True Differences Research Articles

Considerations for pooling real-world data as a comparator cohort to a single arm trial: a simulation study on assessment of heterogeneity

BackgroundNovel precision medicine therapeutics target increasingly granular, genomically-defined populations. Rare sub-groups make it challenging to study within a clinical trial or single real-world data (RWD) source; therefore, pooling from disparate sources of RWD may be required for feasibility. Heterogeneity assessment for pooled data is particularly complex when contrasting a pooled real-world comparator cohort (rwCC) with a single-arm clinical trial (SAT), because the individual comparisons are not independent as all compare a rwCC to the same SAT. Our objective was to develop a methodological framework for pooling RWD focused on the rwCC use case, and simulate novel approaches of heterogeneity assessment, especially for small datasets.MethodsWe present a framework with the following steps: pre-specification, assessment of dataset eligibility, and outcome analyses (including assessment of outcome heterogeneity). We then simulated heterogeneity assessments for a binary response outcome in a SAT compared to two rwCCs, using standard methods for meta-analysis, and an Adjusted Cochran’s Q test, and directly comparing the individual participant data (IPD) from the rwCCs.ResultsWe found identical power to detect a true difference for the adjusted Cochran’s Q test and the IPD method, with both approaches superior to a standard Cochran’s Q test. When assessing the impact of heterogeneity in the null scenario of no difference between the SAT and rwCCs, a lack of statistical power led to Type 1 error inflation. Similarly, in the alternative scenario of a true difference between SAT and rwCCs, we found substantial Type 2 error, with underpowered heterogeneity testing leading to underestimation of the treatment effect.ConclusionsWe developed a methodological framework for pooling RWD sources in the context of designing a rwCC for a SAT. When testing for heterogeneity during this process, the adjusted Cochran’s Q test matches the statistical power of IPD heterogeneity testing. Limitations of quantitative heterogeneity testing in protecting against Type 1 or Type 2 error indicate these tests are best used descriptively, and after careful selection of datasets based on clinical/data considerations. We hope these findings will facilitate the rigorous pooling of RWD to unlock insights to benefit oncology patients.

Seeing Behavior as Black, Brown, or White: Teachers’ Racial/Ethnic Bias in Perceptions of Routine Classroom Misbehavior

Building on social psychological research on individual bias, this article uses the concept of “perceived blameworthiness” to investigate whether Black and Latino boys are perceived by teachers as being more culpable, or “blameworthy,” than White boys for objectively identical, routine classroom misbehavior at school. To isolate teacher bias from true differences in behavior, I use an original video experiment involving 1,339 teachers in 295 U.S. schools. Teachers in the experiment are randomly assigned to view and respond to a video of a White, Black, or Latino boy committing identical misbehavior. I find that Black boys experience teacher blaming bias, where they are perceived as being more “blameworthy” than White boys for identical misbehavior. Results for Latino boys are directionally similar to those for Black boys but do not reach statistical significance. Findings have implications for racialized assessments of behavior across a range of evaluative contexts.

The effect of the feed additive «Kormogran selen-3» on fish breeding, morphometric indicators and marketable qualities of Rainbow trout

An experimental cultivation of rainbow trout was carried out using the selenium-containing feed additive «Kormogran Selen-3». According to a number of morphometric parameters, there were no significant true differences between the experimental and control groups, however, an intensification of fat metabolism in the trout of the experimental group was established, which slowed down the process of accumulation of intracavitary fat by individuals. This caused some lag in the process of total mass accumulation and some decrease in fish-breeding and biological indicators. At the same time, there was no decrease in the rate of linear growth and overall development of fish. The main accumulation of selenium occurred in the liver, where its content increased by 613,9 times (from 1112 to 15363 μg/kg). At the same time, the content of this element in white muscles increased by 5,2 times, and in red – by 2 times, which indicates the possibility of intravital enrichment of muscle tissue of rainbow trout with selenium. The analysis of the quality of commercial fish and its nutritional value showed the advantages of the experimental batch in comparison with the control of the yield of edible parts, organoleptic evaluation of smoked products, which at the same time can be attributed to a functional product as a source of selenium.

A Potential Source of Bias in Group-Level EEG Microstate Analysis.

