947 resultados para Sykes, Arthur Ashley, 1683 or 4-1756.


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Objective To assess several baseline risk factors that may predict patellofemoral and tibiofemoral cartilage loss during a 6-month period. Methods For 177 subjects with chronic knee pain, 3T magnetic resonance imaging (MRI) of both knees was performed at baseline and followup. Knees were semiquantitatively assessed, evaluating cartilage morphology, subchondral bone marrow lesions, meniscal morphology/extrusion, synovitis, and effusion. Age, sex, and body mass index (BMI), bone marrow lesions, meniscal damage/extrusion, synovitis, effusion, and prevalent cartilage damage in the same subregion were evaluated as possible risk factors for cartilage loss. Logistic regression models were applied to predict cartilage loss. Models were adjusted for age, sex, treatment, and BMI. Results Seventy-nine subregions (1.6%) showed incident or worsening cartilage damage at followup. None of the demographic risk factors was predictive of future cartilage loss. Predictors of patellofemoral cartilage loss were effusion, with an adjusted odds ratio (OR) of 3.5 (95% confidence interval [95% CI] 1.39.4), and prevalent cartilage damage in the same subregion with an adjusted OR of 4.3 (95% CI 1.314.1). Risk factors for tibiofemoral cartilage loss were baseline meniscal extrusion (adjusted OR 3.6 [95% CI 1.310.1]), prevalent bone marrow lesions (adjusted OR 4.7 [95% CI 1.119.5]), and prevalent cartilage damage (adjusted OR 15.3 [95% CI 4.947.4]). Conclusion Cartilage loss over 6 months is rare, but may be detected semiquantitatively by 3T MRI and is most commonly observed in knees with Kellgren/Lawrence grade 3. Predictors of patellofemoral cartilage loss were effusion and prevalent cartilage damage in the same subregion. Predictors of tibiofemoral cartilage loss were prevalent cartilage damage, bone marrow lesions, and meniscal extrusion.

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OBJECTIVE: To assess the prevalence and vulnerability of homeless people to HIV infection. METHODS: Cross-sectional study conducted with a non-probabilistic sample of 1,405 homeless users of shelters in the city of Sao Paulo, southeastern Brazil, from 2006 to 2007. They were all tested for HIV and a structured questionnaire was applied. Their vulnerability to HIV was determined by the frequency of condom use: those who reported using condoms only occasionally or never were considered the most vulnerable. Multinomial and logistic regression models were used to estimate effect measures and 95% confidence intervals. RESULTS: There was a predominance of males (85.6%), with a mean age of 40.9 years, 72.0% had complete elementary schooling, and 71.5% were non-white. Of all respondents, 15.7% reported being homosexual or bisexual and 62,0% reported having casual sex. The mean number of sexual partners in the last 12 months was 5.4. More than half (55.7%) of the respondents reported lifetime drug use, while 25.7% reported frequent use. Sexually-transmitted disease was reported by 39.6% of the homeless and 38.3% reported always using condoms. The prevalence of HIV infection was 4.9% (17.4% also tested positive for syphilis) and about half of the respondents (55.4%) had access to prevention programs. Higher HIV prevalence was associated with younger age (18-29 years, OR = 4.0 [95% CI 1.54; 10.46]); past history of sexually-transmitted disease (OR = 3.3 [95% CI 1.87; 5.73]); homosexual sex (OR = 3.0 [95% CI 1.28; 6.92]); and syphilis (OR = 2.4 [95% CI 1.13; 4.93]). Increased vulnerability to HIV infection was associated with being female; young; homosexual sex; having few partners or a steady partner; drug and alcohol use; not having access to prevention programs and social support. CONCLUSIONS: The HIV epidemic has a major impact on homeless people reflecting a cycle of exclusion, social vulnerability, and limited access to prevention.

