Chemical and biological characterisation of solvent extracts and essential oils from leaves and fruit of two Australian species of Pittosporum (Pittosporaceae) used in aboriginal medicinal practice.

Although no known medicinal use for Pittosporum undulatum Vent. (Pittosporaceae) has been recorded, anecdotal evidence suggests that Australian Aboriginal people used Pittosporum angustifolium Lodd., G. Lodd. & W. Lodd. topically for eczema, pruritis or to induce lactation in mothers following child-birth and internally for coughs, colds or cramps. Essential oil composition and bioactivity as well as differential solvent extract antimicrobial activity from Pittosporum angustifolium are investigated here first, to partially describe the composition of volatiles released in traditional applications of Pittosporum angustifolium for colds or as a lactagogue, and second to investigate antibacterial activity related to topical applications. Essential oils were also investigated from Pittosporum undulatum Vent., first to enhance essential oil data produced in previous studies, and second as a comparison to Pittosporum angustifolium. Essential oils were hydrodistilled from fruit and leaves of both species using a modified approach to lessen the negative (frothing) effect of saponins. This was achieved by floating pumice or pearlite obsidian over the mixture to crush the suds formed while boiling. Essential oil extracts were analysed using GC-MS, quantified using GC-FID then screened for antimicrobial activity using a micro-titre plate broth dilution assay (MIC). Using dichloromethane, methanol, hexane and H(2)O as solvents, extracts were produced from leaves and fruit of Pittosporum angustifolium and screened for antimicrobial activity and qualitative phytochemical character. Although the essential oil from leaves and fruit of Pittosporum undulatum demonstrated some component variation, the essential oil from fruits of Pittosporum angustifolium had major constituents that strongly varied according to the geographical location of collection, suggesting the existence of at least two chemotypes; one with high abundance of acetic acid decyl ester. This chemotype had high antimicrobial activity whilst the other chemotype had only moderate antimicrobial activity against the three microbial species investigated here. This result may support the occurrence of geographical specificity with regard to ethnopharmacological use. Antimicrobial activity screening of the solvent extracts from Pittosporum angustifolium revealed the leaves to be superior to fruit, with water being the most suitable extraction solvent. To the best of our knowledge, this study constitutes the first time essential oils, and solvent extracts from the fruits of Pittosporum angustifolium, have been examined employing comprehensive chemical and biological analysis. The essential oil composition presented in this paper, includes components with structural similarity as chemosemiotic compounds involved in mother-infant identification, which may have significance with regard to traditional applications as a lactagogue.

Sadgrove NJ ，Jones GL 《-》

Falls prevention interventions for community-dwelling older adults: systematic review and meta-analysis of benefits, harms, and patient values and preferences.

