Prognostic and Predictive Role of SPOP Mutations in Prostate Cancer: A Systematic Review and Meta-analysis.

CONTEXT: Mutations in the speckle-type POZ (SPOP) gene are frequently identified in prostate cancer (PC); yet, prognostic implications for affected patients remain unclear. Limited consensus exists regarding tailored treatments for SPOP-mutant (SPOPmut) PC. OBJECTIVE: To elucidate the prognostic and predictive significance of SPOP mutations across distinct PC stages and treatments. EVIDENCE ACQUISITION: A systematic literature search of PubMed, Embase, and Scopus was conducted up to January 29, 2024. The meta-analysis included studies comparing survival outcomes between SPOPmut and SPOP wild-type (SPOPwt) PC. EVIDENCE SYNTHESIS: From 669 records, 26 studies (including five abstracts) were analyzed. A meta-analysis of metastasis-free survival in localized (hazard ratio [HR]: 0.72, 95% confidence interval [CI]: 0.59-0.88; p < 0.01) and overall survival (OS) in metastatic PC (HR: 0.64, 95% CI: 0.53-0.76; p < 0.01) showed a favorable prognosis for patients with SPOPmut PC. In metastatic settings, SPOP mutations correlated with improved progression-free survival (PFS) and OS in patients undergoing androgen deprivation therapy ± androgen receptor signaling inhibitor (HR: 0.51, 95% CI: 0.35-0.76, p < 0.01, and HR: 0.60, 95% CI:0.46-0.79, p < 0.01, respectively). In metastatic castration-resistant PC, only abiraterone provided improved PFS and OS to patients with SPOP mutations compared with patients with SPOPwt, but data were limited. SPOP mutations did not correlate with improved PFS (p = 0.80) or OS (p = 0.27) for docetaxel. CONCLUSIONS: Patients with SPOPmut PC seem to exhibit superior oncological outcomes compared with patients with SPOPwt. Tailored risk stratification and treatment approaches should be explored in such patients. PATIENT SUMMARY: Speckle-type POZ (SPOP) mutations could be a favorable prognostic factor in patients with prostate cancer (PC) and may also predict better progression-free and overall survival than treatment with hormonal agents. Therefore, less intensified treatments omitting chemotherapy for patients with SPOP-mutant PC should be explored in clinical trials.

Quality Appraisal in Systematic Literature Reviews of Studies Eliciting Health State Utility Values: Conceptual Considerations.

BACKGROUND: The increasing number of studies that generate health state utility values (HSUVs) and the impact of HSUVs on cost-utility analyses make a robust tailored quality appraisal (QA) tool for systematic reviews of these studies necessary. OBJECTIVE: This study aimed to address conceptual issues regarding QA in systematic reviews of studies eliciting HSUVs by establishing a consensus on the definitions, dimensions and scope of a QA tool specific to this context. METHODS: A modified Delphi method was used in this study. An international multidisciplinary panel of seven experts was purposively assembled. The experts engaged in two anonymous online survey rounds. After each round, the experts received structured and controlled feedback on the previous phase. Controlled feedback allowed the experts to re-evaluate and adjust their positions based on collective insights. Following these surveys, a virtual face-to-face meeting was held to resolve outstanding issues. Consensus was defined a priori at all stages of the modified Delphi process. RESULTS: The response rates to the first-round and second-round questionnaires and the virtual consensus meeting were 100%, 86% and 71%, respectively. The entire process culminated in a consensus on the definitions of scientific quality, QA, the three QA dimensions-reporting, relevance and  methodological quality-and the scope of a QA tool specific to studies that elicit HSUVs. CONCLUSIONS: Achieving this consensus marks a pivotal step towards developing a QA tool specific to systematic reviews of studies eliciting HSUVs. Future research will build on this foundation, identify QA items, signalling questions and response options, and develop a QA tool specific to studies eliciting HSUVs.

Secondary Analysis of the Salt Substitute and Stroke Study (SSaSS): Effects of Potassium-Enriched Salt on Cardiac Outcomes.

