Paediatric medication incident reporting: a multicentre comparison study of medication errors identified at audit, detected by staff and reported to an incident system.

OBJECTIVES: To compare medication errors identified at audit and via direct observation with medication errors reported to an incident reporting system at paediatric hospitals and to investigate differences in types and severity of errors detected and reported by staff. METHODS: This is a comparison study at two tertiary referral paediatric hospitals between 2016 and 2020 in Australia. Prescribing errors were identified from a medication chart audit of 7785 patient records. Medication administration errors were identified from a prospective direct observational study of 5137 medication administration doses to 1530 patients. Medication errors reported to the hospitals' incident reporting system were identified and matched with errors identified at audit and observation. RESULTS: Of 11 302 clinical prescribing errors identified at audit, 3.2 per 1000 errors (95% CI 2.3 to 4.4, n=36) had an incident report. Of 2224 potentially serious prescribing errors from audit, 26.1% (95% CI 24.3 to 27.9, n=580) were detected by staff and 11.2 per 1000 errors (95% CI 7.6 to 16.5, n=25) were reported to the incident system. Although the prescribing error detection rates varied between the two hospitals, there was no difference in incident reporting rates regardless of error severity. Of 40 errors associated with actual patient harm, only 7 (17.5%; 95% CI 8.7% to 31.9%) were detected by staff and 4 (10.0%; 95% CI 4.0% to 23.1%) had an incident report. None of the 2883 clinical medication administration errors observed, including 903 potentially serious errors and 144 errors associated with actual patient harm, had incident reports. CONCLUSION: Incident reporting data do not provide an accurate reflection of medication errors and related harm to children in hospitals. Failure to detect medication errors is likely to be a significant contributor to low error reporting rates. In an era of electronic health records, new automated approaches to monitor medication safety should be pursued to provide real-time monitoring.

Normative Data on Serum and Plasma Tryptophan and Kynurenine Concentrations from 8089 Individuals Across 120 Studies: A Systematic Review and Meta-Analysis.

In this systematic review and meta-analysis, a normative dataset is generated from the published literature on the kynurenine pathway in control participants extracted from case-control and methodological validation studies. Study characteristics were mapped, and studies were evaluated in terms of analytical rigour and methodological validation. Meta-analyses of variance between types of instruments, sample matrices and metabolites were conducted. Regression analyses were applied to determine the relationship between metabolite, sample matrix, biological sex, participant age and study age. The grand mean concentrations of tryptophan in the serum and plasma were 60.52 ± 15.38 µM and 51.45 ± 10.47 µM, respectively. The grand mean concentrations of kynurenine in the serum and plasma were 1.96 ± 0.51 µM and 1.82 ± 0.54 µM, respectively. Regional differences in metabolite concentrations were observed across America, Asia, Australia, Europe and the Middle East. Of the total variance within the data, mode of detection (MOD) accounted for up to 2.96%, sample matrix up to 3.23%, and their interaction explained up to 1.53%; the latter of which was determined to be negligible. This review was intended to inform future empirical research and method development studies and successfully synthesised pilot data. The pilot data reported in this study will inform future precision medicine initiatives aimed at targeting the kynurenine pathway by improving the availability and quality of normative data.

A randomized, double-blind, placebo-controlled, parallel-group 12-week pilot phase II trial of SaiLuoTong (SLT) for cognitive function in older adults with mild cognitive impairment.

