Category: Statistics

JAMA Netw Open. 2024 Oct 1;7(10):e2440673. doi: 10.1001/jamanetworkopen.2024.40673.

ABSTRACT

IMPORTANCE: The impact of patient-specific, disease-related, and social factors on outcomes in limited-stage small cell lung cancer (LS-SCLC) is not well defined. A post hoc secondary analysis of such factors from the Cancer and Leukemia Group B (CALGB) 30610-Radiation Therapy Oncology Group (RTOG) 0538 trial may impact future trial design.

OBJECTIVE: To assess the comprehensive demographic, disease-related, treatment-related, and social factors for potential associations with survival outcomes and understand whether specific subpopulations may benefit from radiotherapy (RT) dose escalation in LS-SCLC.

DESIGN, SETTING, AND PARTICIPANTS: This post hoc secondary analysis of a randomized clinical trial included 638 adults with LS-SCLC treated at 186 unique treatment sites with at least 1 accrual for all patients from March 15, 2008, to December 1, 2019; 313 patients were randomized to receive RT twice daily to a dosage of 45 Gy for 3 weeks and 325 to receive RT once daily to a dosage of 70 Gy for 7 weeks. Data were locked February 28, 2022, and analyzed from November 28, 2022, to June 4, 2024.

INTERVENTIONS: Twice-daily RT or once-daily RT.

MAIN OUTCOMES AND MEASURES: Multivariable Cox proportional hazards models evaluated the association of treatment groups and other risk factors with progression-free survival (PFS) and overall survival (OS). Patient-specific factors included age, sex, and Eastern Cooperative Oncology Group performance status. Disease-related factors included tumor, nodal, and overall cancer stages. Treatment-related factors included type of chemotherapy, timing of concurrent RT, RT technique, and prophylactic cranial irradiation. Social factors included marital status and treatment center accrual volume.

RESULTS: Among 507 patients (260 [51.3%] female and 247 [48.7%] male; mean [SD] age, 62.6 [7.9] years) included in the multivariate survival analysis, with a median follow-up of 4.7 (IQR, 3.7-7.1) years, female sex was associated with improved OS (hazard ratio [HR], 0.73 [95% CI, 0.58-0.91]; P = .006), while being 70 years or older was associated with decreased OS (HR, 1.50 [95% CI, 1.14-1.98]; P = .004). Neither age nor sex was associated with PFS. When compared with those with N1 disease, OS and PFS were worse in patients with N2 (HRs, 1.64 [95% CI, 1.19-2.26]; P = .002 and 1.36 [95% CI, 1.02-1.81]; P = .04, respectively) and N3 (HRs, 2.03 [95% CI, 1.40-2.93]; P < .001 and 1.63 [95% CI, 1.17-2.26]; P = .004) disease. Compared with stage II cancer, OS was worse for stage IIIA (HR, 1.65 [95% CI, 1.17-2.31]; P = .004) and stage IIIB (HR, 1.94 [95% CI, 1.34-2.83]; P < .001). Compared with high-volume accrual centers, treatment at low- or middle-volume accrual centers was associated with worse PFS (HRs, 1.94 [95% CI, 1.33-2.82; P < .001] and 1.44 [95% CI, 1.15-1.82; P = .002], respectively) and worse OS (HRs, 1.55 [95% CI, 1.03-2.32; P = .03] and 1.33 [95% CI, 1.04-1.70; P = .02], respectively).

CONCLUSIONS AND RELEVANCE: This secondary analysis of the CALGB 30610-RTOG 0538 randomized clinical trial of patients with LS-SCLC found associations between female sex or being younger than 70 years and improved overall survival and between advanced nodal stage or treatment at low- or middle-volume accrual centers and worse outcomes. These findings suggest that stratification by nodal stage, clinical stage, and age should be considered in future randomized trials.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00632853.

PMID:39446327 | DOI:10.1001/jamanetworkopen.2024.40673

JAMA Netw Open. 2024 Oct 1;7(10):e2441056. doi: 10.1001/jamanetworkopen.2024.41056.

ABSTRACT

IMPORTANCE: Racial disparities in receipt of guideline-concordant care (GCC) among older patients with potentially curable breast cancer are understudied.

