Surrogate Outcome Measures Research Articles

Validation of a Novel MRI Biomarker of Infarct Severity to Predict Functional Outcome After Endovascular Thrombectomy.

Background: Endovascular thrombectomy (EVT) dramatically improves clinical outcomes, but the final infarct volume (FIV) on MRI only accounts for a minority of the treatment effect. An imaging biomarker that more strongly correlates with post-EVT functional outcome would be helpful for clinical prognosis and serve as a surrogate outcome measure in trials of EVT-adjuvant therapies. Here, we aimed to validate a novel MRI-based metric, infarct density, which leverages post-EVT apparent diffusion coefficient (ADC) as a marker of infarct severity. Methods:A retrospective cohort was derived from a single-center prospective EVT registry. Consecutive anterior circulation EVT patients were included from 2018-2019 who achieved successful reperfusion (mTICI ≥2b). MRI was performed 12-48 hours post-EVT and processed via RAPID to quantify FIV using the ADC <620 threshold. Lesion volume was also collected using ADC <470 threshold, and infarct density was calculated as: (volume <470/volume <620)x100%. Good outcome was defined as ≤2 on the 90-day modified Rankin Scale. Multivariable logistic regression models quantified the association between clinical/imaging variables and outcome. ROC analysis quantified model classification performance. Results: Of 319 EVT patients, 272 met inclusion criteria. The mean age was 69 ±13 years, 41% were female, and 62% achieved a good outcome. After adjusting for clinical and radiographic factors, FIV (aOR 0.99 per 1mL; 95%CI: 0.98-1.00; p=0.03) and infarct density (aOR 0.95 per 1%; 95%CI: 0.94-0.97; p<0.001) were both independently inversely associated with good outcome. The final model incorporating both FIV and infarct density achieved excellent classification performance (AUC 0.87; 95%CI: 0.83-0.91). Removing infarct density from the model diminished its performance (AUC 0.83; 95%CI: 0.78-0.88; p=0.01). Conclusion: ADC-based infarct density after EVT is independently associated with long-term outcome and provides greater prognostic information than FIV alone. Post-EVT infarct density may be useful in clinical care and as a surrogate outcome measure in trials of EVT-adjuvant therapies.

A New Perspective on Drugs for Duchenne Muscular Dystrophy: Proposals for Better Respiratory Outcomes and Improved Regulatory Pathways.

New drugs for Duchenne muscular dystrophy (DMD) are emerging rapidly. However, we and others believe these drugs are achieving regulatory approval prematurely. It is the cardiorespiratory complications of DMD that cause the disease's major morbidities and that determine survival. Thus, to be truly effective, a new drug must improve cardiorespiratory function; instead, new drugs are approved for patient use via accelerated regulatory pathways that rely on surrogate outcome measures with unproven clinical benefits (such as tissue levels of non-biologic, truncated dystrophin) and on scales that reflect muscle strength (such as small improvements in timed activities). In DMD, cardiorespiratory complications occur in "older" individuals who are in the non-ambulatory stage of the disease. In contrast, accelerated approvals are based on data from young, ambulatory subjects, a group that essentially never experiences cardiorespiratory complications. When drug studies do obtain cardiorespiratory data, their methodologies are suboptimal. We critically review these methodologies in detail, including problems with the use of threshold levels of respiratory function as outcome measures; problems with the use of historical controls, whose results vary widely, and are influenced by uncontrolled variables related to their observational nature; and the limitations of using percent predicted forced vital capacity (FVC %pred), and its single rate of decline across a wide range of age and function, as a preferred respiratory outcome measure. We discuss the advantages of an alternative respiratory outcome, the absolute value of FVC with aging (the "Rideau plot"). Unlike FVC %pred, the Rideau plot considers distinct phenotypes rather than aggregating all individuals into a single respiratory trajectory. Key features of the Rideau plot can show the nature and timing of a drug's effect on respiratory function, making it a potentially better outcome measure for assessing the respiratory effects of a drug. With this article, we use our respiratory perspective to critically examine the DMD drug development process and to propose improvements in study methodologies and in the regulatory processes that approve new drugs.