About 20-30% of older adults (≥ 65 years old) experience one or more falls each year, and falls are associated with substantial burden to the health care system, individuals, and families from resulting injuries, fractures, and reduced functioning and quality of life. Many interventions for preventing falls have been studied, and their effectiveness, factors relevant to their implementation, and patient preferences may determine which interventions to use in primary care. The aim of this set of reviews was to inform recommendations by the Canadian Task Force on Preventive Health Care (task force) on fall prevention interventions. We undertook three systematic reviews to address questions about the following: (i) the benefits and harms of interventions, (ii) how patients weigh the potential outcomes (outcome valuation), and (iii) patient preferences for different types of interventions, and their attributes, shown to offer benefit (intervention preferences). We searched four databases for benefits and harms (MEDLINE, Embase, AgeLine, CENTRAL, to August 25, 2023) and three for outcome valuation and intervention preferences (MEDLINE, PsycINFO, CINAHL, to June 9, 2023). For benefits and harms, we relied heavily on a previous review for studies published until 2016. We also searched trial registries, references of included studies, and recent reviews. Two reviewers independently screened studies. The population of interest was community-dwelling adults ≥ 65 years old. We did not limit eligibility by participant fall history. The task force rated several outcomes, decided on their eligibility, and provided input on the effect thresholds to apply for each outcome (fallers, falls, injurious fallers, fractures, hip fractures, functional status, health-related quality of life, long-term care admissions, adverse effects, serious adverse effects). For benefits and harms, we included a broad range of non-pharmacological interventions relevant to primary care. Although usual care was the main comparator of interest, we included studies comparing interventions head-to-head and conducted a network meta-analysis (NMAs) for each outcome, enabling analysis of interventions lacking direct comparisons to usual care. For benefits and harms, we included randomized controlled trials with a minimum 3-month follow-up and reporting on one of our fall outcomes (fallers, falls, injurious fallers); for the other questions, we preferred quantitative data but considered qualitative findings to fill gaps in evidence. No date limits were applied for benefits and harms, whereas for outcome valuation and intervention preferences we included studies published in 2000 or later. All data were extracted by one trained reviewer and verified for accuracy and completeness. For benefits and harms, we relied on the previous review team's risk-of-bias assessments for benefit outcomes, but otherwise, two reviewers independently assessed the risk of bias (within and across study). For the other questions, one reviewer verified another's assessments. Consensus was used, with adjudication by a lead author when necessary. A coding framework, modified from the ProFANE taxonomy, classified interventions and their attributes (e.g., supervision, delivery format, duration/intensity). For benefit outcomes, we employed random-effects NMA using a frequentist approach and a consistency model. Transitivity and coherence were assessed using meta-regressions and global and local coherence tests, as well as through graphical display and descriptive data on the composition of the nodes with respect to major pre-planned effect modifiers. We assessed heterogeneity using prediction intervals. For intervention-related adverse effects, we pooled proportions except for vitamin D for which we considered data in the control groups and undertook random-effects pairwise meta-analysis using a relative risk (any adverse effects) or risk difference (serious adverse effects). For outcome valuation, we pooled disutilities (representing the impact of a negative event, e.g. fall, on one's usual quality of life, with 0 = no impact and 1 = death and ~ 0.05 indicating important disutility) from the EQ-5D utility measurement using the inverse variance method and a random-effects model and explored heterogeneity. When studies only reported other data, we compared the findings with our main analysis. For intervention preferences, we used a coding schema identifying whether there were strong, clear, no, or variable preferences within, and then across, studies. We assessed the certainty of evidence for each outcome using CINeMA for