BACKGROUND: The SSaSS (Salt Substitute and Stroke Study) has shown that use of a potassium-enriched salt lowers the risk of stroke, total cardiovascular events, and premature death. The effects on cause-specific cardiac outcomes are reported here. METHODS: SSaSS was an unblinded, cluster-randomised trial assessing the effects of potassium-enriched salt compared with regular salt among 20 995 Chinese adults with established stroke and older age and uncontrolled hypertension. Post hoc efficacy analyses were performed using an intention-to-treat method and a hierarchical Poisson regression model adjusting for clustering to obtain rate ratios and 95% CIs. We assessed acute coronary syndrome, heart failure, arrhythmia, and sudden death. RESULTS: Over a mean 4.74 years follow-up, there were 695 acute coronary syndrome events, 454 heart failure events, 230 arrhythmia events, and 1133 sudden deaths recorded. The rates of events were lower in potassium-enriched salt group for all outcomes but CIs were wide for most: acute coronary syndrome (6.32 versus 7.65 events per 1000 person-years; rate ratio, 0.80 [95% CI, 0.65-0.99]); heart failure (9.14 versus 11.32 events per 1000 person-years; rate ratio, 0.88 [95% CI, 0.60-1.28]); arrhythmia (4.43 versus 6.20 events per 1000 person-years; rate ratio, 0.59 [95% CI, 0.35-0.98]); and sudden death (11.01 versus 11.76 events per 1000 person-years; rate ratio, 0.94 [95% CI, 0.82-1.07]; all P>0.05 with adjustment for multiple comparisons). CONCLUSIONS: These results suggest that use of potassium-enriched salt is more likely to prevent than cause cardiac disease but the post hoc nature of these analyses precludes definitive conclusions. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02092090.

Bayesian approach for meta-analyses in biomedical research: a scoping review protocol.

OBJECTIVE: The overarching aim of this scoping review is to describe and analyze the scope of use and reporting of Bayesian methods in meta-analyses in biomedical research. INTRODUCTION: The Bayesian approach provides a powerful and flexible framework for meta-analysis, particularly suited for dealing with complex, sparse, or heterogeneous data. Due to these advantages and its appeal, Bayesian methods have been increasingly used in many areas of biomedical research; however, their use in meta-analysis remains scarce. INCLUSION CRITERIA: This review will include studies that used Bayesian methods for meta-analysis of primary studies in biomedical research. METHODS: The proposed review will be conducted in accordance with the JBI methodology for scoping reviews. PubMed, Embase, CINAHL, and the Cochrane Database of Systematic Reviews will be searched to identify relevant full-text papers published since 2016 in English. No geographical restriction will be applied. Two reviewers will screen the articles and extract the data using a tool that will be pilot-tested and revised, as necessary. Analysis will involve frequency counts, narrative synthesis, and mapping concepts to propose an appropriate workflow. The details of the scoping review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guideline. REVIEW REGISTRATION: Open Science Framework https://osf.io/jenp4/.

The effect of salt substitution on frequency and severity of headache: results from the SSaSS cluster-randomised controlled trial of 20,995 participants.

BACKGROUND: Headache is one of the most common neurological symptoms. Headache disorders are associated with a high global burden of disease. Prior studies indicate that short-to-medium term sodium reduction reduces headache symptom. This study evaluated the effects of long-term reduced-sodium, added-potassium salt on headache frequency and severity in rural China. METHODS: The Salt substitute and stroke study (SSaSS) was an open-label cluster-randomised trial in rural China designed to evaluate the effect of salt substitution on mortality and cardiovascular events. Participants included adults with a history of prior stroke and those aged ≥60 years with uncontrolled high blood pressure (BP). Villages were randomly assigned in a 1:1 ratio either to intervention with salt substitute (75% sodium chloride and 25% potassium chloride by mass) or to control with continued use of regular salt (100% sodium chloride). In this pre-specified analysis, between-group differences in headache frequency and severity were evaluated. The study was registered with ClinicalTrials.gov (identifier number: NCT02092090). RESULTS: A total of 20,995 participants were included in the trial (mean age 64.3 years, 51% female, mean follow-up 4.7 years). At final follow-up at the end of the study, headache outcome data including frequency and severity of headaches was available for 16,486 (98%) of 16,823 living participants. Overall, 4454/16,486 (27%) individuals reported having headache: 27.4% in the intervention group (2301/8386) vs 26.6% in the control group (2153/8100) (RR 1.04, 95% CI: 0.93, 1.16, p = 0.48). There was no difference in headache severity between intervention and control groups (p = 0.90). CONCLUSION: Long term salt substitution did not reduce the frequency or severity of headaches in this population.

Rationale for a New Low-Dose Triple Single Pill Combination for the Treatment of Hypertension.

Two recent large trials showed the potential of single pill combinations (SPCs) with ≥3 low-dose components among people with hypertension who were untreated or receiving monotherapy. In both trials, these 'hypertension polypills' were superior to usual care, achieving >80% BP control without increasing withdrawal due to side effects. However, there are no such products available for prescribers. To address this unmet need, George Medicines developed GMRx2 with telmisartan/amlodipine/indapamide in three strengths (mg): 10/1.25/0.625, 20/2.5/1.25; 40/5/2.5. Two pivotal trials are ongoing to support FDA submission for the treatment of hypertension, including initial treatment. These assess efficacy and safety of GMRx2 compared to: placebo, and each of the three possible dual combinations. Regulatory submissions are planned for 2024, with the aim of providing access to GMRx2 in developed and developing regions. Wider implementation of GMRx2-based treatment strategies will be guided by further research to inform access and appropriate scale up.

