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Sample records for adverse patient outcomes

  1. Adverse events and outcomes of procedural sedation and analgesia in major trauma patients

    PubMed Central

    Green, Robert S.; Butler, Michael B.; Campbell, Samuel G.; Erdogan, Mete

    2015-01-01

    Context: Trauma patients requiring procedural sedation and analgesia (PSA) may have increased risk of adverse events (AEs) and poor outcomes. Aims: To determine the incidence of AEs in adult major trauma patients who received PSA and to evaluate their postprocedural outcomes. Settings and Design: Retrospective analysis of adult patients (age >16) who received PSA between 2006 and 2014 at a Canadian academic tertiary care center. Materials and Methods: We compared the incidence of PSA-related AEs in trauma patients with nontrauma patients. Postprocedural outcomes including Intensive Care Unit admission, length of hospital stay, and mortality were compared between trauma patients who did or did not receive PSA. Statistical Analysis Used: Descriptive statistics and multivariable logistic regression. Results: Overall, 4324 patients received PSA during their procedure, of which 101 were trauma patients (107 procedures). The majority (77%) of these 101 trauma patients were male, relatively healthy (78% with American Society of Anesthesiologists Physical Status [ASA-PS] 1), and most (85%) of the 107 procedures were orthopedic manipulations. PSA-related AEs were experienced by 45.5% of the trauma group and 45.9% of the nontrauma group. In the trauma group, the most common AEs were tachypnea (23%) and hypotension (20%). After controlling for age, gender, and ASA-PS, trauma patients were more likely than nontrauma patients to develop hypotension (odds ratio 1.79; 95% confidence interval 1.11-2.89). Conclusion: Although trauma patients were more likely than nontrauma patients to develop hypotension during PSA, their outcomes were not worse compared to trauma patients who did not have PSA. PMID:26604527

  2. Low Mitochondrial DNA Copy Number is Associated With Adverse Clinical Outcomes in Peritoneal Dialysis Patients.

    PubMed

    Yoon, Chang-Yun; Park, Jung Tak; Kee, Youn Kyung; Han, Seung Gyu; Han, In Mee; Kwon, Young Eun; Park, Kyoung Sook; Lee, Mi Jung; Han, Seung Hyeok; Kang, Shin-Wook; Yoo, Tae-Hyun

    2016-02-01

    Mitochondrial dysfunction may play an important role in abnormal glucose metabolism and systemic inflammation. We aimed to investigate the relationship between mitochondrial DNA (mtDNA) copy number and clinical outcomes in peritoneal dialysis (PD) patients. We recruited 120 prevalent PD patients and determined mtDNA copy number by PCR. Primary outcome was all-cause mortality, whereas secondary outcomes included cardiovascular events, technical PD failure, and incident malignancy. Cox proportional hazards analysis determined the independent association of mtDNA copy number with outcomes. The mean patient age was 52.3 years; 42.5% were men. The mean log mtDNA copy number was 3.30 ± 0.50. During a follow-up period of 35.4 ± 19.3 months, all-cause mortality and secondary outcomes were observed in 20.0% and 59.2% of patients, respectively. Secondary outcomes were significantly lower in the highest mtDNA copy number group than in the lower groups. In multiple Cox analysis, the mtDNA copy number was not associated with all-cause mortality (lower two vs highest tertile: hazard ratio [HR] = 1.208, 95% confidence interval [CI] = 0.477-3.061). However, the highest tertile group was significantly associated with lower incidences of secondary outcomes (lower two vs highest tertile: HR [95% CI] = 0.494 [0.277-0.882]) after adjusting for confounding factors. The decreased mtDNA copy number was significantly associated with adverse clinical outcomes in PD patients. PMID:26886611

  3. Low Mitochondrial DNA Copy Number is Associated With Adverse Clinical Outcomes in Peritoneal Dialysis Patients

    PubMed Central

    Yoon, Chang-Yun; Park, Jung Tak; Kee, Youn Kyung; Han, Seung Gyu; Han, In Mee; Kwon, Young Eun; Park, Kyoung Sook; Lee, Mi Jung; Han, Seung Hyeok; Kang, Shin-Wook; Yoo, Tae-Hyun

    2016-01-01

    Abstract Mitochondrial dysfunction may play an important role in abnormal glucose metabolism and systemic inflammation. We aimed to investigate the relationship between mitochondrial DNA (mtDNA) copy number and clinical outcomes in peritoneal dialysis (PD) patients. We recruited 120 prevalent PD patients and determined mtDNA copy number by PCR. Primary outcome was all-cause mortality, whereas secondary outcomes included cardiovascular events, technical PD failure, and incident malignancy. Cox proportional hazards analysis determined the independent association of mtDNA copy number with outcomes. The mean patient age was 52.3 years; 42.5% were men. The mean log mtDNA copy number was 3.30 ± 0.50. During a follow-up period of 35.4 ± 19.3 months, all-cause mortality and secondary outcomes were observed in 20.0% and 59.2% of patients, respectively. Secondary outcomes were significantly lower in the highest mtDNA copy number group than in the lower groups. In multiple Cox analysis, the mtDNA copy number was not associated with all-cause mortality (lower two vs highest tertile: hazard ratio [HR] = 1.208, 95% confidence interval [CI] = 0.477–3.061). However, the highest tertile group was significantly associated with lower incidences of secondary outcomes (lower two vs highest tertile: HR [95% CI] = 0.494 [0.277–0.882]) after adjusting for confounding factors. The decreased mtDNA copy number was significantly associated with adverse clinical outcomes in PD patients. PMID:26886611

  4. Malnutrition in Hospitalized Pediatric Patients: Assessment, Prevalence, and Association to Adverse Outcomes.

    PubMed

    Daskalou, Efstratia; Galli-Tsinopoulou, Assimina; Karagiozoglou-Lampoudi, Thomais; Augoustides-Savvopoulou, Persefone

    2016-01-01

    Malnutrition is a frequent finding in pediatric health care settings in the form of undernutrition or excess body weight. Its increasing prevalence and impact on overall health status, which is reflected in the adverse outcomes, renders imperative the application of commonly accepted and evidence-based practices and tools by health care providers. Nutrition risk screening on admission and nutrition status evaluation are key points during clinical management of hospitalized pediatric patients, in order to prevent health deterioration that can lead to serious complications and growth consequences. In addition, anthropometric data based on commonly accepted universal growth standards can give accurate results for nutrition status. Both nutrition risk screening and nutrition status assessment are techniques that should be routinely implemented, based on commonly accepted growth standards and methodology, and linked to clinical outcomes. The aim of the present review was to address the issue of hospital malnutrition in pediatric settings in terms of prevalence, outline nutrition status evaluation and nutrition screening process using different criteria and available tools, and present its relationship with outcome measures. Key teaching points • Malnutrition-underweight or excess body weight-is a frequent imbalance in pediatric settings that affects physical growth and results in undesirable clinical outcomes. • Anthropometry interpretation through growth charts and nutrition screening are cornerstones for the assessment of malnutrition.To date no commonly accepted anthropometric criteria or nutrition screening tools are used in hospitalized pediatric patients. • Commonly accepted nutrition status and screening processes based on the World Health Organization's growth standards can contribute to the overall hospital nutrition care of pediatric patients. PMID:26709552

  5. Patient-reported outcomes and the evolution of adverse event reporting in oncology.

    PubMed

    Trotti, Andy; Colevas, A Dimitrios; Setser, Ann; Basch, Ethan

    2007-11-10

    Adverse event (AE) reporting in oncology has evolved from informal descriptions to a highly systematized process. The Common Terminology Criteria for Adverse Events (CTCAE) is the predominant system for describing the severity of AEs commonly encountered in oncology clinical trials. CTCAE clinical descriptors have been developed empirically during more than 30 years of use. The method of data collection is clinician based. Limitations of the CTC system include potential for incomplete reporting and limited guidance on data analysis and presentation methods. The Medical Dictionary for Regulatory Activities (MedDRA) is a comprehensive medical terminology system used for regulatory reporting and drug labeling. MedDRA does not provide for severity ranking of AEs. CTC-based data presentations are the primary method of AE data reporting used in scientific journals and oncology meetings. Patient-reported outcome instruments (PROs) cover the subjective domain of AEs. Exploratory work suggests PROs can be used with a high degree of patient engagement and compliance. Additional studies are needed to determine how PROs can be used to complement current AE reporting systems. Potential models for integrating PROs into AE reporting are described in this review. AE reporting methods will continue to evolve in response to changing therapies and growing interest in measuring the impact of cancer treatment on health status. Although integration of PROs into AE reporting may ultimately improve the comprehensiveness and quality of collected data, it may also increase the administrative burden and cost of conducting trials. Therefore, care must be used when developing health outcomes and safety data collection plans. PMID:17991931

  6. Exposing physicians to reduced residency work hours did not adversely affect patient outcomes after residency.

    PubMed

    Jena, Anupam B; Schoemaker, Lena; Bhattacharya, Jay

    2014-10-01

    In 2003, work hours for physicians-in-training (residents) were capped by regulation at eighty hours per week, leading to the hotly debated but unexplored issue of whether physicians today are less well trained as a result of these work-hour reforms. Using a unique database of nearly all hospitalizations in Florida during 2000-09 that were linked to detailed information on the medical training history of the physician of record for each hospitalization, we studied whether hospital mortality and patients' length-of-stay varied according to the number of years a physician was exposed to the 2003 duty-hour regulations during his or her residency. We examined this database of practicing Florida physicians, using a difference-in-differences analysis that compared trends in outcomes of junior physicians (those with one-year post-residency experience) pre- and post-2003 to a control group of senior physicians (those with ten or more years of post-residency experience) who were not exposed to these reforms during their residency. We found that the duty-hour reforms did not adversely affect hospital mortality and length-of-stay of patients cared for by new attending physicians who were partly or fully exposed to reduced duty hours during their own residency. However, assessment of the impact of the duty-hour reforms on other clinical outcomes is needed. PMID:25288430

  7. Association of Increased Epicardial Adipose Tissue Thickness With Adverse Cardiovascular Outcomes in Patients With Atrial Fibrillation

    PubMed Central

    Chu, Chun-Yuan; Lee, Wen-Hsien; Hsu, Po-Chao; Lee, Meng-Kuang; Lee, Hung-Hao; Chiu, Cheng-An; Lin, Tsung-Hsien; Lee, Chee-Siong; Yen, Hsueh-Wei; Voon, Wen-Chol; Lai, Wen-Ter; Sheu, Sheng-Hsiung; Su, Ho-Ming

    2016-01-01

    Abstract The thickness of epicardial adipose tissue (EAT) was reported to be highly associated with the incidence and severity of atrial fibrillation (AF). This study was conducted to analyze the ability of EAT thickness in predicting adverse cardiovascular (CV) events in AF. In 190 persistent AF patients, we performed a comprehensive transthoracic echocardiographic examination with assessment of EAT thickness. The definition of CV events included CV mortality, hospitalization for heart failure, myocardial infarction, and stroke. There were 69 CV events including 19 CV deaths, 32 hospitalizations for heart failure, 3 myocardial infarctions, and 15 strokes during a mean follow-up of 29 (25th–75th percentile: 17–36) months. The multivariable analysis demonstrates that chronic heart failure, increased left ventricular (LV) mass index and the ratio of transmitral E-wave velocity to early diastolic mitral annulus velocity, decreased body mass index, and increased EAT thickness (per 1-mm increase, odds ratio 1.224, 95% confidence interval [CI] 1.096–1.368, P < 0.001) were associated with adverse CV events. Additionally, the addition of EAT thickness to a model containing CHA2DS2-VASc score, left atrial volume index, and LV systolic and diastolic function significantly improved the values in predicting CV events (global χ2 increase 14.65, P < 0.001 and integrated discrimination improvement 0.10, 95% CI 0.04–0.16, P < 0.001). In AF, EAT thickness was useful in predicting adverse CV events. Additionally, EAT thickness could provide incremental value for CV outcome prediction over traditional clinical and echocardiographic parameters in AF. PMID:26986099

  8. Association of Increased Epicardial Adipose Tissue Thickness With Adverse Cardiovascular Outcomes in Patients With Atrial Fibrillation.

    PubMed

    Chu, Chun-Yuan; Lee, Wen-Hsien; Hsu, Po-Chao; Lee, Meng-Kuang; Lee, Hung-Hao; Chiu, Cheng-An; Lin, Tsung-Hsien; Lee, Chee-Siong; Yen, Hsueh-Wei; Voon, Wen-Chol; Lai, Wen-Ter; Sheu, Sheng-Hsiung; Su, Ho-Ming

    2016-03-01

    The thickness of epicardial adipose tissue (EAT) was reported to be highly associated with the incidence and severity of atrial fibrillation (AF). This study was conducted to analyze the ability of EAT thickness in predicting adverse cardiovascular (CV) events in AF.In 190 persistent AF patients, we performed a comprehensive transthoracic echocardiographic examination with assessment of EAT thickness. The definition of CV events included CV mortality, hospitalization for heart failure, myocardial infarction, and stroke.There were 69 CV events including 19 CV deaths, 32 hospitalizations for heart failure, 3 myocardial infarctions, and 15 strokes during a mean follow-up of 29 (25th-75th percentile: 17-36) months. The multivariable analysis demonstrates that chronic heart failure, increased left ventricular (LV) mass index and the ratio of transmitral E-wave velocity to early diastolic mitral annulus velocity, decreased body mass index, and increased EAT thickness (per 1-mm increase, odds ratio 1.224, 95% confidence interval [CI] 1.096-1.368, P < 0.001) were associated with adverse CV events. Additionally, the addition of EAT thickness to a model containing CHA2DS2-VASc score, left atrial volume index, and LV systolic and diastolic function significantly improved the values in predicting CV events (global χ increase 14.65, P < 0.001 and integrated discrimination improvement 0.10, 95% CI 0.04-0.16, P < 0.001).In AF, EAT thickness was useful in predicting adverse CV events. Additionally, EAT thickness could provide incremental value for CV outcome prediction over traditional clinical and echocardiographic parameters in AF. PMID:26986099

  9. LUPUS ANTICOAGULANT, BUT NOT ANTICARDIOLIPIN ANTIBODY, PREDICTS ADVERSE PREGNANCY OUTCOME IN PATIENTS WITH ANTIPHOSPHOLIPID ANTIBODIES

    PubMed Central

    Lockshin, Michael D.; Kim, Mimi; Laskin, Carl A.; Guerra, Marta; Branch, D. Ware; Merrill, Joan; Petri, Michelle; Porter, Flint; Sammaritano, Lisa; Stephenson, Mary D.; Buyon, Jill; Salmon, Jane E.

    2012-01-01

    BACKGROUND Which serologic and clinical findings predict adverse pregnancy outcome (APO) in patients with antiphospholipid antibody (aPL) is controversial. METHODS PROMISSE is a multicenter, prospective observational study of risk factors for APO in patients with aPL (lupus anticoagulant [LAC], anticardiolipin antibody [aCL] and/or antibody to β2 glycoprotein I [anti-β2-GP-I]). We tested the hypothesis that a pattern of clinical and serological variables can identify women at highest risk for APO. RESULTS Between 2003 and 2011 we enrolled 144 pregnant patients, of whom 28 had APO. Thirty-nine percent of patients with LAC had APO, compared to 3% who did not have LAC (p < 0.0001). Only 8% of women with IgG aCL ≥40 u/mL but not LAC suffered APO, compared to 43% of those with LAC (p = 0.002). IgM aCL or IgG or IgM anti-β2-GP-I did not predict APO. In bivariate analysis, APO occurred in 52% of patients with and 13% of patients without prior thrombosis (p = 0.00005), and in 23% with SLE compared to 17% without SLE (not significant); SLE was a predictor in multivariate analysis. Prior pregnancy loss did not predict APO, nor did maternal race. Simultaneous aCL, anti-β2-GP-I, and LAC did not predict APO better than did LAC alone. CONCLUSIONS LAC is the primary predictor of APO after 12 weeks gestation in aPL-associated pregnancies. ACL and anti-β2-GP-I, if LAC is not also present, do not predict APO. PMID:22275304

  10. Reverse Engineering Adverse Outcome Pathways

    SciTech Connect

    Perkins, Edward; Chipman, J.K.; Edwards, Stephen; Habib, Tanwir; Falciani, Francesco; Taylor, Ronald C.; Van Aggelen, Graham; Vulpe, Chris; Antczak, Philipp; Loguinov, Alexandre

    2011-01-30

    The toxicological effects of many stressors are mediated through unknown, or poorly characterized, mechanisms of action. We describe the application of reverse engineering complex interaction networks from high dimensional omics data (gene, protein, metabolic, signaling) to characterize adverse outcome pathways (AOPs) for chemicals that disrupt the hypothalamus-pituitary-gonadal endocrine axis in fathead minnows. Gene expression changes in fathead minnow ovaries in response to 7 different chemicals, over different times, doses, and in vivo versus in vitro conditions were captured in a large data set of 868 arrays. We examined potential AOPs of the antiandrogen flutamide using two mutual information theory methods, ARACNE and CLR to infer gene regulatory networks and potential adverse outcome pathways. Representative networks from these studies were used to predict a network path from stressor to adverse outcome as a candidate AOP. The relationship of individual chemicals to an adverse outcome can be determined by following perturbations through the network in response to chemical treatment leading to the nodes associated with the adverse outcome. Identification of candidate pathways allows for formation of testable hypotheses about key biologic processes, biomarkers or alternative endpoints, which could be used to monitor an adverse outcome pathway. Finally, we identify the unique challenges facing the application of this approach in ecotoxicology, and attempt to provide a road map for the utilization of these tools. Key Words: mechanism of action, toxicology, microarray, network inference

  11. Using patient safety indicators to estimate the impact of potential adverse events on outcomes.

    PubMed

    Rivard, Peter E; Luther, Stephen L; Christiansen, Cindy L; Shibei Zhao; Loveland, Susan; Elixhauser, Anne; Romano, Patrick S; Rosen, Amy K

    2008-02-01

    The authors estimated the impact of potentially preventable patient safety events, identified by Agency for Healthcare Research and Quality (AHRQ) Patient Safety Indicators (PSIs), on patient outcomes: mortality, length of stay (LOS), and cost. The PSIs were applied to all acute inpatient hospitalizations at Veterans Health Administration (VA) facilities in fiscal 2001. Two methods-regression analysis and multivariable case matching- were used independently to control for patient and facility characteristics while predicting the effect of the PSI on each outcome. The authors found statistically significant (p < .0001) excess mortality, LOS, and cost in all groups with PSIs. The magnitude of the excess varied considerably across the PSIs. These VA findings are similar to those from a previously published study of nonfederal hospitals, despite differences between VA and non-VA systems. This study contributes to the literature measuring outcomes of medical errors and provides evidence that AHRQ PSIs may be useful indicators for comparison across delivery systems. PMID:18184870

  12. Adverse Outcomes after Major Surgery in Patients with Pressure Ulcer: A Nationwide Population-Based Retrospective Cohort Study

    PubMed Central

    Chou, Chia-Lun; Lee, Woan-Ruoh; Yeh, Chun-Chieh; Shih, Chun-Chuan

    2015-01-01

    Background Postoperative adverse outcomes in patients with pressure ulcer are not completely understood. This study evaluated the association between preoperative pressure ulcer and adverse events after major surgeries. Methods Using reimbursement claims from Taiwan’s National Health Insurance Research Database, we conducted a nationwide retrospective cohort study of 17391 patients with preoperative pressure ulcer receiving major surgery in 2008-2010. With a propensity score matching procedure, 17391 surgical patients without pressure ulcer were selected for comparison. Eight major surgical postoperative complications and 30-day postoperative mortality were evaluated among patients with pressure ulcer of varying severity. Results Patients with preoperative pressure ulcer had significantly higher risk than controls for postoperative adverse outcomes, including septicemia, pneumonia, stroke, urinary tract infection, and acute renal failure. Surgical patients with pressure ulcer had approximately 1.83-fold risk (95% confidence interval 1.54-2.18) of 30-day postoperative mortality compared with control group. The most significant postoperative mortality was found in those with serious pressure ulcer, such as pressure ulcer with local infection, cellulitis, wound or treatment by change dressing, hospitalized care, debridement or antibiotics. Prolonged hospital or intensive care unit stay and increased medical expenditures were also associated with preoperative pressure ulcer. Conclusion This nationwide propensity score-matched retrospective cohort study showed increased postoperative complications and mortality in patients with preoperative pressure ulcer. Our findings suggest the urgency of preventing and managing preoperative pressure ulcer by a multidisciplinary medical team for this specific population. PMID:26000606

  13. Adverse Outcomes after Non-Chest Surgeries in Patients with Pulmonary Tuberculosis: A Nationwide Study

    PubMed Central

    Lin, Chao-Shun; Yeh, Chun-Chieh; Chung, Chi-Li; Hung, Chih-Jen; Chen, Ta-Liang

    2015-01-01

    Background The association between pulmonary tuberculosis (TB) and postoperative outcomes remains unknown. This study investigated outcomes following non-chest surgeries in patients with previous pulmonary TB. Methods Using Taiwan’s National Health Insurance Research Database, we analyzed 6911 patients (aged ≥ 20 years) with preoperative diagnosis of pulmonary TB and 6911 propensity score-matched controls receiving non-chest surgeries in 2008–2010. Postoperative outcomes were compared between patients with or without pulmonary TB by calculating adjusted odds ratios (ORs) and 95% confidence intervals (CIs) in the multivariate logistic regressions. Results Surgical patients with pulmonary TB had a significantly higher postoperative complication rates than controls, including septicemia, pneumonia, acute renal failure, deep wound infection, overall complications, and 30-day postoperative mortality (OR 1.41; 95% CI 1.07–1.86). The ORs of patients with low-income status were as high as 2.27 (95% CI 1.03–5.03). Preoperative use of TB drugs and TB-related medical expenditure also associated with higher postoperative mortality among surgical patients with pulmonary TB. Conclusions Surgical patients with pulmonary TB have significantly increased risks of postoperative complications and mortality after non-chest surgeries. This study suggests the need to improve postoperative care for surgical patients with pulmonary TB. PMID:26172153

  14. Adverse Symptom Event Reporting by Patients vs Clinicians: Relationships With Clinical Outcomes

    PubMed Central

    Jia, Xiaoyu; Heller, Glenn; Barz, Allison; Sit, Laura; Fruscione, Michael; Appawu, Mark; Iasonos, Alexia; Atkinson, Thomas; Goldfarb, Shari; Culkin, Ann; Kris, Mark G.; Schrag, Deborah

    2009-01-01

    Background In cancer treatment trials, the standard source of adverse symptom data is clinician reporting by use of items from the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE). Patient self-reporting has been proposed as an additional data source, but the implications of such a shift are not understood. Methods Patients with lung cancer receiving chemotherapy and their clinicians independently reported six CTCAE symptoms and Karnofsky Performance Status longitudinally at sequential office visits. To compare how patient's vs clinician's reports relate to sentinel clinical events, a time-dependent Cox regression model was used to measure associations between reaching particular CTCAE grade severity thresholds with the risk of death and emergency room visits. To measure concordance of CTCAE reports with indices of daily health status, Kendall tau rank correlation coefficients were calculated for each symptom with EuroQoL EQ-5D questionnaire and global question scores. Statistical tests were two-sided. Results A total of 163 patients were enrolled for an average of 12 months (range = 1–28 months), with a mean of 11 visits and 67 (41%) deaths. CTCAE reports were submitted by clinicians at 95% of visits and by patients at 80% of visits. Patients generally reported symptoms earlier and more frequently than clinicians. Statistically significant associations with death and emergency room admissions were seen for clinician reports of fatigue (P < .001), nausea (P = .01), constipation (P = .038), and Karnofsky Performance Status (P < .001) but not for patient reports of these items. Higher concordance with EuroQoL EQ-5D questionnaire and global question scores was observed for patient-reported symptoms than for clinician-reported symptoms. Conclusions Longitudinally collected clinician CTCAE assessments better predict unfavorable clinical events, whereas patient reports better reflect daily health status. These perspectives are

  15. Statin therapy and long-term adverse limb outcomes in patients with peripheral artery disease: insights from the REACH registry

    PubMed Central

    Kumbhani, Dharam J.; Steg, Ph. Gabriel; Cannon, Christopher P.; Eagle, Kim A.; Smith, Sidney C.; Goto, Shinya; Ohman, E. Magnus; Elbez, Yedid; Sritara, Piyamitr; Baumgartner, Iris; Banerjee, Subhash; Creager, Mark A.; Bhatt, Deepak L.

    2014-01-01

    Aims Due to a high burden of systemic cardiovascular events, current guidelines recommend the use of statins in all patients with peripheral artery disease (PAD). We sought to study the impact of statin use on limb prognosis in patients with symptomatic PAD enrolled in the international REACH registry. Methods Statin use was assessed at study enrolment, as well as a time-varying covariate. Rates of the primary adverse limb outcome (worsening claudication/new episode of critical limb ischaemia, new percutaneous/surgical revascularization, or amputation) at 4 years and the composite of cardiovascular death/myocardial infarction/stroke were compared among statin users vs. non-users. Results A total of 5861 patients with symptomatic PAD were included. Statin use at baseline was 62.2%. Patients who were on statins had a significantly lower risk of the primary adverse limb outcome at 4 years when compared with those who were not taking statins [22.0 vs. 26.2%; hazard ratio (HR), 0.82; 95% confidence interval (CI), 0.72–0.92; P = 0.0013]. Results were similar when statin use was considered as a time-dependent variable (P = 0.018) and on propensity analysis (P < 0.0001). The composite of cardiovascular death/myocardial infarction/stroke was similarly reduced (HR, 0.83; 95% CI, 0.73–0.96; P = 0.01). Conclusion Among patients with PAD in the REACH registry, statin use was associated with an ∼18% lower rate of adverse limb outcomes, including worsening symptoms, peripheral revascularization, and ischaemic amputations. These findings suggest that statin therapy not only reduces the risk of adverse cardiovascular events, but also favourably affects limb prognosis in patients with PAD. PMID:24585266

  16. Collateral Adverse Outcomes After Lumbar Spine Surgery.

    PubMed

    Daniels, Alan H; Gundle, Kenneth; Hart, Robert A

    2016-01-01

    Collateral adverse outcomes are the expected or unavoidable results of a procedure that is performed in a standard manner and typically experienced by the patient. Collateral adverse outcomes do not result from errors, nor are they rare. Collateral adverse outcomes occur as the direct result of a surgical procedure and must be accepted as a trade-off to attain the intended benefits of the surgical procedure. As such, collateral adverse outcomes do not fit into the traditional definition of a complication or adverse event. Examples of collateral adverse outcomes after lumbar spine arthrodesis include lumbar stiffness, postoperative psychological stress, postoperative pain, peri-incisional numbness, paraspinal muscle denervation, and adjacent-level degeneration. Ideally, a comparison of interventions for the treatment of a clinical condition should include information on both the negative consequences (expected and unexpected) and potential benefits of the treatment options. The objective evaluation and reporting of collateral adverse outcomes will provide surgeons with a more complete picture of invasive interventions and, thus, the improved ability to assess alternative treatment options. PMID:27049197

  17. Sleep apnoea adversely affects the outcome in patients who undergo posterior lumbar fusion

    PubMed Central

    Stundner, O.; Chiu, Y-L.; Sun, X.; Ramachandran, S-K.; Gerner, P.; Vougioukas, V.; Mazumdar, M.; Memtsoudis, S. G.

    2014-01-01

    Despite the increasing prevalence of sleep apnoea, little information is available regarding its impact on the peri-operative outcome of patients undergoing posterior lumbar fusion. Using a national database, patients who underwent lumbar fusion between 2006 and 2010 were identified, sub-grouped by diagnosis of sleep apnoea and compared. The impact of sleep apnoea on various outcome measures was assessed by regression analysis. The records of 84 655 patients undergoing posterior lumbar fusion were identified and 7.28% also had a diagnostic code for sleep apnoea. Compared with patients without sleep apnoea, these patients were older, more frequently female, had a higher comorbidity burden and higher rates of peri-operative complications, post-operative mechanical ventilation, blood transfusion, and intensive care. Patients with sleep apnoea also had longer and more costly periods of hospitalisation. In the regression analysis, sleep apnoea emerged as an independent risk factor for the development of peri-operative complications (Odds Ratio (OR) 1.50, Confidence Interval (CI) 1.38;1.62), blood transfusions (OR 1.12, CI 1.03;1.23), mechanical ventilation (OR 6.97, CI 5.90;8.23), critical care services (OR 1.86, CI 1.71;2.03), prolonged hospitalisation and increased cost (OR 1.28, CI 1.19;1.37; OR 1.10, CI 1.03;1.18). Patients with sleep apnoea who undergo posterior lumbar fusion pose significant challenges to clinicians. PMID:24493191

  18. An Elevated Glycemic Gap is Associated with Adverse Outcomes in Diabetic Patients with Acute Myocardial Infarction.

    PubMed

    Liao, Wen-I; Lin, Chin-Sheng; Lee, Chien-Hsing; Wu, Ya-Chieh; Chang, Wei-Chou; Hsu, Chin-Wang; Wang, Jen-Chun; Tsai, Shih-Hung

    2016-01-01

    Acute hyperglycemia is a frequent finding in patients presenting to the emergency department (ED) with acute myocardial infarction (AMI). The prognostic role of hyperglycemia in diabetic patients with AMI remains controversial. We retrospectively reviewed patients' medical records to obtain demographic data, clinical presentation, major adverse cardiac events (MACEs), several clinical scores and laboratory data, including the plasma glucose level at initial presentation and HbA1c levels. The glycemic gap, which represents changes in serum glucose levels during the index event, was calculated from the glucose level upon ED admission minus the HbA1c-derived average glucose (ADAG). We enrolled 331 patients after the review of medical records. An elevated glycemic gap between admission serum glucose levels and ADAG were associated with an increased risk of mortality in patients. The glycemic gap showed superior discriminative power regarding the development of MACEs when compared with the admission glucose level. The calculation of the glycemic gap may increase the discriminative powers of established clinical scoring systems in diabetic patients presenting to the ED with AMI. In conclusion, the glycemic gap could be used as an adjunct parameter to assess the severity and prognosis of diabetic patients presenting with AMI. However, the usefulness of the glycemic gap should be further explored in prospective longitudinal studies. PMID:27291987

  19. Management of patients with chronic lymphocytic leukemia with a high risk of adverse outcome: the Mayo Clinic approach

    PubMed Central

    ZENT, CLIVE S.; KAY, NEIL E.

    2012-01-01

    Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) is usually an incidental diagnosis in patients with early–intermediate stage disease. However, most patients with a diagnosis of CLL will subsequently have significant morbidity and die from their disease and its complications. For these patients, CLL is not the ‘good leukemia’ with a predictably ‘benign’ outcome. Indeed, we can now identify a cohort of patients with high-risk CLL at diagnosis who will have rapid disease progression, poor response to treatment, and poor survival based on prognostic methods developed from an improved understanding of the biology of CLL. The concomitant development of improved treatments has led to risk-adjusted management approaches that could improve outcomes. We discuss the clinical and laboratory components of comprehensive risk evaluation of patients with CLL and our approach to the management of patients with a high to very high risk of disease progression and poor outcome. In addition, we review the challenges and prospects for improving prognostic precision and the development of new drugs to improve the treatment of patients with CLL with a high risk of adverse outcome. PMID:21649549

  20. An Elevated Glycemic Gap is Associated with Adverse Outcomes in Diabetic Patients with Acute Myocardial Infarction

    PubMed Central

    Liao, Wen-I; Lin, Chin-Sheng; Lee, Chien-Hsing; Wu, Ya-Chieh; Chang, Wei-Chou; Hsu, Chin-Wang; Wang, Jen-Chun; Tsai, Shih-Hung

    2016-01-01

    Acute hyperglycemia is a frequent finding in patients presenting to the emergency department (ED) with acute myocardial infarction (AMI). The prognostic role of hyperglycemia in diabetic patients with AMI remains controversial. We retrospectively reviewed patients’ medical records to obtain demographic data, clinical presentation, major adverse cardiac events (MACEs), several clinical scores and laboratory data, including the plasma glucose level at initial presentation and HbA1c levels. The glycemic gap, which represents changes in serum glucose levels during the index event, was calculated from the glucose level upon ED admission minus the HbA1c-derived average glucose (ADAG). We enrolled 331 patients after the review of medical records. An elevated glycemic gap between admission serum glucose levels and ADAG were associated with an increased risk of mortality in patients. The glycemic gap showed superior discriminative power regarding the development of MACEs when compared with the admission glucose level. The calculation of the glycemic gap may increase the discriminative powers of established clinical scoring systems in diabetic patients presenting to the ED with AMI. In conclusion, the glycemic gap could be used as an adjunct parameter to assess the severity and prognosis of diabetic patients presenting with AMI. However, the usefulness of the glycemic gap should be further explored in prospective longitudinal studies. PMID:27291987

  1. Low Plasma α-Tocopherol Concentrations and Adverse Clinical Outcomes in Diabetic Hemodialysis Patients

    PubMed Central

    Espe, Katharina M.; Raila, Jens; Henze, Andrea; Blouin, Katja; Schneider, Andreas; Schmiedeke, Daniel; Krane, Vera; Pilz, Stefan; Schweigert, Florian J.; Hocher, Berthold; Wanner, Christoph

    2013-01-01

    Summary Background and objectives Trials with the antioxidant vitamin E have failed to show benefit in the general population. Considering the different causes of death in ESRD, this study investigated the association between plasma concentrations of α-tocopherol and specific clinical outcomes in diabetic hemodialysis patients. Design, settings, participants, & measurements In 1046 diabetic hemodialysis patients (participants of the German Diabetes and Dialysis Study), α-tocopherol was measured in plasma by reversed-phase HPLC. By Cox regression analyses, hazard ratios were determined for prespecified end points according to baseline plasma α-tocopherol levels: sudden death (n=134), myocardial infarction (n=172), stroke (n=89), combined cardiovascular events (n=398), fatal infection (n=107), and all-cause mortality (n=508). Results Patients had a mean age of 66±8 years, and mean plasma α-tocopherol level was 22.8±9.6 µmol/L. Levels of α-tocopherol were highly correlated to triglycerides (r=0.63, P<0.001). Patients in the lowest α-tocopherol quartile had (in unadjusted analyses) a 79% higher risk of stroke and a 31% higher risk of all-cause mortality compared with patients in the highest quartile. The associations were attenuated after adjustment for confounders (hazard ratiostroke=1.56, 95% confidence interval=0.75–3.25; hazard ratiomortality=1.22, 95% confidence interval=0.89–1.69, respectively). There was no association between α-tocopherol and myocardial infarction, sudden death, or infectious death. Conclusions Plasma α-tocopherol concentrations were not independently associated with cardiovascular outcomes, infectious deaths, or all-cause mortality in diabetic hemodialysis patients. The lack of association can partly be explained by a confounding influence of malnutrition, which should be considered in the planning of trials to reduce cardiovascular risk in dialysis patients. PMID:23335039

  2. Clinical Characteristics and Predictors of Adverse Outcome in Adult and Pediatric Patients With Healthcare-Associated Ventriculitis and Meningitis

    PubMed Central

    Srihawan, Chanunya; Castelblanco, Rodrigo Lopez; Salazar, Lucrecia; Wootton, Susan H.; Aguilera, Elizabeth; Ostrosky-Zeichner, Luis; Sandberg, David I.; Choi, HuiMahn A.; Lee, Kiwon; Kitigawa, Ryan; Tandon, Nitin; Hasbun, Rodrigo

    2016-01-01

    Background. Healthcare-associated meningitis or ventriculitis is a serious and life-threatening complication of invasive neurosurgical procedures or penetrating head trauma. Methods. We performed a retrospective study of adults and children with the diagnosis of healthcare-associated meningitis or ventriculitis, as defined by the 2015 Centers of Disease Control and Prevention case definition, at 2 large tertiary care hospitals in Houston, Texas from July 2003 to November 2014. Patients were identified by infection control practitioners and by screening cerebrospinal fluid samples sent to the central laboratory. We collected data on demographics, clinical presentations, laboratory results, imaging studies, treatments, and outcomes. Results. A total of 215 patients were included (166 adults and 49 children). A positive cerebrospinal fluid culture was seen in 106 (49%) patients, with the majority of the etiologies being Staphylococcus and Gram-negative rods. An adverse clinical outcome was seen in 167 patients (77.7%) and was defined as death in 20 patients (9.3%), persistent vegetative state in 31 patients (14.4%), severe disability in 77 patients (35.8%), or moderate disability in 39 patients (18.1%). On logistic regression analysis, age >45 years (adjusted odds ratio [OR], 6.47; 95% confidence interval [CI], 2.31–18.11; P ≤ .001), abnormal neurological exam (adjusted OR, 3.04; 95% CI, 1.27–7.29; P = .013), and mechanical ventilation (adjusted OR, 5.34; 95% CI, 1.51–18.92; P = .01) were associated with an adverse outcome. Conclusions. Healthcare-associated meningitis or ventriculitis is associated with significant morbidity and mortality. PMID:27419154

  3. Left Atrial Volume and Adverse Cardiovascular Outcomes in Unselected Patients with and without CKD

    PubMed Central

    Hee, Leia; Nguyen, Tuan; Whatmough, Melinda; Descallar, Joseph; Chen, Jack; Kapila, Shruti; French, John K.

    2014-01-01

    Background and objectives Patients with CKD have increased cardiovascular morbidity and mortality. This study investigated the prognostic value of common clinical echocardiographic parameters. Design, setting, participants, & measurements There were 289 unselected consecutive patients who had a transthoracic echocardiogram between January and June 2003. Patients with stage 3 or 4 CKD (n=49) were compared with those with eGFR≥60 ml/min per 1.73 m2, n=240). Left ventricular volume, ejection fraction and mass, left atrial volume, and function parameters were measured. The primary endpoint, determined a priori, was a composite of cardiac death, myocardial infarction, and congestive cardiac failure. Results Patients were followed for a median 5.6 years. The incidence of the primary endpoint was higher in patients with CKD (29% versus 12%, P=0.001), who were older and had a higher prevalence of hypertension and ischemic heart disease. Indexed left ventricular mass (LVMI) and left atrial volume (LAVI) were higher in patients with CKD. Furthermore, patients with LAVI>32 ml/m2 had significantly lower event-free survival than patients with normal (<28 ml/m2) or mildly dilated LAVI (28–32 ml/m2) (P<0.001). Multivariate analysis showed that age (odds ratio [OR], 1.19; 95% confidence interval [95% CI], 1.08 to 1.31; P=0.001) and LVMI (OR, 3.66; 95% CI, 2.47 to 5.41; P<0.001) were independently associated with LAVI>32 ml/m2. Multivariate Cox regression analysis demonstrated that CKD (hazard ratio [HR], 1.13; 95% CI, 1.01 to 1.26; P=0.04), hypertension (HR, 2.18; 95% CI, 1.05 to 4.54; P=0.04), and a larger LAVI (HR, 1.35; 95% CI, 1.02 to 1.77; P=0.04) were independent predictors of the primary endpoint. Conclusions Patients with CKD were at higher risk for cardiovascular events. LAVI was significantly larger in the CKD group and was a predictor of adverse cardiac events. PMID:24923578

  4. The effect of obesity on adverse outcomes and metabolism in pediatric burn patients

    PubMed Central

    Kraft, Robert; Herndon, David N.; Williams, Felicia N.; Al-Mousawi, Ahmed M; Finnerty, Celeste C.; Jeschke, Marc G

    2011-01-01

    Hypothesis Obesity influences metabolism and increases the incidence of clinical complications and worsens outcomes in pediatric burn patients. Design Retrospective, single-center study. Subjects Five hundred ninety-two severely burned pediatric patients who had burns covering more than 30% of the total body surface area and who were treated between 2001 and 2008 were enrolled in this study. Patients were divided into ≥ 85th percentile (n = 277) and normal (n = 315) weight groups based on body mass index percentiles. Results Patients stratified below (normal) and ≥ 85th percentile had similar age, gender distribution, and total burn size. No significant differences were detected in the incidence of sepsis (11% for obese vs. 10% for normal), the incidence of multiple organ failure (21% for obese and 16% for normal), or mortality (11% for obese vs. 8% for normal). Compared to the normal group, the ≥ 85th percentile group had low levels of constitutive proteins (α2macroglobulin and Apolipoprotein A-1) (p < 0.05 for both) as well as high levels of triglycerides and the acute-phase protein, C-reactive protein (p < 0.05 for both) up to 60 days after injury. Patients ≥ 85th percentile showed a significant higher loss of bone mineral density and lipolysis compared to normal individuals. Stepwise logistic regression analysis revealed that body mass index had a positive predictive value towards the maximum DENVER2 score, an index of organ failure (p < 0.001). Conclusions BMI ≥ 85th percentile altered the post-burn acute phase and catabolic response but did not increase the incidence of sepsis, multiple organ failure, or mortality in pediatric burn patients. Our results suggest that impaired metabolism and an altered inflammatory response occurs already in patients starting at the 85th percentile BMI. PMID:22143622

  5. Patient-Reported Outcomes in Cancer Clinical Trials: Measuring Symptomatic Adverse Events With the National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

    PubMed

    Kluetz, Paul G; Chingos, Diana T; Basch, Ethan M; Mitchell, Sandra A

    2016-01-01

    Systematic capture of the patient perspective can inform the development of new cancer therapies. Patient-reported outcomes (PROs) are commonly included in cancer clinical trials; however, there is heterogeneity in the constructs, measures, and analytic approaches that have been used making these endpoints challenging to interpret. There is renewed effort to identify rigorous methods to obtain high-quality and informative PRO data from cancer clinical trials. In this setting, PROs are used to address specific research objectives, and an important objective that spans the product development life cycle is the assessment of safety and tolerability. The U.S. Food and Drug Administration's (FDA) Office of Hematology and Oncology Products (OHOP) has identified symptomatic adverse events (AEs) as a central PRO concept, and a systematic assessment of patient-reported symptomatic AEs can provide data to complement clinician reporting. The National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) is being evaluated by multiple stakeholders, including the FDA, and is considered a promising tool to provide a standard yet flexible method to assess symptomatic AEs from the patient perspective. In this article, we briefly review the FDA OHOP's perspective on PROs in cancer trials submitted to the FDA and focus on the assessment of symptomatic AEs using PRO-CTCAE. We conclude by discussing further work that must be done to broaden the use of PRO-CTCAE as a method to provide patient-centered data that can complement existing safety and tolerability assessments across cancer clinical trials. PMID:27249687

  6. Trauma patient adverse outcomes are independently associated with rib cage fracture burden and severity of lung, head, and abdominal injuries

    PubMed Central

    Dunham, C Michael; Hileman, Barbara M; Ransom, Kenneth J; Malik, Rema J

    2015-01-01

    Objective: We hypothesized that lung injury and rib cage fracture quantification would be associated with adverse outcomes. Subjects and methods: Consecutive admissions to a trauma center with Injury Severity Score ≥ 9, age 18-75, and blunt trauma. CT scans were reviewed to score rib and sternal fractures and lung infiltrates. Sternum and each anterior, lateral, and posterior rib fracture was scored 1 = non-displaced and 2 = displaced. Rib cage fracture score (RCFS) = total rib fracture score + sternal fracture score + thoracic spine Abbreviated Injury Score (AIS). Four lung regions (right upper/middle, right lower, left upper, and left lower lobes) were each scored for % of infiltrate: 0% = 0; ≤ 20% = 1, ≤ 50% = 2, > 50% = 3; total of 4 scores = lung infiltrate score (LIS). Results: Of 599 patients, 193 (32%) had 854 rib fractures. Rib fracture patients had more abdominal injuries (p < 0.001), hemo/pneumothorax (p < 0.001), lung infiltrates (p < 0.001), thoracic spine injuries (p = 0.001), sternal fractures (p = 0.0028) and death or need for mechanical ventilation ≥ 3 days (Death/Vdays ≥ 3) (p < 0.001). Death/Vdays ≥ 3 was independently associated with RCFS (p < 0.001), LIS (p < 0.001), head AIS (p < 0.001) and abdominal AIS (p < 0.001). Of the 193 rib fracture patients, Glasgow Coma Score 3-12 or head AIS ≥ 2 occurred in 43%. A lung infiltrate or hemo/pneumothorax occurred in 55%. Thoracic spine injury occurred in 23%. RCFS was 6.3 ± 4.4 and Death/Vdays ≥ 3 occurred in 31%. Death/Vdays ≥ 3 rates correlated with RCFS values: 19% for 1-3; 24% for 4-6; 42% for 7-12 and 65% for ≥ 13 (p < 0.001). Death/Vdays ≥ 3 was independently associated with RCFS (p = 0.02), LIS (p = 0.001), head AIS (p < 0.001) and abdominal AIS (p < 0.001). Death/Vdays ≥ 3 association was better for RCFS (p = 0.005) than rib fracture score (p = 0.08) or number of fractured ribs (p = 0.80). Conclusion: Rib fracture patients have increased risk for truncal injuries and

  7. Dynamical System Modeling of Immune Reconstitution after Allogeneic Stem Cell Transplantation Identifies Patients at Risk for Adverse Outcomes.

    PubMed

    Toor, Amir A; Sabo, Roy T; Roberts, Catherine H; Moore, Bonny L; Salman, Salman R; Scalora, Allison F; Aziz, May T; Shubar Ali, Ali S; Hall, Charles E; Meier, Jeremy; Thorn, Radhika M; Wang, Elaine; Song, Shiyu; Miller, Kristin; Rizzo, Kathryn; Clark, William B; McCarty, John M; Chung, Harold M; Manjili, Masoud H; Neale, Michael C

    2015-07-01

    Systems that evolve over time and follow mathematical laws as they evolve are called dynamical systems. Lymphocyte recovery and clinical outcomes in 41 allograft recipients conditioned using antithymocyte globulin (ATG) and 4.5-Gy total body irradiation were studied to determine if immune reconstitution could be described as a dynamical system. Survival, relapse, and graft-versus-host disease (GVHD) were not significantly different in 2 cohorts of patients receiving different doses of ATG. However, donor-derived CD3(+) cell reconstitution was superior in the lower ATG dose cohort, and there were fewer instances of donor lymphocyte infusion (DLI). Lymphoid recovery was plotted in each individual over time and demonstrated 1 of 3 sigmoid growth patterns: Pattern A (n = 15) had rapid growth with high lymphocyte counts, pattern B (n = 14) had slower growth with intermediate recovery, and pattern C (n = 10) had poor lymphocyte reconstitution. There was a significant association between lymphocyte recovery patterns and both the rate of change of donor-derived CD3(+) at day 30 after stem cell transplantation (SCT) and clinical outcomes. GVHD was observed more frequently with pattern A, relapse and DLI more so with pattern C, with a consequent survival advantage in patients with patterns A and B. We conclude that evaluating immune reconstitution after SCT as a dynamical system may differentiate patients at risk of adverse outcomes and allow early intervention to modulate that risk. PMID:25849208

  8. Dynamical System Modeling of Immune Reconstitution after Allogeneic Stem Cell Transplantation Identifies Patients at Risk for Adverse Outcomes

    PubMed Central

    Toor, Amir A.; Sabo, Roy T.; Roberts, Catherine H.; Moore, Bonny L.; Salman, Salman R.; Scalora, Allison F.; Aziz, May T.; Shubar Ali, Ali S.; Hall, Charles E.; Meier, Jeremy; Thorn, Radhika M.; Wang, Elaine; Song, Shiyu; Miller, Kristin; Rizzo, Kathryn; Clark, William B.; McCarty, John M.; Chung, Harold M.; Manjili, Masoud H.; Neale, Michael C.

    2016-01-01

    Systems that evolve over time and follow mathematical laws as they evolve are called dynamical systems. Lymphocyte recovery and clinical outcomes in 41 allograft recipients conditioned using antithymocyte globulin (ATG) and 4.5-Gy total body irradiation were studied to determine if immune reconstitution could be described as a dynamical system. Survival, relapse, and graft-versus-host disease (GVHD) were not significantly different in 2 cohorts of patients receiving different doses of ATG. However, donor-derived CD3+ cell reconstitution was superior in the lower ATG dose cohort, and there were fewer instances of donor lymphocyte infusion (DLI). Lymphoid recovery was plotted in each individual over time and demonstrated 1 of 3 sigmoid growth patterns: Pattern A (n = 15) had rapid growth with high lymphocyte counts, pattern B (n = 14) had slower growth with intermediate recovery, and pattern C (n = 10) had poor lymphocyte reconstitution. There was a significant association between lymphocyte recovery patterns and both the rate of change of donor-derived CD3+ at day 30 after stem cell transplantation (SCT) and clinical outcomes. GVHD was observed more frequently with pattern A, relapse and DLI more so with pattern C, with a consequent survival advantage in patients with patterns A and B. We conclude that evaluating immune reconstitution after SCT as a dynamical system may differentiate patients at risk of adverse outcomes and allow early intervention to modulate that risk. PMID:25849208

  9. The sumoylation pathway is dysregulated in multiple myeloma and is associated with adverse patient outcome.

    PubMed

    Driscoll, James J; Pelluru, Dheeraj; Lefkimmiatis, Konstantinos; Fulciniti, Mariateresa; Prabhala, Rao H; Greipp, Philip R; Barlogie, Bart; Tai, Yu-Tzu; Anderson, Kenneth C; Shaughnessy, John D; Annunziata, Christina M; Munshi, Nikhil C

    2010-04-01

    Multiple myeloma (MM) is a plasma cell neoplasm that proceeds through a premalignant state of monoclonal gammopathy of unknown significance; however, the molecular events responsible for myelomagenesis remain uncharacterized. To identify cellular pathways deregulated in MM, we addressed that sumoylation is homologous to ubiquitination and results in the attachment of the ubiquitin-like protein Sumo onto target proteins. Sumoylation was markedly enhanced in MM patient lysates compared with normal plasma cells and expression profiling indicated a relative induction of sumoylation pathway genes. The Sumo-conjugating enzyme Ube2I, the Sumo-ligase PIAS1, and the Sumo-inducer ARF were elevated in MM patient samples and cell lines. Survival correlated with expression because 80% of patients with low UBE2I and PIAS1 were living 6 years after transplantation, whereas only 45% of patients with high expression survived 6 years. UBE2I encodes the sole Sumo-conjugating enzyme in mammalian cells and cells transfected with a dominant-negative sumoylation-deficient UBE2I mutant exhibited decreased survival after radiation exposure, impaired adhesion to bone marrow stroma cell and decreased bone marrow stroma cell-induced proliferation. UBE2I confers cells with multiple advantages to promote tumorigenesis and predicts decreased survival when combined with PIAS1. The sumoylation pathway is a novel therapeutic target with implications for existing proteasomal-based treatment strategies. PMID:19965618

  10. Reduced fractional shortening of right ventricular outflow tract is associated with adverse outcomes in patients with left ventricular dysfunction

    PubMed Central

    2013-01-01

    Background Recent studies suggest the significance of right ventricular (RV) function in the outcome in patients with left ventricular dysfunction (LVSD); however, global assessment of RV remains to be determined by echocardiogram because of its complex geometry. This study aimed to validate RV outflow tract fractional shortening (RVOT-FS) in the evaluation of RV function and its prognostic value in patients with LVSD. Methods This study included eighty-one patients (62 ± 17 years, mean ± SD, male 79%) with reduced LV ejection fraction (LVEF) (≤40%). Two-dimensional echocardiogram of the parasternal short axis view was obtained at the level of the aortic root, and RVOT-FS was calculated as the ratio of end-diastole minus end-systole dimension to end-diastole dimension. Results RVOT-FS ranged from 0.04 to 0.8 (0.3 ± 0.2, mean ± SD), and correlated with LVEF (r = 0.33, p = 0.0028), RV fractional area change (r = 0.37, p = 0.0008) and brain natriuretic peptide level (r = -0.38, p = 0.0005). In Cox multivariate regression analysis, RVOT-FS [hazard ratio (HR) 0.028, 95% confidence interval (CI): 0.002-0.397]; p = 0.008] and New York Heart Association functional class III-IV [HR 2.233, 95% CI: 1.048-4.761]; p = 0.037] were independent factors to predict the events. During a median follow-up period of 319 days (1 to 1862 days), patients with RVOT-FS ≥ 0.2 showed a higher event-free rate than those < 0.2 by Kaplan-Meier analysis (log-rank test, p = 0.0016). Conclusions Our data suggest that RVOT-FS is a simple parameter reflecting the severity of both ventricular function in patients with LVSD. In addition, RVOT-FS might be useful to predict adverse outcomes in such a patient population. PMID:23731725

  11. A systematic review of patient-reported outcome instruments of dermatologic adverse events associated with targeted cancer therapies

    PubMed Central

    Chan, Alexandre; Cameron, Michael C.; Garden, Benjamin; Boers-Doets, Christine B.; Schindler, Katja; Epstein, Joel B.; Choi, Jennifer; Beamer, Laura; Roeland, Eric; Russi, Elvio G.; Bensadoun, René-Jean; Teo, Yi Ling; Chan, Raymond J.; Shih, Vivianne; Bryce, Jane; Raber-Durlacher, Judith; Gerber, Peter Arne; Freytes, César O.; Rapoport, Bernardo; LeBoeuf, Nicole; Sibaud, Vincent; Lacouture, Mario E.

    2016-01-01

    Purpose Dermatologic adverse events (dAE) in cancer treatment are frequent with use of targeted therapies. These dAEs have been shown to have significant impact on health-related quality of life (HRQoL). While standardized assessment tools have been developed for physicians to assess severity of dAEs, there is a discord between objective and subjective measures. The identification of patient-reported outcome (PRO) instruments useful in the context of targeted cancer therapies is therefore important in both the clinical and research settings for the overall evaluation of dAEs and their impact on HRQoL. Methods A comprehensive, systematic literature search of published articles was conducted by two independent reviewers in order to identify PRO instruments previously utilized in patient populations with dAEs from targeted cancer therapies. The identified PRO instruments were studied to determine which HRQoL issues relevant to dAEs were addressed, as well as the process of development and validation of these instruments. Results Thirteen articles identifying six PRO instruments met the inclusion criteria. Four instruments were general dermatology (Skindex-16©, Skindex-29©, Dermatology Life Quality Index [DLQI], and DIELH-24), and two were symptom-specific (Functional Assessment of Cancer Therapy-Epidermal Growth Factor Receptor Inhibitors-18 [FACT-EGFRI-18] and Hand-Foot Syndrome 14 [HFS-14]). Conclusions While there are several PRO instruments that have been tested in the context of targeted cancer therapy, additional work is needed to develop new instruments and to further validate the instruments identified in this study in patients receiving targeted therapies. PMID:25564221

  12. Strategic approaches to adverse outcome pathway development

    EPA Science Inventory

    Adverse outcome pathways (AOPs) are conceptual frameworks for organizing biological and toxicological knowledge in a manner that supports extrapolation of data pertaining to the initiation or early progression of toxicity to an apical adverse outcome that occurs at a level of org...

  13. Adverse Outcome Pathways: From Definition to Application

    EPA Science Inventory

    A challenge for both human health and ecological toxicologists is the transparent application of mechanistic (e.g., molecular, biochemical, histological) data to risk assessments. The adverse outcome pathway (AOP) is a conceptual framework designed to meet this need. Specifical...

  14. RACIAL RESIDENTIAL SEGREGATION AND ADVERSE BIRTH OUTCOMES

    EPA Science Inventory

    INTRODUCTION. The disparity between black and white women's adverse birth outcomes has been subject to much investigation, yet the factors underlying its persistence remain elusive, which has encouraged research on neighborhood-level influences, including racial residential segr...

  15. The complement system and adverse pregnancy outcomes.

    PubMed

    Regal, Jean F; Gilbert, Jeffrey S; Burwick, Richard M

    2015-09-01

    Adverse pregnancy outcomes significantly contribute to morbidity and mortality for mother and child, with lifelong health consequences for both. The innate and adaptive immune system must be regulated to insure survival of the fetal allograft, and the complement system is no exception. An intact complement system optimizes placental development and function and is essential to maintain host defense and fetal survival. Complement regulation is apparent at the placental interface from early pregnancy with some degree of complement activation occurring normally throughout gestation. However, a number of pregnancy complications including early pregnancy loss, fetal growth restriction, hypertensive disorders of pregnancy and preterm birth are associated with excessive or misdirected complement activation, and are more frequent in women with inherited or acquired complement system disorders or complement gene mutations. Clinical studies employing complement biomarkers in plasma and urine implicate dysregulated complement activation in components of each of the adverse pregnancy outcomes. In addition, mechanistic studies in rat and mouse models of adverse pregnancy outcomes address the complement pathways or activation products of importance and allow critical analysis of the pathophysiology. Targeted complement therapeutics are already in use to control adverse pregnancy outcomes in select situations. A clearer understanding of the role of the complement system in both normal pregnancy and complicated or failed pregnancy will allow a rational approach to future therapeutic strategies for manipulating complement with the goal of mitigating adverse pregnancy outcomes, preserving host defense, and improving long term outcomes for both mother and child. PMID:25802092

  16. Stakeholder perspectives on implementing the National Cancer Institute's patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

    PubMed

    Bruner, Deborah Watkins; Hanisch, Laura J; Reeve, Bryce B; Trotti, Andy M; Schrag, Deborah; Sit, Laura; Mendoza, Tito R; Minasian, Lori; O'Mara, Ann; Denicoff, Andrea M; Rowland, Julia H; Montello, Michael; Geoghegan, Cindy; Abernethy, Amy P; Clauser, Steven B; Castro, Kathleen; Mitchell, Sandra A; Burke, Laurie; Trentacosti, Ann Marie; Basch, Ethan M

    2011-03-01

    The National Cancer Institute (NCI) is developing a patient-reported version of its Common Terminology Criteria for Adverse Events, called the "PRO-CTCAE." The PRO-CTCAE consists of a library of patient-reported items which can be administered in clinical trials to directly capture the patient experience of adverse events during cancer treatment, as well as a software platform for administering these items via computer or telephone. In order to better understand the impressions of stakeholders involved in cancer clinical research about the potential value of the PRO-CTCAE approach to capturing adverse event information in clinical research, as well as their perspectives about barriers and strategies for implementing the PRO-CTCAE in NCI-sponsored cancer trials, a survey was conducted. A survey including structured and open-ended questions was developed to elicit perceptions about the use of patient-reported outcomes (PROs) for adverse event reporting, and to explore logistical considerations for implementing the PRO-CTCAE in cancer trials. The survey was distributed electronically and by paper to a convenience sample of leadership and committee members in the NCI's cooperative group network, including principal investigators, clinical investigators, research nurses, data managers, patient advocates, and representatives of the NCI and Food and Drug Administration. Between October, 2008 through February, 2009, 727 surveys were collected. Most respondents (93%) agreed that patient reporting of adverse symptoms would be useful for improving understanding of the patient experience with treatment in cancer trials, and 88%, 80%, and 76%, respectively, endorsed that administration of PRO-CTCAE items in clinical trials would improve the completeness, accuracy, and efficiency of symptom data collection. More than three fourths believed that patient reports would be useful for informing treatment dose modifications and towards FDA regulatory evaluation of drugs. Eighty

  17. Immune-related Adverse Events of Dendritic Cell Vaccination Correlate With Immunologic and Clinical Outcome in Stage III and IV Melanoma Patients

    PubMed Central

    Boudewijns, Steve; Westdorp, Harm; Koornstra, Rutger H.T.; Aarntzen, Erik H.J.G.; Schreibelt, Gerty; Creemers, Jeroen H.A.; Punt, Cornelis J.A.; Figdor, Carl G.; Gerritsen, Winald R.; Bol, Kalijn F.

    2016-01-01

    The purpose of this study was to determine the toxicity profile of dendritic cell (DC) vaccination in stage III and IV melanoma patients, and to evaluate whether there is a correlation between side effects and immunologic and clinical outcome. This is a retrospective analysis of 82 stage III and 137 stage IV melanoma patients, vaccinated with monocyte-derived or naturally circulating autologous DCs loaded with tumor-associated antigens gp100 and tyrosinase. Median follow-up time was 54.3 months in stage III patients and 12.9 months in stage IV patients. Treatment-related adverse events occurred in 84% of patients; grade 3 toxicity was present in 3% of patients. Most common adverse events were flu-like symptoms (67%) and injection site reactions (50%), and both correlated with the presence of tetramer-positive CD8+ T cells (both P<0.001). In stage III melanoma patients experiencing flu-like symptoms, median overall survival (OS) was not reached versus 32.3 months in patients without flu-like symptoms (P=0.009); median OS in patients with an injection site reaction was not reached versus 53.7 months in patients without an injection site reaction (P<0.05). In stage IV melanoma patients (primary uveal and mucosal melanomas excluded), median OS in patients with or without flu-like symptoms was 13.1 versus 8.9 months, respectively (P=0.03); median OS in patients with an injection site reaction was 15.7 months versus 9.8 months in patients without an injection site reaction (P=0.003). In conclusion, DC vaccination is safe and tolerable and the occurrence of the immune-related side effects, such as flu-like symptoms and injection site reactions, correlates with immunologic and clinical outcome. PMID:27227325

  18. Immune-related Adverse Events of Dendritic Cell Vaccination Correlate With Immunologic and Clinical Outcome in Stage III and IV Melanoma Patients.

    PubMed

    Boudewijns, Steve; Westdorp, Harm; Koornstra, Rutger H T; Aarntzen, Erik H J G; Schreibelt, Gerty; Creemers, Jeroen H A; Punt, Cornelis J A; Figdor, Carl G; de Vries, I Jolanda M; Gerritsen, Winald R; Bol, Kalijn F

    2016-01-01

    The purpose of this study was to determine the toxicity profile of dendritic cell (DC) vaccination in stage III and IV melanoma patients, and to evaluate whether there is a correlation between side effects and immunologic and clinical outcome. This is a retrospective analysis of 82 stage III and 137 stage IV melanoma patients, vaccinated with monocyte-derived or naturally circulating autologous DCs loaded with tumor-associated antigens gp100 and tyrosinase. Median follow-up time was 54.3 months in stage III patients and 12.9 months in stage IV patients. Treatment-related adverse events occurred in 84% of patients; grade 3 toxicity was present in 3% of patients. Most common adverse events were flu-like symptoms (67%) and injection site reactions (50%), and both correlated with the presence of tetramer-positive CD8 T cells (both P<0.001). In stage III melanoma patients experiencing flu-like symptoms, median overall survival (OS) was not reached versus 32.3 months in patients without flu-like symptoms (P=0.009); median OS in patients with an injection site reaction was not reached versus 53.7 months in patients without an injection site reaction (P<0.05). In stage IV melanoma patients (primary uveal and mucosal melanomas excluded), median OS in patients with or without flu-like symptoms was 13.1 versus 8.9 months, respectively (P=0.03); median OS in patients with an injection site reaction was 15.7 months versus 9.8 months in patients without an injection site reaction (P=0.003). In conclusion, DC vaccination is safe and tolerable and the occurrence of the immune-related side effects, such as flu-like symptoms and injection site reactions, correlates with immunologic and clinical outcome. PMID:27227325

  19. The adverse outcome pathway knowledge base

    EPA Science Inventory

    The rapid advancement of the Adverse Outcome Pathway (AOP) framework has been paralleled by the development of tools to store, analyse, and explore AOPs. The AOP Knowledge Base (AOP-KB) project has brought three independently developed platforms (Effectopedia, AOP-Wiki, and AOP-X...

  20. Adverse outcome pathway (AOP) development and evaluation

    EPA Science Inventory

    The Adverse Outcome Pathway provides a construct for assembling mechanistic information at different levels of biological organization in a form designed to support regulatory decision making. In particular, it frames the link between molecular and cellular events that can be mea...

  1. Prognostic Utility of Neutrophil-to-Lymphocyte Ratio on Adverse Clinical Outcomes in Patients with Severe Calcific Aortic Stenosis

    PubMed Central

    Cho, Kyoung Im; Cho, Sang Hoon; Her, Ae-Young; Singh, Gillian Balbir; Shin, Eun-Seok

    2016-01-01

    Background Inflammation is an important factor in the pathogenesis of calcific aortic stenosis (AS). We aimed to evaluate the association between an inflammatory marker, neutrophil-to-lymphocyte ratio (NLR) and major adverse cardiovascular events (MACE) in patients with severe calcific AS. Methods A total of 336 patients with isolated severe calcific AS newly diagnosed between 2010 and 2015 were enrolled in this study. Using Cox proportional hazards (PH) regression models, we investigated the prognostic value of NLR adjusted for baseline covariates including logistic European System for Cardiac Operative Risk Evaluation score (EuroSCORE-I) and undergoing aortic valve replacement (AVR). We also evaluated the clinical relevance of NLR risk groups (divided into low, intermediate, high risk) as categorized by NLR cutoff values. MACE was defined as a composite of all-cause mortality, cardiac death and non-fatal myocardial infarction during the follow-up period. Results The inflammatory marker NLR was an independent prognostic factor most significantly associated with MACE [hazard ratio (HR), 1.06; 95% confidence interval (CI), 1.04–1.09; p-value <0.001]. The goodness-of-fit and discriminability of the model including EuroSCORE-I and AVR (loglikelihood difference, 15.49; p-value <0.001; c-index difference, 0.035; p-value = 0.03) were significantly improved when NLR was incorporated into the model. The estimated Kaplan-Meier survival rates at 5 years for the NLR risk groups were 84.6% for the low risk group (NLR ≤ 2), 67.7% for the intermediate risk group (2 < NLR ≤ 9), and 42.6% for the high risk group (NLR > 9), respectively. Conclusion The findings of the present study demonstrate the potential utility of NLR in risk stratification of patients with severe calcific AS. PMID:27548384

  2. Drug-Associated Adverse Events and Their Relationship with Outcomes in Patients Receiving Treatment for Extensively Drug-Resistant Tuberculosis in South Africa

    PubMed Central

    Shean, Karen; Streicher, Elizabeth; Pieterson, Elize; Symons, Greg; van Zyl Smit, Richard; Theron, Grant; Lehloenya, Rannakoe; Padanilam, Xavier; Wilcox, Paul; Victor, Tommie C.; van Helden, Paul; Groubusch, Martin; Warren, Robin; Badri, Motasim; Dheda, Keertan

    2013-01-01

    Background Treatment-related outcomes in patients with extensively drug-resistant tuberculosis (XDR-TB) are poor. However, data about the type, frequency and severity of presumed drug-associated adverse events (AEs) and their association with treatment-related outcomes in patients with XDR-TB are scarce. Methods Case records of 115 South-African XDR-TB patients were retrospectively reviewed by a trained researcher. AEs were estimated and graded according to severity [grade 0 = none; grade 1–2 = mild to moderate; and grade 3–5 = severe (drug stopped, life-threatening or death)]. Findings 161 AEs were experienced by 67/115(58%) patients: 23/67(34%) required modification of treatment, the offending drug was discontinued in 19/67(28%), reactions were life-threatening in 2/67(3.0%), and 6/67(9.0%) died. ∼50% of the patients were still on treatment at the time of data capture. Sputum culture-conversion was less likely in those with severe (grade 3–5) vs. grade 0–2 AEs [2/27(7%) vs. 24/88(27%); p = 0.02]. The type, frequency and severity of AEs was similar in HIV-infected and uninfected patients. Capreomycin, which was empirically administered in most cases, was withdrawn in 14/104(14%) patients, implicated in (14/34) 41% of the total drug withdrawals, and was associated with all 6 deaths in the severe AE group (renal failure in five patients and hypokalemia in one patient). Conclusion Drug-associated AEs occur commonly with XDR-TB treatment, are often severe, frequently interrupt therapy, and negatively impact on culture conversion outcomes. These preliminary data inform on the need for standardised strategies (including pre-treatment counselling, early detection, monitoring, and follow-up) and less toxic drugs to optimally manage patients with XDR-TB. PMID:23667572

  3. Creatinine clearance and adverse hospital outcomes in patients with acute coronary syndromes: findings from the global registry of acute coronary events (GRACE)

    PubMed Central

    Santopinto, J J; Fox, K A A; Goldberg, R J; Budaj, A; Piñero, G; Avezum, A; Gulba, D; Esteban, J; Gore, J M; Johnson, J; Gurfinkel, E P

    2003-01-01

    Objective: To determine whether creatinine clearance at the time of hospital admission is an independent predictor of hospital mortality and adverse outcomes in patients with acute coronary syndromes (ACS). Design: A prospective multicentre observational study, GRACE (global registry of acute coronary events), of patients with the full spectrum of ACS. Setting: Ninety four hospitals of varying size and capability in 14 countries across four continents. Patients: 11 774 patients hospitalised with ACS, including ST and non-ST segment elevation acute myocardial infarction and unstable angina. Main outcome measures: Demographic and clinical characteristics, medication use, and in-hospital outcomes were compared for patients with creatinine clearance rates of > 60 ml/min (normal and minimally impaired renal function), 30–60 ml/min (moderate renal dysfunction), and < 30 ml/min (severe renal dysfunction). Results: Patients with moderate or severe renal dysfunction were older, were more likely to be women, and presented to participating hospitals with more comorbidities than those with normal or minimally impaired renal function. In comparison with patients with normal or minimally impaired renal function, patients with moderate renal dysfunction were twice as likely to die (odds ratio 2.09, 95% confidence interval 1.55 to 2.81) and those with severe renal dysfunction almost four times more likely to die (odds ratio 3.71, 95% confidence interval 2.57 to 5.37) after adjustment for other potentially confounding variables. The risk of major bleeding episodes increased as renal function worsened. Conclusion: In patients with ACS, creatinine clearance is an important independent predictor of hospital death and major bleeding. These data reinforce the importance of increased surveillance efforts and use of targeted intervention strategies in patients with acute coronary disease complicated by renal dysfunction. PMID:12923009

  4. Cognitive interviewing of the U.S. National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

    PubMed Central

    Hay, Jennifer L.; Atkinson, Thomas M.; Reeve, Bryce B.; Mitchell, Sandra A.; Mendoza, Tito R.; Willis, Gordon; Minasian, Lori M.; Clauser, Steven B.; Denicoff, Andrea; O’Mara, Ann; Chen, Alice; Bennett, Antonia V.; Paul, Diane B.; Gagne, Joshua; Rogak, Lauren; Sit, Laura; Viswanath, Vish; Schrag, Deborah; Basch, Ethan

    2013-01-01

    Purpose The National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) is a library of question items that enables patient reporting of adverse events (AEs) in clinical trials. This study contributes content validity evidence of the PRO-CTCAE by incorporating cancer patient input of the relevance and comprehensiveness of the item library. Methods Cognitive interviews were conducted among patients undergoing chemotherapy or radiation therapy at multiple sites to evaluate comprehension, memory retrieval, judgment, and response mapping related to AE terms (e.g., nausea); attribute terms (regarding frequency, severity, or interference); response options; and recall period. Three interview rounds were conducted with ≥20 patients completing each item per round. Items were modified and retested if ≥3 patients exhibited cognitive difficulties or if experienced by ≤25% patients. Results 127 patients participated (35% ≤high school; 28% non-white; 59% female). Most AE terms (63/80) generated no cognitive difficulties. The remaining 17 were modified without further difficulties by Round 3. Terms were comprehended regardless of education level. Attribute terms and response options required no modifications. Patient adherence to recall period (7-days) was improved when the reference period was incorporated. Conclusions This study provides evidence confirming comprehension of the U.S. English language versions of items in the PRO-CTCAE library for measuring symptomatic AEs from the patient perspective within the context of cancer treatment. Several minor changes were made to the items to improve item clarity, comprehension, and ease of response judgment. This study helps establish the content validity of PRO-CTCAE items for patient reporting of AEs during cancer treatment. PMID:23868457

  5. Aurora Kinase A expression predicts platinum-resistance and adverse outcome in high-grade serous ovarian carcinoma patients.

