Cough in Children and Adults: Diagnosis, Assessment and Management (CICADA). Summary of an updated position statement on chronic cough in Australia.

INTRODUCTION: Cough is the most common symptom leading to medical consultation. Chronic cough results in significant health care costs, impairs quality of life, and may indicate the presence of a serious underlying condition. Here, we present a summary of an updated position statement on cough management in the clinical consultation. MAIN RECOMMENDATIONS: Assessment of children and adults requires a focused history of chronic cough to identify any red flag cough pointers that may indicate an underlying disease. Further assessment with examination should include a chest x-ray and spirometry (when age > 6 years). Separate paediatric and adult diagnostic management algorithms should be followed. Management of the underlying condition(s) should follow specific disease guidelines, as well as address adverse environmental exposures and patient/carer concerns. First Nations adults and children should be considered a high risk group. The full statement from the Thoracic Society of Australia and New Zealand and Lung Foundation Australia for managing chronic cough is available at https://lungfoundation.com.au/resources/cicada-full-position-statement. CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: Algorithms for assessment and diagnosis of adult and paediatric chronic cough are recommended. High quality evidence supports the use of child-specific chronic cough management algorithms to improve clinical outcomes, but none exist in adults. Red flags that indicate serious underlying conditions requiring investigation or referral should be identified. Early and effective treatment of chronic wet/productive cough in children is critical. Culturally specific strategies for facilitating the management of chronic cough in First Nations populations should be adopted. If the chronic cough does not resolve or is unexplained, the patient should be referred to a respiratory specialist or cough clinic.

Smoking, respiratory symptoms, lung function and life expectancy: A longitudinal study of ageing.

BACKGROUND AND OBJECTIVE: Prognostic indices have been developed to predict various outcomes, including mortality. These indices and hazard ratios may be difficult for patients to understand. We investigated the association between smoking, respiratory symptoms and lung function with remaining life expectancy (LE) in older adults. METHODS: Data were from the 2004/05 English Longitudinal Study of Ageing (ELSA) (n = 8930), participants aged ≥50-years, with mortality data until 2012. Respiratory symptoms included were chronic phlegm and shortness of breath (SOB). The association between smoking, respiratory symptoms and FEV1/FVC, and remaining LE was estimated using a parametric survival function and adjusted for covariates including age at baseline and sex. RESULTS: The extent to which symptoms and FEV1/FVC predicted differences in remaining LE varied by smoking. Compared to asymptomatic never smokers with normal lung function (the reference group), in never smokers, only those with SOB had a significant reduction in remaining LE. In former and current smokers, those with respiratory symptoms had significantly lower remaining LE compared to the reference group if they had FEV1/FVC <0.70 compared to those with FEV1/FVC ≥0.70. Males aged 50-years, current smokers with SOB and FEV1/FVC <0.70, had a remaining LE of 19.2 (95%CI: 16.5-22.2) years, a decrease of 8.1 (5.3-10.8) years, compared to the reference group. CONCLUSION: Smoking, respiratory symptoms and FEV1/FVC are strongly associated with remaining LE in older people. The use of remaining LE to communicate mortality risk to patients needs further investigation.

Multi-domain prognostic models used in middle-aged adults without known cognitive impairment for predicting subsequent dementia.

