Selection Bias Research Articles

Association of Body Mass Index and Parkinson Disease: A Bidirectional Mendelian Randomization Study.

The role of body mass index (BMI) in Parkinson disease (PD) is unclear. Based on the Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in PD (Courage-PD) consortium, we used 2-sample Mendelian randomization (MR) to replicate a previously reported inverse association of genetically predicted BMI with PD and investigated whether findings were robust in analyses addressing the potential for survival and incidence-prevalence biases. We also examined whether the BMI-PD relation is bidirectional by performing a reverse MR. We used summary statistics from a genome-wide association study (GWAS) to extract the association of 501 single-nucleotide polymorphisms (SNPs) with BMI and from the Courage-PD and international Parkinson Disease Genomics Consortium (iPDGC) to estimate their association with PD. Analyses are based on participants of European ancestry. We used the inverse-weighted method to compute odds ratios (ORIVW per 4.8 kg/m2 [95% CI]) of PD and additional pleiotropy robust methods. We performed analyses stratified by age, disease duration, and sex. For reverse MR, we used SNPs associated with PD from 2 iPDGC GWAS to assess the effect of genetic liability toward PD on BMI. Summary statistics for BMI are based on 806,834 participants (54% women). Summary statistics for PD are based on 8,919 (40% women) cases and 7,600 (55% women) controls from Courage-PD, and 19,438 (38% women) cases and 24,388 (51% women) controls from iPDGC. In Courage-PD, we found an inverse association between genetically predicted BMI and PD (ORIVW 0.82 [0.70-0.97], p = 0.012) without evidence for pleiotropy. This association tended to be stronger in younger participants (≤67 years, ORIVW 0.71 [0.55-0.92]) and cases with shorter disease duration (≤7 years, ORIVW 0.75 [0.62-0.91]). In pooled Courage-PD + iPDGC analyses, the association was stronger in women (ORIVW 0.85 [0.74-0.99], p = 0.032) than men (ORIVW 0.92 [0.80-1.04], p = 0.18), but the interaction was not statistically significant (p-interaction = 0.48). In reverse MR, there was evidence for pleiotropy, but pleiotropy robust methods showed a significant inverse association. Using an independent data set (Courage-PD), we replicate an inverse association of genetically predicted BMI with PD, not explained by survival or incidence-prevalence biases. Moreover, reverse MR analyses support an inverse association between genetic liability toward PD and BMI, in favor of a bidirectional relation.

Postoperative Outcomes of Bascom Cleft Lift Versus Excision With Secondary Wound Healing for Pilonidal Sinus Disease: A Multicenter Retrospective Analysis.

Pilonidal sinus disease impacts patient's quality of life. In the Netherlands, it is often treated with excision and secondary healing, which is associated with high recurrence rates and poor wound healing. The Bascom cleft lift, an alternative technique, has shown favorable healing times and recurrence rates. The present study aims to compare successful wound healing, time to healing, complications, and recurrence rate between excision with secondary wound healing and Bascom cleft lift. This is a multicenter retrospective study. Three institutions in the Rotterdam region of the Netherlands participated in the study. Patients who underwent excision with secondary healing or Bascom Cleft Lift between July 2015 and August 2021 were included. Primary endpoints included the rate of successful wound healing and the time to achieve healing. Secondary endpoints included postoperative complications and recurrence rate within twelve months after surgery. Out of 272 patients, 128 underwent Bascom cleft lift and 144 patients excision and secondary healing. Recurrent PSD (47.7% vs 22.2%) and abscess history (53.1% vs 40.3%) were more common in the Bascom cleft lift group compared to excision with secondary wound healing. The median follow-up period at the outpatient clinic was 43 days. Wound healing was 84.4% after Bascom cleft lift vs. 32.6% after excision and secondary healing (p < 0.001), with median time to wound healing of 55 days and 101 days, respectively (p < 0.001). Complications were 28.9% for Bascom cleft lift vs. 13.2% for excision and secondary healing (p = 0.003). Recurrent disease was 6.3% after Bascom Cleft Lift and 11.8% after excision and secondary healing (p = 0.113). It has a retrospective design which makes it prone to selection bias and residual confounding. Additionally, the study's short follow-up period further adds to these limitations as longer follow-up may better identify true recurrence rates. Finally, a deficiency is the absence of collected patient satisfaction data, which is nowadays a common scientific issue. This retrospective study shows that Bascom cleft lift is superior to excision and secondary healing given the higher percentage of patients with successful wound healing within a shorter time. See Video Abstract.

