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1.
Acta Orthop Belg ; 87(3): 553-556, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34808732

RESUMO

Septic arthritis is a serious condition that can lead to rapid destruction of joint if it is not rapidly diagnosed and treated appropriately. The reported annual incidence is 10 in 100 000 although this increases to 70 in 100 000 in those with risk factors for developing septic arthritis mainly rheumatoid arthritis and immune-compromised patients. The aim of this study is to examine the sensitivity and specificity, and thus the clinical usefulness, of gram stain results. This was a single centre, retrospective case series. All joint aspirates over a three year period from May 2015 to April 2018 were reviewed. The gram stain and final culture results noted. 830 samples were included from both native and replaced joints. Native joints accounted for a total of 701 cases (84%) of the aspirates, whilst those obtained from prosthetic joints 129 (16%). In 74 (9%) cases there was a discrepancy between the gram stain and culture results. The sensitivity of the gram stain in this case series is 22% and the specificity of the test is 99.6%. The clinician should have a low threshold for overlooking a negative gram stain result and place greater emphases on the clinical findings in conjunction with biochemical markers.


Assuntos
Artrite Infecciosa , Microscopia , Artrite Infecciosa/diagnóstico , Humanos , Estudos Retrospectivos , Sensibilidade e Especificidade , Coloração e Rotulagem
2.
Crit Rev Toxicol ; 49(3): 215-261, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-31192763

RESUMO

The potential association between major adverse cardiovascular events (MACE) and concomitant treatment with proton pump inhibitors (PPIs) and clopidogrel has been debated since 2009. Recent reports, however, suggest that PPIs may increase the risk of MACE independently of clopidogrel. This review evaluates epidemiological findings relevant to the association between PPIs, taken alone or concomitantly with antiplatelets, and the risk of MACE. A systematic review and meta-analysis were conducted. Relevant studies were identified from MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials and then screened. Included studies were categorized into three groups: Group A: PPIs versus no PPIs; Group B: combined PPIs and clopidogrel versus clopidogrel alone; Group C: combined PPIs and other drugs versus other drugs. Pooled risk ratios (RRs) were calculated for each outcome of interest in each comparison group. Of the 1667 studies identified, 118 were included in the systematic review, of which 66 were included in the meta-analyses. Among Group A observational studies, RRs for MACE outcomes were statistically significant for some patient populations but not others. Pooled RRs from Group A RCTs were not statistically significant for any outcome. Pooled RRs for Group B observational studies were statistically significant for all-cause mortality and MI, but were diminished in magnitude when pooling was restricted to propensity score matched studies or post hoc analyses of RCTs. Group C studies did not demonstrate an association with MACE. Findings do not consistently support an association between MACE and PPIs when taken alone, or concomitantly with antiplatelets.


Assuntos
Doenças Cardiovasculares/induzido quimicamente , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Bomba de Prótons/efeitos adversos , Doenças Cardiovasculares/epidemiologia , Interações Medicamentosas
3.
J Toxicol Environ Health B Crit Rev ; 22(7-8): 288-359, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31631808

RESUMO

This review summarizes the carcinogenic mechanisms for 109 Group 1 human carcinogens identified as causes of human cancer through Volume 106 of the IARC Monographs. The International Agency for Research on Cancer (IARC) evaluates human, experimental and mechanistic evidence on agents suspected of inducing cancer in humans, using a well-established weight of evidence approach. The monographs provide detailed mechanistic information about all carcinogens. Carcinogens with closely similar mechanisms of action (e.g. agents emitting alpha particles) were combined into groups for the review. A narrative synopsis of the mechanistic profiles for the 86 carcinogens or carcinogen groups is presented, based primarily on information in the IARC monographs, supplemented with a non-systematic review. Most carcinogens included a genotoxic mechanism.