Understanding the Natural History of Chronic Hepatitis D: Proposal of a Model for Cost-Effectiveness Studies.

BACKGROUND: As new therapeutic options become available, better understanding the potential impact of emerging therapies on clinical outcomes of hepatits D virus (HDV) is critical. OBJECTIVE: The aim of this study was to develop a natural history model for patients with hepatitis D virus. METHODS: We developed a model (decision tree followed by a Markov cohort model) in adults with chronic HDV infection to assess the natural history and impact of novel treatments on disease progression versus best supportive care (BSC). The model time horizon was over a lifetime (up to 100 years of age); state transitions and health states were defined by responder status. Patients in fibrosis stages 0 through 4 received treatment; decompensated patients were not treated. Response was defined as the combined response endpoint of achievement of HDV-RNA undetectability/≥2-log10 decline and alanine aminotransferase normalization; response rates of 50% and 75% were explored. Health events associated with advanced liver disease were modeled as the number of events per 10,000 patients. Scenario analyses of early treatment, alternate treatment response, and no fibrosis regression for treatment responders were also explored. RESULTS: The model was able to reflect disease progression similarly to published natural history studies for patients with HBV/HDV infection. In a hypothetical cohort of patients reflecting a population enrolled in a recent clinical trial, fewer advanced liver disease events were observed with a novel HDV treatment versus BSC. Fewer liver-related deaths were observed under 50% and 75% response (900 and 1,358 fewer deaths, respectively, per 10,000 patients). Scenario analyses showed consistently fewer advanced liver disease events with HDV treatment compared with BSC, with greater reductions observed with earlier treatment. CONCLUSION: This HDV disease progression model replicated findings from natural history studies. Furthermore, it found that a hypothetical HDV treatment results in better clinical outcomes for patients versus BSC, with greater benefit observed when starting treatment early. This validated natural history model for HBV/HDV infection can serve as a foundation for future clinical and economic analyses of novel HDV treatments that can support healthcare stakeholders in the management of patients with chronic HDV.

The association between influenza vaccination, cardiovascular mortality and hospitalization: A living systematic review and prospective meta-analysis.

BACKGROUND: The effects of seasonal influenza vaccination on cardiovascular disease (CVD) outcomes, including among individuals with established CVD, are uncertain. METHODS: To evaluate the efficacy and safety of influenza vaccines compared to no vaccines or placebo for preventing all-cause/CVD mortality or all-cause/CVD hospitalization in the general population and in populations with pre-existing CVD, we conducted a living systematic review (LSR) and prospective meta-analysis (PMA). Published randomized controlled trials (RCT) and observational studies between 1994 and 2023 were searched. PRISMA guidelines were followed in the extraction of study details, and risk of bias was assessed using the Cochrane tools. Analyses were stratified by study design and CVD history. Study quality was evaluated using GRADE system. Meta analyses based on random-effects models were performed between July and October 2022. Pooled risk ratios (RRs) for all-cause/CVD mortality and all-cause/CVD hospitalization were main outcomes. RESULTS: Six published RCTs comprising 12,662 participants (mean age, 62 years; 45 % women; 8,797 with pre-existing CVD) and 37 observational studies comprising 6,311,703 participants (mean age, 49 years; 50 % women; 1,189,955 with pre-existing CVD) were included. Only those RCTs judged to be low risk were included in the analyses, and observational studies at anything greater than moderate risk of bias were excluded. In RCTs, influenza vaccine was not significantly associated with lower all-cause mortality (RR, 0.85; 95 %CI, 0.61-1.17), cardiovascular death (RR, 0.80; 95 %CI, 0.60-1.07), or CVD hospitalization (RR, 0.69; 95 %CI, 0.47-1.02). A statistically significant reduction in all-cause hospitalization (RR, 0.86; 95 %CI, 0.76-0.97) was observed. The evidence level was assessed as moderate for all-cause hospitalization, and low for other outcomes. Overall, observational studies suggested a stronger protective association between influenza vaccination and outcomes, except for CVD hospitalization. Based on RCTs, there was no difference in the effects of influenza vaccination on all-cause mortality among the general population compared to those with pre-existing CVD, although the summary point estimate favored benefits only in those with pre-existing CVD. CONCLUSIONS: While observational studies suggest that influenza vaccination may be associated with lower all-cause and CVD mortality and all-cause hospitalization, RCTs reported to date suggest a reduction in the risk of all-cause hospitalization but do not provide clear evidence to support preventive effects on mortality (all-cause or CVD) or CVD hospitalization.

Association of hepatitis delta virus with liver morbidity and mortality: A systematic literature review and meta-analysis.