When R&amp;D investment improves firm value: the role of board gender diversity

Purpose Agency theory postulates that research and development (R&amp;D) investments are subject to managerial discretion and thus may not enhance firm value as expected. The inconclusive empirical findings in the literature is a testament of that. This paper aims to investigate the interplay between board gender diversity (i.e. women on boards) and value relevance of firms’ effort to innovate as indicated by firms’ R&amp;D investments. Design/methodology/approach Through a sample of 1,626 US-listed firms from the period 2004 to 2019, the authors examine whether board gender diversity promotes or hampers value relevance of firms’ efforts to innovate. The authors use ordinary least squares as the baseline model and address potential endogeneity through instrumental variable two-stage least square, and selection bias through Heckman selection model. Finally, the authors use the financial crisis of 2008 as a natural experiment to investigate the effect of board gender diversity during the crisis period. Findings The results show that board gender diversity positively moderates the relation between R&amp;D and firm value. In times of financial crisis, R&amp;D does not destroy firm value in firms with gender diverse board. The results are robust to measurement error, endogeneity issue, particularly simultaneity and selection bias. Practical implications The findings in this study have several practical implications. Firms that invest heavily in R&amp;D should be mindful of gender diversity in their board recruitment strategies to enhance innovation outputs and firm value. Current and potential investors (i.e. shareholders) should take into consideration board gender diversity in their investment decision-making processes as the results show that gender diverse boards promote more effective governance, which, in turn, leads to better alignment of R&amp;D investments with shareholder value. Regulators aiming to improve corporate governance policies should encourage gender diversity on the boards. The results align with global initiatives such as the United Nations Sustainable Development Goals, particularly Goal 5 on gender equality. Policymakers may use the findings in this study to advocate for more gender diverse governance structures within corporations. Originality/value This study investigates the role gender diverse boards play in creating value from firms’ R&amp;D activities.

Comparison between DaVinci® and Hugo™-RAS Roux-en-Y Gastric Bypass in bariatric surgery

The application of a robotic platform in the bariatric surgical field is intended to enhance the already established advantages of minimally invasive surgery in terms of both technical and clinical outcomes. These advantages are especially relevant for technically challenging multiquadrant operations such as Roux-en-Y Gastric Bypass (RYGB). Consequently, robotic-assisted surgery has emerged as a possible application for bariatric surgeries. The study attempts to assess feasibility and safety of the Hugo™-Robotic-Assisted Surgery System (Hugo™-RAS) platform compared to the DaVinci® Surgical System (DaVinci®-SS) with a focus on complication rates and operative times. We retrospectively reviewed bariatric procedures performed from January 2013 until December 2023. We included all robotic RYGBs performed using Hugo™-RAS and DaVinci®-SS platforms. The study utilized Propensity Score Matching (PSM) analysis to address bias in selection, matching patients based on age, gender, body mass index, comorbidities and past abdominal operations. One hundred thirty-five patients were identified: 90 DaVinci®-SS and 45 Hugo™-RAS procedures. After PSM, each group consisted of 45 patients. There was no discernible disparity observed in relation to early (≤ 30 days) postoperative complications rate (p = 1), mean operative time (for docking time, console time and total operative time: p = 0.176, p = 0.678, p = 0.229, respectively) and postoperative hospital stay (p = 0.052) between DaVinci®-RSS and Hugo™-RAS procedures. Our results suggest that application of both Hugo™-RAS and DaVinci®-SS robotic platforms to RYGB is related to comparable safety profiles. Although DaVinci®-SS remains the most widely adopted platform in clinical practice, this study underscores the potential role of the Hugo™-RAS to provide effective solutions in robotic bariatric procedures.

