Category: Statistics

Am J Respir Crit Care Med. 2025 Feb 20. doi: 10.1164/rccm.202411-2169OC. Online ahead of print.

ABSTRACT

RATIONALE: Extended continuous positive airway pressure (eCPAP) in the neonatal intensive care unit (NICU) for stable preterm infants increases lung volumes. Its effect on lung growth after discharge is unknown.

OBJECTIVE: To assess whether 2-weeks of eCPAP in stable preterm infants is associated with increased alveolar volume (V_A) at 6-months corrected age.

METHODS: Randomized controlled trial conducted at Oregon Health & Science University. Outpatient assessors unaware of treatment assignment. 100 infants randomized to eCPAP versus CPAP discontinuation (dCPAP) to room air.

MEASUREMENTS: The primary outcome was V_A by the single breath hold technique at 6-months corrected age. Secondary outcomes included lung diffusion capacity to carbon monoxide (D_L) and forced expiratory flows (FEFs). Functional residual capacity (FRC) was measured in the NICU.

MAIN RESULTS: Infants randomized to eCPAP (n=54) versus dCPAP (n=46) had the following measurements shown as adjusted mean [SE] : V_A (500.2 [24.9 ] vs 418.1 [23.4] mL; adjusted mean difference, 82.1 [ 95% CI, 8.3-155.9]; p =0.033); D_L (3.4 [0.2] vs 2.8 [0.1] mL/min/mmHg; adjusted mean difference, 0.6 [95% CI, 0.1-1.1]; p = 0.018); FEF₅₀ (500.6 [18.2] vs 437.9 [17.9] mL/sec; adjusted mean difference, 62.7 [95% CI 4.5-121.0]; p = 0.039); FEF_25-75 (452.0 [17.4] vs 394.4 [17.4] mL/sec; adjusted mean difference, 57.5 [95% CI 1.3-113.8]; p=0.046).

CONCLUSIONS: Infants randomized to eCPAP vs dCPAP had significantly increased V_A at 6-months corrected age. D_L and FEFs were also increased. Extending CPAP in stable preterm infants in the NICU may be a non-pharmacologic and safe therapy to promote lung growth. Clinical trial registration available at www.

CLINICALTRIALS: gov, ID: NCT04295564.

PMID:39977011 | DOI:10.1164/rccm.202411-2169OC

Clin Exp Rheumatol. 2025 Feb 13. doi: 10.55563/clinexprheumatol/4g8g9q. Online ahead of print.

ABSTRACT

OBJECTIVES: Rheumatoid arthritis (RA) is a prevalent autoimmune disorder. This study examines the comparative efficacy of Janus kinase inhibitors (JAKi) and adalimumab (ADA) in managing RA.

METHODS: As of May 2024, four electronic databases were systematically reviewed: PubMed, Web of Science, Embase, and the Cochrane Library. Data were analysed using Review Manager (RevMan) software. The risk ratio (RR) and its 95% confidence interval (CI) represented dichotomous outcomes. Evaluated outcome measures included ACR20, ACR50, ACR70, Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), and Disease Activity Score 28-4 (C-reactive protein) (DAS28-4(CRP)).

RESULTS: The analysis encompassed 6 studies, totalling 4048 patients with RA. There was no statistically significant difference in efficacy between JAKi and ADA when assessing ACR20 (p=0.25) and DAS28-4(CRP) (p=0.57). However, JAKi demonstrated superior efficacy compared to ADA for ACR50 (RR=1.20; p=0.02), ACR70 (RR=1.24; p=0.03), CDAI (RR=1.17; p=0.01), and SDAI (RR=1.19; p=0.006) outcomes. Longitudinal analysis revealed that over a 52-week period, JAKi did not exhibit superior efficacy to ADA for ACR50 (RR=1.16; p=0.19) and ACR70 (RR=1.10; p=0.26). Specifically, the tofacitinib subgroup outperformed ADA (RR=1.49; p=0.003), while other JAKi treatments did not show a significant difference (RR=1.19; p=0.11) compared to ADA.

