Incidence of lower limb amputation in Central Australia.

Stuart L ，Kimmel L ，Jolly A 《-》

Vaccine preventable diseases and vaccination coverage in Aboriginal and Torres Strait Islander people, Australia 2006-2010.

This report outlines the major positive impacts of vaccines on the health of Aboriginal and Torres Strait Islander people from 2007 to 2010, as well as highlighting areas that require further attention. Hepatitis A disease is now less common in Aboriginal and Torres Strait Islander children than in their non-Indigenous counterparts. Hepatitis A vaccination for Aboriginal and Torres Strait Islander children was introduced in 2005 in the high incidence jurisdictions of the Northern Territory, Queensland, South Australia and Western Australia. In 2002–2005, there were 20 hospitalisations for hepatitis A in Aboriginal and Torres Strait Islander children aged<5 years--over 100 times more common than in other children--compared to none in 2006/07–2009/10. With respect to invasive pneumococcal disease (IPD), there has been a reduction of 87% in notifications of IPD caused by serotypes contained in 7-valent pneumococcal conjugate vaccine (7vPCV) since the introduction of the childhood 7vPCV program among Aboriginal and Torres Strait Islander children. However, due to a lower proportion of IPD caused by 7vPCV types prior to vaccine introduction, the decline in total IPD notifications has been less marked in Aboriginal and Torres Strait Islander children than in other children. Higher valency vaccines (10vPCV and 13vPCV) which replaced 7vPCV from 2011 are likely to result in a greater impact on IPD and potentially also non-invasive disease, although disease caused by non-vaccine serotypes appears likely to be an ongoing problem. Among Aboriginal and Torres Strait Islander people aged ≥50 years, there have been recent increases in IPD, which appear related to low vaccination coverage and highlight the need for improved coverage in this high-risk target group. Since routine meningococcal C vaccination for infants and the high-school catch-up program were implemented in 2003, there has been a significant decrease in cases caused by serogroup C. However, the predominant serogroup responsible for disease remains serogroup B, and Aboriginal and Torres Strait Islander children have significantly higher incidence of serogroup B disease than other children. A vaccine against meningococcus type B has now been licensed in Australia. The decline in severe rotavirus disease after vaccine introduction in 2007 was less marked in Aboriginal and Torres Strait Islander children than in other children. By far the highest hospitalisation rates continue to occur among Aboriginal and Torres Strait Islander children in the Northern Territory. Consideration of the role of age cut-offs and 2-dose versus 3-dose schedules may be necessary. Genotype surveillance is critically important to allow detection of any possible emergence of genotypes for which there is lower vaccine-derived immunity. Although Haemophilus influenzae type b disease rates have decreased significantly since the introduction of vaccines in 1993, the plateauing of rates in Aboriginal and Torres Strait Islander children, and increasing disparity with other children, are concerning. While it is possible that higher disease rates in young infants could be associated with the later age of protection from the newer 4-dose schedule, it is also possible that higher vaccine immunogenicity will result in reduced carriage. Close monitoring is important to detect any re-emergence of Hib disease as soon as possible. Pandemic and seasonal influenza and pneumonia are other diseases with comparatively higher rates in Aboriginal and Torres Strait Islander people. For Aboriginal and Torres Strait Islander people aged≥50 years, it is unclear whether or not there has been a decline in influenza hospitalisations since the start of the National Indigenous Pneumococcal and Influenza Immunisation Program in 1999, but hospitalisation rates are still higher in Aboriginal and Torres Strait Islander people. Achieving high coverage in those aged≥15 years should now be a priority. A prolonged mumps outbreak occurred in 2007/2008 predominantly affecting Aboriginal and Torres Strait Islander adolescents and young adults in north-western Australia. A potential contributor to this mumps outbreak was greater waning of immunity after receipt of the first dose of mumps-containing vaccine at 9, rather than 12, months of age in the Northern Territory in the 1980s and 1990s. However, outbreaks in Australia and overseas have subsided without additional boosters being routinely implemented. Pertussis epidemics continue to occur in Australia and affect both Aboriginal and Torres Strait Islander and other people. Parents are now encouraged to have their infant’s first vaccination given at 6 weeks of age, instead of the usual 2 months, and this is being successfully implemented for Aboriginal and Torres Strait Islander and other infants. Timely provision of the 4- and 6-month doses remains very important. High coverage for standard vaccines, poor timeliness of vaccination and lower coverage for ‘Indigenous only’ vaccines are continuing features of vaccination programs for Aboriginal and Torres Strait Islander people. There have been some improvements in vaccination timeliness in recent years for all children, but disparities remain between Aboriginal and Torres Strait Islander and other children. Poor timeliness reduces the potential benefits of vaccination, most importantly for pneumococcal, Hib and rotavirus vaccines in infants. The age cut-offs for rotavirus vaccines present a particular challenge for timely vaccination, limiting the capacity for catching up on late vaccination and resulting in lower overall coverage. This is more pronounced for the 3-dose than for the 2-dose rotavirus schedule. Coverage for vaccines recommended only for Aboriginal and Torres Strait Islander children continues to remain substantially lower than that for universal vaccines. This underlines the importance of immunisation providers establishing the Indigenous status of their clients, so that additional vaccines are offered as appropriate. The absence of any coverage data for Aboriginal and Torres Strait Islander adolescents, or for adults since 2004/2005, is a substantial obstacle to implementing and improving programs in these age groups.

Naidu L ，Chiu C ，Habig A ，Lowbridge C ，Jayasinghe S ，Wang H ，McIntyre P ，Menzies R ... -  《-》

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 ... -  《-》

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》

Lamotrigine versus levetiracetam or zonisamide for focal epilepsy and valproate versus levetiracetam for generalised and unclassified epilepsy: two SANAD II non-inferiority RCTs.

Marson AG ，Burnside G ，Appleton R ，Smith D ，Leach JP ，Sills G ，Tudur-Smith C ，Plumpton CO ，Hughes DA ，Williamson PR ，Baker G ，Balabanova S ，Taylor C ，Brown R ，Hindley D ，Howell S ，Maguire M ，Mohanraj R ，Smith PE ... -  《-》