INTRODUCTION: This study primarily aimed to evaluate the efficacy and safety of SaiLuoTong (SLT) on cognition in mild cognitive impairment (MCI). METHODS: Community-dwelling people with MCI aged ≥60 years were randomly assigned to 180 mg/day SLT or placebo for 12 weeks. RESULTS: Thirty-nine participants were randomized to each group (N = 78); 65 were included in the final analysis. After 12 weeks, the between-groups difference in Logical Memory delayed recall scores was 1.40 (95% confidence interval [CI]: 0.22 to 2.58; P = 0.010); Delis-Kaplan Executive Function System Trail Making Test Condition 4 switching and contrast scaled scores were 1.42 (95% CI: -0.15 to 2.99; P = 0.038) and 1.56 (95% CI: -0.09 to 3.20; P = 0.032), respectively; Rey Auditory Verbal Learning Test delayed recall was 1.37 (95% CI: -0.10 to 2.84; P = 0.034); and Functional Activities Questionnaire was 1.21 (95% CI: -0.21 to 2.63; P = 0.047; P < 0.001 after controlling for baseline scores). DISCUSSION: SLT is well tolerated and may be useful in supporting aspects of memory retrieval and executive function in people with MCI. Highlights: SaiLuoTong (SLT) improves delayed memory retrieval and executive function in people with mild cognitive impairment (MCI).SLT is well tolerated in people ≥ 60 years.The sample of community dwellers with MCI was well characterized and homogeneous.

Effect of kava (Piper methysticum) on peripheral gene expression among individuals with generalized anxiety disorder: A post hoc analysis of a randomized controlled trial.

Kava is a South Pacific plant-based medicine with anxiolytic properties, but little is known about the impact kava has on gene expression or whether gene expression can serve as a marker of kava response. This study aimed to determine whether kava treatment alters the expression of genes with physiological relevance to anxiety pathophysiology and whether the baseline expression of these physiologically relevant genes modifies the efficacy of kava treatment. In this post hoc analysis, we examined the expression of 48 genes relevant to the pathophysiology of anxiety collected from a double-blind randomized controlled trial that assessed the efficacy of kava treatment in generalized anxiety disorder. Peripheral blood gene expression was measured in 71 (34 kava, 37 placebo) adults at baseline and in 40 (19 kava, 21 placebo) after 8 weeks of treatment by reverse transcription polymerase chain reaction (PCR). Results revealed that kava decreased the expression of a subunit of the GABAA -rho receptor gene (GABRR2) and catechol-O-methyltransferase (COMT), a gene related to catecholamine metabolism. Kava efficacy was not found to be modified by baseline (pretreatment) expression of relevant genes. Although these results did not withstand statistical correction for multiple comparisons and require external validation, they support the notion that kava's mechanism of action includes interaction with GABAergic and catecholaminergic systems.

Brain function effects of exercise interventions for cognitive decline: a systematic review and meta-analysis.

Introduction: Exercise is recognized as a modifiable lifestyle factor that can mitigate cognitive decline and dementia risk. While the benefits of exercise on cognitive aging have been reported on extensively, neuronal effects in adults experiencing cognitive decline have not been systematically synthesized. The aim of this systematic review was to assess the effects of exercise on cognition and brain function in people with cognitive decline associated with dementia risk. Method: A systematic search was conducted for randomized controlled trials of ≥ 4 weeks exercise (aerobic, resistance, or mind-body) that assessed cognition and brain function using neuroimaging and neurophysiological measures in people with subjective or objective cognitive decline. Study characteristics and brain function effects were narratively synthesized, while domain-specific cognitive performance was subjected to meta-analysis. Study quality was also assessed. Results: 5,204 records were identified and 12 unique trials met the eligibility criteria, representing 646 adults classified with cognitive frailty, mild or vascular cognitive impairment. Most interventions involved 40-minute sessions conducted 3 times/week. Exercise improved global cognition (g = -0.417, 95% CI, -0.694 to -0.140, p = 0.003, I2 = 43.56%), executive function (g = -0.391, 95% CI, -0.651 to -0.131, p = 0.003, I2 = 13.28%), but not processing speed or general short-term memory (both p >0.05). Across fMRI and ERP studies, significant neuronal adaptations were found with exercise cf. control throughout the brain and were linked with improved global cognition, memory, and executive function. Cerebral blood flow was also found to improve with 24 weeks of exercise, but was not linked with cognitive changes. Discussion: The cognitive improvements associated with exercise are likely driven by increased metabolic activity, cerebrovascular mechanisms, and neuroplasticity throughout the brain. Our paper shows the promise in, and need for, high-quality trials integrating cognitive and brain function measures to elucidate the functional relationship between exercise and brain health in populations with a high risk of dementia. Systematic review registration: PROSPERO, identifier: CRD42022291843.