Assuntos
Carcinogênese/induzido quimicamente , Carcinógenos/toxicidade , Neoplasias/induzido quimicamente , Animais , Humanos , Mutagênicos/toxicidade , Neoplasias/patologia
4.
J Toxicol Environ Health B Crit Rev ; 22(7-8): 264-287, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31379270

RESUMO

A database on mechanistic characteristics of human carcinogenic agents was developed by collecting mechanistic information on agents identified as human carcinogens (Group 1) by the International Agency for Research on Cancer (IARC) in the IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. A two-phase process is described for the construction of the database according to 24 toxicological endpoints, derived from appropriate test systems that were acquired from data obtained from the mechanisms sections of the IARC Monographs (Section 4) and a supplementary PubMed search. These endpoints were then aligned with 10 key characteristics of human carcinogens that reflect the broader attributes of these agents relating to the development of cancer in humans. The considerations involved in linking of toxicological endpoints to key characteristics are described and specific examples of the determination of key characteristics for six specific agents (tamoxifen, hepatitis B virus, arsenic, ultraviolet and solar radiation, tobacco smoking, and dioxin) are provided. Data for humans and animals were tabulated separately, as were results for in-vivo and for in-vitro sources of information. The database was constructed to support a separate analysis of the expression of these endpoints by 86 Group 1 carcinogens, in-vivo and in-vitro along with an analysis of the key characteristics of these agents.


Assuntos
Carcinógenos/toxicidade , Bases de Dados Factuais , Neoplasias/induzido quimicamente , Animais , Carcinogênese/induzido quimicamente , Testes de Carcinogenicidade , Humanos
5.
J Toxicol Environ Health B Crit Rev ; 22(7-8): 244-263, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31637961

RESUMO

Since the inception of the International Agency for Research on Cancer (IARC) in the early 1970s, the IARC Monographs Programme has evaluated more than 1000 agents with respect to carcinogenic hazard; of these, up to and including Volume 119 of the IARC Monographs, 120 agents met the criteria for classification as carcinogenic to humans (Group 1). Volume 100 of the IARC Monographs provided a review and update of Group 1 carcinogens. These agents were divided into six broad categories: (I) pharmaceuticals; (II) biological agents; (III) arsenic, metals, fibers, and dusts; (IV) radiation; (V) personal habits and indoor combustions; and (VI) chemical agents and related occupations. Data on biological mechanisms of action (MOA) were extracted from the Monographs to assemble a database on the basis of ten key characteristics attributed to human carcinogens. After some grouping of similar agents, the characteristic profiles were examined for 86 Group 1 agents for which mechanistic information was available in the IARC Monographs up to and including Volume 106, based upon data derived from human in vivo, human in vitro, animal in vivo, and animal in vitro studies. The most prevalent key characteristic was "is genotoxic", followed by "alters cell proliferation, cell death, or nutrient supply" and "induces oxidative stress". Most agents exhibited several of the ten key characteristics, with an average of four characteristics per agent, a finding consistent with the notion that cancer development in humans involves multiple pathways. Information on the key characteristics was often available from multiple sources, with many agents demonstrating concordance between human and animal sources, particularly with respect to genotoxicity. Although a detailed comparison of the characteristics of different types of agents was not attempted here, the overall characteristic profiles for pharmaceutical agents and for chemical agents and related occupations appeared similar. Further in-depth analyses of this rich database of characteristics of human carcinogens are expected to provide additional insights into the MOA of human cancer development.


Assuntos
Carcinógenos/toxicidade , Mutagênicos/toxicidade , Neoplasias/induzido quimicamente , Animais , Carcinogênese/induzido quimicamente , Testes de Carcinogenicidade , Humanos , Agências Internacionais , Mutagênese , Neoplasias/patologia
6.
Eur J Clin Pharmacol ; 75(2): 227-235, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30324301