CONCLUSIONS: JAKi generally offers better efficacy than ADA in the treatment of RA, though this advantage appears to be influenced by the duration of treatment.

PMID:39977004 | DOI:10.55563/clinexprheumatol/4g8g9q

J Am Chem Soc. 2025 Feb 20. doi: 10.1021/jacs.4c16922. Online ahead of print.

ABSTRACT

Triplet-triplet annihilation (TTA) enables photon upconversion by combining two lower-energy triplet excitons to produce a higher-energy singlet exciton. This mechanism enhances light-harvesting efficiency for solar energy conversion and enables the use of lower-energy photons in bioimaging and photoredox catalysis applications. The magnetic modulation of such high-energy excitons presents an exciting opportunity to develop molecular quantum information technologies. While the spin dynamics of triplet exciton pairs are sensitive to external magnetic fields, the magnetic field effects (MFEs) associated with these pairs are generally limited by spin statistics to at most 10% at low fields (<1 T), making them challenging to apply in technological advancements. In contrast, MFEs on spin-correlated radical pairs (SCRPs) can be significantly greater, surpassing those on triplet pairs. By using SCRPs-based molecular qubits as triplet sensitizers in the sensitized TTA scheme, we can magnetically modulate TTA and consequently, the delayed fluorescence of annihilators. In our current system, we have achieved more than 70% magnetic modulation of delayed fluorescence, effectively harnessing and even amplifying magnetic modulation within SCRPs to influence high-energy excitons. This work opens new opportunities for advancing spin-controlled chemical reactions and molecular quantum information technologies.

PMID:39976998 | DOI:10.1021/jacs.4c16922

Transplantation. 2025 Mar 1;109(3):496-503. doi: 10.1097/TP.0000000000005178. Epub 2024 Aug 28.

ABSTRACT

BACKGROUND: The number of deceased donor kidney transplants has been increasing and is at a record high, yet nonuse of kidneys recovered for transplantation has risen to 25.8% following circular kidney allocation system based on 250-nautical-mile circles implemented on March 15, 2021 (KAS250).

METHODS: Using Scientific Registry of Transplant Recipients data, we studied all deceased donor kidneys recovered for transplant from March 15, 2019, to January 31, 2023. We calculated the association of multiple factors with kidney nonuse, including increasing recovery of kidneys from nonideal donors, delays in offer acceptance observed under KAS250, and impacts of COVID-19.

RESULTS: In the 2 y before KAS250, the nonuse rate was 21.2%. Had this rate continued, 2334 more kidneys would have been transplanted through January 2023. We estimated that about 769 of these nonused kidneys (33%) were associated with offer acceptance delays under KAS250; about 994 of these nonused kidneys (43%) were associated with increased prevalence of nonideal donors: donation after circulatory death donors, older donors, and donors with elevated peak serum creatinine; and about 542 of these nonused kidneys (23%) were associated with an otherwise unexplained gradual upward trend in nonuse of recovered kidneys across the pre-KAS250 and KAS250 eras. The overall impact of COVID-19 on the nonuse rate was not significant.

CONCLUSIONS: The rise in kidney nonuse rate was significantly associated with both increased recovery of nonideal donors, and with KAS250 allocation complexity and delays. Increasing recovery of kidneys from nonideal donors benefits patients because recovering more kidneys increases the number of kidneys available for transplant.

PMID:39976985 | DOI:10.1097/TP.0000000000005178

JAMA Otolaryngol Head Neck Surg. 2025 Feb 20. doi: 10.1001/jamaoto.2024.5251. Online ahead of print.

ABSTRACT

IMPORTANCE: The internet has changed the way that medical information by journals is disseminated, with a shift toward online distribution. Given this, it is important to include alternative metrics that measure online attention when determining the influence of otolaryngology journals.

OBJECTIVE: To describe a ranking system for otolaryngology journals that reflects the amount of publicity received online and to determine factors associated with these rankings.