    PubMed

    Mignogna, Chiara; Staropoli, Nicoletta; Botta, Cirino; De Marco, Carmela; Rizzuto, Antonia; Morelli, Michele; Di Cello, Annalisa; Franco, Renato; Camastra, Caterina; Presta, Ivan; Malara, Natalia; Salvino, Angela; Tassone, Pierfrancesco; Tagliaferri, Pierosandro; Barni, Tullio; Donato, Giuseppe; Di Vito, Anna

    2016-01-01

    High-Grade Serous Ovarian Carcinoma (HGSOC) is the predominant histotype of epithelial ovarian cancer (EOC), characterized by advanced stage at diagnosis, frequent TP53 mutation, rapid progression, and high responsiveness to platinum-based-chemotherapy. To date, standard first-line-chemotherapy in advanced EOC includes platinum salts and paclitaxel with or without bevacizumab. The major prognostic factor is the response duration from the end of the platinum-based treatment (platinum-free interval) and about 10-0 % of EOC patients bear a platinum-refractory disease or develop early resistance (platinum-free interval shorter than 6 months). On these bases, a careful selection of patients who could benefit from chemotherapy is recommended to avoid unnecessary side effects and for a better disease outcome. In this retrospective study, an immunohistochemical evaluation of Aurora Kinase A (AURKA) was performed on 41 cases of HGSOC according to platinum-status. Taking into account the number and intensity of AURKA positive cells we built a predictive score able to discriminate with high accuracy platinum-sensitive patients from platinum-resistant patients (p < 0.001). Furthermore, we observed that AURKA overexpression correlates to worse overall survival (p = 0.001; HR 0.14). We here suggest AURKA as new effective tool to predict the biological behavior of HGSOC. Particularly, our results indicate that AURKA has a role both as predictor of platinum-resistance and as prognostic factor, that deserves further investigation in prospective clinical trials. Indeed, in the era of personalized medicine, AURKA could assist the clinicians in selecting the best treatment and represent, at the same time, a promising new therapeutic target in EOC treatment. PMID:27209210

  6. Moderate altitude is not associated with adverse postoperative outcomes for patients undergoing bidirectional cavopulmonary anastomosis and Fontan operation: A comparative study among Denver, Edmonton, and Toronto

    PubMed Central

    Zhou, Zhi; Malhotra, Sunil P.; Yu, Xiaoyang; Rutledge, Jennifer; Rebeyka, Ivan M.; Ross, David B.; Rausch, Christopher; Gu, Hong; McCrindle, Brian; Lacour-Gayet, Francois; Ivy, Dunbar; Li, Jia

    2013-01-01

    Objective Outcomes of patients with single ventricle physiology undergoing cavopulmonary palliations depend on pulmonary vascular resistance (PVR) and have been suggested to be adversely affected by living at elevated altitude. We compared the pulmonary hemodynamic data in correlation with postoperative outcomes at the 3 centers of Denver, Edmonton, and Toronto at altitudes of 1604, 668, and 103 meters, respectively. Methods Hemodynamic data at pre-bidirectional cavopulmonary anastomosis (BCPA) and pre-Fontan catheterization between 1995 and 2007 were collected. Death from cardiac failure or heart transplantation in the same period was used to define palliation failure. Results There was no significant correlation between altitude (ranged from 1 to 2572 meters) and PVR, pulmonary artery pressure (PAP) or transpulmonary gradient (TPG) at pre-BCPA and pre-Fontan catheterization. BCPA failure occurred in 11 (9.2%) patients in Denver, 3 (2.9%) in Edmonton, and 34 (11.9%) in Toronto. Fontan failure occurred in 3 (6.1%) patients in Denver, 5 (7.2%) in Edmonton, and 11 (7.0%) in Toronto. There was no significant difference in BCPA and Fontan failure among the 3 centers. BCPA failure positively correlated with PVR and the presence of a right ventricle as the systemic ventricle. Fontan failure positively correlated with PAP and TPG. Conclusions Moderate altitude is not associated with an increased PVR or adverse outcomes in patients with a functional single ventricle undergoing BCPA and the Fontan operation. The risk factors for palliation failure are higher PVR, PAP, and TPG and a systemic right ventricle, but not altitude. Our study reemphasizes the importance of cardiac catheterization assessments of pulmonary hemodynamics before BCPA and Fontan operations. PMID:23353110

  7. Development of the National Cancer Institute's patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE).

    PubMed

    Basch, Ethan; Reeve, Bryce B; Mitchell, Sandra A; Clauser, Steven B; Minasian, Lori M; Dueck, Amylou C; Mendoza, Tito R; Hay, Jennifer; Atkinson, Thomas M; Abernethy, Amy P; Bruner, Deborah W; Cleeland, Charles S; Sloan, Jeff A; Chilukuri, Ram; Baumgartner, Paul; Denicoff, Andrea; St Germain, Diane; O'Mara, Ann M; Chen, Alice; Kelaghan, Joseph; Bennett, Antonia V; Sit, Laura; Rogak, Lauren; Barz, Allison; Paul, Diane B; Schrag, Deborah

    2014-09-01

    The standard approach for documenting symptomatic adverse events (AEs) in cancer clinical trials involves investigator reporting using the National Cancer Institute's (NCI's) Common Terminology Criteria for Adverse Events (CTCAE). Because this approach underdetects symptomatic AEs, the NCI issued two contracts to create a patient-reported outcome (PRO) measurement system as a companion to the CTCAE, called the PRO-CTCAE. This Commentary describes development of the PRO-CTCAE by a group of multidisciplinary investigators and patient representatives and provides an overview of qualitative and quantitative studies of its measurement properties. A systematic evaluation of all 790 AEs listed in the CTCAE identified 78 appropriate for patient self-reporting. For each of these, a PRO-CTCAE plain language term in English and one to three items characterizing the frequency, severity, and/or activity interference of the AE were created, rendering a library of 124 PRO-CTCAE items. These items were refined in a cognitive interviewing study among patients on active cancer treatment with diverse educational, racial, and geographic backgrounds. Favorable measurement properties of the items, including construct validity, reliability, responsiveness, and between-mode equivalence, were determined prospectively in a demographically diverse population of patients receiving treatments for many different tumor types. A software platform was built to administer PRO-CTCAE items to clinical trial participants via the internet or telephone interactive voice response and was refined through usability testing. Work is ongoing to translate the PRO-CTCAE into multiple languages and to determine the optimal approach for integrating the PRO-CTCAE into clinical trial workflow and AE analyses. It is envisioned that the PRO-CTCAE will enhance the precision and patient-centeredness of adverse event reporting in cancer clinical research. PMID:25265940

  8. Development of the National Cancer Institute’s Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

    PubMed Central

    Reeve, Bryce B.; Mitchell, Sandra A.; Clauser, Steven B.; Minasian, Lori M.; Dueck, Amylou C.; Mendoza, Tito R.; Hay, Jennifer; Atkinson, Thomas M.; Abernethy, Amy P.; Bruner, Deborah W.; Cleeland, Charles S.; Sloan, Jeff A.; Chilukuri, Ram; Baumgartner, Paul; Denicoff, Andrea; St. Germain, Diane; O’Mara, Ann M.; Chen, Alice; Kelaghan, Joseph; Bennett, Antonia V.; Sit, Laura; Rogak, Lauren; Barz, Allison; Paul, Diane B.; Schrag, Deborah

    2014-01-01

    The standard approach for documenting symptomatic adverse events (AEs) in cancer clinical trials involves investigator reporting using the National Cancer Institute’s (NCI’s) Common Terminology Criteria for Adverse Events (CTCAE). Because this approach underdetects symptomatic AEs, the NCI issued two contracts to create a patient-reported outcome (PRO) measurement system as a companion to the CTCAE, called the PRO-CTCAE. This Commentary describes development of the PRO-CTCAE by a group of multidisciplinary investigators and patient representatives and provides an overview of qualitative and quantitative studies of its measurement properties. A systematic evaluation of all 790 AEs listed in the CTCAE identified 78 appropriate for patient self-reporting. For each of these, a PRO-CTCAE plain language term in English and one to three items characterizing the frequency, severity, and/or activity interference of the AE were created, rendering a library of 124 PRO-CTCAE items. These items were refined in a cognitive interviewing study among patients on active cancer treatment with diverse educational, racial, and geographic backgrounds. Favorable measurement properties of the items, including construct validity, reliability, responsiveness, and between-mode equivalence, were determined prospectively in a demographically diverse population of patients receiving treatments for many different tumor types. A software platform was built to administer PRO-CTCAE items to clinical trial participants via the internet or telephone interactive voice response and was refined through usability testing. Work is ongoing to translate the PRO-CTCAE into multiple languages and to determine the optimal approach for integrating the PRO-CTCAE into clinical trial workflow and AE analyses. It is envisioned that the PRO-CTCAE will enhance the precision and patient-centeredness of adverse event reporting in cancer clinical research. PMID:25265940

  9. Coexistence of Low Vitamin D and High Fibroblast Growth Factor-23 Plasma Levels Predicts an Adverse Outcome in Patients with Coronary Artery Disease

    PubMed Central

    Tuñón, José; Cristóbal, Carmen; Tarín, Nieves; Aceña, Álvaro; González-Casaus, María Luisa; Huelmos, Ana; Alonso, Joaquín; Lorenzo, Óscar; González-Parra, Emilio; Mahíllo-Fernández, Ignacio; Pello, Ana María; Carda, Rocío; Farré, Jerónimo; Rodríguez-Artalejo, Fernando

    2014-01-01

    Objective Vitamin D and fibroblast growth factor-23 (FGF-23) are related with cardiovascular disorders. We have investigated the relationship of calcidiol (vitamin D metabolite) and FGF-23 plasma levels with the incidence of adverse outcomes in patients with coronary artery disease. Methods Prospective follow-up study of 704 outpatients, attending the departments of Cardiology of four hospitals in Spain, 6–12 months after an acute coronary event. Baseline calcidiol, FGF-23, parathormone, and phosphate plasma levels were assessed. The outcome was the development of acute ischemic events (any acute coronary syndrome, stroke, or transient ischemic attack), heart failure, or death. Cox regression adjusted for the main confounders was performed. Results Calcidiol levels showed a moderate-severe decrease in 57.3% of cases. Parathormone, FGF-23, and phosphate levels were increased in 30.0%, 11.5% and 0.9% of patients, respectively. Only 22.4% of patients had glomerular filtration rate<60 ml/min1.73 m2. After a mean follow-up was 2.15±0.99 years, 77 patients developed the outcome. Calcidiol (hazard ratio [HR] = 0.67; 95% confidence interval [CI] = 0.48–0.94; p = 0.021) and FGF-23 (HR = 1.13; 95% CI = 1.04–1.23; p = 0.005) plasma levels predicted independently the outcome. There was a significant interaction between calcidiol and FGF-23 levels (p = 0.025). When the population was divided according to FGF-23 levels, calcidiol still predicted the outcome independently in patients with FGF-23 levels higher than the median (HR = 0.50; 95% CI = 0.31–0.80; p = 0.003) but not in those with FGF-23 levels below this value (HR = 1.03; 95% CI = 0.62–1.71; p = 0.904). Conclusions Abnormalities in mineral metabolism are frequent in patients with stable coronary artery disease. In this population, low calcidiol plasma levels predict an adverse prognosis in the presence of high FGF-23 levels. PMID:24748388

  10. Lupus anticoagulant is the main predictor of adverse pregnancy outcomes in aPL-positive patients: validation of PROMISSE study results

    PubMed Central

    Yelnik, Cecile M; Laskin, Carl A; Porter, T Flint; Branch, D Ware; Buyon, Jill P; Guerra, Marta M; Lockshin, Michael D; Petri, Michelle; Merrill, Joan T; Sammaritano, Lisa R; Kim, Mimi Y; Salmon, Jane E

    2016-01-01

    Objective We previously reported that lupus anticoagulant (LAC) is the main predictor of poor pregnancy outcome in antiphospholipid antibody (aPL)-positive patients. We sought to confirm this finding in an independent group of patients who were subsequently recruited into the PROMISSE study. Methods The PROMISSE study is a multicentre, prospective, observational study of pregnancy outcomes in women with aPL and/or systemic lupus erythematosus (SLE) that enrolled patients from 2003 to 2015. All consecutive, aPL-positive patients from the PROMISSE study who completed their pregnancy between April 2011 and January 2015 (after the previous PROMISSE report) are included in the current report. Patients were followed monthly until delivery, and aPL was tested at first, second and third trimesters of pregnancy and at 12 weeks post partum. Adverse pregnancy outcomes (APOs) were defined as fetal death after 12 weeks of gestation, neonatal death, delivery prior to 36 weeks of gestation due to pre-eclampsia or placental insufficiency or small-for-gestational age (birth weight <5th percentile). Results Forty-four aPL-positive patients are included in this paper. Thirteen patients had APOs, which occurred in 80% of cases during the second trimester of pregnancy. LAC was present in 69% of patients with APOs compared with 27% of patients without APOs (p=0.01). No association was found between anticardiolipin antibodies (aCL) or anti-β2 glycoprotein I antibodies (aβ2GPI) IgG or IgM positivity and APOs. Definite antiphospholipid syndrome (history of thrombosis and/or pregnancy morbidity and aPL) was found in 92% of patients with any APOs compared with 45% of patients without APOs (p=0.004). Conversely, the frequency of SLE was not statistically different between those with and without APOs (30% vs 39%). Conclusions Our findings, in an independent group of aPL-positive patients from the PROMISSE study, confirm that LAC, but not aCL and aβ2GPI, is predictive of poor pregnancy

  11. Reduced-Function CYP2C19 Genotype and Risk of Adverse Clinical Outcomes Among Patients Treated With Clopidogrel Predominantly for PCI: A Meta-Analysis

    PubMed Central

    Mega, Jessica L.; Simon, Tabassome; Collet, Jean-Philippe; Anderson, Jeffrey L.; Antman, Elliott M.; Bliden, Kevin; Cannon, Christopher P.; Danchin, Nicolas; Giusti, Betti; Gurbel, Paul; Horne, Benjamin D.; Hulot, Jean-Sebastian; Kastrati, Adnan; Montalescot, Gilles; Neumann, Franz-Josef; Shen, Lei; Sibbing, Dirk; Steg, P. Gabriel; Trenk, Dietmar; Wiviott, Stephen D.; Sabatine, Marc S.

    2011-01-01

    Content Clopidogrel, one of the most commonly prescribed medications, is a pro-drug requiring CYP450 biotransformation. Data suggest its pharmacologic effect varies based on CYP2C19 genotype, but there is uncertainty regarding the clinical risk imparted by specific genotypes. Objective In patients treated with clopidogrel, to define the risk of major adverse cardiovascular outcomes among carriers of one (∼26% prevalence in whites) and carriers of two (∼2% prevalence in whites) reduced-function CYP2C19 variants. Data Sources and Study Selection A literature search was conducted (January 2000-August 2010) of the MEDLINE, Cochrane, and EMBASE databases. Genetic studies were included where clopidogrel was initiated in predominantly invasively managed patients in a manner consistent with the current guideline recommendations and where clinical outcomes were ascertained. Data Extraction Investigators from nine studies evaluating CYP2C19 genotype and clinical outcomes in patients treated with clopidogrel contributed the relevant hazard ratios (HRs) and their 95% confidence intervals (CI) for specific cardiovascular outcomes by genotype. Results Among 9685 patients [91.3% of whom underwent percutaneous coronary intervention (PCI) and 54.5% of whom had an acute coronary syndrome (ACS)], 863 experienced the composite endpoint of cardiovascular death, myocardial infarction, or stroke; 84 patients had stent thrombosis among the 5894 evaluated for such. Overall, 71.5% were non-carriers, 26.3% had one, and 2.2% had two CYP2C19 reduced-function alleles. A significantly increased risk of the composite endpoint was evident in both carriers of one (HR 1.55, 95% CI 1.11-2.27, P=0.01) and two (HR 1.76, 95% CI 1.24-2.50, P=0.002) CYP2C19 reduced-function alleles. Similarly, there was a significantly increased risk of stent thrombosis in both carriers of one (HR 2.67, 95% CI 1.69-4.22, P<0.0001) and two (HR 3.97, 95% CI 1.75-9.02, P=0.001) CYP2C19 reduced-function alleles

  12. Adverse Pregnancy Outcomes Following Motor Vehicle Crashes

    PubMed Central

    Vladutiu, Catherine J.; Marshall, Stephen W.; Poole, Charles; Casteel, Carri; Menard, M. Kathryn; Weiss, Harold B.

    2013-01-01

    Background Motor vehicle crashes are a leading cause of serious trauma during pregnancy, but little is known about their relationships with pregnancy outcomes. Purpose To estimate the association between motor vehicle crashes and adverse pregnancy outcomes. Methods A retrospective cohort study of 878,546 pregnant women, aged 16–46 years, who delivered a singleton infant in North Carolina (NC) from 2001 to 2008. Pregnant drivers in crashes were identified by probabilistic linkage of vital records and crash reports. Poisson regression modeled the association among crashes, vehicle safety features, and adverse pregnancy outcomes. Analyses were conducted in 2012. Results In 2001–2008, 2.9% of pregnant NC women were drivers in one or more crashes. After a single crash, compared to not being in a crash, pregnant drivers had slightly elevated rates of preterm birth (adjusted rate ratio, aRR=1.23, 95% CI=1.19, 1.28); placental abruption (aRR=1.34, 95% CI=1.15, 1.56); and premature rupture of the membranes (PROM; aRR=1.32, 95% CI=1.21, 1.43). Following a second or subsequent crash, pregnant drivers had more highly elevated rates of preterm birth (aRR=1.54, 95% CI=1.24, 1.90); stillbirth (aRR=4.82, 95% CI=2.85, 8.14); placental abruption (aRR=2.97, 95% CI=1.60, 5.53); and PROM (aRR=1.95, 95% CI=1.27, 2.99). Stillbirth rates were elevated following crashes involving unbelted pregnant drivers (aRR=2.77, 95% CI=1.22, 6.28) compared to belted pregnant drivers. Conclusions Crashes while driving during pregnancy were associated with elevated rates of adverse pregnancy outcomes, and multiple crashes were associated with even higher rates of adverse pregnancy outcomes. Crashes were especially harmful if drivers were unbelted. PMID:24139777

  13. Adverse Outcomes of Anticoagulant Use among Hospitalized Patients with Chronic Kidney Disease: A Comparison of the Rates of Major Bleeding Events between Unfractionated Heparin and Enoxaparin

    PubMed Central

    Saheb Sharif-Askari, Fatemeh; Syed Sulaiman, Syed Azhar; Saheb Sharif-Askari, Narjes; Al Sayed Hussain, Ali; Railey, Mohammad Jaffar

    2014-01-01

    Background Anticoagulation therapy is usually required in patients with chronic kidney disease (CKD) for treatment or prevention of thromboembolic diseases. However, this benefit could easily be offset by the risk of bleeding. Objectives To determine the incidence of adverse outcomes of anticoagulants in hospitalized patients with CKD, and to compare the rates of major bleeding events between the unfractionated heparin (UFH) and enoxaparin users. Methods One year prospective observational study was conducted in patients with CKD stages 3 to 5 (estimated GFR, 10–59 ml/min/1.73 m2) who were admitted to the renal unit of Dubai Hospital. Propensity scores for the use of anticoagulants, estimated for each of the 488 patients, were used to identify a cohort of 117 pairs of patients. Cox regression method was used to estimate association between anticoagulant use and adverse outcomes. Results Major bleeding occurred in 1 in 3 patients who received anticoagulation during hospitalization (hazard ratio [HR], 4.61 [95% confidence interval [CI], 2.05–10.35]). Compared with enoxaparin users, patients who received anticoagulation with unfractionated heparin had a lower mean [SD] serum level of platelet counts (139.95 [113]×103/µL vs 205.56 [123] ×103/µL; P<0.001), and had a higher risk of major bleeding (HR, 4.79 [95% CI, 1.85–12.36]). Furthermore, compared with those who did not receive anticoagulants, patients who did had a higher in-hospital mortality (HR, 2.54 [95% CI, 1.03–6.25]); longer length of hospitalization (HR, 1.04 [95% CI, 1.01–1.06]); and higher hospital readmission at 30 days (HR, 1.79 [95% CI, 1.10–2.91]). Conclusions Anticoagulation among hospitalized patients with CKD was significantly associated with an increased risk of bleeding and in-hospital mortality. Hence, intensive monitoring and preventive measures such as laboratory monitoring and/or dose adjustment are warranted. PMID:25181525

  14. Adverse blood transfusion outcomes: establishing causation.

    PubMed

    Isbister, James P; Shander, Aryeh; Spahn, Donat R; Erhard, Jochen; Farmer, Shannon L; Hofmann, Axel

    2011-04-01

    The transfusion of allogeneic red blood cells (RBCs) and other blood components is ingrained in modern medical practice. The rationale for administering transfusions is based on key assumptions that efficacy is established and risks are acceptable and minimized. Despite the cliché that, "the blood supply is safer than ever," data about risks and lack of efficacy of RBC transfusions in several clinical settings have steadily accumulated. Frequentist statisticians and clinicians demand evidence from randomized clinical trials (RCTs); however, causation for the recognized serious hazards of allogeneic transfusion has never been established in this manner. On the other hand, the preponderance of evidence implicating RBC transfusions in adverse clinical outcomes related to immunomodulation and the storage lesion comes from observational studies, and a broad and critical analysis to evaluate causation is overdue. It is suggested in several circumstances that this cannot wait for the design, execution, and conduct of rigorous RCTs. We begin by examining the nature and definition of causation with relevant examples from transfusion medicine. Deductive deterministic methods may be applied to most of the well-accepted and understood serious hazards of transfusion, with modified Koch's postulates being fulfilled in most circumstances. On the other hand, when several possible interacting risk factors exist and RBC transfusions are associated with adverse clinical outcomes, establishing causation requires inferential probabilistic methodology. In the latter circumstances, the case for RBC transfusions being causal for adverse clinical outcomes can be strengthened by applying modified Bradford Hill criteria to the plethora of existing observational studies. This being the case, a greater precautionary approach to RBC transfusion is necessary and equipoise that justifying RCTs may become problematic. PMID:21345639

  15. Adverse Outcome Pathways – Tailoring Development to Support Use

    EPA Science Inventory

    Adverse Outcome Pathways (AOPs) represent an ideal framework for connecting high-throughput screening (HTS) data and other toxicity testing results to adverse outcomes of regulatory importance. The AOP Knowledgebase (AOP-KB) captures AOP information to facilitate the development,...

  16. Adverse Outcome Pathway (AOP) Network Development for Fatty Liver

    EPA Science Inventory

    Adverse outcome pathways (AOPs) are descriptive biological sequences that start from a molecular initiating event (MIE) and end with an adverse health outcome. AOPs provide biological context for high throughput chemical testing and further prioritize environmental health risk re...

  17. Adverse outcome pathway (AOP) development I: Strategies and principles

    EPA Science Inventory

    An adverse outcome pathway (AOP) is a conceptual framework that organizes existing knowledge concerning biologically plausible, and empirically-supported, links between molecular-level perturbation of a biological system and an adverse outcome at a level of biological organizatio...

  18. Very early posttraumatic serum alterations are significantly associated to initial massive RBC substitution, injury severity, multiple organ failure and adverse clinical outcome in multiple injured patients

    PubMed Central

    2009-01-01

    Background Multiple severe trauma frequently leads to massive dysbalances of the human immune system. This phenomenon is known as "Systemic Inflammatory Response Syndrome (SIRS)". SIRS is connected to multiple organ failure and thereby entails higher morbidity and mortality in trauma patients. Pro-and anti-inflammatory cytokines such as Il-6, Il-8 and Il-10 seem to play a superior role in the development of SIRS. Several studies support the hypothesis that the very early cytokine release pattern determines the patients' subsequent clinical course. Most data about interleukins in trauma patients however refer to serum concentrations assessed sometime in the first 24 h, but there is only little information about release dynamics in a small-meshed time frame in the very initial post-trauma period. Patients and methods 58 multiple injured patients (Injury Severity Score > 16 points) were included. Blood samples were drawn on patient admission (not later then 90 minutes after trauma) and at 6 h, 12 h, 24 h, 48 h and 72 h. Il-6, Il-8 and Il-10 were measured using an automated chemiluminescence assay (IMMULITE, Siemens Healthcare Diagnostics GmbH). Interleukin levels were correlated to distinct epidemiological and clinical parameters. Results Interleukin serum concentrations are thoroughly elevated after trauma. Patients with haemorrhagic shock and consecutive massive RBC substitution (n = 27) exhibit higher Il-6, Il-8 and Il-10 levels as compared to patients with minor RBC transfusion extent (n = 31). Interleukin levels also differentiate patients with MOF (n = 43) from such without MOF (n = 15) already at the earliest post trauma time (90 minutes). Il-6, Il-8 and Il-10 concentrations also significantly distinguish patients with adverse outcome (n = 11) from such with favourable outcome (n = 47). Exclusively Il-10 has significant correlation to injury severity (ISS > 35). Conclusion The current study presents an image of the serum Il-6, 8 and 10 releases in multiple

  19. Adverse Outcome Pathway Development II: Best Practices

    PubMed Central

    Villeneuve, Daniel L.; Crump, Doug; Garcia-Reyero, Natàlia; Hecker, Markus; Hutchinson, Thomas H.; LaLone, Carlie A.; Landesmann, Brigitte; Lettieri, Teresa; Munn, Sharon; Nepelska, Malgorzata; Ottinger, Mary Ann; Vergauwen, Lucia; Whelan, Maurice

    2014-01-01

    Organization of existing and emerging toxicological knowledge into adverse outcome pathway (AOP) descriptions can facilitate greater application of mechanistic data, including those derived through high-throughput in vitro, high content omics and imaging, and biomarker approaches, in risk-based decision making. The previously ad hoc process of AOP development is being formalized through development of internationally harmonized guidance and principles. The goal of this article was to outline the information content desired for formal AOP description and some rules of thumb and best practices intended to facilitate reuse and connectivity of elements of an AOP description in a knowledgebase and network context. For example, key events (KEs) are measurements of change in biological state that are indicative of progression of a perturbation toward a specified adverse outcome. Best practices for KE description suggest that each KE should be defined as an independent measurement made at a particular level of biological organization. The concept of “functional equivalence” can help guide both decisions about how many KEs to include in an AOP and the specificity with which they are defined. Likewise, in describing both KEs and evidence that supports a causal linkage or statistical association between them (ie, a key event relationship; KER), best practice is to build from and contribute to existing KE or KER descriptions in the AOP knowledgebase rather than creating redundant descriptions. The best practices proposed address many of the challenges and uncertainties related to AOP development and help promote a consistent and reliable, yet flexible approach. PMID:25466379

  20. Complex Disease, Partial Revascularization, and Adverse Outcomes in Patients Treated With Long-Term Warfarin Therapy Who Underwent Percutaneous Coronary Intervention.

    PubMed

    Yazji, Khaled; Kakhi, Sorayya; Ossei-Gerning, Nick; Choudhury, Anirban; Anderson, Richard; Kinnaird, Tim

    2015-08-01

    Patients treated with warfarin who undergo percutaneous coronary intervention (PCI) present a difficult therapeutic problem. Their baseline demographics, procedural characteristics, and 12-month outcomes are poorly defined. We conducted a retrospective analysis of all patients who underwent PCI at a major UK Cardiac Center from 2012 to 2013. Of the 2,675 patients who underwent PCI, 155 were on long-term warfarin treatment (5.8%). Patients on warfarin were older and more likely to have significant co-morbidity than those not on warfarin. The modified Mehran bleed score was higher in patients treated with warfarin versus those not treated (19.0 ± 5.8 vs 15.4 ± 8.0, p = 0.004). Baseline SYNTAX scores were higher in the patients treated with warfarin (18.5 ± 9.1 vs 12.4 ± 3.8, p = 0.0006) as were residual SYNTAX scores (8.3 ± 1.1 vs 3.8 ± 5.9, p = 0.001). Bare metal stents were more frequently used in warfarin-treated patients than those not treated (44.8% vs 26.3%, p <0.0001). Antiplatelet monotherapy was prescribed after PCI in 14.4% of patients treated with warfarin and 0.7% of non-warfarin (p <0.0001), whereas average dual anti-platelet therapy duration was also significantly shorter (4.3 vs 10.7 months, p <0.0001). At 1-year follow-up, target-vessel revascularization (6.5% vs 3.3%, p <0.05), stent thrombosis (5.0% vs 2.6%, p = 0.14), death (10.1% vs 4.6%, p <0.01), and target-vessel revascularization/stent thrombosis/death (21.6% vs 10.5%, p = 0.004) were all more common in the warfarin cohort. In conclusion, patients treated with warfarin who need PCI are a complex cohort, more likely to receive incomplete revascularization, less intense, and shorter durations of antiplatelet therapy, and have adverse 1-year outcomes. More trials of both current DES and newer DES technologies in warfarin-treated patients are needed. PMID:26048850

  1. Are PRO discharge screens associated with postdischarge adverse outcomes?

    PubMed Central

    Wei, F.; Mark, D.; Hartz, A.; Campbell, C.

    1995-01-01

    OBJECTIVE. We evaluate whether patient outcomes may be affected by possible errors in care at discharge as assessed by Peer Review Organizations (PROs). DATA SOURCES/STUDY SETTING. The three data sources for the study were (1) the generic screen results of a 3 percent random sample of Medicare beneficiaries age 65 years or older who were admitted to California hospitals between 1 July 1987 and 30 June 1988 (n = 20,136 patients); (2) the 1987 and 1988 California Medicare Provided Analysis and Review (MEDPAR) data files; and (3) the American Hospital Association (AHA) 1988 Annual Survey of Hospitals. STUDY DESIGN. Multivariate logistic regression analysis was used to evaluate the association between the results of generic discharge administered by the PROs and two patient outcomes: mortality and readmission within 30 days. The analysis was adjusted for other patient characteristics recorded on the uniform discharge abstract. PRINCIPAL FINDINGS. Four discharge screens indicated an increased risk of an adverse outcome-absence of documentation of discharge planning, elevated temperature, abnormal pulse, and unaddressed abnormal test results at discharge. The other three discharge screens examined-abnormal blood pressure, IV fluids or drugs, and wound drainage before discharge-were unrelated to postdischarge adverse outcomes. CONCLUSIONS. Generic discharge screens based on inadequate discharge planning, abnormal pulse, increased temperature, or unaddressed abnormal tests may be important indicators of substandard care. Other discharge screens apparently do not detect errors in care associated with major consequences for patients. PMID:7649753

  2. Early Childhood Adversity and Pregnancy Outcomes

    PubMed Central

    Smith, Megan V.; Gotman, Nathan; Yonkers, Kimberly A.

    2016-01-01

    Objectives To examine the association between adverse childhood experiences (ACEs) and pregnancy outcomes; to explore mediators of this association including psychiatric illness and health habits. Methods Exposure to ACEs was determined by the Early Trauma Inventory Self Report Short Form; psychiatric diagnoses were generated by the Composite International Diagnostic Interview administered in a cohort of 2303 pregnant women. Linear regression and structural equation modeling bootstrapping approaches tested for multiple mediators. Results Each additional ACE decreased birth weight by 16.33 g and decreased gestational age by 0.063. Smoking was the strongest mediator of the effect on gestational age. Conclusions ACEs have an enduring effect on maternal reproductive health, as manifested by mothers’ delivery of offspring that were of reduced birth weight and shorter gestational age. PMID:26762511

  3. Early Childhood Adversity and Pregnancy Outcomes.

    PubMed

    Smith, Megan V; Gotman, Nathan; Yonkers, Kimberly A

    2016-04-01

    Objectives To examine the association between adverse childhood experiences (ACEs) and pregnancy outcomes; to explore mediators of this association including psychiatric illness and health habits. Methods Exposure to ACEs was determined by the Early Trauma Inventory Self Report Short Form; psychiatric diagnoses were generated by the Composite International Diagnostic Interview administered in a cohort of 2303 pregnant women. Linear regression and structural equation modeling bootstrapping approaches tested for multiple mediators. Results Each additional ACE decreased birth weight by 16.33 g and decreased gestational age by 0.063. Smoking was the strongest mediator of the effect on gestational age. Conclusions ACEs have an enduring effect on maternal reproductive health, as manifested by mothers' delivery of offspring that were of reduced birth weight and shorter gestational age. PMID:26762511

  4. Incident hyperglycemia, parenteral nutrition administration and adverse outcomes in patients with myeloma admitted for initial auto-SCT.

    PubMed

    Sheean, P M; Kilkus, J M; Liu, D; Maciejewski, J; Braunschweig, C A

    2013-08-01

    Parenteral nutrition (PN) exacerbates hyperglycemia, which is associated with increased morbidity and mortality in various cancer populations. By using a retrospective design, we examined incident hyperglycemia in PN and non-PN recipients and the associations with clinical events and 5-year survival in a cohort treated for myeloma with melphalan and auto-SCT (n=112). Clinical comparisons were made at admission, and 'before' and 'after' initiating PN to discern differences and temporality. Actual infusion times were used for PN patients; time frames based on mean PN infusion days were created for the non-PN recipients. Oral intake was lower 'before' in PN vs non-PN patients (P<0.001); however, no differences in mucositis, emesis, infections or transfusions were detected 'before.' Incident hyperglycemia (≥7.0 mmol/L) was significant 'after' PN initiation, and PN recipients experienced delays in WBC (P<0.05) and platelet engraftment (P=0.009), and required significantly greater RBC (P=0.0014) and platelet (P=0.001) support 'after' than non-PN patients. Neutropenic fever and longer hospital stay were more frequent among PN vs non-PN recipients (P<0.001). Differences in 5-year mortality were not apparent. The findings fail to support clinical benefits of PN administration during auto-SCT for myeloma. Further study is needed to discern if hyperglycemia or feeding per se was deleterious in this patient population. PMID:23419432

  5. Peak Cardiac Power Measured Non-Invasively with a Bioreactance Technique is a Predictor of Adverse Outcomes in Patients with Advanced Heart Failure

    PubMed Central

    Rosenblum, Hannah; Helmke, Stephen; Williams, Paula; Teruya, Sergio; Jones, Margaret; Burkhoff, Daniel; Mancini, Donna; Maurer, Mathew S.

    2010-01-01

    Summary Background Peak oxygen consumption (VO2) during cardiopulmonary exercise testing (CPET) is a powerful predictor of survival, providing an indirect assessment of cardiac output (CO). Hypothesis Non-invasive indices of CO derived from bioreactance methodology would add significantly to peak VO2 as a means of risk stratifying patients with heart failure. Methods 127 patients (53±14 years of age, 66% male) with heart failure and an average EF = 31±15 underwent a symptom-limited CPET using a bicycle ergometer while measuring CO noninvasively by a bioreactance technique. Peak cardiac power was derived from the product of the peak mean arterial blood pressure and CO divided by 451. Results Follow-up averaged 404±179 days (median, 366 days) to assess end points including death (n=3), heart transplant (n=10), or left ventricular assisted device (LVAD) implantation (n=2). Peak VO2 and peak power had similar area under the curves (0.77 and 0.76), which increased to 0.83 when combined. Kaplan-Meier cumulative survival curves demonstrated different outcomes in the subgroup with a VO2 <14 ml*kg-1*min-1 when stratified by a cardiac power above or below 1.5 Watts (92.2% vs. 82.1% at 1 year and 81.6% vs. 58.3% at last follow-up, p=0.02 by log-rank test). Conclusions Among patients with heart failure, peak cardiac power measured with bioreactance methodology and peak VO2 had similar associations with adverse outcomes and peak power added independent prognostic information to peak VO2 in subjects with advanced disease (e.g. VO2 < 14 ml*kg-1*min-1). PMID:21091609

  6. miR-205 negatively regulates the androgen receptor and is associated with adverse outcome of prostate cancer patients

    PubMed Central

    Hagman, Z; Haflidadóttir, B S; Ceder, J A; Larne, O; Bjartell, A; Lilja, H; Edsjö, A; Ceder, Y

    2013-01-01

    Background: The microRNA-205 (miR-205) has been shown to be deregulated in prostate cancer (PCa). Here we continue to investigate the prognostic and therapeutic potential of this microRNA. Methods: The expression of miR-205 is measured by qRT–PCR and in situ hybridisation in a well-documented PCa cohort. An AGO2-based RIP-Chip assay is used to identify targets that are verified with western blots, luciferase reporter assay, ELISA and immunohistochemistry. Results: The expression of miR-205 is inversely correlated to the occurrence of metastases and shortened overall survival, and is lower in castration-resistant PCa patients. The miR-205 expression is mainly localised to the basal cells of benign prostate tissues. Genes regulated by miR-205 are enriched in, for example, the MAPK/ERK, Toll-like receptor and IL-6 signaling pathways. We demonstrate binding of miR-205 to the 3′UTR of androgen receptor (AR) and decrease of both AR transcript and protein levels. This finding was corroborated in the patient cohort were miR-205 expression inversely correlated to AR immunostaining in malignant prostate cells and to serum levels of prostate-specific antigen, an androgen-regulated protein. Conclusion: Taken together, these findings imply that miR-205 might have therapeutic potential, especially for the castration resistant and currently untreatable form of PCa. PMID:23571738

  7. Unknown Safety and Efficacy of Smartphone Bolus Calculator Apps Puts Patients at Risk for Severe Adverse Outcomes.

    PubMed

    Hirsch, Irl B; Parkin, Christopher G

    2016-07-01

    Manual calculation of bolus insulin dosages can be challenging for individuals treated with multiple daily insulin injections (MDI) therapy. Automated bolus calculator capability has recently been made available via enhanced blood glucose meters and smartphone apps. Use of this technology has been shown to improve glycemic control and reduce glycemic variability without changing hypoglycemia; however, the clinical utility of app-based bolus calculators has not been demonstrated. Moreover, recent evidence challenges the safety and efficacy of these smartphone apps. Although the ability to automatically calculate bolus insulin dosages addresses a critical need of MDI-treated individuals, this technology raises concerns about efficacy of treatment and the protection of patient safety. This article discusses key issues and considerations associated with automated bolus calculator use. PMID:26798082

  8. Renal function trajectory over time and adverse clinical outcomes.

    PubMed

    Sohel, Badrul Munir; Rumana, Nahid; Ohsawa, Masaki; Turin, Tanvir Chowdhury; Kelly, Martina Ann; Al Mamun, Mohammad

    2016-06-01

    The growing burden of chronic kidney disease (CKD), with its associated morbidity and mortality, is recognized as a major public health problem globally and causing substantial load on health care systems. The current framework for the definition and staging of CKD, based on eGFR levels or presence of kidney damage, is useful for clinical classification of patients, but identifies a huge number of people as having CKD which is too many to target for intervention. The ability to identify a subset of patients, at high risk for adverse outcomes, would be useful to inform clinical management. The current staging system applies static definitions of kidney function that fail to capture the dynamic nature of the kidney disease over time. Now-a-days, it is possible to capture multiple measurements of different laboratory test results for an individual including eGFR values. A new possibility for identifying individuals at higher risk of adverse outcomes is being explored through assessment and consideration of the rate of change in kidney function over time, and this approach will be feasible in the current context of digitalization of health record keeping system. On the basis of the existing evidence, this paper summarizes important findings that support the concept of dynamic changes in kidney function over time, and discusses how the magnitude of these changes affect the future adverse outcomes of kidney disease, particularly the End Stage Renal Disease (ESRD), CVD and mortality. PMID:26728745

  9. Sequential analysis of uncommon adverse outcomes.

    PubMed

    Morton, A; Mengersen, K; Waterhouse, M; Steiner, S; Looke, D

    2010-10-01

    Sequential analysis of uncommon adverse outcomes (AEs) such as surgical site infections (SSIs) is desirable. Short postoperative lengths of stay (LOS) result in many SSIs occurring after discharge and they are often superficial. Deep and organ space (complex) SSIs occur less frequently but are detected more reliably and are suitable for monitoring wound care. Those occurring post-discharge usually require readmissison and can be counted accurately. Sequential analysis of meticillin-resistant Staphylococcus aureus bacteraemia is also needed. The key to prevention is to implement systems based on evidence, e.g. using 'bundles' and checklists. Regular mortality and morbidity audit meetings are required and these may need to be followed by independent audits. Sequential statistical analysis is desirable for data presentation, to detect changes, and to discourage tampering with processes when occasional AEs occur in a reliable system. Tabulations and cumulative observed minus expected (O-E) charts and funnel plots are valuable, supplemented in the presence of apparent 'runs' of AEs by cumulative sum analysis. Used prospectively, they may enable staff to visualise and detect patterns or shifts in rates and counts that might not otherwise be apparent. PMID:20656377

  10. Earliest Bedside Assessment of Hemodynamic Parameters and Cardiac Biomarkers: Their Role as Predictors of Adverse Outcome in Patients with Septic Shock

    PubMed Central

    Sasko, Benjamin; Butz, Thomas; Prull, Magnus Wilhelm; Liebeton, Jeanette; Christ, Martin; Trappe, Hans-Joachim

    2015-01-01

    Background: Early assessment and aggressive hemodynamic treatment have been shown to increase the survival of patients in septic shock. Current and past sepsis guidelines recommend a resuscitation protocol including central venous pressure (CVP), mean arterial blood pressure (MAP), urine output and central venous oxygen saturation (ScvO2) for resuscitation within the first six hours. Currently, the established severity score systems like APACHE II score, SOFA score or SAPS II score predict the outcome of critically ill patients on the bases of variables obtained only after the first 24 hours. The present study aims to evaluate the risk of short-term mortality for patients with septic shock by the earliest possible assessment of hemodynamic parameters and cardiac biomarkers as well as their role for the prediction of the adverse outcome. Methods: 52 consecutive patients treated for septic shock in the intensive care unit of one centre (Marien Hospital Herne, Ruhr University Bochum, Germany) were prospectively enrolled in this study. Hemodynamic parameters (MAP, CVP, ScvO2, left ventricular ejection fraction, Hematocrit) and cardiac biomarkers (Troponin I) at the ICU admission were evaluated in regard to their influence on mortality. The primary endpoint was all-cause mortality within 28 days after the admission. Results: A total of 52 patients (31 male, 21 female) with a mean age of 71.4±8.5 years and a mean APACHE II score of 37.0±7.6 were enrolled in the study. 28 patients reached the primary endpoint (mortality 54%). Patients presenting with hypotension (MAP <65 mmHg) at ICU admission had significantly higher rates of 28-day mortality as compared with the group of patients without hypotension (28-day mortality rate 74 % vs. 32 %, p<0.01). Furthermore, the patients in the hypotension present group had significantly higher lactate concentration (p=0.002), higher serum creatinin (p=0.04), higher NTproBNP (p=0.03) and after the first 24 hours higher APACHE II

  11. Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study

    PubMed Central

    2009-01-01

    OBJECTIVE—To examine associations of neonatal adiposity with maternal glucose levels and cord serum C-peptide in a multicenter multinational study, the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study, thereby assessing the Pederson hypothesis linking maternal glycemia and fetal hyperinsulinemia to neonatal adiposity. RESEARCH DESIGN AND METHODS—Eligible pregnant women underwent a standard 75-g oral glucose tolerance test between 24 and 32 weeks gestation (as close to 28 weeks as possible). Neonatal anthropometrics and cord serum C-peptide were measured. Associations of maternal glucose and cord serum C-peptide with neonatal adiposity (sum of skin folds >90th percentile or percent body fat >90th percentile) were assessed using multiple logistic regression analyses, with adjustment for potential confounders, including maternal age, parity, BMI, mean arterial pressure, height, gestational age at delivery, and the baby's sex. RESULTS—Among 23,316 HAPO Study participants with glucose levels blinded to caregivers, cord serum C-peptide results were available for 19,885 babies and skin fold measurements for 19,389. For measures of neonatal adiposity, there were strong statistically significant gradients across increasing levels of maternal glucose and cord serum C-peptide, which persisted after adjustment for potential confounders. In fully adjusted continuous variable models, odds ratios ranged from 1.35 to 1.44 for the two measures of adiposity for fasting, 1-h, and 2-h plasma glucose higher by 1 SD. CONCLUSIONS—These findings confirm the link between maternal glucose and neonatal adiposity and suggest that the relationship is mediated by fetal insulin production and that the Pedersen hypothesis describes a basic biological relationship influencing fetal growth. PMID:19011170

  12. Factors associated with adverse clinical outcomes among obstetric trainees

    PubMed Central

    Aiken PhD, Catherine E.; Aiken, Abigail; Park, Hannah; Brockelsby, Jeremy C.; Prentice, Andrew

    2016-01-01

    Objective To determine whether UK obstetric trainees transitioning from directly to indirectly-supervised practice have a higher likelihood of adverse patient outcomes from operative deliveries compared to other indirectly supervised trainees and to examine whether performing more procedures under direct supervision is associated with fewer adverse outcomes in initial indirect practice. Methods We examined all deliveries (13,861) conducted by obstetricians at a single centre over 5 years (2008-2013). Mixed-effects logistic regression models were used to compare estimated blood loss, maternal trauma, umbilical arterial pH, delayed neonatal respiration, failed instrumental delivery, and critical incidents for trainees in their first indirectly-supervised year with trainees in all other years of indirect practice. Outcomes for trainees in their first indirectly-supervised 3 months were compared to their outcomes for the remainder of the year. Linear regression was used to examine the relationship between number of procedures performed under direct supervision and initial outcomes under indirect supervision. Results Trainees in their first indirectly-supervised year had a higher likelihood of >2 litres estimated blood loss at any delivery (OR 1.32;CI(1.01-1.64) p<0.05) and of failed instrumental delivery (OR 2.33;CI(1.37-3.29) p<0.05) compared with other indirectly-supervised trainees. Other measured outcomes showed no significant differences. Within the first three months of indirect supervision, the likelihood of operative vaginal deliveries with >1litre estimated blood loss (OR 2.54;CI(1.88-3.20) p<0.05) was higher compared to the remainder of the first year. Performing more deliveries under direct supervision prior to beginning indirectly-supervised training was associated with decreased risk of >1litre estimated blood loss (p<0.05). Conclusions Obstetric trainees in their first year of indirectly-supervised practice have a higher likelihood of immediate adverse

  13. Adverse Outcome Pathways: From Research to Regulation - Scientific Workshop Report

    EPA Science Inventory

    An adverse outcome pathway (AOP) organizes existing knowledge on chemical mode of action, starting with a molecular initiating event such as receptor binding, continuing through key events, and ending with an adverse outcome such as reproductive impairment. AOPs can help identify...

  14. Intimate Partner Violence, PTSD, and Adverse Health Outcomes

    ERIC Educational Resources Information Center

    Dutton, Mary Ann; Green, Bonnie L.; Kaltman, Stacey I.; Roesch, Darren M.; Zeffiro, Thomas A.; Krause, Elizabeth D.

    2006-01-01

    The high prevalence of adverse health outcomes related to intimate partner violence (IPV) is well documented. Yet we know little about the pathways that lead to adverse health outcomes. Research concerning the psychological, biological, neurological, behavioral, and physiological alterations following exposure to IPV--many of which are associated…

  15. Adverse obstetric outcome for the vanishing twin syndrome.

    PubMed

    Almog, Benny; Levin, Ishai; Wagman, Israel; Kapustiansky, Rita; Lessing, Joseph B; Amit, Ami; Azem, Foad

    2010-02-01

    The aim was to compare obstetric outcomes of IVF singleton pregnancies diagnosed with vanishing twin (VT) syndrome with those pregnancies originating as singleton pregnancies and with twin pregnancies. In this case control study, 57 patients diagnosed with VT syndrome were matched and compared with 171 singleton controls and 171 twin controls. Mean gestational age was 35.1+/-3.7 versus 38.2+/-2.6 weeks (P=0.001) for patients and singleton controls respectively. Birth weights were 2834.4+/-821.2 versus 3036+/-489.3g (P=0.02), proportion of low birth weight (< 2500 g) was 33.3 versus 11.7% (P=0.0001) and very low birth weight (< 1500 g) 3.5 versus 0.6% for patients and singleton controls respectively. The proportion of deliveries before 28 weeks of gestation was 7.0 versus 1.2% (P=0.01) for patients and singleton controls respectively. When comparing the study group to twin control pregnancies, a similar gestational age at delivery (35 weeks) and rate of preterm birth (23%) were found. In conclusion, pregnancies diagnosed with the VT syndrome after IVF carry a higher rate of adverse obstetric outcomes in terms of preterm deliveries and lower birth weight, compared with IVF pregnancies that were originally singleton. Additionally, significant similarities were observed in the obstetrics outcome of vanishing twin pregnancies and twin pregnancies. PMID:20113963

  16. Alanine aminotransferase as a predictor of adverse perinatal outcomes in women with intrahepatic cholestasis of pregnancy

    PubMed Central

    Ekiz, Ali; Kaya, Basak; Avci, Muhittin Eftal; Polat, Ibrahim; Dikmen, Selin; Yildirim, Gokhan

    2016-01-01

    Objective: To evaluate the associations between adverse perinatal outcomes and serum transaminase levels at the time of diagnosis in patients with intrahepatic cholestasis of pregnancy. Methods: We performed a retrospective analysis of patients hospitalized for evaluation of intrahepatic cholestasis of pregnancy from January 2013 to June 2014 in a tertiary center. Seventy-one patients were divided into two groups according to the presence (Group I) or absence of adverse perinatal outcomes (Group II). Results: The mean aminotransferase levels and conjugated bilirubin levels at the time of diagnosis were significantly higher in Group I than in Group II. Receiver operating characteristic curve analysis revealed that the alanine aminotransferase level could predict adverse perinatal outcomes with 76.47% sensitivity and 78.38% specificity, and the cut-off value was 95 IU/L. Among patients with intrahepatic cholestasis of pregnancy, those with adverse perinatal outcomes were significantly older, had an earlier diagnosis, and had higher alanine aminotransferase levels. Using the 95-IU/L cut-off value, patients with intrahepatic cholestasis of pregnancy had a 3.54-fold increased risk for adverse perinatal outcomes. Conclusions: Patients with intrahepatic cholestasis of pregnancy and high alanineaminotransferase levels should be followed up for possible adverse perinatal outcomes.

  17. Adverse outcome pathway (AOP) development: Guiding principles and best practices

    EPA Science Inventory

    Adverse outcome pathways (AOPs) represent a conceptual framework that can support greater application of mechanistic data in regulatory decision-making. However, in order for the scientific community to collectively address the daunting challenge of describing relevant toxicologi...

  18. Adverse outcome pathway (AOP) development II: Best practices

    EPA Science Inventory

    Organization of existing and emerging toxicological knowledge into adverse outcome pathway (AOP) descriptions can facilitate greater application of mechanistic data, including high throughput in vitro, high content omics and imaging, and biomarkers, in risk-based decision-making....

  19. Accelerating Adverse Outcome Pathway Development via Systems Approaches

    EPA Science Inventory

    The Adverse Outcome Pathway has emerged as an internationally harmonized mechanism for organizing biological information in a chemical agnostic manner. This construct is valuable for interpreting the results from high-throughput toxicity (HTT) assessment by providing a mechanisti...

  20. Association of assisted reproductive technology with adverse pregnancy outcomes

    PubMed Central

    Jie, Zhang; Yiling, Ding; Ling, Yu

    2015-01-01

    Background: More and more infertile patients have accepted the assisted reproductive technique (ART) therapy. Concerns have been raised over an increased risk of adverse maternal outcomes in ART populations as compared with natural conception (NC). Objective: The aim was to improve the ART in clinicial work and to reduce the incidence of pregnancy complications in ART group according to analyzing the reasons of high incidence of pregnancy complications in ART group, comparing the incidence of pregnancy complications in different controlled ovarian hyperstimulation (COH) programs and evaluating the effects of ART which attribute to adverse pregnancy outcomes. Materials and Methods: In this prospective population-based cohort study,3216 pregnant women with gestational age ≤12 weeks, regular antenatal examination,and ultrasound identification of intrauterine pregnancy were enrolled from January 2010 to June 2013. According to having ART history, the participantswere divided into two groups: ART group (contains fresh embryo transfer group or frozen-thawed embryo transfer group) and NC group. We compared the incidence of pregnancy complications between different groups and evaluated the factors which could affect the occurrence of these complications. Results: When compared to NC group, significantly increased rates of gestational diabetes mellitus (GDM) (p<0.01), preeclampsia (PE) (p<0.01) and intrahepatic cholestasis of pregnancy (ICP) (p˂0.01) were observed in ART group. There was no significant difference in the incidence of birth defect between the two groups (p=0.07). Multiple pregnancies and Gonadotropin (Gn) were risk factors in GDM, PE, and ICP. The exogenous progesterone treatment had no effect on GDM, PE or ICP. Conclusion: ART increases the risk of adverse maternal complications such as GDM, PE and ICP. The dosages of Gn should be reduced to an extent and the number of embryo implantation should be controlled. Exogenous progesterone treatment is safe

  1. Placental Features of Late-Onset Adverse Pregnancy Outcome

    PubMed Central

    Higgins, Lucy E.; Wareing, Mark; Greenwood, Susan L.; Jones, Rebecca L.; Sibley, Colin P.; Johnstone, Edward D.; Heazell, Alexander E. P.

    2015-01-01

    Objective Currently, no investigations reliably identify placental dysfunction in late pregnancy. To facilitate the development of such investigations we aimed to identify placental features that differ between normal and adverse outcome in late pregnancy in a group of pregnancies with reduced fetal movement. Methods Following third trimester presentation with reduced fetal movement (N = 100), placental structure ex vivo was measured. Placental function was then assessed in terms of (i) chorionic plate artery agonist responses and length-tension characteristics using wire myography and (ii) production and release of placentally derived hormones (by quantitative polymerase chain reaction and enzyme linked immunosorbant assay of villous tissue and explant conditioned culture medium). Results Placentas from pregnancies ending in adverse outcome (N = 23) were ~25% smaller in weight, volume, length, width and disc area (all p<0.0001) compared with those from normal outcome pregnancies. Villous and trophoblast areas were unchanged, but villous vascularity was reduced (median (interquartile range): adverse outcome 10 (10–12) vessels/mm2 vs. normal outcome 13 (12–15), p = 0.002). Adverse outcome pregnancy placental arteries were relatively insensitive to nitric oxide donated by sodium nitroprusside compared to normal outcome pregnancy placental arteries (50% Effective Concentration 30 (19–50) nM vs. 12 (6–24), p = 0.02). Adverse outcome pregnancy placental tissue contained less human chorionic gonadotrophin (20 (11–50) vs. 55 (24–102) mIU/mg, p = 0.007) and human placental lactogen (11 (6–14) vs. 27 (9–50) mg/mg, p = 0.006) and released more soluble fms-like tyrosine kinase-1 (21 (13–29) vs. 5 (2–15) ng/mg, p = 0.01) compared with normal outcome pregnancy placental tissue. Conclusion These data provide a description of the placental phenotype of adverse outcome in late pregnancy. Antenatal tests that accurately reflect elements of this phenotype may

  2. Accelerating Adverse Outcome Pathway Development Using Publicly Available Data Sources

    EPA Science Inventory

    The adverse outcome pathway (AOP) concept links molecular perturbations with organism and population-level outcomes to support high-throughput toxicity testing. International efforts are underway to define AOPs and store the information supporting these AOPs in a central knowledg...

  3. The epidemiology of disasters and adverse reproductive outcomes: lessons learned.

    PubMed

    Cordero, J F

    1993-07-01

    A disaster has been defined as a disruption of human ecology that exceeds the capacity of the community to function normally. Little is known about the adverse effects of natural disasters on reproductive outcomes. Important lessons can be derived from several disasters caused by human factors, such as the Minamata Bay disaster. Adverse reproductive outcomes include infertility, early pregnancy loss, stillbirths, congenital malformations, and serious developmental disabilities such as cerebral palsy and mental retardation. Recent disasters like the Chernobyl and Bhopal explosions have provided important lessons on the need for accurate and sound information about the risk of prenatal exposures for adverse reproductive outcomes. To study questions of adverse reproductive outcomes and disasters requires a well-planned approach. It should include early development of surveillance for adverse reproductive outcomes, analytic studies on the risk of disasters from direct and indirect effects, sensitive methods to measure early pregnancy loss, and long-term follow-up programs to assess outcomes such as developmental disabilities. PMID:8243383

  4. The epidemiology of disasters and adverse reproductive outcomes: lessons learned.

    PubMed Central

    Cordero, J F

    1993-01-01

    A disaster has been defined as a disruption of human ecology that exceeds the capacity of the community to function normally. Little is known about the adverse effects of natural disasters on reproductive outcomes. Important lessons can be derived from several disasters caused by human factors, such as the Minamata Bay disaster. Adverse reproductive outcomes include infertility, early pregnancy loss, stillbirths, congenital malformations, and serious developmental disabilities such as cerebral palsy and mental retardation. Recent disasters like the Chernobyl and Bhopal explosions have provided important lessons on the need for accurate and sound information about the risk of prenatal exposures for adverse reproductive outcomes. To study questions of adverse reproductive outcomes and disasters requires a well-planned approach. It should include early development of surveillance for adverse reproductive outcomes, analytic studies on the risk of disasters from direct and indirect effects, sensitive methods to measure early pregnancy loss, and long-term follow-up programs to assess outcomes such as developmental disabilities. PMID:8243383

  5. Development of a Screening Tool for Predicting Adverse Outcomes of Gestational Diabetes Mellitus

    PubMed Central

    Park, Jee Soo; Kim, Deok Won; Kwon, Ja-Young; Park, Yong Won; Kim, Young Han; Cho, Hee Young

    2016-01-01

    Abstract Gestational diabetes mellitus (GDM) is a common disease in pregnancy causing maternal and fetal complications. To prevent these adverse outcomes, optimal screening and diagnostic criteria must be adequate, timely, and efficient. This study suggests a novel approach that is practical, efficient, and patient- and clinician-friendly in predicting adverse outcomes of GDM. The authors conducted a retrospective cohort study via medical record review of patients admitted between March 2001 and April 2013 at the Severance Hospital, Seoul, South Korea. Patients diagnosed by a conventional 2-step method were evaluated according to the presence of adverse outcomes (neonatal hypoglycemia, hyperbilirubinemia, and hyperinsulinemia; admission to the neonatal intensive care unit; large for gestational age; gestational insulin therapy; and gestational hypertension). Of 802 women who had an abnormal 50-g, 1-hour glucose challenge test, 306 were diagnosed with GDM and 496 did not have GDM (false-positive group). In the GDM group, 218 women (71.2%) had adverse outcomes. In contrast, 240 women (48.4%) in the false-positive group had adverse outcomes. Women with adverse outcomes had a significantly higher body mass index (BMI) at entry (P = 0.03) and fasting blood glucose (FBG) (P = 0.03). Our logistic regression model derived from 2 variables, BMI at entry and FBG, predicted GDM adverse outcome with an area under the curve of 0.642, accuracy of 61.3%, sensitivity of 57.2%, and specificity of 66.9% compared with the conventional 2-step method with an area under the curve of 0.610, accuracy of 59.1%, sensitivity of 47.6%, and specificity of 74.4%. Our model performed better in predicting GDM adverse outcomes than the conventional 2-step method using only BMI at entry and FBG. Moreover, our model represents a practical, inexpensive, efficient, reproducible, easy, and patient- and clinician-friendly approach. PMID:26735528

  6. 1991 Gulf War Exposures and Adverse Birth Outcomes

    PubMed Central

    Arnetz, Bengt; Drutchas, Alexis; Sokol, Robert; Kruger, Michael; Jamil, Hikmet

    2014-01-01

    We studied 1991 Gulf War (GW)-related environmental exposures and adverse birth outcomes in Iraqis. A random cross-sectional sample of 307 Iraqi families that immigrated to the United States responded to a structured interview covering socioeconomics, lifestyle, environmental exposures, and birth outcome. Data per each family was collected either from the man or the woman in the respective family. The respondents were divided into those that resided in Iraq during and following the GW (post-GW, n=185) and those that had left before (pre-GW, n=122). The primary outcome was lifetime prevalence of adverse birth outcomes, ie, congenital anomalies, stillbirth, low birth weight, and preterm delivery and its relationship to GW exposures. Mean number of adverse birth outcomes increased from 3.43 (SD=2.11) in the pre-GW to 4.63 (SD=2.63) in the post-GW group (P<.001). Mean chemical (Ch) and nonchemical (NCh) environmental exposure scores increased from pre-GW scores of 0.38 units (SD=1.76) and 0.43 (SD=1.86), respectively, to post-GW scores of 5.65 units (SD=6.23) and 7.26 (SD =5.67), P <.001 between groups for both exposures. There was a significant dose-response relationship between Ch environmental exposure (P=.001), but not NCh exposure, and number of adverse birth outcomes. Exposure to burning oil pits and mustard gas increased the risks for specific adverse birth outcomes by 2 to 4 times. Results indicate that Gulf War Ch, but not NCh exposures are related to adverse birth outcomes. Pregnancies in women with a history of war exposures might benefit from more intensive observation. PMID:23584910

  7. A Quantative Adverse Outcome Pathway Linking Aromatase Inhibition in Fathead Minnows with Population Dynamics

    EPA Science Inventory

    A Quantitative Adverse Outcome Pathway Linking Aromatase Inhibition in Fathead Minnows with Population DynamicsAn adverse outcome pathway (AOP) is a qualitative description linking a molecular initiating event (MIE) with measureable key events leading to an adverse outcome (AO). ...

  8. Sleep Disordered Breathing and Adverse Pregnancy Outcomes.

    PubMed

    Cain, Mary Ashley; Louis, Judette M

    2016-06-01

    Sleep disordered breathing (SDB) occurs in 0.6% to 15% of reproductive-aged women. Because of an overlap in symptoms of SDB and normal pregnancy findings, the diagnosis of SDB in pregnancy is challenging. The repetitive arousals, sleep fragmentation, and hypoxias experienced by patients with SDB lead to an increase in oxidative stress and inflammation. In the nonpregnant population SDB is associated with an increased risk of diabetes mellitus, heart disease, and stroke. Increasing evidence identifies an association between SDB in pregnancy and gestational diabetes, preeclampsia, and fetal growth abnormalities. PMID:27235923

  9. Low 25(OH) Vitamin D3 Levels Are Associated with Adverse Outcome in Newly-Diagnosed Intensively-Treated Adult Acute Myeloid Leukemia Patients

    PubMed Central

    Lee, Hun Ju; Muindi, Josephia R.; Tan, Wei; Hu, Qiang; Wang, Dan; Liu, Song; Wilding, Gregory E.; Ford, Laurie A.; Sait, Sheila N.J.; Block, Annemarie W.; Adjei, Araba A.; Barcos, Maurice; Griffiths, Elizabeth A; Thompson, James E.; Wang, Eunice S.; Johnson, Candace S; Trump, Donald L.; Wetzler, Meir

    2013-01-01

    Background Several studies suggest that low 25(OH) vitamin D3 levels may be prognostic in some malignancies, but no studies have evaluated their impact on treatment outcome in acute myeloid leukemia (AML). Methods VD levels were evaluated in 97 consecutive newly diagnosed, intensively-treated AML patients. MicroRNA-expression profiles and single nucleotide polymorphisms (SNPs) in the 25(OH) vitamin D3 pathway genes were evaluated and correlated with 25(OH) vitamin D3 levels and treatment outcome. Results Thirty-four (35%) patients had normal 25(OH) vitamin D3 levels (32–100 ng/ml), 34 (35%) insufficient (20–31.9 ng/ml) and 29 (30%) deficient levels (<20 ng/ml). Insufficient/deficient 25(OH) vitamin D3 levels were associated with worse relapse-free survival (RFS) compared to normal vitamin D3 levels. In multivariate analyses, deficient 25(OH) vitamin D3, smoking, European LeukemiaNet Genetic Groups and white blood cell count retained their statistical significance for RFS. A number of microRNAs and SNPs were found to be associated with 25(OH) vitamin D3 level, although none remained significant after multiple test corrections; one 25(OH) vitamin D3 receptor SNP, rs10783219, was associated with lower complete remission rate (p=0.0442), shorter RFS (p=0.0058) and overall survival (p=0.0011). Conclusions It remains to be determined what role microRNA and SNP profiles play in contributing to low 25(OH) vitamin D3 level and/or outcome and whether supplementation will improve AML outcome. PMID:24166051

  10. Frailty as a predictor of short-term adverse outcomes

    PubMed Central

    Coelho, Tiago; Paúl, Constança; Gobbens, Robbert J.J.

    2015-01-01

    The objectives of this study were to compare how different frailty measures (Frailty Phenotype/FP, Groningen Frailty Indicator/GFI and Tilburg Frailty Indicator/TFI) predict short-term adverse outcomes. Secondarily, adopting a multidimensional approach to frailty (integral conceptual model–TFI), this study aims to compare how physical, psychological and social frailty predict the outcomes. A longitudinal study was carried out with 95 community-dwelling elderly. Participants were assessed at baseline for frailty, determinants of frailty, and adverse outcomes (healthcare utilization, quality of life, disability in basic and instrumental activities of daily living/ADL and IADL). Ten months later the outcomes were assessed again. Frailty was associated with specific healthcare utilization indicators: the FP with a greater utilization of informal care; GFI with an increased contact with healthcare professionals; and TFI with a higher amount of contacts with a general practitioner. After controlling for the effect of life-course determinants, comorbidity and adverse outcome at baseline, GFI predicted IADL disability and TFI predicted quality of life. The effect of the FP on the outcomes was not significant, when compared with the other measures. However, when comparing TFI’s domains, the physical domain was the most significant predictor of the outcomes, even explaining part of the variance of ADL disability. Frailty at baseline was associated with adverse outcomes at follow-up. However, the relationship of each frailty measure (FP, GFI and TFI) with the outcomes was different. In spite of the role of psychological frailty, TFI’s physical domain was the determinant factor for predicting disability and most of the quality of life. PMID:26246968

  11. Adverse pregnancy and neo-natal outcomes after assisted reproductive treatment in patients with pelvic endometriosis: a case-control study.

    PubMed

    Jacques, Marianne; Freour, Thomas; Barriere, Paul; Ploteau, Stéphane

    2016-06-01

    To assess the impact of endometriosis on obstetric outcomes and to determine whether the severity, location and surgical treatment of the disease before the pregnancy had an impact on the prevalence of these disorders, a monocentric, case-control study was performed. In total, 113 pregnancies obtained by assisted reproductive treatment among patients with endometriosis were matched with control selected among assisted reproductive treatment pregnancies due to male infertility. The main result measures were pregnancy outcome at the obstetrical and neo-natal levels. The incidence of first trimester bleeding, pre-eclampsia, premature delivery threat, pelvic pain and Caesarean section was significantly higher (P < 0.05) in women with endometriosis. Except for gestational diabetes and intrauterine growth restriction (IUGR), the severity, location of lesions and surgical treatment of endometriosis did not have an impact on either pregnancy outcome or risk of obstetric complications. The IUGR is mainly due to deep locations and the revised American Fertility Society (rAFS) stages III-IV. Newborns with a mother suffering from endometriosis are at greater risk of being premature, smaller for their gestational age and more frequently hospitalized than the control group. Deep location of endometriosis is associated with more prematurity, hospitalization and smaller birthweight than ovarian locations. PMID:27068240

  12. Women, poverty and adverse maternal outcomes in Nairobi, Kenya

    PubMed Central

    2010-01-01

    Background The link between poverty and adverse maternal outcomes has been studied largely by means of quantitative data. We explore poor urban Kenyan women's views and lived experiences of the relationship between economic disadvantage and unpleasant maternal outcomes. Method Secondary analysis of focus group discussions and in-depth individual interviews data with women in two slums in Nairobi, Kenya. Results Urban poor women in Nairobi associate poverty with adverse maternal outcomes. However, their accounts and lived experiences of the impact of poverty on maternal outcomes underscore dynamics other than those typically stressed in the extant literature. To them, poverty primarily generates adverse maternal outcomes by exposing women to exceedingly hard and heavy workloads during pregnancy and the period surrounding it; to intimate partner violence; as well as to inhospitable and unpleasant treatment by service providers. Conclusions Poverty has wider and more intricate implications for maternal outcomes than are acknowledged in extant research. To deliver their expected impact, current efforts to promote better maternal outcomes must be guided by a more thorough perspective of the link between women's livelihoods and their health and wellbeing. PMID:21122118

  13. Proteomics for Adverse Outcome Pathway Discovery using Human Kidney Cells?

    EPA Science Inventory

    An Adverse Outcome Pathway (AOP) is a conceptual framework that applies molecular-based data for use in risk assessment and regulatory decision support. AOP development is based on effects data of chemicals on biological processes (i.e., molecular initiating events, key intermedi...

  14. Thyroid-Disrupting Chemicals: Interpreting Upstream Biomarkers of Adverse Outcomes

    PubMed Central

    Miller, Mark D.; Crofton, Kevin M.; Rice, Deborah C.; Zoeller, R. Thomas

    2009-01-01

    Background There is increasing evidence in humans and in experimental animals for a relationship between exposure to specific environmental chemicals and perturbations in levels of critically important thyroid hormones (THs). Identification and proper interpretation of these relationships are required for accurate assessment of risk to public health. Objectives We review the role of TH in nervous system development and specific outcomes in adults, the impact of xenobiotics on thyroid signaling, the relationship between adverse outcomes of thyroid disruption and upstream causal biomarkers, and the societal implications of perturbations in thyroid signaling by xenobiotic chemicals. Data sources We drew on an extensive body of epidemiologic, toxicologic, and mechanistic studies. Data synthesis THs are critical for normal nervous system development, and decreased maternal TH levels are associated with adverse neuropsychological development in children. In adult humans, increased thyroid-stimulating hormone is associated with increased blood pressure and poorer blood lipid profiles, both risk factors for cardiovascular disease and death. These effects of thyroid suppression are observed even within the “normal” range for the population. Environmental chemicals may affect thyroid homeostasis by a number of mechanisms, and multiple chemicals have been identified that interfere with thyroid function by each of the identified mechanisms. Conclusions Individuals are potentially vulnerable to adverse effects as a consequence of exposure to thyroid-disrupting chemicals. Any degree of thyroid disruption that affects TH levels on a population basis should be considered a biomarker of adverse outcomes, which may have important societal outcomes. PMID:19654909

  15. Application of the adverse outcome pathway framework - advances and challenges

    EPA Science Inventory

    The adverse outcome pathway (AOP) framework, while not new in concept, has gained attention in recent years as a set of organizing principles and tools that can help facilitate greater use of mechanistic or pathway-based data in risk assessment and regulatory decision-making. Reg...

  16. Risk-Adjusted Models for Adverse Obstetric Outcomes and Variation in Risk Adjusted Outcomes Across Hospitals

    PubMed Central

    Bailit, Jennifer L.; Grobman, William A.; Rice, Madeline Murguia; Spong, Catherine Y.; Wapner, Ronald J.; Varner, Michael W.; Thorp, John M.; Leveno, Kenneth J.; Caritis, Steve N.; Shubert, Phillip J.; Tita, Alan T. N.; Saade, George; Sorokin, Yoram; Rouse, Dwight J.; Blackwell, Sean C.; Tolosa, Jorge E.; Van Dorsten, J. Peter

    2014-01-01

    Objective Regulatory bodies and insurers evaluate hospital quality using obstetrical outcomes, however meaningful comparisons should take pre-existing patient characteristics into account. Furthermore, if risk-adjusted outcomes are consistent within a hospital, fewer measures and resources would be needed to assess obstetrical quality. Our objective was to establish risk-adjusted models for five obstetric outcomes and assess hospital performance across these outcomes. Study Design A cohort study of 115,502 women and their neonates born in 25 hospitals in the United States between March 2008 and February 2011. Hospitals were ranked according to their unadjusted and risk-adjusted frequency of venous thromboembolism, postpartum hemorrhage, peripartum infection, severe perineal laceration, and a composite neonatal adverse outcome. Correlations between hospital risk-adjusted outcome frequencies were assessed. Results Venous thromboembolism occurred too infrequently (0.03%, 95% CI 0.02% – 0.04%) for meaningful assessment. Other outcomes occurred frequently enough for assessment (postpartum hemorrhage 2.29% (95% CI 2.20–2.38), peripartum infection 5.06% (95% CI 4.93–5.19), severe perineal laceration at spontaneous vaginal delivery 2.16% (95% CI 2.06–2.27), neonatal composite 2.73% (95% CI 2.63–2.84)). Although there was high concordance between unadjusted and adjusted hospital rankings, several individual hospitals had an adjusted rank that was substantially different (as much as 12 rank tiers) than their unadjusted rank. None of the correlations between hospital adjusted outcome frequencies was significant. For example, the hospital with the lowest adjusted frequency of peripartum infection had the highest adjusted frequency of severe perineal laceration. Conclusions Evaluations based on a single risk-adjusted outcome cannot be generalized to overall hospital obstetric performance. PMID:23891630

  17. Residential Proximity to Environmental Hazards and Adverse Health Outcomes

    PubMed Central

    Maantay, Juliana A.; Chakraborty, Jayajit

    2011-01-01

    How living near environmental hazards contributes to poorer health and disproportionate health outcomes is an ongoing concern. We conducted a substantive review and critique of the literature regarding residential proximity to environmental hazards and adverse pregnancy outcomes, childhood cancer, cardiovascular and respiratory illnesses, end-stage renal disease, and diabetes. Several studies have found that living near hazardous wastes sites, industrial sites, cropland with pesticide applications, highly trafficked roads, nuclear power plants, and gas stations or repair shops is related to an increased risk of adverse health outcomes. Government agencies should consider these findings in establishing rules and permitting and enforcement procedures to reduce pollution from environmentally burdensome facilities and land uses. PMID:22028451

  18. [Development and application of adverse outcome pathway in toxicology research].

    PubMed

    Wang, Yanhua; Duan, Huawei

    2015-12-01

    Adverse outcome pathway (AOP) was a conceptual construct that integrated existing knowledge concerning the pathway of causal linkages between a molecular initiating event (MIE) and a final adverse effect at individual or population levels. The AOP methodology could be used as a basis for effects extrapolation and was an approach towards providing a framework for collecting and evaluating relevant chemical, biological and toxicological information. The framework would play an important role in risk assessment. We reviewed the concept of AOP, the development and assessment of the framework and the established models in toxicology researches. And the prospects and challenges of its application in toxicology were also introduced. PMID:26887310

  19. Drinking water contaminants and adverse pregnancy outcomes: a review.

    PubMed Central

    Bove, Frank; Shim, Youn; Zeitz, Perri

    2002-01-01

    Concern for exposures to drinking water contaminants and their effects on adverse birth outcomes has prompted several studies evaluating chlorination disinfection by-products and chlorinated solvents. Some of these contaminants are found to be teratogenic in animal studies. This review evaluates 14 studies on chlorination disinfection by-products such as trihalomethanes (THMs) and five studies on chlorinated solvents such as trichloroethylene (TCE). The adverse birth outcomes discussed in this review include small for gestational age (SGA), low birth weight, preterm birth, birth defects, spontaneous abortions, and fetal deaths. Because of heterogeneities across the studies in the characterization of birth outcomes, the assessment and categorization of exposures, and the levels and mixtures of contaminants, a qualitative review was conducted. Generally, the chief bias in these studies was exposure misclassification that most likely underestimated the risk, as well as distorted exposure-response relationships. The general lack of confounding bias by risk factors resulted from these factors not being associated with drinking water exposures. The studies of THMs and adverse birth outcomes provide moderate evidence for associations with SGA, neural tube defects (NTDs), and spontaneous abortions. Because fewer studies have been conducted for the chlorinated solvents than for THMs, the evidence for associations is less clear. Nevertheless, the findings of excess NTDs, oral clefts, cardiac defects, and choanal atresia in studies that evaluated TCE-contaminated drinking water deserve follow-up. PMID:11834464

  20. Accelerating Adverse Outcome Pathway (AOP) development via computationally predicted AOP networks

    EPA Science Inventory

    The Adverse Outcome Pathway (AOP) framework is increasingly being adopted as a tool for organizing and summarizing the mechanistic information connecting molecular perturbations by environmental stressors with adverse outcomes relevant for ecological and human health outcomes. Ho...

