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Results for “Real-world data”

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PubMed2026

SPEN inactivation drives resistance to androgen receptor pathway inhibitors in metastatic prostate cancer.

PURPOSE: Treatment intensification with androgen receptor pathway inhibitors (ARPIs) has become the standard of care for patients with metastatic prostate cancer. However, there remains an unmet need to identify biomarkers for treatment resistance. Here, we identify SPEN inactivation as a driver of ARPI resistance. EXPERIMENTAL DESIGN: Pre-clinical studies were performed in LNCaP and VCaP cell lines. Data from a nationwide prostate cancer clinico-genomic database were extracted. Log-rank test and Cox proportional hazards models were used to compare time to next treatment (TTNT) on ARPI with/without SPEN mutations. SPEN immunohistochemistry was performed on a rapid autopsy metastatic tissue microarray. RESULTS: SPEN was identified as a top enzalutamide resistance hit in an unbiased genome-wide loss-of-function screen. SPEN inactivation results in upregulation of cell cycle proliferation and basal/stem cell activity as well as increased translation of pro-oncogenic genes. In a large patient cohort (N=6828), SPEN mutations are enriched following treatment with ARPIs (2.1% to 3.6%, p=0.001) and correlate with shorter TTNT on ARPI in patients with metastatic hormone-sensitive prostate cancer (6.4 vs 29.7 months, HR 2.67, p=0.02). In a metastatic rapid autopsy cohort (N=181), low SPEN H-score is associated with shorter time on abiraterone (5.0 vs 7.9 months, p=0.023) in metastatic castration-resistant prostate cancer. CONCLUSIONS: In real-world cohorts, loss of SPEN function across genomic, transcriptomic, and protein levels is associated with reduced benefit from ARPI therapy in metastatic prostate cancer. These findings identify SPEN inactivation as a clinically relevant biomarker of ARPI resistance that warrants prospective evaluation to guide treatment selection.

Journal Article↗

PubMed2024

Increased risk of hearing loss associated with MT-RNR1 gene mutations: a real-world investigation among Han Taiwanese Population.

BACKGROUND: Previous studies have implicated inherited mutations in mitochondrial DNA (mtDNA) in sensorineural hearing loss (SNHL). However, the definitive association between mitochondrial 12S rRNA (MT-RNR1) variants and hearing loss in the population has not been well established, particularly in Asia. The objective of this retrospective cohort study was to assess the association between MT-RNR1 variants and the risk of SNHL in patients in Taiwan. METHODS: The cohort included 306,068 participants from Taiwan between January 2003 and December 2020. Participants were classified based on genetic variants, particularly mitochondrial mutations (rs267606618, rs267606619, rs267606617). MT-RNR1 variant cases were matched 1:10 with non-mutant patients by age, gender, and visit year, excluding those with pre-existing hearing loss. The primary endpoint was SNHL, identified using specific ICD-TM codes with a 90% positive predictive value. Medication exposure history was determined via self-report or electronic medical records in the hospital. Cox proportional hazard regression models were used to assess the association between MT-RNR1 variants and hearing loss, adjusting for various covariates. Kaplan-Meier survival curves and log-rank tests compared hearing loss incidence between groups. RESULTS: The mean age of the mtDNA variants group is 32.4 years, with a standard deviation of 19.2 years. The incidence density of hearing loss for the mutation group was 36.42 per 10,000 person-years (95% Confidence Interval [CI], 27.21-47.73), which was higher than the 23.77per 10,000 person-years (95% CI, 21.32-26.42) in the wild-type group (p = 0.0036). Additionally, diabetes mellitus was associated with an increased risk of developing SNHL in individuals with MT-RNR1 variants (adjusted hazard ratio = 1.76 [95% CI, 1.00-3.09], p < 0.05). CONCLUSION: This study highlights the increased risk of hearing loss in patients carrying MT-RNR1 variants, particularly those with diabetes mellitus. Future research that integrates genetic and clinical data is crucial for developing more precise interventions to monitor and treat hearing loss in this vulnerable population.

Adolescent↗

PubMed2025

Integration of Gene Expression and Digital Histology to Predict Treatment-Specific Responses in Breast Cancer.