Microstate analysis is a promising technique for analyzing high-density electroencephalographic data, but there are multiple questions about methodological best practices. Between and within individuals, microstates can differ both in terms of characteristic topographies and temporal dynamics, which leads to analytic challenges as the measurement of microstate dynamics is dependent on assumptions about their topographies. Here we focus on the analysis of group differences, using simulations seeded on real data from healthy control subjects to compare approaches that derive separate sets of maps within subgroups versus a single set of maps applied uniformly to the entire dataset. In the absence of true group differences in either microstate maps or temporal metrics, we found that using separate subgroup maps resulted in substantially inflated type I error rates. On the other hand, when groups truly differed in their microstate maps, analyses based on a single set of maps confounded topographic effects with differences in other derived metrics. We propose an approach to alleviate both classes of bias, based on a paired analysis of all subgroup maps. We illustrate the qualitative and quantitative impact of these issues in real data by comparing waking versus non-rapid eye movement sleep microstates. Overall, our results suggest that even subtle chance differences in microstate topography can have profound effects on derived microstate metrics and that future studies using microstate analysis should take steps to mitigate this large source of error.

Refining Incidence and Characteristics of Inflammatory Myopathies: A Quadruple-Source Capture-Recapture Survey Using the 2017 European League Against Rheumatism/American College of Rheumatology Classification Criteria.

Inflammatory myopathies (IM), characterized by muscle inflammation and weakness, are rare systemic diseases. Our previous study estimated an IM incidence rate of 7.98 cases per million people per year (95% confidence interval 7.38-8.66) and highlighted important variations that were likely because of methodologic issues rather than true epidemiologic differences. In this study, we aimed to refine the incidence of IM, using the 2017 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for IM and a quadruple-source capture-recapture method during a 6-year period in Alsace, France, a region with a population of 2 million having benefits of good access to health care and accredited IM referral centers. Clinical data of potential IM patients were obtained from 4 sources (general practitioners and community specialists, public and private hospital records, public and private laboratories, and archives from the pathology department). Patients residing in Alsace and who fulfilled the 2017 EULAR/ACR criteria for IM between January 1, 2006, and January 1, 2013, were included. We corrected potentially incomplete ascertainment of cases with capture-recapture analyses. We studied both spatial and temporal distributions of incidence of IM. We also assessed systemic manifestations of the disease. Our review of 1,742 potential cases identified 106 patients with IM. No spatial or temporal heterogeneity was observed. Use of log-linear models showed an estimated 14.9 additional missed cases. Thus, the incidence rate of IM was 8.22 new cases per million inhabitants per year (95% confidence interval 6.76-9.69). Extramuscular manifestations other than dermatomyositis rash were frequently recorded. The stringent methodology used in our study provides an accurate estimation of the incidence of IM. This study also demonstrates, in a population-based cohort, the systemic nature of IM.

Identity-by-descent-based estimation of the X chromosome effective population size with application to sex-specific demographic history.

The effective size of a population (Ne) in the recent past can be estimated through analysis of identity-by-descent (IBD) segments. Several methods have been developed for estimating Ne from autosomal IBD segments, but no such effort has been made with X chromosome IBD segments. In this work, we propose a method to estimate the X chromosome effective population size from X chromosome IBD segments. We show how to use the estimated autosome Ne and X chromosome Ne to estimate the female and male effective population sizes. We demonstrate the accuracy of our autosome and X chromosome Ne estimation with simulated data. We find that the estimated female and male effective population sizes generally reflect the simulated sex-specific effective population sizes across the past 100 generations but that short-term differences between the estimated sex-specific Ne across tens of generations may not reliably indicate true sex-specific differences. We analyzed the effective size of populations represented by samples of sequenced UK White British and UK Indian individuals from the UK Biobank.

Data repeatability for the Cosmed K4 b2 portable metabolic cart during non-steady state exercise

