded distinct but valuable results. Antibacterials with antianaerobic activity and antifungals might have "indirect" and "direct" effect on triazole-resistant IC, respectively.

Anaemia in patients undergoing major bowel surgery - Prevalence and current practice: A public and private institution experience.

AIM: The study aimed to compare the frequency and alignment of preoperative anaemia screening and treatment with Australian guidelines in elective bowel surgery and determine the impact on clinical outcomes. METHODS: We performed a retrospective observational study, with an audit of 559 adult patients who underwent major elective bowel surgery in an Australian metropolitan hospital, January 2016-December 2018. Outcome measures included rate of anaemia, guideline compliance, hospital length of stay, and transfusion rate. RESULTS: Preoperative anaemia assessment occurred in 82.6% of patients. However, only 5.2% received recommended biochemical tests at least one week before surgery. Only 25.2% of anaemic patients received preoperative treatment; they experienced a longer hospital length of stay (9.93 days versus 7.88 days, p < 0.001) and an increased rate of transfusion (OR: 3.186, p < 0.05). CONCLUSION: The gaps between current preoperative anaemia screening, management and national guidelines may place patients at higher risk of poor surgical outcome.

Homeopathic Preparations for Preventing and Treating Acute Upper Respiratory Tract Infections in Children: A Systematic Review and Meta-Analysis.

BACKGROUND: Acute upper respiratory tract infections (ARTIs) are common and mostly self-limiting. A range of treatments are used with the aim to cure or treat symptoms, including widespread use of homeopathic treatments. OBJECTIVE: To undertake a systematic review and meta-analysis of trials with the highest level of evidence, to establish the benefits and risks for oral homeopathic remedies used to treat and prevent ARTIs in children. DATA SOURCES: MEDLINE, Embase, CINAHL, AMED, CAMbase, British Homeopathic Library, CENTRAL, WHO ICTRP and ClinicalTrials.gov registers to March 2018. STUDY ELIGIBILITY, PARTICIPANTS, AND INTERVENTIONS: Double-blinded randomized trials in children, treated with oral homeopathic remedies versus placebo or conventional treatments for ARTI. APPRAISAL AND SYNTHESIS METHODS: Studies were reviewed in duplicate for inclusion, data extraction, and risk of bias. Meta-analysis was performed on only 4 outcomes. Other outcomes were reported narratively. RESULTS: Eight studies (1562 children) were included. Four studies examined treatment and 4 prevention of ARTIs. Four studies involved homeopaths individualizing treatment versus four with non-individualized treatments. Three studies had high risk of bias in at least 1 domain. All studies with low risk of bias showed no benefit from homeopathy; trials at uncertain and high risk of bias reported beneficial effects. Two individualized treatment studies (N = 155) did not show benefit on short-term or long-term cure. Prevention trials showed no significant outcomes: recurrence of ARTIs. No serious events were reported. LIMITATIONS: Methodological inconsistencies and heterogeneity. CONCLUSIONS: The effectiveness for homeopathic remedies for childhood ARTIs is not supported in higher quality trials.

Withdrawal and Misuse Concerns of Consumers regarding Opioid Analgesic and Anxiolytic, Hypnotic and Sedative Medicines.

BACKGROUND: Opioid analgesic (OA) and anxiolytic, hypnotic and sedative (AHS) medicines use raise community concerns about risks of dependence: dose escalation, unintentional misuse. Objectives: We aimed to identify common consumer OA and AHS information gaps and concerns that led to information seeking from a hotline. Methods: We conducted a retrospective, mixed-method observational study of consumers' OA and AHS-related calls to an Australian national medicines call center (September 2002-30 June 2010). We analyzed these medicines' call characteristics compared to their respective rest of calls (ROC) and thematically explored narratives concerning withdrawal and misuse. Results: Of 123,217 calls, 7,395 (6.0%) involved OA and 7,789 (6.2%) AHS, with consistency between call characteristics. While female middle-aged callers predominated, more males called for these medicines than their complementary ROC. Uncertainty about unresolved OA and AHS concerns led to help-seeking that was consistent over eight years. Main motivations were inadequate information (OA 44.5%; AHS 41.2%), seeking a second opinion (OA 24.2%; AHS 24.2%), worrying symptoms (OA 21.6%; AHS 23.1%), and conflicting information (OA 4.9%; AHS 5.1%). Callers focused on withdrawal and issues related to inadvertent overuse or deliberate misuse (OA 9.2% vs. non-OA ROC 2.9%; AHS 12.6% vs. non-AHS ROC 2.7%). Primary themes were similar for both cohorts: concern about harm or aiming to minimize harm by information seeking, requesting a strategy, or reassurance. Conclusions: Consumers have under-recognized perceptions of harm from OA and AHS use, particularly withdrawal and misuse. Resources based on real world consumer concerns can encourage open dialogue between patients and their prescribers.