OBJECTIVE: To determine whether rates of GCC, time to treatment initiation, and all-cause mortality in stage I to III breast cancer differ by race among older adults.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from the National Cancer Database and included patients aged 65 years and older with stage I to III breast cancer, diagnosed between 2010 and 2019. Data analysis was conducted between July 2022 to July 2023.

EXPOSURES: Race, defined as non-Hispanic Black or non-Hispanic White.

MAIN OUTCOMES AND MEASURES: The primary outcome was nonreceipt of GCC, defined using the National Comprehensive Cancer Network guidelines, and all-cause mortality. The secondary outcome was time to treatment initiation. Univariate and multivariate regression analysis were used to determine association between exposure and outcomes. Models for GCC and all-cause mortality included age, stage, receptor status, year of diagnosis, Charlson-Deyo comorbidity index, insurance, health care setting, and neighborhood-level educational attainment and median income.

RESULTS: The analytic cohort included 258 531 participants (mean [SD] age, 72.5 [6.0] years), with 25 174 participants who identified as non-Hispanic Black (9.7%) and 233 357 participants who identified as non-Hispanic White (90.3%), diagnosed between 2010 and 2017. A total of 4563 non-Hispanic Black participants (18.1%) and 35 374 non-Hispanic White participants (15.2%) did not receive GCC. Non-Hispanic Black race, compared with non-Hispanic White race, was associated with increased odds of not receiving GCC in the multivariate analysis (adjusted odds ratio [aOR], 1.13; 95% CI, 1.08-1.17; P < .001). Non-Hispanic Black race was associated with 26.1% increased risk of all-cause mortality in the univariate analysis, which decreased to 4.7%, after adjusting for GCC and clinical and sociodemographic factors (adjusted hazard ratio, 1.05; 95% CI, 1.01-1.08; P = .006). Non-Hispanic White race, compared with non-Hispanic Black race, was associated with increased odds of initiating treatment within 30 (OR, 1.65; 95% CI, 1.6-1.69), 60 (OR, 2.11; 95% CI, 2.04-2.18), and 90 (OR, 2.39; 95% CI, 2.27-2.51) days of diagnosis.

CONCLUSIONS AND RELEVANCE: In this cohort study, non-Hispanic Black race was associated with increased odds of not receiving GCC and less timely treatment initiation. Non-Hispanic Black race was associated with increased all-cause mortality, which was reduced after adjusting for GCC and clinical and sociodemographic factors. These findings suggest that optimizing timely receipt of GCC may represent a modifiable pathway to improving inferior survival outcomes among older non-Hispanic Black patients with breast cancer.

PMID:39446324 | DOI:10.1001/jamanetworkopen.2024.41056

JAMA Netw Open. 2024 Oct 1;7(10):e2441063. doi: 10.1001/jamanetworkopen.2024.41063.

ABSTRACT

IMPORTANCE: The US is experiencing a protracted drug overdose crisis primarily associated with exposure to illicitly manufactured fentanyl (IMF), methamphetamine, and cocaine. Overdose risk and treatment responses may be directly affected by absolute drug exposure concentrations and drug use prevalence.

OBJECTIVE: To quantify changes in absolute drug exposure concentrations from 2013 to 2023.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study analyzed urine drug testing (UDT) results from urine specimens collected between January 1, 2013, and August 22, 2023, in 49 states and the District of Columbia. Urine specimens were obtained from patients aged 18 years or older who presented to substance use disorder treatment clinics. The UDT was ordered by clinicians based on medical necessity.

EXPOSURES: Urine specimens were analyzed for the following drugs or metabolites (analytes tested in parentheses): fentanyl (fentanyl), heroin (6-monoacetylmorphine), cocaine (benzoylecgonine), and methamphetamine (methamphetamine) using liquid chromatography with tandem mass spectrometry.

MAIN OUTCOMES AND MEASURES: Relative concentrations of fentanyl, heroin, cocaine, and methamphetamine. Creatinine-normalized drug concentration values were log-transformed prior to visualization and statistical analyses. The Mann-Kendall trend test was performed to examine trends over time. To estimate the geospatial and temporal patterns of drug concentration, a second series of models (1 for each drug) with an interaction effect for clinic location and collection year were fit.