Deep learning models applied to digital histology can predict gene expression signatures (GES) and offer a low-cost, rapidly available alternative to molecular testing at the time of diagnosis. We optimized transformer-based models to infer GES results and applied this approach to pre-treatment H&E-stained biopsies from 1,940 breast cancer patients treated with neoadjuvant chemotherapy in clinical trial and real-world cohorts. The most predictive histology-derived GES for pathologic complete response (pCR) in the I-SPY2 trial was validated in four external cohorts: CALGB 40601, CALGB 40603, a trial of durvalumab plus CT, and standard-of-care CT-treated patients from the University of Chicago. Among HER2-negative patients, a transformer-based model trained using a signature composed of estrogen-regulated genes, proliferation, apoptosis, and interferon response genes predicted pCR with an AUC of 0.794, outperforming models based on clinical features alone (AUC 0.704, p = 0.001), pathologist TIL assessment, and a model trained directly to predict response from I-SPY2 cases. Tertiles of this signature stratify patients into clinically relevant groups with increasing likelihood of complete response, with pCR rates ≥50% in the top tertile regardless of treatment or hormone receptor status. Additional transformer-based signature models predicted response to specific therapies (but not chemotherapy alone), including a HER2 signaling signature in IO-treated patients, and a claudin-low signature in bevacizumab treated patients. In HER2- cohorts with available gene expression data and histology, models trained on expression data performed similarly to digital histology predictions, but the combination of gene expression and histology outperformed histology alone. These findings suggest that histology-based GES provides additive information to RNA sequencing data and can inform precision treatment selection across breast cancer subtypes.

Journal Article↗

PubMed1999

Effect of initial drug choice on persistence with antihypertensive therapy: the importance of actual practice data.

BACKGROUND: Rational medical decisions should be based on the best possible evidence. Clinical trial results, however, may not reflect conditions in actual practice. In hypertension, for example, trials indicate equivalent antihypertensive efficacy and safety for many medications, yet blood pressure frequently remains uncontrolled, perhaps owing to poor compliance. This paper examines the effect of initial choice of treatment on persistence with therapy in actual practice. METHODS: The authors examined all outpatient prescriptions for antihypertensive medications filled in Saskatchewan between 1989 and 1994 by over 22,000 patients with newly diagnosed hypertension whose initial treatment was with a diuretic, beta-blocker, calcium-channel blocker or angiotensin-converting-enzyme (ACE) inhibitor. Rates of persistence over the first year of treatment were compared. RESULTS: After 6 months, persistence with therapy was poor and differed according to the class of initial therapeutic agent: 80% for diuretics, 85% for beta-blockers, 86% for calcium-channel blockers and 89% for ACE inhibitors (p < 0.001). These differences remained significant when age, sex and health status in the previous year were controlled for. Changes in the therapeutic regimen were also associated with lack of persistence. INTERPRETATION: A relation not seen in clinical trials--between persistence with treatment and initial antihypertensive medication prescribed--was found in actual practice. This relation also indicates the importance of real-world studies for evidence-based medicine.

Adult↗

PubMed1999

Changing patterns of care for war-related post-traumatic stress disorder at Department of Veterans Affairs medical centers: the use of performance data to guide program development.

This study traces the development of services for war-related post-traumatic stress disorder (PTSD) provided at Department of Veterans Affairs (VA) medical centers. During the 1980s, long-stay inpatient programs were the major source of specialized VA treatment for PTSD, and an initial effort at development of specialized outpatient clinics resulted in incomplete implementation. In 1988, a full continuum of inpatient and outpatient services was designed and a national program of performance monitoring and outcome assessment was implemented to standardize program structure, monitor delivery, and evaluate outcomes. A series of multisite outcome studies showed significant but modest improvement in association with specialized outpatient treatment; they also showed that traditional long-term inpatient programs were no more effective and were far more costly than short-term specialized inpatient programs. Since 1995, the VA has shifted the emphasis of care substantially from inpatient to outpatient settings. National monitoring efforts have documented maintenance of specialized PTSD treatment capacity, increased access, improvement on available administrative measures of quality of care, and improved inpatient outcomes. Although there have been major changes in the treatment of mental illness in most health care systems in recent years, change in the treatment of PTSD at VA medical centers is unique in that it has been guided by the results of multisite outcome studies conducted in a "real-world" setting and has been supported by ongoing nationwide performance monitoring.

