Tag: pubmed

Pain Physician. 2024 Nov;27(8):469-478.

ABSTRACT

BACKGROUND: Because of its side effects, a morphine replacement has been searched for in the field of postoperative analgesia. Hydromorphone is a derivative of morphine with no active metabolites.

OBJECTIVES: We conducted a meta-analysis of hydromorphone and morphine to compare their clinical effects in postoperative analgesia.

STUDY DESIGN: Systematic review and meta-analysis.

METHODS: The methodological quality of the studies included in this meta-analysis was assessed according to the Cochrane risk-of-bias tool. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria were used to evaluate the quality of evidence and recommendation grade for inclusion of randomized controlled trials. The primary outcome was postoperative pain score. Secondary outcomes were severe sedation, nausea, vomiting, and pruritus. The meta-analysis was performed using RevMan 5.4 (The Nordic Cochrane Centre for The Cochrane Collaboration).

RESULTS: Eight randomized controlled trials comprising 833 patients were found. There was no significant difference in pain scores between the hydromorphone and morphine groups at any measured postoperative time point: 8 hours (mean difference [MD] = -0.42; 95%CI, -2.08 to 1.24; P = 0.62); 12 hours (MD = -0.19; 95%CI, -0.62 to 0.24; P = 0.39); 24 hours (MD = -0.22; 95%CI, -0.54 to 0.09; P = 0.17); 36 hours (MD = 0.01; 95%CI, -0.67 to 0.69; P = 0.98) and 48 hours (MD = -0.14; 95%CI, -1.25 to 0.96; P = 0.80). There was no significant difference in the incidence of nausea and vomiting at 24 hours postoperative. The incidence of pruritus at 24 hours postoperative was lower in the hydromorphone group (relative risk = 0.24; 95%CI, 0.09 to 0.66; P = 0.005).

LIMITATIONS: The perioperative multimodal analgesia measures were varying in the included studies, such as different medication doses. The sample size was small for some outcomes and high heterogeneity was observed.

CONCLUSIONS: There was no significant statistical difference in postoperative analgesic effect between hydromorphone and morphine, as well as side effects, including severe sedation, nausea, and vomiting at 24 hours postoperative. However, the incidence of pruritus was lower in the hydromorphone group at 24 hours postoperative.

PMID:39621972

J Clin Oncol. 2024 Dec 2:JCO2401715. doi: 10.1200/JCO-24-01715. Online ahead of print.

ABSTRACT

PURPOSE: Several genomic subsets of NPM1 mutations with varying sequences (type A, B, D, etc) have been identified. Despite molecular heterogeneity, NPM1 mutations cumulatively portend a more favorable outcome, but biology and prognostic implications of different genomic subsets have not been extensively studied. In this multicentric study, we investigated the impact of NPM1 genotypes on patient’s outcomes and interrogated the underlying biology of the different subtypes.

MATERIALS AND METHODS: Of more than 4,000 patients enrolled in multiple pediatric cooperative (AIEOP, BFM, ELAM02, NOPHO, DCOG, and COG trials), or adult (SWOG) trials, 348 pediatric and 75 adult AML patients with known NPM1 genotype and available outcome were selected for this study. Diverse NPM1 variants were correlated with the probabilities of overall survival (OS) and event-free survival. Nuclear localization and translational efficiency of the NPM1 variants was studied.

RESULTS: Evaluation of clinical outcome on the basis of NPM1 genotypes showed that patients with type A, B, and other rare variants had similarly favorable outcomes, whereas those with type D had a significantly worse outcome (OS of 63% for type D v 86% for type non-D, P = .005). Multivariate analysis confirmed type D as an independent prognostic factor associated with inferior OS (hazard ratio, 3; P = .005). In vitro, we demonstrated that in type D versus type A synonymous variants, codon optimality plays major roles in determining gene expression levels, and translation efficiency, which resulted in a more expressed NPM1-D mRNA and protein, mediating peculiar mitochondrial gene expression.