RESUMO

PURPOSE: The US Food and Drug Administration (FDA) issued three safety announcements between January 2009 and October 2010 warning against concomitant use of clopidogrel and proton pump inhibitors (PPIs) due to a potential drug-drug interaction that may attenuate clopidogrel's antiplatelet activity. This primary objective of this study was to examine trends in concomitant clopidogrel/PPI use among acute coronary syndrome (ACS) inpatients in the US between 2000 and 2016, in relation to the FDA safety communications. METHODS: Adult inpatients with a primary diagnosis of ACS were identified from the Cerner Health Facts® database. The standardized (age, sex, race, and census region) prevalence of clopidogrel use with PPIs was calculated yearly and quarterly. Findings were stratified by PPIs' potential to inhibit clopidogrel's activity and by age. RESULTS: A total of 204,533 inpatients were identified. In 2008, the prevalence of concomitant clopidogrel and PPI treatment was 34.9%, decreasing to 24.4 and 16.4% in 2009 and 2010, respectively, with the decline being similar across age groups. Treatment with inhibiting PPIs (omeprazole and esomeprazole) and clopidogrel has continued to decrease since 2010, with a prevalence of 0.8% in 2016. A similar reduction was not observed with clopidogrel and non-inhibiting PPIs (pantoprazole, lansoprazole, rabeprazole, and dexlansoprazole). During the FDA warning period, the combined treatment with clopidogrel and H2 receptor antagonists, an alternative to PPIs suggested by the FDA, temporarily increased from 7.8% in 2008 to 12.8 and 14.5% in 2009 and 2010, respectively. CONCLUSIONS: Findings suggest that clinical practice recommendations made by the FDA were followed. Further research is needed to determine how changes in drug labels and the availability of new drugs may have influenced the observed trends.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Clopidogrel/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Interações Medicamentosas/fisiologia , Quimioterapia Combinada/métodos , Feminino , Humanos , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/uso terapêutico , Estados Unidos , United States Food and Drug Administration , Adulto Jovem
7.
J Environ Manage ; 247: 449-461, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31254760

RESUMO

The objective of this analysis is to estimate the incremental cost effectiveness ratios for the 2012 populations in Canada, each province/territory, and 17 census metropolitan areas, for practical radon mitigation scenarios to reduce residential radon exposures. Sixteen intervention scenarios compare radon mitigation implemented at differing rates in new and existing housing relative to preventive measures installed at construction, using three different radon mitigation thresholds. A period life-table analysis was conducted using data derived from two recent Canadian radon surveys, along with Canadian mortality and quality of life data. Analyses adopted a lifetime horizon and a discount rate of 1.5%. It is practical to reduce residential radon and associated lung cancer mortality in Canada, and the most cost effective scenario at each radon mitigation threshold is the combination of the activation of the preventive measures in new housing and mitigation of existing housing.


Assuntos
Poluição do Ar em Ambientes Fechados , Radônio , Canadá , Análise Custo-Benefício , Exposição Ambiental , Habitação , Qualidade de Vida
8.
Risk Anal ; 37(2): 265-279, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27043736

RESUMO

Essential elements such as copper and manganese may demonstrate U-shaped exposure-response relationships due to toxic responses occurring as a result of both excess and deficiency. Previous work on a copper toxicity database employed CatReg, a software program for categorical regression developed by the U.S. Environmental Protection Agency, to model copper excess and deficiency exposure-response relationships separately. This analysis involved the use of a severity scoring system to place diverse toxic responses on a common severity scale, thereby allowing their inclusion in the same CatReg model. In this article, we present methods for simultaneously fitting excess and deficiency data in the form of a single U-shaped exposure-response curve, the minimum of which occurs at the exposure level that minimizes the probability of an adverse outcome due to either excess or deficiency (or both). We also present a closed-form expression for the point at which the exposure-response curves for excess and deficiency cross, corresponding to the exposure level at which the risk of an adverse outcome due to excess is equal to that for deficiency. The application of these methods is illustrated using the same copper toxicity database noted above. The use of these methods permits the analysis of all available exposure-response data from multiple studies expressing multiple endpoints due to both excess and deficiency. The exposure level corresponding to the minimum of this U-shaped curve, and the confidence limits around this exposure level, may be useful in establishing an acceptable range of exposures that minimize the overall risk associated with the agent of interest.