BACKGROUND: Dementia, a global health priority, has no current cure. Around 50 million people worldwide currently live with dementia, and this number is expected to treble by 2050. Some health conditions and lifestyle behaviours can increase or decrease the risk of dementia and are known as 'predictors'. Prognostic models combine such predictors to measure the risk of future dementia. Models that can accurately predict future dementia would help clinicians select high-risk adults in middle age and implement targeted risk reduction. OBJECTIVES: Our primary objective was to identify multi-domain prognostic models used in middle-aged adults (aged 45 to 65 years) for predicting dementia or cognitive impairment. Eligible multi-domain prognostic models involved two or more of the modifiable dementia predictors identified in a 2020 Lancet Commission report and a 2019 World Health Organization (WHO) report (less education, hearing loss, traumatic brain injury, hypertension, excessive alcohol intake, obesity, smoking, depression, social isolation, physical inactivity, diabetes mellitus, air pollution, poor diet, and cognitive inactivity). Our secondary objectives were to summarise the prognostic models, to appraise their predictive accuracy (discrimination and calibration) as reported in the development and validation studies, and to identify the implications of using dementia prognostic models for the management of people at a higher risk for future dementia. SEARCH METHODS: We searched MEDLINE, Embase, PsycINFO, CINAHL, and ISI Web of Science Core Collection from inception until 6 June 2022. We performed forwards and backwards citation tracking of included studies using the Web of Science platform.  SELECTION CRITERIA: We included development and validation studies of multi-domain prognostic models. The minimum eligible follow-up was five years. Our primary outcome was an incident clinical diagnosis of dementia based on validated diagnostic criteria, and our secondary outcome was dementia or cognitive impairment determined by any other method. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the references, extracted data using a template based on the CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies (CHARMS), and assessed risk of bias and applicability of included studies using the Prediction model Risk Of Bias ASsessment Tool (PROBAST). We synthesised the C-statistics of models that had been externally validated in at least three comparable studies.  MAIN RESULTS: We identified 20 eligible studies; eight were development studies and 12 were validation studies. There were 14 unique prognostic models: seven models with validation studies and seven models with development-only studies. The models included a median of nine predictors (range 6 to 34); the median number of modifiable predictors was five (range 2 to 11). The most common modifiable predictors in externally validated models were diabetes, hypertension, smoking, physical activity, and obesity. In development-only models, the most common modifiable predictors were obesity, diabetes, hypertension, and smoking. No models included hearing loss or air pollution as predictors. Nineteen studies had a high risk of bias according to the PROBAST assessment, mainly because of inappropriate analysis methods, particularly lack of reported calibration measures. Applicability concerns were low for 12 studies, as their population, predictors, and outcomes were consistent with those of interest for this review. Applicability concerns were high for nine studies, as they lacked baseline cognitive screening or excluded an age group within the range of 45 to 65 years. Only one model, Cardiovascular Risk Factors, Ageing, and Dementia (CAIDE), had been externally validated in multiple studies, allowing for meta-analysis. The CAIDE model included eight predictors (four modifiable predictors): age, education, sex, systolic blood pressure, body mass index (BMI), total cholesterol, physical activity and APOEƐ4 status. Overall, our confidence in the prediction accuracy of CAIDE was very low; our main reasons for downgrading the certainty of the evidence were high risk of bias across all the studies, high concern of applicability, non-overlapping confidence intervals (CIs), and a high degree of heterogeneity. The summary C-statistic was 0.71 (95% CI 0.66 to 0.76; 3 studies; very low-certainty evidence) for the incident clinical diagnosis of dementia, and 0.67 (95% CI 0.61 to 0.73; 3 studies; very low-certainty evidence) for dementia or cognitive impairment based on cognitive scores. Meta-analysis of calibration measures was not possible, as few studies provided these data. AUTHORS' CONCLUSIONS: We identified 14 unique multi-domain prognostic models used in middle-aged adults for predicting subsequent dementia. Diabetes, hypertension, obesity, and smoking were the most common modifiable risk factors used as predictors in the models. We performed meta-analyses of C-statistics for one model (CAIDE), but the summary values were unreliable. Owing to lack of data, we were unable to meta-analyse the calibration measures of CAIDE. This review highlights the need for further robust external validations of multi-domain prognostic models for predicting future risk of dementia in middle-aged adults.

Which smokers enroll in a hospital based smoking cessation trial? Survey of smoking related behaviors, quit attempts, and motivation to quit.

BACKGROUND: Understanding smoking behaviors in hospital patients who smoke may improve inpatient cessation treatments. This study aimed to describe smoking-related behaviors, past-quit attempts, and self-reported difficulties experienced in quitting among those who enrolled in a smoking cessation trial of varenicline. METHODS: Baseline data were obtained from adult hospitalized smokers (average ≥ 10 cigarettes/day in 4-weeks prior to hospitalization) who enrolled in a randomized, placebo-controlled trial of varenicline ± nicotine lozenges at five Australian public hospitals. A logistic regression model tested the association between participant characteristics and quitting in the previous 12 months. RESULTS: Participants' (n = 320; 57% male, 52.5 ± 12.1 years old) motivation and confidence in quitting were high. A total of 120 participants (37.5%) had attempted quitting in the previous 12-months. Prior hospitalization (P = .008) and employment status (P = .015) were significantly associated with past quit attempts. No statistically significant differences were noted in the reason for hospitalization or the level of nicotine dependence between participants who attempted quitting in the previous 12 months and their counterparts. Smoking cessation pharmacotherapy was used by 55% of those attempting to quit; nicotine replacement therapy (65.2%) and varenicline (16.7%) most common. Stress or anxiety, urges to smoke and a lack of motivation were the difficulties experienced in past quit attempts. CONCLUSIONS: Those who had a prior hospitalization and were unemployed had significantly greater odds of reporting past quit attempts. Further research is needed to investigate the degree of adherence among inpatient smokers with the smoke-free hospital policies and the frequency of NRT provision and uptake on admission.

COPD-X Australian guidelines for the diagnosis and management of chronic obstructive pulmonary disease: 2022 update.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a treatable and preventable disease characterised by persistent respiratory symptoms and chronic airflow limitation on spirometry. COPD is highly prevalent and is associated with exacerbations and comorbid conditions. "COPD-X" provides quarterly updates in COPD care and is published by the Lung Foundation Australia and the Thoracic Society of Australia and New Zealand. MAIN RECOMMENDATIONS: The COPD-X guidelines (version 2.65) encompass 26 recommendations addressing: case finding and confirming diagnosis; optimising function; preventing deterioration; developing a plan of care; and managing an exacerbation. CHANGES IN MANAGEMENT AS A RESULT OF THESE GUIDELINES: Both non-pharmacological and pharmacological strategies are included within these recommendations, reflecting the importance of a holistic approach to clinical care for people living with COPD to delay disease progression, optimise quality of life and ensure best practice care in the community and hospital settings when managing exacerbations. Several of the new recommendations, if put into practice in the appropriate circumstances, and notwithstanding known variations in the social determinants of health, could improve quality of life and reduce exacerbations, hospitalisations and mortality for people living with COPD.

Validity of three risk prediction models for dementia or cognitive impairment in Australia.

