Category: Statistics

JAMA Ophthalmol. 2024 Mar 28. doi: 10.1001/jamaophthalmol.2024.0363. Online ahead of print.

ABSTRACT

IMPORTANCE: Effects of genetic variants on primary angle-closure disease remained uncertain.

OBJECTIVE: To systematically review the associations of common single-nucleotide variants (SNVs) and rare coding variants with primary angle-closure disease, its subtypes (including primary angle-closure glaucoma, primary angle-closure suspect, and primary angle-closure) and progression.

DATA SOURCES: Eligible studies from PubMed, Embase, and Web of Science were retrieved up to April 3, 2023. SNV information was extracted from eligible reports and 2 genome-wide association studies summary statistics, UK BioBank and FinnGen.

STUDY SELECTION: Studies providing analyzable genotype or allele data in a case-control design for primary angle-closure disease association and longitudinal case-only design for primary angle-closure disease progression.

DATA EXTRACTION AND SYNTHESIS: PRISMA guidelines were used for literature screening and the Newcastle Ottawa Scale for data quality assessment. Pooled effect size with 95% CIs of SNV associations were calculated using fixed- or random-effect models according to I2 statistics.

MAIN OUTCOMES AND MEASURES: SNVs reported in 2 or more studies were meta-analyzed to generate pooled odds ratios and P values. Common and rare coding variants from single reports were summarized.

RESULTS: Sixty-nine citations were eligible for meta-analysis on overall primary angle-closure disease, involving 206 SNVs in 64 genes or loci. Seventeen SNVs in 15 genes or loci showed associations with primary angle-closure disease, and 15 SNVs in 13 genes or loci showed associations with primary angle-closure glaucoma. Two SNVs, ABCA1 rs2422493 and ZNRF3 rs3178915, were associated only with primary angle-closure disease. Two SNVs, PCMTD1-ST18 rs1015213 and COL11A1 rs3753841, were associated with primary angle-closure suspect, and 1 SNV, MMP9 rs3918249, was associated with primary angle-closure. This systematic review and meta-analysis newly confirmed 7 genes or loci associated with primary angle-closure glaucoma: ATOH7, CALCRL, FBN1, IL6, LOXL1, MMP19, and VAV3. Common and rare coding variants in 16 genes or loci that have been associated with primary angle-closure disease were cataloged. Stratification analysis revealed different primary angle-closure disease-associated genes in different ethnic populations. Only 1 study regarding the genetic association of primary angle-closure glaucoma progression was identified.

CONCLUSIONS AND RELEVANCE: This study revealed the genetic complexity of primary angle-closure disease, involving common SNVs and rare coding variants in more than 30 genes or loci, with ethnic and phenotypic diversities. Further replication, genotype-phenotype correlation, and pathway analyses are warranted.

PMID:38546604 | DOI:10.1001/jamaophthalmol.2024.0363

Am J Orthopsychiatry. 2024 Mar 28. doi: 10.1037/ort0000732. Online ahead of print.

ABSTRACT

Black and Latinx people are disproportionately impacted by HIV, COVID-19, and other syndemic health crises with similar underlying social determinants of health. Lessons learned from the HIV pandemic and COVID-19 response have been invoked to improve health equity at the systemic level in the face of other emergent health crises. However, few have examined the potential translation of strategies between syndemics at the individual level. The current mixed-methods study examined strategies used to manage HIV during the COVID-19 pandemic and the extent to which they were helpful in managing COVID-19 vulnerability among Black and Latinx people living with HIV. Participants (n = 30) were interviewed by telephone and completed demographic, mental health, alcohol and substance use, health literacy, and clinical measures in October and November 2020 in Los Angeles County. Rapid qualitative analysis, descriptive statistics, and mixed-methods merging were used to analyze the data. Qualitative results demonstrated that participants found HIV self-management strategies translated to aspects of the COVID-19 pandemic including hygiene and social distancing and coping with a health-related stressor. Although telemedicine provided continuity of HIV care for most participants, technology access and literacy posed a potential barrier, particularly to those facing other sociodemographic marginalization (i.e., low education, disability). Findings suggest providers can encourage leveraging individual HIV self-management strategies in response to other public health crises. However, these interventions must be culturally responsive and address intersecting social determinants of health. Future research should examine mechanisms that predict individual translation of HIV management strategies to other health concerns. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

PMID:38546560 | DOI:10.1037/ort0000732

JAMA Oncol. 2024 Mar 28. doi: 10.1001/jamaoncol.2023.7333. Online ahead of print.