  1. Impact of Obstructive Sleep Apnea on the Levels of Placental Growth Factor (PlGF) and Their Value for Predicting Short-Term Adverse Outcomes in Patients with Acute Coronary Syndrome

    PubMed Central

    Barcelo, Antonia; Bauça, Josep Miquel; Yañez, Aina; Fueyo, Laura; Gomez, Cristina; de la Peña, Monica; Pierola, Javier; Rodriguez, Alberto; Sanchez-de-la-Torre, Manuel; Abad, Jorge; Mediano, Olga; Amilibia, Jose; Masdeu, Maria Jose; Teran, Joaquin; Montserrat, Josep Maria; Mayos, Mercè; Sanchez-de-la-Torre, Alicia; Barbé, Ferran

    2016-01-01

    Background Placental growth factor (PlGF) induces angiogenesis and promotes tissue repair, and plasma PlGF levels change markedly during acute myocardial infarction (AMI). Currently, the impact of obstructive sleep apnea (OSA) in patients with AMI is a subject of debate. Our objective was to evaluate the relationships between PlGF levels and both the severity of acute coronary syndrome (ACS) and short-term outcomes after ACS in patients with and without OSA. Methods A total of 538 consecutive patients (312 OSA patients and 226 controls) admitted for ACS were included in this study. All patients underwent polygraphy in the first 72 hours after hospital admission. The severity of disease and short-term prognoses were evaluated during the hospitalization period. Plasma PlGF levels were measured using an electrochemiluminescence immunoassay. Results Patients with OSA were significantly older and more frequently hypertensive and had higher BMIs than those without OSA. After adjusting for age, smoking status, BMI and hypertension, PlGF levels were significantly elevated in patients with OSA compared with patients without OSA (19.9 pg/mL, interquartile range: 16.6–24.5 pg/mL; 18.5 pg/mL, interquartile range: 14.7–22.7 pg/mL; p<0.001), and a higher apnea-hypopnea index (AHI) was associated with higher PlGF concentrations (p<0.003). Patients with higher levels of PlGF had also an increased odds ratio for the presence of 3 or more diseased vessels and for a Killip score>1, even after adjustment. Conclusions The results of this study show that in patients with ACS, elevated plasma levels of PlGF are associated with the presence of OSA and with adverse outcomes during short-term follow-up. Trial Registration ClinicalTrials.gov NCT01335087 PMID:26930634

  2. Adverse Pregnancy Outcomes after Abnormal First Trimester Screening for Aneuploidy

    PubMed Central

    Goetzl, Laura

    2010-01-01

    Women with abnormal first trimester screening but with a normal karyotype are at risk for adverse pregnancy outcomes. A nuchal translucency >3.5mm is associated with an increased risk of subsequent pregnancy loss, fetal infection, fetal heart abnormalities and other structural abnormalities. Abnormal first trimester analytes are also associated with adverse pregnancy outcomes but the predictive value is less impressive. As a single marker, PAPP-A <1st%ile has a good predictive value for subsequent fetal growth restriction. Women with PAPP-A<5th%ile should undergo subsequent risk assessment with routine MSAFP screening with the possible addition of uterine artery PI assessment in the midtrimester. PMID:20638576

  3. The adverse outcome pathway concept: a pragmatic tool in toxicology.

    PubMed

    Vinken, Mathieu

    2013-10-01

    Adverse outcome pathways (AOPs) are novel tools in toxicology and human risk assessment with broad potential. AOPs are designed to provide a clear-cut mechanistic representation of critical toxicological effects that span over different layers of biological organization. AOPs share a common structure consisting of a molecular initiating event, a series of intermediate steps and key events, and an adverse outcome. Development of AOPs ideally complies with OECD guidelines. This also holds true for AOP evaluation, which includes consideration of the Bradford Hill criteria for weight-of-evidence assessment and meeting a set of key questions defined by the OECD. Elaborate AOP frameworks have yet been proposed for chemical-induced skin sensitization, cholestasis, liver fibrosis and liver steatosis. These newly postulated AOPs can serve a number of ubiquitous purposes, including the establishment of (quantitative) structure-activity relationships, the development of novel in vitro toxicity screening tests and the elaboration of prioritization strategies. PMID:23978457

  4. Adverse Outcome Pathways and Drug-Induced Liver Injury Testing.

    PubMed

    Vinken, Mathieu

    2015-07-20

    Drug-induced liver injury is a prominent reason for premarketing and postmarketing drug withdrawal and can be manifested in a number of ways, such as cholestasis, steatosis, and fibrosis. The mechanisms driving these toxicological processes have been well characterized and have been emdedded in adverse outcome pathway frameworks in recent years. This review evaluates these constructs and simultaneously illustrates their use in the preclinical testing of drug-induced liver injury. PMID:26119269

  5. Adverse outcome pathways and drug-induced liver injury testing

    PubMed Central

    Vinken, Mathieu

    2015-01-01

    Drug-induced liver injury is a prominent reason for premarketing and postmarketing drug withdrawal and can be manifested in a number of ways, such as cholestasis, steatosis and fibrosis. The mechanisms driving these toxicological processes have been well characterized and have been emdedded in adverse outcome pathway frameworks in recent years. This paper reviews these constructs and simultaneously illustrates their use in the preclinical testing of drug-induced liver injury. PMID:26119269

  6. Maternal Serum Screening Markers and Adverse Outcome: A New Perspective

    PubMed Central

    Krantz, David; Hallahan, Terrence; Janik, David; Carmichael, Jonathan

    2014-01-01

    There have been a number of studies evaluating the association of aneuploidy serum markers with adverse pregnancy outcome. More recently, the development of potential treatments for these adverse outcomes as well as the introduction of cell-free fetal DNA (cffDNA) screening for aneuploidy necessitates a re-evaluation of the benefit of serum markers in the identification of adverse outcomes. Analysis of the literature indicates that the serum markers tend to perform better in identifying pregnancies at risk for the more severe but less frequent form of individual pregnancy complications rather than the more frequent but milder forms of the condition. As a result, studies which evaluate the association of biomarkers with a broad definition of a given condition may underestimate the ability of such markers to identify pregnancies that are destined to develop the more severe form of the condition. Consideration of general population screening using cffDNA solely must be weighed against the fact that traditional screening using serum markers enables detection of severe pregnancy complications, not detectable with cffDNA, of which many may be amenable to treatment options. PMID:26237472

  7. Adverse outcome pathways: From research to regulation scientific workshop report.

    PubMed

    Kleinstreuer, Nicole C; Sullivan, Kristie; Allen, David; Edwards, Stephen; Mendrick, Donna L; Embry, Michelle; Matheson, Joanna; Rowlands, J Craig; Munn, Sharon; Maull, Elizabeth; Casey, Warren

    2016-04-01

    An adverse outcome pathway (AOP) helps to organize existing knowledge on chemical mode of action, starting with a molecular initiating event such as receptor binding, continuing through key events, and ending with an adverse outcome such as reproductive impairment. AOPs can help identify knowledge gaps where more research is needed to understand the underlying mechanisms, aid in chemical hazard characterization, and guide the development of new testing approaches that use fewer or no animals. A September 2014 workshop in Bethesda, Maryland considered how the AOP concept could improve regulatory assessments of chemical toxicity. Scientists from 21 countries, representing industry, academia, regulatory agencies, and special interest groups, attended the workshop, titled Adverse Outcome Pathways: From Research to Regulation. Workshop plenary presentations were followed by breakout sessions that considered regulatory acceptance of AOPs and AOP-based tools, criteria for building confidence in an AOP for regulatory use, and requirements to build quantitative AOPs and AOP networks. Discussions during the closing session emphasized a need to increase transparent and inclusive collaboration, especially with disciplines outside of toxicology. Additionally, to increase impact, working groups should be established to systematically prioritize and develop AOPs. Multiple collaborative projects and follow-up activities resulted from the workshop. PMID:26774756

  8. Maternal Serum Screening Markers and Adverse Outcome: A New Perspective.

    PubMed

    Krantz, David; Hallahan, Terrence; Janik, David; Carmichael, Jonathan

    2014-01-01

    There have been a number of studies evaluating the association of aneuploidy serum markers with adverse pregnancy outcome. More recently, the development of potential treatments for these adverse outcomes as well as the introduction of cell-free fetal DNA (cffDNA) screening for aneuploidy necessitates a re-evaluation of the benefit of serum markers in the identification of adverse outcomes. Analysis of the literature indicates that the serum markers tend to perform better in identifying pregnancies at risk for the more severe but less frequent form of individual pregnancy complications rather than the more frequent but milder forms of the condition. As a result, studies which evaluate the association of biomarkers with a broad definition of a given condition may underestimate the ability of such markers to identify pregnancies that are destined to develop the more severe form of the condition. Consideration of general population screening using cffDNA solely must be weighed against the fact that traditional screening using serum markers enables detection of severe pregnancy complications, not detectable with cffDNA, of which many may be amenable to treatment options. PMID:26237472

  9. Heart-type fatty acid binding protein and high-sensitivity troponin T are myocardial damage markers that could predict adverse clinical outcomes in patients with peripheral artery disease

    PubMed Central

    Otaki, Yoichiro; Takahashi, Hiroki; Watanabe, Tetsu; Yamaura, Gensai; Funayama, Akira; Arimoto, Takanori; Shishido, Tetsuro; Miyamoto, Takuya; Kubota, Isao

    2015-01-01

    Background Despite many recent advances in endovascular therapy (EVT), peripheral artery disease (PAD) is an increasing health problem with high mortality. Heart-type fatty acid-binding protein (H-FABP) and high-sensitivity troponin T (hsTnT) are markers of ongoing myocardial damage and have been reported to be useful indicators of future cardiovascular events. However, it remains to be determined whether H-FABP and hsTnT can predict adverse clinical outcomes in patients with PAD. Methods and results We enrolled 208 de novo PAD patients who underwent EVT. Serum H-FABP and hsTnT were measured in all patients before EVT. During the median follow-up period of 694 days, there were 40 major adverse cardiovascular and cerebrovascular events (MACCEs) including all-cause deaths, and re-hospitalizations due to cardiovascular and cerebrovascular diseases and amputations. H-FABP and hsTnT were found to be higher in patients with critical limb ischemia (CLI) compared to those without this condition. Multivariate Cox proportional hazard regression analysis revealed that both H-FABP and hsTnT were independent predictors of MACCEs after adjustment for confounding factors. Kaplan–Meier analysis demonstrated that patients in the highest tertile according to H-FABP levels, as well as those in the highest hsTnT tertile, were at greatest risk for MACCEs. The net reclassification index was significantly improved by the addition of H-FABP as well as the addition of hsTnT to traditional risk factors. Conclusion The myocardial damage markers H-FABP and hsTnT were increased in PAD patients with CLI and could predict MACCEs in PAD patients. PMID:26673681

  10. Emergency Department Discharge Diagnosis and Adverse Health Outcomes in Older Adults

    PubMed Central

    Hastings, S. Nicole; Whitson, Heather E.; Purser, Jama L.; Sloane, Richard J.; Johnson, Kimberly S.

    2010-01-01

    Objectives To determine the relationship between the reason for an emergency department (ED) visit and subsequent risk of adverse health outcomes in older adults discharged from the ED. Design Secondary analysis of data from the Medicare Current Beneficiary Survey. Setting ED. Participants One thousand eight hundred fifty-one community-dwelling Medicare fee-for-service enrollees aged 65 and older discharged from the ED between January 2000 and September 2002. Measurements Independent variables were ED discharge diagnosis groups: injury or musculoskeletal (MSK) (e.g., fracture, open wound), chronic condition (e.g., chronic obstructive pulmonary disorder, heart failure), infection, non-MSK symptom (e.g., chest pain, abdominal pain), and unclassified. Adverse health outcomes were hospitalization or death within 30 days of the index ED visit. Results Injury or MSK was the largest ED diagnosis group (31.4%), followed by non-MSK symptom (22.2%), chronic condition (20.9%), and infection (7.8%); 338 (17.8%) had ED discharge diagnoses that were unclassified. In adjusted analyses, a discharge diagnosis of injury or MSK condition was associated with lower risk of subsequent adverse health outcomes (hazard ratio (HR) = 0.69, 95% confidence interval (CI) = 0.50–0.96) than for all other diagnosis groups. Patients seen in the ED for chronic conditions were at greater risk of adverse outcomes (HR = 1.86, 95% CI = 1.37–2.52) than all others. There were no significant differences in risk between patients with infections, those with non-MSK symptoms, and the unclassified group. Conclusion Adverse health outcomes were common in older patients with an ED discharge diagnosis classified as a chronic condition. ED discharge diagnosis may improve risk assessment and inform the development of targeted interventions to reduce adverse health outcomes in older adults discharged from the ED. PMID:19694872

  11. Magnitude of income-related disparities in adverse perinatal outcomes

    PubMed Central

    2014-01-01

    Background To assess and compare multiple measurements of socioeconomic position (SEP) in order to determine the relationship with adverse perinatal outcomes across various contexts. Methods A birth registry, the Nova Scotia Atlee Perinatal Database, was confidentially linked to income tax and related information for the year in which delivery occurred. Multiple logistic regression was used to examine odds ratios between multiple indicators of SEP and multiple adverse perinatal outcomes in 117734 singleton births between 1988 and 2003. Models for after tax family income were also adjusted for neighborhood deprivation to gauge the relative magnitude of effects related to SEP at both levels. Effects of SEP were stratified by single- versus multiple-parent family composition, and by urban versus rural location of residence. Results The risk of small for gestational age and spontaneous preterm birth was higher across all the indicators of lower SEP, while risk for large for gestational age was lower across indicators of lower SEP. Higher risk of postneonatal death was demonstrated for several measures of lower SEP. Higher material deprivation in the neighborhood of residence was associated with increased risk for perinatal death, small for gestational age birth, and iatrogenic and spontaneous preterm birth. Family composition and urbanicity were shown to modify the association between income and some perinatal outcomes. Conclusions This study highlights the importance of understanding the definitions of SEP and the mechanisms that lead to the association between income and poor perinatal outcomes, and broadening the types of SEP measures used in some cases. PMID:24589212

  12. First- and second-trimester maternal serum markers for aneuploidy and adverse obstetric outcomes.

    PubMed

    Dugoff, Lorraine

    2010-05-01

    Maternal serum levels of the first- and second-trimester markers for aneuploidy have been shown to be associated with adverse obstetric outcomes in the absence of aneuploidy or neural-tube defects. The likelihood of an adverse obstetric outcome increases as the values of the marker become more extreme, and as the number of abnormal markers increases. Although many of the associations between maternal serum markers for aneuploidy and adverse obstetric outcomes are statistically significant, the sensitivity and positive predictive values for the individual outcomes are too low for them to be clinically useful as screening tests. Currently in the United States there is not a uniformly accepted practice for the care of women with abnormal maternal serum markers regarding risk of future obstetric complications. There are no randomized trials assessing any type of intervention or treatment for patients with abnormal serum markers. Various strategies to manage patients with unexplained abnormal serum markers have been proposed. This article reviews the relationships between these markers and adverse obstetric outcomes. In addition, potential management strategies and future areas of research are discussed. PMID:20410782

  13. Prenatal Depression and Adverse Birth Outcomes: An Updated Systematic Review

    PubMed Central

    Accortt, Eynav Elgavish; Cheadle, Alyssa C. D.; Schetter, Christine Dunkel

    2015-01-01

    Complications related to preterm birth (PTB) and low birth weight (LBW) are leading causes of infant morbidity and mortality. Prenatal depression is a hypothesized psychosocial risk factor for both birth outcomes. The purpose of this systematic review was to examine evidence published between 1977 and 2013 on prenatal depression and risks of these primary adverse birth outcomes. A systematic search of the PUBMED and PsycINFO databases was conducted to identify studies testing the associations between prenatal depressive symptoms, or diagnoses of depression, and risk of PTB or LBW. We systematically selected 50 published reports on PTB and length of gestation, and 33 reports on LBW and BW. Results were reviewed by two independent reviewers and we evaluated the quality of the evidence with an established systematic review method, the Newcastle Ottawa Scale. We then undertook a narrative synthesis of the results following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Less than a quarter of 50 published reports found that prenatal depression was significantly associated with PTB or gestational age. In contrast, slightly more than half of the 33 reports found that prenatal depression was associated with LBW or BW. When weighing methodological features, we determined that the effects of prenatal depression on LBW are more consistent than effects on length of gestation or PTB. Although the evidence may not be strong enough to support routine depression screening for risk of adverse outcomes, screening to enable detection and timely treatment to reduce risk of postpartum depression is warranted. Further rigorous research on prenatal depression and adverse birth outcomes is needed. PMID:25452215

  14. The role of Mycoplasma and Ureaplasma in adverse pregnancy outcomes.

    PubMed

    Murtha, Amy P; Edwards, James M

    2014-12-01

    Genital mycoplasmas are frequently found in the vaginal flora across socioeconomic and ethnic groups and have been demonstrated to be involved in adverse perinatal outcomes. Both Mycoplasma and Ureaplasma spp cause inflammation potentially leading to spontaneous preterm birth and PPROM as well as postdelivery infectious complications and neonatal infections. Herein we have provided an overview of the existing literature and supportive evidence for genital mycoplasma's role in perinatal complications. Future research will need to focus on clearly delineating the species, allowing for discrimination of their effects. PMID:25454994

  15. Periodontal Disease and Adverse Birth Outcomes: A Study from Pakistan

    PubMed Central

    Mobeen, N; Jehan, I; Banjay, N; Moore, J; McClure, EM; Pasha, O; Wright, LL; Goldenberg, RL

    2013-01-01

    OBJECTIVES Periodontal disease may increase the risk of adverse birth outcomes; however, results have been mixed. Few studies have examined periodontal disease in developing countries. We describe the relationship between periodontal disease and birth outcomes in a community setting in Pakistan. METHODS Enrollment occurred at 20–26 wks. A study dentist performed the periodontal examination to assess probing depth (PD), clinical attachment level (CAL), gingivitis index (GI) and plaque index (PI). Outcomes included stillbirth, neonatal mortality, <32 wk preterm birth (PTB), 32–36 wk PTB, and low birthweight (LBW), and are presented for increasing periodontal disease severity by quartiles (Q1-4). RESULTS Dental examinations and outcome data were completed for 1152 women. 81% were multiparous with a mean age of 27 yrs. 33% had no education. Dental caries were present in 47%, missing teeth in 27%, and 92% had no dental care in the last year. Periodontal disease was common: 87% had ≥ 4 teeth with a PD of >3mm, 54% had ≥4 teeth with a PI = 3, and 58% had ≥ 4 teeth with a GI = 3. In general, as the measure of periodontal disease increased, stillbirth, PTB <32 wks and neonatal mortality also increased. Late PTB and LBW were not related to measures of periodontal disease. Adjustment for demographic characteristics did not significantly change the relationships. CONCLUSION Pregnant Pakistani women have high levels of moderate to severe dental disease. Both stillbirth and neonatal mortality increased with the severity of periodontal disease. PMID:18455527

  16. Paternal employment in solvent related occupations and adverse pregnancy outcomes.

    PubMed

    Daniell, W E; Vaughan, T L

    1988-03-01

    Washington State birth certificates were examined for associations between adverse pregnancy outcomes and paternal employment in solvent exposed occupations. Four cohorts defined by live, singleton births to fathers usually employed as auto body shop workers, painters (construction and maintenance), printers, or fibreglass workers were compared retrospectively with both a systematically selected control cohort and a low solvent exposed, occupationally defined control cohort (paternal electricians). The effects of maternal race and medical illness were controlled by sample restriction; maternal age and gravidity by stratified analysis. There was evidence of increased risk of low birth weight for infants born to fathers employed as body shop workers (relative risk = 1.6; 95% confidence interval = 1.1-2.4) or painters (RR = 1.4; CI = 0.9-2.1) when compared with the systematically selected controls but not with the electrician controls. The excess risk appeared stronger when only term infants were analysed suggesting a mechanism of growth retardation rather than prematurity. There was no evidence of increased risk among the other exposed cohorts or for other adverse pregnancy outcomes. Several design features limit the interpretation of the findings and confirmation by other studies is needed. PMID:3348995

  17. Spousal Military Deployment During Pregnancy and Adverse Birth Outcomes.

    PubMed

    Spieker, Amy; Schiff, Melissa A; Davis, Beth E

    2016-03-01

    Pregnant women with a military-deployed spouse have increased risk of depression and self-reported stress. In nonmilitary populations, depression and stress during pregnancy are associated with adverse birth outcomes. This study assesses the association between a spouse's military deployment and adverse birth outcomes. We conducted a retrospective cohort study at a large military medicine center in the Northwest and evaluated records of singleton deliveries to dependent Army spouses from September 2001 to September 2011. We used logistic regression to estimate relative risks and 95% confidence intervals (CI) of the associations between deployment and low birth weight (<2,500 g), preterm delivery (<37 weeks), small for gestational age (SGA, <10 percentile for gestational age), and cesarean delivery. We identified 10,536 births; 1,364 (12.9%) spouses were deployed at delivery. No associations were observed in the overall population. Among women with two or more children, we observed an 81% increased risk of SGA (95% CI 1.18-2.79). Women 30 to 34 years old had an 82% (95% CI 1.06-3.14) increased risk of low birth weight and an 84% increased risk of SGA (95% CI 1.13-2.98). Deployment's effects vary by maternal age and the number of children in the household. These findings may inform programs and practitioners to best serve women with military-deployed spouses. PMID:26926749

  18. Evaluating competing adverse and beneficial outcomes using a mixture model

    PubMed Central

    Lau, Bryan; Cole, Stephen R.; Moore, Richard D.; Gange, Stephen J.

    2008-01-01

    SUMMARY A competing risk framework occurs when individuals have the potential to experience only one of several mutually exclusive outcomes. Standard survival methods often overestimate the cumulative incidence of events when competing events are censored. Mixture distributions have been previously applied to the competing risk framework to obtain inferences regarding the subdistribution of an event of interest. Often the competing event is treated as a nuisance, but it may be of interest to compare adverse events against the beneficial outcome when dealing with an intervention. In this paper, methods for using a mixture model to estimate an adverse-benefit ratio curve (ratio of the cumulative incidence curves for the two competing events) and the ratio of the subhazards for the two competing events are presented. Both parametric and semi-parametric approaches are described with some remarks for extending the model to include uncertainty in the event type that occurred, left-truncation in order to allow for time-dependent analyses, and uncertainty in the timing of the event resulting in interval censoring. The methods are illustrated with data from a HIV clinical cohort examining whether individuals initiating effective antiretroviral therapy have a greater risk of antiretroviral discontinuation or switching compared to HIV RNA suppression. PMID:18416435

  19. Constructing, Quantifying, and Validating an Adverse Outcome Pathway for Vascular Developmental Toxicity

    EPA Science Inventory

    Constructing, Quantifying, and Validating an Adverse Outcome Pathway for Vascular Developmental Toxicity The adverse outcome pathway (AOP) for embryonic vascular disruption1 leading to a range of adverse prenatal outcomes was recently entered into the AOP wiki and accepted as par...

  20. The effects of air pollution on adverse birth outcomes

    PubMed Central

    Ha, Sandie; Hu, Hui; Roussos-Ross, Dikea; Haidong, Kan; Roth, Jeffrey; Xu, Xiaohui

    2014-01-01

    Background Air pollution has been shown to have adverse effects on many health outcomes including cardiorespiratory diseases and cancer. However, evidence on the effects of prenatal exposure is still limited. The purpose of this retrospective cohort study is to evaluate the effects of prenatal exposure to air pollutants including particulate matter with aerodynamic diameter less than 2.5 micrometer (PM2.5) and ozone (O3) on the risk of adverse birth outcomes (ABOs) including term low birth weight (LBW), preterm delivery (PTD) and very PTD (VPTD). Methods Singleton births from 2004–2005 in Florida were included in the study (N=423,719). Trimester-specific exposures to O3 and PM2.5 at maternal residence at delivery were estimated using the National Environmental Public Health Tracking Network data, which were interpolated using Hierarchical Bayesian models. Results After adjustment for potential confounders such as demographics, medical and lifestyle factors PM2.5 exposures in all trimesters were found to be significantly and positively associated with the risk of all ABOs. Second-trimester exposure had the strongest effects. For an interquartile range (IQR) increase in PM2.5 during the second trimester, the risk of term LBW, PTD and VPTD increased by 3% [95% confidence interval (CI): 1–6%)], 12% (11–14%) and 22% (18–25%), respectively. O3 was also found to be positively associated with PTD and VPTD with the strongest effects over the whole pregnancy period [3% (1–5%) for PTD and 13% (7–19%) for VPTD for each IQR increase]. However, O3 was observed to have protective effects on term LBW. Results were consistent for multi-pollutant models. Conclusion PM2.5 has consistent adverse effects on ABOs whereas O3 has inconsistent effects. These findings warrant further investigation. PMID:25173052

  1. Should we continue using amphotericin B deoxycholate for the treatment of fungal infections? Adverse events and clinical outcomes.

    PubMed

    Garbino, Jorge; Markham, Lydia; Matulionyte, Raimonda; Rives, Vincent; Lew, Daniel

    2006-01-01

    Amphotericin B deoxycholate (AmBd) has been a standard therapy for IFI but is associated with high adverse event and mortality rates. A retrospective review was undertaken to describe adverse events and clinical outcomes in adult patients with IFI treated with only AmBd as initial therapy. PMID:16449001

  2. Perioperative hypoxemia is common with horizontal positioning during general anesthesia and is associated with major adverse outcomes: a retrospective study of consecutive patients

    PubMed Central

    2014-01-01

    Background Reported perioperative pulmonary aspiration (POPA) rates have substantial variation. Perioperative hypoxemia (POH), a manifestation of POPA, has been infrequently studied beyond the PACU, for patients undergoing a diverse array of surgical procedures. Methods Consecutive adult patients with ASA I-IV and pre-operative pulmonary stability who underwent a surgical procedure requiring general anesthesia were investigated. Using pulse oximetry, POH was documented in the operating room and during the 48 hours following PACU discharge. POPA was the presence of an acute pulmonary infiltrate with POH. Results The 500 consecutive, eligible patients had operative body-positions of prone 13%, decubitus 8%, sitting 1%, and supine/lithotomy 78%, with standard practice of horizontal recumbency. POH was found in 150 (30%) patients. Post-operative stay with POH was 3.7 ± 4.7 days and without POH was 1.7 ± 2.3 days (p < 0.0001). POH rate varied from 14% to 58% among 11 of 12 operative procedure-categories. Conditions independently associated with POH (p < 0.05) were acute trauma, BMI, ASA level, glycopyrrolate administration, and duration of surgery. POPA occurred in 24 (4.8%) patients with higher mortality (8.3%), when compared to no POPA (0.2%; p = 0.0065). Post-operative stay was greater with POPA (7.7 ± 5.7 days), when compared to no POPA (2.0 ± 2.9 days; p = 0.0001). Conditions independently associated with POPA (p < 0.05) were cranial procedure, ASA level, and duration of surgery. POPA, acute trauma, duration of surgery, and inability to extubate in the OR were independently associated with post-operative stay (p < 0.05). POH, gastric dysmotility, acute trauma, cranial procedure, emergency procedure, and duration of surgery had independent correlations with post-operative length of stay (p < 0.05). Conclusions Adult surgical patients undergoing general anesthesia with horizontal recumbency have substantial POH and

  3. Prognostic indicators of adverse renal outcome and death in acute kidney injury hospital survivors

    PubMed Central

    Hamzić-Mehmedbašić, Aida; Rašić, Senija; Balavac, Merima; Rebić, Damir; Delić-Šarac, Marina; Durak-Nalbantić, Azra

    2016-01-01

    Introduction: Data regarding prognostic factors of post-discharge mortality and adverse renal function outcome in acute kidney injury (AKI) hospital survivors are scarce and controversial. Objectives: We aimed to identify predictors of post-discharge mortality and adverse renal function outcome in AKI hospital survivors. Patients and Methods: The study group consisted of 84 AKI hospital survivors admitted to the tertiary medical center during 2-year period. Baseline clinical parameters, with renal outcome 3 months after discharge and 6-month mortality were evaluated. According survival and renal function outcome, patients were divided into two groups. Results: Patients who did not recover renal function were statistically significantly older (P < 0.007) with higher Charlson comorbidity index (CCI) score (P < 0.000) and more likely to have anuria and oliguria (P = 0.008) compared to those with recovery. Deceased AKI patients were statistically significantly older (P < 0.000), with higher CCI score (P < 0.000), greater prevalence of sepsis (P =0.004), higher levels of C-reactive protein (CRP) (P < 0.017) and ferritin (P < 0.051) and lower concentrations of albumin (P<0.01) compared to survivors. By multivariate analysis, independent predictors of adverse renal outcome were female gender (P =0.033), increasing CCI (P =0.000), presence of pre-existing chronic kidney disease (P =0.000) and diabetes mellitus (P =0.019) as well as acute decompensated heart failure (ADHF) (P =0.032), while protective factor for renal function outcome was higher urine output (P =0.009). Independent predictors of post-discharge mortality were female gender (P =0.04), higher CCI score (P =0.001) and sepsis (P =0.034). Conclusion: Female AKI hospital survivors with increasing burden of comorbidities, diagnosis of sepsis and ADHF seem to be at high-risk for poor post-discharge outcome. PMID:27471736

  4. Perfluorinated Compounds in Umbilical Cord Blood and Adverse Birth Outcomes

    PubMed Central

    Chen, Mei-Huei; Ha, Eun-Hee; Wen, Ting-Wen; Su, Yi-Ning; Lien, Guang-Wen; Chen, Chia-Yang; Chen, Pau-Chung; Hsieh, Wu-Shiun

    2012-01-01

    Background Previous animal studies have shown that perfluorinated compounds (PFCs) have adverse impacts on birth outcomes, but the results have been inconclusive in humans. We investigated associations between prenatal exposure to perfluorooctanoic acid (PFOA), perfluorooctyl sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluoroundecanoic acid (PFUA) and birth outcomes. Methods In total, 429 mother-infant pairs were recruited from the Taiwan Birth Panel Study (TBPS). Demographic data were obtained by interviewing mothers using a structured questionnaire and birth outcomes were extracted from medical records. Cord blood was collected for PFOA, PFOS, PFNA, and PFUA analysis by ultra-high-performance liquid chromatography/tandem mass spectrometry. Results The geometric mean (standard deviation) levels of PFOA, PFOS, PFNA, and PFUA in cord blood plasma were 1.84 (2.23), 5.94 (1.95), 2.36(4.74), and 10.26 (3.07) ng/mL, respectively. Only PFOS levels were found to be inversely associated with gestational age, birth weight, and head circumference [per ln unit: adjusted β (95% confidence interval, CI) = −0.37 (−0.60, −0.13) wks, −110.2 (−176.0, −44.5) gm and −0.25 (−0.46, −0.05) cm]. Additionally, the odds ratio of preterm birth, low birth weight, and small for gestational age increased with PFOS exposure [per ln unit: adjusted odds ratio (OR) (95%CI) = 2.45 (1.47, 4.08), 2.61(0.85, 8.03) and 2.27 (1.25, 4.15)]. When PFOS levels were divided into quartiles, a dose-response relation was observed. However, PFOA, PFNA, and PFUA were not observed to have any convincing impact on birth outcomes. Conclusions An adverse dose-dependent association was observed between prenatal PFOS exposure and birth outcomes. However, no associations were found for the other examined PFCs. PMID:22879996

  5. Excessive folic acid intake and relation to adverse health outcome.

    PubMed

    Selhub, Jacob; Rosenberg, Irwin H

    2016-07-01

    The recent increase in the intake of folic acid by the general public through fortified foods and supplements, has raised safety concern based on early reports of adverse health outcome in elderly with low B12 status who took high doses of folic acid. These safety concerns are contrary to the 2015 WHO statement that "high folic acid intake has not reliably been shown to be associated with negative healeffects". In the folic acid post-fortification era, we have shown that in elderly participants in NHANES 1999-2002, high plasma folate level is associated with exacerbation of both clinical (anemia and cognitive impairment) and biochemical (high MMA and high Hcy plasma levels) signs of vitamin B12 deficiency. Adverse clinical outcomes in association with high folate intake were also seen among elderly with low plasma B12 levels from the Framingham Original Cohort and in a study from Australia which combined three elderly cohorts. Relation between high folate and adverse biochemical outcomes were also seen in the Sacramento Area Latino Study on Aging (High Hcy, high MMA and lower TC2) and at an outpatient clinic at Yale University where high folate is associated with higher MMA in the elderly but not in the young. Potential detrimental effects of high folic acid intake may not be limited to the elderly nor to those with B12 deficiency. A study from India linked maternal high RBC folate to increased insulin resistance in offspring. Our study suggested that excessive folic acid intake is associated with lower natural killer cells activity in elderly women. In a recent study we found that the risk for unilateral retinoblastoma in offspring is 4 fold higher in women that are homozygotes for the 19 bp deletion in the DHFR gene and took folic acid supplement during pregnancy. In the elderly this polymorphism is associated with lower memory and executive scores, both being significantly worse in those with high plasma folate. These and other data strongly imply that

  6. Development of a Screening Tool for Predicting Adverse Outcomes of Gestational Diabetes Mellitus: A Retrospective Cohort Study.

    PubMed

    Park, Jee Soo; Kim, Deok Won; Kwon, Ja-Young; Park, Yong Won; Kim, Young Han; Cho, Hee Young

    2016-01-01

    Gestational diabetes mellitus (GDM) is a common disease in pregnancy causing maternal and fetal complications. To prevent these adverse outcomes, optimal screening and diagnostic criteria must be adequate, timely, and efficient. This study suggests a novel approach that is practical, efficient, and patient- and clinician-friendly in predicting adverse outcomes of GDM. The authors conducted a retrospective cohort study via medical record review of patients admitted between March 2001 and April 2013 at the Severance Hospital, Seoul, South Korea. Patients diagnosed by a conventional 2-step method were evaluated according to the presence of adverse outcomes (neonatal hypoglycemia, hyperbilirubinemia, and hyperinsulinemia; admission to the neonatal intensive care unit; large for gestational age; gestational insulin therapy; and gestational hypertension). Of 802 women who had an abnormal 50-g, 1-hour glucose challenge test, 306 were diagnosed with GDM and 496 did not have GDM (false-positive group). In the GDM group, 218 women (71.2%) had adverse outcomes. In contrast, 240 women (48.4%) in the false-positive group had adverse outcomes. Women with adverse outcomes had a significantly higher body mass index (BMI) at entry (P = 0.03) and fasting blood glucose (FBG) (P = 0.03). Our logistic regression model derived from 2 variables, BMI at entry and FBG, predicted GDM adverse outcome with an area under the curve of 0.642, accuracy of 61.3%, sensitivity of 57.2%, and specificity of 66.9% compared with the conventional 2-step method with an area under the curve of 0.610, accuracy of 59.1%, sensitivity of 47.6%, and specificity of 74.4%. Our model performed better in predicting GDM adverse outcomes than the conventional 2-step method using only BMI at entry and FBG. Moreover, our model represents a practical, inexpensive, efficient, reproducible, easy, and patient- and clinician-friendly approach. PMID:26735528

  7. Mycoplasma, Ureaplasma, and Adverse Pregnancy Outcomes: A Fresh Look

    PubMed Central

    Larsen, Bryan; Hwang, Joseph

    2010-01-01

    Recent work on the Molicutes that associate with genital tract tissues focuses on four species that may be of interest in potential maternal, fetal, and neonatal infection and in contributing to adverse pregnancy outcomes. Mycoplasma hominis and Ureaplasma urealyticum have historically been the subject of attention, but Mycoplasma genitalis which causes male urethritis in addition to colonizing the female genital tract and the division of Ureaplasma into two species, urealyticum and parvum, has also added new taxonomic clarity. The role of these genital tract inhabitants in infection during pregnancy and their ability to invade and infect placental and fetal tissue is discussed. In particular, the role of some of these organisms in prematurity may be mechanistically related to their ability to induce inflammatory cytokines, thereby triggering pathways leading to preterm labor. A review of this intensifying exploration of the mycoplasmas in relation to pregnancy yields several questions which will be important to examine in future research. PMID:20706675

  8. Adverse Outcome Pathway (AOP) Development I: Strategies and Principles

    PubMed Central

    Villeneuve, Daniel L.; Crump, Doug; Garcia-Reyero, Natàlia; Hecker, Markus; Hutchinson, Thomas H.; LaLone, Carlie A.; Landesmann, Brigitte; Lettieri, Teresa; Munn, Sharon; Nepelska, Malgorzata; Ottinger, Mary Ann; Vergauwen, Lucia; Whelan, Maurice

    2014-01-01

    An adverse outcome pathway (AOP) is a conceptual framework that organizes existing knowledge concerning biologically plausible, and empirically supported, links between molecular-level perturbation of a biological system and an adverse outcome at a level of biological organization of regulatory relevance. Systematic organization of information into AOP frameworks has potential to improve regulatory decision-making through greater integration and more meaningful use of mechanistic data. However, for the scientific community to collectively develop a useful AOP knowledgebase that encompasses toxicological contexts of concern to human health and ecological risk assessment, it is critical that AOPs be developed in accordance with a consistent set of core principles. Based on the experiences and scientific discourse among a group of AOP practitioners, we propose a set of five fundamental principles that guide AOP development: (1) AOPs are not chemical specific; (2) AOPs are modular and composed of reusable components—notably key events (KEs) and key event relationships (KERs); (3) an individual AOP, composed of a single sequence of KEs and KERs, is a pragmatic unit of AOP development and evaluation; (4) networks composed of multiple AOPs that share common KEs and KERs are likely to be the functional unit of prediction for most real-world scenarios; and (5) AOPs are living documents that will evolve over time as new knowledge is generated. The goal of the present article was to introduce some strategies for AOP development and detail the rationale behind these 5 key principles. Consideration of these principles addresses many of the current uncertainties regarding the AOP framework and its application and is intended to foster greater consistency in AOP development. PMID:25466378

  9. Adverse outcome pathway (AOP) development I: strategies and principles.

    PubMed

    Villeneuve, Daniel L; Crump, Doug; Garcia-Reyero, Natàlia; Hecker, Markus; Hutchinson, Thomas H; LaLone, Carlie A; Landesmann, Brigitte; Lettieri, Teresa; Munn, Sharon; Nepelska, Malgorzata; Ottinger, Mary Ann; Vergauwen, Lucia; Whelan, Maurice

    2014-12-01

    An adverse outcome pathway (AOP) is a conceptual framework that organizes existing knowledge concerning biologically plausible, and empirically supported, links between molecular-level perturbation of a biological system and an adverse outcome at a level of biological organization of regulatory relevance. Systematic organization of information into AOP frameworks has potential to improve regulatory decision-making through greater integration and more meaningful use of mechanistic data. However, for the scientific community to collectively develop a useful AOP knowledgebase that encompasses toxicological contexts of concern to human health and ecological risk assessment, it is critical that AOPs be developed in accordance with a consistent set of core principles. Based on the experiences and scientific discourse among a group of AOP practitioners, we propose a set of five fundamental principles that guide AOP development: (1) AOPs are not chemical specific; (2) AOPs are modular and composed of reusable components-notably key events (KEs) and key event relationships (KERs); (3) an individual AOP, composed of a single sequence of KEs and KERs, is a pragmatic unit of AOP development and evaluation; (4) networks composed of multiple AOPs that share common KEs and KERs are likely to be the functional unit of prediction for most real-world scenarios; and (5) AOPs are living documents that will evolve over time as new knowledge is generated. The goal of the present article was to introduce some strategies for AOP development and detail the rationale behind these 5 key principles. Consideration of these principles addresses many of the current uncertainties regarding the AOP framework and its application and is intended to foster greater consistency in AOP development. PMID:25466378

  10. Predictors of Adverse Cosmetic Outcome in the RAPID Trial: An Exploratory Analysis

    SciTech Connect

    Peterson, David; Truong, Pauline T.; Parpia, Sameer; Olivotto, Ivo A.; Berrang, Tanya; Kim, Do-Hoon; Kong, Iwa; Germain, Isabelle; Nichol, Alan; Akra, Mohamed; Roy, Isabelle; Reed, Melanie; Fyles, Anthony; Trotter, Theresa; Perera, Francisco; Balkwill, Susan; Lavertu, Sophie; Elliott, Elizabeth; and others

    2015-04-01

    Purpose: To evaluate factors associated with adverse cosmesis outcome in breast cancer patients randomized to accelerated partial breast irradiation (APBI) using 3-dimensional conformal radiation therapy or whole-breast irradiation in the RAPID (Randomized Trial of Accelerated Partial Breast Irradiation) trial. Methods and Materials: Subjects were trial participants with nurse-assessed global cosmetic scores at baseline and at 3 years. Adverse cosmesis was defined as a score of fair or poor. Cosmetic deterioration was defined as any adverse change in score from baseline to 3 years. The analysis is based on data from the previously reported interim analysis. Logistic regression models were used to assess the association of risk factors for these outcomes among all patients and those treated with APBI only. Results: Clinicopathologic characteristics were similar between subjects randomized to APBI (n=569) or whole-breast irradiation (n=539). For all subjects, factors associated with adverse cosmesis at 3 years were older age, central/inner tumor location, breast infection, smoking, seroma volume, breast volume, and use of APBI; factors associated with cosmetic deterioration were smoking, seroma volume, and use of APBI (P<.05). For APBI subjects, tumor location, smoking, age, and seroma volume were associated with adverse cosmesis (P<.05), and smoking was associated with cosmetic deterioration (P=.02). An independent association between the V95/whole-breast volume ratio and adverse cosmesis (P=.28) or cosmetic deterioration (P=.07) was not detected. On further exploration a V95/whole-breast volume ratio <0.15 was associated with a lower risk of cosmetic deterioration (p=.04), but this accounted for only 11% of patients. Conclusion: In the RAPID trial, a number of patient tumor and treatment-related factors, including the use of APBI, were associated with adverse cosmesis and cosmetic deterioration. For patients treated with APBI alone, the high-dose treatment

  11. Teleophthalmology: improving patient outcomes?

    PubMed

    Sreelatha, Omana Kesary; Ramesh, Sathyamangalam VenkataSubbu

    2016-01-01

    Teleophthalmology is gaining importance as an effective eye care delivery modality worldwide. In many developing countries, teleophthalmology is being utilized to provide quality eye care to the underserved urban population and the unserved remote rural population. Over the years, technological innovations have led to improvement in evidence and teleophthalmology has evolved from a research tool to a clinical tool. The majority of the current teleophthalmology services concentrate on patient screening and appropriate referral to experts. Specialty care using teleophthalmology services for the pediatric group includes screening as well as providing timely care for retinopathy of prematurity (ROP). Among geriatric eye diseases, specialty teleophthalmology care is focused toward screening and referral for diabetic retinopathy (DR), glaucoma, age-related macular degeneration (ARMD), and other sight-threatening conditions. Comprehensive vision screening and refractive error services are generally covered as part of most of the teleophthalmology methods. Over the past decades, outcome assessment of health care system includes patients' assessments on their health, care, and services they receive. Outcomes, by and large, remain the ultimate validators of the effectiveness and quality of medical care. Teleophthalmology produces the same desired clinical outcome as the traditional system. Remote portals allow specialists to provide care over a larger region, thereby improving health outcomes and increasing accessibility of specialty care to a larger population. A high satisfaction level and acceptance is reported in the majority of the studies because of increased accessibility and reduced traveling cost and time. Considering the improved quality of patient care and patient satisfaction reported for these telemedicine services, this review explores how teleophthalmology helps to improve patient outcomes. PMID:26929592

  12. Aspirin use for primary prophylaxis: Adverse outcomes in non-variceal upper gastrointestinal bleeding

    PubMed Central

    Souk, Karina M; Tamim, Hani M; Abu Daya, Hussein A; Rockey, Don C; Barada, Kassem A

    2016-01-01

    AIM: To compare outcomes of patients with non-variceal upper gastrointestinal bleeding (NVUGIB) taking aspirin for primary prophylaxis to those not taking it. METHODS: Patients not known to have any vascular disease (coronary artery or cerebrovascular disease) who were admitted to the American University of Beirut Medical Center between 1993 and 2010 with NVUGIB were included. The frequencies of in-hospital mortality, re-bleeding, severe bleeding, need for surgery or embolization, and of a composite outcome defined as the occurrence of any of the 4 bleeding related adverse outcomes were compared between patients receiving aspirin and those on no antithrombotics. We also compared frequency of in hospital complications and length of hospital stay between the two groups. RESULTS: Of 357 eligible patients, 94 were on aspirin and 263 patients were on no antithrombotics (control group). Patients in the aspirin group were older, the mean age was 58 years in controls and 67 years in the aspirin group (P < 0.001). Patients in the aspirin group had significantly more co-morbidities, including diabetes mellitus and hypertension [25 (27%) vs 31 (112%) and 44 (47%) vs 74 (28%) respectively, (P = 0.001)], as well as dyslipidemia [21 (22%) vs 16 (6%), P < 0.0001). Smoking was more frequent in the aspirin group [34 (41%) vs 60 (27%), P = 0.02)]. The frequencies of endoscopic therapy and surgery were similar in both groups. Patients who were on aspirin had lower in-hospital mortality rates (2.1% vs 13.7%, P = 0.002), shorter hospital stay (4.9 d vs 7 d, P = 0.01), and fewer composite outcomes (10.6% vs 24%, P = 0.01). The frequencies of in-hospital complications and re-bleeding were similar in the two groups. CONCLUSION: Patients who present with NVUGIB while receiving aspirin for primary prophylaxis had fewer adverse outcomes. Thus aspirin may have a protective effect beyond its cardiovascular benefits. PMID:27462392

  13. Teleophthalmology: improving patient outcomes?

    PubMed Central

    Sreelatha, Omana Kesary; Ramesh, Sathyamangalam VenkataSubbu

    2016-01-01

    Teleophthalmology is gaining importance as an effective eye care delivery modality worldwide. In many developing countries, teleophthalmology is being utilized to provide quality eye care to the underserved urban population and the unserved remote rural population. Over the years, technological innovations have led to improvement in evidence and teleophthalmology has evolved from a research tool to a clinical tool. The majority of the current teleophthalmology services concentrate on patient screening and appropriate referral to experts. Specialty care using teleophthalmology services for the pediatric group includes screening as well as providing timely care for retinopathy of prematurity (ROP). Among geriatric eye diseases, specialty teleophthalmology care is focused toward screening and referral for diabetic retinopathy (DR), glaucoma, age-related macular degeneration (ARMD), and other sight-threatening conditions. Comprehensive vision screening and refractive error services are generally covered as part of most of the teleophthalmology methods. Over the past decades, outcome assessment of health care system includes patients’ assessments on their health, care, and services they receive. Outcomes, by and large, remain the ultimate validators of the effectiveness and quality of medical care. Teleophthalmology produces the same desired clinical outcome as the traditional system. Remote portals allow specialists to provide care over a larger region, thereby improving health outcomes and increasing accessibility of specialty care to a larger population. A high satisfaction level and acceptance is reported in the majority of the studies because of increased accessibility and reduced traveling cost and time. Considering the improved quality of patient care and patient satisfaction reported for these telemedicine services, this review explores how teleophthalmology helps to improve patient outcomes. PMID:26929592

  14. Adverse obstetric and neonatal outcomes in women with mental disorders.

    PubMed

    Hoirisch-Clapauch, Silvia; Brenner, Benjamin; Nardi, Antonio Egidio

    2015-02-01

    The brain and the placenta synthesize identical peptides and proteins, such as brain-derived neurotrophic factor, oxytocin, vascular endothelial growth factor, cortisol, and matrix metalloproteinases. Given the promiscuity between neurochemistry and the mechanism of placentation, it would be expected that mental disorders occurring during pregnancy would increase the risk of adverse obstetric and neonatal outcomes. Indeed, expectant mothers with anxiety disorders, post-traumatic stress disorder, schizophrenia, or depressive disorders are at higher risk of preterm birth, low-birth-weight and small-for-gestational-age infants than controls. These mental illnesses are accompanied by a procoagulant phenotype and low activity of tissue plasminogen activator, which may contribute to placental insufficiency. Another risk factor for pregnancy complications is hyperemesis gravidarum, more common among women with eating disorders or anxiety disorders than in controls. Severe hyperemesis gravidarum is associated with dehydration, electrolyte imbalance and malnutrition, all of which may increase the risk of miscarriages, of low-birth-weight babies and preterm birth. This paper reviews some aspects of mental disorders that may influence pregnancy and neonatal outcomes. PMID:25903540

  15. Accelerating Adverse Outcome Pathway Development Using Publicly Available Data Sources.

    PubMed

    Oki, Noffisat O; Nelms, Mark D; Bell, Shannon M; Mortensen, Holly M; Edwards, Stephen W

    2016-03-01

    The adverse outcome pathway (AOP) concept links molecular perturbations with organism and population-level outcomes to support high-throughput toxicity (HTT) testing. International efforts are underway to define AOPs and store the information supporting these AOPs in a central knowledge base; however, this process is currently labor-intensive and time-consuming. Publicly available data sources provide a wealth of information that could be used to define computationally predicted AOPs (cpAOPs), which could serve as a basis for creating expert-derived AOPs in a much more efficient way. Computational tools for mining large datasets provide the means for extracting and organizing the information captured in these public data sources. Using cpAOPs as a starting point for expert-derived AOPs should accelerate AOP development. Coupling this with tools to coordinate and facilitate the expert development efforts will increase the number and quality of AOPs produced, which should play a key role in advancing the adoption of HTT testing, thereby reducing the use of animals in toxicity testing and greatly increasing the number of chemicals that can be tested. PMID:26809562

  16. Simulation: improving patient outcomes.

    PubMed

    Smith, Abi; Siassakos, Dimitrios; Crofts, Joanna; Draycott, Tim

    2013-06-01

    Effective training has been shown to improve perinatal care and outcome, decrease litigation claims and reduce midwifery sick leave. To be effective, training should be incentivised, in a realistic context, and delivered to inter-professional teams similar to those delivering actual care. Teamwork training is a useful addition, but it should be based on the characteristics of effective teamwork as derived from the study of frontline teams. Implementation of simulation and teamwork training is challenging, with constraints on staff time, facilities and finances. Local adoption and adaptation of effective programmes can help keep costs down, and make them locally relevant whilst maintaining effectiveness. Training programmes need to evolve continually in line with new evidence. To do this, it is vital to monitor outcomes and robustly evaluate programmes for their impact on patient care and outcome, not just on participants. PMID:23721770

  17. Evidence for adverse reproductive outcomes among women microelectronic assembly workers.

    PubMed Central

    Huel, G; Mergler, D; Bowler, R

    1990-01-01

    Microelectronics assembly entails complex processes where several potentially fetotoxic chemical compounds are used extensively. This study was undertaken to assess the potential adverse reproductive outcomes among former women workers in a microelectronics assembly plant in New Mexico with respect to a comparable population from the same geographical region and to examine the relation between these outcomes and employment history in this plant. After matching a pool of 143 former microelectronic female workers and 105 referents, 90 former microelectronic female worker-referent pairs were constituted (representing 302 and 324 pregnancies in former workers and referents respectively). The odds ratio (for pair matching design) of spontaneous abortion among women workers, before beginning to assemble microelectronic components, was 0.9 (chi 2 = 0.04; NS). After the beginning of employment this odds ratio became 5.6 (chi 2 = 9.8; p less than 1%). This estimated odds ratio decreased to 4.0, taking into account the increased risk for spontaneous abortion in previous pregnancies before employment (chi 2 = 5.4; p less than 5%). It was not possible to determine if this effect was reversible owing to the small number of pairs available after employment. The findings of this study corroborate the results of former studies that suggest a potential association between electronic manufacturing activity and risk of spontaneous abortion. Although the organic solvents were suspected of being the potential risk factor, this study was inconclusive from this point of view. Nevertheless, these investigations may provide some insight into reproductive outcomes among female workers exposed to solvents. PMID:2378817

  18. Adverse health outcomes among cosmetologists and noncosmetologists in the Reproductive Outcomes of Salon Employees (ROSE) study.

    PubMed

    Gallicchio, Lisa; Miller, Susan R; Greene, Teresa; Zacur, Howard; Flaws, Jodi A

    2011-01-01

    The purpose of this study was to examine adverse health outcomes, including those related to cardiovascular and skin health as well as respiratory functions, among cosmetologists aged 21 to 55 yr and to compare data to women of the same age working in other occupations. Self-reported data were analyzed from 450 cosmetologists and 511 women in other occupations who participated in the Reproductive Outcomes of Salon Employees (ROSE) study in Maryland. Odds ratios (OR) and 95% confidence intervals (95% CI) were computed using logistic regression to examine the associations between cosmetologist occupation and each adverse health outcome adjusted for age, education, and smoking status. Cosmetologists were at significantly increased risk of depression compared to noncosmetologists after adjustment for age, education, and smoking status (OR 1.49; 95% CI 1.10, 2.00). There were no statistically significant associations between cosmetology occupation and the other adverse health outcomes, including those related to allergies and skin disorders, in both the unadjusted and adjusted analyses. Cosmetologists may be exposed to chemicals in the salon that lead to depression. Future study needs to be conducted to examine specific chemical exposures in the salon. This will help to provide information required for the development of best occupational safety practices among salon workers. PMID:21120748

  19. Antenatal psychosocial risk factors associated with adverse postpartum family outcomes.

    PubMed Central

    Wilson, L M; Reid, A J; Midmer, D K; Biringer, A; Carroll, J C; Stewart, D E

    1996-01-01

    OBJECTIVE: To determine the strength of the association between antenatal psychosocial risk factors and adverse postpartum outcomes in the family, such as assault of women by their partner, child abuse, postpartum depression, marital dysfunction and physical illness. DATA SOURCES: MEDLINE, Cinahl, Famli, Psych Abstracts and the Oxford Database of Perinatal Trials were searched from relevant articles published from Jan. 1, 1980, to Dec. 31, 1993, with the use of MeSH terms "depression, involutional," "child abuse," "child neglect," "domestic violence," "family," "marital adjustment," "family health," "newborn health," "child health," "physical illness," "social support," "psychosocial risk," "prediction," "risk factors," "obstetrics" and "prenatal care." Further articles were identified from bibliographies. STUDY SELECTION: Of the 370 articles identified through the search, 118 were included for review. Studies were included if they examined the association between psychosocial risk factors and the outcomes of interest. Articles were excluded if they were reviews of poor quality or they had one or more of the following features: insufficient description of the sample, a high attrition rate, a lack of standardized outcome measures, outcomes other than the ones of interest or results that had already been reported in a previous study. DATA EXTRACTION: The strength of evidence of each study was evaluated. On the basis of the evidence, each risk factor was assigned a rating of the strength of its association with each of the postpartum outcomes. The ratings were class A (good evidence of association), class B (fair evidence) and class C (no clear evidence). Of the 129 antenatal psychosocial risk factors studied, 15 were found to have a class A association with at least one of the postpartum outcomes. DATA SYNTHESIS: Child abuse and abuse of the mother by her partner were most strongly correlated (class A evidence) with a history of lack of social support, recent life

  20. Developing and applying adverse outcome pathways: What you need to know

    EPA Science Inventory

    Adverse outcome pathways (AOPs) are a conceptual framework for organizing existing information concerning the predictive linkages between the initiation or early progression of a biological perturbation in an organism and the adverse outcome(s) of regulatory relevance (e.g., impa...

  1. Modeling risk for severe adverse outcomes using angiogenic factor measurements in women with suspected preterm preeclampsia

    PubMed Central

    Palomaki, Glenn E; Haddow, James E; Haddow, Hamish R M; Salahuddin, Saira; Geahchan, Carl; Cerdeira, Ana Sofia; Verlohren, Stefan; Perschel, Frank H; Horowitz, Gary; Thadhani, Ravi; Karumanchi, S Ananth; Rana, Sarosh

    2015-01-01

    Introduction Preeclampsia (PE) is a pregnancy-specific syndrome associated with adverse maternal and fetal outcomes. Patient-specific risks based on angiogenic factors might better categorize those who might have a severe adverse outcome. Methods Women evaluated for suspected PE at a tertiary hospital (2009–2012) had pregnancy outcomes categorized as ‘referent’ or ‘severe’, based solely on maternal/fetal findings. Outcomes that may have been influenced by a PE diagnosis were considered ‘unclassified’. Soluble fms-like tyrosine kinase (sFlt1) and placental growth factor (PlGF) were subjected to bivariate discriminant modeling, allowing patient-specific risks to be assigned for severe outcomes. Results Three hundred twenty-eight singleton pregnancies presented at ≤34.0 weeks' gestation. sFlt1 and PlGF levels were adjusted for gestational age. Risks above 5 : 1 (10-fold over background) occurred in 77% of severe (95% CI 66 to 87%) and 0.7% of referent (95% CI <0.1 to 3.8%) outcomes. Positive likelihood ratios for the modeling and validation datasets were 19 (95% CI 6.2–58) and 15 (95% CI 5.8–40) fold, respectively. Conclusions This validated model assigns patient-specific risks of any severe outcome among women attending PE triage. In practice, women with high risks would receive close surveillance with the added potential for reducing unnecessary preterm deliveries among remaining women. © 2015 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd. PMID:25641027

  2. Adverse outcomes of frailty in the elderly: the Rotterdam Study.

    PubMed

    Lahousse, Lies; Maes, Bastiaan; Ziere, Gijsbertus; Loth, Daan W; Verlinden, Vincentius J A; Zillikens, M Carola; Uitterlinden, André G; Rivadeneira, Fernando; Tiemeier, Henning; Franco, Oscar H; Ikram, M Arfan; Hofman, Albert; Brusselle, Guy G; Stricker, Bruno H

    2014-06-01

    To investigate the prevalence of frailty in a Dutch elderly population and to identify adverse health outcomes associated with the frailty phenotype independent of the comorbidities. Cross-sectional and longitudinal analyses within the Rotterdam Study (the Netherlands), a prospective population-based cohort study in persons aged ≥55 years. Frailty was defined as meeting three or more of five established criteria for frailty, evaluating nutritional status, physical activity, mobility, grip strength and exhaustion. Intermediate frailty was defined as meeting one or two frailty criteria. Comorbidities were objectively measured. Health outcomes were assessed by means of questionnaires, physical examinations and continuous follow-up through general practitioners and municipal health authorities for mortality. Of 2,833 participants (median age 74.0 years, inter quartile range 9) with sufficiently evaluated frailty criteria, 163 (5.8 %) participants were frail and 1,454 (51.3 %) intermediate frail. Frail elderly were more likely to be older and female, to have an impaired quality of life and to have fallen or to have been hospitalized. 108 (72.0 %) frail participants had ≥2 comorbidities, compared to 777 (54.4 %) intermediate frail and 522 (44.8 %) non-frail participants. Adjusted for age, sex and comorbidities, frail elderly had a significantly increased risk of dying within 3 years (HR 3.4; 95 % CI 1.9-6.4), compared to the non-frail elderly. This study in a general Dutch population of community-dwelling elderly able to perform the frailty tests, demonstrates that frailty is common and that frail elderly are at increased risk of death independent of comorbidities. PMID:24935872

  3. Adverse pregnancy outcomes and cardiovascular risk factor management.

    PubMed

    Mehta, Puja K; Minissian, Margo; Bairey Merz, C Noel

    2015-06-01

    Cardiovascular disease (CVD) is the leading health threat to American women. In addition to establish risk factors for hypertension, hyperlipidemia, diabetes, smoking, and obesity, adverse pregnancy outcomes (APOs) including pre-eclampsia, eclampsia, and gestational diabetes are now recognized as factors that increase a woman's risk for future CVD. CVD risk factor burden is disproportionately higher in those of low socioeconomic status and in ethnic/racial minority women. Since younger women often use their obstetrician/gynecologist as their primary health provider, this is an opportune time to diagnose and treat CVD risk factors early. Embedding preventive care providers such as nurse practitioners or physician assistants within OB/GYN practices can be considered, with referral to family medicine or internist for ongoing risk assessment and management. The American Heart Association (AHA)/American Stroke Association (ASA) stroke prevention guidelines tailored to women recommend that women with a history of pre-eclampsia can be evaluated for hypertension and other CVD risk factors within 6 months to 1-year post-partum. Given the burden and impact of CVD on women in our society, the entire medical community must work to establish feasible practice and referral patterns for assessment and treatment of CVD risk factors. PMID:26159741

  4. Adverse Pregnancy Outcomes and Cardiovascular Risk Factor Management

    PubMed Central

    Mehta, Puja K.; Minissian, Margo; Merz, C. Noel Bairey

    2015-01-01

    Cardiovascular disease (CVD) is the leading health threat to American women. In addition to established risk factors for hypertension, hyperlipidemia, diabetes, smoking, and obesity, adverse pregnancy outcomes (APOs) including pre-eclampsia, eclampsia, and gestational diabetes are now recognized as factors that increase a woman’s risk for future CVD. CVD risk factor burden is disproportionately higher in those of low socioeconomic status and in ethnic/racial minority women. Since younger women often use their obstetrician/gynecologist as their primary health provider, this is an opportune time to diagnose and treat CVD risk factors early. Embedding preventive care providers such as nurse practitioners or physician assistants within OB/GYN practices can be considered, with referral to family medicine or internist for ongoing risk assessment and management. The American Heart Association (AHA)/American Stroke Association (ASA) stroke prevention guidelines tailored to women recommend that women with a history of pre-eclampsia be evaluated for hypertension and other CVD risk factors within 6 months to 1 year post-partum. Given the burden and impact of CVD on women our society, the entire medical community must work to establish feasible practice and referral patterns for assessment and treatment of CVD risk factors. PMID:26159741

  5. Candida Virulence Properties and Adverse Clinical Outcomes in Neonatal Candidiasis

    PubMed Central

    Bliss, Joseph M.; Wong, Angela Y.; Bhak, Grace; Laforce-Nesbitt, Sonia S.; Taylor, Sarah; Tan, Sylvia; Stoll, Barbara J.; Higgins, Rosemary D.; Shankaran, Seetha; Benjamin, Daniel K.

    2012-01-01

    Objective To determine if premature infants with invasive Candida infection caused by strains with increased virulence properties have worse clinical outcomes than those infected with less virulent strains. Study design Clinical isolates were studied from 2 populations; premature infants colonized with Candida (commensal, n=27), and those with invasive candidiasis (n=81). Individual isolates of C. albicans and C. parapsilosis were tested for virulence in each of 3 assays: phenotypic switching, adhesion, and cytotoxicity. Invasive isolates were considered to have enhanced virulence if they measured more than 1 SD above the mean for the commensal isolates in at least 1 assay. Outcomes of patients with invasive isolates with enhanced virulence were compared with those with invasive isolates lacking enhanced virulence characteristics. Results 61% of invasive isolates of C. albicans and 42% of invasive isolates of C. parapsilosis had enhanced virulence. All C. albicans cerebrospinal fluid (CSF) isolates (n=6) and 90% of urine isolates (n=10) had enhanced virulence, compared with 48% of blood isolates (n=40). Infants with more virulent isolates were younger at the time of positive culture and had higher serum creatinine. Conclusions Individual isolates of Candida species vary in their virulence properties. Strains with higher virulence are associated with certain clinical outcomes. PMID:22504098

  6. Prediction of adverse outcomes of acute coronary syndrome using intelligent fusion of triage information with HUMINT

    NASA Astrophysics Data System (ADS)

    McCullough, Claire L.; Novobilski, Andrew J.; Fesmire, Francis M.

    2006-04-01

    Faculty from the University of Tennessee at Chattanooga and the University of Tennessee College of Medicine, Chattanooga Unit, have used data mining techniques and neural networks to examine a set of fourteen features, data items, and HUMINT assessments for 2,148 emergency room patients with symptoms possibly indicative of Acute Coronary Syndrome. Specifically, the authors have generated Bayesian networks describing linkages and causality in the data, and have compared them with neural networks. The data includes objective information routinely collected during triage and the physician's initial case assessment, a HUMINT appraisal. Both the neural network and the Bayesian network were used to fuse the disparate types of information with the goal of forecasting thirty-day adverse patient outcome. This paper presents details of the methods of data fusion including both the data mining techniques and the neural network. Results are compared using Receiver Operating Characteristic curves describing the outcomes of both methods, both using only objective features and including the subjective physician's assessment. While preliminary, the results of this continuing study are significant both from the perspective of potential use of the intelligent fusion of biomedical informatics to aid the physician in prescribing treatment necessary to prevent serious adverse outcome from ACS and as a model of fusion of objective data with subjective HUMINT assessment. Possible future work includes extension of successfully demonstrated intelligent fusion methods to other medical applications, and use of decision level fusion to combine results from data mining and neural net approaches for even more accurate outcome prediction.

  7. Vitamin D Deficiency Strongly Predicts Adverse Medical Outcome Across Different Medical Inpatient Populations

    PubMed Central

    Graedel, Lena; Merker, Meret; Felder, Susan; Kutz, Alexander; Haubitz, Sebastian; Faessler, Lukas; Kaeslin, Martha; Huber, Andreas; Mueller, Beat; Schuetz, Philipp

    2016-01-01

    Abstract Vitamin D deficiency has been associated with several adverse outcomes mainly in the outpatient setting. The objective of this study was to examine the prevalence of vitamin D deficiency and its association with risk of adverse clinical outcomes in a large prospective cohort of medical inpatients. We collected clinical data and measured 25(OH)D levels in adult medical patients upon hospital admission and followed them for 30 days. Regression analyses adjusted for age, gender, comorbidities, and main medical diagnosis were performed to study the effect of vitamin D deficiency on several hospital outcomes. Of 4257 included patients, 1510 (35.47%) had 25(OH)D levels of 25 to 50 nmol/L (vitamin D insufficiency) and 797 (18.72%) had levels of <25nmol/L (severe deficiency). Vitamin D insufficiency and severe deficiency were associated (OR/HR, 95%CI) with an increased risk of 30-day mortality (OR 1.70, 1.22–2.36 and 2.70, 1.22–2.36) and increased length of stay (HR 0.88, 0.81–0.97 and 0.72, 0.65–0.81). Severe deficiency was associated with risk of falls (OR 1.77, 1.18–2.63), impaired Barthel index (OR 1.80, 1.42–2.28), and impairment in quality of life. Most associations remained robust after multivariate adjustment and in subgroups stratified by gender, age, comorbidities, and main diagnoses (P for interaction >0.05). In this comprehensive and large medical inpatient cohort, vitamin D deficiency was highly prevalent and strongly associated with adverse clinical outcome. Interventional research is urgently needed to prove the effect of vitamin D supplementation on these outcomes. PMID:27175650

  8. A clinical risk score of myocardial fibrosis predicts adverse outcomes in aortic stenosis

    PubMed Central

    Chin, Calvin W.L.; Messika-Zeitoun, David; Shah, Anoop S.V.; Lefevre, Guillaume; Bailleul, Sophie; Yeung, Emily N.W.; Koo, Maria; Mirsadraee, Saeed; Mathieu, Tiffany; Semple, Scott I.; Mills, Nicholas L.; Vahanian, Alec; Newby, David E.; Dweck, Marc R.

    2016-01-01

    Aims Midwall myocardial fibrosis on cardiovascular magnetic resonance (CMR) is a marker of early ventricular decompensation and adverse outcomes in aortic stenosis (AS). We aimed to develop and validate a novel clinical score using variables associated with midwall fibrosis. Methods and results One hundred forty-seven patients (peak aortic velocity (Vmax) 3.9 [3.2,4.4] m/s) underwent CMR to determine midwall fibrosis (CMR cohort). Routine clinical variables that demonstrated significant association with midwall fibrosis were included in a multivariate logistic score. We validated the prognostic value of the score in two separate outcome cohorts of asymptomatic patients (internal: n = 127, follow-up 10.3 [5.7,11.2] years; external: n = 289, follow-up 2.6 [1.6,4.5] years). Primary outcome was a composite of AS-related events (cardiovascular death, heart failure, and new angina, dyspnoea, or syncope). The final score consisted of age, sex, Vmax, high-sensitivity troponin I concentration, and electrocardiographic strain pattern [c-statistic 0.85 (95% confidence interval 0.78–0.91), P < 0.001; Hosmer–Lemeshow χ2 = 7.33, P = 0.50]. Patients in the outcome cohorts were classified according to the sensitivity and specificity of this score (both at 98%): low risk (probability score <7%), intermediate risk (7–57%), and high risk (>57%). In the internal outcome cohort, AS-related event rates were >10-fold higher in high-risk patients compared with those at low risk (23.9 vs. 2.1 events/100 patient-years, respectively; log rank P < 0.001). Similar findings were observed in the external outcome cohort (31.6 vs. 4.6 events/100 patient-years, respectively; log rank P < 0.001). Conclusion We propose a clinical score that predicts adverse outcomes in asymptomatic AS patients and potentially identifies high-risk patients who may benefit from early valve replacement. PMID:26491110

  9. Adverse Outcome Pathways for Embryonic Vascular Disruption and Alternative Methods to Identify Chemical Vascular Disruptor

    EPA Science Inventory

    Chemically induced vascular toxicity during embryonic development can result in a wide range of adverse prenatal outcomes. We used information from genetic mouse models linked to phenotypic outcomes and a vascular toxicity knowledge base to construct an embryonic vascular disrupt...

  10. Prenatal exposure to amphetamines. Risks and adverse outcomes in pregnancy.

    PubMed

    Plessinger, M A

    1998-03-01

    Based on findings in humans and the confirmation of prenatal exposures in animals, amphetamines and methamphetamines increase the risk of an adverse outcome when abused during pregnancy. Clefting, cardiac anomalies, and fetal growth reduction deficits that have been seen in infants exposed to amphetamines during pregnancy have all been reproduced in animal studies involving prenatal exposures to amphetamines. The differential effects of amphetamines between genetic strains of mice and between species demonstrate that pharmacokinetics and the genetic disposition of the mother and developing embryo can have an enormous influence on enhancing or reducing these potential risks. The effects of prenatal exposure to amphetamines in producing altered behavior in humans appear less compelling when one considers other confounding variables of human environment, genetics, and polydrug abuse. In view of the animal data concerning altered behavior and learning tasks in comparison with learning deficits observed in humans, the influence of the confounding variables in humans may serve to increase the sensitivity of the developing embryo/fetus to prenatal exposure to amphetamines. These factors and others may predispose the developing conceptus to the damaging effects of amphetamines by actually lowering the threshold of susceptibility at the sites where damage occurs. Knowledge of the effects of prenatal exposure of the fetus and the mother to designer amphetamines is lacking. Based on the few studies in which designer drugs have been examined in animal models, more questions are raised than answered. Possible reasons why no malformations or significant fetal effects were found in the study by St. Omer include the genetic strain of rat used, the conservative exposure profile, or the fact that the placenta metabolized MDMA before reaching the embryo. These questions underscore the need for further investigations concerning the prenatal exposure effects of designer compounds and

  11. Plasma Osteopontin Levels and Adverse Cardiovascular Outcomes in the PEACE Trial

    PubMed Central

    Austin, Erin E.; Gersh, Bernard J.; Solak, Nusret; Rizvi, Syed A.; Bailey, Kent R.; Kullo, Iftikhar J.

    2016-01-01

    Osteopontin (OPN) is a secreted glycophosphoprotein that has a role in inflammation, immune response and calcification. We hypothesized that plasma OPN levels are associated with adverse cardiovascular outcomes in patients with stable coronary artery disease (CAD) and preserved ejection fraction (EF) enrolled in the PEACE trial. We measured plasma OPN levels at baseline in 3567 CAD patients (mean age 64.5 ± 8.1 years, 81% men) by a sandwich chemiluminescent assay (coefficient of variation = 4.1%). OPN levels were natural log (Ln) transformed prior to analyses. We assessed whether Ln OPN levels were associated with the composite primary endpoint of cardiovascular death, non-fatal myocardial infarction and hospitalization for heart failure using multiple event multivariable Cox proportional hazards regression. Adjustment was performed for: (a) age and sex; (b) additional potential confounders; and (c) a parsimonious set of statistically significant 10 variates. During a median follow-up of 4.8 years, 416 adverse cardiovascular outcomes occurred in 366 patients. Ln OPN was significantly associated with the primary endpoint; HR (95% CI) = 1.56 (1.27, 1.92); P <0.001, and remained significant after adjustment for age and sex [1.31 (1.06, 1.61); P = 0.01] and after adjustment for relevant covariates [1.24 (1.01, 1.52); P = 0.04]. In a secondary analysis of the individual event types, Ln OPN was significantly associated with incident hospitalization for heart failure: HR (95% CI) = 2.04 (1.44, 2.89); P <0.001, even after adjustment for age, sex and additional relevant covariates. In conclusion, in patients with stable CAD and preserved EF on optimal medical therapy, plasma OPN levels were independently associated with the composite incident endpoint of adverse cardiovascular outcomes as well as incident hospitalization for heart failure. PMID:27284698

  12. Patient-reported missed nursing care correlated with adverse events.

    PubMed

    Kalisch, Beatrice J; Xie, Boqin; Dabney, Beverly Waller

    2014-01-01

    The aim of this study was to determine the extent and type of missed nursing care as reported by patients and the association with patient-reported adverse outcomes. A total of 729 inpatients on 20 units in 2 acute care hospitals were surveyed. The MISSCARE Survey-Patient was used to collect patient reports of missed care. Patients reported more missed nursing care in the domain of basic care (2.29 ± 1.06) than in communication (1.69 ± 0.71) and in time to respond (1.52 ± 0.64). The 5 most frequently reported elements of missed nursing care were the following: (a) mouth care (50.3%), (b) ambulation (41.3%), (c) getting out of bed into a chair (38.8%), (d) providing information about tests/procedures (27%), and (e) bathing (26.4%). Patients who reported skin breakdown/pressure ulcers, medication errors, new infections, IVs running dry, IVs infiltrating, and other problems during the current hospitalization reported significantly more overall missed nursing care. PMID:24006031

  13. Assessing Adverse Events of Postprostatectomy Radiation Therapy for Prostate Cancer: Evaluation of Outcomes in the Regione Emilia-Romagna, Italy

    SciTech Connect

    Showalter, Timothy N.; Hegarty, Sarah E.; Rabinowitz, Carol; Maio, Vittorio; Hyslop, Terry; Dicker, Adam P.; Louis, Daniel Z.

    2015-03-15

    Purpose: Although the likelihood of radiation-related adverse events influences treatment decisions regarding radiation therapy after prostatectomy for eligible patients, the data available to inform decisions are limited. This study was designed to evaluate the genitourinary, gastrointestinal, and sexual adverse events associated with postprostatectomy radiation therapy and to assess the influence of radiation timing on the risk of adverse events. Methods: The Regione Emilia-Romagna Italian Longitudinal Health Care Utilization Database was queried to identify a cohort of men who received radical prostatectomy for prostate cancer during 2003 to 2009, including patients who received postprostatectomy radiation therapy. Patients with prior radiation therapy were excluded. Outcome measures were genitourinary, gastrointestinal, and sexual adverse events after prostatectomy. Rates of adverse events were compared between the cohorts who did and did not receive postoperative radiation therapy. Multivariable Cox proportional hazards models were developed for each class of adverse events, including models with radiation therapy as a time-varying covariate. Results: A total of 9876 men were included in the analyses: 2176 (22%) who received radiation therapy and 7700 (78%) treated with prostatectomy alone. In multivariable Cox proportional hazards models, the additional exposure to radiation therapy after prostatectomy was associated with increased rates of gastrointestinal (rate ratio [RR] 1.81; 95% confidence interval [CI] 1.44-2.27; P<.001) and urinary nonincontinence events (RR 1.83; 95% CI 1.83-2.80; P<.001) but not urinary incontinence events or erectile dysfunction. The addition of the time from prostatectomy to radiation therapy interaction term was not significant for any of the adverse event outcomes (P>.1 for all outcomes). Conclusion: Radiation therapy after prostatectomy is associated with an increase in gastrointestinal and genitourinary adverse events. However

  14. Adverse inpatient outcomes during the transition to a new electronic health record system: observational study

    PubMed Central

    Barnett, Michael L; Mehrotra, Ateev

    2016-01-01

    Objective To assess the short term association of inpatient implementation of electronic health records (EHRs) with patient outcomes of mortality, readmissions, and adverse safety events. Design Observational study with difference-in-differences analysis. Setting Medicare, 2011-12. Participants Patients admitted to 17 study hospitals with a verifiable “go live” date for implementation of inpatient EHRs during 2011-12, and 399 control hospitals in the same hospital referral region. Main outcome measures All cause readmission within 30 days of discharge, all cause mortality within 30 days of admission, and adverse safety events as defined by the patient safety for selected indicators (PSI)-90 composite measure among Medicare beneficiaries admitted to one of these hospitals 90 days before and 90 days after implementation of the EHRs (n=28 235 and 26 453 admissions), compared with the control group of all contemporaneous admissions to hospitals in the same hospital referral region (n=284 632 and 276 513 admissions). Analyses were adjusted for beneficiaries’ sociodemographic and clinical characteristics. Results Before and after implementation, characteristics of admissions were similar in both study and control hospitals. Among study hospitals, unadjusted 30 day mortality (6.74% to 7.15%, P=0.06) and adverse safety event rates (10.5 to 11.4 events per 1000 admissions, P=0.34) did not significantly change after implementation of EHRs. There was an unadjusted decrease in 30 day readmission rates, from 19.9% to 19.0% post-implementation (P=0.02). In difference-in-differences analysis, however, there was no significant change in any outcome between pre-implementation and post-implementation periods (all P≥0.13). Conclusions Despite concerns that implementation of EHRs might adversely impact patient care during the acute transition period, we found no overall negative association of such implementation on short term inpatient mortality, adverse safety

  15. An “ADME Module” in the Adverse Outcome Pathway Knowledgebase

    EPA Science Inventory

    The Adverse Outcome Pathway (AOP) framework has generated intense interest for its utility to organize knowledge on the toxicity mechanisms, starting from a molecular initiating event (MIE) to an adverse outcome across various levels of biological organization. While the AOP fra...

  16. The Association between Rural-Urban Continuum, Maternal Education and Adverse Birth Outcomes in Quebec, Canada

    ERIC Educational Resources Information Center

    Auger, Nathalie; Authier, Marie-Andree; Martinez, Jerome; Daniel, Mark

    2009-01-01

    Context: Rural relative to urban area and low socioeconomic status (SES) are associated with adverse birth outcomes. Whether a graded association of increasing magnitude is present across the urban-rural continuum, accounting for SES, is unclear. We examined the association between rural-urban continuum, SES and adverse birth outcomes. Methods:…

  17. Development of an adverse outcome pathway for acetylcholinesterase inhibition leading to acute mortality

    EPA Science Inventory

    Adverse outcome pathways (AOPs) are designed to describe linkages of key events (KEs) within a biological pathway that result in an adverse outcome associated with chemical perturbation of a well-defined molecular initiating event (MIE). Risk assessors have traditionally relied ...

  18. Development of Quantitative Adverse Outcome Pathways Using Health-Protective Assumptions to Fill Data Gaps

    EPA Science Inventory

    In an adverse outcome pathway (AOP), the target site dose participates in a molecular initiating event (MIE), which in turn triggers a sequence of key events leading to an adverse outcome (AO). Quantitative AOPs (QAOP) are needed if AOP characterization is to address risk as well...

  19. Evaluation of hypothesized adverse outcome pathway linking thyroid peroxidase inhibition to fish early life stage toxicity

    EPA Science Inventory

    There is an interest in developing alternatives to the fish early-life stage (FELS) test (OECD test guideline 210), for predicting adverse outcomes (e.g., impacts on growth and survival) using less resource-intensive methods. Development and characterization of adverse outcome pa...

