Category: Statistics

Nat Commun. 2024 Nov 6;15(1):9573. doi: 10.1038/s41467-024-54035-1.

ABSTRACT

Atopic eczema may be related to multiple subsequent adverse health outcomes. Here, we provide evidence to judge and compare associations between eczema and a comprehensive set of outcomes. We conducted 71 cohort studies (age, sex, general practice-matched) using Clinical Practice Research Datalink Aurum primary care records (1997-2023), comparing up to 3.6 million people with eczema to 16.8 million without. Eczema was associated with subsequent diagnosis of outcomes with adjusted hazard ratios (99% confidence intervals) from Cox regression of up to 4.02(3.95-4.10) for food allergy (rate difference [RD] per 1,000 person-years of 1.5). Besides strong associations with atopic and allergic conditions (e.g., asthma 1.87[1.39-1.82], RD5.4) and skin infections (e.g., molluscum contagiosum 1.81[1.64-1.96], RD1.8), the strongest associations were with Hodgkin’s lymphoma (1.85[1.66-2.06], RD0.02), Alopecia Areata (1.77[1.71-1.83], RD0.2), Crohn’s disease (1.62[1.54-1.69], RD0.1), Urticaria (1.58[1.57-1.60], RD1.9), Coeliac disease (1.42[1.37-1.47], RD0.1), Ulcerative colitis (1.40[1.34-1.46], RD0.1), Autoimmune liver disease (1.32[1.21-1.43], RD0.01), and Irritable bowel syndrome (1.31[1.29-1.32], RD0.7). Sensitivity analyses revealed the impact of consultation bias or choice of cohort age cut-off on findings. Comparatively large HRs in severe eczema were seen for some liver, gastrointestinal and cardiovascular conditions, osteoporosis, and fractures. Most cancers and neurological conditions were not associated with eczema.

PMID:39505873 | DOI:10.1038/s41467-024-54035-1

Nat Commun. 2024 Nov 6;15(1):9604. doi: 10.1038/s41467-024-54095-3.

ABSTRACT

There is a growing interest in the health impacts of PM_2.5 originating from landscape fires. We conducted a time-series study to investigate the association between daily exposure to landscape fire PM_2.5 and hospital admissions for cardiovascular events in 184 major Chinese cities. We developed a machine learning model combining outputs from chemical transport models, meteorological information and observed air pollution data to determine daily concentrations of landscape fire PM_2.5. Furthermore, we fitted quasi-Poisson regression to evaluate the link between landscape fire PM_2.5 concentrations and cardiovascular hospitalizations in each city, and conducted random-effects meta-analysis to pool the city-specific estimates. Here we show that, on a national scale, a rise of 1-μg/m³ in landscape fire PM_2.5 concentrations is positively related to a same-day 0.16% (95% confidence interval: 0.01%-0.32%) increase in hospital admissions for cardiovascular disease, 0.28% (0.12%-0.44%) for ischemic heart disease, and 0.25% (0.02%-0.47%) for ischemic stroke. The associations remain significant even after adjusting for other sources of PM_2.5. Our findings indicate that transient elevation in landscape fire PM_2.5 levels may increase risk of cardiovascular diseases.

PMID:39505861 | DOI:10.1038/s41467-024-54095-3

Nat Commun. 2024 Nov 6;15(1):9587. doi: 10.1038/s41467-024-52472-6.

ABSTRACT

Genetic variation at the 19q13.3 KLK locus is linked with prostate cancer susceptibility in men. The non-synonymous KLK3 single nucleotide polymorphism (SNP), rs17632542 (c.536 T > C; Ile163Thr-substitution in PSA) is associated with reduced prostate cancer risk, however, the functional relevance is unknown. Here, we identify that the SNP variant-induced change in PSA biochemical activity mediates prostate cancer pathogenesis. The ‘Thr’ PSA variant leads to small subcutaneous tumours, supporting reduced prostate cancer risk. However, ‘Thr’ PSA also displays higher metastatic potential with pronounced osteolytic activity in an experimental metastasis in-vivo model. Biochemical characterisation of this PSA variant demonstrates markedly reduced proteolytic activity that correlates with differences in in-vivo tumour burden. The SNP is associated with increased risk for aggressive disease and prostate cancer-specific mortality in three independent cohorts, highlighting its critical function in mediating metastasis. Carriers of this SNP allele have reduced serum total PSA and a higher free/total PSA ratio that could contribute to late biopsy decisions and delay in diagnosis. Our results provide a molecular explanation for the prominent 19q13.3 KLK locus, rs17632542 SNP, association with a spectrum of prostate cancer clinical outcomes.