DESIGN AND SETTING: In this cross-sectional study, online attention was measured using Altmetric Attention Scores obtained for all 26 112 articles published by the 43 journals classified under the Journal Citation Reports category of otorhinolaryngology from 2018 to 2022. Data were analyzed from January to June 2023.

MAIN OUTCOMES AND MEASURES: Altmetric journal rankings were created from the top 500 articles with the highest Altmetric Attention Scores, using a rank sum weight-based method to assign credit for an article’s attention online to its respective journal. The association of article content, study design and type, and social media presence on X (formerly Twitter) with ranking was examined. Comparisons between Altmetric journal rankings and bibliometric rankings (5-year Impact Factor) were also performed.

RESULTS: Of 43 otolaryngology journals, JAMA Otolaryngology-Head & Neck Surgery had the highest Altmetric journal ranking. Most articles in the Altmetric top 500 were nonoperative clinical studies (220 articles [43.5%]) or described the natural history of disease (176 articles [34.9%]) and involved otology/neurotology (158 articles [29.9%]) or rhinology/allergy (134 articles [25.4%]). The COVID-19 pandemic was a common topic (169 articles [33.5%]). The presence of an active X account for the entire 5-year period was associated with a higher Altmetric total rank sum score for journals (η2 = 0.07; 95% CI, 0.02-0.13 [moderate effect size]). There was a moderate statistically significant correlation between Altmetric journal rankings and 5-year Impact Factor rankings (r = 0.5; 95% CI, 0.2-0.7).

CONCLUSIONS AND RELEVANCE: This cross-sectional study demonstrates that metrics based on online attention provide an alternative way to assess the reach and influence of medical journals. Journals seeking to expand their influence online may benefit from a presence on social media.

PMID:39976975 | DOI:10.1001/jamaoto.2024.5251

JAMA Netw Open. 2025 Feb 3;8(2):e2460565. doi: 10.1001/jamanetworkopen.2024.60565.

ABSTRACT

IMPORTANCE: Newborn mortality accounts for approximately 47% of all mortality of children under the age of 5 years. Virtual simulation may be a viable approach to support retention of essential newborn care knowledge and skills among health care professionals in low- and middle-income countries.

OBJECTIVE: To evaluate the association between mobile virtual simulation using Virtual Essential Newborn Care (vENC) and knowledge and skills retention in early newborn care in low-resource settings and to propose a frequency of virtual simulation use for among health care professionals who care for newborns in low-resource settings.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted at 23 primary, secondary, and tertiary health care facilities in Lagos, Nigeria, for 6 months between December 1, 2022, and June 30, 2023. Participants included nurses and midwives who participated in deliveries and provided newborn care. Potential participants who attended a Helping Babies Breathe or Essential Newborn Care (ENC) course within the past 1 year were excluded.

EXPOSURES: All participants received in-person training using the World Health Organization ENC 1 and ENC 2 curricula along with virtual simulation practice at variable recommended frequencies for 6 months after course completion.

MAIN OUTCOMES AND MEASURES: Primary outcomes included assessments of bag-valve-mask (BVM) ventilation skills, and performance on ENC 1 and ENC 2 case A and B scenarios conducted by trained research assistants before, immediately after, and 6 months after the in-person course. All scores ranged from 0% to 100%, with higher scores indicating better performance.