  20. Correlation of Clinical and Dosimetric Factors With Adverse Pulmonary Outcomes in Children After Lung Irradiation

    SciTech Connect

    Venkatramani, Rajkumar; Kamath, Sunil; Wong, Kenneth; Malvar, Jemily; Sposto, Richard; Goodarzian, Fariba; Freyer, David R.; Keens, Thomas G.; and others

    2013-08-01

    Purpose: To identify the incidence and the risk factors for pulmonary toxicity in children treated for cancer with contemporary lung irradiation. Methods and Materials: We analyzed clinical features, radiographic findings, pulmonary function tests, and dosimetric parameters of children receiving irradiation to the lung fields over a 10-year period. Results: We identified 109 patients (75 male patients). The median age at irradiation was 13.8 years (range, 0.04-20.9 years). The median follow-up period was 3.4 years. The median prescribed radiation dose was 21 Gy (range, 0.4-64.8 Gy). Pulmonary toxic chemotherapy included bleomycin in 58.7% of patients and cyclophosphamide in 83.5%. The following pulmonary outcomes were identified and the 5-year cumulative incidence after irradiation was determined: pneumonitis, 6%; chronic cough, 10%; pneumonia, 35%; dyspnea, 11%; supplemental oxygen requirement, 2%; radiographic interstitial lung disease, 40%; and chest wall deformity, 12%. One patient died of progressive respiratory failure. Post-irradiation pulmonary function tests available from 44 patients showed evidence of obstructive lung disease (25%), restrictive disease (11%), hyperinflation (32%), and abnormal diffusion capacity (12%). Thoracic surgery, bleomycin, age, mean lung irradiation dose (MLD), maximum lung dose, prescribed dose, and dosimetric parameters between V{sub 22} (volume of lung exposed to a radiation dose ≥22 Gy) and V{sub 30} (volume of lung exposed to a radiation dose ≥30 Gy) were significant for the development of adverse pulmonary outcomes on univariate analysis. MLD, maximum lung dose, and V{sub dose} (percentage of volume of lung receiving the threshold dose or greater) were highly correlated. On multivariate analysis, MLD was the sole significant predictor of adverse pulmonary outcome (P=.01). Conclusions: Significant pulmonary dysfunction occurs in children receiving lung irradiation by contemporary techniques. MLD rather than prescribed

  1. Organ-specific systemic lupus erythematosus activity during pregnancy is associated with adverse pregnancy outcomes.

    PubMed

    Tedeschi, Sara K; Guan, Hongshu; Fine, Alexander; Costenbader, Karen H; Bermas, Bonnie

    2016-07-01

    Systemic lupus erythematosus (SLE) is a disease of reproductive-age women, and thus questions regarding how disease influences pregnancy outcomes arise. We investigated whether five specific types of SLE activity during the 6 months before conception or during pregnancy (nephritis, cytopenias, skin disease, arthritis, serositis) were associated with adverse pregnancy outcomes. We performed a retrospective cohort study of pregnancy outcomes among women with SLE at the Brigham and Women's Hospital Lupus Center. Adverse pregnancy outcomes included pre-eclampsia, pre-term delivery, elective termination due to SLE, spontaneous miscarriage at weeks 12-20, and stillbirth. SLE and obstetric history, laboratories, and medications were obtained from electronic medical records. Generalized linear mixed models adjusting for potential confounders were used to identify predictors of any adverse pregnancy outcome. Most pregnancies resulted in a live term delivery (76.5 %). After adjustment for Hispanic ethnicity, prior adverse pregnancy outcome and medication use 6 months before conception, nephritis during pregnancy (odds ratio (OR) 3.6, 95 % confidence interval (CI) 1.0-12.8), cytopenias during pregnancy (OR 3.9, 95 % CI 1.3-11.4), and serositis during pregnancy (OR 5.9, 95 % CI 1.0-34.0) were significantly associated with adverse pregnancy outcome. Specific types of SLE disease activity during pregnancy were related to adverse pregnancy outcome. Nephritis, cytopenias, and serositis carried a higher risk of adverse pregnancy outcome, suggesting that these abnormalities should be carefully monitored during pregnancy. PMID:27166627

  2. Adverse Outcomes After Hospitalization and Delirium in Persons With Alzheimer Disease

    PubMed Central

    Fong, Tamara G.; Jones, Richard N.; Marcantonio, Edward R.; Tommet, Douglas; Gross, Alden L.; Habtemariam, Daniel; Schmitt, Eva; Yap, Liang; Inouye, Sharon K.

    2012-01-01

    Background Hospitalization, frequently complicated by delirium, can be a life-changing event for patients with Alzheimer disease (AD). Objective To determine risks for institutionalization, cognitive decline, or death associated with hospitalization and delirium in patients with AD. Design Prospective cohort enrolled between 1991 and 2006 into the Massachusetts Alzheimer’s Disease Research Center (MADRC) patient registry. Setting Community-based. Participants 771 persons aged 65 years or older with a clinical diagnosis of AD. Measurements Hospitalization, delirium, death, and institutionalization were identified through administrative databases. Cognitive decline was defined as a decrease of 4 or more points on the Blessed Information-Memory-Concentration test score. Multivariate analysis was used to calculate adjusted relative risks (RRs). Results Of 771 participants with AD, 367 (48%) were hospitalized and 194 (25%) developed delirium. Hospitalized patients who did not have delirium had an increased risk for death (adjusted RR, 4.7 [95% CI, 1.9 to 11.6]) and institutionalization (adjusted RR, 6.9 [CI, 4.0 to 11.7]). With delirium, risk for death (adjusted RR, 5.4 [CI, 2.3 to 12.5]) and institutionalization (adjusted RR, 9.3 [CI, 5.5 to 15.7]) increased further. With hospitalization and delirium, the adjusted RR for cognitive decline for patients with AD was 1.6 (CI, 1.2 to 2.3). Among hospitalized patients with AD, 21% of the incidences of cognitive decline, 15% of institutionalization, and 6% of deaths were associated with delirium. Limitations Cognitive outcome was missing in 291 patients. Sensitivity analysis was performed to test the effect of missing data, and a composite outcome was used to decrease the effect of missing data. Conclusion Approximately 1 in 8 hospitalized patients with AD who develop delirium will have at least 1 adverse outcome, including death, institutionalization, or cognitive decline, associated with delirium. Delirium prevention may

  3. The adverse effect of spasticity on 3-month poststroke outcome using a population-based model.

    PubMed

    Belagaje, S R; Lindsell, C; Moomaw, C J; Alwell, K; Flaherty, M L; Woo, D; Dunning, K; Khatri, P; Adeoye, O; Kleindorfer, D; Broderick, J; Kissela, B

    2014-01-01

    Several devices and medications have been used to address poststroke spasticity. Yet, spasticity's impact on outcomes remains controversial. Using data from a cohort of 460 ischemic stroke patients, we previously published a validated multivariable regression model for predicting 3-month modified Rankin Score (mRS) as an indicator of functional outcome. Here, we tested whether including spasticity improved model fit and estimated the effect spasticity had on the outcome. Spasticity was defined by a positive response to the question "Did you have spasticity following your stroke?" on direct interview at 3 months from stroke onset. Patients who had expired by 90 days (n = 30) or did not have spasticity data available (n = 102) were excluded. Spasticity affected the 3-month functional status (β = 0.420, 95 CI = 0.194 to 0.645) after accounting for age, diabetes, leukoaraiosis, and retrospective NIHSS. Using spasticity as a covariable, the model's R (2) changed from 0.599 to 0.622. In our model, the presence of spasticity in the cohort was associated with a worsened 3-month mRS by an average of 0.4 after adjusting for known covariables. This significant adverse effect on functional outcomes adds predictive value beyond previously established factors. PMID:25147752

  4. The Adverse Effect of Spasticity on 3-Month Poststroke Outcome Using a Population-Based Model

    PubMed Central

    Belagaje, S. R.; Lindsell, C.; Moomaw, C. J.; Alwell, K.; Flaherty, M. L.; Woo, D.; Dunning, K.; Khatri, P.; Adeoye, O.; Kleindorfer, D.; Broderick, J.; Kissela, B.

    2014-01-01

    Several devices and medications have been used to address poststroke spasticity. Yet, spasticity's impact on outcomes remains controversial. Using data from a cohort of 460 ischemic stroke patients, we previously published a validated multivariable regression model for predicting 3-month modified Rankin Score (mRS) as an indicator of functional outcome. Here, we tested whether including spasticity improved model fit and estimated the effect spasticity had on the outcome. Spasticity was defined by a positive response to the question “Did you have spasticity following your stroke?” on direct interview at 3 months from stroke onset. Patients who had expired by 90 days (n = 30) or did not have spasticity data available (n = 102) were excluded. Spasticity affected the 3-month functional status (β = 0.420, 95 CI = 0.194 to 0.645) after accounting for age, diabetes, leukoaraiosis, and retrospective NIHSS. Using spasticity as a covariable, the model's R2 changed from 0.599 to 0.622. In our model, the presence of spasticity in the cohort was associated with a worsened 3-month mRS by an average of 0.4 after adjusting for known covariables. This significant adverse effect on functional outcomes adds predictive value beyond previously established factors. PMID:25147752

  5. Adverse outcome pathways (AOPs): A framework to support predictive toxicology

    EPA Science Inventory

    High throughput and in silico methods are providing the regulatory toxicology community with capacity to rapidly and cost effectively generate data concerning a chemical’s ability to initiate one or more biological perturbations that may culminate in an adverse ecological o...

  6. Interventions designed to prevent adverse programming outcomes resulting from exposure to maternal obesity during development

    PubMed Central

    Nathanielsz, PW; Ford, SP; Long, NM; Vega, CC; Reyes-Castro, LA; Zambrano, E

    2013-01-01

    Maternal obesity is a global epidemic affecting the developed and developing world. Human and animal studies indicate that maternal obesity programs development predisposing offspring to later-life chronic diseases. Several mechanisms act together to produce these adverse health problems. There is a need for effective interventions that prevent these outcomes and guide management in human pregnancy. We report here dietary and exercise intervention studies in both altricial and precocial species, rats and sheep, designed to prevent adverse offspring outcomes. Both interventions present exciting opportunities to at least in part prevent adverse metabolic and other outcomes in mother and offspring. PMID:24147928

  7. Effect of RAAS blockers on adverse clinical outcomes in high CVD risk subjects with atrial fibrillation

    PubMed Central

    Chaugai, Sandip; Sherpa, Lhamo Yanchang; Sepehry, Amir A.; Arima, Hisatomi; Wang, Dao Wen

    2016-01-01

    Abstract Recent studies have demonstrated that atrial fibrillation significantly increases the risk of adverse clinical outcomes in high cardiovascular disease risk subjects. Application of renin–angiotensin–aldosterone system blockers for prevention of recurrence of atrial fibrillation and adverse clinical outcomes in subjects with atrial fibrillation is a theoretically appealing concept. However, results of clinical trials evaluating the effect of renin–angiotensin–aldosterone blockers on adverse clinical outcomes in high cardiovascular disease risk subjects with atrial fibrillation remain inconclusive. A pooled study of 6 randomized controlled trials assessing the efficacy of renin–angiotensin–aldosterone blockers on subjects with atrial fibrillation was performed. A total of 6 randomized controlled trials enrolled a total of 53,510 patients followed for 1 to 5 years. RAAS blockade therapy was associated with 14% reduction in the incidence of heart failure (OR: 0.86, [95%CI: 0.76– 0.97], P=0.018) and 17% reduction in the incidence of CVE (OR: 0.83, [95%CI: 0.70–0.99], P = 0.038). The corresponding decline in absolute risk against heart failure (ARR: 1.4%, [95%CI: 0.2–2.6%], P = 0.018) and CVE (ARR: 3.5%, [95%CI: 0.0–6.9%], P = 0.045) in the AF group was much higher than the non-AF group for heart failure (ARR: 0.4%, [95%CI: 0.0–0.7%], P = 0.057) and CVE (ARR: 1.6%, [95%CI: –0.1% to 3.3%], P = 0.071). No significant effect was noted on all-cause or cardiovascular mortality, stroke, or myocardial infarction. This study suggests that RAAS blockade offers protection against heart failure and cardiovascular events in high cardiovascular disease risk subjects with atrial fibrillation. PMID:27368043

  8. [Frequency of drug adverse reactions among hospitalized patients].

    PubMed

    González Martínez, L

    1995-01-01

    This article describes the frequency of adverse reactions to drugs in a sample of hospitalized patients in the internal medicine ward seen during a year's term. Of 61 medical charts, we found 8 patients with adverse reactions to drugs during their hospital stay and another 4 patients hospitalized due to adverse reactions to drugs. The majority of the adverse reactions were of moderate degree (75%) and were related to drugs of cardiovascular action (58%). The frequency of reactions in hospitalized patients (13%) is comparable with the results obtained from other hospitals. Yet, the real magnitude of the problem is probably greater since the source of information (hospital charts) the totality of the clinical manifestations are not registered. PMID:8581452

  9. Impact of Different Childhood Adversities on 1-Year Outcomes of Psychotic Disorder in the Genetics and Psychosis Study.

    PubMed

    Trotta, Antonella; Murray, Robin M; David, Anthony S; Kolliakou, Anna; O'Connor, Jennifer; Di Forti, Marta; Dazzan, Paola; Mondelli, Valeria; Morgan, Craig; Fisher, Helen L

    2016-03-01

    While the role of childhood adversity in increasing the risk of psychosis has been extensively investigated, it is not clear what the impact of early adverse experiences is on the outcomes of psychotic disorders. Therefore, we investigated associations between childhood adversity and 1-year outcomes in 285 first-presentation psychosis patients. Exposure to childhood adversity prior to 17 years of age was assessed using the Childhood Experience of Care and Abuse Questionnaire. Data on illness course, symptom remission, length of psychiatric hospitalization, compliance with medication, employment, and relationship status were extracted from clinical records for the year following first contact with mental health services for psychosis. Seventy-one percent of patients reported exposure to at least 1 type of childhood adversity (physical abuse, sexual abuse, parental separation, parental death, disrupted family arrangements, or being taken into care). No robust associations were found between childhood adversity and illness course or remission. However, childhood physical abuse was associated with almost 3-fold increased odds of not being in a relationship at 1-year follow-up compared to patients who did not report such adverse experiences. There was also evidence of a significant association between parental separation in childhood and longer admissions to psychiatric wards during 1-year follow-up and 2-fold increased odds of noncompliance with medication compared to those not separated from their parents. Therefore, our findings suggest that there may be some specificity in the impact of childhood adversity on service use and social functioning among psychosis patients over the first year following presentation to mental health services. PMID:26373540

  10. Impact of Different Childhood Adversities on 1-Year Outcomes of Psychotic Disorder in the Genetics and Psychosis Study

    PubMed Central

    Trotta, Antonella; Murray, Robin M.; David, Anthony S.; Kolliakou, Anna; O’Connor, Jennifer; Di Forti, Marta; Dazzan, Paola; Mondelli, Valeria; Morgan, Craig; Fisher, Helen L.

    2016-01-01

    While the role of childhood adversity in increasing the risk of psychosis has been extensively investigated, it is not clear what the impact of early adverse experiences is on the outcomes of psychotic disorders. Therefore, we investigated associations between childhood adversity and 1-year outcomes in 285 first-presentation psychosis patients. Exposure to childhood adversity prior to 17 years of age was assessed using the Childhood Experience of Care and Abuse Questionnaire. Data on illness course, symptom remission, length of psychiatric hospitalization, compliance with medication, employment, and relationship status were extracted from clinical records for the year following first contact with mental health services for psychosis. Seventy-one percent of patients reported exposure to at least 1 type of childhood adversity (physical abuse, sexual abuse, parental separation, parental death, disrupted family arrangements, or being taken into care). No robust associations were found between childhood adversity and illness course or remission. However, childhood physical abuse was associated with almost 3-fold increased odds of not being in a relationship at 1-year follow-up compared to patients who did not report such adverse experiences. There was also evidence of a significant association between parental separation in childhood and longer admissions to psychiatric wards during 1-year follow-up and 2-fold increased odds of noncompliance with medication compared to those not separated from their parents. Therefore, our findings suggest that there may be some specificity in the impact of childhood adversity on service use and social functioning among psychosis patients over the first year following presentation to mental health services. PMID:26373540

  11. Adjuvant Chemotherapy Use and Adverse Events among Older Patients with Stage III Colon Cancer

    PubMed Central

    Kahn, Katherine L.; Adams, John L.; Weeks, Jane C.; Chrischilles, Elizabeth A.; Schrag, Deborah; Ayanian, John Z.; Kiefe, Catarina I.; Ganz, Patricia A.; Bhoopalam, Nirmala; Potosky, Arnold L.; Harrington, David P.; Fletcher, Robert H.

    2010-01-01

    Context Randomized trials suggest adjuvant chemotherapy is effective for elderly patients with stage III colon cancer. However, the elderly are less likely to receive this therapy than younger patients, perhaps because of concern about adverse effects. Objective To evaluate adjuvant chemotherapy use and outcomes for older patients with stage III colon cancer from well-defined population-based settings and healthcare systems. Design Observational study of adjuvant chemotherapy use and outcomes by age, using Poisson regression to estimate the number of adverse events adjusted for demographic and clinical factors, including comorbid illness and specific elements of chemotherapy regimens documented with clinically detailed medical record reviews and patient and surrogate surveys. Setting Five geographically defined regions (Alabama, Iowa, Los Angeles County, Northern California, and North Carolina), five integrated health-care delivery systems, and 15 Veterans hospitals. Patients All 675 patients diagnosed with stage III colon cancer during 2003-2005 who underwent surgical resection were followed up to 15 months post-diagnosis. Main outcome measures Chemotherapy regimen, dose, duration and annualized mean number of adverse events stratified by age. Results Half of the 202 patients >=75 years received adjuvant chemotherapy compared with 87% of 473 younger patients (diff 37%, 95% CI 30%-45%). Among adjuvant chemotherapy users, 14 (14%) of patients >=75 years and 178 (44%) of younger patients received a regimen containing oxaliplatin (diff 30%, 95% CI 21%-38%). Older patients were less likely to continue. By 150 days, 99 (40%) patients >= 65 years and 68 (25%) younger patients had discontinued chemotherapy (diff 15%, 95% CI 7%-23%). Overall, 162 (24%) patients had at least one adverse clinical event, with more events among patients treated with vs. without adjuvant chemotherapy (mean 0.394 vs. 0.160, diff 0.234, 95% CI 0.11-0.36, p<0.001). Among adjuvant chemotherapy

  12. Waterlow score as a surrogate marker for predicting adverse outcome in acute pancreatitis.

    PubMed

    Gillick, K; Elbeltagi, H; Bhattacharya, S

    2016-01-01

    Introduction Introduced originally to stratify risk for developing decubitus ulcers, the Waterlow scoring system is recorded routinely for surgical admissions. It is a composite score, reflecting patients' general condition and co-morbidities. The aim of this study was to investigate whether the Waterlow score can be used as an independent surrogate marker to predict severity and adverse outcome in acute pancreatitis. Methods In this retrospective analysis, a consecutive cohort was studied of 250 patients presenting with acute pancreatitis, all of whom had their Waterlow score calculated on admission. Primary outcome measures were length of hospital stay and mortality. Secondary outcome measures included rate of intensive care unit (ICU) admission and development of complications such as peripancreatic free fluid, pancreatic necrosis and pseudocyst formation. Correlation of the Waterlow score with some known markers of disease severity and outcomes was also analysed. Results The Waterlow score correlated strongly with the most commonly used marker of disease severity, the Glasgow score (analysis of variance, p=0.0012). Inpatient mortality, rate of ICU admission and length of hospital stay increased with a higher Waterlow score (Mann-Whitney U test, p=0.0007, p=0.049 and p=0.0002 respectively). There was, however, no significant association between the Waterlow score and the incidence of three known complications of pancreatitis: presence of peripancreatic fluid, pancreatic pseudocyst formation and pancreatic necrosis. Receiver operating characteristic curve analysis demonstrated good predictive power of the Waterlow score for mortality (area under the curve [AUC]: 0.73), ICU admission (AUC: 0.65) and length of stay >7 days (AUC: 0.64). This is comparable with the predictive power of the Glasgow score and C-reactive protein. Conclusions The Waterlow score for patients admitted with acute pancreatitis could provide a useful tool in prospective assessment of disease

  13. Adverse Outcome Pathways and Extrapolation Tools to Advance the Three Rs in Ecotoxicology

    EPA Science Inventory

    Adverse outcome pathways (AOPs) are conceptual frameworks for identifying and organizing predictive and causal linkages between cellular-level responses and endpoints conventionally considered in ecological risk assessment (e.g., effects on survival, growth/development, and repro...

  14. Development & Use of Adverse Outcome Pathways for 21st Century Decision Support

    EPA Science Inventory

    The Adverse Outcome Pathway has emerged as an internationally harmonized mechanism for organizing biological information in a chemical agnostic manner. This construct is valuable for interpreting the results from high-throughput toxicity (HTT) assessment by providing a mechanisti...

  15. Overview of an internationally-harmonized program for adverse outcome pathway development

    EPA Science Inventory

    Adverse outcome pathways (AOPs) are critical frameworks for organizing knowledge concerning the scientifically-credible predictive linkages between toxicological observations made at molecular and cellular levels (e.g., via molecular screening assays, biomarker responses, or chem...

  16. Adverse outcome pathways linked to population models as a methodology for investigating effects of chemical stressors

    EPA Science Inventory

    In addressing the complexity and toxicity of chemical contaminants in Great Lakes ecosystems, we describe an approach to link chemically induced alterations in molecular and biochemical endpoints to adverse outcomes in whole organisms and populations. Analysis of population impac...

  17. Establishing Adverse Outcome Pathways of Thyroid Hormone Disruption in an Amphibian Model

    EPA Science Inventory

    The Adverse Outcome Pathway (AOP) provides a framework for understanding the relevance of toxicology data in ecotoxicological hazard assessments. The AOP concept can be applied to many toxicological pathways including thyroid hormone disruption. Thyroid hormones play a critical r...

  18. VIOLENT CRIME EXPOSURE CLASSIFICATION AND ADVERSE BIRTH OUTCOMES: A GEOGRAPHICALLY-DEFINED COHORT STUDY

    EPA Science Inventory

    Background

    Area-level socioeconomic disparities have long been associated with adverse pregnancy outcomes. Crime is an important element of the neighborhood environment inadequately investigated in the public health literature. Using geocoded linked birth, crime and cens...

  19. Experimental Approaches to Systematic Discovery and Development of Reproductive Adverse Outcome Pathways in Fish

    EPA Science Inventory

    Adverse outcome pathways (AOPs) are conceptual frameworks that portray causal and predictive linkages between key events at multiple scales of biological organization that connect molecular initiating events and early cellular perturbations (e.g., initiation of toxicity pathways)...

  20. Long-term outcome of individuals with pure red cell aplasia and antierythropoietin antibodies in patients treated with recombinant epoetin: a follow-up report from the Research on Adverse Drug Events and Reports (RADAR) Project

    PubMed Central

    Bennett, Charles L.; Cournoyer, Denis; Carson, Kenneth R.; Rossert, Jerome; Luminari, Stefano; Evens, Andrew M.; Locatelli, Francesco; Belknap, Steven M.; McKoy, June M.; Lyons, E. Alison; Kim, Benjamin; Sharma, Rishi; Costello, Stacey; Toffelmire, Edwin B.; Wells, George A.; Messner, Hans A.; Yarnold, Paul R.; Trifilio, Steven M.; Raisch, Dennis W.; Kuzel, Timothy M.; Nissenson, Allen; Lim, Lay-Cheng; Tallman, Martin S.; Casadevall, Nicole

    2005-01-01

    Since its introduction in 1988, recombinant human erythropoietin (epoetin) has been standard treatment for patients with anemia due to chronic kidney disease. From 1998 to 2004, nearly 200 epoetin-treated persons with chronic kidney disease developed antibodies to epoetin, resulting in pure red cell aplasia (PRCA). The majority of these patients received Eprex, an epoetin alfa product marketed exclusively outside the United States. Herein, we report on the long-term outcome of these individuals. For 170 chronic kidney disease patients who developed epoetin-associated PRCA and had 3 months or more follow-up information available, case reports from the Food and Drug Administration and epoetin manufacturers were reviewed for information on clinical characteristics of the patients, immunosuppressive treatments, epoetin responsiveness, and hematologic recovery. Overall, 64% of the PRCA patients received immunosuppressive therapy, including 19 who also underwent a renal transplantation. Thirty-seven percent experienced a hematologic recovery, with higher hematologic recovery rates among PRCA patients who received immunosuppressive therapy (57% vs 2%, P < .001). Among 34 patients who received epoetin after the onset of PRCA, 56% regained epoetin responsiveness. The highest rates of epoetin responsiveness were observed among persons whose antierythropoietin antibodies were undetectable when epoetin was administered (89%). Among chronic kidney disease patients with epoetin-associated PRCA, epoetin discontinuation and immunosuppressive therapy or renal transplantation is necessary for hematologic recovery. Reinitiation of epoetin therapy among individuals could be considered if antierythropoietin antibodies are undetectable. PMID:16099877

  1. Serum 25-Hydroxyvitamin D Levels are not Associated with Adverse Outcomes in Clostridium Difficile Infection

    PubMed Central

    Micic, Dejan; Rao, Krishna; Trindade, Bruno Caetano; Walk, Seth T.; Chenoweth, Elizabeth; Jain, Ruchika; Trivedi, Itishree; Santhosh, Kavitha; Young, Vincent B.; Aronoff, David M.

    2015-01-01

    Clostridium difficile infection (CDI) is a significant source of healthcare-associated morbidity and mortality. This study investigated whether serum 25-hydroxyvitamin D is associated with adverse outcomes from CDI. Patients with CDI were prospectively enrolled. Charts were reviewed and serum 25-hydroxyvitamin D was measured. The primary outcome was a composite definition of severe disease: fever (temperature >38°C), acute organ dysfunction, or serum white blood cell count >15,000 cells/µL within 24-48 hours of diagnosis; lack of response to therapy by day 5; and intensive care unit admission; colectomy; or death within 30 days. Sixty-seven patients were included in the final analysis. Mean (±SD) serum 25-hydroxyvitamin D was 26.1 (±18.54) ng/mL. Severe disease, which occurred in 26 (39%) participants, was not associated with serum 25-hydroxyvitamin D [odds ratio (OR) 1.00; 95% confidence interval (CI) 0.96-1.04]. In the adjusted model for severe disease only serum albumin (OR 0.12; 95%CI 0.02-0.64) and diagnosis by detection of stool toxin (OR 5.87; 95%CI 1.09-31.7) remained independent predictors. We conclude that serum 25-hydroxyvitamin D is not associated with the development of severe disease in patients with CDI. PMID:26500740

  2. Theoretical Framework to Extend Adverse Outcome Pathways to Include Pharmacokinetic Considerations

    EPA Science Inventory

    Adverse Outcome Pathways (AOPs) have generated intense interest for their utility in linking known population outcomes to a molecular initiating event (MIE) that can be quantified using in vitro methods. While there are tens of thousands of chemicals in commercial use, biology h...

  3. Use of Adverse Outcome Pathways for Assessing Effects of the Fungicide Propiconazole on Fish Reproduction

    EPA Science Inventory

    Adverse outcome pathways (AOP) are used to describe the linkage of biological events from a molecular initiating point, to individual-level-endpoints relevant to risk assessment. This study was done to assess toxicity outcomes for the conazole fungicide propiconazole based on a p...

  4. Cortisol Reactivity to Social Stress as a Mediator of Early Adversity on Risk and Adaptive Outcomes

    ERIC Educational Resources Information Center

    Conradt, Elisabeth; Abar, Beau; Lester, Barry M.; LaGasse, Linda L.; Shankaran, Seetha; Bada, Henrietta; Bauer, Charles R.; Whitaker, Toni M.; Hammond, Jane A.

    2014-01-01

    Children chronically exposed to stress early in life are at increased risk for maladaptive outcomes, though the physiological mechanisms driving these effects are unknown. Cortisol reactivity was tested as a mediator of the relation between prenatal substance exposure and/or early adversity on adaptive and maladaptive outcomes. Data were drawn…

  5. Sex Differences in Device Therapy for Heart Failure: Utilization, Outcomes, and Adverse Events

    PubMed Central

    Herz, Naomi D.; Engeda, Joseph; Zusterzeel, Robbert; Sanders, William E.; O'Callaghan, Kathryn M.; Strauss, David G.; Jacobs, Samantha B.; Selzman, Kimberly A.; Piña, Ileana L.

    2015-01-01

    Abstract Background: Multiple studies of heart failure patients demonstrated significant improvement in exercise capacity, quality of life, cardiac left ventricular function, and survival from cardiac resynchronization therapy (CRT), but the underenrollment of women in these studies is notable. Etiological and pathophysiological differences may result in different outcomes in response to this treatment by sex. The observed disproportionate representation of women suggests that many women with heart failure either do not meet current clinical criteria to receive CRT in trials or are not properly recruited and maintained in these studies. Methods: We performed a systematic literature review through May 2014 of clinical trials and registries of CRT use that stratified outcomes by sex or reported percent women included. One-hundred eighty-three studies contained sex-specific information. Results: Ninety percent of the studies evaluated included ≤35% women. Fifty-six articles included effectiveness data that reported response with regard to specific outcome parameters. When compared with men, women exhibited more dramatic improvement in specific parameters. In the studies reporting hazard ratios for hospitalization or death, women generally had greater benefit from CRT. Conclusions: Our review confirms women are markedly underrepresented in CRT trials, and when a CRT device is implanted, women have a therapeutic response that is equivalent to or better than in men, while there is no difference in adverse events reported by sex. PMID:25793483

  6. Adverse Perinatal Outcome in Subsequent Pregnancy after Stillbirth by Placental Vascular Disorders

    PubMed Central

    Monari, Francesca; Pedrielli, Giulia; Vergani, Patrizia; Pozzi, Elisa; Mecacci, Federico; Serena, Caterina; Neri, Isabella; Facchinetti, Fabio

    2016-01-01

    Objective To evaluate outcome in the pregnancy following a stillbirth (SB) by a placental vascular disorders. Study Design A prospective, observational, multicenter study was conducted in woman with a history of stillbirth (> 22 weeks) between 2005 and June 2013, in 3 Italian University Hospitals. Causes of SB were previously identified after extensive investigations. Pregnant women were enrolled within the first trimester. The main outcome was “adverse neonatal outcome”, including perinatal death, fetal growth restriction, early preterm birth <33+6 weeks, hypoxic-ischemic encephalopathy, intracranial hemorrhage or respiratory distress. Results Out of 364 index pregnancies, 320 women (87.9%) had a subsequent pregnancy during the study period. Forty-seven had an early pregnancy loss. Out of 273 babies, 67 (24.5%) had an adverse perinatal outcome, including 1 SB and 1 early neonatal death (3.7/1000). Women who had a SB related to placental vascular disorders (39.6%), were at higher risk of an adverse neonatal outcome compared with women whose SB was unexplained or resulted from other causes (Adj. OR = 2.1, 95%CI: 1.2–3.8). Moreover, also obesity independently predicts an adverse perinatal outcome (Adj OR = 2.1, 95%CI: 1.1–4.3). Conclusion When previous SB is related to placental vascular disorders there is a high risk for adverse neonatal outcomes in the subsequent pregnancy. Maternal obesity is an additional risk factor. PMID:27228078

  7. Adverse pregnancy outcome in a petrochemical polluted area in Taiwan.

    PubMed

    Lin, M C; Yu, H S; Tsai, S S; Cheng, B H; Hsu, T Y; Wu, T N; Yang, C Y

    2001-08-24

    The petrochemical industry is the main source of industrial air pollution in Taiwan. Reported here are the results from an ongoing study of outdoor air pollution and the health of individuals living in a community in close proximity to petrochemical industrial complexes. The prevalences of term low birth weight (LBW) in the petrochemical municipality and control municipality were 3.22%, and 1.84%, respectively. After controlling for several possible confounders (including maternal age, season, marital status, maternal education, and infant sex), the adjusted odds ratio was 1.767 (1.002-3.116) for term LBW in the petrochemical municipality. Data provide further support for the hypothesis that air pollution can affect the outcome of pregnancy. PMID:11549116

  8. Attention-deficit/hyperactivity disorder and adverse health outcomes

    PubMed Central

    Nigg, Joel

    2015-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is defined by extreme levels of inattention–disorganization and/or hyperactivity–impulsivity. In DSM-IV, the diagnostic criteria required impairment in social, academic, or occupational functioning. With DSM-5 publication imminent in 2013, further evaluation of impairment in ADHD is timely. This article reviews the current state of knowledge on health-related impairments of ADHD, including smoking, drug abuse, accidental injury, sleep, obesity, hypertension, diabetes, and suicidal behavior. It concludes by suggesting the need for new avenues of research on mechanisms of association and the potential for ADHD to be an early warning sign for secondary prevention of some poor health outcomes. PMID:23298633

  9. Substantiation and adverse appeal outcomes: content analysis and testing of Drake's harm/evidence model.

    PubMed

    Fakunmoju, Sunday Bolanle

    2009-02-01

    Little is known about the influence of evidentiary and case characteristics on adverse appeal outcomes for substantiated cases of maltreatment. This article, therefore, reports on a sample of adverse appeal outcomes during a 2-year period. Using Drake's Harm/Evidence model to examine the adverse outcomes, the study describes differences between substantiated cases that were "modified" versus "overturned" during appeal, as well as differences in their evidentiary characteristics across different types of maltreatment. Content analysis and logistic regression analysis of administrative data were used to predict overturned versus modified outcome. Overall, child neglect, substantiated cases that did not meet basic evidentiary standards, and cases that were deemed as not credible were more likely to be overturned in comparison to being modified. A substantiation assessment framework (SAF) is developed and implications of Drake's Harm/Evidence model for investigating maltreatment as well as for understanding judicial decision making in appealed cases of maltreatment is highlighted. PMID:18612040

  10. Diurnal Cortisol Rhythm Is Associated With Adverse Cardiac Events and Mortality in Coronary Artery Bypass Patients

    PubMed Central

    Kidd, Tara; Poole, Lydia; Leigh, Elizabeth; Jahangiri, Marjan; Steptoe, Andrew

    2015-01-01

    Purpose: There is growing evidence that the hypothalamic-pituitary-adrenal axis plays a role in the progression of cardiovascular disease. We examined the relationship between diurnal cortisol rhythm and adverse events in patients undergoing coronary artery bypass graft (CABG) surgery. We hypothesized that a flatter presurgical diurnal cortisol slope would be associated with higher rates of adverse cardiac events and death in the years following the CABG procedure. Methods: Repeated measures of saliva were taken over the day from 250 CABG patients 1 month before surgery to assess diurnal cortisol slope and overall output (area under the curve). Long-term clinical outcomes were occurrence of a major adverse cardiac event (MACE) and death, and were collected up to 2.68 (SD = 0.40) years after surgery. Cox proportional hazard models were used to determine relationships between presurgical cortisol and clinical outcomes. EuroSCORE, chronic illness burden, and whether or not the patient had undergone cardiopulmonary bypass were included as covariates in the models. Results: Diurnal cortisol slope predicted the occurrence of MACE or death after surgery (hazard ratio = 0.73; 95% confidence interval = 0.56–0.96; P = .023). Patients with a steeper slope were at reduced risk of adverse outcomes. This association was driven by changes in both waking and evening cortisol levels. Conclusion: These results provide evidence for a link between diurnal cortisol rhythm and recovery after CABG. Measuring diurnal cortisol slope before surgery may help to identify those patients at risk of adverse outcomes in the years after the procedure. PMID:26305622

  11. [Adverse events in patients from a pediatric hospital.

    PubMed

    Ornelas-Aguirre, José Manuel; Arriaga-Dávila, José de Jesús; Domínguez-Serrano, María Isabel; Guzmán-Bihouet, Beatriz Filomena; Navarrete-Navarro, Susana

    2013-01-01

    Background: detection of adverse events is part of the safety management in hospitalized patients. The objective of this study was to describe the incidence of adverse events that occurred in a pediatric hospital. Methods: cross-sectional study of the adverse events occurred in a pediatric hospital from 2007 to 2009. Factors associated with their developmental causes were identified. The statistical analysis was descriptive and bivariate, with contingency tables to estimate the relationship between those factors. A p value = 0.05 was considered significant. Results: a total of 177 adverse events were registered. When they began, human factor occurred in 23 cases (13 %, OR = 1.41, p = 0.001), organizational factor was present in 71 cases (40 %, OR = 1.91, p = 0.236) and technical factor in 46 cases (26 %, OR = 0.87, p = 0.01). Blows or bruises from falls as a result of adverse events occurred in 71 cases (40 %, 95 % CI = 64-78). Conclusions: we found 1.84 events per 100 hospital discharges during the study period. The fall of patients ranked first of the adverse events identified. PMID:24290022

  12. Identification of patients at high risk for adverse coronary events while awaiting routine coronary angioplasty.

    PubMed Central

    Chester, M.; Chen, L.; Kaski, J. C.

    1995-01-01

    BACKGROUND--Identification of patients at risk for progression of coronary stenosis and adverse clinical events while awaiting coronary angioplasty is desirable. OBJECTIVE--To determine the standard clinical or angiographic variables, or both, present at initial angiography associated with the development of adverse coronary events (unstable angina, myocardial infarction, and angiographic total coronary occlusion) in patients awaiting routine percutaneous transluminal coronary angioplasty (PTCA). PATIENTS AND METHODS--Consecutive male patients on a waiting list for routine PTCA. Routine clinical details were obtained at initial angiography. Stenosis severity was measured using computerised angiography. OUTCOME MEASURES--Development of one or more of myocardial infarction, unstable angina, or angiographic total coronary occlusion while awaiting PTCA were recorded as an adverse event. RESULTS--Some 214 of 219 patients underwent a second angiogram. One had a fatal myocardial infarction and four (2%) were lost to follow up. Fifty patients (23%) developed one or more adverse events (myocardial infarction five, unstable angina 35, total coronary occlusion 23) at a median (range) interval of 8 (3-25) months. Twenty (57%) of the 35 patients with unstable angina developed adverse events compared with 30 (17%) of the 180 with stable angina (P = 0.0001). Plasma triglyceride concentration was 2.6 (1.2) mmol/l in patients with adverse coronary events compared with 2.2 (1.1) mmol/l in those without such events (P < 0.05). Patients with adverse events were younger than those without (54 (9) years v 58 (9) years, P < 0.01). The relative risk of an adverse event in patients with unstable angina and increased plasma triglyceride concentrations was 6.9 compared with those presenting with stable angina and a normal triglyceride concentration (P < 0.02). CONCLUSIONS--The study shows that adverse events are not uncommon in patients awaiting PTCA. Patients at high risk for adverse events

  13. Using a sibling design to compare childhood adversities in female patients with BPD and their sisters.

    PubMed

    Laporte, Lise; Paris, Joel; Guttman, Herta; Russell, Jennifer; Correa, José A

    2012-11-01

    Abuse and neglect are well-established risk correlates of borderline personality disorder (BPD). The goal of this study was to examine whether BPD probands can be differentiated from their sisters with respect to a range of developmental adversity and maltreatment indicators, including retrospective self-reports of past experiences of childhood abuse and neglect, dysfunctional parent-child relationships and peer victimization and dysfunctional peer relationships. A total of 53 patients with BPD were compared to 53 sisters who were currently free of psychopathology on measures assessing childhood adversities. Both probands and sisters reported similar prevalence of intrafamilial abuse, although BPD patients reported more severe physical and emotional abuse. BPD patients reported higher prevalence of physical abuse by peers. These findings generally support the principle of multifinality, in which similar histories of adversities can be associated with a variety of outcomes, ranging from psychopathology to resilience. PMID:23076835

  14. Socioeconomic disparities in ectopic pregnancy: predictors of adverse outcomes from Illinois hospital-based care, 2000-2006.

    PubMed

    Stulberg, Debra B; Zhang, James X; Lindau, Stacy Tessler

    2011-02-01

    This study aimed to identify the incidence of adverse outcomes from ectopic pregnancy hospital care in Illinois (2000-2006), and assess patient, neighborhood, hospital and time factors associated with these outcomes. Discharge data from Illinois hospitals were retrospectively analyzed and ectopic pregnancies were identified using DRG and ICD-9 diagnosis codes. The primary outcome was any complication identified by ICD-9 procedure codes. Secondary outcomes were length of stay and discharge status. Residential zip codes were linked to 2000 U.S. Census data to identify patients' neighborhood demographics. Logistic regression was used to identify risk factors for adverse outcomes. Independent variables were insurance status, age, co-morbidities, neighborhood demographics, hospital type, hospital ectopic pregnancy service volume, and year of discharge. Of 13,007 ectopic pregnancy hospitalizations, 7.4% involved at least one complication identified by procedure codes. Hospitalizations covered by Medicare (for women with chronic disabilities) were more likely than those with other source or without insurance to result in surgical sterilization (OR 4.7, P = 0.012). Hospitalization longer than 2 days was more likely with Medicaid (OR 1.46, P < 0.0005) or no insurance (OR 1.35, P < 0.0005) versus other payers, and among church-operated versus secular hospitals (OR 1.21, P < 0.0005). Compared to public hospitals, private hospitals had lower rates of complications (OR 0.39, P < 0.0005) and of hospitalization longer than 2 days (OR 0.57, P < 0.0005). With time, hospitalizations became shorter (OR 0.53, P < 0.0005) and complication rates higher (OR 1.33, P = 0.024). Ectopic pregnancy patients with Medicaid, Medicare or no insurance, and those admitted to public or religious hospitals, were more likely to experience adverse outcomes. PMID:20177756

  15. Late childbearing and changing risks of adverse birth outcomes in Korea.

    PubMed

    Cho, Youngtae; Hummer, Robert A; Choi, Yoon-Jung; Jung, Sung Won

    2011-05-01

    This study aimed to examine whether the relative importance of maternal age as a correlate of adverse birth outcomes has changed and to investigate if social inequalities in birth outcomes have widened during the past decade when the marriage and fertility related social environment has undergone tremendous change in Korea. Probabilities of adverse birth outcomes (prematurity and intrauterine growth retardation [IUGR]) were estimated with multinomial logistic regression models, utilizing the Korean birth registration data of 1995 and 2005. The main effects of maternal age and parental socioeconomic characteristics were compared between two study years, net of infant sex, birth order, and plurality. The association between maternal age and adverse birth outcomes, relative to the maternal and parental social characteristics, has clearly diminished between 1995 and 2005. During this period, differences in prematurity and IUGR by maternal age have also diminished, while those by parental social characteristics, particularly maternal education, have substantially widened. The intensified overall socioeconomic polarization since the economic crisis of the late 1990s is most likely responsible for the increased social inequality in adverse birth outcomes in Korea. A massive structural change in macro-economic conditions and culture during the study period may have modified the relationship between maternal age and birth outcomes. PMID:20432060

  16. Excess risk of adverse pregnancy outcomes in women with porphyria: a population-based cohort study

    PubMed Central

    Aarsand, Aasne Karine; Sandberg, Sverre

    2010-01-01

    The porphyrias comprise a heterogeneous group of rare, primarily hereditary, metabolic diseases caused by a partial deficiency in one of the eight enzymes involved in the heme biosynthesis. Our aim was to assess whether acute or cutaneous porphyria has been associated with excess risks of adverse pregnancy outcomes. A population-based cohort study was designed by record linkage between the Norwegian Porphyria Register, covering 70% of all known porphyria patients in Norway, and the Medical Birth Registry of Norway, based on all births in Norway during 1967–2006. The risks of the adverse pregnancy outcomes preeclampsia, delivery by caesarean section, low birth weight, premature delivery, small for gestational age (SGA), perinatal death, and congenital malformations were compared between porphyric mothers and the rest of the population. The 200 mothers with porphyria had 398 singletons during the study period, whereas the 1,100,391 mothers without porphyria had 2,275,317 singletons. First-time mothers with active acute porphyria had an excess risk of perinatal death [adjusted odds ratio (OR) 4.9, 95% confidence interval (CI) 1.5–16.0], as did mothers with the hereditable form of porphyria cutanea tarda (PCT) (3.0, 1.2–7.7). Sporadic PCT was associated with an excess risk of SGA [adjusted relative risk (RR) 2.0, 1.2–3.4], and for first-time mothers, low birth weight (adjusted OR 3.4, 1.2–10.0) and premature delivery (3.5, 1.2–10.5) in addition. The findings suggest women with porphyria should be monitored closely during pregnancy. PMID:20978938

  17. Hypertension: An Unstudied Potential Risk Factor for Adverse Outcomes during Continuous Flow Ventricular Assist Device Support

    PubMed Central

    Wasson, Lauren T.; Yuzefpolskaya, Melana; Wakabayashi, Michiyori; Takayama, Hiroo; Naka, Yoshifumi; Uriel, Nir; Jorde, Ulrich P.; Demmer, Ryan T.; Colombo, Paolo C.

    2014-01-01

    In end-stage heart failure, left ventricular assist devices (LVADs) represent an exciting new frontier in which post-device-implantation survival approaches that of heart transplant. However, expansion of this technology is still limited by complications that impact morbidity and mortality. Thus, it is essential to identify and optimize modifiable predictors of poor outcomes. One such predictor may be hypertension (HTN). Not only may chronic HTN as a traditional cardiovascular risk factor be present during long-term LVAD support, but HTN may also contribute to device malfunction or device-associated complications. Although current guidelines identify blood pressure (BP) control as important to outpatient continuous flow (CF) LVAD management, there is no evidence base to support these guidelines. Indeed, our comprehensive literature search did not identify any studies that evaluated post-device-implantation HTN as a potential predictor of adverse CF-LVAD outcomes. Hypertension among CF-LVAD patients is likely a relatively unstudied factor because of difficulties using standard non-invasive techniques to measure BP in the setting of reduced pulsatile flow. Fortunately, recent research has elucidated the meaning of Doppler BP measurements and validated a slow-deflation cuff system for BP measurements in the setting of CF-LVAD support. Therefore, CF-LVAD researchers and clinicians may i) consider potential mechanisms relating HTN to poor outcomes, ii) realize that HTN management is a stated goal despite scarce evidence, and iii) utilize the new reliable and valid methods for outpatient BP measurement that make research and management possible. It is critical and now feasible that research on HTN in the CF-LVAD patient population move forward. PMID:25283767

  18. Hypertension: an unstudied potential risk factor for adverse outcomes during continuous flow ventricular assist device support.

    PubMed

    Wasson, Lauren T; Yuzefpolskaya, Melana; Wakabayashi, Michiyori; Takayama, Hiroo; Naka, Yoshifumi; Uriel, Nir; Jorde, Ulrich P; Demmer, Ryan T; Colombo, Paolo C

    2015-05-01

    In end-stage heart failure, left ventricular assist devices (LVADs) represent an exciting new frontier in which post-device implantation survival approaches that of heart transplant. However, expansion of this technology is still limited by complications that impact morbidity and mortality. Thus, it is essential to identify and optimize modifiable predictors of poor outcomes. One such predictor may be hypertension (HTN). Not only may chronic HTN as a traditional cardiovascular risk factor be present during long-term LVAD support, but HTN may also contribute to device malfunction or device-associated complications. Although current guidelines identify blood pressure (BP) control as important to outpatient continuous flow (CF) LVAD management, there is no evidence base to support these guidelines. Indeed, our comprehensive literature search did not identify any studies that evaluated post-device implantation HTN as a potential predictor of adverse CF-LVAD outcomes. HTN among CF-LVAD patients is likely a relatively unstudied factor because of difficulties using standard noninvasive techniques to measure BP in the setting of reduced pulsatile flow. Fortunately, recent research has elucidated the meaning of Doppler BP measurements and validated a slow-cuff deflation system for BP measurements in the setting of CF-LVAD support. Therefore, CF-LVAD researchers and clinicians may (1) consider potential mechanisms relating HTN to poor outcomes, (2) realize that HTN management is a stated goal despite scarce evidence, and (3) utilize the new reliable and valid methods for outpatient BP measurement that make research and management possible. It is critical and now feasible that research on HTN in the CF-LVAD patient population move forward. PMID:25283767

  19. Perioperative outcomes and adverse events of minimally invasive versus open posterior lumbar fusion: meta-analysis and systematic review.

    PubMed

    Goldstein, Christina L; Macwan, Kevin; Sundararajan, Kala; Rampersaud, Y Raja

    2016-03-01

    OBJECT The objective of this study was to determine the clinical comparative effectiveness and adverse event rates of posterior minimally invasive surgery (MIS) compared with open transforaminal or posterior lumbar interbody fusion (TLIF/PLIF). METHODS A systematic review of the Medline, EMBASE, PubMed, Web of Science, and Cochrane databases was performed. A hand search of reference lists was conducted. Studies were reviewed by 2 independent assessors to identify randomized controlled trials (RCTs) or comparative cohort studies including at least 10 patients undergoing MIS or open TLIF/PLIF for degenerative lumbar spinal disorders and reporting at least 1 of the following: clinical outcome measure, perioperative clinical or process measure, radiographic outcome, or adverse events. Study quality was assessed using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) protocol. When appropriate, a meta-analysis of outcomes data was conducted. RESULTS The systematic review and reference list search identified 3301 articles, with 26 meeting study inclusion criteria. All studies, including 1 RCT, were of low or very low quality. No significant difference regarding age, sex, surgical levels, or diagnosis was identified between the 2 cohorts (856 patients in the MIS cohort, 806 patients in the open cohort). The meta-analysis revealed changes in the perioperative outcomes of mean estimated blood loss, time to ambulation, and length of stay favoring an MIS approach by 260 ml (p < 0.00001), 3.5 days (p = 0.0006), and 2.9 days (p < 0.00001), respectively. Operative time was not significantly different between the surgical techniques (p = 0.78). There was no significant difference in surgical adverse events (p = 0.97), but MIS cases were significantly less likely to experience medical adverse events (risk ratio [MIS vs open] = 0.39, 95% confidence interval 0.23-0.69, p = 0.001). No difference in nonunion (p = 0.97) or reoperation rates (p = 0.97) was

  20. Delay of Treatment Initiation Does Not Adversely Affect Survival Outcome in Breast Cancer

    PubMed Central

    Yoo, Tae-Kyung; Han, Wonshik; Moon, Hyeong-Gon; Kim, Jisun; Lee, Jun Woo; Kim, Min Kyoon; Lee, Eunshin; Kim, Jongjin; Noh, Dong-Young

    2016-01-01

    Purpose Previous studies examining the relationship between time to treatment and survival outcome in breast cancer have shown inconsistent results. The aim of this study was to analyze the overall impact of delay of treatment initiation on patient survival and to determine whether certain subgroups require more prompt initiation of treatment. Materials and Methods This study is a retrospective analysis of stage I-III patients who were treated in a single tertiary institution between 2005 and 2008. Kaplan-Meier survival analysis and Cox proportional hazards regression model were used to evaluate the impact of interval between diagnosis and treatment initiation in breast cancer and various subgroups. Results A total of 1,702 patients were included. Factors associated with longer delay of treatment initiation were diagnosis at another hospital, medical comorbidities, and procedures performed before admission for surgery. An interval between diagnosis and treatment initiation as a continuous variable or with a cutoff value of 15, 30, 45, and 60 days had no impact on disease-free survival (DFS). Subgroup analyses for hormone-responsiveness, triple-negative breast cancer, young age, clinical stage, and type of initial treatment showed no significant association between longer delay of treatment initiation and DFS. Conclusion Our results show that an interval between diagnosis and treatment initiation of 60 days or shorter does not appear to adversely affect DFS in breast cancer. PMID:26511801

  1. Socioeconomic Disparities in Ectopic Pregnancy: Predictors of Adverse Outcomes from Illinois Hospital-Based Care, 2000–2006

    PubMed Central

    Zhang, James X.; Lindau, Stacy Tessler

    2010-01-01

    This study aimed to identify the incidence of adverse outcomes from ectopic pregnancy hospital care in Illinois (2000–2006), and assess patient, neighborhood, hospital and time factors associated with these outcomes. Discharge data from Illinois hospitals were retrospectively analyzed and ectopic pregnancies were identified using DRG and ICD-9 diagnosis codes. The primary outcome was any complication identified by ICD-9 procedure codes. Secondary outcomes were length of stay and discharge status. Residential zip codes were linked to 2000 U.S. Census data to identify patients’ neighborhood demographics. Logistic regression was used to identify risk factors for adverse outcomes. Independent variables were insurance status, age, co-morbidities, neighborhood demographics, hospital type, hospital ectopic pregnancy service volume, and year of discharge. Of 13,007 ectopic pregnancy hospitalizations, 7.4% involved at least one complication identified by procedure codes. Hospitalizations covered by Medicare (for women with chronic disabilities) were more likely than those with other source or without insurance to result in surgical sterilization (OR 4.7, P = 0.012). Hospitalization longer than 2 days was more likely with Medicaid (OR 1.46, P<0.0005) or no insurance (OR 1.35, P<0.0005) versus other payers, and among church-operated versus secular hospitals (OR 1.21, P<0.0005). Compared to public hospitals, private hospitals had lower rates of complications (OR 0.39, P< 0.0005) and of hospitalization longer than 2 days (OR 0.57, P<0.0005). With time, hospitalizations became shorter (OR 0.53, P<0.0005) and complication rates higher (OR 1.33, P = 0.024). Ectopic pregnancy patients with Medicaid, Medicare or no insurance, and those admitted to public or religious hospitals, were more likely to experience adverse outcomes. PMID:20177756

  2. The adverse effects of sorafenib in patients with advanced cancers.

    PubMed

    Li, Ye; Gao, Zu-Hua; Qu, Xian-Jun

    2015-03-01

    Sorafenib is the first multi-kinase inhibitor (TKI) approved for the treatment of advanced hepatocellular cancer (HCC) and metastatic renal cell cancer (RCC) and is increasingly being used to treat patients with well-differentiated radioiodine-resistant thyroid cancer (DTC). Sorafenib demonstrates targeted activity on several families of receptor and non-receptor tyrosine kinases that are involved in angiogenesis, tumour growth and metastatic progression of cancer. Sorafenib treatment results in long-term efficacy and low incidence of life-threatening toxicities. Although sorafenib has demonstrated many benefits in patients, the adverse effects cannot be ignored. The most common treatment-related toxicities include diarrhoea, fatigue, hand-foot skin reaction and hypertension. Most of these toxicities are considered mild to moderate and manageable to varying degrees; however, cardiovascular events might lead to death. In this MiniReview, we summarize the adverse effects of sorafenib that commonly occur in patients with advanced cancers. PMID:25495944

  3. Exposure and Dosimetry Considerations for Adverse Outcome Pathways (AOPs) (NIH-AOP)

    EPA Science Inventory

    Risk is a function of both of hazard and exposure. Toxicokinetic (TK) models can determine whether chemical exposures produce potentially hazardous tissue concentrations. Whether or not the initial molecular event (MIE) in an Adverse Outcome Pathway (AOP) occurs depends on both e...

  4. Physical Performance Characteristics of Assisted Living Residents and Risk for Adverse Health Outcomes

    ERIC Educational Resources Information Center

    Giuliani, Carol A.; Gruber-Baldini, Ann L.; Park, Nan S.; Schrodt, Lori A.; Rokoske, Franzi; Sloane, Philip D.; Zimmerman, Sheryl

    2008-01-01

    Purpose: Researchers know little about the physical performance ability of residential care/assisted living (RC/AL) residents and its relationship to adverse outcomes such as fracture, nursing home placement, functional decline, and death. The purposes of this article are to (a) describe the functional characteristics of RC/AL residents, (b)…

  5. Studying Biology to Understand Risk: Dosimetry Models and Quantitative Adverse Outcome Pathways

    EPA Science Inventory

    Confidence in the quantitative prediction of risk is increased when the prediction is based to as great an extent as possible on the relevant biological factors that constitute the pathway from exposure to adverse outcome. With the first examples now over 40 years old, physiologi...

  6. Defining Adverse Outcome Pathways for Effects of the Fungicide Propiconazole of Fish Reproduction

    EPA Science Inventory

    Adverse outcome pathways (AOPs) are used to describe the linkage of chemical interactions in terms of molecular initiating events to whole organism responses suitable for risk assessment. This study was conducted to develop AOPs for the model fungicide propiconazole relative to r...

  7. USE OF CASE REPORTS IN ASSESSING ADVERSE OUTCOMES OF HUMAN PRENATAL DRUG EXPOSURES: AN APPROACH

    EPA Science Inventory

    The use of case reports for assessing the developmental consequences of prenatal drug exposure is limited by the inability to determine the incidence of adverse outcomes and by the high likelihood for bias. Yet, because it is impossible to conduct clinical trials for the assessme...

  8. Retinal artery and vein thrombotic occlusion during pregnancy: markers for familial thrombophilia and adverse pregnancy outcomes

    PubMed Central

    Kurtz, Will S; Glueck, Charles J; Hutchins, Robert K; Sisk, Robert A; Wang, Ping

    2016-01-01

    Background Ocular vascular occlusion (OVO), first diagnosed during or immediately after giving birth, often reflects superposition of the physiologic thrombophilia of pregnancy on previously undiagnosed underlying familial or acquired thrombophilia associated with spontaneous abortion, eclampsia, or maternal thrombosis. Specific aim We describe OVO, first diagnosed during pregnancy or immediately postpartum, in three young females (ages 32, 35, 40) associated with previously undiagnosed familial thrombophilia. Results Branch retinal artery occlusion (BRAO) occurred at 9 and 13 weeks gestation in two females, aged 32 and 35. Central retinal vein occlusion occurred immediately postpartum in a 40-year-old. One of the two females with BRAO subsequently developed eclampsia, and one had a history of unexplained first trimester spontaneous abortion. All three females were found to have previously unexplained familial thrombophilia. The two females with BRAO had low first trimester free protein S 42 (41%), lower normal limit (50%), and one of these two had high factor VIII (165%, upper normal limit 150%). The woman with central retinal vein occlusion had high factor XI (169%, upper normal limit 150%). Enoxaparin (40–60 mg/day) was started and continued throughout pregnancy in both females with BRAO to prevent maternal–placental thrombosis, and of these two females, one had an uncomplicated pregnancy course and term delivery, and the second was at gestational week 22 without complications at the time of this manuscript. There were no further OVO events in the two females treated with enoxaparin or in the untreated patient with postpartum eclampsia. Conclusion OVO during pregnancy may be a marker for familial or acquired thrombophilia, which confers increased thrombotic risk to the mother and pregnancy, associated with spontaneous abortion or eclampsia. OVO during pregnancy, particularly when coupled with antecedent adverse pregnancy outcomes, should prompt urgent

  9. Population Attributable Risk Fractions of Maternal Overweight and Obesity for Adverse Perinatal Outcomes.

    PubMed

    MacInnis, Natasha; Woolcott, Christy G; McDonald, Sarah; Kuhle, Stefan

    2016-01-01

    The objective of the current study was to determine the proportion of adverse perinatal outcomes that could be potentially prevented if maternal obesity were to be reduced or eliminated (population attributable risk fractions, PARF); and the number needed to treat (NNT) of overweight or obese women to prevent one case of adverse perinatal outcome. Data from the Atlee Perinatal Database on 66,689 singleton infants born in Nova Scotia, Canada, between 2004 and 2014, and their mothers were used. Multivariable-adjusted PARFs and NNTs of maternal pre-pregnancy weight status were determined for various perinatal outcomes under three scenarios: If all overweight and obese women were to i) become normal weight before pregnancy; ii) shift down one weight class; or iii) lose 10% of their body weight, significant relative reductions would be seen for gestational diabetes mellitus (GDM, 57/33/15%), hypertensive disorders of pregnancy (HDP, 26/16/6%), caesarean section (CS, 18/10/3%), and large for gestational age births (LGA, 24/14/3%). The NNT were lowest for the outcomes GDM, induction of labour, CS, and LGA, where they ranged from 13 to 73. The study suggests that a substantial proportion of adverse perinatal outcomes may be preventable through reductions in maternal pre-pregnancy weight. PMID:26961675

  10. Cortisol Reactivity to Social Stress as a Mediator of Early Adversity on Risk and Adaptive Outcomes

    PubMed Central

    Conradt, Elisabeth; Abar, Beau; Lester, Barry M.; LaGasse, Linda L.; Shankaran, Seetha; Bada, Henrietta; Bauer, Charles R.; Whitaker, Toni M.; Hammond, Jane A.

    2014-01-01

    Children chronically exposed to stress early in life are at increased risk for maladaptive outcomes, though the physiological mechanisms driving these effects are unknown. Cortisol reactivity was tested as a mediator of the relation between prenatal substance exposure and/or early adversity on adaptive and maladaptive outcomes. Data were drawn from a prospective longitudinal study of prenatal substance exposure (N = 860). Cortisol reactivity was assessed at age 11. Among African-Americans, prenatal substance exposure exerted an indirect effect through early adversity and cortisol reactivity to predict externalizing behavior, delinquency, and a positive student-teacher relationship at age 11. Decreased cortisol reactivity was related to maladaptive outcomes, and increased cortisol reactivity predicted better executive functioning and a more positive student-teacher relationship. PMID:25376131

  11. Understanding the Association of Biomedical, Psychosocial and Behavioral Risks with Adverse Pregnancy Outcomes

    PubMed Central

    Kiely, Michele; El-Mohandes, Ayman A.E.; Gantz, Marie G.; Chowdhury, Dhuly; Thornberry, Jutta S.; El-Khorazaty, M. Nabil

    2011-01-01

    Objectives This study investigates the relationship between diabetes, hypertension, preeclampsia, and Body Mass Index (BMI) -- the most common and interrelated medical conditions occurring during pregnancy; sociodemographic and behavioral risk factors; and adverse pregnancy outcomes in high-risk urban African American women in Washington, DC. Methods Data are from a randomized controlled trial conducted in 6 prenatal clinics. Women in their 1st or 2nd trimester were screened for behavioral risks (smoking, environmental tobacco smoke exposure, depression, and intimate partner violence) and demographic eligibility. 1,044 were eligible, interviewed and followed through their pregnancies. Classification and Regression Trees (CART) methodology was used to: 1) explore the relationship between medical and behavioral risks (reported at enrollment), sociodemographic factors and pregnancy outcomes, 2) identify the relative importance of various predictors of adverse pregnancy outcomes, and 3) characterize women at the highest risk of poor pregnancy outcomes. Results Overall, the strongest predictors of poor outcomes were prepregnancy BMI, preconceptional diabetes, employment status, intimate partner violence, and depression. In CART analysis, preeclampsia was the first splitter for low birthweight; preconceptional diabetes was the first splitter for preterm birth (PTB) and neonatal intensive care admission; BMI was the first splitter for very PTB, large for gestational age, Cesarean section and perinatal death; and employment was the first splitter for miscarriage. Conclusions Preconceptional factors play a very important role in pregnancy outcomes. For many of these women, the risks that they bring into the pregnancy were more likely to impact their pregnancy outcome than events during pregnancy. PMID:21785892

  12. A prognostic model for short term adverse events in normotensive patients with pulmonary embolism.

    PubMed

    Agterof, Mariette J; Schutgens, Roger E G; Moumli, Noureddine; Eijkemans, M J C; van der Griend, René; Tromp, Ellen A M; Biesma, Douwe H

    2011-08-01

    Risk stratification of patients with PE has gained interest in terms of the identification of patients in whom treatment on an outpatient base can be considered. Previous studies are of limited value due to their focus on adverse clinical events within several months after diagnosis of PE. We developed a prognostic model, based on easily accessible, clinical, and laboratory parameters, to predict adverse events during the first 10 days after the diagnosis of acute PE. We have analyzed the data of 210 outpatients with confirmed PE. Collected data included medical history, pulse rate, blood pressure, NT-proBNP, and D-dimer concentrations. The primary outcome was the occurrence of adverse clinical events in a 10 day follow-up period. Our final prognostic model to predict short-term adverse events consists of NT-proBNP levels, D-dimer concentrations, pulse rate, and the occurrence of active malignancy; the total score ranges from 0 to 37 points. Patients with a low score (no active malignancy, pulse rate <90 bpm, NT-proBNP <500 pg/ml, and D-dimer <3,000 μg/l FEU) have a 10-day adverse event risk <1.5%. This risk increases to over 30% in patients with a maximum score, based on high pulse rate, D-dimer concentrations, and NT-proBNP levels. Our prognostic model, once prospectively validated in an independent sample of patients, can be used in the early risk stratification of PE to estimate the risk of adverse events and to differentiate between candidates for in- or out- hospital treatment. PMID:21630313

  13. Adverse Outcome Pathway for Embryonic Vascular Disruption and Alternative Methods to Identify Chemical Vascular Disruptors During Development

    EPA Science Inventory

    Chemically induced vascular toxicity during embryonic development can result in a wide range of adverse prenatal outcomes. We used information from genetic mouse models linked to phenotypic outcomes and a vascular toxicity knowledge base to construct an embryonic vascular disrupt...

  14. Hematological Parameters Improve Prediction of Mortality and Secondary Adverse Events in Coronary Angiography Patients

    PubMed Central

    Gijsberts, Crystel M.; den Ruijter, Hester M.; de Kleijn, Dominique P.V.; Huisman, Albert; ten Berg, Maarten J.; van Wijk, Richard H.A.; Asselbergs, Folkert W.; Voskuil, Michiel; Pasterkamp, Gerard; van Solinge, Wouter W.; Hoefer, Imo E.

    2015-01-01

    Abstract Prediction of primary cardiovascular events has been thoroughly investigated since the landmark Framingham risk score was introduced. However, prediction of secondary events after initial events of coronary artery disease (CAD) poses a new challenge. In a cohort of coronary angiography patients (n = 1760), we examined readily available hematological parameters from the UPOD (Utrecht Patient Oriented Database) and their addition to prediction of secondary cardiovascular events. Backward stepwise multivariable Cox regression analysis was used to test their ability to predict death and major adverse cardiovascular events (MACE). Continuous net reclassification improvement (cNRI) and integrated discrimination improvement (IDI) measures were calculated for the hematological parameters on top of traditional risk factors to assess prediction improvement. Panels of 3 to 8 hematological parameters significantly improved prediction of death and adverse events. The IDIs ranged from 0.02 to 0.07 (all P < 0.001) among outcome measures and the cNRIs from 0.11 to 0.40 (P < 0.001 in 5 of 6 outcome measures). In the hematological panels red cell distribution width (RDW) appeared most often. The multivariable adjusted hazard ratio of RDW per 1 standard deviation (SD) increase for MACE was 1.19 [1.08–1.32], P < 0.001. Routinely measured hematological parameters significantly improved prediction of mortality and adverse events in coronary angiography patients. Accurately indicating high-risk patients is of paramount importance in clinical decision-making. PMID:26559287

  15. High level amplification of N-MYC is not associated with adverse histology or outcome in primary retinoblastoma tumours

    PubMed Central

    Lillington, D M; Goff, L K; Kingston, J E; Onadim, Z; Price, E; Domizio, P; Young, B D

    2002-01-01

    Twenty-five primary retinoblastoma tumours were analysed by real-time quantitative polymerase chain reaction to determine the genomic copy number of the N-MYC gene (2p24) relative to the copy number for REL, B2M, ALB, AF10 and MLL. Twenty-one of these tumours were shown by Comparative Genomic Hybridization to contain variable copy number increases of chromosomal material mapping to 2p. High level amplification (>30-fold) of N-MYC was found in three tumours, none of which showed adverse histological features and all patients are surviving at between 54 and 108 months post enucleation. Furthermore, the three tumours associated with metastasis and adverse patient outcome showed normal N-MYC copy number. Although high level amplification of N-MYC is an unfavourable prognostic indicator in neuroblastoma, these data show no evidence of a correlation between amplification of N-MYC and adverse outcome in retinoblastoma. British Journal of Cancer (2002) 87, 779–782. doi:10.1038/sj.bjc.6600532 www.bjcancer.com © 2002 Cancer Research UK PMID:12232763

  16. CN-15ADVERSE EFFECTS OF BEVACIZUMAB IN BRAIN TUMOR PATIENTS

    PubMed Central

    Pawar, Tushar; Ladha, Harshad; Mandel, Jacob; Gilbert, Mark; O'Brien, Barbara; Hamza, Mohamed; Armstrong, Terri

    2014-01-01

    BACKGROUND: Bevacizumab is humanized monoclonal antibody inhibiting angiogenesis and the only FDA approved treatment for recurrent glioblastoma. The aim of this study was to look at the occurrence of various adverse effects associated with use of bevacizumab in recurrent glioblastoma. METHODS: In this retrospective chart review, we studied 280 patients with recurrent glioblastoma treated with Bevacizumab between 2005-2011 to characterize the known adverse effects of bevacizumab including hypertension, grade 3-4 myelosuppression, wound healing complications, thrombo-embolic events, stroke, hemorrhage and gastrointestinal complications. RESULTS: The study population included 168 males and 112 females. The median age was 53.5 years(range 8.1-81.3). TREATMENT: Bevacizumab only(58), Bevacizumab + CPT(11), Bevacizumab + TMZ(32) or Bevacizumab + Other(34). Patients were treated at recurrence(1st = 96; 2nd = 126, 3rd = 58). Hypertension was the most common adverse effect occurring in 131(49%). The median duration from treatment start to development was 82 days (Range 7-1143). However, only 33(25%) were started on antihypertensive medication. Grade 3-4 Myelosuppression occurred in 52(19%)causing treatment discontinuation in 8. Thrombo-embolic events were reported in 5%(15) patients including DVT(9), PE(2), Central venous thrombosis(1) and Stroke(3). Thirty-six patients (13%) were on anti-coagulant medication at bevacizumab initiation. Median time to a thromboembolic complication was 113 days (Range 8-1145). Wound healing complications were noted in 7(3%) patients, 3 craniotomy dehiscence and 4 at soft tissue sites. Five patients (2%) developed GI complications, including perforations(3), pancreatitis(1), and diverticulitis(1). Median time to development was 92 days(Range 10-651). There was a high rate 46%(129) of grade 3-4 lymphocytopenia; median time to develop lymphocytopenia was 50 days(Range = 3-564). CONCLUSION: The range of toxicities was similar to other reports

  17. Are Women With Uterine Fibroids at Increased Risk for Adverse Pregnancy Outcome?

    PubMed

    Ezzedine, Dima; Norwitz, Errol R

    2016-03-01

    Uterine fibroids (leiomyomas) are common in reproductive age women. Most women with fibroids have uneventful pregnancies. The most common complication is painful degeneration. Are fibroids associated with adverse pregnancy outcomes? If so, can we predict which fibroids are most likely to cause complications? And is there anything that can be done to prevent these complications, such as performing a myomectomy before pregnancy? Here we review the published literature looking at the impact of uterine fibroids on adverse pregnancy events, such as miscarriage, preterm labor, placental abruption, fetal growth restriction, and fetal malpresentation. A series of clinical recommendations for the management of pregnancy in women with uterine fibroids are included. PMID:26670833

  18. Clinical picture and outcome of Serious Adverse Events in the treatment of Onchocerciasis

    PubMed Central

    Awadzi, Kwablah

    2003-01-01

    Ivermectin (Mectizan®) is the only drug currently recommended for the treatment and control of onchocerciasis. Serious adverse events rarely occur during treatment, except in subjects heavily infected with Loa Loa. This review of drug-related serious adverse events in the treatment of onchocerciasis therefore revisited the pre-Mectizan® reference drugs, DEC and suramin, and other candidate drugs studied extensively for the treatment of human onchocerciasis. The benzimidazole carbamate derivatives and the antibiotic doxycycline were excluded, since no serious adverse events have been reported regarding their use. Using recommended definitions, serious adverse events reported or observed after the use of each drug were summarised, the level of attribution determined, and the results tabulated. Prominence was given to treatment-related deaths. The clinical picture of severe symptomatic postural hypotension is described and used to illustrate the difference between the severity and the seriousness of an adverse event. The epidemiology, management and outcome of serious adverse events are presented. The role of future research is discussed. PMID:14975063

  19. Periodontal Disease: A Possible Risk-Factor for Adverse Pregnancy Outcome

    PubMed Central

    Parihar, Anuj Singh; Katoch, Vartika; Rajguru, Sneha A; Rajpoot, Nami; Singh, Pinojj; Wakhle, Sonal

    2015-01-01

    Bacterial invasion in subgingival sites especially of gram-negative organisms are initiators for periodontal diseases. The periodontal pathogens with persistent inflammation lead to destruction of periodontium. In recent years, periodontal diseases have been associated with a number of systemic diseases such as rheumatoid arthritis, cardiovascular-disease, diabetes mellitus, chronic respiratory diseases and adverse pregnancy outcomes including pre-term low-birth weight (PLBW) and pre-eclampsia. The factors like low socio-economic status, mother's age, race, multiple births, tobacco and drug-abuse may be found to increase risk of adverse pregnancy outcome. However, the same are less correlated with PLBW cases. Even the invasion of both aerobic and anerobic may lead to inflammation of gastrointestinal tract and vagina hence contributing to PLBW. The biological mechanism involved between PLBW and Maternal periodontitis is the translocation of chemical mediators of inflammation. Pre-eclampsia is one of the commonest cause of both maternal and fetal morbidity as it is characterized by hypertension and hyperprotenuria. Improving periodontal health before or during pregnancy may prevent or reduce the occurrences of these adverse pregnancy outcomes and, therefore, reduce the maternal and perinatal morbidity and mortality. Hence, this article is an attempt to review the relationship between periodontal condition and altered pregnancy outcome. PMID:26229389

  20. Risk for Gestational Diabetes Mellitus and Adverse Birth Outcomes in Chinese Women with Polycystic Ovary Syndrome

    PubMed Central

    Xiao, Qing; Cui, Yong-Yi; Lu, Jine; Zhang, Guo-Zheng

    2016-01-01

    Objective. To examine the association of polycystic ovary syndrome (PCOS) in early pregnancy with gestational diabetes mellitus (GDM) and adverse birth outcomes. Methods. In this retrospective cohort study including 2389 pregnant women, the medical records of 352 women diagnosed with PCOS were evaluated. Outcomes included GDM, preterm birth, low birth weight, macrosomia, and being small and large for gestational age. Multivariable logistic regression models were used to examine the association of the risk for GDM and adverse birth outcomes with PCOS after adjusting for confounders. Results. Women previously diagnosed with PCOS had a higher risk of GDM (adjusted odds ratio [OR] 1.55, 95% confidence interval [CI]: 1.14–2.09). A strong association was seen between PCOS and preterm birth (adjusted OR 1.69, 95% CI: 1.08–2.67). On stratified analysis, the adjusted OR for GDM among women with PCOS undergoing assisted reproductive technology was 1.44 (95% CI: 1.03–1.92) and among women with PCOS who conceived spontaneously was 1.60 (1.18–2.15). No increased risk for other adverse birth outcomes was observed. Conclusions. Women with PCOS were more likely to experience GDM and preterm birth. PMID:27066074

  1. Periodontal Disease: A Possible Risk-Factor for Adverse Pregnancy Outcome.

    PubMed

    Parihar, Anuj Singh; Katoch, Vartika; Rajguru, Sneha A; Rajpoot, Nami; Singh, Pinojj; Wakhle, Sonal

    2015-07-01

    Bacterial invasion in subgingival sites especially of gram-negative organisms are initiators for periodontal diseases. The periodontal pathogens with persistent inflammation lead to destruction of periodontium. In recent years, periodontal diseases have been associated with a number of systemic diseases such as rheumatoid arthritis, cardiovascular-disease, diabetes mellitus, chronic respiratory diseases and adverse pregnancy outcomes including pre-term low-birth weight (PLBW) and pre-eclampsia. The factors like low socio-economic status, mother's age, race, multiple births, tobacco and drug-abuse may be found to increase risk of adverse pregnancy outcome. However, the same are less correlated with PLBW cases. Even the invasion of both aerobic and anerobic may lead to inflammation of gastrointestinal tract and vagina hence contributing to PLBW. The biological mechanism involved between PLBW and Maternal periodontitis is the translocation of chemical mediators of inflammation. Pre-eclampsia is one of the commonest cause of both maternal and fetal morbidity as it is characterized by hypertension and hyperprotenuria. Improving periodontal health before or during pregnancy may prevent or reduce the occurrences of these adverse pregnancy outcomes and, therefore, reduce the maternal and perinatal morbidity and mortality. Hence, this article is an attempt to review the relationship between periodontal condition and altered pregnancy outcome. PMID:26229389

  2. The Canadian Adverse Events Study: the incidence of adverse events among hospital patients in Canada

    PubMed Central

    Baker, G. Ross; Norton, Peter G.; Flintoft, Virginia; Blais, Régis; Brown, Adalsteinn; Cox, Jafna; Etchells, Ed; Ghali, William A.; Hébert, Philip; Majumdar, Sumit R.; O'Beirne, Maeve; Palacios-Derflingher, Luz; Reid, Robert J.; Sheps, Sam; Tamblyn, Robyn

    2004-01-01

    Background Research into adverse events (AEs) has highlighted the need to improve patient safety. AEs are unintended injuries or complications resulting in death, disability or prolonged hospital stay that arise from health care management. We estimated the incidence of AEs among patients in Canadian acute care hospitals. Methods We randomly selected 1 teaching, 1 large community and 2 small community hospitals in each of 5 provinces (British Columbia, Alberta, Ontario, Quebec and Nova Scotia) and reviewed a random sample of charts for nonpsychiatric, nonobstetric adult patients in each hospital for the fiscal year 2000. Trained reviewers screened all eligible charts, and physicians reviewed the positively screened charts to identify AEs and determine their preventability. Results At least 1 screening criterion was identified in 1527 (40.8%) of 3745 charts. The physician reviewers identified AEs in 255 of the charts. After adjustment for the sampling strategy, the AE rate was 7.5 per 100 hospital admissions (95% confidence interval [CI] 5.7– 9.3). Among the patients with AEs, events judged to be preventable occurred in 36.9% (95% CI 32.0%–41.8%) and death in 20.8% (95% CI 7.8%–33.8%). Physician reviewers estimated that 1521 additional hospital days were associated with AEs. Although men and women experienced equal rates of AEs, patients who had AEs were significantly older than those who did not (mean age [and standard deviation] 64.9 [16.7] v. 62.0 [18.4] years; p = 0.016). Interpretation The overall incidence rate of AEs of 7.5% in our study suggests that, of the almost 2.5 million annual hospital admissions in Canada similar to the type studied, about 185 000 are associated with an AE and close to 70 000 of these are potentially preventable. PMID:15159366

  3. Elevated Cardiac Troponin in Acute Stroke without Acute Coronary Syndrome Predicts Long-Term Adverse Cardiovascular Outcomes

    PubMed Central

    Bhatt, Reema; Bove, Alfred A.