ABSTRACT

IMPORTANCE: Despite the clear potential benefits of neoadjuvant therapy, the optimal neoadjuvant regimen for patients with high-risk resectable melanoma (HRRM) is not known.

OBJECTIVE: To compare the safety and efficacy of dual checkpoint inhibitors with anti-programmed cell death protein-1 (anti-PD1) therapy in a neoadjuvant setting among patients with HRRM.

DESIGN, SETTING, AND PARTICIPANTS: In this pooled analysis of clinical trials, studies were selected provided they investigated immune checkpoint inhibitor treatment, were published between January 2018 and March 2023, and were phase 1, 2, or 3 clinical trials. Participant data included in the analysis were derived from trials evaluating the efficacy and safety of anti-PD1 monotherapy and the combination of anti-cytotoxic T lymphocyte-associated protein-4 with anti-PD1 in the neoadjuvant setting, specifically among patients with HRRM.

INTERVENTIONS: Patients were treated with either anti-PD1 monotherapy; dual checkpoint inhibition (DCPI) with a conventional dose of 3-mg/kg ipilimumab and 1-mg/kg nivolumab; or DCPI with an alternative-dose regimen of 1-mg/kg ipilimumab and 3-mg/kg nivolumab.

MAIN OUTCOMES AND MEASURES: The main outcomes were radiologic complete response (rCR), radiologic overall objective response (rOOR), and radiologic progressive disease. Also, pathologic complete response (pCR), the proportion of patients undergoing surgical resection, and occurrence of grade 3 or 4 immune-related adverse events (irAEs) were considered.

RESULTS: Among 573 patients enrolled in 6 clinical trials, neoadjuvant therapy with DCPI was associated with higher odds of achieving pCR compared with anti-PD1 monotherapy (odds ratio [OR], 3.16; P < .001). DCPI was associated with higher odds of grade 3 or 4 irAEs compared with anti-PD1 monotherapy (OR, 3.75; P < .001). When comparing the alternative-dose ipilimumab and nivolumab (IPI-NIVO) regimen with conventional-dose IPI-NIVO, no statistically significant difference in rCR, rOOR, radiologic progressive disease, or pCR was noted. However, the conventional-dose IPI-NIVO regimen was associated with increased grade 3 or 4 irAEs (OR, 4.76; P < .001). Conventional-dose IPI-NIVO was associated with greater odds of achieving improved rOOR (OR, 1.95; P = .046) and pCR (OR, 2.99; P < .001) compared with anti-PD1 monotherapy. The alternative dose of IPI-NIVO also was associated with higher odds of achieving rCR (OR, 2.55; P = .03) and pCR (OR, 3.87; P < .001) compared with anti-PD1 monotherapy. The risk for grade 3 or 4 irAEs is higher with both the conventional-dose (OR, 9.59; P < .001) and alternative-dose IPI-NIVO regimens (OR, 2.02; P = .02) compared with anti-PD1 monotherapy.

CONCLUSION AND RELEVANCE: In this pooled analysis of 6 clinical trials, although DCPI was associated with increased likelihood of achieving pathological and radiologic responses, the associated risk for grade 3 or 4 irAEs was significantly lower with anti-PD1 monotherapy in the neoadjuvant setting for HRRM. Additionally, compared with alternative-dose IPI-NIVO, the conventional dose of IPI-NIVO was associated with increased risk for grade 3 or 4 irAEs, with no significant distinctions in radiologic or pathologic efficacy.

PMID:38546551 | DOI:10.1001/jamaoncol.2023.7333

Can J Diet Pract Res. 2024 Mar 28:1-6. doi: 10.3148/cjdpr-2023-026. Online ahead of print.