BACKGROUND: no studies have compared the predictive validity of different dementia risk prediction models in Australia. OBJECTIVES: (i) to investigate the predictive validity of the Australian National University-Alzheimer's Disease Risk Index (ANU-ADRI), LIfestyle for BRAin Health (LIBRA) Index and cardiovascular risk factors, ageing and dementia study (CAIDE) models for predicting probable dementia/cognitive impairment in an Australian cohort. (ii) To develop and assess the predictive validity of a new hybrid model combining variables from the three models. METHODS: the Hunter Community Study (HCS) included 3,306 adults aged 55-85 years with a median follow-up of 7.1 years. Probable dementia/cognitive impairment was defined using Admitted Patient Data Collection, dispensing of cholinesterase inhibitors or memantine, or a cognitive test. Model validity was assessed by calibration and discrimination. A hybrid model was developed using deep neural network analysis, a machine learning method. RESULTS: 120 (3.6%) participants developed probable dementia/cognitive impairment. Mean calibration by ANU-ADRI, LIBRA, CAIDE and the hybrid model was 19, 0.5, 4.7 and 3.4%, respectively. The discrimination of the models was 0.65 (95% CI 0.60-0.70), 0.65 (95% CI 0.60-0.71), 0.54 (95% CI 0.49-0.58) and 0.80 (95% CI 0.78-0.83), respectively. CONCLUSION: ANU-ADRI and LIBRA were better dementia prediction tools than CAIDE for identification of high-risk individuals in this cohort. ANU-ADRI overestimated and LIBRA underestimated the risk. The new hybrid model had a higher predictive performance than the other models but it needs to be validated independently in longitudinal studies.

Educational interventions for health professionals managing chronic obstructive pulmonary disease in primary care.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common, preventable and treatable health condition. COPD is associated with substantial burden on morbidity, mortality and healthcare resources. OBJECTIVES: To review existing evidence for educational interventions delivered to health professionals managing COPD in the primary care setting. SEARCH METHODS: We searched the Cochrane Airways Trials Register from inception to May 2021. The Register includes records from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Allied and Complementary Medicine Database (AMED) and PsycINFO. We also searched online trial registries and reference lists of included studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and cluster-RCTs. Eligible studies tested educational interventions aimed at any health professionals involved in the management of COPD in primary care. Educational interventions were defined as interventions aimed at upskilling, improving or refreshing existing knowledge of health professionals in the diagnosis and management of COPD. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed abstracts and full texts of eligible studies, extracted data and assessed the risk of bias of included studies. We conducted meta-analyses where possible and used random-effects models to yield summary estimates of effect (mean differences (MDs) with 95% confidence intervals (CIs)). We performed narrative synthesis when meta-analysis was not possible. We assessed the overall certainty of evidence for each outcome using Grades of Recommendation, Assessment, Development and Evaluation (GRADE). Primary outcomes were: 1) proportion of COPD diagnoses confirmed with spirometry; 2) proportion of patients with COPD referred to, participating in or completing pulmonary rehabilitation; and 3) proportion of patients with COPD prescribed respiratory medication consistent with guideline recommendations. MAIN RESULTS: We identified 38 studies(22 cluster-RCTs and 16 RCTs) involving 4936 health professionals (reported in 19/38 studies) and 71,085 patient participants (reported in 25/38 studies). Thirty-six included studies evaluated interventions versus usual care; seven studies also reported a comparison between two or more interventions as part of a three- to five-arm RCT design. A range of simple to complex interventions were used across the studies, with common intervention features including education provided to health professionals via training sessions, workshops or online modules (31 studies), provision of practice support tools, tool kits and/or algorithms (10 studies), provision of guidelines (nine studies) and training on spirometry (five studies). Health professionals targeted by the interventions were most commonly general practitioners alone (20 studies) or in combination with nurses or allied health professionals (eight studies), and the majority of studies were conducted in general practice clinics. We identified performance bias as high risk for 33 studies. We also noted risk of selection, detection, attrition and reporting biases, although to a varying extent across studies. The evidence of efficacy was equivocal for all the three primary endpoints evaluated: 1) proportion of COPD diagnoses confirmed with spirometry (of the four studies that reported this outcome, two supported the intervention); 2) proportion of patients with COPD who are referred to, participate in or complete pulmonary rehabilitation (of the four studies that reported this outcome, two supported the intervention); and 3) proportion of patients with COPD prescribed respiratory medications consistent with guideline recommendations (12 studies reported this outcome, the majority evaluated multiple drug classes and reported a mixed effect). Additionally, the low quality of evidence and potential risk of bias make the interpretation more difficult. Moderate-quality evidence (downgraded due to risk of bias concerns) suggests that educational interventions for health professionals probably improve the proportion of patients with COPD vaccinated against influenza (three studies) and probably have little impact on the proportion of patients vaccinated against pneumococcal infection (two studies). Low-quality evidence suggests that educational interventions for health professionals may have little or no impact on the frequency of COPD exacerbations (10 studies). There was a high degree of heterogeneity in the reporting of health-related quality of life (HRQoL). Low-quality evidence suggests that educational interventions for health professionals may have little or no impact on HRQoL overall, and when using the COPD-specific HRQoL instrument, the St George's Respiratory Questionnaire (at six months MD 0.87, 95% CI -2.51 to 4.26; 2 studies, 406 participants, and at 12 months MD -0.43, 95% CI -1.52 to 0.67, 4 studies, 1646 participants; reduction in score indicates better health). Moderate-quality evidence suggests that educational interventions for health professionals may improve patient satisfaction with care (one study). We identified no studies that reported adverse outcomes. AUTHORS' CONCLUSIONS: The evidence of efficacy was equivocal for educational interventions for health professionals in primary care on the proportion of COPD diagnoses confirmed with spirometry, the proportion of patients with COPD who participate in pulmonary rehabilitation, and the proportion of patients prescribed guideline-recommended COPD respiratory medications. Educational interventions for health professionals may improve influenza vaccination rates among patients with COPD and patient satisfaction with care. The quality of evidence for most outcomes was low or very low due to heterogeneity and methodological limitations of the studies included in the review, which means that there is uncertainty about the benefits of any currently published educational interventions for healthcare professionals to improve COPD management in primary care. Further well-designed RCTs are needed to investigate the effects of educational interventions delivered to health professionals managing COPD in the primary care setting.