Evaluation of Retinal Sensitivity in Complete Retinal-Pigment-Epithelium and Outer Retinal Atrophy (cRORA) Lesions in Intermediate Age-Related Macular Degeneration (iAMD) by High-Resolution Microperimetry

Objective: Lesions characterized as complete retinal pigment epithelium and outer retinal atrophy (cRORA) are linked to the progression of intermediate age-related macular degeneration (iAMD). However, the extent of functional impairment of such precursor lesions remains uncertain. Methods: In this cross-sectional study, 4 participants (mean age ± standard deviation: 71.5 ± 2.1 years) underwent extensive multimodal imaging and psychophysical testing of cRORA lesions secondary to iAMD. Lesion-specific functional testing was performed using patient individualized testing grids with clinical conventional available (Stimulus size: 0.43°, ~125 µm) and experimental adaptive optics scanning light ophthalmoscope (AOSLO, stimulus size 0.07°, ~20 µm) based microperimetry (MP). One cRORA lesion site and one in-eye control region were tested per patient, respectively. Results: AOSLO imaging revealed an overall decrease in photoreceptor reflectivity, areas of hyporeflectivity over drusen, interspersed with hyperreflective foci, and disrupted photoreceptor mosaic in regions of cRORA. Localized retinal sensitivity assessment with clinical conventional MP yielded an average loss of −14.0 ± 3.3 dB at cRORA lesions compared to the in-eye control regions. In contrast, localized visual impairment assessed by high-resolution AOSLO-MP with smaller test stimuli (20 µm) revealed a sensitivity loss of −15.1 ± 5.1 dB at cRORA lesions (p &lt; 0.01). Notably, also the area surrounding cRORA lesions can be impacted. Conclusions: We demonstrated that cRORA lesions are associated with severe localized functional impairment. cRORA precursor lesions may thus be considered as a surrogate outcome measure in future interventional iAMD trials.

Patient-Clinician Communication Interventions Across Multiple Primary Care Sites

Despite various attempts to improve patient-clinician communication, there has been limited head-to-head comparison of these efforts. To assess whether clinician coaching (mobile application or in-person) is more effective than reminder posters in examination rooms and whether mobile app use is noninferior to in-person coaching. A cluster randomized clinical trial with 3 arms. A total of 21 primary care clinics participated in 3 health systems in the US; participants were patients and primary care clinicians with clinic visits between August 28, 2019, and December 31, 2021. Data were analyzed from August 4, 2022, to November 10, 2024. Data analysis was based on intention to treat. In-person coaching of clinicians with standardized patient instructor training (high-touch), mobile application-based coaching (high-tech), and posters placed in examination rooms encouraging shared decision-making (AskShareKnow [ASK]). Before visits, patients in the high-touch and high-tech groups were prompted to inform their clinicians of the most important matter for discussion using online check-in. The primary outcome was a patient engagement measure (CollaboRATE) of patient perceptions of communication and shared decision-making during the visit. Difference-in-differences mixed-effect regression with random intercepts for primary care clinician were used for analyses. Secondary outcomes included the net promoter score (patient's likelihood of recommending this clinician to others) and patient's confidence in managing their health. Participants included 4852 patients with a median age of 54 years (IQR, 39-66 years); 63.6% were women. A total of 114 clinicians (median age range, 40-59 years; 48 were women [42.1%]) participated. The 3 interventions did not differ significantly in probability of CollaboRATE top score (marginal difference, high-tech vs ASK, -0.021; 95% CI, -0.073 to 0.030; high-touch vs ASK, -0.018, 95% CI, -0.069 to 0.033; high-tech vs high-touch, -0.003, 95% CI, -0.057 to 0.052; P = .14). Patients in the high-tech group were less likely to recommend their clinician to others than patients in the high-touch group (difference in marginal probability, -0.056; 95% CI, -0.118 to 0.019; P = .04). After 3 months, patients in the high-tech group had a significantly lower score than patients in the high-touch group (mean difference, -0.176; 95% CI, -0.341 to -0.011; P = .04) in confidence in managing their health. This cluster randomized clinical trial found no evidence of intervention effects, although there were differences across systems. Some secondary outcomes suggested positive effect of clinicians receiving in-person coaching. Alternative outcome measures of patient engagement may be needed. ClinicalTrials.gov Identifier: NCT03385512.