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Objective: To compare the polymerization status of mouse oocyte spindles exposed to various temperatures at various stages of meiosis. Design: Experimental animal study. Setting: University animal laboratory. Animal(s): CF1 mice. Intervention(s): Immature oocytes matured to metaphase I (MI), telophase I (TI), and metaphase II (MII) were incubated at 37 degrees C (control), room temperature (RT), or 4 degrees C for 0, 10, 30, and 60 minutes. Spindle analysis subsequently was performed using polarized field microscopy and immunocytochemistry. Spindles of TI and MII oocytes that underwent vitrification and warming were analyzed also by immunocytochemistry. Main Outcome Measure(s): Detection of polymerized meiotic spindles. Result(s): At RT, and after 60 minutes at 4 degrees C, a significant time-dependent decrease in the percentage of polymerized meiotic spindles was observed in MI and MII oocytes, but not in TI oocytes. The polymerization of TI spindles at 4 degrees C was similar to that of TI spindles at 4 degrees C that underwent vitrification and warming. Conclusion(s): Significant differences in the microtubule dynamics of MI, TI, and MII oocytes incubated at different temperatures were observed. In particular, meiotic spindles in TI oocytes exhibited less depolymerization than did metaphase spindles. (Fertil Steril (R) 2012; 97: 714-9. (C) 2012 by American Society for Reproductive Medicine.)

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Objectives: To investigate the effect of Si addition on a nanometer-scale roughness Ca and P implant surfaces in a canine tibia model by biomechanical and histomorphometric evaluations. Material and methods: The implant surfaces comprised a resorbable media CaP microblasted (control) and a CaP resorbable media + silica-boost microblasted (experimental) surfaces. Surfaces were characterized by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and optical interferometry (IFM) down to the nanometric level. The animal model involved the bilateral placement of control (n = 24) and experimental surface (n = 24) implants along the proximal tibiae of six dogs, remaining in vivo for 2 or 4 weeks. After euthanization, half of the specimens were torquedto- interface failure, and the other half was subjected to histomorphologic and bone-to-implant contact (BIC) evaluation. Torque and BIC statistical evaluation was performed by the Friedman test at 95% level of significance, and comparisons between groups was performed by the Dunn test. Results: IFM and SEM observations depicted comparable roughness parameters for both implant surfaces on the micrometer and nanometer scales. XPS analysis revealed similar chemical composition, except for the addition of Si on the experimental group. Torque-to-interface failure and BIC mean values showed no significant differences (P = 0.25 and 0.51, respectively) at both 2- and 4-week evaluation points for experimental and control groups. Early bone healing histomorphologic events were similar between groups. Conclusions: The experimental surface resulted in not significantly different biomechanical fixation and BIC relative to control. Both surfaces were biocompatible and osseoconductive.

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This study investigated the association between physician education in EOL and variability in EOL practice, as well as the differences between beliefs and practices regarding EOL in the ICU. Physicians from 11 ICUs at a university hospital completed a survey presenting a patient in a vegetative state with no family or advance directives. Questions addressed approaches to EOL care, as well physicians' personal, professional and EOL educational characteristics. The response rate was 89%, with 105 questionnaires analyzed. Mean age was 38 +/- A 8 years, with a mean of 14 +/- A 7 years since graduation. Physicians who did not apply do-not-resuscitate (DNR) orders were less likely to have attended EOL classes than those who applied written DNR orders [0/7 vs. 31/47, OR = 0.549 (0.356-0.848), P = 0.001]. Physicians who involved nurses in the decision-making process were more likely to be ICU specialists [17/22 vs. 46/83, OR = 4.1959 (1.271-13.845), P = 0.013] than physicians who made such decisions among themselves or referred to ethical or judicial committees. Physicians who would apply "full code" had less often read about EOL [3/22 vs. 11/20, OR = 0.0939 (0.012-0.710), P = 0.012] and had less interest in discussing EOL [17/22 vs. 20/20, OR = 0.210 (0.122-0.361), P < 0.001], than physicians who would withdraw life-sustaining therapies. Forty-four percent of respondents would not do what they believed was best for their patient, with 98% of them believing a less aggressive attitude preferable. Legal concerns were the leading cause for this dichotomy. Physician education about EOL is associated with variability in EOL decisions in the ICU. Moreover, actual practice may differ from what physicians believe is best for the patient.