Real-world questions and concerns about disease-modifying antirheumatic drugs (DMARDs): a retrospective analysis of questions to a medicine call center.

BACKGROUND: Disease-modifying antirheumatic drugs (DMARDs) have transformed the treatment of numerous autoimmune and inflammatory diseases but their perceived risk of harm may be a barrier to use. METHODS: In a retrospective mixed-methods study, we analysed conventional (c) and biologic (b) DMARDs-related calls and compared them with rest of calls (ROC) from consumers to an Australian national medicine call center operated by clinical pharmacists from September 2002 to June 2010. This includes the period where bDMARDs became available on the Pharmaceutical Benefits Scheme, the government-subsidized prescription medicines formulary. We compared caller and patient demographics, enquiry types and motivation to information-seek for both cDMARDs and bDMARDs with ROC, using a t-test for continuous data and a chi-square test for categorical data. We explored call narratives to identify common themes. RESULTS: There were 1547 calls involving at least one DMARD. The top three cDMARD enquiry types were side effects (27.2%), interactions (21.9%), and risk versus benefit (11.7%). For bDMARDs, the most common queries involved availability and subsidized access (18%), mechanism and profile (15.8%), and side effects (15.1%). The main consumer motivations to information-seek were largely independent of medicines type and included: inadequate information (44%), wanting a second opinion (23.6%), concern about a worrying symptom (18.8%), conflicting information (6.9%), or information overload (2.3%). Question themes common to conventional and biological DMARDs were caller overemphasis on medication risk and the need for reassurance. Callers seeking information about bDMARDs generally overestimated effectiveness and focused their attention on availability, cost, storage, and medicine handling. CONCLUSION: Consumers have considerable uncertainty regarding DMARDs and may overemphasise risk. Patients cautiously assess the benefits and risks of their DMARDs but when new treatments emerge, they tend to overestimate their effectiveness.

Implementing a sustainable medication reconciliation process in Australian hospitals: The World Health Organization High 5s project.

BACKGROUND: Medication reconciliation (medrec) is a mandated patient safety strategy by national, including Australian, accreditation bodies. Yet there are no validated performance measures. OBJECTIVE: To determine the feasibility of implementing the World Health Organization (WHO) Medrec Standard Operating Protocol (SOP) in a range of Australian acute care facilities to achieve measurable and sustainable reductions in medication discrepancies occurring at admission. METHODS: A multicentre, prospective national study was conducted in ten academic, urban and regional hospitals to implement the SOP using WHO High 5s project and quality improvement methodology. Sites collected data on the rate of medrec performed within 24 h of admission in a random selection of 50 patients aged ≥65 years admitted via the emergency department, monthly for four years. Medrec quality was reviewed in a subset of 30 patients using three performance measures. Barriers, enablers and benefits of SOP implementation were collected using qualitative surveys. RESULTS: Ten health services reviewed 42,003 patient records. Of these, 20,162 (49.5%) had medicines reconciled within 24 h of admission. Four services increased, two decreased, and in four, medrec completion rates remained static. Mean number of unintentional and undocumented intentional medication discrepancies per patient decreased: 0.21 to 0.16 (p = 0.001) and 0.34 to 0.08 (p = 0.003), respectively. Unintentional discrepancies decreased from 15.2% to 11.1% (p = 0.001). Barriers to full implementation included: medrec not seen as a priority, limited resources and lack of electronic systems integration. Enablers included: use of medrec measures for feedback, educational resources, and 7-day week clinical pharmacy services. Benefits included improvements in medication safety culture and multidisciplinary teamwork. CONCLUSIONS: The WHO SOP was feasible, although challenging, to implement in a range of acute health services, and produced measureable and sustainable improvements in medicines information accuracy on admission. Sustaining the quantum of quality and timely medrec requires investment in pharmacist resources and electronic systems integration.

Consumption of medicines used for gastric acid-related disorders in Australia and South Korea: a cross-country comparison.