BACKGROUND AND AIMS: Studies have suggested that patients with chronic hepatitis B, either co- or superinfected, have more aggressive liver disease progression than those with the HDV. This systematic literature review and meta-analysis examined whether HDV RNA status is associated with increased risk of advanced liver disease events in patients who are HBsAg and HDV antibody positive. APPROACH AND RESULTS: A total of 12 publications were included. Relative rates of progression to advanced liver disease event for HDV RNA+/detectable versus HDV RNA-/undetectable were extracted for analysis. Reported OR and HRs with 95% CI were pooled using the Hartung-Knapp-Sidik-Jonkman method for random-effects models. The presence of HDV RNA+ was associated with an increased risk of any advanced liver disease event [random effect (95% CI): risk ratio: 1.48 (0.93, 2.33); HR: 2.62 (1.55, 4.44)]. When compared to the patients with HDV RNA- status, HDV RNA+ was associated with a significantly higher risk of progressing to compensated cirrhosis [risk ratio: 1.74 (1.24, 2.45)] decompensated cirrhosis [HR: 3.82 (1.60, 9.10)], HCC [HR: 2.97 (1.87, 4.70)], liver transplantation [HR: 7.07 (1.61, 30.99)], and liver-related mortality [HR: 3.78 (2.18, 6.56)]. CONCLUSIONS: The patients with HDV RNA+ status have a significantly greater risk of liver disease progression than the patients who are HDV RNA-. These findings highlight the need for improved HDV screening and linkage to treatment to reduce the risk of liver-related morbidity and mortality.

Balanced crystalloids versus saline for critically ill patients (BEST-Living): a systematic review and individual patient data meta-analysis.

BACKGROUND: The effect of balanced crystalloids compared with that of saline in critically ill patients overall and in specific subgroups is unclear. We aimed to assess whether use of balanced solutions, compared with 0·9% sodium chloride (saline), decreased in-hospital mortality in adult patients in intensive care units (ICUs). METHODS: For this systematic review and individual patient data meta-analysis, we searched PubMed, Embase, and CENTRAL databases from inception until March 1, 2022 (updated Sept 1, 2023) for individually randomised and cluster-randomised trials comparing balanced solutions with saline for adult patients in the ICU. Eligible trials were those that allocated patients to receive balanced solutions or saline for fluid resuscitation and maintenance fluids, or for maintenance fluids only; and administered the allocated fluid throughout ICU admission or, for trials using landmark mortality as their primary outcome, until the timepoint at which mortality was assessed (if ≥28 days). Authors of eligible trials were contacted to request individual patient data. Data obtained from eligible trials were merged, checked for accuracy, and centrally analysed by use of Bayesian regression models. The primary outcome was in-hospital mortality. Prespecified subgroups included patients with traumatic brain injury. This study was registered with PROSPERO (CRD42022299282). FINDINGS: Our search identified 5219 records, yielding six eligible randomised controlled trials. Data obtained for 34 685 participants from the six trials, 17 407 assigned to receive balanced crystalloids and 17 278 to receive saline, were included in the analysis. The mean age of participants was 58·8 years (SD 17·5). Of 34 653 participants with available data, 14 579 (42·1%) were female and 20 074 (57·9%) were male. Among patients who provided consent to report in-hospital mortality, 2907 (16·8%) of 17 313 assigned balanced solutions and 2975 (17·3%) of 17 166 assigned saline died in hospital (odds ratio [OR] 0·962 [95% CrI 0·909 to 1·019], absolute difference -0·4 percentage points [-1·5 to 0·2]). The posterior probability that balanced solutions reduced mortality was 0·895. In patients with traumatic brain injury, 191 (19·1%) of 999 assigned balanced and 141 (14·7%) of 962 assigned saline died (OR 1·424 [1·100 to 1·818], absolute difference 3·2 percentage points [0·7 to 8·7]). The probability that balanced solutions increased mortality in patients with traumatic brain injury was 0·975. In an independent risk of bias assessment, two trials were deemed to be at low risk of bias and four at high risk of bias. INTERPRETATION: The probability that using balanced solutions in the ICU reduces in-hospital mortality is high, although the certainty of the evidence was moderate and the absolute risk reduction was small. In patients with traumatic brain injury, using balanced solutions was associated with increased in-hospital mortality. FUNDING: HCor (Brazil) and The George Institute for Global Health (Australia).

EARLY PERSISTENT LYMPHOPENIA AND RISK OF DEATH IN CRITICALLY ILL PATIENTS WITH AND WITHOUT SEPSIS.