PMID:39505858 | DOI:10.1038/s41467-024-52472-6

Nat Commun. 2024 Nov 6;15(1):9552. doi: 10.1038/s41467-024-53213-5.

ABSTRACT

In response to gradual nanoindentation, the surface of muscovite mica deforms by sudden stochastic nanometer-scale displacement bursts. Here, the statistics of these displacement events are interpreted using a statistical model previously used to model earthquakes to understand how chemically reactive environments alter the surface properties of this material. We show that the statistics of nanoindentation displacement bursts in muscovite mica are tuned by chemomechanical weakening in a manner similar to how the statistics of model events are tuned by a mechanical weakening parameter that describes how easily system-spanning cracks can be nucleated. Because the predictions of this model are independent of any surface defects or structural details, these results suggest this simple model can be universally used to describe chemomechanical weakening in many systems prone to slip avalanches on a wide range of spatio-temporal scales.

PMID:39505851 | DOI:10.1038/s41467-024-53213-5

J Aging Soc Policy. 2024 Nov 6:1-17. doi: 10.1080/08959420.2024.2423102. Online ahead of print.

ABSTRACT

Increase in life expectancy around the world puts aging societies with all their challenges on the Global Public Health agenda. In Austria, additional years of life gained are not spent in good health, as healthy life expectancy is far below the European average. Using repeated cross-sectional data from three waves of the Austrian Health Interview Survey (2006, 2014 and 2019), including a total of 10,056 participants aged 65 years and above, this study examined the change in self-reported quality-of-life (QoL) over time and explored associated factors. QoL, estimated by domain scores of the WHOQOL-BREF questionnaire, increased over time but decreased with age in all survey waves. Observed mean scores were significantly higher in males than in females in all QoL domains except the social domain but sex differences disappeared in most domains in the multivariable regression analyses. Instead, factors associated with significantly higher QoL scores included younger age, higher socioeconomic status, living in Western Austria and having no chronic conditions. Statistically significant observed sex differences in QoL in the older-aged Austrian population disappeared when adjusting for income and education. Strategies and measures to increase financial capabilities may have a significant impact on QoL and well-being in this age group.

PMID:39505834 | DOI:10.1080/08959420.2024.2423102

Acad Psychiatry. 2024 Nov 6. doi: 10.1007/s40596-024-02080-9. Online ahead of print.

ABSTRACT

OBJECTIVE: This study was designed to investigate if artificial intelligence (AI) detection software can determine the use of AI in personal statements for residency applications.

METHOD: Previously written personal statements were collected from physicians who had already matched to residency through the Electronic Residency Application System. Physicians were recruited for the study through collegial relationships and were given study information via email. The study team constructed five parallel statements from the shared personal statements to prompt AI to create a personal statement of similar content. An online AI detection tool, GPTZero, was used to assess all the personal statements. Statistical analyses were conducted using R. Descriptive statistics, t-tests, and Pearson correlations were used to assess the data.

RESULTS: Eight physicians’ statements were compared to eight AI-generated statements. GPTZero was able to correctly identify AI-generated writing, assigning them significantly higher AI probability scores compared to human-authored essays. Human-generated statements were considered more readable, used shorter words with fewer syllables, and had more sentences compared to AI-generated essays. Longer average sentence length, low readability scores, and high SAT word percentages were strongly associated with AI-generated essays.

CONCLUSIONS: This study shows the capacity of GPTZero to distinguish human-created versus AI-generated writing. Use of AI can pose significant ethical challenges and carries a risk of inadvertent harm to certain applicants and erosion of trust in the application process. Authors suggest standardization of protocol regarding the use of AI prior to its integration in post-graduate medical education.

PMID:39505810 | DOI:10.1007/s40596-024-02080-9

Braz J Otorhinolaryngol. 2024 Nov 5;91(2):101520. doi: 10.1016/j.bjorl.2024.101520. Online ahead of print.