Assuntos
Cobre/toxicidade , Relação Dose-Resposta a Droga , Exposição Ambiental , Medição de Risco/métodos , Animais , Simulação por Computador , Bases de Dados Factuais , Humanos , Funções Verossimilhança , Camundongos , Ratos , Análise de Regressão , Especificidade da Espécie
9.
Nutr Cancer ; 66(3): 500-5, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24033341

RESUMO

Cooking methods have been implicated in the etiology of gastrointestinal cancers, reflecting exposure to potential carcinogens as results of cooking. We used a validated food frequency questionnaire and a pretested cooking method questionnaire in 3 groups: 40 esophageal squamous cell carcinoma (ESCC) cases from a high-risk area in northeast of Iran, 40 healthy subjects from the same high-risk area, and 40 healthy subjects from a low-risk area in Southern Iran. We compared the frequency of boiling, grilling, and frying, and the frying score among these 3 groups. We also calculated "frying index" by multiplying the frequency of each fried food item by its frying score. Mean frying to boiling ratios were 18.2:1, 12.8:1, and 2.6:1 for cases, high-risk controls, and low-risk controls, respectively (P < 0.01). Reuse of cooking oil for frying was reported in 37.5% of the ESCC cases, 25% of high-risk controls, and 7.5% of low-risk controls (P < 0.001). Frying index was higher in the high-risk than in the low-risk controls (P < 0.001) and in cases than in the high-risk controls (P < 0.05) after adjusting for smoking, opium use, rural residence, education, and ethnicity. High-temperature cooking and frying may be associated with increased risk of ESCC in high-risk areas.


Assuntos
Carcinoma de Células Escamosas/etiologia , Culinária/métodos , Neoplasias Esofágicas/etiologia , Idoso , Estudos de Casos e Controles , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Irã (Geográfico) , Masculino , Carne , Pessoa de Meia-Idade , Análise de Regressão , Fatores de Risco , Inquéritos e Questionários , Verduras
10.
Environ Res ; 120: 33-42, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22959329

RESUMO

BACKGROUND: Epidemiological studies of the health effects of air pollution have traditionally relied upon ground-monitoring stations to measure ambient concentrations. Satellite derived air pollution measures offer the advantage of providing global coverage. OBJECTIVE: To undertake a global assessment of mortality associated with long-term exposure to fine particulate air pollution using remote sensing data. METHODS: Global PM(2.5) exposure levels were derived from the MODIS and MISR satellite instruments. Relative risks and attributable fractions of mortality were modeled using previously developed concentration-response functions for the association between PM(2.5) and mortality. RESULTS: The global fraction of adult mortality attributable to the anthropogenic component of PM(2.5) (95% CI) was 8.0% (5.3-10.5) for cardiopulmonary disease, 12.8% (5.9-18.5) for lung cancer, and 9.4% (6.6-11.8) for ischemic heart disease. CONCLUSION: This study demonstrates the feasibility of using satellite derived pollution concentrations in assessing the population health impacts of air pollution at the global scale. This approach leads to global estimates of mortality attributable to PM(2.5) that are greater than those based on fixed site ground-level measures of urban PM(2.5), but more similar to estimates based on global chemical transport model simulations of anthropogenic PM(2.5).


Assuntos
Poluição do Ar/estatística & dados numéricos , Mortalidade , Material Particulado/efeitos adversos , Poluição do Ar/efeitos adversos , Cidades , Estudos Transversais , Humanos , Neoplasias Pulmonares/mortalidade , Isquemia Miocárdica/mortalidade , Doença Cardiopulmonar/mortalidade , Comunicações Via Satélite , Sensibilidade e Especificidade , Incerteza
11.
Can J Diabetes ; 46(5): 480-486, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35718690