benefit outcomes and GRADE for all other outcomes. A total of 290 studies were included across the reviews, with two studies included in multiple questions. For benefits and harms, we included 219 trials reporting on 167,864 participants and created 59 interventions (nodes). Transitivity and coherence were assessed as adequate. Across eight NMAs, the number of contributing trials ranged between 19 and 173, and the number of interventions ranged from 19 to 57. Approximately, half of the interventions in each network had at least low certainty for benefit. The fallers outcome had the highest number of interventions with moderate certainty for benefit (18/57). For the non-fall outcomes (fractures, hip fracture, long-term care [LTC] admission, functional status, health-related quality of life), many interventions had very low certainty evidence, often from lack of data. We prioritized findings from 21 interventions where there was moderate certainty for at least some benefit. Fourteen of these had a focus on exercise, the majority being supervised (for > 2 sessions) and of long duration (> 3 months), and with balance/resistance and group Tai Chi interventions generally having the most outcomes with at least low certainty for benefit. None of the interventions having moderate certainty evidence focused on walking. Whole-body vibration or home-hazard assessment (HHA) plus exercise provided to everyone showed moderate certainty for some benefit. No multifactorial intervention alone showed moderate certainty for any benefit. Six interventions only had very-low certainty evidence for the benefit outcomes. Two interventions had moderate certainty of harmful effects for at least one benefit outcome, though the populations across studies were at high risk for falls. Vitamin D and most single-component exercise interventions are probably associated with minimal adverse effects. Some uncertainty exists about possible adverse effects from other interventions. For outcome valuation, we included 44 studies of which 34 reported EQ-5D disutilities. Admission to long-term care had the highest disutility (1.0), but the evidence was rated as low certainty. Both fall-related hip (moderate certainty) and non-hip (low certainty) fracture may result in substantial disutility (0.53 and 0.57) in the first 3 months after injury. Disutility for both hip and non-hip fractures is probably lower 12 months after injury (0.16 and 0.19, with high and moderate certainty, respectively) compared to within the first 3 months. No study measured the disutility of an injurious fall. Fractures are probably more important than either falls (0.09 over 12 months) or functional status (0.12). Functional status may be somewhat more important than falls. For intervention preferences, 29 studies (9 qualitative) reported on 17 comparisons among single-component interventions showing benefit. Exercise interventions focusing on balance and/or resistance training appear to be clearly preferred over Tai Chi and other forms of exercise (e.g., yoga, aerobic). For exercise programs in general, there is probably variability among people in whether they prefer group or individual delivery, though there was high certainty that individual was preferred over group delivery of balance/resistance programs. Balance/resistance exercise may be preferred over education, though the evidence was low certainty. There was low certainty for a slight preference for education over cognitive-behavioral therapy, and group education may be preferred over individual education. To prevent falls among community-dwelling older adults, evidence is most certain for benefit, at least over 1-2 years, from supervised, long-duration balance/resistance and group Tai Chi interventions, whole-body vibration, high-intensity/dose education or cognitive-behavioral therapy, and interventions of comprehensive multifactorial assessment with targeted treatment plus HHA, HHA plus exercise, or education provided to everyone. Adding other interventions to exercise does not appear to substantially increase benefits. Overall, effects appear most applicable to those with elevated fall risk. Choice among effective interventions that are available may best depend on individual patient preferences, though when implementing new balance/resistance programs delivering individual over group sessions when feasible may be most acceptable. Data on more patient-important outcomes including fall-related fractures and adverse effects would be beneficial, as would studies focusing on equity-deserving populations and on programs delivered virtually. Not registered.