The Prognostic Value of Single and Repeated ≥10% FEV1 Declines for Chronic Lung Allograft Dysfunction

There is a paucity of data reporting the positive and negative predictive values (PPV, NPV) of acute declines in lung function on chronic lung allograft dysfunction (CLAD). We sought to define the predictive ability of single or repeated FEV1 declines for at least 3 weeks on the development of CLAD or death by 1-year. We analyzed 340 subjects with at least 3 years of follow-up data from two lung transplant centers. A single ≥10% FEV1 decline had a PPV of 35% and NPV of 63%, and a repeated ≥10% FEV1 decline for at least 3 weeks had a PPV of 44% and NPV of 65%. Notably, the proportion of individuals with incipient CLAD at the time of a single or repeated ≥20% FEV1 decline was 50% and 71%, respectively. These estimates could inform the development of acute lung allograft dysfunction FEV1 thresholds as enrollment criteria or surrogate outcome measures.

Impact of Fractional Ablative Laser Therapy on Function, Symptoms, and Quality of Life in the Management of Traumatic Scars: A Review.

A substantial and expanding body of literature addresses the safety and efficacy of fractional ablative laser therapy for traumatic scarring resulting from burns and other trauma. However, available scar research commonly employs standardized assessment scales that generally do not directly address the impact on function and overall quality of life. Unlike past reviews, this manuscript will explore available evidence with a focus explicitly on function and quality of life (QoL) outcomes and de-emphasize surrogate outcome measures that rely primarily on visual characteristics. Through literature review conducted up to January 2024, the authors examined relevant studies focusing on function and quality of life outcomes in traumatic and burn scar management with fractional ablative laser therapy. PubMed, EMBASE, MEDLINE, and Cochrane Library were utilized as primary databases. Reference lists were secondarily reviewed to supplement the literature review process. Studies that did not highlight functional or QoL endpoints or were not in the English language were excluded. The reviewed studies demonstrated that fractional ablative therapy led to consistent significant and meaningful improvements in functional outcomes, relief from pruritus and pain, and overall enhancements in quality of life for patients with traumatic scarring. Adverse events associated with fractional ablative therapy were infrequent and generally of mild severity, indicating a favorable safety profile. The findings from this literature review document ample existing evidence supporting the efficacy and safety of fractional ablative therapy to enhance function, mobility, reduce pruritus and pain, and improve overall QoL. Fractional ablative laser therapy should be integrated more widely into standard management protocols. Given the previous reliance on standardized scar assessment tools that heavily integrate visual characteristics, future studies should prioritize functional and QoL outcomes to further advance scar management protocols and optimize patient care.

Latently Mediating: A Bayesian Take on Causal Mediation Analysis with Structured Survey Data

In this paper, we propose a Bayesian causal mediation approach to the analysis of experimental data when both the outcome and the mediator are measured through structured questionnaires based on Likert-scaled inquiries. Our estimation strategy builds upon the error-in-variables literature and, specifically, it leverages Item Response Theory to explicitly model the observed surrogate mediator and outcome measures. We employ their elicited latent counterparts in a simple g-computation algorithm, where we exploit the fundamental identifying assumptions of causal mediation analysis to impute all the relevant counterfactuals and estimate the causal parameters of interest. We finally devise a sensitivity analysis procedure to test the robustness of the proposed methods to the restrictive requirement of mediator’s conditional ignorability. We demonstrate the functioning of our proposed methodology through an empirical application using survey data from an online experiment on food purchasing intentions and the effect of different labeling regimes.

Update on Clinical Trial Endpoints in Gene Therapy Trials for Inherited Retinal Diseases.

Inherited retinal diseases (IRDs) encompass a wide spectrum of rare conditions characterized by diverse phenotypes associated with hundreds of genetic variations, often leading to progressive visual impairment and profound vision loss. Multiple natural history studies and clinical trials exploring gene therapy for various IRDs are ongoing. Outcomes for ophthalmic trials measure visual changes in three main categories-structural, functional, and patient-focused outcomes. Since IRDs may range from congenital with poor central vision from birth to affecting the peripheral retina initially and progressing insidiously with visual acuity affected late in the disease course, typical outcome measures such as central visual acuity and ocular coherence tomography (OCT) imaging of the macula may not provide adequate representation of therapeutic outcomes including alterations in disease course. Thus, alternative unique outcome measures are necessary to assess loss of peripheral vision, color vision, night vision, and contrast sensitivity in IRDs. These differences have complicated the assessment of clinical outcomes for IRD therapies, and the clinical trials for IRDs have had to design novel specialized endpoints to demonstrate treatment efficacy. As genetic engineering and gene therapy techniques continue to advance with growing investment from industry and accelerated approval tracks for orphan conditions, the clinical trials must continue to improve their assessments to demonstrate safety and efficacy of new gene therapies that aim to come to market. Here, we will provide an overview of the current gene therapy approaches, review various endpoints for measuring visual function, highlight those that are utilized in recent gene therapy trials, and provide an overview of stage 2 and 3 IRD trials through the second quarter of 2024.