RESULTS: A total of 921 931 unique UDT samples were collected from patients (549 042 males [59.6%]; median [IQR] age, 34 [27-44] years). The adjusted fentanyl concentration in urine specimens was 38.23 (95% CI, 35.93-40.67) ng/mg creatinine in 2023 and 4.61 (95% CI, 3.59-5.91) ng/mg creatinine in 2013. The adjusted methamphetamine concentration was 3461.59 (95% CI, 3271.88-3662.30) ng/mg creatinine in 2023 and 665.27 (95% CI, 608.51-727.32) ng/mg creatinine in 2013. The adjusted cocaine concentration was 1122.23 (95% CI, 1032.41-1219.87) ng/mg creatinine in 2023 and 559.71 (95% CI, 524.69-597.06) ng/mg creatinine in 2013. The adjusted heroin concentration was 58.36 (95% CI, 48.26-70.58) ng/mg creatinine in 2023 and 146.59 (95% CI, 136.06-157.92) ng/mg creatinine in 2013. Drug concentrations varied across US Census divisions.

CONCLUSIONS AND RELEVANCE: This cross-sectional study found that absolute concentrations of fentanyl, methamphetamine, and cocaine in urine specimens increased from 2013 to 2023, with a decrease in heroin concentration during that period. The findings suggest that exposure to these substances, as well as the illicit drug supply, has fundamentally changed in many parts of the US, highlighting the need to reinforce surveillance initiatives and accelerate efforts to treat individuals with IMF and/or stimulant exposure.

PMID:39446323 | DOI:10.1001/jamanetworkopen.2024.41063

JAMA Netw Open. 2024 Oct 1;7(10):e2441152. doi: 10.1001/jamanetworkopen.2024.41152.

ABSTRACT

IMPORTANCE: Although trial data support the omission of axillary surgery and radiation therapy (RT) in women aged 70 years or older with T1N0 hormone receptor-positive (HR+) breast cancer, potential overtreatment in older adults with frailty persists.

OBJECTIVE: To determine how much geospatial variation in locoregional therapy may be attributed to region vs patient factors.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cross-sectional study included women aged 70 years or older who were diagnosed with HR+/ERBB2-negative (ERBB2-) breast cancer from January 1, 2013, to December 31, 2017. Data came from Surveillance, Epidemiology, and End Results-Medicare. Hierarchical multivariable modeling was used to evaluate the variance in deescalated care attributable to 4 domains, ie, (1) random, (2) region (health service area [HSA]), (3) patient factors, and (4) unexplained. Patient factors included age, frailty (validated claims-based measure), Charlson Comorbidity Index (CCI), and socioeconomic status (Yost index). Analyses were performed from January to October 2023.

EXPOSURE: HSA.

MAIN OUTCOMES AND MEASURES: Deescalated care, defined as omission of axillary surgery, RT, or both. Standard therapy was defined as lumpectomy, axillary surgery, and RT or mastectomy with axillary surgery. Multivariable logistic regression was used to identify factors associated with deescalated care receipt.

RESULTS: Of 9173 patients (mean [SD] age, 76.5 [5.2] years), 2363 (25.8%) were aged 80 years or older, 705 (7.7%) had frailty, and 419 (4.6%) had a CCI of 2 or greater. While 4499 (49.1%) underwent standard therapy, 4674 (50.9%) underwent deescalated therapy (1193 [13.0%] of the population omitted axillary surgery and 4342 [55.5%] of patients undergoing lumpectomy omitted RT). Of the total variance, random variation explained 27.3%, region/HSA explained 35.3%, patient factors explained 2.8%, and 34.5% was unexplained. In adjusted models, frailty and increased age were associated with a higher likelihood of undergoing deescalated therapy (frailty: odds ratio [OR], 1.70; 95% CI, 1.43-2.02; age, by 1-year increment: OR, 1.10; 95% CI, 1.09-1.11), but CCI was not. Patients in rural areas compared with those in urban areas (OR, 0.82; 95% CI, 0.68-0.99) and Asian and Pacific Islander patients compared with non-Hispanic White patients (OR, 0.68; 95% CI, 0.54-0.85) had a lower likelihood of undergoing deescalated therapy.