Ambulatory Care↗

PubMed2026

Predicting training outcomes for developmental dyslexia from EEG data.

Developmental dyslexia (DD) is characterised by lower-than-average reading abilities and is diagnosed in approximately 10% of individuals. The societal barriers may limit professional fulfilment and psychological wellbeing of individuals with DD, calling for the development of effective interventions to counteract them. As DD is associated with challenges in both phonological and visuo-attentional domains, different longitudinal training approaches were developed to strengthen them. However, they require a considerable amount of personal, social and economic resources and the outcomes may vary depending on individual differences in behavioural and neurophysiological functionality. Hence, predicting training outcomes might help in developing personalised treatment protocols and optimising the use of resources. In the present work we applied machine learning to resting-state EEG to predict longitudinal training outcomes in adults with DD enrolled in a randomized clinical trial. In particular, one group received a visuo-attentional training combined with transcranial alternating current stimulation (tACS), another group received visuo-attentional training with sham/placebo stimulation, and the third group received a phonological training with sham/placebo stimulation. The improvement in text reading speed was associated with spectral power in low-beta and individual frequencies in the alpha (IAF) and beta (IBF) bands, while the improvement in pseudoword reading was associated with IBF. The findings highlight the potential of capturing neural markers of treatment responsiveness in DD. Future studies should focus on the generalisability of predictive models to real-world settings, while investigating whether specific EEG markers predict responsiveness to distinct remediation protocols, thus supporting the development of personalised interventions.

Humans↗

PubMed1993

The case for chaos in childhood epidemics. II. Predicting historical epidemics from mathematical models.

The case for chaos in childhood epidemics rests on two observations. The first is that historical epidemics show various 'fieldmarks' of chaos, such as positive Lyapunov exponents. Second, phase portraits reconstructed from real-world epidemiological time series bear a striking resemblance to chaotic solutions obtained from certain epidemiological models. Both lines of evidence are subject to dispute: the algorithms used to look for the fieldmarks can be fooled by short, noisy time series, and the same fieldmarks can be generated by stochastic models in which there is demonstrably no chaos at all. In the present paper, we compare the predictive abilities of stochastic models with those of mechanistic scenarios that admit to chaotic solutions. The main results are as follows: (i) the mechanistic models outperform their stochastic counterparts; (ii) forecasting efficacy of the deterministic models is maximized by positing parameter values that induce chaotic behaviour; (iii) simple mechanistic models are equal if not superior to more detailed schemes that include age structure; and (iv) prediction accuracy for monthly notifications declines rapidly with time, so that, from a practical standpoint, the results are of little value. By way of contrast, next amplitude maps can successfully forecast successive changes in maximum incidence one or more years into the future.

Child↗

PubMed2026

Diagnostic Performance of Machine Learning for Systemic Lupus Erythematosus: Systematic Review and Meta-Analysis.