The effects of physical activity prescription on mental health: Evidence from primary care

While the benefits of physical activity on health are well documented, in high-income countries 1 in 3 adults do not reach the recommended levels. Thus, policy makers have developed interventions to promote physical activity. The aim of this research is to evaluate the effectiveness of physical activity prescription on mental health outcomes, by studying an intervention that prescribes physical activity at the primary care level in Catalonia (PAFES). This intervention specifically targets the adult population with high cardiovascular risk. We use data from the Health Survey of Catalonia (2011–2016) and exploit the variation in the number of trained General Practitioners that prescribe physical activity. Our results show that physical activity prescription reduces the probability of suffering from poor mental health. This effect is mainly driven by females within the targeted population. We also explore the main effect (or the output) of the intervention. While PAFES increases the probability of patients undertaking high-level physical activity, it does not affect rates of sedentarism or minutes walked per day. Results are consistent when using alternative mental health outcome measures, including self-reported depression and anxiety. We conclude that the prescription of physical activity not only contributes to the improvement of physical health but is also a useful tool to help preserve mental wellbeing.

Auditory Localization Performance in Cochlear Implant Recipients With Single-Sided Deafness: The Challenges and Limitations of Current Outcome Metrics.

Acoustic localization accuracy metrics currently employed in clinical literature both overestimate and underestimate performance benefit of cochlear implantation (CI) for single-sided deafness (SSD). Although localization in SSD with CI has been investigated, performance characterization has relied heavily on average error. Although attractively concise, this measure may misrepresent performance. Here, we characterize frequency-specific localization on a granular level in subjects with CI for SSD as a critical analysis of localization outcome metrics. Eight CI recipients with SSD were recruited. Stimuli of broadband (BBN) and narrowband noise (NBN) at low (500 Hz), mid (1000 Hz), and high (4000 Hz) frequencies were presented in a semianechoic chamber. Localization accuracy was quantified in mean angular error (MAE) and linear regression slope. Use of a CI for SSD subjects improved localization performance by slope for all stimuli ( p ≤ 0.0033) to a level that was equal to normal-hearing controls at 1 and 4 kHz ( p ≥ 0.2281). MAE was also significantly improved for SSD subjects using CI for BBN stimuli ( p ≪ 0.0001); however, no statistically significant improvement in MAE was seen for NBN ( p ≥ 0.5773) with CI use. Descriptive analysis of individual subject performance highlights the reasons for contradictory results. There is inherent challenge in characterizing localization benefit for individuals with CI for SSD. Our data demonstrate the limitations of utilization of average error as the sole metric for outcome benefit. We emphasize the importance of continued research investigating alternative outcome measures as we work toward a more refined understanding of the potential benefits and limitations of cochlear implantation for SSD.

Pathophysiology, Diagnosis, Prognosis, and Prevention of Poststroke Epilepsy: Clinical and Research Implications.