N-acetyl cysteine (NAC) augmentation in the treatment of obsessive-compulsive disorder: A phase III, 20-week, double-blind, randomized, placebo-controlled trial.

OBJECTIVE: Preliminary evidence has suggested that adjunctive N-acetylcysteine (NAC), an antioxidant precursor to glutathione, may reduce symptoms of obsessive-compulsive disorder (OCD). We conducted a 20-week, multi-site, randomized controlled trial to investigate the safety and efficacy of the adjunctive use of NAC in OCD. METHODS: The study was a phase III, 20-week, double-blind, randomized controlled trial across multiple sites in Australia investigating 2 g to 4 g per day of NAC (titrated according to response) in 98 participants with DSM-5 diagnosed OCD. Data were analysed using linear mixed effects models for the 89 participants who attended at least one follow-up visit. RESULTS: A modified intention-to-treat analysis of the primary outcome found no evidence that NAC reduced symptoms of OCD measured on the Yale-Brown Obsessive-Compulsive Scale, relative to placebo (mean difference at week 20 = 0.53, 95% compatibility interval = -2.18, 3.23; p = 0.70; favouring placebo). There was also no evidence that NAC, compared to placebo, improved outcomes on the secondary measures including anxiety, depression, quality of life, functioning, or clinician/participant impression. NAC was well-tolerated with only mild gastrointestinal adverse events associated with the treatment. CONCLUSION: We found no evidence supporting the efficacy of the adjunctive use of NAC in OCD.

Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce.