CONCLUSION: The evaluation of specific NPM1 genotypes identified AML patients with type D mutations being significantly associated with inferior outcomes, suggesting a reclassification of D cases to higher-risk groups.

PMID:39621969 | DOI:10.1200/JCO-24-01715

J Clin Oncol. 2024 Dec 2:JCO2401507. doi: 10.1200/JCO-24-01507. Online ahead of print.

ABSTRACT

PURPOSE: Clinicopathological factors and the 21-gene Oncotype DX Breast Recurrence Score (RS) test both influence prognosis. Our goal was to develop a new tool, RSClinN+, to individualize recurrence risk and chemotherapy benefit predictions by menopausal status for patients with HR+/human epidermal growth factor receptor 2-negative, lymph node-positive breast cancer by integrating the RS result with clinicopathological factors (grade, tumor size, age).

METHODS: We used patient-level data from 5,283 patients treated with chemoendocrine therapy (CET) versus endocrine therapy alone (ET) in the S1007 (N = 4,916) and S8814 (N = 367) trials to develop the tool. Cox proportional hazards regression models stratified by trial were used to estimate 5-year invasive disease-free survival for pre- and postmenopausal woman, respectively. The integrated RSClinN+ model was compared with RS alone and clinicopathological models using likelihood ratio tests. Absolute CET benefit was estimated as the difference between ET and CET risk estimates. Validation of RSClinN+ was performed in 592 patients with node-positive disease in the Clalit Health Services registry.

RESULTS: RSClinN+ provides better prognostic information than RS model alone (premenopausal P = .034; postmenopausal P < .001) or clinicopathological model alone (premenopausal P = .002; postmenopausal, P < .001). In postmenopausal women, RS showed interaction with CET benefit (P = .016), with RSClinN+ absolute CET benefit ranging from <0.1% to 21.5% over RS ranges 0-50. In premenopausal patients with RS ≤25, there was no significant interaction between RS and CET benefit. In external validation, RSClinN+ risk estimates were prognostic (hazard ratio, 1.75 [95% CI, 1.38 to 2.20]) and concordant with observed risk (Lin’s concordance, 0.92).

CONCLUSION: RSClinN+ provides improved estimates of prognosis and absolute CET benefit for individual patients compared with RS or with clinical data alone and could be used in patient counseling.

PMID:39621968 | DOI:10.1200/JCO-24-01507

J Occup Environ Med. 2024 Dec 1;66(12):e646-e652. doi: 10.1097/JOM.0000000000003250.

ABSTRACT

OBJECTIVE: To assess the relationship between metabolic syndrome (MetS) and physical fitness in firefighters.

METHODS: Firefighters (n = 309) were systematically recruited to participate in this study. A questionnaire and physical measures were used to collect data on firefighters’ cardiometabolic health and physical fitness levels. Data were analyzed using binary and multinomial logistic regressions.

RESULTS: The prevalence of MetS was 23.0%, which was most prevalent in station and platoon commanders. Multivariable analysis showed that age (P < 0.001), lean body mass (P < 0.001), absolute aerobic capacity (P < 0.001), and leg strength (P < 0.001) was significantly associated with MetS. In addition, relative aerobic capacity (P < 0.001), push-ups (P = 0.016), and sit-ups (P < 0.001) were inversely associated with MetS.

CONCLUSIONS: Firefighters with MetS had a higher absolute aerobic capacity and strength, and healthier fighters had a higher relative aerobic capacity, muscular endurance capacity, and flexibility.

PMID:39621962 | DOI:10.1097/JOM.0000000000003250

J Occup Environ Med. 2024 Dec 1;66(12):e642-e645. doi: 10.1097/JOM.0000000000003249.

ABSTRACT

OBJECTIVE: The aim of the study is to measure cancer’s incidence in endemic fight agents in a Brazil’s Northeast state.

METHODS: This is a historical cohort with 1053 endemic fight agents. A survival analysis was performed using Kaplan-Meier method.