ABSTRACT: Purpose: To examine the relationship of early persistent lymphopenia with hospital survival in critically ill patients with and without sepsis to assess whether it can be considered a treatable trait. Methods: Retrospective database analysis of patients with nonelective admission to intensive care units (ICUs) during January 2015 to December 2018. Patients were classified as having sepsis if the Acute Physiology and Chronic Health Evaluation III admission diagnostic code included sepsis or coded for an infection combined with a Sequential Organ Failure Assessment score of ≥2. We defined early persistent lymphopenia at two thresholds (absolute lymphocyte count [ALC] <1.0 and <0.75 × 10 9 /L) based on two qualifying values recorded during the first 4 days in ICU. The main outcome measure was time to in-hospital death. Results: Of 8,507 eligible patients, 7,605 (89.4%) had two ALCs recorded during their first 4 days in ICU; of these, 1,482 (19.5%) had sepsis. Persistent lymphopenia (ALC <1.0) was present in 728 of 1,482 (49.1%) and 2,302 of 6,123 (37.6%) patients with and without sepsis, respectively. For ALC <0.75, the results were 487 of 1,482 (32.9%) and 1,125 of 6,123 (18.4%), respectively. Of 3,030 patients with persistent lymphopenia (ALC <1.0), 562 (18.5%) died compared with 439 of 4,575 (9.6%) without persistent lymphopenia. Persistent lymphopenia was an independent risk factor for in-hospital death in all patients. The hazard ratios for death at ALC <1.0 were 1.89 (95% confidence interval, 1.32-2.71; P = 0.0005) and 1.17 (95% confidence interval, 1.02-1.35; P = 0.0246) in patients with and without sepsis respectively. Conclusions: Early persistent lymphopenia is common in critically ill patients and associated with increased risk of death in patients with and without sepsis. Although the association is stronger in patients with sepsis, lymphopenia is a candidate to be considered a treatable trait; drugs that reverse lymphopenia should be trialed in critically ill patients.

Bayesian structural time series, an alternative to interrupted time series in the right circumstances.

OBJECTIVES: Compare two approaches to analyzing time series data-interrupted time series with segmented regression (ITS-SR) and Bayesian structural time series using the CausalImpact R package (BSTS-CI)-highlighting advantages, disadvantages, and implementation considerations. STUDY DESIGN AND SETTING: We analyzed electronic health records using each approach to estimate the antibiotic prescribing reduction associated with an educational program delivered to Australian primary care physicians between 2012 and 2017. Two outcomes were considered: antibiotics for upper respiratory tract infections (URTIs) and antibiotics of specified formulations. RESULTS: For URTI indication prescribing, average monthly prescriptions changes were estimated at -4,550; (95% confidence interval, -5,486 to -3,614) and -4,270; (95% credible interval, -5,934 to -2,626) for ITS-SR and BSTS-CI, respectively. Similarly for specified formulation prescribing, monthly average changes were estimated at -7,923; (95% confidence interval, -15,887 to 40) for ITS-SR and -20,269; (95% credible interval, -25,011 to -15,635) for BSTS-CI. CONCLUSION: Differing results between ITS-SR and BSTS-CI appear driven by divergent explanatory and outcome series trends. The BSTS-CI may be a suitable alternative to ITS-SR only if the explanatory series represent the secular trend of the outcome series before the intervention and are equally affected by exogenous or confounding factors. When appropriately applied, BSTS-CI provides an alternative to ITS with more readily interpretable Bayesian effect estimates.

Communication to promote and support physical distancing for COVID-19 prevention and control.