    2014-01-01

    Background. Elevated cardiac troponin in acute stroke in absence of acute coronary syndrome (ACS) has unclear long-term outcomes. Methods. Retrospective analysis of 566 patients admitted to Temple University Hospital from 2008 to 2010 for acute stroke was performed. Patients were included if cardiac troponin I was measured and had no evidence of ACS and an echocardiogram was performed. Of 200 patients who met the criteria, baseline characteristics, electrocardiograms, and major adverse cardiovascular events (MACE) were reviewed. Patients were characterized into two groups with normal and elevated troponins. Primary end point was nonfatal myocardial infarction during follow-up period after discharge. The secondary end points were MACE and death from any cause. Results. For 200 patients, 17 patients had positive troponins. Baseline characteristics were as follows: age 63.1 ± 13.8, 64% African Americans, 78% with hypertension, and 22% with previous CVA. During mean follow-up of 20.1 months, 7 patients (41.2%) in elevated troponin and 6 (3.3%) patients in normal troponin group had nonfatal myocardial infarction (P = 0.0001). MACE (41.2% versus 14.2%, P = 0.01) and death from any cause (41.2% versus 14.5%, P = 0.017) were significant in the positive troponin group. Conclusions. Elevated cardiac troponin in patients with acute stroke and no evidence of ACS is strong predictor of long-term cardiac outcomes. PMID:25530906

  4. Effective pain management and improvements in patients' outcomes and satisfaction.

    PubMed

    Glowacki, Diane

    2015-06-01

    Adequate pain management is a compelling and universal requirement in health care. Despite considerable advancements, the adverse physiological and psychological implications of unmanaged pain remain substantially unresolved. Ineffective pain management can lead to a marked decrease in desirable clinical and psychological outcomes and patients' overall quality of life. Effective management of acute pain results in improved patient outcomes and increased patient satisfaction. Although research and advanced treatments in improved practice protocols have documented progressive improvements in management of acute and postoperative pain, little awareness of the effectiveness of best practices persists. Improved interventions can enhance patients' attitudes to and perceptions of pain. What a patient believes and understands about pain is critical in influencing the patient's reaction to the pain therapy provided. Use of interdisciplinary pain teams can lead to improvements in patients' pain management, pain education, outcomes, and satisfaction. PMID:26033099

  5. Development of computationally predicted Adverse Outcome Pathway (AOP) networks through data mining and integration of publicly available in vivo, in vitro, phenotype, and biological pathway data

    EPA Science Inventory

    The Adverse Outcome Pathway (AOP) framework is increasingly being adopted as a tool for organizing and summarizing the mechanistic information connecting molecular perturbations by environmental stressors with adverse outcomes relevant for ecological and human health outcomes. Ho...

  6. Adverse Pregnancy Outcomes: Opportunity for Analysis of Biospecimens and Co-development of Prognostics | NCI Technology Transfer Center | TTC

    Cancer.gov

    The Eunice Kennedy Shriver National Institute of Child Health and Human Development’s Pregnancy and Perinatology Branch seeks partners interested in collaborative research to: (i) evaluate data and samples taken from women for potential biomarkers indicative for adverse pregnancy outcomes and (ii) co-develop diagnostic kits useful as predictors of adverse pregnancy outcomes.

  7. Baby on board: do responses to stress in the maternal brain mediate adverse pregnancy outcome?

    PubMed

    Douglas, Alison J

    2010-07-01

    Stress and adverse environmental surroundings result in suboptimal conditions in a pregnant mother such that she may experience poor pregnancy outcome including complete pregnancy failure and preterm labor. Furthermore her developing baby is at risk of adverse programming, which confers susceptibility to long term ill health. While some mechanisms at the feto-maternal interface underlying these conditions are understood, the underlying cause for their adverse adaptation is often not clear. Progesterone plays a key role at many levels, including control of neuroendocrine responses to stress, procuring the required immune balance and controlling placental and decidual function, and lack of progesterone can explain many of the unwanted consequences of stress. How stress that is perceived by the mother inhibits progesterone secretion and action is beginning to be investigated. This overview of maternal neuroendocrine responses to stress throughout pregnancy analyses how they interact to compromise progesterone secretion and precipitate undesirable effects in mother and offspring. PMID:20546772

  8. Cannabis and Neuropsychiatry, 2: The Longitudinal Risk of Psychosis as an Adverse Outcome.

    PubMed

    Andrade, Chittaranjan

    2016-06-01

    Psychosis is one of the most serious among the adverse effects associated with cannabis use. The association between cannabis use and psychosis has been variously explored in a series of recent meta-analyses. The results of these meta-analyses show that persons who develop psychosis experience onset of psychosis about 2-3 years earlier if they are cannabis users; this effect is not observed with alcohol or other substance use. Higher levels of cannabis use are associated with greater risk of psychosis. Current cannabis abuse or dependence (but not past use or lower levels of current use) increases the risk of transition into psychosis in persons at ultrahigh risk of psychosis. About a third of patients with first-episode psychosis are cannabis users, and, at follow-up, about half of these users are found to continue their cannabis use. Continued cannabis use (in those who are treated after developing psychosis) is associated with higher risk of relapse into psychosis, and discontinuation of cannabis use reduces the risk of relapse to that in cannabis nonusers. Finally, persons with psychosis who continue to use cannabis have more severe positive symptoms and poorer levels of functioning. Because experimental studies in humans show that cannabinoids and cannabis can induce psychotic symptoms, it is reasonable to assume that the epidemiologic data indicate a causal effect of cannabis in anticipating, triggering, or exacerbating psychosis in vulnerable individuals and in worsening the course and outcome of the illness in those who continue to use the substance. Given the public health implications of these findings, the trend to legalize medical marijuana must be viewed with concern, and efforts are necessary to educate patients and the public about the serious mental and physical health risks associated with cannabis use and abuse. PMID:27337422

  9. Adverse Outcome Pathways as Tools to Assess Drug-Induced Toxicity.

    PubMed

    Vinken, Mathieu

    2016-01-01

    Adverse outcome pathways (AOPs) are novel tools in toxicology and human risk assessment with broad potential. AOPs are designed to provide a clear-cut mechanistic representation of toxicological effects that span over different layers of biological organization. AOPs share a common structure consisting of a molecular initiating event, a series of key events connected by key event relationships, and an adverse outcome. Development and evaluation of AOPs ideally complies with guidelines issued by the Organization for Economic Cooperation and Development. AOP frameworks have yet been proposed for major types of drug-induced injury, especially in the liver, including steatosis, fibrosis, and cholestasis. These newly postulated AOPs can serve a number of purposes pertinent to safety assessment of drugs, in particular the establishment of quantitative structure-activity relationships, the development of novel in vitro toxicity screening tests, and the elaboration of prioritization strategies. PMID:27311472

  10. Adverse reproductive outcomes in families of atomic veterans: The feasibility of epidemiologic studies

    SciTech Connect

    1995-12-31

    This is an outstanding report from a distinguished academy committee, which in 71 pages of text provides the scientific basis for the carefully crafted 8-page executive summary. The principles and issues of the required epidemiological study are presented calmly and concisely, as are the ensuing short chapters on radiation biology, genetics and risk estimation, and all other adverse reproductive outcomes. The committee was mandated by Congress to determine the feasibility, cost and duration of a study on adverse reproductive outcomes in families of atomic veteran. The committee found that a scientifically adequate and epidemiologically valid study could not be mounted and the cost would be tens of millions of dollars lasting a decade. The Committee presents a number of well-discussed approaches in support of their position.

  11. [Analgesics in geriatric patients. Adverse side effects and interactions].

    PubMed

    Gosch, Markus

    2015-07-01

    Pain is a widespread symptom in clinical practice. Older adults and chronically ill patients are particularly affected. In multimorbid geriatric patients, pharmacological pain treatment is an extension of a previously existing multimedication. Besides the efficacy of pain treatment, drug side effects and drug-drug interactions have to be taken into account to minimize the health risk for these patients. Apart from the number of prescriptions, the age-related pharmacokinetic and pharmacodynamic changes significantly increase the risk among older adults. The use of non-steroidal anti-inflammatory drugs (NSAID) is widespread but NSAIDs have the highest risk of adverse drug reactions and drug interactions. In particular, the gastrointestinal, cardiovascular, renal and coagulation systems are affected. Apart from the known toxic effect on the liver (in high doses), paracetamol (acetaminophen) has similar risks although to a lesser degree. According to current data, metamizol is actually better than its reputation suggests. The risk of potential drug interactions seems to be low. Apart from the risk of sedation in combination with other drugs, tramadol and other opioids can induce the serotonin syndrome. Among older adults, especially in the case of polypharmacy, an individualized approach should be considered instead of sticking to the pain management recommended by the World Health Organization (WHO) in order to minimize drug-drug interactions and adverse drug reactions. PMID:26152872

  12. Oral Sedation Postdischarge Adverse Events in Pediatric Dental Patients

    PubMed Central

    Huang, Annie; Tanbonliong, Thomas

    2015-01-01

    The study investigated patient discharge parameters and postdischarge adverse events after discharge among children who received oral conscious sedation for dental treatment. This prospective study involved 51 patients needing dental treatment under oral conscious sedation. Each patient received one of various regimens involving combinations of a narcotic (ie, morphine or meperidine), a sedative-hypnotic (ie, chloral hydrate), a benzodiazepine (ie, midazolam or diazepam), and/or an antihistamine (ie, hydroxyzine HCl). Nitrous oxide and local anesthesia were used in conjunction with all regimens. After written informed consent was obtained, each guardian was contacted by phone with specific questions in regard to adverse events following the dental appointment. Out of 51 sedation visits, 46 were utilized for analysis including 23 boys and 23 girls ranging from 2 years 2 months to 10 years old (mean 5.8 years). 60.1% of patients slept in the car on the way home, while 21.4% of that group was difficult to awaken upon reaching home. At home, 76.1% of patients slept; furthermore, 85.7% of patients who napped following the dental visit slept longer than usual. After the appointment, 19.6% exhibited nausea, 10.1% vomited, and 7.0% experienced a fever. A return to normal behavior was reported as follows: 17.4% in <2 hours, 39.1% in 2–6 hours, 28.3% in 6–10 hours, and 15.2% in >10 hours. Postdischarge excessive somnolence, nausea, and emesis were frequent complications. The time to normality ranged until the following morning demonstrating the importance of careful postdischarge adult supervision. PMID:26398124

  13. Oral Sedation Postdischarge Adverse Events in Pediatric Dental Patients.

    PubMed

    Huang, Annie; Tanbonliong, Thomas

    2015-01-01

    The study investigated patient discharge parameters and postdischarge adverse events after discharge among children who received oral conscious sedation for dental treatment. This prospective study involved 51 patients needing dental treatment under oral conscious sedation. Each patient received one of various regimens involving combinations of a narcotic (ie, morphine or meperidine), a sedative-hypnotic (ie, chloral hydrate), a benzodiazepine (ie, midazolam or diazepam), and/or an antihistamine (ie, hydroxyzine HCl). Nitrous oxide and local anesthesia were used in conjunction with all regimens. After written informed consent was obtained, each guardian was contacted by phone with specific questions in regard to adverse events following the dental appointment. Out of 51 sedation visits, 46 were utilized for analysis including 23 boys and 23 girls ranging from 2 years 2 months to 10 years old (mean 5.8 years). 60.1% of patients slept in the car on the way home, while 21.4% of that group was difficult to awaken upon reaching home. At home, 76.1% of patients slept; furthermore, 85.7% of patients who napped following the dental visit slept longer than usual. After the appointment, 19.6% exhibited nausea, 10.1% vomited, and 7.0% experienced a fever. A return to normal behavior was reported as follows: 17.4% in <2 hours, 39.1% in 2-6 hours, 28.3% in 6-10 hours, and 15.2% in >10 hours. Postdischarge excessive somnolence, nausea, and emesis were frequent complications. The time to normality ranged until the following morning demonstrating the importance of careful postdischarge adult supervision. PMID:26398124

  14. Risk-adjusted outcomes in Medicare inpatient nephrectomy patients.

    PubMed

    Fry, Donald E; Pine, Michael; Nedza, Susan M; Locke, David G; Reband, Agnes M; Pine, Gregory

    2016-09-01

    Without risk-adjusted outcomes of surgical care across both the inpatient and postacute period of time, hospitals and surgeons cannot evaluate the effectiveness of current performance in nephrectomy and other operations, and will not have objective metrics to gauge improvements from care redesign efforts.We compared risk-adjusted hospital outcomes following elective total and partial nephrectomy to demonstrate differences that can be used to improve care. We used the Medicare Limited Dataset for 2010 to 2012 for total and partial nephrectomy for benign and malignant neoplasms to create prediction models for the adverse outcomes (AOs) of inpatient deaths, prolonged length-of-stay outliers, 90-day postdischarge deaths without readmission, and 90-day relevant readmissions. From the 4 prediction models, total predicted adverse outcomes were determined for each hospital in the dataset that met a minimum of 25 evaluable cases for the study period. Standard deviations (SDs) for each hospital were used to identify specific z-scores. Risk-adjusted adverse outcomes rates were computed to permit benchmarking each hospital's performance against the national standard. Differences between best and suboptimal performing hospitals defined the potential margin of preventable adverse outcomes for this operation.A total of 449 hospitals with 23,477 patients were evaluated. Overall AO rate was 20.8%; 17 hospitals had risk-adjusted AO rates that were 2 SDs poorer than predicted and 8 were 2 SDs better. The top performing decile of hospitals had a risk-adjusted AO rate of 10.2% while the lowest performing decile had 32.1%. With a minimum of 25 cases for each study hospital, no statistically valid improvement in outcomes was seen with increased case volume.Inpatient and 90-day postdischarge risk-adjusted adverse outcomes demonstrated marked variability among study hospitals and illustrate the opportunities for care improvement. This analytic design is applicable for comparing provider

  15. Addressing Psychosocial Adversity Within the Patient-Centered Medical Home: Expert-Created Measurable Standards

    PubMed Central

    Bair-Merritt, Megan H; Mandal, Mahua; Garg, Arvin; Cheng, Tina L.

    2016-01-01

    The Patient-Centered Medical Home (PCMH) may be improved by embedding identification and response for patients’ experiences with psychosocial adversity, but how this might optimally occur in practice has not been well-specified. We sought input from an expert panel to define feasible elements that could adapt the PCMH to adequately respond to patients’ experiences with psychosocial adversity. From December 2012 through September 2013, we used a Delphi process to systematically obtain expert opinions and reach consensus. We invited 37 experts to participate in three successive and iterative rounds of questionnaires, with each round based on aggregated, de-identified data from the prior round. We first asked experts to generate elements to adapt the PCMH, using the National Committee for Quality Assurance (NCQA’s) established six PCMH standards as the foundation. We then asked the experts to rate these elements on a 5-point Likert scale, and finally specify what they considered the most and least valuable elements. Eighteen of the 37 (49%) invited experts responded to the first survey, and constituted our sample. Experts identified 35 elements that fell under the six NCQA standards. The top rated elements included using a screening tool to identify adversity; training providers to address psychosocial adversity; having a team member with mental health expertise; providing culturally-competent care; and having written patient information related to adversity and coping. This study derived key elements that may enhance the PCMH’s ability to improve patient outcomes by purposefully identifying and responding to their psychosocial adversity. PMID:25787893

  16. Adverse incidents and patient safety - improving the learning experience of junior doctors.

    PubMed

    Baruch, Nina

    2014-02-01

    The need to ensure patient safety in the National Health Service (NHS) is a national priority. However, it has long been recognised that a culture of blame impedes learning from previous adverse incidents. It is important to feedback the outcomes of investigations into incidents to NHS staff, but junior doctors have little knowledge of learning points from investigations into adverse incidents. Learning from past mistakes would improve practice and the level of care provided by junior doctors. A forum for learning from mistakes could also provide an opportunity to review past incidents in an open and supportive environment. This could, in turn, start to change the current culture of blame in the NHS and contribute to higher standards of patient safety in the future. PMID:24532743

  17. A Review of Nitrates in Drinking Water: Maternal Exposure and Adverse Reproductive and Developmental Outcomes

    PubMed Central

    Manassaram, Deana M.; Backer, Lorraine C.; Moll, Deborah M.

    2006-01-01

    In this review we present an update on maternal exposure to nitrates in drinking water in relation to possible adverse reproductive and developmental effects, and also discuss nitrates in drinking water in the United States. The current standard for nitrates in drinking water is based on retrospective studies and approximates a level that protects infants from methemoglobinemia, but no safety factor is built into the standard. The current standard applies only to public water systems. Drinking water source was related to nitrate exposure (i.e., private systems water was more likely than community system water to have nitrate levels above the maximum contaminant limit). Animal studies have found adverse reproductive effects resulting from higher doses of nitrate or nitrite. The epidemiologic evidence of a direct exposure–response relationship between drinking water nitrate level and adverse reproductive effect is still not clear. However, some reports have suggested an association between exposure to nitrates in drinking water and spontaneous abortions, intrauterine growth restriction, and various birth defects. Uncertainties in epidemiologic studies include the lack of individual exposure assessment that would rule out confounding of the exposure with some other cause. Nitrates may be just one of the contaminants in drinking water contributing to adverse outcomes. We conclude that the current literature does not provide sufficient evidence of a causal relationship between exposure to nitrates in drinking water and adverse reproductive effects. Future studies incorporating individual exposure assessment about users of private wells—the population most at risk—should be considered. PMID:16507452

  18. Endothelial dysfunction is associated with major adverse cardiovascular events in peritoneal dialysis patients.

    PubMed

    Lee, Mi Jung; Han, Seung Hyeok; Lee, Jung Eun; Choi, Hoon Young; Yoon, Chang-Yun; Kim, Eun Jin; Han, Jae Hyun; Han, Ji Suk; Oh, Hyung Jung; Park, Jung Tak; Kang, Shin-Wook; Yoo, Tae-Hyun

    2014-09-01

    Endothelial dysfunction is implicated in increased cardiovascular risk in nondialyzed population. However, the prognostic impact of endothelial dysfunction on cardiovascular outcome has not been investigated in peritoneal dialysis (PD) patients. We prospectively determined endothelial function by brachial artery endothelium-dependent vasodilation (flow-mediated dilation [FMD]) in 143 nondiabetic PD patients and 32 controls. Primary outcome was a major adverse cardiac and cerebrovascular event (MACCE). Brachial FMD was significantly lower in PD patients than in controls (2.9% [1.3-4.7] vs 6.2% [5.4-8.3], P < 0.001). During a mean follow-up of 42 months, primary outcome was observed in 25 patients (17.5%). When patients were dichotomized by the median value of FMD (2.9%), incidence rates of MACCEs were significantly higher in the group with lower FMD compared with higher FMD (7.2 vs 3.0/100 person-years, P = 0.03). In multivariate Cox analysis, low FMD (≤2.9%) was a significant independent predictor of MACCEs (hazard ratio = 2.73, 95% confidence interval = 1.03-7.22, P = 0.04). Furthermore, multivariate fractional polynomial analysis showed that the risk of MACCE decreased steadily with higher FMD values. Impaired brachial FMD was a significant independent predictor of MACCEs in PD patients. Estimating endothelial dysfunction by brachial FMD could be useful for stratifying cardiovascular risk in these patients. PMID:25192486

  19. Psychiatrists' Attitudes toward Metabolic Adverse Events in Patients with Schizophrenia

    PubMed Central

    Sugawara, Norio; Yasui-Furukori, Norio; Yamazaki, Manabu; Shimoda, Kazutaka; Mori, Takao; Sugai, Takuro; Suzuki, Yutaro; Someya, Toshiyuki

    2014-01-01

    Background There is growing concern about the metabolic abnormalities in patients with schizophrenia. Aims The aim of this study was to assess the attitudes of psychiatrists toward metabolic adverse events in patients with schizophrenia. Method A brief questionnaire was constructed to cover the following broad areas: the psychiatrists' recognition of the metabolic risk of antipsychotic therapy, pattern of monitoring patients for physical risks, practice pattern for physical risks, and knowledge of metabolic disturbance. In March 2012, the questionnaire was mailed to 8,482 psychiatrists who were working at hospitals belonging to the Japan Psychiatric Hospitals Association. Results The overall response rate was 2,583/8,482 (30.5%). Of the respondents, 85.2% (2,200/2,581) reported that they were concerned about prescribing antipsychotics that have a risk of elevating blood sugar; 47.6% (1,201/2,524) stated that their frequency of monitoring patients under antipsychotic treatment was based on their own experiences; and only 20.6% (5,22/2,534) of respondents answered that the frequency with which they monitored their patients was sufficient to reduce the metabolic risks. Conclusions Psychiatrists practicing in Japan were generally aware and concerned about the metabolic risks for patients being treated with antipsychotics. Although psychiatrists should monitor their patients for metabolic abnormalities to balance these risks, a limited number of psychiatrists answered that the frequency with which they monitored patients to reduce the metabolic risks was sufficient. Promotion of the best practices of pharmacotherapy and monitoring is needed for psychiatrists treating patients with schizophrenia. PMID:24466260

  20. Maternal Ethnic Ancestry and Adverse Perinatal Outcomes in New York City

    PubMed Central

    Stein, Cheryl R.; Savitz, David A.; Janevic, Teresa; Ananth, Cande V.; Kaufman, Jay S.; Herring, Amy H.; Engel, Stephanie M.

    2009-01-01

    Objective To examine the association between narrowly defined subsets of maternal ethnicity and birth outcomes. Study Design Analysis of 1995-2003 New York City birth certificates linked to hospital discharge data for 949,210 singleton births to examine the multivariable associations between maternal ethnicity and preterm birth, subsets of spontaneous and medically indicated preterm birth, term small for gestational age (SGA), and term birthweight. Results Compared to non-Hispanic whites, Puerto Ricans had an elevated odds ratio (OR 1.9, 95% CI 1.9-2.0) for delivering at 32-36 weeks (adjusted for nativity, maternal age, parity, education, tobacco use, pre-pregnancy weight, birth year). We found an excess of adverse outcomes among most Latino groups. Outcomes also varied within regions, with North African infants nearly 100g (adjusted) heavier than sub-Saharan Africans. Conclusions The considerable heterogeneity in risk of adverse perinatal outcomes is obscured in broad categorizations of maternal race/ethnicity, and may help to formulate etiologic hypotheses. PMID:19729145

  1. The Violence Proneness Scale of the DUSI-R predicts adverse outcomes associated with substance abuse.

    PubMed

    Kirisci, Levent; Tarter, Ralph; Reynolds, Maureen

    2009-01-01

    Accuracy of the Violence Proneness Scale (VPS) of the Drug Use Screening Inventory (DUSI-R) was evaluated in 328 boys for predicting use of illegal drugs, DUI, selling drugs, sexually transmitted disease, car accident while under acute effects of drugs/alcohol, trading drugs for sex, injuries from a fight, and traumatic head injury. Boys were prospectively tracked from age 16 to 19 at which time these outcomes were documented in the interim period. The results demonstrated that the VPS score is a significant predictor of all outcomes. Prediction accuracy ranged between 62%-83%. These findings suggest that the VPS may be useful for identifying youths who are at high risk for using illicit drugs and commonly associated adverse outcomes. PMID:19283571

  2. [Patient evaluation and outcome measures].

    PubMed

    Nieto Pol, Enrique

    2014-01-01

    Both the initial evaluation and follow-up of patients with osteoarthritis require systematic evaluation of the indicators that provide information on the degree of involvement of the disease and allow its quantification. Reliable measures of disease progression help decision-making by clinicians and provide valid information on treatment response and the effectiveness of the distinct therapeutic interventions. The instruments recommended in research, as outcome measures in osteoarthritis, are pain evaluation, assessment of physical function, and self-reported global evaluation. In studies lasting more than 1 year, structural changes are evaluated through simple X-ray. Self-reported quality of life assessment and physician global assessment are also recommended as options. These indicators should be incorporated into routine clinical practice for adequate evaluation and correct follow-up of patients with osteoarthritis. The recommended pain evaluation method for use in clinical practice is the visual analog scale (VAS). The best instrument to evaluate physical function in patients with hip or knee osteoarthritis is the WOMAC scale (Western Ontario and McMaster Universities Osteoarthritis Index). For patient-reported global assessment in routine practice, the recommended scales are VAS or the SF-12 (12-item short-form health survey). PMID:24467959

  3. Obesity and Outcomes in Patients with Metastatic Urothelial Carcinoma1

    PubMed Central

    Leiter, Amanda; Doucette, John; Krege, Susan; Lin, Chia-Chia; Hahn, Noah; Ecke, Thorsten; Sonpavde, Guru; Bamias, Aristotle; Oh, William K.; Galsky, Matthew D.

    2016-01-01

    Background: Obesity has been associated with worse outcomes in patients with clinically localized urothelial cancer. However, this impact has not been evaluated in metastatic disease. Objective: To assess the impact of obesity on outcomes of patients with metastatic urothelial cancer. Methods: Data from 537 patients were aggregated from eight phase II and phase III clinical trials investigating first-line cisplatin-based combination therapy in metastatic urothelial cancer. Chemotherapy regimen, adverse events, treatment response, and survival outcomes were compared across body mass index (BMI) and body surface area (BSA) categories. Results: BMI was classified according to WHO criteria (<18.5 underweight, 18.5–24.99 normal weight, 25–29.99 overweight, >30 obese). BSA was classified as either below or greater than or equal to (average for this cohort (1.87 m2 for males and 1.66 m2 for females). There was no significant difference in number of chemotherapy cycles, adverse events, and response rate or survival outcomes (overall and progression-free) across BMI and BSA categories. There was no significant difference in adverse events across BMI categories, but the incidences of embolic events and renal failure were higher in patients with an average or higher BSA than those with a lower than average BSA (6.6% vs. 3.1% for renal failure p = 0.06; 5.9% vs. 2.7% for renal failure, p = 0.07). There was no significant difference in response rate or survival outcomes (overall and progression-free) amongst BMI and BSA categories. Conclusions: Obese patients with metastatic urothelial cancer on cisplatin-based therapies have similar response rates, survival outcomes, and tolerability of cisplatin-based therapy to non-obese patients. PMID:27500201

  4. Parental drinking and adverse outcomes in children: A scoping review of cohort studies

    PubMed Central

    Felix, Lambert; Keating, Patrick; McCambridge, Jim

    2015-01-01

    Abstract Introduction and Aims There is a growing interest in measuring alcohol's harms to people other than the drinker themselves. ‘Children of alcoholics’ and foetal alcohol spectrum disorder have received widespread attention. Less is known about how children are affected by post‐natal exposure to parental drinking other than alcohol abuse/dependence. In this scoping review, we aim to assemble and map existing evidence from cohort studies on the consequences of parental alcohol use for children, and to identify limitations and gaps in this literature. Design and Methods Systematic review methods were used. Electronic databases were searched (1980 to October 2013) and a total of 3215 abstracts were screened, 326 full text papers examined and 99 eligible for inclusion according to selection criteria including separation of exposure and outcome measurement in time and report of a quantitative effect size. Results The main finding is the large literature available. Adolescent drinking behaviour was the most common outcome measure and outcomes other than substance use were rarely analysed. In almost two of every three published associations, parental drinking was found to be statistically significantly associated with a child harm outcome measure. Several limitations in the literature are noted regarding its potential to address a possible causal role of parental drinking in children's adverse outcomes. Discussion and Conclusions This study identifies targets for further study and provides a platform for more targeted analytic investigations which ascertain risk of bias, and which are capable of considering the appropriateness of causal inferences for the observed associations. [Rossow I, Felix L, Keating P, McCambridge J. Parental drinking and adverse outcomes in children: A scoping review of cohort studies. Drug Alcohol Rev 2016;35:397–405] PMID:26332090

  5. Acculturation and Adverse Birth Outcomes in a Predominantly Puerto Rican Population

    PubMed Central

    de Mendoza, Veronica Barcelona; Harville, Emily; Theall, Katherine; Buekens, Pierre; Chasan-Taber, Lisa

    2016-01-01

    Introduction Latinas in the United States on average have poorer birth outcomes than Whites, yet considerable heterogeneity exists within Latinas. Puerto Ricans have some of the highest rates of adverse outcomes and are understudied. The goal of this study was to determine if acculturation was associated with adverse birth outcomes in a predominantly Puerto Rican population. Methods We conducted a secondary analysis of Proyecto Buena Salud, a prospective cohort study conducted from 2006 to 2011. A convenience sample of pregnant Latina women were recruited from a tertiary care hospital in Massachusetts. Acculturation was measured in early pregnancy; directly via the Psychological Acculturation Scale, and via proxies of language preference and generation in the United States. Birth outcomes (gestational age and birthweight) were abstracted from medical records (n = 1362). Results After adjustment, psychological acculturation, language preference, and generation was not associated with odds of preterm birth. However, every unit increase in psychological acculturation score was associated with an increase in gestational age of 0.22 weeks (SE = 0.1, p = 0.04) among all births. Women who preferred to speak Spanish (β = −0.39, SE = 0.2, p = 0.02) and who were first generation in the US (β = −0.33, SE = 0.1, p = 0.02) had significantly lower gestational ages than women who preferred English or who were later generation, respectively. Similarly, women who were first generation had babies who weighed 76.11 g less (SE = 35.2, p = 0.03) than women who were later generation. Discussion We observed a small, but statistically significant adverse impact of low acculturation on gestational age and birthweight in this predominantly Puerto Rican population. PMID:26694041

  6. Acculturation and Adverse Birth Outcomes in a Predominantly Puerto Rican Population.

    PubMed

    Barcelona de Mendoza, Veronica; Harville, Emily; Theall, Katherine; Buekens, Pierre; Chasan-Taber, Lisa

    2016-06-01

    Introduction Latinas in the United States on average have poorer birth outcomes than Whites, yet considerable heterogeneity exists within Latinas. Puerto Ricans have some of the highest rates of adverse outcomes and are understudied. The goal of this study was to determine if acculturation was associated with adverse birth outcomes in a predominantly Puerto Rican population. Methods We conducted a secondary analysis of Proyecto Buena Salud, a prospective cohort study conducted from 2006 to 2011. A convenience sample of pregnant Latina women were recruited from a tertiary care hospital in Massachusetts. Acculturation was measured in early pregnancy; directly via the Psychological Acculturation Scale, and via proxies of language preference and generation in the United States. Birth outcomes (gestational age and birthweight) were abstracted from medical records (n = 1362). Results After adjustment, psychological acculturation, language preference, and generation was not associated with odds of preterm birth. However, every unit increase in psychological acculturation score was associated with an increase in gestational age of 0.22 weeks (SE = 0.1, p = 0.04) among all births. Women who preferred to speak Spanish (β = -0.39, SE = 0.2, p = 0.02) and who were first generation in the US (β = -0.33, SE = 0.1, p = 0.02) had significantly lower gestational ages than women who preferred English or who were later generation, respectively. Similarly, women who were first generation had babies who weighed 76.11 g less (SE = 35.2, p = 0.03) than women who were later generation. Discussion We observed a small, but statistically significant adverse impact of low acculturation on gestational age and birthweight in this predominantly Puerto Rican population. PMID:26694041

  7. Placental DNA Methylation Related to Both Infant Toenail Mercury and Adverse Neurobehavioral Outcomes

    PubMed Central

    Maccani, Jennifer Z.J.; Koestler, Devin C.; Lester, Barry; Houseman, E. Andrés; Armstrong, David A.; Kelsey, Karl T.

    2015-01-01

    Background Prenatal mercury (Hg) exposure is associated with adverse child neurobehavioral outcomes. Because Hg can interfere with placental functioning and cross the placenta to target the fetal brain, prenatal Hg exposure can inhibit fetal growth and development directly and indirectly. Objectives We examined potential associations between prenatal Hg exposure assessed through infant toenail Hg, placental DNA methylation changes, and newborn neurobehavioral outcomes. Methods The methylation status of > 485,000 CpG loci was interrogated in 192 placental samples using Illumina’s Infinium HumanMethylation450 BeadArray. Hg concentrations were analyzed in toenail clippings from a subset of 41 infants; neurobehavior was assessed using the NICU Network Neurobehavioral Scales (NNNS) in an independent subset of 151 infants. Results We identified 339 loci with an average methylation difference > 0.125 between any two toenail Hg tertiles. Variation among these loci was subsequently found to be associated with a high-risk neurodevelopmental profile (omnibus p-value = 0.007) characterized by the NNNS. Ten loci had p < 0.01 for the association between methylation and the high-risk NNNS profile. Six of 10 loci reside in the EMID2 gene and were hypomethylated in the 16 high-risk profile infants’ placentas. Methylation at these loci was moderately correlated (correlation coefficients range, –0.33 to –0.45) with EMID2 expression. Conclusions EMID2 hypomethylation may represent a novel mechanism linking in utero Hg exposure and adverse infant neurobehavioral outcomes. Citation Maccani JZ, Koestler DC, Lester B, Houseman EA, Armstrong DA, Kelsey KT, Marsit CJ. 2015. Placental DNA methylation related to both infant toenail mercury and adverse neurobehavioral outcomes. Environ Health Perspect 123:723–729; http://dx.doi.org/10.1289/ehp.1408561 PMID:25748564

  8. Associations between Anticholinergic Burden and Adverse Health Outcomes in Parkinson Disease

    PubMed Central

    Crispo, James A. G.; Willis, Allison W.; Thibault, Dylan P.; Fortin, Yannick; Hays, Harlen D.; McNair, Douglas S.; Bjerre, Lise M.; Kohen, Dafna E.; Perez-Lloret, Santiago; Mattison, Donald R.; Krewski, Daniel

    2016-01-01

    Background Elderly adults should avoid medications with anticholinergic effects since they may increase the risk of adverse events, including falls, delirium, and cognitive impairment. However, data on anticholinergic burden are limited in subpopulations, such as individuals with Parkinson disease (PD). The objective of this study was to determine whether anticholinergic burden was associated with adverse outcomes in a PD inpatient population. Methods Using the Cerner Health Facts® database, we retrospectively examined anticholinergic medication use, diagnoses, and hospital revisits within a cohort of 16,302 PD inpatients admitted to a Cerner hospital between 2000 and 2011. Anticholinergic burden was computed using the Anticholinergic Risk Scale (ARS). Primary outcomes were associations between ARS score and diagnosis of fracture and delirium. Secondary outcomes included associations between ARS score and 30-day hospital revisits. Results Many individuals (57.8%) were prescribed non-PD medications with moderate to very strong anticholinergic potential. Individuals with the greatest ARS score (≥4) were more likely to be diagnosed with fractures (adjusted odds ratio (AOR): 1.56, 95% CI: 1.29–1.88) and delirium (AOR: 1.61, 95% CI: 1.08–2.40) relative to those with no anticholinergic burden. Similarly, inpatients with the greatest ARS score were more likely to visit the emergency department (adjusted hazard ratio (AHR): 1.32, 95% CI: 1.10–1.58) and be readmitted (AHR: 1.16, 95% CI: 1.01–1.33) within 30-days of discharge. Conclusions We found a positive association between increased anticholinergic burden and adverse outcomes among individuals with PD. Additional pharmacovigilance studies are needed to better understand risks associated with anticholinergic medication use in PD. PMID:26939130

  9. Intimate partner violence, substance use, and adverse neonatal outcomes among urban women

    PubMed Central

    Alhusen, Jeanne L.; Lucea, Marguerite B.; Bullock, Linda; Sharps, Phyllis

    2013-01-01

    Objective To assess the prevalence of intimate partner violence, substance use, and their co-occurrence during pregnancy and examines their associations with adverse neonatal outcomes. Study design Between February 2009 and February 2010, pregnant women receiving obstetrical care at three urban clinics were screened for intimate partner violence and substance use between 24-28 weeks gestation. A chart review was conducted upon delivery to assess for adverse neonatal outcomes of low birth weight (LBW), preterm birth, and small for gestational age (SGA). Results Maternal and neonatal data were collected on 166 mothers and their neonates. Overall, 19% of the sample reported intimate partner violence during their pregnancies. Of the study's neonates 41% had at least one adverse neonatal outcome. Nearly half of the mothers reported using at least one substance during pregnancy. Women experiencing intimate partner violence had a higher prevalence of marijuana use than their non-abused counterparts (p < 0.01). Experiencing intimate partner violence was associated with a fourfold increase in having a SGA neonate (aOR = 4.00; 95% CI 1.58 – 9.97). Women who reported marijuana use had five times the odds of having a neonate classified as SGA (aOR = 5.16, 95% CI 2.24 – 11.89) or LBW (aOR 5.00; 95% CI 1.98 – 12.65). Conclusions The prevalence of intimate partner violence during pregnancy and substance use is high in urban mothers, the risks of which extend to their neonates. Pediatric providers are urged to routinely screen for both issues and recognize the impact of co-occurrence of these risk factors on poor neonatal and childhood outcomes. PMID:23485028

  10. Surgical Correction of Scoliosis in Children with Spastic Quadriplegia: Benefits, Adverse Effects, and Patient Selection

    PubMed Central

    Legg, Julian; Davies, Evan; Raich, Annie L.; Dettori, Joseph R.; Sherry, Ned

    2014-01-01

    Study Rationale Cerebral palsy (CP) is a group of nonprogressive syndromes of posture and motor impairment associated with lesions of the immature brain. Spastic quadriplegia is the most severe form with a high incidence of scoliosis, back pain, respiratory compromise, pelvic obliquity, and poor sitting balance. Surgical stabilization of the spine is an effective technique for correcting deformity and restoring sitting posture. The decision to operate in this group of patients is challenging. Objectives The aim of this study is to determine the benefits of surgical correction of scoliosis in children with spastic quadriplegia, the adverse effects of this treatment, and what preoperative factors affect patient outcome after surgical correction. Materials and Methods A systematic review was undertaken to identify studies describing benefits and adverse effects of surgery in spastic quadriplegia. Factors affecting patient outcome following surgical correction of scoliosis were assessed. Studies involving adults and nonspastic quadriplegia were excluded. Results A total of 10 case series and 1 prospective and 3 retrospective cohort studies met inclusion criteria. There was significant variation in the overall risk of complications (range, 10.9−70.9%), mortality (range, 2.8−19%), respiratory/pulmonary complications (range, 26.9−57.1%), and infection (range, 2.5−56.8%). Factors associated with a worse outcome were a significant degree of thoracic kyphosis, days in the intensive care unit, and poor nutritional status. Conclusion Caregivers report a high degree of satisfaction with scoliosis surgery for children with spastic quadriplegia. There is limited evidence of preoperative factors that can predict patient outcome after scoliosis. There is a need for well-designed prospective studies of scoliosis surgery in spastic quadriplegia. PMID:24715871

  11. Depression and Risk for Adverse Falls in Older Home Health Care Patients

    PubMed Central

    Byers, Amy L.; Sheeran, Thomas; Mlodzianowski, Amy E.; Meyers, Barnett S.; Nassisi, Pamella; Bruce, Martha L.

    2013-01-01

    Because falls are highly prevalent, harmful events for older adults, identification of patients at risk is a high priority for home health care agencies. Using routine administrative data, we demonstrated that patients with depressive symptoms on the Outcome and Assessment Information Set are at risk for falls. A prospective case-control study that matched 54 patients who experienced an adverse fall with 854 controls showed that patients who fell had twice the odds of being depressed (odds ratio = 1.90, 95% confidence interval = 1.01 to 3.59). Bowel incontinence, high medical comorbidity, stair use, injury and poisoning, memory deficit, and antipsychotic medication use were also predictors, but no association was found for antidepressant medications. These data suggest the potential benefit of including depression screening for multifactorial fall prevention interventions. PMID:20077999

  12. Pivmecillinam and adverse birth and neonatal outcomes: a population-based cohort study.

    PubMed

    Vinther Skriver, Mette; Nørgaard, Mette; Pedersen, Lars; Carl Schønheyder, Henrik; Sørensen, Henrik Toft

    2004-01-01

    A previous study unexpectedly showed an increased, statistically imprecise, risk of low Apgar score in children of women redeeming prescriptions for pivmecillinam in late pregnancy. To improve statistical precision we extended the previous dataset with data for 5 more y, and in addition added more neonatal outcomes. We thus examined the risk of adverse birth and neonatal outcomes among pregnant users of pivmecillinam based on population-based registries in North Jutland County, Denmark. We included 63,659 women with a live birth, or stillbirth after the 28th week of gestation. 2031 had redeemed prescriptions for pivmecillinam any time during pregnancy, 559 in the first trimester and 371 within 28 d before delivery. Adjusted odds ratios were: birth defects 0.83 (95% confidence interval (95% CI) 0.53-1.32) for exposure during first trimester, preterm delivery 0.96 (95% CI 0.79-1.18) and low birth weight 0.79 (95% CI 0.52-1.20) for exposure any time during pregnancy, and stillbirth 1.19 (95% CI 0.30-4.80), low Apgar score 1.17 (95% CI 0.37-3.66), hypoglycaemia 1.03 (95% CI 0.53-2.00), and respiratory distress syndrome 0.79 (95% CI 0.38-1.68) for exposure within 28 d before delivery. Use of pivmecillinam during pregnancy did not appear to increase the risk of adverse birth and neonatal outcomes; however, statistical precision is still low. PMID:15513399

  13. Adverse Geriatric Outcomes Secondary to Polypharmacy in a Mouse Model: The Influence of Aging.

    PubMed

    Huizer-Pajkos, Aniko; Kane, Alice E; Howlett, Susan E; Mach, John; Mitchell, Sarah J; de Cabo, Rafael; Le Couteur, David G; Hilmer, Sarah N

    2016-05-01

    We aimed to develop a mouse model of polypharmacy, primarily to establish whether short-term exposure to polypharmacy causes adverse geriatric outcomes. We also investigated whether old age increased susceptibility to any adverse geriatric outcomes of polypharmacy. Young (n= 10) and old (n= 21) male C57BL/6 mice were administered control diet or polypharmacy diet containing therapeutic doses of five commonly used medicines (simvastatin, metoprolol, omeprazole, acetaminophen, and citalopram). Mice were assessed before and after the 2- to 4-week intervention. Over the intervention period, we observed no mortality and no change in food intake, body weight, or serum biochemistry in any age or treatment group. In old mice, polypharmacy caused significant declines in locomotor activity (pre minus postintervention values in control 2 ± 13 counts, polypharmacy 32 ± 7 counts,p< .05) and front paw wire holding impulse (control -2.45 ± 1.02 N s, polypharmacy +1.99 ± 1.19 N s,p< .05), loss of improvement in rotarod latency (control -59 ± 11 s, polypharmacy -1.7 ± 17 s,p< .05), and lowered blood pressure (control -0.2 ± 3 mmHg, polypharmacy 11 ± 4 mmHg,p< .05). In young mice, changes in outcomes over the intervention period did not differ between control and polypharmacy groups. This novel model of polypharmacy is feasible. Even short-term polypharmacy impairs mobility, balance, and strength in old male mice. PMID:25940962

  14. Collaborative activities and treatment outcomes in patients with HIV-associated tuberculosis in Viet Nam

    PubMed Central

    Nhung, N. V.; Shewade, H. D.; Hoa, N. B.; Harries, A. D.

    2016-01-01

    Setting: The National Tuberculosis (TB) Programme in Viet Nam and Ho Chi Minh City (HCMC). Objectives: To determine 1) at national level between 2011 and 2013, the relationship between human immunodeficiency virus (HIV) testing, uptake of TB-HIV interventions and adverse treatment outcomes among TB-HIV patients; and 2) in HCMC in 2013, patient characteristics associated with adverse outcomes. Design: An ecological study reviewing aggregate nationwide data and a retrospective cohort review in HCMC. Results: Nationwide, from 2011 to 2013, HIV testing increased in TB patients from 58% to 68% and antiretroviral therapy (ART) increased in TB-HIV patients from 54% to 63%. Adverse treatment outcomes in TB-HIV patients increased from 24% to 27%, largely due to transfer out (5–9% increase) and death. The Northern and Highland regions showed poor uptake of TB-HIV interventions. In HCMC, 303 (27%) of 1110 TB-HIV patients had adverse outcomes, with higher risks observed in those with previously treated TB, those diagnosed as HIV-positive before TB onset and those never placed on cotrimoxazole or ART. Conclusion: Despite improving HIV testing rates and TB-HIV interventions, adverse outcomes in TB-HIV patients remain at about 26%. Characteristics predicting higher risk of adverse outcomes must be addressed if Viet Nam wishes to end the TB epidemic by 2030. PMID:27051604

  15. Systems Toxicology of Male Reproductive Development: Profiling 774 Chemicals for Molecular Targets and Adverse Outcomes

    PubMed Central

    Leung, Maxwell C.K.; Phuong, Jimmy; Baker, Nancy C.; Sipes, Nisha S.; Klinefelter, Gary R.; Martin, Matthew T.; McLaurin, Keith W.; Setzer, R. Woodrow; Darney, Sally Perreault; Judson, Richard S.; Knudsen, Thomas B.

    2015-01-01

    Background: Trends in male reproductive health have been reported for increased rates of testicular germ cell tumors, low semen quality, cryptorchidism, and hypospadias, which have been associated with prenatal environmental chemical exposure based on human and animal studies. Objective: In the present study we aimed to identify significant correlations between environmental chemicals, molecular targets, and adverse outcomes across a broad chemical landscape with emphasis on developmental toxicity of the male reproductive system. Methods: We used U.S. EPA’s animal study database (ToxRefDB) and a comprehensive literature analysis to identify 774 chemicals that have been evaluated for adverse effects on male reproductive parameters, and then used U.S. EPA’s in vitro high-throughput screening (HTS) database (ToxCastDB) to profile their bioactivity across approximately 800 molecular and cellular features. Results: A phenotypic hierarchy of testicular atrophy, sperm effects, tumors, and malformations, a composite resembling the human testicular dysgenesis syndrome (TDS) hypothesis, was observed in 281 chemicals. A subset of 54 chemicals with male developmental consequences had in vitro bioactivity on molecular targets that could be condensed into 156 gene annotations in a bipartite network. Conclusion: Computational modeling of available in vivo and in vitro data for chemicals that produce adverse effects on male reproductive end points revealed a phenotypic hierarchy across animal studies consistent with the human TDS hypothesis. We confirmed the known role of estrogen and androgen signaling pathways in rodent TDS, and importantly, broadened the list of molecular targets to include retinoic acid signaling, vascular remodeling proteins, G-protein coupled receptors (GPCRs), and cytochrome P450s. Citation: Leung MC, Phuong J, Baker NC, Sipes NS, Klinefelter GR, Martin MT, McLaurin KW, Setzer RW, Darney SP, Judson RS, Knudsen TB. 2016. Systems toxicology of male

  16. Adolescent Alcohol Abuse and Adverse Adult Outcomes: Evaluating Confounds with Drinking-Discordant Twins

    PubMed Central

    Rose, Richard J.; Winter, Torsten; Viken, Richard J.; Kaprio, Jaakko

    2014-01-01

    Background Adolescent alcohol abuse is associated with adverse outcomes in early adulthood, but differences in familial status and structure and household and community environments correlate with both adolescent drinking and adverse adult outcomes and may explain their association. We studied drinking-discordant twin pairs to evaluate such confounds to ask: Will between-family associations replicate in within-family comparisons? Methods With longitudinal data from > 3,000 Finnish twins, we associated drinking problems at age 18½ with 13 outcomes assessed at age 25; included were sustained substance abuse, poor health, physical symptoms, early coital debut, multiple sexual partners, life dissatisfaction, truncated education, and financial problems. We assessed associations among twins as individuals with linear regression adjusted for correlated observations; within-family analyses of discordant twin pairs followed, comparing paired means for adult outcomes among co-twins discordant for adolescent problem drinking. Defining discordance by extreme scores on self-reported problem drinking at age 18½ permitted parallel analyses of twins as individuals and discordant twin pairs. Alternate definitions of pair-wise discordance and difference score correlations across the entire twin sample yielded supplementary analyses. Results All individual associations were highly significant for all definitions of discordance we employed. Depending on definitions of discordance, 11 to 13 comparisons of all drinking-discordant twin pairs and 3 to 6 comparisons of discordant monozygotic twin pairs replicated between-family associations. For most outcomes, effect size attenuated from individual level analysis to that within discordant MZ twin pairs providing evidence of partial confounding in associations reported in earlier research. The exception was the General Health Questionnaire; at age 25, GHQ-12 had equivalent associations with age 18½ RAPI across all comparisons

  17. Defining and Modeling Known Adverse Outcome Pathways: Domoic Acid and Neuronal Signaling as a Case Study

    SciTech Connect

    Watanabe, Karen H.; Andersen, Melvin E.; Basu, Nil; Carvan, Michael J.; Crofton, Kevin M.; King, Kerensa A.; Sunol, Cristina; Tiffany-Castiglioni, Evelyn; Schultz, Irvin R.

    2011-01-01

    An adverse outcome pathway (AOP) is a sequence of key events from a molecular-level initiating event and an ensuing cascade of steps to an adverse outcome with population level significance. To implement a predictive strategy for ecotoxicology, the multiscale nature of an AOP requires computational models to link salient processes (e.g., in chemical uptake, toxicokinetics, toxicodynamics, and population dynamics). A case study with domoic acid was used to demonstrate strategies and enable generic recommendations for developing computational models in an effort to move toward a toxicity testing paradigm focused on toxicity pathway perturbations applicable to ecological risk assessment. Domoic acid, an algal toxin with adverse effects on both wildlife and humans, is a potent agonist for kainate receptors (ionotropic glutamate receptors whose activation leads to the influx of Na+ and Ca2+). Increased Ca2+ concentrations result in neuronal excitotoxicity and cell death primarily in the hippocampus, which produces seizures, impairs learning and memory, and alters behavior in some species. Altered neuronal Ca2+ is a key process in domoic acid toxicity which can be evaluated in vitro. Further, results of these assays would be amenable to mechanistic modeling for identifying domoic acid concentrations and Ca2+ perturbations that are normal, adaptive, or clearly toxic. In vitro assays with outputs amenable to measurement in exposed populations can link in vitro to in vivo conditions, and toxicokinetic information will aid in linking in vitro results to the individual organism. Development of an AOP required an iterative process with three important outcomes: (1) a critically reviewed, stressor-specific AOP; (2) identification of key processes suitable for evaluation with in vitro assays; and (3) strategies for model development.

  18. Hyperactive children as young adults: driving abilities, safe driving behavior, and adverse driving outcomes.

    PubMed

    Fischer, Mariellen; Barkley, Russell A; Smallish, Lori; Fletcher, Kenneth

    2007-01-01

    ADHD has been linked to poorer driving abilities and greater adverse outcomes (crashes, citations) in clinic-referred cases of teens and adults with ADHD. No study, however, has focused systematically on ADHD children followed into adulthood. The present paper does so while measuring driving-related cognitive abilities, driving behavior, and history of adverse driving outcomes. A multi-method, multi-source battery of driving measures was collected at the young adult follow-up on hyperactive (H; N=147; mean age=21.1) and community control children (CC; N=71; mean age=20.5) followed for more than 13 years. More of the H than CC groups had been ticketed for reckless driving, driving without a license, hit-and-run crashes, and had their licenses suspended or revoked. Official driving records found more of the H group having received traffic citations and a greater frequency of license suspensions. The cost of damage in their initial crashes was also significantly greater in the H than CC group. Both self-report and other ratings of actual driving behavior revealed less safe driving practices being used by the H group. Observations by driving instructors during a behind-the-wheel road test indicated significantly more impulsive errors. Performance on a simulator further revealed slower and more variable reaction times, greater errors of impulsiveness (false alarms, poor rule following), more steering variability, and more scrapes and crashes of the simulated vehicle against road boundaries in the H than in the CC group. These findings suggest that children growing up with ADHD may either have fewer driving risks or possibly under-report those risks relative to clinic-referred adults with this disorder. Deficits in simulator performance and safe driving behavior, however, are consistent with clinic-referred adults with ADHD suggesting ongoing risks for such adverse driving outcomes in children growing up with ADHD. PMID:16919226

  19. Physical Performance Characteristics of Assisted Living Residents and Risk for Adverse Health Outcomes

    PubMed Central

    Giuliani, Carol A.; Gruber-Baldini, Ann L.; Park, Nan S.; Schrodt, Lori A.; Rokoske, Franzi; Sloane, Philip D.; Zimmerman, Sheryl

    2013-01-01

    Purpose Little is known about the physical performance ability of residential care/assisted living (RC/AL) residents and its relationship to adverse outcomes such as fracture, nursing home placement, functional decline, and death. The purposes of this paper are to: 1) describe the functional characteristics of RC/AL residents; 2) examine the relationships between resident- and facility-characteristics and physical performance; and 3) determine the predictive value of physical performance for adverse outcomes. Design and Methods Data were derived from 1791 residents in 189 RC/AL facilities, participating in the Collaborative Studies of Long-Term Care. At baseline, residents were tested on four performance measures (grip strength, chair rise, balance, and walking speed), and other resident- and facility-level information was collected. Adverse outcomes were measured over one year. Results Average grip strength was 14 ± 7 kg; 61% of residents walked < 0.6 m/second (average 0.41 m/second); 26% could perform five chair rises; and only 19% could perform a tandem stand for a least one second. Multivariable analyses showed that more cognitive and functional impairment, depressive symptoms and comorbid conditions, and for-profit ownership, were associated with poorer physical performance. Controlling for individual characteristics, better performance on the four physical performance measures was associated with a reduced risk of nursing home placement, fracture, and decline in function over one year. Implication Simple performance measures identify modifiable functional deficits, and suggest targeted interventions to prolong independent mobility and aging in place in RC/AL facilities. PMID:18483432

  20. Generation of computationally predicted Adverse Outcome Pathway networks through integration of publicly available in vivo, in vitro, phenotype, and biological pathway data.

    EPA Science Inventory

    The Adverse Outcome Pathway (AOP) framework is becoming a widely used tool for organizing and summarizing the mechanistic information connecting molecular perturbations by environmental stressors with adverse ecological and human health outcomes. However, the conventional process...

  1. Use of the adverse outcome pathway framework to represent cross-species consequences of specific pathway perturbations

    EPA Science Inventory

    The adverse outcome pathway (AOP) framework has been developed as a means for assembling scientifically defensible descriptions of how particular molecular perturbations, termed molecular initiating events (MIEs), can evoke a set of predictable responses at different levels of bi...

  2. Conceptual Model for Assessing Criteria Air Pollutants in a Multipollutant Context: A Modified Adverse Outcome Pathway Approach

    EPA Science Inventory

    Background: Air pollution consists of a complex mixture of particulate and gaseous components. Individual criteria and other hazardous air pollutants have been linked to adverse respiratory and cardiovascular health outcomes. However, assessing risk of air pollutant mixtures is d...

  3. Merging Adverse Outcome Pathway (AOP) and Mode of Action (MOA) Frameworks: Assembling Knowledge for Use in Risk Assessment

    EPA Science Inventory

    The Adverse Outcome Pathway has emerged as an internationally harmonized mechanism for organizing biological information in a chemical agnostic manner. This construct is valuable for interpreting the results from high-throughput toxicity (HTT) assessment by providing a mechanisti...

  4. Characterization of the Risks of Adverse Outcomes Following Rubella Infection in Pregnancy.

    PubMed

    Thompson, Kimberly M; Simons, Emily A; Badizadegan, Kamran; Reef, Susan E; Cooper, Louis Z

    2016-07-01

    Although most infections with the rubella virus result in relatively minor sequelae, rubella infection in early pregnancy may lead to severe adverse outcomes for the fetus. First recognized in 1941, congenital rubella syndrome (CRS) can manifest with a diverse range of symptoms, including congenital cataracts, glaucoma, and cardiac defects, as well as hearing and intellectual disability. The gestational age of the fetus at the time of the maternal rubella infection impacts the probability and severity of outcomes, with infection in early pregnancy increasing the risks of spontaneous termination (miscarriage), fetal death (stillbirth), birth defects, and reduced survival for live-born infants. Rubella vaccination continues to change the epidemiology of rubella and CRS globally, but no models currently exist to evaluate the economic benefits of rubella management. This systematic review provides an overall assessment of the weight of the evidence for the outcomes associated with rubella infections in the first 20 weeks of pregnancy. We identified, evaluated, and graded 31 studies (all from developed countries) that reported on the pregnancy outcomes of at least 30 maternal rubella infections. We used the available evidence to estimate the increased risks of spontaneous termination, fetal death, infant death, and CRS as a function of the timing of rubella infection in pregnancy and decisions about induced termination. These data support the characterization of the disability-adjusted life years for outcomes associated with rubella infection in pregnancy. We find significant impacts associated with maternal rubella infections in early pregnancy, which economic analyses will miss if they only focus on live births of CRS cases. Our estimates of fetal loss from increased induced terminations due to maternal rubella infections provide context that may help to explain the relatively low numbers of observed CRS cases per year despite potentially large burdens of disease. Our

  5. Aldosterone predicts major adverse cardiovascular events in patients with acute myocardial infarction

    PubMed Central

    Yuyun, Matthew Fomonyuy; Jutla, Sandeep K; Quinn, Paulene A; Ng, Leong L

    2012-01-01

    Objective Aldosterone is associated with increased mortality in chronic heart failure patients and correlates with adverse outcomes after an acute myocardial infarction (AMI) in smaller cohorts. We evaluated the prognostic significance of plasma aldosterone in a large cohort of post-AMI patients in relation to major adverse cardiovascular events (MACE). Design A prospective cohort study. Setting University Hospitals of Leicester, UK. Patients Consecutive 955 patients admitted with AMI. Plasma aldosterone levels were measured in these patients. Main outcome measures During the 2 years follow-up, MACE which was a composite of all-cause mortality, myocardial reinfarction, and hospitalisation for heart failure as well as secondary endpoints (all-cause mortality and a combination of all-cause mortality and hospitalisation for heart failure), were ascertained. Results MACE occured in N=261, 27.3%, all-cause mortality (N=114, 11.9%) and a combination of all-cause mortality and hospitalisation for heart failure (N=176, 18.4%). Patients with MACE had significantly higher median levels of aldosterone than those without (1150.1 vs 950.4 pmol/l, p=0.0118). The multivariate adjusted HR (95% CI) for log aldosterone on MACE was 1.26 (1.01 to 1.56), p=0.041; all-cause mortality 1.60 (1.13 to 2.27), p=0.008; and combination of all-cause mortality and heart failure 1.50 (1.14 to 1.97), p=0.003. Conclusions The prognostic significance of aldosterone for a variety of endpoints in this large cohort of post-AMI patients is not new and adds to the findings by others. The magnitude of the increase in aldosterone secretion post infarction is higher than previously believed.

  6. Related Factors and Adverse Neonatal Outcomes in Women with Preterm Premature Rupture of Membranes Complicated by Histologic Chorioamnionitis

    PubMed Central

    Xie, Ailan; Zhang, Wenwen; Chen, Miaomiao; Wang, Yuhuan; Wang, Ying; Zhou, Qingfeng; Zhu, Xueqiong

    2015-01-01

    Background The aim of this study was to identify factors predicting histologic chorioamnionitis (HCA) in women with preterm premature rupture of membranes (PPROM). Material/Methods We retrospectively enrolled 371 women diagnosed with PPROM at less than 34 weeks of gestation at the Second Affiliated Hospital of Wenzhou Medical University between January 2008 and December 2012. HCA was diagnosed by placental histopathology in 70% of participants. Binary logistic regression was used to identify factors associated with HCA and neonatal outcomes. Results Patient age, rate of parity, tocolysis, cesarean section, serum C reactive protein (CRP) level at admission, white blood cell count, and latency duration did not significantly differ between the 2 groups. Binary logistic regression revealed that oligohydramnios at admission, gestational age at PPROM, and serum CRP >8 mg/L before delivery were significantly associated with HCA. Gestational age at delivery and birth weight were significantly lower in HCA patients than control patients. The rate of 1-min Apgar score <7, abnormal neonatal intracranial ultrasound findings, neonatal pneumonia, bronchopulmonary dysplasia, early-onset neonatal sepsis, and mortality were higher in HCA patients, but no significant difference was observed in the incidence of neonatal respiratory distress syndrome, necrotizing enterocolitis, hyperbilirubinemia, or hypoglycemia. Conclusions Younger gestational age at time of PPROM, higher CRP level before delivery, and oligohydramnios at admission in women with PPROM are associated with HCA, and HCA is associated with some adverse neonatal outcomes. PMID:25644559

  7. Adverse Health Events Following Intermittent and Continuous Androgen Deprivation in Metastatic Prostate Cancer Patients

    PubMed Central

    Hershman, Dawn L.; Unger, Joseph M.; Wright, Jason D.; Ramsey, Scott; Till, Cathee; Tangen, Catherine M.; Barlow, William E.; Blanke, Charles; Thompson, Ian M; Hussain, Maha

    2016-01-01

    Importance Although intermittent androgen deprivation therapy (ADT) has not been associated with better overall survival in prostate cancer (PC), it has the potential for lower side effects. The incidence of long-term adverse health events has not been reported. Objective Given that older patients are more likely to suffer long-term complications from ADT, we examined long-term late events in elderly patients randomized to intermittent or continuous ADT. Our hypothesis was that late cardiovascular and endocrine events would be lower in patients on intermittent ADT. Design Linkage between patient trial data and corresponding Medicare claims. Setting Multicenter clinical trial. Participants Patients from S9346, a randomized SWOG trial of intermittent vs. continuous ADT in men with metastatic PC. Main Outcomes and Measures The main outcome was to identify long-term adverse health events by treatment arm. Patients were classified as having an adverse health event if they had any hospital claim – or at least 2 physician or outpatient claims at least 30 days apart – for any of the following diagnoses: ischemic and thrombotic events; endocrine events; sexual dysfunction, dementia and depression. To incorporate time from beginning of observation through evidence of an event, we determined the cumulative incidence of each event. Competing risks Cox regression was used, adjusting for covariates. Results In total, n=1134 eligible U.S.-based patients with metastatic PC were randomized to continuous vs. intermittent ADT on S9346. A total of 636 (56%) of trial participants had ≥1 year of continuous Medicare parts A & B coverage and no HMO participation. The median age was 71.3 years. The most common long-term events were hypercholesterolemia (31%) and osteoporosis (19%). The 10-year cumulative incidence of ischemic and thrombotic events differed by arm; 24% for continuous and 33% for intermittent ADT (Hazard Ratio=0.69, p=.02). There were no statistically significant

  8. [Patient-reported and patient-weighted outcomes in ophthalmology].

    PubMed

    Scheibler, F; Finger, R P; Grosselfinger, R; Dintsios, C-M

    2010-03-01

    Considering patients' values and preferences in comparative effectiveness research (CER) is one of the main challenges in ophthalmology (value-based medicine). This article defines core terms in CER. The concept of patient-relevant (or patient-important) outcomes is distinguished from patient-reported outcomes (PRO) by means of examples in the field of ophthalmology. In order to be able to give a consistant recommendation if an intervention leads to conflicting results for different outcomes (trade-off), a ranking of outcomes will be necessary. Examples of studies in glaucoma patients are provided that demonstrate the possibilities of ranking of outcomes based on patient preferences. PMID:20024566

  9. Stromal cell-derived factor 1 gene polymorphism is associated with susceptibility to adverse long-term allograft outcomes in non-diabetic kidney transplant recipients.

    PubMed

    Wang, Chung-Jieh; Tsai, Jen-Pi; Yang, Shun-Fa; Lian, Jong-Da; Chang, Horng-Rong

    2014-01-01

    Although the genetic polymorphism of Stromal Cell-Derived Factor 1 (SDF-1) is associated with higher mortality of liver allograft recipients, the role of SDF-1 in the modulation of renal allograft outcomes is unclear. Between March 2000 and January 2008, we recruited 252 non-diabetic renal transplant recipients (RTRs). Baseline characteristics and blood chemistry were recorded. Genomic DNA extraction with polymerase chain reaction-restriction fragment length polymorphism was utilized to analyze the genetic polymorphisms of SDF-1 (rs1801157). The influence of SDF-1 on an adverse renal allograft outcome, defined as either a doubling of serum creatinine, graft failure, or patient death was evaluated. Sixteen patients with the SDF-1 AA/AG genotype and nine with the SDF-1 GG genotype reached an adverse outcome. According to Kaplan-Meier analysis, patients carrying the SDF-1 AA/AG genotype or A allele showed a significantly higher risk of reaching an adverse outcome than those carrying the SDF-1 GG genotype or G allele (p=0.041; p=0.0051, respectively; log rank test). Stepwise multivariate Cox proportional regression analysis revealed that patients carrying the SDF-1 AA/AG genotype and A allele had a 2.742-fold (95% CI. 1.106-6.799, p=0.03) and 2.306-fold (95% CI. 1.254-4.24, p=0.008) risk of experiencing an adverse outcome. The SDF-1 AA/AG genotype and A allele have a detrimental impact on the long-term outcome of RTRs. PMID:25029540

  10. Stromal Cell-Derived Factor 1 Gene Polymorphism Is Associated with Susceptibility to Adverse Long-Term Allograft Outcomes in Non-Diabetic Kidney Transplant Recipients

    PubMed Central

    Wang, Chung-Jieh; Tsai, Jen-Pi; Yang, Shun-Fa; Lian, Jong-Da; Chang, Horng-Rong

    2014-01-01

    Although the genetic polymorphism of Stromal Cell-Derived Factor 1 (SDF-1) is associated with higher mortality of liver allograft recipients, the role of SDF-1 in the modulation of renal allograft outcomes is unclear. Between March 2000 and January 2008, we recruited 252 non-diabetic renal transplant recipients (RTRs). Baseline characteristics and blood chemistry were recorded. Genomic DNA extraction with polymerase chain reaction-restriction fragment length polymorphism was utilized to analyze the genetic polymorphisms of SDF-1 (rs1801157). The influence of SDF-1 on an adverse renal allograft outcome, defined as either a doubling of serum creatinine, graft failure, or patient death was evaluated. Sixteen patients with the SDF-1 AA/AG genotype and nine with the SDF-1 GG genotype reached an adverse outcome. According to Kaplan-Meier analysis, patients carrying the SDF-1 AA/AG genotype or A allele showed a significantly higher risk of reaching an adverse outcome than those carrying the SDF-1 GG genotype or G allele (p = 0.041; p = 0.0051, respectively; log rank test). Stepwise multivariate Cox proportional regression analysis revealed that patients carrying the SDF-1 AA/AG genotype and A allele had a 2.742-fold (95% CI. 1.106–6.799, p = 0.03) and 2.306-fold (95% CI. 1.254–4.24, p = 0.008) risk of experiencing an adverse outcome. The SDF-1 AA/AG genotype and A allele have a detrimental impact on the long-term outcome of RTRs. PMID:25029540

  11. Maternal Snoring May Predict Adverse Pregnancy Outcomes: A Cohort Study in China

    PubMed Central

    Ge, Xing; Tao, Fangbiao

    2016-01-01

    Objective To examine the prevalence of snoring during pregnancy and its effects on key pregnancy outcomes. Methods Pregnant women were consecutively recruited in their first trimester. Habitual snoring was screened by using a questionnaire in the 1st and 3rd trimester, respectively. According to the time of snoring, participants were divided into pregnancy onset snorers, chronic snorers and non-snorers. Logistic regressions were performed to examine the associations between snoring and pregnancy outcomes. Results Of 3 079 pregnant women, 16.6% were habitual snorers, with 11.7% were pregnancy onset snorers and 4.9% were chronic snorers. After adjusting for potential confounders, chronic snorers were independently associated with gestational diabetes mellitus (GDM) (RR 1.66, 95%CI 1.09–2.53). Both pregnancy onset and chronic snorers were independently associated with placental adhesion (RR 1.96, 95%CI 1.17–3.27, and RR 2.33, 95%CI 1.22–4.46, respectively). Pregnancy onset snorers were at higher risk of caesarean delivery (RR 1.37, 95%CI 1.09–1.73) and having macrosomia (RR 1.54, 95%CI 1.05–2.27) and large for gestational age (LGA) (RR 1.71, 95%CI 1.31–2.24) infants. In addition, being overweight or obese before pregnancy plays an important role in mediating snoring and adverse pregnancy outcomes. Conclusions Maternal snoring may increase the risk of adverse pregnancy outcomes, and being overweight or obese before pregnancy with snoring is remarkable for researchers. Further studies are still needed to confirm our results. PMID:26871434

  12. Bisphenol A--Why an adverse outcome pathway framework needs to be applied.

    PubMed

    FitzGerald, R E; Wilks, M F

    2014-10-15

    Bisphenol A (BPA) is one of the most widely used and extensively studied chemicals. Numerous studies have reported in vitro effects or animal adverse findings at BPA doses lower than the no observed adverse effect levels (NOAELs) established in regulatory toxicity studies and used for human health risk assessment. Intensive discussions on the adequacy and relevance of test systems have not satisfactorily resolved whether positive or negative animal and/or in vitro findings are more relevant for human health risk assessment purposes. BPA imperfectly mimics endogenous estrogens at membrane-bound estrogen receptors in the fM-nM concentration range, and may have downstream pleiotropic effects such as human seminoma proliferation and mammary gland hyperplasia after in utero exposure which are not detectable in regulatory toxicology studies. We argue that a structured approach like the OECD Adverse Outcome Pathway (AOP) framework is needed to help researchers in designing relevant studies, and risk assessors in evaluating them. The huge amount of experimental data generated for BPA has highlighted data gaps in basic biology and the shortcomings of current approaches to hazard characterization and risk assessment. Establishing AOPs for BPA, and other endocrine active chemicals, will require major scientific as well as training investments by all responsible stakeholders. PMID:24831966

  13. Effect of abciximab on late adverse events in patients with diabetes mellitus undergoing stent implantation.

    PubMed

    Velianou, J L; Mathew, V; Wilson, S H; Barsness, G W; Grill, D E; Holmes, D R

    2000-11-15

    Percutaneous coronary intervention (PCI) in patients with diabetes mellitus (DM) is associated with higher rates of adverse cardiac events. Recent data suggest that adverse events are reduced in DM after PCI using stents with abciximab. We performed a retrospective analysis of a prospective PCI registry for all patients with DM who underwent stent placement at the Mayo Clinic from 1995 to 1997 (n = 570), and divided them into 2 groups based on whether abciximab was administered. Characterization and comparison of the clinical and angiographic variables, procedural outcomes, and short- and long-term event rates between groups was performed. The baseline clinical characteristics of the groups were similar, but patients treated with abciximab were more likely to be men with a lower left ventricular ejection fraction. Patients treated with abciximab had more multivessel intervention, saphenous vein graft intervention, and thrombus before intervention. The 30-day mortality rate (0.6% vs 3.0%, p = 0.03) and repeat PCI (0% vs 1.1%, p = 0.03) was lower in patients treated with abciximab. The 30-day rates of bypass surgery, myocardial infarction (MI), and a composite of death, MI, and revascularization were similar. The 1-year event rates did not differ significantly between patients taking and not taking abciximab for the end points of death (8.9% vs 8.8%, p = 0.97), MI (13.3% vs 11.4%, p = 0.57), bypass surgery (10.3% vs 6.2%, p = 0.20), repeat PCI (14.7% vs 15.9%, p = 0.76), and a composite of death, MI, and revascularization (30.4% vs 26.7%, p = 0.43). After adjusting for baseline variables, abciximab did not influence the occurrence of late adverse events. PMID:11074200

  14. Adverse neonatal outcomes in women with pre-eclampsia in Mulago Hospital, Kampala, Uganda: a cross-sectional study

    PubMed Central

    Kiondo, Paul; Tumwesigye, Nazarius Mbona; Wandabwa, Julius; Wamuyu-Maina, Gakenia; Bimenya, Gabriel S; Okong, Pius

    2014-01-01

    Introduction Pre-eclampsia, which is more prevalent in resource-limited settings, contributes significantly to maternal, fetal and neonatal morbidity and mortality. However, the factors associated with these adverse outcomes are poorly understood in low resource settings. In this paper we examine the risk factors for adverse neonatal outcomes among women with pre-eclampsia at Mulago Hospital in Kampala, Uganda. Methods Pre-eclampsia, which is more prevalent in resource-limited settings, contributes significantly to maternal, fetal and neonatal morbidity and mortality. However, the factors associated with these adverse outcomes are poorly understood in low resource settings. In this paper we examine the risk factors for adverse neonatal outcomes among women with pre-eclampsia at Mulago Hospital in Kampala, Uganda. Resuls Predictors of adverse neonatal outcomes were: preterm delivery (OR 5.97, 95% CI: 2.97-12.7) and severe pre-eclampsia (OR 5.17, 95% CI: 2.36-11.3). Conclusion Predictors of adverse neonatal outcomes among women with pre-eclampsia were preterm delivery and severe pre-eclampsia. Health workers need to identify women at risk, offer them counseling and, refer them if necessary to a hospital where they can be managed successfully. This may in turn reduce the neonatal morbidity and mortality associated with pre-eclampsia. PMID:24643210

  15. Common Sleep Disorders Increase Risk of Motor Vehicle Crashes and Adverse Health Outcomes in Firefighters

    PubMed Central

    Barger, Laura K.; Rajaratnam, Shantha M.W.; Wang, Wei; O'Brien, Conor S.; Sullivan, Jason P.; Qadri, Salim; Lockley, Steven W.; Czeisler, Charles A.