RESULTS: The overall neoplasm incidence rate has been 5508 cases per 105, and 4843 cases per 105 when nonmelanoma skin tumors were excluded. The increase in incidence of neoplasms occurred in 2019 and has conferred a risk of neoplasms 20 times higher than the national and state incidence.

CONCLUSIONS: We believe in an occupational factor for these results: the chronic exposure to insecticides used in public health campaigns. The peak incidence of neoplasms, in 2019, may corroborate with long induction period of these compounds, in addition to consistency with specialized literature.

PMID:39621961 | DOI:10.1097/JOM.0000000000003249

JAMA Netw Open. 2024 Dec 2;7(12):e2445497. doi: 10.1001/jamanetworkopen.2024.45497.

ABSTRACT

IMPORTANCE: A diagnosis of bacterial meningitis in childhood can lead to permanent neurological disabilities. Few studies have examined long-term consequences for work ability in adulthood.

OBJECTIVE: To compare earnings, work loss, and educational attainment between adults diagnosed with bacterial meningitis in childhood and population comparators.

DESIGN, SETTING, AND PARTICIPANTS: This nationwide registry-based matched cohort study included individuals in Sweden diagnosed with bacterial meningitis in childhood (aged <18 years) from January 1, 1987, to December 31, 2019, and general population comparators matched 1:9 on age, sex, and place of residence. Follow-up was completed December 31, 2020. Data were analyzed from February 7 to September 12, 2023.

EXPOSURE: A diagnosis of bacterial meningitis in childhood recorded in the National Patient Register.

MAIN OUTCOMES AND MEASURES: Annual taxable earnings (in 2020 US dollars), work loss (sum of sick leave and disability insurance), and educational attainment.

RESULTS: The cohort included 2534 individuals diagnosed with bacterial meningitis in childhood (mean [SD] age at diagnosis, 4.7 [5.3] years) and 22 806 comparators (13 510 [53.3%] male). Among those with childhood bacterial meningitis, 812 (32.0%) were diagnosed at younger than 1 year and 1351 (53.3%) were male. From 18 to 34 years of age, those with childhood meningitis had lower adjusted earnings relative to comparators and higher adjusted work loss. When pooling observations for individuals 28 years or older, the annual mean reduction in earnings was -$1295 (95% CI, -$2587 to -$4), representing a 4.0% (95% CI, 0%-8.0%) reduction relative to comparators, and the annual increase in work loss was 13.5 (95% CI, 8.6-18.5) days. There was a larger reduction in earnings for those with childhood meningitis relative to comparators with pneumococcal (Streptococcus pneumoniae) vs meningococcal (Neisseria meningitidis) meningitis. For work loss, there was a difference among all 3 major causes of meningitis, with the largest increase for pneumococcal meningitis. Individuals diagnosed at a younger age (below the median) had lower earnings relative to comparators and higher work loss than individuals diagnosed at an older age (above the median). Fewer individuals with childhood meningitis relative to comparators had obtained a high school degree at age 30 years (adjusted odds ratio, 0.68 [95% CI, 0.56-0.81]).

CONCLUSIONS AND RELEVANCE: In this cohort study of adults diagnosed with bacterial meningitis in childhood, findings suggest that work ability decreases relative to population comparators, with lower earnings and higher work loss, especially among adults diagnosed with pneumococcal meningitis or diagnosed at a young age, with long-lasting costs for the individual patient and society at large.

PMID:39621349 | DOI:10.1001/jamanetworkopen.2024.45497

JAMA Netw Open. 2024 Dec 2;7(12):e2447325. doi: 10.1001/jamanetworkopen.2024.47325.

ABSTRACT

IMPORTANCE: Patients with lung cancer have poor physical functioning and quality of life. Despite promising outcomes for those who undertake exercise programs, implementation into practice of previously tested hospital-based programs is rare.

OBJECTIVE: To evaluate a home-based exercise and self-management program for patients after lung resection.

DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial with assessor blinding was conducted among 116 patients undergoing surgery for non-small cell lung cancer from November 23, 2017, to July 31, 2023, at tertiary hospitals in Australia. Patients were followed up for 12 months postoperatively.

INTERVENTION: Patients randomized to the intervention group received a postoperative 3-month home-based exercise and self-management program, supported by weekly physiotherapist-led telephone consultations. Patients randomized to the control group received usual care.

MAIN OUTCOMES AND MEASURES: The primary outcome was self-reported physical function (30-item European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire [EORTC QLQ-C30] score) at 3 months. Secondary outcomes included objective measures of physical function and exercise capacity (at 3 and 6 months) and patient-reported outcomes including quality of life (at 3 and 6 months, with some questionnaires completed at 12 months). Analysis was performed on an intent-to-treat basis.

RESULTS: A total of 1370 patients were screened, with 177 eligible and 116 consented (mean [SD] age, 66.4 [9.6] years; 68 women [58.6%]). Of these 116 patients, 58 were randomized to the intervention and 58 to the control. A total of 103 patients (88.8%) completed assessments at 3 months, 95 (81.9%) at 6 months, and 95 (81.9%) at 12 months. There were no statistically significant differences between the intervention and control groups for self-reported physical function (EORTC QLQ-C30 physical functioning domain score) at the 3-month primary end point (mean [SD] score, 77.3 [20.9] vs 76.3 [18.8]; mean difference, 1.0 point [95% CI, -6.0 to 8.0 points]). Patients in the intervention group, compared with the control group, had significantly greater exercise capacity (6-minute walk distance: mean difference, 39.7 m [95% CI, 6.8-72.6 m]), global quality of life (mean difference, 7.1 points [95% CI, 0.4-13.8 points]), and exercise self-efficacy (mean difference, 16.0 points [95% CI, 7.0-24.9 points]) at 3 months as well as greater objectively measured physical function (Short Physical Performance Battery score: mean difference, 0.8 points [95% CI, 0.1-1.6 points]), exercise capacity (6-minute walk distance: mean difference, 50.9 m [95% CI, 6.7-95.1 m]), and exercise self-efficacy (mean difference, 10.1 points [95% CI, 1.9-18.2 points]) at 6 months. One minor adverse event and no serious adverse events occurred.

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, a postoperative home-based exercise and self-management program did not improve self-reported physical function in patients with lung cancer. However, it did improve other important clinical outcomes. Implementation of this program into lung cancer care should be considered.

TRIAL REGISTRATION: http://anzctr.org.au Identifier: ACTRN12617001283369.

PMID:39621348 | DOI:10.1001/jamanetworkopen.2024.47325

JAMA Netw Open. 2024 Dec 2;7(12):e2448208. doi: 10.1001/jamanetworkopen.2024.48208.

ABSTRACT

IMPORTANCE: Fragility fractures are often defined as those that occur after a certain age (eg, 40-50 years). Whether fractures occurring in early adulthood are equally associated with future fractures is unclear.

OBJECTIVE: To examine whether the age at which a prior fracture occurred is associated with future fracture risk.

DESIGN, SETTING, AND PARTICIPANTS: This observational, population-based cohort study included individuals from the Manitoba Bone Mineral Density Registry with a first bone mineral density (BMD) measurement between January 1, 1996, and March 31, 2018, with and without prior fracture in adulthood. Data analysis was completed between April 1, and May 31, 2023.

EXPOSURE: Individuals with fractures before their first dual-energy x-ray absorptiometry were stratified by the age at first fracture (10-year intervals from 20-29 to ≥80 years of age).

MAIN OUTCOMES AND MEASURES: Incident fractures occurring after dual-energy x-ray absorptiometry (index date) and before March 31, 2021, were identified using linked provincial administrative health data.