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Background: A considerable number of metastatic colorectal cancer (mCRC) patients who progress on standard treatment with 5-fluorouracil (5FU), oxaliplatin, irinotecan and monoclonal antibodies, still have adequate performance status and desire further treatment. Mitomycin C (MMC) has been widely used in this context, and despite good tolerability, there are doubts regarding its true benefit. Methods: In order to assess the activity of MMC in the refractory mCRC setting, we retrospectively evaluated 109 heavily pre-treated patients who received MMC as single agent or in combination for mCRC at three different institutions in two countries. Results: Median patient's age was 54 years old, 57% were male and 94% had performance status ECOG 0 or 1. MMC was used in second line in 11%, third line in 38% and fourth line or beyond in 51% of patients. 58% received MMC combinations, mainly with capecitabine. Grade 3 or 4 toxicity was observed in 5% of patients and 6% required dose reductions. Median time to treatment failure (TTF) was 1.7 months with MMC and 3.6 months on the regimen prior to MMC, with a ratio between these TTF below 1 in 82% of patients. Median survival was only 4.5 months (95% confidence interval (CI) of 3.48-5.56). Conclusions: This retrospective data represent the largest reported series of unselected refractory mCRC patients treated with MMC. The median survival of 4.5 months is similar to the survival expected for best supportive care. This lack of activity strongly suggests that MMC should not be routinely used in refractory mCRC. (C) 2012 Elsevier Ltd. All rights reserved.

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Objectives: This study compared the biomechanical fixation and bone-to-implant contact (BIC) of implants with different surfaces treatment (experimental resorbable blasting media-processed nanometer roughness scale surface, and control dual acid-etched) in a dog model. Material and methods: Surface characterization was made in six implants by means of scanning electron microscopic imaging, atomic force microscopy to evaluate roughness parameters, and X-ray photoelectron spectroscopy (XPS) for chemical assessment. The animal model comprised the bilateral placement of control (n = 24) and experimental surface (n = 24) implants along the proximal tibiae of six mongrel dogs, which remained in place for 2 or 4 weeks. Half of the specimens were biomechanically tested (torque), and the other half was subjected to histomorphologic/ morphometric evaluation. BIC and resistance to failure measures were each evaluated as a function of time and surface treatment in a mixed model ANOVA. Results: Surface texturing was significantly higher for the experimental compared with the control surface. The survey XPS spectra detected O, C, Al, and Ti at the control group, and Ca (similar to 0.2-0.9%) and P (similar to 1.7-4.1%) besides O, C, Al, and Ti at experimental surfaces. While no statistical difference in BIC was found between experimental and control surfaces or between 2 and 4 weeks in vivo, both longer time and use of experimental surface significantly increased resistance to failure. Conclusions: The experimental surface resulted in enhanced biomechanical fixation but comparable BIC relative to control, suggesting higher bone mechanical properties around the experimental implants.

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Hemophilia A is the most common X-linked bleeding disorder; it is caused by deficiency of coagulation factor VIII (FVIII). Replacement therapy with rFVIII produced from human cell line is a major goal for treating hemophilia patients. We prepared a full-length recombinant FVIII (FVIII-FL), using the pMFG-P140K retroviral vector. The IRES DNA fragment was cloned upstream to the P140K gene, providing a 9.34-kb bicistronic vector. FVIII-FL cDNA was then cloned upstream to IRES, resulting in a 16.6-kb construct. In parallel, an eGFP control vector was generated, resulting in a 10.1-kb construct. The 293T cells were transfected with these constructs, generating the 293T-FVIII-FL/P140K and 293T-eGFP/P140K cell lines. In 293T-FVIII-FL/P140K cells, FVIII and P140K mRNAs levels were 4,410 (+/- 931.7)- and 295,400 (+/- 75,769)-fold higher than in virgin cells. In 293T-eGFP/P140K cells, the eGFP and P140K mRNAs levels were 1,501,000 (+/- 493,700)- and 308,000 (+/- 139,300)-fold higher than in virgin cells. The amount of FVIII-FL was 0.2 IU/mL and 45 ng/mL FVIII cells or 4.4 IU/mu g protein. These data demonstrate the efficacy of the bicistronic retroviral vector expressing FVIII-FL and MGMT(P140K), showing that it could be used for producing the FVIII-FL protein in a human cell line.

