RESUMO
Introduced in the 1950s, acetaminophen is one of the most widely used antipyretics and analgesics worldwide. In 1999, the International Agency for Research on Cancer (IARC) reviewed the epidemiologic studies of acetaminophen and the data were judged to be "inadequate" to conclude that it is carcinogenic. In 2019 the California Office of Environmental Health Hazard Assessment initiated a review process on the carcinogenic hazard potential of acetaminophen. To inform this review process, the authors performed a comprehensive literature search and identified 136 epidemiologic studies, which for most cancer types suggest no alteration in risk associated with acetaminophen use. For 3 cancer types, renal cell, liver, and some forms of lymphohematopoietic, some studies suggest an increased risk; however, multiple factors unique to acetaminophen need to be considered to determine if these results are real and clinically meaningful. The objective of this publication is to analyze the results of these epidemiologic studies using a framework that accounts for the inherent challenge of evaluating acetaminophen, including, broad population-wide use in multiple disease states, challenges with exposure measurement, protopathic bias, channeling bias, and recall bias. When evaluated using this framework, the data do not support a causal association between acetaminophen use and cancer.
Assuntos
Acetaminofen/efeitos adversos , Analgésicos não Narcóticos/efeitos adversos , Neoplasias/induzido quimicamente , Causalidade , Humanos , Modelos BiológicosRESUMO
A case-control study was conducted to investigate the association of HLA-A alleles, HLA-B alleles including HLA-B*15:02 and HLA-B75 serotype with carbamazepine-induced SJS/TEN in Filipino patients. A retrospective review of medical records was performed. Pertinent clinical data were collected. Eight (8) carbamazepine-induced SJS/TEN cases and 32 tolerant controls were recruited. Genomic DNA was extracted from the saliva samples and genotyping was performed by employing allele-specific polymerase chain reaction. Data were analyzed using the Fisher's exact test, Mann-Whitney U test, univariate logistic regression, and multivariate logistic regression. Single allele association analysis was done. The strength of association was expressed as odds ratio with 95% confidence interval. Positive predictive value, negative predictive value, sensitivity, and specificity were computed. Of all the alleles tested, the HLA-B75 serotype (p = 0.007, OR = 23.25, 95% CI = 2.33-232.21) and HLA-B*15:21 (p = 0.026, OR = 7.53, 95% CI = 1.27-44.79) were significantly associated with carbamazepine-induced SJS/TEN. The HLA-B75 serotype or HLA-B*15:21 allele may be used as a genetic risk assessment prior to prescription for prevention of carbamazepine-induced SJS/TEN in Filipino patients.
Assuntos
Anticonvulsivantes/efeitos adversos , Povo Asiático/genética , Carbamazepina/efeitos adversos , Antígenos HLA-B/genética , Sorogrupo , Síndrome de Stevens-Johnson/genética , Adulto , Alelos , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Filipinas/epidemiologia , Síndrome de Stevens-Johnson/epidemiologia , Adulto JovemRESUMO
Background: There is no consensus on the effectiveness of surgical stabilization in multiple rib fractures in Asia, especially among patients with a non-flail rib fracture pattern. We aim to synthesize the evidence on the effectiveness of surgical stabilization of rib fractures (SSRF) in an Asian population with multiple non-flail rib fractures. Methods: The MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Cochrane Database of Systematic Reviews were searched in this systematic literature review and meta-analysis to identify studies conducted in Asia that included patients with multiple non-flail rib fractures in at least one of their treatment groups. The intervention of interest was SSRF, and the comparator was a nonoperative treatment. The duration of mechanical ventilation (DMV) was the primary outcome. Posttreatment pain score, pneumonia, atelectasis, intensive care unit length of stay (ICU LOS), hospital length of stay (HLOS), need for tracheostomy, respiratory function, functional outcomes, quality of life (QoL), and mortality were identified as the secondary outcomes. A random effects model (REM) was used to pool data for outcomes reported in two or more studies. Results: A total of 12 studies (n=2,440 patients) were included. There was a significantly shorter DMV {mean difference (MD): -5.23 [95% confidence interval (CI): -9.64 to -0.81], P=0.02}, lower 4-week post-treatment pain score [standard mean difference (SMD): -2.24 (95% CI: -3.18 to -1.31), P<0.00001], lower risk for pneumonia [risk ratio (RR): 0.46 (95% CI: 0.23 to 0.95), P=0.04], lower risk for atelectasis [RR: 0.44, (95% CI: 0.29 to 0.65), P<0.0001], shorter ICU LOS [MD: -4.00 (95% CI: -6.33 to -1.66), P=0.0008], and shorter HLOS [MD: -6.54 (95% CI: -9.28 to -3.79), P<0.00001] in favor of SSRF. Effect estimates for the need for tracheostomy [RR: 0.67 (95% CI: 0.42 to 1.08), P=0.10] and mortality [RR: 0.94 (95% CI: 0.37 to 2.41), P=0.90] were nonsignificant. Conclusions: In the Asian population with mainly non-flail rib fracture patterns, SSRF was associated with shorter DMV, ICU LOS, and HLOS as well as lower risks for atelectasis and pneumonia, and pain scores after 4 weeks. The risk of mortality was comparable between treatment groups.
RESUMO
Aim: A case-control study was conducted in Filipino patients to determine the association between HLA alleles and carbamazepine-induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Materials & methods: A retrospective review of medical records and data collection were performed. A total of 10 carbamazepine-induced SJS/TEN cases and 40 tolerant controls were recruited. Genomic DNA extracted from saliva samples was genotyped. Statistical analysis was done. Results: The HLA-B75 serotype (p = 0.003; odds ratio [OR] = 13.8; 95% CI = 2.5-76.8), HLA-B*15:21 (p = 0.041; OR = 4.7; 95% CI = 1.1-20.8) and HLA-A*24:07 (p = 0.032; OR = 6; 95% CI = 1.2-30.7) were significantly associated with carbamazepine-induced SJS/TEN. Conclusion: The HLA-B75 serotype, HLA-B*15:21 or HLA-A*24:07 may be used for pharmacogenetic screening prior to prescribing carbamazepine in Filipinos.