Poststroke epilepsy (PSE) is associated with higher mortality and poor functional and cognitive outcomes in patients with stroke. With the remarkable development of acute stroke treatment, there is a growing number of survivors with PSE. Although approximately 10% of patients with stroke develop PSE, given the significant burden of stroke worldwide, PSE is a significant problem in stroke survivors. Therefore, the attention of health policymakers and significant funding are required to promote PSE prevention research. The current PSE definition includes unprovoked seizures occurring more than 7 days after stroke onset, given the high recurrence risks of seizures. However, the pathologic cascade of stroke is not uniform, indicating the need for a tissue-based approach rather than a time-based one to distinguish early seizures from late seizures. EEG is a commonly used tool in the diagnostic work-up of PSE. EEG findings during the acute phase of stroke can potentially stratify the risk of subsequent seizures and predict the development of poststroke epileptogenesis. Recent reports suggest that cortical superficial siderosis, which may be involved in epileptogenesis, is a promising marker for PSE. By incorporating such markers, future risk-scoring models could guide treatment strategies, particularly for the primary prophylaxis of PSE. To date, drugs that prevent poststroke epileptogenesis are lacking. The primary challenge involves the substantial cost burden due to the difficulty of reliably enrolling patients who develop PSE. There is, therefore, a critical need to determine reliable biomarkers for PSE. The goal is to be able to use them for trial enrichment and as a surrogate outcome measure for epileptogenesis. Moreover, seizure prophylaxis is essential to prevent functional and cognitive decline in stroke survivors. Further elucidation of factors that contribute to poststroke epileptogenesis is eagerly awaited. Meanwhile, the regimen of antiseizure medications should be based on individual cardiovascular risk, psychosomatic comorbidities, and concomitant medications. This review summarizes the current understanding of poststroke epileptogenesis, its risks, prognostic models, prophylaxis, and strategies for secondary prevention of seizures and suggests strategies to advance research on PSE.

Antimicrobial stewardship programs in acute-care hospitals: A multicenter assessment of structure, process, and outcome indicators in Italy and Spain

BackgroundAntimicrobial stewardship (AMS) programs have been differently implemented across Europe. This study primarily aimed to compare AMS in two European regions. Secondarily, the study explored the COVID-19 pandemic impact on surrogate outcome indicators of AMS. MethodsA retrospective observational study was conducted in Piedmont (Italy) and Catalonia (Spain). AMS programs were compared through structure and process indicators in 2021. Changes in surrogate outcome indicators (antimicrobial usage; alcohol-based sanitizer consumption; antimicrobial resistance, AMR) from 2017 to 2021 described the pandemic impact. ResultsSeventy-eight facilities provided structure and process indicators. Catalonia showed better structure scores (p < 0.001) and less dispersion in both indicators. The greatest areas to improve were accountability (Piedmont) and diversification of strategies (Catalonia). Overall, the regions reported consistent changes in outcome indicators. Antimicrobial usage decreased in 2020, returning to near-pre-pandemic levels in 2021. Alcohol-based sanitizer consumption surged in 2020, then dipped remaining above pre-pandemic levels. AMR trends were minimally affected. ConclusionsThe centralized approach of Catalonia ensured consistent attainment of quality objectives across all facilities, but it may limit facility-specific strategies. In Piedmont, accountability remain one of the most critical factors as in previous years. The pandemic did not substantially disrupt surrogate outcome measures of AMS. However, the data on AMR suggest that maintaining vigilance against this issue remains paramount.

Outcome Measures of Clinical Trials in Pediatric Chronic Kidney Disease

Clinical trials of chronic kidney disease (CKD) in children have important implications for the early identification and management of CKD. The selection of clinical trial outcomes is critical for assessing the effectiveness of interventions in pediatric CKD clinical trials. This review systematically examines the spectrum of outcome measures deployed in pediatric CKD clinical trials, which includes clinical and alternative outcomes, patient-reported outcome measures (PROMs), and safety indicators. Alternative outcome measures were stratified into four levels of evidence strength: convincing, probable, suggestive, and inconclusive. Consequently, the selection of outcome measures for pediatric CKD clinical trials mandates careful consideration of both their methodological feasibility and the robustness of their evidence base. Moreover, the burgeoning field of PROMs warrants integration into the design of future pediatric clinical trials to enrich the relevance and impact of research findings.

Breast Cancer Screening: Can We Justify Deescalation?

Novel breast cancer screening methods that detect greater numbers of occult (nonpalpable) tumors have been rapidly incorporated into clinical practice, with the aim of reducing mortality. Yet, tumor detection has never been validated as a proper surrogate outcome measure for breast cancer mortality. Moreover, the detection of greater numbers of occult cancers increases the risk of overdiagnosis, which refers to detection of tumors that pose no threat to life and would never have been detected in the absence of screening. With recent advances in breast cancer therapy, many cancers that were previously curable only if detected as occult tumors with mammography screening are perhaps now curable even when detected as small palpable tumors, thereby giving us an opportunity to deescalate screening and mitigate the risk of overdiagnosis. Thus, a randomized trial comparing screening mammography versus screening clinical breast examination (CBE), with breast cancer mortality as the endpoint, is now warranted. In such a trial, hand-held ultrasound might aid in the interpretation of screening CBE findings. In conclusion, recent improvements in breast cancer therapy provide the justification to assess the deescalation of breast cancer screening. See related article by Farber et al., p. 671.