RESULTS: Of 70 enrolled participants (67 of 69 [97%] female), 62 (89%) completed the 6-month follow-up. Immediate posttraining performance (median [IQR] scores: BVM ventilation skills, 93% [86%-100%]; ENC 1 case scenario A, 72% [61%-78%]; ENC 1 case scenario B, 76% [68%-88%]; ENC 2 case scenario A, 80% [73%-87%]; and ENC 2 case scenario B, 88% [70%-95%]) improved compared with pretraining performance for all skill assessments (median [IQR] scores: BVM ventilation skills, 57% [29%-64%]; ENC 1 case scenario A, 39% [28%-50%]); ENC 2 case scenario A, 33% [20%-45%]) (all P < .001). There were further gains in performance at the 6-month follow-up assessment for BVM ventilation (median [IQR], 100% [86%-100%]; P = .04) and the ENC1 and ENC2 assessments by case scenario (case scenario A: ENC 1 median [IQR] score, 78% [72%-83%]; P = .001 and ENC 2 median [IQR] score, 87% [80%-93%]; P = .008; and case scenario B: ENC 1 median [IQR] score, 88% [76%-92%]; P = .009 and ENC 2 median [IQR] score, 93% [80%-100%]; P = .004) relative to the immediate postcourse assessment scores.

CONCLUSIONS AND RELEVANCE: Findings of this cohort study suggest that the app-based simulations may be effective in supporting the retention of knowledge and skills following ENC training and may contribute to further performance gains for health care professionals in low- and middle-income countries. More clinical and implementation research is needed to explore the impact of virtual simulations on health professionals’ clinical practices and neonatal outcomes.

PMID:39976968 | DOI:10.1001/jamanetworkopen.2024.60565

JAMA Netw Open. 2025 Feb 3;8(2):e2460794. doi: 10.1001/jamanetworkopen.2024.60794.

ABSTRACT

IMPORTANCE: New persistent opioid use after surgery is contributing to the opioid crisis affecting the US, and interventions to limit postoperative opioid prescriptions have been proposed to mitigate the opioid-related health care burden. Limited information is available regarding the incidence of new persistent use after surgery in other countries.

OBJECTIVE: To determine the incidence of new persistent opioid use and to evaluate factors associated with its risk after surgery in Austria.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective, population-based cohort study used administrative data from the national Austrian social insurance database for adult patients undergoing surgery between January 1, 2016, and December 31, 2021. Exclusion criteria were incomplete exposure or outcome data, early postoperative death, and ongoing opioid use at the time of surgery. Data were analyzed from September 2023 to August 2024.

EXPOSURES: General, gynecological, urological, orthopedic, and cardiac surgery.

MAIN OUTCOMES AND MEASURES: The primary study outcome was the incidence of new persistent opioid use up to 6 months after surgery in the Austrian population; the factors associated with use, including patient factors and surgical procedures, were analyzed. A logistic regression model was used to evaluate the association between the primary outcome and the independent variables after controlling for multicollinearity.

RESULTS: Among 559 096 patients undergoing 642 857 surgical procedures (median [IQR] age, 60 [48-71] years; 318 391 male patients [49.5%]), new persistent opioid use was documented in 10 810 cases (1.7%) overall, and the rates ranged from 0.3% for appendectomy (130 cases per 40 565 procedures) to 0.7% for abdominal surgery (2198 cases per 335 034 procedures) to 6.8% for spinal surgery (3495 cases per 51 348 procedures). The median (IQR) daily opioid dose in oral morphine equivalents was 7.4 (4.1-14.9) mg. Specific procedures, including spinal surgery (odds ratio [OR], 5.36; 95% CI, 5.04-5.69) and arthroplasty (OR, 1.57; 95% CI, 1.48-1.67), and patient characteristics, such as previous opioid use that was discontinued before surgery (OR, 3.06; 95% CI, 2.93-3.19) and the frequency of previously filled opioid prescriptions (OR, 16.49; 95% CI, 13.63-19.95), were associated with new persistent opioid use.

CONCLUSIONS AND RELEVANCE: In Austria, the incidence of new persistent opioid use after surgery is lower than that in North America, but the factors associated with risk are similar. These findings suggest the need for studies comparing pain management strategies, as well as systemic and organizational factors, that contribute to the development of new persistent opioid use after surgery in North American and European health care systems, where less evidence about new persistent opioid use has been available.

PMID:39976966 | DOI:10.1001/jamanetworkopen.2024.60794

JAMA Netw Open. 2025 Feb 3;8(2):e2460854. doi: 10.1001/jamanetworkopen.2024.60854.