Pillay J ，Gaudet LA ，Saba S ，Vandermeer B ，Ashiq AR ，Wingert A ，Hartling L ... -  《Systematic Reviews》

Qualitative evidence synthesis informing our understanding of people's perceptions and experiences of targeted digital communication.

Health communication is an area where changing technologies, particularly digital technologies, have a growing role to play in delivering and exchanging health information between individuals, communities, health systems, and governments.[1] Such innovation has the potential to strengthen health systems and services, with substantial investments in digital health already taking place, particularly in low‐ and middle‐income countries. Communication using mobile phones is an important way of contacting individual people and the public more generally to deliver and exchange health information. Such technologies are used increasingly in this capacity, but poor planning and short‐term projects may be limiting their potential for health improvement. The assumption that mobile devices will solve problems that other forms of communication have not is also prevalent. In this context, understanding people's views and experiences may lead to firmer knowledge on which to build better programs. A qualitative evidence synthesis by Heather Ames and colleagues on clients' perceptions and experiences of targeted digital communication focuses on a particular type of messaging – targeted messages from health services delivered to particular group(s) via mobile devices, in this case looking at communicating with pregnant women and parents of young children, and with adults and teenagers about sexual health and family planning.[2] These areas of reproductive, maternal, newborn, child, and adolescent health (RMNCAH) are where important gains have been made worldwide, but there remains room for improvement. Ames and colleagues sought to examine and understand people's perceptions and experiences of using digital targeted client communication. This might include communication in different formats and with a range of purposes related to RMNCAH – for example, receiving text message reminders to take medicines (e.g. HIV medicines) or go to appointments (such as childhood vaccination appointments), or phone calls offering information or education (such as about breastfeeding or childhood illnesses), support (e.g. providing encouragement to change behaviours) or advice (such as advising about local healthcare services). These communication strategies have the potential to improve health outcomes by communicating with people or by supporting behaviour change. However, changing people's health behaviours to a significant and meaningful degree is notoriously challenging and seldom very effective across the board. There are a multitude of systematic reviews of interventions aiming to change behaviours of both patients and providers, with the overall objective of improving health outcomes – many of which show little or no average effects across groups of people.[3] This evidence synthesis is therefore important as it may help to understand why communicating with people around their health might (or might not) change behaviours and improve consequent health outcomes. By examining the experiences and perspectives of those receiving the interventions, this qualitative evidence synthesis allows us to better understand the interventions' acceptability and usefulness, barriers to their uptake, and factors to be considered when planning implementation. The synthesis looked at 35 studies from countries around the world, focussing on communication related to RMNCAH. Of the 35 studies, 16 were from high‐income countries, mainly the United States, and 19 were from low‐ or middle‐income countries, mainly African countries. Many of the studies presented hypothetical scenarios. The findings from the synthesis are mixed and give us a more nuanced picture of the role of targeted digital communication. People receiving targeted digital communications from health services often liked and valued these contacts, feeling supported and connected by them. However, some also reported problems with the use of these technologies, which may represent barriers to their use. These included practical or technical barriers like poor network or Internet access, as well as cost, language, technical literacy, reading or issues around confidentiality, especially where personal health conditions were involved. Access to mobile phones may also be a barrier, particularly for women and adolescents who may have to share or borrow a phone or who have access controlled by others. In such situations it may be difficult to receive communications or to maintain privacy of content. The synthesis also shows that people's experiences of these interventions are influenced by factors such as the timing of messages, their frequency and content, and their trust in the sender. Identifying key features of such communications by the people who use them might therefore help to inform future choices about how and when such messaging is used. The authors used their knowledge from 25 separate findings to list ten implications for practice. This section of the review is hugely valuable, making a practical contribution to assist governments and public health agencies wishing to develop or improve their delivery of digital health. The implications serve as a list of points to consider, including issues of access (seven different aspects are considered), privacy and confidentiality, reliability, credibility and trust, and responsiveness to the needs and preferences of users. In this way, qualitative evidence is building a picture of how to better communicate with people about health. For example, an earlier 2017 Cochrane qualitative evidence synthesis by Ames, Glenton and Lewin on parents' and informal caregivers' views and experiences of communication about routine childhood vaccination provides ample evidence that may help program managers to deliver or plan communication interventions in ways that are responsive to and acceptable to parents.[4] The qualitative synthesis method, therefore, puts a spotlight on how people's experiences of health and health care in the context of their lives may lead to the design of better interventions, as well as to experimental studies which take more account of the diversity that exists in people's attitudes and decision‐making experiences.[5] In the case of this qualitative evidence synthesis by Ames and colleagues, the method pulled together a substantial body of research (35 data‐rich studies were sampled from 48 studies identified, with the high‐to‐moderate confidence in the evidence for 13 of the synthesized findings). The evidence from this review can inform the development of interventions, and the design of trials and their implementation. While waiting for such new trials or trial evidence on effects to emerge, decision‐makers can build their programs on the highly informative base developed by this review. This qualitative evidence synthesis, alongside other reviews, has informed development by the World Health Organization of its first guideline for using digital technologies for health systems strengthening,[1, 6] part of a comprehensive program of work to better understand and support implementation of such new technologies.

Ryan R ，Hill S 《Cochrane Database of Systematic Reviews》

Isolation and characterisation of (-)-genifuranal: the principal antimicrobial component in traditional smoking applications of Eremophila longifolia (Scrophulariaceae) by Australian aboriginal peoples.