RESUMO

OBJECTIVES: The impact of type 2 diabetes (T2DM) on biomarkers denoting lipoprotein compositional status was studied in mild and moderate hypertriglyceridemia (HTG). Diabetic dyslipidemia pathophysiology could contribute to differences in lipoprotein compositional status, which could be reflected in the preferred cardiovascular disease risk prediction markers in HTG: non-high-density lipoprotein cholesterol (non-HDLC) and apolipoprotein B (apoB). METHODS: A total of 2,775 fasting lipid profiles from a tertiary care lipid clinic were analyzed as 2 subgroups (with and without T2DM), stratified by triglyceride (TG) levels: normotriglyceridemia (TG 0.01 to 1.7 mmol/L), mild HTG (TG 1.71 to 5 mmol/L) and moderate HTG (TG 5.01 to 10 mmol/L). The mean non-HDLC:apoB ratio in each TG stratum and subgroup was analyzed. We also used linear regression to assess the correlation between non-HDLC and apoB. RESULTS: The mean non-HDLC:apoB ratio was increased in both subgroups in patients with mild and moderate HTG, compared to those with normotriglyceridemia. In moderate HTG, the mean non-HDLC:apoB ratio in the subgroup with T2DM was significantly lower than the subgroup without T2DM. In mild and moderate HTG, the subgroup with T2DM had a stronger correlation between non-HDLC and apoB than did the subgroup without T2DM. DISCUSSION AND CONCLUSIONS: In mild and moderate HTG, adults with T2DM exhibit lipid profiles that represent a different and more atherogenic lipoprotein compositional status, when compared with adults without T2DM. For the same severity of HTG, the lipoprotein compositional status in diabetic dyslipidemia suggests that there is increased abundance of smaller non-HDL particles and their remnants, which are highly atherogenic.


Assuntos
Diabetes Mellitus Tipo 2 , Dislipidemias , Hiperlipidemias , Hipertrigliceridemia , Adulto , Apolipoproteínas B , Colesterol , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Hipertrigliceridemia/complicações , Lipoproteínas , Triglicerídeos
12.
J Clin Orthop Trauma ; 32: 101946, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35875411

RESUMO

Introduction: Healthcare systems across the world have struggled as a result of the Covid-19 pandemic. Most specialties have redeployed their staff and resources to deal with the pandemic whilst ceasing their planned elective activity. However acute specialties such as Trauma and Orthopaedics still have a significant emergency caseload that must be safely managed, even in a pandemic. The aim of this study was to investigate the change in Orthopaedic Trauma caseload in a Trauma Unit and a Major Trauma Centre during a pandemic compared to pre-pandemic levels and the associated staffing requirements. Methods: The data presented was collected from a Trauma Unit and a Major Trauma Centre in the United Kingdom. We compared the number of accident and emergency referrals, fracture clinic appointments, inpatient admissions and operations during the six weeks of the first lockdown from 23rd March to May 3, 2020, to the same time period in 2019. Results: The results showed that the orthopaedic trauma caseload was approximately half that of pre-pandemic levels, reducing by an average of 54.2%. Conclusion: A significant orthopaedic trauma caseload still remains to be safely managed during a pandemic and appropriate resources must be allocated. Staff allocation must take into account sick cover and staff wellbeing. A proportion of staff may need to be ring fenced from redeployment to facilitate this.

13.
ALTEX ; 39(4): 656-666, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35353900

RESUMO

Exposure-response assessment methods have shifted towards more quantitative approaches, with health risk assessors exploring more statistically driven techniques. These assessments, however, usually rely on one critical health effect from a single key study. Categorical regression addresses this limitation by incorporating data from all relevant studies ­ including human, animal, and mechanistic studies ­ thereby including a broad spectrum of health endpoints and exposure levels for exposure-response analysis in an objective manner. Categorical regression requires the establishment of ordered response categories corresponding to increasingly severe adverse health outcomes and the availability of a comprehensive database that summarizes all data on different outcomes from different studies, including the exposure or dose at which these out-comes are observed and their severity. It has found application in the risk assessment of essential nutrients and trace metals. Since adverse effects may arise from either deficient or excess exposure, the exposure-response curve is U-shaped, which provides a basis for determining optimal intake levels that minimize the joint risks of deficiency and excess. This article provides an overview of the use of categorical regression fit exposure-response models incorporating data from multiple evidence streams. An extension of categorical regression that permits the simultaneous analysis of excess and deficiency toxicity data is presented and applied to comprehensive databases on copper and manganese. Future applications of cat-egorical regression will be able to make greater use of diverse data sets developed using new approach methodologies, which can be expected to provide valuable information on toxic responses of varying severity.