Pregnant women's experiences with the management of hypertensive disorders of pregnancy: a qualitative study.

BACKGROUND: Hypertensive disorders are a leading cause of mortality and morbidity during pregnancy. Despite multiple national and international clinical guidelines and a plethora of research in the field of optimising management, there has been limited research describing the perspectives and experiences of pregnant women with the management of hypertensive disorders of pregnancy (HDP). Understanding these perceptions and experiences is imperative to the optimisation of HDP management. METHODS: A qualitative study involving face-to-face, in-depth interviews were undertaken with 27 pregnant women diagnosed with and being treated for HDP to explore their perspectives of and experiences with clinical management. Written consent was obtained individually from each participant, and the interviews ranged from 16 to 54 min. Inductive codes were generated systematically for the entire data set. Line-by-line analysis was then performed and nodes were created within NVivo, a qualitative data management software. Data collection was continued until thematic saturation was reached. Thematic analysis was employed to interpret the data. RESULTS: Three major descriptive themes were discerned regarding the women's perspectives on and experiences with the management of HDP: attitudes towards monitoring of HDP, attitudes and perceptions towards development and management of complications, and perceptions of pregnant women with chronic hypertension. Trust in the hospital system, positive attitudes towards close blood pressure monitoring as well as self-monitoring of blood pressure, and a realistic approach to emergency antenatal hospital admissions contributed to a positive attitude towards monitoring of HDP. Women with prior experiences of HDP complications, including pre-eclampsia, were more confident in their clinical management and knew what to expect. Those without prior experience were often in shock when they developed pre-eclampsia. Some women with chronic hypertension displayed limited understanding of the potential risks that they may experience during pregnancy and thus lacked comprehension of the seriousness of the condition. CONCLUSIONS: The clinical management experiences of pregnant women with HDP were varied. Many women did not feel that they were well informed of management decisions and had a desire to be more informed and involved in decision-making. Clear, concise information about various facets of HDP management including blood pressure monitoring, prescription of the appropriate antihypertensive agent, and planning for potential early delivery are required.

De novo transcriptome sequencing assisted identification of terpene synthases from black pepper (Piper nigrum) berry.

Though the volatile profiles of black pepper have been reported already, the information on terpene synthase family genes is not known. In this study, using a combinatorial approach, the berry hybrid transcriptome assembly of llumina and nanopore sequencing, the entire terpene synthase family responsible for the biosynthesis of the flavor-imparting volatiles in black pepper berries was profiled. The profile shows 98 terpene synthases from various terpene synthesis pathways. Three important monoterpene synthases were also validated by targeted amplification, sequencing and homology modeling. This study provides the first of its kind information on the terpene synthase family profile in Piper nigrum, which is potentially a major step for further characterization of the functional terpene synthase genes in black pepper. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-021-00986-4.

Systematic review and meta-analysis of the prevalence of smokeless tobacco consumption among adults in Bangladesh, India and Myanmar.

OBJECTIVE: To estimate the pooled prevalence of smokeless tobacco consumption (STC) by gender and location in Bangladesh, India and Myanmar and to identify periodic changes in STC prevalence using data extracted from published studies. METHODS: We searched for a combination of keywords in electronic databases and used a standard form to extract data from each article. We undertook a meta-analysis to estimate pooled prevalence and confidence intervals within these countries. To compare periodic changes in STC prevalence, we grouped studies into five-year periods (2000-2004, 2005-2009, 2010-2014 and 2015-2019). RESULTS: The pooled estimates of STC prevalence were 25% (95% CI: 22-28%), 22% (95% CI: 15-28%) and 21% (95% CI: 14-28%) for Bangladesh, India and Myanmar, respectively. In pooled estimates across these countries, we found higher STC prevalence for men (30%; 95% CI: 24-35%) than women (16%; 95% CI: 10-23%) and for rural dwellings (24%; 95% CI: 18-31%) than urban dwellings (17%; 95% CI: 10-24%). We found significant decrease in STC in Bangladesh and India in the period 2010-2014 and 2015-2019, respectively. In Myanmar, STC prevalence increased significantly and substantially in 2010-2014, to levels higher than in Bangladesh and India. CONCLUSIONS: The prevalence of STC in Bangladesh, India and Myanmar is highest in rural areas and among men. Public health prevention strategies are needed to maintain decrease in STC in Bangladesh and India, and to reverse the increased use in Myanmar.