    2015-01-01

    Study Objectives: Heart attacks and motor vehicle crashes are the leading causes of death in US firefighters. Given that sleep disorders are an independent risk factor for both of these, we examined the prevalence of common sleep disorders in a national sample of firefighters and their association with adverse health and safety outcomes. Methods: Firefighters (n = 6,933) from 66 US fire departments were assessed for common sleep disorders using validated screening tools, as available. Firefighters were also surveyed about health and safety, and documentation was collected for reported motor vehicle crashes. Results: A total of 37.2% of firefighters screened positive for any sleep disorder including obstructive sleep apnea (OSA), 28.4%; insomnia, 6.0%; shift work disorder, 9.1%; and restless legs syndrome, 3.4%. Compared with those who did not screen positive, firefighters who screened positive for a sleep disorder were more likely to report a motor vehicle crash (adjusted odds ratio 2.00, 95% CI 1.29–3.12, p = 0.0021) and were more likely to self-report falling asleep while driving (2.41, 2.06–2.82, p < 0.0001). Firefighters who screened positive for a sleep disorder were more likely to report having cardiovascular disease (2.37, 1.54–3.66, p < 0.0001), diabetes (1.91, 1.31–2.81, p = 0.0009), depression (3.10, 2.49–3.85, p < 0.0001), and anxiety (3.81, 2.87–5.05, p < 0.0001), and to report poorer health status (p < 0.0001) than those who did not screen positive. Adverse health and safety associations persisted when OSA and non-OSA sleep disorders were examined separately. Conclusions: Sleep disorders are prevalent in firefighters and are associated with increased risk of adverse health and safety outcomes. Future research is needed to assess the efficacy of occupational sleep disorders prevention, screening, and treatment programs in fire departments to reduce these safety and health risks. Citation: Barger LK, Rajaratnam SM, Wang W, O'Brien CS

  16. Management and outcome of Bacille Calmette-Guérin vaccine adverse reactions

    PubMed Central

    Venkataraman, Aishwarya; Yusuff, Michael; Liebeschuetz, Susan; Riddell, Anna; Prendergast, Andrew J.

    2015-01-01

    Background Bacille Calmette-Guérin (BCG) vaccine is one of the most widely used vaccines globally. Management of local BCG complications (injection site reactions and suppurative or non-suppurative lymphadenitis) varies between clinicians, and the optimal approach remains uncertain. Aim To determine the clinical features, management and outcome of BCG complications at two large acute hospitals in London, United Kingdom. Methods All children presenting with complications of BCG vaccination between January 2008 and December 2013 were included in this observational study. Medical and electronic laboratory records were reviewed to determine clinical features, treatment and outcome. Results Sixty children presented with adverse reactions. Two-thirds (65%) presented with BCG lymphadenitis, one-third (30%) presented with injection site complications and two children (3%) presented with both injection site reaction and lymphadenitis; only one child (2%) had disseminated BCG disease. The majority (88%) of children with injection site reactions were managed conservatively; overall, 95% showed complete resolution within 6 months. Among children with lymphadenitis, 46% were managed conservatively, whilst 54% had anti-tuberculous therapy and/or a procedure (aspiration mostly, or surgery); complete resolution was seen in 59% of cases. Conclusions Injection site reactions and non-suppurative lymphadenitis were generally managed conservatively, with good outcomes. There was more variation in management and outcome of suppurative lymphadenitis and the optimal approach remains uncertain. PMID:26275478

  17. Common variants of the vitamin D binding protein gene and adverse health outcomes

    PubMed Central

    Malik, Suneil; Fu, Lei; Juras, David James; Karmali, Mohamed; Wong, Betty Y. L.; Gozdzik, Agnes

    2013-01-01

    The vitamin D binding protein (DBP) is the major plasma carrier for vitamin D and its metabolites, but it is also an actin scavenger, and is the precursor to the immunomodulatory protein, Gc-MAF. Two missense variants of the DBP gene – rs7041 encoding Asp432Glu and rs4588 encoding Thr436Lys – change the amino acid sequence and alter the protein function. They are common enough to generate population-wide constitutive differences in vitamin D status, based on assay of the serum metabolite, 25-hydroxyvitamin D (25OHD). Whether these variants also influence the role of vitamin D in an immunologic milieu is not known. However, the issue is relevant, given the immunomodulatory effects of DBP and the role of protracted innate immune-related inflammation in response to tissue injury or repeated infection. Indeed, DBP and vitamin D may jointly or independently contribute to a variety of adverse health outcomes unrelated to classical notions of their function in bone and mineral metabolism. This review summarizes the reports to date of associations between DBP variants, and various chronic and infectious diseases. The available information leads us to conclude that DBP variants are a significant and common genetic factor in some common disorders, and therefore, are worthy of closer attention. In view of the heightened interest in vitamin D as a public health target, well-designed studies that look simultaneously at vitamin D and its carrier in relation to genotypes and adverse health outcome should be encouraged. PMID:23427793

  18. Adverse Childhood Experiences and Adult Health Outcomes Among Veteran and Non-Veteran Women

    PubMed Central

    Blosnich, John R.; Dichter, Melissa E.

    2015-01-01

    Abstract Background: Women veterans represent a vulnerable population with unique health needs and disparities in access to care. One constellation of exposures related to subsequent poor health includes adverse childhood experiences (ACEs; e.g., physical and sexual child abuse), though research on impacts of ACEs among women veterans is limited. Methods: Data were drawn from the 2010 Behavioral Risk Factor Surveillance System for the 11 states that included the ACE module (n=36,485). Weighted chi-squared tests and multivariable logistic regression were used to assess the prevalence of ACEs among women veterans compared with women non-veterans and differences in the following outcomes, controlling for ACEs: social support, inadequate sleep, life satisfaction, mental distress, smoking, heavy alcohol use, obesity, diabetes, cardiovascular disease symptoms, asthma, and disability. Results: Women veterans (1.6% of the total sample) reported a higher prevalence of 7 out of 11 childhood adversities and higher mean ACE score than women non-veterans. Women veterans were more likely to be current smokers and report a disability, associations which were attenuated when controlling for ACE. Conclusions: Despite women veterans' higher prevalence of ACE, their health outcomes did not differ substantially from non-veterans. Further research is needed to understand the intersections of traumatic experiences and sources of resilience over the lifecourse among women veterans. PMID:26390379

  19. Adverse Outcome Pathways-Organizing Toxicological Information to Improve Decision Making.

    PubMed

    Edwards, Stephen W; Tan, Yu-Mei; Villeneuve, Daniel L; Meek, M E; McQueen, Charlene A

    2016-01-01

    The number of chemicals for which environmental regulatory decisions are required far exceeds the current capacity for toxicity testing. High-throughput screening commonly used for drug discovery has the potential to increase this capacity. The adverse outcome pathway (AOP) concept has emerged as a framework for connecting high-throughput toxicity testing (HTT) and other results to potential impacts on human and wildlife populations. As a result of international efforts, the AOP development process is now well-defined and efforts are underway to broaden the participation through outreach and training. One key principle is that AOPs represent the chemical-agnostic portions of pathways to increase the generalizability of their application from early key events to overt toxicity. The closely related mode of action framework extends the AOP as needed when evaluating the potential risk of a specific chemical. This in turn enables integrated approaches to testing and assessment (IATA), which incorporate results of assays at various levels of biologic organization such as in silico; HTT; chemical-specific aspects including absorption, distribution, metabolism, and excretion (ADME); and an AOP describing the biologic basis of toxicity. Thus, it is envisaged that provision of limited information regarding both the AOP for critical effects and the ADME for any chemical associated with any adverse outcome would allow for the development of IATA and permit more detailed AOP and ADME research, where higher precision is needed based on the decision context. PMID:26537250

  20. The adverse outcome pathway (AOP) for chemical binding to tubulin in oocytes leading to aneuploid offspring.

    PubMed

    Marchetti, Francesco; Massarotti, Alberto; Yauk, Carole L; Pacchierotti, Francesca; Russo, Antonella

    2016-03-01

    The Organisation for Economic Co-operation and Development (OECD) has launched the Adverse Outcome Pathway (AOP) Programme to advance knowledge of pathways of toxicity and improve the use of mechanistic information in risk assessment. An AOP links a molecular initiating event (MIE) to an adverse outcome (AO) through intermediate key events (KE). Here, we present the scientific evidence in support of an AOP whereby chemicals that bind to tubulin cause microtubule depolymerization resulting in spindle disorganization followed by altered chromosome alignment and segregation and the generation of aneuploidy in female germ cells, ultimately leading to aneuploidy in the offspring. Aneuploidy, an abnormal number of chromosomes that is not an exact multiple of the haploid number, is a well-known cause of human disease and represents a major cause of infertility, pregnancy failure, and serious genetic disorders in the offspring. Among chemicals that induce aneuploidy in female germ cells, a large majority impairs microtubule dynamics and spindle function. Colchicine, a prototypical chemical that binds to tubulin and causes microtubule depolymerization, is used here to illustrate the AOP. This AOP is specific to female germ cells exposed during the periovulation period. Although the majority of the data come from rodent studies, the available evidence suggests that the MIE and KEs are conserved across species and would occur in human oocytes. The development of AOPs related to mutagenicity in germ cells is expected to aid the identification of potential hazards to germ cell genomic integrity and support regulatory efforts to protect population health. PMID:26581746

  1. Infertility, Pregnancy Loss and Adverse Birth Outcomes in Relation to Maternal Secondhand Tobacco Smoke Exposure

    PubMed Central

    Meeker, John D.; Benedict, Merle D.

    2013-01-01

    A substantial proportion of the etiology involved in female infertility and adverse pregnancy outcomes remains idiopathic. Recent scientific research has suggested a role for environmental factors in these conditions. Secondhand tobacco smoke (STS) contains a number of known or suspected reproductive toxins, and human exposure to STS is prevalent worldwide. Robust evidence exists for the toxic effects of active smoking on fertility and pregnancy, but studies of passive exposure are much more limited in number. While the association between maternal STS exposure and declined birth weight has been fairly well-documented, only recently have epidemiologic studies begun to provide suggestive evidence for delayed conception, altered menstrual cycling, early pregnancy loss (e.g. spontaneous abortion), preterm delivery, and congenital malformations in relation to STS exposure. There is also new evidence that developmental exposures to tobacco smoke may be associated with reproductive effects in adulthood. To date, most studies have estimated maternal STS exposure through self-report even though exposure biomarkers are less prone to error and recall bias. In addition to utilizing biomarkers of STS exposure, future studies should aim to identify vital windows of STS exposure, important environmental co-exposures, individual susceptibility factors, and specific STS constituents associated with female infertility and adverse pregnancy outcomes. The role of paternal exposures/factors should also be investigated. PMID:23888128

  2. Time-Dependent Effects in Algae for Chemicals with Different Adverse Outcome Pathways: A Novel Approach.

    PubMed

    Vogs, Carolina; Altenburger, Rolf

    2016-07-19

    Chemicals affect unicellular algae as a result of toxicokinetic and toxicodynamic processes. The internal concentration of chemicals in algae cells typically reaches equilibrium within minutes, while damage cumulatively increases over hours. The time gap between the steady state of internal exposure and damage development is thus suspected to span up to hours, mainly due to toxicodynamic processes. The quantification of rate-limited toxicodynamic processes, aggregated as a progressive effect from an initiating molecular event through biological key events toward the adverse outcome on algae growth inhibition, might discriminate between different adverse outcome pathways (AOPs). To support our hypothesis, we selected six chemicals according to different physicochemical properties and three distinctly dissimilar AOPs. The time courses of internal concentrations were linked to the observed affected Scenedesmus vacuolatus growth using toxicokinetic-toxicodynamic modeling. Effects on cell growth were explained by effect progression and not by the time to reach internal equilibrium concentration. Effect progression rates ranged over 6 orders of magnitude for all chemicals but varied by less than 1 order of magnitude within similar AOP (photosystem II inhibitors > reactive chemicals > lipid biosynthesis inhibitors), meaning that inhibitors of photosystem II advance an effect toward algae growth fastest compared to reactive chemicals and inhibitors of lipid biosynthesis. PMID:27149222

  3. Applying Adverse Outcome Pathways (AOPs) to support Integrated Approaches to Testing and Assessment (IATA).

    PubMed

    Tollefsen, Knut Erik; Scholz, Stefan; Cronin, Mark T; Edwards, Stephen W; de Knecht, Joop; Crofton, Kevin; Garcia-Reyero, Natalia; Hartung, Thomas; Worth, Andrew; Patlewicz, Grace

    2014-12-01

    Chemical regulation is challenged by the large number of chemicals requiring assessment for potential human health and environmental impacts. Current approaches are too resource intensive in terms of time, money and animal use to evaluate all chemicals under development or already on the market. The need for timely and robust decision making demands that regulatory toxicity testing becomes more cost-effective and efficient. One way to realize this goal is by being more strategic in directing testing resources; focusing on chemicals of highest concern, limiting testing to the most probable hazards, or targeting the most vulnerable species. Hypothesis driven Integrated Approaches to Testing and Assessment (IATA) have been proposed as practical solutions to such strategic testing. In parallel, the development of the Adverse Outcome Pathway (AOP) framework, which provides information on the causal links between a molecular initiating event (MIE), intermediate key events (KEs) and an adverse outcome (AO) of regulatory concern, offers the biological context to facilitate development of IATA for regulatory decision making. This manuscript summarizes discussions at the Workshop entitled "Advancing AOPs for Integrated Toxicology and Regulatory Applications" with particular focus on the role AOPs play in informing the development of IATA for different regulatory purposes. PMID:25261300

  4. Plasma neutrophil gelatinase-associated lipocalin as a potential predictor of adverse renal outcomes in immunoglobulin A nephropathy

    PubMed Central

    Park, Ga-Young; Yu, Chung-Hoon; Kim, Jun-Seop; Kang, Yun-Jeong; Kwon, Owen; Choi, Ji-Young; Cho, Jang-Hee; Kim, Chan-Duck; Kim, Yong-Lim

    2015-01-01

    Background/Aims Neutrophil gelatinase-associated lipocalin (NGAL) is a well-known biomarker of acute kidney injury. We evaluated the value of plasma NGAL (pNGAL) as an independent predictor of prognosis in immunoglobulin A nephropathy (IgAN). Methods In total, 91 patients with biopsy-proven IgAN at a single center were evaluated. pNGAL was measured using a commercial enzyme-linked immunosorbent assay kit (R&D Systems). Adverse renal outcome was defined as chronic kidney disease (CKD) stage 3 or above at the last follow-up. Pearson correlation coefficient and Cox regression were used for analyses. Results The mean age of all patients (male:female, 48:43) was 35 years (range, 18 to 77). pNGAL ranged between 21.68 and 446.40 ng/mL (median, 123.97) and showed a correlation with age (r = 0.332, p = 0.001), creatinine (r = 0.336, p = 0.001), estimated glomerular filtration rate (r = -0.397, p < 0.001), uric acid (r = 0.289, p = 0.006), and the protein-to-creatinine ratio (r = 0.288, p = 0.006). During a mean follow-up period of 37.6 months, 11 patients (12.1%) had CKD stage 3 or above. In a multivariate Cox regression model, hypertension (hazard ratio [HR], 8.779; 95% confidence interval [CI], 1.526 to 50.496; p = 0.015), proteinuria > 1 g/day (HR, 5.184; 95% CI, 1.124 to 23.921; p = 0.035), and pNGAL (HR, 1.012; 95% CI, 1.003 to 1.022; p = 0.013) were independent predictors associated with adverse renal outcome. Conclusions pNGAL showed strong correlations with other clinical prognostic factors and was also an independent predictor of adverse renal outcome. We suggest pNGAL as a potential predictor for prognosis in IgAN, while further studies are needed to confirm the clinical value. PMID:25995665

  5. Intimate Partner Violence During Pregnancy and Adverse Neonatal Outcomes in Low-Income Women

    PubMed Central

    Bullock, Linda; Sharps, Phyllis; Schminkey, Donna; Comstock, Emily; Campbell, Jacquelyn

    2014-01-01

    Abstract Background: Intimate partner violence (IPV) affects an estimated 1.5 million U.S. women annually. IPV impacts maternal and neonatal health with higher rates of depression and low birth weight (LBW). Less studied is experiencing IPV and delivering a small for gestational age (SGA) baby. SGA neonates are at increased risk of developmental and behavioral problems. The negative sequelae persist into adulthood with increased rates of diabetes mellitus and coronary heart disease. Methods: In a sample of 239 pregnant women experiencing IPV, in urban and rural settings, we examined cross-sectional associations of severity of IPV and neonatal outcomes (i.e., birth weight and gestational age). Severity of IPV was measured by the Conflict Tactics Scale 2 and neonatal outcomes were collected at the time of delivery. Results: Outcomes were collected on 194 neonates; 14.9% (n=29) were classified as LBW, 19.1% (n=37) classified as SGA, and 9.8% (n=19) as LBW and SGA. Women reporting higher severity of IPV during pregnancy had a greater likelihood of delivering an SGA neonate (odds ratio [OR] 4.81; 95% confidence interval [95% CI] 1.86–12.47), and LBW neonate (OR 4.20; 95% CI 1.46–12.10). Conclusions: In a sample of pregnant women experiencing perinatal IPV, women experiencing greater severities of IPV were more likely to deliver a neonate with an adverse outcome. Early recognition and intervention of IPV is essential to reduce disparities in birth outcomes and long-term health outcomes for these neonates. PMID:25290007

  6. Defining Catastrophic Costs and Comparing Their Importance for Adverse Tuberculosis Outcome with Multi-Drug Resistance: A Prospective Cohort Study, Peru

    PubMed Central

    Wingfield, Tom; Boccia, Delia; Tovar, Marco; Gavino, Arquímedes; Zevallos, Karine; Montoya, Rosario; Lönnroth, Knut; Evans, Carlton A.

    2014-01-01

    Background Even when tuberculosis (TB) treatment is free, hidden costs incurred by patients and their households (TB-affected households) may worsen poverty and health. Extreme TB-associated costs have been termed “catastrophic” but are poorly defined. We studied TB-affected households' hidden costs and their association with adverse TB outcome to create a clinically relevant definition of catastrophic costs. Methods and Findings From 26 October 2002 to 30 November 2009, TB patients (n = 876, 11% with multi-drug-resistant [MDR] TB) and healthy controls (n = 487) were recruited to a prospective cohort study in shantytowns in Lima, Peru. Patients were interviewed prior to and every 2–4 wk throughout treatment, recording direct (household expenses) and indirect (lost income) TB-related costs. Costs were expressed as a proportion of the household's annual income. In poorer households, costs were lower but constituted a higher proportion of the household's annual income: 27% (95% CI = 20%–43%) in the least-poor houses versus 48% (95% CI = 36%–50%) in the poorest. Adverse TB outcome was defined as death, treatment abandonment or treatment failure during therapy, or recurrence within 2 y. 23% (166/725) of patients with a defined treatment outcome had an adverse outcome. Total costs ≥20% of household annual income was defined as catastrophic because this threshold was most strongly associated with adverse TB outcome. Catastrophic costs were incurred by 345 households (39%). Having MDR TB was associated with a higher likelihood of incurring catastrophic costs (54% [95% CI = 43%–61%] versus 38% [95% CI = 34%–41%], p<0.003). Adverse outcome was independently associated with MDR TB (odds ratio [OR] = 8.4 [95% CI = 4.7–15], p<0.001), previous TB (OR = 2.1 [95% CI = 1.3–3.5], p = 0.005), days too unwell to work pre-treatment (OR = 1.01 [95% CI = 1.00–1.01], p = 0.02), and catastrophic costs (OR = 1

  7. Periodontal Treatment Reduces Risk of Adverse Respiratory Events in Patients With Chronic Obstructive Pulmonary Disease

    PubMed Central

    Shen, Te-Chun; Chang, Pei-Ying; Lin, Cheng-Li; Chen, Chia-Hung; Tu, Chih-Yen; Hsia, Te-Chun; Shih, Chuen-Ming; Hsu, Wu-Huei; Sung, Fung-Chang; Kao, Chia-Hung

    2016-01-01

    Abstract Treatment of periodontal diseases has been associated with benefit outcomes for patients with chronic obstructive pulmonary disease (COPD). However, no population-based cohort study has been conducted. We evaluated this relationship by retrospective cohort study using a large population data. Using the National Health Insurance claims data of Taiwan, we identified 5562 COPD patients with periodontal diseases who had received periodontal treatment as the treatment group. The comparison group was selected at a 1:1 ratio matched by the propensity score estimated with age, sex, date of COPD diagnosis and periodontal treatment, and comorbidities. Both groups were followed up for 5 years to compare risks of acute exacerbation, pneumonia, and acute respiratory failure. The incidence rates of adverse respiratory events were significantly lower in the treatment group than in the comparison group: 3.79 versus 4.21 per 100 person-years for emergency room visits, 2.75 versus 3.65 per 100 person-years for hospitalizations, and 0.66 versus 0.75 per 100 person-years for intensive care unit admissions. The treatment group also had a 37% reduced risk of deaths (1.81 vs 2.87 per 100 person-years), with an adjusted hazard ratio of 0.57 (95% confidence interval 0.52–0.62). Periodontal treatment for COPD patients could reduce the risk of adverse respiratory events and mortality. The adequate periodontal health care is important for COPD patients with periodontal diseases. PMID:27196497

  8. High risk of adverse events in hospitalised hip fracture patients of 65 years and older: results of a retrospective record review study

    PubMed Central

    Merten, Hanneke; Johannesma, Paul C; Lubberding, Sanne; Zegers, Marieke; Langelaan, Maaike; Jukema, Gerrolt N; Heetveld, Martin J; Wagner, Cordula

    2015-01-01

    Objectives Hip fracture patients of 65 years and older are a complex patient group who often suffer from complications and difficult rehabilitation with disappointing results. It is unknown to what extent suboptimal hospital care contributes to these poor outcomes. This study reports on the scale, preventability, causes and prevention strategies of adverse events in patients, aged 65 years and older, admitted to the hospital with a primary diagnosis of hip fracture. Design, setting and outcome measures A retrospective record review study was conducted of 616 hip fracture patients (≥65 years) admitted to surgical or orthopaedic departments in four Dutch hospitals in 2007. Experienced physician reviewers determined the presence and preventability of adverse events, causes and prevention strategies using a structured review form. The main outcome measures were frequency of adverse events and preventable adverse events in hospitalised hip fracture patients of 65 years and older, and strategies to prevent them in the future. Results 114 (19%) of the 616 patients in the study experienced one or more adverse events; 49 of these were preventable. The majority of the adverse events (70%) was related to the surgical procedure and many resulted in an intervention or additional treatment (67%). Human causes contributed to 53% of the adverse events, followed by patient-related factors (39%). Training and close monitoring of quality of care and the health professional's performance were the most often selected strategies to prevent these adverse events in the future. Conclusions The high percentage of preventable adverse events found in this study shows that care for older hospitalised hip fracture patients should be improved. More training and quality assurance is required to provide safer care and to reduce the number of preventable adverse events in this vulnerable patient group. PMID:26346870

  9. Cytomegalovirus Seroprevalence in Pregnant Women and Association with Adverse Pregnancy/Neonatal Outcomes in Jiangsu Province, China

    PubMed Central

    Chen, Jie; Xu, Biyun; Zhou, Yi-Hua; Hu, Yali

    2014-01-01

    Background In this study, we aimed to determine the provincial population-based seroprevalence in pregnant women and to further explore the association of maternal CMV infection status and adverse pregnancy/neonatal/growth outcomes in Jiangsu, China. Methods In this case-control study, the sera from 527 pregnant women with adverse pregnancy/neonatal outcomes and 496 mothers of healthy infants in Jiangsu Province, collected at gestation age of 15–20 weeks, were tested for anti-CMV IgG, IgM and IgG avidity. Adverse pregnancy/neonatal outcomes were identified based on pregnancy/neonatal outcomes. Results The overall seroprevalence of anti-CMV IgG was 98.7%, with 99.4% and 98.0% in the case and control groups, respectively (P = 0.039). The prevalence of anti-CMV IgG+/IgM+, was higher in the case group than that in the control group (3.8% vs. 1.6%, P = 0.033). Anti-CMV IgG avidity assay showed that none in the control group were primarily infected, but five (0.9%) in the case group underwent primary infection (P = 0.084); all five infants of these women presented severe adverse neonatal/growth outcomes. Exact logistic regression analysis showed that anti-CMV IgG+/IgM+ was associated with adverse pregnancy/neonatal/growth outcomes (aOR = 2.44, 95% CI 1.01–6.48, P = 0.047). Maternal low education level and prior abnormal pregnancies also were risk factors for adverse pregnancy/neonatal outcomes. Conclusions In populations with very high prevalence of latent CMV infection, active maternal CMV infection during pregnancy might be a risk factor for adverse pregnancy/neonatal outcomes. PMID:25211647

  10. Integrating Publicly Available Data to Generate Computationally Predicted Adverse Outcome Pathways for Fatty Liver.

    PubMed

    Bell, Shannon M; Angrish, Michelle M; Wood, Charles E; Edwards, Stephen W

    2016-04-01

    Newin vitrotesting strategies make it possible to design testing batteries for large numbers of environmental chemicals. Full utilization of the results requires knowledge of the underlying biological networks and the adverse outcome pathways (AOPs) that describe the route from early molecular perturbations to an adverse outcome. Curation of a formal AOP is a time-intensive process and a rate-limiting step to designing these test batteries. Here, we describe a method for integrating publicly available data in order to generate computationally predicted AOP (cpAOP) scaffolds, which can be leveraged by domain experts to shorten the time for formal AOP development. A network-based workflow was used to facilitate the integration of multiple data types to generate cpAOPs. Edges between graph entities were identified through direct experimental or literature information, or computationally inferred using frequent itemset mining. Data from the TG-GATEs and ToxCast programs were used to channel large-scale toxicogenomics information into a cpAOP network (cpAOPnet) of over 20 000 relationships describing connections between chemical treatments, phenotypes, and perturbed pathways as measured by differential gene expression and high-throughput screening targets. The resulting fatty liver cpAOPnet is available as a resource to the community. Subnetworks of cpAOPs for a reference chemical (carbon tetrachloride, CCl4) and outcome (fatty liver) were compared with published mechanistic descriptions. In both cases, the computational approaches approximated the manually curated AOPs. The cpAOPnet can be used for accelerating expert-curated AOP development and to identify pathway targets that lack genomic markers or high-throughput screening tests. It can also facilitate identification of key events for designing test batteries and for classification and grouping of chemicals for follow up testing. PMID:26895641

  11. What Can Hospitalized Patients Tell Us About Adverse Events? Learning from Patient-Reported Incidents

    PubMed Central

    Weingart, Saul N; Pagovich, Odelya; Sands, Daniel Z; Li, Joseph M; Aronson, Mark D; Davis, Roger B; Bates, David W; Phillips, Russell S

    2005-01-01

    Purpose Little is known about how well hospitalized patients can identify errors or injuries in their care. Accordingly, the purpose of this study was to elicit incident reports from hospital inpatients in order to identify and characterize adverse events and near-miss errors. Subjects We conducted a prospective cohort study of 228 adult inpatients on a medicine unit of a Boston teaching hospital. Methods Investigators reviewed medical records and interviewed patients during the hospitalization and by telephone 10 days after discharge about “problems,”“mistakes,” and “injuries” that occurred. Physician investigators classified patients' reports. We calculated event rates and used multivariable Poisson regression models to examine the factors associated with patient-reported events. Results Of 264 eligible patients, 228 (86%) agreed to participate and completed 528 interviews. Seventeen patients (8%) experienced 20 adverse events; 1 was serious. Eight patients (4%) experienced 13 near misses; 5 were serious or life threatening. Eleven (55%) of 20 adverse events and 4 (31%) of 13 near misses were documented in the medical record, but none were found in the hospital incident reporting system. Patients with 3 or more drug allergies were more likely to report errors compared with patients without drug allergies (incidence rate ratio 4.7, 95% CI 1.7, 13.4). Conclusion Inpatients can identify adverse events affecting their care. Many patient-identified events are not captured by the hospital incident reporting system or recorded in the medical record. Engaging hospitalized patients as partners in identifying medical errors and injuries is a potentially promising approach for enhancing patient safety. PMID:16117751

  12. Endothelial Dysfunction Is Associated With Major Adverse Cardiovascular Events in Peritoneal Dialysis Patients

    PubMed Central

    Lee, Mi Jung; Han, Seung Hyeok; Lee, Jung Eun; Choi, Hoon Young; Yoon, Chang-Yun; Kim, Eun Jin; Han, Jae Hyun; Han, Ji Suk; Oh, Hyung Jung; Park, Jung Tak; Kang, Shin-Wook; Yoo, Tae-Hyun

    2014-01-01

    Abstract Endothelial dysfunction is implicated in increased cardiovascular risk in nondialyzed population. However, the prognostic impact of endothelial dysfunction on cardiovascular outcome has not been investigated in peritoneal dialysis (PD) patients. We prospectively determined endothelial function by brachial artery endothelium-dependent vasodilation (flow-mediated dilation [FMD]) in 143 nondiabetic PD patients and 32 controls. Primary outcome was a major adverse cardiac and cerebrovascular event (MACCE). Brachial FMD was significantly lower in PD patients than in controls (2.9% [1.3–4.7] vs 6.2% [5.4–8.3], P < 0.001). During a mean follow-up of 42 months, primary outcome was observed in 25 patients (17.5%). When patients were dichotomized by the median value of FMD (2.9%), incidence rates of MACCEs were significantly higher in the group with lower FMD compared with higher FMD (7.2 vs 3.0/100 person-years, P = 0.03). In multivariate Cox analysis, low FMD (≤2.9%) was a significant independent predictor of MACCEs (hazard ratio = 2.73, 95% confidence interval = 1.03–7.22, P = 0.04). Furthermore, multivariate fractional polynomial analysis showed that the risk of MACCE decreased steadily with higher FMD values. Impaired brachial FMD was a significant independent predictor of MACCEs in PD patients. Estimating endothelial dysfunction by brachial FMD could be useful for stratifying cardiovascular risk in these patients. PMID:25192486

  13. Adverse Outcomes After Palliative Radiation Therapy for Uncomplicated Spine Metastases: Role of Spinal Instability and Single-Fraction Radiation Therapy

    SciTech Connect

    Lam, Tai-Chung; Krishnan, Monica; Groff, Michael; Cheney, Matthew; Balboni, Tracy

    2015-10-01

    Purpose: Level I evidence demonstrates equivalent pain response after single-fraction (SF) or multifraction (MF) radiation therapy (RT) for bone metastases. The purpose of this study is to provide additional data to inform the incidence and predictors of adverse outcomes after RT for spine metastases. Methods and Materials: At a single institution, 299 uncomplicated spine metastases (without cord compression, prior RT, or surgery) treated with RT from 2008 to 2013 were retrospectively reviewed. The spinal instability neoplastic score (SINS) was used to assess spinal instability. The primary outcome was time to first spinal adverse event (SAE) at the site, including symptomatic vertebral fracture, hospitalization for site-related pain, salvage surgery, interventional procedure, new neurologic symptoms, or cord compression. Fine and Gray's multivariable model assessed associations of the primary outcome with SINS, SF RT, and other significant baseline factors. Propensity score matched analysis further assessed the relationship of SF RT to first SAEs. Results: The cumulative incidence of first SAE after SF RT (n=66) was 6.8% at 30 days, 16.9% at 90 days, and 23.6% at 180 days. For MF RT (n=233), the incidence was 3.5%, 6.4%, and 9.2%, respectively. In multivariable analysis, SF RT (hazard ratio [HR] = 2.8, 95% confidence interval [CI] 1.5-5.2, P=.001) and SINS ≥11 (HR=2.5 , 95% CI 1.3-4.9, P=.007) were predictors of the incidence of first SAE. In propensity score matched analysis, first SAEs had developed in 22% of patients with SF RT versus 6% of those with MF RT cases (HR=3.9, 95% CI 1.6-9.6, P=.003) at 90 days after RT. Conclusion: In uncomplicated spinal metastases treated with RT alone, spinal instability with SINS ≥11 and SF RT were associated with a higher rate of SAEs.

  14. Exposure to Mixtures of Metals and Neurodevelopmental Outcomes: A Multidisciplinary Review Using an Adverse Outcome Pathway Framework.

    PubMed

    von Stackelberg, Katherine; Guzy, Elizabeth; Chu, Tian; Claus Henn, Birgit

    2015-06-01

    Current risk assessment guidance calls for an individual chemical-by-chemical approach that fails to capture potential interactive effects of exposure to environmental mixtures and genetic variability. We conducted a review of the literature on relationships between prenatal and early life exposure to mixtures of lead (Pb), arsenic (As), cadmium (Cd), and manganese (Mn) with neurodevelopmental outcomes. We then used an adverse outcome pathway (AOP) framework to integrate lines of evidence from multiple disciplines based on evolving guidance developed by the Organization for Economic Cooperation and Development (OECD). Toxicological evidence suggests a greater than additive effect of combined exposures to As-Pb-Cd and to Mn with any other metal, and several epidemiologic studies also suggest synergistic effects from binary combinations of Pb-As, Pb-Cd, and Pb-Mn. The exposure levels reported in these epidemiologic studies largely fall at the high-end (e.g., 95th percentile) of biomonitoring data from the National Health and Nutrition Examination Survey (NHANES), suggesting a small but significant potential for high-end exposures. This review integrates multiple data sources using an AOP framework and provides an initial application of the OECD guidance in the context of potential neurodevelopmental toxicity of several metals, recognizing the evolving nature of regulatory interpretation and acceptance. PMID:26096925

  15. Anhedonia Predicts Major Adverse Cardiac Events and Mortality in Patients 1 Year After Acute Coronary Syndrome

    PubMed Central

    Davidson, Karina W.; Burg, Matthew M.; Kronish, Ian M.; Shimbo, Daichi; Dettenborn, Lucia; Mehran, Roxana; Vorchheimer, David; Clemow, Lynn; Schwartz, Joseph E.; Lespérance, Francois; Rieckmann, Nina

    2010-01-01

    Context Depression is a consistent predictor of recurrent events and mortality in ACS patients, but it has 2 core diagnostic criteria with distinct biological correlates—depressed mood and anhedonia. Objective To determine if depressed mood and/or anhedonia (loss of pleasure or interest) predict 1-year medical outcomes for patients with Acute Coronary Syndrome (ACS). Design Observational cohort study of post-ACS patients hospitalized between May 2003 and June 2005. Within one week of admission, patients underwent a structured psychiatric interview to assess clinically impairing depressed mood, anhedonia, and major depressive episode (MDE); also assessed were the Global Registry of Acute Coronary Events risk score, Charlson comorbidity index, left ventricular ejection fraction, antidepressant use, and depressive symptom severity. Setting Coronary care and cardiac care step-down units of 3 university hospitals in New York and Connecticut. Participants Consecutive sample of 453 ACS patients (aged 25–93 years; 42% women). Main Outcomes Measures All-cause mortality (ACM) and documented major adverse cardiac events (MACE; myocardial infarction, hospitalization for unstable angina, or urgent revascularization) were actively surveyed for 1 year after admission. Results There were 67 events (16 deaths and 51 MACE; 14.8%). 108 (24%) and 77 (17%) patients with anhedonia and depressed mood, respectively. After controlling for sex, age, and medical covariates, anhedonia (adjusted hazard ratio, 1.58; 95% confidence interval, 1.16–2.14; P<.01) and MDE (adjusted hazard ratio, 1.48; 95% confidence interval, 1.07–2.04; P=.02) were significant predictors of combined MACE/ACM, but depressed mood was not. Anhedonia continued to significantly predict outcomes controlling for MDE diagnosis and depressive symptom severity, each of which were no longer significant. Conclusions Anhedonia identifies risk for MACE/ACM beyond that of established medical prognostic indicators

  16. Acidosis: A potential explanation for adverse fetal outcome in intrahepatic cholestasis of pregnancy. A case report

    PubMed Central

    Visser, W; Smit, LS; Cornette, J

    2014-01-01

    Background Intrahepatic cholestasis of pregnancy is a cholestatic disorder with an increased risk for adverse perinatal outcome. The mechanism underlying intrauterine demise is poorly understood. Case A nulliparous woman with gestational age of 36 plus 6 weeks presented with suspected intrahepatic cholestasis. Continuous CTG monitoring evolved from a normal pattern towards a non-reassuring pattern. A male neonate was delivered by caesarean section. Apgar scores 0, 1 and 4 at 1, 5 and 10 min. Fetal cord gas analysis showed pH 6.98, base deficit –15 mmol/L. Blood results showed maternal serum bile acid concentration of 220 µmol/L. Conclusion Our case suggests gradual evolution towards hypoxia and acidosis. It is unknown whether certain components in the bile acid concentrations might contribute to a fetal metabolic component of the acidosis.

  17. Identifying exposure disparities in air pollution epidemiology specific to adverse birth outcomes

    NASA Astrophysics Data System (ADS)

    Geer, Laura A.

    2014-10-01

    More than 147 million people in the US live in areas where pollutant levels are above regulatory limits and pose a risk to health. Most of the vast network of air pollutant monitors in the US are located in places with higher pollution levels and a higher density of pollutant sources (e.g., point sources from industrial pollution). Vulnerable populations are more likely to live closer to pollutant sources, and thus closer to pollutant monitors. These differential exposures have an impact on maternal and child health; maternal air pollutant exposures have been linked to adverse outcomes such as preterm birth and infant low birth weight. Several studies are highlighted that address methodological approaches in the study of air pollution and health disparities.

  18. Chlorinated drinking water, cancers and adverse health outcomes in Gangtok, Sikkim, India.

    PubMed

    Sharma, Rabi N; Goel, Sudha

    2007-10-01

    Long-term impacts of drinking chlorinated water on the incidence of cancers and other adverse health outcomes were assessed in a population-based cross-sectional study. The study was conducted by comparing a group exposed to chlorinated drinking water for more than thirty years with control groups with less or no exposure to chlorine. A house-to-house survey was completed to gather information on residential history, age, education, income, source and extent of treatment of water and health characteristics. All residents below thirty years of age were excluded from the database used for analyses to ensure that the groups were comparable. Fourteen cancer cases were found in the long-term exposed groups of 1085 persons and 9 cancer cases in the two control populations of 725 persons. The odds ratio for cancers (OR) was 1.05 (95% CI = 0.43-2.65) and is not statistically significant. Reciprocal or inverse odds [corrected] ratios for gastrointestinal disorders, kidney problems and skin infections were statistically significant ranging from 2.06 (95% CI = 1.01-4.17) to 2.2 (95% CI = 1.45-3.33). These OR values indicate that there is no significant association between the incidence of cancer and exposure to chlorinated water while chlorinating drinking water significantly reduced the incidence of non-carcinogenic adverse health effects like gastrointestinal diseases, skin infections, and kidney diseases. PMID:18476370

  19. Reducing Adverse Polypharmacy in Patients With Borderline Personality Disorder: An Empirical Case Study

    PubMed Central

    Oldham, John M.; Gonzalez, Sylvia; Fowler, J. Christopher

    2015-01-01

    Objective: Polypharmacy is common and especially challenging in the context of borderline personality disorder in light of impulsivity and self-harm associated with the disorder, risk of adverse drug-drug interactions, and financial burden. Reduction in polypharmacy could be conceptualized as a high priority in the treatment of borderline personality disorder. This case aims to demonstrate that potential. Method: This case report presents outcomes data for an individual with borderline personality disorder during the course of an extended psychiatric hospitalization. Symptomatic change is based on the Patient Health Questionnaire Somatic, Anxiety, and Depression Symptoms scales and World Health Organization 5-Item Well-Being Index. Change in polypharmacy is presented both in terms of absolute number and complexity of the medication regimen. Clinical outcomes data are provided at 2, 12, and 24 weeks postdischarge. Results: During a 56-day hospitalization, the patient demonstrated clinical improvement across clinical domains—all occurred within the context of reduced number (43%) and complexity (40%) of her medication regimen. Symptomatic improvement was sustained up to 6 months postdischarge. Conclusions: Despite good intentions, polypharmacy can be associated with iatrogenic harm and contribute to functional impairment, especially in the context of borderline personality disorder, in which symptomatic fluctuations are part of the illness itself. A reduction in the patient’s high-risk polypharmacy during treatment represents a noteworthy treatment outcome in and of itself. Additional measures of medication risk and liability have the potential to become markers of clinical effectiveness. PMID:26693036

  20. Is growth-discordance in twins a substantial risk factor in adverse neonatal outcomes?

    PubMed

    Frezza, Simonetta; Gallini, Francesca; Puopolo, Maria; De Carolis, Maria P; D'Andrea, Vito; Guidone, Paola I; Luciano, Rita; Zuppa, Antonio A; Romagnoli, Costantino

    2011-10-01

    To evaluate whether growth discordance is an independent risk factor in the neonatal outcome of the smaller twin, all medical records of twin pregnancies delivered between 26 and 41 weeks during a 5-year period (January 2004-December 2008) were reviewed. Among the 49 selected twins, weight discordance was 15-20% in 7 infants, 21-30% in 16 infants, 31-40% in 16 infants and > 40% in 10 infants. No significant differences between the four groups were found with regards to obstetric complications and neonatal disease. Occurrence of birthweight below the 10th percentile and rate of admission to the neonatal intensive care unit significantly increased as intra-pair birthweight difference increased (p = .03). The > 40% discordant group had a significantly lower gestational age (p = .03), lower birthweight (p = .007) and a significantly higher mortality rate (4/10 versus 3/39 p = .04) in comparison with the other discordant groups. Multiple logistic regression analysis showed that birthweight was the single independent and consistent factor associated with elevated risks of mortality. For every 250 g increase in birthweight, the risk for mortality decreased by about 84% [RR 0.16(CI 0.00-0.70)]. Gestational age was the most reliable predictor for major neonatal complications. For every 1-week increase in gestational age a significant decreased risk for all outcomes was found. Discordance alone should not be considered as a predictor for adverse neonatal outcome. Neonatal outcome in discordant twins appears to be related to gestational age and birthweight rather than to the degree of discordance. PMID:21962140

  1. Periodontal Treatment for Preventing Adverse Pregnancy Outcomes: A Meta- and Trial Sequential Analysis

    PubMed Central

    Schwendicke, Falk; Karimbux, Nadeem; Allareddy, Veerasathpurush; Gluud, Christian

    2015-01-01

    Objectives Periodontal treatment might reduce adverse pregnancy outcomes. The efficacy of periodontal treatment to prevent preterm birth, low birth weight, and perinatal mortality was evaluated using meta-analysis and trial sequential analysis. Methods An existing systematic review was updated and meta-analyses performed. Risk of bias, heterogeneity, and publication bias were evaluated, and meta-regression performed. Subgroup analysis was used to compare different studies with low and high risk of bias and different populations, i.e., risk groups. Trial sequential analysis was used to assess risk of random errors. Results Thirteen randomized clinical trials evaluating 6283 pregnant women were meta-analyzed. Four and nine trials had low and high risk of bias, respectively. Overall, periodontal treatment had no significant effect on preterm birth (odds ratio [95% confidence interval] 0.79 [0.57-1.10]) or low birth weight (0.69 [0.43-1.13]). Trial sequential analysis demonstrated that futility was not reached for any of the outcomes. For populations with moderate occurrence (<20%) of preterm birth or low birth weight, periodontal treatment was not efficacious for any of the outcomes, and trial sequential analyses indicated that further trials might be futile. For populations with high occurrence (≥20%) of preterm birth and low birth weight, periodontal treatment seemed to reduce the risk of preterm birth (0.42 [0.24-0.73]) and low birth weight (0.32 [0.15-0.67]), but trial sequential analyses showed that firm evidence was not reached. Periodontal treatment did not significantly affect perinatal mortality, and firm evidence was not reached. Risk of bias, but not publication bias or patients’ age modified the effect estimates. Conclusions Providing periodontal treatment to pregnant women could potentially reduce the risks of perinatal outcomes, especially in mothers with high risks. Conclusive evidence could not be reached due to risks of bias, risks of random

  2. An integrative data mining approach to identifying adverse outcome pathway signatures.

    PubMed

    Oki, Noffisat O; Edwards, Stephen W

    2016-03-28

    The Adverse Outcome Pathway (AOP) framework is a tool for making biological connections and summarizing key information across different levels of biological organization to connect biological perturbations at the molecular level to adverse outcomes for an individual or population. Computational approaches to explore and determine these connections can accelerate the assembly of AOPs. By leveraging the wealth of publicly available data covering chemical effects on biological systems, computationally-predicted AOPs (cpAOPs) were assembled via data mining of high-throughput screening (HTS) in vitro data, in vivo data and other disease phenotype information. Frequent Itemset Mining (FIM) was used to find associations between the gene targets of ToxCast HTS assays and disease data from Comparative Toxicogenomics Database (CTD) by using the chemicals as the common aggregators between datasets. The method was also used to map gene expression data to disease data from CTD. A cpAOP network was defined by considering genes and diseases as nodes and FIM associations as edges. This network contained 18,283 gene to disease associations for the ToxCast data and 110,253 for CTD gene expression. Two case studies show the value of the cpAOP network by extracting subnetworks focused either on fatty liver disease or the Aryl Hydrocarbon Receptor (AHR). The subnetwork surrounding fatty liver disease included many genes known to play a role in this disease. When querying the cpAOP network with the AHR gene, an interesting subnetwork including glaucoma was identified. While substantial literature exists to support the potential for AHR ligands to elicit glaucoma, it was not explicitly captured in the public annotation information in CTD. The subnetwork from this analysis suggests a cpAOP that includes changes in CYP1B1 expression, which has been previously established in the literature as a primary cause of glaucoma. These case studies highlight the value in integrating multiple data

  3. The influence of heart developmental anatomy on cardiotoxicity-based adverse outcome pathways in fish.

    PubMed

    Incardona, John P; Scholz, Nathaniel L

    2016-08-01

    The developing fish heart is vulnerable to a diverse array of toxic chemical contaminants in freshwater, estuarine, and marine habitats. Globally occurring examples of cardiotoxic agents include dioxins, polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs). The disruption of cardiac function during the process of heart morphogenesis can lead to adverse outcome pathways (AOPs) that can negatively affect fish survival at hatching as well as later life stages. Proximal impacts include cardiogenic fluid accumulation (edema) and defects of the body axis and jaw that preclude larval feeding. More subtle changes in heart development can produce permanent structural defects in the heart that reduce cardiac output and swimming performance in older fish. In recent decades, the presence of edema in fish embryos and larvae has been a very common bioindicator of cardiotoxicity. However, the different ways that edema forms in fish from different habitats (i.e., freshwater vs. marine, pelagic vs. demersal) has not been rigorously examined. Oil spills are an important source of PAHs in fish spawning areas worldwide, and research is revealing how patterns of cardiogenic edema are shaped by species-specific differences in developmental anatomy and ionoregulatory physiology. Here we review the visible evidence for circulatory disruption across nine freshwater and marine fish species, exposed to crude oils from different parts of the world. We focus on the close interconnectedness of the cardiovascular and osmoregulatory systems during early development, and corresponding implications for fish in hyperosmotic and hyposmotic habitats. Finally, we suggest there may be poorly understood adverse outcomes pathways related to osmotic gradients and water movement within embryos, the latter causing extreme shifts in tissue osmolality. PMID:27447099

  4. Adverse Outcome Pathways can drive non-animal approaches for safety assessment

    PubMed Central

    Burden, Natalie; Sewell, Fiona; Andersen, Melvin E; Boobis, Alan; Chipman, J Kevin; Cronin, Mark T D; Hutchinson, Thomas H; Kimber, Ian; Whelan, Maurice

    2015-01-01

    Adverse Outcome Pathways (AOPs) provide an opportunity to develop new and more accurate safety assessment processes for drugs and other chemicals, and may ultimately play an important role in regulatory decision making. Not only can the development and application of AOPs pave the way for the development of improved evidence-based approaches for hazard and risk assessment, there is also the promise of a significant impact on animal welfare, with a reduced reliance on animal-based methods. The establishment of a useable and coherent knowledge framework under which AOPs will be developed and applied has been a first critical step towards realizing this opportunity. This article explores how the development of AOPs under this framework, and their application in practice, could benefit the science and practice of safety assessment, while in parallel stimulating a move away from traditional methods towards an increased acceptance of non-animal approaches. We discuss here the key areas where current, and future initiatives should be focused to enable the translation of AOPs into routine chemical safety assessment, and lasting 3Rs benefits. © 2015 The Authors. Journal of Applied Toxicology published by John Wiley & Sons Ltd. This article explores how the development and application of Adverse Outcome Pathways (AOPs) could benefit the science and practice of chemical safety assessment, with a particular focus on how their use in practice could reduce reliance on traditional animal toxicity tests. This includes discussion of the key areas where current and future initiatives should be focused to enable the translation of AOPs into routine chemical safety assessment, and lasting 3Rs benefits. PMID:25943792

  5. Mechanistic study of chlordecone-induced endocrine disruption: Based on an adverse outcome pathway network.

    PubMed

    Yang, Lihua; Zhou, Bingsheng; Zha, Jinmiao; Wang, Zijian

    2016-10-01

    The adverse outcome pathway (AOP) framework could be helpful for chemical risk assessment and mechanistic research. The aim of the present study was to unravel the mechanism of chlordecone-induced endocrine disruption by illustrating the main molecular initiating event (MIE)/perturbations responsible for the observed effects. In silico simulations were performed to predict the MIE(s), and the results pointed to agonistic interaction with estrogen receptors (ERα, ERβ), androgen receptor (AR), cytochrome P450 (CYP19A) by chlordecone. In vivo endocrine disruptions were evaluated in rare minnow (Gobiocypris rarus) exposed to 0.01, 0.1, 1 and 10 μg L(-1) chlordecone from 2 h post-fertilization until sexually mature. In the females, increases of vitellogenin (vtg) mRNA levels in liver and gonad, plasma estradiol (E2), testosterone (T) and E2/T, and renalsomatic index confirmed the role of agonism of ER and CYP19A as MIEs, but the decreased gonadosomatic index, degenerated ovaries as well as the feed-forward response pointed to other potential but important MIEs and corresponding AOPs. In the males, increased E2/T ratio, increased testis vtg mRNA levels and occurrence of intersex confirmed the roles of agonism of ERα and CYP19A as main MIEs in chlordecone-induced endocrine disruptions. Our results also fetches out the limit of AOPs in predicting the adverse outcomes and explaining the mechanism of chemicals at present, thus reflected a critical need for expanding AOPs and AOP network before using it in chemical risk assessment. PMID:27448318

  6. Associations Between Residential Proximity to Power Plants and Adverse Birth Outcomes.

    PubMed

    Ha, Sandie; Hu, Hui; Roth, Jeffrey; Kan, Haidong; Xu, Xiaohui

    2015-08-01

    Few studies have assessed the associations between residential proximity to power plants and adverse birth outcomes including preterm delivery (PTD), very preterm delivery (VPTD), and term low birth weight (LBW). We geocoded 423,719 singleton Florida births born from 2004 to 2005 and all active power plants and determined residential proximity to the nearest power plant for each birth. Prenatal exposure to particulate matter less than 2.5 µm in diameter for women living near different types of power plants was also determined by using National Environmental Public Health Tracking Network data. Logistic regression models were used to test the hypothesized associations. Women who lived closer to coal and solid waste power plants were exposed to higher levels of particulate matter less than 2.5 µm in diameter compared with other types. We observed a 1.8% (95% confidence interval (CI): 1.3, 2.3) increased odds for PTD, 2.2% (95% CI: 1.0, 3.4) for VPTD, and 1.1% (95% CI: 0.2, 2.0) for term LBW for each 5 km closer to any power plant. When stratifying by different fuel type, we found that only solid waste had an association with term LBW, whereas oil, gas, and solid waste all had an association with PTD and VPTD. Results were consistent when exposure was categorized by number of power plants. Our study found evidence of increasing odds of adverse birth outcomes among infants born to pregnant women living closer to power plants. More research is warranted to better understand the causal relationship. PMID:26121989

  7. Adverse psychosocial outcomes associated with drug use among US high school seniors: a comparison of alcohol and marijuana

    PubMed Central

    Palamar, Joseph J.; Fenstermaker, Michael; Kamboukos, Dimitra; Ompad, Danielle C.; Cleland, Charles M.; Weitzman, Michael

    2015-01-01

    Objectives There is debate about whether marijuana (cannabis) use is more dangerous than alcohol use. Although difficult to make objective comparisons, research is needed to compare relative dangers in order to help inform preventive efforts and policy. Methods Data were analyzed from a nationally representative sample of high school seniors in the Monitoring the Future study (2007–2011; Weighted n = 7437; modal age: 18) who reported lifetime use of alcohol or marijuana. Students were asked to indicate whether they experienced various adverse psychosocial outcomes resulting from use of each substance. We examined which outcomes were more prevalent for each substance. Results Compared to alcohol use, marijuana use was more commonly reported to compromise relationships with teachers or supervisors, result in less energy or interest, and result in lower school or job performance. Compared to marijuana use, alcohol was more commonly reported to compromise relationships with friends and significant others; it was also reported to lead to more regret (particularly among females), and driving unsafely. Marijuana users were more likely to report no adverse outcomes. Females and white students were more likely to report various adverse outcomes and higher frequency use of each substance also increased occurrences of reported adverse outcomes. Conclusions Marijuana and alcohol are associated with unique adverse psychosocial outcomes. Outcomes differ by sex and race/ethnicity, and perception or experience of outcomes may also be related to legal status and associated stigma. Public health interventions may be more effective by focusing on harm reduction strategies for these drug-specific outcomes. PMID:25169838

  8. Cardiovascular recovery from psychological and physiological challenge and risk for adverse cardiovascular outcomes and all-cause mortality

    PubMed Central

    Panaite, Vanessa; Salomon, Kristen; Jin, Alvin; Rottenberg, Jonathan

    2015-01-01

    Objective Exaggerated cardiovascular (CV) reactivity to laboratory challenge has been shown to predict future CV morbidity and mortality. CV recovery, has been less studied, and has yielded inconsistent findings, possibly due to presence of moderators. Reviews on the relationship between CV recovery and CV outcomes have been limited to cross-sectional studies and have not considered methodological factors. We performed a comprehensive meta-analytic review of the prospective literature investigating CV recovery to physical and psychological challenge and adverse cardiovascular outcomes. Methods We searched PsycINFO and PubMed for prospective studies investigating the relationship between CV recovery and adverse CV outcomes. Studies were coded for variables of interest and for effect sizes (ES). We conducted a random effects weighted meta-analysis. Moderators were examined with ANOVA-analog and meta-regression analyses. Results Thirty seven studies met inclusion criteria (N=125386). Impaired recovery from challenge predicted adverse cardiovascular outcomes (summary effect, r = .17, p < .001). Physical challenge was associated with larger predictive effects than psychological challenge. Moderator analyses revealed that recovery measured at 1 minute post-exercise, passive recovery, use of mortality as an outcome measure, and older sample age were associated with larger effects. Conclusions Poor recovery from laboratory challenges predicts adverse CV outcomes, with recovery from exercise serving as a particularly strong predictor of CV outcomes. The overall ES for recovery and CV outcomes is similar to that observed for CV reactivity and suggests that the study of recovery may have incremental value for understanding adverse CV outcomes. PMID:25829236

  9. Demoralization, Patient Activation, and the Outcome of Spine Surgery.

    PubMed

    Block, Andrew R

    2016-01-01

    It is now well established that psychosocial factors can adversely impact the outcome of spine surgery. This article discusses in detail one such recently-identified "risk" factor: demoralization. Several studies conducted by the author indicate that demoralization, an emotional construct distinct from depression, is associated with poorer pain reduction, less functional improvement and decreased satisfaction among spine surgery patients. However, there are indications that the adverse impact of risk factors such as demoralization can be mitigated by psychosocial "maximizing" factors-characteristics that propel the patient towards positive surgical results. One of these maximizing factors, patient activation, is discussed in depth. The patient activation measure (PAM), an inventory assessing the extent to which patients are active and engaged in their health care, is associated not only with improved spine surgery results, but with better outcomes across a broad range of medical conditions. Other maximizing factors are discussed in this article. The author concludes that the past research focus on psychosocial risk factors has limited the value of presurgical psychological screening, and that future research, as well as clinical assessment, should recognize that the importance of evaluating patients' strengths as well as their vulnerabilities. PMID:27417599

  10. Effects of a psychosocial couple-based prevention program on adverse birth outcomes.

    PubMed

    Feinberg, Mark E; Roettger, Michael E; Jones, Damon E; Paul, Ian M; Kan, Marni L

    2015-01-01

    Although maternal stress and depression have been linked to adverse birth outcomes (ABOs), few studies have investigated preventive interventions targeting maternal mental health as a means of reducing ABOs. This randomized controlled study examines the impact of Family Foundations (FF)-a transition to parenthood program for couples focused on promoting coparenting quality, with previously documented impact on maternal stress and depression-on ABOs. We also examine whether intervention buffers birth outcomes from the negative effect of elevated salivary cortisol levels. We use intent-to-treat analyses to assess the main effects of the FF intervention on ABOs (prematurity, birth weight, pregnancy complications, Cesarean section, and days in hospital for mothers and infants) among 148 expectant mothers. We also test the interaction of cortisol with intervention condition status in predicting ABOs. FF participation was associated with reduced risk of C-section (OR .357, p < 0.05, 95 % CI 0.149, 0.862), but did not have main effects on other ABOs. FF significantly buffered (p < 0.05) the negative impact of maternal cortisol on birth weight, gestational age, and days in hospital for infants; that is, among women with relatively higher levels of prenatal cortisol, the intervention reduced ABOs. These results demonstrate that a psycho-educational program for couples reduces incidence of ABOs among higher risk women. Future work should test whether reduced maternal stress and depression mediate these intervention effects. PMID:24969352

  11. Adverse birth outcomes in the vicinity of industrial installations in Spain 2004-2008.

    PubMed

    Castelló, Adela; Río, Isabel; García-Pérez, Javier; Fernández-Navarro, Pablo; Waller, Lance A; Clennon, Julie A; Bolúmar, Francisco; López-Abente, Gonzalo

    2013-07-01

    Industrial activity is one of the main sources of ambient pollution in developed countries. However, research analyzing its effect on birth outcomes is inconclusive. We analyzed the association between proximity of mother's municipality of residence to industries from 24 different activity groups and risk of very (VPTB) and moderate (MPTB) preterm birth, very (VLBW) and moderate (MLBW) low birth weight, and small for gestational age (SGA) in Spain, 2004-2008. An ecological study was defined, and a "near vs. far" analysis (3.5 km threshold) was carried out using Hierarchical Bayesian models implemented via Integrated Nested Laplace Approximation. VPTB risk was higher for mothers living near pharmaceutical companies. Proximity to galvanization and hazardous waste management industries increased the risk of MPTB. Risk of VLBW was higher for mothers residing near pharmaceutical and non-hazardous or animal waste management industries. For MLBW many associations were found, being notable the proximity to mining, biocides and animal waste management plants. The strongest association for SGA was found with proximity to management animal waste plants. These results highlight the importance of further research on the relationship between proximity to industrial sites and the occurrence of adverse birth outcomes especially for the case of pharmaceutical and animal waste management activities. PMID:23322413

  12. Effects of a Psychosocial Couple-Based Prevention Program on Adverse Birth Outcomes

    PubMed Central

    Roettger, Michael E.; Jones, Damon E.; Paul, Ian M.; Kan, Marni L.

    2015-01-01

    Although maternal stress and depression have been linked to adverse birth outcomes (ABOs), few studies have investigated preventive interventions targeting maternal mental health as a means of reducing ABOs. This randomized controlled study examines the impact of Family Foundations (FF)—a transition to parenthood program for couples focused on promoting coparenting quality, with previously documented impact on maternal stress and depression—on ABOs. We also examine whether intervention buffers birth outcomes from the negative effect of elevated salivary cortisol levels. We use intent-to-treat analyses to assess the main effects of the FF intervention on ABOs (prematurity, birth weight, pregnancy complications, Cesarean section, and days in hospital for mothers and infants) among 148 expectant mothers. We also test the interaction of cortisol with intervention condition status in predicting ABOs. FF participation was associated with reduced risk of C-section (OR .357, p < 0.05, 95 % CI 0.149, 0.862), but did not have main effects on other ABOs. FF significantly buffered (p < 0.05) the negative impact of maternal cortisol on birth weight, gestational age, and days in hospital for infants; that is, among women with relatively higher levels of prenatal cortisol, the intervention reduced ABOs. These results demonstrate that a psycho-educational program for couples reduces incidence of ABOs among higher risk women. Future work should test whether reduced maternal stress and depression mediate these intervention effects. PMID:24969352

  13. Child marriage and its association with adverse reproductive outcomes for women in Bangladesh.

    PubMed

    Kamal, S M Mostafa; Hassan, Che Hashim

    2015-03-01

    This study examines the prevalence of child marriage and its effect on reproductive outcomes among women in Bangladesh using the most recent 2011 Bangladesh Demographic and Health Survey data. Both bivariate and multivariate statistical techniques used in the study yielded quantitatively important and reliable estimates of child marriage and its impact on adverse reproductive and health outcomes. Overall, 77% of the marriages among women aged 20 to 49 years old took place before the age of 18 years. Women's education is the most single significant determinant of child marriage. Findings revealed that after being adjusted for sociodemographic factors, child marriage significantly (P < .001) increases the likelihood of stillbirth/miscarriage (odds ratio [OR] = 1.80; 95% confidence interval [CI] = 1.45-2.24) and pregnancy termination (OR = 1.24; 95% CI = 1.12-1.38). Programs should aim to retain girls in school for longer periods not only to raise the age at first marriage but also for sound reproductive health and overall social development of Bangladesh. PMID:24097938

  14. Current Perspectives on Arthroplasty in Systemic Lupus Erythematosus: Rates, Outcomes, and Adverse Events.

    PubMed

    Kasturi, Shanthini; Goodman, Susan

    2016-09-01

    Systemic lupus erythematosus (SLE) is a chronic debilitating condition with significant impact on the musculoskeletal system. Arthroplasty may be indicated for damage related to active lupus or its treatment. As therapies for SLE have advanced, morbidity and mortality have declined, while the rate of joint replacement has increased. The age of SLE patients undergoing arthroplasty is increasing, and the indication for surgery is evolving-while avascular necrosis was previously the predominant indication for arthroplasty, osteoarthritis now accounts for a larger proportion of surgeries. Pain and functional outcomes of arthroplasty in SLE patients are comparable to those of the general population with osteoarthritis, but lupus remains an independent risk factor for post-hip arthroplasty complications and mortality. Further research is needed to characterize the impact of lupus disease activity and severity on arthroplasty outcomes. PMID:27443850

  15. Planned Repeat Cesarean Section at Term and Adverse Childhood Health Outcomes: A Record-Linkage Study

    PubMed Central

    Black, Mairead; Bhattacharya, Siladitya; Philip, Sam; Norman, Jane E.; McLernon, David J.

    2016-01-01

    Background Global cesarean section (CS) rates range from 1% to 52%, with a previous CS being the commonest indication. Labour following a previous CS carries risk of scar rupture, with potential for offspring hypoxic brain injury, leading to high rates of repeat elective CS. However, the effect of delivery by CS on long-term outcomes in children is unclear. Increasing evidence suggests that in avoiding exposure to maternal bowel flora during labour or vaginal birth, offspring delivered by CS may be adversely affected in terms of energy uptake from the gut and immune development, increasing obesity and asthma risks, respectively. This study aimed to address the evidence gap on long-term childhood outcomes following repeat CS by comparing adverse childhood health outcomes after (1) planned repeat CS and (2) unscheduled repeat CS with those that follow vaginal birth after CS (VBAC). Methods and Findings A data-linkage cohort study was performed. All second-born, term, singleton offspring delivered between 1 January 1993 and 31 December 2007 in Scotland, UK, to women with a history of CS (n = 40,145) were followed up until 31 January 2015. Outcomes assessed included obesity at age 5 y, hospitalisation with asthma, learning disability, cerebral palsy, and death. Cox regression and binary logistic regression were used as appropriate to compare outcomes following planned repeat CS (n = 17,919) and unscheduled repeat CS (n = 8,847) with those following VBAC (n = 13,379). Risk of hospitalisation with asthma was greater following both unscheduled repeat CS (3.7% versus 3.3%, adjusted hazard ratio [HR] 1.18, 95% CI 1.05–1.33) and planned repeat CS (3.6% versus 3.3%, adjusted HR 1.24, 95% CI 1.09–1.42) compared with VBAC. Learning disability and death were more common following unscheduled repeat CS compared with VBAC (3.7% versus 2.3%, adjusted odds ratio 1.64, 95% CI 1.17–2.29, and 0.5% versus 0.4%, adjusted HR 1.50, 95% CI 1.00–2.25, respectively). Risk of obesity

  16. Sexual Dimorphism in Adverse Pregnancy Outcomes - A Retrospective Australian Population Study 1981-2011

    PubMed Central

    Verburg, Petra E.; Tucker, Graeme; Scheil, Wendy; Erwich, Jan Jaap H. M.; Dekker, Gus A.; Roberts, Claire Trelford

    2016-01-01

    Objectives Sexual inequality starts in utero. The contribution of biological sex to the developmental origins of health and disease is increasingly recognized. The aim of this study was to assess and interpret sexual dimorphisms for three major adverse pregnancy outcomes which affect the health of the neonate, child and potentially adult. Methods Retrospective population-based study of 574,358 South Australian singleton live births during 1981–2011. The incidence of three major adverse pregnancy outcomes [preterm birth (PTB), pregnancy induced hypertensive disorders (PIHD) and gestational diabetes mellitus (GDM)] in relation to fetal sex was compared according to traditional and fetus-at-risk (FAR) approaches. Results The traditional approach showed male predominance for PTB [20–24 weeks: Relative Risk (RR) M/F 1.351, 95%-CI 1.274–1.445], spontaneous PTB [25–29 weeks: RR M/F 1.118, 95%-CI 1.044–1.197%], GDM [RR M/F 1.042, 95%-CI 1.011–1.074], overall PIHD [RR M/F 1.053, 95%-CI 1.034–1.072] and PIHD with term birth [RR M/F 1.074, 95%-CI 1.044–1.105]. The FAR approach showed that males were at increased risk for PTB [20–24 weeks: RR M/F 1.273, 95%-CI 1.087–1.490], for spontaneous PTB [25–29 weeks: RR M/F 1.269, 95%-CI 1.143–1.410] and PIHD with term birth [RR M/F 1.074, 95%-CI 1.044–1.105%]. The traditional approach demonstrated female predominance for iatrogenic PTB [25–29 weeks: RR M/F 0.857, 95%-CI 0.780–0.941] and PIHD associated with PTB [25–29 weeks: RR M/F 0.686, 95%-CI 0.581–0.811]. The FAR approach showed that females were at increased risk for PIHD with PTB [25–29 weeks: RR M/F 0.779, 95%-CI 0.648–0.937]. Conclusions This study confirms the presence of sexual dimorphisms and presents a coherent framework based on two analytical approaches to assess and interpret the sexual dimorphisms for major adverse pregnancy outcomes. The mechanisms by which these occur remain elusive, but sex differences in placental gene

  17. Highly Active Antiretroviral Therapy and Adverse Birth Outcomes Among HIV-Infected Women in Botswana

    PubMed Central

    Chen, Jennifer Y.; Ribaudo, Heather J.; Souda, Sajini; Parekh, Natasha; Ogwu, Anthony; Lockman, Shahin; Powis, Kathleen; Dryden-Peterson, Scott; Creek, Tracy; Jimbo, William; Madidimalo, Tebogo; Makhema, Joseph; Essex, Max; Shapiro, Roger L

    2012-01-01

    Background. It is unknown whether adverse birth outcomes are associated with maternal highly active antiretroviral therapy (HAART) in pregnancy, particularly in resource-limited settings. Methods. We abstracted obstetrical records at 6 sites in Botswana for 24 months. Outcomes included stillbirths (SBs), preterm delivery (PTD), small for gestational age (SGA), and neonatal death (NND). Among human immunodeficiency virus (HIV)–infected women, comparisons were limited to HAART exposure status at conception, and those with similar opportunities for outcomes. Comparisons were adjusted for CD4+ lymphocyte cell count. Results. Of 33 148 women, 32 113 (97%) were tested for HIV, of whom 9504 (30%) were HIV infected. Maternal HIV was significantly associated with SB, PTD, SGA, and NND. Compared with all other HIV-infected women, those continuing HAART from before pregnancy had higher odds of PTD (adjusted odds ratio [AOR], 1.2; 95% confidence interval [CI], 1.1, 1.4), SGA (AOR, 1.8; 95% CI, 1.6, 2.1) and SB (AOR, 1.5; 95% CI, 1.2, 1.8). Among women initiating antiretroviral therapy in pregnancy, HAART use (vs zidovudine) was associated with higher odds of PTD (AOR, 1.4; 95% CI, 1.2, 1.8), SGA (AOR, 1.5; 95% CI, 1.2, 1.9), and SB (AOR, 2.5; 95% CI, 1.6, 3.9). Low CD4+ was independently associated with SB and SGA, and maternal hypertension during pregnancy with PTD, SGA, and SB. Conclusions. HAART receipt during pregnancy was associated with increased PTD, SGA, and SB. PMID:23066160

  18. A Meta Analysis on Risks of Adverse Pregnancy Outcomes in Toxoplasma gondii Infection

    PubMed Central

    Zhang, Hao; Peng, Hong-Juan; Lindsay, David S.

    2014-01-01

    Objective Quantified risks of congenital Toxoplasma gondii infection and abnormal pregnancy outcomes following primary maternal infection were evaluated with meta- analysis based on published studies. Methods The related literatures were searched in multiple literature databases regardless of languages. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the risks of vertical transmission of Toxoplasma gondii and abnormal pregnancy outcomes following primary maternal infection with meta-analysis. Results 53 of the 2632 searched literatures were included in our analysis. The incidence of abnormal pregnancy outcomes in T. gondii infected pregnant women (infected group) was significantly higher than that in the uninfected pregnant women (control group) (OR = 5.10; 95% CI, 3.85–6.75). Toxoplasma gondii infection rate in the abnormal-pregnancy-outcome group was significantly higher than in the normal-pregnancy group (OR = 3.71; 95% CI, 3.31–4.15). The pooled rate of vertical transmission was 20% (95% CI, 15%–26%) in maternal infection of T. gondii. The incidences of vertical transmission in women who were infected in the first, second or third trimester of pregnancy were 5% (95%CI, 2%–16%), 13% (95%CI, 7%–23%), and 32% (95%CI, 24%–41%), respectively. The rates of vertical transmission in women who were treated with spiramycin-only, PSF (pyrimethamine + sulfadiazine + folinic acid) or PS (pyrimethamine + sulfadiazine) combined with spiramycin, or other untypical treatments were 13% (95%CI, 7%–22%), 13%(95%CI, 7%–25%), and 24%(95%CI, 18%–32%), respectively. Conclusions Toxoplasma gondii infection can result in adverse pregnancy outcomes in pregnant women. The pooled rate of vertical transmission was 20% in maternal infection and the incidences of vertical transmission increased in the first, second or third trimester of pregnancy. The pooled rates of transmission in groups treated with spiramycin-only, PSF or PS combined with

  19. A Genomic Score Prognostic of Outcome in Trauma Patients

    PubMed Central

    Warren, H Shaw; Elson, Constance M; Hayden, Douglas L; Schoenfeld, David A; Cobb, J Perren; Maier, Ronald V; Moldawer, Lyle L; Moore, Ernest E; Harbrecht, Brian G; Pelak, Kimberly; Cuschieri, Joseph; Herndon, David N; Jeschke, Marc G; Finnerty, Celeste C; Brownstein, Bernard H; Hennessy, Laura; Mason, Philip H; Tompkins, Ronald G

    2009-01-01

    Traumatic injuries frequently lead to infection, organ failure, and death. Health care providers rely on several injury scoring systems to quantify the extent of injury and to help predict clinical outcome. Physiological, anatomical, and clinical laboratory analytic scoring systems (Acute Physiology and Chronic Health Evaluation [APACHE], Injury Severity Score [ISS]) are utilized, with limited success, to predict outcome following injury. The recent development of techniques for measuring the expression level of all of a person’s genes simultaneously may make it possible to develop an injury scoring system based on the degree of gene activation. We hypothesized that a peripheral blood leukocyte gene expression score could predict outcome, including multiple organ failure, following severe blunt trauma. To test such a scoring system, we measured gene expression of peripheral blood leukocytes from patients within 12 h of traumatic injury. cRNA derived from whole blood leukocytes obtained within 12 h of injury provided gene expression data for the entire genome that were used to create a composite gene expression score for each patient. Total blood leukocytes were chosen because they are active during inflammation, which is reflective of poor outcome. The gene expression score combines the activation levels of all the genes into a single number which compares the patient’s gene expression to the average gene expression in uninjured volunteers. Expression profiles from healthy volunteers were averaged to create a reference gene expression profile which was used to compute a difference from reference (DFR) score for each patient. This score described the overall genomic response of patients within the first 12 h following severe blunt trauma. Regression models were used to compare the association of the DFR, APACHE, and ISS scores with outcome. We hypothesized that patients with a total gene response more different from uninjured volunteers would tend to have poorer

  20. Demoralization, Patient Activation, and the Outcome of Spine Surgery

    PubMed Central

    Block, Andrew R

    2016-01-01

    It is now well established that psychosocial factors can adversely impact the outcome of spine surgery. This article discusses in detail one such recently-identified “risk” factor: demoralization. Several studies conducted by the author indicate that demoralization, an emotional construct distinct from depression, is associated with poorer pain reduction, less functional improvement and decreased satisfaction among spine surgery patients. However, there are indications that the adverse impact of risk factors such as demoralization can be mitigated by psychosocial “maximizing” factors—characteristics that propel the patient towards positive surgical results. One of these maximizing factors, patient activation, is discussed in depth. The patient activation measure (PAM), an inventory assessing the extent to which patients are active and engaged in their health care, is associated not only with improved spine surgery results, but with better outcomes across a broad range of medical conditions. Other maximizing factors are discussed in this article. The author concludes that the past research focus on psychosocial risk factors has limited the value of presurgical psychological screening, and that future research, as well as clinical assessment, should recognize that the importance of evaluating patients’ strengths as well as their vulnerabilities. PMID:27417599

  1. Urine Injury Biomarkers and Risk of Adverse Outcomes in Recipients of Prevalent Kidney Transplants: The Folic Acid for Vascular Outcome Reduction in Transplantation Trial.

    PubMed

    Bansal, Nisha; Carpenter, Myra A; Weiner, Daniel E; Levey, Andrew S; Pfeffer, Marc; Kusek, John W; Cai, Jianwen; Hunsicker, Lawrence G; Park, Meyeon; Bennett, Michael; Liu, Kathleen D; Hsu, Chi-Yuan

    2016-07-01

    Recipients of kidney transplants (KTR) are at increased risk for cardiovascular events, graft failure, and death. It is unknown whether urine kidney injury biomarkers are associated with poor outcomes among KTRs. We conducted a post hoc analysis of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial using a case-cohort study design, selecting participants with adjudicated cardiovascular events, graft failure, or death. Urine neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), IL-18, and liver-type fatty acid binding protein (L-FABP) were measured in spot urine samples and standardized to urine creatinine concentration. We adjusted for demographics, cardiovascular risk factors, eGFR, and urine albumin-to-creatinine ratio. Patients had 291 cardiovascular events, 257 graft failure events, and 359 deaths. Each log increase in urine NGAL/creatinine independently associated with a 24% greater risk of cardiovascular events (adjusted hazard ratio [aHR], 1.24; 95% confidence interval [95% CI], 1.06 to 1.45), a 40% greater risk of graft failure (aHR, 1.40; 95% CI, 1.16 to 1.68), and a 44% greater risk of death (aHR, 1.44; 95% CI, 1.26 to 1.65). Urine KIM-1/creatinine and IL-18/creatinine independently associated with greater risk of death (aHR, 1.29; 95% CI, 1.03 to 1.61 and aHR, 1.25; 95% CI, 1.04 to 1.49 per log increase, respectively) but not with risk of cardiovascular events or graft failure. Urine L-FABP did not associate with any study outcomes. In conclusion, among prevalent KTRs, higher urine NGAL, KIM-1, and IL-18 levels independently and differentially associated with greater risk of adverse outcomes. PMID:26538631

  2. Clinical characteristics associated with adverse events in patients with exacerbation of chronic obstructive pulmonary disease: a prospective cohort study

    PubMed Central

    Stiell, Ian G.; Clement, Catherine M.; Aaron, Shawn D.; Rowe, Brian H.; Perry, Jeffrey J.; Brison, Robert J.; Calder, Lisa A.; Lang, Eddy; Borgundvaag, Bjug; Forster, Alan J.; Wells, George A.