Assuntos
Cobre , Nutrientes , Animais , Humanos , Cobre/toxicidade , Bases de Dados Factuais , Nutrientes/deficiência , Medição de Risco
14.
Neurotoxicology ; 83: 157-165, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32360354

RESUMO

Epidemiological evidence linking aluminum in drinking water and Alzheimer's disease (AD) has been inconsistent, with previous studies often limited by small sample sizes. The present study addresses this issue using data from the Canadian Study of Health and Aging (CSHA), a prospective cohort of 10,263 subjects followed-up from 1991-1992 through 2001-2002. Participants' residential histories were linked to municipal drinking water sources in 35 Canadian municipalities to obtain ecologic pH, aluminum, fluoride, iron and silica concentrations in drinking water. Cox proportional hazards models were used to examine associations between aluminum and incident AD [Hazard Ratios (HRs), 95% confidence intervals (CIs)], adjusting for age, gender, history of stroke, education, and high blood pressure. A total of 240 incident AD cases were identified during follow-up of 3, 638 subjects derived from the CSHA cohort with complete data on all covariates. With categorical aluminum measurements, there was an increasing, but not statistically significant, exposure-response relationship (HR = 1.34, 95% CI 0.88-2.04, in the highest aluminum exposure category; p = 0.13 for linear trend). Similar results were observed using continuous aluminum measurements (HR=1.21, 95% CI 0.97-1.52, at the interquartile range of 333.8 µg/L; p = 0.09 for linear trend). In a subsample genotyped for ApoE-ε4, there was some evidence of an association between aluminum and AD (p = 0.03 for linear trend). Although a clear association between aluminum in drinking water and AD was not found, the linear trend observed in ApoE-ε4 subsample warrants further examination.


Assuntos
Compostos de Alumínio/efeitos adversos , Doença de Alzheimer/epidemiologia , Água Potável/efeitos adversos , Poluentes Químicos da Água/efeitos adversos , Fatores Etários , Idoso , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/genética , Apolipoproteína E4/genética , Apolipoproteínas E/genética , Canadá/epidemiologia , Feminino , Predisposição Genética para Doença , Humanos , Incidência , Estudos Longitudinais , Masculino , Estudos Prospectivos , Medição de Risco , Fatores de Risco
15.
J Toxicol Environ Health B Crit Rev ; 13(7-8): 546-78, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21170809

RESUMO

There is a need to define exposure-response curves for both Cu excess and deficiency to assist in determining the acceptable range of oral intake. A comprehensive database has been developed where different health outcomes from elevated and deficient Cu intakes were assigned ordinal severity scores to create common measures of response. A generalized linear model for ordinal data was used to estimate the probability of response associated with dose, duration and severity. The model can account for differences in animal species, the exposure medium (drinking water and feed), age, sex, and solubility. Using this model, an optimal intake level of 2.6 mg Cu/d was determined. This value is higher than the current U.S. recommended dietary intake (RDI; 0.9 mg/d) that protects against toxicity from Cu deficiency. It is also lower than the current tolerable upper intake level (UL; 10 mg/d) that protects against toxicity from Cu excess. Compared to traditional risk assessment approaches, categorical regression can provide risk managers with more information, including a range of intake levels associated with different levels of severity and probability of response. To weigh the relative harms of deficiency and excess, it is important that the results be interpreted along with the available information on the nature of the responses that were assigned to each severity score.