BACKGROUND: This review is an update of a rapid review undertaken in 2020 to identify relevant, feasible and effective communication approaches to promote acceptance, uptake and adherence to physical distancing measures for COVID-19 prevention and control. The rapid review was published when little was known about transmission, treatment or future vaccination, and when physical distancing measures (isolation, quarantine, contact tracing, crowd avoidance, work and school measures) were the cornerstone of public health responses globally. This updated review includes more recent evidence to extend what we know about effective pandemic public health communication. This includes considerations of changes needed over time to maintain responsiveness to pandemic transmission waves, the (in)equities and variable needs of groups within communities due to the pandemic, and highlights again the critical role of effective communication as integral to the public health response. OBJECTIVES: To update the evidence on the question 'What are relevant, feasible and effective communication approaches to promote acceptance, uptake and adherence to physical distancing measures for COVID-19 prevention and control?', our primary focus was communication approaches to promote and support acceptance, uptake and adherence to physical distancing. SECONDARY OBJECTIVE: to explore and identify key elements of effective communication for physical distancing measures for different (diverse) populations and groups. SEARCH METHODS: We searched MEDLINE, Embase and Cochrane Library databases from inception, with searches for this update including the period 1 January 2020 to 18 August 2021. Systematic review and study repositories and grey literature sources were searched in August 2021 and guidelines identified for the eCOVID19 Recommendations Map were screened (November 2021). SELECTION CRITERIA: Guidelines or reviews focusing on communication (information, education, reminders, facilitating decision-making, skills acquisition, supporting behaviour change, support, involvement in decision-making) related to physical distancing measures for prevention and/or control of COVID-19 or selected other diseases (sudden acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), influenza, Ebola virus disease (EVD) or tuberculosis (TB)) were included. New evidence was added to guidelines, reviews and primary studies included in the 2020 review. DATA COLLECTION AND ANALYSIS: Methods were based on the original rapid review, using methods developed by McMaster University and informed by Cochrane rapid review guidance. Screening, data extraction, quality assessment and synthesis were conducted by one author and checked by a second author. Synthesis of results was conducted using modified framework analysis, with themes from the original review used as an initial framework. MAIN RESULTS: This review update includes 68 studies, with 17 guidelines and 20 reviews added to the original 31 studies. Synthesis identified six major themes, which can be used to inform policy and decision-making related to planning and implementing communication about a public health emergency and measures to protect the community. Theme 1: Strengthening public trust and countering misinformation: essential foundations for effective public health communication Recognising the key role of public trust is essential. Working to build and maintain trust over time underpins the success of public health communications and, therefore, the effectiveness of public health prevention measures. Theme 2: Two-way communication: involving communities to improve the dissemination, accessibility and acceptability of information Two-way communication (engagement) with the public is needed over the course of a public health emergency: at first, recognition of a health threat (despite uncertainties), and regularly as public health measures are introduced or adjusted. Engagement needs to be embedded at all stages of the response and inform tailoring of communications and implementation of public health measures over time. Theme 3: Development of and preparation for public communication: target audience, equity and tailoring Communication and information must be tailored to reach all groups within populations, and explicitly consider existing inequities and the needs of disadvantaged groups, including those who are underserved, vulnerable, from diverse cultural or language groups, or who have lower educational attainment. Awareness that implementing public health measures may magnify existing or emerging inequities is also needed in response planning, enactment and adjustment over time. Theme 4: Public communication features: content, timing and duration, delivery Public communication needs to be based on clear, consistent, actionable and timely (up-to-date) information about preventive measures, including the benefits (whether for individual, social groupings or wider society), harms (likewise) and rationale for use, and include information about supports available to help follow recommended measures. Communication needs to occur through multiple channels and/or formats to build public trust and reach more of the community. Theme 5: Supporting behaviour change at individual and population levels Supporting implementation of public health measures with practical supports and services (e.g. essential supplies, financial support) is critical. Information about available supports must be widely disseminated and well understood. Supports and communication related to them require flexibility and tailoring to explicitly consider community needs, including those of vulnerable groups. Proactively monitoring and countering stigma related to preventive measures (e.g. quarantine) is also necessary to support adherence. Theme 6: Fostering and sustaining receptiveness and responsiveness to public health communication Efforts to foster and sustain public receptiveness and responsiveness to public health communication are needed throughout a public health emergency. Trust, acceptance and behaviours change over time, and communication needs to be adaptive and responsive to these changing needs. Ongoing community engagement efforts should inform communication and public health response measures. AUTHORS' CONCLUSIONS: Implications for practice Evidence highlights the critical role of communication throughout a public health emergency. Like any intervention, communication can be done well or poorly, but the consequences of poor communication during a pandemic may mean the difference between life and death. The approaches to effective communication identified in this review can be used by policymakers and decision-makers, working closely with communication teams, to plan, implement and adjust public communications over the course of a public health emergency like the COVID-19 pandemic. Implications for research Despite massive growth in research during the COVID-19 period, gaps in the evidence persist and require high-quality, meaningful research. This includes investigating the experiences of people at heightened COVID-19 risk, and identifying barriers to implementing public communication and protective health measures particular to lower- and middle-income countries, and how to overcome these.

Associations between vision impairment and vision-related interventions on crash risk and driving cessation: systematic review and meta-analysis.

OBJECTIVES: To systematically investigate the associations between vision impairment and risk of motor vehicle crash (MVC) involvement, and evaluate vision-related interventions to reduce MVCs. DESIGN: Medline (Ovid), EMBASE and Global Health electronic databases were systematically searched from inception to March 2022 for observational and interventional English-language studies. Screening, data extraction and appraisals using the Joanna Briggs Institute appraisal tools were completed by two reviewers independently. Where appropriate, measures of association were converted into risk ratios (RRs) or ORs for meta-analysis. PARTICIPANTS: Drivers of four-wheeled vehicles of all ages with no cognitive declines. PRIMARY AND SECONDARY OUTCOMES: MVC involvement (primary) and driving cessation (secondary). RESULTS: 101 studies (n=778 052) were included after full-text review. 57 studies only involved older drivers (≥65 years) and 85 were in high-income settings. Heterogeneity in the data meant that most meta-analyses were underpowered as only 25 studies, further split into different groups of eye diseases and measures of vision, could be meta-analysed. The limited evidence from the meta-analyses suggests that visual field defects (four studies; RR 1.51 (95% CI 1.23, 1.85); p<0.001; I2=46.79%), and contrast sensitivity (two studies; RR 1.40 (95% CI 1.08, 1.80); p=0.01, I2=0.11%) and visual acuity loss (five studies; RR 1.21 (95% CI 1.02, 1.43); p=0.03, I2=28.49%) may increase crash risk. The results are more inconclusive for available evidence for associations of glaucoma (five studies, RR 1.27 (95% CI 0.67, 2.42); p=0.47; I2=93.48%) and cataract (two studies RR 1.15 (95% CI 0.97, 1.36); p=0.11; I2=3.96%) with crashes. Driving cessation may also be linked with glaucoma (two studies; RR 1.62 (95% CI 1.20, 2.19); p<0.001, I2=22.45%), age-related macular degeneration (AMD) (three studies; RR 2.21 (95% CI 1.47, 3.31); p<0.001, I2=75.11%) and reduced contrast sensitivity (three studies; RR 1.30 (95% CI 1.05, 1.61); p=0.02; I2=63.19%). Cataract surgery halved MVC risk (three studies; RR 0.55 (95% CI 0.34, 0.92); p=0.02; I2=97.10). Ranibizumab injections (four randomised controlled trials) prolonged driving in persons with AMD. CONCLUSION: Impaired vision identified through a variety of measures is associated with both increased MVC involvement and cessation. Cataract surgery can reduce MVC risk. Despite literature being highly heterogeneous, this review shows that detection of vision problems and appropriate treatment are critical to road safety. PROSPERO REGISTRATION NUMBER: CRD42020172153.