Eremophila longifolia is considered by some Australian Aboriginal tribal groups to be among the most significant of the medicinal plants in contemporary and traditional use. Usage modalities traditionally involved lipophilic extraction into animal fats and most importantly, ceremonial or medicinal smoking applications, involving the fumigation of mothers and infants following childbirth or boys following circumcision. An attempt was made to replicate the smoking modalities used by Australian Aboriginal people in the laboratory to identify bioactive compounds. Two methods were used to produce smoke extracts; smoke was channelled through a condenser then bubbled into solvent, or bubbled directly into H2O then partitioned into chloroform followed by butanol. Extracts were used, firstly for antimicrobial screening using micro-titre plate broth dilution to produce minimum inhibitory concentrations (MIC), and secondly for chemical analysis. Structure elucidation of an abundant compound isolated from the smoke extract was performed using 2D-NMR and derivatisation. Significant antimicrobial activity (<1.0 mg/ml) was produced using the smoke extracts against the Gram-positive species Staphylococcus aureus, Bacillus subtilis and the yeast Candida albicans. A major component of the smoke with strong antimicrobial activity (0.13-0.5 mg/ml) was isolated which we have named (-)-genifuranal. Structure elucidation using 2D-NMR and derivatisation demonstrated genifuranal to be 5,6-dihydro-4H-cyclopenta[c]furan-4-ylacetaldehyde. Genifuranal is not observed in the leaves before heating, but is produced in the smoking or heating process and is thought to derive from hydrolysis and rearrangement of geniposidic acid or a related glycoside. Only geographically specific specimens of Eremophila longifolia produced (-)-genifuranal, which strongly supports previous hypothesised geographical variation in traditional usage, reflective of phytochemical variation. It would appear that genifuranal is the medicinal principal involved in traditional use of Eremophila longifolia when smoking modalities are used. Topical treatments traditionally produced by lipophilic extraction into animal fats are not likely to have had genifuranal present, as the mechanism for its formation requires heat.

Sadgrove NJ ，Jones GL ，Greatrex BW 《-》

Comparison of Two Modern Survival Prediction Tools, SORG-MLA and METSSS, in Patients With Symptomatic Long-bone Metastases Who Underwent Local Treatment With Surgery Followed by Radiotherapy and With Radiotherapy Alone.