Assuntos
Cobre/deficiência , Cobre/toxicidade , Adulto , Fatores Etários , Animais , Relação Dose-Resposta a Droga , Exposição Ambiental , Feminino , Humanos , Masculino , Camundongos , Política Nutricional , Ratos , Valores de Referência , Fatores Sexuais , Especificidade da Espécie
16.
J Toxicol Environ Health A ; 73(2): 187-207, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20077290

RESUMO

Characterization of the exposure-response relationship for copper (Cu) is an essential step in identifying a range of exposures that can prevent against toxicity from either excess or deficiency. Categorical regression is a exposure-response modeling technique that can be used to model data from multiple studies with diverse endpoints simultaneously by organizing the toxicity data into ordered categories of severity. This study describes how categorical regression can be used to model the exposure-response relationship for Cu and presents a preliminary analysis of the comprehensive database on Cu-induced toxicity due to either excess or deficiency. Categorical regression provides a useful tool for summarizing and describing the available data on Cu excess and deficiency, as well as in identifying data gaps in Cu exposure-response. This methodology also allows for a diverse database with considerable variability in animal species, strain, age, and study design to be analyzed in its entirety. The present application of the Cu toxicity database suggests that there is a lack of information on the potential adverse health effects from chronic exposure to Cu; there are also a limited number of studies using marginally excess and deficient levels of Cu. The database presently includes insufficient data to create a complex model that accounts for a large proportion of the heterogeneity in toxicity seen among the available studies on Cu-induced toxicity. The current Cu database is presently being updated in order to permit more comprehensive categorical regression analyses with finer stratification options. The resulting exposure-response model could be used to provide information in the determination of an acceptable range of oral intake for Cu.


Assuntos
Cobre/efeitos adversos , Cobre/farmacologia , Oligoelementos/efeitos adversos , Oligoelementos/farmacologia , Animais , Relação Dose-Resposta a Droga , Humanos , Modelos Logísticos , Modelos Biológicos , Necessidades Nutricionais , Ratos
17.
Orthop Res Rev ; 12: 45-52, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32273780

RESUMO

OBJECTIVE: Lateral humeral condyle fractures are the second most common elbow fractures in children. Both K-wire fixation and screw fixation have been advocated as suitable treatment options for displaced fractures. This study aimed to identify which fixation method was associated with the best functional outcomes. METHODS: A systematic review was conducted. Studies reporting functional outcomes following surgical fixation of lateral condyle fractures were included for review. The primary outcome measure was functional outcome. The secondary outcome measure was major complications. A narrative analysis was undertaken, as meta-analysis was felt to be inappropriate due to the differences between included studies. RESULTS: Ten retrospective non-randomised, comparative studies were eligible and included. No randomised-controlled trials were identified. The highest rate of excellent functional outcomes was seen with screw fixation (120/126 [95%]), compared with K-wire fixation (135/162 [86%]). The incidence of major complications was comparable, with complications in 6/95 (6%) of screw fixations and 6/141 (4%) K-wire fixations. A small sample of data on closed reduction demonstrated excellent functional results in 73 of 76 (96%) of patients. Closed reduction of displaced fractures is associated with a significant learning curve however. CONCLUSION: The evidence was of poor quality and comprised of retrospective case series. This prevented meta-analysis and any firm conclusions being drawn from the available data. Screw fixation may be associated with improved functional outcomes. Complication rates between the two methods are comparable. Further prospective studies are recommended.