CONCLUSIONS AND RELEVANCE: In this retrospective cross-sectional study of women aged 70 years or older diagnosed with T1N0 HR+/ERBB2- breast cancer, region/HSA contributed more to the variation in deescalated therapy use than patient factors. Unexplained variation may be attributed to unmeasured characteristics, such as multidisciplinary environment and patient preference. Decision support efforts to address overtreatment should target regions with low rates of evidence-based deescalation.

PMID:39446322 | DOI:10.1001/jamanetworkopen.2024.41152

JAMA Netw Open. 2024 Oct 1;7(10):e2441166. doi: 10.1001/jamanetworkopen.2024.41166.

ABSTRACT

IMPORTANCE: Age-related macular degeneration (AMD) is the leading cause of blindness among people aged 50 years or older worldwide. There is a need for new strategies for the prevention and treatment of AMD. There is some limited evidence to suggest the possibility of a protective association of dementia medications with the development of some types of AMD, but the evidence is weak.

OBJECTIVE: To investigate whether the dementia medications memantine and donepezil are associated with the risk of developing AMD.

DESIGN, SETTING, AND PARTICIPANTS: Three population-based cohort studies were performed using data from the Clinical Practice Research Datalink GOLD and Aurum databases from May 15, 2002, to June 21, 2022. Participants included individuals with dementia (vascular dementia, nonvascular dementia, or Alzheimer disease) aged 40 years or older. Statistical analysis was carried out between February and November 2023.

EXPOSURES: Exposures were dementia medications. Cohort 1 compared patients prescribed donepezil with those prescribed rivastigmine or galantamine using the new-user design. Cohort 2 compared memantine with donepezil, rivastigmine, or galantamine using the prevalent new-user design. In a sensitivity analysis, cohort 3 compared memantine with rivastigmine or galantamine only.

MAIN OUTCOMES AND MEASURES: New diagnosis of AMD.

RESULTS: There were 132 846 individuals (mean [SD] age, 80.4 [7.6] years; 61.8% women; mean [SD] body mass index [BMI], 25.5 [4.6]) with a diagnosis of dementia included in cohort 1, 159 419 individuals (mean [SD] age, 81.2 [7.6] years; 59.7% women; mean [SD] body mass index [BMI], 25.6 [4.7]) with a diagnosis of dementia included in cohort 2, and 92 328 individuals with a diagnosis of dementia included in cohort 3 (mean [SD] age, 80.9 [7.7] years; 58.5% women; mean [SD] body mass index [BMI], 25.5 [4.7]). The adjusted hazard ratio (HR) for donepezil compared with rivastigmine or galantamine (cohort 1) was 0.95 (95% CI, 0.67-1.35). The adjusted HR for memantine compared with donepezil, rivastigmine, or galantamine (cohort 2) was 1.03 (95% CI, 0.83-1.27). The adjusted HR for memantine vs rivastigmine or galantamine only (cohort 3) was 1.24 (95% CI, 0.83-1.86).

CONCLUSIONS AND RELEVANCE: This cohort study of patients with dementia found no significant associations between memantine or donepezil compared with other dementia medications and the risk of development of AMD. Further research is recommended to examine any possible pathophysiological protective action of memantine and other dementia medications against the development of AMD.

PMID:39446320 | DOI:10.1001/jamanetworkopen.2024.41166

JAMA Netw Open. 2024 Oct 1;7(10):e2441203. doi: 10.1001/jamanetworkopen.2024.41203.

ABSTRACT

IMPORTANCE: Rural adolescents are at high risk for firearm-related injury, yet most existing prevention efforts are informed by research conducted in urban areas. Despite the need to account for rural perspectives, few studies have investigated the unique social ecological context of firearms for rural adolescents or have directly engaged with rural adolescents to understand their views on firearm use.