OBJECTIF: Estimer la prévalence poolée de la consommation de tabac sans fumée (CTSF) par sexe et lieu au Bangladesh, en Inde et au Myanmar et identifier les changements périodiques de la prévalence des CTSF à l'aide de données extraites d'études publiées. MÉTHODES: Nous avons recherché une combinaison de mots-clés dans les bases de données électroniques et utilisé un formulaire standard pour extraire les données de chaque article. Nous avons entrepris une méta-analyse pour estimer la prévalence poolée et les intervalles de confiance dans ces pays. Pour comparer les changements périodiques de la prévalence des CTSF, nous avons regroupé les études en périodes de cinq ans (2000-2004, 2005-2009, 2010-2014, 2015-2019). RÉSULTATS: Les estimations poolées de la prévalence des CTSF étaient de 25% (IC95%: 22-28%), 22% (IC95%: 15-28%) et 21% (IC95%: 14-28%) pour le Bangladesh, l'Inde et le Myanmar, respectivement. Dans les estimations poolées de ces pays, nous avons constaté une prévalence des CTSF plus élevée pour les hommes (30%; IC95%: 24-35%) que pour les femmes (16%; IC95%: 10-23%) et pour les habitations rurales (24%; IC95%: 18-31%) que les habitations urbaines (17%; IC95%: 10-24%). Nous avons constaté une diminution significative des CTSF au Bangladesh et en Inde au cours de la période 2010-2014 et 2015-2019 respectivement. Au Myanmar, la prévalence des CTSF a augmenté de manière significative et substantielle en 2010-2014, à des niveaux plus élevés qu'au Bangladesh et en Inde. CONCLUSIONS: La prévalence des CTSF au Bangladesh, en Inde et au Myanmar est la plus élevée dans les zones rurales et chez les hommes. Des stratégies de prévention de la santé publique sont nécessaires pour maintenir la diminution des CTSF au Bangladesh et en Inde et pour inverser l'augmentation de la consommation au Myanmar.

Predicting life expectancy of older people using respiratory symptoms and smoking status: Data from the Australian Longitudinal Study of Ageing.

BACKGROUND AND OBJECTIVE: Respiratory symptoms are recognizable to patients and may be markers of chronic disease and mortality risk. This risk may be easier to conceptualize if presented as remaining life expectancy (LE) rather than hazard ratios. We aimed to predict the remaining LE of older people with respiratory symptoms using data from the Australian Longitudinal Study of Ageing (ALSA). METHODS: The ALSA is a prospective longitudinal cohort of older Australians (n = 2087) with 22 years of follow-up. The symptoms analysed were cough, shortness of breath (SOB) and wheeze. The implied impact on LE was estimated using a parametric survival function. RESULTS: SOB predicted shorter LE irrespective of smoking status. Cough predicted shorter LE in former smokers and wheeze predicted shorter LE in current smokers. The estimated remaining LE of a 70-year-old male never smoker with no symptoms was 16.6 (95% CI: 14.8-17.7) years. The years of life lost for a 70-year-old male current smoker with cough, SOB and wheeze compared to a never smoker with no symptoms was 4.93 (95% CI: 2.87-7.36) years with only 2.99 (95% CI: 1.35-4.97) years being attributed to their current smoking and the remainder to their respiratory symptoms. CONCLUSION: Respiratory symptoms predict mortality in older people. Cough in former smokers, wheeze in current smokers and all those with SOB require further investigations and disease-specific management.

Interventions for improving medication-taking ability and adherence in older adults prescribed multiple medications.