    2014-01-01

    Background: To assist physicians with difficult decisions about hospital admission for patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) presenting in the emergency department, we sought to identify clinical characteristics associated with serious adverse events. Methods: We conducted this prospective cohort study in 6 large Canadian academic emergency departments. Patients were assessed for standardized clinical variables and then followed for serious adverse events, defined as death, intubation, admission to a monitored unit or new visit to the emergency department requiring admission. Results: We enrolled 945 patients, of whom 354 (37.5%) were admitted to hospital. Of 74 (7.8%) patients with a subsequent serious adverse event, 36 (49%) had not been admitted after the initial emergency visit. Multivariable modelling identified 5 variables that were independently associated with adverse events: prior intubation, initial heart rate ≥ 110/minute, being too ill to do a walk test, hemoglobin < 100 g/L and urea ≥ 12 mmol/L. A preliminary risk scale incorporating these and 5 other clinical variables produced risk categories ranging from 2.2% for a score of 0 to 91.4% for a score of 10. Using a risk score of 2 or higher as a threshold for admission would capture all patients with a predicted risk of adverse events of 7.2% or higher, while only slightly increasing admission rates, from 37.5% to 43.2%. Interpretation: In Canada, many patients with COPD suffer a serious adverse event or death after being discharged home from the emergency department. We identified high-risk characteristics and developed a preliminary risk scale that, once validated, could be used to stratify the likelihood of poor outcomes and to enable rational and safe admission decisions. PMID:24549125

  3. [Electronic fetal monitoring and management of adverse outcomes: how to perform and improve a training program for clinicians?].

    PubMed

    Secourgeon, J-F

    2012-10-01

    Electronic fetal monitoring during labor is the most commonly used method to evaluate the fetal status, but it remains exposed to some criticism. By comparison with intermittent auscultation and in the light of the results of the great studies in the last 30 years, it may be accused its failure to improve the neonatal outcome and its responsibility in the increase on operative deliveries. Actually, the electronic fetal monitoring is a tool whose effectiveness is linked to the accuracy of the analysis developed by the clinician. Studies on assessment of the tracing interpretation indicate that there is always a lack of quality, which may be improved through training programs. It also reveals the benefit of the fetal blood sampling to reduce operative deliveries and the generalization of this method, in addition to electronic fetal monitoring, is recommended by referral agencies. More generally, the continuous monitoring is only a part of the patient safety strategy in the labour ward and we are currently observing, in some European countries and in the United States, the development of training programs concerning the management of the adverse outcomes in obstetrics. The good performances related to the quality of care are demonstrated by the findings of the studies performed in the centers that have implemented an active training policy. In France, the professionals directly involved in the field of the perinatology should benefit from such educational programs that could be organized within the care networks under the authority of referral agencies. PMID:22819781

  4. Geospatial association between adverse birth outcomes and arsenic in groundwater in New Hampshire, USA

    USGS Publications Warehouse

    Xun Shi; Ayotte, Joseph; Akikazu Onda; Stephanie Miller; Judy Rees; Diane Gilbert-Diamond; Onega, Tracy L; Gui, Jiang; Karagas, Margaret R.; Moeschler, John B

    2015-01-01

    There is increasing evidence of the role of arsenic in the etiology of adverse human reproductive outcomes. Because drinking water can be a major source of arsenic to pregnant women, the effect of arsenic exposure through drinking water on human birth may be revealed by a geospatial association between arsenic concentration in groundwater and birth problems, particularly in a region where private wells substantially account for water supply, like New Hampshire, USA. We calculated town-level rates of preterm birth and term low birth weight (term LBW) for New Hampshire, by using data for 1997–2009 stratified by maternal age. We smoothed the rates by using a locally weighted averaging method to increase the statistical stability. The town-level groundwater arsenic probability values are from three GIS data layers generated by the US Geological Survey: probability of local groundwater arsenic concentration >1 µg/L, probability >5 µg/L, and probability >10 µg/L. We calculated Pearson’s correlation coefficients (r) between the reproductive outcomes (preterm birth and term LBW) and the arsenic probability values, at both state and county levels. For preterm birth, younger mothers (maternal age <20) have a statewider = 0.70 between the rates smoothed with a threshold = 2,000 births and the town mean arsenic level based on the data of probability >10 µg/L; for older mothers, r = 0.19 when the smoothing threshold = 3,500; a majority of county level r values are positive based on the arsenic data of probability >10 µg/L. For term LBW, younger mothers (maternal age <25) have a statewide r = 0.44 between the rates smoothed with a threshold = 3,500 and town minimum arsenic concentration based on the data of probability >1 µg/L; for older mothers, r = 0.14 when the rates are smoothed with a threshold = 1,000 births and also adjusted by town median household income in 1999, and the arsenic values are the town minimum based on probability

  5. Geospatial association between adverse birth outcomes and arsenic in groundwater in New Hampshire, USA.

    PubMed

    Shi, Xun; Ayotte, Joseph D; Onda, Akikazu; Miller, Stephanie; Rees, Judy; Gilbert-Diamond, Diane; Onega, Tracy; Gui, Jiang; Karagas, Margaret; Moeschler, John

    2015-04-01

    There is increasing evidence of the role of arsenic in the etiology of adverse human reproductive outcomes. Because drinking water can be a major source of arsenic to pregnant women, the effect of arsenic exposure through drinking water on human birth may be revealed by a geospatial association between arsenic concentration in groundwater and birth problems, particularly in a region where private wells substantially account for water supply, like New Hampshire, USA. We calculated town-level rates of preterm birth and term low birth weight (term LBW) for New Hampshire, by using data for 1997-2009 stratified by maternal age. We smoothed the rates by using a locally weighted averaging method to increase the statistical stability. The town-level groundwater arsenic probability values are from three GIS data layers generated by the US Geological Survey: probability of local groundwater arsenic concentration >1 µg/L, probability >5 µg/L, and probability >10 µg/L. We calculated Pearson's correlation coefficients (r) between the reproductive outcomes (preterm birth and term LBW) and the arsenic probability values, at both state and county levels. For preterm birth, younger mothers (maternal age <20) have a statewide r = 0.70 between the rates smoothed with a threshold = 2,000 births and the town mean arsenic level based on the data of probability >10 µg/L; for older mothers, r = 0.19 when the smoothing threshold = 3,500; a majority of county level r values are positive based on the arsenic data of probability >10 µg/L. For term LBW, younger mothers (maternal age <25) have a statewide r = 0.44 between the rates smoothed with a threshold = 3,500 and town minimum arsenic concentration based on the data of probability >1 µg/L; for older mothers, r = 0.14 when the rates are smoothed with a threshold = 1,000 births and also adjusted by town median household income in 1999, and the arsenic values are the town minimum based on probability >10 µg/L. At the county level for

  6. Negotiating outcomes with patients and families.

    PubMed

    Zander, K S

    1996-09-01

    Negotiating outcomes is a complex skill that is crucial to attaining quality care, particularly in an environment characterized by an accelerated speed of care and regimented options for care. In this environment, patients and their families need a realistic view of achievable outcomes. Caregivers must be able to reformulate and renegotiate outcomes quickly with patients and their families. Caregivers act as a catalyst in the outcome-achievement process and, to be successful, seek new and creative strategies to accomplish this. Being a catalyst also involves determining the patients' personal feelings about their illnesses and the proposed interventions, assisting patients in planning how to translate their new knowledge into behaviors, and to build in feedback mechanisms. PMID:8920372

  7. Dectin-1 predicts adverse postoperative prognosis of patients with clear cell renal cell carcinoma.

    PubMed

    Xia, Yu; Liu, Li; Bai, Qi; Wang, Jiajun; Xi, Wei; Qu, Yang; Xiong, Ying; Long, Qilai; Xu, Jiejie; Guo, Jianming

    2016-01-01

    Dectin-1, a classical pattern-recognition receptor, was now identified as an important regulator in immune homeostasis and cancer immunity through its extensive ligands binding functions and subsequent cytokines production. The aim of this study was to assess the clinical significance of dectin-1 expression in 290 patients with clear cell renal cell carcinoma (ccRCC) through immunohistochemistry on tissue microarrays. We found that dectin-1 was predominantly expressed on ccRCC cells, in accordance with several other online databases. Moreover, Kaplan-Meier method was conducted and high expression of tumoral dectin-1 was associated with shorter patient recurrence free survival (RFS) and overall survival (OS) (P < 0.001 for both). In multivariate analyses, tumoral dectin-1 expression was also confirmed as an independent prognostic factor for patients' survival together with other clinical parameters (P < 0.001 for RFS and OS). After incorporating these characteristics including tumoral dectin-1 expression, two nomograms were constructed to predict ccRCC patients' RFS and OS (c-index 0.796 and 0.812, respectively) and performed better than existed integrated models (P < 0.001 for all models comparisons). In conclusion, high tumoral dectin-1 expression was an independent predictor of adverse clinical outcome in ccRCC patients. This molecule and established nomograms might help clinicians in future decision making and therapeutic developments. PMID:27600310

  8. Oxygen desaturation in 6-min walk test is a risk factor for adverse outcomes in COPD.

    PubMed

    Waatevik, Marie; Johannessen, Ane; Gomez Real, Francisco; Aanerud, Marianne; Hardie, Jon Andrew; Bakke, Per Sigvald; Lind Eagan, Tomas Mikal

    2016-07-01

    The 6-min walk test (6MWT) is an exercise test that measures functional status in chronic obstructive pulmonary disease (COPD) patients and provides information on oxygen desaturation. We investigated oxygen desaturation during 6MWT as a risk factor for important COPD outcomes: mortality, frequency of exacerbations, decline in lung function and decline in lean body mass.433 COPD patients were included in the Bergen COPD Cohort Study 2006-2009, and followed-up for 3 years. Patients were characterised using spirometry, bioelectrical impedance measurements, Charlson comorbidity score, exacerbation history, smoking and arterial blood gases. 370 patients completed the 6MWT at the baseline of the study. Information on all-cause mortality was collected in 2011.Patients who experienced oxygen desaturation during the 6MWT had an approximately twofold increased risk of death (hazard ratio 2.4, 95% CI 1.2-5.1), a 50% increased risk for experiencing later COPD exacerbations (incidence rate ratio 1.6, 95% CI 1.1-2.2), double the yearly rate of decline in both forced vital capacity and forced expiratory volume in 1 s (3.2% and 1.7% versus 1.7% and 0.9%, respectively) and manifold increased yearly rate of loss of lean body mass (0.18 kg·m(-2) versus 0.03 kg·m(-2) among those who did not desaturate).Desaturating COPD patients had a significantly worse prognosis than non-desaturating COPD patients, for multiple important disease outcomes. PMID:27076586

  9. Outcome Preferences in Patients With Noninfectious Uveitis: Results of a Best–Worst Scaling Study

    PubMed Central

    Yu, Tsung; Holbrook, Janet T.; Thorne, Jennifer E.; Flynn, Terry N.; Van Natta, Mark L.; Puhan, Milo A.

    2015-01-01

    Purpose To estimate patient preferences regarding potential adverse outcomes of local versus systemic corticosteroid therapies for noninfectious uveitis by using a best–worst scaling (BWS) approach. Methods Local and systemic therapies are alternatives for noninfectious uveitis that have different potential adverse outcomes. Patients participating in the Multicenter Uveitis Steroid Treatment Trial Follow-up Study (MUST FS) and additional patients with a history of noninfectious uveitis treated at two academic medical centers (Johns Hopkins University and University of Pennsylvania) were surveyed about their preferences regarding six adverse outcomes deemed important to patients. Using “case 1” BWS, patients were asked to repeatedly select the most and least worrying from a list of outcomes (in the survey three outcomes per task). Results Eighty-two patients in the MUST FS and 100 patients treated at the academic medical centers completed the survey. According to BWS, patients were more likely to select vision not meeting the requirement for driving (individual BWS score: median = 3, interquartile range, 0–5), development of glaucoma (2, 1–4), and needing eye surgery (1, 0–3) as the most worrying outcomes as compared to needing medicine for high blood pressure/cholesterol (−2, −4 to 0), development of cataracts (−2, −3 to −1), or infection (sinusitis) (−3, −5 to 0). Larger BWS scores indicated the outcomes were more worrying to patients. Conclusions Patients with noninfectious uveitis considered impaired vision, development of glaucoma, and need for eye surgery worrying adverse outcomes, which suggests that it is especially desirable to avoid these outcomes if possible. (ClinicalTrials.gov number, NCT00132691.) PMID:26501236

  10. Periodontal disease as a risk factor for adverse pregnancy outcomes: a systematic review and meta-analysis of case-control studies.

    PubMed

    Corbella, Stefano; Taschieri, Silvio; Francetti, Luca; De Siena, Francesca; Del Fabbro, Massimo

    2012-07-01

    Periodontal disease is a highly prevalent group of illnesses of microbial etiology, whose consequence is a severe breakdown of tooth-supporting structures. A link between periodontal infection and several systemic conditions, among which adverse pregnancy outcomes, has been suggested in the recent years. The aim of this review based on case-control studies was to evaluate if periodontal disease could be considered as a risk factor for preterm birth, low birth-weight and preterm low birth-weight. An electronic search (via Pubmed) was performed for case-control studies investigating the relationship between periodontal disease and adverse pregnancy outcomes. From the initially retrieved 417 articles, 17 case-control studies, accounting for a total of 10,148 patients, were included in the review and in the meta-analysis. The estimated odds ratio was 1.78 (CI 95%: 1.58, 2.01) for preterm birth, 1.82 (CI 95%: 1.51, 1.20) for low birth-weight and 3.00 (CI 95%: 1.93, 4.68) for preterm low birth-weight. Despite the results of the analysis of pooled data suggested a link between periodontal diseases and adverse pregnancy outcomes, the presence of important confounders, whose effect could not be addressed, prevents a validation of the meta-analysis outcomes. Further more accurate investigations based on individual data analysis could give a better insight into the topic of the present review. PMID:21739194

  11. Mercury in fish and adverse reproductive outcomes: results from South Carolina

    PubMed Central

    2014-01-01

    Background Mercury is a metal with widespread distribution in aquatic ecosystems and significant neurodevelopmental toxicity in humans. Fish biomonitoring for total mercury has been conducted in South Carolina (SC) since 1976, and consumption advisories have been posted for many SC waterways. However, there is limited information on the potential reproductive impacts of mercury due to recreational or subsistence fish consumption. Methods To address this issue, geocoded residential locations for live births from the Vital Statistics Registry (1995–2005, N = 362,625) were linked with spatially interpolated total mercury concentrations in fish to estimate potential mercury exposure from consumption of locally caught fish. Generalized estimating equations were used to test the hypothesis that risk of low birth weight (LBW, <2,500 grams) or preterm birth (PTB, <37 weeks clinical gestation) was greater among women living in areas with elevated total mercury in fish, after adjustment for confounding. Separate analyses estimated term LBW and PTB risks using residential proximity to rivers with fish consumption advisories to characterize exposure. Results Term LBW was more likely among women residing in areas in the upper quartile of predicted total mercury in fish (odds ratio [OR] = 1.04; 95% confidence interval [CI]: 1.00-1.09) or within 8 kilometers of a river with a ‘do not eat’ fish advisory (1.05; 1.00-1.11) compared to the lowest quartile, or rivers without fish consumption restrictions, respectively. When stratified by race, risks for term LBW or PTB were 10-18% more likely among African-American (AA) mothers living in areas with the highest total fish mercury concentrations. Conclusions To our knowledge, this is the first study to examine the relationship between fish total mercury concentrations and adverse reproductive outcomes in a large population-based sample that included AA women. The ecologic nature of exposure assessment in this study

  12. Human Cytomegalovirus-Induces Cytokine Changes in the Placenta with Implications for Adverse Pregnancy Outcomes

    PubMed Central

    Hamilton, Stuart T.; Scott, Gillian; Naing, Zin; Iwasenko, Jenna; Hall, Beverley; Graf, Nicole; Arbuckle, Susan; Craig, Maria E.; Rawlinson, William D.

    2012-01-01

    Human cytomegalovirus (CMV) infection of the developing fetus can result in adverse pregnancy outcomes including death in utero. Fetal injury results from direct viral cytopathic damage to the CMV-infected fetus, although evidence suggests CMV placental infection may indirectly cause injury to the fetus, possibly via immune dysregulation with placental dysfunction. This study investigated the effects of CMV infection on expression of the chemokine MCP-1 (CCL2) and cytokine TNF-α in placentae from naturally infected stillborn babies, and compared these changes with those found in placental villous explant histocultures acutely infected with CMV ex vivo. Tissue cytokine protein levels were assessed using quantitative immunohistochemistry. CMV-infected placentae from stillborn babies had significantly elevated MCP-1 and TNF-α levels compared with uninfected placentae (p = 0.001 and p = 0.007), which was not observed in placentae infected with other microorganisms (p = 0.62 and p = 0.71) (n = 7 per group). Modelling acute clinical infection using ex vivo placental explant histocultures showed infection with CMV laboratory strain AD169 (0.2 pfu/ml) caused significantly elevated expression of MCP-1 and TNF-α compared with uninfected explants (p = 0.0003 and p<0.0001) (n = 25 per group). Explant infection with wild-type Merlin at a tenfold lower multiplicity of infection (0.02 pfu/ml), caused a significant positive correlation between increased explant infection and upregulation of MCP-1 and TNF-α expression (p = 0.0001 and p = 0.017). Cytokine dysregulation has been associated with adverse outcomes of pregnancy, and can negatively affect placental development and function. These novel findings demonstrate CMV infection modulates the placental immune environment in vivo and in a multicellular ex vivo model, suggesting CMV-induced cytokine modulation as a potential initiator and/or exacerbator of placental and fetal injury. PMID

  13. A Workflow to Investigate Exposure and Pharmacokinetic Influences on High-Throughput in Vitro Chemical Screening Based on Adverse Outcome Pathways

    EPA Science Inventory

    Background: Adverse outcome pathways (AOPs) link adverse effects in individuals or populations to a molecular initiating event (MIE) that can be quantified using in vitro methods. Practical application of AOPs in chemical-specific risk assessment requires incorporation of knowled...

  14. Outcomes and Adverse Events of Enlarged Tracheoesophageal Puncture after Total Laryngectomy

    PubMed Central

    Hutcheson, Katherine A.; Lewin, Jan S.; Sturgis, Erich M.; Risser, Jan

    2014-01-01

    Objective Enlargement of the tracheoesophageal puncture (TEP) results in aspiration around the voice prosthesis (VP) and may lead to pneumonia. The primary objective was to summarize control of leakage around the VP after conservative management of enlarged TEP. Study Design Retrospective cohort study. Methods This 5-year cohort included 194 patients who underwent total laryngectomy (± pharyngectomy) and TEP at the University of Texas MD Anderson Cancer Center. Control of leakage around the VP was analyzed at last follow-up after enlarged TEP. Adverse events were compared in patients with and without enlarged TEP. Results The incidence of enlarged TEP was 18.6% (36/194, 95% CI: 13.0%-24.1%). Conservative methods commonly attempted in lieu of complete TEP closure included placement of an enlarged-flange VP (34/36, 94%), temporary VP removal (14/36, 39%), and TEP-site injection (8/36, 22%). At last follow-up, conservative methods controlled leakage around the VP in 81% (29/36) of patients. Only 2 patients required complete TEP closure due to persistent leakage after enlarged TEP. Unresolved leakage was more common in patients with recurrent cancer after laryngectomy (p=0.081) and irregular TEP contour (p=0.003). Relative to controls without TEP enlargement, patients with enlarged TEP had 3-fold higher risk of pneumonia (RR: 3.4, 95% CI: 1.9-6.2) and aspiration of the prosthesis (RR: 3.3, 95% CI: 0.8-14.1). Conclusions Although the rate of enlarged TEP is relatively low, the complication significantly elevates risk of pneumonia. Prosthetic leakage related to TEP enlargement can often be managed conservatively to avoid complete closure of the TEP. Level of evidence: 2b PMID:21647906

  15. Oligohydramnios in Women with Preterm Prelabor Rupture of Membranes and Adverse Pregnancy and Neonatal Outcomes

    PubMed Central

    Kacerovsky, Marian; Musilova, Ivana; Andrys, Ctirad; Drahosova, Marcela; Hornychova, Helena; Rezac, Adam; Kostal, Milan; Jacobsson, Bo

    2014-01-01

    Objective To determine the association between the presence of oligohydramnios, determined as an amniotic fluid index ≤ 5 cm and the intra-amniotic inflammatory response, fetal inflammatory response and neonatal outcomes in actively managed preterm prelabor rupture of membranes (PPROM). Methods Women with singleton pregnancies complicated by PPROM at a gestational age of between 24+0 and 36+6 weeks were included in the study. Ultrasound assessments of the amniotic fluid index and evaluation of the amniotic fluid interleukin (IL)-6 levels were performed at admission. The umbilical cord blood IL-6 levels were evaluated after delivery. Results In total, 74 women were included. The women with oligohydramnios did not have different amniotic fluid IL-6 levels [with oligohydramnios: median 342 pg/mL, interquartile range (IQR) 110-1809 vs. without oligohydramnios: median 256 pg/mL, IQR 122–748; p = 0.71] or umbilical cord blood IL-6 levels (with oligohydramnios: median 8.2 pg/mL, IQR 3.8–146.9 vs. without oligohydramnios: median 5.9 pg/mL, IQR 2.1–27.9; p = 0.14) than those without oligohydramnios. No association between oligohydramnios and neonatal morbidity was found. A correlation between the amniotic fluid index and the interval from rupture of membranes to amniocentesis was observed (rho = −0.34; p = 0.003). Conclusion The presence of oligohydramnios is not associated with an adverse outcome in actively managed PPROM in singleton pregnancies in the absence of other complications. PMID:25171293

  16. Inadequate gestational weight gain and adverse pregnancy outcomes among normal weight women in China

    PubMed Central

    Wen, Tingyuan; Lv, Yanwei

    2015-01-01

    Objective: The objective of the paper is to find the association between inadequate gestational weight gain and pregnancy outcomes in normal weight women in China. Method: A retrospective study was conducted among 13,776 normal weight pregnant women who received antenatal care and delivered singleton infants at the participating hospital during August, 2009 to July, 2013. Adverse pregnancy outcomes like low birth weight (LBW), preterm birth, birth asphyxia, neonatal intensive care unit (NICU) admission and length of hospital stay were compared and analyzed between two groups with inadequate and adequate gestational weight gain. Results: According to the IOM recommendations, inadequate gestational weight gain was found to be 14.7% in this study. Women with inadequate gestational weight gain (GWG) were found to be at a higher risk for LBW (aOR = 2.13, 95% CI: 1.75, 2.86) and preterm birth (aOR = 1.44, 95% CI: 1.21, 1.67) than those in the adequate gestational weight gain group, after adjusting for monthly family income, maternal education, occupation, and whether they received any advice regarding benefits of gestational weight gain and residential area. However, inadequate GWG was not associated with longer hospital stay (aOR = 1.13, 95% CI: 0.91-1.43) in adjusted model. In addition, the rate of birth asphyxia and NICU admission were similar in both groups (P > 0.05). Conclusions: Normal weight pregnant women with GWG below the recommended AIOM 2009 guidelines were found to be at an increased risk of low birth weight and preterm birth. PMID:25932249

  17. Prenatal Exposure to Tetrachloroethylene-Contaminated Drinking Water and the Risk of Adverse Birth Outcomes

    PubMed Central

    Aschengrau, Ann; Weinberg, Janice; Rogers, Sarah; Gallagher, Lisa; Winter, Michael; Vieira, Veronica; Webster, Thomas; Ozonoff, David

    2008-01-01

    Background Prior studies of prenatal exposure to tetrachloroethylene (PCE) have shown mixed results regarding its effect on birth weight and gestational age. Objectives In this retrospective cohort study we examined whether PCE contamination of public drinking-water supplies in Massachusetts influenced the birth weight and gestational duration of children whose mothers were exposed before the child’s delivery. Methods The study included 1,353 children whose mothers were exposed to PCE-contaminated drinking water and a comparable group of 772 children of unexposed mothers. Birth records were used to identify subjects and provide information on the outcomes. Mothers completed a questionnaire to gather information on residential histories and confounding variables. PCE exposure was estimated using EPANET water distribution system modeling software that incorporated a fate and transport model. Results We found no meaningful associations between PCE exposure and birth weight or gestational duration. Compared with children whose mothers were unexposed during the year of the last menstrual period (LMP), adjusted mean differences in birth weight were 20.9, 6.2, 30.1, and 15.2 g for children whose mothers’ average monthly exposure during the LMP year ranged from the lowest to highest quartile. Similarly, compared with unexposed children, adjusted mean differences in gestational age were −0.2, 0.1, −0.1, and −0.2 weeks for children whose mothers’ average monthly exposure ranged from the lowest to highest quartile. Similar results were observed for two other measures of prenatal exposure. Conclusions These results suggest that prenatal PCE exposure does not have an adverse effect on these birth outcomes at the exposure levels experienced by this population. PMID:18560539

  18. Prevalence of Adverse Pregnancy Outcomes, by Maternal Diabetes Status at First and Second Deliveries, Massachusetts, 1998–2007

    PubMed Central

    Kotelchuck, Milton; Wilson, Hoyt G.; Diop, Hafsatou; Shapiro-Mendoza, Carrie K.; England, Lucinda J.

    2015-01-01

    Introduction Understanding patterns of diabetes prevalence and diabetes-related complications across pregnancies could inform chronic disease prevention efforts. We examined adverse birth outcomes by diabetes status among women with sequential, live singleton deliveries. Methods We used data from the 1998–2007 Massachusetts Pregnancy to Early Life Longitudinal Data System, a population-based cohort of deliveries. We restricted the sample to sets of parity 1 and 2 deliveries. We created 8 diabetes categories using gestational diabetes mellitus (GDM) and chronic diabetes mellitus (CDM) status for the 2 deliveries. Adverse outcomes included large for gestational age (LGA), macrosomia, preterm birth, and cesarean delivery. We computed prevalence estimates for each outcome by diabetes status. Results We identified 133,633 women with both parity 1 and 2 deliveries. Compared with women who had no diabetes in either pregnancy, women with GDM or CDM during any pregnancy had increased risk for adverse birth outcomes; the prevalence of adverse outcomes was higher in parity 1 deliveries among women with no diabetes in parity 1 and GDM in parity 2 (for LGA [8.5% vs 15.1%], macrosomia [9.7% vs. 14.9%], cesarean delivery [24.7% vs 31.3%], and preterm birth [7.7% vs 12.9%]); and higher in parity 2 deliveries among those with GDM in parity 1 and no diabetes in parity 2 (for LGA [12.3% vs 18.2%], macrosomia [12.3% vs 17.2%], and cesarean delivery [27.0% vs 37.9%]). Conclusions Women with GDM during one of 2 sequential pregnancies had elevated risk for adverse outcomes in the unaffected pregnancy, whether the diabetes-affected pregnancy preceded or followed it. PMID:26652218

  19. Internal exposure dynamics drive the Adverse Outcome Pathways of synthetic glucocorticoids in fish

    NASA Astrophysics Data System (ADS)

    Margiotta-Casaluci, Luigi; Owen, Stewart F.; Huerta, Belinda; Rodríguez-Mozaz, Sara; Kugathas, Subramanian; Barceló, Damià; Rand-Weaver, Mariann; Sumpter, John P.

    2016-02-01

    The Adverse Outcome Pathway (AOP) framework represents a valuable conceptual tool to systematically integrate existing toxicological knowledge from a mechanistic perspective to facilitate predictions of chemical-induced effects across species. However, its application for decision-making requires the transition from qualitative to quantitative AOP (qAOP). Here we used a fish model and the synthetic glucocorticoid beclomethasone dipropionate (BDP) to investigate the role of chemical-specific properties, pharmacokinetics, and internal exposure dynamics in the development of qAOPs. We generated a qAOP network based on drug plasma concentrations and focused on immunodepression, skin androgenisation, disruption of gluconeogenesis and reproductive performance. We showed that internal exposure dynamics and chemical-specific properties influence the development of qAOPs and their predictive power. Comparing the effects of two different glucocorticoids, we highlight how relatively similar in vitro hazard-based indicators can lead to different in vivo risk. This discrepancy can be predicted by their different uptake potential, pharmacokinetic (PK) and pharmacodynamic (PD) profiles. We recommend that the development phase of qAOPs should include the application of species-species uptake and physiologically-based PK/PD models. This integration will significantly enhance the predictive power, enabling a more accurate assessment of the risk and the reliable transferability of qAOPs across chemicals.

  20. Adverse Outcomes Among Homeless Adolescents and Young Adults Who Report a History of Traumatic Brain Injury

    PubMed Central

    Harpin, Scott B.; Grubenhoff, Joseph A.; Rivara, Frederick P.

    2014-01-01

    Objectives. We examined the prevalence of self-reported traumatic brain injury (TBI) among homeless young people and explored whether sociodemographic characteristics, mental health diagnoses, substance use, exposure to violence, or difficulties with activities of daily living (ADLs) were associated with TBI. Methods. We analyzed data from the Wilder Homelessness Study, in which participants were recruited in 2006 and 2009 from streets, shelters, and locations in Minnesota that provide services to homeless individuals. Participants completed 30-minute interviews to collect information about history of TBI, homelessness, health status, exposure to violence (e.g., childhood abuse, assault), and other aspects of functioning. Results. Of the 2732 participating adolescents and young adults, 43% reported a history of TBI. Participants with TBI became homeless at a younger age and were more likely to report mental health diagnoses, substance use, suicidality, victimization, and difficulties with ADLs. The majority of participants (51%) reported sustaining their first injury prior to becoming homeless or at the same age of their first homeless episode (10%). Conclusions. TBI occurs frequently among homeless young people and is a marker of adverse outcomes such as mental health difficulties, suicidal behavior, substance use, and victimization. PMID:25122029

  1. Adverse Outcome Pathways and Ecological Risk Assessment: Bridging to Population-Level Effects

    SciTech Connect

    Kramer, Vincent J.; Etterson, Matthew A.; Hecker, Markus; Murphy, Cheryl A.; Roesijadi, Guritno; Spade, Daniel J.; Spromberg, Julann A.; Wang, Magnus; Ankley, Gerald T.

    2010-11-24

    The viability of populations of plants and animals is a key focus for environmental regulation. Population-level responses integrate the cumulative effects of chemical stressors on individuals as those individuals interact with and are affected by their con-specifics, competitors, predators, prey, habitat and other biotic and abiotic factors. Models of population-level effects of contaminants can integrate information from lower levels of biological organization and feed that information into higher-level community and ecosystem models. As individual-level endpoints are utilized to predict population responses, this requires that biological responses at lower levels of organization be translated into a form that is useable by the population modeler. In this paper we describe how mechanistic data, as captured in adverse outcome pathways, can be translated into modeling focused on population-level risk assessments. First, we present a succinct overview of different approaches to population modeling, and discuss the types of data needed for these models. Then we discuss how toxicity data are used currently for population modeling, and provide recommendations as to how testing might be modified to better generate information to support modeling. From this we describe how different key processes measured at the level of the individual serve as the bridge between mechanistic toxicology data and predictions of population status, and provide case examples of how this linkage has been/can be achieved.

  2. Adverse pregnancy outcomes in relation to water contamination, Santa Clara County, California, 1980-1981

    SciTech Connect

    Deane, M.; Swan, S.H.; Harris, J.A.; Epstein, D.M.; Neutra, R.R.

    1989-05-01

    An epidemiologic study was conducted to investigate a suspected cluster of adverse outcomes of pregnancies conceived in 1980-1981 among women who resided in a census tract in Santa Clara County, California that was thought to be exposed to drinking water from a well contaminated by an organic solvent, trichloroethane. A comparison census tract that received water from a different source was selected on the basis of demographic comparability. The cluster was confirmed; the odds ratio for spontaneous abortion was 2.3 (95% confidence interval (Cl) 1.3-4.2) after adjustment by multiple logistic regression for maternal risk factors, including maternal age, alcohol consumption, smoking, and prior fetal loss. The relative risk for congenital malformations was 3.1 (95% Cl 1.1-10.4). Because of the lack of precise information on the timing and extent of contamination, the pattern of spontaneous abortion rates throughout the study period cannot be used to either support or refute a causal inference.

  3. Periodontal disease and some adverse perinatal outcomes in a cohort of low risk pregnant women

    PubMed Central

    2010-01-01

    Objective To evaluate the association of periodontal disease (PD) in pregnancy with some adverse perinatal outcomes. Method This cohort study included 327 pregnant women divided in groups with or without PD. Indexes of plaque and gingival bleeding on probing, probing pocket depth, clinical attachment level and gingival recession were evaluated at one periodontal examination below 32 weeks of gestation. The rates of preterm birth (PTB), low birth weight (LBW), small for gestational age (SGA) neonates and prelabor rupture of membranes (PROM) were evaluated using Risk Ratios (95%CI) and Population Attributable Risk Fractions. Results PD was associated with a higher risk of PTB (RRadj. 3.47 95%CI 1.62-7.43), LBW (RRadj. 2.93 95%CI 1.36-6.34) and PROM (RRadj. 2.48 95%CI 1.35-4.56), but not with SGA neonates (RR 2.38 95%CI 0.93 - 6.10). Conclusions PD was a risk factor for PT, LBW and PROM among Brazilian low risk pregnant women. PMID:21047427

  4. Internal exposure dynamics drive the Adverse Outcome Pathways of synthetic glucocorticoids in fish

    PubMed Central

    Margiotta-Casaluci, Luigi; Owen, Stewart F.; Huerta, Belinda; Rodríguez-Mozaz, Sara; Kugathas, Subramanian; Barceló, Damià; Rand-Weaver, Mariann; Sumpter, John P.

    2016-01-01

    The Adverse Outcome Pathway (AOP) framework represents a valuable conceptual tool to systematically integrate existing toxicological knowledge from a mechanistic perspective to facilitate predictions of chemical-induced effects across species. However, its application for decision-making requires the transition from qualitative to quantitative AOP (qAOP). Here we used a fish model and the synthetic glucocorticoid beclomethasone dipropionate (BDP) to investigate the role of chemical-specific properties, pharmacokinetics, and internal exposure dynamics in the development of qAOPs. We generated a qAOP network based on drug plasma concentrations and focused on immunodepression, skin androgenisation, disruption of gluconeogenesis and reproductive performance. We showed that internal exposure dynamics and chemical-specific properties influence the development of qAOPs and their predictive power. Comparing the effects of two different glucocorticoids, we highlight how relatively similar in vitro hazard-based indicators can lead to different in vivo risk. This discrepancy can be predicted by their different uptake potential, pharmacokinetic (PK) and pharmacodynamic (PD) profiles. We recommend that the development phase of qAOPs should include the application of species-species uptake and physiologically-based PK/PD models. This integration will significantly enhance the predictive power, enabling a more accurate assessment of the risk and the reliable transferability of qAOPs across chemicals. PMID:26917256

  5. Internal exposure dynamics drive the Adverse Outcome Pathways of synthetic glucocorticoids in fish.

    PubMed

    Margiotta-Casaluci, Luigi; Owen, Stewart F; Huerta, Belinda; Rodríguez-Mozaz, Sara; Kugathas, Subramanian; Barceló, Damià; Rand-Weaver, Mariann; Sumpter, John P

    2016-01-01

    The Adverse Outcome Pathway (AOP) framework represents a valuable conceptual tool to systematically integrate existing toxicological knowledge from a mechanistic perspective to facilitate predictions of chemical-induced effects across species. However, its application for decision-making requires the transition from qualitative to quantitative AOP (qAOP). Here we used a fish model and the synthetic glucocorticoid beclomethasone dipropionate (BDP) to investigate the role of chemical-specific properties, pharmacokinetics, and internal exposure dynamics in the development of qAOPs. We generated a qAOP network based on drug plasma concentrations and focused on immunodepression, skin androgenisation, disruption of gluconeogenesis and reproductive performance. We showed that internal exposure dynamics and chemical-specific properties influence the development of qAOPs and their predictive power. Comparing the effects of two different glucocorticoids, we highlight how relatively similar in vitro hazard-based indicators can lead to different in vivo risk. This discrepancy can be predicted by their different uptake potential, pharmacokinetic (PK) and pharmacodynamic (PD) profiles. We recommend that the development phase of qAOPs should include the application of species-species uptake and physiologically-based PK/PD models. This integration will significantly enhance the predictive power, enabling a more accurate assessment of the risk and the reliable transferability of qAOPs across chemicals. PMID:26917256

  6. Adverse outcome pathway and risks of anticoagulant rodenticides to predatory wildlife

    USGS Publications Warehouse

    Rattner, Barnett A.; Lazarus, Rebecca; Elliott, John E.; Shore, Richard F.; van den Brink, Nico

    2014-01-01

    Despite a long history of successful use, routine application of some anticoagulant rodenticides (ARs) may be at a crossroad due to new regulatory guidelines intended to mitigate risk. An adverse outcome pathway for ARs was developed to identify information gaps and end points to assess the effectiveness of regulations. This framework describes chemical properties of ARs, established macromolecular interactions by inhibition of vitamin K epoxide reductase, cellular responses including altered clotting factor processing and coagulopathy, organ level effects such as hemorrhage, organism responses with linkages to reduced fitness and mortality, and potential consequences to predator populations. Risk assessments have led to restrictions affecting use of some second-generation ARs (SGARs) in North America. While the European regulatory community highlighted significant or unacceptable risk of ARs to nontarget wildlife, use of SGARs in most EU member states remains authorized due to public health concerns and the absence of safe alternatives. For purposes of conservation and restoration of island habitats, SGARs remain a mainstay for eradication of invasive species. There are significant data gaps related to exposure pathways, comparative species sensitivity, consequences of sublethal effects, potential hazards of greater AR residues in genetically resistant prey, effects of low-level exposure to multiple rodenticides, and quantitative data on the magnitude of nontarget wildlife mortality.

  7. Adverse Outcome Pathways can drive non-animal approaches for safety assessment.

    PubMed

    Burden, Natalie; Sewell, Fiona; Andersen, Melvin E; Boobis, Alan; Chipman, J Kevin; Cronin, Mark T D; Hutchinson, Thomas H; Kimber, Ian; Whelan, Maurice

    2015-09-01

    Adverse Outcome Pathways (AOPs) provide an opportunity to develop new and more accurate safety assessment processes for drugs and other chemicals, and may ultimately play an important role in regulatory decision making. Not only can the development and application of AOPs pave the way for the development of improved evidence-based approaches for hazard and risk assessment, there is also the promise of a significant impact on animal welfare, with a reduced reliance on animal-based methods. The establishment of a useable and coherent knowledge framework under which AOPs will be developed and applied has been a first critical step towards realizing this opportunity. This article explores how the development of AOPs under this framework, and their application in practice, could benefit the science and practice of safety assessment, while in parallel stimulating a move away from traditional methods towards an increased acceptance of non-animal approaches. We discuss here the key areas where current, and future initiatives should be focused to enable the translation of AOPs into routine chemical safety assessment, and lasting 3Rs benefits. PMID:25943792

  8. Quantitative Adverse Outcome Pathway Analysis of Hatching in Zebrafish with CuO Nanoparticles.

    PubMed

    Muller, Erik B; Lin, Sijie; Nisbet, Roger M

    2015-10-01

    This study develops and evaluates a mechanistic model of the hatching of zebrafish eggs that were exposed to CuO engineered nanoparticles (ENP) in a high-throughput screening system and places this model in an adverse outcome pathway (AOP) that also includes CuO ENP dissolution and Cu bioaccumulation. Cu(2+) inhibits the proteolytic activity of Zebrafish Hatching Enzyme 1 and thereby delay or impair hatching success. This study demonstrates that noncompetitive inhibition kinetics describe the impact of dissolved Cu on hatching; it is estimated that indefinitely long exposure to 1.88 μM dissolved Cu in the environment reduces hatching enzyme activity by 50%. The complexity arising from CuO ENP dissolution and CuO ENP assisted bioaccumulation of Cu has led to apparently contradictory findings about ion versus "nano" effects on hatching. Model-mediated data analyses indicate that, relative to copper salts, CuO ENPs increase the uptake rates of Cu into the perivitelline space up to 8 times. The toxicity assessment framework in this study can be adapted to accommodate other types of toxicant, environmental samples and other aquatic oviparous species. PMID:26378804

  9. Adverse neuro-immune-endocrine interactions in patients with active tuberculosis.

    PubMed

    Bottasso, Oscar; Bay, María Luisa; Besedovsky, Hugo; Del Rey, Adriana

    2013-03-01

    The nervous, endocrine and immune systems play a crucial role in maintaining homeostasis and interact with each other for a successful defensive strategy against injurious agents. However, the situation is different in long-term diseases with marked inflammation, in which defensive mechanisms become altered. In the case of tuberculosis (TB), this is highlighted by several facts: an imbalance of plasma immune and endocrine mediators, that results in an adverse environment for mounting an adequate response against mycobacteria and controlling inflammation; the demonstration that dehidroepiandrosterone (DHEA) secretion by a human adrenal cell line can be inhibited by culture supernatants from Mycobacterium tuberculosis-stimulated peripheral blood mononuclear cells - PBMC - of TB patients, with this effect being partly reverted when neutralizing transforming growth factor-β in such supernantants; the in vitro effects of adrenal steroids on the specific immune response of PBMC from TB patients, that is a cortisol inhibition of mycobacterial antigen-driven lymphoproliferation and interferon-γ production as well as a suppression of TGF-β production in DHEA-treated PBMC; and lastly the demonstration that immune and endocrine compounds participating in the regulation of energy sources and immune activity correlated with the consumption state of TB patients. Collectively, immune-endocrine disturbances of TB patients are involved in critical components of disease pathology with implications in the impaired clinical status and unfavorable disease outcome. This article is part of a Special Issue entitled 'Neuroinflammation in neurodegeneration and neurodysfunction'. PMID:23147110

  10. Do sugar-sweetened beverages cause adverse health outcomes in children? A systematic review protocol

    PubMed Central

    2014-01-01

    Background Cardiovascular disease and type 2 diabetes are examples of chronic diseases that impose significant morbidity and mortality in the general population worldwide. Most chronic diseases are associated with underlying preventable risk factors, such as elevated blood pressure, high blood glucose or glucose intolerance, high lipid levels, physical inactivity, excessive sedentary behaviours, and overweight/obesity. The occurrence of intermediate outcomes during childhood increases the risk of disease in adulthood. Sugar-sweetened beverages are known to be significant sources of additional caloric intake, and given recent attention to their contribution in the development of chronic diseases, a systematic review is warranted. We will assess whether the consumption of sugar-sweetened beverages in children is associated with adverse health outcomes and what the potential moderating factors are. Methods/Design Of interest are studies addressing sugar-sweetened beverage consumption, taking a broad perspective. Both direct consumption studies as well as those evaluating interventions that influence consumption (e.g. school policy, educational) will be relevant. Non-specific or multi-faceted behavioural, educational, or policy interventions may also be included subject to the level of evidence that exists for the other interventions/exposures. Comparisons of interest and endpoints of interest are pre-specified. We will include randomized controlled trials, controlled clinical trials, interrupted time series studies, controlled before-after studies, prospective and retrospective comparative cohort studies, case–control studies, and nested case–control designs. The MEDLINE®, Embase, The Cochrane Library, CINAHL, ERIC, and PsycINFO® databases and grey literature sources will be searched. The processes for selecting studies, abstracting data, and resolving conflicts are described. We will assess risk of bias using design-specific tools. To determine sets of

  11. Building an Adverse Outcome Pathway Framework through HTS Data and Literature Mining Integration (FutureToxII)

    EPA Science Inventory

    Interpreting EPA’s ToxCast in vitro assay data in the context of Adverse Outcome Pathway (AOP) development is a significant challenge. While chemical activation in these assays may shed light on the molecular initiating event, the downstream effect of these activities at higher ...

  12. Discovering and annotating fish early life-stage (FELS) adverse outcome pathways: Putting the research strategy into practice

    EPA Science Inventory

    In May 2012, a HESI-sponsored expert workshop yielded a proposed research strategy for systematically discovering, characterizing, and annotating fish early life-stage (FELS) adverse outcome pathways (AOPs) as well as prioritizing AOP development in light of current restrictions ...

  13. Increasing scientific confidence in adverse outcome pathways: Application of tailored Bradford-Hill considerations for evaluating weight of evidence

    EPA Science Inventory

    Systematic consideration of scientific support is a critical element in developing and, ultimately, using adverse outcome pathways (AOPs) for various regulatory applications. Though weight of evidence (WoE) analysis has been proposed as a basis for assessment of the maturity and...

  14. Weight of evidence evaluation of adverse outcome pathways converging at impaired vitellogenin synthesis leading to reproductive impairment

    EPA Science Inventory

    Adverse outcome pathways (AOPs) provide a framework that supports greater use of mechanistic data measured at lower levels of biological organization as a basis for regulatory decision-making. However, it is recognized that different types of regulatory applications and decisions...

  15. Physiologically-based Pharmacokinetic(PBPK) Models Application to Screen Environmental Hazards Related to Adverse Outcome Pathways(AOPs)

    EPA Science Inventory

    PBPK models are useful in estimating exposure levels based on in vitro to in vivo extrapolation (IVIVE) calculations. Linkage of large sets of chemically screened vitro signature effects to in vivo adverse outcomes using IVIVE is central to the concepts of toxicology in the 21st ...

  16. Adverse Outcome Pathway (AOP) for a Mutagenic Mode of Action for Cancer: AFB1 and Hepatocellular Carcinoma (HCC)

    EPA Science Inventory

    AOPs provide a framework to describe a sequence of measureable key events (KEs), beginning with a molecular initiating event (MIE), followed by a series of identified KEs linked to one another by KE Relationships (KERs), all anchored by a specific adverse outcome (AO). Each KE/KE...

  17. Using adverse outcome pathway analysis to guide development of high-throughput screening assays for thyroid-disruptors

    EPA Science Inventory

    Using Adverse Outcome Pathway Analysis to Guide Development of High-Throughput Screening Assays for Thyroid-Disruptors Katie B. Paul1,2, Joan M. Hedge2, Daniel M. Rotroff4, Kevin M. Crofton4, Michael W. Hornung3, Steven O. Simmons2 1Oak Ridge Institute for Science Education Post...

  18. Maternal adverse effects of different antenatal magnesium sulphate regimens for improving maternal and infant outcomes: a systematic review

    PubMed Central

    2013-01-01

    Background Antenatal magnesium sulphate, widely used in obstetrics to improve maternal and infant outcomes, may be associated with adverse effects for the mother sufficient for treatment cessation. This systematic review aimed to quantify maternal adverse effects attributed to treatment, assess how adverse effects vary according to different regimens, and explore women’s experiences with this treatment. Methods Bibliographic databases were searched from their inceptions to July 2012 for studies of any design that reported on maternal adverse effects associated with antenatal magnesium sulphate given to improve maternal or infant outcomes. Primary outcomes were life-threatening adverse effects of treatment (death, cardiac arrest, respiratory arrest). For randomised controlled trials, data were meta-analysed, and risk ratios (RR) pooled using fixed-effects or random-effects models. For non-randomised studies, data were tabulated by design, and presented as RR, odds ratios or percentages, and summarised narratively. Results A total of 143 publications were included (21 randomised trials, 15 non-randomised comparative studies, 32 case series and 75 reports of individual cases), of mixed methodological quality. Compared with placebo or no treatment, magnesium sulphate was not associated with an increased risk of maternal death, cardiac arrest or respiratory arrest. Magnesium sulphate significantly increased the risk of 'any adverse effects’ overall (RR 4.62, 95% CI 2.42-8.83; 4 trials, 13,322 women), and treatment cessation due to adverse effects (RR 2.77; 95% CI 2.32-3.30; 5 trials, 13,666 women). Few subgroup differences were observed (between indications for use and treatment regimens). In one trial, a lower dose regimen (2 g/3 hours) compared with a higher dose regimen (5 g/4 hours) significantly reduced treatment cessation (RR 0.05; 95% CI 0.01-0.39, 126 women). Adverse effect estimates from studies of other designs largely supported data from randomised

  19. Risk of adverse birth outcomes in populations living near landfill sites

    PubMed Central

    Elliott, Paul; Briggs, David; Morris, Sara; de Hoogh, Cornelis; Hurt, Christopher; Jensen, Tina Kold; Maitland, Ian; Richardson, Sylvia; Wakefield, Jon; Jarup, Lars

    2001-01-01

    Objective To investigate the risk of adverse birth outcomes associated with residence near landfill sites in Great Britain. Design Geographical study of risks of adverse birth outcomes in populations living within 2 km of 9565 landfill sites operational at some time between 1982 and 1997 (from a total of 19 196 sites) compared with those living further away. Setting Great Britain. Subjects Over 8.2 million live births, 43 471 stillbirths, and 124 597 congenital anomalies (including terminations). Main outcome measures All congenital anomalies combined, some specific anomalies, and prevalence of low and very low birth weight (<2500 g and <1500 g). Results For all anomalies combined, relative risk of residence near landfill sites (all waste types) was 0.92 (99% confidence interval 0.907 to 0.923) unadjusted, and 1.01 (1.005 to 1.023) adjusted for confounders. Adjusted risks were 1.05 (1.01 to 1.10) for neural tube defects, 0.96 (0.93 to 0.99) for cardiovascular defects, 1.07 (1.04 to 1.10) for hypospadias and epispadias (with no excess of surgical correction), 1.08 (1.01 to 1.15) for abdominal wall defects, 1.19 (1.05 to 1.34) for surgical correction of gastroschisis and exomphalos, and 1.05 (1.047 to 1.055) and 1.04 (1.03 to 1.05) for low and very low birth weight respectively. There was no excess risk of stillbirth. Findings for special (hazardous) waste sites did not differ systematically from those for non-special sites. For some specific anomalies, higher risks were found in the period before opening compared with after opening of a landfill site, especially hospital admissions for abdominal wall defects. Conclusions We found small excess risks of congenital anomalies and low and very low birth weight in populations living near landfill sites. No causal mechanisms are available to explain these findings, and alternative explanations include data artefacts and residual confounding. Further studies are needed to help differentiate between the various

  20. No adverse effects were identified on the perinatal outcomes after laser-assisted hatching treatment.

    PubMed

    Zhou, Hanying; Zao, Wanqiu; Zhang, Wei; Shi, Juanzi; Shi, Wenhao

    2014-12-01

    The aim of this study was to evaluate the safety of laser-assisted hatching (LAH) by comparing obstetric and neonatal outcomes between assisted hatching and control groups in cryopreserved embryo transfer cycles. A retrospective cohort analysis was carried out. A total of 699 women with 392 infants delivered were included. Laser- assisted hatching was carried out on D-3 thawed and warmed embryos before transfer in 480 cryopreserved embryos transfer cycles. Obstetric outcomes, neonatal outcomes, and congenital birth defects were recorded. A total of 815 cryopreserved embryo transfer cycles (480 in LAH group and 335 in control group) in 699 patients were analysed. Statistically significantly higher implantation (31.85% versus 16.95%), clinical pregnancy (53.96% versus 33.43%) and live delivery (44.58% versus 23.88%) rates were observed in the LAH group (all P < 0.001). For either singleton or multiple gestations, no statistically significant differences were found in mean gestational age, mean birth weight and mean Apgar score. Four major malformations occurred in the assisted hatching group and three malformations (one major and two minor) in the control group. This study did not identify any harmful effect of LAH on neonates, which suggested that LAH may be a safe treatment in cryopreserved embryo transfer cycles. PMID:25444502

  1. Orthogeriatric care: improving patient outcomes

    PubMed Central

    Tarazona-Santabalbina, Francisco José; Belenguer-Varea, Ángel; Rovira, Eduardo; Cuesta-Peredó, David

    2016-01-01

    Hip fractures are a very serious socio-economic problem in western countries. Since the 1950s, orthogeriatric units have introduced improvements in the care of geriatric patients admitted to hospital because of hip fractures. During this period, these units have reduced mean hospital stays, number of complications, and both in-hospital mortality and mortality over the middle term after hospital discharge, along with improvements in the quality of care and a reduction in costs. Likewise, a recent clinical trial has reported greater functional gains among the affected patients. Studies in this field have identified the prognostic factors present upon admission or manifesting themselves during admission and that increase the risk of patient mortality or disability. In addition, improved care afforded by orthogeriatric units has proved to reduce costs. Nevertheless, a number of management issues remain to be clarified, such as the optimum anesthetic, analgesic, and thromboprophylactic protocols; the type of diagnostic and therapeutic approach best suited to patients with cognitive problems; or the efficiency of the programs used in convalescence units or in home rehabilitation care. Randomized clinical trials are needed to consolidate the evidence in this regard. PMID:27445466

  2. Adverse events during intrahospital transport of critically ill patients: incidence and risk factors

    PubMed Central

    2013-01-01

    Background Transport of critically ill patients for diagnostic or therapeutic procedures is at risk of complications. Adverse events during transport are common and may have significant consequences for the patient. The objective of the study was to collect prospectively adverse events that occurred during intrahospital transports of critically ill patients and to determine their risk factors. Methods This prospective, observational study of intrahospital transport of consecutively admitted patients with mechanical ventilation was conducted in a 38-bed intensive care unit in a university hospital from May 2009 to March 2010. Results Of 262 transports observed (184 patients), 120 (45.8%) were associated with adverse events. Risk factors were ventilation with positive end-expiratory pressure >6 cmH2O, sedation before transport, and fluid loading for intrahospital transports. Within these intrahospital transports with adverse events, 68 (26% of all intrahospital transports) were associated with an adverse event affecting the patient. Identified risk factors were: positive end-expiratory pressure >6 cmH2O, and treatment modification before transport. In 44 cases (16.8% of all intrahospital transports), adverse event was considered serious for the patient. In our study, adverse events did not statistically increase ventilator-associated pneumonia, time spent on mechanical ventilation, or length of stay in the intensive care unit. Conclusions This study confirms that the intrahospital transports of critically ill patients leads to a significant number of adverse events. Although in our study adverse events have not had major consequences on the patient stay, efforts should be made to decrease their incidence. PMID:23587445

  3. Culprit versus non-culprit lesion related adverse cardiac events in patients with obstructive sleep apnoea

    PubMed Central

    Li, Ruogu; Loh, Kelvin; Loo, Germaine; Tai, Bee-Choo; Lee, Chi-Hang

    2013-01-01

    Background In patients with obstructive sleep apnoea (OSA), the relative contribution of culprit versus non-culprit lesions to subsequent major adverse cardiac events (MACE) after acute myocardial infarction (AMI) remains unknown. Elucidating this relationship will shed light on the contributions of OSA to the advancement of coronary artery disease. Methods In a cohort of 105 patients who underwent an overnight sleep study after AMI, 98 were diagnosed with OSA (Apnoea–Hypopnoea Index (AHI) ≥5). The clinical outcomes at 5-year follow-up were determined. MACE was defined as a composite of cardiac death, reinfarction and repeat revascularisation. A culprit lesion was defined as the lesion involved in the initial AMI, and a non-culprit lesion as any lesion in the entire coronary tree outside the culprit lesion. Results Eighteen patients (median AHI: 28.1) developed MACE, of whom 12 presented with reinfarction and 6 with repeat revascularisation for stable angina. There was no cardiac death. Based on repeated coronary angiography, the MACE was related to the culprit lesion in 4 patients and the non-culprit lesion in 12 patients. The lesion responsible for the MACE was indeterminate in 2 patients, as coronary angiography was declined. The median duration from index AMI to culprit lesion-related and non-culprit lesion-related MACE were 10.5 and 20 months, respectively. Conclusions The incidence of MACE among patients with OSA and AMI was 18.4%, and most of the events were related to non-culprit lesions rather than the culprit lesion during the initial AMI.

  4. Metal-on-Metal Hip Arthroplasty: A Review of Adverse Reactions and Patient Management.

    PubMed

    Drummond, James; Tran, Phong; Fary, Camdon

    2015-01-01

    Recent alarming joint registry data highlighting increased revision rates has prompted further research into the area of metal-on-metal hip replacements and resurfacings. This review article examines the latest literature on the topic of adverse reactions to metal debris and summarises the most up-to-date guidelines on patient management. Adverse reactions to metal debris can cause significant damage to soft tissue and bone if not diagnosed early. Furthermore, not every patient with an adverse reaction to metal debris will be symptomatic. As such, clinicians must remain vigilant when assessing and investigating these patients in order to detect failing implants and initiate appropriate management. PMID:26132653

  5. Multidisciplinary in-hospital teams improve patient outcomes: A review

    PubMed Central

    Epstein, Nancy E.

    2014-01-01

    Background: The use of multidisciplinary in-hospital teams limits adverse events (AE), improves outcomes, and adds to patient and employee satisfaction. Methods: Acting like “well-oiled machines,” multidisciplinary in-hospital teams include “staff” from different levels of the treatment pyramid (e.g. staff including nurses’ aids, surgical technicians, nurses, anesthesiologists, attending physicians, and others). Their enhanced teamwork counters the “silo effect” by enhancing communication between the different levels of healthcare workers and thus reduces AE (e.g. morbidity/mortality) while improving patient and healthcare worker satisfaction. Results: Multiple articles across diverse disciplines incorporate a variety of concepts of “teamwork” for staff covering emergency rooms (ERs), hospital wards, intensive care units (ICUs), and most critically, operating rooms (ORs). Cohesive teamwork improved communication between different levels of healthcare workers, and limited adverse events, improved outcomes, decreased the length of stay (LOS), and yielded greater patient “staff” satisfaction. Conclusion: Within hospitals, delivering the best medical/surgical care is a “team sport.” The goals include: Maximizing patient safety (e.g. limiting AE) and satisfaction, decreasing the LOS, and increasing the quality of outcomes. Added benefits include optimizing healthcare workers’ performance, reducing hospital costs/complications, and increasing job satisfaction. This review should remind hospital administrators of the critical need to keep multidisciplinary teams together, so that they can continue to operate their “well-oiled machines” enhancing the quality/safety of patient care, while enabling “staff” to optimize their performance and enhance their job satisfaction. PMID:25289149

  6. Promoting positive outcomes in obese patients.

    PubMed

    Troia, Cecilia

    2002-01-01

    Obese patients are seen in every practice setting. Obesity is a chronic disease that may lead to physical and emotional problems, which may have an impact on the social and psychological functioning of the patient. With appropriate preoperative, intraoperative, and postoperative precautions; monitoring; and restructuring the environment to promote care and safety, the incidence of poor surgical outcomes can be minimized. This paper will address the significance of obesity, related diseases, and proper care of the obese patient. PMID:12035338

  7. Dectin-1 predicts adverse postoperative prognosis of patients with clear cell renal cell carcinoma

    PubMed Central

    Xia, Yu; Liu, Li; Bai, Qi; Wang, Jiajun; Xi, Wei; Qu, Yang; Xiong, Ying; Long, Qilai; Xu, Jiejie; Guo, Jianming

    2016-01-01

    Dectin-1, a classical pattern-recognition receptor, was now identified as an important regulator in immune homeostasis and cancer immunity through its extensive ligands binding functions and subsequent cytokines production. The aim of this study was to assess the clinical significance of dectin-1 expression in 290 patients with clear cell renal cell carcinoma (ccRCC) through immunohistochemistry on tissue microarrays. We found that dectin-1 was predominantly expressed on ccRCC cells, in accordance with several other online databases. Moreover, Kaplan-Meier method was conducted and high expression of tumoral dectin-1 was associated with shorter patient recurrence free survival (RFS) and overall survival (OS) (P < 0.001 for both). In multivariate analyses, tumoral dectin-1 expression was also confirmed as an independent prognostic factor for patients’ survival together with other clinical parameters (P < 0.001 for RFS and OS). After incorporating these characteristics including tumoral dectin-1 expression, two nomograms were constructed to predict ccRCC patients’ RFS and OS (c-index 0.796 and 0.812, respectively) and performed better than existed integrated models (P < 0.001 for all models comparisons). In conclusion, high tumoral dectin-1 expression was an independent predictor of adverse clinical outcome in ccRCC patients. This molecule and established nomograms might help clinicians in future decision making and therapeutic developments. PMID:27600310

  8. Association of the Frontal QRS-T Angle with Adverse Cardiac Remodeling, Impaired Left and Right Ventricular Function, and Worse Outcomes in Heart Failure with Preserved Ejection Fraction

    PubMed Central

    Selvaraj, Senthil; Ilkhanoff, Leonard; Burke, Michael A.; Freed, Benjamin H.; Lang, Roberto M.; Martinez, Eva E.; Shah, Sanjiv J.

    2013-01-01

    Background No prior studies have investigated the association of QRS-T angle with cardiac structure/function and outcomes in heart failure with preserved ejection fraction (HFpEF). We hypothesized that increased frontal QRS-T angle is associated with worse cardiac function/remodeling and adverse outcomes in HFpEF. Methods We prospectively studied 376 patients with HFpEF (i.e. symptomatic HF with left ventricular [LV] ejection fraction >50%.) The frontal QRS-T angle was calculated from the 12-lead electrocardiogram. Patients were divided into tertiles by frontal QRS-T angle (0–26°, 27–75°, and 76–179°), and clinical, laboratory, and echocardiographic data were compared among groups. Cox proportional hazards analyses were performed to determine the association between QRS-T angle and outcomes. Results The mean age of the cohort was 64±13 years, 65% were women, and the mean QRS-T angle was 61±51°. Patients with increased QRS-T angle were older, had a lower body-mass index, more frequently had coronary artery disease, diabetes, chronic kidney disease, and atrial fibrillation, and had higher B-type natriuretic peptide (BNP) levels (P<0.05 for all comparisons). After multivariable adjustment, patients with increased QRS-T angle had higher BNP levels in addition to higher LV mass index, worse diastolic function parameters, more right ventricular (RV) remodeling, and worse RV systolic function (P<0.05 for all associations). QRS-T angle was independently associated with the composite outcome of cardiovascular hospitalization or death on multivariable analysis, even after adjusting for BNP (HR for the highest QRS-T tertile = 2.0, 95% CI 1.2–3.4; P=0.008). Conclusions In HFpEF, increased QRS-T angle is independently associated with worse left and right ventricular function/remodeling and adverse outcomes. PMID:24075945

  9. Vital Sign Prediction of Adverse Maternal Outcomes in Women with Hypovolemic Shock: The Role of Shock Index

    PubMed Central

    El Ayadi, Alison M.; Nathan, Hannah L.; Seed, Paul T.; Butrick, Elizabeth A.; Hezelgrave, Natasha L.; Shennan, Andrew H.; Miller, Suellen

    2016-01-01

    Objective To determine the optimal vital sign predictor of adverse maternal outcomes in women with hypovolemic shock secondary to obstetric hemorrhage and to develop thresholds for referral/intensive monitoring and need for urgent intervention to inform a vital sign alert device for low-resource settings. Study Design We conducted secondary analyses of a dataset of pregnant/postpartum women with hypovolemic shock in low-resource settings (n = 958). Using receiver-operating curve analysis, we evaluated the predictive ability of pulse, systolic blood pressure, diastolic blood pressure, shock index, mean arterial pressure, and pulse pressure for three adverse maternal outcomes: (1) death, (2) severe maternal outcome (death or severe end organ dysfunction morbidity); and (3) a combined severe maternal and critical interventions outcome comprising death, severe end organ dysfunction morbidity, intensive care admission, blood transfusion ≥ 5 units, or emergency hysterectomy. Two threshold parameters with optimal rule-in and rule-out characteristics were selected based on sensitivities, specificities, and positive and negative predictive values. Results Shock index was consistently among the top two predictors across adverse maternal outcomes. Its discriminatory ability was significantly better than pulse and pulse pressure for maternal death (p<0.05 and p<0.01, respectively), diastolic blood pressure and pulse pressure for severe maternal outcome (p<0.01), and systolic and diastolic blood pressure, mean arterial pressure and pulse pressure for severe maternal outcome and critical interventions (p<0.01). A shock index threshold of ≥ 0.9 maintained high sensitivity (100.0) with clinical practicality, ≥ 1.4 balanced specificity (range 70.0–74.8) with negative predictive value (range 93.2–99.2), and ≥ 1.7 further improved specificity (range 80.7–90.8) without compromising negative predictive value (range 88.8–98.5). Conclusions For women with hypovolemic

  10. Application of the structured history taking of medication use tool to optimise prescribing for older patients and reduce adverse events.

    PubMed

    Cullinan, Shane; O'Mahony, Denis; Byrne, Stephen

    2016-04-01

    Background Older patients, due to polypharmacy, co-morbidities and often multiple prescribing doctors are particularly susceptible to medication history errors, leading to adverse drug events, patient harm and increased costs. Medication reconciliation at the point of admission to hospital can reduce medication discrepancies and adverse events. The Structured HIstory taking of Medication use (SHiM) tool was developed to provide a structure to the medication reconciliation process. There has been very little research with regards to SHiM, it's application to older patients and it's potential to reduce adverse events. Objective To determine whether application of SHiM could optimise older patients' prescriptions on admission to hospital, and in-turn reduce adverse events, compared to standard care. Setting A sub-study of a large clinical trial involving hospital inpatients over the age of 65 in five hospitals across Europe. Method A modified version of SHiM was used to obtain accurate drug histories for patients after the attending physician had obtained a medication list via standard methods. Discrepancies between the two lists were recorded and classified, and the clinical relevance of the discrepancies was determined. Whether discrepancies in patients' medication histories, as revealed by SHiM, resulted in actual clinical consequences was then investigated. As this study was carried out during the observation phase of the clinical trial, results were not communicated to the medical teams. Main outcome measure Discrepancies between medication lists and whether these resulted in clinical consequences. Results SHiM was applied to 123 patients. The mean age of the participants was 78 (±6). 200 discrepancies were identified. 90 patients (73 %) had at least one discrepancy with a median of 1.0 discrepancies per patient (IQR 0.00-2.25). 53 (26.5 %) were classified as 'unlikely to cause patient discomfort or clinical deterioration', 145 (72.5 %) as 'having potential

  11. A meta-analysis of exposure to particulate matter and adverse birth outcomes

    PubMed Central

    2015-01-01

    Objectives The objective of this study was to conduct a systematic review to provide summarized evidence on the association between maternal exposure to particulate air pollution and birth weight (BW) and preterm birth (PTB) after taking into consideration the potential confounding effect of maternal smoking. Methods We systematically searched all published cohort and case-control studies examining BW and PTB association with particulate matter (PM, less than or equal to 2.5μm and 10.0 μm in diameter, PM2.5 and PM10, respectively) from PubMed and Web of Science, from January 1980 to April 2015. We extracted coefficients for continuous BW and odds ratio (OR) for PTB from each individual study, and meta-analysis was used to combine the coefficient and OR of individual studies. The methodological quality of individual study was assessed using a standard protocol proposed by Downs and Black. Forty-four studies met the inclusion criteria. Results In random effects meta-analyses, BW as a continuous outcome was negativelyassociated with 10 μg/m3 increase in PM10 (-10.31 g; 95% confidence interval [CI], -13.57 to -3.13 g; I-squared=0%, p=0.947) and PM2.5 (-22.17 g; 95% CI, -37.93 to -6.41 g; I-squared=92.3%, p <0.001) exposure during entire pregnancy, adjusted for maternal smoking. A significantly increased risk of PTB per 10 μg/m3 increase in PM10 (OR, 1.23; 95% CI, 1.04 to 1.41; I-squared=0%, p =0.977) and PM2.5 (OR, 1.14; 95% CI, 1.06 to 1.22; I-squared=92.5%, p <0.001) exposure during entire pregnancy was observed. Effect size of change in BW per 10 μg/m3 increase in PM tended to report stronger associations after adjustment for maternal smoking. Conclusions While this systematic review supports an adverse impact of maternal exposure to particulate air pollution on birth outcomes, variation in effects by exposure period and sources of heterogeneity between studies should be further explored. PMID:26796890

  12. Do sugar-sweetened beverages cause adverse health outcomes in adults? A systematic review protocol

    PubMed Central

    2014-01-01

    Background Chronic diseases, such as cardiovascular disease and type 2 diabetes, impose significant burden to public health. Most chronic diseases are associated with underlying preventable risk factors, such as elevated blood pressure, blood glucose, and lipids, physical inactivity, excessive sedentary behaviours, overweight and obesity, and tobacco usage. Sugar-sweetened beverages are known to be significant sources of additional caloric intake, and given recent attention to their contribution in the development of chronic diseases, a systematic review is warranted. We will assess whether the consumption of sugar-sweetened beverages in adults is associated with adverse health outcomes and what the potential moderating factors are. Methods/Design Of interest are studies addressing sugar-sweetened beverage consumption, taking a broad perspective. Both direct consumption studies as well as those evaluating interventions that influence consumption (e.g. school policy, educational) will be relevant. Non-specific or multi-faceted behavioural, educational, or policy interventions may also be included subject to the level of evidence that exists for the other interventions/exposures. Comparisons of interest and endpoints of interest are pre-specified. We will include randomized controlled trials, controlled clinical trials, interrupted time series studies, controlled before-after studies, prospective and retrospective comparative cohort studies, case-control studies, and nested case-control designs. The MEDLINE®, Embase, The Cochrane Library, CINAHL, ERIC, and PsycINFO® databases and grey literature sources will be searched. The processes for selecting studies, abstracting data, and resolving conflicts are described. We will assess risk of bias using design-specific tools. To determine sets of confounding variables that should be adjusted for, we have developed causal directed acyclic graphs and will use those to inform our risk of bias assessments. Meta-analysis will

  13. Antiretroviral adherence and treatment outcomes among adult Ethiopian patients.

    PubMed

    Bezabhe, Woldesellassie M; Chalmers, Leanne; Bereznicki, Luke R; Gee, Peter; Peterson, Gregory M

    2016-08-01

    Developing appropriate strategies to sustain optimal medication adherence among the increasing number of HIV-positive patients taking antiretroviral therapy (ART) in sub-Saharan Africa is a major challenge. The objective of this study was to determine patient, regimen, disease, patient-provider, and healthcare-related factors associated with adherence with ART over a one-year period, and assess the impact of adherence on treatment outcomes. We performed a prospective, observational study among 246 patients who were initiated on ART in Ethiopia. Of 172 who completed follow-up, 130 (75.6%) had ≥95% adherence. In the multivariate analyses, a higher baseline BMI (OR, 1.2; 95% CI 1.0, 1.4) and use of reminder devices (OR, 9.1; 95% CI 2.0, 41.6) remained positively associated with adherence, while a higher HIV symptom and adverse drug reaction distress score was an independent negative predictor of adherence (OR, 0.90; 95% CI 0.9, 1.0) CD4 count increase was significantly higher in the adherent patients compared to non-adherent patients at 12 months (159 cells/µL [interquartile range (IQR), 72-324 cells/µL] vs. 132 cells/µL [IQR, 43-190 cells/µL]; p = 0.026). Our findings indicate that interventions aimed at improving adherence and thereby treatment outcomes in patients initiated on ART should promote the use of reminder devices, and monitor HIV symptoms and adverse reaction distress and nutritional status. PMID:26829232

  14. Patient-reported Outcomes in Cystic Fibrosis

    PubMed Central

    Goss, Christopher H.; Quittner, Alexandra L.

    2007-01-01

    Over the past 20 years, there has been tremendous progress in the area of patient-reported outcomes (PROs). A PRO instrument is defined as any measure of a patient's health status that is elicited directly from the patient and assesses how the patient “feels or functions with respect to his or her health condition.” The advances seen in clinical research regarding PROs has been mirrored in research in cystic fibrosis (CF). A large number of instruments have been used for both therapeutic and nontherapeutic clinical research for many chronic conditions. This review will summarize a history of the development of PROs and how PROs are viewed by the U.S. Food and Drug Administration. We will then review the current state of the art of patient-reported outcomes in CF, specifically addressing the evaluation of different PRO instruments in terms of their reliability and validity. Finally, we will delineate further areas for development of PROs in CF. We believe that the future of CF research will incorporate a more diverse selection of PRO outcome measures; these outcome measures ultimately may be incorporated into clinical care to standardize symptom assessment and provide information regarding the need for specific clinical interventions to improve the quality of care delivered to these patients. PMID:17652505

  15. Taxonomic applicability of inflammatory cytokines in adverse outcome pathway (AOP) development.

    PubMed

    Angrish, Michelle M; Pleil, Joachim D; Stiegel, Matthew A; Madden, Michael C; Moser, Virginia C; Herr, David W

    2016-01-01

    Cytokines, low-molecular-weight messenger proteins that act as intercellular immunomodulatory signals, have become a mainstream preclinical marker for assessing the systemic inflammatory response to external stressors. The challenge is to quantitate from healthy subjects cytokine levels that are below or at baseline and relate those dynamic and complex cytokine signatures of exposures with the inflammatory and repair pathways. Thus, highly sensitive, specific, and precise analytical and statistical methods are critically important. Investigators at the U.S. Environmental Protection Agency (EPA) have implemented advanced technologies and developed statistics for evaluating panels of inflammatory cytokines in human blood, exhaled breath condensate, urine samples, and murine biological media. Advanced multiplex, bead-based, and automated analytical platforms provided sufficient sensitivity, precision, and accuracy over the traditional enzyme-linked immunosorbent assay (ELISA). Thus, baseline cytokine levels can be quantified from healthy human subjects and animals and compared to an in vivo exposure response from an environmental chemical. Specifically, patterns of cytokine responses in humans exposed to environmental levels of ozone and diesel exhaust, and in rodents exposed to selected pesticides (such as fipronil and carbaryl), were used as case studies to generally assess the taxonomic applicability of cytokine responses. The findings in this study may aid in the application of measureable cytokine markers in future adverse outcome pathway (AOP)-based toxicity testing. Data from human and animal studies were coalesced and the possibility of using cytokines as key events (KE) to bridge species responses to external stressors in an AOP-based framework was explored. PMID:26914248

  16. Peri-Implantation Hormonal Milieu: Elucidating Mechanisms of Adverse Neurodevelopmental Outcomes.

    PubMed

    Mainigi, Monica; Rosenzweig, Jason M; Lei, Jun; Mensah, Virginia; Thomaier, Lauren; Talbot, C Conover; Olalere, Devvora; Ord, Teri; Rozzah, Rayyan; Johnston, Michael V; Burd, Irina

    2016-06-01

    While live births resulting from assisted reproductive technology (ART) exceed 1% of total births annually, the effect of ART on fetal development is not well understood. Data have demonstrated that IVF leads to alterations in DNA methylation and gene expression in the placenta that may have long-term effects on health and disease. Studies have linked adverse neurodevelopmental outcomes to ART, although human studies are inconclusive. In order to isolate the peri-implantation environment and its effects on brain development, we utilized a mouse model with and without superovulation and examined the effect of adult behavior as well as adult cortical neuronal density. Adult offspring of superovulated dams showed increased anxiety-like behavior compared to offspring of naturally mated dams (P < .05). There was no difference in memory and learning tests between the 2 groups. The adult brains from offspring of superovulated recipients had fewer neurons per field compared to naturally mated control offspring (P < .05). In order to examine potential pathways leading to these changes, we measured messenger RNA and microRNA (miRNA) expression in fetal brains at E18.5. Microarray analysis found that miRNAs miR-122, miR-144, and miR-211, involved in regulation of neuronal migration and differentiation, were downregulated in brains of offspring exposed to a superovulated environment(P < .05). There was also altered expression of genes involved in neuronal development. These results suggest that the peri-implantation environment can affect neurodevelopment and can lead to behavioral changes in adulthood. Human studies with long-term follow-up of children from ART are necessary to further investigate the influence of ART on the offspring. PMID:26614264

  17. Limitations of toxicity characterization in life cycle assessment: Can adverse outcome pathways provide a new foundation?