Investigating the sign of stratocumulus adjustments to aerosols in the ICON global storm-resolving model

Abstract. Aerosols can cause brightening of stratocumulus clouds, thereby cooling the climate. Observations and models disagree on the magnitude of this cooling, partly because of the aerosol-induced liquid water path (LWP) adjustment, with climate models predicting an increase in the LWP and satellites observing a weak decrease in response to increasing aerosols. With higher-resolution global climate models, which allow the simulation of mesoscale circulations in which stratocumulus clouds are embedded, there is hope to start bridging this gap. In this study, we present boreal summertime simulations conducted with the ICOsahedral Non-hydrostatic (ICON) global storm-resolving model (GSRM). Compared to geostationary satellite data, ICON produces realistic cloud coverage in the stratocumulus regions; however, these clouds look cumuliform, and the sign of LWP adjustments disagrees with observations. We investigate this disagreement with a causal approach, which combines time series with knowledge of cloud processes, allowing us to diagnose the sources of observation–model discrepancies. The positive ICON LWP adjustment results from a superposition of processes, with an overestimated positive response due to (1) precipitation suppression, (2) a lack of wet scavenging, and (3) cloud deepening under a weak inversion, despite (4) small negative influences from cloud-top entrainment enhancement. We also find that precipitation suppression and entrainment enhancement occur at different intensities during the day and the night, implying that daytime satellite studies suffer from selection bias. This causal methodology can guide modelers on how to modify model parameterizations and setups to reconcile conflicting studies concerning the sign and magnitude of LWP adjustments across different data sources.

Utilization of Real-World Data to Facilitate Clinical Trials for Patients with Lymphoma

The future directions in leveraging real-world evidence (RWE) and real-world data (RWD) in the field of lymphoma, as compared to traditional experimental clinical trials, are poised to significantly impact research methodologies, treatment strategies, and patient care. Current methods of clinical trials involve a well-controlled design and patient selection bias. Integrating RWE and RWD with experimental clinical trials offers a multifaceted approach to understanding lymphoma and enhancing patient outcomes. In this review, we discuss how RWE has helped shape lymphoma clinical trials, and we compare and evaluate evidence obtained from real-world lymphoma studies/databases with that obtained from clinical trials. We also discuss methods for utilizing surrogate endpoints to facilitate clinical trials and expedite drug development. RWE can be leveraged to bridge the gap between data obtained from clinical trial populations and the broader patient population encountered in clinical practice, by highlighting differences in outcomes and the need for effective treatment strategies across diverse patient groups.

Effect of Different Durations of Treatment With Antihypertensive Drugs With Anticholinergic Effects on the Risk of Dementia: A Target Trial Emulation Study.

Studying the effect of duration of treatment on prognostic outcomes using real-world data is challenging because only people who survive for a long time can receive a treatment for a long time. Specifying a target trial helps overcome such challenge. We aimed to estimate the effect of different durations of treatment with antihypertensive drugs with anticholinergic properties (AC AHT) on the risk of vascular dementia and Alzheimer's disease by emulating a target trial using the UK CPRD GOLD database (2001-2017). Comparing treatment for 3-6 years versus ≤3 years yielded null results for both types of dementia. Comparing a longer duration of treatment, >6 years versus ≤3 years, yielded a 10-year risk ratio of 0.69 (95% CI, 0.54-0.90) for vascular dementia and 0.91 (95% CI, 0.77-1.10) for Alzheimer's disease. For illustration, we performed an analysis that failed to emulate a target trial by assigning exposure categories using post-baseline information, obtaining implausible beneficial estimates. Our findings indicate a modest benefit of longer duration of treatment with AC AHT on vascular dementia and highlight the value of the target trial emulation to avoid selection bias in the evaluation of the effect of different durations of treatment.

New Biomarkers to Define A Biological Borderline Situation for Pancreatic Adenocarcinoma - Results of An Ancillary Study of the PANACHE01-PRODIGE48 Trial.