BACKGROUND: Older people taking multiple medications represent a large and growing proportion of the population. Managing multiple medications can be challenging, and this is especially the case for older people, who have higher rates of comorbidity and physical and cognitive impairment than younger adults. Good medication-taking ability and medication adherence are necessary to ensure safe and effective use of medications. OBJECTIVES: To evaluate the effectiveness of interventions designed to improve medication-taking ability and/or medication adherence in older community-dwelling adults prescribed multiple long-term medications. SEARCH METHODS: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PsycINFO, CINAHL Plus, and International Pharmaceutical Abstracts from inception until June 2019. We also searched grey literature, online trial registries, and reference lists of included studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs), quasi-RCTs, and cluster-RCTs. Eligible studies tested interventions aimed at improving medication-taking ability and/or medication adherence among people aged ≥ 65 years (or of mean/median age > 65 years), living in the community or being discharged from hospital back into the community, and taking four or more regular prescription medications (or with group mean/median of more than four medications). Interventions targeting carers of older people who met these criteria were also included. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed abstracts and full texts of eligible studies, extracted data, and assessed risk of bias of included studies. We conducted meta-analyses when possible and used a random-effects model to yield summary estimates of effect, risk ratios (RRs) for dichotomous outcomes, and mean differences (MDs) or standardised mean differences (SMDs) for continuous outcomes, along with 95% confidence intervals (CIs). Narrative synthesis was performed when meta-analysis was not possible. We assessed overall certainty of evidence for each outcome using Grades of Recommendation, Assessment, Development and Evaluation (GRADE). Primary outcomes were medication-taking ability and medication adherence. Secondary outcomes included health-related quality of life (HRQoL), emergency department (ED)/hospital admissions, and mortality. MAIN RESULTS: We identified 50 studies (14,269 participants) comprising 40 RCTs, six cluster-RCTs, and four quasi-RCTs. All included studies evaluated interventions versus usual care; six studies also reported a comparison between two interventions as part of a three-arm RCT design. Interventions were grouped on the basis of their educational and/or behavioural components: 14 involved educational components only, 7 used behavioural strategies only, and 29 provided mixed educational and behavioural interventions. Overall, our confidence in results regarding the effectiveness of interventions was low to very low due to a high degree of heterogeneity of included studies and high or unclear risk of bias across multiple domains in most studies. Five studies evaluated interventions for improving medication-taking ability, and 48 evaluated interventions for improving medication adherence (three studies evaluated both outcomes). No studies involved educational or behavioural interventions alone for improving medication-taking ability. Low-quality evidence from five studies, each using a different measure of medication-taking ability, meant that we were unable to determine the effects of mixed interventions on medication-taking ability. Low-quality evidence suggests that behavioural only interventions (RR 1.22, 95% CI 1.07 to 1.38; 4 studies) and mixed interventions (RR 1.22, 95% CI 1.08 to 1.37; 12 studies) may increase the proportions of people who are adherent compared with usual care. We could not include in the meta-analysis results from two studies involving mixed interventions: one had a positive effect on adherence, and the other had little or no effect. Very low-quality evidence means that we are uncertain of the effects of educational only interventions (5 studies) on the proportions of people who are adherent. Low-quality evidence suggests that educational only interventions (SMD 0.16, 95% CI -0.12 to 0.43; 5 studies) and mixed interventions (SMD 0.47, 95% CI -0.08 to 1.02; 7 studies) may have little or no impact on medication adherence assessed through continuous measures of adherence. We excluded 10 studies (4 educational only and 6 mixed interventions) from the meta-analysis including four studies with unclear or no available results. Very low-quality evidence means that we are uncertain of the effects of behavioural only interventions (3 studies) on medication adherence when assessed through continuous outcomes. Low-quality evidence suggests that mixed interventions may reduce the number of ED/hospital admissions (RR 0.67, 95% CI 0.50 to 0.90; 11 studies) compared with usual care, although results from six further studies that we were unable to include in meta-analyses indicate that the intervention may have a smaller, or even no, effect on these outcomes. Similarly, low-quality evidence suggests that mixed interventions may lead to little or no change in HRQoL (7 studies), and very low-quality evidence means that we are uncertain of the effects on mortality (RR 0.93, 95% CI 0.67 to 1.30; 7 studies). Moderate-quality evidence shows that educational interventions alone probably have little or no effect on HRQoL (6 studies) or on ED/hospital admissions (4 studies) when compared with usual care. Very low-quality evidence means that we are uncertain of the effects of behavioural interventions on HRQoL (1 study) or on ED/hospital admissions (2 studies). We identified no studies evaluating effects of educational or behavioural interventions alone on mortality. Six studies reported a comparison between two interventions; however due to the limited number of studies assessing the same types of interventions and comparisons, we are unable to draw firm conclusions for any outcomes. AUTHORS' CONCLUSIONS: Behavioural only or mixed educational and behavioural interventions may improve the proportion of people who satisfactorily adhere to their prescribed medications, but we are uncertain of the effects of educational only interventions. No type of intervention was found to improve adherence when it was measured as a continuous variable, with educational only and mixed interventions having little or no impact and evidence of insufficient quality to determine the effects of behavioural only interventions. We were unable to determine the impact of interventions on medication-taking ability. The quality of evidence for these findings is low due to heterogeneity and methodological limitations of studies included in the review. Further well-designed RCTs are needed to investigate the effects of interventions for improving medication-taking ability and medication adherence in older adults prescribed multiple medications.

Interdisciplinary COPD intervention in primary care: a cluster randomised controlled trial.

We evaluated the effectiveness of an interdisciplinary, primary care-based model of care for chronic obstructive pulmonary disease (COPD).A cluster randomised controlled trial was conducted in 43 general practices in Australia. Adults with a history of smoking and/or COPD, aged ≥40 years with two or more clinic visits in the previous year were enrolled following spirometric confirmation of COPD. The model of care comprised smoking cessation support, home medicines review (HMR) and home-based pulmonary rehabilitation (HomeBase). Main outcomes included changes in St George's Respiratory Questionnaire (SGRQ) score, COPD Assessment Test (CAT), dyspnoea, smoking abstinence and lung function at 6 and 12 months.We identified 272 participants with COPD (157 intervention, 115 usual care); 49 (31%) out of 157 completed both HMR and HomeBase. Intention-to-treat analysis showed no statistically significant difference in change in SGRQ at 6 months (adjusted between-group difference 2.45 favouring intervention, 95% CI -0.89-5.79). Per protocol analyses showed clinically and statistically significant improvements in SGRQ in those receiving the full intervention compared to usual care (difference 5.22, 95% CI 0.19-10.25). No statistically significant differences were observed in change in CAT, dyspnoea, smoking abstinence or lung function.No significant evidence was found for the effectiveness of this interdisciplinary model of care for COPD in primary care over usual care. Low uptake was a limitation.

The Prevalence and Nature of Medication Errors and Adverse Events Related to Preadmission Medications When Patients Are Admitted to an Orthopedic Inpatient Unit: An Observational Study.