OBJECTIVES: The therapeutic use of nutrient-based 'nutraceuticals' and plant-based 'phytoceuticals' for the treatment of mental disorders is common; however, despite recent research progress, there have not been any updated global clinical guidelines since 2015. To address this, the World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Disorders (CANMAT) convened an international taskforce involving 31 leading academics and clinicians from 15 countries, between 2019 and 2021. These guidelines are aimed at providing a definitive evidence-informed approach to assist clinicians in making decisions around the use of such agents for major psychiatric disorders. We also provide detail on safety and tolerability, and clinical advice regarding prescription (e.g. indications, dosage), in addition to consideration for use in specialised populations. METHODS: The methodology was based on the WFSBP guidelines development process. Evidence was assessed based on the WFSBP grading of evidence (and was modified to focus on Grade A level evidence - meta-analysis or two or more RCTs - due to the breadth of data available across all nutraceuticals and phytoceuticals across major psychiatric disorders). The taskforce assessed both the 'level of evidence' (LoE) (i.e. meta-analyses or RCTs) and the assessment of the direction of the evidence, to determine whether the intervention was 'Recommended' (+++), 'Provisionally Recommended' (++), 'Weakly Recommended' (+), 'Not Currently Recommended' (+/-), or 'Not Recommended' (-) for a particular condition. Due to the number of clinical trials now available in the field, we firstly examined the data from our two meta-reviews of meta-analyses (nutraceuticals conducted in 2019, and phytoceuticals in 2020). We then performed a search of additional relevant RCTs and reported on both these data as the primary drivers supporting our clinical recommendations. Lower levels of evidence, including isolated RCTs, open label studies, case studies, preclinical research, and interventions with only traditional or anecdotal use, were not assessed. RESULTS: Amongst nutraceuticals with Grade A evidence, positive directionality and varying levels of support (recommended, provisionally recommended, or weakly recommended) was found for adjunctive omega-3 fatty acids (+++), vitamin D (+), adjunctive probiotics (++), adjunctive zinc (++), methylfolate (+), and adjunctive s-adenosyl methionine (SAMe) (+) in the treatment of unipolar depression. Monotherapy omega-3 (+/-), folic acid (-), vitamin C (-), tryptophan (+/-), creatine (+/-), inositol (-), magnesium (-), and n-acetyl cysteine (NAC) (+/-) and SAMe (+/-) were not supported for this use. In bipolar disorder, omega-3 had weak support for bipolar depression (+), while NAC was not currently recommended (+/-). NAC was weakly recommended (+) in the treatment of OCD-related disorders; however, no other nutraceutical had sufficient evidence in any anxiety-related disorder. Vitamin D (+), NAC (++), methylfolate (++) were recommended to varying degrees in the treatment of the negative symptoms in schizophrenia, while omega-3 fatty acids were not, although evidence suggests a role for prevention of transition to psychosis in high-risk youth, with potential pre-existing fatty acid deficiency. Micronutrients (+) and vitamin D (+) were weakly supported in the treatment of ADHD, while omega-3 (+/-) and omega-9 fatty acids (-), acetyl L carnitine (-), and zinc (+/-) were not supported. Phytoceuticals with supporting Grade A evidence and positive directionality included St John's wort (+++), saffron (++), curcumin (++), and lavender (+) in the treatment of unipolar depression, while rhodiola use was not supported for use in mood disorders. Ashwagandha (++), galphimia (+), and lavender (++) were modestly supported in the treatment of anxiety disorders, while kava (-) and chamomile (+/-) were not recommended for generalised anxiety disorder. Ginkgo was weakly supported in the adjunctive treatment of negative symptoms of schizophrenia (+), but not supported in the treatment of ADHD (+/-). With respect to safety and tolerability, all interventions were deemed to have varying acceptable levels of safety and tolerability for low-risk over-the-counter use in most circumstances. Quality and standardisation of phytoceuticals was also raised by the taskforce as a key limiting issue for firmer confidence in these agents. Finally, the taskforce noted that such use of nutraceuticals or phytoceuticals be primarily recommended (where supportive evidence exists) adjunctively within a standard medical/health professional care model, especially in cases of more severe mental illness. Some meta-analyses reviewed contained data from heterogenous studies involving poor methodology. Isolated RCTs and other data such as open label or case series were not included, and it is recognised that an absence of data does not imply lack of efficacy. CONCLUSIONS: Based on the current data and clinician input, a range of nutraceuticals and phytoceuticals were given either a supportive recommendation or a provisional recommendation across a range of various psychiatric disorders. However several had only a weak endorsement for potential use; for a few it was not possible to reach a clear recommendation direction, largely due to mixed study findings; while some other agents showed no obvious therapeutic benefit and were clearly not recommended for use. It is the intention of these guidelines to inform psychiatric/medical, and health professional practice globally.

Effects of a high-prebiotic diet versus probiotic supplements versus synbiotics on adult mental health: The "Gut Feelings" randomised controlled trial.

Background: Preliminary evidence supports the use of dietary interventions and gut microbiota-targeted interventions such as probiotic or prebiotic supplementation for improving mental health. We report on the first randomised controlled trial (RCT) to examine the effects of a high-prebiotic dietary intervention and probiotic supplements on mental health. Methods: "Gut Feelings" was an 8-week, 2 × 2 factorial RCT of 119 adults with moderate psychological distress and low prebiotic food intake. Treatment arms: (1) probiotic supplement and diet-as-usual (probiotic group); (2) high-prebiotic diet and placebo supplement (prebiotic diet group); (3) probiotic supplement and high-prebiotic diet (synbiotic group); and (4) placebo supplement and diet-as-usual (placebo group). The primary outcome was assessment of total mood disturbance (TMD; Profile of Mood States Short Form) from baseline to 8 weeks. Secondary outcomes included anxiety, depression, stress, sleep, and wellbeing measures. Results: A modified intention-to-treat analysis using linear mixed effects models revealed that the prebiotic diet reduced TMD relative to placebo at 8 weeks [Cohen's d = -0.60, 95% confidence interval (CI) = -1.18, -0.03; p = 0.039]. There was no evidence of symptom improvement from the probiotic (d = -0.19, 95% CI = -0.75, 0.38; p = 0.51) or synbiotic treatments (d = -0.03, 95% CI = -0.59, 0.53; p = 0.92). Improved anxiety, stress, and sleep were noted in response to the prebiotic diet while the probiotic tentatively improved wellbeing, relative to placebo. No benefit was found in response to the synbiotic intervention. All treatments were well tolerated with few adverse events. Conclusion: A high-prebiotic dietary intervention may improve mood, anxiety, stress, and sleep in adults with moderate psychological distress and low prebiotic intake. A synbiotic combination of high-prebiotic diet and probiotic supplement does not appear to have a beneficial effect on mental health outcomes, though further evidence is required. Results are limited by the relatively small sample size. Clinical trial registration: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372753, identifier ACTRN12617000795392.