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This study identified the prevalence and prevalence and predictors of fatigue in colorectal cancer (CRC) patients. Cross-sectional study with 157 adult CRC outpatients (age 60 +/- 11.7 years; 54% male; cancer stage IV 44.8%). The Piper Fatigue Scale-revised was used to assess fatigue scores. Socio-demographic, clinical, depression, performance status, pain and sleep disturbance data were assessed. Associations between fatigue and these data were analyzed through logistic regression models. Fatigue was reported by 26.8% patients. Logistic regression identified three predictors: depression (OR: 4.2; 95%CI 1.68-10.39), performance status (OR: 3.2; 95%CI 1.37-7.51) and sleep disturbance (OR: 3.2; 95%CI 1.30-8.09). When all predictors were present, the probability of fatigue occurrence was 80%; when none were present, the probability was 8%. The model's specificity and sensitivity were 81.9% and 58.6%, respectively. Through the assessment of depression, performance status and sleep disturbance, the probability of fatigue occurrence can be estimated, and preventive and treatment strategies can be rapidly implemented in clinical practice.

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Purpose: Oral mucositis is a major complication of concurrent chemoradiotherapy (CRT) in head-and-neck cancer patients. Low-level laser (LLL) therapy is a promising preventive therapy. We aimed to evaluate the efficacy of LLL therapy to decrease severe oral mucositis and its effect on RT interruptions. Methods and Materials: In the present randomized, double-blind, Phase III study, patients received either gallium-aluminum-arsenide LLL therapy 2.5 J/cm(2) or placebo laser, before each radiation fraction. Eligible patients had to have been diagnosed with squamous cell carcinoma or undifferentiated carcinoma of the oral cavity, pharynx, larynx, or metastases to the neck with an unknown primary site. They were treated with adjuvant or definitive CRT, consisting of conventional RT 60-70 Gy (range, 1.8-2.0 Gy/d, 5 times/wk) and concurrent cisplatin. The primary endpoints were the oral mucositis severity in Weeks 2, 4, and 6 and the number of RT interruptions because of mucositis. The secondary endpoints included patient-reported pain scores. To detect a decrease in the incidence of Grade 3 or 4 oral mucositis from 80% to 50%, we planned to enroll 74 patients. Results: A total of 75 patients were included, and 37 patients received preventive LLL therapy. The mean delivered radiation dose was greater in the patients treated with LLL (69.4 vs. 67.9 Gy, p = .03). During CRT, the number of patients diagnosed with Grade 3 or 4 oral mucositis treated with LLL vs. placebo was 4 vs. 5 (Week 2, p = 1.0), 4 vs. 12 (Week 4, p = .08), and 8 vs. 9 (Week 6, p = 1.0), respectively. More of the patients treated with placebo had RT interruptions because of mucositis (6 vs. 0, p = .02). No difference was detected between the treatment arms in the incidence of severe pain. Conclusions: LLL therapy was not effective in reducing severe oral mucositis, although a marginal benefit could not be excluded. It reduced RT interruptions in these head-and-neck cancer patients, which might translate into improved CRT efficacy. (C) 2012 Elsevier Inc.