BACKGROUND: Early and accurate diagnosis of systemic lupus erythematosus (SLE) and its organ involvement is essential. Previous reviews of machine learning (ML) in SLE combined heterogeneous tasks and validation strategies and may have overinterpreted model performance. OBJECTIVE: This study evaluated the diagnostic performance of ML and deep learning (DL) models for 3 clinically distinct SLE-related tasks: SLE classification or diagnosis, lupus nephritis (LN) diagnosis, and neuropsychiatric systemic lupus erythematosus (NPSLE) discrimination. We also assessed methodological quality and certainty of evidence. METHODS: PubMed, Embase, Cochrane Library, Web of Science, and IEEE Xplore were searched from January 2014 to April 2026. Eligible peer-reviewed diagnostic accuracy studies developed or validated ML or DL models for 1 of the 3 prespecified tasks, used an accepted reference standard, and provided data for a 2×2 contingency table. Bivariate random-effects meta-analyses with the Hartung-Knapp-Sidik-Jonkman adjustment were used to pool sensitivity and specificity. We reported 95% prediction intervals (PIs), assessed risk of bias using the Quality Assessment of Diagnostic Accuracy Studies for Artificial Intelligence tool (QUADAS-AI; Viknesh Sounderajah [Imperial College London]), and evaluated certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation framework for diagnostic test accuracy. RESULTS: Twenty-nine studies were included: 17 for SLE classification, 5 for LN diagnosis, and 7 for NPSLE discrimination. In the primary task-stratified analysis, pooled sensitivity was 0.91 (95% CI 0.86-0.94; 95% PI 0.56-0.99), and pooled specificity was 0.94 (95% CI 0.91-0.96; 95% PI 0.69-0.99), with low heterogeneity (I²=23.9% and 22.9%, respectively). DL models showed a sensitivity of 0.93 and specificity of 0.95, compared with 0.88 and 0.94 for traditional ML models. Certainty of evidence was high for most analyses but low for LN diagnosis because of inconsistency and imprecision. All studies were retrospective, and only 9 of 29 (31%) performed independent external validation. Overall risk of bias was high or unclear in 22 of 29 (75.9%) studies. No study reported model calibration, decision-curve analysis, or net clinical benefit. CONCLUSIONS: ML models showed promising diagnostic accuracy across 3 distinct SLE-related tasks, but wide PIs, limited external validation, and pervasive risk of bias restrict conclusions about real-world generalizability. Prospective multicenter studies with standardized tasks and reference standards, independent external validation, and formal assessment of calibration and clinical utility are required before clinical implementation.

Humans↗

PubMed1994

Use of transdermal nicotine in a state-level prescription plan for the elderly. A first look at 'real-world' patch users.

OBJECTIVE: To assess transdermal nicotine use patterns and outcomes in a population of low-income older smokers. DESIGN: A 6-month telephone follow-up survey of smokers filling prescriptions for transdermal nicotine in the first 3 months of 1992. SETTING: Pennsylvania's Pharmaceutical Assistance Plan for the Elderly, the nation's largest state-level prescription plan for the elderly. POPULATION: A total of 1070 noninstitutionalized male and female smokers aged 65 through 74 years. MAIN OUTCOME MEASURES: Self-reported physician/pharmacist advice and adjunctive treatments, concomitant smoking, and 6-month smoking abstinence. RESULTS: Respondents were predominantly long-term heavy smokers. They used nicotine patches for an average of 5 weeks, with few reporting use beyond 3 months or recalling bothersome side effects. Most of those with previous quit attempts rated quitting with the patch "easier." The 29% self-reported 6-month quit rate observed is encouraging. However, compliance with patch use guidelines was far from ideal in this high-risk population: only 54% of respondents received any initial advice or materials from their physicians or pharmacists, fewer than 2% took part in a formal clinic or one-to-one treatment program, and almost half (47%) smoked while using the patch, including 20% who smoked every day. Concomitant smoking was strongly associated with failure to achieve abstinence (P < .001). More frequent contact with physicians and/or pharmacists was associated with less concomitant smoking (P < .001) and higher quit rates (P = .005). CONCLUSIONS: This survey offers an important first look at problems and prospects for nicotine patch therapy in older adults, with implications for other groups as well. Prospective studies are needed to clarify optimal treatment regimens and adjuncts.

Administration, Cutaneous↗

PubMed2026

Real-World Experience With TRBC1 Immunohistochemistry Across Cutaneous T-Cell Lymphoma Subtypes: A Large Cohort Study.