What we need as we get older: needs assessment for the development of a community geriatrics service in an Australian context.

BACKGROUND: The aim of this study was to inform the development of a Community Geriatrics Service (CGS) that addressed the healthcare and social needs of community dwelling older people in an Australian context. METHODS: Stakeholders (N = 108) took part in a 'needs assessment' involving 30-min semi-structured interviews with general practitioners (GPs; N = 49), and three 2-h focus groups (community engagement meetings; N = 59) with older people, informal caregivers, allied healthcare workers, and nursing home directors. Data were transcribed and thematically coded, mapped to source and weighted to the frequency that the theme was raised across sources. RESULTS: Five themes informing CGS development and delivery emerged: active health conditions (management of behavioural and psychological symptoms of dementia, falls, multimorbidity, and other relevant conditions), active social challenges (patient non-compliance, need for aged care social workers, caregiver stress, elder abuse, social isolation, and stigma), referrals (availability of specialists, communication, specialist input, and advance care directives), access (lack of transport options, and inaccessibility of local geriatrics clinics and specialists), and awareness (lack of awareness, knowledge, and resources). CONCLUSIONS: The CGS will need to address access, referral processes and health system navigation, which were perceived by stakeholders as significant challenges. These findings warrant the development of a CGS with an integrated approach to aged care, pertinent for the health and social needs of the elderly.

Use of complementary medicines and lifestyle approaches by people living with dementia: Exploring experiences, motivations and attitudes.

BACKGROUND: Lack of effective treatments for chronic conditions is associated with high rates of complementary medicine (CM) use. However, little is known about CM use for dementia. AIMS AND OBJECTIVES: The aim of this study was to explore the experiences, motivations, and attitudes towards CM use by people living with dementia in an Australian setting. DESIGN: This study had a qualitative research design; quantitative demographic information was also collected. METHODS: In-depth interviews were conducted with people living with dementia and their caregivers (N = 18). A thematic (inductive) analysis approach was taken to interpret data. RESULTS: Three in four participants used CM for dementia, spending ~AUD$100/month (USD$70/month). Within three overarching themes, a range of sub-themes was identified: (1) CM knowledge and use: people living with dementia and caregivers understanding of CM, types of CM used, and CM usage patterns; (2) Self-determined reasons for use/non-use: maintain or improve quality of life, hope, management of dementia symptoms, level of awareness, willingness and evidence, perceptions on efficacy and safety of CM, experiences of conventional medicine, and holistic approach to wellness; (3) External determinants of use: information on CM, relationship influences on CM use, and experiences with General Practitioners (GPs) and CM. CONCLUSION: Findings highlight that CM use is widespread and positively viewed by people living with dementia and their caregivers. Decisions regarding CM use were based on personal opinions. Findings have important implications for conversations with health professionals regarding CM use by people living with dementia to improve communication, health literacy, and reduce the risk of adverse effects through polypharmacy. IMPLICATIONS FOR PRACTICE: This study showed that CM is a valued approach for dementia management by people living with dementia, their families, and healthcare providers. Future international research is required to evaluate the efficacy and safety of these approaches and promote accurate advice in nursing care.