BACKGROUND: Portable metabolic carts are a popular tool to assess aerobic capacity and affirm many cardiorespiratory conditions. They may also measure strength training performance. Given their popularity and increased usage to assess strength training performance; their data accuracy and consistency are important to determine. OBJECTIVE: Measure Cosmed K4 b2 portable metabolic cart data repeatability from consecutive seated calf press workouts. METHODS: Fifteen women and twelve men did two workouts that began with a stationary cycling warm-up followed by calf presses. Gases were measured before the calf press portion of workouts to establish baseline VO2 and VCO2 values, as well as continually throughout and after the calf press protocol. Subjects were detached from the cart once gas values returned to baseline after workouts concluded. In addition to VO2 and VCO2, repeatability was quantified for: breaths per minute, tidal volume, ventilation, O2 uptake relative to body mass, expired O2 and CO2 fractions, percent fat and carbohydrate utilization, METS and total energy cost. Mean and peak values per variable were analyzed. Repeatability was assessed separately for male and female data, as well as with values pooled, by the following: intraclass correlation coefficients, eta squared, limits of agreement, coefficient of variation and smallest real difference percent. RESULTS: Per variable, repeatability values across workouts were low. Female intraclass correlation coefficient mean values were more repeatable for variables related to gas measurements, yet male data were generally more repeatable for those related to substrate usage. CONCLUSIONS: Results for some repeatability indices were influenced by measurement magnitude. Peak values were predictably less repeatable than those for mean values. Most smallest real differences percent scores are so high they were rendered irrelevant or meaningless to determine true differences among paired values. Results suggest low data repeatability that are likely appropriate and realistic for the exercise protocol, hardware and intensity examined.

Enhancing measurement validity in diverse populations: Modern approaches to evaluating differential item functioning.

When developing and evaluating psychometric measures, a key concern is to ensure that they accurately capture individual differences on the intended construct across the entire population of interest. Inaccurate assessments of individual differences can occur when responses to some items reflect not only the intended construct but also construct-irrelevant characteristics, like a person's race or sex. Unaccounted for, this item bias can lead to apparent differences on the scores that do not reflect true differences, invalidating comparisons between people with different backgrounds. Accordingly, empirically identifying which items manifest bias through the evaluation of differential item functioning (DIF) has been a longstanding focus of much psychometric research. The majority of this work has focused on evaluating DIF across two (or a few) groups. Modern conceptualizations of identity, however, emphasize its multi-determined and intersectional nature, with some aspects better represented as dimensional than categorical. Fortunately, many model-based approaches to modelling DIF now exist that allow for simultaneous evaluation of multiple background variables, including both continuous and categorical variables, and potential interactions among background variables. This paper provides a comparative, integrative review of these new approaches to modelling DIF and clarifies both the opportunities and challenges associated with their application in psychometric research.

Subacromial Balloon Spacer Versus Partial Rotator Cuff Repair in the Treatment of Massive Irreparable Rotator Cuff Tears: Facility Personnel Allocation and Procedural Cost Analysis.

Background The subacromial balloon is a novel technology that has shown promise in managing a select patient population with massive irreparable rotator cuff tears. The purpose of this study was to quantify the true facility cost difference between subacromial balloon placement (SBP) and partial rotator cuff repair (PCR). Methodology A prospective cohort of patients with massive irreparable rotator cuff tears randomized to SBP versus PCR between2015 and 2018 was retrospectively reviewed. Demographic variables, medical comorbidities, and range-of-motion (ROM) outcomes for all patients were recorded. True facility costs with respect to personnel were calculated using a time-driven activity based-costing (TDABC) algorithm and were classified into personnel costs and supply costs. Results Seven patients were treated with PCR compared to nine treated with SBP. No significant differences were observed with respect to demographic characteristics. Postoperative mean external rotation was 37° in SBP patients significantly higher than that of PCR patients at 8° (P= 0.023). Personnel time and cost differences while in the operating room (OR) were significantly less for the SBP ($605.58) compared to PCR ($1362.76) (P< 0.001). Implant costs were higher for SBP when compared to PCR, whereas disposable equipment costs were higher for PCR when compared to SBP. The total mean true facility cost was $7658.00 for SBP, significantly higher than that of PCR at $3429.00 (P< 0.001). Conclusions Despite the substantial reduction in personnel costs seen with SBP, the true facility cost of SBP was significantly higher than that of PCR. As this novel technology is used more ubiquitously and its price is negotiated down, the cost savings seen in personnel and OR time will become more significant. Future prospective cost analyses should follow up on the changes in implant costs and account for potential anesthesia cost savings.