To investigate in patients treated for a resectable pancreatic ductal adenocarcinoma (PA), the prognostic value of baseline CA19-9 and circulating tumour DNA (ctDNA) for overall survival (OS), to improve death risk stratification, based on a planned ancillary study from PANACHE01-PRODIGE 48 trial. Biological borderline situation that was first used by the MD Anderson, became a standard practice following the international consensus conference in 2016 to manage PA. Regarding the risk of systemic disease especially in the setting of "markedly elevated" CA19-9, neoadjuvant therapy is advised to avoid unnecessary surgery, with risk of early recurrence. To best define biological borderline situations, new biomarkers are needed. Characteristics at diagnosis and OS were compared between patients with or without ctDNA status available. OS was estimated with Kaplan Meier method and compared with log-rank test. Restricted cubic spline approach was used to identify optimal threshold for biological parameters for death risk stratification. Univariate and multivariate Cox proportional hazard models were estimated to assess the association of ctDNA status and other parameters with OS. Among the 132 patients from the primary population for analysis in the PANACHE01 -PRODIGE 48 trial, 92(71%) were available for ctDNA status at diagnosis. No selection bias was identified between patients with or without ctDNA status. 14 patients (15%) were ctDNA+ and exhibited a higher risk for death (P=0,0188; HR95% CI: 2.28 (1.12-4.63). In the 92 patients with ctDNA status available among the others parameter analysed only CA19-9 was statically associated with OS in univariate analysis. Patients with log of CA19-9 equal or superior to 4.4 that corresponds to a CA19-9 of 80 UI/mL were identified at higher risk for death (P=0,0143; HR95% CI: 2.2 (1.15-4.19). In multivariate analysis CA19-19 remained independently associated with OS (p-value=0.0323). When combining the two biomarkers, median OS was of 19.4 (IC 95% 3.8-Not reached) months, 30.2 (IC 95% 17.1-NR) months and not reached (IC 95% 39.3-NR) for "CA19-9 high and ctDNA+ group", "CA19-9 high or ctDNA+ group", and "CA19-9 low and ctDNA- group", respectively (logrank P=0,0069). Progress in the management of potentially operable PA remains limited, relying solely on strategies to optimize the sequence of complete treatment, based on modern multidrug chemotherapy (FOLFIRINOX, GemNabPaclitaxel) and surgical resection. The identification of risk criteria, such as the existence of systemic disease, is an important issue, currently referred to as "biologic borderline disease". Few data, particularly from prospective studies, allow us to identify biomarkers other than CA19-9. Combining ctDNA to CA19-9 could be of interest to best define biological borderline situations in PA.

Uranium in Drinking Water and Bladder Cancer: A Case-Control Study in Michigan.

Uranium is naturally occurring in groundwater used for drinking; however, health risks from naturally occurring concentrations are uncertain. Uranium can cause both radiological and chemical toxicity following ingestion. Bladder and kidneys receive a dose when uranium is excreted into the urine. Investigate the association between uranium in drinking water and bladder cancer risk in a case-control study. A population-based bladder cancer case-control study was conducted in 11 counties of southeastern Michigan. A total of 411 cases and 566 controls provided drinking water and toenail samples and answered questions about lifestyle and residential history. Uranium was measured in drinking water and toenails, and its association with bladder cancer was assessed via unconditional logistic regression models. Median uranium concentration in water was 0.12 μg L-1, with a maximum of 4.99 μg L-1, and median uranium concentration in toenails was 0.0031 μg g-1. In adjusted regression models, there was a suggestion of a protective effect among those exposed to the upper quartile of uranium in drinking water (HR = 0.64, 95% CI: 0.43, 0.96) and toenails (HR 0.66; 95% CI 0.45, 0.96) compared to those in the lowest quartile. Our objective is to investigate additional adjustment of drinking water source at home residence at time of recruitment to address potential selection bias and confounding attenuated results toward the null for drinking water uranium (HR = 0.68, 95% CI: 0.44, 1.05) and toenail uranium (HR = 0.80, 95% CI: 0.53, 1.20). This case-control study showed no increased risk of bladder cancer associated with uranium found in drinking water or toenails.

Improving spatial exposure data for everyone - lifecourse social context and ascertaining residential history.