18.
Drugs Real World Outcomes ; 7(3): 191-203, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32617885

RESUMO

BACKGROUND: The clinical implications of potential interactions between proton pump inhibitors (PPIs) and clopidogrel have been debated for over a decade. OBJECTIVE: We assessed the association between combined clopidogrel-PPI treatment and the risk of recurrent myocardial infarction (MI) and three secondary outcomes. PATIENTS AND METHODS: A nested case-control study was conducted within Cerner Corporation's Health Facts® database. A retrospective cohort of patients who experienced a first MI and started clopidogrel treatment was created. Within this cohort, patients experiencing a second MI (cases) were matched with up to five controls. Logistic regression was used to estimate adjusted odds ratios (aORs). Findings were compared with those obtained from models with three negative control exposure drugs: H2 receptor antagonists, prasugrel, and ticagrelor. RESULTS: In total, 2890 recurrent MI cases were identified within 12 months following entry into the cohort of clopidogrel users (N = 52,006). aOR for PPI use versus non-use among clopidogrel users was 1.08 [95% confidence interval (CI) 0.95-1.23]. Similar ORs were obtained for secondary endpoints. A positive association between combined use of clopidogrel/PPIs and increased risk of MI was seen in the group aged 80-89 years (aOR 1.26; 95% CI 1.05-1.51). No associations with MI were observed for (1) H2 receptor antagonist use versus non-use among clopidogrel users or (2) PPI use versus non-use among prasugrel users or among ticagrelor users. CONCLUSIONS: Overall, our findings do not support a significant adverse clinical impact of concomitant clopidogrel/PPI use by patients with MI. Nonetheless, investigation of the possible association seen in those aged 80-89 years may be warranted.

19.
J Toxicol Environ Health A ; 72(10): 658-75, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19308851

RESUMO

An investigation based on a large population-based case-control study in British Columbia, Canada, was conducted to identify high-risk occupations for lung cancer by histological subtypes. Subjects were 14,755 male incident cancer cases for whom lifetime occupational histories and information on smoking and relevant covariates were collected. Occupational associations for 2998 lung cancer cases, including histological subtypes, were assessed by logistic regression using other cancer cases, excluding smoking-related cancers, as controls. An excess risk of lung cancer was found among workers in metal processing, bakers, and ship deck crew for all histological subtypes, and construction workers, chefs and cooks, and medical workers for specific histological subtypes. Occupational associations that are unique to histological subtypes of lung cancer were identified. Owing to a scarcity of literature in this area, future research needs to focus on confirming these histological associations, and identifying the risk from key exposures found within these occupations (e.g., medical radiation, electromagnetic fields, and cooking fumes).


Assuntos
Neoplasias Pulmonares/epidemiologia , Ocupações/estatística & dados numéricos , Adenocarcinoma/epidemiologia , Adulto , Idade de Início , Idoso , Consumo de Bebidas Alcoólicas/epidemiologia , Colúmbia Britânica/epidemiologia , Carcinoma de Células Grandes/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Estudos de Casos e Controles , Interpretação Estatística de Dados , Educação , Etnicidade , Humanos , Masculino , Metalurgia , Pessoa de Meia-Idade , Ocupações/classificação , População , Carcinoma de Pequenas Células do Pulmão/epidemiologia , Fumar/epidemiologia , Adulto Jovem
20.
Appetite ; 53(3): 345-53, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19635512

RESUMO

Consuming a diet lower in total fat is important for the prevention of many chronic diseases. Individual and population-based programs targeting this behavior must be theoretically grounded and consider the context within which dietary behavior change may be attempted. To identify the factors differentiating stage of readiness to follow a low-fat diet, a sample (N=1216) of adults was surveyed using 4 different staging algorithms to assess stages of change and associated social-cognitive variables (pros, cons, and temptation). Approximately 75% of the sample occupied the Action/Maintenance stages for all staging algorithms. In general, pros increased and cons decreased with higher stage occupation. Temptation decreased from the early pre-action to the action stages for the different staging algorithms. When developing programs to decrease dietary-fat intake, social-cognitive variables associated with stage transition for behaviors related to consuming a low-fat diet may have relevance to researchers and clinicians.


Assuntos
Dieta com Restrição de Gorduras/psicologia , Comportamento Alimentar/psicologia , Comportamentos Relacionados com a Saúde , Adulto , Algoritmos , Terapia Comportamental , Índice de Massa Corporal , Cognição , Escolaridade , Feminino , Promoção da Saúde , Humanos , Masculino , Estado Civil , Pessoa de Meia-Idade , Ontário , Comportamento Social , Inquéritos e Questionários
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