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Background: Cellulose consisting of arrays of linear beta-1,4 linked glucans, is the most abundant carbon-containing polymer present in biomass. Recalcitrance of crystalline cellulose towards enzymatic degradation is widely reported and is the result of intra-and inter-molecular hydrogen bonds within and among the linear glucans. Cellobiohydrolases are enzymes that attack crystalline cellulose. Here we report on two forms of glycosyl hydrolase family 7 cellobiohydrolases common to all Aspergillii that attack Avicel, cotton cellulose and other forms of crystalline cellulose. Results: Cellobiohydrolases Cbh1 and CelD have similar catalytic domains but only Cbh1 contains a carbohydrate-binding domain (CBD) that binds to cellulose. Structural superpositioning of Cbh1 and CelD on the Talaromyces emersonii Cel7A 3-dimensional structure, identifies the typical tunnel-like catalytic active site while Cbh1 shows an additional loop that partially obstructs the substrate-fitting channel. CelD does not have a CBD and shows a four amino acid residue deletion on the tunnel-obstructing loop providing a continuous opening in the absence of a CBD. Cbh1 and CelD are catalytically functional and while specific activity against Avicel is 7.7 and 0.5 U. mg prot-1, respectively specific activity on pNPC is virtually identical. Cbh1 is slightly more stable to thermal inactivation compared to CelD and is much less sensitive to glucose inhibition suggesting that an open tunnel configuration, or absence of a CBD, alters the way the catalytic domain interacts with the substrate. Cbh1 and CelD enzyme mixtures on crystalline cellulosic substrates show a strong combinatorial effort response for mixtures where Cbh1 is present in 2: 1 or 4: 1 molar excess. When CelD was overrepresented the combinatorial effort could only be partially overcome. CelD appears to bind and hydrolyze only loose cellulosic chains while Cbh1 is capable of opening new cellulosic substrate molecules away from the cellulosic fiber. Conclusion: Cellobiohydrolases both with and without a CBD occur in most fungal genomes where both enzymes are secreted, and likely participate in cellulose degradation. The fact that only Cbh1 binds to the substrate and in combination with CelD exhibits strong synergy only when Cbh1 is present in excess, suggests that Cbh1 unties enough chains from cellulose fibers, thus enabling processive access of CelD.

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INTRODUÇÃO: A esternotomia mediana longitudinal é a via de acesso mais utilizada no tratamento das doenças cardíacas. As infecções profundas da ferida operatória no pós-operatório das cirurgias cardiovasculares são uma complicação séria, com alto custo durante o tratamento. Diferentes estudos têm encontrado fatores de risco para o desenvolvimento de mediastinite e as variáveis pré-operatórias têm tido especial destaque. OBJETIVO: O objetivo deste estudo é identificar fatores de risco pré-operatórios para o desenvolvimento de mediastinite em pacientes submetidos a revascularização do miocárdio e a substituição valvar. MÉTODOS: Este estudo observacional representa uma coorte de 2768 pacientes operados consecutivamente. O período considerado para análise foi de maio de 2007 a maio de 2009 e não houve critérios de exclusão. Foi realizada análise univariada e multivariada pelo modelo de regressão logística das 38 variáveis pré-operatórias eleitas. RESULTADOS: Nesta série, 35 (1,3%) pacientes evoluíram com mediastinite e 19 (0,7%) com osteomielite associada. A idade média dos pacientes foi de 59,9 ± 13,5 anos e o EuroSCORE de 4,5 ± 3,6. A mortalidade hospitalar foi de 42,8%. Na análise multivariada, foram identificadas três variáveis como preditoras independentes de mediastinite: balão intra-aórtico (OR 5,41, 95% IC [1,83 -16,01], P=0,002), hemodiálise (OR 4,87, 95% IC [1,41 - 16,86], P=0,012) e intervenção vascular extracardíaca (OR 4,39, 95% IC [1,64 - 11,76], P=0,003). CONCLUSÃO: O presente estudo demonstrou que necessidade do suporte hemodinâmico pré-operatório com balão intra-aórtico, hemodiálise e intervenção vascular extracardíaca são fatores de risco para o desenvolvimento de mediastinite após cirurgia cardíaca.

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Case fatality rate is considered a main determinant of stroke mortality trends. We applied the World Health Organization's Stroke STEPS to identify case fatality rates in a community hospital in Brazil. We evaluated all patients with first-ever stroke seeking acute care at the hospital's emergency ward between April 2006 and December 2008 to verify early and late case fatality according to stroke subtype. We used years of formal education as a surrogate for socioeconomic status. Of 430 first-ever stroke events, 365 (84.9%) were ischemic and 65 (15.1%) were intracerebral hemorrhage. After 1 year, we adjudicated 108 deaths (86 ischemic; 22 hemorrhagic). Age-adjusted case fatality rates for ischemic stroke and intracerebral hemorrhage were 6.0% v 19.8% at 10 days, 10.6% v 22.1% at 28 days, 17.6% v 29.1% at 6 months, and 21.0% v 31.5% at 1 year. Illiteracy or no formal education was a predictor of death at 6 months (odds ratio [OR], 4.31; 95% confidence interval [CI] 1.34-13.91) and 1 year (OR, 4.21; 95% CI, 1.45-12.28) in patients with ischemic stroke, as well as at 6 months (OR, 3.19; 95% CI, 1.17-8.70) and 1 year (OR, 3.30; 95% CI, 1.30-8.45) for all stroke patients. Other variables, including previous cardiovascular risk factors and acute medical care, did not change this association to a statistically significant degree. In conclusion, case fatality, particularly up to 6 months, was higher in hemorrhagic stroke, and lack of formal education was associated with increased stroke mortality.