Measuring age-specific, contextual exposures is crucial for lifecourse epidemiology research. Longitudinal residential data offers a "golden ticket" to cumulative exposure metrics and can enhance our understanding of health disparities. Residential history can be linked to myriad spatiotemporal databases to characterize environmental, socioeconomic, and policy contexts that a person experienced throughout life. However, obtaining accurate residential history is challenging in the United States due to the limitations of administrative registries and self-reports. Xu et al. (Am J Epidemiol. 2024; 193(2):348-359) detail an approach to linking residential history sourced from LexisNexis ® Accurint ® to a Wisconsin-based research cohort, offering insights into challenges with residential history collection. Researchers must analyze the magnitude of selection and misclassification biases inherent to ascertaining residential history from cohort data. A lifecourse framework can provide insights into why the frequency and distance of moves is patterned by age, birth cohort, racial/ethnic identity, socioeconomic status, and urbanicity. Historic and contemporary migration patterns of marginalized people seeking economic and political opportunities must guide interpretations of residential history data. We outline methodologic priorities for use of residential history in health disparities research, including contextualizing residential history data with determinants of residential moves, triangulating spatial exposure assessment methods, and transparently quantifying measurement error.

Characteristics and career outcomes of dermatology-focused medical student research grant recipients

Although several dermatology-focused research grants for medical students exist, studies have yet to evaluate the outcomes of grant recipients, such as entry into dermatology residency and academic careers. We have described the characteristics of recipients of dermatology-focused medical student research grants and outcomes, including entry into dermatology residency and academic careers, and we have focused on seven dermatology-focused national and regional research grants eligible for U.S. medical students. Data were obtained from publicly available online sources for grants from 2004 to 2023. Of the 235 medical student recipients of dermatology research grants between 2004 and 2023, 45.5% attended one of the top 20 medical schools funded by National Institutes of Health research. Of those who completed medical school, 68.3% advanced to a dermatology residency (n=123/180). Among board-certified dermatologists, 44.7% held an academic position (n=34/76); among those who attended a top 20 medical school, 50% held an academic position (n=23/46) compared to 36.7% who did not (n=11/30). Limitations of this study include selection bias and incomplete data availability. Medical student research grants allow students to thoughtfully engage in dermatology research early in medical education. They may facilitate entry into dermatology residency and academic careers and lead to continued research endeavors.

Effectiveness of pharmacological treatments for severe agitation in real-world emergency settings: protocol of individual-participant-data network meta-analysis

BackgroundSevere psychomotor agitation and aggression often require immediate pharmacological intervention, but clear evidence-based recommendations for choosing among the multiple options are lacking. To address this gap, we plan a systematic review and individual-participant-data network meta-analysis to investigate their comparative effectiveness in real-world emergency settings with increased precision.MethodsWe will include randomized controlled trials investigating intramuscular or intravenous pharmacological interventions, as monotherapy or in combination, in adults with severe psychomotor agitation irrespective of the underlying diagnosis and requiring rapid tranquilization in general or psychiatric emergency settings. We will exclude studies before 2002, those focusing on specific reasons for agitation and placebo-controlled trials to avoid concerns related to the transitivity assumption and potential selection biases. We will search for eligible studies in BIOSIS, CENTRAL, CINAHL Plus, Embase, LILACS, MEDLINE via Ovid, PubMed, ProQuest, PsycINFO, ClinicalTrials.gov, and WHO-ICTRP. Individual-participant data will be requested from the study authors and harmonized into a uniform format, and aggregated data will also be extracted from the studies. At least two independent reviewers will conduct the study selection, data extraction, risk-of-bias assessment using RoB 2, and applicability evaluation using the RITES tool. The primary outcome will be the number of patients achieving adequate sedation within 30 min after treatment, with secondary outcomes including the need for additional interventions and adverse events, using odds ratios as the effect size. If enough individual-participant data will be collected, we will synthesize them in a network meta-regression model within a Bayesian framework, incorporating study- and participant-level characteristics to explore potential sources of heterogeneity. In cases where individual-participant data are unavailable, potential data availability bias will be explored, and models allowing for the inclusion of studies reporting only aggregated data will be considered. We will assess the confidence in the evidence using the Confidence in Network Meta-Analysis (CINeMA) approach.DiscussionThis individual-participant-data network meta-analysis aims to provide a fine-tuned synthesis of the evidence on the comparative effectiveness of pharmacological interventions for severe psychomotor agitation in real-world emergency settings. The findings from this study can greatly be provided clearer evidence-based guidance on the most effective treatments.Systematic review registrationPROSPERO CRD42023402365.