Endodontic operative field asepsis: a comparison between general dentists and specialists

Objective The aim was to evaluate the establishment of an aseptic endodontic operative field in general dentistry by assessing general dentists’ ability to reduce the amount of contamination to a non-cultivable level, and to compare the operative field asepsis at a general dentistry clinic with that at an endodontic specialist clinic. Materials and Methods A total of 353 teeth were included in the study (153 in general dentistry, 200 at the specialist clinic). After isolation, control samples were taken, the operative fields disinfected with 30% hydrogen peroxide (1 min) followed by 5% iodine tincture or .5% chlorhexidine solution. Samples were collected from the access cavity area and buccal area, placed in a fluid thioglycolate medium, incubated (37°, 7 d), evaluated for growth/non-growth. Results Significantly more contamination was observed at the general dentistry clinic (31.6%, 95/301), than at the endodontic specialist clinic (7.0%, 27/386) (p <.001). In general dentistry, significantly more positive samples were collected in the buccal area than in the occlusal area. Significantly more positive samples were collected when the chlorhexidine protocol had been used, both in general dentistry (p <.001) and at the specialist clinic (p =.028). Conclusions The result from this study shows insufficient endodontic aseptic control in general dentistry. At the specialist clinic, both disinfection protocols were able to reduce the amount of microorganisms to a non-cultivable level. The observed difference between the protocols may not reflect a true difference in the effectiveness of the antimicrobial solutions, as confounding factors may have contributed to the result.

Topical pharmacokinetics of brinzolamide suspensions in rabbits and variability analysis for sample size and design considerations

Identifying critical attributes for complex locally acting ophthalmic formulations and establishing in vitro-in vivo correlations can facilitate selection of appropriate thresholds for formulation changes that reflect lack of impact on in vivo performance. In this study the marketed antiglaucoma product Azopt® (1% brinzolamide suspension) and five other brinzolamide formulations varying in particle size distributions and apparent viscosities were topically administered in rabbits, and their ocular pharmacokinetics was determined in multiple ocular tissues. Statistical evaluation with ANOVA showed no significant differences between the formulations in the peak drug concentration (Cmax) in the aqueous humor and iris-ciliary body. As a post-hoc analysis, the within animal and total variability was determined for Cmax in the aqueous humor and iris-ciliary body. Based on the observed variability, we investigated the sample size needed for two types of study designs to observe statistically significant differences in Cmax. For the sample size calculations, assuming both 25% and 50% true differences in Cmax between two formulations, two study designs were compared: paired-eye dosing design (one formulation in one eye and another formulation in the other eye of the same animal at the same time) versus parallel-group design. The number of rabbits needed in the paired-eye dosing design are much lower than in the parallel-group design. For example, when the true difference in aqueous humor Cmax is 25%, nine rabbits are required in the paired-eye design versus seventy rabbits (35 per treatment) in the parallel-group design to observe a statistically significant difference with a power of 80%. Therefore, the proposed paired-eye dosing design is a viable option for the design of pharmacokinetic studies comparing ophthalmic products to determine the impact of formulation differences.

French Validation of the Camouflaging Autistic Traits Questionnaire (CAT-Q).

Autistic camouflaging is a collection of strategies used to hide autistic characteristics. It can have serious consequences on autistic people's mental health and needs to be addressed and measured in clinical practice. The purpose of this study is to evaluate the psychometric properties of the French adaptation of the Camouflaging Autistic Traits Questionnaire. 1227 participants (744 autistic, 483 non-autistic) answered the French version of the CAT-Q in an online survey or on paper. Confirmatory factor analysis, measurement invariance testing, internal consistency analysis (McDonald's ω), and convergent validity with the DASS-21 depression subscale were conducted. Test-rest reliability was assessed on a sample of 22 autistic volunteers using intraclass correlation coefficient. A good fit was found for the original three-factor structure as well as a good internal consistency, excellent test-retest reliability and highly significant convergent validity. Measurement invariance testing indicates however that the meaning behind items is different for autistic vs. non-autistic people. The French version of the CAT-Q can be used in clinical settings to assess camouflaging behaviors and intent to camouflage. Further research is needed to clarify the camouflage construct and whether reported measurement noninvariance are due to cultural differences or a true difference in what camouflaging might mean for non-autistic people.

Atopic Dermatitis Across Shades of Skin.