BACKGROUND: Medication errors commonly occur when patients move from the community into hospital. Whereas medication reconciliation by pharmacists can detect errors, delays in undertaking this can increase the risk that patients receive incorrect admission medication regimens. Orthopedic patients are an at-risk group because they are often elderly and use multiple medications. OBJECTIVE: To evaluate the prevalence and nature of medication errors when patients are admitted to an orthopedic unit where pharmacists routinely undertake postprescribing medication reconciliation. METHODS: A 10-week retrospective observational study was conducted at a major metropolitan hospital in Australia. Medication records of orthopedic inpatients were evaluated to determine the number of prescribing and administration errors associated with patients' preadmission medications and the number of related adverse events that occurred within 72 hours of admission. RESULTS: Preadmission, 198 patients were taking at least 1 regular medication, of whom 176 (88.9%) experienced at least 1 medication error. The median number of errors per patient was 6 (interquartile range 3-10). Unintended omission of a preadmission medication was the most common prescribing error (87.4%). There were 17 adverse events involving 24 medications in 16 (8.1%) patients that were potentially related to medication errors; 6 events were deemed moderate consequence (moderate injury or harm, increased length of stay, or cancelled/delayed treatment), and the remainder were minor. Conclusion and Relevance: Medication errors were common when orthopedic patients were admitted to hospital, despite postprescribing pharmacist medication reconciliation. Some of these errors led to patient harm. Interventions that ensure that medications are prescribed correctly at admission are required.

Comorbid tobacco and other substance use and symptoms of anxiety and depression among hospitalised orthopaedic trauma patients.

BACKGROUND: No study has examined the prevalence of tobacco, other substance use, and symptoms of anxiety and depression, and rates of comorbidities among the orthopaedic trauma population, despite the impact they have on recovery from surgery. This study aims to 1) describe the rates of symptoms and substance use; 2) compare rates of symptoms and substance use among smokers versus non-smokers; and 3) examine the relationship between symptoms and substance use with smoking status. METHODS: A cross-sectional survey of orthopaedic trauma patients was conducted in two Australian public hospitals. Demographic characteristics, smoking status, alcohol consumption, recent cannabis use, and symptoms of anxiety and/or depression were examined. Differences between current and non-smokers were compared using Pearson Chi2 tests. Multivariate logistic regression explored variables related to tobacco smoking. RESULTS: Eight hundred nineteen patients participated. Over one-fifth (21.8%) identified as a current smoker, half (51.8%) reported consuming alcohol at hazardous levels in the last 12 months, and about 10% stated that they had used cannabis in the last 30 days (9.7%), or experienced symptoms of either anxiety (12.4%), or depression (12.9%) in the last two weeks. Over one-fifth of current tobacco smokers (21.8%) reported drinking heavily in the last 12 months and using cannabis recently. Males, with a lower educational attainment, who were unmarried, had used cannabis recently, and report drinking heavily were more likely to be current smokers. CONCLUSIONS: Health behaviour interventions addressing comorbidities are warranted among the orthopaedic trauma population given the high rate of comorbidity and impact these may have on recovery.

Diagnosing COPD and supporting smoking cessation in general practice: evidence-practice gaps.

OBJECTIVES: To review the accuracy of diagnoses of chronic obstructive pulmonary disease (COPD) in primary care in Australia, and to describe smokers' experiences with and preferences for smoking cessation. DESIGN, SETTING AND PARTICIPANTS: Patients were invited to participate if they were at least 40 years old and had visited participating general practice clinics in Melbourne at least twice during the previous 12 months, reported being current or ex-smokers with a smoking history of at least 10 pack-years, or were being managed for COPD. Interviews based on a structured questionnaire and case finding (FEV1/FEV6 measurement) were followed, when appropriate, by spirometry testing and assessment of health-related quality of life, dyspnoea and symptoms. RESULTS: 1050 patients attended baseline interviews (February 2015 - April 2017) at 41 practices. Of 245 participants managed for COPD, 130 (53.1%) met the spirometry-based definition (post-bronchodilator FEV1/FVC < 0.7) or had a clinical correlation; in 37% of cases COPD was not confirmed, and no definitive result was obtained for 9.8% of patients. Case finding and subsequent spirometry testing identified 142 new COPD cases (17.6% of participants without prior diagnosis; 95% CI, 15.1-20.5%). 690 participants (65.7%) were current smokers, of whom 360 had attempted quitting during the previous 12 months; 286 (81.0% of those attempting to quit) reported difficulties during previous quit attempts. Nicotine replacement therapy (205, 57.4%) and varenicline (110, 30.8%) were the most frequently employed pharmacological treatments; side effects were common. Hypnotherapy was the most popular non-pharmacological option (62 smokers, 17%); e-cigarettes were tried by 38 (11%). 187 current smokers (27.6%) would consider using e-cigarettes in future attempts to quit. CONCLUSIONS: COPD was both misdiagnosed and missed. Case finding and effective use of spirometry testing could improve diagnosis. Side effects of smoking cessation medications and difficulties during attempts to quit smoking are common. Health professionals should emphasise evidence-based treatments, and closely monitor quitting difficulties and side effects of cessation aids. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12614001155684.

Medication management for community palliative care patients and the role of a specialist palliative care pharmacist: A qualitative exploration of consumer and health care professional perspectives.