Ten questions concerning statistical data analysis in human-centric buildings research: a focus on thermal comfort investigations

Given the large amount of time we spend indoors, designing and operating buildings that are safe, comfortable, and conducive to productivity and well-being is essential. To achieve this goal, in the past decades, research has been conducted to investigate the influence of the indoor environment on occupants. Thermal comfort has been the subject of most investigations in this field. However, despite being a consolidated research topic since the 1920s, statistical practices for analysing thermal comfort data often rely on simplified premises, which may be due to several possible factors (e.g., limited computational capabilities and lack of training). Consequently, important aspects of data analysis are often absent or overlooked. Recent statistics and statistical software advances have provided more options for effectively modelling complex issues. However, properly using these tools requires a solid understanding of statistical analysis, increasing the risk of misuse in practice. This paper presents ten questions highlighting the most critical issues regarding statistical analysis for thermal comfort research and practice. The first four questions provide general perspectives concerning statistical data analysis, while the remaining ones address specific problems related to thermal comfort research, but that can extend to all human-centric research in the built environment. Additionally, the last five questions demonstrate the practical significance of analysis pitfalls (i.e., sampling variability, selection bias, variable selection, clustered/nested observations, and measurement error) through examples with synthetic data. This study provides insights into the current statistical ‘habits’ in thermal comfort research and, more importantly, help researchers better define and conduct their statistical analyses.

Short- and Long-Term Outcomes of Thoracoscopic and Open RepairFor Esophageal Atresia and Tracheoesophageal Fistula

BackgroundThe aim was to evaluate short- and long-term outcomes for thoracoscopic repair of EA/TEF and compare with open repair. MethodsPatients who underwent EA/TEF repair during 2000-2020 were evaluated retrospectively. Patients with delayed repair were excluded. Demographic, operative, outcome data was collected. Outcomes were compared using Wilcoxon-rank sum tests for continuous, Chi-squared/Fisher’s exact tests for categorical data. ResultsThere were 104 patients with primary repair, 49 (47.1%) underwent thoracoscopic repair per surgeon’s choice. Type C accounted for 101 (97.1%) of the cases. Gestational age and birth weight were higher in the thoracoscopy group (p=0.001). The rate of ≥3 VACTERL anomalies was higher in the OR group (p=0.016). Operative time, rate of anastomotic leak, time to first oral feeding were similar (p>0.05). Thoracoscopy group had decreased length of ventilation (p=0.026) and length of stay (p=0.029). The incidence of anastomotic stricture was higher in the thoracoscopy group (p=0.012). Recurrent TEF was one case in each group. Rates of tube feeding at discharge and in first year were similar (p>0.05), rate in third year was decreased (p=0.032) in the thoracoscopy group. Rates of anti-reflux medication in first and third years, and fundoplication rate were similar (p>0.05). ConclusionsMany of the short- and long-term outcomes are comparable between thoracoscopic and open repair of EA/TEF. Length of ventilation, length of stay are decreased in the thoracoscopy group. Anastomotic stricture is higher, the need for long-term tube feeding is lower after thoracoscopic repair. Although these results could be affected by selection bias, they are still promising for advancing thoracoscopic repair of EA/TEF safely and efficiently. Level of EvidenceLevel III

Real-world evidence to support regulatory submissions: Alandscape review and assessment of use cases.