Atopic dermatitis (AD) is a chronic, heterogeneous inflammatory skin disease that is associated with immense patient burden globally. There is increasing appreciation of disparities among patients identified as having skin of color (SOC), which often refers to patients of non-White race or non-European ancestry, but can broadly include individuals from a number of different racial, ethnic, ancestral, and skin pigmentation groups based on definition. In this narrative review, we discuss key terminology as it relates to AD across shades of skin, including modern definitions of 'race', 'ethnicity', and 'SOC'. We then synthesize the current literature describing disparities in AD prevalence, disease recognition, and burden alongside current data regarding genetic and immunologic findings across SOC populations. In the context of these findings, we highlight key concomitant social determinants of health, including environmental factors, socioeconomic status, and access to care, for which race often serves as a proxy for true biological and genetic differences. Finally, we discuss future efforts to shift to a more inclusive understanding of AD to encompass all shades of skin, toensure equitable representation of diverse populations in high impact research, and intensify efforts to address the critical upstream factors driving observed disparities.

Socioeconomic indices guided linear mixed-effects and meta-regression modelling of the temporal, global and regional prevalence of Helicobacter pylori in environmental waters: A class I carcinogen

Environmental waters (EW) substantially lend to the transmission of Helicobacter pylori (Hp). But the increase in Hp infections and antimicrobial resistance is often attributed to socioeconomic status. The connection between socioeconomic status and Hp prevalence in EW is however yet to be investigated. This study aimed to assess the impacts of socioeconomic indices (SI: continent, world bank region (WBR), world bank income (WBI), WHO region, Socio-demographic Index (SDI quintile), Sustainable Development Index (SuDI), and Human Development Index (HDI)) on the prevalence of Hp in EW. Hp-EW data were fitted to a generalized linear mixed-effects model and SI-guided meta-regression models with a 1000-resampling test. The worldwide prevalence of Hp in EW was 21.76% [95% confidence interval [CI]: 10.29–40.29], which declined significantly from 59.52% [43.28–74.37] in 1990–99 to 19.36% [3.99–58.09] in 2010–19 and with increasing trend in 2020–22 (33.33%, 22.66–45.43). Hp prevalence in EW was highest in North America (45.12%, 17.07–76.66), then Europe (22.38%, 5.96–56.74), South America (22.09%, 13.76–33.49), Asia (2.98%, 0.02–85.17), and Africa (2.56%, 0.00–99.99). It was negligibly different among sampling settings, WBI, and WHO regions demonstrating highest prevalence in rural location [42.62%, 3.07–94.56], HIEs [32.82%, 13.19–61.10], and AMR [39.43%, 19.92–63.01], respectively. However, HDI, sample size, and microbiological method robustly predict Hp prevalence in EW justifying 26.08%, 21.15%, and 16.44% of the true difference, respectively. In conclusion, Hp is highly prevalence in EW across regional/socioeconomic strata and thus challenged the uses of socioeconomic status as surrogate for hygienic/sanitary practices in estimating Hp infection prevalence.

Associations between micro-geographic social vulnerability and disparities in cancer incidence.

e18523 Background: Disparities in cancer incidence and diagnosis are the result of complex physical-social-environmental interactions. Geography is one crucial lens for assessment of these disparities. The CDC’s Social Vulnerability Index (SVI) ranks micro-geographies such as Census Tracts based on social factors and can be used to identify health disparities in measures such as cancer incidence. Methods: Actual and age-adjusted expected incidence of common cancers were obtained from the New York State Cancer Registry for 2013-2017 at the Census Tract level. Data were merged with the CDC’s Overall SVI rating for 2016 at the Census Tract level. Analysis included 4,647 Census Tracts, accounting for 97.71% of New York State’s 2016 population (19,078,306 population included). For each cancer, actual and expected incidence were grouped by overall SVI percentile, then percentage deviation from expected cancer incidence was calculated. Pearson correlational test and two-tailed t-test were performed for incidence deviation of each cancer by overall SVI percentile. Results: In New York State, significant correlations between Census Tract Overall Social Vulnerability Index (SVI) percentile and percentage deviation from expected cancer incidence were found for 5 out of 6 cancers reported in the State Cancer Registry. Strong positive relationships between degree of vulnerability and deviation from expected incidence were found for Lung Cancer (R = 0.75, p &lt; 0.001) and Colorectal Cancer (R = 0.67, p &lt; 0.001). Strong negative relationships were found for Female Breast Cancer (R = -0.90, p &lt; 0.001), Urinary Bladder Cancer (R = -0.76, p &lt; 0.001), and Non-Hodgkin Lymphoma (R = -0.73, p &lt; 0.001). A significant correlation was not found for Prostate Cancer, which demonstrated a bimodal relationship with higher excess incidence at low and high vulnerability ratings. Conclusions: There are statistically significant increases in reported incidence of Colorectal and Lung Cancers in more vulnerable Census Tracts in NY State. Paradoxically, there are significant decreases in reported incidence of Breast Cancer, Bladder Cancer, and Non-Hodgkin Lymphoma in more vulnerable Census Tracts. Further exploration of micro-geographic trends is critical to understand the extent to which these disparities are explained by true differences in cancer incidence or by variations in screening access and utilization. [Table: see text]