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OBJECTIVE: During the neonatal and infancy periods, some chronic liver diseases may lead to progressive hepatic fibrosis, which is a condition that can ultimately result in the loss of organ function and severe portal hypertension necessitating hepatic transplantation. In a previous report, pharmacological interventions were demonstrated to modulate hepatic fibrosis induced by bile duct ligation in young rats. The administration of pentoxifylline or prednisolone, or the combination of both, resulted in reduced fibrogenesis in portal spaces. The objectives of the present study were to evaluate the expression of transforming growth factor beta and vascular endothelial growth factor after bile duct ligation in young rats and to assess the effect of those same drugs on cytokine expression. METHODS: In this experimental study, 80 young rats (21 or 22 days old) were submitted either to laparotomy and common bile duct ligation or to sham surgery. The animals were allocated into four groups according to surgical procedure, and the following treatments were administered: (1) common bile duct ligation + distilled water, (2) sham surgery + distilled water, (3) common bile duct ligation + pentoxifylline, or (4) common bile duct ligation + prednisolone. After 30 days, a hepatic fragment was collected from each animal for immunohistochemical analysis using monoclonal antibodies against transforming growth factor beta and vascular endothelial growth factor. Digital morphometric and statistical analyses were performed. RESULTS: The administration of pentoxifylline reduced the transforming growth factor beta-marked area and the amount of transforming growth factor beta expressed in liver tissue. This effect was not observed after the administration of prednisolone. There was a significant reduction in vascular endothelial growth factor expression after the administration of either drug compared with the non-treatment group. CONCLUSIONS: The administration of pentoxifylline to cholestatic young rats resulted in the diminished expression of transforming growth factor beta and vascular endothelial growth factor in liver tissue. The administration of steroids resulted in the diminished expression of vascular endothelial growth factor only. These pathways may be involved in hepatic fibrogenesis in young rats submitted to bile duct ligation and exposed to pentoxifylline or prednisolone.

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Background: Few cross-sectional studies involving adults and elderly patients with major DDIs have been conducted in the primary care setting. The study aimed to investigate the prevalence of potential drug-drug interactions (DDIs) in patients treated in primary care. Methodology/Principal Findings: A cross-sectional study involving patients aged 45 years or older was conducted at 25 Basic Health Units in the city of Maringa (southern Brazil) from May to December 2010. The data were collected from prescriptions at the pharmacy of the health unit at the time of the delivery of medication to the patient. After delivery, the researcher checked the electronic medical records of the patient. A total of 827 patients were investigated (mean age: 64.1; mean number of medications: 4.4). DDIs were identified in the Micromedex (R) database. The prevalence of potential DDIs and major DDIs was 63.0% and 12.1%, respectively. In both the univariate and multivariate analyses, the number of drugs prescribed was significantly associated with potential DDIs, with an increasing risk from three to five drugs (OR = 4.74; 95% CI: 2.90-7.73) to six or more drugs (OR = 23.03; 95% CI: 10.42-50.91). Forty drugs accounted for 122 pairs of major DDIs, the most frequent of which involved simvastatin (23.8%), captopril/enalapril (16.4%) and fluoxetine (16.4%). Conclusions/Significance: This is the first large-scale study on primary care carried out in Latin America. Based on the findings, the estimated prevalence of potential DDIs was high, whereas clinically significant DDIs occurred in a smaller proportion. Exposing patients to a greater number of prescription drugs, especially three or more, proved to be a significant predictor of DDIs. Prescribers should be more aware of potential DDIs. Future studies should assess potential DDIs in primary care over a longer period of time.