Real-world evidence (RWE) has an increasing role in preapproval settings to support the approval of new medicines and indications. The main objectives of this study were to identify and characterize regulatory use cases that utilized RWE and other related observational approaches through targeted review of publications and regulatory review documents. After screening and inclusion/exclusion, the review characterized 85 regulatory applications with RWE. A total of 31 were in oncology and 54 were in non-oncology therapeutic areas. Most were for indications in adults only (N = 42, 49.4%), while 13 were in pediatrics only (15.3%), and 30 were in both (35.3%). In terms of regulatory context, 59 cases (69.4%) were for an original marketing application, 24 (28.2%) were for label expansion, and 2 (2.4%) were for label modification. Most also received special regulatory designations (e.g., orphan indication, breakthrough therapy, fast track, conditional, and accelerated approvals). There were 42 cases that utilized RWE to support single-arm trials. External data to support single-arm trials were utilized in various ways across use cases, including direct matching, benchmarking, natural history studies as well as literature or previous trials. A variety of data sources were utilized, including electronic health records, claims, registries, site-based charts. Endpoints in oncology use cases commonly included overall survival, progression-free survival. In 13 use cases, RWE was not considered supportive/definitive in regulatory decision-making due to design issues (e.g., small sample size, selection bias, missing data). Overall, RWE is utilized in regulatory approval processes for new indications/label expansion across various therapeutic areas with wide range of approaches. Multifaceted cross-sector efforts are needed to further improve the quality and utility of RWE in regulatory decision-making.

Secondary cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent colorectal peritoneal metastases

BackgroundSecondary treatment of recurrent colorectal peritoneal metastases after previous cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is poorly investigated. ObjectivesTo evaluate the overall survival outcome of secondary (repeat) CRS + HIPEC compared to palliative treatment in recurrent peritoneal disease. MethodsPatients with colorectal peritoneal metastases treated with an index CRS + HIPEC and subsequently having recurrent peritoneal disease were identified from the prospective Swedish national HIPEC registry. Patients were divided into interventional group (secondary CRS + HIPEC) or palliative group. Multivariable logistic regression, propensity-score matching, and survival outcomes were calculated. ResultsAmong 575 patients who underwent complete CRS between 2010 and 2021, 208 (36 %) were diagnosed with a subsequent recurrent peritoneal disease. Forty-two patients (20 %) were offered secondary CRS + HIPEC. Propensity-score matching of secondary interventional cases with palliative cases succeeded in 88 % (n = 37) in which female sex, lower peritoneal cancer index at index surgery, longer disease-free interval, and absence of extra-peritoneal metastases were identified as the most relevant matching covariates. Median OS from date of recurrence was 38 months (95%CI 30–58) in the interventional group and 19 months (95%CI: 15–24) in the palliative group (HR 0.35 95%CI: 0.20–0.63, p = 0.0004). Sensitivity analyses confirmed the results. As reference, the median OS from index CRS + HIPEC in the whole colorectal registry (n = 575) was 41 months (95%CI: 38–45). ConclusionAfter matching for relevant factors, the hazard ratio for death was significantly reduced in patients who were offered a secondary CRS + HIPEC procedure for recurrent peritoneal disease. Selection bias is inherent, but survival outcomes were comparable to those achieved after the initial procedure.

Predicting hurricane evacuation behavior synthesizing data from travel surveys and social media

Evacuation behavior models estimated using post-disaster surveys are not adequate to predict real-time dynamic population response as a hurricane unfolds. With the emergence of ubiquitous technology and devices in recent times, social media data with its higher spatio-temporal coverage has become a potential alternative for understanding evacuation behaviour during hurricanes. However, these data are often associated with selection bias and population representativeness issues. To that extent, the current study proposes a novel data fusion algorithm to combine heterogeneous data sources from transportation systems and social media, in a unified framework to understand and predict real-time population response during hurricanes. Specifically, Twitter data of 2300 users are collected for evacuation response during Hurricane Irma and augmented behaviourally (probabilistically) with a representative National Household Travel Survey (NHTS) data, thus creating a hybrid dataset to improve the representativeness as well as provide a rich set of explanatory variables for understanding the evacuation behavior. The fusion process is conducted using a probabilistic matching method based on a set of common attributes across NHTS and Twitter. The fused dataset is employed to estimate the evacuation model and a comparison exercise is conducted to evaluate the performance of the model via fusion. The model fitness measures clearly demonstrate the improvement in data fit for the evacuation model through the proposed fusion algorithm. Further, we conduct a prediction assessment to illustrate the applicability of the proposed fusion technique and the results clearly highlight the improvement in the evacuation prediction rate achieved through the fused models. The proposed data-driven methods will enhance our ability to predict time-dependent evacuation demand for better hurricane response operations such as targeted warning dissemination and improved evacuation traffic management, allowing emergency plans to be more adaptive.