T-cell receptor β-chain constant region 1 (TRBC1) immunohistochemistry identifies clonal αβ T-cell populations on tissue sections, but its real-world performance across cutaneous T-cell lymphoma (CTCL) and related infiltrates is uncharacterized. The analytic cohort comprised 665 biopsies (566 patients) with paired T-cell receptor (TCR) clonality testing, classified clinicopathologically as mycosis fungoides (MF; MF-Patch, MF-Plaque, MF-Tumor, and MF-Folliculotropic); MF or Sézary syndrome; primary cutaneous small or medium T-cell lymphoproliferative disorders (LPDs); other CTCL-cutaneous LPDs; or reactive. At the primary <15%/>85% threshold, TRBC1 IHC achieved 85.8% sensitivity (337/393), 79.8% specificity (217/272), 86.0% positive and 79.5% negative predictive value, and 83.3% accuracy. Sensitivity was lowest in MF-Patch (84.2%). Three-reader agreement (Fleiss κ = 0.943) fell to κ = 0.776 in 176 reflexed biopsies, with disagreement concentrated on MF-Patch and CD30-positive LPDs. Monotypic TRBC1 predicted neoplasia, with odds rising with infiltrate density: MF-Patch (odds ratio, 5.41), MF-Plaque (10.40), MF/Sézary syndrome with MF-Tumor (15.19), and CTCL-cutaneous LPD (18.16). Polytypic TRBC1 was associated with reactive disease (odds ratio, 53.65), effectively excluded clonality (negative likelihood ratio, 0.18), and was uniformly observed in an independent 270-biopsy reactive cohort. For observer-independent validation, digital image analysis-derived TRBC1 quantification (QuPath) was applied to a stratified random subset of 250 biopsies representative of the cohort's tumor-burden distribution. The digital read-tracked molecular clonality (85.1% sensitivity, 80.1% specificity against TCR; area under the curve, 0.842) agreed with the dermatopathologist's manual read in 87.6% of cases (κ = 0.752), with the data-derived cutoff matching the prespecified <15%/>85% threshold value. Discordance was directional for both manual scoring and digital quantification: in MF-Patch, 25 of 38 (65.8%) and 12 of 17 (70.6%) cases were polytypic with monoclonal TCR (false-negative-dominant); in reactive biopsies, 34 of 45 (75.6%) and 19 of 20 (95%) were monotypic with polyclonal TCR (false-positive-dominant). These findings support a TRBC1-first approach, reserving reflex TCR testing for borderline expression or clinicopathologic discordance, preserving diagnostic accuracy while reducing molecular testing and reimbursement-based costs.

Sézary syndrome↗

PubMed1993

The health care status of the diabetic population as reflected by physician claims to a major insurer.

BACKGROUND: Conventional epidemiologic data suggest that diabetic patients use more health care resources than nondiabetic patients, yet overall health care use by diabetic individuals has never been fully quantitated. We took a new approach to this issue based on the actual economics of the provision of health care to diabetic insured individuals. METHODS: The claims records in the Mutual of Omaha Current Trends database, which contains information on more than 400,000 individuals, were surveyed to identify patients with diabetes and create the contrast population of nondiabetic patients by exclusion. International Classification of Diseases, Ninth Revision, Clinical Modification, codes and Physicians' Current Procedural Terminology, Fourth Edition, codes were used to determine all diagnoses recorded and all physician services rendered to the contrast populations. Age- and sex-adjusted comparisons were performed using Mantel-Haenszel procedures to determine an adjusted odds ratio (AOR). RESULTS: A total of 13,304 diabetic individuals and 388,053 nondiabetic individuals who received health care services from January 1, 1988, to January 1, 1989, were identified. Diabetic insured individuals constituted 3.1% of the overall insured population yet accounted for 8.3% of the charges (P < .01). Inpatient charges accounted for 81% of total diabetic charges but only 61.5% of total nondiabetic charges (P < .001). Diabetic insured individuals had twice as many physician office visits (AOR = 1.87; 95% confidence interval [CI], 1.79 to 1.96), with 2.5 times more physician hospital visits [AOR = 2.50; 95% CI, 2.27 to 2.75). However, the increases in physician care were not uniformly distributed across the diagnostic spectrum. The frequencies of well-established complications of diabetes, such as ischemic heart disease (AOR = 3.32; 95% CI, 3.12 to 3.53), peripheral vascular disease (AOR = 3.14; 95% CI, 2.79 to 3.53), and eye disease (AOR = 3.10; 95% CI, 2.94 to 3.27), were threefold higher in the diabetic group, with parallel increases in related medical services, such as cardiac catheterization (AOR = 3.02; 95% CI, 2.27 to 4.0), vascular surgery (AOR = 2.94; 95% CI, 2.64 to 3.27), and ophthalmologic procedures (AOR = 2.94; 95% CI, 2.72 to 3.18). In contrast, most diagnostic categories showed little or no increase. For example, the frequency of neoplasms (AOR = 1.11; 95% CI, 1.03 to 1.19) was minimally increased, and the associated procedural concomitants of therapeutic radiology (AOR = 0.81; 95% CI, 0.47 to 1.39) and chemotherapy (AOR = 0.98; 95% CI, 0.60 to 1.60) were not increased in the diabetic group. CONCLUSIONS: Our most important new finding is that diabetic patients have neither an elevated risk for a wide spectrum of diseases nor an increase in the receipt of physician services for diagnostic categories without increased risk, despite more frequent physician encounters. We provide real-world risk estimates that help in calculating the effect of offering specific insurance to diabetic individuals or including them in group health plans. The techniques we have developed to analyze computerized claims databases in this way may serve to better quantify the true impact of chronic diseases on the health care system.