ABSTRACT

OBJECTIVE: To understand the characteristics of cervical lymph node metastasis in Oropharyngeal Squamous Cell Carcinoma (OPSCC) patients, explore the risk factors for lymph node metastasis, and its impact on prognosis.

METHODS: Retrospective cohort study. Statistical analysis of the relationship between various clinicopathological factors and lymph node involvement, as well as the independent risk factors affecting lymph node metastasis and their impact on prognosis.

RESULTS: The cervical lymph node metastasis rate in this group was 89.2%, with the palatine tonsils and base of the tongue more prone to cervical lymph node metastasis (p=0.007); lower pathological differentiation of OPSCC was more likely to develop cervical lymph node metastasis (p=0.017). The P16 protein positive rate in this group was 58.8%. P16 protein expression did not affect the incidence rate of cervical lymph node metastasis in OPSCC (p=1.000) but influenced the risk of multiple lymph node metastases (p=0.011) and was a risk factor affecting the prognosis of OPSCC (p=0.003). However, the lymph node metastasis status did not affect the survival time of OPSCC patients.

CONCLUSION: In the Shanxi region of China, HPV-related OPSCC accounts for a higher proportion; OPSCC has a high rate of cervical lymph node metastasis, but lymph node metastasis does not significantly increase the mortality risk of OPSCC patients, which may be related to the unique characteristics of HPV-related OPSCC. LEVEL OF EVIDENCE Ⅳ: Retrospective cohort study.

PMID:39504599 | DOI:10.1016/j.bjorl.2024.101520

Sleep Med. 2024 Oct 30;124:618-626. doi: 10.1016/j.sleep.2024.10.037. Online ahead of print.

ABSTRACT

Narcolepsy is a rare, chronic neurological disorder characterized by a dysregulated sleep-wake cycle, with core clinical features including excessive daytime sleepiness (EDS), cataplexy, hypnopompic/hypnagogic hallucinations, and sleep paralysis. Several treatment options are available for the symptomatic management of narcolepsy, but they have limitations. Comorbidities of narcolepsy further limit the treatment choices. Blocking of histamine 3 (H3) receptors has been demonstrated to be a viable approach for the management of symptoms of narcolepsy. Samelisant (SUVN-G3031) is a new H3 receptor inverse agonist. The efficacy, safety, tolerability, and pharmacokinetics of Samelisant in narcolepsy patients were evaluated in a phase 2, double-blind, placebo-controlled study (ClinicalTrials.gov identifier: NCT04072380). Patients diagnosed with narcolepsy according to the International Classification of Sleep Disorders criteria and having an Epworth Sleepiness Scale (ESS) score of ≥12 and a mean Maintenance of Wakefulness Test (MWT) time of <12 min across the 4 sessions at baseline were enrolled. The total study duration was up to 7 weeks, which included a screening period of 4 weeks, a treatment period of 2 weeks, and a safety follow-up 1 week after the last study drug administration. The primary efficacy measure was the change in total ESS score compared to placebo. Secondary and exploratory assessments included the Clinical Global Impression of Severity, MWT, Clinical Global Impression of Change, Patient Global Impression of Change and cataplexy rate. Safety assessments included monitoring adverse events (AEs) and laboratory assessments. Of the 426 patients screened, 190 were randomized. The safety and intention-to-treat population included 188 and 164 patients, respectively. A statistically significant treatment effect of Samelisant was observed on the primary endpoint, indicating improvements in EDS. The treatment’s impact on EDS was also evident on the other patients’ and clinicians’ perspectives scales. The AEs reported in ≥5 % patients in any treatment groups were insomnia, abnormal dreams, nausea, and hot flush. Global phase 3 studies and long-term safety and efficacy assessments of Samelisant are planned to reaffirm the current findings.

PMID:39504585 | DOI:10.1016/j.sleep.2024.10.037

JMIR Cancer. 2024 Nov 6;10:e51936. doi: 10.2196/51936.

ABSTRACT

BACKGROUND: Tobacco use has been identified as a risk factor for oral cancer worldwide. However, relative oral cancer incidence among adults who smoke cigarettes, use smokeless tobacco products (ST), have transitioned from cigarettes to ST, quit cigarettes and/or ST (“quitters”), or never used tobacco has not been well studied.

OBJECTIVE: We aim to present population-based oral cancer incidence rates for adults who smoke cigarettes, use ST, are former smokers who now use ST, or quit.