BACKGROUND: Pharmacists have a key role to play in optimisation of medication regimens and promotion of medication safety. The role of specialist pharmacists as part of the multidisciplinary palliative care team, especially in the primary care setting, is not widely recognised. AIM: To explore the perspectives of stakeholders about the gaps in the current model of community palliative care services in relation to medication management and to assess their opinions pertaining to the role of a specialist palliative care pharmacist in addressing some of those gaps. DESIGN: Qualitative study utilising three focus groups involving 20 stakeholders. Thematic analysis was carried out using a framework approach and interpreted in the context of the Chronic Care Model for improving primary care for patients with chronic illness. SETTING/PARTICIPANTS: Setting was a large regional Australian palliative care service. Participants included palliative care consumers and clinicians specifically patients, caregivers, physicians, nurses and pharmacists. RESULTS: Five major themes emerged from the focus groups: access to resources, medicines and information; shared care; challenges of polypharmacy; informal caregiver needs and potential roles of a palliative care pharmacist. Gaps in access to medicines/resources, training for generalist practitioners, communication between treating teams and lack of support for patients and carers were cited as factors adversely impacting medication management in community-based palliative care. CONCLUSION: While community-based palliative care is an essential aspect of meeting the health care demands of an ageing society, the current model has several gaps and limitations. An appropriately qualified and skilled pharmacist within the palliative care team may help to address some of the gaps in relation to medication access and appropriateness.

Proteomics assisted profiling of antimicrobial peptide signatures from black pepper (Piper nigrum L.).

Plant antimicrobial peptides are the interesting source of studies in defense response as they are essential components of innate immunity which exert rapid defense response. In spite of abundant reports on the isolation of antimicrobial peptides (AMPs) from many sources, the profile of AMPs expressed/identified from single crop species under certain stress/physiological condition is still unknown. This work describes the AMP signature profile of black pepper and their expression upon Phytophthora infection using label-free quantitative proteomics strategy. The differential expression of 24 AMPs suggests that a combinatorial strategy is working in the defense network. The 24 AMP signatures belonged to the cationic, anionic, cysteine-rich and cysteine-free group. As the first report on the possible involvement of AMP signature in Phytophthora infection, our results offer a platform for further study on regulation, evolutionary importance and exploitation of theses AMPs as next generation molecules against pathogens.

Self-monitoring of blood pressure in hypertension: A systematic review and individual patient data meta-analysis.

BACKGROUND: Self-monitoring of blood pressure (BP) appears to reduce BP in hypertension but important questions remain regarding effective implementation and which groups may benefit most. This individual patient data (IPD) meta-analysis was performed to better understand the effectiveness of BP self-monitoring to lower BP and control hypertension. METHODS AND FINDINGS: Medline, Embase, and the Cochrane Library were searched for randomised trials comparing self-monitoring to no self-monitoring in hypertensive patients (June 2016). Two reviewers independently assessed articles for eligibility and the authors of eligible trials were approached requesting IPD. Of 2,846 articles in the initial search, 36 were eligible. IPD were provided from 25 trials, including 1 unpublished study. Data for the primary outcomes-change in mean clinic or ambulatory BP and proportion controlled below target at 12 months-were available from 15/19 possible studies (7,138/8,292 [86%] of randomised participants). Overall, self-monitoring was associated with reduced clinic systolic blood pressure (sBP) compared to usual care at 12 months (-3.2 mmHg, [95% CI -4.9, -1.6 mmHg]). However, this effect was strongly influenced by the intensity of co-intervention ranging from no effect with self-monitoring alone (-1.0 mmHg [-3.3, 1.2]), to a 6.1 mmHg (-9.0, -3.2) reduction when monitoring was combined with intensive support. Self-monitoring was most effective in those with fewer antihypertensive medications and higher baseline sBP up to 170 mmHg. No differences in efficacy were seen by sex or by most comorbidities. Ambulatory BP data at 12 months were available from 4 trials (1,478 patients), which assessed self-monitoring with little or no co-intervention. There was no association between self-monitoring and either lower clinic or ambulatory sBP in this group (clinic -0.2 mmHg [-2.2, 1.8]; ambulatory 1.1 mmHg [-0.3, 2.5]). Results for diastolic blood pressure (dBP) were similar. The main limitation of this work was that significant heterogeneity remained. This was at least in part due to different inclusion criteria, self-monitoring regimes, and target BPs in included studies. CONCLUSIONS: Self-monitoring alone is not associated with lower BP or better control, but in conjunction with co-interventions (including systematic medication titration by doctors, pharmacists, or patients; education; or lifestyle counselling) leads to clinically significant BP reduction which persists for at least 12 months. The implementation of self-monitoring in hypertension should be accompanied by such co-interventions.

A Review of Electronic Devices to Assess Inhaler Technique.

PURPOSE OF REVIEW: Multiple electronic devices exist that provide feedback on the accuracy of patient inhaler technique. Our purpose is to describe the inhaler technique feedback provided by these devices, including specific technique steps measured, how feedback is displayed, target of feedback (patient, provider, researcher), and compatibility with inhaler type (metered-dose inhaler [MDI], diskus, etc.). RECENT FINDINGS: We identified eight devices that provide feedback on inhaler technique. Only one device assessed all evidence-based MDI technique steps. Most devices provide limited real-time feedback to patients, if any feedback at all. Technologies to assess inhaler technique are advancing and hold great potential for improving patient inhaler technique. Many devices are limited in their ability to detect all evidence-based technique steps and provide real-time user-friendly feedback to patients and providers. Usability tests with patients and providers could identify ways to improve these devices to improve their utility in clinical settings.