Adult↗

PubMed2026

2024-2025 BNT162b2 KP.2 COVID-19 full season vaccine effectiveness from vaccine registries linked to administrative claims in two states: A cohort study in non-immunocompromised adults.

BACKGROUND: Data on effectiveness of COVID-19 vaccinations during the 2024-2025 respiratory season are limited, particularly among those with underlying medical conditions (UMC). We estimated BNT162b2 KP.2 vaccine effectiveness (VE) against COVID-19-associated hospital admission, emergency department (ED), and urgent care (UC) visits in two U.S. states. METHODS: Retrospective cohort study of non-immunocompromised adults living in Louisiana or California, with ≥1 year prior continuous enrollment in insurance plans contributing to the HealthVerity claims database beginning August 22, 2024. The effectiveness of BNT162b2 KP.2 vaccine (2024-2025 formulation, hereafter referred to as BNT162b2), measured as a time-varying exposure against hospital admission, ED, or UC encounters with International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) code U07.1 was calculated as 1 - adjusted hazard ratio using Cox proportional hazard models adjusted for age group, sex, state, insurance payor, presence or absence of UMCs, and pre-index healthcare utilization. Stratifications included those aged 65 years and older, those aged 18-64 years with UMCs, and those aged 18-64 years without UMCs. RESULTS: The cohort included 6,256,421 individuals (93% California, 7% Louisiana); 330,565 (5%) received the BNT162b2 vaccine. Vaccinated individuals were older and had more comorbidities, wellness visits, and prior influenza vaccination. Overall, 66% of the study population had ≥1 UMC; the most prevalent conditions were obesity (25%), history of immunocompromised conditions (23%), and mental health conditions (19%). COVID-19-related encounter rates for ED, UC or hospitalization were lower among vaccinated compared to unvaccinated persons (25.1 vs 36.3 per 100,000 person-months). Among all adults, VE was 37% against hospitalization, 12% against ED/UC encounters, and 16% against ED/UC/hospitalization encounters. Results were similar across age groups and UMCs. CONCLUSIONS: BNT162b2 provided protection against COVID-19-associated outcomes of ED, UC or hospitalization among non-immunocompromised U.S. adults, including those with UMCs, over the course of the 2024-2025 respiratory virus season, supporting continued vaccine recommendations. REGISTRATION: This study was posted on clinicaltrials.gov prior to analyses (NCT06923137).

Adolescent↗

PubMed2000

Helmets for preventing head and facial injuries in bicyclists.