ABSTRACT

Purpose: The Canadian federal government has expressed an intention to work with provinces and territories to develop a national school food program (SFP). This study aimed to explore caregivers’ perception of attributes important to include in a future SFP.Methods: An online cross-sectional survey was conducted. Fifteen elementary schools from high, medium, or low median income neighbourhoods in Saskatoon were invited to participate. School principals sent a survey link to students’ caregivers. The 37-item survey included an item with 15 statements asking caregivers to rate the importance of various components of a SFP. Descriptive statistics and exploratory factor analysis were conducted.Results: A total of 510 caregivers completed the survey (response rate of 52%). The factor analysis indicated four key components of a future SFP: (1) learning opportunities on growing and preparing food, (2) offering healthy food following Canada’s Food Guide, (3) affordability of the meals offered, and (4) cultural adaptability of the meal program. Over 90% of caregivers thought providing healthy meals and ample time to eat meals to be very important.Conclusion: Our results indicate caregivers support multicomponent meal programs that, along with providing nutritious food, help children build healthy habits and sustainable food systems. These findings will help dietitians understand caregivers’ perspectives to inform the design of a national SFP.

PMID:38546536 | DOI:10.3148/cjdpr-2023-026

Environ Sci Process Impacts. 2024 Mar 28. doi: 10.1039/d3em00464c. Online ahead of print.

ABSTRACT

Diabetes is a global public health problem, and the impact of air pollutants on type 2 diabetes mellitus (T2DM) has attracted people’s attention. This study aimed to assess the association of short-term exposure to six criteria air pollutants with T2DM outpatient visits in Lanzhou, China. We collected data on daily outpatient visits for T2DM, daily meteorological data and hourly concentrations of air pollutants in Lanzhou from 2013 to 2019. An over-dispersed passion generalized addictive model combined with a distributed lag non-linear model was applied to estimate the associations and stratified analyses were performed by gender, age, and season. The models were fitted with different lag structures, including single lag days from the current to the previous seven days (lag0 to lag7) and moving average concentrations over seven lag days (lag01 to lag07). A positive association between multiple air pollutants, especially PM_2.5, NO₂, O₃8h and CO and hospital outpatient visits for T2DM was observed. The largest association between T2DM outpatient visits and PM_2.5 was observed at lag06 (RR 1.013, 95% CI: 1.001, 1.027), NO₂ at lag03 (RR 1.034, 95% CI: 1.018, 1.050), O₃8h at lag05 (RR 1.012, 95% CI: 1.001, 1.023) for an increase of 10 μg m^-3 and CO at lag03 (RR 1.084, 95% CI: 1.029, 1.142) for an increase of 1 mg m^-3 in the concentrations. In addition, people aged <65 and males are more susceptible, and air pollutants have a greater impact on the cold season. This study showed that although the air pollution in Lanzhou was improved, there was still a statistical correlation between air pollution exposure and T2DM outpatient visits. Therefore, the local government still needs to strengthen the control of air pollution and enhance the protection awareness of the diabetic population through education and publicity.

PMID:38546508 | DOI:10.1039/d3em00464c

J Laparoendosc Adv Surg Tech A. 2024 Mar 28. doi: 10.1089/lap.2024.0076. Online ahead of print.