ABSTRACT

IMPORTANCE: Lithium is a naturally occurring element in drinking water and is commonly used as a mood-stabilizing medication. Although clinical studies have reported associations between receiving lithium treatment and reduced cancer risk among patients with bipolar disorder, to our knowledge, the association between environmental lithium exposure and cancer risk has never been studied in the general population.

OBJECTIVES: To evaluate the association between exposure to lithium in drinking groundwater and cancer risk in the general population.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included participants with electronic health record and residential address information but without cancer history at baseline from the All of Us Research Program between May 31, 2017, and June 30, 2022. Participants were followed up until February 15, 2023. Statistical analysis was performed from September 2023 through October 2024.

EXPOSURE: Lithium concentration in groundwater, based on kriging interpolation of publicly available US Geological Survey data on lithium concentration for 4700 wells across the contiguous US between May 12, 1999, and November 6, 2018.

MAIN OUTCOME AND MEASURES: The main outcome was cancer diagnosis or condition, obtained from electronic health records. Stratified Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) and 95% CIs for risk of cancer overall and individual cancer types for increasing quintiles of the estimated lithium exposure in drinking groundwater, adjusting for socioeconomic, behavioral, and neighborhood-level variables. The analysis was further conducted in the western and eastern halves of the US and restricted to long-term residents living at their current address for at least 3 years.

RESULTS: A total of 252 178 participants were included (median age, 52 years [IQR, 36-64 years]; 60.1% female). The median follow-up time was 3.6 years (IQR, 3.0-4.3 years), and 7573 incident cancer cases were identified. Higher estimated lithium exposure was consistently associated with reduced cancer risk. Compared with the first (lowest) quintile of lithium exposure, the HR for all cancers was 0.49 (95% CI, 0.31-0.78) for the fourth quintile and 0.29 (95% CI, 0.15-0.55) for the fifth quintile. These associations were found for all cancer types investigated in both females and males, among long-term residents, and in both western and eastern states. For example, for the fifth vs first quintile of lithium exposure for all cancers, the HR was 0.17 (95% CI, 0.07-0.42) in females and 0.13 (95% CI, 0.04-0.38) in males; for long-term residents, the HR was 0.32 (95% CI, 0.15-0.66) in females and 0.24 (95% CI, 0.11-0.52) in males; and the HR was 0.01 (95% CI, 0.00-0.09) in western states and 0.34 (95% CI, 0.21-0.57) in eastern states.

CONCLUSIONS AND RELEVANCE: In this cohort study of 252 178 participants, estimated lithium exposure in drinking groundwater was associated with reduced cancer risk. Given the sparse evidence and unknown mechanisms of this association, follow-up investigation is warranted.

PMID:39976965 | DOI:10.1001/jamanetworkopen.2024.60854

JAMA Netw Open. 2025 Feb 3;8(2):e2461079. doi: 10.1001/jamanetworkopen.2024.61079.

ABSTRACT

IMPORTANCE: Behavioral flags in the electronic health record (EHR) may introduce bias and perpetuate structural racism and discrimination. Descriptions of differences in the way that markers of behavioral risk are communicated will help clarify the inequities that pediatric patients and their families experience in the hospital.

OBJECTIVE: To assess whether racially and socioeconomically marginalized pediatric patients and families are more likely than their counterparts to be assigned a behavioral flag in their EHR.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used EHR data for pediatric patients (aged <18 years) hospitalized from June 2012 to July 2021 across care settings at the University of California, San Francisco health care facilities, an academic quaternary care hospital system that includes 2 pediatric inpatient facilities. The analysis was completed from December 29, 2022, to November 22, 2024.

MAIN OUTCOME AND MEASURES: The primary outcome of interest was any of the following behavioral flags placed in a patient’s EHR: witnessed substance abuse, history of inappropriate behavior, security, violent behavior, dismissal from practice, and child protective services (CPS) hold. The primary variables were patients’ race, ethnicity, insurance status, and primary language.