RESULTS: The cohort included 88 696 individuals (80 066 [90.3%] female; mean [SD] age, 64.6 [11.0] years) with a mean (SD) femoral neck T score of -1.4 (1.0). A total of 21 105 individuals (23.8%) had sustained a prior fracture at a mean (SD) age of 57.7 (13.6) years (range, 20.0-102.4 years) at the time of first prior fracture. During a mean (SD) of 9.0 (5.5) years of follow-up, incident fractures occurred in 13 239 individuals (14.6%), including 12 425 osteoporotic fractures (14.0%), 9440 major osteoporotic fractures (MOFs) (10.6%), and 3068 hip fractures (3.5%). The sex- and age-adjusted hazard ratios for all incident fractures, osteoporotic fractures, and MOFs, according to age at first fracture, were all significantly elevated, with point estimates ranging from 1.55 (95% CI, 1.28-1.88) to 4.07 (95% CI, 2.99-5.52). After adjusting for the additional covariates, the effect estimates were similar and remained significantly elevated, with point estimates ranging from fully adjusted hazard ratios of 1.51 (95% CI, 1.42-1.60) to 2.12 (95% CI, 1.67-2.71) across age categories. Sensitivity analyses examining age at last prior fracture and in those with multiple prior fractures showed similar results.

CONCLUSIONS AND RELEVANCE: In this cohort study, fractures in adulthood were associated with future fractures regardless of the age at which they occurred. Thus, fractures in early adulthood should not be excluded when assessing an individual’s ongoing fracture risk.

PMID:39621347 | DOI:10.1001/jamanetworkopen.2024.48208

JAMA Netw Open. 2024 Dec 2;7(12):e2448277. doi: 10.1001/jamanetworkopen.2024.48277.

ABSTRACT

IMPORTANCE: Older adults are at high risk for cognitive impairments following natural disasters, but the persistence of such effects is not well understood.

OBJECTIVE: To track older adults’ postdisaster cognitive disability trajectories over a decade and examine associations of cognitive disability with disaster damage exposure.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study used predisaster baseline surveys conducted in August 2010 and 4 follow-ups approximately every 3 years until November 10, 2022. Invitations were mailed at baseline to all citizens 65 years or older in Iwanuma City, Japan, a coastal municipality significantly impacted by the 2011 Great East Japan Earthquake and Tsunami. A total of 1988 respondents who were cognitively independent (ie, without cognitive disability) before the disaster completed the 4 postdisaster cognitive assessments.

EXPOSURES: Experiences of residential damage, worsening financial conditions, loss of loved ones, and disruption in health care services. A composite score quantified these experiences, with higher scores indicating greater overall damage.

MAIN OUTCOMES AND MEASURES: Cognitive disability level was assessed using a standardized in-home evaluation under a national long-term care insurance scheme. Trained investigators evaluated participants’ activities of daily living, cognitive function, and presence of mental and/or behavioral disorders. Latent class growth analyses (LCGA) identified distinct cognitive disability trajectories. Primary outcomes consisted of inclusion in these trajectories.

RESULTS: The analytic sample consisted of 1988 participants who were cognitively independent at baseline, with a mean (SD) age of 72.4 (5.4) years, of whom 1159 (58.3%) were female. LCGA identified 3 cognitive disability trajectories: high and gradual deterioration (277 [13.9%]; high levels of cognitive disability with increasing impairment over time), low and progressive deterioration (541 [27.2%]; low levels of cognitive disability with accelerated decline in cognitive function over time), and low and stable (1170 [58.9%]; low levels of cognitive disability that remained stable). In multinomial regression analyses with the low and stable trajectory serving as the reference, housing damage (adjusted odds ratio [AOR], 2.52; 95% CI, 1.26-5.04), worsening financial conditions (AOR, 1.83; 95% CI, 1.15-2.90), and disruption in health care services (AOR, 1.76; 95% CI, 1.03-2.99) were associated with high and gradual deterioration. Worsening financial conditions (AOR, 1.38; 95% CI, 1.01-1.90) and higher composite damage scores (AOR, 1.16; 95% CI, 1.01-1.34) were associated with low and progressive deterioration. These associations no longer remained after adjusting for postdisaster depressive symptoms.