Do Commercial Place Managers Explain Crime Across Places? Yes and NO(PE)

ObjectivesSome criminologists of place have argued that property owners and place managers are the key actors exerting guardianship over crime and driving differences in crime across places, giving rise to the “Neighborhoods Out of Places Explanation” (NOPE) theory of crime. However, research to date has yet to fully evaluate if crime statistically varies across properties, their owners, or surrounding geographies.MethodsData scraped from Yelp.com is used to identify 1070 land parcels that had at least one business receiving reviews from 2014 to 2020. 911 dispatches for disturbances are linked to parcels and measured as the rate of events per Yelp reviewer in the average year. Hierarchical negative binomial modeling-based variance decomposition techniques are used to evaluate how variation in disturbance rates is distributed across parcels, owners, census blocks, and census tracts. Hierarchical negative binomial models are used to assess the correlates of disturbance rates. Sensitivity analyses assess the correlates of disturbance rates using a single-level negative binomial model with bootstrapped standard errors as well as an alternative outcome measure based on count of 911 events.ResultsCommercial disturbance rates vary across parcels, parcel owners, and blocks. At the parcel level, higher Yelp ratings are associated with lower disturbance rates while parcel square footage and land value are associated with increased disturbance rates. Additionally, parcel-level crime disturbance rates are explained by block features such as poverty, violent crime, and the number of Yelp restaurants on the block.ConclusionsParcel, owner, and block features can all help explain why some restaurants have more crime than others. Future research should build on the place management perspective by investigating the wider breadth of potential actors who may exert guardianship over properties while acknowledging that offenders and targets systematically vary across geographies, making effective guardianship more difficult in some locations than others.

Persistent neurocognitive deficits in cognitively impaired survivors of sepsis are explained by reductions in working memory capacity.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Mounting evidence suggests that many cognitively impaired sepsis survivors show long-term neurocognitive deficits in neuropsychological tasks. To date, the underlying mechanisms of these deficits are insufficiently understood. Based on previous evaluations we hypothesized that visual attention and working memory may be affected in a sample of cognitively impaired sepsis survivors. We utilized psychophysical whole-and partial-report paradigms based on the computational theory of visual attention (TVA) to determine (i) whether sepsis survivors show changes in basic parameters of visual attention and working memory, (ii) whether the affected parameters are related to neuropsychological test results in a standard battery in sepsis survivors and matched healthy control participants, (iii) whether between-group differences in these basic parameters of visual attention could account for underperformance of sepsis survivors in neuropsychological tests when adjusting for potentially relevant clinical variables. We showed that, in sepsis survivors, the maximum number of elements consciously maintained in an instant, i.e. the working memory storage capacity K, is reduced (sepsis survivors: M = 3.0; healthy controls: M = 3.4). Moreover, K explained variance in neurocognitive outcomes -17% in attentional and 16 % in executive functions - in a standard neuropsychological battery. The association remained stable when adjusting for clinical variables. Thus, in our sample of cognitively impaired sepsis survivors, a reduction in working memory capacity seems to be a critical determinant of the neurocognitive sequelae. It should be the subject of future work on mechanisms but may also serve as surrogate outcome measure in interventional studies.

The economic impact of water diversion: evidence from China

Abstract Many areas in the world are facing the problem of sustainable development due to water scarcity. One of the reasons for this issue is that the regional distribution of water resources is inequitable worldwide. The water diversion is a potential way to ease the water shortages as a result of the unequal distribution of water resources. As is well known, the South-to-North Water Diversion Project (SNWDP) in China is the largest project of water diversion over the world, which is transferring water resources between two river basins. This paper analyses the economic impact of the water diversion with the example of the SNWDP. It was found that the economic status of the areas affected by the SNWDP increased, relative to other regions. This result is robust when estimating with alternative outcome measure or subsample, and with alternative methods. The mechanism analysis shows that the main reason for the increased economic development level is that the water diversion encourages growth of the service industry in the water-receiving areas by supplying water for domestic use. These results imply that the sectors with more value-added may benefit better from the water diversion.