    PubMed

    Gust, Kurt A; Collier, Zachary A; Mayo, Michael L; Stanley, Jacob K; Gong, Ping; Chappell, Mark A

    2016-07-01

    Life cycle assessment (LCA) has considerable merit for holistic evaluation of product planning, development, production, and disposal, with the inherent benefit of providing a forecast of potential health and environmental impacts. However, a technical review of current life cycle impact assessment (LCIA) methods revealed limitations within the biological effects assessment protocols, including: simplistic assessment approaches and models; an inability to integrate emerging types of toxicity data; a reliance on linear impact assessment models; a lack of methods to mitigate uncertainty; and no explicit consideration of effects in species of concern. The purpose of the current study is to demonstrate that a new concept in toxicological and regulatory assessment, the adverse outcome pathway (AOP), has many useful attributes of potential use to ameliorate many of these problems, to expand data utility and model robustness, and to enable more accurate and defensible biological effects assessments within LCIA. Background, context, and examples have been provided to demonstrate these potential benefits. We additionally propose that these benefits can be most effectively realized through development of quantitative AOPs (qAOPs) crafted to meet the needs of the LCIA framework. As a means to stimulate qAOP research and development in support of LCIA, we propose 3 conceptual classes of qAOP, each with unique inherent attributes for supporting LCIA: 1) mechanistic, including computational toxicology models; 2) probabilistic, including Bayesian networks and supervised machine learning models; and 3) weight of evidence, including models built using decision-analytic methods. Overall, we have highlighted a number of potential applications of qAOPs that can refine and add value to LCIA. As the AOP concept and support framework matures, we see the potential for qAOPs to serve a foundational role for next-generation effects characterization within LCIA. Integr Environ Assess Manag

  18. Quality of community drinking water and the occurrence of late adverse pregnancy outcomes.

    PubMed

    Aschengrau, A; Zierler, S; Cohen, A

    1993-01-01

    The relationship between community drinking water quality and the occurrence of late adverse pregnancy outcomes was investigated by conducting a case-control study among women who delivered infants during August 1977 through March 1980 at Brigham and Women's Hospital in Massachusetts. The water quality indices were compared among 1,039 congenital anomaly cases, 77 stillbirth cases, 55 neonatal death cases, and 1,177 controls. Trace element levels were gathered from routine analyses of public water supplies from the communities in which the women resided during pregnancy. It was observed that, after adjustment for confounding, the frequency of stillbirths was increased for women exposed to chlorinated surface water (OR 2.6 95% CI 0.9-7.5) and for women exposed to detectable lead levels (OR 2.1; 95% CI 0.6-7.2); the frequency of cardiovascular defects was increased relative to detectable lead levels (OR 2.2, 95% CI 0.9-5.7); and the frequency of central nervous system defects was increased relative to the highest tertile of potassium (OR 6.3, 95% CI 1.1-37.3). The frequency of ear, face, and neck anomalies was increased in relation to detectable silver levels (OR 3.3, 95% CI 0.9-12.2), but the frequency decreased relative to high potassium levels (OR 0.2, 95% CI 0.1-0.7). The frequency of neonatal deaths was decreased relative to detectable fluoride levels (OR 0.4, 95% CI 0.2-1.0), and the frequency of musculoskeletal defects was decreased relative to detectable chromium levels (OR 0.4, 95% CI 0.2-1.0). The majority of these associations were not stable statistically. Further research is needed to corroborate these findings. PMID:8476301

  19. Birth malformations and other adverse perinatal outcomes in four U.S. Wheat-producing states.

    PubMed Central

    Schreinemachers, Dina M

    2003-01-01

    Chlorophenoxy herbicides are widely used in the United States and Western Europe for broadleaf weed control in grain farming and park maintenance. Most of the spring and durum wheat produced in the United States is grown in Minnesota, Montana, North Dakota, and South Dakota, with more than 85% of the acreage treated with chlorophenoxy herbicides such as 2,4-dichlorophenoxyacetic acid (2,4-D) and 4-chloro-2-methylphenoxyacetic acid (MCPA). Rates of adverse birth outcomes in rural, agricultural counties of these states during 1995-1997 were studied by comparing counties with a high proportion of wheat acreage and those with a lower proportion. Information routinely collected and made available by federal agencies was used for this ecologic study. Significant increases in birth malformations were observed for the circulatory/respiratory category for combined sexes [odds ratio (OR) = 1.65; 95% confidence interval (CI), 1.07-2.55]. A stronger effect was observed for the subcategory, which excluded heart malformations (OR = 2.03; 95% CI, 1.14-3.59). In addition, infants conceived during April-June--the time of herbicide application--had an increased chance of being diagnosed with circulatory/respiratory (excluding heart) malformations compared with births conceived during other months of the year (OR = 1.75; 95% CI, 1.09-2.80). Musculoskeletal/integumental anomalies increased for combined sexes in the high-wheat counties (OR = 1.50; 95% CI, 1.06-2.12). Infant death from congenital anomalies significantly increased in high-wheat counties for males (OR = 2.66; 95% CI, 1.52-4.65) but not for females (OR = 0.48; 95% CI, 0.20-1.15). These results are especially of concern because of widespread use of chlorophenoxy herbicides. PMID:12842783

  20. Porphyromonas gingivalis within Placental Villous Mesenchyme and Umbilical Cord Stroma Is Associated with Adverse Pregnancy Outcome

    PubMed Central

    Vanterpool, Sizzle F.; Been, Jasper V.; Houben, Michiel L.; Nikkels, Peter G. J.; De Krijger, Ronald R.; Zimmermann, Luc J. I.; Kramer, Boris W.; Progulske-Fox, Ann; Reyes, Leticia

    2016-01-01

    Intrauterine presence of Porphyromonas gingivalis (Pg), a common oral pathobiont, is implicated in preterm birth. Our aim was to determine if the location of Pg within placental and/or umbilical cord sections was associated with a specific delivery diagnosis at preterm delivery (histologic chorioamnionitis, chorioamnionitis with funisitis, preeclampsia, and preeclampsia with HELLP-syndrome, small for gestational age). The prevalence and location of Pg within archived placental and umbilical cord specimens from preterm (25 to 32 weeks gestation) and term control cohorts were evaluated by immunofluorescent histology. Detection of Pg was performed blinded to pregnancy characteristics. Multivariate analyses were performed to evaluate independent effects of gestational age, being small for gestational age, specific preterm delivery diagnosis, antenatal steroids, and delivery mode, on the odds of having Pg in the preterm tissue. Within the preterm cohort, 49 of 97 (51%) placentas and 40 of 97 (41%) umbilical cord specimens were positive for Pg. Pg within the placenta was significantly associated with shorter gestation lengths (OR 0.63 (95%CI: 0.48–0.85; p = 0.002) per week) and delivery via caesarean section (OR 4.02 (95%CI: 1.15–14.04; p = 0.03), but not with histological chorioamnionitis or preeclampsia. However, the presence of Pg in the umbilical cord was significantly associated with preeclampsia: OR 6.73 (95%CI: 1.31–36.67; p = 0.02). In the term cohort, 2 of 35 (6%) placentas and no umbilical cord term specimens were positive for Pg. The location of Pg within the placenta was different between preterm and term groups in that Pg within the villous mesenchyme was only detected in the preterm cohort, whereas Pg associated with syncytiotrophoblasts was found in both preterm and term placentas. Taken together, our results suggest that the presence of Pg within the villous stroma or umbilical cord may be an important determinant in Pg-associated adverse pregnancy

  1. Maternal Factors and Adverse Perinatal Outcomes in Women with Preeclampsia in Maceió, Alagoas

    PubMed Central

    de Oliveira, Alane Cabral Menezes; Santos, Arianne Albuquerque; Bezerra, Alexandra Rodrigues; de Barros, Amanda Maria Rocha; Tavares, Myrian Cicyanne Machado

    2016-01-01

    Background Preeclampsia has been associated with several risk factors and events. However, it still deserves further investigation, considering the multitude of related factors that affect different populations. Objective To evaluate the maternal factors and adverse perinatal outcomes in a cohort of pregnant women with preeclampsia receiving care in the public health network of the city of Maceió. Methods Prospective cohort study carried out in 2014 in the public health network of the city with a sample of pregnant women calculated based on a prevalence of preeclampsia of 17%, confidence level of 90%, power of 80%, and ratio of 1:1. We applied a questionnaire to collect socioeconomic, personal, and anthropometric data, and retrieved perinatal variables from medical records and certificates of live birth. The analysis was performed with Poisson regression and chi-square test considering p values < 0.05 as significant. Results We evaluated 90 pregnant women with preeclampsia (PWP) and 90 pregnant women without preeclampsia (PWoP). A previous history of preeclampsia (prevalence ratio [PR] = 1.57, 95% confidence interval [95% CI] 1.47 - 1.67, p = 0.000) and black skin color (PR = 1.15, 95% CI 1.00 - 1.33, p = 0.040) were associated with the occurrence of preeclampsia. Among the newborns of PWP and PWoP, respectively, 12.5% and 13.1% (p = 0.907) were small for gestational age and 25.0% and 23.2% (p = 0.994) were large for gestational age. There was a predominance of cesarean delivery. Conclusion Personal history of preeclampsia and black skin color were associated with the occurrence of preeclampsia. There was a high frequency of birth weight deviations and cesarean deliveries. PMID:26761076

  2. Chronic fluoxetine treatment and maternal adversity differentially alter neurobehavioral outcomes in the rat dam.

    PubMed

    Pawluski, Jodi L; Charlier, Thierry D; Fillet, Marianne; Houbart, Virginie; Crispin, Hilda T; Steinbusch, Harry W; van den Hove, Daniël L

    2012-03-01

    The incidence of stress and stress-related disorders with the transition to motherhood, such as postpartum depression, is estimated to be 20%. Selective serotonin reuptake inhibitor (SSRI) medications are currently the antidepressant of choice to treat maternal mood disorders. However, little is known about the effects of these medications on the maternal brain and behavior. Therefore, the present study investigated how a commonly used SSRI, fluoxetine, affects neurobehavioral outcomes in the mother using a model of maternal adversity. To do this, gestationally stressed and non-stressed Sprague-Dawley rat dams were treated with either fluoxetine (5 mg/kg/day) or vehicle. Dams were divided into four groups: (1) Control + Vehicle, (2) Control + Fluoxetine, (3) Stress + Vehicle and (4) Stress + Fluoxetine. Fluoxetine or vehicle was administered to the dam during the postpartum period via osmotic minipump implants (Alzet) for 28 days. Results show that chronic fluoxetine treatment, after exposure to gestational stress, significantly decreased serum levels of corticosteroid binding globulin and increased hippocampal neurogenesis. In the absence of maternal stress, fluoxetine treatment alone significantly increased maternal arched-back nursing of pups, increased anxiety-related behavior, and decreased serum levels of corticosterone and corticosteroid binding globulin in the dam. This research provides important information on how SSRIs may act on the behavior, physiology, and neural plasticity of the mother. Although this is a first step in investigating the role of antidepressant treatment on the mother, much more work is needed before we can understand and improve the efficacy of these medications to treat mood disorders in pregnant and postpartum women. PMID:22173000

  3. EMPADE Study: Evaluation of Medical Prescriptions and Adverse Drug Events in COPD Patients Admitted to Intensive Care Unit

    PubMed Central

    Khan, M. Amer; Khan, M. Nematullah; Sultan, Ihtisham; Khan, M. Aamer; Ali, S. Amir; Farooqui, Afroze

    2015-01-01

    Introduction Inappropriate drug usage may preclude ideal benefit due to increased medical cost, antimicrobial resistance, adverse effects and mortality. Therefore drug utilization studies have become a plausible means in evaluating the healthcare systems. COPD management usually involves more than one drug which may escalate the risk of ADEs (adverse drug events). Aim The present study was aimed at assessing the current drug practice and ADEs in COPD management in ICU. Materials and Methods A total of 1,044 patients admitted for the treatment of COPD were included in the study. Their prescriptions were recorded for evaluation of drug utilization and patients were counseled for assessing ADEs. Results were evaluated by Chi-square test and percentages. Result All-embracing 15,360 drugs were prescribed at an average of 14.71 drugs per patient, wherein β2-agonists were extensively prescribed agents followed by inhaled-corticosteroids and anti-cholinergics. 372 ADEs were reported in 252 patients, wherein restlessness was the most frequent ADE and theophylline was found to be associated with highest cases of ADEs. Conclusion Practitioners should prescribe least number of drugs to mitigate the likelihood of adverse outcomes in patients due to numerous drugs usage, which may be achieved by following GOLD guidelines. The present work may help in improving the current management of COPD by rectifying the flaws delineated in this article. PMID:26675667

  4. Evaluation of Proper Usage of Glucocorticosteroid Inhalers and Their Adverse Effects in Asthmatic Patients

    PubMed Central

    Hejazi, Mohammad Esmayil; Shafiifar, Afsaneh; Mashayekhi, Siminozar

    2016-01-01

    Background: The frequent use of corticosteroid inhalers (CSIs), especially at higher doses, has been accompanied by concern about both systemic and local adverse reactions. The local adverse reactions of inhaled corticosteroids (ICSs) are considered to constitute infrequent and minor problems. However, while not usually serious, these local adverse reactions are of clinical importance. This study assessed the prevalence of local adverse reactions, their clinical features, role of inhaler devices and current measures that have been suggested to prevent the problem. Materials and Methods: This study was performed in YAS clinic in Tabriz on 500 asthmatic patients. A questionnaire about the patients’ demographic information, methods of using CSIs, local care after using CSIs, using spacer devices, doses of ICSs, and adverse reactions were filled then the patients were clinically examined for local adverse reactions. Results: Only 56% patients were using CSIs properly. In general, the incidence of complications was: oropharyngeal candidiasis 25.6%, laryngeal weakness 8.8%, choking 17.6%, tooth decay 15.2%, speechlessness 36.2%, taste decrease 20.8%, tongue burning 29.8% and tongue abrasion 27.8%. Conclusion: Persistent asthma can be effectively controlled with currently available CSIs. Although not life-threatening, local adverse reactions of ICSs are clinically significant and warrant attention. Use of spacer devices and changes in CSI usage, dosage amount and frequency and rinsing and gargling are the methods that have been used to reduce the incidence of local adverse reactions. PMID:27403173

  5. Adverse Clinical Outcome Associated With Mutations That Typify African American Colorectal Cancers.

    PubMed

    Wang, Zhenghe; Li, Li; Guda, Kishore; Chen, Zhengyi; Barnholtz-Sloan, Jill; Park, Young Soo; Markowitz, Sanford D; Willis, Joseph

    2016-12-01

    African Americans have the highest incidence and mortality from colorectal cancer (CRC) of any US racial group. We recently described a panel of 15 genes that are statistically significantly more likely to be mutated in CRCs from African Americans than in Caucasians (AA-CRC genes). The current study investigated the outcomes associated with these mutations in African American CRCs (AA-CRCs). In a cohort of 66 patients with stage I-III CRCs, eight of 27 CRCs with AA-CRC gene mutations (Mut+) developed metastatic disease vs only four of 39 mutation-negative (Mut-) cases (P = .03, Cox regression model with two-sided Wald test). Moreover, among stage III cases (n = 33), Mut+ cancers were nearly three times more likely to relapse as Mut- cases (7 of 15 Mut+ vs 3 of 18 Mut-; P = .03, Cox regression model with two-sided Wald test). AA-CRC mutations may thus define a high-risk subset of CRCs that contributes to the overall disparity in CRC outcomes observed in African Americans. PMID:27582379

  6. Periodontal bacteria in the genital tract: are they related to adverse pregnancy outcome?

    PubMed

    Cassini, M A; Pilloni, A; Condò, S G; Vitali, L A; Pasquantonio, G; Cerroni, L

    2013-01-01

    One of the most important factors implicated in preterm birth (PTB) is acute genitourinary tract infection. The bacteria causing chronic periodontal inflammation include Gram-negative rods and anaerobes similar to those found in women with bacterial vaginosis. The aim of this prospective study is to investigate the relationship between oral and vaginal microflora and preterm low birth weight. Real-time polymerase chain reaction was used to detect both the presence and level of six periodontitis-related species: Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Tannerella forsythia (Tf), Treponema denticola (Td), Fusobacterium nucleatum ssp(Fn), and Prevotella intermedia (Pi) for both oral samples of subgingival plaque and cervical samples, obtained from 80 patients, during gynaecological examinations. The more representative oral pathogen (less than 60 percent) species in oral samples of preterm and term group were Tf, Td, and Fn. 24.4 percent of pregnant women presented periodontal pathogens in vaginal swab; the most representative species with a percentage over 0.1 percent of total bacteria in genital tract of preterm group were Tf, Td, and Piwith a positive correlation (less than 0.5). The presence of the bacterium T. denticolain the vagina, regardless of the amount, adversely affects preterm delivery. PMID:24355228

  7. Determinants of outcome in patients eligible for thrombolysis for ischemic stroke

    PubMed Central

    Caso, Valeria; Paciaroni, Maurizio; Venti, Michele; Palmerini, Francesco; Silvestrelli, Giorgio; Milia, Paolo; Biagini, Sergio; Agnelli, Giancarlo

    2007-01-01

    Objectives Eligibility criteria for thrombolysis in ischemic stroke have been clearly defined. However, not all eligible patients benefit from this treatment. This study aimed to assess the determinants for clinical outcome in consecutive, eligible patients with ischemic stroke treated with thrombolysis in a single-center study. Methods Consecutive patients with ischemic stroke were treated with tissue plasminogen activator (t-PA) following the established eligibility National Institute of Neurological Disorders and Stroke (NINDS) and European Stroke Initiative (EUSI) criteria. Risk factors including blood pressure and pre-treatment glycemia were properly managed. Death and disability at 3 months were the study outcomes. Disability was evaluated by the Rankin-scale. Favorable outcome was defined as 0–2 and adverse outcome as 3–6 including death. Results Seventy-eight patients were included in the study in a single stroke unit. The mean age was 70.9 ± 13.2 years (range 36–94). Follow-up at 3 months was completed in 73 patients. A favorable outcome was observed in 37 patients (50%) and adverse outcome in 36 (36%). Nine patients (12.3%) died within 3 months. The presence of an occluded carotid artery was a strong predictor for adverse outcome (p < 0.0001). A low NIH Stroke Scale-Score (NIHSS) at admission was a associated with a favorable outcome, while history of diabetes mellitus led to an unfavorable outcome. Conclusion Among patients eligible for thrombolysis, many do not benefit from this treatment. These include patients with carotid occlusion and diabetes. PMID:18078026

  8. Attention-deficit/hyperactivity disorder and adverse health outcomes in adults.

    PubMed

    Spencer, Thomas J; Faraone, Stephen V; Tarko, Laura; McDermott, Katie; Biederman, Joseph

    2014-10-01

    Whereas the adverse impact of attention-deficit/hyperactivity disorder (ADHD) on emotional and psychosocial well-being has been well investigated, its impact on physical health has not. The main aim of this study was to assess the impact of ADHD on lifestyle behaviors and measures of adverse health risk indicators. Subjects were 100 untreated adults with ADHD and 100 adults without ADHD of similar age and sex. Unhealthy lifestyle indicators included assessments of bad health habits, frequency of visits to healthcare providers, and follow through with recommended prophylactic tests. Assessments of adverse health risk indicators included measurements of cardiovascular and metabolic parameters, weight, body mass index, and waist circumference. No differences were identified in health habits between subjects with and without ADHD, but robust differences were found in a wide range of adverse health risk indicators. ADHD is associated with an adverse impact in health risk indicators well known to be associated with high morbidity and mortality. PMID:25211634

  9. Maternal pre-pregnancy BMI and adverse pregnancy outcomes among Chinese women: Results from the C-ABCS.

    PubMed

    Ding, X-X; Xu, S-J; Hao, J-H; Huang, K; Su, P-Y; Tao, F-B

    2016-04-01

    The aim of this study was to investigate associations between pre-pregnancy body mass index (BMI) and adverse pregnancy outcomes among Chinese pregnant women. A prospective population-based cohort study was performed using data collected as part of the China-Anhui Birth Cohort Study or C-ABCS. A total of 13,121 pregnant women who received the first prenatal visit were enrolled from November 2008 to October 2010. Logistic regression analysis was used to calculate associations between pre-pregnancy BMI and pregnancy outcomes. Results indicated that the increased pre-pregnancy BMI was associated with a number of adverse pregnancy outcomes such as hypertensive disorder (adjusted relative risk (ARR) 2.3, 95% confidence interval [CI] 1.5-3.6), gestational diabetes (ARR 3.5, 95% CI 2.3-5.2), caesarean delivery (ARR 2.0, 95% CI 1.6-2.4), and medically indicated preterm delivery (ARR 1.8, 95% CI 1.1-2.9). Women with pre-pregnancy BMI above the normal range pose an increased risk of adverse pregnancy outcomes. PMID:26492517

  10. APCR, factor V gene known and novel SNPs and adverse pregnancy outcomes in an Irish cohort of pregnant women

    PubMed Central

    2010-01-01

    Background Activated Protein C Resistance (APCR), a poor anticoagulant response of APC in haemostasis, is the commonest heritable thrombophilia. Adverse outcomes during pregnancy have been linked to APCR. This study determined the frequency of APCR, factor V gene known and novel SNPs and adverse outcomes in a group of pregnant women. Methods Blood samples collected from 907 pregnant women were tested using the Coatest® Classic and Modified functional haematological tests to establish the frequency of APCR. PCR-Restriction Enzyme Analysis (PCR-REA), PCR-DNA probe hybridisation analysis and DNA sequencing were used for molecular screening of known mutations in the factor V gene in subjects determined to have APCR based on the Coatest® Classic and/or Modified functional haematological tests. Glycosylase Mediated Polymorphism Detection (GMPD), a SNP screening technique and DNA sequencing, were used to identify SNPs in the factor V gene of 5 APCR subjects. Results Sixteen percent of the study group had an APCR phenotype. Factor V Leiden (FVL), FV Cambridge, and haplotype (H) R2 alleles were identified in this group. Thirty-three SNPs; 9 silent SNPs and 24 missense SNPs, of which 20 SNPs were novel, were identified in the 5 APCR subjects. Adverse pregnancy outcomes were found at a frequency of 35% in the group with APCR based on Classic Coatest® test only and at 45% in the group with APCR based on the Modified Coatest® test. Forty-eight percent of subjects with FVL had adverse outcomes while in the group of subjects with no FVL, adverse outcomes occurred at a frequency of 37%. Conclusions Known mutations and novel SNPs in the factor V gene were identified in the study cohort determined to have APCR in pregnancy. Further studies are required to investigate the contribution of these novel SNPs to the APCR phenotype. Adverse outcomes including early pregnancy loss (EPL), preeclampsia (PET) and intrauterine growth restriction (IGUR) were not significantly more frequent

  11. Risk factors for adverse in-hospital outcomes in acute colonic diverticular hemorrhage

    PubMed Central

    Nagata, Naoyoshi; Niikura, Ryota; Aoki, Tomonori; Moriyasu, Shiori; Sakurai, Toshiyuki; Shimbo, Takuro; Sekine, Katsunori; Okubo, Hidetaka; Watanabe, Kazuhiro; Yokoi, Chizu; Akiyama, Junichi; Yanase, Mikio; Mizokami, Masashi; Fujimoto, Kazuma; Uemura, Naomi

    2015-01-01

    AIM: To investigate the factors associated with transfusion, further bleeding, and prolonged length of stay. METHODS: In total, 153 patients emergently hospitalized for diverticular bleeding who were examined by colonoscopy were prospectively enrolled. Patients in whom the bleeding source was identified received endoscopic treatment such as clipping or endoscopic ligation. After spontaneous cessation of bleeding with conservative treatment or hemostasis with endoscopic treatment, all patients were started on a liquid food diet and gradually progressed to a solid diet over 3 d, and were discharged. At enrollment, we assessed smoking, alcohol, medications [non-steroidal anti-inflammatory drugs (NSAIDs)], low-dose aspirin, and other antiplatelets, warfarin, acetaminophen, and oral corticosteroids), and co-morbidities [hypertension, diabetes mellitus, dyslipidemia, cerebro-cardiovascular disease, chronic liver disease, and chronic kidney disease (CKD)]. The in-hospital outcomes were need for transfusion, further bleeding after spontaneous cessation of hemorrhage, and length of hospital stay. The odds ratio (OR) for transfusion need, further bleeding, and prolonged length of stay were estimated by logistic regression analysis. RESULTS: No patients required angiographic embolization or surgery. Stigmata of bleeding occurred in 18% of patients (27/153) and was treated by endoscopic procedures. During hospitalization, 40 patients (26%) received a median of 6 units of packed red blood cells. Multivariate analysis revealed that female sex (OR = 2.5, P = 0.02), warfarin use (OR = 9.3, P < 0.01), and CKD (OR = 5.9, P < 0.01) were independent risk factors for transfusion need. During hospitalization, 6 patients (3.9%) experienced further bleeding, and NSAID use (OR = 5.9, P = 0.04) and stigmata of bleeding (OR = 11, P < 0.01) were significant risk factors. Median length of hospital stay was 8 d. Multivariate analysis revealed that age > 70 years (OR = 2.1, P = 0.04) and NSAID

  12. Patient-Reported Outcomes in Rheumatoid Arthritis.

    PubMed

    van Tuyl, Lilian H D; Michaud, Kaleb

    2016-05-01

    Patient-reported outcomes (PROs) and their measures have a long and important history for determining the status and treatment of patients with rheumatoid arthritis (RA). This article describes the history and evolution of PROs for RA and the current state of the field, with key examples of accepted and widely used measures, and offers some reflection on the roles of PROs for the study and management of RA. PMID:27133486

  13. Needle phobia: etiology, adverse consequences, and patient management.

    PubMed

    Sokolowski, Chester J; Giovannitti, Joseph A; Boynes, Sean G

    2010-10-01

    Needle phobia has profound health, dental, societal, and legal implications, and severe psychological, social, and physiologic consequences. There is genetic evidence for the physiologic response to needle puncture, and a significant familial psychological component, showing evidence of inheritance. Needle phobia is also a learned behavior. The dental practitioner must recognize patients with needle phobia before the administration of local anesthetics to identify patients who are potentially reactive and to prevent untoward sequelae. Needle phobia is highly associated with avoidance behavior, and the dentist must exhibit compassion and respect. To avoid bradycardia, hypotension, unconsciousness, convulsions, and possibly asystole, oral premedication with benzodiazepines or other antianxiety agents must be considered for patients who are needle phobic. Management of needle phobiaeinduced syncope includes perioperative monitoring, oxygen administration, positioning, atropine, and vasopressors. PMID:20831935

  14. Patient reported outcome measures in septorhinoplasty surgery

    PubMed Central

    Fraser, LR; Ward, MJ; Sunkaraneni, VS; Harries, PG; Salib, RJ

    2015-01-01

    Introduction Surgical procedures incorporating a cosmetic element such as septorhinoplasty and otoplasty are currently under threat in the National Health Service (NHS) as they are deemed to be procedures of ‘limited clinical benefit’ by many primary care providers. Patient reported outcome measures (PROMs), which assess the quality of care delivered from the patients’ perspective, are becoming increasingly important in documenting the effectiveness of such procedures. Methods The Rhinoplasty Outcomes Evaluation (ROE) questionnaire, a validated PROM tool, was used to assess patient satisfaction in 141 patients undergoing septorhinoplasty surgery over a 90-month period at the University Hospital Southampton NHS Foundation Trust. Results Overall, 100 patients with a mean follow-up period of 36 months completed the study. The mean ROE score was 73.3%. In addition, 75% of patients questioned were happy with the final result of their operation and 83% would undergo the procedure again if required. These benefits occurred irrespective of age, sex and primary versus revision surgery, and were maintained for up to 71 months following surgery. Conclusions This study has shown that patients are generally satisfied with their functional and cosmetic outcomes following septorhinoplasty surgery. These results help support the case for septorhinoplasty surgery to continue being funded as an NHS procedure. PMID:25519270

  15. Associations of prenatal exposure to five chlorophenols with adverse birth outcomes.

    PubMed

    Guo, Jianqiu; Wu, Chunhua; Lv, Shenliang; Lu, Dasheng; Feng, Chao; Qi, Xiaojuan; Liang, Weijiu; Chang, Xiuli; Xu, Hao; Wang, Guoquan; Zhou, Zhijun

    2016-07-01

    Exposures to chlorophenols (CPs) have been linked with adverse health effects on wildlife and humans. This study aimed to evaluate prenatal exposure to five CP compounds using maternal urinary concentrations during pregnancy and the potential associations with birth outcomes of their infants at birth. A total of 1100 mother-newborn pairs were recruited during June 2009 to January 2010 in an agricultural region, China. Urinary concentrations of five CPs from dichlorophenol (DCP) to pentachlorophenol (PCP), namely, 2,5-DCP, 2,4-DCP, 2,4,5-trichlorophenol (2,4,5-TCP), 2,4,6-TCP and PCP, were measured using large-volume-injection gas chromatography-tandem mass spectrometry (LVI-GC-MS-MS), and associations between CP levels and weight, length as well as head circumference at birth were examined. Median urinary creatinine-adjusted concentrations of 2,5-DCP, 2,4-DCP, 2,4,5-TCP, 2,4,6-TCP and PCP were 3.34 μg/g, 1.03 μg/g, < LOD, 1.78 μg/g and 0.39 μg/g creatinine, respectively. We found lower birth weight 30 g [95% confidence interval (CI): -57, -3; p = 0.03] for per SD increase in log10-transformed concentrations of 2,4,6-TCP and lower birth weight 37 g (95% CI: -64, -10; p = 0.04) for PCP, respectively. Similarly, head circumference decrease in associations with creatinine-corrected 2,4,6-TCP and PCP concentrations were also achieved. Considering sex difference, the associations of lower birth weight were only found among male neonates, while head circumference was associated with 2,4-DCP and 2,5-DCP only found among female neonates. This study showed significant negative associations between CPs exposure and reduction in neonatal anthropometric measures. The biological mechanisms concerning CPs exposure on fetal growth deserved further investigations. PMID:27131805

  16. Analysis of adverse events of sunitinib in patients treated for advanced renal cell carcinoma

    PubMed Central

    Cedrych, Ida; Jasiówka, Marek; Niemiec, Maciej; Skotnicki, Piotr

    2016-01-01

    Introduction Treatment of the metastatic stage of renal cell carcinoma is specific because classical chemotherapy is not applicable here. The treatment is mainly based on molecularly targeted drugs, including inhibitors of tyrosine kinases. In many cases the therapy takes many months, and patients often report to general practitioners due to adverse events. In this article, the effectiveness and side effects of one of these drugs are presented. The aim of the study was to analyse of the toxicity and safety of treatment with sunitinib malate in patients with clear cell renal cell carcinoma in the metastatic stage. Material and methods Adverse events were analyzed using retrospective analysis of data collected in a group of 39 patients treated in the Department of Systemic and Generalized Malignancies in the Cancer Center in Krakow, Poland. Results Toxicity of treatment affected 50% of patients. The most common side effects observed were hypertension, thrombocytopenia, stomatitis, diarrhea and weakness. Grade 3 serious adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) version 4 affected up to 10% of patients. The most common serious adverse events were hypertension and fatigue. Conclusions Sunitinib malate is characterized by a particular type of toxicity. Knowledge of the types and range of adverse events of this drug is an important part of oncological and internal medicine care. PMID:27186181

  17. Can aircraft noise less than or equal 115 to dBA adversely affect reproductive outcome in USAF women?

    NASA Astrophysics Data System (ADS)

    Brubaker, P. A.

    1985-06-01

    It has been suggested, mainly through animal studies, that exposure to high noise levels may be associated with lower birth weight, reduced gestational length and other adverse reproductive outcomes. Few studies have been done on humans to show this association. The Air Force employs pregnant women in areas where there is a high potential for exposure to high noise levels. This study proposes a method to determine if there is an association between high frequency noise levels or = 115 dBA and adverse reproductive outcomes through a review of records and self-administered questionnaires in a case-comparison design. Prevelance rates will be calculated and a multiple logistic regression analysis computed for the independent variables that can affect reproduction.

  18. TOXICOLOGY OF MALE REPRODUCTIVE DEVELOPMENT: PROFILING 774 CHEMICALS FOR MOLECULAR TARGETS AND ADVERSE OUTCOMES (SOT)

    EPA Science Inventory

    Adverse trends in male reproductive health have been reported for increased rates of testicular germ cell tumor, low semen quality, cryptorchidism, and hypospadias. An association with prenatal environmental exposure has been inferred from human and animal studies underlying male...

  19. Systems Toxicology of Male Reproductive Development: Profiling 774 Chemicals for Molecular Targets and Adverse Outcomes

    EPA Science Inventory

    Adverse trends in male reproductive health have been reported for increased rates of testicular germ cell tumor, low semen quality, cryptorchidism, and hypospadias. An association with prenatal environmental exposure has been inferred from human and animal studies underlying male...

  20. [Novel oral anticancer drugs: a review of adverse drug reactions, interactions and patient adherence].

    PubMed

    Bartal, Alexandra; Mátrai, Zoltán; Szucs, Attila; Belinszkaja, Galina; Langmár, Zoltán; Rosta, András

    2012-01-15

    Each aspect of oncological care is widely affected by the spread of oral anticancer agents, which raises several questions in terms of safe medication use and patient adherence. Over the past decade targeted therapies have appeared in clinical practice and revolutionized the pharmacological treatment of malignancies. Regular patient - doctor visits and proper patient education is crucial in order to comply with the therapy previously agreed upon with the oncologist, to increase patient adherence, to detect and to treat adverse effects in early stages. Since the information on the new medicines in Hungarian language is sparse it is the intention of the authors to give an overview of the basic knowledge, patient safety issues, adverse effects and interactions. Official drug information summaries and data on pharmacokinetics, interactions and adverse effects from the literature are reviewed as the basis for this overview. PMID:22217686

  1. A retrospective study of patient outcomes and satisfaction following pinnaplasty

    PubMed Central

    Hope, Nicholas; Smith, Caroline P; Cullen, Jim R; McCluney, Neil

    2016-01-01

    Introduction Up to 5% of all children have prominent ears. Psychological distress and bullying adversely affect these children and can cause significant social exclusion. In times of austerity, cosmetic procedures such as surgical correction of prominent ears are felt to be an unnecessary cost to the health service. Materials and methods A retrospective case note review of all patients undergoing pinnaplasty was undertaken. Postoperative outcomes were compared against the Royal College of Surgeons of England standards. The Glasgow Benefit Inventory, a validated post-intervention questionnaire, was then posted out to all patients. Results A total of 72 patients were identified. Average age at procedure was 13 years. Eleven patients were above the age of 19 years. Twenty-eight patients were male and forty-four female. Sixty-two cases underwent bilateral pinnaplasty. No patients developed hematoma, and there were no readmissions within 30 days of surgery. Twenty-nine patients responded to the questionnaire (40%), of whom 27 reported a positive impact on their psychosocial well-being with a mean score of 36. Conclusion Pinnaplasty offers patients an opportunity to alleviate the psychological distress of bullying and harassment secondary to the appearance of prominent ears. PMID:27307775

  2. Patient-Reported Outcomes in Psoriatic Arthritis.

    PubMed

    Orbai, Ana-Maria; Ogdie, Alexis

    2016-05-01

    Patient-reported outcome (PRO) measures are an important component to assessing disease impact and therapy response in patients with psoriatic arthritis (PsA). Overall, there are few PsA-specific PROs. Most PROs used in PsA are borrowed from other diseases (eg, rheumatoid arthritis and ankylosing spondylitis) or general population PROs. PROs are used in PsA clinical trials and in the clinical management of PsA. In this review, we discuss the most commonly used PRO in PsA, including their inclusion in composite measures. Future studies may be helpful to determine the best performing PROs in patients with PsA. PMID:27133489

  3. Health Literacy: An Educationally Sensitive Patient Outcome.

    PubMed

    Yin, H Shonna; Jay, Melanie; Maness, Leslie; Zabar, Sondra; Kalet, Adina

    2015-09-01

    We have previously proposed that by identifying a set of Educationally Sensitive Patient Outcomes (ESPOs), medical education outcomes research becomes more feasible and likely to provide meaningful guidance for medical education policy and practice. ESPOs are proximal outcomes that are sensitive to provider education, measurable, and linked to more distal health outcomes. Our previous model included Patient Activation and Clinical Microsystem Activation as ESPOs. In this paper, we discuss how Health Literacy, defined as "the degree to which individuals have the capacity to obtain, process, and understand basic health information and services needed to make appropriate health decisions," is another important ESPO. Between one-third and one-half of all US adults have limited health literacy skills. Providers can be trained to adopt a "universal precautions approach" to addressing patient health literacy, through the acquisition of specific skills (e.g., teachback, "chunking" information, use of plain language written materials) and by learning how to take action to improve the "health literacy environment." While there are several ways to measure health literacy, identifying which measurement tools are most sensitive to provider education is important, but challenging and complex. Further research is needed to test this model and identify additional ESPOs. PMID:26173523

  4. The Coping with Asthma Study: a randomised controlled trial of a home based, nurse led psychoeducational intervention for adults at risk of adverse asthma outcomes

    PubMed Central

    Smith, J; Mildenhall, S; Noble, M; Shepstone, L; Koutantji, M; Mugford, M; Harrison, B

    2005-01-01

    Background: Morbidity and mortality associated with severe asthma might be reduced by interventions that address psychosocial factors contributing to adverse outcomes. A study was undertaken to assess the effectiveness of a 6 month home based psychoeducational intervention delivered by a respiratory nurse specialist for adults at risk of adverse asthma outcomes. Methods: A pragmatic randomised controlled trial was performed in 92 adults registered with hospital or primary care asthma clinics. All had previous hospital admissions and/or were on British Thoracic Society step 4–5 treatment and had failed to attend clinic appointments or were considered to have poor adherence to other aspects of their agreed management. Patients were visited in their homes for assessment and, where appropriate, intervention. The main outcomes measured were symptom control, asthma specific quality of life, and generic health status. Results: At the 6 month primary time point there were no significant differences between usual care and intervention groups in mean symptom control, physical functioning, or mental health scores (differences (with 95% CI) –0.35 (–1.83 to 1.13), 3.10 (–11.42 to 17.63), 0.42 (–10.22 to 11.07), respectively). Small effects on asthma specific quality of life up to 12 months (e.g. adjusted difference at 12 months 0.13 (95% CI 0.02 to 0.25)) and short term effects on generic health status, which mirrored improvements in aspects of self-care observed at the end of the intensive phase of the intervention, were apparent only from fully adjusted analyses. Conclusions: A home based intervention provided by a nurse receiving psychological supervision may have effects on quality of life but is overall of limited long term benefit to adults at risk of adverse asthma outcomes. PMID:16055616

  5. Adverse drug reactions in veterinary patients associated with drug transporters.

    PubMed

    Mealey, Katrina L

    2013-09-01

    For many drugs used in veterinary practice, plasma and tissue concentrations are highly dependent on the activity of drug transporters. This article describes how functional changes in drug transporters, whether mediated by genetic variability or drug-drug interactions, affect drug disposition and, ultimately, drug safety and efficacy in veterinary patients. A greater understanding of species, breed, and individual (genetic) differences in drug transporter function, as well as drug-drug interactions involving drug transporters, will result in improved strategies for drug design and will enable veterinarians to incorporate individualized medicine in their practices. PMID:23890239

  6. Obesity Adversely Affects Survival in Pancreatic Cancer Patients

    PubMed Central

    McWilliams, Robert R.; Matsumoto, Martha E.; Burch, Patrick A.; Kim, George P.; Halfdanarson, Thorvardur R.; de Andrade, Mariza; Reid-Lombardo, Kaye; Bamlet, William R.

    2010-01-01

    Purpose Higher body-mass index (BMI) has been implicated as a risk factor for developing pancreatic cancer, but its effect on survival has not been thoroughly investigated. We assessed the association of BMI with survival in a sample of pancreatic cancer patients and utilized epidemiologic and clinical information to understand the contribution of diabetes and hyperglycemia. Methods A survival analysis using Cox proportional hazards by usual adult BMI was performed on 1,861 unselected patients with pancreatic adenocarcinoma; analyses were adjusted for covariates that included clinical stage, age, and sex. Secondary analyses incorporated self reported diabetes and fasting blood glucose in the survival model. Results BMI as a continuous variable was inversely associated with survival from pancreatic adenocarcinoma [hazard ratio 1.019 for each increased unit of BMI (kg/m2), p < 0.001] after adjustment for age, stage, and sex. In analysis by National Institutes of Health BMI category, BMI of 30–34.99 kg/m2 (HR 1.14, 95% confidence interval 0.98–1.33), 35–39.99 kg/m2 (HR 1.32, 95% CI 1.08–1.62), and ≥40 (HR 1.60, 95% CI 1.26–2.04) were associated with decreased survival compared to normal BMI of 18,5–24.99 kg/m2 (overall trend test p<0.001). Fasting blood glucose and diabetes did not affect the results. Conclusions Higher BMI is associated with decreased survival in pancreatic cancer. Although the mechanism of this association remains undetermined, diabetes and hyperglycemia do not appear to account for the observed association. PMID:20665496

  7. 'The patient': at the center of patient-reported outcomes.

    PubMed

    Awad, A George

    2015-01-01

    The recent emphasis of including patient reports in their own care management is reviewed in terms of the factors that contributed to its popularity. The role change of patients as being active participants in their own care as a result of the rising consumerism and advocacy has led to increased pressures for including patients in the therapeutic decision-making process. As consumers of clinical services, their perspectives and attitudes towards health and illness acquired more importance. The rising cost of healthcare has added another dimension in cost containment by empowering patients and sharing responsibility in their recovery, which hopefully can improve outcomes. Challenges in the development and implementation of patient-reported outcomes in psychiatry are reviewed and include the still unresolved subjective/objective dichotomy, identification of the most appropriate and relevant patient-reported outcomes. Few outcomes are identified and include: subjective tolerability of medication, self-reported health-related quality of life, preferences, patients' attitudes towards health and illness, satisfaction with medication and overall satisfaction of quality of care, and functional state, with particular focus on social functioning. PMID:26289737

  8. Impact of Patient Sex on Clinical Outcomes

    PubMed Central

    Teitsma, Xavier M.; van der Hoeven, Henk; Tamminga, Rob; de Bie, Rob A.

    2014-01-01

    Background: The Combined Quality Care Anterior Cruciate Ligament registry provides data for clinical research regarding primary anterior cruciate ligament (ACL) surgery. Purpose: To explore the data with regard to the clinical outcomes between sexes after ACL reconstruction in a Dutch population. Study Design: Cohort study; Level of evidence, 3. Methods: Data involving patients diagnosed with an ACL tear and eligible for surgery were recorded. Isokinetic muscle strength, functional muscle performance, and anterior-posterior translation of the knee joint were documented preoperatively and at 3, 6, 9, and 12 months postoperatively. Patients completed the Knee Injury and Osteoarthritis Outcome Score (KOOS), Lysholm, and Tegner rating scales during each examination using a web-based questionnaire. Results: Approximately 90% of ACL injuries occurred during sport activities. The mean (SD) age at surgery was 28 (11) years for both men and women, and the majority of patients were treated with hamstring tendon autografts (94%). Four percent received bone–patellar tendon–bone autografts, and 2% of the patients received other grafts. Preoperatively, the KOOS, Lysholm, and Tegner scores were significantly higher in males. Twelve months postoperatively, both sexes showed comparable isokinetic strength (P = .336), knee laxity (P = .680), and hop test for distance (P = .122) when comparing the injured with the uninjured side. Self-reported knee function was comparable between sexes as assessed by the KOOS (P = .202), Lysholm (P = .872), and Tegner (P = .767) questionnaires during the 12-month follow-up. Conclusion: One year after ACL surgery, all patients had improved greatly, showing only minor differences between sexes. The male group showed slightly better results when evaluating self-reported knee questionnaires. Comparable outcomes and knee function between sexes can therefore be presumed with patients who are treated with hamstring tendon autografts in a Dutch

  9. Inflammatory Adverse Events are Associated with Disease-Free Survival after Vaccine Therapy among Patients with Melanoma

    PubMed Central

    Hu, Yinin; Smolkin, Mark E.; White, Emily J.; Petroni, Gina R.; Neese, Patrice Y.; Slingluff, Craig L.

    2014-01-01

    Background Multipeptide vaccines for melanoma may cause inflammatory adverse events (IAE). We hypothesize that IAE's are associated with a higher rate of immune response to vaccination (IR) and improved clinical outcomes. Methods Adult patients with resected, high-risk (stage IIB-IV) melanoma were vaccinated with a combination of 12 Class I MHC-restricted melanoma epitopes (12MP) and IAE's were recorded. A separate category for hypopigmentation (vitiligo) was also assessed. CD8+ T cell immune response was assessed by direct IFN-γ ELIspot. Overall survival and disease-free survival were analyzed by Cox proportional hazards modeling. Results Out of 332 patients, 57 developed IAE's, the majority of which were dermatologic (minimum CTCAE grade 3). Most non-dermatologic IAE's were CTCAE grade 1 and 2. Vitiligo developed in 23 patients (7%). 174 patients (53%) developed a CD8+ response. Presence of IAE was significantly associated with development of IR (70% vs 49%, p = 0.005) and with disease-free survival (HR 0.54, p = 0.043). There were no significant associations relating vitiligo or immune response alone with clinical outcomes. Conclusions Inflammatory adverse events are associated with a higher rate of CD8+ T-cell response following vaccination therapy for high-risk melanoma. Our findings suggest either that antitumor activity induced by Class I-restricted peptide vaccines may depend on immunologic effects beyond simple expansion of CD8+ T-cells or that the intrinsic inflammatory response of patients contributes to clinical outcome in melanoma. PMID:24841355

  10. The use of fluoroquinolones in neutropenic patients--analysis of adverse effects.

    PubMed

    Rubinstein, E; Potgieter, P; Davey, P; Norrby, S R

    1994-07-01

    The fluoroquinolones have been extensively used in the neutropenic patient. When fluoroquinolone monotherapy was used as prophylaxis, frequently for extended periods, the rate of adverse effect of ciprofloxacin (6.9%) ofloxacin (11.6%) and norfloxacin (5.5%) were significantly lower than those of the comparator agents--co-trimoxazole, vancomycin and polymycin. Rash and gastrointestinal upset were the commonest adverse effects associated with the fluoroquinolones. When used as monotherapy for bacterial infections, often intravenously and in high dosages, the cumulative rate of adverse effects caused by the fluoroquinolones (12.6%) was similar to that caused by the comparator agents (10.3%), but significantly higher than reported for non-neutropenic patients (6.4%) and for prophylactic use. The main adverse events were also rashes (15.4%) and gastrointestinal upset (6.1%). When fluoroquinolones were used as therapy of bacterial infections in combination with other agents, the incidence of adverse events was 14.9%, which was similar to the comparator agents (13.5%). Adverse events were also similar except that nephrotoxicity was commonest with comparator combinations (4.0%). The data suggest that fluoroquinolone prophylaxis in neutropenic patients, even for prolonged periods, is safer than the comparator agents, but is associated with more frequent adverse events than in non-neutropenic patients. Fluoroquinolone therapy, frequently with high dosages, is associated with similar rate of adverse events as the comparator agents. When used in combination with the other antibiotics, fluoroquinolones are as safe as the comparator agents. PMID:7961217

  11. Risk stratification for major adverse cardiac events and ventricular tachyarrhythmias by cardiac MRI in patients with cardiac sarcoidosis

    PubMed Central

    Yasuda, Masakazu; Iwanaga, Yoshitaka; Kato, Takao; Izumi, Toshiaki; Inuzuka, Yasutaka; Nakamura, Takashi; Miyaji, Yuki; Kawamura, Takayuki; Ikeguchi, Shigeru; Inoko, Moriaki; Kurita, Takashi; Miyazaki, Shunichi

    2016-01-01

    Background The presence of myocardial fibrosis by cardiac MRI has prognostic value in cardiac sarcoidosis, and localisation may be equally relevant to clinical outcomes. Objective We aimed to analyse cardiac damage and function in detail and explore the relationship with clinical outcomes in patients with cardiac sarcoidosis using cardiac MRI. Methods We included 81 consecutive patients with cardiac sarcoidosis undergoing cardiac MR. Left ventricular mass and fibrosis mass were calculated, and localisation was analysed using a 17-segment model. Participants underwent follow-up through 2015, and the development of major adverse cardiac events including ventricular tachyarrhythmias was recorded. Results Increased left ventricular fibrosis mass was associated with increased prevalence of ventricular tachyarrhythmias (p<0.001). When localisation was defined as the sum of late gadolinium enhancement in the left ventricular basal anterior and basal anteroseptal areas, or the right ventricular area, it was associated with ventricular tachyarrhythmias (p<0.001). Kaplan-Meier analysis during a median follow-up of 22.1 months showed that both the mass and localisation groupings for fibrosis were significantly associated with major adverse cardiac events or ventricular tachyarrhythmias and that when combined, the risk stratification was better than for each variable alone (p<0.001, respectively). By Cox-proportional hazard risk analysis, the localisation grouping was an independent predictor for the both. Conclusions In patients with cardiac sarcoidosis, both fibrosis mass and its localisation to the basal anterior/anteroseptal left ventricle, or right ventricle was associated with the development of major adverse cardiac events or ventricular tachyarrhythmias. Cardiac MR with late gadolinium enhancement may be useful for improving risk stratification in patients with cardiac sarcoidosis. PMID:27547432

  12. Urinary Tissue Inhibitor of Metalloproteinase-2 (TIMP-2) • Insulin-Like Growth Factor-Binding Protein 7 (IGFBP7) Predicts Adverse Outcome in Pediatric Acute Kidney Injury

    PubMed Central

    Westhoff, Jens H.; Tönshoff, Burkhard; Waldherr, Sina; Pöschl, Johannes; Teufel, Ulrike; Westhoff, Timm H.; Fichtner, Alexander

    2015-01-01

    Background The G1 cell cycle inhibitors tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) have been identified as promising biomarkers for the prediction of adverse outcomes including renal replacement therapy (RRT) and mortality in critically ill adult patients who develop acute kidney injury (AKI). However, the prognostic value of urinary TIMP-2 and IGFBP7 in neonatal and pediatric AKI for adverse outcome has not been investigated yet. Methods The product of the urinary concentration of TIMP-2 and IGFBP7 ([TIMP-2]•[IGFBP7]) was assessed by a commercially available immunoassay (NephroCheck™) in a prospective cohort study in 133 subjects aged 0–18 years including 46 patients with established AKI according to pRIFLE criteria, 27 patients without AKI (non-AKI group I) and 60 apparently healthy neonates and children (non-AKI group II). AKI etiologies were: dehydration/hypovolemia (n = 7), hemodynamic instability (n = 7), perinatal asphyxia (n = 9), septic shock (n = 7), typical hemolytic-uremic syndrome (HUS; n = 5), interstitial nephritis (n = 5), vasculitis (n = 4), nephrotoxic injury (n = 1) and renal vein thrombosis (n = 1). Results When AKI patients were classified into pRIFLE criteria, 6/46 (13%) patients fulfilled the criteria for the category “Risk”, 13/46 (28%) for “Injury”, 26/46 (57%) for “Failure” and 1/46 (2%) for “Loss”. Patients in the “Failure” stage had a median 3.7-fold higher urinary [TIMP-2]•[IGFBP7] compared to non-AKI subjects (P<0.001). When analyzed for AKI etiology, highest [TIMP-2]•[IGFBP7] values were found in patients with septic shock (P<0.001 vs. non-AKI I+II). Receiver operating characteristic (ROC) curve analyses in the AKI group revealed good performance of [TIMP-2]•[IGFBP7] in predicting 30-day (area under the curve (AUC) 0.79; 95% CI, 0.61–0.97) and 3-month mortality (AUC 0.84; 95% CI, 0.67–0.99) and moderate performance in predicting RRT

  13. Validating administrative data for the detection of adverse events in older hospitalized patients

    PubMed Central

    Ackroyd-Stolarz, Stacy; Bowles, Susan K; Giffin, Lorri

    2014-01-01

    Older hospitalized patients are at risk of experiencing adverse events including, but not limited to, hospital-acquired pressure ulcers, fall-related injuries, and adverse drug events. A significant challenge in monitoring and managing adverse events is lack of readily accessible information on their occurrence. Purpose The objective of this retrospective cross-sectional study was to validate diagnostic codes for pressure ulcers, fall-related injuries, and adverse drug events found in routinely collected administrative hospitalization data. Methods All patients 65 years of age or older discharged between April 1, 2009 and March 31, 2011 from a provincial academic health sciences center in Canada were eligible for inclusion in the validation study. For each of the three types of adverse events, a random sample of 50 patients whose records were positive and 50 patients whose records were not positive for an adverse event was sought for review in the validation study (n=300 records in total). A structured health record review was performed independently by two health care providers with experience in geriatrics, both of whom were unaware of the patient’s status with respect to adverse event coding. A physician reviewed 40 records (20 reviewed by each health care provider) to establish interrater agreement. Results A total of 39 pressure ulcers, 56 fall-related injuries, and 69 adverse drug events were identified through health record review. Of these, 34 pressure ulcers, 54 fall-related injuries, and 47 adverse drug events were also identified in administrative data. Overall, the diagnostic codes for adverse events had a sensitivity and specificity exceeding 0.67 (95% confidence interval [CI]: 0.56–0.99) and 0.89 (95% CI: 0.72–0.99), respectively. Conclusion It is feasible and valid to identify pressure ulcers, fall-related injuries, and adverse drug events in older hospitalized patients using routinely collected administrative hospitalization data. The

  14. Cumulative Adverse Financial Circumstances: Associations with Patient Health Status and Behaviors

    ERIC Educational Resources Information Center

    Bisgaier, Joanna; Rhodes, Karin V.

    2011-01-01

    This article examines associations between cumulative adverse financial circumstances and patient health in a sample of 1,506 urban emergency department (ED) patients. Study participants completed a previously validated Social Health Survey between May and October 2009. Five categories of economic deprivation were studied: food insecurity, housing…

  15. Infliximab in patients with psoriasis and other inflammatory diseases: evaluation of adverse events in the treatment of 168 patients*

    PubMed Central

    Antonio, João Roberto; Sanmiguel, Jessica; Cagnon, Giovana Viotto; Augusto, Marília Silveira Faeda; de Godoy, Moacir Fernandes; Pozetti, Eurides Maria Oliveira

    2016-01-01

    Background Psoriasis is immune-mediated chronic inflammatory disease with preference for skin and joints. The skin involvement occurs by hyperproliferation and abnormal differentiation of keratinocytes. It is associated with comorbidities, mainly related to the clinical manifestations of the metabolic syndrome. Increased TNF-alpha expression (TNF-α) is related to its pathophysiology. Infliximab is an intravenous drug that acts neutralizing the biological activity of TNF-α and prevents the binding of the molecule to the target cell receptor, inhibiting cell proliferation of psoriasis and other diseases mediated by TNF-α. A lot of infusion reactions have been described in the literature. Objective To evaluate the adverse effects of intravenous treatment with infliximab, analyzing patients with psoriasis compared to those with other chronic inflammatory diseases (rheumatoid arthritis, ankylosing spondylitis, Crohn's disease and ulcerative colitis). Method Analysis of medical records and adverse events of 168 patients undergoing infliximab infusion for psoriasis and chronic inflammatory diseases treatment. Results 168 patients who have used infliximab were evaluated, 24 had psoriasis and 144 had chronic inflammatory diseases. Only 2 (8.3%) patients with psoriasis showed adverse events requiring treatment discontinuation, and just 6 (4.2%) female patients with chronic inflammatory diseases experienced adverse events. Conclusion Infliximab is a safe drug, with a low percentage of adverse events and there were more adverse events in women with chronic inflammatory diseases and in patients who received more infliximab infusions. PMID:27438197

  16. Self-reported adverse reactions among patients initiating antiretroviral therapy in Brazil.

    PubMed

    Pádua, Cristiane A Menezes de; César, Cibele C; Bonolo, Palmira F; Acurcio, Francisco A; Guimarães, Mark Drew C

    2007-02-01

    A cross-sectional analysis was carried out to describe adverse reactions to antiretroviral therapy (ART) reported by HIV-infected patients initiating treatment at two public health AIDS referral centers in Belo Horizonte, Brazil, 2001-2003 and to verify their association with selected variables. Adverse reactions were obtained through interview at the first follow-up visit (first month) after the antiretroviral prescription. Socio-demographic and behavioral variables related to ART were obtained from baseline and follow-up interviews and clinical variables from medical charts. Patients with four or more reactions were compared to those with less than four. Odds ratio with 95% confidence interval were estimated using logistic regression model for both univariate and multivariate analyses. At least one adverse reaction was reported by 92.2% of the participants while 56.2% reported four or more different reactions. Antiretroviral regimens including indinavir/ritonavir, irregular use of antiretrovirals and switch in regimens were independently associated with four or more adverse reactions (OR=7.92, 5.73 and 2.03, respectively). The initial period of ARV treatment is crucial and patients' perception of adverse reactions should be carefully taken into account. Strategies for monitoring and management of adverse reactions including the choice of regimens and the prevention of irregular ART should be developed in AIDS/HIV referral centers in Brazil to promote better adherence to antiretroviral therapy. PMID:17625721

  17. Impact of positive chest X-ray findings and blood cultures on adverse outcomes following hospitalized pneumococcal lower respiratory tract infection: a population-based cohort study

    PubMed Central

    2013-01-01

    Background Little is known about the clinical presentation and outcome of pneumococcal lower respiratory tract infection (LRTI) without positive chest X-ray findings and blood cultures. We investigated the prognostic impact of a pulmonary infiltrate and bacteraemia on the clinical course of hospitalized patients with confirmed pneumococcal LRTI. Methods We studied a population-based multi-centre cohort of 705 adults hospitalized with LRTI and Streptococcus pneumoniae in LRT specimens or blood: 193 without pulmonary infiltrate or bacteraemia, 250 with X-ray confirmed pneumonia, and 262 with bacteraemia. We compared adverse outcomes in the three groups and used multiple regression analyses to adjust for differences in age, sex, comorbidity, and lifestyle factors. Results Patients with no infiltrate and no bacteraemia were of similar age but had more comorbidity than the other groups (Charlson index score ≥1: no infiltrate and no bacteraemia 81% vs. infiltrate without bacteraemia 72% vs. bacteraemia 61%), smoked more tobacco, and had more respiratory symptoms. In contrast, patients with a pulmonary infiltrate or bacteraemia had more inflammation (median C-reactive protein: no infiltrate and no bacteraemia 82 mg/L vs. infiltrate without bacteraemia 163 mg/L vs. bacteraemia 316 mg/L) and higher acute disease severity scores. All adverse outcomes increased from patients with no infiltrate and no bacteraemia to those with an infiltrate and to those with bacteraemia: Length of hospital stay (5 vs. 6 vs. 8 days); intensive care admission (7% vs. 20% vs. 23%); pulmonary complications (1% vs. 5% vs. 14%); and 30-day mortality (5% vs. 11% vs. 21%). Compared with patients with no infiltrate and no bacteraemia, the adjusted 30-day mortality rate ratio was 1.9 (95% confidence interval (CI) 0.9-4.1) in patients with an infiltrate without bacteraemia and 4.1 (95% CI 2.0-8.5) in bacteraemia patients. Adjustment for acute disease severity and inflammatory markers weakened these

  18. Increasing Number and Proportion of Adverse Obstetrical Outcomes among Women Living with HIV in the Ottawa Area: A 20-Year Clinical Case Series.

    PubMed

    Buchan, Sarah; Muldoon, Katherine A; Spaans, Johanna N; Balfour, Louise; Samson, Lindy; Walker, Mark; Cameron, D William

    2016-01-01

    Background. The prevalence and associated risks with adverse obstetrical outcomes among women living with HIV are not well measured. The objective of this study was to longitudinally investigate the prevalence and correlates of adverse obstetrical outcomes among women with HIV. Methods. This 20-year (1990-2010) clinical case series assessed the prevalence of adverse obstetrical outcomes among pregnant women with HIV receiving care at The Ottawa Hospital (TOH). General estimating equation modeling was used to identify factors independently associated with adverse obstetrical outcomes, while controlling for year of childbirth clustering. Results. At TOH, there were 127 deliveries among 94 women (1990-2010): 22 preterm births, 9 births with low birth weight, 12 births small for gestational age, and 4 stillbirths. Per year, the odds of adverse obstetrical outcomes increased by 15% (OR: 1.15, 95% CI: 1.03-1.30). Psychiatric illness (AOR: 2.64, 95% CI: 1.12-6.24), teen pregnancy (AOR: 3.35, 95% CI: 1.04-1.46), and recent immigrant status (AOR: 7.24, 95% CI: 1.30-40.28) were the strongest correlates of adverse obstetrical outcomes. Conclusions. The increasing number and proportion of adverse obstetrical outcomes among pregnant women with HIV over the past 20 years highlight the need for social supports and maternal and child health interventions, especially among adolescents, new immigrants, and those with a history of mental illness. PMID:27528877

  19. Increasing Number and Proportion of Adverse Obstetrical Outcomes among Women Living with HIV in the Ottawa Area: A 20-Year Clinical Case Series

    PubMed Central

    Buchan, Sarah; Spaans, Johanna N.; Balfour, Louise

    2016-01-01

    Background. The prevalence and associated risks with adverse obstetrical outcomes among women living with HIV are not well measured. The objective of this study was to longitudinally investigate the prevalence and correlates of adverse obstetrical outcomes among women with HIV. Methods. This 20-year (1990–2010) clinical case series assessed the prevalence of adverse obstetrical outcomes among pregnant women with HIV receiving care at The Ottawa Hospital (TOH). General estimating equation modeling was used to identify factors independently associated with adverse obstetrical outcomes, while controlling for year of childbirth clustering. Results. At TOH, there were 127 deliveries among 94 women (1990–2010): 22 preterm births, 9 births with low birth weight, 12 births small for gestational age, and 4 stillbirths. Per year, the odds of adverse obstetrical outcomes increased by 15% (OR: 1.15, 95% CI: 1.03–1.30). Psychiatric illness (AOR: 2.64, 95% CI: 1.12–6.24), teen pregnancy (AOR: 3.35, 95% CI: 1.04–1.46), and recent immigrant status (AOR: 7.24, 95% CI: 1.30–40.28) were the strongest correlates of adverse obstetrical outcomes. Conclusions. The increasing number and proportion of adverse obstetrical outcomes among pregnant women with HIV over the past 20 years highlight the need for social supports and maternal and child health interventions, especially among adolescents, new immigrants, and those with a history of mental illness. PMID:27528877

  20. [Patient-reported outcomes: definition and measurement].

    PubMed

    Botturi, Davide; Rodella, Stefania

    2014-06-01

    The concept of "patient-reported outcomes" have been proposed by the Food and Drug Administration in the year 2000, in order to describe one of the different and potential sources of information on the drug's safety and effectiveness. It represents an "umbrella" term, which covers a multiplicity of meanings and primarily identifies a conceptual approach and a methodology specifically oriented to the patients' point of view on outcomes, instead of the traditional clinical and professional perspective. The patient-reported outcomes measures are frequently self-completed questionnaires. The measures can be classified in general and specific. The first one, general, relates to the assessment of the quality of life or the health status, in the general population or in subgroups with particular health problems (eg. SF-36 Health Survey, EQ-5D). The second one, specific, mainly relates to the assessment of particular types of symptoms (eg. pain, anxiety, fear, depression) and functions (eg. daily living activities), in population's subgroups with definite health problems, undergoing or not to a healthcare procedure (eg. Adult Asthma Quality of Life Questionnaire, Kidney Disease Quality of Life Instrument, Oxford Hip Score, Oxford Knee Score). For the selection of an instrument a series of criteria needs to be taken into account, among which the psychometric properties, the expert judgement, the interpretability, the acceptability, and the feasibility of the entire process. PMID:25002284

  1. Adverse outcome pathways (AOPs): A framework to support predictive toxicology (presentation)

    EPA Science Inventory

    High throughput and in silico methods are providing the regulatory toxicology community with capacity to rapidly and cost effectively generate data concerning a chemical’s ability to initiate one or more biological perturbations that may culminate in an adverse ecological o...

  2. Childhood adversity and behavioral health outcomes for youth: An investigation using state administrative data.

    PubMed

    Lucenko, Barbara A; Sharkova, Irina V; Huber, Alice; Jemelka, Ron; Mancuso, David

    2015-09-01

    This study aimed to measure the relative contribution of adverse experiences to adolescent behavioral health problems using administrative data. Specifically, we sought to understand the predictive value of adverse experiences on the presence of mental health and substance abuse problems for youth receiving publicly funded social and health services. Medicaid claims and other service records were analyzed for 125,123 youth age 12-17 and their biological parents. Measures from administrative records reflected presence of parental domestic violence, mental illness, substance abuse, criminal justice involvement, child abuse and/or neglect, homelessness, and death of a biological parent. Mental health and substance abuse status of adolescents were analyzed as functions of adverse experiences and other youth characteristics using logistic regression. In multivariate analyses, all predictors except parental domestic violence were statistically significant for substance abuse; parental death, parental mental illness, child abuse or neglect and homelessness were statistically significant for mental illness. Odds ratios for child abuse/neglect were particularly high in both models. The ability to identify risks during childhood using administrative data suggests the potential to target prevention and early intervention efforts for children with specific family risk factors who are at increased risk for developing behavioral health problems during adolescence. This study illustrates the utility of administrative data in understanding adverse experiences on children and the advantages and disadvantages of this approach. PMID:26234784

  3. Potential roles of omics data in the use of adverse outcome pathways for environmental risk assessment

    EPA Science Inventory

    The current approach to assessing adverse effects of chemicals in the environment is largely based on a battery of in-vivo study methods and a limited number of accepted in-silico approaches. For most substances the pool of data from which to predict ecosystem effects is limited ...

  4. Childhood Adverse Events and Health Outcomes among Methamphetamine-Dependent Men and Women

    ERIC Educational Resources Information Center

    Messina, Nena P.; Marinelli-Casey, Patricia; Hillhouse, Maureen; Ang, Alfonso; Hunter, Jeremy; Rawson, Richard

    2008-01-01

    To describe the prevalence of childhood adverse events (CAEs) among methamphetamine-dependent men and women, and assess the relationship of cumulative CAEs to health problems. Data for 236 men and 351 women were analyzed assessing CAEs. Dependent variables included 14 self-reported health problems or psychiatric symptom domains. Mental health was…

  5. Health care costs for prostate cancer patients receiving androgen deprivation therapy: treatment and adverse events

    PubMed Central

    Krahn, M.D.; Bremner, K.E.; Luo, J.; Alibhai, S.M.H.

    2014-01-01

    Background Serious adverse events have been associated with androgen deprivation therapy (adt) for prostate cancer (pca), but few studies address the costs of those events. Methods All pca patients (ICD-9-CM 185) in Ontario who started 90 days or more of adt or had orchiectomy at the age of 66 or older during 1995–2005 (n = 26,809) were identified using the Ontario Cancer Registry and drug and hospital data. Diagnosis dates of adverse events—myocardial infarction, acute coronary syndrome, congestive heart failure, stroke, deep vein thrombosis or pulmonary embolism, any diabetes, and fracture or osteoporosis—before and after adt initiation were determined from administrative data. We excluded patients with the same diagnosis before and after adt, and we allocated each patient’s time from adt initiation to death or December 31, 2007, into health states: adt (no adverse event), adt-ae (specified single adverse event), Multiple (>1 event), and Final (≤180 days before death). We used methods for Canadian health administrative data to estimate annual total health care costs during each state, and we examined monthly trends. Results Approximately 50% of 21,811 patients with no pre-adt adverse event developed 1 or more events after adt. The costliest adverse event state was stroke ($26,432/year). Multiple was the most frequent (n = 2,336) and the second most costly health state ($24,374/year). Costs were highest in the first month after diagnosis (from $1,714 for diabetes to $14,068 for myocardial infarction). Costs declined within 18 months, ranging from $784 per 30 days (diabetes) to $1,852 per 30 days (stroke). Adverse events increased the costs of adt by 100% to 265%. Conclusions The economic burden of adverse events is relevant to programs and policies from clinic to government, and that burden merits consideration in the risks and benefits of adt. PMID:24940106

  6. Conscious Sedation for Upper Endoscopy in the Gastric Bypass Patient: Prevalence of Cardiopulmonary Adverse Events and Predictors of Sedation Requirement

    PubMed Central

    Jirapinyo, Pichamol; Abu Dayyeh, Barham K.

    2016-01-01

    Background Safety of conscious sedation for performing esophagoduodenoscopy (EGD) in obese and Roux-en-Y gastric bypass (RYGB) patients remains controversial. Additionally, it has been suggested that patients with higher body mass index (BMI) require higher sedation doses, imparting greater risk. Aim The aim of this study is to assess the prevalence of sedation-related adverse events and the independent predictors of sedation requirements in RYGB patients. Methods This study is a retrospective database review of RYGB patients who underwent EGD under conscious sedation. Database analysis was performed and linear regression applied to identify significant predictors of sedation requirement. Primary outcomes are sedation-related adverse events and predictors of sedation requirement. Results Data on 1,385 consecutive procedures (diagnostic 967; therapeutic 418) performed under conscious sedation were analyzed. Unplanned events were reported in 1.6 %, with 0.6 % being cardiopulmonary in nature and 0.7 % requiring early termination. Multivariable linear regression revealed procedural time was the only significant predictor of fentanyl (standardized β 0.34; P value < 0.001) and midazolam (standardized β 0.30; P value < 0.001) doses. Post-RYGB BMI was not significantly associated with the dose of fentanyl (standardized β 0.08; P value 0.29) or midazolam administered (standardized β 0.01; P value 0.88). Conclusions Upper endoscopy can be safely performed in RYGB patients under conscious sedation with a similar cardiopulmonary risk profile to that of standard EGD. The non-cardiopulmonary adverse events were procedure-specific and unrelated to sedation. Procedure length, and not absolute BMI, was the only predictor of sedation requirement in this patient population. PMID:24723069

  7. Effect of RAAS blockers on adverse clinical outcomes in high CVD risk subjects with atrial fibrillation: A meta-analysis and systematic review of randomized controlled trials.

    PubMed

    Chaugai, Sandip; Sherpa, Lhamo Yanchang; Sepehry, Amir A; Arima, Hisatomi; Wang, Dao Wen

    2016-06-01

    Recent studies have demonstrated that atrial fibrillation significantly increases the risk of adverse clinical outcomes in high cardiovascular disease risk subjects. Application of renin-angiotensin-aldosterone system blockers for prevention of recurrence of atrial fibrillation and adverse clinical outcomes in subjects with atrial fibrillation is a theoretically appealing concept. However, results of clinical trials evaluating the effect of renin-angiotensin-aldosterone blockers on adverse clinical outcomes in high cardiovascular disease risk subjects with atrial fibrillation remain inconclusive.A pooled study of 6 randomized controlled trials assessing the efficacy of renin-angiotensin-aldosterone blockers on subjects with atrial fibrillation was performed.A total of 6 randomized controlled trials enrolled a total of 53,510 patients followed for 1 to 5 years. RAAS blockade therapy was associated with 14% reduction in the incidence of heart failure (OR: 0.86, [95%CI: 0.76- 0.97], P=0.018) and 17% reduction in the incidence of CVE (OR: 0.83, [95%CI: 0.70-0.99], P = 0.038). The corresponding decline in absolute risk against heart failure (ARR: 1.4%, [95%CI: 0.2-2.6%], P = 0.018) and CVE (ARR: 3.5%, [95%CI: 0.0-6.9%], P = 0.045) in the AF group was much higher than the non-AF group for heart failure (ARR: 0.4%, [95%CI: 0.0-0.7%], P = 0.057) and CVE (ARR: 1.6%, [95%CI: -0.1% to 3.3%], P = 0.071). No significant effect was noted on all-cause or cardiovascular mortality, stroke, or myocardial infarction.This study suggests that RAAS blockade offers protection against heart failure and cardiovascular events in high cardiovascular disease risk subjects with atrial fibrillation. PMID:27368043

  8. Adverse drug reactions associated with the use of disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis.

    PubMed

    Machado-Alba, Jorge Enrique; Ruiz, Andrés Felipe; Machado-Duque, Manuel Enrique

    2014-12-01

    This study describes the adverse drug reactions (ADRs) and their incidence in patients with rheumatoid arthritis who were treated in the Colombian health system. A retrospective cohort study was conducted using information from all patients who were diagnosed with rheumatoid arthritis and attended specialized health care centers in the cities of Bogotá, Cali, Manizales, Medellin, and Pereira between 1 December 2009 and 30 August 2013. The ADRs were obtained from medical records and the pharmacovigilance system registry and sorted by frequency and affected tissue according to World Health Organization Adverse Reaction Terminology (WHO-ART). A total of 949 reports of ADRs were obtained from 419 patients (32.8 ADRs per 100 patient-years); these patients were from a cohort of 1,364 patients being treated for rheumatoid arthritis and followed up for an average of 23.8 months (± 12.9). The cohort was mostly female (366, 87.4%) and had a mean age of 52.7 years (± 13.1). The highest numbers of ADRs were reported following the use of tocilizumab, rituximab, and infliximab (28.8, 23.1, and 13.3 reports per 100 patient-years respectively). The most frequently reported ADRs were elevated transaminase levels and dyspepsia. Overall, 87.7% of ADRs were classified as type A, 36.6% as mild, 40.7% as moderate, and 22.7% as severe. As a result, 73.2% of patients who experienced an ADR stopped taking their drugs. The occurrence of ADRs in patients treated for rheumatoid arthritis is common, especially in those associated with the use of biotechnologically produced anti-rheumatic drugs. This outcome should be studied in future research and monitoring is needed to reduce the risks in these patients. PMID:25711751

  9. Application of in silico and in vitro methods in the development of adverse outcome pathway constructs in wildlife

    PubMed Central

    Madden, Judith C.; Rogiers, Vera; Vinken, Mathieu

    2014-01-01

    There is a long history of using both in silico and in vitro methods to predict adverse effects in humans and environmental species where toxicity data are lacking. Currently, there is a great deal of interest in applying these methods to the development of so-called ‘adverse outcome pathway’ (AOP) constructs. The AOP approach provides a framework for organizing information at the chemical and biological level, allowing evidence from both in silico and in vitro studies to be rationally combined to fill gaps in knowledge concerning toxicological events. Fundamental to this new paradigm is a greater understanding of the mechanisms of toxicity and, in particular, where these mechanisms may be conserved across taxa, such as between model animals and related wild species. This presents an opportunity to make predictions across diverse species, where empirical data are unlikely to become available as is the case for most species of wildlife. PMID:25405971

  10. Prognostic significance of adverse events in patients with hepatocellular carcinoma treated with sorafenib

    PubMed Central

    Granito, Alessandro; Marinelli, Sara; Negrini, Giulia; Menetti, Saverio; Benevento, Francesca; Bolondi, Luigi

    2016-01-01

    Sorafenib is the standard treatment for patients with hepatocellular carcinoma (HCC) with advanced stage disease. Although its effectiveness has been demonstrated by randomized clinical trials and confirmed by field practice studies, reliable markers predicting therapeutic response have not yet been identified. Like other tyrosine kinase inhibitors, treatment with sorafenib is burdened by the development of adverse effects, the most frequent being cutaneous toxicity, diarrhoea, arterial hypertension and fatigue. In recent years, several studies have analysed the correlation between off-target effects and sorafenib efficacy in patients with HCC. In this review, an overview of the studies assessing the prognostic significance of sorafenib-related adverse events is provided. PMID:26929785