CONCLUSIONS AND RELEVANCE: In this cohort study of older adults who survived the 2011 Great East Japan Earthquake and Tsunami, disaster-related exposures were associated with worse long-term cognitive disability trajectories. These findings could inform tailored interventions to preserve cognitive function in older disaster survivors.

PMID:39621346 | DOI:10.1001/jamanetworkopen.2024.48277

JAMA Netw Open. 2024 Dec 2;7(12):e2448286. doi: 10.1001/jamanetworkopen.2024.48286.

ABSTRACT

IMPORTANCE: Metals are established neurotoxicants, but evidence of their association with cognitive performance at low chronic exposure levels is limited.

OBJECTIVE: To investigate the association of urinary metal levels, individually and as a mixture, with cognitive tests and dementia diagnosis, including effect modification by apolipoprotein ε4 allele (APOE4).

DESIGN, SETTING, AND PARTICIPANTS: The multicenter prospective cohort Multi-Ethnic Study of Atherosclerosis (MESA) was started from July 2000 to August 2002, with follow-up through 2018. A total of 6303 MESA participants were included. Data analysis was performed from October 12, 2023, to June 13, 2024.

EXPOSURE: Urine samples were collected at baseline (2000-2002), and arsenic, cadmium, cobalt, copper, lead, manganese, tungsten, uranium, and zinc levels were measured in 2020-2022.

MAIN OUTCOMES AND MEASURES: Digit Symbol Coding (DSC) (n = 3819) (possible score range, 0-133), Cognitive Abilities Screening Instrument (CASI) (n = 3918) (possible score range, 0-100), and Digit Span (DS) (n = 4176) (possible score range, 0-30) cognitive tests were administered in 2010-2012; higher scores of each test indicate increasing levels of positive response.

RESULTS: A total of 6303 participants were followed up for dementia diagnosis through 2018. The median age at baseline was 60 (IQR, 53-70) years, and 3303 participants (52.4%) were female. The median cognitive scores were 51 (IQR, 38-64) for DSC, 90 (IQR, 84-95) for CASI, and 15 (IQR, 12-18) for DS. There were 559 cases of dementia through the follow-up period. Inverse associations with DSC were identified: mean differences in z scores per IQR increase in metal levels were -0.03 (95% CI, -0.07 to 0.00) for arsenic, -0.05 (95% CI, -0.09 to -0.004) for cobalt, -0.05 (95% CI, -0.07 to -0.02) for copper, -0.04 (95% CI, -0.08 to -0.001) for uranium, and -0.03 (95% CI, -0.06 to -0.01) for zinc. Among 1058 APOE4 carriers, manganese was also inversely associated with DSC. The joint mean difference of DSC comparing percentile 95th with the 25th of the 9-metal mixture was -0.30 (95% CI, -0.47 to -0.14) for APOE4 carriers and -0.10 (95% CI, -0.19 to -0.01) for noncarriers. Arsenic, cadmium, cobalt, copper, tungsten, uranium, and zinc were individually associated with dementia, with hazard ratios per IQR of metal ranging from 1.15 (95% CI, 1.03-1.29) for tungsten to 1.46 (95% CI, 1.06-2.02) for uranium. The joint hazard ratio of dementia comparing percentiles 95th with the 25th of the 9-metal mixture was 1.71 (95% CI, 1.24-3.89), with no significant difference by APOE4 status.

CONCLUSIONS AND RELEVANCE: In this study, participants with higher concentrations of metals in their urine, compared with those with lower concentrations, had worse performance on cognitive tests and greater likelihood of developing dementia. The findings of this multicenter multiethnic cohort study might inform screening and potential interventions for prevention of dementia based on individuals’ metal exposure levels and genetic profiles.

PMID:39621345 | DOI:10.1001/jamanetworkopen.2024.48286