PURPOSE: The study's aim was to compare the use of proton pump inhibitors (PPIs), histamine 2-receptor antagonists (H2RAs) and mucoprotective medicines (MPs) used for gastric acid-related disorders (GARD) in Australia and South Korea (Korea) from 2004 to 2017. METHODS: Prescription data for PPIs, H2RAs and MPs for Australian outpatients were extracted from the Australian Statistics on Medicines annual reports, with dose-specific and expenditure data obtained from Medicare. Similar data were obtained from Korean National Health Insurance Service claims data. We analysed the volume and expenditure of medicines use annually using the defined daily dose per 1,000 population per day. We calculated which medicines accounted for 90% of use and estimated the proportions of use for low- and high-dose PPIs. RESULTS: While total utilisation for GARD medicines increased over time in both countries, patterns of use differed. Overall, use was somewhat higher in Australia but increased more rapidly in Korea. PPIs were used more extensively in Australia, while more MPs and H2RAs were used in Korea. Expenditure and use of low-dose PPIs is escalating in Korea. CONCLUSION: There were substantial differences in the use of GARD medicines in Australia and Korea over 14 years. Both countries face similar challenges to promote rational medicines use and contain medical care costs. The discrepant prescribing patterns can be attributed to differences in healthcare systems, pharmaceutical policies and demographics. This study provides a baseline to influence more rational use of these medicines. It provides insight into medicines policies for other countries that face similar challenges.

Antifungal agents for invasive candidiasis in non-neutropenic critically ill adults: What do the guidelines recommend?

OBJECTIVES: Recommendations in clinical practice guidelines (CPG) may differ and cause confusion. Our objective was to appraise CPGs for antifungal treatment of invasive candidiasis (IC) in non-neutropenic critically ill adult patients. METHODS: We systematically searched the literature for CPGs published between 2008 and 2018. We assessed the quality of each guideline using six domains of the AGREE II instrument. We extracted and compared recommendations for different treatment strategies and assessed content quality. RESULTS: Of 19 guidelines, the mean overall AGREE II score was 58%. The domain 'clarity of presentation' received the highest scores (88%) and 'applicability' the lowest (18%). CPGs provided detailed recommendations on antifungal prophylaxis (n = 10), with fluconazole recommended as initial prophylaxis in all seven CPGs citing a specific drug. Echinocandin was recommended as the initial drug in all 16 CPGs supporting empirical/pre-emptive treatment; and in 18 of 19 for targeted invasive candidiasis treatment. However, it remains unclear when to initiate prophylaxis, empirical or pre-emptive therapy or when to step down. CONCLUSIONS: The methodological quality of CPGs for antifungal treatment of IC in non-neutropenic critically ill patients is suboptimal. Some treatment recommendations were inconsistent across indications and require local guidance to help clinicians make better informed decisions.

Network meta-analysis and pharmacoeconomic evaluation of antibiotics for the treatment of patients infected with complicated skin and soft structure infection and hospital-acquired or ventilator-associated penumonia.

Background: Infections due to methicillin-resistant Staphylococcus aureus (MRSA) cause serious health risks and significant economic burdens and the preferred drugs are still controversial. Methods: We performed a network meta-analysis (NMA) to compare the efficacy and safety of antibiotics used to treat inpatients with complicated skin and soft structure infections (cSSSI) or hospital-acquired or ventilator-associated pneumonia (HAP/VAP). We also developed a decision tree model to assess the cost-effectiveness of antibiotics. Results: Forty-nine randomized controlled trials met the inclusion criteria (34 for cSSSI, 15 for HAP/VAP) and compared the efficacy and safety of 16 antibiotics. For cSSSI, NMA indicated that for clinical cure, linezolid was superior than vancomycin (odds ratio (OR) 1.55, 95% confidence interval (CI) 1.19-2.02), while tedizolid (OR 1.39, CI 0.70-2.76) was similar to vancomycin. In terms of safety, there were no significant differences between any two interventions on total adverse events. Based on drug and hospital costs in America, the incremental cost-effectiveness ratios (ICERs) per life-year saved for linezolid and tedizolid compared with vancomycin were US$2833 and US$5523. For HAP/VAP, there were no significant effects either for clinical cure or for safety endpoints between linezolid and vancomycin in NMA. ICERs per life-year saved for linezolid compared with vancomycin were US$2185. Conclusion: In these clinical trials, considering efficacy, safety, and cost-effectivenes, linezolid and tedizolid showed their superiority in MRSA cSSSI; while linezolid might be recommended to treat MRSA pneumonia. Although vancomycin was not cost-effective in pharmacoeconomic evaluation, it is still the first-line treatment for MRSA infection in the clinical practice. This study might provide new insights of therapeutic choices for patients with MRSA infections whilst awaiting the arrival of higher quality evidence.