RESULTS: Of 55 865 pediatric encounters (52.2% among males; median patient age at the first encounter, 3 years [IQR, 0-12 years]), 236 (0.4%) had behavioral flags. Compared with encounters among patients who identified as White, encounters among patients who identified as Black or African American were more likely to have a behavioral flag (incidence rate ratio [IRR], 2.07; 95% CI, 1.32-3.25). Behavioral flags were also more likely among encounters of individuals with government insurance compared with those with private insurance (IRR, 2.60; 95% CI, 1.85-3.65). Black or African American patients younger than 1 year (IRR, 3.53; 95% CI, 1.80-6.91) and aged 1 to 7 years (IRR, 2.87; 95% CI, 1.34-6.15) had a higher likelihood of flag placement compared with their White counterparts.

CONCLUSIONS AND RELEVANCE: This cohort study found significant inequities in incidence of behavioral flags in the EHR among racially and socioeconomically marginalized pediatric patients. This finding was most pronounced for Black or African American patients younger than 8 years, suggesting that this phenomenon may be a response to Black families rather than specific patient behavior.

PMID:39976964 | DOI:10.1001/jamanetworkopen.2024.61079

JAMA Ophthalmol. 2025 Feb 20. doi: 10.1001/jamaophthalmol.2024.6492. Online ahead of print.

ABSTRACT

IMPORTANCE: Primary selective laser trabeculoplasty (SLT) is a safe primary treatment for open-angle glaucoma (OAG) and ocular hypertension (OHT). However, there is limited evidence on its use as a secondary treatment, ie, after prior use of ocular hypotensive eye drops.

OBJECTIVE: To evaluate outcomes following SLT after using hypotensive eye drops for at least 3 years.

DESIGN, SETTING, AND PARTICIPANTS: This is a post hoc exploratory analysis of data from a multicenter randomized clinical trial conducted within the UK National Health Service. Participants were patients with OAG or OHT who participated in the LiGHT trial. Data were analyzed from February 2021 to December 2024.

INTERVENTION: Participants were initially randomized to either primary SLT or primary hypotensive eye drops and remained on the allocated treatment pathway for 3 years. Participants using eye drops were then allowed to have secondary SLT as a treatment switch (to reduce their medication load) or as a treatment escalation (if more intense treatment was needed). Participants were treated and monitored according to a predefined protocol.

MAIN OUTCOMES AND MEASURES: The outcomes of interest were rates of incisional glaucoma surgery, medication use, and intraocular pressure.

RESULTS: In total, 633 participants entered the extension of the LiGHT trial, and 524 participants (82.8%) completed the extension (72 months). Of 320 participants receiving primary hypotensive eye drops, 112 (35.0%) received SLT: 70 participants switched to SLT, 29 participants had SLT as a treatment escalation, and 13 participants had SLT as a treatment escalation in 1 eye and as a treatment switch in the other eye. Switching to SLT was associated with a reduction in the number of medications (mean [SD], 1.38 [0.62] to 0.59 [0.92] active ingredients; mean difference, 0.79 [95% CI 0.66 to 0.93] active ingredients; P < .001). At 72 months, 69 eyes that switched to SLT (60.5%) needed no medical or surgical treatment, and 62 eyes receiving 1 drug before switching (83.8%) needed no medical treatment. Escalating to SLT was associated with a mean intraocular pressure reduction of 4.6 mm Hg (21.8%), and 30 eyes (62.5%) reached target intraocular pressure at 72 months without the need for surgery; 9 eyes (18.7%) needed a trabeculectomy.

CONCLUSIONS AND RELEVANCE: This secondary analysis of a randomized clinical trial found that secondary SLT was associated with a reduction in the medication load for stable, medically treated eyes. For medically uncontrolled eyes, there is evidence that SLT could provide additional intraocular pressure control, but the need for trabeculectomy was not eliminated.

TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN32038223.

PMID:39976961 | DOI:10.1001/jamaophthalmol.2024.6492