Survival estimation for patients with symptomatic skeletal metastases ideally should be made before a type of local treatment has already been determined. Currently available survival prediction tools, however, were generated using data from patients treated either operatively or with local radiation alone, raising concerns about whether they would generalize well to all patients presenting for assessment. The Skeletal Oncology Research Group machine-learning algorithm (SORG-MLA), trained with institution-based data of surgically treated patients, and the Metastases location, Elderly, Tumor primary, Sex, Sickness/comorbidity, and Site of radiotherapy model (METSSS), trained with registry-based data of patients treated with radiotherapy alone, are two of the most recently developed survival prediction models, but they have not been tested on patients whose local treatment strategy is not yet decided. (1) Which of these two survival prediction models performed better in a mixed cohort made up both of patients who received local treatment with surgery followed by radiotherapy and who had radiation alone for symptomatic bone metastases? (2) Which model performed better among patients whose local treatment consisted of only palliative radiotherapy? (3) Are laboratory values used by SORG-MLA, which are not included in METSSS, independently associated with survival after controlling for predictions made by METSSS? Between 2010 and 2018, we provided local treatment for 2113 adult patients with skeletal metastases in the extremities at an urban tertiary referral academic medical center using one of two strategies: (1) surgery followed by postoperative radiotherapy or (2) palliative radiotherapy alone. Every patient's survivorship status was ascertained either by their medical records or the national death registry from the Taiwanese National Health Insurance Administration. After applying a priori designated exclusion criteria, 91% (1920) were analyzed here. Among them, 48% (920) of the patients were female, and the median (IQR) age was 62 years (53 to 70 years). Lung was the most common primary tumor site (41% [782]), and 59% (1128) of patients had other skeletal metastases in addition to the treated lesion(s). In general, the indications for surgery were the presence of a complete pathologic fracture or an impending pathologic fracture, defined as having a Mirels score of ≥ 9, in patients with an American Society of Anesthesiologists (ASA) classification of less than or equal to IV and who were considered fit for surgery. The indications for radiotherapy were relief of pain, local tumor control, prevention of skeletal-related events, and any combination of the above. In all, 84% (1610) of the patients received palliative radiotherapy alone as local treatment for the target lesion(s), and 16% (310) underwent surgery followed by postoperative radiotherapy. Neither METSSS nor SORG-MLA was used at the point of care to aid clinical decision-making during the treatment period. Survival was retrospectively estimated by these two models to test their potential for providing survival probabilities. We first compared SORG to METSSS in the entire population. Then, we repeated the comparison in patients who received local treatment with palliative radiation alone. We assessed model performance by area under the receiver operating characteristic curve (AUROC), calibration analysis, Brier score, and decision curve analysis (DCA). The AUROC measures discrimination, which is the ability to distinguish patients with the event of interest (such as death at a particular time point) from those without. AUROC typically ranges from 0.5 to 1.0, with 0.5 indicating random guessing and 1.0 a perfect prediction, and in general, an AUROC of ≥ 0.7 indicates adequate discrimination for clinical use. Calibration refers to the agreement between the predicted outcomes (in this case, survival probabilities) and the actual outcomes, with a perfect calibration curve having an intercept of 0 and a slope of 1. A positive intercept indicates that the actual survival is generally underestimated by the prediction model, and a negative intercept suggests the opposite (overestimation). When comparing models, an intercept closer to 0 typically indicates better calibration. Calibration can also be summarized as log(O:E), the logarithm scale of the ratio of observed (O) to expected (E) survivors. A log(O:E) > 0 signals an underestimation (the observed survival is greater than the predicted survival); and a log(O:E) < 0 indicates the opposite (the observed survival is lower than the predicted survival). A model with a log(O:E) closer to 0 is generally considered better calibrated. The Brier score is the mean squared difference between the model predictions and the observed outcomes, and it ranges from 0 (best prediction) to 1 (worst prediction). The Brier score captures both discrimination and calibration, and it is considered a measure of overall model performance. In Brier score analysis, the "null model" assigns a predicted probability equal to the prevalence of the outcome and represents a model that adds no new information. A prediction model should achieve a Brier score at least lower than the null-model Brier score to be considered as useful. The DCA was developed as a method to determine whether using a model to inform treatment decisions would do more good than harm. It plots the net benefit of making decisions based on the model's predictions across all possible risk thresholds (or cost-to-benefit ratios) in relation to the two default strategies of treating all or no patients. The care provider can decide on an acceptable risk threshold for the proposed treatment in an individual and assess the corresponding net benefit to determine whether consulting with the model is superior to adopting the default strategies. Finally, we examined whether laboratory data, which were not included in the METSSS model, would have been independently associated with survival after controlling for the METSSS model's predictions by using the multivariable logistic and Cox proportional hazards regression analyses. Between the two models, only SORG-MLA achieved adequate discrimination (an AUROC of > 0.7) in the entire cohort (of patients treated operatively or with radiation alone) and in the subgroup of patients treated with palliative radiotherapy alone. SORG-MLA outperformed METSSS by a wide margin on discrimination, calibration, and Brier score analyses in not only the entire cohort but also the subgroup of patients whose local treatment consisted of radiotherapy alone. In both the entire cohort and the subgroup, DCA demonstrated that SORG-MLA provided more net benefit compared with the two default strategies (of treating all or no patients) and compared with METSSS when risk thresholds ranged from 0.2 to 0.9 at both 90 days and 1 year, indicating that using SORG-MLA as a decision-making aid was beneficial when a patient's individualized risk threshold for opting for treatment was 0.2 to 0.9. Higher albumin, lower alkaline phosphatase, lower calcium, higher hemoglobin, lower international normalized ratio, higher lymphocytes, lower neutrophils, lower neutrophil-to-lymphocyte ratio, lower platelet-to-lymphocyte ratio, higher sodium, and lower white blood cells were independently associated with better 1-year and overall survival after adjusting for the predictions made by METSSS. Based on these discoveries, clinicians might choose to consult SORG-MLA instead of METSSS for survival estimation in patients with long-bone metastases presenting for evaluation of local treatment. Basing a treatment decision on the predictions of SORG-MLA could be beneficial when a patient's individualized risk threshold for opting to undergo a particular treatment strategy ranged from 0.2 to 0.9. Future studies might investigate relevant laboratory items when constructing or refining a survival estimation model because these data demonstrated prognostic value independent of the predictions of the METSSS model, and future studies might also seek to keep these models up to date using data from diverse, contemporary patients undergoing both modern operative and nonoperative treatments. Level III, diagnostic study.

Lee CC ，Chen CW ，Yen HK ，Lin YP ，Lai CY ，Wang JL ，Groot OQ ，Janssen SJ ，Schwab JH ，Hsu FM ，Lin WH ... -  《-》