BACKGROUND: Each year, in the United states, approximately 900 persons die from injuries due to bicycle crashes and over 500,000 persons are treated in emergency departments. Head injury is by far the greatest risk posed to bicyclists, comprising one-third of emergency department visits, two-thirds of hospital admissions, and three-fourths of deaths. Facial injuries to cyclists occur at a rate nearly identical to that of head injuries. Although it makes inherent sense that helmets would be protective against head injury, establishing the real-world effectiveness of helmets is important. A number of case-control studies have been conducted demonstrating the effectiveness of bicycle helmets. Because of the magnitude of the problem and the potential effectiveness of bicycle helmets, the objective of this review is to determine whether bicycle helmets reduce head, brain and facial injury for bicyclists of all ages involved in a bicycle crash or fall. OBJECTIVES: To determine whether bicycle helmets reduce head, brain and facial injury for bicyclists of all ages involved in a bicycle crash or fall. SEARCH STRATEGY: We searched The Cochrane Controlled Trials Register, MEDLINE, EMBASE, Sport, ERIC, NTIS, Expanded Academic Index, CINAHL, PsycINFO, Occupational Safety and Health, and Dissertations Abstracts. We checked reference lists of past reviews and review articles, studies from government agencies in the United States, Europe and Australia, and contacted colleagues from the International Society for Child and Adolescent Injury Prevention, World Injury Network, CDC funded Injury Control and Research Centers, and staff in injury research agencies around the world. SELECTION CRITERIA: Controlled studies that evaluated the effect of helmet use in a population of bicyclists who had experienced a crash. We required that studies have complete outcome ascertainment, accurate exposure measurement, appropriate selection of the comparison group and elimination or control of factors such as selection bias, observation bias and confounding. DATA COLLECTION AND ANALYSIS: Five published studies met the selection criteria. Two abstractors using a standard abstraction form independently abstracted data. Odds ratios with 95% CI were calculated for the protective effect of helmet for head and facial injuries. Study results are presented individually. Head and brain injury results were also summarized using meta-analysis techniques. MAIN RESULTS: No randomized controlled trials were found. This review identified five well conducted case control studies which met our selection criteria. Helmets provide a 63%-88% reduction in the risk of head, brain and severe brain injury for all ages of bicyclists. Helmets provide equal levels of protection for crashes involving motor vehicles (69%) and crashes from all other causes (68%). Injuries to the upper and mid facial areas are reduced 65%. REVIEWER'S CONCLUSIONS: Helmets reduce bicycle-related head and facial injuries for bicyclists of all ages involved in all types of crashes including those involving motor vehicles.

Bicycling↗

PubMed2026

Real-world clinical utility of exome sequencing in pediatric drug-resistant epilepsy: Experience from a tertiary center in Thailand.

BACKGROUND: Genomic testing has increasingly contributed to the diagnosis and management of pediatric drug-resistant epilepsy (DRE), particularly in patients with suspected genetic etiologies. This study evaluated the diagnostic yield and real- world clinical utility of whole-exome sequencing (WES) in children with DRE. METHODS: Children with DRE and seizure onset before 15 years of age were enrolled between January 2020 and December 2023. Clinical data, including demographics, seizure characteristics, developmental history, electroencephalography (EEG), brain magnetic resonance imaging (MRI), and prior investigations, were reviewed. WES was performed in all probands and, when available, their parents. Variants were interpreted according to standard guidelines. Clinical utility and 1-year seizure and developmental outcomes were assessed from follow-up records. RESULTS: Fifty-six patients (23 males, 33 females) were included. The median age at seizure onset was 1 year (interquartile range [IQR] 0.3-4 years), and 96.4% had developmental comorbidities. Pathogenic or likely pathogenic variants were identified in 39% (22/56), with the highest diagnostic yield in children with seizure onset before 3 years of age. Channelopathies accounted for most genetically solved cases (68%), predominantly involving sodium channel genes. Genetic diagnoses provided clinical utility in 73% (16/22) of solved cases by guiding treatment and precision management. At 1-year follow-up, genetically solved patients showed more favorable seizure and developmental outcomes than those with genetically unsolved patients. CONCLUSION: WES achieved a 39% diagnostic yield and substantial clinical utility in pediatric DRE, particularly in early-onset and channelopathy-related disorders. These findings support early molecular diagnosis to facilitate genotype-informed management in appropriately selected children. However, the more favorable developmental and seizure outcomes observed in genetically solved patients should be interpreted with caution, as they may have been influenced by multiple factors beyond genetic diagnosis. In resource-limited settings, careful clinical phenotyping remains essential for treatment decisions and for prioritizing children for genomic testing.

Clinical utility↗

PubMed1998

Comparative performance of species richness estimation methods.