Effect of COVID-19 containment measures on access to snakebite care in India.

INTRODUCTION: The extensive spread of COVID-19 meant action to address the pandemic took precedence over routine service delivery, thus impacting access to care for many health conditions, including the effects of snakebite. METHOD: We prospectively collected facility-level data from several health facilities in India, including number of snakebite admissions and snakebite envenoming admissions on modality of transport to reach the health facility. To analyse the effect of a health facility being in cluster-containment zone, we used negative binomial regression analysis. RESULTS: Our findings suggest that that health facilities located within a COVID containment zone saw a significant decrease in total snakebite admissions (incidence rate ratio 0.64 (0.43-0.94), standard error 0.13, p≤0.02)) and envenoming snakebite admissions (incidence rate ratio 0.43 (0.23-0.81), standard error 0.14, p≤0.01) compared to when health facilities were not within a COVID containment zone. There was no statistically significant difference in non-envenoming admissions and modalities of transport used to reach health facilities. CONCLUSION: This article provides the first quantitative estimate of the impact of COVID-19 containment measures on access to snakebite care. More research is needed to understand how containment measures altered care-seeking pathways and the nature of snake-human-environment conflict. Primary healthcare systems need to be safeguarded for snakebite care to mitigate effects of cluster-containment measures.

Protocol for a randomized controlled trial of medically tailored meals compared to usual care among individuals with type 2 diabetes in Australia.

BACKGROUND: 'Food is medicine' strategies aim to integrate food-based nutrition interventions into healthcare systems and are of growing interest to healthcare providers and policy makers. 'Medically Tailored Meals' (MTM) is one such intervention, which involves the 'prescription' by healthcare providers of subsidized, pre-prepared meals for individuals to prevent or manage chronic conditions, combined with nutrition education. OBJECTIVE: This study will test the efficacy of an MTM program in Australia among participants with type 2 diabetes (T2D) and hyperglycemia, who experience difficulties accessing and eating nutritious food. METHODS: This study will be a two-arm parallel trial (goal n = 212) with individuals randomized in a 1:1 ratio to a MTM intervention group or a control group (106 per arm). Over 26 weeks, the intervention group will be prescribed 20 MTM per fortnight and up to 3 sessions with an accredited dietitian. Controls will continue with their usual care. The primary outcome is glycated hemoglobin (HbA1c, %) and secondary outcomes include differences in blood pressure, blood lipids and weight, all measured at 26 weeks. Process and economic data will be analyzed to assess the feasibility, acceptability, scalability, and cost-effectiveness of the intervention. Recruitment commenced in the first quarter of 2023, with analyses and results anticipated to be available by March 2025. DISCUSSION: Few randomized controlled trials have assessed the impact of MTM on clinical outcomes. This Australian-first trial will generate robust data to inform the case for sustained, large-scale implementation of MTM to improve the management of T2D among vulnerable populations. ANZCTR: ACTRN12622000852752. PROTOCOL VERSION: Version 1.1, July 2023.

Handling Missing Data in Health Economics and Outcomes Research (HEOR): A Systematic Review and Practical Recommendations.