0511 An observational retrospective study of the efficacy of oral appliance therapy (OAT) in treating obstructive sleep apnea (OSA)

Abstract Introduction Obstructive sleep apnea (OSA) affects approximately 15-30% of males and 10-15% of females in North America. While positive airway pressure (PAP) therapy remains the standard in the treatment of OSA, oral appliance therapy (OAT) has emerged as a viable non-invasive alternative. However, there are limited data on OAT efficacy published, and therefore many sleep clinicians question its efficacy. We conducted a 14-month single-center consecutive chart review to evaluate OAT efficacy. Methods A manual chart review was performed for records from 11/1/2020 to 12/10/2022. Potential charts were identified in the electronic health record by searching for prescriptions for OAT and orders for home sleep apnea tests (HSAT). If there was a test performed after the prescription was written, the chart was reviewed manually for previous test results and verified that post-OAT testing was conducted. Extracted information included age, BMI, gender, pre-OAT HSAT apnea-hypopnea index (AHI), and post-OAT HSAT AHI. The 4% desaturation criteria for AHI was used in accordance with current Medicare guidelines. A paired t-test was performed after ensuring there were no outliers and a normal distribution. Results There were 10 patients included in the analysis: 6 women, 4 men. The average age was 61.1 years (95% CI 49.9-72.3), and average BMI was 28.9 (95% CI 253-32.4). Prior to intervention, 2 patients had moderate OSA with the rest mild (average pre-OAT AHI 13). After OAT device, 4 patients had mild OSA and the rest did not have residual OSA (average post-OAT AHI 4). The results of the paired t-test showed that the mean AHI was statistically significantly different between the two groups (t=-4.54 with df=9, p=0.0014). The mean difference was -8.1 with 95% confidence interval for the true difference in the population mean AHI of -12.1, -4.06. Conclusion The results demonstrate efficacy of OAT in treating OSA. Clinicians should consider OAT as both primary and secondary therapy for mild-to-moderate OSA. Support (if any) N/A

Parent-adolescent informant discrepancy on the Strengths and Difficulties Questionnaire in the UK Millennium Cohort Study

BackgroundDevelopmental researchers often use a multi-informant approach to measure adolescent behaviour and adjustment, but informant discrepancies are common. In general population samples, it is often found that parents report more positive and less negative outcomes than adolescents themselves. This study aimed to investigate factors associated with informant discrepancy, including adolescent sex, and parental level of psychological distress and education.MethodsInformant discrepancy on the Strengths and Difficulties Questionnaire was investigated using a Latent Difference Score (LDS) approach, which estimates the true difference between parent and adolescent reports in a structural equation model. The sample were parent-adolescent dyads from the seventh wave of the UK Millennium Cohort Study (N = 6947, 49.3% female, aged 17 years).ResultsParents reported lower levels of difficulties (emotion symptoms, peer problems, conduct problems), and higher levels of pro-social behaviour than adolescents themselves. Conditional effects were found, as discrepancy was greater amongst parent-daughter dyads for emotion and peer problems, and greater amongst parent-son dyads for conduct problems and pro-social behaviour. Parent-adolescent discrepancy was also greater generally if parents had a lower level of psychological distress or a higher level of education.ConclusionsIn a large general population sample from the UK, it was found that adolescents tended to report more negative and less positive outcomes than parents reported about them. Conditional effects were found at the parent and adolescent level suggesting that specific informant biases are likely to impact the measurement of adolescent behaviour and adjustment across reporters.

The Edge Effect in High-Throughput Proteomics: A Cautionary Tale.