ABSTRACT

Backgrounds: In the renal intrarenal stone surgery (RIRS) procedure, ureteral access sheath (UAS) is still used in the majority of surgeries to both protect the flexible ureteroscope (FURS) and reduce intrarenal pressure. ClearPETRA is a new UAS that has an integrated aspiration port. We aimed to evaluate the clinical outcomes and effectiveness of Aspiration-Assisted UAS (ClearPETRA) in the RIRS procedure. Methods: One thousand six hundred twenty patients who underwent RIRS between January 2021 and January 2024 were evaluated retrospectively and 512 patients were included in the study. According to stone size, patients with stones less than 2 cm and those with stones between 2 and 3 cm were analyzed separately. Patient’s demographic data, stone size, body mass index, Extracoporeal Shockwave Lithotripsy (ESWL) history, stone side, stone density (Hounsfield Unit), operation time, stone-free rate (SFR), and the number of patients with sepsis were recorded. SFR was evaluated with kidney urinary bladder 3 months after surgery for opaque calculi. Nonopaque calculi patients were evaluated with noncontrast computed tomography 3 months after surgery. In the postoperative evaluation, patients with stones less than 4 mm were evaluated as SFR. P value of <0.01 was considered statistically significant. Results: Patient’s demographic data, stone characteristics, and history of ESWL were similar in the ClearPETRA and UAS groups (P > .05). A total of 328 patients who underwent RIRS for stones less than 2 cm were included (80 ClearPETRA, 248 UAS). Length of hospital stay, operation time, SFR, secondary intervention, or postoperative sepsis (P ≥ .01) were similar in both groups. The incidence of postoperative fever was statistically significantly lower in the ClearPETRA group (P = .006). A total of 184 patients who underwent RIRS for stones between 2 and 3 cm were included (42 ClearPETRA, 142 UAS). In the ClearPETRA group, operation time was statistically significantly shorter (P = .002), SFR was statistically significantly higher (P = .003), and the number of fever and sepsis were statistically significantly less (P = .003 and 0.002, respectively). Conclusion: We found that ClearPETRA reduces the likelihood of postoperative fever after RIRS surgeries. Moreover, we can say that the use of ClearPETRA in RIRS, especially for stones larger than 2 cm, reduces the operation time, increases the SFR, and also reduces sepsis rates.

PMID:38546503 | DOI:10.1089/lap.2024.0076

Cancer Med. 2024 Apr;13(7):e7141. doi: 10.1002/cam4.7141.

ABSTRACT

BACKGROUND: Although socioeconomic factors are important determinants of population mortality, the effect of educational level on the survival of patients with cancer in China is unclear. This study aimed to assess whether educational level is associated with the prognosis of patients with cancer and to explore the mediators of this association.

METHODS: This multicentre cohort study included 18,251 patients diagnosed with cancer between May 2013 and December 2018. The main parameters measured were overall survival (OS) and all-cause mortality. The relationship between educational level and all-cause mortality was assessed using multifactor-corrected Cox survival analysis. Logistic regression was used to analyze the association between educational level and patient-generated subjective global assessment (PG-SGA).

RESULTS: The mean age of the 18,251 participants (men, 9939 [54.4%]) was 57.37 ± 11.66 years. Multifactorial survival analysis showed that patients survived longer with increasing education (university and above vs. elementary school and below; p = p = <0.001, HR = 0.84, 95% CI: 0.77-0.92), and the differences were statistically significant in different subgroups. The potential impact factors included sex, age, TNM stage, and PG-SGA score. Logistic regression showed a significant negative association between educational level and the modifiable factor PG-SGA (secondary vs. primary and below; p = 0.004, HR = 0.90, 95% CI: 0.83-0.97; university and above vs. primary and below; p < 0.001, HR = 0.79, 95% CI: 0.71-0.88).

CONCLUSIONS: Educational level was a significant prognostic factor for patients with cancer, independent of other known prognostic factors. This association was further improved by modifying the nutritional status.

PMID:38545856 | DOI:10.1002/cam4.7141

Stat Med. 2024 Mar 28. doi: 10.1002/sim.10066. Online ahead of print.

ABSTRACT

This study is to give a systematic account of sample size adaptation designs (SSADs) and to provide direct proof of the efficiency advantage of general SSADs over group sequential designs (GSDs) from a different perspective. For this purpose, a class of sample size mapping functions to define SSADs is introduced. Under the two-stage adaptive clinical trial setting, theorems are developed to describe the properties of SSADs. Sufficient conditions are derived and used to prove analytically that SSADs based on the weighted combination test can be uniformly more efficient than GSDs in a range of likely values of the true treatment difference $\delta$ . As shown in various scenarios, given a GSD, a fully adaptive SSAD can be obtained that has sufficient statistical power similar to that of the GSD but has a smaller average sample size for all $\delta$ in the range. The associated sample size savings can be substantial. A practical design example and suggestions on the steps to find efficient SSADs are also provided.

PMID:38545849 | DOI:10.1002/sim.10066

Stroke. 2024 Mar 28. doi: 10.1161/STROKEAHA.123.043691. Online ahead of print.

ABSTRACT

BACKGROUND: Predicting stroke recurrence for individual patients is difficult, but individualized prediction may improve stroke survivors’ engagement in self-care. We developed PRERISK: a statistical and machine learning classifier to predict individual risk of stroke recurrence.