OBJECTIVE: To describe rural adolescents’ firearm behaviors and perceptions of firearm-related social norms within their communities, peer groups, and families.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used a convergent mixed-methods design and involved a community-based participatory research approach. Participants comprised 93 adolescents residing in rural Washington state and enrolled in a county or tribal reservation 4-H youth development program as an intermediate or senior age-level grouping (ie, aged 12-19 years). Adolescents completed a survey and participated in a semistructured focus group or interview between September 1, 2021, and September 30, 2022. Data were analyzed using descriptive and thematic analysis.

MAIN OUTCOMES AND MEASURES: Individual handgun behavior and peer, family, and community perceptions of firearm-related social norms.

RESULTS: The sample included 93 adolescents (mean [SD] age, 15.7 [1.7] years; 49 female participants [52.7%]). Approximately half of participants (52 [55.9%]) had carried a handgun at some point in their lives, with a mean (SD) age at first carry of 10.9 (3.1) years. Primary themes across quantitative and qualitative data focused on social norms (specifically, acceptable and unacceptable ways to engage with firearms, reasons for carrying firearms, and places to carry a firearm).

CONCLUSIONS AND RELEVANCE: In this cross-sectional study, rural adolescents in 4-H programs generally understood acceptable and unacceptable firearm carrying behaviors, which aligned with state laws. Findings provide context for rural adolescent behaviors such as carrying a firearm predominantly for prosocial reasons (hunting, recreation, and sport) and adult behavior such as carrying for protection of person and personal property. Understanding firearm-related social norms in rural communities holds implications for firearm injury prevention efforts, especially related to enhancing training, developing norms-based prevention approaches, and tailoring efforts to rural settings.

PMID:39446319 | DOI:10.1001/jamanetworkopen.2024.41203

J Med Toxicol. 2024 Oct 24. doi: 10.1007/s13181-024-01040-x. Online ahead of print.

ABSTRACT

Digital health refers to the use of information and communication technologies in medicine (including smartphone apps, wearables, other non-invasive sensors, informatics and telehealth platforms) to prevent illness, deliver treatment, and promote wellness. This rapidly proliferating group of technologies has the potential to reduce harm for people with opioid use disorder (OUD) and facilitate the recovery process; however, development in this space for OUD has been slower compared to that for other medical conditions. Unique issues with OUD management surrounding patient provider relationships, interaction with the healthcare system, autonomy and trust sometimes hinder care approaches, including those in digital health. The trauma informed care framework (TIC), developed for use by organizations to support individuals who have experienced trauma, has particular applicability for digital health interventions in OUD care. This manuscript will serve as a review of TIC principles and how they can be applied to digital health interventions to increase access, equity, and empowerment for people with OUD. We will highlight representative current and pipeline digital technologies for OUD, challenges with these technologies, TIC models for OUD, and the integration of TIC principles into digital technology development to better serve people with OUD. Finally, we will posit strategies to incorporate the aforementioned principles into future research efforts. We ultimately aim to use TIC as a lens through which to develop digital technologies to help individuals with OUD while minimizing harm.

PMID:39446308 | DOI:10.1007/s13181-024-01040-x

Updates Surg. 2024 Oct 24. doi: 10.1007/s13304-024-02025-9. Online ahead of print.

ABSTRACT

There is a debate over whether to transect or completely reduce the hernia sac during laparoscopic tension-free repair of inguinal hernia. This study endeavors to systematically assess the efficacy and safety of two approaches, namely transected sac (TS) and completely reduced sac (RS), in laparoscopic tension-free repair of inguinal hernia. Utilizing a meta-analysis methodology, we aim to provide a comprehensive analysis of these techniques. A comprehensive search was conducted across PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov databases to identify comparative studies focusing on laparoscopic tension-free repair of inguinal hernia, specifically comparing TS and RS techniques. The selected studies were subjected to meta-analysis using RevMan 5.3 software. A total of 8 studies, involving 2995 patients with inguinal hernia, were included in the analysis. The meta-analysis results revealed that the TS group had a higher incidence of seroma compared to the RS group [OR = 1.74, 95% CI (1.35, 2.25), P < 0.0001], and a prolonged time to return to normal activity postoperatively [MD = 0.99, 95% CI (0.85, 1.14), P < 0.00001]. However, no statistically significant differences were observed between the two groups in terms of operation time [MD = -1.75, 95% CI (- 8.72, 5.22), P = 0.62], incidence of postoperative pain [OR = 1.00, 95% CI (0.41, 2.44), P = 1.00], overall postoperative complication rate [OR = 0.98, 95% CI (0.43, 2.20), P = 0.95], and recurrence rate fOR = 2.53, 95% CI (0.61, 10.39), P = 0.20]. Transected sac in laparoscopic inguinal hernia repair is associated with an increased incidence of seroma and a longer recovery time for patients to return to normal activity. Clinical trial registration Registration number is INPLASY20223110070.