METHODS: We estimated cross-sectional incidence rates and incidence rate ratios (IRRs) using data from statewide cancer registries (Colorado, Florida, North Carolina, and Texas) and population counts derived from national surveys using combined data from 2014-2017. A random-effect meta-analysis approach was used to summarize estimates among these groups, based on multiple imputation-based IRR estimates by state and age group while considering potential heterogeneity.

RESULTS: A total of 19,536 oral cancer cases were identified among adult males 35 years and older in the study geographies and period. The oral cancer incidence rate among adults who smoke was significantly higher than the ST group (2.6 times higher, 95% CI 2.0-3.3, P<.001), 3.6 (95% CI 3.2-4.1, P<.001) times higher than the never users, and 2.4 (95% CI 1.8-3.1, P<.001) times higher compared to former smokers who now use ST. The IRR among the ST group relative to never users was 1.4 (95% CI 1.1-1.9, P=.02). The IRR between former smokers who now use ST and those who quit was 1.4 (95% CI 1.0-2.1, P=.08).

CONCLUSIONS: Findings from this population-based study with a large number of oral cancer cases support significantly high oral cancer incidence among adults who smoke and a lower risk of oral cancer incidence among never users, quitters, users of ST, and former smokers who now use ST compared to cigarettes. Future studies with detailed control of tobacco history and other relevant confounders are needed to confirm these findings.

PMID:39504575 | DOI:10.2196/51936

JMIR Med Inform. 2024 Nov 6;12:e58276. doi: 10.2196/58276.

ABSTRACT

BACKGROUND: Coprescribing naloxone with opioid analgesics is a Centers for Disease Control and Prevention (CDC) best practice to mitigate the risk of fatal opioid overdose, yet coprescription by emergency medicine clinicians is rare, occurring less than 5% of the time it is indicated. Clinical decision support (CDS) has been associated with increased naloxone prescribing; however, key CDS design characteristics and pragmatic outcome measures necessary to understand replicability and effectiveness have not been reported.

OBJECTIVE: This study aimed to rigorously evaluate and quantify the impact of CDS designed to improve emergency department (ED) naloxone coprescribing. We hypothesized CDS would increase naloxone coprescribing and the number of naloxone prescriptions filled by patients discharged from EDs in a large health care system.

METHODS: Following user-centered design principles, we designed and implemented a fully automated, interruptive, electronic health record-based CDS to nudge clinicians to coprescribe naloxone with high-risk opioid prescriptions. “High-risk” opioid prescriptions were defined as any opioid analgesic prescription ≥90 total morphine milligram equivalents per day or for patients with a prior diagnosis of opioid use disorder or opioid overdose. The Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework was used to evaluate pragmatic CDS outcomes of reach, effectiveness, adoption, implementation, and maintenance. Effectiveness was the primary outcome of interest and was assessed by (1) constructing a Bayesian structural time-series model of the number of ED visits with naloxone coprescriptions before and after CDS implementation and (2) calculating the percentage of naloxone prescriptions associated with CDS that were filled at an outpatient pharmacy. Mann-Kendall tests were used to evaluate longitudinal trends in CDS adoption. All outcomes were analyzed in R (version 4.2.2; R Core Team).

Between November 2019 and July 2023, there were 1,994,994 ED visits. CDS reached clinicians in 0.83% (16,566/1,994,994) of all visits and 15.99% (16,566/103,606) of ED visits where an opioid was prescribed at discharge. Clinicians adopted CDS, coprescribing naloxone in 34.36% (6613/19,246) of alerts. CDS was effective, increasing naloxone coprescribing from baseline by 18.1 (95% CI 17.9-18.3) coprescriptions per week or 2,327% (95% CI 3390-3490). Patients filled 43.80% (1989/4541) of naloxone coprescriptions. The CDS was implemented simultaneously at every ED and no adaptations were made to CDS postimplementation. CDS was maintained beyond the study period and maintained its effect, with adoption increasing over time (τ=0.454; P<.001).

CONCLUSIONS: Our findings advance the evidence that electronic health record-based CDS increases the number of naloxone coprescriptions and improves the distribution of naloxone. Our time series analysis controls for secular trends and strongly suggests that minimally interruptive CDS significantly improves process outcomes.

PMID:39504560 | DOI:10.2196/58276