In most real-world contexts the sampling effort needed to attain an accurate estimate of total species richness is excessive. Therefore, methods to estimate total species richness from incomplete collections need to be developed and tested. Using real and computer-simulated parasite data sets, the performances of 9 species richness estimation methods were compared. For all data sets, each estimation method was used to calculate the projected species richness at increasing levels of sampling effort. The performance of each method was evaluated by calculating the bias and precision of its estimates against the known total species richness. Performance was evaluated with increasing sampling effort and across different model communities. For the real data sets, the Chao2 and first-order jackknife estimators performed best. For the simulated data sets, the first-order jackknife estimator performed best at low sampling effort but, with increasing sampling effort, the bootstrap estimator outperformed all other estimators. Estimator performance increased with increasing species richness, aggregation level of individuals among samples and overall population size. Overall, the Chao2 and the first-order jackknife estimation methods performed best and should be used to control for the confounding effects of sampling effort in studies of parasite species richness. Potential uses of and practical problems with species richness estimation methods are discussed.

Animals↗

PubMed2000

Determination of biokinetic interactions in chemical mixtures using real-time breath analysis and physiologically based pharmacokinetic modeling.

Regulatory agencies are challenged to conduct risk assessments on chemical mixtures without full information on toxicological interactions that may occur at real-world, low-dose exposure levels. The present study was undertaken to investigate the pharmacokinetic impact of low-dose coexposures to toluene and trichloroethylene in vivo in male F344 rats using a real-time breath analysis system coupled with physiologically based pharmacokinetic (PBPK) modeling. Rats were exposed to compounds alone or as a binary mixture, at low (5 to 25 mg/kg) or high (240 to 800 mg/kg) dose levels. Exhaled breath from the exposed animals was monitored for the parent compounds and a PBPK model was used to analyze the data. At low doses, exhaled breath kinetics from the binary mixture exposure compared with those obtained during single exposures, thus indicating that no metabolic interaction occurred with these low doses. In contract, at higher doses the binary PBPK model simulating independent metabolism was found to underpredict the exhaled breath concentration, suggesting an inhibition of metabolism. Therefore the binary mixture PBPK model was used to compare the measured exhaled breath levels from high- and low-dose exposures with the predicted levels under various metabolic interaction simulations (competitive, noncompetitive, or uncompetitive inhibition). Of these simulations, the optimized competitive metabolic interaction description yielded a Ki value closest to the Km of the inhibitor solvent, indicating that competitive inhibition is the most plausible type of metabolic interaction between these two solvents.

Anesthetics, Inhalation↗

PubMed2000

Social categorizations, social comparisons and stigma: presentations of self in people with learning difficulties.

Self-categorization theory stresses the importance of the context in which the meta-contrast principle is proposed to operate. This study is concerned with how 'the pool of psychologically relevant stimuli' (Turner, Hogg, Oakes, Reicher & Wetherell, 1987, p. 47) comprising the context is determined. Data from interviews with 33 people with learning difficulties were used to show how a positive sense of self might be constructed by members of a stigmatized social category through the social worlds that they describe, and therefore the social comparisons and categorizations that are made possible. Participants made downward comparisons which focused on people with learning difficulties who were less able or who displayed challenging behaviour, and with people who did not have learning difficulties but who, according to the participants, behaved badly, such as beggars, drunks and thieves. By selection of dimensions and comparison others, a positive sense of self and a particular set of social categorizations were presented. It is suggested that when using self-categorization theory to study real-world social categories, more attention needs to be paid to the involvement of the perceiver in determining which stimuli are psychologically relevant since this is a crucial determinant of category salience.

Adolescent↗

PubMed1997

A volumetric approach to virtual simulation of functional endoscopic sinus surgery.

Advanced display technologies have made the virtual exploration of relatively complex models feasible in many applications. Unfortunately, only a few human interfaces allow natural interaction with the environment. Moreover, in surgical applications, such realistic interaction requires real-time rendering of volumetric data-placing an overwhelming performance burden on the system. We report on a collaboration of an interdisciplinary group developing a virtual reality system that provides intuitive interaction with volume data by employing real-time volume rendering and force feedback (haptic) sensations. We describe our rendering methods and the haptic devices and explain its utility of this system in the real-world application of Endoscopic Sinus Surgery (ESS) simulation.

Computer Simulation↗