PMID:39446302 | DOI:10.1007/s13304-024-02025-9

Acad Psychiatry. 2024 Oct 24. doi: 10.1007/s40596-024-02079-2. Online ahead of print.

ABSTRACT

OBJECTIVE: Journal clubs are a common element of many residency programs. However, there is little data showing that they improve residents’ ability to interpret and use the scientific literature. The authors developed a structured journal club curriculum intended to improve scientific literacy skills among residents and increase acceptability and participation in meaningful discussion of high-quality articles among both residents and facilitators. This study examined the impact of the curriculum on objective skills, subjective skills, and engagement.

METHODS: Psychiatry residents from three academic medical centers completed 10-12 virtual journal clubs during academic year 2022-2023. At the start and end of that year, residents completed a knowledge assessment and a self-rating of scientific literacy skills; at the end of the year, residents self-rated participation in, preparation for, and attitudes towards journal club sessions and assessment of scientific literacy skills.

RESULTS: Twenty-seven residents completed self-reports at both time points. Performance on the objective skills assessment did not improve over the course of the year. Subjectively, residents reported increased understanding of common statistical techniques, ability to determine if techniques used in an article are appropriate, and the extent to which information learned from articles informs clinical practice. In the sample of 62 resident engagement surveys at follow-up, the journal club curriculum was well-received.

CONCLUSIONS: Use of a structured journal club curriculum was associated with improvements in self-rated scientific literacy skills among residents and had high acceptability. More work is needed to understand the impact of teaching methodology on journal club success.

PMID:39446299 | DOI:10.1007/s40596-024-02079-2

Can J Public Health. 2024 Oct 24. doi: 10.17269/s41997-024-00933-2. Online ahead of print.

ABSTRACT

OBJECTIVES: Experiences of discrimination reported during pregnancy are common and are associated with poor mental health and adverse birth outcomes. No Canadian studies have investigated interpersonal discrimination during pregnancy. This study aimed to quantify and identify lived-experiences of discrimination in a Canadian cohort of pregnant individuals, and examine associations with concurrent prenatal anxiety and depression symptoms.

METHODS: Pregnant individuals from the pan-Canadian Pregnancy During the Pandemic (PdP) study (n = 1943) completed the Everyday Discrimination Scale (EDS), demographic measures and self-report measures of depression and anxiety symptoms. Descriptive statistics and ANCOVA were used to assess prevalence of discrimination and associated mental health outcomes. Open-text responses (n = 189) to a question investigating reasons for discrimination were analyzed using conventional content analysis.

RESULTS: Approximately three quarters (72%) of pregnant individuals experienced at least one instance of discrimination during their pregnancy or within the year prior. Pregnant individuals experiencing more frequent and/or more types of discrimination were more likely to identify as non-white, not be partnered, have lower socioeconomic status, and have a pre-pregnancy history of anxiety and depression. The most common attributions for interpersonal discrimination were gender, age, and education/income level. Pregnant individuals who experienced more frequent discrimination and/or more types of discrimination were more likely to report clinically significant symptoms of depression and anxiety (n = 623; 35.2% and 49.1%, respectively) compared to those who reported no discrimination (n = 539; 11.5% and 19.1%, respectively). Conventional content analysis of open-text responses generated the following main themes: (1) personal attributes and sociodemographic characteristics, (2) occupation, (3) the COVID-19 pandemic, (4) pregnancy and parenting, and (5) causes outside the self.

CONCLUSION: Frequent discrimination was associated with more adverse concurrent mental health symptoms. Understanding experiences of discrimination can inform interventions that better address the needs of pregnant individuals and their infants.

PMID:39446296 | DOI:10.17269/s41997-024-00933-2