BACKGROUND: Missing data in costs and/or health outcomes and in confounding variables can create bias in the inference of health economics and outcomes research studies, which in turn can lead to inappropriate policies. Most of the literature focuses on handling missing data in randomized controlled trials, which are not necessarily always the data used in health economics and outcomes research. OBJECTIVES: We aimed to provide an overview on missing data issues and how to address incomplete data and report the findings of a systematic literature review of methods used to deal with missing data in health economics and outcomes research studies that focused on cost, utility, and patient-reported outcomes. METHODS: A systematic search of papers published in English language until the end of the year 2020 was carried out in PubMed. Studies using statistical methods to handle missing data for analyses of cost, utility, or patient-reported outcome data were included, as were reviews and guidance papers on handling missing data for those outcomes. The data extraction was conducted with a focus on the context of the study, the type of missing data, and the methods used to tackle missing data. RESULTS: From 1433 identified records, 40 papers were included. Thirteen studies were economic evaluations. Thirty studies used multiple imputation with 17 studies using multiple imputation by chained equation, while 15 studies used a complete-case analysis. Seventeen studies addressed missing cost data and 23 studies dealt with missing outcome data. Eleven studies reported a single method while 20 studies used multiple methods to address missing data. CONCLUSIONS: Several health economics and outcomes research studies did not offer a justification of their approach of handling missing data and some used only a single method without a sensitivity analysis. This systematic literature review highlights the importance of considering the missingness mechanism and including sensitivity analyses when planning, analyzing, and reporting health economics and outcomes research studies.

15-year incidence of driving cessation and associated risk factors: The Blue Mountains Eye Study.

OBJECTIVES: To report the 15-year incidence of driving cessation and its associated vision-related risk factors in an older Australian population-based cohort. STUDY DESIGN: 15-year data from a sample of 2379 participants who indicated that they were driving at baseline from The Blue Mountains Eye Study was analysed. Questions about driving cessation was asked at all four visits and was recorded as a binary response (Yes/No). Clinical vision examinations were performed at each visit to determine presenting and best-corrected visual acuity and any incident eye diseases (Yes/No). MAIN OUTCOME MEASURES: The cumulative 15-year incidence of driving cessation was calculated using interval-censored data progression-free survival analyses. Age- and sex-adjusted and multivariable-adjusted interval-censored Cox proportional hazard models were used to report the hazard ratios (HRs) for associations of baseline and incident vision status with driving cessation. RESULTS: The 15-year cumulative incidence of driving cessation amongst the 2379 participants was 20.7 %, with women more likely to cease driving than men (p = 0.0005). Cataract (HR 1.98 (95 % confidence interval(Cl) 1.45-2.71)) and age-related macular degeneration (HR 1.85 (95%Cl 1.37-2.50)) were associated with increased risk of driving cessation whilst presenting and best-corrected visual acuity in the better eye were protective against cessation (presenting: HR 0.96 (95%Cl 0.95-0.98); best-corrected: HR 0.93 (95%Cl 0.91-0.95)) in age- and sex-adjusted models, with these factors remaining independently associated in the multivariable-adjusted models. CONCLUSION: Cumulative incidence of driving cessation increased with older age and was higher in females. Cataract and age-related macular degeneration were independently associated with cessation, whilst better visual acuity at baseline helped prolong driving.

Changes in sodium levels in Australian packaged foods between 2014 and 2019: an interrupted time series analysis of the impact of the Victorian Salt Reduction Partnership's media advocacy strategy.

BACKGROUND: The Victorian Salt Reduction Partnership (VSRP) implemented a media advocacy strategy (intervention) to stimulate food manufacturers to reduce sodium levels across targeted Australian packaged foods between 2017 and 2019. This study assessed changes in sodium levels of targeted and non-targeted packaged foods during the intervention (2017 to 2019) compared to before the intervention (2014 to 2016) in Australia. METHODS: Annually collected branded-food composition data from 2014 to 2019 were used. Interrupted time series analyses was conducted to compare the trend in sodium levels in packaged foods during the intervention (2017-2019) to the trend in the pre-intervention period (2014-2016). The difference between these trends was derived to estimate the effect of the intervention. RESULTS: A total of 90,807 products were included in the analysis, of which 14,743 were targeted by the intervention. The difference in before and during intervention trends between targeted and non-targeted food categories was 2.59 mg/100 g (95% CI: -13.88 to 19.06). There was a difference in the pre-intervention slope (2014, 2015, 2016) and intervention slope (2017, 2018, 2019) for four of 17 targeted food categories. There was a decrease in sodium levels (mg/100 g) in one food category: frozen ready meals (-13.47; 95% CI: -25.40 to -1.53), and an increase in three categories: flat bread (20.46; 95% CI: 9.11 to 31.81), plain dry biscuits (24.53; 95% CI: 5.87 to 43.19), and bacon (44.54; 95% CI: 6.36 to 82.72). For the other 13 targeted categories, the difference in slopes crossed the line of null effect. CONCLUSIONS: The VSRP's media advocacy strategy did not result in a meaningful reduction in sodium levels of targeted packaged food products during the intervention years compared to trends in sodium levels before the intervention. Our study suggests media advocacy activities highlighting the differences in sodium levels in packaged food products and industry meetings alone are not sufficient to lower average sodium levels in packaged foods in the absence of government leadership and measurable sodium targets.