Relationship between objectively measured physical activity and subclinical cardiovascular disease: a systematic review

IntroductionThe association of physical activity (PA) with subclinical cardiovascular disease (CVD) is unclear. Clarifying this relationship may inform cardiovascular prevention strategies.MethodsWe performed a systematic review (CRD42021226089) using Medline, Embase, CINAHL...

Socioeconomic position, modifiable dementia risk and cognitive decline: results of 12‐year Maastricht Aging Study

AbstractBackgroundEvidence of modifiable risk factors for cognitive decline and dementia is accumulating, showing the potential of dementia risk reduction via lifestyle modification and cardiovascular risk management. People with low socioeconomic status (SES) have increased dementia risk and on average worse health. This study investigated whether the association between a modifiable dementia risk score and rate of cognitive decline differs across SES strata.MethodData were used from Maastricht Aging Study (MAAS), a prospective cohort study with a 12‐year follow‐up. Participants aged ≥40 years with complete dementia risk profiles were included (n = 1223). The validated ’LIfestyle for BRAin health’ (LIBRA) index was used to assess the modifiable dementia risk fraction. Cognitive performance was serially assessed at baseline, 6 and 12 years and measured in the domains of information processing speed, executive functioning and verbal memory function. A SES compound score was calculated from equivalent income and educational level and divided into tertiles (low, middle, high). Linear mixed models were used to study the association between LIBRA, SES and their interaction on the rate of cognitive decline.ResultParticipants in the lowest SES tertile displayed more decline in information processing speed (vs. middle SES: X2 = 7.08, p = 0.029; vs. high SES: X2 = 9.49, p = 0.009) and verbal memory (vs. middle SES: X2 = 9.28, p&lt;0.001; vs. high SES: X2 = 16.68, p&lt;0.001) compared to their middle‐ and high‐SES counterparts. Higher (unhealthier) LIBRA scores were also associated with more decline in information processing speed (X2 = 12.66, p = 0.002) and verbal memory (X2 = 4.63, p = 0.032). No consistent effect modification by SES on the association between LIBRA and cognition was found.ConclusionThis study shows that lower SES and higher modifiable dementia risk predict faster decline in information processing speed and verbal memory function over 12 years. Results suggest that lifestyle is an important determinant of cognitive decline across SES groups. Yet, people with low SES had a more unfavourable modifiable risk score suggesting more potential for lifestyle‐based interventions. LIBRA could be useful as a participant selection tool or as a surrogate outcome measure in lifestyle intervention trials, and can inform people about individual risk behaviours as part of public health initiatives.

Fair and efficient vaccine allocation: A generalized Gini index approach

The paper proposes an optimization model for the allocation of vaccines to a heterogeneous population composed of several subpopulations with different sizes and epidemiological disease transmission parameters. As the objective, an aggregated function combining a standard utilitarian efficiency criterion with a Gini index–related penalty term is considered. Contrary to previous work, we adopt an outcome equity view: The inequity measure is not based on vaccination fractions or other input factors, but on the fractions of individuals escaping infection, as predicted by an susceptible‐infectious‐removed (SIR) model. An adjusted pro rata (APR) policy of vaccine allocation minimizing inequity in this outcome view is introduced, and a numerical procedure for its determination is presented. The concepts are developed both for the case of segregated subpopulations and for that of interactions between the subpopulations. Interestingly, in a large number of instances, the optimal solution under the aggregated objective function turns out to be identical to APR. Whether APR is locally or even globally optimal in a concrete case depends on the relation of an inequity aversion parameter to certain threshold values. While the local optimality threshold can be determined by linear programming, the determination of the global optimality threshold, as the vaccine allocation problem itself, is a problem of nonconvex optimization. We suggest an exact optimization approach for smaller instances, and propose algorithms building on particle swarm optimization for threshold determination and allocation optimization at larger instances. Extensions to alternative outcome measures such as the number of fatalities are presented as well. In addition to the investigation of randomly generated instances, two test cases from the literature are revisited in the context of the present work. Moreover, a new case study based on data from the COVID‐19 outbreak in Austria in 2020 is introduced and analyzed.