METHODS: We analyzed clinical and socioeconomic data from a prospectively collected public health care-based data set of 41 975 patients admitted with stroke diagnosis in 88 public health centers over 6 years (2014-2020) in Catalonia-Spain. A new stroke diagnosis at least 24 hours after the index event was considered as a recurrent stroke, which was considered as our outcome of interest. We trained several supervised machine learning models to provide individualized risk over time and compared them with a Cox regression model. Models were trained to predict early, late, and long-term recurrence risk, within 90, 91 to 365, and >365 days, respectively. C statistics and area under the receiver operating characteristic curve were used to assess the accuracy of the models.

RESULTS: Overall, 16.21% (5932 of 36 114) of patients had stroke recurrence during a median follow-up of 2.69 years. The most powerful predictors of stroke recurrence were time from previous stroke, Barthel Index, atrial fibrillation, dyslipidemia, age, diabetes, and sex, which were used to create a simplified model with similar performance, together with modifiable vascular risk factors (glycemia, body mass index, high blood pressure, cholesterol, tobacco dependence, and alcohol abuse). The areas under the receiver operating characteristic curve were 0.76 (95% CI, 0.74-0.77), 0.60 (95% CI, 0.58-0.61), and 0.71 (95% CI, 0.69-0.72) for early, late, and long-term recurrence risk, respectively. The areas under the receiver operating characteristic curve of the Cox risk class probability were 0.73 (95% CI, 0.72-0.75), 0.59 (95% CI, 0.57-0.61), and 0.67 (95% CI, 0.66-0.70); machine learning approaches (random forest and AdaBoost) showed statistically significant improvement (P<0.05) over the Cox model for the 3 recurrence time periods. Stroke recurrence curves can be simulated for each patient under different degrees of control of modifiable factors.

CONCLUSIONS: PRERISK is a novel approach that provides a personalized and fairly accurate risk prediction of stroke recurrence over time. The model has the potential to incorporate dynamic control of risk factors.

PMID:38545798 | DOI:10.1161/STROKEAHA.123.043691

Arterioscler Thromb Vasc Biol. 2024 Mar 28. doi: 10.1161/ATVBAHA.124.320674. Online ahead of print.

ABSTRACT

BACKGROUND: Hundreds of biomarkers for peripheral artery disease (PAD) have been reported in the literature; however, the observational nature of these studies limits causal inference due to the potential of reverse causality and residual confounding. We sought to evaluate the potential causal impact of putative PAD biomarkers identified in human observational studies through genetic causal inference methods.

METHODS: Putative circulating PAD biomarkers were identified from human observational studies through a comprehensive literature search based on terms related to PAD using PubMed, Cochrane, and Embase. Genetic instruments were generated from publicly available genome-wide association studies of circulating biomarkers. Two-sample Mendelian randomization was used to test the association of genetically determined biomarker levels with PAD using summary statistics from a genome-wide association study of 31 307 individuals with and 211 753 individuals without PAD in the VA Million Veteran Program and replicated in data from FinnGen comprised of 11 924 individuals with and 288 638 individuals without PAD.

RESULTS: We identified 204 unique circulating biomarkers for PAD from the observational literature, of which 173 were genetically instrumented using genome-wide association study results. After accounting for multiple testing (false discovery rate, <0.05), 10 of 173 (5.8%) biomarkers had significant associations with PAD. These 10 biomarkers represented categories including plasma lipoprotein regulation, lipid homeostasis, and protein-lipid complex remodeling. Observational literature highlighted different pathways including inflammatory response, negative regulation of multicellular organismal processes, and regulation of response to external stimuli.

CONCLUSIONS: Integrating human observational studies and genetic causal inference highlights several key pathways in PAD pathophysiology. This work demonstrates that a substantial portion of biomarkers identified in observational studies are not well supported by human genetic evidence and emphasizes the importance of triangulating evidence to understand PAD pathophysiology. Although the identified biomarkers offer insights into atherosclerotic development in the lower limb, their specificity to PAD compared with more widespread atherosclerosis requires further study.

PMID:38545784 | DOI:10.1161/ATVBAHA.124.320674