Sonoanatomy of injecting botulinum neurotoxin into the facial muscles.

Ultrasonography (US) has become an essential tool for guiding botulinum neurotoxin (BoNT) injections in facial muscles, enhancing precision and safety. This narrative review explores the role of US in BoNT administration, particularly in complex anatomical regions, highlighting its impact on treatment customization, real-time visualization, and complication reduction. A comprehensive literature search was conducted using PubMed, MEDLINE, Embase, and Cochrane Library for articles published from January 2018 to December 2023. Search terms included "Botulinum neurotoxin," "facial anatomy," "ultrasonography guided injection," and "facial muscle sonoanatomy." Studies focusing on US-guided BoNT injections in facial muscles were included. Data extraction and synthesis were performed independently by two reviewers, focusing on study design, ultrasonography techniques, outcomes, and conclusions. The review found that US guidance significantly enhances the precision of BoNT injections by providing real-time visualization of facial muscles and blood vessels, thereby reducing the risk of adverse events. US enables tailored injection strategies, ensuring symmetrical facial expressions and minimizing over-treatment. The technique also offers immediate feedback, allowing for on-the-spot adjustments to improve treatment efficacy and safety. However, the review identified limitations, including potential selection bias and variability in US techniques across different studies. US guidance for BoNT injections into facial muscles offers substantial benefits in terms of precision, safety, and treatment customization. Despite the identified limitations, the integration of US into clinical practice is poised to enhance patient outcomes in aesthetic and therapeutic procedures. Further research is needed to standardize US techniques and broaden the inclusivity of studies to validate these findings comprehensively.

Postnatally acquired cytomegalovirus infection among preterm infants.

Although there are multiple benefits of mother's own milk feeding for very-low birth weight, low gestation infants, those born to cytomegalovirus (CMV)-seropositive mothers are at risk for acquiring postnatal CMV infection. This review will describe the risk and consequences of postnatal CMV infection among very preterm infants. Postnatal CMV may manifest as clinically silent infection or as mild to severe and occasionally fatal disease. The risk of disease is balanced by the health benefits of human milk feeding to preterm infants. Postnatal CMV infection has been associated with increased risks of multiple preterm morbidities such as bronchopulmonary dysplasia, necrotizing enterocolitis and neurodevelopmental impairment, but current evidence is limited by the selection bias inherent to reporting in case series and retrospective cohort studies. Knowledge gaps exist regarding the risk-benefit balance of pasteurization to inactivate CMV in fresh breast milk, as well as the optimal dosing, duration and efficacy of treating infected infants with antiviral medications. Multicenter, prospective studies are urgently needed to accurately determine the true burden that postnatal CMV infection presents to very preterm infants. Such studies will inform the need for preventive strategies and treatment guidance.

The proactive and reactive mechanisms of learned spatial suppression.

Selection history refers to the notion that previous allocations of attention or suppression have the potential to elicit lingering and enduring selection biases that are isolated from goal-driven or stimulus-driven attention. However, in the singleton detection mode task, manipulating the selection history of distractors cannot give rise to pure proactive inhibition. Therefore, we employed a combination of a working memory task and a feature search mode task, simultaneously recording cortical activity using EEG, to investigate the mechanisms of suppression guided by selection history. The results from event-related potential and reaction times showed an enhanced inhibitory performance when the distractor was presented at the high-probability location, along with instances where the target appeared at the high-probability location of distractors. These findings demonstrate that a generalized proactive inhibition bias is learned and processed independent of cognitive resources, which is supported by selection history. In contrast, reactive rejection toward the low-probability location was evident through the Pd component under varying cognitive resource conditions. Taken together, our findings indicated that participants learned proactive inhibition when the distractor was at the high-probability location, whereas reactive rejection was involved at low-probability location.