In order for mass spectrometry to continue to grow as a platform for high-throughput clinical and translational research, careful consideration must be given to quality control by ensuring that the assay performs reproducibly and accurately and precisely. In particular, the throughput required for large cohort clinical validation in biomarker discovery and diagnostic screening has driven the growth of multiplexed targeted liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) assays paired with sample preparation and analysis in multiwell plates. However, large scale MS-based proteomics studies are often plagued by batch effects: sources of technical variation in the data, which can arise from a diverse array of sources such as sample preparation batches, different reagent lots, or indeed MS signal drift. These batch effects can confound the detection of true signal differences, resulting in incorrect conclusions being drawn about significant biological effects or lack thereof. Here, we present an intraplate batch effect termed the edge effect arising from temperature gradients in multiwell plates, commonly reported in preclinical cell culture studies but not yet reported in a clinical proteomics setting. We present methods herein to ameliorate the phenomenon including proper assessment of heating techniques for multiwell plates and incorporation of surrogate standards, which can normalize for intraplate variation.

OC-027 RANDOMISED CONTROLLED TRIAL OF THE DESARDA TECHNIQUE AND SUTURE REPAIR FOR OBSTRUCTED INGUINAL HERNIA

Abstract Aim Open inguinal hernia repair remains one of the most commonly performed operations worldwide. For elective surgery, mesh implantation is an established global ‘gold standard’. However, for emergency repair of obstructed hernia, non-mesh techniques may be utilised. We designed a randomised controlled trial to compare the open, non-mesh ‘Desarda’ against non-mesh suture darn repair in the treatment of obstructed inguinal hernias. Materials &amp; Methods A prospective randomized controlled trial was undertaken between Feb and Aug 2020 at the Emergency Unit, of a busy hospital in a resource-constrained setting. To identify a true difference in operating time, a sample size of 100 patients was calculated using WHO calculator. Exclusion criteria were patients ASA 3+ or with recurrent or strangulated intestine; ethical approval was obtained from the hospital Ethics’ Committee and informed consent obtained from all participants. Randomisation was by the sealed opaque envelope method. Data analysis by SPSS version 25 using Student t-test; p-value ≤0.05 was considered significant. Results Total 100 patients were included (71 male and 29 female). Mean age of patients: 39.1 years±6.1SD. Mean operative time was significantly lower in Desarda group (50.5±1.7) compared to sutured repair (58.8±2.1SD) p=0.000. Intra-operative and immediately postoperative complications were not identified in any of the patients. Patient reported outcomes will be reviewed at the 2-year point. Conclusion In this RCT of emergency repair of obstructed inguinal hernia, Desarda's repair was safe and effective and took significantly less surgical time compared to a standard sutured darn repair. Longer term, patient reported outcomes are awaited.

Health and economic outcomes of a universal early intervention for parents and children from birth to age five: evaluation of the Salut Programme using a natural experiment

BackgroundThe aim of this study was to investigate the health and economic outcomes of a universal early intervention for parents and children, the Salut Programme, from birth to when the child completed five years of age.MethodsThis study adopted a retrospective observational design using routinely collected linked register data with respect to both exposures and outcomes from Västerbotten county, in northern Sweden. Making use of a natural experiment, areas that received care-as-usual (non-Salut area) were compared to areas where the Programme was implemented after 2006 (Salut area) in terms of: (i) health outcomes, healthcare resource use and costs around pregnancy, delivery and birth, and (ii) healthcare resource use and related costs, as well as costs of care of sick child. We estimated total cumulative costs related to inpatient and specialised outpatient care for mothers and children, and financial benefits paid to mothers to stay home from work to care for a sick child. Two analyses were conducted: a matched difference-in difference analysis using the total sample and an analysis including a longitudinal subsample.ResultsThe longitudinal analysis on mothers who gave birth in both pre- and post-measure periods showed that mothers exposed to the Programme had on average 6% (95% CI 3–9%) more full-term pregnancies and 2% (95% CI 0.03-3%) more babies with a birth weight ≥ 2500 g, compared to mothers who had care-as-usual. Savings were incurred in terms of outpatient care costs for children of mothers in the Salut area ($826). The difference-in-difference analysis using the total sample did not result in any significant differences in health outcomes or cumulative resource use over time.ConclusionsThe Salut Programme achieved health gains, as a health promotion early intervention for children and parents, in terms of more full-term pregnancies and more babies with a birth weight ≥ 2500 g, at reasonable cost, and may lead to lower usage of outpatient care. Other indicators point towards positive effects, but the small sample size may have led to underestimation of true differences.